Pediatrics

Approximately 3% of youth who tested positive for COVID-19 in an emergency department setting had severe outcomes after 2 weeks, but this risk was 0.5% among those not admitted to the hospital, based on data from more than 3,000 individuals aged 18 and younger.

In the early stages of the COVID-19 pandemic, youth younger than 18 years accounted for fewer than 5% of reported cases, but now account for approximately 25% of positive cases, wrote Anna L. Funk, PhD, of the University of Calgary, Alberta, Canada, and colleagues.

However, the risk of severe outcomes of youth with COVID-19 remains poorly understood and data from large studies are lacking, they noted.

In a prospective cohort study published in JAMA Network Open, the researchers reviewed data from 3,221 children and adolescents who were tested for COVID-19 at one of 41 emergency departments in 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States between March 2020 and June 2021. Positive infections were confirmed by polymerase chain reaction (PCR) testing. At 14 days’ follow-up after a positive test, 735 patients (22.8%), were hospitalized, 107 (3.3%) had severe outcomes, and 4 (0.12%) had died. Severe outcomes were significantly more likely in children aged 5-10 years and 10-18 years vs. less than 1 year (odds ratios, 1.60 and 2.39, respectively), and in children with a self-reported chronic illness (OR, 2.34) or a prior episode of pneumonia (OR, 3.15).

Severe outcomes were more likely in patients who presented with symptoms that started 4-7 days before seeking care, compared with those whose symptoms started 0-3 days before seeking care (OR, 2.22).

The researchers also reviewed data from a subgroup of 2,510 individuals who were discharged home from the ED after initial testing. At 14 days’ follow-up, 50 of these patients (2.0%) were hospitalized and 12 (0.5%) had severe outcomes. In addition, the researchers found that the risk of severe outcomes among hospitalized COVID-19–positive youth was nearly four times higher, compared with hospitalized youth who tested negative for COVID-19 (risk difference, 3.9%).

Previous retrospective studies of severe outcomes in children and adolescents with COVID-19 have yielded varying results, in part because of the variation in study populations, the researchers noted in their discussion of the findings. “Our study population provides a risk estimate for youths brought for ED care.” Therefore, “Our lower estimate of severe disease likely reflects our stringent definition, which required the occurrence of complications or specific invasive interventions,” they said.

The study limitations included the potential overestimation of the risk of severe outcomes because patients were recruited in the ED, the researchers noted. Other limitations included variation in regional case definitions, screening criteria, and testing capacity among different sites and time periods. “Thus, 5% of our SARS-CoV-2–positive participants were asymptomatic – most of whom were tested as they were positive contacts of known cases or as part of routine screening procedures,” they said. The findings also are not generalizable to all community EDs and did not account for variants, they added.

However, the results were strengthened by the ability to compare outcomes for children with positive tests to similar children with negative tests, and add to the literature showing an increased risk of severe outcomes for those hospitalized with positive tests, the researchers concluded.
 

Data may inform clinical decisions

“The data [in the current study] are concerning for severe outcomes for children even prior to the Omicron strain,” said Margaret Thew, DNP, FP-BC, of Children’s Wisconsin-Milwaukee Hospital, in an interview. “Presently, the number of children infected with the Omicron strain is much higher and hospitalizations among children are at their highest since COVID-19 began,” she said. “For medical providers caring for this population, the study sheds light on pediatric patients who may be at higher risk of severe illness when they become infected with COVID-19,” she added.

“I was surprised by how high the number of pediatric patients hospitalized (22%) and the percentage (3%) with severe disease were during this time,” given that the timeline for these data preceded the spread of the Omicron strain, said Ms. Thew. “The risk of prior pneumonia was quite surprising. I do not recall seeing prior pneumonia as a risk factor for more severe COVID-19 with children or adults,” she added.

The take-home messaging for clinicians caring for children and adolescents is the added knowledge of the risk factors for severe outcomes from COVID-19, including the 10-18 age range, chronic illness, prior pneumonia, and longer symptom duration before seeking care in the ED, Ms. Thew emphasized.

However, additional research is needed on the impact of the new strains of COVID-19 on pediatric and adolescent hospitalizations, Ms. Thew said. Research also is needed on the other illnesses that have resulted from COVID-19, including illness requiring antibiotic use or medical interventions or treatments, and on the risk of combined COVID-19 and influenza viruses, she noted.

The study was supported by the Canadian Institutes of Health Research, Alberta Innovates, the Alberta Health Services University of Calgary Clinical Research Fund, the Alberta Children’s Hospital Research Institute, the COVID-19 Research Accelerator Funding Track (CRAFT) Program at the University of California, Davis, and the Cincinnati Children’s Hospital Medical Center Division of Emergency Medicine Small Grants Program. Lead author Dr. Funk was supported by the University of Calgary Eyes-High Post-Doctoral Research Fund, but had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.

Approximately 3% of youth who tested positive for COVID-19 in an emergency department setting had severe outcomes after 2 weeks, but this risk was 0.5% among those not admitted to the hospital, based on data from more than 3,000 individuals aged 18 and younger.

In the early stages of the COVID-19 pandemic, youth younger than 18 years accounted for fewer than 5% of reported cases, but now account for approximately 25% of positive cases, wrote Anna L. Funk, PhD, of the University of Calgary, Alberta, Canada, and colleagues.

However, the risk of severe outcomes of youth with COVID-19 remains poorly understood and data from large studies are lacking, they noted.

In a prospective cohort study published in JAMA Network Open, the researchers reviewed data from 3,221 children and adolescents who were tested for COVID-19 at one of 41 emergency departments in 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States between March 2020 and June 2021. Positive infections were confirmed by polymerase chain reaction (PCR) testing. At 14 days’ follow-up after a positive test, 735 patients (22.8%), were hospitalized, 107 (3.3%) had severe outcomes, and 4 (0.12%) had died. Severe outcomes were significantly more likely in children aged 5-10 years and 10-18 years vs. less than 1 year (odds ratios, 1.60 and 2.39, respectively), and in children with a self-reported chronic illness (OR, 2.34) or a prior episode of pneumonia (OR, 3.15).

Severe outcomes were more likely in patients who presented with symptoms that started 4-7 days before seeking care, compared with those whose symptoms started 0-3 days before seeking care (OR, 2.22).

The researchers also reviewed data from a subgroup of 2,510 individuals who were discharged home from the ED after initial testing. At 14 days’ follow-up, 50 of these patients (2.0%) were hospitalized and 12 (0.5%) had severe outcomes. In addition, the researchers found that the risk of severe outcomes among hospitalized COVID-19–positive youth was nearly four times higher, compared with hospitalized youth who tested negative for COVID-19 (risk difference, 3.9%).

Previous retrospective studies of severe outcomes in children and adolescents with COVID-19 have yielded varying results, in part because of the variation in study populations, the researchers noted in their discussion of the findings. “Our study population provides a risk estimate for youths brought for ED care.” Therefore, “Our lower estimate of severe disease likely reflects our stringent definition, which required the occurrence of complications or specific invasive interventions,” they said.

The study limitations included the potential overestimation of the risk of severe outcomes because patients were recruited in the ED, the researchers noted. Other limitations included variation in regional case definitions, screening criteria, and testing capacity among different sites and time periods. “Thus, 5% of our SARS-CoV-2–positive participants were asymptomatic – most of whom were tested as they were positive contacts of known cases or as part of routine screening procedures,” they said. The findings also are not generalizable to all community EDs and did not account for variants, they added.

However, the results were strengthened by the ability to compare outcomes for children with positive tests to similar children with negative tests, and add to the literature showing an increased risk of severe outcomes for those hospitalized with positive tests, the researchers concluded.
 

Data may inform clinical decisions

“The data [in the current study] are concerning for severe outcomes for children even prior to the Omicron strain,” said Margaret Thew, DNP, FP-BC, of Children’s Wisconsin-Milwaukee Hospital, in an interview. “Presently, the number of children infected with the Omicron strain is much higher and hospitalizations among children are at their highest since COVID-19 began,” she said. “For medical providers caring for this population, the study sheds light on pediatric patients who may be at higher risk of severe illness when they become infected with COVID-19,” she added.

“I was surprised by how high the number of pediatric patients hospitalized (22%) and the percentage (3%) with severe disease were during this time,” given that the timeline for these data preceded the spread of the Omicron strain, said Ms. Thew. “The risk of prior pneumonia was quite surprising. I do not recall seeing prior pneumonia as a risk factor for more severe COVID-19 with children or adults,” she added.

The take-home messaging for clinicians caring for children and adolescents is the added knowledge of the risk factors for severe outcomes from COVID-19, including the 10-18 age range, chronic illness, prior pneumonia, and longer symptom duration before seeking care in the ED, Ms. Thew emphasized.

However, additional research is needed on the impact of the new strains of COVID-19 on pediatric and adolescent hospitalizations, Ms. Thew said. Research also is needed on the other illnesses that have resulted from COVID-19, including illness requiring antibiotic use or medical interventions or treatments, and on the risk of combined COVID-19 and influenza viruses, she noted.

The study was supported by the Canadian Institutes of Health Research, Alberta Innovates, the Alberta Health Services University of Calgary Clinical Research Fund, the Alberta Children’s Hospital Research Institute, the COVID-19 Research Accelerator Funding Track (CRAFT) Program at the University of California, Davis, and the Cincinnati Children’s Hospital Medical Center Division of Emergency Medicine Small Grants Program. Lead author Dr. Funk was supported by the University of Calgary Eyes-High Post-Doctoral Research Fund, but had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.

Approximately 3% of youth who tested positive for COVID-19 in an emergency department setting had severe outcomes after 2 weeks, but this risk was 0.5% among those not admitted to the hospital, based on data from more than 3,000 individuals aged 18 and younger.

In the early stages of the COVID-19 pandemic, youth younger than 18 years accounted for fewer than 5% of reported cases, but now account for approximately 25% of positive cases, wrote Anna L. Funk, PhD, of the University of Calgary, Alberta, Canada, and colleagues.

However, the risk of severe outcomes of youth with COVID-19 remains poorly understood and data from large studies are lacking, they noted.

In a prospective cohort study published in JAMA Network Open, the researchers reviewed data from 3,221 children and adolescents who were tested for COVID-19 at one of 41 emergency departments in 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States between March 2020 and June 2021. Positive infections were confirmed by polymerase chain reaction (PCR) testing. At 14 days’ follow-up after a positive test, 735 patients (22.8%), were hospitalized, 107 (3.3%) had severe outcomes, and 4 (0.12%) had died. Severe outcomes were significantly more likely in children aged 5-10 years and 10-18 years vs. less than 1 year (odds ratios, 1.60 and 2.39, respectively), and in children with a self-reported chronic illness (OR, 2.34) or a prior episode of pneumonia (OR, 3.15).

Severe outcomes were more likely in patients who presented with symptoms that started 4-7 days before seeking care, compared with those whose symptoms started 0-3 days before seeking care (OR, 2.22).

The researchers also reviewed data from a subgroup of 2,510 individuals who were discharged home from the ED after initial testing. At 14 days’ follow-up, 50 of these patients (2.0%) were hospitalized and 12 (0.5%) had severe outcomes. In addition, the researchers found that the risk of severe outcomes among hospitalized COVID-19–positive youth was nearly four times higher, compared with hospitalized youth who tested negative for COVID-19 (risk difference, 3.9%).

Previous retrospective studies of severe outcomes in children and adolescents with COVID-19 have yielded varying results, in part because of the variation in study populations, the researchers noted in their discussion of the findings. “Our study population provides a risk estimate for youths brought for ED care.” Therefore, “Our lower estimate of severe disease likely reflects our stringent definition, which required the occurrence of complications or specific invasive interventions,” they said.

The study limitations included the potential overestimation of the risk of severe outcomes because patients were recruited in the ED, the researchers noted. Other limitations included variation in regional case definitions, screening criteria, and testing capacity among different sites and time periods. “Thus, 5% of our SARS-CoV-2–positive participants were asymptomatic – most of whom were tested as they were positive contacts of known cases or as part of routine screening procedures,” they said. The findings also are not generalizable to all community EDs and did not account for variants, they added.

However, the results were strengthened by the ability to compare outcomes for children with positive tests to similar children with negative tests, and add to the literature showing an increased risk of severe outcomes for those hospitalized with positive tests, the researchers concluded.
 

Data may inform clinical decisions

“The data [in the current study] are concerning for severe outcomes for children even prior to the Omicron strain,” said Margaret Thew, DNP, FP-BC, of Children’s Wisconsin-Milwaukee Hospital, in an interview. “Presently, the number of children infected with the Omicron strain is much higher and hospitalizations among children are at their highest since COVID-19 began,” she said. “For medical providers caring for this population, the study sheds light on pediatric patients who may be at higher risk of severe illness when they become infected with COVID-19,” she added.

“I was surprised by how high the number of pediatric patients hospitalized (22%) and the percentage (3%) with severe disease were during this time,” given that the timeline for these data preceded the spread of the Omicron strain, said Ms. Thew. “The risk of prior pneumonia was quite surprising. I do not recall seeing prior pneumonia as a risk factor for more severe COVID-19 with children or adults,” she added.

The take-home messaging for clinicians caring for children and adolescents is the added knowledge of the risk factors for severe outcomes from COVID-19, including the 10-18 age range, chronic illness, prior pneumonia, and longer symptom duration before seeking care in the ED, Ms. Thew emphasized.

However, additional research is needed on the impact of the new strains of COVID-19 on pediatric and adolescent hospitalizations, Ms. Thew said. Research also is needed on the other illnesses that have resulted from COVID-19, including illness requiring antibiotic use or medical interventions or treatments, and on the risk of combined COVID-19 and influenza viruses, she noted.

The study was supported by the Canadian Institutes of Health Research, Alberta Innovates, the Alberta Health Services University of Calgary Clinical Research Fund, the Alberta Children’s Hospital Research Institute, the COVID-19 Research Accelerator Funding Track (CRAFT) Program at the University of California, Davis, and the Cincinnati Children’s Hospital Medical Center Division of Emergency Medicine Small Grants Program. Lead author Dr. Funk was supported by the University of Calgary Eyes-High Post-Doctoral Research Fund, but had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.

The evidence is in: Less is more when it comes to treating uncomplicated community-acquired pneumonia (CAP) in young children. Five days of antibiotic therapy resulted in a superior clinical response compared to 10 days of treatment and had the added benefit of a lower risk of inducing antibiotic resistance, according to the randomized, controlled SCOUT-CAP trial.

“Several studies have shown shorter antibiotic courses to be non-inferior to the standard treatment strategy, but in our study, we show that a shortened 5-day course of therapy was superior to standard therapy because the short course achieved similar outcomes with fewer days of antibiotics,” Derek Williams, MD, MPH, Vanderbilt University Medical Center, Nashville, Tenn., said in an email.

“These data are immediately applicable to frontline clinicians, and we hope this study will shift the paradigm towards more judicious treatment approaches for childhood pneumonia, resulting in care that is safer and more effective,” he added.

The study was published online Jan. 18 in JAMA Pediatrics.
 

Uncomplicated CAP

The study enrolled children aged 6 months to 71 months diagnosed with uncomplicated CAP who demonstrated early clinical improvement in response to 5 days of antibiotic treatment. Participants were prescribed either amoxicillin, amoxicillin and clavulanate, or cefdinir according to standard of care and were randomized on day 6 to another 5 days of their initially prescribed antibiotic course or to placebo.

“Those assessed on day 6 were eligible only if they had not yet received a dose of antibiotic therapy on that day,” the authors write. The primary endpoint was end-of-treatment response, adjusted for the duration of antibiotic risk as assessed by RADAR. As the authors explain, RADAR is a composite endpoint that ranks each child’s clinical response, resolution of symptoms, and antibiotic-associated adverse effects (AEs) in an ordinal desirability of outcome ranking, or DOOR.

“There were no differences between strategies in the DOOR or in its individual components,” Dr. Williams and colleagues point out. A total of 380 children took part in the study. The mean age of participants was 35.7 months, and half were male.

Over 90% of children randomized to active therapy were prescribed amoxicillin. “Fewer than 10% of children in either strategy had an inadequate clinical response,” the authors report.

However, the 5-day antibiotic strategy had a 69% (95% CI, 63%-75%) probability of children achieving a more desirable RADAR outcome compared with the standard, 10-day course, as assessed either on days 6 to 10 at outcome assessment visit one (OAV1) or at OAV2 on days 19 to 25.

There were also no significant differences between the two groups in the percentage of participants with persistent symptoms at either assessment point, they note. At assessment visit one, 40% of children assigned to the short-course strategy and 37% of children assigned to the 10-day strategy reported an antibiotic-related AE, most of which were mild.
 

Resistome analysis

Some 171 children were included in a resistome analysis in which throat swabs were collected between study days 19 and 25 to quantify antibiotic resistance genes in oropharyngeal flora. The total number of resistance genes per prokaryotic cell (RGPC) was significantly lower in children treated with antibiotics for 5 days compared with children who were treated for 10 days.

Specifically, the median number of total RGPC was 1.17 (95% CI, 0.35-2.43) for the short-course strategy and 1.33 (95% CI, 0.46-11.08) for the standard-course strategy (P = .01). Similarly, the median number of β-lactamase RGPC was 0.55 (0.18-1.24) for the short-course strategy and 0.60 (0.21-2.45) for the standard-course strategy (P = .03).

“Providing the shortest duration of antibiotics necessary to effectively treat an infection is a central tenet of antimicrobial stewardship and a convenient and cost-effective strategy for caregivers,” the authors observe. For example, reducing treatment from 10 to 5 days for outpatient CAP could reduce the number of days spent on antibiotics by up to 7.5 million days in the U.S. each year.

“If we can safely reduce antibiotic exposure, we can minimize antibiotic side effects while also helping to slow antibiotic resistance,” Dr. Williams pointed out.

Fewer days of having to give their child repeated doses of antibiotics is also more convenient for families, he added.

Asked to comment on the study, David Greenberg, MD, professor of pediatrics and infectious diseases, Ben Gurion University of the Negev, Israel, explained that the length of antibiotic therapy as recommended by various guidelines is more or less arbitrary, some infections being excepted.

“There have been no studies evaluating the recommendation for a 100-day treatment course, and it’s kind of a joke because if you look at the treatment of just about any infection, it’s either for 7 days or 14 days or even 20 days because it’s easy to calculate – it’s not that anybody proved that treatment of whatever infection it is should last this long,” he told this news organization.

Moreover, adherence to a shorter antibiotic course is much better than it is to a longer course. If, for example, physicians tell a mother to take two bottles of antibiotics for a treatment course of 10 days, she’ll finish the first bottle which is good for 5 days and, because the child is fine, “she forgets about the second bottle,” Dr. Greenberg said.

In one of the first studies to compare a short versus long course of antibiotic therapy in uncomplicated CAP in young children, Dr. Greenberg and colleagues initially compared a 3-day course of high-dose amoxicillin to a 10-day course of the same treatment, but the 3-day course was associated with an unacceptable failure rate. (At the time, the World Health Organization was recommending a 3-day course of antibiotics for the treatment of uncomplicated CAP in children.)

They stopped the study and then initiated a second study in which they compared a 5-day course of the same antibiotic to a 10-day course and found the 5-day course was comparable to the 10-day course in terms of clinical cure rates. As a result of his study, Dr. Greenberg has long since prescribed a 5-day course of antibiotics for his own patients.

“Five days is good,” he affirmed. “And if patients start a 10-day course of an antibiotic for, say, a urinary tract infection and a subsequent culture comes back negative, they don’t have to finish the antibiotics either.” Dr. Greenberg said.

Dr. Williams said he has no financial ties to industry. Dr. Greenberg said he has served as a consultant for Pfizer, Merck, Johnson & Johnson, and AstraZeneca. He is also a founder of the company Beyond Air.

A version of this article first appeared on Medscape.com.

The evidence is in: Less is more when it comes to treating uncomplicated community-acquired pneumonia (CAP) in young children. Five days of antibiotic therapy resulted in a superior clinical response compared to 10 days of treatment and had the added benefit of a lower risk of inducing antibiotic resistance, according to the randomized, controlled SCOUT-CAP trial.

“Several studies have shown shorter antibiotic courses to be non-inferior to the standard treatment strategy, but in our study, we show that a shortened 5-day course of therapy was superior to standard therapy because the short course achieved similar outcomes with fewer days of antibiotics,” Derek Williams, MD, MPH, Vanderbilt University Medical Center, Nashville, Tenn., said in an email.

“These data are immediately applicable to frontline clinicians, and we hope this study will shift the paradigm towards more judicious treatment approaches for childhood pneumonia, resulting in care that is safer and more effective,” he added.

The study was published online Jan. 18 in JAMA Pediatrics.
 

Uncomplicated CAP

The study enrolled children aged 6 months to 71 months diagnosed with uncomplicated CAP who demonstrated early clinical improvement in response to 5 days of antibiotic treatment. Participants were prescribed either amoxicillin, amoxicillin and clavulanate, or cefdinir according to standard of care and were randomized on day 6 to another 5 days of their initially prescribed antibiotic course or to placebo.

“Those assessed on day 6 were eligible only if they had not yet received a dose of antibiotic therapy on that day,” the authors write. The primary endpoint was end-of-treatment response, adjusted for the duration of antibiotic risk as assessed by RADAR. As the authors explain, RADAR is a composite endpoint that ranks each child’s clinical response, resolution of symptoms, and antibiotic-associated adverse effects (AEs) in an ordinal desirability of outcome ranking, or DOOR.

“There were no differences between strategies in the DOOR or in its individual components,” Dr. Williams and colleagues point out. A total of 380 children took part in the study. The mean age of participants was 35.7 months, and half were male.

Over 90% of children randomized to active therapy were prescribed amoxicillin. “Fewer than 10% of children in either strategy had an inadequate clinical response,” the authors report.

However, the 5-day antibiotic strategy had a 69% (95% CI, 63%-75%) probability of children achieving a more desirable RADAR outcome compared with the standard, 10-day course, as assessed either on days 6 to 10 at outcome assessment visit one (OAV1) or at OAV2 on days 19 to 25.

There were also no significant differences between the two groups in the percentage of participants with persistent symptoms at either assessment point, they note. At assessment visit one, 40% of children assigned to the short-course strategy and 37% of children assigned to the 10-day strategy reported an antibiotic-related AE, most of which were mild.
 

Resistome analysis

Some 171 children were included in a resistome analysis in which throat swabs were collected between study days 19 and 25 to quantify antibiotic resistance genes in oropharyngeal flora. The total number of resistance genes per prokaryotic cell (RGPC) was significantly lower in children treated with antibiotics for 5 days compared with children who were treated for 10 days.

Specifically, the median number of total RGPC was 1.17 (95% CI, 0.35-2.43) for the short-course strategy and 1.33 (95% CI, 0.46-11.08) for the standard-course strategy (P = .01). Similarly, the median number of β-lactamase RGPC was 0.55 (0.18-1.24) for the short-course strategy and 0.60 (0.21-2.45) for the standard-course strategy (P = .03).

“Providing the shortest duration of antibiotics necessary to effectively treat an infection is a central tenet of antimicrobial stewardship and a convenient and cost-effective strategy for caregivers,” the authors observe. For example, reducing treatment from 10 to 5 days for outpatient CAP could reduce the number of days spent on antibiotics by up to 7.5 million days in the U.S. each year.

“If we can safely reduce antibiotic exposure, we can minimize antibiotic side effects while also helping to slow antibiotic resistance,” Dr. Williams pointed out.

Fewer days of having to give their child repeated doses of antibiotics is also more convenient for families, he added.

Asked to comment on the study, David Greenberg, MD, professor of pediatrics and infectious diseases, Ben Gurion University of the Negev, Israel, explained that the length of antibiotic therapy as recommended by various guidelines is more or less arbitrary, some infections being excepted.

“There have been no studies evaluating the recommendation for a 100-day treatment course, and it’s kind of a joke because if you look at the treatment of just about any infection, it’s either for 7 days or 14 days or even 20 days because it’s easy to calculate – it’s not that anybody proved that treatment of whatever infection it is should last this long,” he told this news organization.

Moreover, adherence to a shorter antibiotic course is much better than it is to a longer course. If, for example, physicians tell a mother to take two bottles of antibiotics for a treatment course of 10 days, she’ll finish the first bottle which is good for 5 days and, because the child is fine, “she forgets about the second bottle,” Dr. Greenberg said.

In one of the first studies to compare a short versus long course of antibiotic therapy in uncomplicated CAP in young children, Dr. Greenberg and colleagues initially compared a 3-day course of high-dose amoxicillin to a 10-day course of the same treatment, but the 3-day course was associated with an unacceptable failure rate. (At the time, the World Health Organization was recommending a 3-day course of antibiotics for the treatment of uncomplicated CAP in children.)

They stopped the study and then initiated a second study in which they compared a 5-day course of the same antibiotic to a 10-day course and found the 5-day course was comparable to the 10-day course in terms of clinical cure rates. As a result of his study, Dr. Greenberg has long since prescribed a 5-day course of antibiotics for his own patients.

“Five days is good,” he affirmed. “And if patients start a 10-day course of an antibiotic for, say, a urinary tract infection and a subsequent culture comes back negative, they don’t have to finish the antibiotics either.” Dr. Greenberg said.

Dr. Williams said he has no financial ties to industry. Dr. Greenberg said he has served as a consultant for Pfizer, Merck, Johnson & Johnson, and AstraZeneca. He is also a founder of the company Beyond Air.

A version of this article first appeared on Medscape.com.

The evidence is in: Less is more when it comes to treating uncomplicated community-acquired pneumonia (CAP) in young children. Five days of antibiotic therapy resulted in a superior clinical response compared to 10 days of treatment and had the added benefit of a lower risk of inducing antibiotic resistance, according to the randomized, controlled SCOUT-CAP trial.

“Several studies have shown shorter antibiotic courses to be non-inferior to the standard treatment strategy, but in our study, we show that a shortened 5-day course of therapy was superior to standard therapy because the short course achieved similar outcomes with fewer days of antibiotics,” Derek Williams, MD, MPH, Vanderbilt University Medical Center, Nashville, Tenn., said in an email.

“These data are immediately applicable to frontline clinicians, and we hope this study will shift the paradigm towards more judicious treatment approaches for childhood pneumonia, resulting in care that is safer and more effective,” he added.

The study was published online Jan. 18 in JAMA Pediatrics.
 

Uncomplicated CAP

The study enrolled children aged 6 months to 71 months diagnosed with uncomplicated CAP who demonstrated early clinical improvement in response to 5 days of antibiotic treatment. Participants were prescribed either amoxicillin, amoxicillin and clavulanate, or cefdinir according to standard of care and were randomized on day 6 to another 5 days of their initially prescribed antibiotic course or to placebo.

“Those assessed on day 6 were eligible only if they had not yet received a dose of antibiotic therapy on that day,” the authors write. The primary endpoint was end-of-treatment response, adjusted for the duration of antibiotic risk as assessed by RADAR. As the authors explain, RADAR is a composite endpoint that ranks each child’s clinical response, resolution of symptoms, and antibiotic-associated adverse effects (AEs) in an ordinal desirability of outcome ranking, or DOOR.

“There were no differences between strategies in the DOOR or in its individual components,” Dr. Williams and colleagues point out. A total of 380 children took part in the study. The mean age of participants was 35.7 months, and half were male.

Over 90% of children randomized to active therapy were prescribed amoxicillin. “Fewer than 10% of children in either strategy had an inadequate clinical response,” the authors report.

However, the 5-day antibiotic strategy had a 69% (95% CI, 63%-75%) probability of children achieving a more desirable RADAR outcome compared with the standard, 10-day course, as assessed either on days 6 to 10 at outcome assessment visit one (OAV1) or at OAV2 on days 19 to 25.

There were also no significant differences between the two groups in the percentage of participants with persistent symptoms at either assessment point, they note. At assessment visit one, 40% of children assigned to the short-course strategy and 37% of children assigned to the 10-day strategy reported an antibiotic-related AE, most of which were mild.
 

Resistome analysis

Some 171 children were included in a resistome analysis in which throat swabs were collected between study days 19 and 25 to quantify antibiotic resistance genes in oropharyngeal flora. The total number of resistance genes per prokaryotic cell (RGPC) was significantly lower in children treated with antibiotics for 5 days compared with children who were treated for 10 days.

Specifically, the median number of total RGPC was 1.17 (95% CI, 0.35-2.43) for the short-course strategy and 1.33 (95% CI, 0.46-11.08) for the standard-course strategy (P = .01). Similarly, the median number of β-lactamase RGPC was 0.55 (0.18-1.24) for the short-course strategy and 0.60 (0.21-2.45) for the standard-course strategy (P = .03).

“Providing the shortest duration of antibiotics necessary to effectively treat an infection is a central tenet of antimicrobial stewardship and a convenient and cost-effective strategy for caregivers,” the authors observe. For example, reducing treatment from 10 to 5 days for outpatient CAP could reduce the number of days spent on antibiotics by up to 7.5 million days in the U.S. each year.

“If we can safely reduce antibiotic exposure, we can minimize antibiotic side effects while also helping to slow antibiotic resistance,” Dr. Williams pointed out.

Fewer days of having to give their child repeated doses of antibiotics is also more convenient for families, he added.

Asked to comment on the study, David Greenberg, MD, professor of pediatrics and infectious diseases, Ben Gurion University of the Negev, Israel, explained that the length of antibiotic therapy as recommended by various guidelines is more or less arbitrary, some infections being excepted.

“There have been no studies evaluating the recommendation for a 100-day treatment course, and it’s kind of a joke because if you look at the treatment of just about any infection, it’s either for 7 days or 14 days or even 20 days because it’s easy to calculate – it’s not that anybody proved that treatment of whatever infection it is should last this long,” he told this news organization.

Moreover, adherence to a shorter antibiotic course is much better than it is to a longer course. If, for example, physicians tell a mother to take two bottles of antibiotics for a treatment course of 10 days, she’ll finish the first bottle which is good for 5 days and, because the child is fine, “she forgets about the second bottle,” Dr. Greenberg said.

In one of the first studies to compare a short versus long course of antibiotic therapy in uncomplicated CAP in young children, Dr. Greenberg and colleagues initially compared a 3-day course of high-dose amoxicillin to a 10-day course of the same treatment, but the 3-day course was associated with an unacceptable failure rate. (At the time, the World Health Organization was recommending a 3-day course of antibiotics for the treatment of uncomplicated CAP in children.)

They stopped the study and then initiated a second study in which they compared a 5-day course of the same antibiotic to a 10-day course and found the 5-day course was comparable to the 10-day course in terms of clinical cure rates. As a result of his study, Dr. Greenberg has long since prescribed a 5-day course of antibiotics for his own patients.

“Five days is good,” he affirmed. “And if patients start a 10-day course of an antibiotic for, say, a urinary tract infection and a subsequent culture comes back negative, they don’t have to finish the antibiotics either.” Dr. Greenberg said.

Dr. Williams said he has no financial ties to industry. Dr. Greenberg said he has served as a consultant for Pfizer, Merck, Johnson & Johnson, and AstraZeneca. He is also a founder of the company Beyond Air.

A version of this article first appeared on Medscape.com.

Most children with multisystem inflammatory syndrome related to COVID-19 infection show recovery of cardiac function by 3 months, but longer term follow-up is still needed, suggests a new retrospective longitudinal cohort study.

While 80%-85% of children with multisystem inflammatory syndrome have cardiovascular involvement, “lack of knowledge about the short-term consequences of MIS-C has led to uncertainty among physicians in making recommendations about follow-up,” Daisuke Matsubara, MD, PhD, and colleagues wrote in their paper, which was published in the Journal of the American Heart Association.

Dr. Matsubara, of the department of pediatrics at the Children’s Hospital of Philadelphia, and colleagues examined cardiac outcomes among 60 patients aged 18 years or under admitted to two Philadelphia hospitals with MIS-C between April 2020 and January 2021. They compared those with outcomes in 60 age-matched healthy children who had undergone echocardiography for a range of non–COVID-related conditions such as chest pain or syncope.

The study used echocardiography, MRI, biochemistry, and functional and clinical parameters to assess the degree of change and damage to the heart at 3 months after admission.

When the patients first presented to a hospital, 42 had biochemical signs of myocardial injury, such as elevated brain-type natriuretic peptide and troponin levels. However, most patients’ symptoms were no longer present by the time they were discharged from hospital.

The researchers found that 81% of patients who presented with myocardial injury had lost the left atrial contraction phase. This dropped to 51% during the subacute phase, then 30% at 1 month. By 3-4 months, all patients achieved normal left atrial contraction phase.

At 1 month after admission, all MIS-C patients had significant signs of cardiac strain, compared with controls, including changes to global longitudinal strain, global circumferential strain, circumferential early diastolic strain rate, and right ventricular free wall longitudinal strain.
 

Parameters of strain normalized by 3 months

All parameters of strain had normalized, compared with controls, by 3 months. In the case of global longitudinal strain and left atrial strain, the median time to normalization was 6 days. For left ventricular ejection fraction the median time to normalization was 8 days and for right ventricular free wall longitudinal strain it was 9 days.

A small difference persisted with global longitudinal strain, but the authors said the difference was within the range of normal published values and not clinically relevant. The dysfunction appeared to be spread evenly across the heart rather than varying between segments, they noted.

“Deformation analysis could detect subtle myocardial changes; therefore, our study suggests the absence of persistent subclinical myocardial dysfunction after 3-4 months,” Dr. Matsubara said in an interview.

Four patients experienced small coronary aneurysms during the acute phase of MIS-C, but all had resolved within 2 months and none experienced any further lesions.

Among the 14 patients who underwent cardiac MRI at presentation, 2 had evidence of myocardial edema and fibrosis during the subacute phase of illness, despite having normal left ventricular systolic function and conventional echocardiography.

At follow-up, only one patient had residual edema; this individual had no evidence of fibrosis and had normal systolic function.
 

Study provides reassurance, but longer follow-up needed

Commenting on the study, pediatric cardiologist Devyani Chowdhury, MD, director of Cardiology Care for Children in Lancaster, Pa., said that overall it provided reassurance that most children do recover from MIS-C – and fits with her own clinical experience of the condition – but cautioned that longer-term follow-up was still needed.

“Three months is really not long term for a child,” Dr. Chowdhury said in an interview. “I’ve had a couple of patients whose MRIs have not normalized even after 1 year.”

Dr. Chowdhury also noted that it was a relatively small sample size, and it was also not yet possible to work out what host factors might play a role in increasing the risk of longer-term effects of MIS-C.

“I think it is a disease in evolution and we have to give it time, but in the very short term at least these kids are not dying, they are recovering, going home, and returning to activity and the heart is getting better,” she said.

The study authors suggested their findings could provide an evidence base for recommendations on when children with MIS-C can return to sports and physical activity, given that current consensus statements on the issue treat MIS-C as being equivalent to myocarditis in adults.

Dr. Matsubara noted that the cardiac outcomes of MIS-C were very different from those in COVID-19–affected adults, where echocardiography and MRI show longer-term evidence of myocardial impairments.

“This finding is also different from that of adult COVID-19, where the high troponin is reported to be the prognostic factor,” he said, suggesting this could explain different mechanisms of myocardial injury between MIS-C and COVID-19 myocarditis.

One author was supported by the National Institutes of Health. No conflicts of interest were declared.

Most children with multisystem inflammatory syndrome related to COVID-19 infection show recovery of cardiac function by 3 months, but longer term follow-up is still needed, suggests a new retrospective longitudinal cohort study.

While 80%-85% of children with multisystem inflammatory syndrome have cardiovascular involvement, “lack of knowledge about the short-term consequences of MIS-C has led to uncertainty among physicians in making recommendations about follow-up,” Daisuke Matsubara, MD, PhD, and colleagues wrote in their paper, which was published in the Journal of the American Heart Association.

Dr. Matsubara, of the department of pediatrics at the Children’s Hospital of Philadelphia, and colleagues examined cardiac outcomes among 60 patients aged 18 years or under admitted to two Philadelphia hospitals with MIS-C between April 2020 and January 2021. They compared those with outcomes in 60 age-matched healthy children who had undergone echocardiography for a range of non–COVID-related conditions such as chest pain or syncope.

The study used echocardiography, MRI, biochemistry, and functional and clinical parameters to assess the degree of change and damage to the heart at 3 months after admission.

When the patients first presented to a hospital, 42 had biochemical signs of myocardial injury, such as elevated brain-type natriuretic peptide and troponin levels. However, most patients’ symptoms were no longer present by the time they were discharged from hospital.

The researchers found that 81% of patients who presented with myocardial injury had lost the left atrial contraction phase. This dropped to 51% during the subacute phase, then 30% at 1 month. By 3-4 months, all patients achieved normal left atrial contraction phase.

At 1 month after admission, all MIS-C patients had significant signs of cardiac strain, compared with controls, including changes to global longitudinal strain, global circumferential strain, circumferential early diastolic strain rate, and right ventricular free wall longitudinal strain.
 

Parameters of strain normalized by 3 months

All parameters of strain had normalized, compared with controls, by 3 months. In the case of global longitudinal strain and left atrial strain, the median time to normalization was 6 days. For left ventricular ejection fraction the median time to normalization was 8 days and for right ventricular free wall longitudinal strain it was 9 days.

A small difference persisted with global longitudinal strain, but the authors said the difference was within the range of normal published values and not clinically relevant. The dysfunction appeared to be spread evenly across the heart rather than varying between segments, they noted.

“Deformation analysis could detect subtle myocardial changes; therefore, our study suggests the absence of persistent subclinical myocardial dysfunction after 3-4 months,” Dr. Matsubara said in an interview.

Four patients experienced small coronary aneurysms during the acute phase of MIS-C, but all had resolved within 2 months and none experienced any further lesions.

Among the 14 patients who underwent cardiac MRI at presentation, 2 had evidence of myocardial edema and fibrosis during the subacute phase of illness, despite having normal left ventricular systolic function and conventional echocardiography.

At follow-up, only one patient had residual edema; this individual had no evidence of fibrosis and had normal systolic function.
 

Study provides reassurance, but longer follow-up needed

Commenting on the study, pediatric cardiologist Devyani Chowdhury, MD, director of Cardiology Care for Children in Lancaster, Pa., said that overall it provided reassurance that most children do recover from MIS-C – and fits with her own clinical experience of the condition – but cautioned that longer-term follow-up was still needed.

“Three months is really not long term for a child,” Dr. Chowdhury said in an interview. “I’ve had a couple of patients whose MRIs have not normalized even after 1 year.”

Dr. Chowdhury also noted that it was a relatively small sample size, and it was also not yet possible to work out what host factors might play a role in increasing the risk of longer-term effects of MIS-C.

“I think it is a disease in evolution and we have to give it time, but in the very short term at least these kids are not dying, they are recovering, going home, and returning to activity and the heart is getting better,” she said.

The study authors suggested their findings could provide an evidence base for recommendations on when children with MIS-C can return to sports and physical activity, given that current consensus statements on the issue treat MIS-C as being equivalent to myocarditis in adults.

Dr. Matsubara noted that the cardiac outcomes of MIS-C were very different from those in COVID-19–affected adults, where echocardiography and MRI show longer-term evidence of myocardial impairments.

“This finding is also different from that of adult COVID-19, where the high troponin is reported to be the prognostic factor,” he said, suggesting this could explain different mechanisms of myocardial injury between MIS-C and COVID-19 myocarditis.

One author was supported by the National Institutes of Health. No conflicts of interest were declared.

Most children with multisystem inflammatory syndrome related to COVID-19 infection show recovery of cardiac function by 3 months, but longer term follow-up is still needed, suggests a new retrospective longitudinal cohort study.

While 80%-85% of children with multisystem inflammatory syndrome have cardiovascular involvement, “lack of knowledge about the short-term consequences of MIS-C has led to uncertainty among physicians in making recommendations about follow-up,” Daisuke Matsubara, MD, PhD, and colleagues wrote in their paper, which was published in the Journal of the American Heart Association.

Dr. Matsubara, of the department of pediatrics at the Children’s Hospital of Philadelphia, and colleagues examined cardiac outcomes among 60 patients aged 18 years or under admitted to two Philadelphia hospitals with MIS-C between April 2020 and January 2021. They compared those with outcomes in 60 age-matched healthy children who had undergone echocardiography for a range of non–COVID-related conditions such as chest pain or syncope.

The study used echocardiography, MRI, biochemistry, and functional and clinical parameters to assess the degree of change and damage to the heart at 3 months after admission.

When the patients first presented to a hospital, 42 had biochemical signs of myocardial injury, such as elevated brain-type natriuretic peptide and troponin levels. However, most patients’ symptoms were no longer present by the time they were discharged from hospital.

The researchers found that 81% of patients who presented with myocardial injury had lost the left atrial contraction phase. This dropped to 51% during the subacute phase, then 30% at 1 month. By 3-4 months, all patients achieved normal left atrial contraction phase.

At 1 month after admission, all MIS-C patients had significant signs of cardiac strain, compared with controls, including changes to global longitudinal strain, global circumferential strain, circumferential early diastolic strain rate, and right ventricular free wall longitudinal strain.
 

Parameters of strain normalized by 3 months

All parameters of strain had normalized, compared with controls, by 3 months. In the case of global longitudinal strain and left atrial strain, the median time to normalization was 6 days. For left ventricular ejection fraction the median time to normalization was 8 days and for right ventricular free wall longitudinal strain it was 9 days.

A small difference persisted with global longitudinal strain, but the authors said the difference was within the range of normal published values and not clinically relevant. The dysfunction appeared to be spread evenly across the heart rather than varying between segments, they noted.

“Deformation analysis could detect subtle myocardial changes; therefore, our study suggests the absence of persistent subclinical myocardial dysfunction after 3-4 months,” Dr. Matsubara said in an interview.

Four patients experienced small coronary aneurysms during the acute phase of MIS-C, but all had resolved within 2 months and none experienced any further lesions.

Among the 14 patients who underwent cardiac MRI at presentation, 2 had evidence of myocardial edema and fibrosis during the subacute phase of illness, despite having normal left ventricular systolic function and conventional echocardiography.

At follow-up, only one patient had residual edema; this individual had no evidence of fibrosis and had normal systolic function.
 

Study provides reassurance, but longer follow-up needed

Commenting on the study, pediatric cardiologist Devyani Chowdhury, MD, director of Cardiology Care for Children in Lancaster, Pa., said that overall it provided reassurance that most children do recover from MIS-C – and fits with her own clinical experience of the condition – but cautioned that longer-term follow-up was still needed.

“Three months is really not long term for a child,” Dr. Chowdhury said in an interview. “I’ve had a couple of patients whose MRIs have not normalized even after 1 year.”

Dr. Chowdhury also noted that it was a relatively small sample size, and it was also not yet possible to work out what host factors might play a role in increasing the risk of longer-term effects of MIS-C.

“I think it is a disease in evolution and we have to give it time, but in the very short term at least these kids are not dying, they are recovering, going home, and returning to activity and the heart is getting better,” she said.

The study authors suggested their findings could provide an evidence base for recommendations on when children with MIS-C can return to sports and physical activity, given that current consensus statements on the issue treat MIS-C as being equivalent to myocarditis in adults.

Dr. Matsubara noted that the cardiac outcomes of MIS-C were very different from those in COVID-19–affected adults, where echocardiography and MRI show longer-term evidence of myocardial impairments.

“This finding is also different from that of adult COVID-19, where the high troponin is reported to be the prognostic factor,” he said, suggesting this could explain different mechanisms of myocardial injury between MIS-C and COVID-19 myocarditis.

One author was supported by the National Institutes of Health. No conflicts of interest were declared.

Behavior problems, anxiety, and depression in youths were associated with these individuals participating in remote schooling during broader social lockdowns in a new study.

The systematic review, which was published in JAMA Pediatrics on Jan. 18, 2022, was based on data from 36 studies from 11 countries on mental health, physical health, and well-being in children and adolescents aged 0-18 years. The total population included 79,781 children and 18,028 parents or caregivers. The studies reflected the first wave of pandemic school closures and lockdowns from February to July 2020, with the duration of school closure ranging from 1 week to 3 months.

“There are strong theoretical reasons to suggest that school closures may have contributed to a considerable proportion of the harms identified here, particularly mental health harms, through reduction in social contacts with peers and teachers,” Russell Viner, PhD, of UCL Great Ormond St Institute of Child Health, London, and colleagues wrote in their paper.

The researchers included 9 longitudinal pre-post studies, 5 cohort studies, 21 cross-sectional studies, and 1 modeling study in their analysis. Overall, approximately one-third of the studies (36%) were considered high quality, and approximately two-thirds (64%) of the studies were published in journals. Twenty-five of the reports analyzed focused on mental health and well-being.

Schools provide not only education, but also services including meals, health care, and health supplies. Schools also serve as a safety net and source of social support for children, the researchers noted.

The losses children may have experienced during school closures occurred during a time when more than 167,000 children younger than 18 years lost a parent or caregiver to COVID-19, according to a recent report titled “Hidden Pain” by researchers at the University of Pennsylvania, Nemours Children’s Health, and the COVID Collaborative. Although not addressed in the current study, school closures would prevent bereaved children from receiving social-emotional support from friends and teachers. This crisis of loss also prompted the American Academy of Pediatrics to issue a National State of Emergency in Children’s Mental Health in October 2021.
 

New study results

These studies identified associations between school closures during broader lockdowns and increased emotional and behavioral problems, as well as increased restlessness and inattention. Across these studies, 18%-60% of children and adolescents scored higher than the risk thresholds for diagnoses of distress, especially depressive symptoms and anxiety.

Although two studies showed no significant association with suicide in response to school closures during lockdowns, three studies suggested increased use of screen time, two studies reported increased social media use, and six studies reported lower levels of physical activity.

Three studies of child abuse showed decreases in notifications during lockdowns, likely driven by lack of referrals from schools, the authors noted. A total of 10 studies on sleep and 5 studies on diet showed inconsistent evidence of harm during the specific period of school closures and social lockdowns.

“The contrast of rises in distress with decreases in presentations suggests that there was an escalation of unmet mental health need during lockdowns in already vulnerable children and adolescents,” the researchers wrote. “More troubling still is evidence of a reduction in the ability of the health and social care systems to protect children in many countries, as shown by the large falls in child protection referrals seen in high-quality cohort studies.”
 

‘Study presents concrete assessments rather than speculation’

“Concerns have been widely expressed in the lay media and beyond that school closures could negatively impact the mental and physical health of children and adolescents,” M. Susan Jay, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview. “The authors presented a narrative synthesis summarizing available evidence for the first wave of COVID-19 on school closures during the broader social lockdown occurring during this period.”

The “importance” of this research is that “it is not a single convenience sample study, but a systematic review from 11 countries including the United States, United Kingdom, China, and Turkey, among others, and that the quality of the information was graded,” Dr. Jay said. “Although not a meta-analysis, the study presents concrete assessments rather than speculation and overviews its limitations so that the clinician can weigh this information. Importantly, the authors excluded closure of schools with transmission of infection.

“Clearly, school lockdowns as a measure of controlling infectious disease needs balance with potential of negative health behaviors in children and adolescents. Ongoing prospective longitudinal studies are needed as sequential waves of the pandemic continue,” she emphasized.

“Clinically, this study highlights the need for clinicians to consider [asking] about the impact of school closures and remote versus hybrid versus in-person education [as part of their] patients and families question inventory,” Dr. Jay said. “Also, the use of depression inventories can be offered to youth to assess their mental health state at a visit, either via telemedicine or in person, and ideally at sequential visits for a more in-depth assessment.”
 

Schools play key role in social and emotional development

“It was important to conduct this study now, because this current time is unprecedented,” Peter L. Loper Jr., MD, of the University of South Carolina, Columbia, said in an interview. “We know based on evolutionary biology, anthropology, and developmental psychology, among other disciplines, that meaningful interpersonal interactions embedded in the context of community are vital to supporting human well-being.

“In our current time, the primary framework of community for our children is the school setting; it is the predominant space where they engage in the interpersonal interactions necessary for developing resilience, their sense of purpose, belonging, and fidelity,” he emphasized.

“Rarely in the course of human existence have kids been removed from the broader context of community to this extent and for this duration,” Dr. Loper said. “This study capitalizes on this unprecedented moment to begin to further understand how compromises in our sociocultural infrastructure of community, like school closures and lockdowns, may manifest as mental health problems in children and adolescents. More importantly, it contributes to the exploration of potential unintended consequences of our current infection control measures so we can adapt to support the overall well-being of our children in this ‘new normal.’ ”

Dr. Loper added that he was not surprised by the new study’s findings.

“We were already seeing a decline in pediatric mental health and overall well-being in the years preceding COVID-19 because of the ‘isolation epidemic’ involving many of the factors that this study explored,” he said. “I think this review further illustrates the vital necessity of community to support the health and well-being of humans, and specifically children and adolescents.”

From a clinical standpoint, “we need to be intentional and consistent in balancing infection control measures with our kids’ fundamental psychosocial needs,” Dr. Loper said.

“We need to recognize that, when children and adolescents are isolated from community, their fundamental psychosocial needs go unmet,” he emphasized. “If children and adolescents cannot access the meaningful interpersonal interactions necessary for resilience, then they cannot overcome or navigate distress. They will exhibit the avoidance and withdrawal behaviors that accumulate to manifest as adverse mental health symptoms like anxiety and depression.

“Additional research is needed to further explore how compromises in the psychosocial infrastructure of community manifest as downstream symptom indicators such as anxiety and depression,” which are often manifestations of unmet needs, Dr. Loper said.
 

Limitations and strengths, according to authors

The findings were limited by several factors, including a lack of examination of school closures’ effects on mental health independent of broader social lockdowns, according to the researchers. Other limitations included the authors potentially having missed studies, inclusion of cross-sectional studies with relatively weak evidence, potential bias from studies using parent reports, and a focus on the first COVID-19 wave, during which many school closures were of limited duration. Also, the researchers said they did not include studies focused on particular groups, such as children with learning difficulties or autism.

The use of large databases from education as well as health care in studies analyzed were strengths of the new research, they said. The investigators received no outside funding for their study. The researchers, Dr. Jay, and Dr. Loper had no financial conflicts to disclose. Dr. Jay serves on the editorial advisory board of Pediatric News.

Behavior problems, anxiety, and depression in youths were associated with these individuals participating in remote schooling during broader social lockdowns in a new study.

The systematic review, which was published in JAMA Pediatrics on Jan. 18, 2022, was based on data from 36 studies from 11 countries on mental health, physical health, and well-being in children and adolescents aged 0-18 years. The total population included 79,781 children and 18,028 parents or caregivers. The studies reflected the first wave of pandemic school closures and lockdowns from February to July 2020, with the duration of school closure ranging from 1 week to 3 months.

“There are strong theoretical reasons to suggest that school closures may have contributed to a considerable proportion of the harms identified here, particularly mental health harms, through reduction in social contacts with peers and teachers,” Russell Viner, PhD, of UCL Great Ormond St Institute of Child Health, London, and colleagues wrote in their paper.

The researchers included 9 longitudinal pre-post studies, 5 cohort studies, 21 cross-sectional studies, and 1 modeling study in their analysis. Overall, approximately one-third of the studies (36%) were considered high quality, and approximately two-thirds (64%) of the studies were published in journals. Twenty-five of the reports analyzed focused on mental health and well-being.

Schools provide not only education, but also services including meals, health care, and health supplies. Schools also serve as a safety net and source of social support for children, the researchers noted.

The losses children may have experienced during school closures occurred during a time when more than 167,000 children younger than 18 years lost a parent or caregiver to COVID-19, according to a recent report titled “Hidden Pain” by researchers at the University of Pennsylvania, Nemours Children’s Health, and the COVID Collaborative. Although not addressed in the current study, school closures would prevent bereaved children from receiving social-emotional support from friends and teachers. This crisis of loss also prompted the American Academy of Pediatrics to issue a National State of Emergency in Children’s Mental Health in October 2021.
 

New study results

These studies identified associations between school closures during broader lockdowns and increased emotional and behavioral problems, as well as increased restlessness and inattention. Across these studies, 18%-60% of children and adolescents scored higher than the risk thresholds for diagnoses of distress, especially depressive symptoms and anxiety.

Although two studies showed no significant association with suicide in response to school closures during lockdowns, three studies suggested increased use of screen time, two studies reported increased social media use, and six studies reported lower levels of physical activity.

Three studies of child abuse showed decreases in notifications during lockdowns, likely driven by lack of referrals from schools, the authors noted. A total of 10 studies on sleep and 5 studies on diet showed inconsistent evidence of harm during the specific period of school closures and social lockdowns.

“The contrast of rises in distress with decreases in presentations suggests that there was an escalation of unmet mental health need during lockdowns in already vulnerable children and adolescents,” the researchers wrote. “More troubling still is evidence of a reduction in the ability of the health and social care systems to protect children in many countries, as shown by the large falls in child protection referrals seen in high-quality cohort studies.”
 

‘Study presents concrete assessments rather than speculation’

“Concerns have been widely expressed in the lay media and beyond that school closures could negatively impact the mental and physical health of children and adolescents,” M. Susan Jay, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview. “The authors presented a narrative synthesis summarizing available evidence for the first wave of COVID-19 on school closures during the broader social lockdown occurring during this period.”

The “importance” of this research is that “it is not a single convenience sample study, but a systematic review from 11 countries including the United States, United Kingdom, China, and Turkey, among others, and that the quality of the information was graded,” Dr. Jay said. “Although not a meta-analysis, the study presents concrete assessments rather than speculation and overviews its limitations so that the clinician can weigh this information. Importantly, the authors excluded closure of schools with transmission of infection.

“Clearly, school lockdowns as a measure of controlling infectious disease needs balance with potential of negative health behaviors in children and adolescents. Ongoing prospective longitudinal studies are needed as sequential waves of the pandemic continue,” she emphasized.

“Clinically, this study highlights the need for clinicians to consider [asking] about the impact of school closures and remote versus hybrid versus in-person education [as part of their] patients and families question inventory,” Dr. Jay said. “Also, the use of depression inventories can be offered to youth to assess their mental health state at a visit, either via telemedicine or in person, and ideally at sequential visits for a more in-depth assessment.”
 

Schools play key role in social and emotional development

“It was important to conduct this study now, because this current time is unprecedented,” Peter L. Loper Jr., MD, of the University of South Carolina, Columbia, said in an interview. “We know based on evolutionary biology, anthropology, and developmental psychology, among other disciplines, that meaningful interpersonal interactions embedded in the context of community are vital to supporting human well-being.

“In our current time, the primary framework of community for our children is the school setting; it is the predominant space where they engage in the interpersonal interactions necessary for developing resilience, their sense of purpose, belonging, and fidelity,” he emphasized.

“Rarely in the course of human existence have kids been removed from the broader context of community to this extent and for this duration,” Dr. Loper said. “This study capitalizes on this unprecedented moment to begin to further understand how compromises in our sociocultural infrastructure of community, like school closures and lockdowns, may manifest as mental health problems in children and adolescents. More importantly, it contributes to the exploration of potential unintended consequences of our current infection control measures so we can adapt to support the overall well-being of our children in this ‘new normal.’ ”

Dr. Loper added that he was not surprised by the new study’s findings.

“We were already seeing a decline in pediatric mental health and overall well-being in the years preceding COVID-19 because of the ‘isolation epidemic’ involving many of the factors that this study explored,” he said. “I think this review further illustrates the vital necessity of community to support the health and well-being of humans, and specifically children and adolescents.”

From a clinical standpoint, “we need to be intentional and consistent in balancing infection control measures with our kids’ fundamental psychosocial needs,” Dr. Loper said.

“We need to recognize that, when children and adolescents are isolated from community, their fundamental psychosocial needs go unmet,” he emphasized. “If children and adolescents cannot access the meaningful interpersonal interactions necessary for resilience, then they cannot overcome or navigate distress. They will exhibit the avoidance and withdrawal behaviors that accumulate to manifest as adverse mental health symptoms like anxiety and depression.

“Additional research is needed to further explore how compromises in the psychosocial infrastructure of community manifest as downstream symptom indicators such as anxiety and depression,” which are often manifestations of unmet needs, Dr. Loper said.
 

Limitations and strengths, according to authors

The findings were limited by several factors, including a lack of examination of school closures’ effects on mental health independent of broader social lockdowns, according to the researchers. Other limitations included the authors potentially having missed studies, inclusion of cross-sectional studies with relatively weak evidence, potential bias from studies using parent reports, and a focus on the first COVID-19 wave, during which many school closures were of limited duration. Also, the researchers said they did not include studies focused on particular groups, such as children with learning difficulties or autism.

The use of large databases from education as well as health care in studies analyzed were strengths of the new research, they said. The investigators received no outside funding for their study. The researchers, Dr. Jay, and Dr. Loper had no financial conflicts to disclose. Dr. Jay serves on the editorial advisory board of Pediatric News.

Behavior problems, anxiety, and depression in youths were associated with these individuals participating in remote schooling during broader social lockdowns in a new study.

The systematic review, which was published in JAMA Pediatrics on Jan. 18, 2022, was based on data from 36 studies from 11 countries on mental health, physical health, and well-being in children and adolescents aged 0-18 years. The total population included 79,781 children and 18,028 parents or caregivers. The studies reflected the first wave of pandemic school closures and lockdowns from February to July 2020, with the duration of school closure ranging from 1 week to 3 months.

“There are strong theoretical reasons to suggest that school closures may have contributed to a considerable proportion of the harms identified here, particularly mental health harms, through reduction in social contacts with peers and teachers,” Russell Viner, PhD, of UCL Great Ormond St Institute of Child Health, London, and colleagues wrote in their paper.

The researchers included 9 longitudinal pre-post studies, 5 cohort studies, 21 cross-sectional studies, and 1 modeling study in their analysis. Overall, approximately one-third of the studies (36%) were considered high quality, and approximately two-thirds (64%) of the studies were published in journals. Twenty-five of the reports analyzed focused on mental health and well-being.

Schools provide not only education, but also services including meals, health care, and health supplies. Schools also serve as a safety net and source of social support for children, the researchers noted.

The losses children may have experienced during school closures occurred during a time when more than 167,000 children younger than 18 years lost a parent or caregiver to COVID-19, according to a recent report titled “Hidden Pain” by researchers at the University of Pennsylvania, Nemours Children’s Health, and the COVID Collaborative. Although not addressed in the current study, school closures would prevent bereaved children from receiving social-emotional support from friends and teachers. This crisis of loss also prompted the American Academy of Pediatrics to issue a National State of Emergency in Children’s Mental Health in October 2021.
 

New study results

These studies identified associations between school closures during broader lockdowns and increased emotional and behavioral problems, as well as increased restlessness and inattention. Across these studies, 18%-60% of children and adolescents scored higher than the risk thresholds for diagnoses of distress, especially depressive symptoms and anxiety.

Although two studies showed no significant association with suicide in response to school closures during lockdowns, three studies suggested increased use of screen time, two studies reported increased social media use, and six studies reported lower levels of physical activity.

Three studies of child abuse showed decreases in notifications during lockdowns, likely driven by lack of referrals from schools, the authors noted. A total of 10 studies on sleep and 5 studies on diet showed inconsistent evidence of harm during the specific period of school closures and social lockdowns.

“The contrast of rises in distress with decreases in presentations suggests that there was an escalation of unmet mental health need during lockdowns in already vulnerable children and adolescents,” the researchers wrote. “More troubling still is evidence of a reduction in the ability of the health and social care systems to protect children in many countries, as shown by the large falls in child protection referrals seen in high-quality cohort studies.”
 

‘Study presents concrete assessments rather than speculation’

“Concerns have been widely expressed in the lay media and beyond that school closures could negatively impact the mental and physical health of children and adolescents,” M. Susan Jay, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview. “The authors presented a narrative synthesis summarizing available evidence for the first wave of COVID-19 on school closures during the broader social lockdown occurring during this period.”

The “importance” of this research is that “it is not a single convenience sample study, but a systematic review from 11 countries including the United States, United Kingdom, China, and Turkey, among others, and that the quality of the information was graded,” Dr. Jay said. “Although not a meta-analysis, the study presents concrete assessments rather than speculation and overviews its limitations so that the clinician can weigh this information. Importantly, the authors excluded closure of schools with transmission of infection.

“Clearly, school lockdowns as a measure of controlling infectious disease needs balance with potential of negative health behaviors in children and adolescents. Ongoing prospective longitudinal studies are needed as sequential waves of the pandemic continue,” she emphasized.

“Clinically, this study highlights the need for clinicians to consider [asking] about the impact of school closures and remote versus hybrid versus in-person education [as part of their] patients and families question inventory,” Dr. Jay said. “Also, the use of depression inventories can be offered to youth to assess their mental health state at a visit, either via telemedicine or in person, and ideally at sequential visits for a more in-depth assessment.”
 

Schools play key role in social and emotional development

“It was important to conduct this study now, because this current time is unprecedented,” Peter L. Loper Jr., MD, of the University of South Carolina, Columbia, said in an interview. “We know based on evolutionary biology, anthropology, and developmental psychology, among other disciplines, that meaningful interpersonal interactions embedded in the context of community are vital to supporting human well-being.

“In our current time, the primary framework of community for our children is the school setting; it is the predominant space where they engage in the interpersonal interactions necessary for developing resilience, their sense of purpose, belonging, and fidelity,” he emphasized.

“Rarely in the course of human existence have kids been removed from the broader context of community to this extent and for this duration,” Dr. Loper said. “This study capitalizes on this unprecedented moment to begin to further understand how compromises in our sociocultural infrastructure of community, like school closures and lockdowns, may manifest as mental health problems in children and adolescents. More importantly, it contributes to the exploration of potential unintended consequences of our current infection control measures so we can adapt to support the overall well-being of our children in this ‘new normal.’ ”

Dr. Loper added that he was not surprised by the new study’s findings.

“We were already seeing a decline in pediatric mental health and overall well-being in the years preceding COVID-19 because of the ‘isolation epidemic’ involving many of the factors that this study explored,” he said. “I think this review further illustrates the vital necessity of community to support the health and well-being of humans, and specifically children and adolescents.”

From a clinical standpoint, “we need to be intentional and consistent in balancing infection control measures with our kids’ fundamental psychosocial needs,” Dr. Loper said.

“We need to recognize that, when children and adolescents are isolated from community, their fundamental psychosocial needs go unmet,” he emphasized. “If children and adolescents cannot access the meaningful interpersonal interactions necessary for resilience, then they cannot overcome or navigate distress. They will exhibit the avoidance and withdrawal behaviors that accumulate to manifest as adverse mental health symptoms like anxiety and depression.

“Additional research is needed to further explore how compromises in the psychosocial infrastructure of community manifest as downstream symptom indicators such as anxiety and depression,” which are often manifestations of unmet needs, Dr. Loper said.
 

Limitations and strengths, according to authors

The findings were limited by several factors, including a lack of examination of school closures’ effects on mental health independent of broader social lockdowns, according to the researchers. Other limitations included the authors potentially having missed studies, inclusion of cross-sectional studies with relatively weak evidence, potential bias from studies using parent reports, and a focus on the first COVID-19 wave, during which many school closures were of limited duration. Also, the researchers said they did not include studies focused on particular groups, such as children with learning difficulties or autism.

The use of large databases from education as well as health care in studies analyzed were strengths of the new research, they said. The investigators received no outside funding for their study. The researchers, Dr. Jay, and Dr. Loper had no financial conflicts to disclose. Dr. Jay serves on the editorial advisory board of Pediatric News.

Another record week for COVID-19 brought almost 1 million new cases to the children of the United States, according to new data from the American Academy of Pediatrics and the Children’s Hospital Association.

The pre-Omicron high for new cases in a week – 252,000 during the Delta surge of the late summer and early fall – has been surpassed each of the last 3 weeks and now stands at 981,000 (Jan. 7-13), according to the AAP/CHA weekly COVID-19 report. Over the 3-week stretch from Dec. 17 to Jan. 13, weekly cases increased by 394%.

Hospitalizations also climbed to new heights, as daily admissions reached 1.23 per 100,000 children on Jan. 14, an increase of 547% since Nov. 30, when the rate was 0.19 per 100,000. Before Omicron, the highest rate for children was 0.47 per 100,000, based on data from the Centers for Disease Control and Prevention.

The inpatient population count, meanwhile, has followed suit. On Jan. 16, there were 3,822 children hospitalized in pediatric inpatient beds with laboratory-confirmed COVID-19, which is 523% higher than the 613 children who were hospitalized on Nov. 14, according to the Department of Health & Human Services. In the last week, though, the population was up by just 10%.

The one thing that has not surged in the last few weeks is vaccination. Among children aged 5-11 years, the weekly count of those who have received at least one dose dropped by 34% over the last 5 weeks, falling from 527,000 for Dec.11-17 to 347,000 during Jan. 8-14, the CDC said on the COVID Data Tracker, which also noted that just 18.4% of this age group is fully vaccinated.

The situation was reversed in children aged 12-15, who were up by 36% over that same time, but their numbers were much smaller: 78,000 for the week of Dec. 11-17 and 106,000 for Jan. 8-14. Those aged 16-17 were up by just 4% over that 5-week span, the CDC data show.

Over the course of the entire pandemic, almost 9.5 million cases of COVID-19 in children have been reported, and children represent 17.8% of all cases reported in 49 states (excluding New York but including New York City), the District of Columbia, Puerto Rico, and Guam, the AAP and CHA said in their report.

Three states (Alabama, Nebraska, and Texas) stopped public reporting over the summer, but many states count individuals up to age 19 as children, and others (South Carolina, Tennessee, and West Virginia) go up to age 20, the AAP and CHA noted. The CDC, by comparison, puts the number of cases for those aged 0-17 at 8.3 million, but that estimate is based on only 51 million of the nearly 67 million U.S. cases as of Jan. 18.

Another record week for COVID-19 brought almost 1 million new cases to the children of the United States, according to new data from the American Academy of Pediatrics and the Children’s Hospital Association.

The pre-Omicron high for new cases in a week – 252,000 during the Delta surge of the late summer and early fall – has been surpassed each of the last 3 weeks and now stands at 981,000 (Jan. 7-13), according to the AAP/CHA weekly COVID-19 report. Over the 3-week stretch from Dec. 17 to Jan. 13, weekly cases increased by 394%.

Hospitalizations also climbed to new heights, as daily admissions reached 1.23 per 100,000 children on Jan. 14, an increase of 547% since Nov. 30, when the rate was 0.19 per 100,000. Before Omicron, the highest rate for children was 0.47 per 100,000, based on data from the Centers for Disease Control and Prevention.

The inpatient population count, meanwhile, has followed suit. On Jan. 16, there were 3,822 children hospitalized in pediatric inpatient beds with laboratory-confirmed COVID-19, which is 523% higher than the 613 children who were hospitalized on Nov. 14, according to the Department of Health & Human Services. In the last week, though, the population was up by just 10%.

The one thing that has not surged in the last few weeks is vaccination. Among children aged 5-11 years, the weekly count of those who have received at least one dose dropped by 34% over the last 5 weeks, falling from 527,000 for Dec.11-17 to 347,000 during Jan. 8-14, the CDC said on the COVID Data Tracker, which also noted that just 18.4% of this age group is fully vaccinated.

The situation was reversed in children aged 12-15, who were up by 36% over that same time, but their numbers were much smaller: 78,000 for the week of Dec. 11-17 and 106,000 for Jan. 8-14. Those aged 16-17 were up by just 4% over that 5-week span, the CDC data show.

Over the course of the entire pandemic, almost 9.5 million cases of COVID-19 in children have been reported, and children represent 17.8% of all cases reported in 49 states (excluding New York but including New York City), the District of Columbia, Puerto Rico, and Guam, the AAP and CHA said in their report.

Three states (Alabama, Nebraska, and Texas) stopped public reporting over the summer, but many states count individuals up to age 19 as children, and others (South Carolina, Tennessee, and West Virginia) go up to age 20, the AAP and CHA noted. The CDC, by comparison, puts the number of cases for those aged 0-17 at 8.3 million, but that estimate is based on only 51 million of the nearly 67 million U.S. cases as of Jan. 18.

Another record week for COVID-19 brought almost 1 million new cases to the children of the United States, according to new data from the American Academy of Pediatrics and the Children’s Hospital Association.

The pre-Omicron high for new cases in a week – 252,000 during the Delta surge of the late summer and early fall – has been surpassed each of the last 3 weeks and now stands at 981,000 (Jan. 7-13), according to the AAP/CHA weekly COVID-19 report. Over the 3-week stretch from Dec. 17 to Jan. 13, weekly cases increased by 394%.

Hospitalizations also climbed to new heights, as daily admissions reached 1.23 per 100,000 children on Jan. 14, an increase of 547% since Nov. 30, when the rate was 0.19 per 100,000. Before Omicron, the highest rate for children was 0.47 per 100,000, based on data from the Centers for Disease Control and Prevention.

The inpatient population count, meanwhile, has followed suit. On Jan. 16, there were 3,822 children hospitalized in pediatric inpatient beds with laboratory-confirmed COVID-19, which is 523% higher than the 613 children who were hospitalized on Nov. 14, according to the Department of Health & Human Services. In the last week, though, the population was up by just 10%.

The one thing that has not surged in the last few weeks is vaccination. Among children aged 5-11 years, the weekly count of those who have received at least one dose dropped by 34% over the last 5 weeks, falling from 527,000 for Dec.11-17 to 347,000 during Jan. 8-14, the CDC said on the COVID Data Tracker, which also noted that just 18.4% of this age group is fully vaccinated.

The situation was reversed in children aged 12-15, who were up by 36% over that same time, but their numbers were much smaller: 78,000 for the week of Dec. 11-17 and 106,000 for Jan. 8-14. Those aged 16-17 were up by just 4% over that 5-week span, the CDC data show.

Over the course of the entire pandemic, almost 9.5 million cases of COVID-19 in children have been reported, and children represent 17.8% of all cases reported in 49 states (excluding New York but including New York City), the District of Columbia, Puerto Rico, and Guam, the AAP and CHA said in their report.

Three states (Alabama, Nebraska, and Texas) stopped public reporting over the summer, but many states count individuals up to age 19 as children, and others (South Carolina, Tennessee, and West Virginia) go up to age 20, the AAP and CHA noted. The CDC, by comparison, puts the number of cases for those aged 0-17 at 8.3 million, but that estimate is based on only 51 million of the nearly 67 million U.S. cases as of Jan. 18.

With the country looking increasingly to rapid testing as an off-ramp from the COVID-19 pandemic, a new study shows that the performance of the tests in children falls below standards set by regulatory agencies in the United States and elsewhere for diagnostic accuracy.

Experts said the findings, from a meta-analysis by researchers in the United Kingdom and Germany, underscore that, while a positive result on a rapid test is almost certainly an indicator of infection, negative results often are unreliable and can lead to a false sense of security.

“Real-life performance of current antigen tests for professional use in pediatric populations is below the minimum performance criteria set by WHO, the United States Food and Drug Administration, or the Medicines and Healthcare products Regulatory Agency (U.K.),” according to Naomi Fujita-Rohwerder, PhD, a research associate at the Cologne-based German Institute for Quality and Efficiency in Health Care (IQWiG), and her colleagues, whose study appears in BMJ Evidence-Based Medicine.

The researchers said that the study suggests that performance of rapid testing in a pediatric population is comparable to that in adults. However, they said they could not identify any studies investigating self-testing in children, which also could affect test performance.

Egon Ozer, MD, PhD, director of the center for pathogen genomics and microbial evolution at Northwestern University in Chicago, said the finding that specificity was high but sensitivity was middling “suggests that we should be very careful about interpreting negative antigen test results in children and recognize that there is a fair amount of uncertainty in the tests in this situation.”

Researchers from IQWiG, which examines the advantages and disadvantages of medical interventions, and the University of Manchester (England), conducted the systematic review and meta-analysis, which they described as the first of its kind to evaluate the diagnostic accuracy of rapid point-of-care tests for current SARS-CoV-2 infections in children.

They compiled information from 17 studies with a total 6,355 participants. They compared all antigen tests to reverse-transcription polymerase chain reaction (PCR). The studies compared eight antigen tests from six different brands. The rapid antigen tests, available from pharmacies and online stores, are widely used for self-testing in schools and testing toddlers before kindergarten.

The pooled diagnostic sensitivity of antigen tests was 64.2% and specificity was 99.1%.

Dr. Ozer noted that the analysis “was not able to address important outstanding questions such as the likelihood of transmitting infection with a false-negative antigen test versus a true-negative antigen test or how much repeated testing can increase the sensitivity.”

“In Europe, we don’t know how most tests perform in real life,” Dr. Fujita-Rohwerder said. “And even in countries like the United States, where market access is more stringent, we don’t know whether self-testing performed by children or sample collection in toddlers by laypersons has a significant impact on the diagnostic accuracy. Also, diagnostic accuracy estimates reported in our study may not apply to the current omicron or future variants of SARS-CoV-2 or vaccinated children. Hopefully, these essential gaps in the evidence will get addressed soon.”

Dr. Ozer said one takeaway from this study is negative antigen tests should not be considered a “free pass” in children, especially if the child is symptomatic, has been recently exposed to COVID-19, or is planning to spend time with individuals with conditions that place them at high risk for complications of COVID-19 infection. “In such cases, consider getting PCR testing or at least performing a repeat antigen test 36-48 hours after the first negative,” he said.

Dr. Fujita-Rohwerder said the low diagnostic sensitivity may affect the use of the tests. The gaps in evidence her group found in their study point to research needed to support evidence-based decision-making. “In particular, evidence is needed on real-life performance of tests in schools, self-testing performed by children, and kindergarten, [particularly] sample collection in toddlers by laypersons,” she said.

However, she stressed, testing is only a single measure. “Effectively reducing the spread of SARS-CoV-2 during the current pandemic requires multilayered mitigation measures,” she said. “Rapid testing represents one single layer. It can have its use at the population level, even though the sensitivity of antigen tests is lower than expected. However, antigen-based rapid testing is not a magic bullet: If your kid tests negative, do not disregard other mitigation measures.”

Edward Campbell, PhD, a virologist at Loyola University of Chicago, who serves on the board of LaGrange Elementary School District 102 outside Chicago, said the findings were unsurprising.

“This study generally looks consistent with what is known for adults. These rapid antigen tests are less sensitive than other tests,” said Dr. Campbell, who also runs a testing company for private schools in the Chicago area using reverse transcription-loop-mediated isothermal amplification technology. Even so, he said, “These tests are still effective at identifying people who are infectious to some degree. Never miss an opportunity to test.”

Dr. Fujita-Rohwerder disclosed no relevant financial conflicts of interest. Dr. Campbell owns Safeguard Surveillance.

With the country looking increasingly to rapid testing as an off-ramp from the COVID-19 pandemic, a new study shows that the performance of the tests in children falls below standards set by regulatory agencies in the United States and elsewhere for diagnostic accuracy.

Experts said the findings, from a meta-analysis by researchers in the United Kingdom and Germany, underscore that, while a positive result on a rapid test is almost certainly an indicator of infection, negative results often are unreliable and can lead to a false sense of security.

“Real-life performance of current antigen tests for professional use in pediatric populations is below the minimum performance criteria set by WHO, the United States Food and Drug Administration, or the Medicines and Healthcare products Regulatory Agency (U.K.),” according to Naomi Fujita-Rohwerder, PhD, a research associate at the Cologne-based German Institute for Quality and Efficiency in Health Care (IQWiG), and her colleagues, whose study appears in BMJ Evidence-Based Medicine.

The researchers said that the study suggests that performance of rapid testing in a pediatric population is comparable to that in adults. However, they said they could not identify any studies investigating self-testing in children, which also could affect test performance.

Egon Ozer, MD, PhD, director of the center for pathogen genomics and microbial evolution at Northwestern University in Chicago, said the finding that specificity was high but sensitivity was middling “suggests that we should be very careful about interpreting negative antigen test results in children and recognize that there is a fair amount of uncertainty in the tests in this situation.”

Researchers from IQWiG, which examines the advantages and disadvantages of medical interventions, and the University of Manchester (England), conducted the systematic review and meta-analysis, which they described as the first of its kind to evaluate the diagnostic accuracy of rapid point-of-care tests for current SARS-CoV-2 infections in children.

They compiled information from 17 studies with a total 6,355 participants. They compared all antigen tests to reverse-transcription polymerase chain reaction (PCR). The studies compared eight antigen tests from six different brands. The rapid antigen tests, available from pharmacies and online stores, are widely used for self-testing in schools and testing toddlers before kindergarten.

The pooled diagnostic sensitivity of antigen tests was 64.2% and specificity was 99.1%.

Dr. Ozer noted that the analysis “was not able to address important outstanding questions such as the likelihood of transmitting infection with a false-negative antigen test versus a true-negative antigen test or how much repeated testing can increase the sensitivity.”

“In Europe, we don’t know how most tests perform in real life,” Dr. Fujita-Rohwerder said. “And even in countries like the United States, where market access is more stringent, we don’t know whether self-testing performed by children or sample collection in toddlers by laypersons has a significant impact on the diagnostic accuracy. Also, diagnostic accuracy estimates reported in our study may not apply to the current omicron or future variants of SARS-CoV-2 or vaccinated children. Hopefully, these essential gaps in the evidence will get addressed soon.”

Dr. Ozer said one takeaway from this study is negative antigen tests should not be considered a “free pass” in children, especially if the child is symptomatic, has been recently exposed to COVID-19, or is planning to spend time with individuals with conditions that place them at high risk for complications of COVID-19 infection. “In such cases, consider getting PCR testing or at least performing a repeat antigen test 36-48 hours after the first negative,” he said.

Dr. Fujita-Rohwerder said the low diagnostic sensitivity may affect the use of the tests. The gaps in evidence her group found in their study point to research needed to support evidence-based decision-making. “In particular, evidence is needed on real-life performance of tests in schools, self-testing performed by children, and kindergarten, [particularly] sample collection in toddlers by laypersons,” she said.

However, she stressed, testing is only a single measure. “Effectively reducing the spread of SARS-CoV-2 during the current pandemic requires multilayered mitigation measures,” she said. “Rapid testing represents one single layer. It can have its use at the population level, even though the sensitivity of antigen tests is lower than expected. However, antigen-based rapid testing is not a magic bullet: If your kid tests negative, do not disregard other mitigation measures.”

Edward Campbell, PhD, a virologist at Loyola University of Chicago, who serves on the board of LaGrange Elementary School District 102 outside Chicago, said the findings were unsurprising.

“This study generally looks consistent with what is known for adults. These rapid antigen tests are less sensitive than other tests,” said Dr. Campbell, who also runs a testing company for private schools in the Chicago area using reverse transcription-loop-mediated isothermal amplification technology. Even so, he said, “These tests are still effective at identifying people who are infectious to some degree. Never miss an opportunity to test.”

Dr. Fujita-Rohwerder disclosed no relevant financial conflicts of interest. Dr. Campbell owns Safeguard Surveillance.

With the country looking increasingly to rapid testing as an off-ramp from the COVID-19 pandemic, a new study shows that the performance of the tests in children falls below standards set by regulatory agencies in the United States and elsewhere for diagnostic accuracy.

Experts said the findings, from a meta-analysis by researchers in the United Kingdom and Germany, underscore that, while a positive result on a rapid test is almost certainly an indicator of infection, negative results often are unreliable and can lead to a false sense of security.

“Real-life performance of current antigen tests for professional use in pediatric populations is below the minimum performance criteria set by WHO, the United States Food and Drug Administration, or the Medicines and Healthcare products Regulatory Agency (U.K.),” according to Naomi Fujita-Rohwerder, PhD, a research associate at the Cologne-based German Institute for Quality and Efficiency in Health Care (IQWiG), and her colleagues, whose study appears in BMJ Evidence-Based Medicine.

The researchers said that the study suggests that performance of rapid testing in a pediatric population is comparable to that in adults. However, they said they could not identify any studies investigating self-testing in children, which also could affect test performance.

Egon Ozer, MD, PhD, director of the center for pathogen genomics and microbial evolution at Northwestern University in Chicago, said the finding that specificity was high but sensitivity was middling “suggests that we should be very careful about interpreting negative antigen test results in children and recognize that there is a fair amount of uncertainty in the tests in this situation.”

Researchers from IQWiG, which examines the advantages and disadvantages of medical interventions, and the University of Manchester (England), conducted the systematic review and meta-analysis, which they described as the first of its kind to evaluate the diagnostic accuracy of rapid point-of-care tests for current SARS-CoV-2 infections in children.

They compiled information from 17 studies with a total 6,355 participants. They compared all antigen tests to reverse-transcription polymerase chain reaction (PCR). The studies compared eight antigen tests from six different brands. The rapid antigen tests, available from pharmacies and online stores, are widely used for self-testing in schools and testing toddlers before kindergarten.

The pooled diagnostic sensitivity of antigen tests was 64.2% and specificity was 99.1%.

Dr. Ozer noted that the analysis “was not able to address important outstanding questions such as the likelihood of transmitting infection with a false-negative antigen test versus a true-negative antigen test or how much repeated testing can increase the sensitivity.”

“In Europe, we don’t know how most tests perform in real life,” Dr. Fujita-Rohwerder said. “And even in countries like the United States, where market access is more stringent, we don’t know whether self-testing performed by children or sample collection in toddlers by laypersons has a significant impact on the diagnostic accuracy. Also, diagnostic accuracy estimates reported in our study may not apply to the current omicron or future variants of SARS-CoV-2 or vaccinated children. Hopefully, these essential gaps in the evidence will get addressed soon.”

Dr. Ozer said one takeaway from this study is negative antigen tests should not be considered a “free pass” in children, especially if the child is symptomatic, has been recently exposed to COVID-19, or is planning to spend time with individuals with conditions that place them at high risk for complications of COVID-19 infection. “In such cases, consider getting PCR testing or at least performing a repeat antigen test 36-48 hours after the first negative,” he said.

Dr. Fujita-Rohwerder said the low diagnostic sensitivity may affect the use of the tests. The gaps in evidence her group found in their study point to research needed to support evidence-based decision-making. “In particular, evidence is needed on real-life performance of tests in schools, self-testing performed by children, and kindergarten, [particularly] sample collection in toddlers by laypersons,” she said.

However, she stressed, testing is only a single measure. “Effectively reducing the spread of SARS-CoV-2 during the current pandemic requires multilayered mitigation measures,” she said. “Rapid testing represents one single layer. It can have its use at the population level, even though the sensitivity of antigen tests is lower than expected. However, antigen-based rapid testing is not a magic bullet: If your kid tests negative, do not disregard other mitigation measures.”

Edward Campbell, PhD, a virologist at Loyola University of Chicago, who serves on the board of LaGrange Elementary School District 102 outside Chicago, said the findings were unsurprising.

“This study generally looks consistent with what is known for adults. These rapid antigen tests are less sensitive than other tests,” said Dr. Campbell, who also runs a testing company for private schools in the Chicago area using reverse transcription-loop-mediated isothermal amplification technology. Even so, he said, “These tests are still effective at identifying people who are infectious to some degree. Never miss an opportunity to test.”

Dr. Fujita-Rohwerder disclosed no relevant financial conflicts of interest. Dr. Campbell owns Safeguard Surveillance.

Antibiotics were administered to newborns at low risk for early-onset sepsis as frequently as to newborns with EOS risk factors, based on data from approximately 7,500 infants.

EOS remains a significant cause of morbidity and mortality, and predicting which newborns are at risk remains a challenge for neonatal care that often drives high rates of antibiotic use, Dustin D. Flannery, DO, of Children’s Hospital of Philadelphia and colleagues wrote.

Antibiotic exposures are associated with short- and long-term adverse effects in both preterm and term infants, which highlights the need for improved risk assessment in this population, the researchers said.

“A robust estimate of EOS risk in relation to delivery characteristics among infants of all gestational ages at birth could significantly contribute to newborn clinical management by identifying newborns unlikely to benefit from empirical antibiotic therapy,” they emphasized.

In a study published in Pediatrics, the researchers identified 7,540 infants born between Jan. 1, 2009, and Dec. 31, 2014, at two high-risk perinatal units in Philadelphia. Gestational age ranged from 22 to 43 weeks. Criteria for low risk of EOS were determined via an algorithm that included cesarean delivery (with or without labor or membrane rupture), and no antepartum concerns for intra-amniotic infection or nonreassuring fetal status.

A total of 6,428 infants did not meet the low-risk criteria; another 1,121 infants met the low-risk criteria. The primary outcome of EOS was defined as growth of a pathogen in at least 1 blood and/or cerebrospinal fluid culture obtained at 72 hours or less after birth. Overall, 41 infants who did not meet the low-risk criteria developed EOS; none of the infants who met the low-risk criteria developed EOS. Secondary outcomes included initiation of empirical antibiotics at 72 hours or less after birth and the duration of antibiotic use.

Although fewer low-risk infants received antibiotics, compared with infants with EOS (80.4% vs. 91.0%, P < .001), the duration of antibiotic use was not significantly different between the groups, with an adjusted difference of 0.6 hours.

Among infants who did not meet low-risk criteria, 157 were started on antibiotics for each case of EOS, the researchers noted in their discussion of the findings. “Because no cases of EOS were identified in the low-risk group, this proportion could not be calculated but suggests that antibiotic exposure in this group was disproportionately higher for incidence of EOS.”

The study findings were limited by several factors including the possible lack of generalizability to other centers and the use of data from a period before more refined EOS strategies, the researchers noted. Other limitations include the inability to assess the effect of lab results on antibiotic use, a lack of data on the exact indication for delivery, and potential misclassification bias.

Risk assessment tools should not be used alone, but should be used to inform clinical decision-making, the researchers emphasized. However, the results were strengthened by the inclusion of moderately preterm infants, who are rarely studied, and the clinical utility of the risk algorithm used in the study. “The implications of our study include potential adjustments to sepsis risk assessment in term infants, and confirmation and enhancement of previous studies that identify a subset of lower-risk preterm infants,” who may be spared empirical or prolonged antibiotic exposure, they concluded.
 

Data inform intelligent antibiotic use

“Early-onset sepsis is predominantly caused by exposure of the fetus or neonate to ascending maternal colonization or infection by gastrointestinal or genitourinary bacteria,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “Scenarios where there is limited neonatal exposure to these organisms would decrease the risk of development of EOS, therefore it is not surprising that delivery characteristics of low-risk deliveries as defined by investigators – the absence of labor, absence of intra-amniotic infection, rupture of membranes at time of delivery, and cesarean delivery – would have resulted in decreased likelihood of EOS.”

Inappropriate antibiotic use contributes to the development of resistant and more virulent strains of bacteria. A growing body of literature also suggests that early antibiotic usage in newborns may affect the neonatal gut microbiome, which is important for development of the neonatal immune system. Early alterations of the microbiome may have long-term implications,” Dr. Krishna said.

“Understanding the delivery characteristics that increase the risk of EOS are crucial to optimizing the use of antibiotics and thereby minimize potential harm to newborns,” she said. “Studies such as the current study are needed develop EOS prediction tools to improve antibiotic utilization.” More research is needed not only to adequately predict EOS, but to explore how antibiotics affect the neonatal microbiome, and how clinicians can circumvent potential adverse implications with antibiotic use to improve long-term health, Dr. Krishna concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Krishna had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Antibiotics were administered to newborns at low risk for early-onset sepsis as frequently as to newborns with EOS risk factors, based on data from approximately 7,500 infants.

EOS remains a significant cause of morbidity and mortality, and predicting which newborns are at risk remains a challenge for neonatal care that often drives high rates of antibiotic use, Dustin D. Flannery, DO, of Children’s Hospital of Philadelphia and colleagues wrote.

Antibiotic exposures are associated with short- and long-term adverse effects in both preterm and term infants, which highlights the need for improved risk assessment in this population, the researchers said.

“A robust estimate of EOS risk in relation to delivery characteristics among infants of all gestational ages at birth could significantly contribute to newborn clinical management by identifying newborns unlikely to benefit from empirical antibiotic therapy,” they emphasized.

In a study published in Pediatrics, the researchers identified 7,540 infants born between Jan. 1, 2009, and Dec. 31, 2014, at two high-risk perinatal units in Philadelphia. Gestational age ranged from 22 to 43 weeks. Criteria for low risk of EOS were determined via an algorithm that included cesarean delivery (with or without labor or membrane rupture), and no antepartum concerns for intra-amniotic infection or nonreassuring fetal status.

A total of 6,428 infants did not meet the low-risk criteria; another 1,121 infants met the low-risk criteria. The primary outcome of EOS was defined as growth of a pathogen in at least 1 blood and/or cerebrospinal fluid culture obtained at 72 hours or less after birth. Overall, 41 infants who did not meet the low-risk criteria developed EOS; none of the infants who met the low-risk criteria developed EOS. Secondary outcomes included initiation of empirical antibiotics at 72 hours or less after birth and the duration of antibiotic use.

Although fewer low-risk infants received antibiotics, compared with infants with EOS (80.4% vs. 91.0%, P < .001), the duration of antibiotic use was not significantly different between the groups, with an adjusted difference of 0.6 hours.

Among infants who did not meet low-risk criteria, 157 were started on antibiotics for each case of EOS, the researchers noted in their discussion of the findings. “Because no cases of EOS were identified in the low-risk group, this proportion could not be calculated but suggests that antibiotic exposure in this group was disproportionately higher for incidence of EOS.”

The study findings were limited by several factors including the possible lack of generalizability to other centers and the use of data from a period before more refined EOS strategies, the researchers noted. Other limitations include the inability to assess the effect of lab results on antibiotic use, a lack of data on the exact indication for delivery, and potential misclassification bias.

Risk assessment tools should not be used alone, but should be used to inform clinical decision-making, the researchers emphasized. However, the results were strengthened by the inclusion of moderately preterm infants, who are rarely studied, and the clinical utility of the risk algorithm used in the study. “The implications of our study include potential adjustments to sepsis risk assessment in term infants, and confirmation and enhancement of previous studies that identify a subset of lower-risk preterm infants,” who may be spared empirical or prolonged antibiotic exposure, they concluded.
 

Data inform intelligent antibiotic use

“Early-onset sepsis is predominantly caused by exposure of the fetus or neonate to ascending maternal colonization or infection by gastrointestinal or genitourinary bacteria,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “Scenarios where there is limited neonatal exposure to these organisms would decrease the risk of development of EOS, therefore it is not surprising that delivery characteristics of low-risk deliveries as defined by investigators – the absence of labor, absence of intra-amniotic infection, rupture of membranes at time of delivery, and cesarean delivery – would have resulted in decreased likelihood of EOS.”

Inappropriate antibiotic use contributes to the development of resistant and more virulent strains of bacteria. A growing body of literature also suggests that early antibiotic usage in newborns may affect the neonatal gut microbiome, which is important for development of the neonatal immune system. Early alterations of the microbiome may have long-term implications,” Dr. Krishna said.

“Understanding the delivery characteristics that increase the risk of EOS are crucial to optimizing the use of antibiotics and thereby minimize potential harm to newborns,” she said. “Studies such as the current study are needed develop EOS prediction tools to improve antibiotic utilization.” More research is needed not only to adequately predict EOS, but to explore how antibiotics affect the neonatal microbiome, and how clinicians can circumvent potential adverse implications with antibiotic use to improve long-term health, Dr. Krishna concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Krishna had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Antibiotics were administered to newborns at low risk for early-onset sepsis as frequently as to newborns with EOS risk factors, based on data from approximately 7,500 infants.

EOS remains a significant cause of morbidity and mortality, and predicting which newborns are at risk remains a challenge for neonatal care that often drives high rates of antibiotic use, Dustin D. Flannery, DO, of Children’s Hospital of Philadelphia and colleagues wrote.

Antibiotic exposures are associated with short- and long-term adverse effects in both preterm and term infants, which highlights the need for improved risk assessment in this population, the researchers said.

“A robust estimate of EOS risk in relation to delivery characteristics among infants of all gestational ages at birth could significantly contribute to newborn clinical management by identifying newborns unlikely to benefit from empirical antibiotic therapy,” they emphasized.

In a study published in Pediatrics, the researchers identified 7,540 infants born between Jan. 1, 2009, and Dec. 31, 2014, at two high-risk perinatal units in Philadelphia. Gestational age ranged from 22 to 43 weeks. Criteria for low risk of EOS were determined via an algorithm that included cesarean delivery (with or without labor or membrane rupture), and no antepartum concerns for intra-amniotic infection or nonreassuring fetal status.

A total of 6,428 infants did not meet the low-risk criteria; another 1,121 infants met the low-risk criteria. The primary outcome of EOS was defined as growth of a pathogen in at least 1 blood and/or cerebrospinal fluid culture obtained at 72 hours or less after birth. Overall, 41 infants who did not meet the low-risk criteria developed EOS; none of the infants who met the low-risk criteria developed EOS. Secondary outcomes included initiation of empirical antibiotics at 72 hours or less after birth and the duration of antibiotic use.

Although fewer low-risk infants received antibiotics, compared with infants with EOS (80.4% vs. 91.0%, P < .001), the duration of antibiotic use was not significantly different between the groups, with an adjusted difference of 0.6 hours.

Among infants who did not meet low-risk criteria, 157 were started on antibiotics for each case of EOS, the researchers noted in their discussion of the findings. “Because no cases of EOS were identified in the low-risk group, this proportion could not be calculated but suggests that antibiotic exposure in this group was disproportionately higher for incidence of EOS.”

The study findings were limited by several factors including the possible lack of generalizability to other centers and the use of data from a period before more refined EOS strategies, the researchers noted. Other limitations include the inability to assess the effect of lab results on antibiotic use, a lack of data on the exact indication for delivery, and potential misclassification bias.

Risk assessment tools should not be used alone, but should be used to inform clinical decision-making, the researchers emphasized. However, the results were strengthened by the inclusion of moderately preterm infants, who are rarely studied, and the clinical utility of the risk algorithm used in the study. “The implications of our study include potential adjustments to sepsis risk assessment in term infants, and confirmation and enhancement of previous studies that identify a subset of lower-risk preterm infants,” who may be spared empirical or prolonged antibiotic exposure, they concluded.
 

Data inform intelligent antibiotic use

“Early-onset sepsis is predominantly caused by exposure of the fetus or neonate to ascending maternal colonization or infection by gastrointestinal or genitourinary bacteria,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview. “Scenarios where there is limited neonatal exposure to these organisms would decrease the risk of development of EOS, therefore it is not surprising that delivery characteristics of low-risk deliveries as defined by investigators – the absence of labor, absence of intra-amniotic infection, rupture of membranes at time of delivery, and cesarean delivery – would have resulted in decreased likelihood of EOS.”

Inappropriate antibiotic use contributes to the development of resistant and more virulent strains of bacteria. A growing body of literature also suggests that early antibiotic usage in newborns may affect the neonatal gut microbiome, which is important for development of the neonatal immune system. Early alterations of the microbiome may have long-term implications,” Dr. Krishna said.

“Understanding the delivery characteristics that increase the risk of EOS are crucial to optimizing the use of antibiotics and thereby minimize potential harm to newborns,” she said. “Studies such as the current study are needed develop EOS prediction tools to improve antibiotic utilization.” More research is needed not only to adequately predict EOS, but to explore how antibiotics affect the neonatal microbiome, and how clinicians can circumvent potential adverse implications with antibiotic use to improve long-term health, Dr. Krishna concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Krishna had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Pregnant women’s thyroid hormone trajectories (levels in the first, second, and third trimester) may predict whether their male offspring are aggressive or withdrawn at age 4.

Certain maternal thyroid hormone trajectories were associated with problem behaviors in preschool boys in a study of close to 2,000 mother-child pairs in China.

The researchers identified low, moderate, and high thyroid-stimulating hormone (TSH) and free thyroxine (FT4) trajectories. 

shironosov/Getty Images

‘Study supports monitoring thyroid function in pregnancy’

“Our findings highlight the significance of close monitoring and management of maternal thyroid function during pregnancy,” senior author Kun Huang, PhD, said in a press release from the Endocrine Society.

“This research presents a new perspective in early intervention of children’s emotional and behavioral problems,” added Dr. Huang, from Anhui Medical University, Hefei, China.

The results add to a growing body of literature about a controversial link between maternal thyroid hormones in pregnancy, when the fetal brain is developing, and subsequent behavior in preschool children, Caroline T. Nguyen, MD, who was not involved with this research, commented in an email.

“Some studies show an association between thyroid levels and behavioral outcomes, others not,” added Dr. Nguyen, assistant professor of clinical medicine, Keck School of Medicine, University of Southern California, Los Angeles. And “some studies have found sex-specific associations with maternal thyroid levels and neurocognitive/behavioral outcomes, others have not.”

Women considering pregnancy should be evaluated for possible thyroid disease, she continued. Currently, no universal screening mandates exist for thyroid disease in pregnancy, but the 2017 American Thyroid Association guidelines do recommend screening women at risk for thyroid dysfunction.

“I think screening for thyroid peroxidase antibody (TPOAb) positivity is helpful in women desiring pregnancy,” Dr. Nguyen continued, “because we know that patients with TPOAb positivity are at increased risk for miscarriage and have a blunted response to the increased demands of pregnancy for thyroid hormone production.”

TPOAb positivity is also associated with the increased risk of postpartum and long-term thyroid dysfunction.

This current study, Dr. Nguyen summarized, “adds to a growing body of research of the relationship of thyroid hormone levels and neurocognitive outcomes [in offspring] and supports the monitoring of thyroid disease in pregnancy.”  

“However, we do not have sufficient data to demonstrate the benefits of intervention with levothyroxine treatment,” she noted. 

Nevertheless, the lack of positive data does not suggest there is no theoretical benefit of intervention, she said, as such studies are very challenging to do. 

“Physicians can help reduce stress and anxiety in patients desiring pregnancy by [recommending] preconception counseling, screening patients at risk for thyroid disease, and optimizing thyroid hormone levels before and during pregnancy,” according to Dr. Nguyen.
 

Maternal TSH and FT4 trajectories and preschoolers’ behaviors

Previous studies have reported that during pregnancy, maternal subclinical hypothyroidism (elevated TSH with normal FT4) as well as isolated hypothyroxinemia (decreased FT4 with normal TSH) are associated with adverse maternal and child outcomes, including preterm delivery and low birth weight.

However, most studies have not determined maternal thyroid hormone levels in different trimesters.

Researchers recruited pregnant women going for their first antenatal checkup at the Ma’anshan Maternal and Child Health Hospital in China from May 2013 to September 2014 and identified 1,860 mother-child pairs.

They determined maternal thyroid hormone levels from blood samples taken during the first, second, and third trimester: on average, gestational week 10, 25, and 34, respectively.

The researchers found that TSH levels increased somewhat from trimester 1 to trimester 2 and then decreased slightly in trimester 3. Most women (68%) had a low TSH trajectory, 28% had a moderate TSH trajectory, and 4% had a high TSH trajectory.

FT4 levels dropped sharply from trimester 1 to trimester 2 and then increased somewhat in trimester 3. About half of the women (52%) had a moderate FT4 trajectory, 33% had a low FT4 trajectory, and 15% had a high FT4 trajectory.

Most women (96.5%) had a low and stable TPOAb level, and the rest (3.5%) had high and decreasing TPOAb levels.  

When the children in the study were 4 years old, their main caregiver (parent or grandparent) completed the 100-question Achenbach Child Behavior checklist to identify whether the child often, sometimes, or never displayed three internalizing problem behaviors (emotionally reactive, anxious/depressed, or withdrawn) and/or two externalizing problem behaviors (attention problems or aggressive behavior).
 

Study limitations, more research needed

It is not clear why the associations between maternal hormones and offspring behavior were only seen in boys. Perhaps male fetuses are more sensitive than female fetuses to changing maternal thyroid hormone levels in pregnancy, the researchers speculate.

They acknowledge that study limitations include there were few children with aggressive behavior, so the confidence interval for the association of the moderate TSH trajectory with aggressive behavior was very wide.

In addition, evaluation of children’s behavior by caregivers was subjective. Also, the researchers did not have information about iodine levels, and low iodine levels can impair child brain development.

And there may have been residual confounders that researchers did not account for, such as differences in family upbringing, parental marital status, and the mother’s exposure to endocrine disruptors.

Therefore, further research is needed.

The study was supported by grants from the National Natural Science Foundation of China, the University Synergy Innovation Program of Anhui Province, the Sci-Tech Basic Resources Research Program of China, the National Key Research and Development Program, the Chinese Academy of Medical Sciences, and the Research Fund of Anhui Institute of Translational Medicine. The researchers and Dr. Nguyen have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pregnant women’s thyroid hormone trajectories (levels in the first, second, and third trimester) may predict whether their male offspring are aggressive or withdrawn at age 4.

Certain maternal thyroid hormone trajectories were associated with problem behaviors in preschool boys in a study of close to 2,000 mother-child pairs in China.

The researchers identified low, moderate, and high thyroid-stimulating hormone (TSH) and free thyroxine (FT4) trajectories. 

shironosov/Getty Images

‘Study supports monitoring thyroid function in pregnancy’

“Our findings highlight the significance of close monitoring and management of maternal thyroid function during pregnancy,” senior author Kun Huang, PhD, said in a press release from the Endocrine Society.

“This research presents a new perspective in early intervention of children’s emotional and behavioral problems,” added Dr. Huang, from Anhui Medical University, Hefei, China.

The results add to a growing body of literature about a controversial link between maternal thyroid hormones in pregnancy, when the fetal brain is developing, and subsequent behavior in preschool children, Caroline T. Nguyen, MD, who was not involved with this research, commented in an email.

“Some studies show an association between thyroid levels and behavioral outcomes, others not,” added Dr. Nguyen, assistant professor of clinical medicine, Keck School of Medicine, University of Southern California, Los Angeles. And “some studies have found sex-specific associations with maternal thyroid levels and neurocognitive/behavioral outcomes, others have not.”

Women considering pregnancy should be evaluated for possible thyroid disease, she continued. Currently, no universal screening mandates exist for thyroid disease in pregnancy, but the 2017 American Thyroid Association guidelines do recommend screening women at risk for thyroid dysfunction.

“I think screening for thyroid peroxidase antibody (TPOAb) positivity is helpful in women desiring pregnancy,” Dr. Nguyen continued, “because we know that patients with TPOAb positivity are at increased risk for miscarriage and have a blunted response to the increased demands of pregnancy for thyroid hormone production.”

TPOAb positivity is also associated with the increased risk of postpartum and long-term thyroid dysfunction.

This current study, Dr. Nguyen summarized, “adds to a growing body of research of the relationship of thyroid hormone levels and neurocognitive outcomes [in offspring] and supports the monitoring of thyroid disease in pregnancy.”  

“However, we do not have sufficient data to demonstrate the benefits of intervention with levothyroxine treatment,” she noted. 

Nevertheless, the lack of positive data does not suggest there is no theoretical benefit of intervention, she said, as such studies are very challenging to do. 

“Physicians can help reduce stress and anxiety in patients desiring pregnancy by [recommending] preconception counseling, screening patients at risk for thyroid disease, and optimizing thyroid hormone levels before and during pregnancy,” according to Dr. Nguyen.
 

Maternal TSH and FT4 trajectories and preschoolers’ behaviors

Previous studies have reported that during pregnancy, maternal subclinical hypothyroidism (elevated TSH with normal FT4) as well as isolated hypothyroxinemia (decreased FT4 with normal TSH) are associated with adverse maternal and child outcomes, including preterm delivery and low birth weight.

However, most studies have not determined maternal thyroid hormone levels in different trimesters.

Researchers recruited pregnant women going for their first antenatal checkup at the Ma’anshan Maternal and Child Health Hospital in China from May 2013 to September 2014 and identified 1,860 mother-child pairs.

They determined maternal thyroid hormone levels from blood samples taken during the first, second, and third trimester: on average, gestational week 10, 25, and 34, respectively.

The researchers found that TSH levels increased somewhat from trimester 1 to trimester 2 and then decreased slightly in trimester 3. Most women (68%) had a low TSH trajectory, 28% had a moderate TSH trajectory, and 4% had a high TSH trajectory.

FT4 levels dropped sharply from trimester 1 to trimester 2 and then increased somewhat in trimester 3. About half of the women (52%) had a moderate FT4 trajectory, 33% had a low FT4 trajectory, and 15% had a high FT4 trajectory.

Most women (96.5%) had a low and stable TPOAb level, and the rest (3.5%) had high and decreasing TPOAb levels.  

When the children in the study were 4 years old, their main caregiver (parent or grandparent) completed the 100-question Achenbach Child Behavior checklist to identify whether the child often, sometimes, or never displayed three internalizing problem behaviors (emotionally reactive, anxious/depressed, or withdrawn) and/or two externalizing problem behaviors (attention problems or aggressive behavior).
 

Study limitations, more research needed

It is not clear why the associations between maternal hormones and offspring behavior were only seen in boys. Perhaps male fetuses are more sensitive than female fetuses to changing maternal thyroid hormone levels in pregnancy, the researchers speculate.

They acknowledge that study limitations include there were few children with aggressive behavior, so the confidence interval for the association of the moderate TSH trajectory with aggressive behavior was very wide.

In addition, evaluation of children’s behavior by caregivers was subjective. Also, the researchers did not have information about iodine levels, and low iodine levels can impair child brain development.

And there may have been residual confounders that researchers did not account for, such as differences in family upbringing, parental marital status, and the mother’s exposure to endocrine disruptors.

Therefore, further research is needed.

The study was supported by grants from the National Natural Science Foundation of China, the University Synergy Innovation Program of Anhui Province, the Sci-Tech Basic Resources Research Program of China, the National Key Research and Development Program, the Chinese Academy of Medical Sciences, and the Research Fund of Anhui Institute of Translational Medicine. The researchers and Dr. Nguyen have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pregnant women’s thyroid hormone trajectories (levels in the first, second, and third trimester) may predict whether their male offspring are aggressive or withdrawn at age 4.

Certain maternal thyroid hormone trajectories were associated with problem behaviors in preschool boys in a study of close to 2,000 mother-child pairs in China.

The researchers identified low, moderate, and high thyroid-stimulating hormone (TSH) and free thyroxine (FT4) trajectories. 

shironosov/Getty Images

‘Study supports monitoring thyroid function in pregnancy’

“Our findings highlight the significance of close monitoring and management of maternal thyroid function during pregnancy,” senior author Kun Huang, PhD, said in a press release from the Endocrine Society.

“This research presents a new perspective in early intervention of children’s emotional and behavioral problems,” added Dr. Huang, from Anhui Medical University, Hefei, China.

The results add to a growing body of literature about a controversial link between maternal thyroid hormones in pregnancy, when the fetal brain is developing, and subsequent behavior in preschool children, Caroline T. Nguyen, MD, who was not involved with this research, commented in an email.

“Some studies show an association between thyroid levels and behavioral outcomes, others not,” added Dr. Nguyen, assistant professor of clinical medicine, Keck School of Medicine, University of Southern California, Los Angeles. And “some studies have found sex-specific associations with maternal thyroid levels and neurocognitive/behavioral outcomes, others have not.”

Women considering pregnancy should be evaluated for possible thyroid disease, she continued. Currently, no universal screening mandates exist for thyroid disease in pregnancy, but the 2017 American Thyroid Association guidelines do recommend screening women at risk for thyroid dysfunction.

“I think screening for thyroid peroxidase antibody (TPOAb) positivity is helpful in women desiring pregnancy,” Dr. Nguyen continued, “because we know that patients with TPOAb positivity are at increased risk for miscarriage and have a blunted response to the increased demands of pregnancy for thyroid hormone production.”

TPOAb positivity is also associated with the increased risk of postpartum and long-term thyroid dysfunction.

This current study, Dr. Nguyen summarized, “adds to a growing body of research of the relationship of thyroid hormone levels and neurocognitive outcomes [in offspring] and supports the monitoring of thyroid disease in pregnancy.”  

“However, we do not have sufficient data to demonstrate the benefits of intervention with levothyroxine treatment,” she noted. 

Nevertheless, the lack of positive data does not suggest there is no theoretical benefit of intervention, she said, as such studies are very challenging to do. 

“Physicians can help reduce stress and anxiety in patients desiring pregnancy by [recommending] preconception counseling, screening patients at risk for thyroid disease, and optimizing thyroid hormone levels before and during pregnancy,” according to Dr. Nguyen.
 

Maternal TSH and FT4 trajectories and preschoolers’ behaviors

Previous studies have reported that during pregnancy, maternal subclinical hypothyroidism (elevated TSH with normal FT4) as well as isolated hypothyroxinemia (decreased FT4 with normal TSH) are associated with adverse maternal and child outcomes, including preterm delivery and low birth weight.

However, most studies have not determined maternal thyroid hormone levels in different trimesters.

Researchers recruited pregnant women going for their first antenatal checkup at the Ma’anshan Maternal and Child Health Hospital in China from May 2013 to September 2014 and identified 1,860 mother-child pairs.

They determined maternal thyroid hormone levels from blood samples taken during the first, second, and third trimester: on average, gestational week 10, 25, and 34, respectively.

The researchers found that TSH levels increased somewhat from trimester 1 to trimester 2 and then decreased slightly in trimester 3. Most women (68%) had a low TSH trajectory, 28% had a moderate TSH trajectory, and 4% had a high TSH trajectory.

FT4 levels dropped sharply from trimester 1 to trimester 2 and then increased somewhat in trimester 3. About half of the women (52%) had a moderate FT4 trajectory, 33% had a low FT4 trajectory, and 15% had a high FT4 trajectory.

Most women (96.5%) had a low and stable TPOAb level, and the rest (3.5%) had high and decreasing TPOAb levels.  

When the children in the study were 4 years old, their main caregiver (parent or grandparent) completed the 100-question Achenbach Child Behavior checklist to identify whether the child often, sometimes, or never displayed three internalizing problem behaviors (emotionally reactive, anxious/depressed, or withdrawn) and/or two externalizing problem behaviors (attention problems or aggressive behavior).
 

Study limitations, more research needed

It is not clear why the associations between maternal hormones and offspring behavior were only seen in boys. Perhaps male fetuses are more sensitive than female fetuses to changing maternal thyroid hormone levels in pregnancy, the researchers speculate.

They acknowledge that study limitations include there were few children with aggressive behavior, so the confidence interval for the association of the moderate TSH trajectory with aggressive behavior was very wide.

In addition, evaluation of children’s behavior by caregivers was subjective. Also, the researchers did not have information about iodine levels, and low iodine levels can impair child brain development.

And there may have been residual confounders that researchers did not account for, such as differences in family upbringing, parental marital status, and the mother’s exposure to endocrine disruptors.

Therefore, further research is needed.

The study was supported by grants from the National Natural Science Foundation of China, the University Synergy Innovation Program of Anhui Province, the Sci-Tech Basic Resources Research Program of China, the National Key Research and Development Program, the Chinese Academy of Medical Sciences, and the Research Fund of Anhui Institute of Translational Medicine. The researchers and Dr. Nguyen have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Creators of a pilot program that educates preschoolers about good heart health have validated a template for successful early childhood intervention that, they claim, provides a pathway for translating scientific evidence into the community and classroom for educational purposes to encourage long-lasting lifestyle changes.

That validation supports the creators' plans to take the program into more schools.

They reported key lessons in crafting the program, known as the SI! Program (for Salud Integral-Comprehensive Health), online in the Journal of the American College of Cardiology.

Mount Sinai Hospital

“This is a research-based program that uses randomized clinical trial evidence with implementation strategies to design educational health promotion programs,” senior author Valentin Fuster, MD, PhD, founder and trustees chairman of the Foundation for Science, Health, and Education (SHE) based in Barcelona, under whose aegis the SI! Program was implemented, said in an interview. Dr. Fuster is also director of Mount Sinai Heart and physician-in-chief at Mount Sinai Hospital in New York, and general director of the National Center for Cardiovascular Investigation (CNIC) in Madrid, Spain’s equivalent of the National Heart, Lung, and Blood Institute.

“There are specific times in a child’s life when improvements can be made to enhance long-term cardiovascular health status,” said Rodrigo Fernández-Jiménez, MD, PhD, group leader of the cardiovascular health and imaging lab at CNIC and study coauthor. “Our review, and previous studies, suggest that 4-5 years of age is the most favorable time to start a school-based intervention focused on healthy habits.”

A key piece of the SI! Program used a Sesame Street character, known as Dr. Ruster, a Muppet based on Dr. Fuster, to introduce and convey most messages and activities to the preschool children. The program also used a heart-shaped mascot named “Cardio” to teach about healthy behaviors. Other components include video segments, a colorful storybook, an interactive board game, flash cards, and a teacher’s guide. The activities and messages were tailored based on the country in which the program was implemented.
 

A decade of experience

The review evaluated 10 years of experience with the preschool-based program, drawing upon cluster-randomized clinical trials of the program in three countries with different socioeconomic conditions: Colombia, Spain, and the United States. The studies randomized schools to receive the SI! Program for 4 months or to a control group and included more than 3,800 children from 50 schools, along with their parents or caregivers and teachers. The studies found significant increases in preschoolers’ knowledge, attitudes, and habits toward healthy eating and living an active lifestyle. Now, the SI! Program is expanding into more than 250 schools in Spain and more than 40 schools in all five boroughs of New York City.

“This is a multidimensional program,” Dr. Fuster said. The review identified five stages for implementing the program: dissemination; adoption; implementation; evaluation; and institutionalization.

Dissemination involves three substages for intervention: components, design, and strategy. With regard to the components, said Dr. Fuster, “We’re targeting children to educate them in four topics: how the body works; nutritional and dietary requirements; physical activity; and the need to control emotions – to say no in the future when they’re confronted with alcohol, drugs, and tobacco.”

Design involved a multidisciplinary team of experts to develop the intervention, Dr. Fuster said. The strategy itself enlists parents and teachers in the implementation, but goes beyond that. “This is a community,” Dr. Fuster said. Hence, the school environment and classroom itself are also engaged to support the message of the four topics.

Dr. Fuster said future research should look at knowledge, attitude, and habits and biological outcomes in children who’ve been in the SI! Program when they reach adolescence. “Our hypothesis is that we can do this in older children, but when they reach age 10 we want to reintervene in them,” Dr. Fuster said. “Humans need reintervention. Our findings don’t get into sustainability.” He added that further research should also identify socioeconomic factors that influence child health.

Expanding the program across the New York City’s five boroughs “offers a unique opportunity to explore which socioeconomic factors, at both the family and borough level, and may eventually affect children’s health, how they are implicated in the intervention’s effectiveness, and how they can be addressed to reduce the gap in health inequalities,” he said. 

Karalyn Kinsella, MD, a pediatrician affiliated with Yale New Haven (Conn.) Medical Center, noted the program’s multidimensional nature is an important element. “I think what is so important about this intervention is that it is not one single intervention but a curriculum that takes a significant amount of time (up to 50 hours) that allows for repetition of the information, which allows it to become remembered,” she said in an interview. “I also think incorporating families in the intervention is key as that is where change often has to happen.”

While she said the program may provide a template for a mental health curriculum, she added, “My concern is that teachers are already feeling overwhelmed and this may be viewed as another burden.”

The American Heart Association provided funding for the study in the United States. Dr Fernández-Jiménez has received funding from the Fondo de Investigación Sanitaria–Instituto de Salud Carlos III, which is cofunded by the European Regional Development Fund/European Social Fund. Dr. Fuster and Dr. Kinsella have no relevant disclosures.

Creators of a pilot program that educates preschoolers about good heart health have validated a template for successful early childhood intervention that, they claim, provides a pathway for translating scientific evidence into the community and classroom for educational purposes to encourage long-lasting lifestyle changes.

That validation supports the creators' plans to take the program into more schools.

They reported key lessons in crafting the program, known as the SI! Program (for Salud Integral-Comprehensive Health), online in the Journal of the American College of Cardiology.

Mount Sinai Hospital

“This is a research-based program that uses randomized clinical trial evidence with implementation strategies to design educational health promotion programs,” senior author Valentin Fuster, MD, PhD, founder and trustees chairman of the Foundation for Science, Health, and Education (SHE) based in Barcelona, under whose aegis the SI! Program was implemented, said in an interview. Dr. Fuster is also director of Mount Sinai Heart and physician-in-chief at Mount Sinai Hospital in New York, and general director of the National Center for Cardiovascular Investigation (CNIC) in Madrid, Spain’s equivalent of the National Heart, Lung, and Blood Institute.

“There are specific times in a child’s life when improvements can be made to enhance long-term cardiovascular health status,” said Rodrigo Fernández-Jiménez, MD, PhD, group leader of the cardiovascular health and imaging lab at CNIC and study coauthor. “Our review, and previous studies, suggest that 4-5 years of age is the most favorable time to start a school-based intervention focused on healthy habits.”

A key piece of the SI! Program used a Sesame Street character, known as Dr. Ruster, a Muppet based on Dr. Fuster, to introduce and convey most messages and activities to the preschool children. The program also used a heart-shaped mascot named “Cardio” to teach about healthy behaviors. Other components include video segments, a colorful storybook, an interactive board game, flash cards, and a teacher’s guide. The activities and messages were tailored based on the country in which the program was implemented.
 

A decade of experience

The review evaluated 10 years of experience with the preschool-based program, drawing upon cluster-randomized clinical trials of the program in three countries with different socioeconomic conditions: Colombia, Spain, and the United States. The studies randomized schools to receive the SI! Program for 4 months or to a control group and included more than 3,800 children from 50 schools, along with their parents or caregivers and teachers. The studies found significant increases in preschoolers’ knowledge, attitudes, and habits toward healthy eating and living an active lifestyle. Now, the SI! Program is expanding into more than 250 schools in Spain and more than 40 schools in all five boroughs of New York City.

“This is a multidimensional program,” Dr. Fuster said. The review identified five stages for implementing the program: dissemination; adoption; implementation; evaluation; and institutionalization.

Dissemination involves three substages for intervention: components, design, and strategy. With regard to the components, said Dr. Fuster, “We’re targeting children to educate them in four topics: how the body works; nutritional and dietary requirements; physical activity; and the need to control emotions – to say no in the future when they’re confronted with alcohol, drugs, and tobacco.”

Design involved a multidisciplinary team of experts to develop the intervention, Dr. Fuster said. The strategy itself enlists parents and teachers in the implementation, but goes beyond that. “This is a community,” Dr. Fuster said. Hence, the school environment and classroom itself are also engaged to support the message of the four topics.

Dr. Fuster said future research should look at knowledge, attitude, and habits and biological outcomes in children who’ve been in the SI! Program when they reach adolescence. “Our hypothesis is that we can do this in older children, but when they reach age 10 we want to reintervene in them,” Dr. Fuster said. “Humans need reintervention. Our findings don’t get into sustainability.” He added that further research should also identify socioeconomic factors that influence child health.

Expanding the program across the New York City’s five boroughs “offers a unique opportunity to explore which socioeconomic factors, at both the family and borough level, and may eventually affect children’s health, how they are implicated in the intervention’s effectiveness, and how they can be addressed to reduce the gap in health inequalities,” he said. 

Karalyn Kinsella, MD, a pediatrician affiliated with Yale New Haven (Conn.) Medical Center, noted the program’s multidimensional nature is an important element. “I think what is so important about this intervention is that it is not one single intervention but a curriculum that takes a significant amount of time (up to 50 hours) that allows for repetition of the information, which allows it to become remembered,” she said in an interview. “I also think incorporating families in the intervention is key as that is where change often has to happen.”

While she said the program may provide a template for a mental health curriculum, she added, “My concern is that teachers are already feeling overwhelmed and this may be viewed as another burden.”

The American Heart Association provided funding for the study in the United States. Dr Fernández-Jiménez has received funding from the Fondo de Investigación Sanitaria–Instituto de Salud Carlos III, which is cofunded by the European Regional Development Fund/European Social Fund. Dr. Fuster and Dr. Kinsella have no relevant disclosures.

Creators of a pilot program that educates preschoolers about good heart health have validated a template for successful early childhood intervention that, they claim, provides a pathway for translating scientific evidence into the community and classroom for educational purposes to encourage long-lasting lifestyle changes.

That validation supports the creators' plans to take the program into more schools.

They reported key lessons in crafting the program, known as the SI! Program (for Salud Integral-Comprehensive Health), online in the Journal of the American College of Cardiology.

Mount Sinai Hospital

“This is a research-based program that uses randomized clinical trial evidence with implementation strategies to design educational health promotion programs,” senior author Valentin Fuster, MD, PhD, founder and trustees chairman of the Foundation for Science, Health, and Education (SHE) based in Barcelona, under whose aegis the SI! Program was implemented, said in an interview. Dr. Fuster is also director of Mount Sinai Heart and physician-in-chief at Mount Sinai Hospital in New York, and general director of the National Center for Cardiovascular Investigation (CNIC) in Madrid, Spain’s equivalent of the National Heart, Lung, and Blood Institute.

“There are specific times in a child’s life when improvements can be made to enhance long-term cardiovascular health status,” said Rodrigo Fernández-Jiménez, MD, PhD, group leader of the cardiovascular health and imaging lab at CNIC and study coauthor. “Our review, and previous studies, suggest that 4-5 years of age is the most favorable time to start a school-based intervention focused on healthy habits.”

A key piece of the SI! Program used a Sesame Street character, known as Dr. Ruster, a Muppet based on Dr. Fuster, to introduce and convey most messages and activities to the preschool children. The program also used a heart-shaped mascot named “Cardio” to teach about healthy behaviors. Other components include video segments, a colorful storybook, an interactive board game, flash cards, and a teacher’s guide. The activities and messages were tailored based on the country in which the program was implemented.
 

A decade of experience

The review evaluated 10 years of experience with the preschool-based program, drawing upon cluster-randomized clinical trials of the program in three countries with different socioeconomic conditions: Colombia, Spain, and the United States. The studies randomized schools to receive the SI! Program for 4 months or to a control group and included more than 3,800 children from 50 schools, along with their parents or caregivers and teachers. The studies found significant increases in preschoolers’ knowledge, attitudes, and habits toward healthy eating and living an active lifestyle. Now, the SI! Program is expanding into more than 250 schools in Spain and more than 40 schools in all five boroughs of New York City.

“This is a multidimensional program,” Dr. Fuster said. The review identified five stages for implementing the program: dissemination; adoption; implementation; evaluation; and institutionalization.

Dissemination involves three substages for intervention: components, design, and strategy. With regard to the components, said Dr. Fuster, “We’re targeting children to educate them in four topics: how the body works; nutritional and dietary requirements; physical activity; and the need to control emotions – to say no in the future when they’re confronted with alcohol, drugs, and tobacco.”

Design involved a multidisciplinary team of experts to develop the intervention, Dr. Fuster said. The strategy itself enlists parents and teachers in the implementation, but goes beyond that. “This is a community,” Dr. Fuster said. Hence, the school environment and classroom itself are also engaged to support the message of the four topics.

Dr. Fuster said future research should look at knowledge, attitude, and habits and biological outcomes in children who’ve been in the SI! Program when they reach adolescence. “Our hypothesis is that we can do this in older children, but when they reach age 10 we want to reintervene in them,” Dr. Fuster said. “Humans need reintervention. Our findings don’t get into sustainability.” He added that further research should also identify socioeconomic factors that influence child health.

Expanding the program across the New York City’s five boroughs “offers a unique opportunity to explore which socioeconomic factors, at both the family and borough level, and may eventually affect children’s health, how they are implicated in the intervention’s effectiveness, and how they can be addressed to reduce the gap in health inequalities,” he said. 

Karalyn Kinsella, MD, a pediatrician affiliated with Yale New Haven (Conn.) Medical Center, noted the program’s multidimensional nature is an important element. “I think what is so important about this intervention is that it is not one single intervention but a curriculum that takes a significant amount of time (up to 50 hours) that allows for repetition of the information, which allows it to become remembered,” she said in an interview. “I also think incorporating families in the intervention is key as that is where change often has to happen.”

While she said the program may provide a template for a mental health curriculum, she added, “My concern is that teachers are already feeling overwhelmed and this may be viewed as another burden.”

The American Heart Association provided funding for the study in the United States. Dr Fernández-Jiménez has received funding from the Fondo de Investigación Sanitaria–Instituto de Salud Carlos III, which is cofunded by the European Regional Development Fund/European Social Fund. Dr. Fuster and Dr. Kinsella have no relevant disclosures.

The Food and Drug Administration on Jan. 14 approved two oral JAK-1 inhibitors for patients with moderate-to-severe atopic dermatitis (AD) – upadacitinib and abrocitinib – making them the first oral JAK-inhibitors available for this indication in the United States.

“It’s big news because a few years ago we didn’t have any systemic treatments that are safer than the classical immunosuppressants like cyclosporine and methotrexate,” Emma Guttman-Yassky, MD, PhD, Waldman professor and system chair of dermatology at the Icahn School of Medicine at Mount Sinai in New York, told this news organization commenting on upadacitinib’s approval.

Olivier Le Moal/Getty Images

Upadacitinib

The approval of upadacitinib (Rinvoq), marketed by AbbVie, for moderate to severe AD in patients ages 12 and older, comes on the heels of findings from three pivotal phase 3 studies involving more than 2,500 adults and children 12 years of age and older with moderate to severe AD: Measure Up 1 and 2, led by Dr. Guttman-Yassky, which evaluated upadacitinib compared with placebo, and AD UP, which compared upadacitinib along with topical corticosteroids, compared with placebo.

Across the three studies, upadacitinib – both 15 mg and 30 mg once daily monotherapy – met all primary and secondary endpoints at week 16, with some patients achieving higher levels of skin clearance based on the Eczema Area and Severity Index 90 (EASI-90) and EASI-100.

“I always say that patients with AD need options,” Dr. Guttman-Yassky said. “We need biologics. We need oral medications. Not everybody likes an injectable. The plus of the class of JAK inhibitors in general is the quick onset of action.” Many patients in her clinic are maintained on upadacitinib more than two years later “and are super happy,” she said. “Many of them failed cyclosporine and other immunosuppressants such as methotrexate and prednisone.”

She predicted that health insurance companies will find coverage cost-effective “because it sets a new bar for efficacy, and because many patients have failed other treatments.”

Abrocitinib

Abrocitinib (Cibinqo), marketed by Pfizer, was approved for adults with moderate to severe AD. The approval was based on results of five clinical trials from a large-scale clinical trial program of more than 1,600 patients. The recommended doses are 100 mg and 200 mg, with the 200 mg dose recommended for patients who are not responding to the 100 mg dose.

The labeling of abrocitinib and upadacitinib include a boxed warning for JAK inhibitors, regarding the risk of serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis.

Dr. Guttman-Yassky has served as a principal investigator for AbbVie and has received consulting fees from the company.




 

The Food and Drug Administration on Jan. 14 approved two oral JAK-1 inhibitors for patients with moderate-to-severe atopic dermatitis (AD) – upadacitinib and abrocitinib – making them the first oral JAK-inhibitors available for this indication in the United States.

“It’s big news because a few years ago we didn’t have any systemic treatments that are safer than the classical immunosuppressants like cyclosporine and methotrexate,” Emma Guttman-Yassky, MD, PhD, Waldman professor and system chair of dermatology at the Icahn School of Medicine at Mount Sinai in New York, told this news organization commenting on upadacitinib’s approval.

Olivier Le Moal/Getty Images

Upadacitinib

The approval of upadacitinib (Rinvoq), marketed by AbbVie, for moderate to severe AD in patients ages 12 and older, comes on the heels of findings from three pivotal phase 3 studies involving more than 2,500 adults and children 12 years of age and older with moderate to severe AD: Measure Up 1 and 2, led by Dr. Guttman-Yassky, which evaluated upadacitinib compared with placebo, and AD UP, which compared upadacitinib along with topical corticosteroids, compared with placebo.

Across the three studies, upadacitinib – both 15 mg and 30 mg once daily monotherapy – met all primary and secondary endpoints at week 16, with some patients achieving higher levels of skin clearance based on the Eczema Area and Severity Index 90 (EASI-90) and EASI-100.

“I always say that patients with AD need options,” Dr. Guttman-Yassky said. “We need biologics. We need oral medications. Not everybody likes an injectable. The plus of the class of JAK inhibitors in general is the quick onset of action.” Many patients in her clinic are maintained on upadacitinib more than two years later “and are super happy,” she said. “Many of them failed cyclosporine and other immunosuppressants such as methotrexate and prednisone.”

She predicted that health insurance companies will find coverage cost-effective “because it sets a new bar for efficacy, and because many patients have failed other treatments.”

Abrocitinib

Abrocitinib (Cibinqo), marketed by Pfizer, was approved for adults with moderate to severe AD. The approval was based on results of five clinical trials from a large-scale clinical trial program of more than 1,600 patients. The recommended doses are 100 mg and 200 mg, with the 200 mg dose recommended for patients who are not responding to the 100 mg dose.

The labeling of abrocitinib and upadacitinib include a boxed warning for JAK inhibitors, regarding the risk of serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis.

Dr. Guttman-Yassky has served as a principal investigator for AbbVie and has received consulting fees from the company.




 

The Food and Drug Administration on Jan. 14 approved two oral JAK-1 inhibitors for patients with moderate-to-severe atopic dermatitis (AD) – upadacitinib and abrocitinib – making them the first oral JAK-inhibitors available for this indication in the United States.

“It’s big news because a few years ago we didn’t have any systemic treatments that are safer than the classical immunosuppressants like cyclosporine and methotrexate,” Emma Guttman-Yassky, MD, PhD, Waldman professor and system chair of dermatology at the Icahn School of Medicine at Mount Sinai in New York, told this news organization commenting on upadacitinib’s approval.

Olivier Le Moal/Getty Images

Upadacitinib

The approval of upadacitinib (Rinvoq), marketed by AbbVie, for moderate to severe AD in patients ages 12 and older, comes on the heels of findings from three pivotal phase 3 studies involving more than 2,500 adults and children 12 years of age and older with moderate to severe AD: Measure Up 1 and 2, led by Dr. Guttman-Yassky, which evaluated upadacitinib compared with placebo, and AD UP, which compared upadacitinib along with topical corticosteroids, compared with placebo.

Across the three studies, upadacitinib – both 15 mg and 30 mg once daily monotherapy – met all primary and secondary endpoints at week 16, with some patients achieving higher levels of skin clearance based on the Eczema Area and Severity Index 90 (EASI-90) and EASI-100.

“I always say that patients with AD need options,” Dr. Guttman-Yassky said. “We need biologics. We need oral medications. Not everybody likes an injectable. The plus of the class of JAK inhibitors in general is the quick onset of action.” Many patients in her clinic are maintained on upadacitinib more than two years later “and are super happy,” she said. “Many of them failed cyclosporine and other immunosuppressants such as methotrexate and prednisone.”

She predicted that health insurance companies will find coverage cost-effective “because it sets a new bar for efficacy, and because many patients have failed other treatments.”

Abrocitinib

Abrocitinib (Cibinqo), marketed by Pfizer, was approved for adults with moderate to severe AD. The approval was based on results of five clinical trials from a large-scale clinical trial program of more than 1,600 patients. The recommended doses are 100 mg and 200 mg, with the 200 mg dose recommended for patients who are not responding to the 100 mg dose.

The labeling of abrocitinib and upadacitinib include a boxed warning for JAK inhibitors, regarding the risk of serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis.

Dr. Guttman-Yassky has served as a principal investigator for AbbVie and has received consulting fees from the company.