Key clinical point: African American males aged 14-15 years were more likely than 18- to 19- year-old males to use a condom the last time they had sex.

Major finding: Increased condom use was associated with personal factors including high positive attachment to the boyfriend/girlfriend as was a greater number of sexual partners, younger age at first sexual encounter, and knowledge that the individual had a sexually-transmitted infection in the past year.

Study details: The data come from the Mobile Youth Survey, a community-based survey of adolescents in Mobile, Alabama, between 1998 and 2011; the study population included 3,718 individuals.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chambliss JT et al. Am J Mens Health. 2021 Apr 15. doi: 10.1177/15579883211009039.

Key clinical point: African American males aged 14-15 years were more likely than 18- to 19- year-old males to use a condom the last time they had sex.

Major finding: Increased condom use was associated with personal factors including high positive attachment to the boyfriend/girlfriend as was a greater number of sexual partners, younger age at first sexual encounter, and knowledge that the individual had a sexually-transmitted infection in the past year.

Study details: The data come from the Mobile Youth Survey, a community-based survey of adolescents in Mobile, Alabama, between 1998 and 2011; the study population included 3,718 individuals.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chambliss JT et al. Am J Mens Health. 2021 Apr 15. doi: 10.1177/15579883211009039.

Key clinical point: African American males aged 14-15 years were more likely than 18- to 19- year-old males to use a condom the last time they had sex.

Major finding: Increased condom use was associated with personal factors including high positive attachment to the boyfriend/girlfriend as was a greater number of sexual partners, younger age at first sexual encounter, and knowledge that the individual had a sexually-transmitted infection in the past year.

Study details: The data come from the Mobile Youth Survey, a community-based survey of adolescents in Mobile, Alabama, between 1998 and 2011; the study population included 3,718 individuals.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chambliss JT et al. Am J Mens Health. 2021 Apr 15. doi: 10.1177/15579883211009039.

Key clinical point: Immediate postpartum insertion of copper intrauterine devices is effective and acceptable for women living in low- and middle-income countries.

Major finding: The six-month continuation rate for immediate postpartum copper IUDs was 87% in low- and middle-income countries; pooled estimated rates of adverse outcomes at six months were 6% for expulsion, 5% for removal, and 0.2% for infection.

Study details: The data come from a meta-analysis of 11 studies of the use and continuation of postpartum long-acting reversible contraception in low- and middle-income countries, including 2 randomized, controlled trials and 9 prospective cohort studies.

Disclosures: The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Doris Duke Charitable Foundation. The researchers had no financial conflicts to disclose.

Source: Marchin A et al. J Womens Health Dev. 2021 Mar 18. doi: 10.26502/fjwhd.2644-28840059. 

Key clinical point: Immediate postpartum insertion of copper intrauterine devices is effective and acceptable for women living in low- and middle-income countries.

Major finding: The six-month continuation rate for immediate postpartum copper IUDs was 87% in low- and middle-income countries; pooled estimated rates of adverse outcomes at six months were 6% for expulsion, 5% for removal, and 0.2% for infection.

Study details: The data come from a meta-analysis of 11 studies of the use and continuation of postpartum long-acting reversible contraception in low- and middle-income countries, including 2 randomized, controlled trials and 9 prospective cohort studies.

Disclosures: The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Doris Duke Charitable Foundation. The researchers had no financial conflicts to disclose.

Source: Marchin A et al. J Womens Health Dev. 2021 Mar 18. doi: 10.26502/fjwhd.2644-28840059. 

Key clinical point: Immediate postpartum insertion of copper intrauterine devices is effective and acceptable for women living in low- and middle-income countries.

Major finding: The six-month continuation rate for immediate postpartum copper IUDs was 87% in low- and middle-income countries; pooled estimated rates of adverse outcomes at six months were 6% for expulsion, 5% for removal, and 0.2% for infection.

Study details: The data come from a meta-analysis of 11 studies of the use and continuation of postpartum long-acting reversible contraception in low- and middle-income countries, including 2 randomized, controlled trials and 9 prospective cohort studies.

Disclosures: The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Doris Duke Charitable Foundation. The researchers had no financial conflicts to disclose.

Source: Marchin A et al. J Womens Health Dev. 2021 Mar 18. doi: 10.26502/fjwhd.2644-28840059. 

Key clinical point: Women taking oral contraceptives showed lower volume in the hypothalamic and pituitary gland compared to normally cycling women based on magnetic resonance imaging (MRI) data.

Major finding: Hypothalamic and pituitary volumes were significantly lower in women using oral contraceptives compared to naturally cycling women (B = -81.2 for both; P = 0.002 and P = -0.04, respectively).

Study details: The data come from a prospective study of 50 healthy women aged 18 and older, including 21 oral contraceptive users, and 29 naturally cycling women.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chen KX et al. PLos One. 2021 Apr 21.  doi: 10.1371/journal.pone.0249482. eCollection 2021.

Key clinical point: Women taking oral contraceptives showed lower volume in the hypothalamic and pituitary gland compared to normally cycling women based on magnetic resonance imaging (MRI) data.

Major finding: Hypothalamic and pituitary volumes were significantly lower in women using oral contraceptives compared to naturally cycling women (B = -81.2 for both; P = 0.002 and P = -0.04, respectively).

Study details: The data come from a prospective study of 50 healthy women aged 18 and older, including 21 oral contraceptive users, and 29 naturally cycling women.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chen KX et al. PLos One. 2021 Apr 21.  doi: 10.1371/journal.pone.0249482. eCollection 2021.

Key clinical point: Women taking oral contraceptives showed lower volume in the hypothalamic and pituitary gland compared to normally cycling women based on magnetic resonance imaging (MRI) data.

Major finding: Hypothalamic and pituitary volumes were significantly lower in women using oral contraceptives compared to naturally cycling women (B = -81.2 for both; P = 0.002 and P = -0.04, respectively).

Study details: The data come from a prospective study of 50 healthy women aged 18 and older, including 21 oral contraceptive users, and 29 naturally cycling women.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chen KX et al. PLos One. 2021 Apr 21.  doi: 10.1371/journal.pone.0249482. eCollection 2021.

Key clinical point: Women’s attitudes towards contraceptives affect their willingness to accept a novel HIV prevention product in the form of a vaginal ring; pre-emptive counseling to address women’s concerns may encourage acceptance.

Major finding: Women surveyed about their experience using a monthly dapivirine vaginal ring reported side effects related to menses, and expressed some concern about the long-term impact of the ring and contraception use on fertility.

Study details: The data come from a subset of 214 women of childbearing age enrolled in the ASPIRE trial at 15 sites in Malawi, South Africa, Uganda, and Zambia who received a monthly dapivirine vaginal ring designed for HIV prevention.

Disclosures: The study was supported by the e National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health. The vaginal rings were supplied by the International Partnership for Microbicides (IPM). The researchers had no financial conflicts to disclose.

Source: Leslie J et al. BMC Womens Health. 2021 Apr 23. doi: 10.1186/s12905-021-01321-5.

Key clinical point: Women’s attitudes towards contraceptives affect their willingness to accept a novel HIV prevention product in the form of a vaginal ring; pre-emptive counseling to address women’s concerns may encourage acceptance.

Major finding: Women surveyed about their experience using a monthly dapivirine vaginal ring reported side effects related to menses, and expressed some concern about the long-term impact of the ring and contraception use on fertility.

Study details: The data come from a subset of 214 women of childbearing age enrolled in the ASPIRE trial at 15 sites in Malawi, South Africa, Uganda, and Zambia who received a monthly dapivirine vaginal ring designed for HIV prevention.

Disclosures: The study was supported by the e National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health. The vaginal rings were supplied by the International Partnership for Microbicides (IPM). The researchers had no financial conflicts to disclose.

Source: Leslie J et al. BMC Womens Health. 2021 Apr 23. doi: 10.1186/s12905-021-01321-5.

Key clinical point: Women’s attitudes towards contraceptives affect their willingness to accept a novel HIV prevention product in the form of a vaginal ring; pre-emptive counseling to address women’s concerns may encourage acceptance.

Major finding: Women surveyed about their experience using a monthly dapivirine vaginal ring reported side effects related to menses, and expressed some concern about the long-term impact of the ring and contraception use on fertility.

Study details: The data come from a subset of 214 women of childbearing age enrolled in the ASPIRE trial at 15 sites in Malawi, South Africa, Uganda, and Zambia who received a monthly dapivirine vaginal ring designed for HIV prevention.

Disclosures: The study was supported by the e National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health. The vaginal rings were supplied by the International Partnership for Microbicides (IPM). The researchers had no financial conflicts to disclose.

Source: Leslie J et al. BMC Womens Health. 2021 Apr 23. doi: 10.1186/s12905-021-01321-5.

Key clinical point: Women who used progestin-only contraceptives experienced significantly greater weight gain than those using nonhormonal copper intrauterine devices.

Major finding: After 18 months, all treatment groups gained weight, but the average gain in the DMPA-IM group (3.5 kg) was significantly higher compared with both the LNG implant group (2.4 kg) and copper IUD group (1.5 kg).

Study details: The data come from a secondary analysis of women enrolled in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial and included 7,829 women aged 16-35 years seen at 12 sites in Kenya, South Africa, and Zambia between December 2015 and October 2018. Of these, 2,609 received intramuscular depot medroxyprogesterone acetate (DMPA-IM), 2,613 received a levonorgestrel (LNG) implant, and 2,607 received a copper intrauterine device (IUD).

Disclosures: The study was supported by the Bill & Melinda Gates Foundation, US Agency for International Development (USAID) and the President's Emergency Plan for AIDS Relief, Swedish International Development Cooperation Agency, South African Medical Research Council, and UNFPA.

Source: Beksinska M et al. EClinicalMedicine. 2021 Apr 6. doi: 0.1016/j.eclinm.2021.100800.

Key clinical point: Women who used progestin-only contraceptives experienced significantly greater weight gain than those using nonhormonal copper intrauterine devices.

Major finding: After 18 months, all treatment groups gained weight, but the average gain in the DMPA-IM group (3.5 kg) was significantly higher compared with both the LNG implant group (2.4 kg) and copper IUD group (1.5 kg).

Study details: The data come from a secondary analysis of women enrolled in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial and included 7,829 women aged 16-35 years seen at 12 sites in Kenya, South Africa, and Zambia between December 2015 and October 2018. Of these, 2,609 received intramuscular depot medroxyprogesterone acetate (DMPA-IM), 2,613 received a levonorgestrel (LNG) implant, and 2,607 received a copper intrauterine device (IUD).

Disclosures: The study was supported by the Bill & Melinda Gates Foundation, US Agency for International Development (USAID) and the President's Emergency Plan for AIDS Relief, Swedish International Development Cooperation Agency, South African Medical Research Council, and UNFPA.

Source: Beksinska M et al. EClinicalMedicine. 2021 Apr 6. doi: 0.1016/j.eclinm.2021.100800.

Key clinical point: Women who used progestin-only contraceptives experienced significantly greater weight gain than those using nonhormonal copper intrauterine devices.

Major finding: After 18 months, all treatment groups gained weight, but the average gain in the DMPA-IM group (3.5 kg) was significantly higher compared with both the LNG implant group (2.4 kg) and copper IUD group (1.5 kg).

Study details: The data come from a secondary analysis of women enrolled in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial and included 7,829 women aged 16-35 years seen at 12 sites in Kenya, South Africa, and Zambia between December 2015 and October 2018. Of these, 2,609 received intramuscular depot medroxyprogesterone acetate (DMPA-IM), 2,613 received a levonorgestrel (LNG) implant, and 2,607 received a copper intrauterine device (IUD).

Disclosures: The study was supported by the Bill & Melinda Gates Foundation, US Agency for International Development (USAID) and the President's Emergency Plan for AIDS Relief, Swedish International Development Cooperation Agency, South African Medical Research Council, and UNFPA.

Source: Beksinska M et al. EClinicalMedicine. 2021 Apr 6. doi: 0.1016/j.eclinm.2021.100800.

Key clinical point: Hispanic patients with a higher level of English language acculturation were less likely to use birth control and may require a more detailed discussion of the options for family planning.

Major finding: Hispanic women who reported using birth control had significantly lower English language acculturation compared to those who reported no birth control

Study details: The data come from surveys of 225 Hispanic women that combined the number of years lived in the U.S., the Short Acculturation Scale for Hispanics, and questions about family planning behaviors.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chamberlain R et al. Kans J Med. 2021 Apr 19. doi: 10.17161/kjm.vol1414845.

Key clinical point: Hispanic patients with a higher level of English language acculturation were less likely to use birth control and may require a more detailed discussion of the options for family planning.

Major finding: Hispanic women who reported using birth control had significantly lower English language acculturation compared to those who reported no birth control

Study details: The data come from surveys of 225 Hispanic women that combined the number of years lived in the U.S., the Short Acculturation Scale for Hispanics, and questions about family planning behaviors.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chamberlain R et al. Kans J Med. 2021 Apr 19. doi: 10.17161/kjm.vol1414845.

Key clinical point: Hispanic patients with a higher level of English language acculturation were less likely to use birth control and may require a more detailed discussion of the options for family planning.

Major finding: Hispanic women who reported using birth control had significantly lower English language acculturation compared to those who reported no birth control

Study details: The data come from surveys of 225 Hispanic women that combined the number of years lived in the U.S., the Short Acculturation Scale for Hispanics, and questions about family planning behaviors.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chamberlain R et al. Kans J Med. 2021 Apr 19. doi: 10.17161/kjm.vol1414845.

Immediate postpartum long-acting reversible contraception (LARC) represents a safe and effective contraceptive strategy. Despite national guidelines recommending universal patient access, hospitals face significant barriers to offering inpatient LARCs. It is unclear why some hospitals successfully implement immediate postpartum LARCs, while others do not.

Moniz et al conducted a comparative, multiple case study of immediate postpartum LARC implementation at eleven “early adopter” U.S. hospitals and analyzed each hospital’s implementation strategy to produce generalizable knowledge about how and under what circumstances implementation of immediate postpartum LARCs unfold successfully. Between 2017-2018, the authors conducted single-day site visits and 78 semi-structured interviews with a variety of stakeholders (clinician champions, nurses, pharmacists, revenue cycle staff, and hospital administration). On average, sites used 18 (range 11-22) implementation strategies, including assessing institutional readiness for, and barriers to, implementation of immediate postpartum LARC, engaging reproductive justice experts and community resources to address social determinants of health, involving patients in implementation planning, and developing quality monitoring processes to evaluate clinical processes and outcomes. The researchers found that successful implementation of immediate postpartum LARC required three essential conditions: effective implementation champions who are supported by a multidisciplinary implementation team; creating an enabling financial environment; and engaging hospital administration. Additional findings from this study call for more support for individuals leading change in complex care settings, intentionally designing implementation interventions that take into account local contextual influences, and meaningfully engaging patients in the implementation process.

Of postpartum women, 61% in low- and middle-income countries (LMIC) have an unmet contraceptive need and many face high rates of short interpregnancy intervals (Moore). Additionally, 51%-96% of postpartum women in LMIC use short-acting methods of contraception (Moore), further highlighting the need for increased access to immediate postpartum LARC in LMIC. Data on the use and continuation of immediate postpartum LARC in LMIC is limited. Marchin et al conducted a systematic review and meta-analysis to determine 6-month continuation rates of immediate postpartum LARCs among women in 69 low-income countries that were enrolled in the Family Planning 2020 initiative. The meta-analysis ultimately focused on the copper IUD due to the absence of relevant studies on other LARC methods. The meta-analysis of 12 studies resulted in a pooled 6-month continuation rate for immediate postpartum copper IUDs of 87%, a rate comparable to continuation rates found in higher-income countries. This estimate had significant heterogeneity between studies. Secondary outcomes of expulsion, removal, and infection rates were low at 6%, 5%, and 0.2% respectively. High 6-month continuation rates and a low rate of adverse outcomes suggest immediate postpartum copper IUD insertion represents a feasible and acceptable postpartum contraceptive option for women living in LMIC.

In cases where contraception methods fail, are used incorrectly, or are not used at all, emergency contraception (EC) can be used after intercourse to prevent pregnancy. Timely access to, and accurate knowledge of, EC are especially important for rural women who are more likely to experience an unintended pregnancy resulting in a live birth compared to urban women. Milkowski et al analyzed publicly available data from the National Survey of Family Growth to estimate differences in oral EC use, access, and counseling by rural-urban county of residence among U.S. women aged 15-44 years. 10% of rural and 19% of urban women who had ever been sexually active reported ever using EC pills. Over the course of the study period (2006-2017), the percentage of women reporting ever-use of EC increased linearly in both rural and urban populations, with the prevalence of EC ever-use more than doubling in each group. This observation likely reflects an overall increase in EC use during a time period in which the federal government enacted several policies to improve access to EC. The study findings also highlight the need for improved patient counseling on EC. While the overall prevalence of EC counseling was low among all women, rural women were less likely to have received counseling on EC when compared to urban women.

Although many studies report weight gain in users of progestin-only hormonal contraception (POC), a recent Cochrane systematic review found that there was insufficient evidence to determine the effect of POCs on weight (Lopez). Beksinska et al conducted a secondary analysis of prospective weight change among women enrolled in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial, which was an open label, prospective, randomized multicenter trial that compared the risk of HIV acquisition among women randomized to injectable contraception (DMPA), the copper IUD, or a second generation two rod levonorgestrel (LNG) implant Jadelle^Ò. This trial was conducted at 12 sites across four African countries between 2015 and 2018. Eligible study participants were nonpregnant, HIV negative, sexually active women aged 16-35 years who desired contraception. The final sample size included 7,014 women randomly assigned to receive DMPA (2,293), the LNG implant (2,372), or the copper IUD (2,349). Using a standardized protocol and calibrated equipment across all study sites, weight and height were measured at baseline and at study exit at 12, 15, or 18 months. The mean weight increased amongst all three contraceptive groups and was significantly different in magnitude, with the largest gain in the DMPA group (3.5 kg), 2.4 kg in the LNG implant group, and 1.5 kg in the copper IUD group. Unlike copper IUD users, women in the DMPA and LNG implant group continued to gain weight after 1 year of contraceptive use. It is noteworthy that, regardless of contraceptive method allocation, not all women gained weight and a small proportion of women lost weight. When choosing a contraceptive method, women using POCs should be counselled about the potential side effect of weight gain.

References:
Moniz MH, Bonawitz K, Wetmore MK, et al. Implementing immediate postpartum contraception: a comparative case study at 11 hospitals. Implement Sci Commun. 2021;2(1):42. Published 2021 Apr 12.

Moore Z, Pfitzer A, Gubin R, et al. Missed opportunities for family planning: an analysis of pregnancy risk and contraceptive method use among postpartum women in 21 low- and middle-income countries. Contraception 92 (2015): 31–39.
 

Marchin A, Moss A, Harrison M. A Meta-Analysis of Postpartum Copper IUD Continuation Rates in Low- and Middle-Income Countries. J Womens Health Dev. 2021;4(1):36-46.

Milkowski CM, Ziller EC, Ahrens KA. Rural-urban residence and emergency contraception use, access, and counseling in the United States, 2006-2017. Contracept X. 2021;3:100061.

Lopez L.M., Ramesh S., Chen M. Progestin-only contraceptives: effects on weight. Cochrane Database Syst Rev. 2016 doi: 10.1002/14651858.CD008815.pub2.

Beksinska et al. “Weight change among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Findings from a randomised, multicentre, open-label trial. EClinicalMedicine. 2021;34:100800.

Immediate postpartum long-acting reversible contraception (LARC) represents a safe and effective contraceptive strategy. Despite national guidelines recommending universal patient access, hospitals face significant barriers to offering inpatient LARCs. It is unclear why some hospitals successfully implement immediate postpartum LARCs, while others do not.

Moniz et al conducted a comparative, multiple case study of immediate postpartum LARC implementation at eleven “early adopter” U.S. hospitals and analyzed each hospital’s implementation strategy to produce generalizable knowledge about how and under what circumstances implementation of immediate postpartum LARCs unfold successfully. Between 2017-2018, the authors conducted single-day site visits and 78 semi-structured interviews with a variety of stakeholders (clinician champions, nurses, pharmacists, revenue cycle staff, and hospital administration). On average, sites used 18 (range 11-22) implementation strategies, including assessing institutional readiness for, and barriers to, implementation of immediate postpartum LARC, engaging reproductive justice experts and community resources to address social determinants of health, involving patients in implementation planning, and developing quality monitoring processes to evaluate clinical processes and outcomes. The researchers found that successful implementation of immediate postpartum LARC required three essential conditions: effective implementation champions who are supported by a multidisciplinary implementation team; creating an enabling financial environment; and engaging hospital administration. Additional findings from this study call for more support for individuals leading change in complex care settings, intentionally designing implementation interventions that take into account local contextual influences, and meaningfully engaging patients in the implementation process.

Of postpartum women, 61% in low- and middle-income countries (LMIC) have an unmet contraceptive need and many face high rates of short interpregnancy intervals (Moore). Additionally, 51%-96% of postpartum women in LMIC use short-acting methods of contraception (Moore), further highlighting the need for increased access to immediate postpartum LARC in LMIC. Data on the use and continuation of immediate postpartum LARC in LMIC is limited. Marchin et al conducted a systematic review and meta-analysis to determine 6-month continuation rates of immediate postpartum LARCs among women in 69 low-income countries that were enrolled in the Family Planning 2020 initiative. The meta-analysis ultimately focused on the copper IUD due to the absence of relevant studies on other LARC methods. The meta-analysis of 12 studies resulted in a pooled 6-month continuation rate for immediate postpartum copper IUDs of 87%, a rate comparable to continuation rates found in higher-income countries. This estimate had significant heterogeneity between studies. Secondary outcomes of expulsion, removal, and infection rates were low at 6%, 5%, and 0.2% respectively. High 6-month continuation rates and a low rate of adverse outcomes suggest immediate postpartum copper IUD insertion represents a feasible and acceptable postpartum contraceptive option for women living in LMIC.

In cases where contraception methods fail, are used incorrectly, or are not used at all, emergency contraception (EC) can be used after intercourse to prevent pregnancy. Timely access to, and accurate knowledge of, EC are especially important for rural women who are more likely to experience an unintended pregnancy resulting in a live birth compared to urban women. Milkowski et al analyzed publicly available data from the National Survey of Family Growth to estimate differences in oral EC use, access, and counseling by rural-urban county of residence among U.S. women aged 15-44 years. 10% of rural and 19% of urban women who had ever been sexually active reported ever using EC pills. Over the course of the study period (2006-2017), the percentage of women reporting ever-use of EC increased linearly in both rural and urban populations, with the prevalence of EC ever-use more than doubling in each group. This observation likely reflects an overall increase in EC use during a time period in which the federal government enacted several policies to improve access to EC. The study findings also highlight the need for improved patient counseling on EC. While the overall prevalence of EC counseling was low among all women, rural women were less likely to have received counseling on EC when compared to urban women.

Although many studies report weight gain in users of progestin-only hormonal contraception (POC), a recent Cochrane systematic review found that there was insufficient evidence to determine the effect of POCs on weight (Lopez). Beksinska et al conducted a secondary analysis of prospective weight change among women enrolled in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial, which was an open label, prospective, randomized multicenter trial that compared the risk of HIV acquisition among women randomized to injectable contraception (DMPA), the copper IUD, or a second generation two rod levonorgestrel (LNG) implant Jadelle^Ò. This trial was conducted at 12 sites across four African countries between 2015 and 2018. Eligible study participants were nonpregnant, HIV negative, sexually active women aged 16-35 years who desired contraception. The final sample size included 7,014 women randomly assigned to receive DMPA (2,293), the LNG implant (2,372), or the copper IUD (2,349). Using a standardized protocol and calibrated equipment across all study sites, weight and height were measured at baseline and at study exit at 12, 15, or 18 months. The mean weight increased amongst all three contraceptive groups and was significantly different in magnitude, with the largest gain in the DMPA group (3.5 kg), 2.4 kg in the LNG implant group, and 1.5 kg in the copper IUD group. Unlike copper IUD users, women in the DMPA and LNG implant group continued to gain weight after 1 year of contraceptive use. It is noteworthy that, regardless of contraceptive method allocation, not all women gained weight and a small proportion of women lost weight. When choosing a contraceptive method, women using POCs should be counselled about the potential side effect of weight gain.

References:
Moniz MH, Bonawitz K, Wetmore MK, et al. Implementing immediate postpartum contraception: a comparative case study at 11 hospitals. Implement Sci Commun. 2021;2(1):42. Published 2021 Apr 12.

Moore Z, Pfitzer A, Gubin R, et al. Missed opportunities for family planning: an analysis of pregnancy risk and contraceptive method use among postpartum women in 21 low- and middle-income countries. Contraception 92 (2015): 31–39.
 

Marchin A, Moss A, Harrison M. A Meta-Analysis of Postpartum Copper IUD Continuation Rates in Low- and Middle-Income Countries. J Womens Health Dev. 2021;4(1):36-46.

Milkowski CM, Ziller EC, Ahrens KA. Rural-urban residence and emergency contraception use, access, and counseling in the United States, 2006-2017. Contracept X. 2021;3:100061.

Lopez L.M., Ramesh S., Chen M. Progestin-only contraceptives: effects on weight. Cochrane Database Syst Rev. 2016 doi: 10.1002/14651858.CD008815.pub2.

Beksinska et al. “Weight change among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Findings from a randomised, multicentre, open-label trial. EClinicalMedicine. 2021;34:100800.

Immediate postpartum long-acting reversible contraception (LARC) represents a safe and effective contraceptive strategy. Despite national guidelines recommending universal patient access, hospitals face significant barriers to offering inpatient LARCs. It is unclear why some hospitals successfully implement immediate postpartum LARCs, while others do not.

Moniz et al conducted a comparative, multiple case study of immediate postpartum LARC implementation at eleven “early adopter” U.S. hospitals and analyzed each hospital’s implementation strategy to produce generalizable knowledge about how and under what circumstances implementation of immediate postpartum LARCs unfold successfully. Between 2017-2018, the authors conducted single-day site visits and 78 semi-structured interviews with a variety of stakeholders (clinician champions, nurses, pharmacists, revenue cycle staff, and hospital administration). On average, sites used 18 (range 11-22) implementation strategies, including assessing institutional readiness for, and barriers to, implementation of immediate postpartum LARC, engaging reproductive justice experts and community resources to address social determinants of health, involving patients in implementation planning, and developing quality monitoring processes to evaluate clinical processes and outcomes. The researchers found that successful implementation of immediate postpartum LARC required three essential conditions: effective implementation champions who are supported by a multidisciplinary implementation team; creating an enabling financial environment; and engaging hospital administration. Additional findings from this study call for more support for individuals leading change in complex care settings, intentionally designing implementation interventions that take into account local contextual influences, and meaningfully engaging patients in the implementation process.

Of postpartum women, 61% in low- and middle-income countries (LMIC) have an unmet contraceptive need and many face high rates of short interpregnancy intervals (Moore). Additionally, 51%-96% of postpartum women in LMIC use short-acting methods of contraception (Moore), further highlighting the need for increased access to immediate postpartum LARC in LMIC. Data on the use and continuation of immediate postpartum LARC in LMIC is limited. Marchin et al conducted a systematic review and meta-analysis to determine 6-month continuation rates of immediate postpartum LARCs among women in 69 low-income countries that were enrolled in the Family Planning 2020 initiative. The meta-analysis ultimately focused on the copper IUD due to the absence of relevant studies on other LARC methods. The meta-analysis of 12 studies resulted in a pooled 6-month continuation rate for immediate postpartum copper IUDs of 87%, a rate comparable to continuation rates found in higher-income countries. This estimate had significant heterogeneity between studies. Secondary outcomes of expulsion, removal, and infection rates were low at 6%, 5%, and 0.2% respectively. High 6-month continuation rates and a low rate of adverse outcomes suggest immediate postpartum copper IUD insertion represents a feasible and acceptable postpartum contraceptive option for women living in LMIC.

In cases where contraception methods fail, are used incorrectly, or are not used at all, emergency contraception (EC) can be used after intercourse to prevent pregnancy. Timely access to, and accurate knowledge of, EC are especially important for rural women who are more likely to experience an unintended pregnancy resulting in a live birth compared to urban women. Milkowski et al analyzed publicly available data from the National Survey of Family Growth to estimate differences in oral EC use, access, and counseling by rural-urban county of residence among U.S. women aged 15-44 years. 10% of rural and 19% of urban women who had ever been sexually active reported ever using EC pills. Over the course of the study period (2006-2017), the percentage of women reporting ever-use of EC increased linearly in both rural and urban populations, with the prevalence of EC ever-use more than doubling in each group. This observation likely reflects an overall increase in EC use during a time period in which the federal government enacted several policies to improve access to EC. The study findings also highlight the need for improved patient counseling on EC. While the overall prevalence of EC counseling was low among all women, rural women were less likely to have received counseling on EC when compared to urban women.

Although many studies report weight gain in users of progestin-only hormonal contraception (POC), a recent Cochrane systematic review found that there was insufficient evidence to determine the effect of POCs on weight (Lopez). Beksinska et al conducted a secondary analysis of prospective weight change among women enrolled in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial, which was an open label, prospective, randomized multicenter trial that compared the risk of HIV acquisition among women randomized to injectable contraception (DMPA), the copper IUD, or a second generation two rod levonorgestrel (LNG) implant Jadelle^Ò. This trial was conducted at 12 sites across four African countries between 2015 and 2018. Eligible study participants were nonpregnant, HIV negative, sexually active women aged 16-35 years who desired contraception. The final sample size included 7,014 women randomly assigned to receive DMPA (2,293), the LNG implant (2,372), or the copper IUD (2,349). Using a standardized protocol and calibrated equipment across all study sites, weight and height were measured at baseline and at study exit at 12, 15, or 18 months. The mean weight increased amongst all three contraceptive groups and was significantly different in magnitude, with the largest gain in the DMPA group (3.5 kg), 2.4 kg in the LNG implant group, and 1.5 kg in the copper IUD group. Unlike copper IUD users, women in the DMPA and LNG implant group continued to gain weight after 1 year of contraceptive use. It is noteworthy that, regardless of contraceptive method allocation, not all women gained weight and a small proportion of women lost weight. When choosing a contraceptive method, women using POCs should be counselled about the potential side effect of weight gain.

References:
Moniz MH, Bonawitz K, Wetmore MK, et al. Implementing immediate postpartum contraception: a comparative case study at 11 hospitals. Implement Sci Commun. 2021;2(1):42. Published 2021 Apr 12.

Moore Z, Pfitzer A, Gubin R, et al. Missed opportunities for family planning: an analysis of pregnancy risk and contraceptive method use among postpartum women in 21 low- and middle-income countries. Contraception 92 (2015): 31–39.
 

Marchin A, Moss A, Harrison M. A Meta-Analysis of Postpartum Copper IUD Continuation Rates in Low- and Middle-Income Countries. J Womens Health Dev. 2021;4(1):36-46.

Milkowski CM, Ziller EC, Ahrens KA. Rural-urban residence and emergency contraception use, access, and counseling in the United States, 2006-2017. Contracept X. 2021;3:100061.

Lopez L.M., Ramesh S., Chen M. Progestin-only contraceptives: effects on weight. Cochrane Database Syst Rev. 2016 doi: 10.1002/14651858.CD008815.pub2.

Beksinska et al. “Weight change among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Findings from a randomised, multicentre, open-label trial. EClinicalMedicine. 2021;34:100800.

Attention-deficit/hyperactivity disorder and autism spectrum disorder (ASD) often coexist in children and adults, but the range of cognitive abilities can vary widely in these patients. Researchers from around the world are leveraging symptom, cognitive assessment, and neurobiological measures to gain insights on how individuals with ADHD/ASD approach and solve problems.

Several experts discussed the progress of their research during the session, “Overlap and differences of ADHD and autism – new findings of functional imaging and cognition studies” at the World Congress on ADHD – Virtual Event.

“The overlap of these two disorders is a critical issue for our field,” said Sarah Karalunas, PhD, assistant professor of clinical psychology at Purdue University, West Lafayette, Ind., who moderated the session. Clinicians are often asked to make differential diagnoses between these two disorders. Only recently has the DSM-5 allowed their codiagnosis. “There’s increasing recognition that there may be shared cognitive and physiological features that reflect their shared risk and account for the high levels of symptom overlap,” said Dr. Karalunas.
 

Shared cognitive markers

Under the DSM’s change, “it’s now recognized that an estimated 20%-60% of children with ASD have comorbidities with ADHD, and around 20%-40% of children with ADHD have ASD symptoms,” said Beth Johnson, PhD, a research fellow with the Turner Institute for Brain and Mental Health at Monash University, Melbourne.

The shared overlap on genetic traits and comorbidities such as intellectual disability, anxiety, depression, and oppositional defiant disorder, make it difficult for clinicians to predict clinical outcomes, noted Dr. Johnson.

“We’re now understanding that they’re likely to be multiple autisms and ADHDs, that these symptoms exist on a spectrum of severity or ability,” she said. Dr. Johnson discussed a data-driven subtyping approach based on neurocognitive and symptom profiles in children with ADHD. The aim was to better understand how symptoms are managed across ADHD, ASD and comorbid ASD-ADHD.

As part of this research, her team recruited 295 controls and 117 children with ADHD who underwent clinical phenotyping and also completed working memory tasks, stop signal, and sustained attention tasks.

The researchers divided the children into four stable clusters based on the ADHD rating scale and autism questionnaire data: high ASD/ADHD traits, high ADHD/low ASD, low ADHD/moderate ASD, and low ADHD/ASD. Approximately half of the children with ADHD showed moderate to high ASD symptoms. Looking at neurocognition across the tasks, unsurprisingly, performance was lowest among the high-ASD/ADHD children, with performance on the stop signal being the most pronounced. “Notably, performance on the working memory task worsened with increasing ADHD symptoms,” she reported.
 

Drift model identifies information processing

Dr. Karalunas has also compared subgroups of ADHD and ASD children. “Our analysis examined whether cognitive impairments in ASD reflect a shared risk mechanism or co-occurring ADHD symptoms and why we see an overlap in these types of impairments,” she said.

Her study included 509 children with ADHD, 97 with ASD, and 301 controls (typical development). All three groups underwent a full cognitive assessment battery that measured attention arousal, basic processing speed, and working memory. Those tasks were collapsed into a series of variables as well as a set of tasks measuring response inhibition, switching, interference control, reward discounting, and measure of reaction time variability.

Four cognitive profiles emerged: a typically developing group, an ADHD group, an ASD group with low levels of ADHD symptoms and an ASD group with high levels of ADHD symptoms.

The ADHD group did worse on many of the tasks than the control group, and the ASD group with low ADHD levels also did poorly relative to the typically developing sample. This shows that autism – even in absence of co-occurring ADHD – demonstrates more cognitive impairment than typically developing kids. The ADHD group with high levels of autism did the most poorly across all of the tasks.

The findings also revealed a symptom severity pattern: the group with fewer symptoms did the best and the group with the most symptoms did the worst. “Overall, this reflects severity of impairment,” said Dr. Karalunas.

To identify measures more specific to either ADHD or autism, Dr. Karalunas and colleagues did a follow-up analysis to characterize cognitive performance. To accomplish this, they applied a drift-diffusion model to the same four cognitive profiles. The model assessed three parameters: drift rate, which relates to the speed or efficiency of information processing, boundary separation or speed accuracy trade-offs (impulsivity), and nondecision time such as motor preparation.

Using the same four cognitive profiles, they found that the ADHD group had slower drift rate relative to the control, although the two groups did not differ on boundary separation, which meant there were no differences on waiting to need to respond. The ADHD group had faster nondecision times. “This is a classic pattern, shown in the literature,” said Dr. Karalunas.
 

In other results, an interesting pattern began to evolve

Both ASD groups, for example, had much wider boundary separations, which meant they were waiting to be sure before they responded than the ADHD or typically developing groups. In contrast, the two ADHD groups had much faster non-decision times, whereas the two non-ADHD groups had similar nondecisions times.

Unlike the previous analysis, which saw a symptom severity pattern develop, “we’re getting two parameters that seem to track much more specifically to specific symptom domains,” observed Dr. Karalunas.

The results suggest there’s a substantial overlap in cognitive impairments in ADHD/ASD. “But we have pretty strong evidence at this point that these similarities are not accounted for by symptom overlap, especially for things like response and inhibition, working memory and processing speed. These seem to be independently related to ADHD and autism, regardless of the level of comorbid ADHD symptoms in the autism group,” said Dr. Karalunas.

The hope is to expand on these types of analyses to address the interaction of cognition-emotion and social cognition, and empirically define groups based on cognitive performance, she said.
 

Neurocognitive studies

Researchers have also been studying neural networks to assess ASD and ADHD. Roselyne Chauvin, PhD, a postdoctoral associate at Washington University, St. Louis, discussed the concept of “a task generic connectome,” in which researchers look for a common network between targeted task paradigms to get closer to a common alteration across impairments.

In her research, Dr. Chauvin and colleagues looked at connectivity modulations across three tasks: working memory, reward processing tasks, and stop signal tasks, comparing ADHD patients to siblings and controls. The ADHD group showed reduced sensitivity or a smaller number of connections modulated in the tasks compared with the other groups. Researchers wondered where those missed connections were located.

Dividing the cohorts into task generic and task specific groups, Dr. Chauvin and colleagues found that the ADHD group lacked common processing skills. They were also able to identify reproducible missing circuits in the ADHD participants. Among the cohorts, there was a higher modulation of task-specific edges in the ADHD group.

The ADHD patients seemed to be using more task-tailored alternative strategies that were more challenging and suboptimal.

She also previewed her ongoing work with the EU-AIMS Longitudinal European Autism Project (LEAP) database to study ASD-ADHD comorbidity. In this project, she and her colleagues looked at several tasks: probing emotion processing, inhibitory control, theory of mind, and reward anticipation. Comparing ASD groups with or without ADHD comorbidity or a shared connection, she and her team were able to devise a functional profile predictive of ADHD severity. As an example, “for the connection only used by the ASD with ADHD comorbidity, the more they were using those connections of higher amplitude in the modulation, inside this subset of connection, the higher they would have ADHD severity,” said Dr. Chauvin.

Neural correlates of different behavioral and cognitive profiles haven’t been widely studied, according to Charlotte Tye, PhD, who’s based at the Institute of Psychiatry, Psychology & Neuroscience, King’s College, London. Electroencephalography is a useful technique for understanding the neural correlates of cognitive impairments and teasing apart different models of co-occurrence in ASD and ADHD. 

Dr. Tye and colleagues tested this approach in a cohort of boys aged 8-13 years diagnosed with ASD and/or ADHD, measuring EEG while the children did various continuous performance tasks to assess changes in brain activity. Examining P3 amplitude (event-related potential components) they found that children with ADHD or ADHD+ASD showed an attenuated amplitude of the P3, compared with typically developing children and those with ASD.

“This suggests children with an ADHD diagnosis exhibited reduced inhibitory control,” said Dr. Tye. In contrast, children with ASD showed reduced conflict monitoring as indexed by altered N2 amplitude across task conditions.

These, and other studies conducted by Dr. Tye and colleagues indicate that children with ADHD show reduced neural responses during attentional processing, whereas autistic children show typical neural responses, supporting specific profiles.

“Autistic children with a diagnosis of ADHD appear to show the unique patterns of neural responses of autism and ADHD, supporting an additive co-occurrence rather than a distinct condition. This contributes to identification of transdiagnostic subgroups within neurodevelopmental conditions for targeting of personalized intervention, and suggests that children with co-occurring autism and ADHD require support for both conditions,” said Dr. Tye.

An important takeaway from all of these findings is “we can’t look just at how someone does overall on a single test,” said Dr. Karalunas in an interview. “There is a tremendous amount of variability between people who have the same diagnosis, and our research really needs to account for this.”

Attention-deficit/hyperactivity disorder and autism spectrum disorder (ASD) often coexist in children and adults, but the range of cognitive abilities can vary widely in these patients. Researchers from around the world are leveraging symptom, cognitive assessment, and neurobiological measures to gain insights on how individuals with ADHD/ASD approach and solve problems.

Several experts discussed the progress of their research during the session, “Overlap and differences of ADHD and autism – new findings of functional imaging and cognition studies” at the World Congress on ADHD – Virtual Event.

“The overlap of these two disorders is a critical issue for our field,” said Sarah Karalunas, PhD, assistant professor of clinical psychology at Purdue University, West Lafayette, Ind., who moderated the session. Clinicians are often asked to make differential diagnoses between these two disorders. Only recently has the DSM-5 allowed their codiagnosis. “There’s increasing recognition that there may be shared cognitive and physiological features that reflect their shared risk and account for the high levels of symptom overlap,” said Dr. Karalunas.
 

Shared cognitive markers

Under the DSM’s change, “it’s now recognized that an estimated 20%-60% of children with ASD have comorbidities with ADHD, and around 20%-40% of children with ADHD have ASD symptoms,” said Beth Johnson, PhD, a research fellow with the Turner Institute for Brain and Mental Health at Monash University, Melbourne.

The shared overlap on genetic traits and comorbidities such as intellectual disability, anxiety, depression, and oppositional defiant disorder, make it difficult for clinicians to predict clinical outcomes, noted Dr. Johnson.

“We’re now understanding that they’re likely to be multiple autisms and ADHDs, that these symptoms exist on a spectrum of severity or ability,” she said. Dr. Johnson discussed a data-driven subtyping approach based on neurocognitive and symptom profiles in children with ADHD. The aim was to better understand how symptoms are managed across ADHD, ASD and comorbid ASD-ADHD.

As part of this research, her team recruited 295 controls and 117 children with ADHD who underwent clinical phenotyping and also completed working memory tasks, stop signal, and sustained attention tasks.

The researchers divided the children into four stable clusters based on the ADHD rating scale and autism questionnaire data: high ASD/ADHD traits, high ADHD/low ASD, low ADHD/moderate ASD, and low ADHD/ASD. Approximately half of the children with ADHD showed moderate to high ASD symptoms. Looking at neurocognition across the tasks, unsurprisingly, performance was lowest among the high-ASD/ADHD children, with performance on the stop signal being the most pronounced. “Notably, performance on the working memory task worsened with increasing ADHD symptoms,” she reported.
 

Drift model identifies information processing

Dr. Karalunas has also compared subgroups of ADHD and ASD children. “Our analysis examined whether cognitive impairments in ASD reflect a shared risk mechanism or co-occurring ADHD symptoms and why we see an overlap in these types of impairments,” she said.

Her study included 509 children with ADHD, 97 with ASD, and 301 controls (typical development). All three groups underwent a full cognitive assessment battery that measured attention arousal, basic processing speed, and working memory. Those tasks were collapsed into a series of variables as well as a set of tasks measuring response inhibition, switching, interference control, reward discounting, and measure of reaction time variability.

Four cognitive profiles emerged: a typically developing group, an ADHD group, an ASD group with low levels of ADHD symptoms and an ASD group with high levels of ADHD symptoms.

The ADHD group did worse on many of the tasks than the control group, and the ASD group with low ADHD levels also did poorly relative to the typically developing sample. This shows that autism – even in absence of co-occurring ADHD – demonstrates more cognitive impairment than typically developing kids. The ADHD group with high levels of autism did the most poorly across all of the tasks.

The findings also revealed a symptom severity pattern: the group with fewer symptoms did the best and the group with the most symptoms did the worst. “Overall, this reflects severity of impairment,” said Dr. Karalunas.

To identify measures more specific to either ADHD or autism, Dr. Karalunas and colleagues did a follow-up analysis to characterize cognitive performance. To accomplish this, they applied a drift-diffusion model to the same four cognitive profiles. The model assessed three parameters: drift rate, which relates to the speed or efficiency of information processing, boundary separation or speed accuracy trade-offs (impulsivity), and nondecision time such as motor preparation.

Using the same four cognitive profiles, they found that the ADHD group had slower drift rate relative to the control, although the two groups did not differ on boundary separation, which meant there were no differences on waiting to need to respond. The ADHD group had faster nondecision times. “This is a classic pattern, shown in the literature,” said Dr. Karalunas.
 

In other results, an interesting pattern began to evolve

Both ASD groups, for example, had much wider boundary separations, which meant they were waiting to be sure before they responded than the ADHD or typically developing groups. In contrast, the two ADHD groups had much faster non-decision times, whereas the two non-ADHD groups had similar nondecisions times.

Unlike the previous analysis, which saw a symptom severity pattern develop, “we’re getting two parameters that seem to track much more specifically to specific symptom domains,” observed Dr. Karalunas.

The results suggest there’s a substantial overlap in cognitive impairments in ADHD/ASD. “But we have pretty strong evidence at this point that these similarities are not accounted for by symptom overlap, especially for things like response and inhibition, working memory and processing speed. These seem to be independently related to ADHD and autism, regardless of the level of comorbid ADHD symptoms in the autism group,” said Dr. Karalunas.

The hope is to expand on these types of analyses to address the interaction of cognition-emotion and social cognition, and empirically define groups based on cognitive performance, she said.
 

Neurocognitive studies

Researchers have also been studying neural networks to assess ASD and ADHD. Roselyne Chauvin, PhD, a postdoctoral associate at Washington University, St. Louis, discussed the concept of “a task generic connectome,” in which researchers look for a common network between targeted task paradigms to get closer to a common alteration across impairments.

In her research, Dr. Chauvin and colleagues looked at connectivity modulations across three tasks: working memory, reward processing tasks, and stop signal tasks, comparing ADHD patients to siblings and controls. The ADHD group showed reduced sensitivity or a smaller number of connections modulated in the tasks compared with the other groups. Researchers wondered where those missed connections were located.

Dividing the cohorts into task generic and task specific groups, Dr. Chauvin and colleagues found that the ADHD group lacked common processing skills. They were also able to identify reproducible missing circuits in the ADHD participants. Among the cohorts, there was a higher modulation of task-specific edges in the ADHD group.

The ADHD patients seemed to be using more task-tailored alternative strategies that were more challenging and suboptimal.

She also previewed her ongoing work with the EU-AIMS Longitudinal European Autism Project (LEAP) database to study ASD-ADHD comorbidity. In this project, she and her colleagues looked at several tasks: probing emotion processing, inhibitory control, theory of mind, and reward anticipation. Comparing ASD groups with or without ADHD comorbidity or a shared connection, she and her team were able to devise a functional profile predictive of ADHD severity. As an example, “for the connection only used by the ASD with ADHD comorbidity, the more they were using those connections of higher amplitude in the modulation, inside this subset of connection, the higher they would have ADHD severity,” said Dr. Chauvin.

Neural correlates of different behavioral and cognitive profiles haven’t been widely studied, according to Charlotte Tye, PhD, who’s based at the Institute of Psychiatry, Psychology & Neuroscience, King’s College, London. Electroencephalography is a useful technique for understanding the neural correlates of cognitive impairments and teasing apart different models of co-occurrence in ASD and ADHD. 

Dr. Tye and colleagues tested this approach in a cohort of boys aged 8-13 years diagnosed with ASD and/or ADHD, measuring EEG while the children did various continuous performance tasks to assess changes in brain activity. Examining P3 amplitude (event-related potential components) they found that children with ADHD or ADHD+ASD showed an attenuated amplitude of the P3, compared with typically developing children and those with ASD.

“This suggests children with an ADHD diagnosis exhibited reduced inhibitory control,” said Dr. Tye. In contrast, children with ASD showed reduced conflict monitoring as indexed by altered N2 amplitude across task conditions.

These, and other studies conducted by Dr. Tye and colleagues indicate that children with ADHD show reduced neural responses during attentional processing, whereas autistic children show typical neural responses, supporting specific profiles.

“Autistic children with a diagnosis of ADHD appear to show the unique patterns of neural responses of autism and ADHD, supporting an additive co-occurrence rather than a distinct condition. This contributes to identification of transdiagnostic subgroups within neurodevelopmental conditions for targeting of personalized intervention, and suggests that children with co-occurring autism and ADHD require support for both conditions,” said Dr. Tye.

An important takeaway from all of these findings is “we can’t look just at how someone does overall on a single test,” said Dr. Karalunas in an interview. “There is a tremendous amount of variability between people who have the same diagnosis, and our research really needs to account for this.”

Attention-deficit/hyperactivity disorder and autism spectrum disorder (ASD) often coexist in children and adults, but the range of cognitive abilities can vary widely in these patients. Researchers from around the world are leveraging symptom, cognitive assessment, and neurobiological measures to gain insights on how individuals with ADHD/ASD approach and solve problems.

Several experts discussed the progress of their research during the session, “Overlap and differences of ADHD and autism – new findings of functional imaging and cognition studies” at the World Congress on ADHD – Virtual Event.

“The overlap of these two disorders is a critical issue for our field,” said Sarah Karalunas, PhD, assistant professor of clinical psychology at Purdue University, West Lafayette, Ind., who moderated the session. Clinicians are often asked to make differential diagnoses between these two disorders. Only recently has the DSM-5 allowed their codiagnosis. “There’s increasing recognition that there may be shared cognitive and physiological features that reflect their shared risk and account for the high levels of symptom overlap,” said Dr. Karalunas.
 

Shared cognitive markers

Under the DSM’s change, “it’s now recognized that an estimated 20%-60% of children with ASD have comorbidities with ADHD, and around 20%-40% of children with ADHD have ASD symptoms,” said Beth Johnson, PhD, a research fellow with the Turner Institute for Brain and Mental Health at Monash University, Melbourne.

The shared overlap on genetic traits and comorbidities such as intellectual disability, anxiety, depression, and oppositional defiant disorder, make it difficult for clinicians to predict clinical outcomes, noted Dr. Johnson.

“We’re now understanding that they’re likely to be multiple autisms and ADHDs, that these symptoms exist on a spectrum of severity or ability,” she said. Dr. Johnson discussed a data-driven subtyping approach based on neurocognitive and symptom profiles in children with ADHD. The aim was to better understand how symptoms are managed across ADHD, ASD and comorbid ASD-ADHD.

As part of this research, her team recruited 295 controls and 117 children with ADHD who underwent clinical phenotyping and also completed working memory tasks, stop signal, and sustained attention tasks.

The researchers divided the children into four stable clusters based on the ADHD rating scale and autism questionnaire data: high ASD/ADHD traits, high ADHD/low ASD, low ADHD/moderate ASD, and low ADHD/ASD. Approximately half of the children with ADHD showed moderate to high ASD symptoms. Looking at neurocognition across the tasks, unsurprisingly, performance was lowest among the high-ASD/ADHD children, with performance on the stop signal being the most pronounced. “Notably, performance on the working memory task worsened with increasing ADHD symptoms,” she reported.
 

Drift model identifies information processing

Dr. Karalunas has also compared subgroups of ADHD and ASD children. “Our analysis examined whether cognitive impairments in ASD reflect a shared risk mechanism or co-occurring ADHD symptoms and why we see an overlap in these types of impairments,” she said.

Her study included 509 children with ADHD, 97 with ASD, and 301 controls (typical development). All three groups underwent a full cognitive assessment battery that measured attention arousal, basic processing speed, and working memory. Those tasks were collapsed into a series of variables as well as a set of tasks measuring response inhibition, switching, interference control, reward discounting, and measure of reaction time variability.

Four cognitive profiles emerged: a typically developing group, an ADHD group, an ASD group with low levels of ADHD symptoms and an ASD group with high levels of ADHD symptoms.

The ADHD group did worse on many of the tasks than the control group, and the ASD group with low ADHD levels also did poorly relative to the typically developing sample. This shows that autism – even in absence of co-occurring ADHD – demonstrates more cognitive impairment than typically developing kids. The ADHD group with high levels of autism did the most poorly across all of the tasks.

The findings also revealed a symptom severity pattern: the group with fewer symptoms did the best and the group with the most symptoms did the worst. “Overall, this reflects severity of impairment,” said Dr. Karalunas.

To identify measures more specific to either ADHD or autism, Dr. Karalunas and colleagues did a follow-up analysis to characterize cognitive performance. To accomplish this, they applied a drift-diffusion model to the same four cognitive profiles. The model assessed three parameters: drift rate, which relates to the speed or efficiency of information processing, boundary separation or speed accuracy trade-offs (impulsivity), and nondecision time such as motor preparation.

Using the same four cognitive profiles, they found that the ADHD group had slower drift rate relative to the control, although the two groups did not differ on boundary separation, which meant there were no differences on waiting to need to respond. The ADHD group had faster nondecision times. “This is a classic pattern, shown in the literature,” said Dr. Karalunas.
 

In other results, an interesting pattern began to evolve

Both ASD groups, for example, had much wider boundary separations, which meant they were waiting to be sure before they responded than the ADHD or typically developing groups. In contrast, the two ADHD groups had much faster non-decision times, whereas the two non-ADHD groups had similar nondecisions times.

Unlike the previous analysis, which saw a symptom severity pattern develop, “we’re getting two parameters that seem to track much more specifically to specific symptom domains,” observed Dr. Karalunas.

The results suggest there’s a substantial overlap in cognitive impairments in ADHD/ASD. “But we have pretty strong evidence at this point that these similarities are not accounted for by symptom overlap, especially for things like response and inhibition, working memory and processing speed. These seem to be independently related to ADHD and autism, regardless of the level of comorbid ADHD symptoms in the autism group,” said Dr. Karalunas.

The hope is to expand on these types of analyses to address the interaction of cognition-emotion and social cognition, and empirically define groups based on cognitive performance, she said.
 

Neurocognitive studies

Researchers have also been studying neural networks to assess ASD and ADHD. Roselyne Chauvin, PhD, a postdoctoral associate at Washington University, St. Louis, discussed the concept of “a task generic connectome,” in which researchers look for a common network between targeted task paradigms to get closer to a common alteration across impairments.

In her research, Dr. Chauvin and colleagues looked at connectivity modulations across three tasks: working memory, reward processing tasks, and stop signal tasks, comparing ADHD patients to siblings and controls. The ADHD group showed reduced sensitivity or a smaller number of connections modulated in the tasks compared with the other groups. Researchers wondered where those missed connections were located.

Dividing the cohorts into task generic and task specific groups, Dr. Chauvin and colleagues found that the ADHD group lacked common processing skills. They were also able to identify reproducible missing circuits in the ADHD participants. Among the cohorts, there was a higher modulation of task-specific edges in the ADHD group.

The ADHD patients seemed to be using more task-tailored alternative strategies that were more challenging and suboptimal.

She also previewed her ongoing work with the EU-AIMS Longitudinal European Autism Project (LEAP) database to study ASD-ADHD comorbidity. In this project, she and her colleagues looked at several tasks: probing emotion processing, inhibitory control, theory of mind, and reward anticipation. Comparing ASD groups with or without ADHD comorbidity or a shared connection, she and her team were able to devise a functional profile predictive of ADHD severity. As an example, “for the connection only used by the ASD with ADHD comorbidity, the more they were using those connections of higher amplitude in the modulation, inside this subset of connection, the higher they would have ADHD severity,” said Dr. Chauvin.

Neural correlates of different behavioral and cognitive profiles haven’t been widely studied, according to Charlotte Tye, PhD, who’s based at the Institute of Psychiatry, Psychology & Neuroscience, King’s College, London. Electroencephalography is a useful technique for understanding the neural correlates of cognitive impairments and teasing apart different models of co-occurrence in ASD and ADHD. 

Dr. Tye and colleagues tested this approach in a cohort of boys aged 8-13 years diagnosed with ASD and/or ADHD, measuring EEG while the children did various continuous performance tasks to assess changes in brain activity. Examining P3 amplitude (event-related potential components) they found that children with ADHD or ADHD+ASD showed an attenuated amplitude of the P3, compared with typically developing children and those with ASD.

“This suggests children with an ADHD diagnosis exhibited reduced inhibitory control,” said Dr. Tye. In contrast, children with ASD showed reduced conflict monitoring as indexed by altered N2 amplitude across task conditions.

These, and other studies conducted by Dr. Tye and colleagues indicate that children with ADHD show reduced neural responses during attentional processing, whereas autistic children show typical neural responses, supporting specific profiles.

“Autistic children with a diagnosis of ADHD appear to show the unique patterns of neural responses of autism and ADHD, supporting an additive co-occurrence rather than a distinct condition. This contributes to identification of transdiagnostic subgroups within neurodevelopmental conditions for targeting of personalized intervention, and suggests that children with co-occurring autism and ADHD require support for both conditions,” said Dr. Tye.

An important takeaway from all of these findings is “we can’t look just at how someone does overall on a single test,” said Dr. Karalunas in an interview. “There is a tremendous amount of variability between people who have the same diagnosis, and our research really needs to account for this.”

While it’s possible that residual effects of SARS-CoV-2 could lead to an eruption of attention-deficit/hyperactivity disorder (ADHD) cases, a debate at the World Congress on ADHD – Virtual Event underscored the fact that this is still a hypothesis. The bottom line is there needs to be more data, said Luis Augusto Rohde, MD, PhD, cochair of the congress’ scientific program committee and moderator of the session, “Residual effects of the 2019 pandemic will mirror the 1918 pandemic: Will we have lots of new ADHD cases?”

Considering the current pattern of the pandemic, there is not enough evidence for this to be a concern, Dr. Rohde said in an interview.

James Swanson, PhD, professor of pediatrics at the University of California, Irvine, opined that biological co-effects of COVID-19 are likely to have selective effects in children that may produce symptoms representative of ADHD. Using the 1918 Spanish flu pandemic as a historical reference, he estimated that COVID-19 would produce 5 million individuals with new-onset symptoms related to ADHD. “If these cases meet DSM-5 or ICD-11 criteria, there will be lots of new ADHD cases,” he predicted.

David Coghill, MD, a professor of child adolescent mental health at the University of Melbourne, observed that the sums Dr. Swanson presented “are based on maxing out the potential rather than looking at the sums more realistically.”
 

Could the 1918 pandemic offer clues?

In a commentary, Dr. Swanson and Nora D. Volkow, MD, wrote about “lessons learned” from the 1918 pandemic, and how residual sequelae in that era led to a condition labeled hyperkinetic syndrome in children. “It may be worthwhile to consider the hypothesis that the COVID-19 pandemic may result in a novel etiologic subtype of ADHD that clinicians may recognize in patients in the future,” wrote the commentators. 

In survivors of the 1918 pandemic, brain inflammation or encephalitis sometimes emerged as residual sequelae, said Dr. Swanson. In some adult cases, these symptoms were diagnosed as “encephalitis lethargica” (EL) and were associated with Parkinson’s disease. In 1930, based on patients evaluated after 1918, researchers Franz Kramer and Hans Pollnow at Charité Hospital in Berlin described the behavioral manifestation of EL in children as hyperkinetic syndrome, a condition that was characterized by symptoms similar to the properties of ADHD: lack of concentration, insufficient goal orientation, and increased distractibility. “They even reported on autopsy cases that described brain regions that we now know are associated with ADHD from decades of brain imaging studies,” said Dr. Swanson.

COVID-19 rarely results in severe respiratory problems in children but the absolute number requiring hospitalization has accumulated and is now relatively large, said Dr. Swanson. One study of 1,695 severe COVID-19 cases in children and adolescents used MRI and detected neural effects in specific brain regions such as basal ganglia and frontal lobes that previous research had associated with ADHD. Approximately 22% of these rare but severe cases had documented neurologic involvement, and studies of affected children with mild or none of the initial respiratory symptoms of COVID-19 also detected similar selective effects in these brain regions.

A recent survey of medical records of 80 million people that identified 240,000 COVID cases (mostly adults) revealed that a third had neurological and psychiatric sequelae. Dr. Swanson also mentioned an article he wrote more than a decade ago on environmental as well as genetic factors that resulted in etiologic subtypes of ADHD, which provided a model for the impact of COVID-19 on specific brain regions that are associated with ADHD.

So far, the COVID-19 pandemic has produced 150 million cases worldwide and there are about 100 million survivors, setting an estimate of a maximum number of cases with residual sequelae. “I think that severe COVID-19 will probably be related to severe residual sequelae, and that mild or asymptomatic COVID-19 may be associated with less severe residual sequelae, which may resemble ADHD” said Dr. Swanson. If one-third of the cases manifest in some neurologic or psychiatric systems, this means 27 million would have residual sequelae. If 20% have impaired concentration or brain fog, this could result in about 5 million ADHD cases, he said. 
 

Estimates aren’t evidence

The Swanson/Volkow commentary contains a lot of references to “might, could, and may,” said Dr. Coghill. While it’s true that COVID-19 could produce a novel etiologic subtype of ADHD, “the point here is at the moment, all of this is based on hypotheses,” he said.

The Spanish flu did produce mental health consequences – survivors reported depression, sleep disturbances, mental distraction, dizziness, and difficulties coping at work. In the United States, flu death rates from 1918 to 1920 were directly attributed to suicide rates. Unfortunately, these impacts weren’t widely researched, said Dr. Coghill.

It also seems clear that the 1918 Spanish flu outbreak was associated with significant neurological consequences, said Dr. Coghill. By 1919 and 1920, physicians and researchers in the United Kingdom were reporting increases in a variety of symptoms among some patients recovering from flu, such as neuropathy, neurasthenia, meningitis, degenerative changes in nerve cells, and a decline in visual acuity.

The EL cases Dr. Swanson mentioned did coincide with and reach epidemic proportions alongside the Spanish flu. “But still, a causal relationship is far from proven,” said Dr. Coghill.

Sol Levy, MD, described a “disease of criminals” following the 1918 pandemic, in which patients exhibited a high degree of general hyperkinesis, a difficulty in maintaining quiet attitudes, abruptness and clumsiness, and “explosive motor release of all voluntarily inhibited activities.”

However, these impairments suggest a much broader presentation typically seen in ADHD, noted Dr. Coghill.

Neurological complications occur more commonly than initially thought in severe COVID-19, with estimates ranging from 36% to 84%. But in a systematic review of neuropsychiatric complications of severe coronavirus infection, researchers found few psychiatric sequelae of these infections. While they did mention impaired concentration and difficulties with emotional ability, it’s very important to remember that these conditions “are cardinal symptoms of a wide range of psychiatric disorders,” said Dr. Coghill.

Overall, more neurological and neuropsychiatric symptoms largely confine to those with severe COVID-19, meaning they’re much less likely to occur in children and young adults, he said.

If there are severe effects of COVID-19, Dr. Swanson countered that “they might have more ADHD than the complex residual effects [Dr. Coghill] described. I hope that he’s right, but I do think there will be biological co-effects of COVID-19 that will produce symptoms that are more ADHD than other neurological disorders.”
 

Epigenetic effects

Researchers are now seeing transgenerational and intergenerational effects of potential infection. “So I certainly back high-quality studies looking at the effects of maternal and paternal infection on offspring,” said Dr. Coghill. Establishing clinical cohort studies to follow up on this population would be essential in understanding the risks of SARS-CoV-2. “That might be one way we’ll see an increase in ADHD,” said Dr. Coghill.

The reality is COVID-19 hasn’t been around for that long, and current knowledge about it is limited, he said. Rapid publications, cross-sectional or retrospective data, and poor methodological quality and rigor make generalizability difficult. In addition, limited testing and detection probably underestimate prevalence of neurological and neuropsychiatric complications.

“If history teaches us anything, it is that we should always be measured in how we glean lessons from the past. So let’s not get ahead of ourselves,” he cautioned.

An informal, post-discussion survey of session participants revealed that a slight majority – 55%-60% – expected residual effects of COVID-19 to lead to more ADHD, compared to 40%-45% who didn’t think this would happen.

Dr. Swanson has two patents: (PIXA4), which uses a “time-of-flight” camera to measure growth on infants, and a provisional patent on the mechanism of tolerance to stimulant medication (PATSMTA). Dr. Coghill worked for several pharmaceutical companies but had no disclosures relevant to this debate.

While it’s possible that residual effects of SARS-CoV-2 could lead to an eruption of attention-deficit/hyperactivity disorder (ADHD) cases, a debate at the World Congress on ADHD – Virtual Event underscored the fact that this is still a hypothesis. The bottom line is there needs to be more data, said Luis Augusto Rohde, MD, PhD, cochair of the congress’ scientific program committee and moderator of the session, “Residual effects of the 2019 pandemic will mirror the 1918 pandemic: Will we have lots of new ADHD cases?”

Considering the current pattern of the pandemic, there is not enough evidence for this to be a concern, Dr. Rohde said in an interview.

James Swanson, PhD, professor of pediatrics at the University of California, Irvine, opined that biological co-effects of COVID-19 are likely to have selective effects in children that may produce symptoms representative of ADHD. Using the 1918 Spanish flu pandemic as a historical reference, he estimated that COVID-19 would produce 5 million individuals with new-onset symptoms related to ADHD. “If these cases meet DSM-5 or ICD-11 criteria, there will be lots of new ADHD cases,” he predicted.

David Coghill, MD, a professor of child adolescent mental health at the University of Melbourne, observed that the sums Dr. Swanson presented “are based on maxing out the potential rather than looking at the sums more realistically.”
 

Could the 1918 pandemic offer clues?

In a commentary, Dr. Swanson and Nora D. Volkow, MD, wrote about “lessons learned” from the 1918 pandemic, and how residual sequelae in that era led to a condition labeled hyperkinetic syndrome in children. “It may be worthwhile to consider the hypothesis that the COVID-19 pandemic may result in a novel etiologic subtype of ADHD that clinicians may recognize in patients in the future,” wrote the commentators. 

In survivors of the 1918 pandemic, brain inflammation or encephalitis sometimes emerged as residual sequelae, said Dr. Swanson. In some adult cases, these symptoms were diagnosed as “encephalitis lethargica” (EL) and were associated with Parkinson’s disease. In 1930, based on patients evaluated after 1918, researchers Franz Kramer and Hans Pollnow at Charité Hospital in Berlin described the behavioral manifestation of EL in children as hyperkinetic syndrome, a condition that was characterized by symptoms similar to the properties of ADHD: lack of concentration, insufficient goal orientation, and increased distractibility. “They even reported on autopsy cases that described brain regions that we now know are associated with ADHD from decades of brain imaging studies,” said Dr. Swanson.

COVID-19 rarely results in severe respiratory problems in children but the absolute number requiring hospitalization has accumulated and is now relatively large, said Dr. Swanson. One study of 1,695 severe COVID-19 cases in children and adolescents used MRI and detected neural effects in specific brain regions such as basal ganglia and frontal lobes that previous research had associated with ADHD. Approximately 22% of these rare but severe cases had documented neurologic involvement, and studies of affected children with mild or none of the initial respiratory symptoms of COVID-19 also detected similar selective effects in these brain regions.

A recent survey of medical records of 80 million people that identified 240,000 COVID cases (mostly adults) revealed that a third had neurological and psychiatric sequelae. Dr. Swanson also mentioned an article he wrote more than a decade ago on environmental as well as genetic factors that resulted in etiologic subtypes of ADHD, which provided a model for the impact of COVID-19 on specific brain regions that are associated with ADHD.

So far, the COVID-19 pandemic has produced 150 million cases worldwide and there are about 100 million survivors, setting an estimate of a maximum number of cases with residual sequelae. “I think that severe COVID-19 will probably be related to severe residual sequelae, and that mild or asymptomatic COVID-19 may be associated with less severe residual sequelae, which may resemble ADHD” said Dr. Swanson. If one-third of the cases manifest in some neurologic or psychiatric systems, this means 27 million would have residual sequelae. If 20% have impaired concentration or brain fog, this could result in about 5 million ADHD cases, he said. 
 

Estimates aren’t evidence

The Swanson/Volkow commentary contains a lot of references to “might, could, and may,” said Dr. Coghill. While it’s true that COVID-19 could produce a novel etiologic subtype of ADHD, “the point here is at the moment, all of this is based on hypotheses,” he said.

The Spanish flu did produce mental health consequences – survivors reported depression, sleep disturbances, mental distraction, dizziness, and difficulties coping at work. In the United States, flu death rates from 1918 to 1920 were directly attributed to suicide rates. Unfortunately, these impacts weren’t widely researched, said Dr. Coghill.

It also seems clear that the 1918 Spanish flu outbreak was associated with significant neurological consequences, said Dr. Coghill. By 1919 and 1920, physicians and researchers in the United Kingdom were reporting increases in a variety of symptoms among some patients recovering from flu, such as neuropathy, neurasthenia, meningitis, degenerative changes in nerve cells, and a decline in visual acuity.

The EL cases Dr. Swanson mentioned did coincide with and reach epidemic proportions alongside the Spanish flu. “But still, a causal relationship is far from proven,” said Dr. Coghill.

Sol Levy, MD, described a “disease of criminals” following the 1918 pandemic, in which patients exhibited a high degree of general hyperkinesis, a difficulty in maintaining quiet attitudes, abruptness and clumsiness, and “explosive motor release of all voluntarily inhibited activities.”

However, these impairments suggest a much broader presentation typically seen in ADHD, noted Dr. Coghill.

Neurological complications occur more commonly than initially thought in severe COVID-19, with estimates ranging from 36% to 84%. But in a systematic review of neuropsychiatric complications of severe coronavirus infection, researchers found few psychiatric sequelae of these infections. While they did mention impaired concentration and difficulties with emotional ability, it’s very important to remember that these conditions “are cardinal symptoms of a wide range of psychiatric disorders,” said Dr. Coghill.

Overall, more neurological and neuropsychiatric symptoms largely confine to those with severe COVID-19, meaning they’re much less likely to occur in children and young adults, he said.

If there are severe effects of COVID-19, Dr. Swanson countered that “they might have more ADHD than the complex residual effects [Dr. Coghill] described. I hope that he’s right, but I do think there will be biological co-effects of COVID-19 that will produce symptoms that are more ADHD than other neurological disorders.”
 

Epigenetic effects

Researchers are now seeing transgenerational and intergenerational effects of potential infection. “So I certainly back high-quality studies looking at the effects of maternal and paternal infection on offspring,” said Dr. Coghill. Establishing clinical cohort studies to follow up on this population would be essential in understanding the risks of SARS-CoV-2. “That might be one way we’ll see an increase in ADHD,” said Dr. Coghill.

The reality is COVID-19 hasn’t been around for that long, and current knowledge about it is limited, he said. Rapid publications, cross-sectional or retrospective data, and poor methodological quality and rigor make generalizability difficult. In addition, limited testing and detection probably underestimate prevalence of neurological and neuropsychiatric complications.

“If history teaches us anything, it is that we should always be measured in how we glean lessons from the past. So let’s not get ahead of ourselves,” he cautioned.

An informal, post-discussion survey of session participants revealed that a slight majority – 55%-60% – expected residual effects of COVID-19 to lead to more ADHD, compared to 40%-45% who didn’t think this would happen.

Dr. Swanson has two patents: (PIXA4), which uses a “time-of-flight” camera to measure growth on infants, and a provisional patent on the mechanism of tolerance to stimulant medication (PATSMTA). Dr. Coghill worked for several pharmaceutical companies but had no disclosures relevant to this debate.

While it’s possible that residual effects of SARS-CoV-2 could lead to an eruption of attention-deficit/hyperactivity disorder (ADHD) cases, a debate at the World Congress on ADHD – Virtual Event underscored the fact that this is still a hypothesis. The bottom line is there needs to be more data, said Luis Augusto Rohde, MD, PhD, cochair of the congress’ scientific program committee and moderator of the session, “Residual effects of the 2019 pandemic will mirror the 1918 pandemic: Will we have lots of new ADHD cases?”

Considering the current pattern of the pandemic, there is not enough evidence for this to be a concern, Dr. Rohde said in an interview.

James Swanson, PhD, professor of pediatrics at the University of California, Irvine, opined that biological co-effects of COVID-19 are likely to have selective effects in children that may produce symptoms representative of ADHD. Using the 1918 Spanish flu pandemic as a historical reference, he estimated that COVID-19 would produce 5 million individuals with new-onset symptoms related to ADHD. “If these cases meet DSM-5 or ICD-11 criteria, there will be lots of new ADHD cases,” he predicted.

David Coghill, MD, a professor of child adolescent mental health at the University of Melbourne, observed that the sums Dr. Swanson presented “are based on maxing out the potential rather than looking at the sums more realistically.”
 

Could the 1918 pandemic offer clues?

In a commentary, Dr. Swanson and Nora D. Volkow, MD, wrote about “lessons learned” from the 1918 pandemic, and how residual sequelae in that era led to a condition labeled hyperkinetic syndrome in children. “It may be worthwhile to consider the hypothesis that the COVID-19 pandemic may result in a novel etiologic subtype of ADHD that clinicians may recognize in patients in the future,” wrote the commentators. 

In survivors of the 1918 pandemic, brain inflammation or encephalitis sometimes emerged as residual sequelae, said Dr. Swanson. In some adult cases, these symptoms were diagnosed as “encephalitis lethargica” (EL) and were associated with Parkinson’s disease. In 1930, based on patients evaluated after 1918, researchers Franz Kramer and Hans Pollnow at Charité Hospital in Berlin described the behavioral manifestation of EL in children as hyperkinetic syndrome, a condition that was characterized by symptoms similar to the properties of ADHD: lack of concentration, insufficient goal orientation, and increased distractibility. “They even reported on autopsy cases that described brain regions that we now know are associated with ADHD from decades of brain imaging studies,” said Dr. Swanson.

COVID-19 rarely results in severe respiratory problems in children but the absolute number requiring hospitalization has accumulated and is now relatively large, said Dr. Swanson. One study of 1,695 severe COVID-19 cases in children and adolescents used MRI and detected neural effects in specific brain regions such as basal ganglia and frontal lobes that previous research had associated with ADHD. Approximately 22% of these rare but severe cases had documented neurologic involvement, and studies of affected children with mild or none of the initial respiratory symptoms of COVID-19 also detected similar selective effects in these brain regions.

A recent survey of medical records of 80 million people that identified 240,000 COVID cases (mostly adults) revealed that a third had neurological and psychiatric sequelae. Dr. Swanson also mentioned an article he wrote more than a decade ago on environmental as well as genetic factors that resulted in etiologic subtypes of ADHD, which provided a model for the impact of COVID-19 on specific brain regions that are associated with ADHD.

So far, the COVID-19 pandemic has produced 150 million cases worldwide and there are about 100 million survivors, setting an estimate of a maximum number of cases with residual sequelae. “I think that severe COVID-19 will probably be related to severe residual sequelae, and that mild or asymptomatic COVID-19 may be associated with less severe residual sequelae, which may resemble ADHD” said Dr. Swanson. If one-third of the cases manifest in some neurologic or psychiatric systems, this means 27 million would have residual sequelae. If 20% have impaired concentration or brain fog, this could result in about 5 million ADHD cases, he said. 
 

Estimates aren’t evidence

The Swanson/Volkow commentary contains a lot of references to “might, could, and may,” said Dr. Coghill. While it’s true that COVID-19 could produce a novel etiologic subtype of ADHD, “the point here is at the moment, all of this is based on hypotheses,” he said.

The Spanish flu did produce mental health consequences – survivors reported depression, sleep disturbances, mental distraction, dizziness, and difficulties coping at work. In the United States, flu death rates from 1918 to 1920 were directly attributed to suicide rates. Unfortunately, these impacts weren’t widely researched, said Dr. Coghill.

It also seems clear that the 1918 Spanish flu outbreak was associated with significant neurological consequences, said Dr. Coghill. By 1919 and 1920, physicians and researchers in the United Kingdom were reporting increases in a variety of symptoms among some patients recovering from flu, such as neuropathy, neurasthenia, meningitis, degenerative changes in nerve cells, and a decline in visual acuity.

The EL cases Dr. Swanson mentioned did coincide with and reach epidemic proportions alongside the Spanish flu. “But still, a causal relationship is far from proven,” said Dr. Coghill.

Sol Levy, MD, described a “disease of criminals” following the 1918 pandemic, in which patients exhibited a high degree of general hyperkinesis, a difficulty in maintaining quiet attitudes, abruptness and clumsiness, and “explosive motor release of all voluntarily inhibited activities.”

However, these impairments suggest a much broader presentation typically seen in ADHD, noted Dr. Coghill.

Neurological complications occur more commonly than initially thought in severe COVID-19, with estimates ranging from 36% to 84%. But in a systematic review of neuropsychiatric complications of severe coronavirus infection, researchers found few psychiatric sequelae of these infections. While they did mention impaired concentration and difficulties with emotional ability, it’s very important to remember that these conditions “are cardinal symptoms of a wide range of psychiatric disorders,” said Dr. Coghill.

Overall, more neurological and neuropsychiatric symptoms largely confine to those with severe COVID-19, meaning they’re much less likely to occur in children and young adults, he said.

If there are severe effects of COVID-19, Dr. Swanson countered that “they might have more ADHD than the complex residual effects [Dr. Coghill] described. I hope that he’s right, but I do think there will be biological co-effects of COVID-19 that will produce symptoms that are more ADHD than other neurological disorders.”
 

Epigenetic effects

Researchers are now seeing transgenerational and intergenerational effects of potential infection. “So I certainly back high-quality studies looking at the effects of maternal and paternal infection on offspring,” said Dr. Coghill. Establishing clinical cohort studies to follow up on this population would be essential in understanding the risks of SARS-CoV-2. “That might be one way we’ll see an increase in ADHD,” said Dr. Coghill.

The reality is COVID-19 hasn’t been around for that long, and current knowledge about it is limited, he said. Rapid publications, cross-sectional or retrospective data, and poor methodological quality and rigor make generalizability difficult. In addition, limited testing and detection probably underestimate prevalence of neurological and neuropsychiatric complications.

“If history teaches us anything, it is that we should always be measured in how we glean lessons from the past. So let’s not get ahead of ourselves,” he cautioned.

An informal, post-discussion survey of session participants revealed that a slight majority – 55%-60% – expected residual effects of COVID-19 to lead to more ADHD, compared to 40%-45% who didn’t think this would happen.

Dr. Swanson has two patents: (PIXA4), which uses a “time-of-flight” camera to measure growth on infants, and a provisional patent on the mechanism of tolerance to stimulant medication (PATSMTA). Dr. Coghill worked for several pharmaceutical companies but had no disclosures relevant to this debate.

An examination of coffee consumption habits of almost 400,000 people suggests that those habits are largely driven by a person’s cardiovascular health.

©Elena Moiseeva/fotolia.com

Data from a large population database showed that people with essential hypertension, angina, or cardiac arrhythmias drank less coffee than people who had none of these conditions. When they did drink coffee, it tended to be decaffeinated.

The investigators, led by Elina Hyppönen, PhD, director of the Australian Centre for Precision Health at the University of South Australia, Adelaide, say that this predilection for avoiding coffee, which is known to produce jitteriness and heart palpitations, is based on genetics.

“If your body is telling you not to drink that extra cup of coffee, there’s likely a reason why,” Dr. Hyppönen said in an interview.

The study was published online in the American Journal of Clinical Nutrition.

“People drink coffee as a pick-me-up when they’re feeling tired, or because it tastes good, or simply because it’s part of their daily routine, but what we don’t recognize is that people subconsciously self-regulate safe levels of caffeine based on how high their blood pressure is, and this is likely a result of a protective genetic mechanism, [meaning] that someone who drinks a lot of coffee is likely more genetically tolerant of caffeine, as compared to someone who drinks very little,” Dr. Hyppönen said.

“In addition, we’ve known from past research that when people feel unwell, they tend to drink less coffee. This type of phenomenon, where disease drives behavior, is called reverse causality,” Dr. Hyppönen said.

For this analysis, she and her team used information on 390,435 individuals of European ancestry from the UK Biobank, a large epidemiologic database. Habitual coffee consumption was self-reported, and systolic and diastolic blood pressure and heart rate were measured at baseline. Cardiovascular symptoms at baseline were gleaned from hospital diagnoses, primary care records, and/or self report, the authors note.

To look at the relationship of systolic BP, diastolic BP, and heart rate with coffee consumption, they used a strategy called Mendelian randomization, which allows genetic information such as variants reflecting higher blood pressures and heart rate to be used to provide evidence for a causal association.

Results showed that participants with essential hypertension, angina, or arrhythmia were “all more likely to drink less caffeinated coffee and to be nonhabitual or decaffeinated coffee drinkers compared with those who did not report related symptoms,” the authors write.

Those with higher systolic and diastolic BP based on their genetics tended to drink less caffeinated coffee at baseline, “with consistent genetic evidence to support a causal explanation across all methods,” they noted.

They also found that those people who have a higher resting heart rate due to their genes were more likely to choose decaffeinated coffee.

“These results have two major implications,” Dr. Hyppönen said. “Firstly, they show that our bodies can regulate behavior in ways that we may not realize, and that if something does not feel good to us, there is a likely to be a reason why.”

“Second, our results show that our health status in part regulates the amount of coffee we drink. This is important, because when disease drives behavior, it can lead to misleading health associations in observational studies, and indeed, create a false impression for health benefits if the group of people who do not drink coffee also includes more people who are unwell,” she said.

For now, doctors can tell their patients that this study provides an explanation as to why research on the health effects of habitual coffee consumption has been conflicting, Dr. Hyppönen said.

“Our study also highlights the uncertainty that underlies the claimed health benefits of coffee, but at the same time, it gives a positive message about the ability of our body to regulate our level of coffee consumption in a way that helps us avoid adverse effects.”

“The most common symptoms of excessive coffee consumption are palpitations and rapid heartbeat, also known as tachycardia,” Nieca Goldberg, MD, medical director of the NYU Women’s Heart Program at NYU Langone Health, said in an interview.

“This study was designed to see if cardiac symptoms affect coffee consumption, and it showed that people with hypertension, angina, history of arrhythmias, and poor health tend to be decaffeinated coffee drinkers or no coffee drinkers,” Dr. Goldberg said.

“People naturally alter their coffee intake base on their blood pressure and symptoms of palpitations and/or rapid heart rate,” she said.

The results also suggest that, “we cannot infer health benefit or harm based on the available coffee studies,” Dr. Goldberg added.

The study was funded by the National Health and Medical Research Council, Australia. Dr. Hyppönen and Dr. Goldberg have disclosed no relevant financial relationships.

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

An examination of coffee consumption habits of almost 400,000 people suggests that those habits are largely driven by a person’s cardiovascular health.

©Elena Moiseeva/fotolia.com

Data from a large population database showed that people with essential hypertension, angina, or cardiac arrhythmias drank less coffee than people who had none of these conditions. When they did drink coffee, it tended to be decaffeinated.

The investigators, led by Elina Hyppönen, PhD, director of the Australian Centre for Precision Health at the University of South Australia, Adelaide, say that this predilection for avoiding coffee, which is known to produce jitteriness and heart palpitations, is based on genetics.

“If your body is telling you not to drink that extra cup of coffee, there’s likely a reason why,” Dr. Hyppönen said in an interview.

The study was published online in the American Journal of Clinical Nutrition.

“People drink coffee as a pick-me-up when they’re feeling tired, or because it tastes good, or simply because it’s part of their daily routine, but what we don’t recognize is that people subconsciously self-regulate safe levels of caffeine based on how high their blood pressure is, and this is likely a result of a protective genetic mechanism, [meaning] that someone who drinks a lot of coffee is likely more genetically tolerant of caffeine, as compared to someone who drinks very little,” Dr. Hyppönen said.

“In addition, we’ve known from past research that when people feel unwell, they tend to drink less coffee. This type of phenomenon, where disease drives behavior, is called reverse causality,” Dr. Hyppönen said.

For this analysis, she and her team used information on 390,435 individuals of European ancestry from the UK Biobank, a large epidemiologic database. Habitual coffee consumption was self-reported, and systolic and diastolic blood pressure and heart rate were measured at baseline. Cardiovascular symptoms at baseline were gleaned from hospital diagnoses, primary care records, and/or self report, the authors note.

To look at the relationship of systolic BP, diastolic BP, and heart rate with coffee consumption, they used a strategy called Mendelian randomization, which allows genetic information such as variants reflecting higher blood pressures and heart rate to be used to provide evidence for a causal association.

Results showed that participants with essential hypertension, angina, or arrhythmia were “all more likely to drink less caffeinated coffee and to be nonhabitual or decaffeinated coffee drinkers compared with those who did not report related symptoms,” the authors write.

Those with higher systolic and diastolic BP based on their genetics tended to drink less caffeinated coffee at baseline, “with consistent genetic evidence to support a causal explanation across all methods,” they noted.

They also found that those people who have a higher resting heart rate due to their genes were more likely to choose decaffeinated coffee.

“These results have two major implications,” Dr. Hyppönen said. “Firstly, they show that our bodies can regulate behavior in ways that we may not realize, and that if something does not feel good to us, there is a likely to be a reason why.”

“Second, our results show that our health status in part regulates the amount of coffee we drink. This is important, because when disease drives behavior, it can lead to misleading health associations in observational studies, and indeed, create a false impression for health benefits if the group of people who do not drink coffee also includes more people who are unwell,” she said.

For now, doctors can tell their patients that this study provides an explanation as to why research on the health effects of habitual coffee consumption has been conflicting, Dr. Hyppönen said.

“Our study also highlights the uncertainty that underlies the claimed health benefits of coffee, but at the same time, it gives a positive message about the ability of our body to regulate our level of coffee consumption in a way that helps us avoid adverse effects.”

“The most common symptoms of excessive coffee consumption are palpitations and rapid heartbeat, also known as tachycardia,” Nieca Goldberg, MD, medical director of the NYU Women’s Heart Program at NYU Langone Health, said in an interview.

“This study was designed to see if cardiac symptoms affect coffee consumption, and it showed that people with hypertension, angina, history of arrhythmias, and poor health tend to be decaffeinated coffee drinkers or no coffee drinkers,” Dr. Goldberg said.

“People naturally alter their coffee intake base on their blood pressure and symptoms of palpitations and/or rapid heart rate,” she said.

The results also suggest that, “we cannot infer health benefit or harm based on the available coffee studies,” Dr. Goldberg added.

The study was funded by the National Health and Medical Research Council, Australia. Dr. Hyppönen and Dr. Goldberg have disclosed no relevant financial relationships.

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

An examination of coffee consumption habits of almost 400,000 people suggests that those habits are largely driven by a person’s cardiovascular health.

©Elena Moiseeva/fotolia.com

Data from a large population database showed that people with essential hypertension, angina, or cardiac arrhythmias drank less coffee than people who had none of these conditions. When they did drink coffee, it tended to be decaffeinated.

The investigators, led by Elina Hyppönen, PhD, director of the Australian Centre for Precision Health at the University of South Australia, Adelaide, say that this predilection for avoiding coffee, which is known to produce jitteriness and heart palpitations, is based on genetics.

“If your body is telling you not to drink that extra cup of coffee, there’s likely a reason why,” Dr. Hyppönen said in an interview.

The study was published online in the American Journal of Clinical Nutrition.

“People drink coffee as a pick-me-up when they’re feeling tired, or because it tastes good, or simply because it’s part of their daily routine, but what we don’t recognize is that people subconsciously self-regulate safe levels of caffeine based on how high their blood pressure is, and this is likely a result of a protective genetic mechanism, [meaning] that someone who drinks a lot of coffee is likely more genetically tolerant of caffeine, as compared to someone who drinks very little,” Dr. Hyppönen said.

“In addition, we’ve known from past research that when people feel unwell, they tend to drink less coffee. This type of phenomenon, where disease drives behavior, is called reverse causality,” Dr. Hyppönen said.

For this analysis, she and her team used information on 390,435 individuals of European ancestry from the UK Biobank, a large epidemiologic database. Habitual coffee consumption was self-reported, and systolic and diastolic blood pressure and heart rate were measured at baseline. Cardiovascular symptoms at baseline were gleaned from hospital diagnoses, primary care records, and/or self report, the authors note.

To look at the relationship of systolic BP, diastolic BP, and heart rate with coffee consumption, they used a strategy called Mendelian randomization, which allows genetic information such as variants reflecting higher blood pressures and heart rate to be used to provide evidence for a causal association.

Results showed that participants with essential hypertension, angina, or arrhythmia were “all more likely to drink less caffeinated coffee and to be nonhabitual or decaffeinated coffee drinkers compared with those who did not report related symptoms,” the authors write.

Those with higher systolic and diastolic BP based on their genetics tended to drink less caffeinated coffee at baseline, “with consistent genetic evidence to support a causal explanation across all methods,” they noted.

They also found that those people who have a higher resting heart rate due to their genes were more likely to choose decaffeinated coffee.

“These results have two major implications,” Dr. Hyppönen said. “Firstly, they show that our bodies can regulate behavior in ways that we may not realize, and that if something does not feel good to us, there is a likely to be a reason why.”

“Second, our results show that our health status in part regulates the amount of coffee we drink. This is important, because when disease drives behavior, it can lead to misleading health associations in observational studies, and indeed, create a false impression for health benefits if the group of people who do not drink coffee also includes more people who are unwell,” she said.

For now, doctors can tell their patients that this study provides an explanation as to why research on the health effects of habitual coffee consumption has been conflicting, Dr. Hyppönen said.

“Our study also highlights the uncertainty that underlies the claimed health benefits of coffee, but at the same time, it gives a positive message about the ability of our body to regulate our level of coffee consumption in a way that helps us avoid adverse effects.”

“The most common symptoms of excessive coffee consumption are palpitations and rapid heartbeat, also known as tachycardia,” Nieca Goldberg, MD, medical director of the NYU Women’s Heart Program at NYU Langone Health, said in an interview.

“This study was designed to see if cardiac symptoms affect coffee consumption, and it showed that people with hypertension, angina, history of arrhythmias, and poor health tend to be decaffeinated coffee drinkers or no coffee drinkers,” Dr. Goldberg said.

“People naturally alter their coffee intake base on their blood pressure and symptoms of palpitations and/or rapid heart rate,” she said.

The results also suggest that, “we cannot infer health benefit or harm based on the available coffee studies,” Dr. Goldberg added.

The study was funded by the National Health and Medical Research Council, Australia. Dr. Hyppönen and Dr. Goldberg have disclosed no relevant financial relationships.

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