Antiepileptic drug exposure during pregnancy has been associated with an increased risk for congenital malformations and delayed cognitive development in the offspring,^1-3 but little is known about the risk of other serious neuropsychiatric disorders. Autistic symptoms have been described in case series of children exposed in utero to valproic acid,^4-7 and it has been suggested that valproate given to animals during pregnancy may constitute an experimental model of autism.^8-10

Read the full review for this F1000Prime recommended article: Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study.

Peer reviewed article authored by (Sørensen MJ, Grønborg TK, Christensen J, Parner ET, Vestergaard M, Schendel D, Pedersen LH). Read article or submit your manuscript for publishing.

Objective To investigate the effect of intrauterine selective serotonin reuptake inhibitor (SSRI) exposure on pregnancy outcomes. Design Prospective cohort study. Setting Department of Obstetrics, Aarhus University Hospital, Aarhus, Denmark. Participants Pregnant women receiving prenatal care in our hospital from 1989 to 2006. Main Exposure Maternal SSRI use during pregnancy. Outcome Measures Gestational age, birth weight, head circumference, 5-minute Apgar score, and admission to the neonatal intensive care unit. Results Three hundred twenty-nine pregnant women reported treatment with SSRIs, 4902 were not treated with SSRIs but had a history of psychiatric illness, and 51 770 reported no history of psychiatric illness. Gestational age was 5 days (95% confidence interval [CI], −6 to −3) shorter and the odds ratio (OR) for preterm birth was 2.0 (95% CI, 1.3-3.2) in the women exposed to SSRIs compared with women with no history of psychiatric illness. In utero–exposed newborns had increased risk of admission to the neonatal intensive care unit (OR, 2.4; 95% CI, 1.7-3.4) and of 5-minute Apgar scores of less than 8 (OR, 4.4; 95% CI, 2.6-7.6) compared with those not exposed. Head circumference and birth weight did not differ between infants in the exposed and unexposed groups. The results were similar when compared with infants of women with a psychiatric history. Conclusions Exposure to SSRIs during pregnancy was associated with an increased risk of preterm delivery, a low 5-minute Apgar score, and neonatal intensive care unit admission, which was not explained by lower Apgar scores or gestational age. The study justifies increased awareness to the possible effects of intrauterine exposure to antidepressants.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from −90% to +30%, were reported in many countries following early COVID-19 pandemic response measures (‘lockdowns’). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95–0.98, P value <0.0001), second (0.96, 0.92–0.99, 0.03) and third (0.97, 0.94–1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96–1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88–1.14, 0.98), third (0.99, 0.88–1.12, 0.89) and fourth (1.01, 0.87–1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02–1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03–1.15, 0.002), third (1.10, 1.03–1.17, 0.003) and fourth (1.12, 1.05–1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.