Associations of Maternal Antidepressant Use During the First Trimester of Pregnancy With Preterm Birth, Small for Gestational Age, Autism Spectrum Disorder, and Attention-Deficit/Hyperactivity Disorder in Offspring

Abstract

Importance-Prenatal antidepressant exposure has been associated with adverse outcomes. Previous studies, however, may not have adequately accounted for confounding. Objective-To evaluate alternative hypotheses for associations between first-trimester antidepressant exposure and birth and neurodevelopmental problems. Design, Setting, and Participants-This retrospective cohort study included Swedish offspring born between 1996 and 2012 and followed through 2013 or censored by death or emigration. Analyses controlling for pregnancy, maternal, and paternal covariates, as well as sibling comparisons, timing of exposure comparisons, and paternal comparisons, were used to examine the associations. Exposures-Maternal self-reported first-trimester antidepressant use and first-trimester antidepressant dispensations. Main Outcomes and Measures-Preterm birth (< 37 gestational weeks), small for gestation age (birth weight < 2 SDs below the mean for gestational age), and first inpatient or outpatient clinical diagnosis of autism spectrum disorder and attention-deficit/hyperactivity disorder in offspring. Results-Among 1,580,629 offspring (mean gestational age 279 days; 48.6% female; 1.4% [n = 22,544] with maternal first-trimester self-reported antidepressant use) born to 943,776 mothers (mean age at childbirth 30 years), 7.0% of exposed vs. 4.8% of unexposed offspring were preterm, 2.5% of exposed vs. 2.2% of unexposed were small for gestational age, 5.3% of exposed vs. 2.1%

Prescription drug use in pregnancy and variations according to prior psychiatric history

“…Evidence suggests women are reluctant to take medication in pregnancy, despite this we observed, across various drug classes, a substantial use of prescription drugs. Fetotoxicity is a great concern, also regarding some antidepressants and antiepileptic drugs, but untreated medical conditions are equally worrying and may harm the developing fetus . Any decision regarding medication use in pregnancy should therefore be personalized and based on the risk perceptions of the health care professional and the woman's preferences.…”

Antidepressant use during pregnancy and risk of congenital heart defects: A case‐time‐control study

“…A study on data from five Nordic countries by Furu and colleagues showed that their adjusted findings in a cohort study could not be repeated in a sibling analysis . A recently published study demonstrated that associations between exposure to ADs in early pregnancy and several birth and neurological disorders diminished in the adjusted models and in the sibling design analyses, which indicates confounding, especially confounding by indication, or other types of confounding in the study . Confounding by indication and confounding by background characteristics have been of concern in observational studies and researchers have been exploring different methods to adjust for those factors …”

Variations in Neurodevelopmental Outcomes in Children with Prenatal SSRI Antidepressant Exposure

“…To further examine the role of genetics and maternal mood, two recent population‐level studies have attempted to disentangle potential genetic and environmental mechanisms by using sophisticated statistical methods to adjust for possible measured and unmeasured confounding factors. In one study, using large population‐level data registries from Sweden, Sujan et al examined associations between first trimester antidepressant exposure, birth, and neurodevelopmental outcomes such as autism spectrum disorder and attention deficit‐hyperactivity disorder in over a million children, accounting for family, timing of exposure, and paternal factors (Sujan et al, ). In this study, first trimester maternal antidepressant use was associated with a small increased risk of preterm birth, but not with risk for adverse neurodevelopmental outcomes.…”

“…Importantly, maternal depression and autism may also be related through genetic mechanisms, thereby rendering SSRI exposure as a secondary risk factor underlying the effect of maternal mood (either by means of genetic inheritance or an environmental influence). Research has found a familial association between ASD and depression (Smalley et al, ), although not all associations are consistent (Sujan et al, ) or common (Brown et al, ).…”