INTRODUCTION

Perinatal women may at times need antidepressants to treat mental disorders. Selective serotonin reuptake inhibitors (SSRIs) are the preferred therapeutic choice in this population, and they are taken by 1-5% of pregnant women in Europe to up to 8% in the US;1-3 other antidepressants, such as serotonin-norepinephrine reuptake inhibitors (SNRIs), are less often used (<1%).2 Perinatal antidepressant exposure altered offspring behavior and brain structure in animal research, possibly via serotonin dysregulation.4 Risk for attention-deficit/hyperactivity disorder (ADHD) has therefore been investigated in human pregnancy, but findings remain inconclusive.5-7
Results of one meta-analysis has suggested a moderate increased risk for ADHD in children prenatally exposed to antidepressants relative to unexposed (risk ratio (RR): 1.39, 95% Confidence Interval (CI): 1.21–1.61),6 but the association decreased to the null in sibling-matched analyses.5 Even though familial factors are presumed to largely explain the increased ADHD risk in ever exposed children, whether timing of prenatal antidepressant exposure, and so duration, confer different ADHD risks, remains unresolved.5,8
Quantifying risks for child behavioral disorders from both a diagnostic and symptom perspective is also critical,7 since an additional 5% of children beyond the 2-7% having a diagnosis, display symptoms of ADHD that do not meet fully the diagnostic criteria.9 Given the burden, consequences and unclear etiology of ADHD in children9 a more conclusive understanding of the risk posed by intrauterine antidepressant exposure is needed.7
This study sought to fill these knowledge gaps by quantifying the association of child ADHD, measured both as diagnoses and symptoms, with prenatal SSRI/SNRI antidepressant as ever exposure in pregnancy and according to timing and duration. To address possible bias by exposure misclassification, we replicated the main analysis for ever exposure to SSRI/SNRI in a sub-population of women who both self-reported and redeemed prescriptions for antidepressants.