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.