Behavioural effects of fetal antidepressant exposure in a Norwegian cohort of discordant siblings

Objective: Potential adverse effects of prenatal antidepressant exposure on child development are still debated. The possibility that associations are due to genetic or familial environmental risk factors rather than antidepressant use per se cannot easily be ruled out in conventional studies. Our objective was therefore to evaluate the association between prenatal antidepressant exposure and behavioural problems in a sibling controlled study. Method: This study used data on 20 180 siblings identified from the population-based Norwegian Mother and Child Cohort Study recruited between 1999 and 2008. The mothers were asked to report antidepressant use at gestational weeks 17 and 30 and 6 months post-partum. Child Behavioral Checklist syndrome scales were used to assess externalizing and internalizing behavioural problems by questionnaires sent to mothers at 18 and 36 months postpartum. We performed unmatched and matched sibling analyses using both random-and fixed-effects linear models, respectively, to determine potential behavioural effects of antidepressant exposure. Results: Prenatal exposure to antidepressants was associated with increased levels of anxiety symptoms in 3 year old children after adjusting for maternal familial effects and confounding by indication (i.e. maternal depression). Effect of prenatal exposure to antidepressants was specific to anxiety, and not associated with emotional reactivity, somatic complaints, sleep problems, attention problems or aggression. Conclusion: Using a sibling design, we showed that prenatal antidepressant use was specifically associated with increased anxiety symptoms after adjusting for maternal familial factors and confounding by indication.