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May 21, 2020
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Confounders significantly weaken association between in utero antidepressant exposure and adverse child outcomes

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Adverse psychiatric, neurodevelopmental and physical outcomes among children reportedly associated with in utero exposure to antidepressants appeared to be caused by the underlying maternal disorder, according to results of a systematic review published in Journal of Clinical Psychiatry.

“Some [observational] studies found associations between in utero exposure to antidepressants and adverse neonatal outcomes, including low birth weight, preterm birth, persistent pulmonary hypertension of the neonate, and poor neonatal adaptation, as well as associations between prenatal antidepressant exposure and poorer neurodevelopmental and neurobehavioral outcomes in early childhood,” Anna-Sophie Rommel, PhD, of the department of psychiatry at Icahn School of Medicine at Mount Sinai, and colleagues wrote. “[Although] these short-term outcomes have frequently been investigated and subsequently consolidated in systematic reviews, very few long-term child outcomes were included in these reviews.”

However, more recent studies reported on adverse long-term outcomes beyond infancy and early childhood. In these, researchers looked at intellectual disability at age 8 years, as well as childhood cancer and psychiatric disorders over 15- and 17-year follow-up periods, respectively, according to Rommel and colleagues.

In the current study, the investigators aimed to determine the long-term effects of prenatal antidepressant exposure on psychiatric, neurodevelopmental and physical outcomes among individuals aged 4 years and older. They systematically searched five databases for all relevant articles written in English and published before Nov. 8, 2018. They used terms describing antidepressants, pregnancy and developmental outcomes and included all original research articles on long-term outcomes of prenatal antidepressant exposure. Rommel and colleagues identified 34 studies after screening and removing duplicates. They qualitatively analyzed included articles to determine study bias, imprecision, inconsistency and indirectness.

Results showed statistically significant associations between prenatal antidepressant exposure and multiple psychiatric, neurodevelopmental and physical outcomes; however, the risk for confounding by indication was high. The researchers controlled for confounders and reported that 11 studies investigating psychiatric outcomes showed an association between prenatal antidepressant exposure and affective disorders but not with childhood psychiatric outcomes, including autism spectrum disorder and ADHD. Moreover, 18 studies examining neurodevelopmental outcomes, including cognition, behavior, IQ, motor development, speech, language and scholastic outcomes, showed no consistent associations with antidepressant exposure after accounting for confounders. Lastly, when controlling for confounders, five studies investigating physical outcomes, including asthma, cancer, BMI and epilepsy, showed no association except conflicting outcomes for BMI.

“As time goes on, more data will become available on the long-term effects of prenatal antidepressant exposure, including on physical and mental health outcomes,” Rommel and colleagues wrote. “These data will help to clarify the relationship between prenatal antidepressant exposure and BMI. Future research must also substantiate the association between in utero antidepressant exposure and affective disorders in adolescence and adulthood and investigate the associations between prenatal antidepressant exposure and other psychopathologies arising later in life.” – by Joe Gramigna

Disclosures: The authors report no relevant financial disclosures.