A few days ago, an article was published in the journal Pediatrics on neonatal morbidity observed in children exposed to antidepressants. Although this article is likely to find its way into the headlines, it is important to note that the information presented here is nothing new. Similar to previous studies, the Pediatrics study reveals higher rates of neonatal symptoms or complications in the infants born to women who were treated with SSRI antidepressants. Reassuringly, while there is an increase in neonatal morbidity, the absolute risk of serious adverse events is low.
What differentiates this study from others is its size; this study collected information on pregnant women and their newborn infants from the Swedish Medical Birth Register and the Swedish Neonatal Quality Register. Data from a total of 741,040 singletons, born between 2006 and 2012 were included in the analysis.
In this cohort, 17,736 (2.4%) of the infants were exposed to selective serotonin reuptake inhibitors (SSRIs) taken by the mother at some point during the pregnancy. In order to better account for the contribution of untreated depression in the mother to the overall risk for adverse events in the newborn, the researchers conducted two different types of analyses. First, they compared outcomes in the SSRI-exposed infants to outcomes in infants with no SSRI exposure. In addition, they compared outcomes in infants exposed to SSRIs late in pregnancy to those exposed only during early pregnancy.
The study observed that in the group of infants exposed to SSRIs, 13.7% were admitted to the neonatal intensive care unit (NICU) compared to 8.2% in the unexposed group (adjusted odds ratio: 1.5 [95% confidence interval: 1.4–1.5]). When they looked at the children with late pregnancy exposure to SSRIs, the NICU admission was 16.5% compared to 10.8% with only early pregnancy only (adjusted odds ratio: 1.6 [95% CI: 1.5–1.8]).
The SSRI-exposed children were admitted to the NICU for a variety of reasons. The most common reasons for admission were for respiratory disorders (5.7%), most commonly transient tachypnea (4.6%). Other common reasons for admission included hyperbilirubinemia (5.2%), hypoglycemia (4.0%), and feeding difficulties (1.3%). These were also the most common reasons for admission in non-exposed infants; however, for some, but not all, causes, SSRI-exposed children were more likely than unexposed children to be admitted.
The authors also looked at risk for persistent pulmonary hypertension of the newborn (PPHN) in SSRI-exposed infants. PPHN was more common when comparing SSRI exposure versus nonexposure (OR: 1.3 [95% CI: 1.0–1.6]; P = .03) and when comparing treatment during late versus early in pregnancy (OR: 2.1 [95% CI: 1.3–3.2]).
This is a well-done study; however, this sort of study design will always have certain limitations. The biggest hurdle remains how to best assess the impact of untreated psychiatric illness in the mother on neonatal outcomes in a nonrandomized study. Here, the researchers compared outcomes in infants with early versus late exposure to antidepressants. While we can safely assume that most, if not all, women taking SSRIs have a history of depression and/or anxiety, we cannot assume that the women who take antidepressants only early in the pregnancy are the same as those with late exposure. It is likely that the women with late exposure have more severe or recurrent illness; they elected to remain on medication during pregnancy or they experienced symptoms during the course of pregnancy that prompted them to resume treatment with medication.
Putting aside those limitations, it does appear that this study is consistent with previous studies. Exposure to antidepressants, including SSRIs, have been associated with an increased risk of adverse outcomes, including poor neonatal adaptation. In the current study, the risk of PPHN is also elevated in SSRI-exposed infants, but not to the extent observed in the earliest studies from Chambers and colleagues (2005). It is important to emphasize that even if we assume a modest increase in the risk of neonatal morbidity in infants exposed to SSRIs, the absolute risk is small and it may not justify avoiding or discontinuing antidepressants during pregnancy.
Needless to say, pregnancy is a complicated series of events, where multiple factors influence outcomes. While we cannot say that antidepressants are completely free of risk, we must take into consideration the impact of untreated depression on the well-being of the mother and her pregnancy.
Ruta Nonacs, MD PhD
Nörby U, Forsberg L, Wide K, Sjörs G, Winbladh B, Källén K. Neonatal Morbidity After Maternal Use of Antidepressant Drugs During Pregnancy. Pediatrics October 2016.