A new article published in the Archives of Disease in Childhood: Fetal and Neonatal Edition finds that the use of selective serotonin reuptake inhibitors (SSRIs) in late pregnancy (after 20 weeks) is linked to delayed neonatal adaptation.
According to a recent study conducted by Marie-Coralie Cornet of the University of California, infants who are exposed to selective serotonin reuptake inhibitors (SSRIs) after 20 weeks of pregnancy have lower scores on the Apgar assessment, are at a higher risk for respiratory distress, and are often referred for higher levels of care. The study found that higher doses of SSRIs are associated with greater risks for the infant. The SSRIs that are most commonly linked to delayed neonatal adaptation are escitalopram and fluoxetine. The authors write:
“Low-dose sertraline exposure is associated with a doubling in the odds of delayed neonatal adaptation independent of maternal mental health diagnoses. The odds of delayed adaptation increase with increasing doses of SSRI and are higher for neonates on other types of SSRIs than sertraline.”
Significantly, this study is not confounded by the presence of maternal depression, as the researchers adjusted for variables such as maternal depression and anxiety, finding that a maternal diagnosis of depression was not associated with delayed neonatal adaptation. Additionally, the dose of SSRI and whether the mother withdrew from SSRIs were related to the outcomes in that higher doses of SSRIs were associated with an increased risk of delayed neonatal adaptation, and infants born to mothers who discontinued SSRI use between 20 and 30 weeks of pregnancy showed no increased likelihood of delayed neonatal adaptation compared to those with no SSRI exposure.
The term “delayed neonatal adaptation” is used to describe the condition of a newborn baby who scores five or less on the Apgar assessment, requires resuscitation at birth, or needs respiratory support in a neonatal intensive care unit. The current research aims to investigate the relationship between selective serotonin reuptake inhibitors (SSRIs) use during the latter part of pregnancy (i.e., after 20 weeks) and the likelihood of delayed neonatal adaptation.
To achieve this goal, the researchers collected data on SSRI use during pregnancy, psychiatric diagnosis, newborn health, and demographics at 15 Kaiser Permanente Northern California (KPNC) hospitals between November 1, 2011, and July 31, 2019. Infants born before 37 weeks and those with congenital and genetic abnormalities were excluded from the current study. The authors obtained data on SSRI use during pregnancy by reviewing KPNC pharmacy records for SSRIs dispensed after 20 weeks of pregnancy. Psychiatric diagnosis, newborn health, and demographic data were obtained from existing KPNC databases.
In total, 280,682 infants were born after 37 or more weeks of pregnancy at KPNC during the current study. Five hundred ninety-two infants were excluded due to congenital or genetic abnormalities, leaving the authors with 280,090 infants. Seven thousand five hundred seventy-three of these infants (2.7%) were exposed to SSRIs after 20 weeks of pregnancy.
Delayed neonatal adaptation was present for 11.2% of the infants exposed to SSRIs after 20 weeks compared to 4.4% of those not exposed. This means those exposed to SSRIs in late pregnancy were 2.52 times more likely than those not exposed to exhibit delayed neonatal adaptation. After adjusting for variables such as the age of the mother, drug use, anxiety during pregnancy, etc., the authors found that infants exposed to SSRIs after 20 weeks were still 2.14 times as likely to display delayed neonatal adaptation. Exposure to SSRIs was also associated with infants needing more extended hospital stays and higher levels of care.
While maternal anxiety during pregnancy was weakly associated with delayed neonatal adaptation, a maternal diagnosis of depression, despite the severity of the diagnosis, was not associated with delayed neonatal adaptation.
SSRI exposure after 20 weeks of pregnancy was not associated with pulmonary hypertension or neonatal seizures. Hypoxic-ischaemic encephalopathy was associated with SSRI use in the initial analysis, but the association was not present after adjusting for confounding variables such as drug use, maternal age, anxiety during pregnancy, etc. There was also a weak association between SSRI use and the need for infants to be treated with therapeutic hypothermia.
All of the SSRIs examined showed a link to delayed neonatal adaptation. Higher doses of SSRIs were associated with an increased risk of delayed neonatal adaptation. Sertraline, which nearly doubled the risk of delayed neonatal adaptation, was the least risky of the SSRIs in the current study. Citalopram and fluoxetine more than doubled the risk, while escitalopram nearly quadrupled it.
The authors note that a subgroup of 865 mothers discontinued SSRI use between 20 and 30 weeks of pregnancy. Infants born to this group were no more likely than those with no SSRI exposure to exhibit delayed neonatal adaptation.
The authors acknowledge several limitations to the current work. Data on SSRI use was collected from KPNC pharmacies, which means some mothers could have had prescriptions for SSRIs filled elsewhere. The data on SSRI use was only for prescriptions filled. There was no measure of whether or not the medications were used as recommended. While the authors attempted to adjust results based on the severity of maternal depression and anxiety, these variables may still have distorted the data. The present research did not explore the effects of sudden discontinuation of SSRIs after birth compared to continued SSRI exposure through breast milk. The authors only examined short-term neonatal outcomes of SSRI exposure. The research was also conducted with participants receiving care exclusively in northern California, significantly reducing generalizability to other populations. The authors conclude:
“In utero exposure to SSRIs during late pregnancy was associated with increased odds of delayed neonatal adaptation. This association was independent of maternal mental health and was dose and type-dependent.”
Previous research has found that “babies born to mothers taking antidepressants were more than six times as likely to have neonatal withdrawal syndrome.” Exposure to antidepressants in utero has been linked to an increased risk for speech disorders. Antidepressant use during pregnancy is associated with poor neonatal outcomes. SSRI use during pregnancy has also been shown to alter the child’s brain development.
Cornet, M. C., Wu, Y. W., Forquer, H., Avalos, L. A., Sriram, A., Scheffler, A. W., Newman, T. B., & Kuzniewicz, M. W. (2023). Maternal treatment with selective serotonin reuptake inhibitors during pregnancy and delayed neonatal adaptation: a population-based cohort study. Archives of disease in childhood. Fetal and neonatal edition, fetalneonatal-2023-326049. Advance online publication. https://doi.org/10.1136/archdischild-2023-326049 (Link)