‘Conclusive Answer’ on Antidepressants in Pregnancy and Kids’ Epilepsy Risk

Use of selective serotonin reuptake inhibitors (SSRIs) or selective norepinephrine reuptake inhibitors (SNRIs) during the first trimester of pregnancy was not associated with an increased risk for neonatal seizures and epilepsy in childhood, analysis of a Swedish registry showed.

An unadjusted analysis of more than 1.5 million dyads turned up an elevated risk for neonatal seizures (risk ratio [RR] 1.41, 95% CI 1.03-1.94) and epilepsy in early childhood (HR 1.21, 95% CI 1.03-1.43) among offspring of mothers who used antidepressants in pregnancy, according to researchers led by Kelsey Kathleen Wiggs, a PhD candidate at Indiana University in Bloomington.

But adjusted models showed that maternal indications for SSRI/SNRI use and background factors like sociodemographics and smoking during pregnancy were driving both associations: neonatal seizures (RR 1.10, 95% CI 0.79-1.53); epilepsy diagnosis at 5 years (HR 0.96, 95% CI 0.81-1.14), they reported in Neurology.

Adjustment for parental history of epilepsy did not influence the association, the group found.

“It’s not likely the medications themselves that are causing the seizures and epilepsy in children, but rather the reasons why these women are taking the medication,” Wiggs told MedPage Today, along with the other background factors that differ between women who do and do not use SSRI/SNRIs.

“When it rains, it pours,” Wiggs said. “Women who are taking antidepressants in pregnancy are doing that for lots of different reasons, and they might be at risk for different things than women who aren’t taking those medications in pregnancy.”

The research confirms the results of several studies about the association of epilepsy and seizures in children with the use of antidepressants during pregnancy, noted Richard C. Shelton, MD, of the University of Alabama at Birmingham and the founding director of the Depression and Suicide Research Center there.

Shelton told MedPage Today that he often reassures expectant mothers that the medication is not the risk when it comes to SSRI/SNRIs. “What the study shows, and really what it confirms, is what has been shown before, and that is that the major risks for the unborn child is the depression itself,” he explained. “And we want to keep moms as free of depression as possible during pregnancy.”

The findings provide a “conclusive answer” to these concerns with using SSRI/SNRIs — which can cross the placenta and expose the developing brain — during pregnancy, according to Anne Berg, PhD, of Northwestern University-Feinberg School of Medicine in Chicago, and Torin Glass, BM, Bch, BAO, of the University of British Columbia in Vancouver.

“[SSRI/SNRIs] have been demonstrated to have serotonergic central nervous system effects and are associated with an observable withdrawal syndrome which may be seen in the neonate following in utero exposure,” noted Berg and Glass, in an accompanying editorial.

“The authors understood that with a population-based data registry and huge sample size, they had more than sufficient statistical power to detect even a modest increase in risk,” the editorialists wrote. “They tested this hypothesis and were able to reject it, definitively!”

In order to determine whether antidepressants had a causal association with infant seizures and childhood epilepsy, Wiggs and her fellow researchers analyzed data from a total of 1,721,274 children in Sweden born between 1996 and 2011, using data available from national Swedish healthcare registries on self-reported maternal health assessments, pediatric visits, and prescription drugs databases.

The investigators divided registrants into two groups: one group of mothers who reported use of an SSRI (fluoxetine, citalopram, paroxetine, sertraline, fluvoxamine, escitalopram) or SNRI (venlafaxine, duloxetine) during the first trimester of pregnancy (n=24,308), and another group of mothers who reported no antidepressant use during that time frame (n=1,696,966).

There were 39 cumulative neonatal seizures in the group exposed to SSRI/SNRIs (1.68 events per 1,000) and 1,825 in the unexposed group (1.19 per 1,000). At 5 years, 99 children in the exposed group had received an epilepsy diagnosis (5.35 per 1,000) versus 5,325 of the children in the unexposed group (4.08 per 1,000).