Use of selective serotonin-reuptake inhibitors during early pregnancy and risk of congenital malformations: updated analysis

Abstract

Background:Data on the safety of selective serotonin-reuptake inhibitors (SSRIs) in pregnancy are inconsistent. We examined associations between SSRI use during early pregnancy and risk of congenital malformations in infants.Methods:Set in Northern Denmark, our population-based prevalence study included 216,042 women who had a live birth after the 20th week of gestation. We compared the prevalence of malformation in infants born to women who redeemed at least one SSRI prescription during early pregnancy with the prevalence in infants born to women who redeemed no SSRI prescriptions during their pregnancies. Drug use data were extracted from prescription databases, while data on congenital malformations were obtained from the National Registry of Patients.Results:The 2,062 women with SSRI prescriptions during early pregnancy gave birth to 105 (5.1%) infants with malformations, while the 213,712 women with no SSRI prescriptions gave birth to 7,449 (3.5%) infants with malformations. SSRI use was associated with an increased risk of malformations overall (odds ratio [OR] = 1.3; 95% confidence interval (CI): 1.1–1.6) and cardiac malformations (OR = 1.7; 95% CI: 1.1–2.5). For specific SSRIs, we found an increased risk for septal defects associated with sertraline.Conclusions:We found little overall association between use of SSRIs during pregnancy and congenital malformations, but our findings suggest an association between maternal SSRI use in early pregnancy and cardiac malformations which could be causal.

Antidepressant Exposure During Pregnancy and Congenital Malformations: Is There an Association?

“…Overall, the RRs for the other analyses were small, between 1.07 and 1.10 (Table 2), but statistically significant depending on the subanalysis conducted. Results were not significant for any of the analyses for paroxetine use; however, the risk associated with the *Pedersen et al 54 and Reis and Källén 58 were excluded from this analysis, as these studies were population based and from the same country as Kornum et al 57 and Källén and Olausson, 45 respectively. …”

“…However, the most influential studies were also the large ones, and thus heavily influenced the results; these studies did adjust for several potential confounders. 45,46,50,57,58 Thus, most of our pooled risk estimates were heavily influenced by studies that did use adjusted data, including our subanalyses. Although this is relieving to a certain extent, these studies used data from population-based registries; they provide better evidence than that provided by data derived from convenience samples, but they are not randomized controlled trials, which provide the best evidence.…”

Fetal Effects of Selective Serotonin Reuptake Inhibitor Treatment During Pregnancy: Immediate and Longer Term Child Outcomes

“…A significant association with cardiac defects was reported in six studies 62,64,65,67,69 in comparison to four others which investigated but failed to find an association with cardiac defects 31,58,59,63 . Dubnov-Raz and colleagues 70 reported an association between longer QTc intervals across SSRI types (n = 52).…”

“…Significant associations were reported between SSRI exposure and specific malformation types in seven cohorts 58,60,62,64,65,67,69 . A significant association with cardiac defects was reported in six studies 62,64,65,67,69 in comparison to four others which investigated but failed to find an association with cardiac defects 31,58,59,63 .…”

“…Only two independent studies (three publications) indentified a significant association 57,67,68 ( Table 2).…”