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Background: Previous studies suggest an association between late pregnancy exposure to selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) and increased postpartum hemorrhage (PPH) risk. This is the first pregnancy registry study to compare PPH outcomes among women with psychiatric illness exposed or unexposed to SSRIs/SNRIs proximate to delivery. Methods: This study used data from the National Pregnancy Registry for Psychiatric Medications to evaluate the relationship between SSRI/SNRI exposure in late pregnancy and PPH risk. The sample included n = 953 participants with retrospectively collected medical record data on postpartum blood loss, n = 453 unexposed to SSRIs/SNRIs during pregnancy, and n = 500 exposed at least during the week of delivery. PPH was defined as an estimated blood loss ≥500 mL following vaginal delivery or ≥1,000 mL following cesarean section (C-section), with onset of excessive bleeding occurring within the first 24 hours postpartum. Univariate and multivariate logistic regression analyses were performed to determine odds ratios. Results: Overall PPH incidence was 13.1%. SSRI/SNRI exposure was associated with a PPH unadjusted odds ratio of 1.42 compared to no exposure (95% confidence interval [CI: 0.97, 2.08]) and an adjusted odds ratio of 1.33 (95% CI [0.90, 1.97]). When stratified by delivery type, the odds ratio following vaginal delivery among women exposed to SSRIs/SNRIs was 1.04 (95% CI [0.63, 1.70]) versus 2.31 (95% CI [1.25, 4.26]) for C-section delivery; the adjusted C-section odds ratio was 2.21 (95% CI [1.18, 4.13]). Conclusions: Although these findings align with accumulating evidence suggesting SSRI/SNRI exposure may confer a modestly increased risk of PPH, particularly after C-section, the study was underpowered to make definitive conclusions. These preliminary data highlight the need for further research with larger sample sizes. Nevertheless, the findings underscore the importance of greater clinical monitoring for PPH following C-section, especially in women who may have other known PPH risk factors and are exposed to SSRIs/SNRIs in late pregnancy.

Background: Second-generation antipsychotics (SGAs), also called atypical antipsychotics, are common therapies for women with a spectrum of psychiatric disorders. No systematically ascertained human reproductive safety data are available for lurasidone, and prospective data for quetiapine are limited, making decisions regarding use of these medications during pregnancy complicated. Materials and Methods: The National Pregnancy Registry for Psychiatric Medications is a prospective cohort study designed to collect reproductive safety data relative to SGAs. Pregnant women aged 18-45 years, with psychiatric illness and prenatal psychotropic medication exposure completed three phone interviews during pregnancy and the postpartum period. Cases of presumed malformations are abstracted from medical records for adjudication by a teratologist blinded to medication exposure. Results: Of 2,293 women enrolled at the time of analysis, 134 in the lurasidone group, 264 in the quetiapine group, and 886 controls completed the postpartum interview and were therefore eligible for inclusion. Dropped or lost-to-follow-up participants (13%) and those currently pregnant were excluded. Participants were predominantly White, college-educated, and married (lurasidone = 88.1%, 76.9%, 77.6%; quetiapine = 89.8%, 71.2%, 75.0%; controls = 92.7%, 86.7%, 89.1%). Absolute risks of major malformations were 2.19% (lurasidone), 1.85% (quetiapine), and 1.77% (controls). Odds ratios comparing lurasidone and quetiapine with controls were 1.24 (95% confidence interval [CI] = 0.36-4.32) and 1.04 (95% CI = 0.38-2.85), respectively. Conclusions: No specific patterns of malformations were observed in infants exposed to the medications of interest. Lurasidone and quetiapine did not appear to be major teratogens, but further information is needed to refine risk estimates. Food and Drug Administration guidance underscores the importance of pregnancy registries. Clinical trial number: NCT01246765.