Urinary selective serotonin reuptake inhibitors across critical windows of pregnancy establishment: a prospective cohort study of fecundability and pregnancy loss

Abstract

Objective: To prospectively investigate the association of selective serotonin reuptake inhibitor (SSRI) exposure through critical windows of pregnancy establishment with fecundability and pregnancy loss.

Design: Prospective cohort study using longitudinal urine measurements of common SSRIs while women are actively trying to conceive.

Setting: Four clinical sites.

Patient(s): A total of 1,228 women without uncontrolled depression/anxiety, attempting natural conception while participating in a randomized trial of preconception-initiated low-dose aspirin.

Interventions(s): Not applicable.

Main outcome measure(s): Urinary SSRIs (fluoxetine, sertraline, escitalopram/citalopram) were measured while trying to conceive and, for women who became pregnant, at weeks 0, 4, and 8 of pregnancy. Fecundability odds ratios and incidence of pregnancy loss and live birth were estimated.

Result(s): A total of 172 women (14%) were exposed to SSRIs while trying to conceive. SSRI exposure was associated with 24% reduced fecundability, and accordingly, a nonsignificant 9% lower live birth incidence, with significantly lower live birth in fluoxetine-exposed women. SSRI exposure was not associated with subsequent pregnancy loss, whether exposure was before conception or at 0, 4, or 8 weeks of gestation, although estimates varied by specific SSRI drug.

Conclusion(s): Women using SSRIs may have more difficulty becoming pregnant, and although SSRI exposure overall was not associated with pregnancy loss, fluoxetine deserves caution and future study.

Clinical trial registration number: NCT00467363.

Keywords: Fecundability; SSRI; antidepressant; miscarriage; selective serotonin reuptake inhibitors.

Conflict of interest statement

Conflict of Interest

RMS received support through contracts from NICHD (contracts listed under Funding) for conduct of the study (i.e. data collection) for the submitted work and JGR was funded by the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation (DDCF Grant # 2014194), Genentech, Elsevier, and other private donors. There are no other potential conflicts to disclose.

Published by Elsevier Inc.

Figures

Figure 1.

Fecundability odds ratios for overall SSRI and individual SSRI drug exposure relative to women without preconception antidepressant exposure. Footnote: Horizontal line represents reference group (FOR 1.0) of women with no preconception antidepressant exposure.

Figure 2.

Relative risk of live birth, with absolute birth rate (%), following up to six menstrual cycles of study observation, according to preconception SSRI exposure. Footnote: Horizontal line represents reference group (RR 1.0) of women with no preconception antidepressant exposure (live birth rate 56%).