Abstract
STUDY QUESTION: To what extent is perceived stress during preconception and pregnancy associated with miscarriage incidence? SUMMARY ANSWER: Perceived stress during early pregnancy, but not preconception, was associated with higher miscarriage incidence. WHAT IS KNOWN ALREADY: Some studies have found that higher stress levels are associated with miscarriage risk. However, many of these studies were retrospective, focused on occupational stress only, and/or suffered from under-ascertainment of miscarriage. STUDY DESIGN, SIZE, DURATION: Pregnancy Study Online (PRESTO) is an ongoing prospective preconception cohort study that recruited participants during 2013-2025. Eligible participants were females aged 21-45 years, who resided in the USA or Canada and were trying to conceive without fertility treatments. Eligible partners were males aged ≥21 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected data on perceived stress using the 10-item version of the Perceived Stress Scale (PSS-10) during preconception (every 8 weeks) and early pregnancy for female participants and during preconception only for male participants. We identified pregnancies and miscarriages on bimonthly follow-up questionnaires during preconception and additional questionnaires during early and late pregnancy and postpartum. We fit Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% CIs for the effect of preconception PSS-10 scores (n = 11 189 female and 2656 male participants) and early pregnancy PSS-10 scores (n = 8319 female participants) on miscarriage incidence, adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: About 20% of the pregnancies ended in miscarriage, with the loss occurring at a median of six gestational weeks. Preconception PSS-10 scores in the female or male partner were not appreciably associated with miscarriage incidence. Female PSS-10 scores during gestational weeks 5-8 were strongly associated with higher miscarriage incidence: adjusted HRs for PSS-10 scores of 10-14, 15-19, 20-24, and ≥25 vs <10 in gestational weeks 5-8 were 1.38 (95% CI: 1.07, 1.77), 1.17 (95% CI: 0.89, 1.52), 1.35 (95% CI: 1.00, 1.83), and 2.05 (95% CI: 1.40, 2.99), respectively. In week-specific analyses, an association existed during weeks 4-8 and peaked at week 7. LIMITATIONS, REASONS FOR CAUTION: Our results may be susceptible to reverse causation, unmeasured confounding by nausea and vomiting in pregnancy, and exposure misclassification. WIDER IMPLICATIONS OF THE FINDINGS: Interventions aimed at decreasing stress during early pregnancy may be effective at reducing miscarriage incidence, but confirmation of our results in randomized studies is warranted. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01-HD086742, R01-HD105863). Lauren Wise has received in-kind donations for primary data collection in PRESTO from ChartNeo.com. The other authors have no conflicts to report. TRIAL REGISTRATION NUMBER: N/A.