A prospective study of periconceptional perceived stress and rate of miscarriage

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.