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OBJECTIVE: To evaluate the association between seasonal influenza vaccination and miscarriage using data from an ongoing, prospective cohort study. METHODS: We analyzed 2013-2022 data from PRESTO (Pregnancy Study Online), a prospective prepregnancy cohort study of female pregnancy planners and their male partners in the United States and Canada. Female participants completed a baseline questionnaire and then follow-up questionnaires every 8 weeks until pregnancy, during early and late pregnancy, and during the postpartum period. Vaccine information was self-reported on all questionnaires. Miscarriage was identified from self-reported information during follow-up. Male partners were invited to complete a baseline questionnaire only. We used Cox proportional hazard models to estimate the hazard ratio (HR) and 95% CI for the association between vaccination less than 3 months before pregnancy detection through the 19th week of pregnancy and miscarriage, with gestational weeks as the time scale. We modeled vaccination as a time-varying exposure and used propensity-score fine stratification to control for confounding from seasonal and female partner factors. RESULTS: Of 6,946 pregnancies, 23.3% of female partners reported exposure to influenza vaccine before or during pregnancy: 3.2% during pregnancy (gestational age 4-19 weeks) and 20.1% during the 3 months before pregnancy detection. The miscarriage rate was 16.2% in unvaccinated and 17.0% among vaccinated participants. Compared with no vaccine exposure, influenza vaccination was not associated with increased rate of miscarriage when administered before (HR 0.99, 95% CI 0.81-1.20) or during (HR 0.83, 95% CI 0.47-1.47) pregnancy. Of the 1,135 couples with male partner vaccination data available, 10.8% reported vaccination less than 3 months before pregnancy. The HR for the association between male partner vaccination and miscarriage was 1.17 (95% CI 0.73-1.90). CONCLUSION: Influenza vaccination before or during pregnancy was not associated with miscarriage. [ABSTRACT FROM AUTHOR]

Background: Migraine is common among females of reproductive age (estimated prevalence:17–24%) and may be associated with reproductive health through underlying central nervous system excitability, autoimmune conditions, and autonomic dysfunction. We evaluated the extent to which pre-pregnancy migraine diagnosis and medication use are associated with risk of spontaneous abortion (SAB). Methods: We analyzed data from a preconception study of pregnancy planners (2013–2021). Eligible participants self-identified as female, were aged 21–45 years, resided in the USA or Canada, and conceived during follow-up (n = 7890). Participants completed baseline and bimonthly follow-up questionnaires for up to 12 months or until a reported pregnancy, whichever occurred first. Pregnant participants then completed questionnaires during early (~ 8–9 weeks) and late (~ 32 weeks) gestation. We defined migraineurs as participants who reported a migraine diagnosis or use of a medication to treat migraine. Preconception questionnaires elicited migraine medication use during the past 4 weeks, and SAB on follow-up and pregnancy questionnaires. We used Cox regression models with gestational weeks as the time scale to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations among preconception migraine, migraine medication use, and SAB, controlling for potential demographic, medical, and lifestyle confounders. Results: Nineteen percent of study pregnancies ended in SAB. History of migraine before conception was not appreciably associated with SAB risk (HR = 1.03, 95% CI: 0.91–1.06). Use of any migraine medication was associated with a modest increase in SAB risk overall (HR = 1.14, 95% CI: 0.96–1.36). We observed the greatest increase in risk among those taking migraine medications daily (HR = 1.38, 95% CI: 0.81–2.35) and those taking prescription migraine prophylaxis (HR = 1.43, 95% CI: 0.72–2.84) or combination analgesic and caffeine medications (HR = 1.42, 95% CI: 0.99–2.04). Conclusions: Migraine medication use patterns suggesting greater underlying migraine severity were associated with increased risk of SAB. This research adds to the limited information available on the reproductive effects of migraine. [ABSTRACT FROM AUTHOR]

Spontaneous abortion (SAB), defined as a pregnancy loss before 20 weeks of gestation, affects up to 30% of conceptions, yet few modifiable risk factors have been identified. We estimated the effect of ambient air pollution exposure on SAB incidence in Pregnancy Study Online (PRESTO), a preconception cohort study of North American couples who were trying to conceive. Participants completed questionnaires at baseline, every 8 weeks during preconception follow-up, and in early and late pregnancy. We analyzed data on 4643 United States (U.S.) participants and 851 Canadian participants who enrolled during 2013–2019 and conceived during 12 months of follow-up. We used country-specific national spatiotemporal models to estimate concentrations of particulate matter <2.5 μm (PM 2.5), nitrogen dioxide (NO 2), and ozone (O 3) during the preconception and prenatal periods at each participant's residential address. On follow-up and pregnancy questionnaires, participants reported information on pregnancy status, including SAB incidence and timing. We fit Cox proportional hazards regression models with gestational weeks as the time scale to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of time-varying prenatal concentrations of PM 2.5 , NO 2 , and O 3 with rate of SAB, adjusting for individual- and neighborhood-level factors. Nineteen percent of pregnancies ended in SAB. Greater PM 2.5 concentrations were associated with a higher incidence of SAB in Canada, but not in the U.S. (HRs for a 5 μg/m3 increase = 1.29, 95% CI: 0.99, 1.68 and 0.94, 95% CI: 0.83, 1.08, respectively). NO 2 and O 3 concentrations were not appreciably associated with SAB incidence. Results did not vary substantially by gestational weeks or season at risk. In summary, we found little evidence for an effect of residential ambient PM 2.5 , NO 2 , and O 3 concentrations on SAB incidence in the U.S., but a moderate positive association of PM 2.5 with SAB incidence in Canada. • We found a positive association of ambient PM 2.5 concentrations with spontaneous abortion in Canada, but not the USA. • NO 2 and O 3 concentrations were not appreciably associated with rate of SAB. • Results were relatively consistent across season and weeks of gestation. • Protection of pregnant individuals from air pollutionis an important measure to safeguard maternal and fetal health. [ABSTRACT FROM AUTHOR]

To use self-reported preconception data to derive models that predict the risk of miscarriage. Prospective preconception cohort study. Not applicable. Study participants were female, aged 21–45 years, residents of the United States or Canada, and attempting spontaneous pregnancy at enrollment during 2013–2022. Participants were followed for up to 12 months of pregnancy attempts; those who conceived were followed through pregnancy and postpartum. We restricted analyses to participants who conceived during the study period. On baseline and follow-up questionnaires completed every 8 weeks until pregnancy, we collected self-reported data on sociodemographic factors, reproductive history, lifestyle, anthropometrics, diet, medical history, and male partner characteristics. We included 160 potential predictor variables in our models. The primary outcome was a miscarriage, defined as pregnancy loss before 20 weeks of gestation. We followed participants from their first positive pregnancy test until miscarriage or a censoring event (induced abortion, ectopic pregnancy, loss of follow-up, or 20 weeks of gestation), whichever occurred first. We fit both survival and static models using Cox proportional hazards models, logistic regression, support vector machines, gradient-boosted trees, and random forest algorithms. We evaluated model performance using the concordance index (survival models) and the weighted F1 score (static models). Among the 8,720 participants who conceived, 20.4% reported miscarriage. In multivariable models, the strongest predictors of miscarriage were female age, history of miscarriage, and male partner age. The weighted F1 score ranged from 73%–89% for static models and the concordance index ranged from 53%–56% for survival models, indicating better discrimination for the static models compared with the survival models (i.e., the ability of the model to discriminate between individuals with and without miscarriage). No appreciable differences were observed across strata of miscarriage history or among models restricted to ≥8 weeks of gestation. Our findings suggest that miscarriage is not easily predicted on the basis of preconception lifestyle characteristics and that advancing age and a history of miscarriage are the most important predictors of incident miscarriage. [ABSTRACT FROM AUTHOR]