Search

STUDY QUESTION To what extent is preconception maternal or paternal coronavirus disease 2019 (COVID-19) vaccination associated with miscarriage incidence? SUMMARY ANSWER COVID-19 vaccination in either partner at any time before conception is not associated with an increased rate of miscarriage. WHAT IS KNOWN ALREADY Several observational studies have evaluated the safety of COVID-19 vaccination during pregnancy and found no association with miscarriage, though no study prospectively evaluated the risk of early miscarriage (gestational weeks [GW] <8) in relation to COVID-19 vaccination. Moreover, no study has evaluated the role of preconception vaccination in both male and female partners. STUDY DESIGN, SIZE, DURATION An Internet-based, prospective preconception cohort study of couples residing in the USA and Canada. We analyzed data from 1815 female participants who conceived during December 2020–November 2022, including 1570 couples with data on male partner vaccination. PARTICIPANTS/MATERIALS, SETTING, METHODS Eligible female participants were aged 21–45 years and were trying to conceive without use of fertility treatment at enrollment. Female participants completed questionnaires at baseline, every 8 weeks until pregnancy, and during early and late pregnancy; they could also invite their male partners to complete a baseline questionnaire. We collected data on COVID-19 vaccination (brand and date of doses), history of SARS-CoV-2 infection (yes/no and date of positive test), potential confounders (demographic, reproductive, and lifestyle characteristics), and pregnancy status on all questionnaires. Vaccination status was categorized as never (0 doses before conception), ever (≥1 dose before conception), having a full primary sequence before conception, and completing the full primary sequence ≤3 months before conception. These categories were not mutually exclusive. Participants were followed up from their first positive pregnancy test until miscarriage or a censoring event (induced abortion, ectopic pregnancy, loss to follow-up, 20 weeks' gestation), whichever occurred first. We estimated incidence rate ratios (IRRs) for miscarriage and corresponding 95% CIs using Cox proportional hazards models with GW as the time scale. We used propensity score fine stratification weights to adjust for confounding. MAIN RESULTS AND THE ROLE OF CHANCE Among 1815 eligible female participants, 75% had received at least one dose of a COVID-19 vaccine by the time of conception. Almost one-quarter of pregnancies resulted in miscarriage, and 75% of miscarriages occurred <8 weeks' gestation. The propensity score-weighted IRR comparing female participants who received at least one dose any time before conception versus those who had not been vaccinated was 0.85 (95% CI: 0.63, 1.14). COVID-19 vaccination was not associated with increased risk of either early miscarriage (GW: <8) or late miscarriage (GW: 8–19). There was no indication of an increased risk of miscarriage associated with male partner vaccination (IRR = 0.90; 95% CI: 0.56, 1.44). LIMITATIONS, REASONS FOR CAUTION The present study relied on self-reported vaccination status and infection history. Thus, there may be some non-differential misclassification of exposure status. While misclassification of miscarriage is also possible, the preconception cohort design and high prevalence of home pregnancy testing in this cohort reduced the potential for under-ascertainment of miscarriage. As in all observational studies, residual or unmeasured confounding is possible. WIDER IMPLICATIONS OF THE FINDINGS This is the first study to evaluate prospectively the relation between preconception COVID-19 vaccination in both partners and miscarriage, with more complete ascertainment of early miscarriages than earlier studies of vaccination. The findings are informative for individuals planning a pregnancy and their healthcare providers. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Health [R01-HD086742 (PI: L.A.W.); R01-HD105863S1 (PI: L.A.W. and M.L.E.)], the National Institute of Allergy and Infectious Diseases (R03-AI154544; PI: A.K.R.), and the National Science Foundation (NSF-1914792; PI: L.A.W.). The funders had no role in the study design, data collection, analysis and interpretation of data, writing of the report, or the decision to submit the paper for publication. L.A.W. is a fibroid consultant for AbbVie, Inc. She also receives in-kind donations from Swiss Precision Diagnostics (Clearblue home pregnancy tests) and Kindara.com (fertility apps). M.L.E. received consulting fees from Ro, Hannah, Dadi, VSeat, and Underdog, holds stock in Ro, Hannah, Dadi, and Underdog, is a past president of SSMR, and is a board member of SMRU. K.F.H. reports being an investigator on grants to her institution from UCB and Takeda, unrelated to this study. S.H.-D. reports being an investigator on grants to her institution from Takeda, unrelated to this study, and a methods consultant for UCB and Roche for unrelated drugs. The authors report no other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Study Question: To what extent are ambient concentrations of particulate matter <2.5 microns (PM2.5), nitrogen dioxide (NO2) and ozone (O3) associated with risk of self-reported physician-diagnosed uterine leiomyomata (UL)?Summary Answer: In this large prospective cohort study of Black women, ambient concentrations of O3, but not PM2.5 or NO2, were associated with increased risk of UL.What Is Known Already: UL are benign tumors of the myometrium that are the leading cause of gynecologic inpatient care among reproductive-aged women. Black women are clinically diagnosed at two to three times the rate of white women and tend to exhibit earlier onset and more severe disease. Two epidemiologic studies have found positive associations between air pollution exposure and UL risk, but neither included large numbers of Black women.Study Design, Size, Duration: We conducted a prospective cohort study of 21 998 premenopausal Black women residing in 56 US metropolitan areas from 1997 to 2011.Participants/material, Setting, Methods: Women reported incident UL diagnosis and method of confirmation (i.e. ultrasound, surgery) on biennial follow-up questionnaires. We modeled annual residential concentrations of PM2.5, NO2 and O3 throughout the study period. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for a one-interquartile range (IQR) increase in air pollutant concentrations, adjusting for confounders and co-pollutants.Main Results and the Role Of Chance: During 196 685 person-years of follow-up, 6238 participants (28.4%) reported physician-diagnosed UL confirmed by ultrasound or surgery. Although concentrations of PM2.5 and NO2 were not appreciably associated with UL (HRs for a one-IQR increase: 1.01 (95% CI: 0.93, 1.10) and 1.05 (95% CI: 0.95, 1.16), respectively), O3 concentrations were associated with increased UL risk (HR for a one-IQR increase: 1.19, 95% CI: 1.07, 1.32). The association was stronger among women age <35 years (HR: 1.26, 95% CI: 0.98, 1.62) and parous women (HR: 1.28, 95% CI: 1.11, 1.48).Limitations, Reasons For Caution: Our measurement of air pollution is subject to misclassification, as monitoring data are not equally spatially distributed and we did not account for time-activity patterns. Our outcome measure was based on self-report of a physician diagnosis, likely resulting in under-ascertainment of UL. Although we controlled for several individual- and neighborhood-level confounding variables, residual confounding remains a possibility.Wider Implications Of the Findings: Inequitable burden of air pollution exposure has important implications for racial health disparities, and may be related to disparities in UL. Our results emphasize the need for additional research focused on environmental causes of UL.Study Funding/competing Interest(s): This research was funded by the National Cancer Institute (U01-CAA164974) and the National Institute of Environmental Health Sciences (R01-ES019573). L.A.W. is a fibroid consultant for AbbVie, Inc. and accepts in-kind donations from Swiss Precision Diagnostics, Sandstone Diagnostics, FertilityFriend.com and Kindara.com for primary data collection in Pregnancy Study Online (PRESTO). M.J. declares consultancy fees from the Health Effects Institute (as a member of the review committee). The remaining authors declare they have no actual or potential competing financial interests.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]