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BackgroundProspective cohort studies that enroll participants before conception are crucial for deepening scientific understanding of how the preconception environment influences reproductive outcomes. While web-based research methods provide efficient and effective strategies to collect questionnaire-based data, few of these studies incorporate biospecimen collection, which can enhance the validity of exposure assessment. There is limited literature on the feasibility and cost-effectiveness of collecting biospecimens in web-based preconception cohort studies.MethodsWe evaluated the feasibility and cost-effectiveness of in-clinic and mail-based biospecimen collection in Pregnancy Study Online (PRESTO), a North American web-based preconception cohort study. Both members of the couple were eligible to participate if their conception attempt time was ≤3 months at enrollment. We invited study participants from the Boston, MA and Detroit, MI metropolitan areas to attend a study visit and provide urine and blood (hereafter “in-clinic protocol”). We invited all other participants to complete mail-based collection of urine and blood spots (hereafter “mail-based protocol”). We compared overall consent and protocol completion rates, demographic characteristics of those who consented and completed either of the protocols, and costs between mail-based and in-clinic protocols for biospecimen collection. Finally, we described logistical challenges pertaining to reliance on mail-based delivery of time-sensitive biospecimens compared with in-clinic methods.ResultsDuring January 2022-July 2022, 69% of female participants (134/195) and 42% of male participants (31/74) consented to participate in the mail-based protocol. Consent rates for the in-clinic protocol were 39% for female participants (289/739 during March 2014-July 2022) and 25% for male participants (40/157 during March 2017-July 2022). Participants who consented to participate were generally of higher socioeconomic position than non-participants. Deviations from the protocol occurred more frequently within the mail-based protocol but were easily corrected. The cost per participant enrolled was similar across protocols (mail-based: $276.14 vs. in-clinic: $270.38).ConclusionsOur results indicate that mail-based collection of biospecimens may create opportunities to recruit a larger and more geographically diverse participant population at a comparable cost-per-participant enrolled to in-clinic methods.

Supplemental material, sj-pdf-1-cep-10.1177_03331024231161746 for Migraine and risk of hypertensive disorders of pregnancy: A population-based cohort study by Holly M Crowe, Amelia K Wesselink, Elizabeth E Hatch, Lauren A Wise and Susan S Jick in Cephalalgia

Supplemental material, sj-pdf-1-cep-10.1177_03331024231161746 for Migraine and risk of hypertensive disorders of pregnancy: A population-based cohort study by Holly M Crowe, Amelia K Wesselink, Elizabeth E Hatch, Lauren A Wise and Susan S Jick in Cephalalgia

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.

Supplemental material, sj-docx-1-jmh-10.1177_15579883221075520 for A Prospective Study of Male Depression, Psychotropic Medication Use, and Fecundability by Jennifer J. Yland, Craig J. McKinnon, Elizabeth E. Hatch, Michael L. Eisenberg, Yael I. Nillni, Kenneth J. Rothman and Lauren A. Wise in American Journal of Men's Health

BackgroundA causal link between outdoor air pollution and childhood leukemia has been proposed, but some older studies suffer from methodological drawbacks. To the best of our knowledge, no systematic reviews have summarized the most recently published evidence and no analyses have examined the dose-response relation.ObjectiveWe investigated the extent to which outdoor air pollution, especially as resulting from traffic-related contaminants, affects the risk of childhood leukemia.MethodsWe searched all case-control and cohort studies that have investigated the risk of childhood leukemia in relation to exposure either to motorized traffic and related contaminants, based on various traffic-related metrics (number of vehicles in the closest roads, road density, and distance from major roads), or to measured or modeled levels of air contaminants such as benzene, nitrogen dioxide, 1,3-butadiene, and particulate matter. We carried out a meta-analysis of all eligible studies, including nine studies published since the last systematic review and, when possible, we fit a dose-response curve using a restricted cubic spline regression model.ResultsWe found 29 studies eligible to be included in our review. In the dose-response analysis, we found little association between disease risk and traffic indicators near the child's residence for most of the exposure range, with an indication of a possible excess risk only at the highest levels. In contrast, benzene exposure was positively and approximately linearly associated with risk of childhood leukemia, particularly for acute myeloid leukemia, among children under 6 y of age, and when exposure assessment at the time of diagnosis was used. Exposure to nitrogen dioxide showed little association with leukemia risk except at the highest levels.DiscussionOverall, the epidemiologic literature appears to support an association between benzene and childhood leukemia risk, with no indication of any threshold effect. A role for other measured and unmeasured pollutants from motorized traffic is also possible. https://doi.org/10.1289/EHP4381.