Agreement Between the National Cancer Institute's diet history questionnaire II and III in a preconception cohort.

Food frequency questionnaires require updating over time, due to population changes in diet, posing analytical challenges in consistently measuring diet in prospective studies. We compared reliability and agreement between nutrients in two versions of the National Cancer Institute's web-based Diet History Questionnaire (DHQ, III vs. II) in an ongoing North American preconception study. We invited 51 consecutively-enrolled U.S. female participants aged 21-45 years to complete both DHQ versions within a 2-week period, in a randomized order. We compared 30 nutrients from both DHQ versions and calculated within-person reliability using intraclass correlation coefficients (ICCs). Bland-Altman plots and 95% limits of agreement (LOA) were generated to assess nutrient agreement between DHQ versions. We observed highest reliability in percent energy from carbohydrates and cholesterol (ICCs: 0.88; 95% CI: 0.80-0.93) and lowest for percent energy from protein and vitamin D (ICCs: 0.56; 95% CI: 0.34-0.72). At the group level, all nutrients had most observations within the LOA. Bland-Altman plots showed assessment differences between DHQs for protein, fat, monounsaturated fat, and vitamin D. The remaining nutrients showed good agreement and good-to-moderate reliability. Some nutrients may require adjustment and calibration analysis before using them interchangeably across DHQ versions.

Childhood adversity and time-to-pregnancy in a preconception cohort.

We examined the association between childhood adversity and fecundability (the per-cycle probability of conception), and the extent to which childhood social support modified this association. We used data from 6,318 female participants aged 21-45 years in Pregnancy Study Online (PRESTO), a North American prospective preconception cohort study (2013-2022). Participants completed a baseline questionnaire, bimonthly follow-up questionnaires (until pregnancy or a censoring event), and a supplemental questionnaire on experiences across the life course including adverse childhood experiences (ACE) and social support (using the modified Berkman-Syme Social Network Index [SNI]). We used proportional probabilities regression models to compute fecundability ratios (FR) and 95% confidence intervals (CI), adjusting for potential confounders and precision variables. Adjusted FRs for ACE scores 1-3 and ≥4 vs. 0 were 0.91 (95% CI: 0.85, 0.97) and 0.84 (95% CI: 0.77, 0.91), respectively. FRs for ACE scores ≥4 vs. 0 were 0.86 (95% CI: 0.78, 0.94) among participants reporting high childhood social support (SNI ≥4) and 0.78 (95% CI: 0.56, 1.07) among participants reporting low childhood social support (SNI <4). Our findings confirm results from two previous studies and indicate that high childhood social support slightly buffered the effects of childhood adversity on fecundability.

A Prospective Cohort Study of Persistent Endocrine Disrupting Chemicals and Perceived Stress.

Persistent endocrine disrupting chemicals (EDCs) can dysregulate the stress response. We evaluated associations between persistent EDCs and perceived stress among participants from the Study of Environment, Lifestyle and Fibroids (n=1,394), a prospective cohort study of Black women. Participants completed the Perceived Stress Scale (PSS-4) at baseline, and every 20 months through 60 months (range of scores: 0-16); higher scores indicated higher stress. EDCs, including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides, were quantified in plasma samples at baseline. We fit Bayesian Kernel Machine Regression (BKMR) and linear mixed effects models to estimate associations of EDCs (as a mixture and individually) with PSS-4 scores at baseline and at each follow-up visit, respectively. Increasing percentiles of the mixture were not strongly associated with PSS-4 scores at baseline, and no interactions were observed among EDCs. Several individual EDCs (e.g., PFDA, PCB 118, PBDE 99) were associated with higher PSS-4 scores at baseline or follow-up, while other EDCs (e.g., PCB 138/158) were associated with lower PSS-4 scores at baseline or follow-up. The directionality of associations for individual EDCs was inconsistent across follow-up visits. In conclusion, specific EDCs may be associated with perceived stress in Black women.

Residential Proximity to Oil and Gas Development and Mental Health in a North American Preconception Cohort Study: 2013-2023.

Objectives. To evaluate associations between oil and gas development (OGD) and mental health using cross-sectional data from a preconception cohort study, Pregnancy Study Online. Methods. We analyzed baseline data from a prospective cohort of US and Canadian women aged 21 to 45 years who were attempting conception without fertility treatment (2013-2023). We developed residential proximity measures for active OGD during preconception, including distance from nearest site. At baseline, participants completed validated scales for perceived stress (10-item Perceived Stress Scale, PSS) and depressive symptoms (Major Depression Inventory, MDI) and reported psychotropic medication use. We used log-binomial regression and restricted cubic splines to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs). Results. Among 5725 participants across 37 states and provinces, residence at 2 km versus 20 to 50 km of active OGD was associated with moderate to high perceived stress (PSS ≥ 20 vs < 20: PR = 1.08; 95% CI = 0.98, 1.18), moderate to severe depressive symptoms (MDI ≥ 20 vs < 20: PR = 1.27; 95% CI = 1.11, 1.45), and psychotropic medication use (PR = 1.11; 95% CI = 0.97, 1.28). Conclusions. Among North American pregnancy planners, closer proximity to OGD was associated with adverse preconception mental health symptomatology. (Am J Public Health. Published online ahead of print July 11, 2024:e1-e12. https://doi.org/10.2105/AJPH.2024.307730).

Evaluating participant engagement in a preconception cohort study in relation to the Dobbs decision.

BACKGROUND: On June 24th, 2022, the United States (US) Supreme Court's ruling in Dobbs v. Jackson, et al. (hereafter, the Dobbs decision) removed federal-level protections for induced abortion, sparking concerns about reproductive rights and health privacy. Although other pregnancy outcomes (e.g. spontaneous abortion, ectopic pregnancy) are not explicit targets of post-Dobbs abortion bans, study participants may be worried about how their reproductive health data are used by researchers in the post-Dobbs era. OBJECTIVE: To evaluate the extent to which the Dobbs decision influenced participant's engagement in a preconception cohort study. METHODS: We leveraged data spanning 20 weeks before and after the Dobbs decision (4 February 2022, to 11 November 2022) from US participants in Pregnancy Study Online (PRESTO), an internet-based prospective preconception cohort study of couples attempting conception. We categorised participants' state-level abortion access by residential location: banned or restricted rights; limited access; and protected rights. We evaluated three participant engagement outcomes: follow-up questionnaire completion; report of a pregnancy; and clicking on the invitation link for a fertility-tracking app. We fit separate linear regression models and restricted cubic splines to compare outcome prevalence before and after the Dobbs decision by state-level abortion category. RESULTS: A total of 585 newly enrolled participants and 1247 already-enrolled participants received 2802 invitations to complete a follow-up questionnaire. In states with limited or protected abortion rights, we observed little change in participant engagement. In states with banned or restricted abortion rights, however, we observed a 27.12 percentage point reduction (95% confidence interval -43.68, -10.51) in the prevalence of clicking on the invitation link for the fertility-tracking app comparing the post- versus pre-Dobbs periods. CONCLUSIONS: There was some evidence of reduced participant engagement after the Dobbs decision in states with banned or restricted abortion rights, indicating potentially deleterious effects on the conduct of reproductive health studies.

Personal Care Products, Socioeconomic Status, and Endocrine-Disrupting Chemical Mixtures in Black Women.

Personal care products (PCPs) are sources of exposure to endocrine-disrupting chemicals (EDCs) among women, and socioeconomic status (SES) may influence these exposures. Black women have inequitable exposure to EDCs from PCP use, but no study has investigated how exposure to EDCs through PCPs may vary by SES, independent of race. Using data from the Study of Environment, Lifestyle, and Fibroids, a cohort of reproductive-aged Black women (n = 751), we quantified associations between PCPs and urinary biomarker concentrations of EDC mixtures (i.e., phthalates, phenols, parabens) within SES groups, defined using k-modes clustering based on education, income, marital status, and employment. Information about PCP use and SES was collected through questionnaires and interviews. We used principal component analysis to characterize the EDC mixture profiles. Stratified linear regression models were fit to assess associations between PCP use and EDC mixture profiles, quantified as mean differences in PC scores, by SES group. Associations between PCP use and EDC mixture profiles varied by SES group; e.g., vaginal powder use was associated with a mixture of phenols among lower SES women, whereas this association was null for higher SES women. Findings suggest that SES influences PCP EDC exposure in Black women, which has implications for public health interventions.

Exposure to residential greenness, perceived stress, and depressive symptoms in a North American preconception cohort.

BACKGROUND: Studies suggest that greater exposure to natural vegetation (i.e., greenness) is associated with better mental health. However, there is limited research on greenness and mental health in the preconception period, a critical window of exposure in the life course. We investigated the associations of residential greenness with perceived stress and depressive symptoms using cross-sectional data from a cohort of pregnancy planners. METHODS: From 2013 to 2019, we enrolled female-identified participants aged 21-45 years who were trying to conceive without the use of fertility treatment into a North American preconception cohort study (Pregnancy Study Online [PRESTO]). On the baseline questionnaire, participants completed the 10-item Perceived Stress Scale (PSS) and the Major Depression Inventory (MDI). Using geocoded addresses, we estimated residential greenness exposure via satellite imagery (Normalized Difference Vegetation Index [NDVI]) in a 100m buffer. We estimated mean differences and 95% confidence intervals for the association of greenness with perceived stress and depression scores using linear regression models, adjusting for individual and neighborhood sociodemographic characteristics. We also evaluated the extent to which associations were modified by urbanicity and neighborhood socioeconomic status (SES). RESULTS: Among 9718 participants, mean age was 29.9 years, 81.5% identified as non-Hispanic White, 25% had household incomes <$50,000, and mean neighborhood income was $61,932. In adjusted models, higher greenness was associated with lower stress and depression scores (mean difference per interquartile range in greenness: -0.20, 95% CI: -0.39, -0.01; and -0.19, 95% CI: -0.48, 0.10, respectively). The association was stronger among residents of lower SES neighborhoods in urban areas (PSS: -0.57, 95% CI: -1.00, -0.15; MDI: -0.72, 95% CI: -1.40, -0.04). CONCLUSIONS: Higher greenness exposure was associated with lower stress and depressive symptoms among pregnancy planners, particularly in lower-SES neighborhoods.

Ambient air pollution and rate of spontaneous abortion.

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 (PM2.5), nitrogen dioxide (NO2), and ozone (O3) 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 PM2.5, NO2, and O3 with rate of SAB, adjusting for individual- and neighborhood-level factors. Nineteen percent of pregnancies ended in SAB. Greater PM2.5 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). NO2 and O3 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 PM2.5, NO2, and O3 concentrations on SAB incidence in the U.S., but a moderate positive association of PM2.5 with SAB incidence in Canada.

Use of Chemical Hair Straighteners and Fecundability in a North American Preconception Cohort.

Chemical hair straighteners ("relaxers") are used by millions of North Americans, particularly women of color. Hair relaxers may contain endocrine-disrupting compounds, which can harm fertility. We evaluated the association between hair relaxer use and fecundability among 11,274 participants from Pregnancy Study Online (PRESTO), a North American preconception cohort study. During 2014-2022, participants completed a baseline questionnaire in which they reported their history of relaxer use and completed follow-up questionnaires every 8 weeks for 12 months or until pregnancy, whichever came first. We used multivariable-adjusted proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs). Relative to never use, fecundability was lower among current (FR = 0.81, 95% CI: 0.64, 1.03) and former (FR = 0.89, 95% CI: 0.81, 0.98) users of hair relaxers. FRs for first use of hair relaxers at ages <10, 10-19, and ≥20 years were 0.73 (95% CI: 0.55, 0.96), 0.93 (95% CI: 0.83, 1.04), and 0.85 (95% CI: 0.74, 0.98), respectively. Fecundability was lowest among those with longer durations of use (≥10 years vs. never: FR = 0.71, 95% CI: 0.54, 0.91) and more frequent use (≥5 times/year vs. never: FR = 0.82, 95% CI: 0.60, 1.11), but associations were nonmonotonic. In this preconception cohort study, use of chemical hair straighteners was associated with slightly reduced fecundability.

Association of male fatty acid intake with fecundability among couples planning pregnancy.

STUDY QUESTION: To what extent is male fatty acid intake associated with fecundability among couples planning pregnancy? SUMMARY ANSWER: We observed weak positive associations of male dietary intakes of total and saturated fatty acids with fecundability; no other fatty acid subtypes were appreciably associated with fecundability. WHAT IS KNOWN ALREADY: Male fatty acid intake has been associated with semen quality in previous studies. However, little is known about the extent to which male fatty acid intake is associated with fecundability among couples attempting spontaneous conception. STUDY DESIGN, SIZE, DURATION: We conducted an internet-based preconception prospective cohort study of 697 couples who enrolled during 2015-2022. During 12 cycles of observation, 53 couples (7.6%) were lost to follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were residents of the USA or Canada, aged 21-45 years, and not using fertility treatment at enrollment. At baseline, male participants completed a food frequency questionnaire from which we estimated intakes of total fat and fatty acid subtypes. We ascertained time to pregnancy using questionnaires completed every 8 weeks by female participants until conception or up to 12 months. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs for the associations of fat intakes with fecundability, adjusting for male and female partner characteristics. We used the multivariate nutrient density method to account for energy intake, allowing for interpretation of results as fat intake replacing carbohydrate intake. We conducted several sensitivity analyses to assess the potential for confounding, selection bias, and reverse causation. MAIN RESULTS AND THE ROLE OF CHANCE: Among 697 couples, we observed 465 pregnancies during 2970 menstrual cycles of follow-up. The cumulative incidence of pregnancy during 12 cycles of follow-up after accounting for censoring was 76%. Intakes of total and saturated fatty acids were weakly, positively associated with fecundability. Fully adjusted FRs for quartiles of total fat intake were 1.32 (95% CI 1.01-1.71), 1.16 (95% CI 0.88-1.51), and 1.43 (95% CI 1.09-1.88) for the second, third, and fourth vs the first quartile, respectively. Fully adjusted FRs for saturated fatty acid intake were 1.21 (95% CI 0.94-1.55), 1.16 (95% CI 0.89-1.51), and 1.23 (95% CI 0.94-1.62) for the second, third, and fourth vs the first quartile, respectively. Intakes of monounsaturated, polyunsaturated, trans-, omega-3, and omega-6 fatty acids were not strongly associated with fecundability. Results were similar after adjustment for the female partner's intakes of trans- and omega-3 fats. LIMITATIONS, REASONS FOR CAUTION: Dietary intakes estimated from the food frequency questionnaire may be subject to non-differential misclassification, which is expected to bias results toward the null in the extreme categories when exposures are modeled as quartiles. There may be residual confounding by unmeasured dietary, lifestyle, or environmental factors. Sample size was limited, especially in subgroup analyses. WIDER IMPLICATIONS OF THE FINDINGS: Our results do not support a strong causal effect of male fatty acid intakes on fecundability among couples attempting to conceive spontaneously. The weak positive associations we observed between male dietary fat intakes and fecundability may reflect a combination of causal associations, measurement error, chance, and residual confounding. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the National Institutes of Health, grant numbers R01HD086742 and R01HD105863. In the last 3 years, PRESTO has received in-kind donations from Swiss Precision Diagnostics (home pregnancy tests) and Kindara.com (fertility app). L.A.W. is a consultant for AbbVie, Inc. M.L.E. is an advisor to Sandstone, Ro, Underdog, Dadi, Hannah, Doveras, and VSeat. The other authors have no competing interests to report. TRIAL REGISTRATION NUMBER: N/A.

A prospective cohort study of preconception COVID-19 vaccination and miscarriage.

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.

Glycemic Load, Dietary Fiber, Added Sugar, and Spontaneous Abortion in Two Preconception Cohorts.

BACKGROUND: Spontaneous abortion (SAB)-pregnancy loss before the 20th week of gestation-has adverse psychological and physical sequelae. Some medical conditions known to affect insulin sensitivity, including polycystic ovary syndrome and diabetes, can affect the risk of SAB. No prior studies have examined glycemic load and incidence of SAB in populations without conditions known to affect insulin sensitivity. OBJECTIVES: We prospectively evaluated the association between preconception glycemic load and intake of carbohydrates, dietary fiber, and added sugar and risk of SAB. METHODS: During 2013-2020, we recruited pregnancy planners from Denmark (SnartForaeldre.dk; SF) and the United States and Canada (Pregnancy Study Online; PRESTO). Participants completed a baseline questionnaire and a cohort-specific FFQ evaluated for validity. We estimated preconception glycemic load and intake of carbohydrates, dietary fiber, and added sugar from individual foods and mixed recipes. We included 2238 SF and 4246 PRESTO participants who reported a pregnancy during the course of the study. SAB data were derived from questionnaires and population registries. We used Cox proportional hazards regression to estimate HRs and 95% CIs. RESULTS: In the study population, 15% of SF participants and 22% of PRESTO participants experienced SAB. Across both cohorts, there was no appreciable association between glycemic load, carbohydrate quality, dietary fiber, or added sugar intake and SAB. Compared with daily mean glycemic load <110, the HR for women with daily mean glycemic load ≥130 was 0.76 (95% CI: 0.52, 1.10) in SF and 1.01 (95% CI: 0.86, 1.19) in PRESTO. CONCLUSIONS: Diets with high glycemic load, carbohydrates, and added sugars were not consistently associated with risk of SAB in parallel analyses of 2 preconception cohort studies of women in North America and Denmark.

Migraine and risk of hypertensive disorders of pregnancy: A population-based cohort study.

BACKGROUND: Migraine is associated with hypertensive disorders of pregnancy through common pathophysiological features. This study evaluates the association between migraine diagnosis and treatment, and risk of hypertensive disorders of pregnancy. METHODS: We conducted a prospective cohort study in the Clinical Practice Research Datalink GOLD, a large longitudinal database of patient records in the UK. We analyzed data from liveborn or stillborn singleton deliveries from 1993-2020 with at least 24 months of medical history and no history of cardiovascular disease (n = 1,049,839). We ascertained migraine through diagnosis or prescription codes before 20 weeks of gestation and hypertensive disorders of pregnancy through diagnosis codes between 20 weeks of pregnancy and delivery. We used log-binomial regression models to estimate the risk ratio and 95% confidence intervals, comparing risk of hypertensive disorders of pregnancy among individuals with migraine to those without migraine, adjusting for confounders. CONCLUSIONS: A history of migraine prior to pregnancy was associated with an increased risk of hypertensive disorders of pregnancy (RR = 1.17, 95% CI: 1.09-1.26). The greatest risk was among those with pre-pregnancy migraine that persisted into the first trimester (RR = 1.84, 95% CI: 1.35-2.50). Use of migraine medication was associated with a higher risk of hypertensive disorders of pregnancy compared to non-migraineurs (RR = 1.50, 95% CI: 1.15-1.97). Results from this study indicate that migraine is a potential risk factor for hypertensive disorders of pregnancy.

Sexual dysfunction, distress, and care-seeking among females during the preconception period.

BACKGROUND: Despite the high prevalence of female sexual dysfunction in population-based studies and the importance of sexual functioning for mixed-sex couples attempting conception, little is known about female sexual function in the preconception period. OBJECTIVE: This descriptive study aimed to assess the prevalence of female sexual dysfunction, distress, and pain with intercourse in a preconception population of pregnancy planners. The study also explored the extent to which participants discussed their sex lives with a healthcare provider during a preconception visit. STUDY DESIGN: We used data from Pregnancy Study Online, a web-based preconception cohort study (August 2020-October 2022). Eligible participants identified as female and were aged 21 to 45 years, residents of the United States or Canada, attempting pregnancy, and not using fertility treatments at cohort entry. At enrollment, participants completed a detailed baseline questionnaire. Thirty days after enrollment, participants were invited to complete an optional questionnaire about sexual function. Our study included 1120 participants who responded to the sexual function questionnaire within 1 year of completing their baseline questionnaire. We assessed sexual dysfunction using the 6-item Female Sexual Function Index, and sexual distress using the Female Sexual Distress Scale, which assess sexual function and distress in the previous 4 weeks, respectively. We also asked participants whether they had discussed their plans to conceive with a healthcare provider, and if so, whether they discussed their sex lives. If not, we collected information on perceived barriers. RESULTS: Twenty-five percent of the sample met criteria for female sexual dysfunction, whereas 12.2% met the criteria for sexual distress; 8% of our sample reported both sexual dysfunction and sexual distress. Thirty percent reported at least some pain with intercourse in the past 4 weeks. Although over 80% of the sample reported discussing their conception plans with a healthcare provider, 70% of these participants did not discuss their sex lives. The most commonly reported reasons for not discussing their sex life with a provider was not experiencing a sexual health issue, the provider not asking, feeling nervous/uncomfortable/ashamed, and feeling it was not relevant to becoming pregnant or inappropriate to discuss. The percentage of participants who reported discussing their sex lives varied across provider type, with those seeing midwives having the highest percentage (39%), followed by nurse practitioners (36%) and obstetrician-gynecologists (34%). CONCLUSION: Sexual dysfunction, distress, and painful intercourse are prevalent in the preconception period, but participants frequently did not discuss their sex lives when discussing plans to conceive. The provider not asking was a commonly reported barrier. Providers may consider raising the issue of sexual functioning at the time of a preconception visit to better support patients who may be dealing with a sexual function issue while attempting pregnancy. These findings may not generalize beyond a primarily non-Hispanic White, highly educated, and high-income population.

A prospective ultrasound study of cigarette smoking and uterine leiomyomata incidence and growth.

BACKGROUND: Uterine leiomyomata (fibroids) are common, benign neoplasms that contribute substantially to gynecologic morbidity. Some existing epidemiologic studies indicate that cigarette smoking is associated with lower uterine leiomyomata risk. However, no prospective studies have systematically screened an entire study population for uterine leiomyomata using transvaginal ultrasound or evaluated the association between cigarette smoking and uterine leiomyomata growth. OBJECTIVE: This study aimed to examine the association between cigarette smoking and uterine leiomyomata incidence and growth in a prospective ultrasound study. STUDY DESIGN: We enrolled 1693 residents from the Detroit metropolitan area into the Study of Environment, Lifestyle, and Fibroids during 2010 to 2012. Eligible participants were aged 23 to 34 years, had an intact uterus but no previous diagnosis of uterine leiomyomata, and self-identified as Black or African American. We invited participants to complete a baseline visit and 4 follow-up visits over approximately 10 years. At each visit, we used transvaginal ultrasound to assess uterine leiomyomata incidence and growth. Participants provided extensive self-reported data throughout follow-up including exposures to active and passive cigarette smoking in adulthood. We excluded participants who did not return for any follow-up visits (n=76; 4%). We fit Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals for the association between time-varying smoking history and incidence rates of uterine leiomyomata. We fit linear mixed models to estimate the percentage difference and 95% confidence intervals for the association between smoking history and uterine leiomyomata growth. We adjusted for sociodemographic, lifestyle, and reproductive factors. We interpreted our results based on magnitude and precision rather than binary significance testing. RESULTS: Among 1252 participants without ultrasound evidence of uterine leiomyomata at baseline, uterine leiomyomata were detected in 394 participants (31%) during follow-up. Current cigarette smoking was associated with a lower uterine leiomyomata incidence rate (hazard ratio, 0.67; 95% confidence interval, 0.49-0.92). Associations were stronger among participants who had smoked for longer durations (≥15 years vs never: hazard ratio, 0.49; 95% confidence interval, 0.25-0.95). The hazard ratio for former smokers was 0.78 (95% confidence interval, 0.50-1.20). Among never smokers, the hazard ratio for current passive smoke exposure was 0.84 (95% confidence interval, 0.65-1.07). Uterine leiomyomata growth was not appreciably associated with current (percent difference, -3%; 95% confidence interval, -13% to 8%) or former (percent difference, -9%; 95% confidence interval, -22% to 6%) smoking. CONCLUSION: We provide evidence from a prospective ultrasound study that cigarette smoking is associated with lower uterine leiomyomata incidence.

Organic food consumption and fecundability in a preconception cohort study of Danish couples trying to conceive.

BACKGROUND: Little is known about potential health effects of eating organic food in relation to reproduction. OBJECTIVE: We examined associations between organic food consumption and fecundability. METHODS: Data were derived from a preconception cohort study of Danish couples trying to conceive (SnartForaeldre.dk, SF). Participants completed a baseline questionnaire on socio-demographics, anthropometrics and lifestyle and a validated food-frequency questionnaire, which included questions on proportions of organic food consumed within six food groups. Participants were followed up with bimonthly questionnaires for up to 12 months or until pregnancy. Analyses were restricted to 2061 participants attempting pregnancy for ≤6 cycles at enrollment and 1303 with <3 cycles. Fecundability ratios (FRs) and 95% confidence intervals (CI) were estimated by proportional probabilities regression models adjusted for potential confounders including age, lifestyle and socioeconomic factors. Associations were examined for vegetables, fruits, cereals, dairy products, eggs and meat, separately, and for the overall pattern of organic food consumption (organic sum score). RESULTS: The final analytic sample comprised 2069 participants. In the full cohort, organic food consumption was not meaningfully associated with fecundability. Among participants <3 cycles of pregnancy attempt at study entry (n = 1303), the FR was 1.11 (95% CI 0.93, 1.33) for the category 'less than half', for 'more than half' the FR was 1.17 (95% CI 0.99, 1.38) and for 'almost everything' the FR was 1.12 (95% CI 0.97, 1.28). CONCLUSION: Higher consumption of organic foods was not meaningfully associated with fecundability, although slightly greater fecundability was seen among participants with <3 cycles of pregnancy attempt time.

Exposure to airborne polychlorinated biphenyls and type 2 diabetes in a Danish cohort.

BACKGROUND: Previous research indicates an association between higher-chlorinated polychlorinated biphenyls (PCBs) and type 2 diabetes (T2D). However, less is known about the extent to which PCB exposure in indoor air, composed primarily of lower-chlorinated PCBs, affects T2D risk. We assessed the association between indoor air exposure to PCBs in residential buildings and T2D incidence. METHODS: The register-based 'Health Effects of PCBs in Indoor Air' (HESPAIR) cohort comprises 51,921 Danish residents of two residential areas with apartments built with and without PCB-containing materials (reference apartments). We assessed exposure status by combining register-based information on relocation history with extrapolated values of exposure based on PCB-measurements in indoor air from subsets of the apartments. T2D cases were identified in the Danish registers during 1977-2018. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression analyses with time-varying exposure. RESULTS: We identified 2737 incident T2D cases during the follow-up. Exposure to ≥3300 ng/m3 PCB × year (3rd tertile of PCByear) was associated with higher risk of T2D (HR 1.15, 95% CI 1.02-1.30) compared with exposure to <300 ng/m3 PCB × year (reference). However, among individuals with lower cumulated PCByear, the risk was similar to residents with exposure <300 ng/m3 PCB × year (300-899 ng/m3 PCB × year: HR 0.98, 95% CI 0.87-1.11; 900-3299 ng/m3 PCB × year: HR 0.96, 95% CI 0.83-1.10). DISCUSSION: We observed a marginally higher risk of T2D, but there was no evidence of an exposure-response relationship. The results should be interpreted with caution until confirmed in other independent studies of PCB exposure in indoor air.

Misconceptions About the Direction of Bias From Nondifferential Misclassification.

Measurement error is pervasive in epidemiologic research. Epidemiologists often assume that mismeasurement of study variables is nondifferential with respect to other analytical variables and then rely on the heuristic that "nondifferential misclassification will bias estimates towards the null." However, there are many exceptions to the heuristic for which bias towards the null cannot be assumed. In this paper, we compile and characterize 7 exceptions to this rule and encourage analysts to take a more critical and nuanced approach to evaluating and discussing bias from nondifferential mismeasurement.

A Prospective Cohort Study of COVID-19 Vaccination, SARS-CoV-2 Infection, and Fertility.

Some reproductive-aged individuals remain unvaccinated against coronavirus disease 2019 (COVID-19) because of concerns about potential adverse effects on fertility. Using data from an internet-based preconception cohort study, we examined the associations of COVID-19 vaccination and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with fertility among couples trying to conceive spontaneously. We enrolled 2,126 self-identified female participants aged 21-45 year residing in the United States or Canada during December 2020-September 2021 and followed them through November 2021. Participants completed questionnaires every 8 weeks on sociodemographics, lifestyle, medical factors, and partner information. We fit proportional probabilities regression models to estimate associations between self-reported COVID-19 vaccination and SARS-CoV-2 infection in both partners with fecundability (i.e., the per-cycle probability of conception), adjusting for potential confounders. COVID-19 vaccination was not appreciably associated with fecundability in either partner (female fecundability ratio (FR) = 1.08, 95% confidence interval (CI): 0.95, 1.23; male FR = 0.95, 95% CI: 0.83, 1.10). Female SARS-CoV-2 infection was not strongly associated with fecundability (FR = 1.07, 95% CI: 0.87, 1.31). Male infection was associated with a transient reduction in fecundability (for infection within 60 days, FR = 0.82, 95% CI: 0.47, 1.45; for infection after 60 days, FR = 1.16, 95% CI: 0.92, 1.47). These findings indicate that male SARS-CoV-2 infection may be associated with a short-term decline in fertility and that COVID-19 vaccination does not impair fertility in either partner.

A Prospective Cohort Study of Seasonal Variation in Spontaneous Abortion.

BACKGROUND: Up to 30% of pregnancies end in spontaneous abortion, yet few risk factors have been identified. Examining seasonal patterns in risk of spontaneous abortion can generate new hypotheses regarding environmental and lifestyle determinants. METHODS: We used data from Pregnancy Study Online-a preconception cohort study of pregnancy planners from the United States and Canada-to examine seasonal variation in spontaneous abortion risk. We enrolled 12,197 women during 2013 to 2020, 6104 of whom reported a conception within 12 months of enrollment. On follow-up questionnaires, participants reported date of spontaneous abortion and weeks gestation at time of loss. We used periodic regression to estimate two aspects of seasonal occurrence: peak/low ratio-a measure of intensity of seasonal variation-and peak timing. We examined season at risk (from the date of each gestational week) in relation to spontaneous abortion; in a secondary analysis, we examined season of conception in relation to spontaneous abortion. We controlled for seasonal patterns in attempt initiation via month the pregnancy attempt began. RESULTS: Almost 20% of women experienced spontaneous abortion. Risk was highest in late August, with a peak/low ratio of 1.3 (95% confidence interval [CI] = 1.1, 1.6). This seasonal pattern was evident almost exclusively for spontaneous abortion at <8 weeks since the last menstrual period date (peak/low ratio = 1.4; 95% CI = 1.2, 1.8), and associations were stronger among women living in the Southern and Midwestern United States. CONCLUSIONS: Environmental or lifestyle factors more prevalent in late summer may be associated with increased risk of early spontaneous abortion.