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Epidemiologists face a unique challenge in measuring risk relationships involving time-varying exposures in early pregnancy. Each week in early pregnancy is distinct in its contribution to fetal development, and this period is commonly characterized by shifts in maternal behavior and, consequently, exposures. In this simulation study, we used alcohol as an example of an exposure that often changes during early pregnancy and miscarriage as an outcome affected by early exposures. Data on alcohol consumption patterns from more than 5,000 women in the Right From the Start cohort study (United States, 2000-2012) informed measures of the prevalence of alcohol exposure, the distribution of gestational age at cessation of alcohol use, and the likelihood of miscarriage by week of gestation. We then compared the bias and precision of effect estimates and statistical power from 5 different modeling approaches in distinct simulated relationships. We demonstrate how the accuracy and precision of effect estimates depended on alignment between model assumptions and the underlying simulated relationship. Approaches that incorporated data about patterns of exposure were more powerful and less biased than simpler models when risk depended on timing or duration of exposure. To uncover risk relationships in early pregnancy, it is critical to carefully define the role of exposure timing in the underlying causal hypothesis., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The time between arrest of pregnancy development and miscarriage represents a window in which the pregnancy is nonviable and not developing. In effect, the pregnancy loss has already occurred, and additional exposure cannot influence its outcome. However, epidemiologic studies of miscarriage traditionally use gestational age at miscarriage (GAM) to assign time in survival analyses, which overestimates duration of exposure and time at risk. In Right From the Start, a pregnancy cohort study (2000-2012), we characterized the gap between estimated gestational age at arrest of development (GAAD) and miscarriage using transvaginal ultrasound in 500 women recruited from 3 states (North Carolina, Tennessee, and Texas). We compared effect estimates from models using GAAD with GAM to assign time at risk through a simulation study of several exposure patterns with varying effect sizes. The median gap between GAAD and miscarriage was 23 days (interquartile range, 15-32). Use of GAAD decreased the bias and variance of the estimated association for time-varying exposures, whereas half the time using GAM led to estimates that differed from the true effect by more than 20%. Using GAAD to assign time at risk should result in more accurate and consistent characterization of miscarriage risk associated with time-varying exposures., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We sought to determine the relationship of fibroids to pregnancy loss in a prospective cohort in which fibroid status was uniformly documented in early pregnancy. Participants had an intake interview, transvaginal ultrasonography, computer-assisted telephone interview, and follow-up assessment of outcomes. We recruited diverse participants for the Right From the Start study from 8 metropolitan areas in 3 states in the United States during 2000-2012. Participants were at least 18 years of age, trying to become pregnant or at less than 12 weeks' gestation, not using fertility treatments, fluent in English or Spanish, and available for telephone interviews. Miscarriage was defined as loss before 20 weeks' gestation. Fibroid presence, number, type, and volume were assessed using standardized ultrasonography methods. We used proportional hazards models to estimate associations. Among 5,512 participants, 10.4% had at least 1 fibroid, and 10.8% experienced a miscarriage. Twenty-three percent had experienced a prior miscarriage and 52% prior births. Presence of fibroids was associated with miscarriage in models without adjustments. Adjusting for key confounders indicated no increase in risk (adjusted hazard ratio = 0.83, 95% confidence interval: 0.63, 1.08). No characteristic of fibroids was associated with risk. Prior evidence attributing miscarriage to fibroids is potentially biased. These findings imply that surgical removal of fibroids to reduce risk of miscarriage deserves careful scrutiny., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Age at menarche has been associated with several reproductive conditions, and frequencies differ by race. Racial disparities also impact fibroid risk. We comprehensively examined the relationship between age at menarche, fibroid characteristics, and race. Women were enrolled in Right From the Start (2001-2010), a multistate study that systematically screened for fibroids during very early pregnancy. Endovaginal ultrasounds were conducted, and fibroid presence, number, type, volume, and diameter were recorded according to standardized definitions. Generalized estimating equations adjusted for correlations within study site were used to estimate associations between age at menarche and fibroid status and to test for interactions with race. Of 5,023 participants, 11% had a fibroid. Seven percent underwent menarche before 11 years of age and 11% at 15 years or later. We did not observe interactions between age at menarche and race. A 1-year increase in age at menarche was inversely associated with fibroids (adjusted risk ratio = 0.87, 95% confidence interval: 0.82, 0.91). Early age at menarche had a similar positive association in individual analyses with fibroid size, type, and location but was stronger for multiple fibroids (adjusted risk ratio = 0.75, 95% confidence interval: 0.68, 0.83). Our findings confirm other reports of an association between age at menarche and fibroid development (regardless of characteristics), demonstrate no effect modification by race, and suggest a stronger association for women with multiple fibroids, possibly reflecting a stronger association for early-onset disease.

Many adverse pregnancy outcomes differ by race. We examined the association between self-reported race and miscarriage (pregnancy loss at <20 weeks) in a community-based pregnancy cohort. Women from the southeastern United States (North Carolina, Texas, and Tennessee) were enrolled in "Right from the Start" from 2000 to 2009. They were recruited while trying to conceive or during early pregnancy. Participants completed study ultrasound examinations, interviews, and consent forms for review of medical records. We used proportional hazard models to examine miscarriage risk among black women compared with white women, adjusted for confounders. There were 537 observed miscarriages among 4,070 women, 23% of whom self-identified as black (n = 932). The life table-adjusted cumulative risk of loss after gestational week 5 was 21.3%. With adjustment for age and alcohol use, blacks had increased risk of miscarriage compared with whites (adjusted hazard ratio = 1.57, 95% confidence interval: 1.27, 1.93). When risk of loss before gestational week 10 was dichotomized at the median gestational age, there was little difference, but black women had a greater risk thereafter compared with white women (adjusted hazard ratio = 1.93, 95% confidence interval: 1.48, 2.51). Early pregnancy ultrasound examinations did not differ by race. In summary, self-reported race is independently associated with risk of miscarriage, and the higher risk for black women is concentrated in gestational weeks 10-20.

The World Health Organization estimates that the number of obese and overweight adults has increased to 1.6 billion, with concomitant increases in comorbidity. While genetic factors for obesity have been extensively studied in Caucasians, fewer studies have investigated genetic determinants of body mass index (BMI; weight (kg)/height (m)(2)) in African Americans. A total of 38 genes and 1,086 single nucleotide polymorphisms (SNPs) in African Americans (n = 1,173) and 897 SNPs in Caucasians (n = 1,165) were examined in the Southern Community Cohort Study (2002-2009) for associations with BMI and gene × environment interactions. A statistically significant association with BMI survived correction for multiple testing at rs4140535 (β = -0.04, 95% confidence interval: -0.06, -0.02; P = 5.76 × 10(-5)) in African Americans but not in Caucasians. Gene-environment interactions were observed with cigarette smoking and a SNP in ADIPOR1 in African Americans, as well as between a different SNP in ADIPOR1 and physical activity in Caucasians. A SNP in PPARGC1A interacted with alcohol consumption in African Americans, and a different SNP in PPARGC1A was nominally associated in Caucasians. A SNP in CYP19A1 interacted with dietary energy intake in African Americans, and another SNP in CYP191A had an independent association with BMI in Caucasians.