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Fibroid treatments that have few side-effects and can preserve fertility are a clinical priority. We studied the association between serum vitamin D and uterine fibroid growth, incidence, and loss.A prospective community cohort study (enrollment 2010-2012) with 4 study visits over 5 years to conduct standardized ultrasounds, measure 25-hydroxyvitamin D (25(OH)D), and update covariates.Detroit, Michigan area.Self-identified African American or Black women aged 23-35 at enrollment without previous clinical diagnosis of fibroids.Serum 25(OH)D measured using immunoassay or liquid chromatography-tandem mass spectrometry.The primary outcomes were fibroid growth, as measured by change in log volume per 18 months, and fibroid incidence (first detection of fibroid in previously fibroid-free uterus). Adjusted growth estimates from linear mixed models were converted to estimated difference in volume for high vs. low 25(OH)D. Incidence differences were estimated as hazard ratios from age-specific Cox regression. A secondary outcome fibroid loss (reduction in fibroid number between visits), was modeled using Poisson regression. Covariates (reproductive and hormonal variables, demographics, body mass index, current smoking) and 25(OH)D were modeled as time-varying factors.At enrollment among 1,610 participants with ≥1 follow-up ultrasound, mean age was 29.2 years, 73% had deficient vitamin D (20ng/mL), and only 7% had sufficient vitamin D (≥30ng/mL). Serum 25(OH)D ≥20ng/mL compared with20ng/mL was associated with an estimated 9.7% reduction in fibroid growth (95% confidence interval [CI]: -17.3%, -1.3%), similar to the minimally adjusted estimate -8.4% (95% CI: -16.4, 0.3). Serum 25(OH)D ≥30ng/mL compared with30ng/mL was associated with an imprecise 22% reduction in incidence (adjusted hazard ratio=0.78; 95% CI: 0.47, 1.30), similar to the unadjusted estimate of 0.84 (95% CI: 0.51, 1.39). The30ng/mL group also had a 32% increase in fibroid loss (adjusted risk ratio=1.32; 95% CI: 0.95, 1.83).Our data support the hypothesis that high concentrations of vitamin D decrease fibroid development but are limited by the few participants with serum 25(OH)D ≥30ng/mL. Interventional trials that raise and maintain 25(OH)D concentrations30ng/mL and then prospectively monitor fibroid development are needed to further assess supplemental vitamin D efficacy and determine optimal treatment protocols.

Investigate the association between use of depot medroxyprogesterone acetate (DMPA) (an injectable progestin-only contraceptive) and leiomyoma development.We conducted a cohort study in the Detroit, Michigan, area that involved four clinic visits at 20-month intervals over 5 years (2010-2018) and used a standardized ultrasonography protocol to prospectively measure leiomyomas 0.5 cm or more in diameter. Participants were 1,693 self-identified Black women aged 23-35 years with no prior leiomyoma diagnosis and no hysterectomy. For this substudy, years since last use of DMPA was ascertained from questionnaire data at every visit. Leiomyoma incidence was defined as the first visit with an observed leiomyoma among women who were leiomyoma-free at enrollment. Depot medroxyprogesterone acetate associations were examined with Cox models. Leiomyoma growth was calculated as the change in log-volume for leiomyomas matched at successive visits and was modeled using linear mixed models accounting for clustered data. Leiomyoma loss, defined as a reduction in leiomyoma number in successive visits, was modeled using Poisson regression. All models used time-varying exposure and covariates.Of participants with at least one follow-up visit (N=1,610), 42.9% had ever used DMPA. Participants exposed to DMPA within the previous 2 years experienced reduced leiomyoma development during the subsequent observation interval compared with never users, including lower leiomyoma incidence (5.2% vs 10.7%), adjusted hazard ratio 0.6 (95% CI 0.4-1.0), 42.0% lower leiomyoma growth (95% CI -51.4 to -30.7) and 60% greater leiomyoma loss (adjusted risk ratio 1.6, 95% CI 1.1-2.2). Excess leiomyoma loss was also seen for those who used DMPA 2-4 years before the visit compared with never users, 2.1-fold increase (95% CI 1.4-3.1).Recent use of DMPA was associated with reduced leiomyoma development and increased leiomyoma loss. Such changes in early leiomyoma development in young women could delay symptom onset and reduce the need for invasive treatment.

Adverse pregnancy outcomes (APOs) and early menopause are each associated with increased risk of cardiovascular disease (CVD); whether APOs are associated with age at menopause is unclear. We examined the association of gestational diabetes (GDM), hypertensive disorders of pregnancy (HDP), preterm birth, and multiple gestation with age at natural menopause.Observational, prospective study within the Nurses' Health Study II cohort (1989-2019).Risk of early natural menopause, defined as occurring before the age of 45 years, and age at onset of natural menopause (hazard ratio (HR)1 indicates younger age at menopause).The mean [SD] baseline age of 69,880 parous participants was 34.5 [4.7] years. Compared with participants who had a term singleton first birth, those with a term multiple-gestation first birth had higher risk of early menopause (HR: 1.65, 95% CI: 1.05, 2.60) and younger age at natural menopause (HR: 1.46, 95% CI: 1.31, 1.63). Estimates for preterm multiple gestation were of similar magnitude. Menopause occurred at a younger age for those with a preterm birth with spontaneous labor (HR: 1.08, 95% CI: 1.03, 1.14) compared to those with a term birth with spontaneous labor. Conversely, estimates for GDM (HR: 0.95, 95% CI: 0.89, 1.02) and HDP (preeclampsia, HR: 0.93, 95% CI: 0.89, 0.97) suggested an association with older age at menopause.In this large cohort study, several statistically significant associations between APOs and age at natural menopause were observed. A deeper understanding of the relationships among APOs, menopause, and CVD is needed to help identify people at higher risk for early menopause and later CVD.

Reproductive tract infections have long been hypothesized to be risk factors for development of uterine fibroids, but few studies have investigated the issue. In our 2016 cross-sectional analysis from the Study of Environment, Lifestyle and Fibroids (2010–2018), a large Detroit, Michigan, community-based cohort study of 23- to 35-year-old African-American women with ultrasound fibroid screening, we found no association between a very prevalent reproductive tract infection, herpes simplex virus type 2 (HSV-2), and fibroids. With prospective data from the cohort (ultrasounds performed every 20 months over 5 years), we examined HSV-2’s associations with fibroid incidence (among 1,208 women who were fibroid-free at baseline) and growth (among women with fibroids at baseline or diagnosed during the study). Using Cox proportional hazards models, we computed adjusted hazard ratios and 95% confidence intervals for fibroid incidence comparing HSV-2–seropositive women with HSV-2–seronegative women. The influence of HSV-2 infection on growth was assessed on the basis of the difference in fibroid size between successive ultrasounds (1,323 growth measures) using a linear mixed model, estimating the percent difference in growth scaled to 18 months. HSV-2 seropositivity was not associated with fibroid incidence (adjusted hazard ratio = 0.88, 95% confidence interval: 0.69, 1.12) or growth (estimated growth difference = 3.1%, 95% confidence interval: −5.8, 13.0). Women can be reassured that HSV-2 infection is unlikely to increase their risk of fibroid-related health problems, given these longitudinal measures.

Scientists from multiple basic disciplines and an international group of physician-scientists from the field of obstetrics and gynecology presented recent studies and discussed new and evolving theories of uterine fibroid etiology, growth and development at The Basic Science of the Uterine Fibroids meeting, sponsored by the Campion Fund and the National Institute of Environmental Health Sciences. The purpose was to share up-to date knowledge and to stimulate new concepts regarding the basic molecular biology and pathophysiology of uterine fibroids, and to promote future collaborations. The meeting was held at the National Institutes of Environmental Health Sciences in North Carolina on February 28, 2020. Speakers reviewed recent advances in cellular and molecular processes that contribute to fibroid growth and new opportunities for treatment. At the conclusion of the conference, attendees identified important new directions for future research.

STUDY QUESTION How do the calciotropic hormones (25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and intact parathyroid hormone (iPTH)) vary across the menstrual cycle and do cyclic patterns of reproductive hormones (estradiol, progesterone, LH, FSH) differ by vitamin D status? SUMMARY ANSWER Calciotropic hormones vary minimally across the menstrual cycle; however, women with 25-hydroxyvitamin D below 30 ng/ml have lower mean estradiol across the menstrual cycle. WHAT IS KNOWN ALREADY Prior human studies suggest that vitamin D status is associated with fecundability, but the mechanism is unknown. Exogenous estrogens and prolonged changes in endogenous estradiol (pregnancy or menopause) influence concentrations of 25-hydroxyvitamin D. In vitro, treatment with 1,25-dihydroxyvitamin D increases steroidogenesis in ovarian granulosa cells. There are little data about changes in calciotropic hormones across the menstrual cycle or cyclic patterns of reproductive hormones by categories of vitamin D status. STUDY DESIGN, SIZE, DURATION A prospective cohort study of 89 self-identified white women aged 18–44, across two menstrual cycles. Participants were a subset of the BioCycle Study, a community-based study conducted at the University of Buffalo, 2005–2007. PARTICIPANTS/MATERIALS, SETTING, METHODS Eligible participants had self-reported regular menstrual cycles between 21 and 35 days and were not using hormonal contraception or vitamins. Early morning fasting blood samples were drawn at up to eight study visits per cycle. Visits were timed to capture information in all cycle phases. Serum samples for 89 women (N = 163 menstrual cycles) were analyzed for estradiol, progesterone, LH, FSH and 25-hydroxyvitamin D (25(OH)D). Variability in calciotropic hormones within and across menstrual cycles was assessed using intraclass correlation coefficients and non-linear mixed models. Given the relative stability of the calciotropic hormones across the menstrual cycle, non-linear mixed models were used to examine differences in the cyclic patterns of estradiol, progesterone, LH and FSH by categories of each calciotropic hormone (split at the median). These models were conducted for all ovulatory cycles (N = 142 ovulatory menstrual cycles) and were adjusted for age, BMI (measured in clinic) and self-reported physical activity. MAIN RESULTS AND THE ROLE OF CHANCE Median 25(OH)D concentration was 29.5 ng/ml (SD 8.4), and only 6% of women had vitamin D deficiency ( LIMITATIONS, REASONS FOR CAUTION Women included in this study had self-reported ‘regular’ menstrual cycles and very few were found to have 25(OH)D deficiency. This limits our ability to examine cycle characteristics, anovulation and the effects of concentrations of the calciotropic hormones found in deficient individuals. Additionally, the results may not be generalizable to women with irregular cycles, other races, or populations with a higher prevalence of vitamin D deficiency. WIDER IMPLICATIONS OF THE FINDINGS These findings support current clinical practice that does not time testing for vitamin D deficiency to the menstrual cycle phase. We find that women with lower vitamin D status (lower 25(OH)D or higher iPTH) have lower mean concentrations of estradiol across the menstrual cycle. Although this study cannot identify a mechanism of action, further in vitro work or clinical trials may help elucidate the biologic mechanisms linking calciotropic and reproductive hormones. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Intramural Research Programs of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (contract numbers: HHSN275200403394C, HHSN275201100002I and Task 1 HHSN27500001) and the National Institute of Environmental Health Sciences. There are no competing interests.

Vitamin D may protect against breast cancer. Although Black/African American women and Hispanic/Latina women have lower circulating vitamin D levels than non-Hispanic White women, few studies have examined the association between vitamin D and breast cancer within these racial/ethnic groups.The vitamin D-breast cancer association was evaluated using a case-cohort sample of self-identified Black/African American and non-Black Hispanic/Latina women participating in the US-wide Sister Study cohort. Circulating 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)2D) were measured using liquid chromatography-tandem mass spectrometry in blood samples collected at the baseline from 415 women (290 Black/African American women and 125 non-Black Hispanic/Latina women) who developed breast cancer. These were compared to concentrations in 1545 women (1084 Black/African American women and 461 Hispanic/Latina women) randomly selected from the cohort. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).Over a mean follow-up of 9.2 years, women with circulating 25(OH)D concentrations above the clinical cut point for deficiency (20.0 ng/mL) had lower breast cancer rates than women with concentrations ≤ 20 ng/mL (HR, 0.79; 95% CI, 0.61-1.02). The inverse association was strongest among Hispanic/Latina women (HR, 0.52; 95% CI, 0.29-0.93), with a weaker association observed among Black/African American women (HR, 0.89; 95% CI, 0.68-1.18; P for heterogeneity = 0.13). There were no clear differences by menopausal status, follow-up time, estrogen receptor status, or invasiveness. Neither 24,25(OH)This prospective study supports the hypothesis that vitamin D may be protective against breast cancer incidence in women, including non-Black Hispanic/Latina and Black/African American women.Vitamin D may protect against breast cancer. Although women of color have lower average vitamin D levels than non-Hispanic White women, few studies have considered the role of race/ethnicity. In a sample of self-identified Black/African American and Hispanic/Latina women, we observed that vitamin D concentrations measured in blood were inversely associated with breast cancer, particularly among Latinas. These findings indicate that vitamin D may protect women against breast cancer, including those in racial/ethnic groups with low average circulating levels.

Background Vitamin D has anticarcinogenic properties, but a relationship between vitamin D supplement use and breast cancer is not established. Few studies have accounted for changes in supplement use over time or evaluated racial-ethnic differences. Methods The Sister Study is a prospective cohort of 50,884 women with 35-74 years of age who had a sister with breast cancer, but no breast cancer themselves at enrollment (2003-2009). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between vitamin D supplement use and incident breast cancer (3,502 cases; median follow-up 10.5 years). Results Vitamin D supplement use was common, with 64% reporting ever use (at least once per month) in the year before enrollment. Considering supplement use over time, ever use of vitamin D supplements was not meaningfully associated with breast cancer (HR = 0.96, 95% CI = 0.88, 1.0), relative to never use. However, after adjusting for prior use, recent use of vitamin D supplements ≥1/month was inversely associated with breast cancer (HR = 0.88, 95% CI = 0.78, 1.0), relative to nonrecent use. The inverse association was stronger for ductal carcinoma in situ (HR = 0.67, 95% CI = 0.52, 0.87) than invasive breast cancer (HR = 0.94, 95% CI = 0.72, 1.1, p-for-heterogeneity = 0.02). Supplement use was less common among African American/Black (56%) and non-Black Hispanic/Latina (50%) women than non-Hispanic White women (66%), but there was limited evidence of racial-ethnic differences in HRs (p-for-heterogeneity = 0.16 for ever use, P = 0.55 for recent). Conclusions Our findings are consistent with the hypothesis that recent vitamin D use is inversely associated with breast cancer risk.

Background: Women with one lifetime singleton pregnancy have increased risk of cardiovascular disease (CVD) mortality compared with women who continue reproduction particularly if the pregnancy had complications. Women with twins have higher risk of pregnancy complications, but CVD mortality risk in women with twin pregnancies has not been fully described. Objectives: We estimated risk of long-term CVD mortality in women with naturally conceived twins compared to women with singleton pregnancies, accounting for lifetime number of pregnancies and pregnancy complications. Methods: Using linked data from the Medical Birth Registry of Norway and the Norwegian Cause of Death Registry, we identified 974,892 women with first pregnancy registered between 1967 and 2013, followed to 2020. Adjusted hazard ratios (aHR) with 95% confidence intervals (CI) for maternal CVD mortality were estimated by Cox regression for various reproductive history (exposure categories): (1) Only one twin pregnancy, (2) Only one singleton pregnancy, (3) Only two singleton pregnancies, (4) A first twin pregnancy and continued reproduction, (5) A first singleton pregnancy and twins in later reproduction and (6) Three singleton pregnancies (the referent group). Exposure categories were also stratified by pregnancy complications (pre-eclampsia, preterm delivery or perinatal loss). Results: Women with one lifetime pregnancy, twin or singleton, had increased risk of CVD mortality (adjusted hazard [HR] 1.72, 95% confidence interval [CI] 1.21, 2.43 and aHR 1.92, 95% CI 1.78, 2.07, respectively), compared with the referent of three singleton pregnancies. The hazard ratios for CVD mortality among women with one lifetime pregnancy with any complication were 2.36 (95% CI 1.49, 3.71) and 3.56 (95% CI 3.12, 4.06) for twins and singletons, respectively. Conclusions: Women with only one pregnancy, twin or singleton, had increased long-term CVD mortality, however highest in women with singletons. In addition, twin mothers who continued reproduction had similar CVD mortality compared to women with three singleton pregnancies. publishedVersion

OBJECTIVE: To examine the association of urinary concentrations of phenols, parabens, and triclocarban with incidence and growth of uterine leiomyomata (UL; fibroids). DESIGN: Case-cohort study, nested within the Study of Environment, Lifestyle and Fibroids (SELF), a prospective cohort study. SETTING: Clinic visits at baseline and every 20 months for 60 months. PATIENTS: 754 Black women aged 23–35 years residing in the Detroit, Michigan area (enrolled during 2010–2012). INTERVENTION: None. MAIN OUTCOME MEASURES: At each study visit, women underwent transvaginal ultrasound for measurement of UL incidence and growth and provided urine specimens in which we quantified concentrations of 7 phenols, 4 parabens, and triclocarban. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) characterizing the relation of urinary biomarker concentrations with UL incidence during 60 months of follow-up. In a subset of UL detected and measured at multiple time points, we used linear regression to assess associations between biomarker concentrations and UL growth. RESULTS: Urinary biomarker concentrations were generally inversely associated with UL incidence, but associations were weak and non-monotonic. For example, HRs comparing concentrations ≥90(th) with

Few studies have characterized life course hair product usage beyond ever/never. We investigated hair product use from childhood to adulthood, usage patterns in adulthood, and socioeconomic status (SES) correlates among African-American (AA) women. Using self-reported data from 1,555 AA women enrolled in the Study of Environment, Lifestyle, and Fibroids (2010-2018), we estimated the usage frequency of chemical relaxer/straightener (≥twice/year, once/year, rarely/never) and leave-in/leave-on conditioner (≥once/week, 1-3 times/month, rarely/never) during childhood, adolescence, and adulthood. Latent class analysis was used to identify patterns of adulthood usage of multiple hair products. SES was compared across latent classes. With a mean age of 33±3.4 years, most women reported ever using chemical relaxers/straighteners (89%), and use ≥twice/year increased from childhood (9%) to adolescence (73%) but decreased in adulthood (29%). Leave-in/leave-on conditioner use followed the same pattern. Each of three identified latent classes reported frequent styling product use and similarly low frequency of relaxer/straightener use. Class One was unlikely to use any other products, Class Two moderately used shampoo and conditioner, and Class Three frequently used multiple product types (e.g., moisturizers, conditioners). Participants in the latter two classes reported higher SES. Ever/never characterization may miss important and distinctive patterns of hair product use, which may vary by SES.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals used in commercial and consumer goods. Black women are underrepresented in studies of PFAS exposure. METHODS: We performed a cross-sectional analysis of correlates of plasma PFAS concentrations among 1,499 Black women aged 23–35 participating in the Study of Environment, Lifestyle, and Fibroids (SELF), a Detroit-based cohort study. At baseline (2010–2012), participants provided questionnaire data on socio-demographics; behaviors; diet; and menstrual, contraceptive, and reproductive histories. Using mass spectrometry in non-fasting plasma samples collected at enrollment, we quantified several PFAS, including perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnDA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA). We used linear regression to calculate percentage differences (%D) and 95% confidence intervals (CIs) for associations between selected correlates and PFAS concentrations, adjusting for all other correlates. RESULTS: PFHxS, PFOS, PFOA, and PFNA were detected in ≥97% of women; PFDA in 86%; MeFOSAA in 70%; and PFUnDA in 52%. Age, income, education, and intakes of water, alcohol, and seafood were positively associated with several PFAS. Current smoking was positively associated with MeFOSAA. Body mass index was inversely associated with most PFAS, except PFHxS. Strong inverse associations (%D; 95% CI) were observed between parity (≥3 vs. 0 births) and PFHxS (−34.7; −43.0, −25.1) and PFOA (−33.1; −39.2, −26.3); breastfeeding duration (≥6 months vs. nulliparous) and PFOA (−31.1; −37.8, −23.7), PFHxS (−24.2; −34.5, −12.3), and PFOS (−18.4; −28.3, −7.1); recent birth (

BACKGROUND: Uterine fibroids are a common cause of heavy menstrual bleeding and pain. Treatment with the combination of relugolix (an oral gonadotropin-releasing hormone-receptor antagonist), estradiol, and norethindrone acetate, administered once daily, may have efficacy in women with uterine fibroids and heavy bleeding while avoiding hypoestrogenic effects. METHODS: We conducted two replicate international, double-blind, 24-week, phase 3 trials involving women with fibroid-associated heavy menstrual bleeding. Participants were randomly assigned in a 1:1:1 ratio to receive once-daily placebo, relugolix combination therapy (40 mg of relugolix, 1 mg of estradiol, and 0.5 mg of norethindrone acetate), or delayed relugolix combination therapy (40 mg of relugolix monotherapy, followed by relugolix combination therapy, each for 12 weeks). The primary efficacy end point in each trial was the percentage of participants with a response (volume of menstrual blood loss

Preeclampsia is a heterogeneous disease characterized by new onset of hypertension along with signs of organ damage, affects 2% to 8% of pregnancies, and can result in serious complications to the mother and her child. There is little empirical evidence on the clinical importance of differences in blood pressure trajectories over the course of pregnancy, particularly in pregnancies affected by preeclampsia. We undertook an investigation of longitudinal changes in gestational blood pressure in a nested case-control study of preeclampsia in MoBa (Norwegian Mother, Father and Child Cohort Study). We included 1906 validated preeclampsia cases and 1413 validated controls. We derived blood pressure trajectory clusters using longitudinal k-means clustering and examined demographic and early-pregnancy predictors and birth outcomes, in relation to clusters. Maternal age, prepregnancy body mass index, and parity were substantially different across blood pressure clusters of cases. Pregnancy outcomes, including preterm birth, small for gestational age, and birthweight Z score, were meaningfully worse for individuals with a more rapid increase in blood pressure, as well as for individuals with a high starting blood pressure. For example, risk of preterm birth was 11-fold to 35-fold higher for steep and high trajectory clusters, and risk of small for gestational age was 2-fold higher compared with the reference cluster. Future studies may leverage these trajectories to differentiate preeclampsia cases in relation to circulating biomarkers, which may help in the development of preeclampsia prediction tools.

OBJECTIVE Maternal smoking is associated with as much as a 50% reduced risk of preeclampsia, despite increasing risk of other poor pregnancy outcomes that often co-occur with preeclampsia, such as preterm birth and fetal growth restriction. Researchers have long sought to understand whether this perplexing association is biologically based, or a result of noncausal mechanisms. We examined whether smoking-response genes modify the smoking-preeclampsia association to investigate potential biological explanations. STUDY DESIGN We conducted a nested case-control study within the Norwegian Mother, Father and Child Birth Cohort (1999-2008) of 2,596 mother-child dyads. We used family-based log-linear Poisson regression to examine modification of the maternal smoking-preeclampsia relationship by maternal and fetal single nucleotide polymorphisms involved in cellular processes related to components of cigarette smoke (n = 1,915 with minor allele frequency ≥10%). We further investigated the influence of smoking cessation during pregnancy. RESULTS Three polymorphisms showed overall (p

ObjectiveTo determine the association of prenatal exposure to intimate partner violence (IPV) with birth weight as a continuous variable among term births in a Nigerian population.DesignCross-sectional study.SettingMother–child pairs recruited when their newborns were brought for BCG or other vaccines shortly after birth at the Child Welfare Clinic of Barau Dikko Teaching Hospital, Kaduna, Nigeria.Participants293 women with term birth infants.Main exposure and outcome measuresEmotional, physical and sexual IPV were measured postnatally by interview using the Conflict Tactics Scale. Birth weight in grams was the main outcome measure. Linear regression, with adjustment for covariates, was used to estimate associations between birth weight and exposure to the presence, and frequency, of IPV.ResultsSixty-seven per cent of mothers experienced at least one of the three forms of IPV during pregnancy. Relative to the 33% of women with no prenatal exposure to any form of IPV, we observed a reduction in birth weight of 94 g (95% CI: −202 to 15) for prenatal exposure to emotional IPV, 162 g (95% CI −267 to −58) for physical IPV and 139 g (95% CI −248 to −30) for sexual IPV. The combination of all three forms of IPV was associated with a 223 g reduction in birth weight (95% CI −368 to −77). Increasing occurrences of each of the three types of IPV were associated with greater reductions in birth weight. For physical IPV, relative to no exposure to any form of IPV, birth weight was lower by 112 g (95% CI −219 to −4) with 1–5 instances and 380 g (95% CI −553 to −206) for >5 instances over the pregnancy.ConclusionsMaternal exposure to IPV was associated with shifting of the birth weight distribution among term newborns. A dose–response relationship was observed between frequency of IPV and birth weight.

Objective To assess whether the duration, recency, or type of hormonal contraceptive used is associated with antimullerian hormone (AMH) levels, given that the existing literature regarding the association between hormonal contraceptive use and AMH levels is inconsistent. Design Cross-sectional study. Setting Baseline data from the Study of the Environment, Lifestyle and Fibroids Study, a 5-year longitudinal study of African American women. Patient(s) The patients were 1,643 African American women aged 23–35 years at the time of blood drawing (2010–2012). Intervention(s) None. Main Outcome Measure(s) Serum AMH level was measured by an ultrasensitive enzyme-linked immunosorbent assay. Linear regression models were used to estimate percent differences in mean AMH levels and 95% confidence intervals (CIs) according to use of hormonal contraceptives, with adjustment for potential confounders. Result(s) In multivariable-adjusted analyses, current users of hormonal contraceptives had 25.2% lower mean AMH levels than non-users of hormonal contraceptives (95% CI: −35.3%, −13.6%). There was little difference in AMH levels between former users and non-users of hormonal contraceptives (−4.4%; 95% CI: −16.3%, 9.0%). AMH levels were not appreciably associated with cumulative duration of use among former users or time since last use among non-current users. Current users of combined oral contraceptives (–24.0%; 95% CI: −36.6%, −8.9%), vaginal ring (−64.8%; 95% CI: −75.4%, −49.6%), and depot medroxyprogesterone acetate (−26.7%; 95% CI: −41.0%, −8.9%) had lower mean AMH levels than non-users. Conclusion(s) The present data suggest that AMH levels are significantly lower among current users of most forms of hormonal contraceptives, but that the suppressive effect of hormonal contraceptives on AMH levels is reversible.

Background: Injectable contraceptive use is common, with 74 million users worldwide. Use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) is associated with bone mineral density loss. We hypothesize that increased bone resorption with DMPA use allows for mobilization of the toxic metal lead stored in bone to blood, presenting users with increased systemic exposure to lead. Objective: The objective of our study was to investigate the association between current DMPA use and blood lead concentrations. Methods: We conducted a cross-sectional analysis using enrollment data from the Study of Environment, Lifestyle & Fibroids (SELF), a cohort of 1,693 African-American women who were 23–35 years of age. Data on DMPA use were collected by computer-assisted telephone interview. Blood lead concentrations were measured in whole blood samples among 1,548 participants (91% of cohort). We estimated the adjusted percent difference in blood lead concentrations and 95% confidence intervals (CI) between current DMPA users and nonusers using multivariable linear regression. Results: Geometric mean blood lead concentration was 0.69μg/dL (95% CI: 0.67, 0.71). After adjustment, current DMPA users (7% of cohort) had blood lead concentrations that were 18% higher than those of nonusers (95% CI: 8%, 29%). Similar associations were observed with additional analyses to assess for potential bias from smoking, DMPA-induced amenorrhea, use of estrogen-containing contraceptives, having given birth in the prior year, and history of medical conditions or current medication use associated with bone loss. Discussion: Our results indicate that current DMPA use is associated with increased blood lead concentrations. Further research, particularly in populations highly exposed to lead, is warranted to consider tradeoffs between the adverse effects of lead on human health and the importance of DMPA as a contraceptive option to prevent unintended pregnancy. https://doi.org/10.1289/EHP7017

Background/Aim: Menstrual blood loss is a substantial contributor to body iron deficiency. When body iron stores are low, metal ion transporters in the gut are upregulated to increase intestinal ab...

STUDY QUESTIONWhat proportion of fertilized human ova are lost before implantation?SUMMARY ANSWERAn estimated 40 to 50% of fertilized ova fail to implant.WHAT IS KNOWN ALREADYPreimplantation loss is not detectable with current technology. Published estimates of preimplantation loss range from 10 to 70%.STUDY DESIGN, SIZE, DURATIONWe combine data from epidemiologic, demographic, laboratory and in vitro fertilization studies to construct an empirical framework for the estimation of preimplantation loss. This framework is summarized in a user-friendly Excel file included in supplement.PARTICIPANTS/MATERIALS, SETTING, METHODSWe draw from multiple sources to generate plausible estimates of fecundability, sterility, transient anovulation, intercourse patterns and the proportion of ova fertilized in the presence of sperm. We combine these estimates to generate a summary estimate of preimplantation loss. This estimate can be considered an average for couples in their prime reproductive years.MAIN RESULTS AND THE ROLE OF CHANCEUnder a plausible range of assumptions, we estimate that 40 to 50% of fertilized ova fail to implant.LIMITATIONS, REASONS FOR CAUTIONA crucial factor in estimating preimplantation loss is the probability that an ovum will be fertilized when exposed to sperm. Human data are available only from in vitro fertilization (IVF), which may not accurately represent events in vivo. We therefore assume a range of in vivo fertilization rates, from 64% (human IVF data) to 90% (mouse data).WIDER IMPLICATIONS OF THE FINDINGSOur estimate of preimplantation loss takes into account the biological processes relevant to fertilization and loss. Using this empirical basis for estimation, we find support for the usual assumption that risk of loss is highest in the earliest days following fertilization. Furthermore, this framework can provide improved estimates as better reproductive data become available. To the extent that our estimates are accurate, more fertilized ova are apparently lost in vitro than in vivo, suggesting that further improvements in IVF success rates may be possible.STUDY FUNDING/COMPETING INTEREST(S)This study was supported by the Intramural Program of the National Institute of Environmental Health Sciences, NIH. Professor Adashi serves as Co-Chair of the Safety Advisory Board of Ohana Biosciences, Inc. The other authors have no competing interests.TRIAL REGISTRATION NUMBERN/A.

Importance Preeclampsia during pregnancy has been linked to an increased risk of cerebral palsy in offspring. Less is known about the role of preeclampsia in other neurodevelopmental disorders. Objective To determine the association between preeclampsia and a range of adverse neurodevelopmental outcomes in offspring after excluding preterm births. Design, Setting, and Participants This prospective, population-based cohort study included singleton children born at term from January 1, 1991, through December 31, 2009, and followed up through December 31, 2014 (to 5 years of age), using Norway’s Medical Birth Registry and linked to other demographic, social, and health information by Statistics Norway. Data were analyzed from May 30, 2018, to November 17, 2019. Exposures Maternal preeclampsia. Main Outcomes and Measures Associations between preeclampsia in term pregnancies and cerebral palsy, attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), epilepsy, intellectual disability, and vision or hearing loss using multivariable logistic regression. Results The cohort consisted of 980 560 children born at term (48.8% female and 51.2% male; mean [SD] gestational age, 39.8 [1.4] weeks) with a mean (SD) follow-up of 14.0 (5.6) years. Among these children, 28 068 (2.9%) were exposed to preeclampsia. Exposed children were at increased risk of ADHD (adjusted odds ratio [OR], 1.18; 95% CI, 1.05-1.33), ASD (adjusted OR, 1.29; 95% CI, 1.08-1.54), epilepsy (adjusted OR, 1.50; 95% CI, 1.16-1.93), and intellectual disability (adjusted OR, 1.50; 95% CI, 1.13-1.97); there was also an apparent association between preeclampsia exposure and cerebral palsy (adjusted OR, 1.30; 95% CI, 0.94-1.80). Conclusions and Relevance Preeclampsia is a well-established threat to the mother. Other than the hazards associated with preterm delivery, the risks to offspring from preeclampsia are usually regarded as less important. This study’s findings suggest that preeclampsia at term may have lasting effects on neurodevelopment of the child.

ObjectiveTo explore conditions and outcomes of a first delivery at term that might predict later preterm birth.DesignPopulation based, prospective register based study.SettingMedical Birth Registry of Norway, 1999-2015.Participants302 192 women giving birth (live or stillbirth) to a second singleton child between 1999 and 2015.Main outcome measuresMain outcome was the relative risk of preterm delivery (ResultsWomen with any of the five complications at term showed a substantially increased risk of preterm delivery in the next pregnancy. The absolute risks for preterm delivery in a second pregnancy were 3.1% with none of the five term complications (8202/265 043), 6.1% after term pre-eclampsia (688/11 225), 7.3% after term placental abruption (41/562), 13.1% after term stillbirth (72/551), 10.0% after term neonatal death (22/219), and 6.7% after term small for gestational age (463/6939). The unadjusted relative risk for preterm birth after term pre-eclampsia was 2.0 (95% confidence interval 1.8 to 2.1), after term placental abruption was 2.3 (1.7 to 3.1), after term stillbirth was 4.2 (3.4 to 5.2), after term neonatal death was 3.2 (2.2 to 4.8), and after term small for gestational age was 2.2 (2.0 to 2.4). On average, the risk of preterm birth was increased 2.0-fold (1.9-fold to 2.1-fold) with one term complication in the first pregnancy, and 3.5-fold (2.9-fold to 4.2-fold) with two or more complications. The associations persisted after excluding recurrence of the specific complication in the second pregnancy. These links between term complications and preterm delivery were also seen in the reverse direction: preterm birth in the first pregnancy predicted complications in second pregnancies delivered at term.ConclusionsPre-eclampsia, placental abruption, stillbirth, neonatal death, or small for gestational age experienced in a first term pregnancy are associated with a substantially increased risk of subsequent preterm delivery. Term complications seem to share important underlying causes with preterm delivery that persist from pregnancy to pregnancy, perhaps related to a mother’s predisposition to disorders of placental function.

Preeclampsia is a serious complication of pregnancy, affecting both maternal and fetal health. In genome-wide association meta-analysis of European and Central Asian mothers, we identify sequence variants that associate with preeclampsia in the maternal genome at ZNF831/20q13 and FTO/16q12. These are previously established variants for blood pressure (BP) and the FTO variant has also been associated with body mass index (BMI). Further analysis of BP variants establishes that variants at MECOM/3q26, FGF5/4q21 and SH2B3/12q24 also associate with preeclampsia through the maternal genome. We further show that a polygenic risk score for hypertension associates with preeclampsia. However, comparison with gestational hypertension indicates that additional factors modify the risk of preeclampsia., Studies to identify maternal variants associated with preeclampsia have been limited by sample size. Here, the authors meta-analyze eight GWAS of 9,515 preeclamptic women, identifying five variants associated with preeclampsia and showing that genetic predisposition to hypertension is a major risk factor for preeclampsia.

Background: Bacterial vaginosis (BV), the leading cause of vaginal discharge, is associated with multiple adverse health outcomes; however, its etiology is unknown. BV treatment is not very effective, thus prevention approaches are needed. Studies investigating the impact of vitamin D on the risk of BV have had mixed findings, including two studies reporting increased risk of recurrent BV for women with higher vitamin D. Materials and Methods: Participants were nonpregnant women in a prospective fibroid study of African Americans (ages 23–34 years) from the Detroit area. The exposure was seasonally adjusted annual mean serum 25-hydroxyvitamin D [25(OH)D] at enrollment. The outcome was self-reported doctor-diagnosed BV over ∼20 months between baseline and follow-up. Multivariable-adjusted binomial regression models estimated the risk of BV for a doubling of 25(OH)D and sufficient (≥20 ng/mL) versus deficient (

Preterm delivery is one of the strongest predictors of neonatal mortality. A given exposure may increase neonatal mortality directly, or indirectly by increasing the risk of preterm birth. Efforts to assess these direct and indirect effects are complicated by the fact that neonatal mortality arises from two distinct denominators (i.e. two risk sets). One risk set comprises fetuses, susceptible to intrauterine pathologies (such as malformations or infection), which can result in neonatal death. The other risk set comprises live births, who (unlike fetuses) are susceptible to problems of immaturity and complications of delivery. In practice, fetal and neonatal sources of neonatal mortality cannot be separated – not only because of incomplete information, but because risks from both sources can act on the same newborn. We use simulations to assess the repercussions of this structural problem. We first construct a scenario in which fetal and neonatal factors contribute separately to neonatal mortality. We introduce an exposure that increases risk of preterm birth (and thus neonatal mortality) without affecting the two baseline sets of neonatal mortality risk. We then calculate the apparent gestational-age-specific mortality for exposed and unexposed newborns, using as the denominator either fetuses or live births at a given gestational age. If conditioning on gestational age successfully blocked the mediating effect of preterm delivery, then exposure would have no effect on gestational-age-specific risk. Instead, we find apparent exposure effects with either denominator. Except for prediction, neither denominator provides a meaningful way to define gestational-age-specific neonatal mortality.

Introduction Neighborhood safety has been associated with sleep health among adults; however, few studies have investigated its association with sleep characteristics during childhood. Methods Using data from 1,693 Black/African-American women enrolled in the Study of Environment, Lifestyle and Fibroids from 2010 to 2012, we investigated associations between neighborhood safety and sleep at age 5 years. Participants, aged 23–35 years, reported childhood neighborhood safety (unsafe, somewhat safe, very safe) and light sleep (yes/no). Participants, with assistance from their mothers or others, provided information on participants’ frequency of good sleep hygiene as a child (i.e., to bed by 8 p.m. in a quiet, dark room) as always/most of the time, sometimes, or rarely/never. Adjusting for relative childhood household income and both mother’s and father’s age at participant’s birth, we used Poisson regression with robust variance to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) to compare sleep characteristics for participants who reported unsafe vs. very safe neighborhoods. Results While 20% of participants reported living in an unsafe neighborhood, 41% reported a somewhat safe neighborhood and 39% reported a very safe neighborhood at age 5 years. The unadjusted prevalence of always/most of the time going to bed by 8 p.m. in a quiet, dark room was highest among participants who reported very safe neighborhoods. After adjustment, participants in unsafe neighborhoods were substantially more likely than those in very safe neighborhoods to only sometimes (vs. always/most of the time) go to bed: by 8 p.m. (PR=1.57 [95% CI:1.21–2.03]), in a quiet room (PR=2.11 [1.43–3.11]), and in dark room (PR=1.44 [1.09–1.90]). Patterns were similar for frequencies of rarely/never and often practicing good sleep hygiene. Light sleep was not associated with neighborhood safety. Conclusion Perceived neighborhood safety was associated with multiple sleep dimensions in childhood. Support (if any)

Objective To explore conditions and outcomes of a first delivery at term that might predict later preterm birth. Design Population based, prospective register based study. Setting Medical Birth Registry of Norway, 1999-2015. Participants 302 192 women giving birth (live or stillbirth) to a second singleton child between 1999 and 2015. Main outcome measures Main outcome was the relative risk of preterm delivery ( Results Women with any of the five complications at term showed a substantially increased risk of preterm delivery in the next pregnancy. The absolute risks for preterm delivery in a second pregnancy were 3.1% with none of the five term complications (8202/265 043), 6.1% after term pre-eclampsia (688/11 225), 7.3% after term placental abruption (41/562), 13.1% after term stillbirth (72/551), 10.0% after term neonatal death (22/219), and 6.7% after term small for gestational age (463/6939). The unadjusted relative risk for preterm birth after term pre-eclampsia was 2.0 (95% confidence interval 1.8 to 2.1), after term placental abruption was 2.3 (1.7 to 3.1), after term stillbirth was 4.2 (3.4 to 5.2), after term neonatal death was 3.2 (2.2 to 4.8), and after term small for gestational age was 2.2 (2.0 to 2.4). On average, the risk of preterm birth was increased 2.0-fold (1.9-fold to 2.1-fold) with one term complication in the first pregnancy, and 3.5-fold (2.9-fold to 4.2-fold) with two or more complications. The associations persisted after excluding recurrence of the specific complication in the second pregnancy. These links between term complications and preterm delivery were also seen in the reverse direction: preterm birth in the first pregnancy predicted complications in second pregnancies delivered at term. Conclusions Pre-eclampsia, placental abruption, stillbirth, neonatal death, or small for gestational age experienced in a first term pregnancy are associated with a substantially increased risk of subsequent preterm delivery. Term complications seem to share important underlying causes with preterm delivery that persist from pregnancy to pregnancy, perhaps related to a mother’s predisposition to disorders of placental function.

STUDY QUESTION Are reproductive characteristics associated with genome-wide DNA methylation and epigenetic age? SUMMARY ANSWER Our data suggest that increasing parity is associated with differences in blood DNA methylation and small increases in epigenetic age. WHAT IS KNOWN ALREADY A study of 397 young Filipino women (ages 20–22) observed increasing epigenetic age with an increasing number of pregnancies. STUDY DESIGN, SIZE, DURATION We used data from 2356 non-Hispanic white women (ages 35–74) enrolled in the Sister Study cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS Data on reproductive history were ascertained via questionnaire. Of the 2356 women, 1897 (81%) reported at least one live birth. Among parous women, 487 (26%) women reported ever experiencing a pregnancy complication. Three epigenetic clocks (i.e. Hannum, Horvath and Levine) and genome-wide methylation were measured in DNA from whole blood using Illumina’s HumanMethylation450 BeadChip. We estimated association β-values and 95% CIs using linear regression. MAIN RESULTS AND THE ROLE OF CHANCE All three epigenetic clocks showed weak associations between number of births and epigenetic age (per live birth; Hannum: β = 0.16, 95% CI = 0.02, 0.29, P = 0.03; Horvath: β = 0.12, 95% CI = −0.04, 0.27, P = 0.14; Levine: β = 0.27, 95% CI = 0.08, 0.45, P = 0.01); however, additional adjustment for current BMI attenuated the associations. Among parous women, a history of abnormal glucose tolerance during pregnancy was associated with increased epigenetic age by the Hannum clock (β = 0.96; 95% CI = 0.10, 1.81; P = 0.03) and Levine clocks (β = 1.69; 95% CI = 0.54, 2.84; P < 0.01). In epigenome-wide analysis, increasing parity was associated with methylation differences at 17 CpG sites (Bonferroni corrected P≤ 1.0 × 10-7). LIMITATIONS, REASONS FOR CAUTION We relied on retrospective recall to ascertain reproductive history and pregnancy complications. WIDER IMPLICATIONS OF THE FINDINGS Our findings suggest that parity is associated with small increases in epigenetic age and with DNA methylation at multiple sites in the genome. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the Intramural Research program of the NIH, National Institute of Environmental Health Sciences (Z01-ES049033, Z01-ES049032 and Z01-ES044055). None of the authors have a conflict of interest. TRIAL REGISTRATION NUMBER Not applicable.

Anti-müllerian hormone (AMH) is the preferred biomarker for ovarian reserve testing based on its stability across the menstrual cycle. Despite its increased use, there have been very few studies that have followed AMH levels over time in young, healthy populations. The few existing studies are in women of European descent. The objective of this study was to determine factors that affect AMH levels with the ultimate goal of identifying and providing better counseling to women who are at the highest risk for a rapid decline in ovarian reserve. In this study, African-American women (AAW) aged 23-34 years (yr) at their first visit, were recruited from the Detroit, Michigan metropolitan area, as part of the Study of the Environment, Lifestyle and Fibroids. Anthropometric measurements, health information and blood samples were collected from participants at three time points over 3 years. Serum AMH levels were measured using the Ansh picoAMH assay. Summary statistics were derived for the variables of interest and linear mixed-effect models were used to estimate the effects of a range of exposures on AMH levels (Stata/SE 15.1). A total of 1,646 women with up to three visits were included in the analysis. The mean time between the first and third visit was 38±2.4 months. The median AMH values for the three visits were 4.1, 3.6, and 3.2 ng/mL, respectively. The mean age was 28.7 yr at the first visit, 30.4 yo at the second visit, and 32.1 yo at the third visit. There was a non-linear relationship between age and AMH, with highest levels at age 23 and a rapid decline after age 35. The majority of women were found to be obese at the three visits (60%, 63%, and 64%, respectively), with 45% of women being obese at all three visits. For approximately 1/3 (29%) of visits, there was hormonal contraception use by the participant. In models controlling for age and age2, body mass index and hormonal contraception use were inversely associated with AMH. This large cohort study of 1,646 women with 4,455 measures provides important information on factors affecting AMH concentrations in reproductive aged AAW, a population that is largely underrepresented in the ovarian reserve literature. Further data collection in this cohort will allow us to examine patterns of AMH trajectories. Knowledge of AMH trajectories from diverse populations may lead to development of personalized reproductive-lifespan-estimates which would empower women to make informed and well-timed reproductive choices.

Introduction Stress contributes to poor sleep, and both are associated with adverse mental and physical health outcomes. African-American women are disproportionately burdened by multiple forms of stress as well as poor sleep, but few studies have investigated the stressor-sleep relationship in this population. Methods We investigated associations between multiple measures of both stressors and sleep among African American women participating in the Study of Environment, Lifestyle and Fibroids. Using principal components analysis, we summarized 43 items ascertaining self-reported stressors (e.g., racism) and potential mitigators (e.g., resilience). Components were extracted and factor scores generated. Self-reported sleep included short (4 nights per month). Adjusting for demographics, health behaviors, and body mass index, we used Poisson regression with robust variance to estimate prevalence ratios (PRs) for each factor score dichotomized at the median. Results Among 1,672 women, mean age was 29.2 ± 3.4 years and 45% had a household income Conclusion Multiple stressors were associated with sleep disturbances, but social/emotional support and resilience were associated with more favorable sleep. Support (if any)

BACKGROUND: Uterine leiomyomata (UL) are the leading indication for hysterectomy in the United States. Dietary supplementation with lycopene reduced the size and incidence of oviduct leiomyoma in the Japanese quail. Two U.S. prospective cohort studies of women reported little association between intake of lycopene, or other carotenoids, and UL incidence. However, these studies relied on self-reported physician-diagnosed UL, which is prone to misclassification. OBJECTIVE: This study examines the association between dietary intake of carotenoids and UL incidence. DESIGN: Data were derived from the Study of the Environment, Lifestyle, and Fibroids (SELF), a prospective cohort study. Women completed self-administered baseline questionnaires on demographics, reproductive history, and lifestyle, including a 110-item validated food frequency questionnaire, from which dietary intakes of carotenoids—including α-carotene, β-carotene, cryptoxanthin, lutein-zeaxanthin, and lycopene—and vitamin A were estimated. PARTICIPANTS/SETTING: 1,230 Black women aged 23–35 years who did not have a previous diagnosis of UL, cancer, or autoimmune disease at enrollment (2010–2012). Participants were residents of the Detroit, Michigan metropolitan area. MAIN OUTCOME MEASURES: Transvaginal ultrasound was used to assess UL at baseline and 20, 40, and 60 months of follow-up. STATISTICAL ANALYSES PERFORMED. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for energy intake, age at menarche, education, body mass index, parity, age at first birth, years since last birth, current use of oral contraceptives or progestin-only injectables, alcohol intake, and cigarette smoking. RESULTS: Among 1,230 women without prevalent UL, 301 incident UL cases during follow-up were identified. Intakes of lycopene, other carotenoids, and vitamin A were not appreciably associated with UL incidence. HRs comparing quartiles 2 (2,376–3,397 μg/day), 3 (3,398–4,817 μg/day), and 4 (≥4,818 μg/day) with quartile 1 (

Qualitative studies have identified haircare practices as important culturally specific barriers to physical activity (PA) among Black/African American (AA) women, but quantitative investigations are lacking. Using the Study of Environment, Lifestyle and Fibroids data among 1558 Black/AA women, we investigated associations between hair product usage/hair maintenance behaviors and PA during childhood and adulthood. Participants reported childhood and current chemical relaxer and leave-in conditioner use. Self-reported PA included childhood recreational sports participation, leisure-time PA engagement during adulthood, and, at each life stage, minutes of and intensity of PA. Adjusting for socioeconomic and health characteristics, we used Poisson regression with robust variance to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for each PA measure for more vs. less frequent hair product use/hair maintenance. Thirty-four percent reported &ge, twice/year chemical relaxer use and 22% reported &ge, once/week leave-in conditioner use at age 10 years, and neither were associated with PA at age 10 years. In adulthood, &ge, twice/year chemical relaxer users (30%) were less likely (PR = 0.90 [95% CI: 0.79&ndash, 1.02]) and &ge, once/week leave-in conditioner users (24%) were more likely (PR = 1.09 [95% CI: 0.99&ndash, 1.20]) to report intense PA compared to counterparts reporting rarely/never use. Hair product use/maintenance may influence PA among Black/AA women and impact cardiometabolic health disparities.

Phytoestrogen exposure from soy formula feeding during infancy may disrupt reproductive system development, resulting in altered menstrual bleeding in adulthood.We investigated this relationship in a cohort of 1,696 young African American women using enrollment data from the Study of Environment, Lifestyle,Fibroids (2010-2012). Questionnaire data on soy formula feeding were available for 1,553 participants, 89% based on mother's report. Menstrual bleeding outcomes including those indicative of heavy menstrual bleeding were ascertained by interview. We estimated relative risks (RRs) and 95% confidence intervals (CI) for associations between soy formula feeding and menstrual bleeding outcomes using log-binomial regression and log-multinomial regression, comparing participants ever fed and never fed soy formula.We observed associations between soy formula feeding and variables indicating a history of heavy menstrual bleeding, including ever experiencing heavy, gushing-type bleeding (RR: 1.2, 95% CI: 1.0, 1.4), ever use of nonsteroidal anti-inflammatory drugs for heavy bleeding (RR: 1.3, 95% CI: 1.0, 1.6), and ever use of a contraceptive method for heavy bleeding (RR: 1.2, 95% CI, 0.9, 1.6). Among the subset of participants with menses in the past year who did not use medication that may alter menstrual flow (n = 762), our data suggested that soy formula feeding was associated with heavier flow and the adverse impact of menstrual bleeding on quality of life, but CIs were wide.Our data suggested that soy formula feeding is associated with heavy menstrual bleeding. Our results support the idea that infancy is a susceptible developmental window for female reproductive function.

Context: Small studies suggest exogenous estrogen may improve vitamin D status, but the etiology is unclear because women who use hormones may make lifestyle choices that differentially affect vitamin D status. Objective: Our objective was to investigate the association between use of hormonal contraception and 25-hydroxy-vitamin D (25(OH)D). Design: We used linear regression modeling of cross-sectional data to estimate percent change in season-adjusted serum 25(OH)D with estrogen use after adjustment for other factors. Setting: At the enrollment clinic visit (2010–2012) into a cohort study of uterine fibroids, each subject provided a blood sample, had anthropomorphic variables and skin reflectance measured, and answered questionnaires on demographics, dietary and supplement intake, contraceptive use, reproductive and medical history, and behaviors. Participants: A total of 1662 African American women, community volunteers, 23–34 years old, living in the Detroit, Michigan, area were included. Interventions: None. Main Outcomes and Measures: Serum 25(OH)D was measured. Results: Serum 25(OH)D concentrations were low (70% Conclusions: The increase in 25(OH)D with use of estrogen-containing contraceptives raise mechanistic questions regarding the biological pathways involved, and highlights the need for studies that examine possible endogenous estrogen effects on vitamin D.

Kernel machine learning methods, such as the SNP-set kernel association test (SKAT), have been widely used to test associations between traits and genetic polymorphisms. In contrast to traditional single-SNP analysis methods, these methods are designed to examine the joint effect of a set of related SNPs (such as a group of SNPs within a gene or a pathway) and are able to identify sets of SNPs that are associated with the trait of interest. However, as with many multi-SNP testing approaches, kernel machine testing can draw conclusion only at the SNP-set level, and does not directly inform on which one(s) of the identified SNP set is actually driving the associations. A recently proposed procedure, KerNel Iterative Feature Extraction (KNIFE), provides a general framework for incorporating variable selection into kernel machine methods. In this article, we focus on quantitative traits and relatively common SNPs, and adapt the KNIFE procedure to genetic association studies and propose an approach to identify driver SNPs after the application of SKAT to gene set analysis. Our approach accommodates several kernels that are widely used in SNP analysis, such as the linear kernel and the Identity by State (IBS) kernel. The proposed approach provides practically useful utilities to prioritize SNPs, and fills the gap between SNP set analysis and biological functional studies. Both simulation studies and real data application are used to demonstrate the proposed approach.

Background: Early-life soy phytoestrogen exposure has been shown in Eker rats to increase uterine fibroid incidence in adulthood. Two large epidemiologic cohorts have provided some support for increased fibroid risk with infant soy formula feeding in women, but both cohorts relied on self-report of clinically diagnosed fibroids. Objective: We evaluated the relationship between infant soy formula feeding and ultrasound-detected fibroids. Methods: The Study of Environment, Lifestyle & Fibroids (SELF) is an ongoing cohort study of 1,696 African-American women ages 23–34 years with baseline ultrasound screening to detect and measure fibroids ≥ 0.5 cm in diameter. Questionnaire data on soy formula feeding during infancy was ascertained for 1,553 participants (89% based on mother’s report), of whom 345 were found to have fibroids. We estimated the association between soy formula feeding and fibroid prevalence and tumor number using log-binomial regression. Among those with fibroids, we compared fibroid size between soy formula-exposed and unexposed women using multivariable linear regression. Results: We did not observe an association between soy formula feeding and fibroid prevalence [adjusted prevalence ratio (aPR) 0.9, 95% CI: 0.7, 1.3]. Nor were exposed women with fibroids more likely to have ≥ 2 tumors than unexposed women with fibroids (aPR 1.0, 95% CI: 0.7, 1.6). However, exposed women with fibroids had significantly larger fibroids than unexposed women with fibroids. On average, soy formula feeding was associated with a 32% increase in the diameter of the largest fibroid (95% CI: 6%, 65%) and a 127% increase in total tumor volume (95% CI: 12%, 358%). Conclusions: Our observation that women fed soy formula as infants have larger fibroids than unexposed women provides further support for persistent effects of early life phytoestrogen exposure on the uterus. Citation: Upson K, Harmon QE, Baird DD. 2016. Soy-based infant formula feeding and ultrasound-detected uterine fibroids among young African-American women with no prior clinical diagnosis of fibroids. Environ Health Perspect 124:769–775; http://dx.doi.org/10.1289/ehp.1510082

BACKGROUND: Uterine fibroids are common. Symptoms are debilitating for many, leading to high medical and societal costs. Indirect data suggest that compared to white women, African-Americans develop fibroids at least ten years earlier on average, and their higher health burden has been well documented. OBJECTIVE: To directly measure fibroid incidence and growth in a large, community-based cohort of young African-American women. STUDY DESIGN: This observational, community-based, prospective study enrolled 1693 African American women, ages 23–35 with no prior diagnosis of fibroids. Standardized transvaginal ultrasound examinations at enrollment and after approximately 18-months were conducted to identify and measure fibroids ≥0.5 cm in diameter. Fibroid growth (change in natural log volume per 18 months) was analyzed with mixed model regression (n = 344 fibroids from 251 women whose baseline ultrasound revealed already existing fibroids). RESULTS: Among the 1123 fibroid-free women with follow-up data (88% were followed), incidence was 9.4% (95% confidence interval, CI=7.7,11.2) and increased with age (p(trend)=