The impact of sickle cell disease and its treatment on ovarian reserve in reproductive-aged Black women.

We compared serum anti-Mullerian hormone (AMH) levels in women with sickle cell disease (SCD) (n = 152) to those of Black comparison women (n = 128) between the ages of 20 and 45 years and evaluated the impact of hydroxyurea (HU) and iron overload on ovarian reserve in those with SCD. SCD treatment was abstracted from medical records. Linear regression models were fit to examine the relationship between log(AMH) and SCD, adjusting for age. The analysis was repeated to account for HU use (current, previous, never) and iron overload (ferritin ≥1000 ng/mL vs. <1000 ng/mL). AMH estimates among women with SCD were lower than those among comparison women (2.23, 95% confidence interval [CI] 1.80-2.76 vs. 4.12, 95% CI 3.11-5.45, respectively). Women with SCD who were currently using HU had 63% lower (95% CI 43-76) AMH values than comparison women; those with SCD with prior or no HU use also had lower AMH estimates than comparison women, but the difference was less pronounced. There were no differences in predicted AMH values among women with SCD for those with and without iron overload. Women with SCD and low AMH may have a shorter reproductive window and may benefit from referral to a reproductive specialist.

Mercury, natural fertility and outcomes of assisted reproduction: A systematic review.

The primary route of mercury exposure for the general population is through consumption of contaminated seafood. There is a biological basis for an adverse effect of mercury exposure on human fertility. The goal of this review was to evaluate the existing literature on the association between mercury and pregnancy, among men and women attempting to conceive with and without assisted reproductive technology (ART). Systematic searches were performed in PubMed, EMBASE, Scopus and Web of Science for papers published up to March 2023 with no early date restriction, only including studies with a biomarker measurement of mercury exposure. We identified 11 studies examining mercury and natural fertility and 12 studies examining mercury and outcomes of assisted reproduction (implantation or clinical pregnancy). The accumulated evidence provides some support for a null association between bodily mercury concentrations and natural fertility among women, however, a large proportion of studies did not report adjusted estimates or were extremely imprecise. The majority of studies of natural fertility were also cross-sectional in nature. There was no evidence for an inverse or null association between mercury and natural fertility among men, or mercury and ART outcomes among men or women. In spite of biological plausibility, the existing evidence includes studies that are imprecise and often conflicting and does not allow us to make definitive conclusions on the associations of mercury exposure with successful pregnancy. Additional, larger studies are warranted, especially among individuals with high concentrations of mercury exposure as these individuals may be underrepresented in the current literature.

Referral and evaluation for kidney transplantation among patients with lupus nephritis-related end-stage kidney disease.

OBJECTIVE: For the majority of patients with lupus nephritis-related end-stage kidney disease (LN-ESKD), kidney transplant is associated with better outcomes than dialysis. Access to kidney transplant requires an initial referral to a transplant center and medical evaluation prior to waitlisting. The study's objective was to examine access to these early steps in the kidney transplant process among patients with LN-ESKD. METHODS: Adults who began treatment for ESKD in the Southeast, Northeast, New York, or Ohio River Valley U.S. regions from 1/1/2012 to 12/31/2019, followed through 6/30/2021, were identified from the United States Renal Data System. Referral and evaluation start data were collected from 28 of 48 transplant centers across these regions. The exposure was primary cause of ESKD (LN-ESKD vs other-ESKD). The outcomes were referral and evaluation start at a transplant center. Cox models quantified the association between LN-ESKD (vs other-ESKD) and referral and evaluation start. RESULTS: Among 192,318 patients initiating treatment for ESKD, 0.4% had LN-ESKD. Over half (58%) of LN-ESKD patients were referred before study end, and among those referred, 66% started the evaluation. In adjusted analyses, patients with LN-ESKD were referred (HR: 1.09, 95% CI: 0.99, 1.19) and started the transplant evaluation (HR: 1.13, 95% CI: 1.00, 1.28) at a higher rate than patients with other-ESKD. Among referred patients with LN-ESKD, the median time from ESKD start to referral was 2.9 months (IQR: <1 to 11.7 months), which is similar to patients with other-ESKD (median 2.6 months, IQR: <1 to 8.8 months). CONCLUSIONS: Among incident patients with ESKD, having a primary diagnosis of LN-ESKD versus other-ESKD is associated with higher rates of early transplant access outcomes. Despite this, patients with LN-ESKD (vs other-ESKD) are less likely to be preemptively referred (i.e., referred prior to ESKD start) for kidney transplant. While providers may no longer be delaying the early steps in the kidney transplantation process among this patient population, there is still room for improvement in the rates of preemptive referral. Access to kidney transplant referral prior to ESKD could result in increased transplant rates and better transplant outcomes for patients with LN-ESKD.

In-utero exposure to polybrominated biphenyl (PBB) and menstrual cycle function in adulthood.

BACKGROUND: There is evidence that in-utero exposure to PBBs, and similar chemicals, are associated with several adverse reproductive health outcomes including altered pubertal timing. However, less is known about the effects of in-utero exposure to PBBs on menstrual cycle function and reproductive hormone levels in adulthood. METHODS: For this menstrual cycle study, we recruited reproductive-aged women in the Michigan PBB Registry who were not pregnant, lactating, or taking hormonal medications (2004-2014). A total of 41 women who were born after the PBB contamination incident (1973-1974) and were prenatally exposed to PBBs, were included in this analysis. We estimated in-utero PBB exposure using maternal serum PBB measurements taken after exposure and extrapolated to time of pregnancy using a PBB elimination model. Women were followed for up to 6 months during which they provided daily urine samples and completed daily diaries. The urine samples were assayed for estrone 3-glucuronide (E13G), pregnanediol 3-glucuronide (Pd3G), and follicle stimulating hormone (FSH). RESULTS: Women in our study were, on average, 27.5 (SD:5.3) years old and contributed 4.9 (SD:1.9) menstrual cycles of follow-up. Compared to women with low in-utero PBB exposure (≤1 ppb), women with medium (>1.0-3.0 ppb) and high (>3.0 ppb) exposure had higher maximum 3-day mean Pd3G levels during the luteal phase. Specifically, the age- and creatinine-adjusted maximum 3-day mean luteal phase Pd3G levels (95% CI) in increasing categories of in-utero PBB exposure were 9.2 (4.6,13.9), 14.8 (11.6,18.0), and 16.1 (12.9,19.3) µg/mg creatinine. There were no meaningful differences in average cycle length, follicular or luteal phase cycle length, bleed length, or creatinine-adjusted E13G or FSH levels by category of in-utero PBB exposure. CONCLUSION: Higher exposure to PBB in-utero was associated with increased progesterone levels across the luteal phase, however, most other menstrual cycle characteristics were largely unassociated with in-utero PBB exposure. Given our modest sample size, our results require cautious interpretation.

The use of fertility treatments among reproductive-aged women after cancer.

OBJECTIVE: To examine whether female cancer survivors are more likely to pursue care for infertility after cancer than women without cancer. DESIGN: Population-based cohort study involving detailed interviews regarding reproductive history. SETTING: Not applicable. PATIENTS: Female cancer survivors aged 22-45 years, who were at least 2 years after a cancer diagnosis between the ages of 20 and 35 years (n = 1,036), and age-matched comparison women with no cancer history (n = 1,026). EXPOSURE: History of cancer vs. no history of cancer. MAIN OUTCOME MEASURE(S): Each cancer survivor was randomly matched to a comparison woman, who was assigned an artificial age at cancer diagnosis equal to that of her match. Matching was repeated 1,000 times. Outcomes of visiting a doctor for help becoming pregnant or undergoing fertility treatment were modeled using Cox proportional hazards regression, comparing survivors after a cancer diagnosis to age-matched comparison women, adjusted for race, income, residence, education, and parity. RESULTS: Only 25.5% of cancer survivors reported meeting their desired family size before a cancer diagnosis. The median time from diagnosis to interview among survivors was 7 (interquartile range 5-11) years. Cancer survivors were more likely to report having no children (32.6%) at the interview compared with women with no cancer history (19.5%). Survivors were not more likely to visit a doctor for help becoming pregnant compared with women without a cancer history, matched on birth year and followed by the age at which cancer survivors received their diagnosis (hazard ratio [HR] 1.16, 95% simulation interval [SI] 0.78-1.74). Compared with cancer-free women, cancer survivors had similar probabilities of pursuing any treatment (adjusted HR [aHR] 0.88, 95% SI 0.46-1.56), using hormones or medications (aHR 0.86, 95% SI 0.46-1.63), or undergoing intrauterine insemination (aHR 1.26, 95% SI 0.40-5.88) to conceive. Cancer survivors were slightly more likely to pursue surgical interventions to become pregnant (HR 1.55, 95% SI 0.67-3.71). Of those who visited a doctor but declined to pursue fertility treatment, one-quarter of women reported declining treatment due to cost. CONCLUSION: Cancer survivors did not use fertility treatments at higher rates than the general population. Further counseling and education surrounding fertility options are recommended for young adult female cancer patients after treatment is completed.

Understanding the roles of state demographics and state policies in epidemiologic studies of maternal-child health disparities.

Disparities in maternal-child health outcomes by race and ethnicity highlight structural differences in the opportunity for optimal health in the United States. Examples of these differences include access to state-level social policies that promote maternal-child health. States vary in their racial and ethnic composition as a result of the complex history of policies and laws related to slavery, Indigenous genocide and relocation, segregation, immigration, and settlement in the United States. States also vary in the social policies they enact. As a result, correlations exist between the demographic makeup of a state's population and the presence or absence of social policies in that state. These correlations become a mechanism by which racial and ethnic disparities in maternal-child health outcomes can operate. In this commentary, we use the example of three labor-related policies actively under consideration at state and federal levels (paid parental leave, paid sick leave, and reasonable accommodations during pregnancy) to demonstrate how correlations between state demographics and presence of these state policies could cause or exacerbate racial and ethnic disparities in maternal-child health outcomes. We conclude with a call for researchers to consider how the geographic distribution of racialized populations and state policies could contribute to maternal-child health disparities.

Exposure-response relationships for personal exposure to fine particulate matter (PM2·5), carbon monoxide, and black carbon and birthweight: an observational analysis of the multicountry Household Air Pollution Intervention Network (HAPIN) trial.

BACKGROUND: Household air pollution (HAP) from solid fuel use is associated with adverse birth outcomes, but data for exposure-response relationships are scarce. We examined associations between HAP exposures and birthweight in rural Guatemala, India, Peru, and Rwanda during the Household Air Pollution Intervention Network (HAPIN) trial. METHODS: The HAPIN trial recruited pregnant women (9-<20 weeks of gestation) in rural Guatemala, India, Peru, and Rwanda and randomly allocated them to receive a liquefied petroleum gas stove or not (ie, and continue to use biomass fuel). The primary outcomes were birthweight, length-for-age, severe pneumonia, and maternal systolic blood pressure. In this exposure-response subanalysis, we measured 24-h personal exposures to PM2·5, carbon monoxide, and black carbon once pre-intervention (baseline) and twice post-intervention (at 24-28 weeks and 32-36 weeks of gestation), as well as birthweight within 24 h of birth. We examined the relationship between the average prenatal exposure and birthweight or weight-for-gestational age Z scores using multivariate-regression models, controlling for the mother's age, nulliparity, diet diversity, food insecurity, BMI, the mother's education, neonate sex, haemoglobin, second-hand smoke, and geographical indicator for randomisation strata. FINDINGS: Between March, 2018, and February, 2020, 3200 pregnant women were recruited. An interquartile increase in the average prenatal exposure to PM2·5 (74·5 µg/m3) was associated with a reduction in birthweight and gestational age Z scores (birthweight: -14·8 g [95% CI -28·7 to -0·8]; gestational age Z scores: -0·03 [-0·06 to 0·00]), as was an interquartile increase in black carbon (7·3 µg/m3; -21·9 g [-37·7 to -6·1]; -0·05 [-0·08 to -0·01]). Carbon monoxide exposure was not associated with these outcomes (1·7; -3·1 [-12·1 to 5·8]; -0·003 [-0·023 to 0·017]). INTERPRETATION: Continuing efforts are needed to reduce HAP exposure alongside other drivers of low birthweight in low-income and middle-income countries. FUNDING: US National Institutes of Health (1UM1HL134590) and the Bill & Melinda Gates Foundation (OPP1131279).

The Risk of Infertility After Surgery for Benign Ovarian Cysts.

Background: There is a growing body of evidence that ovarian cystectomy may negatively impact ovarian reserve. However, it is unclear whether ovarian cyst surgery puts women at risk of future infertility. This study investigates whether surgery for benign ovarian cysts is associated with long-term infertility risk. Methods: Women aged 22-45 years (n = 1,537) were invited to participate in an interview about their reproductive histories, including whether they ever had infertility or ovarian cyst surgery. Each woman reporting cyst surgery was randomly matched to a comparison woman, who was assigned an artificial surgery age equal to that of her match. Matching was repeated 1,000 times. Adjusted Cox models were fit to examine time to infertility after surgery for each match. A subset of women was invited to participate in a clinic visit to assess markers of ovarian reserve (anti-Müllerian hormone [AMH], antral follicle count). Results: Approximately 6.1% of women reported cyst surgery. Infertility after surgery was more common for women reporting cyst surgery than those without surgery after adjusting for age, race, body mass index, cancer history, parity before assigned surgery age, history of infertility before surgery age, and endometriosis (median-adjusted hazard ratio 2.41, 95% simulation interval 1.03-6.78). The estimated geometric mean (95% confidence interval [CI]) AMH levels of those who reported a history of ovarian cyst surgery were 1.08 (95% CI: 0.57-2.05) times those of women who reported no history of surgery. Conclusions: Those with a history of ovarian cyst surgery were more likely to report having a history of infertility compared with age-matched women who reported no history of cyst surgery. It is possible that both ovarian surgery to remove cysts and the conditions that lead women to develop cysts requiring surgery may affect subsequent successful conception.

Delayed entry into prenatal care among women with pre-pregnancy health conditions, National Birth Defects Prevention Study, 1997-2011.

First trimester entry into prenatal care is recommended for all women, and especially women with pre-pregnancy conditions. Our objective was to determine whether women with pre-pregnancy conditions were at lower risk of entry after the first trimester (delayed entry) into prenatal care than women without a pre-pregnancy health condition. We used data from 10,890 participants in the National Birth Defects Prevention Study who delivered liveborn infants without birth defects. Women reported pre-pregnancy conditions and timing of entry into prenatal care during a computer-assisted telephone interview. Multivariable logistic regression analyses were conducted to evaluate whether having a pre-pregnancy condition was associated with delayed entry into prenatal care compared to women without pre-pregnancy conditions. Approximately 13% of women reported delayed entry into prenatal care, and 18% of women reported a pre-pregnancy condition. Delayed entry into prenatal care was not associated with pre-pregnancy cardiometabolic or neurologic conditions. Women with thyroid conditions were less likely to report delayed entry into prenatal care (prevalence odds ratio (OR), 95% confidence interval (CI): 0.55 [0.32, 0.94]), but women with hematologic and respiratory conditions were more likely to report delayed entry into prenatal care (OR: 1.95 [1.00, 3.82] and 1.27 [0.95, 1.72], respectively), compared to those without any chronic conditions. Future research investigating the success of early prenatal care among women with thyroid conditions could identify ways to reduce delayed prenatal care among women with other pre-pregnancy conditions.

Factors Associated with Unplanned Pregnancy Among Cancer Survivors.

Background: Approximately half of all pregnancies in the United States are unintended. However, women who are diagnosed with cancer in their reproductive years may be a unique population. This study examines the prevalence of and identifies factors associated with unplanned pregnancy among cancer survivors. Materials and Methods: Female cancer survivors aged 22-45 years, diagnosed between ages 20-35 years and at least 2 years postdiagnosis, and women with no history of cancer were interviewed about their reproductive histories, including pregnancy intention. Using a random matching process, comparison women were assigned an artificial age at cancer diagnosis equal to that of her cancer survivor match. An adjusted Cox model was fit examining time to unintended pregnancy after cancer for each of 1,000 matches. Cox proportional hazards models were also fit to assess associations between participant characteristics and unplanned pregnancy after cancer among survivors. Results: Cancer survivors (n = 1,282) and comparison women (n = 1,073) reported a similar likelihood of having an unplanned pregnancy in models adjusted for race, income, history of sexually-transmitted infection, and history of unplanned pregnancy before diagnosis (adjusted hazard ratio [aHR] 1.06, 95% simulation interval 0.85-1.36). After adjusting for confounders, unplanned pregnancy among survivors was associated with age <30 years at diagnosis (hazard ratio [HR]: 1.79, 95% confidence interval [CI]: 1.32-2.44), black race (HR: 1.55, 95% CI: 1.13-2.12; referent: white), receiving fertility counseling (aHR: 1.41, 95% CI: 1.04-1.92), and having at least one child before diagnosis (aHR: 1.44, 95% CI: 1.05-1.97). Conclusion: Cancer survivors and comparison women had similar likelihood of unplanned pregnancy. Rates of unplanned pregnancy after cancer were not higher for cancer survivors compared with comparison women, but 46.4% of survivors with a postcancer pregnancy reported an unplanned pregnancy. Cancer patients may benefit from patient-centered guidelines and counseling before cancer treatment that covers both risks of infertility and risks of unplanned pregnancy.

Adverse Perinatal Outcomes Before and After Diagnosis of Systemic Lupus Erythematosus Among African American Women.

OBJECTIVE: Women with systemic lupus erythematosus (SLE) may experience adverse perinatal outcomes in the years before an SLE diagnosis. Overall, there is limited research on perinatal outcomes among African American women with SLE. We undertook this study to examine the risk of preterm and small-for-gestational age births among African American women with SLE compared to the general population of African American women in a large metropolitan area. METHODS: Information about women with SLE was identified from the Georgia Lupus Registry and the Georgians Organized Against Lupus Cohort and was linked with birth certificates by the Georgia Department of Public Health. Births were categorized into occurring more than 3 years before SLE diagnosis, 0-3 years before SLE diagnosis, 0-3 years after SLE diagnosis, or more than 3 years after SLE diagnosis. Comparison birth certificates to African American women in the same geographic area were obtained from the National Center for Health Statistics. We used log-risk models to compare the risk of preterm or small-for-gestational age births among SLE births in each diagnosis timing category to the general population, adjusting for maternal age and education and parity. RESULTS: Births to women with SLE were more likely to occur preterm at 0-3 years before SLE diagnosis (risk ratio [RR] 1.71, 95% confidence interval [95% CI] 1.24-2.35), 0-3 years after SLE diagnosis (RR 2.29, 95% CI 1.70-3.09), and 3 or more years after SLE diagnosis (RR 2.83, 95% CI 2.36-3.38), but not 3 or more years before SLE diagnosis compared to the general population (RR 1.03, 95% CI 0.77-1.38). Similar results were observed for small-for-gestational age births. CONCLUSION: Our analysis, conducted among African American women, demonstrates an increased risk of adverse perinatal outcomes even before a clinical diagnosis of SLE.

Misclassification of Neonatal Abstinence Syndrome Surveillance Estimates: Is Considering the Positive Predictive Value Enough?

BACKGROUND: Validation studies estimating the positive predictive value (PPV) of neonatal abstinence syndrome (NAS) have consistently suggested overreporting in hospital discharge records. However, few studies estimate the negative predictive value (NPV). Even slightly imperfect NPVs have the potential to bias estimated prevalences of rare outcomes like NAS. Given the challenges in estimating NPV, our objective was to evaluate whether the PPV was sufficient to understand the influence of NAS misclassification bias on conclusions of the NAS prevalence in surveillance research. METHODS: We used hospital discharge data from the 2016 New Jersey State Inpatient Databases, Healthcare Cost and Utilization Project. We adjusted surveillance data for misclassification using quantitative bias analysis models to estimate the expected NAS prevalence under a range of PPV and NPV bias scenarios. RESULTS: The 2016 observed NAS prevalence was 0.61%. The misclassification-adjusted prevalence estimates ranged from 0.31% to 0.91%. When PPV was assumed to be ≥90%, the misclassification-adjusted prevalence was typically greater than the observed prevalence but the reverse was true for PPV ≤70%. Under PPV 80%, the misclassification-adjusted prevalence was less than the observed prevalence for NPV >99.9% but flipped for NPV <99.9%. CONCLUSIONS: When we varied the NPV below 100%, our results suggested that the direction of bias (over or underestimation) was dependent on the PPV, and sometimes dependent on the NPV. However, NPV was important for understanding the magnitude of bias. This study serves as an example of how quantitative bias analysis methods can be applied in NAS surveillance to supplement existing validation data when NPV estimates are unavailable.

Pre- and postnatal polychlorinated biphenyl exposure and cognitive and behavioral development at age 45 Months in a cohort of Slovak children.

Evidence of associations of pre- and postnatal exposure to polychlorinated biphenyls (PCBs) with cognitive development beyond early childhood is inconsistent. A previous report from this cohort observed adverse associations between early life PCB exposures and infant Bayley scores at age 16 months. The present study examines pre- and postnatal PCB exposures in relation to both behavior and cognitive development at age 45 months. Participants were 472 mother-child pairs residing in an area of eastern Slovakia characterized by environmental contamination with PCBs, which resulted in elevated blood serum concentrations. PCB-153 and PCB-118 concentrations were measured in maternal and in infant 6-, 16-, and 45-month serum samples. At age 45 months, children were administered five subtests of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), and mothers completed the Child Behavior Checklist (CBCL). Negative binomial and multiple linear regressions were used to estimate PCB-CBCL and PCB-WPPSI-III subtest score associations, respectively. Pre- and postnatal levels of PCB-153 and PCB-118 were not associated with cognitive performance on the WPPSI-III in this cohort. There was some suggestion that higher postnatal PCB concentrations were associated with more sleep problems and feelings of depression and anxiousness.

Prenatal exposure to mixtures of persistent endocrine disrupting chemicals and postnatal body size in British girls.

BACKGROUND: Endocrine disrupting chemical (EDC) exposure is ubiquitous. EDC exposure during critical windows of development may interfere with the body's endocrine system, affecting growth. Previous human studies have examined one EDC at a time in relation to infant growth. By studying mixtures, the human experience can be better approximated. AIMS: We investigated the association of prenatal exposure to persistent EDCs (per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs)) as mixtures with postnatal body size among female offspring. SUBJECTS: We used a sub-sample of the Avon Longitudinal Study of Parents and Children (N = 425), based in the United Kingdom. STUDY DESIGN: We quantified 52 EDCs in maternal serum collected during pregnancy. We used Bayesian kernel machine regression with a random intercept to examine the association of prenatal concentrations of EDC mixtures with longitudinal postnatal body size measures for each EDC class separately (PFAS, PCBs, and OCPs) and for all three classes combined. OUTCOME MEASURES: Weight and height measures at 0, 2, 9, and 19 months were obtained by health professionals as part of routine child health surveillance. RESULTS: The mixture representing all three classes combined (31 chemicals) (n = 301) was inversely associated with postnatal body size. Holding all EDCs in the 31-chemical mixture at the 75th percentile compared to the 50th percentile was associated with 0.15 lower weight-for-age z-score (95% credible interval -0.26, -0.03). Weak inverse associations were also seen for height-for-age and body mass index-for-age scores. CONCLUSIONS: These results suggest that prenatal exposure to mixtures of persistent EDCs may affect postnatal body size.

Prenatal Exposure to Mixtures of Persistent Endocrine-disrupting Chemicals and Birth Size in a Population-based Cohort of British Girls.

BACKGROUND: Previous studies of endocrine-disrupting chemicals have examined one of these chemicals at a time in association with an outcome; studying mixtures better approximates human experience. We investigated the association of prenatal exposure to mixtures of persistent endocrine disruptors (perfluoroalkyl and polyfluoroalkyl substances [PFAS], polychlorinated biphenyls [PCBs], and organochlorine pesticides) with birth size among female offspring in the Avon Longitudinal Study of Parents and Children (ALSPAC), based in the United Kingdom in 1991-1992. METHODS: We quantified concentrations of 52 endocrine-disrupting chemicals in maternal serum collected during pregnancy at median 15-week gestation. Birth weight, crown-to-heel length, and head circumference were measured at birth; ponderal index and small for gestational age were calculated from these. We used repeated holdout Weighted Quantile Sum (WQS) regression and Bayesian kernel machine regression to examine mixtures in 313 mothers. RESULTS: Using WQS regression, all mixtures (each chemical class separately and all three together) were inversely associated with birth weight. A one-unit increase in WQS index (a one-decile increase in chemical concentrations) for all three classes combined was associated with 55 g (ß = -55 g, 95% confidence interval [CI] = -89, -22 g) lower birth weight. Associations were weaker but still inverse using Bayesian kernel machine regression. Under both methods, PFAS were the most important contributors to the association with birth weight. We also observed inverse associations for crown-to-heel length. CONCLUSIONS: These results are consistent with the hypothesis that prenatal exposure to mixtures of persistent endocrine-disrupting chemicals affects birth size.

Prenatal exposure to mixtures of persistent endocrine disrupting chemicals and early menarche in a population-based cohort of British girls.

Exposure to endocrine disrupting chemicals (EDCs) is ubiquitous. EDC exposure, especially during critical periods of development like the prenatal window, may interfere with the body's endocrine system, which can affect growth and developmental outcomes such as puberty. Most studies have examined one EDC at a time in relation to disease; however, humans are exposed to many EDCs. By studying mixtures, the human experience can be more closely replicated. We investigated the association of prenatal exposure to persistent EDCs (poly- and perfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs)) as mixtures with early menarche among female offspring in a nested case-control study within the Avon Longitudinal Study of Parents and Children (ALSPAC) recruited in the United Kingdom in 1991-1992. Concentrations of 52 EDCs were quantified in maternal serum samples collected during pregnancy. Daughter's age at menarche was ascertained through mailed questionnaires sent annually. We used repeated holdout weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) to examine the association between prenatal exposure to multiple EDCs and early menarche (<11.5 (n = 218) vs. ≥11.5 years (n = 230)) for each chemical class separately (PFAS, PCBs, and OCPs) and for all three classes combined. Models adjusted for maternal age at menarche, maternal education, parity, pre-pregnancy body mass index, maternal age, prenatal smoking, and gestational week at sample collection. Mixture models showed null associations between prenatal exposure to EDC mixtures and early menarche. Using WQS regression, the odds ratio for early menarche for a one-decile increase in chemical concentrations for all three classes combined was 0.89 (95% CI: 0.76, 1.05); using BKMR, the odds ratio when all exposures were at the 60th percentile compared to the median was 0.98 (95% CI: 0.91, 1.05). Results suggest the overall effect of prenatal exposure to persistent EDC mixtures is not associated with early menarche.

Comparison of Young Adult Female Cancer Survivors Recruited from a Population-Based Cancer Registry to Eligible Survivors.

BACKGROUND: Population-based cancer registries provide a resource to recruit young adult cancer survivors who may not be easily identified otherwise. METHODS: We compared demographic and cancer-related characteristics of participants in a cohort of female young adult cancer survivors to those of eligible survivors in the Georgia Cancer Registry, a population-based registry in the United States. We examined associations between survivor characteristics and nonparticipation using logistic regression and associations between survivor characteristics and different types of nonparticipation (refusal, unable to contact, or unresolved vs. interviewed) using polytomous regression. RESULTS: The Georgia Cancer Registry was able to contact 60% of eligible women (3,061/5,137). Of those, 78% agreed to study contact (n = 2,378), and of those, 56% were interviewed (n = 1,342). Participation was similar across age at contact and at diagnosis but varied across cancer type from 17% for cervical cancer to 32% for breast cancer. White women were slightly more likely to be interviewed (28%) than African American women (23%), which was mostly attributable to greater difficulty in contacting African American women (odds ratio 1.7, 95% confidence interval: 1.5-2.1). CONCLUSIONS: The greatest challenge to recruiting women was contacting them, which differed across some but not all demographic and cancer-related characteristics. When successfully contacted, most survivors agreed to participate. IMPACT: Population-based cancer registries can serve as an invaluable resource to recruit representative samples of young adult cancer survivors, who are otherwise difficult to identify.

Prepregnancy body mass index and spina bifida: Potential contributions of bias.

BACKGROUND: Epidemiologists have consistently observed associations between prepregnancy obesity and spina bifida in offspring. Most studies, however, used self-reported body mass index (potential for exposure misclassification) and incompletely ascertained cases of spina bifida among terminations of pregnancy (potential for selection bias). We conducted a quantitative bias analysis to explore the potential effects of these biases on study results. METHODS: We included 808 mothers of fetuses or infants with spina bifida (case mothers) and 7,685 mothers of infants without birth defects (control mothers) from a population-based case-control study, the National Birth Defects Prevention Study (1997-2011). First, we performed a conventional epidemiologic analysis, adjusting for potential confounders using logistic regression. Then, we used 5,000 iterations of probabilistic bias analysis to adjust for the combination of confounding, exposure misclassification, and selection bias. RESULTS: In the conventional confounding-adjusted analysis, prepregnancy obesity was associated with spina bifida (odds ratio 1.4, 95% confidence interval: 1.2, 1.7). In the probabilistic bias analysis, we tested nine different models for the combined effects of confounding, exposure misclassification, and selection bias. Results were consistent with a weak to moderate association between prepregnancy obesity and spina bifida, with the median odds ratios across the nine models ranging from 1.1 to 1.4. CONCLUSIONS: Given our assumptions about the occurrence of bias in the study, our results suggest that exposure misclassification, selection bias, and confounding do not completely explain the association between prepregnancy obesity and spina bifida.

Maternal dietary patterns during pregnancy and exposure to persistent endocrine disrupting chemicals in two European birth cohorts.

Food consumption, particularly of animal-based products, is considered the most important contributor to persistent endocrine disrupting chemical (EDC) exposure. This study aims to describe the association between maternal diet during pregnancy and exposure to persistent EDCs using dietary pattern analysis. This study is based on subsamples of the Avon Longitudinal Study of Parents and Children (ALSPAC) (N=422) and the Norwegian Mother, Father, and Child Cohort Study (MoBa) (N=276) which uses data from the Medical Birth Registry of Norway (MBRN). Women in both studies completed food frequency questionnaires (FFQs) during pregnancy, from which consumption data were categorized into 38 aggregated food groups. Maternal blood samples were collected during pregnancy and concentrations of perfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs) in serum/plasma were measured. Dietary patterns were identified using reduced rank regression, with blood EDC concentrations as response variables. Within ALSPAC, all patterns (PFAS, PCB, and OCP) were characterized by high consumption of meat, poultry, white fish, and biscuits. In MoBa, high consumption of sausages and burgers (representing processed meats), pasta, and chocolate bars characterized PCB and OCP dietary patterns, while high consumption of cheese characterized the PFAS pattern. Across both cohorts, PFAS patterns were characterized by high consumption of cheese, PCB patterns by high consumption of rice, and OCP patterns by poultry. Dietary patterns explained between 8 and 20% of the variation in serum EDC concentrations, with explained variance being the highest for PCBs in both cohorts. In conclusion, dietary patterns high in animal-based products appear to be associated with persistent EDC concentrations among pregnant women. Diet explains more variation in PCB concentrations than for other persistent EDC classes.