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OBJECTIVE. To evaluate the associations of caffeinated, alcoholic and sweetened beverage intakes with antral follicle count (AFC), a well-accepted biomarker of ovarian reserve. DESIGN. Observational prospective cohort study. SETTING. Fertility center at an academic hospital. PATIENTS. This study includes 567 women seeking fertility care at the Massachusetts General Hospital who participated in the Environment and Reproductive Health Study. INTERVENTION. None. Women self-reported consumption of caffeinated (coffee, tea, soda), alcoholic (wine, beer, liquor), sugar-sweetened and artificially sweetened beverages using a validated food frequency questionnaire. MAIN OUTCOME MEASURE. AFC was assessed using a transvaginal ultrasound performed on the 3rd day of an unstimulated menstrual cycle or on the 3rd day of a progesterone withdrawal bleed. RESULTS. Median (interquartile range) age and AFC were 35.0 (32.0–38.0) years and 13.0 (9.0–18.0). Median (range) intake of caffeinated, alcoholic, sugar-sweetened and artificially sweetened beverages in servings/day were 1.08 (0–7.08), 0.35 (0–3.84), 0.04 (0–4.80) and 0.04 (0–7.50), respectively. All examined beverages were unrelated to AFC. The multivariable adjusted mean AFC (95% confidence interval) for women in the top and bottom quartiles of intake were 13.8 (13.0–14.7) and 13.8 (12.9–14.7) for caffeinated beverages; 13.8 (13.0–14.7) and 13.8 (13.0–14.6) for alcoholic beverages; 13.5 (12.6–14.4) and 13.3 (12.4–14.2) for sugar-sweetened beverages; and 13.2 (12.4–14.1) and 13.4 (12.6–14.3) for artificially sweetened beverages. CONCLUSION. Low-to-moderate intakes of caffeinated, alcoholic, sugar-sweetened and artificially sweetened beverages were unrelated to ovarian reserve, as measured by AFC, in a cohort of women seeking fertility care.

BackgroundWe identified host single-nucleotide variants (SNVs) associated with neurocognitive impairment (NCI) in perinatally HIV-infected (PHIV) children.MethodsWhole-exome sequencing (WES) was performed on 217 PHIV with cognitive score for age (CSA)

Additional file 1.

ObjectiveThe purpose of this study was to test the extent to which pregnancy per- and polyfluoroalkyl substance (PFAS) concentrations were associated with gestational weight gain and postpartum weight changes.MethodsThis study was composed of 1,614 women recruited between 1999 and 2002 via the Project Viva cohort with pregnancy plasma concentrations of six PFAS, including perfluorooctanesulfonic acid, perfluorooctanoic acid (PFOA), and 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid. Gestational weight gain was defined as the difference between last pregnancy weight and prepregnancy weight, 1-year postpartum weight retention as the difference between 1-year postpartum weight and prepregnancy weight, and 3-year postpartum weight change as the difference between 3-year postpartum weight and prepregnancy weight.ResultsDuring pregnancy, women gained 0.37 kg (95% CI: 0.11-0.62) more weight per doubling of 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid. At 1 year post partum, women retained 0.55 kg (95% CI: 0.07-1.04) more weight per doubling of PFOA. At 3 years post partum, women gained 0.91 kg (95% CI: 0.25-1.56) more weight per doubling in PFOA. Findings were similar after adjustment for all PFAS. Other PFAS were not associated with weight changes. Postpartum associations were stronger among women with higher prepregnancy BMI. Models were adjusted for demographics.ConclusionsPregnancy PFAS were associated with greater gestational weight gain, weight retention, and weight gain years after pregnancy.

Additional file 1: Table S1. Distribution of urinary BP-3 concentrations (ng/mL) among NHANES women during 2009–2016. Legend: Abbreviations: BP-3, benzophenone-3; LOD, limit of detection (0.4 ng/ml in NHANES 2009–2016). All estimates incorporated NHANES multistage sub-sample weights for combined survey cycles. BP-3 concentrations below LOD were assigned a value equal to the LOD divided by square root of 2 in NHANES.a Women in NHANES 2009–2016 who had positive lab pregnancy test results or self-reported pregnant at the time of urine sample collection, with available BP-3 concentrations. Due to disclosure risks, pregnancy status was only released for women 20–44 years of age since 2007.b Women in NHANES 2009–2016 who were 23–47 years old, regardless of pregnancy status. Table S2. Quartiles of time-specific BP-3 urinary concentrations and blood glucose levels among pregnant women in the EARTH Study: stratified by infertility diagnosis. Legend: Abbreviations: LOD, limit of detection (0.4 ng/ml for some years and 0.2 ng/ml for other years). *Adjusted for maternal age at pregnancy (years), pre-pregnancy BMI (

Study question Are maternal and paternal preconception urinary bisphenol A (BPA) or bisphenol S (BPS) concentrations associated with offspring birth size? Summary answer Maternal-but not paternal-preconception urinary BPA concentrations were associated with lower birth size among couples seeking fertility evaluation. What is known already Prenatal BPA exposure has been previously associated with reduced birth size in some but not all epidemiologic studies. However, the potential effect of BPA exposure before conception in either parent is unknown. Data on BPS is practically absent. Study design, size, duration Ongoing prospective preconception cohort of women and men seeking fertility evaluation between 2005 and 2016 in a large fertility center in an academic hospital in Boston, MA, USA. Participants/materials, setting, methods We examined the association between maternal and paternal preconception, as well as maternal prenatal urinary BPA and BPS concentrations, and size at birth among 346 singletons from couples recruited in the Environment and Reproductive Health (EARTH) Study using multivariable linear regression. Infant birth weight and head circumference were abstracted from delivery records. Mean preconception and prenatal exposures were estimated by averaging urinary ln-BPA and ln-BPS concentrations in multiple maternal and paternal urine samples collected before pregnancy, and maternal pregnancy samples collected in each trimester. Main results and the role of chance Maternal preconception urinary BPA concentrations were inversely associated with birth weight and head circumference in adjusted models: each ln-unit increase was associated with a decrease in birth weight of 119 g (95% CI: -212, -27), and a head circumference decrease of 0.72 cm (95% CI: -1.3, -0.1). Additional adjustment by gestational age or prenatal BPA exposure modestly attenuated results. Women with higher prenatal BPA concentrations had infants with lower mean birth weight (-75 g, 95% CI: -153, 2) although this did not achieve statistical significance. Paternal preconception urinary BPA concentrations were not associated with either birth weight or head circumference. No consistent patterns emerged for BPS concentrations measured in either parent. Limitations, reasons for caution We observed a strong negative association between maternal-but not paternal-preconception BPA concentrations and offspring birth size among a subfertile population. Although these results are overall consistent with prior studies on prenatal BPA exposure, these findings may not be generalizable to women without fertility concerns. Wider implications of the findings This study suggests that the unexplored maternal preconception period may be a sensitive window for BPA effects on birth outcomes. Study funding/competing interest(s) Work supported by Grants (ES R01 009718, ES 022955 and ES 000002) from the National Institute of Environmental Health Sciences (NIEHS). C.M. was supported by a post-doctoral fellowship award from the Canadian Institutes of Health Research. There are no competing interests to declare.

Background Systemic absorption of phthalates and parabens has been demonstrated after dermal application of body lotion, and medical devices such as intravenous bags and tubing have been identified as a source of exposure to di(2-ethylhexyl) phthalate (DEHP). However, use of products during medical procedures such as aqueous gel applied during obstetrical ultrasound in pregnancy has not been investigated as a potential source of endocrine disrupting chemical (EDC) exposure. Human studies have associated EDCs with various adverse pregnancy outcomes. There is a need to identify sources of inadvertent exposure to EDCs especially during vulnerable developmental periods such as pregnancy. Objectives We conducted a pilot study to determine whether use of gel during routine obstetrical ultrasound increased urinary concentrations of phthalate and phenol biomarkers. Methods We recruited 13 women from the Massachusetts General Hospital who provided spot urine samples at the time of their second trimester anatomic survey. The first sample was collected prior to the procedure (pre-exposure, time 1), and two additional samples were obtained at approximately 1–2 h (time 2) and 7–12 h (time 3) post-exposure following the scan. Results Urinary concentrations of several DEHP metabolites and metabolite of diisononyl cyclohexane-1,2-dicarboxylate (DINCH) increased across time. For example, the geometric mean concentrations of mono(2-ethyl-5-hydroxyhexyl) phthalate increased from 3.1 ng/ml to 7.1 ng/ml (p-value = 0.03) between time 1 and time 3. We also observed significant differences in concentrations of metabolites of butylbenzyl phthalate (BBzP), di-n-butyl phthalate (DnBP), and di-isobutyl phthalate (DiBP). For example, mono-n-butyl phthalate (metabolite of DnBP) decreased from 3.5 ng/ml to 1.8 ng/ml (p-value = 0.04) between time 1 and time 2, but then increased to 6.6 ng/ml (p-value = 0.002) at time 3. Propylparaben concentrations increased from 8.9 ng/ml to 33.6 ng/ml between time 1 and time 2 (p-value = 0.005), followed by a decrease to 12.9 ng/ml at time 3 (p-value = 0.01). However, we cannot rule out the possibility that some of the observed differences are due to other sources of exposure to these compounds. Conclusions While additional research is needed, this pilot study potentially identifies a previously unknown source of phthalate and paraben exposure among pregnant women undergoing routine ultrasound examination.

BackgroundIn a previous trial of antiretroviral therapy (ART) involving pregnant women with human immunodeficiency virus (HIV) infection, those randomly assigned to receive tenofovir, emtricitabine, and ritonavir-boosted lopinavir (TDF-FTC-LPV/r) had infants at greater risk for very premature birth and death within 14 days after delivery than those assigned to receive zidovudine, lamivudine, and ritonavir-boosted lopinavir (ZDV-3TC-LPV/r).MethodsUsing data from two U.S.-based cohort studies, we compared the risk of adverse birth outcomes among infants with in utero exposure to ZDV-3TC-LPV/r, TDF-FTC-LPV/r, or TDF-FTC with ritonavir-boosted atazanavir (ATV/r). We evaluated the risk of preterm birth (

Greater understanding of the pathways through which an environmental mixture operates is important to design effective interventions. We present new methodology to estimate natural direct and indirect effects and controlled direct effects of a complex mixture exposure on an outcome through a mediator variable. We implement Bayesian Kernel Machine Regression (BKMR) to allow for all possible interactions and nonlinear effects of (1) the co-exposures on the mediator, (2) the co-exposures and mediator on the outcome, and (3) selected covariates on the mediator and/or outcome. From the posterior predictive distributions of the mediator and outcome, we simulate counterfactuals to obtain posterior samples, estimates, and credible intervals of the mediation effects. Our simulation study demonstrates that when the exposure-mediator and exposure-mediator-outcome relationships are complex, BKMR--Causal Mediation Analysis performs better than current mediation methods. We applied our methodology to quantify the contribution of birth length as a mediator between in utero co-exposure to arsenic, manganese and lead, and children's neurodevelopmental scores, in a prospective birth cohort in Bangladesh. Among younger children, we found a negative (adverse) association between the metal mixture and neurodevelopment. We also found evidence that birth length mediates the effect of exposure to the metal mixture on neurodevelopment for younger children. If birth length were fixed to its $75^{th}$ percentile value, the harmful effect of the metal mixture on neurodevelopment is attenuated, suggesting nutritional interventions to help increase fetal growth, and thus birth length, could potentially block the harmful effect of the metal mixture on neurodevelopment., Comment: 22 pages, 12 figures, and 1 tables

Evidence from animal studies suggests that exposure to organophosphate flame retardants (PFRs) can disrupt endocrine function and impair embryo development. However, no epidemiologic studies have been conducted to evaluate effects on fertility and pregnancy outcomes.We evaluated associations between urinary concentrations of PFR metabolites and outcomes ofThis analysis included 211 women enrolled in the Environment And Reproductive Health (EARTH) prospective cohort study (2005-2015) who provided one or two urine samples per IVF cycle. We measured five urinary PFR metabolites [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropylphenyl phenyl phosphate (ip-PPP), tert-butylphenyl phenyl phosphate (tb-PPP), and bis(1-chloro-2-propyl) phosphate (BCIPP)] using negative electrospray ionization liquid chromatography tandem mass spectrometry (LC-MS/MS). Molar concentrations of the urinary PFR metabolites were summed. We used multivariable generalized linear mixed models to evaluate the association of the PFR metabolites with IVF outcomes, accounting for multiple IVF cycles per woman.Detection frequencies were high for BDCIPP (87%), DPHP (94%), and ip-PPP (80%), but low for tb-PPP (14%) and BCIPP (0%). We observed decreased success for several IVF outcomes across increasing quartiles of both summed and individual PFR metabolites (DPHP and ip-PPP) in our adjusted multivariable models. Significant declines in adjusted means from the lowest to highest quartile of ΣPFR were observed for the proportion of cycles resulting in successful fertilization (10% decrease), implantation (31%), clinical pregnancy (41%), and live birth (38%).Using IVF to investigate human reproduction and pregnancy outcomes, we found that concentrations of some urinary PFR metabolites were negatively associated with proportions of successful fertilization, implantation, clinical pregnancy, and live birth. https://doi.org/10.1289/EHP1021.

BackgroundPregnancy outcomes of perinatally human immunodeficiency virus-infected women (PHIV) are poorly defined.MethodsWe compared preterm delivery and birth weight (BW) outcomes (low BW [LBW]

ObjectivesWe investigated whether HIV disease severity was associated with alterations in structural brain connectivity, and whether those alterations in turn were associated with cognitive deficits in youth with perinatally acquired HIV (PHIV).DesignPHIV youth (n = 40) from the Pediatric HIV/AIDS Cohort Study (PHACS) (mean age: 16 ± 2 years) were included to evaluate how current and past disease severity measures (recent/nadir CD4%; peak viral load) relate to white matter microstructure within PHIV youth. PHIV youth were compared with 314 controls from the Pediatric Imaging, Neurocognition and Genetics (PING) study.MethodsDiffusion tensor imaging and tractography were utilized to assess white matter microstructure. Mediation analyses were conducted to examine whether microstructure alterations contributed to relationships between higher disease severity and specific cognitive domains in PHIV youth.ResultsWhole brain fractional anisotropy was reduced, but radial and mean diffusivity were increased in PHIV compared with control youth. Within PHIV youth, more severe past HIV disease was associated with reduced fractional anisotropy of the right inferior fronto-occipital (IFO) and left uncinate tracts; elevated mean diffusivity of the F minor; and increased streamlines comprising the left inferior longitudinal fasciculus (ILF). Associations of higher peak viral load with lower working memory performance were partly mediated by reductions in right IFO fractional anisotropy levels.ConclusionOur findings suggest that PHIV youth have a higher risk of alterations in white matter microstructure than typically developing youth, and certain alterations are related to past disease severity. Further, white matter alterations potentially mediate associations between HIV disease and working memory.

Background Human immunodeficiency virus (HIV) coinfection accelerates the rate of liver disease outcomes in individuals chronically infected with hepatitis C virus (HCV). It remains unclear to what degree combination antiretroviral therapy (ART) protects against HCV-associated liver failure.Methods We evaluated 10 090 HIV/HCV-coinfected males from the Veterans Aging Cohort Study Virtual Cohort, who had not initiated ART at entry, for incident hepatic decompensation between 1996 and 2010. We defined ART initiation as the first pharmacy fill date of a qualifying ART regimen of ≥3 drugs from ≥2 classes. Hepatic decompensation was defined as the first occurrence of 1 hospital discharge diagnosis or 2 outpatient diagnoses for ascites, spontaneous bacterial peritonitis, or esophageal variceal hemorrhage. To account for potential confounding by indication, marginal structural models were used to estimate hazard ratios (HRs) of hepatic decompensation, comparing initiation of ART to noninitiation.Results We observed 645 hepatic decompensation events in 46 444 person-years of follow-up (incidence rate, 1.4/100 person-years). Coinfected patients who initiated ART had a significantly reduced rate of hepatic decompensation relative to noninitiators (HR = 0.72; 95% confidence interval [CI], .54-.94). When we removed individuals with HIV RNA ≤400 copies/mL at baseline from the analysis (assuming that they may have received undocumented ART at entry), the hazard ratio became more pronounced (HR = 0.59; 95% CI, .43-.82).Conclusions Initiation of ART significantly reduced the rate of hepatic decompensation by 28%-41% on average. These results suggest that ART should be administered to HIV/HCV-coinfected patients to lower the risk of end-stage liver disease.