Maternal Serum Polychlorinated Biphenyl Concentrations across Critical Windows of Human Development

Background Few data are available on polychlorinated biphenyl (PCB) concentrations over critical windows of human reproduction and development inclusive of the periconception window. Objectives Our goal was to measure changes in PCB concentrations from preconception to pregnancy, through pregnancy, or after a year without becoming pregnant. Methods Seventy-nine women planning pregnancies were prospectively enrolled and followed for up to 12 menstrual cycles of attempting pregnancy. Blood specimens were obtained from participating women preconceptionally (n = 79), after a positive pregnancy test leading to a live birth (n = 54) or pregnancy loss (n= 10), at approximately 6 weeks postpartum (n = 53), and after 12 unsuccessful cycles (n = 9) for toxicologic analysis of 76 PCB congeners. We estimated overall and daily rate of change in PCB concentration (nanograms per gram serum) adjusting for relevant covariates, serum lipids, and baseline PCB concentration. Results Significant (p \u3c 0.0001) decreases in the mean overall and daily rate of change in PCB concentrations were observed between the preconception and first pregnancy samples for total (–1.012 and –0.034, respectively), estrogenic (–0.444 and –0.016, respectively), and antiestrogenic (–0.106 and –0.004, respectively) PCBs among women with live births. Similar significant decreases in total (–1.452 and –0.085), estrogenic (–0.647 and –0.040), and antiestrogenic (–0.093 and –0.004) PCB concentrations were seen for women with pregnancy losses. No significant changes were observed for PCB congener 153. Conclusions These data suggest that PCB concentrations may change during the periconception interval, questioning the stability of persistent compounds during this critical window

A BAYESIAN APPROACH TO JOINT MODELING OF MENSTRUAL CYCLE LENGTH AND FECUNDITY

Female menstrual cycle length is thought to play an important role in couple fecundity, or the biologic capacity for reproduction irrespective of pregnancy intentions. A complete assessment of the association between menstrual cycle length and fecundity requires a model that accounts for multiple risk factors (both male and female) and the couple\u27s intercourse pattern relative to ovulation. We employ a Bayesian joint model consisting of a mixed effects accelerated failure time model for longitudinal menstrual cycle lengths and a hierarchical model for the conditional probability of pregnancy in a menstrual cycle given no pregnancy in previous cycles of trying, in which we include covariates for the male and the female and a flexible spline function of intercourse timing. Using our joint modeling approach to analyze data from the Longitudinal Investigation of Fertility and the Environment Study, a couple based prospective pregnancy study, we found a significant quadratic relation between menstrual cycle length and the probability of pregnancy even with adjustment for other risk factors, including male semen quality, age, and smoking status

Communicating serum chemical concentrations to study participants: follow up survey

<p>Abstract</p> <p>Background</p> <p>A considerable literature now supports the importance of effective communication with study participants, including how best to develop communication plans focusing on the uncertainty of health risks associated with particular environmental exposures. Strategies for communicating individual concentrations of environmental chemicals in human biological samples in the absence of clearly established safe or hazardous levels have been discussed from a conceptual basis and to a lesser extent from an empirical basis. We designed and evaluated an empirically based communication strategy for women of reproductive age who previously participated in a prospective study focusing on persistent environmental chemicals and reproductive outcomes.</p> <p>Methods</p> <p>A cohort of women followed from preconception through pregnancy or up to 12 menstrual cycles without pregnancy was given their individual serum concentrations for lead, dichloro-2,2-bis<it>p</it>-chlorophenyl ethylene, and select polychlorinated biphenyl congeners. Two versions of standardized letters were prepared depending upon women's exposure status, which was characterized as low or high. Letters included an introduction, individual concentrations, population reference values and guidance for minimizing future exposures. Participants were actively monitored for any questions or concerns following receipt of letters.</p> <p>Results</p> <p>Ninety-eight women were sent letters informing them of their individual concentrations to select study chemicals. None of the 89 (91%) participating women irrespective of exposure status contacted the research team with questions or concerns about communicated exposures despite an invitation to do so.</p> <p>Conclusions</p> <p>Our findings suggest that study participants can be informed about their individual serum concentrations without generating unnecessary concern.</p

The role of inflammation in age-related disease.

The National Institutes of Health (NIH) Geroscience Interest Group (GSIG) sponsored workshop, The Role of Inflammation inAge-Related Disease, was held September 6th-7th, 2012 in Bethesda, MD. It is now recognized that a mild pro-inflammatory state is correlated with the major degenerative diseases of the elderly. The focus of the workshop was to better understand the origins and consequences of this low level chronic inflammation in order to design appropriate interventional studies aimed at improving healthspan. Four sessions explored the intrinsic, environmental exposures and immune pathways by which chronic inflammation are generated, sustained, and lead to age-associated diseases. At the conclusion of the workshop recommendations to accelerate progress toward understanding the mechanistic bases of chronic disease were identified

Lipid Adjustment in the Analysis of Environmental Contaminants and Human Health Risks

The literature on exposure to lipophilic agents such as polychlorinated biphenyls (PCBs) is conflicting, posing challenges for the interpretation of potential human health risks. Laboratory variation in quantifying PCBs may account for some of the conflicting study results. For example, for quantification purposes, blood is often used as a proxy for adipose tissue, which makes it necessary to model serum lipids when assessing health risks of PCBs. Using a simulation study, we evaluated four statistical models (unadjusted, standardized, adjusted, and two-stage) for the analysis of PCB exposure, serum lipids, and health outcome risk (breast cancer). We applied eight candidate true causal scenarios, depicted by directed acyclic graphs, to illustrate the ramifications of misspecification of underlying assumptions when interpreting results. Statistical models that deviated from underlying causal assumptions generated biased results. Lipid standardization, or the division of serum concentrations by serum lipids, was observed to be highly prone to bias. We conclude that investigators must consider biology, biologic medium (e.g., nonfasting blood samples), laboratory measurement, and other underlying modeling assumptions when devising a statistical plan for assessing health outcomes in relation to environmental exposures

Age at Menarche and Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study Among 27,482 Women

OBJECTIVE: To examine the association between age at menarche and risk of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: A prospective cohort study of 42,109 eligible pregnancies from 27,482 women in the Nurses' Health Study II. RESULTS: The adjusted risk ratios for GDM across the age at menarche categories (≤11, 12, 13, and ≥14 years) were 1.34 (95% CI 1.14-1.58), 1.13 (0.97-1.31), 1.11 (0.95-1.29), and 1.00 (referent; P for trend = 0.0005), respectively. Analysis of the mediating effect indicated that 42.1% (P = 0.0007) of the association was mediated through prepregnancy BMI. CONCLUSIONS: These findings suggested that earlier menarche was significantly associated with an increased risk of GDM. This association was largely mediated through prepregnancy excessive body adiposity