Mildred Maisonet

Maternal Concentrations of Polyfluoroalkyl Compounds during Pregnancy and Fetal and Postnatal Growth in British Girls

Background: Prenatal exposures to polyfluoroalkyl compounds (PFCs) may be associated with adverse changes in fetal and postnatal growth. Objective: We explored associations of prenatal serum concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexane sulfonate (PFHxS) with fetal and postnatal growth in girls. Methods: We studied a sample of 447 singleton girls and their mothers participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Data on weight and length were obtained at birth and at 2, 9, and 20 months. Serum samples were obtained in 1991–1992, from mothers during pregnancy. We explored associations between prenatal PFC concentrations and weight at birth as well as longitudinal changes in weight-for-age SD scores between birth and 20 months. Results: PFOS (median, 19.6 ng/mL), PFOA (median, 3.7 ng/mL), and PFHxS (median, 1.6 ng/mL) were detected in 100% of samples. On average, girls born to mothers with prenatal concentrations of PFOS in the upper tertile weighed 140 g less [95% confidence interval (CI): –238, –42] at birth than girls born to mothers with concentrations in the lower tertile in adjusted models. Similar patterns were seen for PFOA (–133 g; 95% CI: –237, –30) and PFHxS (–108 g; 95% CI: –206, –10). At 20 months, however, girls born to mothers with prenatal concentrations of PFOS in the upper tertile weighed 580 g more (95% CI: 301, 858) when compared with those in the lower tertile. No differences in weight were found for PFOA and PFHxS. Conclusions: Girls with higher prenatal exposure to each of the PFCs examined were smaller at birth than those with lower exposure. In addition, those with higher exposure to PFOS were larger at 20 months.

Timing of maturation and predictors of menarche in girls enrolled in a contemporary British cohort

This study describes the timing of puberty in 8- to 13-year-old girls enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) and identifies factors associated with earlier achievement of menarche. Women were enrolled during pregnancy and their offspring were followed prospectively. We analysed self-reported Tanner staging and menstrual status information collected annually from daughters up to age 13. We used survival models to estimate median age of attainment of stage >1 and stage >2 of breast and pubic hair development and of menarche. We also constructed multivariable logistic regression models to identify factors associated with earlier achievement of menarche. About 12% of girls reported Tanner breast stage >1 at age 8; 98% of girls were above stage 1 by age 13. For pubic hair, 5% and 95% of girls had attained a stage >1 by 8 and 13 years, respectively. The estimated median age of entry into stage >1 of breast development was 10.14 years (95% confidence interval [CI], 10.08, 10.19), and for pubic hair development the median age was 10.92 years [95% CI, 10.87, 10.97]. One girl (out of 2953) had attained menarche by age 8; 60% had attained menarche by age 13. The estimated median age at menarche was 12.93 years [95% CI, 12.89, 12.98]. Prenatal predictors of menarche by age 11 (12% of girls) included earlier maternal age at menarche, high maternal pre-pregnancy body mass index, smoking during the third trimester, and non-white race; the single postnatal predictor was the girls body size at 8 years. Age at attainment of breast and pubic hair Tanner stage and age at menarche in the ALSPAC cohort are similar to ages reported in other European studies that were conducted during overlapping time periods. The results also give added support to the strong influence of maternal maturation, pre-adolescent body size and race on the timing of a girls menarche. This cohort will continue to be followed for maturational information until age 17.

Associations of Perfluoroalkyl Substances (PFAS) with Lower Birth Weight: An Evaluation of Potential Confounding by Glomerular Filtration Rate Using a Physiologically Based Pharmacokinetic Model (PBPK)

Background Prenatal exposure to perfluoroalkyl substances (PFAS) has been associated with lower birth weight in epidemiologic studies. This association could be attributable to glomerular filtration rate (GFR), which is related to PFAS concentration and birth weight. Objectives We used a physiologically based pharmacokinetic (PBPK) model of pregnancy to assess how much of the PFAS–birth weight association observed in epidemiologic studies might be attributable to GFR. Methods We modified a PBPK model to reflect the association of GFR with birth weight (estimated from three studies of GFR and birth weight) and used it to simulate PFAS concentrations in maternal and cord plasma. The model was run 250,000 times, with variation in parameters, to simulate a population. Simulated data were analyzed to evaluate the association between PFAS levels and birth weight due to GFR. We compared simulated estimates with those from a meta-analysis of epidemiologic data. Results The reduction in birth weight for each 1-ng/mL increase in simulated cord plasma for perfluorooctane sulfonate (PFOS) was 2.72 g (95% CI: –3.40, –2.04), and for perfluorooctanoic acid (PFOA) was 7.13 g (95% CI: –8.46, –5.80); results based on maternal plasma at term were similar. Results were sensitive to variations in PFAS level distributions and the strength of the GFR–birth weight association. In comparison, our meta-analysis of epidemiologic studies suggested that each 1-ng/mL increase in prenatal PFOS and PFOA levels was associated with 5.00 g (95% CI: –21.66, –7.78) and 14.72 g (95% CI: –8.92, –1.09) reductions in birth weight, respectively. Conclusion Results of our simulations suggest that a substantial proportion of the association between prenatal PFAS and birth weight may be attributable to confounding by GFR and that confounding by GFR may be more important in studies with sample collection later in pregnancy. Citation Verner MA, Loccisano AE, Morken NH, Yoon M, Wu H, McDougall R, Maisonet M, Marcus M, Kishi R, Miyashita C, Chen MH, Hsieh WS, Andersen ME, Clewell HJ III, Longnecker MP. 2015. Associations of perfluoroalkyl substances (PFAS) with lower birth weight: an evaluation of potential confounding by glomerular filtration rate using a physiologically based pharmacokinetic model (PBPK). Environ Health Perspect 123:1317–1324; http://dx.doi.org/10.1289/ehp.1408837

Timing of maturation and predictors of Tanner stage transitions in boys enrolled in a contemporary British cohort

This study describes the timing of puberty in 8- to 14-year-old boys enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) and identifies factors associated with earlier achievement of advanced pubic hair stages. Women were enrolled during pregnancy and their offspring were followed prospectively. We analysed self-reported pubic hair Tanner staging collected annually. We used survival models to estimate median age of attainment of pubic hair stage >1, stage >2 and stage >3 of pubic hair development. We also constructed multivariable logistic regression models to identify factors associated with earlier achievement of pubic hair stages. Approximately 5% of the boys reported Tanner pubic hair stage >1 at age 8; 99% of boys were at stage >1 by age 14. The estimated median ages of entry into stages of pubic hair development were 11.4 years [95% confidence interval (CI) 11.3, 11.4] for stage >1, 12.7 years [95% CI 12.7, 12.8] for stage >2 and 13.5 years [95% CI 13.5, 13.6] for stage >3. Predictors of younger age at Tanner stage >1 included low birthweight, younger maternal age at delivery and being taller at age 8. Associations were found between younger age at attainment of stage >2 and gestational diabetes and taller or heavier body size at age 8. Being taller or heavier at age 8 also predicted younger age at Tanner stage >3. The results give added support to the strong influence of pre-adolescent body size on male pubertal development; the tallest and heaviest boys at 8 years achieved each stage earlier and the shortest boys later. Age at attainment of pubic hair Tanner stages in the ALSPAC cohort are similar to ages reported in other European studies that were conducted during overlapping time periods. This cohort will continue to be followed for maturational information until age 17.

Progression Through Puberty in Girls Enrolled in a Contemporary British Cohort

Data from the Avon Longitudinal Study of Parents and Children were used to describe initiation of secondary sexual characteristic development of girls. Tanner stages of breast and pubic hair and menarche status were self-reported via mailed questionnaires, administered from ages 8–14. Initiation pathway was categorized as breast [thelarche] or pubic hair [pubarche] development alone, or synchronous. Average ages at beginning breast and pubic hair development were estimated using survival analysis. Factors associated with initiation pathway were assessed using logistic regression. Among the 3938 participants, the median ages at beginning breast and pubic hair development were 10.19 (95% CI: 10.14–10.24) and 10.95 (95% CI: 10.90–11.00) years. Synchronous initiation was the most commonly reported pathway (46.3%), followed by thelarche (42.1%). Girls in the pubarche pathway were less likely to be obese or overweight at age 8 or have an overweight or obese mother. Girls in the thelarche pathway were less likely to be of nonwhite race or be the third born or later child.

Prenatal Exposure to Perfluoroalkyl Acids and Serum Testosterone Concentrations at 15 Years of Age in Female ALSPAC Study Participants

Background Exposure to perfluorooctane sulfonic acid (PFOS) or to perfluorooctanoic acid (PFOA) increases mouse and human peroxisome proliferator–activated receptor alpha (PPARα) subtype activity, which influences lipid metabolism. Because cholesterol is the substrate from which testosterone is synthesized, exposure to these substances has the potential to alter testosterone concentrations. Objectives We explored associations of total testosterone and sex hormone–binding globulin (SHBG) concentrations at age 15 years with prenatal exposures to PFOS, PFOA, perfluorohexane sulfonic acid (PFHxS), and perfluoronanoic acid (PFNA) in females. Methods Prenatal concentrations of the perfluoroalkyl acids (PFAAs) were measured in serum collected from pregnant mothers at enrollment (1991–1992) in the Avon Longitudinal Study of Parents and Children (ALSPAC). The median gestational age when the maternal blood sample was obtained was 16 weeks (interquartile range, 11–28 weeks). Total testosterone and SHBG concentrations were measured in serum obtained from their daughters at 15 years of age. Associations between prenatal PFAAs concentrations and reproductive outcomes were estimated using linear regression models (n = 72). Results Adjusted total testosterone concentrations were on average 0.18-nmol/L (95% CI: 0.01, 0.35) higher in daughters with prenatal PFOS in the upper concentration tertile compared with daughters with prenatal PFOS in the lower tertile. Adjusted total testosterone concentrations were also higher in daughters with prenatal concentrations of PFOA (β = 0.24; 95% CI: 0.05, 0.43) and PFHxS (β = 0.18; 95% CI: 0.00, 0.35) in the upper tertile compared with daughters with concentrations in the lower tertile. We did not find evidence of associations between PFNA and total testosterone or between any of the PFAAs and SHBG. Conclusions Our findings were based on a small study sample and should be interpreted with caution. However, they suggest that prenatal exposure to some PFAAs may alter testosterone concentrations in females. Citation Maisonet M, Calafat AM, Marcus M, Jaakkola JJ, Lashen H. 2015. Prenatal exposure to perfluoroalkyl acids and serum testosterone concentrations at 15 years of age in female ALSPAC study participants. Environ Health Perspect 123:1325–1330; http://dx.doi.org/10.1289/ehp.1408847

Pubertal Pathways in Girls Enrolled in a Contemporary British Cohort

Data from the Avon Longitudinal Study of Parents and Children were used to describe initiation of secondary sexual characteristic development of girls. Tanner stages of breast and pubic hair and menarche status were self-reported via mailed questionnaires, administered from ages 8–14. Initiation pathway was categorized as breast [thelarche] or pubic hair [pubarche] development alone, or synchronous. Average ages at beginning breast and pubic hair development were estimated using survival analysis. Factors associated with initiation pathway were assessed using logistic regression. Among the 3938 participants, the median ages at beginning breast and pubic hair development were 10.19 (95% CI: 10.14–10.24) and 10.95 (95% CI: 10.90–11.00) years. Synchronous initiation was the most commonly reported pathway (46.3%), followed by thelarche (42.1%). Girls in the pubarche pathway were less likely to be obese or overweight at age 8 or have an overweight or obese mother. Girls in the thelarche pathway were less likely to be of nonwhite race or be the third born or later child.

Characterization of the Correlation Between Ages at Entry Into Breast and Pubic Hair Development

Purpose The timing of breast and pubic hair development in girls are related, but the degree of correlation has not been well characterized. Periodic observations also are complicated by interval censoring. Methods Data used were from the Avon Longitudinal Study of Parents and Children. Mean age at entry into breast and pubic hair development was determined by the use of parametric survival analysis. The bivariate normal cumulative distribution function was evaluated over the region containing the paired event times; the likelihood was maximized with respect to the correlation coefficient ρ. Results Among 3938 participants, estimated mean ages at entry into Tanner stage 2 for breast and pubic hair development were 10.19 and 10.95, respectively. The likelihood was maximized at ρ = 0.503 to 0.506. This value remained relatively constant among subgroups, although some heterogeneity was observed by maternal and child body mass index and birth order. Conclusions The timing of breast and of pubic hair development is moderately correlated and remain so when it is stratified by characteristics associated with puberty.

Prenatal exposures to perfluoroalkyl acids and serum lipids at ages 7 and 15 in females.

BACKGROUND In some cross-sectional epidemiologic studies the shape of the association between serum concentrations of perfluoroalkyl acids (PFAAs) and lipids suggests departures from linearity. OBJECTIVES We used statistical approaches allowing for non-linearity to determine associations of prenatal exposures of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) with lipid concentrations. METHODS PFAAs were measured in serum from pregnant women collected in 1991-1992 at enrollment in the Avon Longitudinal Study of Parents and Children and lipids in serum from their daughters at ages 7 (n=111) and 15 (n=88). The associations of PFAAs with lipids were first explored by cubic splines, followed by piecewise linear regressions by tertiles to obtain regression coefficients (β) and their 95% confidence limits (95% CL) (in mg/dL per 1ng/mL). RESULTS At age 7, total cholesterol was positively associated with prenatal PFOA concentrations in the lower tertile (β=15.01; 95% CL=2.34, 27.69) but not with PFOA concentrations in the middle (β=-3.63; 95% CL=-17.43, 10.16) and upper (β=-1.58; 95% CL=-4.58, 1.42) tertiles. At age 15, a similar pattern was noted as well. Positive associations between LDL-C and prenatal PFOA concentration in the lower tertile were observed in daughters at ages 7 (β=14.91; 95% CL=3.53, 28.12) and 15 (β=13.93; 95% CL=0.60, 27.26). LDL-C was not associated with PFOA concentrations in the middle or upper tertile at any age. Neither HDL-C nor triglycerides was associated with prenatal PFOA exposure. Non-linear patterns of association of total cholesterol and LDL-C with prenatal PFOS were less consistently noted. CONCLUSION Exposure to low levels of PFOA during prenatal development may alter lipid metabolism later in life. Given the small sample size further replication of the association in large independent cohorts is important.

Associations of Lifestyle Factors (Smoking, Alcohol Consumption, Diet and Physical Activity) With Type 2 Diabetes among American Adults from National Health and Nutrition Examination Survey (NHANES) 2005–2014

Over the long term, unhealthy lifestyles can lead to many health problems, especially type 2 diabetes (T2D). The aim of the present study was to determine associations between lifestyle factors (smoking, alcohol consumption, physical activity, and diet) and T2D in American adults (aged ≥20 years) in a nationally representative sample.