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.

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 [per- 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 weeks' 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 regression and Bayesian kernel machine regression to examine mixtures in 313 mothers. RESULTS: Using weighted quantile sum 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 (β: -55 g, 95% 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.

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.

Aflatoxins are carcinogenic mycotoxins that contaminate a variety of crops worldwide. Acute exposure can cause liver failure, and chronic exposure can lead to stunting in children and liver cancer in adults. We estimated aflatoxin exposure across Uganda by measuring a serum biomarker of aflatoxin exposure in a subsample from the 2011 Uganda AIDS Indicator Survey, a nationally representative survey of HIV prevalence, and examined its association with geographic, demographic, and socioeconomic variables. We analysed a subsample of 985 serum specimens selected among HIV-negative participants from 10 survey-defined geographic regions for serum aflatoxin B1-lysine (AFB1-lys) by use of isotope dilution LC-MS/MS and calculated results normalised to serum albumin. We used statistical techniques for censored data to estimate geometric means (GMs), standard deviations, and percentiles. We detected serum AFB1-lys in 71.7% of specimens (LOD = 0.5 pg/mg albumin). Unadjusted GM AFB1-lys (pg/mg albumin) was 1.33 (95% CI: 1.21-1.47). Serum AFB1-lys was higher in males (GM: 1.57; 95% CI: 1.38-1.80) vs. females (GM: 1.12; 95% CI: 0.97-1.30) (P = .0019), and higher in persons residing in urban settings (GM: 2.83; 95% CI: 2.37-3.37) vs. rural (GM: 1.10; 95% CI: 0.99-1.23) (P < .0001). When we used a multivariable censored regression model to assess confounding and interactions among variables we found that survey region, gender, age, occupation, distance to marketplace, and number of meals per day were statistically significant predictors of aflatoxin exposure. While not nationally representative, our findings provide an improved understanding of the widespread burden of aflatoxin exposure throughout Uganda and identify key geographic, demographic, and socioeconomic factors that may modulate aflatoxin exposure risk.

Aflatoxins contaminate approximately 25% of agricultural products worldwide. They can cause liver failure and liver cancer. Kenya has experienced multiple aflatoxicosis outbreaks in recent years, often resulting in fatalities. However, the full extent of aflatoxin exposure in Kenya has been unknown. Our objective was to quantify aflatoxin exposure across Kenya. We analysed aflatoxin levels in serum specimens from the 2007 Kenya AIDS Indicator Survey - a nationally representative, cross-sectional serosurvey. KAIS collected 15,853 blood specimens. Of the 3180 human immunodeficiency virus-negative specimens with ≥1 mL sera, we randomly selected 600 specimens stratified by province and sex. We analysed serum specimens for aflatoxin albumin adducts by using isotope dilution MS/MS to quantify aflatoxin B1-lysine, and normalised with serum albumin. Aflatoxin concentrations were then compared by demographic, socioeconomic and geographic characteristics. We detected serum aflatoxin B1-lysine in 78% of serum specimens (range = <LOD-211 pg/mg albumin, median = 1.78 pg/mg albumin). Aflatoxin exposure did not vary by sex, age group, marital status, religion or socioeconomic characteristics. Aflatoxin exposure varied by province (p < 0.05); it was highest in Eastern (median = 7.87 pg/mg albumin) and Coast (median = 3.70 pg/mg albumin) provinces and lowest in Nyanza (median = <LOD) and Rift Valley (median = 0.70 pg/mg albumin) provinces. Our findings suggest that aflatoxin exposure is a public health problem throughout Kenya, and it could be substantially impacting human health. Wide-scale, evidence-based interventions are urgently needed to decrease exposure and subsequent health effects.

BACKGROUND: Aflatoxin, a potent fungal toxin, contaminates 25% of crops worldwide. Since 2004, 477 aflatoxin poisonings associated with eating contaminated maize have been documented in Eastern Kenya, with a case-fatality rate of 40%. OBJECTIVE: To characterize maize aflatoxin contamination during the high risk season (April-June) following the major harvests in 2005, 2006 (aflatoxicosis outbreak years), and 2007 (a non-outbreak year). METHODS: Households were randomly selected each year from the region in Kenya where outbreaks have consistently occurred. At each household, we obtained at least one maize sample (n = 716) for aflatoxin analysis using immunoaffinity methods and administered a questionnaire to determine the source (i.e. homegrown, purchased or relief) and amount of maize in the household. RESULTS: During outbreak years-2005 and 2006, 41% and 51% of maize samples respectively, had aflatoxin levels above the 20 ppb Kenyan regulatory limit for aflatoxin in grains for human consumption. In 2007 (non-outbreak year), 16% of samples were above the 20 ppb limit. In addition, geometric mean (GM) aflatoxin levels were significantly higher in 2005 (GM=12.92, max=48,000 ppb) and 2006 (GM=26.03, max=24,400 ppb) compared to 2007 (GM=1.95, max=2,500 ppb) (p value<.001). In all three years combined, maize aflatoxin levels were significantly higher in homegrown maize (GM=17.96) when compared to purchased maize (GM=3.64) or relief maize (GM=0.73) (p value<.0001). CONCLUSIONS: Aflatoxin contamination is extreme within this region and homegrown maize is the primary source of contamination. Prevention measures should focus on reducing homegrown maize contamination at the household level to avert future outbreaks.