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Background: Prenatal exposure to metals has been individually associated with birth outcomes. However, little is known about the effect of metal mixture, particularly at low exposure levels. Objectives: To estimate individual and joint effects of metal mixture components on birth outcomes. Methods: We used data from 1,391 mother-infant pairs in Project Viva (1999–2002). We measured 11 metals in maternal 1st trimester erythrocyte; abstracted birth weight from medical records; calculated gestational age from last menstrual period or ultrasound; and obtained birth length (n = 729) and head circumference (n = 791) from research measurements. We estimated individual and joint effects of metals using multivariable linear and Bayesian kernel machine regressions. Results: In both single metal and metal mixture analyses, exposure to higher concentrations of arsenic was associated with lower birth weight in males, zinc with higher head circumference in females, and manganese with higher birth length in sex-combined analysis. We also observed sex-specific metal interactions with birth outcomes. Arsenic and manganese showed a synergistic association with birth weight in males, in whom an interquartile range (IQR) increase in arsenic was associated with 25.3 g (95% CI: −79.9, 29.3), 47.9 g (95% CI: −98.0, 2.1), and 72.2 g (95% CI: −129.8, −14.7) lower birth weight when manganese concentrations were at 25th, 50th, and 75th percentiles, respectively. Lead and zinc showed an antagonistic association with head circumference in males, where an IQR increase in lead was associated with 0.18 cm (95% CI: −0.35, −0.02), 0.10 cm (95% CI: −0.25, 0.04), 0.03 cm (95% CI: −0.2, 0.14) smaller head circumference when zinc concentrations were at 25th, 50th, and 75th percentiles, respectively. Exposure to higher concentrations of arsenic was also associated with lower gestational age in males when concentrations of manganese and lead were higher. Discussion: Maternal erythrocyte concentrations of arsenic, manganese, lead, and zinc were individually and interactively associated with birth outcomes. The associations varied by infant sex and exposure level of other mixture components.

Abstract: Although pesticide use is widespread in China, little is known about levels of exposure to organophosphate pesticides in the population and its potential adverse health effects. We investigated levels of organophosphate exposure in pregnant women and the association between organophosphate exposure and perinatal outcomes in Shanghai, China, by enrolling 187 healthy pregnant women between September 2006 and January 2007. Pesticide exposure was assessed by a questionnaire administered to the mothers in the hospital after delivery as well as by analyses of maternal urinary nonspecific metabolites of organophosphate pesticides (dimethyl and diethyl phosphates). Information on birth weight and length was collected from medical records. Geometric means of metabolites were 25.75μg/L for dimethylphosphate (DMP); 11.99μg/L for dimethylthiophosphate (DMTP); 9.03μg/L for diethylphosphate (DEP); and 9.45μg/L for diethyldithiophosphate (DETP). We found that a log unit increase in urinary DEP was associated with a decrease in gestational duration in girls by 1.79weeks. [ßadjusted =−1.79weeks per log10 unit increase; 95% confidence interval (CI), −2.82 to −0.76; p=0.001]. These data suggest that high pesticide level might adversely affect duration of gestation although this association was not present among boys. No associations for any of the organophosphate exposure measures were present for birth weight and length, suggesting that organophosphate pesticides may have no effects on fetal growth. Given that maternal urine pesticide levels in Shanghai were much higher than those reported in developed countries, more studies on the effects of in utero organophosphate exposure on fetal growth and child neurodevelopment are warranted. [Copyright &y& Elsevier]

In utero exposure to polybrominated diphenyl ethers (PBDEs) reduces the number of ovarian follicles in rat females and causes permanent effects on rat males. Little data have been gathered on the associations between PBDEs exposure and birth outcome and female menstruation characteristics in both epidemiological and animal studies. The aim of this study was to examine how PBDEs in breast milk are associated with infant birth outcome and maternal menstruation characteristics. Study participants were healthy women recruited from central Taiwan between December 2000 and November 2001. Twelve congener levels of PBDEs (BDE-17, 28, 47, 66, 85, 99, 100, 138, 153, 154, 183, 209) in 20 breast milk samples were measured by gas chromatography with high resolution mass spectrometer. The mean level of PBDEs in breast milk was 3.93±1.74 ng/g lipid. The estimated PBDE daily intake for a breastfed infant was 20.6 ng/kg b.w./day after delivery. After maternal age, pre-pregnant BMI, and parity were adjusted, increased PBDEs in breast milk was related with decreased birth outcome, particularly for birth weight and length, chest circumference, and Quetelet''s index of infants. No significant differences in PBDEs were found between the two groups of menstrual cycle length higher and lower than 30 days after we adjusted for maternal age, pre-pregnant BMI, and parity. In utero exposure to low doses of PBDEs may result in lower birth weight and short or birth length. Our findings are limited based on the low doses of PBDEs and the small sampling size. [Copyright &y& Elsevier]

• As, Mn, Pb and Zn in maternal RBC were associated with birth outcomes. • Associations varied by infant sex and exposure level of other mixture components. • Birth weight lowering effect of As was stronger at higher levels of Mn in males. • Head circumference lowering effect of Pb was attenuated at higher levels of Zn. • As was associated with lower gestational age at higher levels of Mn and Pb in males. Prenatal exposure to metals has been individually associated with birth outcomes. However, little is known about the effect of metal mixture, particularly at low exposure levels. To estimate individual and joint effects of metal mixture components on birth outcomes. We used data from 1,391 mother-infant pairs in Project Viva (1999–2002). We measured 11 metals in maternal 1st trimester erythrocyte; abstracted birth weight from medical records; calculated gestational age from last menstrual period or ultrasound; and obtained birth length (n = 729) and head circumference (n = 791) from research measurements. We estimated individual and joint effects of metals using multivariable linear and Bayesian kernel machine regressions. In both single metal and metal mixture analyses, exposure to higher concentrations of arsenic was associated with lower birth weight in males, zinc with higher head circumference in females, and manganese with higher birth length in sex-combined analysis. We also observed sex-specific metal interactions with birth outcomes. Arsenic and manganese showed a synergistic association with birth weight in males, in whom an interquartile range (IQR) increase in arsenic was associated with 25.3 g (95% CI: −79.9, 29.3), 47.9 g (95% CI: −98.0, 2.1), and 72.2 g (95% CI: −129.8, −14.7) lower birth weight when manganese concentrations were at 25th, 50th, and 75th percentiles, respectively. Lead and zinc showed an antagonistic association with head circumference in males, where an IQR increase in lead was associated with 0.18 cm (95% CI: −0.35, −0.02), 0.10 cm (95% CI: −0.25, 0.04), 0.03 cm (95% CI: −0.2, 0.14) smaller head circumference when zinc concentrations were at 25th, 50th, and 75th percentiles, respectively. Exposure to higher concentrations of arsenic was also associated with lower gestational age in males when concentrations of manganese and lead were higher. Maternal erythrocyte concentrations of arsenic, manganese, lead, and zinc were individually and interactively associated with birth outcomes. The associations varied by infant sex and exposure level of other mixture components. [ABSTRACT FROM AUTHOR]

• Our paper reports on adverse pregnancy outcomes of women living in artisanal gold mining communities in Tanzania. • We highlight the prospective longitudinal study design which obtained pregnancy outcomes on 961 women and the use of direct measurement of mercury and arsenic levels during the pregnancy. • Just over 50% of women living in these gold mining communities had an adverse pregnancy outcome. Exposure to arsenic and mercury in artisanal and small-scale gold mining (ASGM) communities is an issue that predominantly affects low and middle-income countries. Large epidemiology studies in these communities are rare, and the impact of such exposures on reproductive outcomes are not well understood. To examine associations between prenatal maternal arsenic and mercury exposure and birth outcomes in both ASGM and non-ASGM communities in Northern Tanzania. This longitudinal prospective study included 961 women (ASGM = 788, non-ASGM = 173) of the original cohort of 1056 who were followed until a pregnancy outcome was registered. Maternal spot urine samples and dried blood spots were used to measure total arsenic (T-As) and total mercury (T-Hg) in the second trimester of pregnancy. Data on adverse birth outcomes were collected in 5 categories: spontaneous abortion, stillbirth, preterm birth, low birth weight, and visible congenital anomalies. Mann-Whitney U -tests were used to test for differences between median T-As and T-Hg by area of residence. Logistic regression models were used to estimate the odds of stillbirth and visible congenital anomalies given maternal T-As and T-Hg levels. Modified Poisson regressions were used to estimate relative risk ratios between maternal T-As and T-Hg levels and composite adverse birth outcome, spontaneous abortion, low birth weight, and preterm birth. Statistically significant differences were found in median T-As (9.6 vs. 6.3 µg/L, Mann-Whitney U -tests , Z = −3.50, p < 0.001) and median T-Hg blood concentrations (1.2 vs. 0.70 µg/L, Z = −9.88, p-value < 0.001) between women living in ASGM and non-ASGM areas respectively. In ASGM areas, the adjusted relative risk (aRR) of a composite adverse birth outcome increased with increasing T-As (aRR 1.23, 95%CI: 1.14–1.33, p < 0.0001) and T-Hg (aRR 1.17, 95%CI: 1.1–1.25, p < 0.0001) exposure. Spontaneous abortion (aRR 1.53, 95%CI: 1.28–1.83), stillbirth (adjusted odds ratio (aOR) 1.97, 95%CI: 1.45–2.66) and preterm birth (1.17, 95%CI: 1.01–1.36) were significantly associated with elevated T-As, whereas elevated T-Hg was significantly associated with stillbirth (aOR 2.49, 95%CI: 1.88–3.29) and visible congenital anomalies (aOR 2.24, 95%CI: 1.3–3.87). Over half (54.7%) of women in ASGM areas of Northern Tanzania had adverse birth outcomes and the risk of adverse birth outcomes was significantly associated with increased prenatal exposure to arsenic and mercury. [ABSTRACT FROM AUTHOR]