Association of exposure to ambient particulate matter with maternal thyroid function in early pregnancy.

BACKGROUND: It is known that maternal thyroid dysfunction during early pregnancy can cause adverse pregnancy complications and birth outcomes. This study was designed to examine the association between ambient particulate matter with aerodynamic diameters ≤2.5 µm (PM2.5) and particulate matter with aerodynamic diameters ≤10 µm (PM10) exposure and maternal thyroid function during early pregnancy. METHODS: This study was based on data from a birth cohort study of 921 pregnant women in China. We estimated associations between ambient PM2.5 and PM10 exposure during the first trimester of pregnancy (estimated with land-use regression models) and maternal thyroid hormone concentrations (free thyroxine (FT4), free tri-iodothyronine (FT3), and thyroid-stimulating hormone (TSH)) collected between weeks 10 and 17 of gestation using linear regression models adjusting for potential confounders. Ambient PM2.5 and PM10 concentrations were modeled per interquartile range (IQR) increment and as tertiles based on the distribution of the exposure levels. RESULTS: An IQR increment (68 µg/m3) in PM2.5 exposure was associated with a significant decrease in maternal FT4 levels (ß = -0.60, 95% CI: -1.07, -0.12); and a significant decrease in FT4/FT3 ratio (ß = -0.13, 95% CI: -0.25, -0.02). Further analyses showed that, relative to the lowest tertile, women in both the middle and highest tertiles of PM2.5 had significantly lower concentrations of maternal FT4 and FT4/FT3 ratio. No significant associations were found between PM2.5 and FT3 or TSH levels. PM10 exposure was not significantly associated with maternal thyroid function. CONCLUSIONS: Our study suggested that higher ambient PM2.5, not PM10, exposed during the first trimester of pregnancy were associated with a significant decrease in maternal serum FT4 concentrations and FT4/FT3 ratio. Studies in populations with different exposure levels are needed to replicate our study results.

Plasma levels of trace element status in early pregnancy and the risk of gestational diabetes mellitus: A nested case-control study.

PURPOSE: We investigated the impacts of plasma levels of magnesium (Mg), zinc (Zn), calcium (Ca), iron (Fe), copper (Cu), selenium (Se), and chromium (Cr) on GDM risk and the potential mediation effect of blood glucose levels on the relationship between trace elements and GDM risk. METHODS: This nested case-control study was based on data from a birth cohort study conducted in Wuhan, China in 2013-2016. A total of 305 GDM cases and 305 individually-matched controls were included in the study. Conditional logistic regression models were used to estimate the associations between plasma trace element concentrations and GDM risk. A mediation analysis was conducted to explore whether blood glucose levels act as a mediator between trace element levels and GDM risk. RESULTS: An IQR increment in plasma levels of Fe and Cu was associated with a significant increase in GDM risk [OR = 2.04 (95 % CI 1.62, 2.57) and OR = 1.52 (95 % CI 1.25, 1.82)], respectively. On the other hand, an IQR increment in plasma levels of Zn and Ca was associated with a significant decrease in GDM risk [OR = 0.55 (95 % CI 0.43, 0.71) and OR = 0.72 (95 % CI 0.56, 0.92)], respectively. The mediation analysis showed significant mediation of the association between Cu and GDM risk via the FBG (%mediated: 19.27 %), 1 h-PBG (12.64 %), 2h-PBG (28.44 %) pathways. CONCLUSIONS: Plasma levels of Zn and Ca were negatively associated with GDM risk, while Fe and Cu were positively associated. Blood glucose levels act as a mediator between plasma trace element exposures and GDM risk.

Dataset of testicular germ cell tumors (TGCT) risk associated with serum polychlorinated biphenyl (PCB) by age at diagnosis and histologic types.

In a population-based case control study of testicular germ cell tumors (TGCT), we reported a strong positive association between serum levels of Wolff's Group 1 (potentially estrogenic) polychlorinated biphenyl (PCBs) and risk of TGCT, and the observed associations were similar for both seminoma and non-seminoma. While the observed specific associations between TGCT and Wolff's Group 1 PCBs cannot be easily explained by bias or confounding, a question can still be asked, that is, could the relationship between PCBs and TGCT differ by age at diagnosis? PCBs tend to bioaccumulate, with more heavily chlorinated PCB congeners tending to have longer half-lives. Half-lives of PCB congeners were reported ranging from 4.6 years for PCB-28 to 41.0 years for PCB-156. The half-life for the heavy PCB congeners (17.8 years) was found to be approximately twice that for the light PCBs (9.6 years) in early studies. Therefore, the same PCB concentration measured in a 20-year-old vs. a 55-year-old is unlikely to represent the same lifetime PCB exposure or type of PCB exposure. In this analysis, we stratified the data by median age of diagnosis of TGCT and further stratified by histologic type of TGCT (seminoma vs non-seminoma) to explore if the risk of TGCT associated with PCB exposures differs by age.

Serum polychlorinated biphenyl (PCB) levels and risk of testicular germ cell tumors: A population-based case-control study in Connecticut and Massachusetts.

The incidence rate of testicular germ cell tumors (TGCT) has continuously increased in Western countries over the last several decades. Some epidemiologic studies have reported that the endocrine disrupting polychlorinated biphenyls (PCBs) in serum may be associated with TGCT risk, but the evidence is inconsistent. Our goal was to investigate whether serum levels of PCBs are associated with the increase of TGCT risk. We conducted a population-based case-control study of 308 TGCT cases and 323 controls, all residents of Connecticut and Massachusetts. Serum levels of 56 PCBs congeners were measured using gas chromatography and unconditional logistic regression model was used to evaluate the risk of TGCT associated with total PCBs exposure, groups of PCBs categorized by Wolff's functional groups, and individual PCB congeners. The results showed that there was no association between total serum levels of PCBs and risk of TGCT overall (quartile 4 (Q4) vs. quartile 1 (Q1) odds ratio (OR) and 95% confidence interval (C.I.) = 1.0 (0.6-1.9), ρ trend = 0.9). However, strong positive association was observed between total serum levels of Wolff's Group 1 (potentially estrogenic) PCBs and risk of overall TGCT (Q4 vs. Q1 OR = 2.5, 95% CI = 1.3-4.7, ρ trend <0.05) as well as seminoma and non-seminoma subtypes. Wolff's Group 1 PCB congeners that showed an increased risk of TGCT included: 25, 44, 49, 52, 70, 101, 174, and 201/177. Considering the continuing increase of TGCT, these associations should be replicated in different populations with larger sample size.

Pregnant women with COVID-19 and risk of adverse birth outcomes and maternal-fetal vertical transmission: a population-based cohort study in Wuhan, China.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. However, little is known about the association between pregnant women with COVID-19 and the risk of adverse birth outcomes. METHOD: We conducted a retrospective cohort study based on the Maternal and Child Health Information System (MCHIMS) of Wuhan, China. All pregnant women with singleton live birth recorded by the system between January 13 and March 18, 2020, were included. The adverse birth outcomes were preterm birth, low birth weight, neonatal asphyxia, premature rupture of membrane (PROM), and cesarean section delivery. Multivariate logistic regression was used to evaluate the associations between maternal COVID-19 diagnosis and adverse birth outcomes. RESULTS: Out of 11,078 pregnant women, 65 were confirmed with coronavirus disease 2019 (COVID-19). No deaths occurred from these confirmed cases or their newborns. Compared to pregnant women without COVID-19, pregnant women with a confirmed COVID-19 diagnosis had an increased risk of preterm birth (OR 3.34, 95% CI 1.60-7.00) and cesarean section (OR 3.63, 95% CI 1.95-6.76). There was no statistical difference in low birth weight, neonatal asphyxia, and PROM between the mothers with and without COVID-19. Among these newborns that were born to mothers with confirmed COVID-19, none was tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive or had abnormal CT results. Only one had diarrhea and three had a fever. CONCLUSIONS: This population-based cohort study suggests that COVID-19 during the later pregnancy is associated with an increased risk of adverse birth outcomes, including iatrogenic preterm birth and cesarean section delivery. Our data provide little evidence for maternal-fetal vertical transmission of SARS-CoV-2. It is important to monitor the long-term health effects of SARS-CoV-2 infection on pregnant women and their children.

The long-term rapid increase in incidence of adenocarcinoma of the kidney in the USA, especially among younger ages.

BACKGROUND: We previously observed a rapid increase in the incidence of renal cell carcinoma (RCC) in men and women between 1935 and 1989 in the USA, using data from the Connecticut Tumor Registry. This increase appeared to be largely explained by a positive cohort effect, but no population-based study has been conducted to comprehensively examine age-period-cohort effects by histologic types for the past decade. METHODS: We calculated age-adjusted and age-specific incidence rates of the two major kidney-cancer subtypes RCC and renal urothelial carcinoma, and conducted an age-period-cohort analysis of 114 138 incident cases of kidney cancer reported between 1992 and 2014 to the Surveillance, Epidemiology, and End Results programme. RESULTS: The age-adjusted incidence rates of RCC have been increasing consistently in the USA among both men and women (from 12.18/100 000 in 1992-1994 to 18.35/100 000 in 2010-2014 among men; from 5.77/100 000 in 1992-1994 to 8.63/100 000 in 2010-2014 among women). Incidence rates generally increased in successive birth cohorts, with a continuing increase in rates among the younger age groups (ages 0-54 years) in both men and women and among both Whites and Blacks. These observations were confirmed by age-period-cohort modelling, which suggested an increasing birth-cohort trend for RCC beginning with 1955 birth cohorts, regardless of the assumed value for the period effect for both men and women and for Whites and Blacks. CONCLUSIONS: Known risk factors for kidney cancer may not fully account for the observed increasing rates or the birth-cohort pattern for RCC, prompting the need for additional etiologic hypotheses (such as environmental exposures) to investigate these descriptive patterns.

Effects of trimester-specific exposure to vanadium on ultrasound measures of fetal growth and birth size: a longitudinal prospective prenatal cohort study.

BACKGROUND: Identification of windows of heightened vulnerability to environmental factors has substantial public health implications. Prenatal exposure to vanadium has been linked to adverse birth outcomes; however, critical windows for such exposure during fetal growth remain unknown. We aimed to assess trimester-specific associations of vanadium exposure with ultrasound measures of fetal growth and birth size in a Chinese longitudinal cohort. METHODS: The present study was embedded in our ongoing prospective prenatal cohort study at the Wuhan Women and Children Medical Care Center (Wuhan, Hubei, China). Pregnant women were eligible for inclusion if they provided signed informed consent and were less than 16 weeks pregnant with a single gestation, and agreed to take in-person interviews, undergo ultrasound examinations, and provide blood and urine samples. We collected urine samples and measured urinary vanadium concentrations using inductively coupled plasma mass spectrometry. We calculated SD scores for ultrasound-measured biparietal diameter, head circumference, occipitofrontal diameter, abdominal circumference, femur length, and estimated fetal weight at 16, 24, and 31 weeks of gestation. We applied linear regressions with generalised estimating equations to estimate associations of urinary vanadium concentrations in each trimester with ultrasound-measured fetal growth parameters or neonatal size at birth. FINDINGS: As of Oct 12, 2016, we recruited 3075 women who were non-smokers and non-drinkers during pregnancy, provided up to three urine samples during the first, second, and third trimesters, and gave birth to live singletons without birth defects. We excluded women who did not provide information on ultrasound measurements (n=20) or who only had one ultrasound measurement of fetal crown-rump length at the first trimester (n=14). We excluded another 16 women because they had missing values for confounding variables, leaving 3025 women retained in the study. Every doubling of urinary vanadium concentration in the first trimester was associated with a significant increase in femur length (adjusted percentage change 6·4%, 95% CI 0·7 to 12·1) at 16 weeks of gestation and reductions in biparietal diameter (-4·2%, -8·2 to -0·1), head circumference (-6·0%, -10·1 to -1·9), occipitofrontal diameter (-5·7%, -9·9 to -1·5), and abdominal circumference (-5·3%, -9·4 to -1·2) at 31 weeks of gestation. Every doubling of urinary vanadium concentration in the second trimester was significantly associated with reductions in SD scores for head circumference (-7·2%, -14·1 to -0·3) and abdominal circumference (-6·9%, -13·8 to -0·1) at 31 weeks of gestation. The highest quartile of urinary vanadium concentration (>1·18 µg/L) in the first trimester, when compared with the lowest quartile (≤0·60 µg/L), was associated with a mean decrease in birthweight of 12·6 g (95% CI 2·5-22·8; ptrend=0·0055) and a mean decrease in ponderal index of 0·07 kg/m3 (0·01-0·12; ptrend=0·0053). Moreover, newborns with restricted birth size had higher vanadium exposure in the first and third trimesters. INTERPRETATION: Vanadium might be toxic to humans and impair fetal growth. The first, early second, and late third trimesters could be critical windows for heightened vulnerability to vanadium for fetal growth. Our findings require further investigation in other populations. FUNDING: National Key R&D Plan of China, National Natural Science Foundation of China, and Fundamental Research Funds for the Central Universities, Huazhong University of Science and Technology.

Critical Windows for Associations between Manganese Exposure during Pregnancy and Size at Birth: A Longitudinal Cohort Study in Wuhan, China.

BACKGROUND: Prenatal overexposure to manganese (Mn), an essential micronutrient, is related to impaired fetal growth and development. Fetuses appear to be highly sensitive to Mn during short periods of gestation. However, little is known about the critical windows of susceptibility to Mn for humans. OBJECTIVES: Our objective was to estimate trimester-specific associations of exposure to Mn with size at birth. METHODS: Urine samples of 3,022 women were collected repeatedly in the first, second, and third trimesters in Wuhan, China. Urinary concentrations of Mn and other toxic metals were measured using an inductively coupled plasma mass spectrometry. Trimester-specific associations of specific gravity­adjusted urinary Mn concentrations with birth weight, birth length, and ponderal index were estimated using multivariable linear regressions with generalized estimating equations. Linear mixed models were applied to evaluate the windows of susceptibility to Mn exposure by comparing the pattern of Mn exposure among newborns with restricted size at birth to those without. RESULTS: When compared with the third quintile of urinary Mn concentrations, both higher and lower quintiles of urinary Mn concentrations in the second and third trimesters were related to reduced birth weight, birth length, and ponderal index. But the observed associations for higher quintiles were stronger and more likely to be statistically significant [e.g., for women who were in the fifth quintile of Mn concentration in the third trimester, the reduction in birth weight was [Formula: see text] (95% CI: [Formula: see text], [Formula: see text]) g and in birth length was [Formula: see text] (95% CI: [Formula: see text], 0.00) cm]. Moreover, newborns with restricted size at birth, compared with those without, had higher levels of Mn exposure in the second and third trimesters. CONCLUSIONS: This prospective prenatal cohort study revealed an association of exposure to Mn during pregnancy, especially late pregnancy, with restricted size at birth. Replications are needed. https://doi.org/10.1289/EHP3423.

Effects of Environmental Exposures on Fetal and Childhood Growth Trajectories.

Delayed fetal growth and adverse birth outcomes are some of the greatest public health threats to this generation of children worldwide because these conditions are major determinants of mortality, morbidity, and disability in infancy and childhood and are also associated with diseases in adult life. A number of studies have investigated the impacts of a range of environmental conditions during pregnancy (including air pollution, endocrine disruptors, persistent organic pollutants, heavy metals) on fetal and child development. The results, while provocative, have been largely inconsistent. This review summarizes up to date epidemiologic studies linking major environmental pollutants to fetal and child development and suggested future directions for further investigation.