Associations between maternal serum neonicotinoid pesticide exposure during pregnancy and newborn telomere length: Effect modification by sampling season.

BACKGROUND: An increasing amount of evidence suggests that telomere length (TL) at birth can predict lifespan and is associated with chronic diseases later in life, but newborn TL may be affected by environmental pollutants. Neonicotinoids (NEOs) are widely used worldwide, and despite an increasing number of studies showing that they may have adverse effects on birth in mammals and even humans, few studies have examined the effect of NEO exposure on newborn TLs. OBJECTIVE: To investigate the effects of prenatal exposure to NEOs and the interactions between NEOs and sampling season on newborn TL. METHODS: We conducted a prospective cohort study of 500 mother-newborn pairs from the Guangxi Zhuang Birth Cohort. Ultraperformance liquid chromatographymass spectrometry was used to detect ten NEOs in maternal serum, and fluorescence quantitative PCR was used to estimate the newborn TL. A generalized linear model (GLM) was used to evaluate the relationships between individual NEO exposures and TLs , and quantile g-computation (Qgcomp) model and Bayesian kernel machine regression (BKMR) model were used to evaluate the combined effect of mixtures of components. RESULTS: The results of the GLM showed that compared with maternal TMX levels < LOD, maternal TMX levels < median were negatively correlated with newborn TL (-6.93%, 95% CI%: -11.92%, -1.66%), and the decrease in newborn TL was more pronounced in girls (-9.60%, 95% CI: -16.84%, -1.72%). Moreover, different kinds of maternal NEO exposure had different effects on newborn TL in different sampling seasons, and the effect was statistically significant in all seasons except in autumn. Mixed exposure analysis revealed a potential positive trend between NEOs and newborn TL, but the association was not statistically significant. CONCLUSION: Prenatal exposure to TMX may shorten newborn TL, and this effect is more pronounced among female newborns. Furthermore, the relationship between NEO exposure and TL may be modified by the sampling season.

Association between maternal exposure to per- and polyfluoroalkyl substances and serum markers of liver function during pregnancy in China: A mixture-based approach.

Previous studies have shown that per- and polyfluoroalkyl substances (PFAS) may have hepatotoxic effects in animals. However, epidemiological evidence in humans, especially pregnant women, is limited. This study aimed to assess the association of single and multiple PFAS exposure with serum markers of liver function in pregnant women. A total of 420 pregnant women from the Guangxi Zhuang Birth Cohort were enrolled from June 2015 to April 2019. Nine PFAS were measured in the maternal serum in early pregnancy. Data for liver function biomarkers, namely, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL), were obtained from medical records. In generalized linear model (GLM), there was a positive association of perfluorooctane sulfonate (PFOS) with ALT, perfluorodecanoic acid (PFDA) and perfluorobutanesulfonic acid (PFBS) with GGT, and perfluorohexane sulfonate (PFHxS) with TBIL and IBIL. In contrast, there was a negative association of perfluoroheptanoic acid (PFHpA) with TBIL. There were inverse U-shaped relationships of PFUnA with ALT and AST and PFDA with ALT by restricted cubic spline. The weighted quantile sum (WQS) regression model revealed the positive effects of the PFAS mixture on GGT, TBIL, DBIL, and IBIL. Bayesian kernel machine regression (BKMR) analysis confirmed that the PFAS mixture was positively associated with GGT, and PFBS was the main contributor. In addition, the BKMR model showed a positive association of individual PFBS with GGT, individual PFHxS with TBIL and IBIL, and a negative association of individual PFHpA with TBIL. Our findings provide evidence of an association between individual PFAS, PFAS mixture and maternal serum markers of liver function during pregnancy. Additionally, these findings also enhance concerns over PFAS exposure on maternal liver function and PFAS monitoring in pregnancy, reducing the effect of maternal liver dysfunction on maternal and infant health.

Effects of prenatal exposure to bisphenols on newborn leucocyte telomere length: a prospective birth cohort study in China.

Telomere length (TL) at birth is related to diseases that may arise in the future and long-term health. Bisphenols exhibit toxic effects and can cross the placenta barrier. However, the effects of prenatal exposure to bisphenols on newborn TL remain unknown. We aimed to explore the effects of prenatal exposure to bisphenols (i.e., bisphenol A [BPA], bisphenol B [BPB], bisphenol F [BPF], bisphenol S [BPS] and tetrabromobisphenol A [TBBPA]) on relative TL in newborns. A total of 801 mother-infant pairs were extracted from the Guangxi Zhuang Birth Cohort. The relationship between bisphenol levels in maternal serum and relative TL in cord blood was examined by generalized linear models and restricted cubic spline (RCS) models. After adjusting for confounders, we observed a 3.19% (95% CI: -6.08%, -0.21%; P = 0.037) reduction in relative cord blood TL among mothers ≥ 28 years old, with each onefold increase in BPS. However, in each onefold increase of TBBPA, we observed a 3.31% (95% CI: 0.67%, 6.01%; P = 0.014) increase in relative cord blood TL among mothers < 28 years old. The adjusted RCS models revealed similar results (P overall < 0.05, P non-linear > 0.05). This study was the first to establish a positive association between serum TBBPA levels and relative TL in newborns born to young mothers. However, BPS levels were inversely correlated with TL in fetus born to old mothers. The results suggested that the fetus of old pregnant women may be more sensitive to BPS exposure. Moreover, BPS exposure early in life may accelerate aging or increase the risk of developing BPS-related diseases in later life.

Associations between prenatal multiple plasma metal exposure and newborn telomere length: Effect modification by maternal age and infant sex.

Exposure to metals during pregnancy may affect maternal and infant health. However, studies on the combined effects of metals on the telomere length (TL) of newborns are limited. A prospective cohort study was conducted among 1313 mother-newborn pairs in the Guangxi Zhuang Birth Cohort. The concentrations of metals in maternal plasma during the first trimester were measured using inductively coupled plasma-mass spectrometry. We explored the associations between nine plasma metals and newborn TL using generalized linear models (GLMs), principal component analysis (PCA), quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR). The GLMs revealed the inverse association between plasma arsenic (percent change, -5.56%; 95% CI: -7.69%, -3.38%) and barium concentrations (-9.84%; 95% CI: -13.81%, -5.68%) and newborn TL. Lead levels were related to significant decreases in newborn TL only in females. The PCA revealed a negative association between the PC3 and newborn TL (-4.52%; 95% CI: -6.34%, -2.68%). In the BKMR, the joint effect of metals was negatively associated with newborn TL. Qgcomp indicated that each one-tertile increase in metal mixture levels was associated with shorter newborn TL (-9.39%; 95% CI: -14.32%, -4.18%). The single and joint effects of multiple metals were more pronounced among pregnant women carrying female fetuses and among pregnant women <28 years of age. The finding suggests that prenatal exposure to arsenic, barium, antimony, and lead and mixed metals may shorten newborn TLs. The relationship between metal exposures and newborn TL may exhibit heterogeneities according to infant sex and maternal age.

Association of single and multiple prefluoroalkyl substances exposure with preterm birth: Results from a Chinese birth cohort study.

BACKGROUND: Perfluoroalkyl substances (PFASs) are persistent organic pollutants that may lead the adverse birth outcomes, including preterm birth (PTB). However, previous studies have reported inconsistent results on the association between PFASs and PTB, and lack of the epidemiological evidence regarding the effect of PFASs mixture on PTB. This study aimed to explore association of individual and multiple exposure to PFASs with PTB. METHODS: The study subjects were consisted of 1341 pregnant women from Guangxi Zhuang Birth Cohort in Guangxi, China, from June 2015 to April 2019. Nine PFASs concentrations in the maternal serum were examined by ultrahigh liquid performance chromatography-tandem mass spectrometry, and the gestational weeks were obtained from medical records. We applied binary logistics regression model to explore correlation between individual PFAS and PTB and inspected the combined effect of PFASs mixture on PTB by applying Bayesian kernel machine regression (BKMR) and weighted quantile sum (WQS) regression models. RESULTS: In adjusted logistics regression model, perfluorooctane sulfonate (PFOS), perfluoroheptanoic acid (PFHpA), perfluorobutanesulfonic acid (PFBS), ∑perfluorinated sulfonic acids (PFSA), and ∑PFASs were positively associated with the risk of PTB. In contrast, perfluoroundecanoic acid (PFUnA), perfluorohexane sulfonate (PFHxS), and perfluorooctanoic acid (PFOA) were negatively associated with the risk of PTB. These associations of n PFOS and PFHpA with PTB were found to be more pronounced in male infants. Restricted cubic splines (RCSs) showed an inverse U-shaped relationship between PFBS and PTB. Analysis from BKMR model showed a positive association between PFASs mixture and PTB, and no evidence of interactions among the nine PFASs were detected. Additionally, PFHpA, PFOS, and PFBS were identified as the main contributors for the effect of PFASs mixture on increasing the risk of PTB by BKMR and WQS models. CONCLUSION: Prenatal exposure to higher levels of PFASs mixture was associated with higher risk of PTB.

Association between maternal per- and polyfluoroalkyl substance exposure and newborn telomere length: Effect modification by birth seasons.

BACKGROUND: Telomere length (TL) is an important biomarker of biological aging and disease that may be affected by prenatal exposure to environmental pollutants. Birth seasons have been linked to reproductive and immune-related diseases. Prenatal exposure to per- and polyfluoroalkyl substance (PFAS) has been associated with adverse birth outcomes, but the effects of PFAS and birth seasons on newborn TL are poorly understood. OBJECTIVES: To explore the individual and combined effects of maternal PFAS exposure on newborn TL, with exploration of the interaction between PFAS and birth seasons on newborn TL. METHODS: Between June 2015 and May 2018, a total of 499 mother-newborn pairs were recruited for a birth cohort study in Guangxi, China. Maternal blood samples were collected during pregnancy. Nine PFASs were measured by ultraperformance liquid chromatography-mass spectrometry. Newborn TL was assessed using quantitative real-time polymerase chain reaction. Modeling newborn TL as the outcome, multivariable linear regressions were performed for individual PFAS exposures, and Bayesian Kernel Machine Regressions were performed for PFAS mixtures. Furthermore, interaction analyses were conducted to evaluate the effect modification by birth seasons in these relationships. RESULTS: For both single and multipollutant models, PFASs exposure were inversely associated with newborn TL, although none of the relationships were significant. The mixture of PFASs showed a potential positive trend of combined effect on newborn TL but non-statistically significant. Each ln-transformed unit concentration increase in PFOA was related to a 20.41% (95% CI: -30.44%, -8.93%) shorter TL in spring-born infants but not in those born in other birth seasons. Mothers in the middle and highest tertiles of PFOA exposure had 11.69% and 10.71% shorter TLs in spring-born infants, respectively. CONCLUSION: Maternal PFAS exposure showed little association with newborn TL. The results suggested potential effect modification by birth season on the association between PFOA exposure and newborn TL.

Maternal overweight but not paternal overweight before pregnancy is associated with shorter newborn telomere length: evidence from Guangxi Zhuang birth cohort in China.

BACKGROUND: Telomere length (TL) is variable at birth and is inversely associated with body mass index (BMI) in adulthood. A growing number of evidences suggested that a higher maternal pre-pregnancy BMI results in adverse offspring health outcomes, especially shorter newborn TL. However, a newborn's genetic endowment is equally derived from both parents, the association between parental pre-pregnancy BMI and newborn TL has been rarely discussed. We aimed to determine the association between parental pre-pregnancy BMI and newborn TL. METHODS: A total of 1082 parent-newborn pairs were recruited from the Guangxi Zhuang Birth Cohort (GZBC). TL in cord blood was measured using quantitative real-time polymerase chain reaction (qPCR) and expressed as the ratio of telomere copy number to single-copy gene number (T/S). A series of linear regressions were performed to assess the associations between parental pre-pregnancy BMI and newborn TL. RESULTS: Mothers who were overweight before pregnancy had significantly shorter cord blood telomere length in their newborns than those who were normal weight before pregnancy [percentage change: - 7.96% (95% CI: - 14.49 to - 0.69%; P = 0.032)]. Further analysis of the combined effects of parental weight status on newborn TL showed that TL was significantly shortened among newborns whose mothers were overweight and fathers were of healthy weight when compared with those whose mothers and fathers were both of normal weight [percentage change: - 8.38% (95% CI: - 15.47 to - 0.92%; P = 0.028)]. Subgroup analysis indicated these effects were more pronounced among male newborns and those whose paternal age < 31 years or maternal age ≥ 28 years at delivery. CONCLUSIONS: Maternal pre-pregnancy overweight, but not paternal pre-pregnancy overweight is associated with shorter newborn TL. Weight control in reproductive women and effective healthy weight management before pregnancy may be of particular benefit for improving longevity and life quality of offspring.

Reference Intervals of Thyroid Hormones and Correlation of BMI with Thyroid Function in Healthy Zhuang Ethnic Pregnant Women.

Ethnic differences in the level of thyroid hormones exist among individuals. The American Thyroid Association (ATA) recommends that an institution or region should establish a specific thyroid hormone reference value for each stage of pregnancy. To date, a limited number of studies have reported the level of thyroid hormones in Chinese minorities, and the exact relationship between BMI and thyroid function in pregnant women is ill. This study was performed to establish trimester-specific reference ranges of thyroid hormones in Zhuang ethnic pregnant women and explore the role of body mass index (BMI) on thyroid function. A total of 3324 Zhuang ethnic health pregnant women were recruited in this Zhuang population-based retrospective cross-sectional study. The values of thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were determined by automatic chemiluminescence immunoassay analyzer. Multivariate linear regression and binary logistic regression were constructed to evaluate the influence of BMI on the thyroid function. The established reference intervals for the serum thyroid hormones in three trimesters were as follows: TSH, 0.02-3.28, 0.03-3.22, and 0.08-3.71 mIU/L; FT4, 10.57-19.76, 10.05-19.23, and 8.96-17.75 pmol/L; FT3, 3.51-5.64, 3.42-5.42, and 2.93-5.03 pmol/L. These values were markedly lower than those provided by the manufacturers for nonpregnant adults which can potentially result in 6.10% to 19.73% misclassification in Zhuang pregnant women. Moreover, BMI was positively correlated with isolated hypothyroxinemia (OR=1.081, 95% CI=1.007-1.161), while the correlation between the BMI and subclinical hypothyroidism was not statistically significant (OR=0.991, 95% CI=0.917-1.072). This is the first study focusing on the reference ranges of thyroid hormones in Guangxi Zhuang ethnic pregnant women, which will improve the care of them in the diagnosis and treatment. We also found that high BMI was positively associated with the risk of isolated hypothyroxinemia.