First-trimester fetal size, accelerated growth in utero, and child neurodevelopment in a cohort study.

BACKGROUND: Early pregnancy is a critical window for neural system programming; however, the association of first-trimester fetal size with children's neurodevelopment remains to be assessed. This study aimed to explore the association between first-trimester fetal size and children's neurodevelopment and to examine whether intrauterine accelerated growth could compensate for the detrimental effects of first-trimester restricted growth on childhood neurodevelopment. METHODS: The participants were from a birth cohort enrolled from March 2014 to March 2019 in Wuhan, China. A total of 2058 fetuses with crown to rump length (CRL) (a proxy of first-trimester fetal size) measurements in the first trimester and neurodevelopmental assessment at age 2 years were included. We measured the first-trimester CRL and defined three fetal growth patterns based on the growth rate of estimated fetal weight from mid to late pregnancy. The neurodevelopment was assessed using the Bayley Scales of Infant Development of China Revision at 2 years. RESULTS: Each unit (a Z score) increase of first-trimester CRL was associated with increased scores in mental developmental index (MDI) (adjusted beta estimate = 1.19, (95% CI: 0.42, 1.95), P = 0.03) and psychomotor developmental index (PDI) (adjusted beta estimate = 1.36, (95% CI: 0.46, 2.26), P < 0.01) at age 2 years, respectively. No significant association was observed between fetal growth rate and PDI. For children with restricted first-trimester fetal size (the lowest tertile of first-trimester CRL), those with "intrauterine accelerated growth" pattern (higher growth rates) had significantly higher MDI (adjusted beta estimate = 6.14, (95% CI: 3.80, 8.49), P < 0.001) but indistinguishable PDI compared to those with "intrauterine faltering growth" pattern (lower growth rates). Main limitations of this study included potential misclassification of gestational age due to recall bias of the last menstrual period and residual confounding. CONCLUSIONS: The current study suggests that restricted first-trimester fetal size is associated with mental and psychomotor developmental delay in childhood. However, in children with restricted first-trimester fetal size, intrauterine accelerated growth was associated with improved mental development but had little effect on psychomotor development. Additional studies are needed to validate the results in diverse populations.

The fetal origins of metabolic health: exploring the association between newborn biological age and metabolism hormones in childhood.

BACKGROUND: Telomere length (TL), mitochondrial DNA copy number (mtDNAcn), and DNA methylation age (DNAmAge) are common aging biomarkers. However, research on the associations between these three markers at birth and subsequent metabolic status was limited. This study aimed to evaluate the association between TL, mtDNAcn, and DNAmAge in newborns and the variation in metabolic hormones of children at 3 years old. METHODS: This research involved 895 mother-child pairs from a birth cohort in China, with TL and mtDNAcn measured using quantitative real-time PCR, DNA methylation (DNAm) assessed using Infinium MethylationEPIC Beadchip, and DNAm age (DNAmAge) determined using Horvath's epigenetic clock. Insulin and leptin levels were measured via electrochemiluminescence assay. Multivariable adjusted linear regression and restricted cubic spline (RCS) analysis were utilized to examine the association between aging markers and metabolic hormones. RESULTS: The linear regression analysis indicated the percentage change of metabolism hormones for per doubling of aging biomarkers alterations and found significant associations between DNAmAge and insulin levels (adjusted percent change (95% CI), - 13.22 (- 23.21 to - 1.94)), TL and leptin levels (adjusted percent change (95% CI), 15.32 (1.32 to 31.24)), and mtDNAcn and leptin levels (adjusted percent change (95% CI), - 14.13 (- 21.59 to - 5.95)). The RCS analysis revealed significant non-linear associations between TL (Ln transformed) and insulin (Ln transformed) (P = 0.024 for nonlinearity), as well as DNAmAge (Ln transformed) and leptin (Ln transformed) (P = 0.043 for nonlinearity). Specifically, for TL and insulin, a positive association was observed when TL (Ln transformed) was less than - 0.05, which transitioned to an inverse association when TL (Ln transformed) was greater than - 0.05. Regarding DNAmAge and leptin, there was a sharp decline when DNAmAge (Ln transformed) was less than - 1.35, followed by a plateau between - 1.35 and - 0.67 and then a further decline when DNAmAge (Ln transformed) was greater than - 0.67. CONCLUSIONS: In this prospective birth cohort study, variation in metabolic hormones of children at 3 years old was associated with TL, mtDNAcn, and DNAmAge at birth. These findings suggested that TL, mtDNAcn, and DNAmAge might play a role in the biological programming of metabolic health from birth.

Trimester-Specific Urinary Strontium Concentrations during Pregnancy and Longitudinally Assessed Fetal Growth: Findings from a Prospective Cohort.

BACKGROUND: Studies have claimed that strontium (Sr) is associated with fetal growth, but the research evidence is insufficient. OBJECTIVES: Our study aimed to evaluate associations of trimester-specific urinary Sr concentrations with fetal growth parameters and birth size indicators. METHODS: In this prospective cohort, 9015 urine samples (first trimester: 3561, 2nd trimester: 2756, 3rd trimester: 2698) from 3810 mothers were measured for urinary Sr levels using inductively coupled plasma mass spectrometry (ICP-MS) and adjusted to urine specific gravity. We calculated standard deviation scores (SD-scores) for ultrasound-measured fetal growth parameters (head circumference, abdominal circumference, femur length, and estimated fetal weight) at 16, 24, 31, and 37 wk of gestation and birth size indicators (birth weight, birth length, and Ponderal index). Generalized linear models and generalized estimating equations models were used. Models were adjusted for potential covariates (gestational age, maternal age, body mass index, parity, passive smoking during pregnancy, education, folic acid supplements use, physical activity, maternal and paternal height, and infant sex). RESULTS: Positive associations of naturally logarithm-transformed Sr concentrations with fetal growth parameters and birth size indicators were observed. With each doubling increase in the urinary ln-Sr level in all 3 trimesters resulting in a percent change in SD-scores fetal growth parameters at 24, 31, and 37 wk of gestation and birth size indicators, 5.09%-8.23% in femur length, 7.57%-11.53% in estimated fetal weight, 6.56%-10.42% in abdominal circumference, 6.25% in head circumference, 5.15%-7.85% in birth weight, and 5.71%-9.39% in birth length, respectively. Most of the above statistical results could only be observed in male fetuses. CONCLUSIONS: Our findings suggest a potential association between Sr concentration and increased fetal growth, but these results and underlying mechanisms need further confirmation and clarification.

Prenatal Exposure to Per- and Polyfluoroalkyl Substances and ASD-Related Symptoms in Early Childhood: Mediation Role of Steroids.

Previous studies regarding the associations between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and autism spectrum disorder (ASD) have yielded inconsistent results, with the underlying mechanisms remaining unknown. In this study, we quantified 13 PFAS in cord serum samples from 396 neonates and followed the children at age 4 to assess ASD-related symptoms. Our findings revealed associations between certain PFAS and ASD-related symptoms, with a doubling of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) concentrations associated with respective increases of 1.79, 1.62, and 1.45 units in language-related symptoms and PFDA exhibiting an association with higher score of sensory stimuli. Nonlinear associations were observed in the associations of 6:2 chlorinated polyfluorinated ether sulfonate (Cl-PFAES) and 8:2 Cl-PFAES with ASD-related symptoms. Employing weighted quantile sum (WQS) regression, we observed significant mixture effects of multiple PFAS on all domains of ASD-related symptoms, with PFNA emerging as the most substantial contributor. Assuming causality, we found that 39-40% of the estimated effect of long-chain PFAS (PFUnDA and PFDoDA) exposure on sensory stimuli was mediated by androstenedione. This study provides novel epidemiological data about prenatal PFAS mixture exposure and ASD-related symptoms.

Association between mode of delivery and early neurodevelopment: A prospective birth cohort study.

Previous research has assessed the effects of caesarean delivery (CD) on child neurodevelopment; however, whether the effects stem from the surgical procedure itself or its related medical conditions has not been conclusively determined. This study aimed to evaluate the associations among delivery mode, CD-related medical conditions and early childhood neurodevelopment. A total of 3829 maternal-infant pairs from a longitudinal birth cohort in Wuhan City, China, were included in the primary analysis. The neurodevelopment of the children was assessed by the Bayley Scales of Infant Development (BSID), the Conners Comprehensive Behaviour Rating Scale and the Chinese version of the Autism Behavior Checklist. Data on delivery mode and medical conditions were collected via medical records from the study hospital. Among the 3829 children for whom the BSID test was completed at two years of age, 50%, 27%, and 23% were delivered vaginally, by necessary CD, and by elective CD, respectively. Compared with vaginally delivered children, Necessary CD was associated with a 16.67% decrease in Mental Development Index (MDI) scores and a 13.37% decrease in Psychomotor Development Index (PDI) scores, while elective CD showed a 20.63% and 20.99% decrease after FDR correction, respectively. Similarly, among the 2448 children for whom the CBRS was completed, necessary CD was found to be associated with conduct disorders (adjusted ß: 0.06; 95% CI: 0.02, 0.09), hyperactivity (adjusted ß: 0.06; 95% CI: 0.02, 0.11), and hyperactivity index (adjusted ß: 0.07; 95% CI: 0.03, 0.11), while elective CD was significantly associated with hyperactivity problem scores (adjusted ß: 0.08, 95% CI: 0.03, 0.13). However, no significant association was found between CD and symptoms of autism in children, as assessed by the Autism Behavior Checklist (ABC). CONCLUSION: This study suggested that the adverse impact of CD on child neurodevelopment stems from the procedure itself rather than CD-related medical conditions. It is important to minimize the use of CD when there is no medical necessity. WHAT IS KNOWN: • Caesarean delivery (CD) may influence child neurodevelopment and other long-term outcomes. • In China, approximately one-quarter of CD are performed due to maternal request without medical indications. WHAT IS NEW: • The negative impact of CD on the neurodevelopmental outcomes of children may be primarily attributed to the procedure itself, as opposed to related medical conditions. • In the absence of medical indications, unnecessary CD may have adverse impacts on children's neurodevelopment.

Pregnancy loss and risk of cardiometabolic multimorbidity in Chinese women: the China Kadoorie Biobank study.

BACKGROUND: While the association between pregnancy loss and individual cardiometabolic diseases (CMDs) is well-established, its impact on the risk of coexisting CMDs remains unclear. Therefore, the aim of this study is to investigate the association between pregnancy loss with the risk of cardiometabolic multimorbidity in Chinese women. METHOD: We analyzed the cross-sectional data of 299,582 female participants aged 30-79 years old from the China Kadoorie biobank. Cardiometabolic multimorbidity was defined as the coexistence of two or more CMDs, including coronary heart disease, stroke, hypertension, and diabetes. Multivariable logistic regression was used to evaluate the odds ratios (ORs) between the number and type of pregnancy loss with the risk of cardiometabolic multimorbidity, characterized by the number and type of CMD. RESULTS: After adjusting for confounding factors, pregnancy loss was found to be significantly associated with increased cardiometabolic multimorbidity risk (OR, 1.13 95% CI 1.08-1.19). Specifically, pregnancy loss due to spontaneous and induced abortion (OR 1.10, 95% CI 1.03-1.18 and OR 1.13, 95% CI 1.08-1.19, respectively). In contrast, no significant association was found between stillbirth and cardiometabolic multimorbidity (OR 1.03, 95% CI 0.95-1.11). The risk of cardiometabolic multimorbidity increases as the number of pregnancy loss increases (one pregnancy loss: OR 1.10, 95% CI 1.05-1.16, two or more pregnancy loss: OR 1.16, 95% CI 1.10-1.22). Similarly, the diagnosis of multiple CMDs increases with increasing number of pregnancy loss. Pregnancy loss was related to higher risk of cardiometabolic multimorbidity across most CMD combinations of CMDs. CONCLUSION: Pregnancy loss, in particular, spontaneous and induced abortion was significantly associated with greater risk of cardiometabolic multimorbidity. The associations were stronger among those with recurrent pregnancy loss.

Associations of Trimester-Specific Exposure to Perchlorate, Thiocyanate, and Nitrate with Childhood Neurodevelopment: A Birth Cohort Study in China.

Studies about the impacts of maternal exposure to perchlorate, thiocyanate, and nitrate on offspring neurodevelopment are scarce. Based on a birth cohort in China, 1,028 mothers provided urine samples at three trimesters for determination of the three target analytes, and their offspring neurodevelopment was evaluated at 2 years old. Associations of maternal exposure to the three chemicals with offspring neurodevelopment were estimated using three statistical methods. Trimester-specific analyses using generalized estimating equation models showed that double increment of thiocyanate and nitrate during the first trimester was associated with 1.56 (95% CI: -2.82, -0.30) and 1.22 (-2.40, -0.03) point decreases in the offspring mental development index (MDI), respectively. Weighted quantile sum (WQS) regression analyses showed that the mixture exposure at the first and second trimesters was negatively associated with the offspring MDI (ß = -2.39, 95% CI: -3.85, -0.93; ß = -1.75, 95% CI: -3.04, -0.47, respectively) and thiocyanate contributed the most to the association (65.0 and 91.6%, respectively). Bayesian kernel machine regression analyses suggested an inverted U-shape relationship of maternal urinary thiocyanate with the offspring MDI. These findings suggested that prenatal exposure to the three chemicals (at current levels), especially thiocyanate and nitrate, may impair neurodevelopment. Early pregnancy seems to be the sensitive window.

Association of arsenic exposure and clinical hematological changes during pregnancy: Findings from a prospective Wuhan birth cohort study.

BACKGROUND: Animal studies have reported arsenic-induced disturbed erythropoiesis parameters. However, the effects of exposure to arsenic on hematological parameters among pregnant women are unclear. OBJECTIVES: We aimed to evaluate trimester-specific associations between arsenic metabolites and erythropoietic parameters measured repeatedly during pregnancy. METHODS: A total of 1945 pregnant women from a birth cohort study were included. We detected arsenic species in urine sampled at each trimester and extracted erythropoietic parameters in different trimesters from the medical records. We used linear regressions with generalized estimating equations (GEEs) to examine the relationship between arsenic metabolites concentrations at different trimesters and erythropoietic parameters. We utilized GEEs to calculate the odds ratio (OR) for anemia during pregnancy. RESULTS: Adjusted trimester-specific analysis showed that higher monomethylated arsenic (MMA) and %MMA were related to remarkably reduced hemoglobin (Hb) and mean corpuscular hemoglobin (MCH). Additionally, elevated urinary MMA concentration and %MMA in the early trimester were associated with an increased risk of microcytic anemias in the late trimester. CONCLUSIONS: Our study demonstrated a significant inverse relationship between gestational arsenic exposure and Hb and MCH. Notably, higher MMA and lower methylation capacity to metabolize inorganic arsenic (iAs) in early pregnancy might increase the likelihood of microcytic anemia among pregnant women in late pregnancy.

Associations of arsenic exposure with blood pressure and platelet indices in pregnant women: A cross-sectional study in Wuhan, China.

BACKGROUND: Environmental inorganic arsenic (iAs) exposure is potentially related to abnormal blood pressure (BP) changes and abnormal platelet activation. However, limited epidemiological studies have explored the impacts of iAs exposure on platelet change mediated by BP, especially for pregnant women. OBJECTIVES: Our purpose was to investigate the associations of arsenic exposure with blood pressure and platelet indices among pregnant women. METHODS: The present study population included 765 pregnant women drawn from a prospective birth cohort study in Wuhan, China, recruited between October 2013 and April 2016. Urine sampled in the second trimester were used to assess arsenic species concentrations. The relative distribution of urinary arsenic species was used to measure human methylation capacity. BP parameters and platelet indices originated from the medical record. We applied multivariable linear regression models to explore the cross-sectional relationships between urinary arsenic metabolites, BP parameters, and platelet indices. We utilized mediation analysis to investigate the impacts of arsenic exposure on platelet indices through BP as mediator variables. RESULTS: We observed significant positive correlations between iAs and systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP). Pregnant women with higher methylation capacity to metabolize iAs characterized by higher secondary methylation index (SMI) and total methylation index (TMI) had a more significant reduction in SBP, DBP, and MAP. Pregnant women with higher DBP and MAP had higher platelet counts (PLC). A decreased PLC was found in subjects wither higher SMI. Additionally, SMI was negatively linked to PLC mediated through MAP. CONCLUSIONS: Obtained results suggested that higher methylation capacity to metabolize iAs might contribute to decreased PLC among pregnant women, and MAP might mediate the influence of SMI on PLC.

Associations of sleep duration with neurocognitive development in the first 2†years of life.

The effect of sleep duration on neurocognitive development in infants and toddlers remains unclear. We aimed to investigate the relationship between sleep duration and neurocognitive development in infancy. Based on a prospective birth cohort, 2220 mother-infant pairs were enrolled in Wuhan, China, between January 2014 and October 2017. Sleep duration was evaluated at 1, 6, 12 and 24 months via parent-report questionnaires. To assess the children's neurocognitive development at 2 years old, the Bayley Scales of Infant Development of China Revision was used to assess the Mental Development Index (MDI) and Psychomotor Development Index (PDI). A group-based semiparametric mixture model was used to estimate the developmental trajectories of the total, nighttime and daytime sleep duration. The associations of sleep duration at each age and sleep duration trajectories with Mental Development Index scores and Psychomotor Development Index scores were analysed using generalized linear models. Daytime sleep duration (≥ 10.0 hr) at 1 month was associated with lower Mental Development Index scores (ß = -3.55, 95% confidence interval: -6.02, -1.08) and lower Psychomotor Development Index scores (ß = -2.87, 95% confidence interval: -4.94, -0.81). Nighttime sleep duration (≤ 7.0 hr) at 6 months was associated with lower Mental Development Index scores (ß = -7.02, 95% confidence interval: -11.02, -3.01). Daytime sleep duration (> 4 hr) and nighttime sleep duration (< 8 hr) at 12 months were associated with lower Mental Development Index scores (ß = -9.17, 95% confidence interval: -15.35, -2.98) and lower Psychomotor Development Index scores (ß = -8.14, 95% confidence interval: -13.56, -2.71), respectively. In further sleep duration trajectories analyses, lower Mental Development Index scores were significantly associated with the "decreased and then increased nighttime sleepers" trajectory (ß = -4.39, 95% confidence interval: -8.02, -0.76), and "long and decreased daytime sleepers" trajectory (ß = -2.44, 95% confidence interval: -4.58, -0.30). These results showed that short nighttime sleep duration and long daytime sleep duration in infancy were detrimental to children's neurocognitive development.

Association between prenatal exposure to metal mixtures and early childhood allergic diseases.

The association between prenatal exposure to the metal mixture and allergic diseases is poorly understood. We aimed to explore the individual effect and the combined effect of prenatal exposure to vanadium (V), chromium (Cr), nickel (Ni), arsenic (As), cadmium (Cd), thallium (Tl), and lead (Pb) on early childhood allergic diseases based on a birth cohort study that included 628 mother-infant pairs. Metals were measured in maternal urine samples collected in the first, second, and third trimesters. Children were prospectively followed up at age 4 years to collect information on allergic rhinitis, wheeze, and eczema status. By applying logistic regression models, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR), the different statistical analyses revealed urinary metals were only associated with early childhood allergic rhinitis. The averaged prenatal As exposure was significantly associated with an increased OR for allergic rhinitis in both single-metal (OR = 2.04, 95% CI: 1.35, 3.07) and multiple-metal logistic regression models (OR = 1.78, 95% CI: 1.15, 2.78). The WQS index of mixed metal exposure was positively associated with allergic rhinitis (OR = 1.66, 95% CI: 1.26, 2.19), and As and Tl had the largest weights in the WQS index (weighted 0.51 and 0.29, respectively). The BKMR analysis also showed the overall effect of the metal mixture was significantly associated with allergic rhinitis when all the metals were at their 55th percentile or above, compared to their 50th percentile. The effect of As and Tl on the risk of allergic rhinitis was significant when all of the other metals were fixed at the specific percentiles. Our findings suggest that prenatal co-exposure to higher levels of the seven metals increases the risk of allergic rhinitis in children, and As and Tl may contribute most to the combined risk.

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.

Prenatal and early postnatal exposure to ambient particulate matter and early childhood neurodevelopment: A birth cohort study.

Adverse impacts of prenatal or postnatal ambient particulate matter exposure have been identified on offspring neurodevelopment. However, it is unclear whether the effect in the two exposure periods is different for early childhood neurodevelopment. This study aimed to evaluate and compare the associations of prenatal and early postnatal exposure to ambient particulate matter with offspring neurodevelopment at 2 years of age and to identify which period was more sensitive to the effects of ambient particulate matter on offspring neurodevelopment. A total of 1331 mother-child pairs from a birth cohort were included in this study from October 2013 to September 2014 in Wuhan, China. The concentrations of ambient daily fine particulate matter (PM2.5) and particulate matter less than 10 µm in aerodynamic diameter (PM10) at each participant's home address during pregnancy and the first two years after birth were estimated by land-use regression models (LUR). Offspring neurodevelopment was measured by the Chinese revision of Bayley Scale of Infant Development (BSID-CR) for each child at 2 years of age. Mental developmental index (MDI) and psychomotor developmental index (PDI) from the BSID-CR were used as outcome variables. A generalized estimating equation (GEE) model was used to estimate the associations of prenatal and postnatal PM2.5 and PM10 exposure with offspring neurodevelopment. After adjusting for potential confounders, we found that both prenatal and early postnatal exposure to PM2.5 and PM10 were associated with decreased offspring MDI and PDI scores. Compared with prenatal exposure, the associations of early postnatal exposure to PM2.5 and PM10 with offspring MDI and PDI were stronger. This study indicates that exposure to ambient particulate matters, mainly during early postnatal period and to a lesser extent prenatally, is associated with impaired offspring neurodevelopment.

Association of exposure to per- and polyfluoroalkyl substances with hemoglobin and hematocrit during pregnancy.

BACKGROUND: Per- and polyfluoroalkyl substances (PFASs) are common environmental contaminants and are widely detected in humans. Previous studies have linked PFASs exposure to adverse birth outcomes. However, the association between maternal exposure to PFASs and hemoglobin (Hb) and hematocrit (HCT) remains unclear. OBJECTIVES: We aimed to explore the relationship between PFASs exposure with Hb and HCT during pregnancy. METHODS: The present birth cohort study included 1044 pregnant women from Wuhan, China. Maternal HCT and Hb were measured in the first, second and third trimesters, and 13 PFASs were detected in the cord sera. Mixed linear models and general linear regression were applied to analyze the association between each single PFASs and Hb and HCT. Weighted quantile sum (WQS) regressions were used to investigate the association between PFASs mixture and Hb and HCT during pregnancy. RESULTS: In single-PFAS models, 10 PFASs were positively associated with HCT and Hb across pregnancy (a 10-fold increase in PFASs was associated with 1.47-3.54 % change in HCT and 1.46-3.20 % change in Hb (All P-FDR < 0.05). In addition, Hb and HCT were more positively related to PFASs in the second and third trimesters rather than the first trimester. The association between PFASs exposure and maternal HCT and Hb was not significant in the iron supplementation group, whereas significant in the non-iron supplementation group. A significant interaction between iron supplementation and non-iron supplementation was also detected. WQS regressions showed that perfluorononanoic acid (PFNA) and perfluorohexane sulfonate (PFHxS) contributed most to the association between PFASs and HCT and Hb in the second and third trimesters, respectively. CONCLUSION: Maternal PFASs exposure was positive with serum Hb and HCT. Moreover, maternal iron supplementation may play a modifying effect in influencing the relationship between PFASs and HCT and Hb.

Impact of the 2017 ACC/AHA Guideline for High Blood Pressure on Evaluating Gestational Hypertension-Associated Risks for Newborns and Mothers.

RATIONALE: In 2017, the American College of Cardiology (ACC)/American Heart Association (AHA) released a new hypertension guideline for nonpregnant adults, using lower blood pressure values to identify hypertension. However, the impact of this new guideline on the diagnosis of gestational hypertension and the associated maternal and neonatal risks are unknown. OBJECTIVE: To estimate the impact of adopting the 2017 ACC/AHA guideline on detecting gestational blood pressure elevations and the relationship with maternal and neonatal risk in the perinatal period using a retrospective cohort design. METHODS AND RESULTS: This study included 16 345 women from China. Systolic and diastolic blood pressures of each woman were measured at up to 22 prenatal care visits across different stages of pregnancy. Logistic and linear regressions were used to estimate associations of blood pressure categories with the risk of preterm delivery, early-term delivery, and small for gestational age, and indicators of maternal liver, renal, and coagulation functions during pregnancy. We identified 4100 (25.1%) women with gestational hypertension using the 2017 ACC/AHA guideline, compared with 4.2% using the former definition. Gestational hypertension, but not elevated blood pressure (subclinical blood pressure elevation), was significantly associated with altered indicators of liver, renal, and coagulation functions during pregnancy for mothers and increased risk of adverse birth outcomes for newborns; adjusted odds ratios (95% CIs) for gestational hypertension stage 2 were 2.23 (1.18-4.24) for preterm delivery, 2.05 (1.67-2.53) for early-term delivery, and 1.43 (1.13-1.81) for small for gestational age. CONCLUSIONS: Adopting the 2017 ACC/AHA guideline would result in a substantial increase in the prevalence of gestational hypertension; subclinical blood pressure elevations during late pregnancy were not associated with increased maternal and neonatal risk in this cohort. Therefore, the 2017 ACC/AHA guideline may improve the detection of high blood pressure during pregnancy and the efforts to reduce maternal and neonatal risk. Replications in other populations are required.

Chronic Exposure to PM2.5 Nitrate, Sulfate, and Ammonium Causes Respiratory System Impairments in Mice.

Water-soluble inorganic (WSI) ions are major components of ambient air PM2.5 (particulate matter of diameter ≤2.5 µm); however, their potential health effects are understudied. On C57BL/6 mice, we quantified the effect of three major PM2.5 WSIs (NO3-, SO42-, and NH4+) on respiratory systems. Exposure scenarios include different WSI types, concentrations, animal development stages (young vs adult), and sex. The exposure effects were comprehensively assessed, with special focus on the respiratory function and tissue/cell level changes. Chronic PM2.5 NO3- exposure produced significant respiratory function decline, mainly presented as airflow obstruction. The decline was more profound in young mice than in adult mice. In young mice, exposure to 22 µg/m3 PM2.5 NO3- reduced FEV0.05 (forced expiratory volume in 0.05 s) by 11.3% (p = 9.6 × 10-3) and increased pulmonary neutrophil infiltration by 7.9% (p = 7.1 × 10-3). Causality tests identified that neutrophil infiltration was involved in the biological mechanism underlying PM2.5 NO3- toxicity. In contrast, the effects of PM2.5 SO42- were considerably weaker than NO3-. PM2.5 NO3- exposure was 3.4 times more potent than PM2.5 SO42- in causing reduction of the peak expiratory flow. PM2.5 NH4+ exposure had no statistically significant effects on the respiratory function. In summary, this study provided strong evidence on the adverse impacts of PM2.5 WSIs, where the impacts were most profound in young mice exposed to PM2.5 NO3-. If confirmed in humans, toxicity of PM2.5 WSI will have broad implications in environment health and policy making.

Association of fine particulate matter with glucose and lipid metabolism: a longitudinal study in young adults.

OBJECTIVES: This study aimed to evaluate whether PM2.5 exposure in a highly polluted area (>100 µg/m3) affects glucose and lipid metabolism in healthy adults. METHODS: We recruited 110 healthy adults in Baoding city, Hebei, China, and followed them up between 2017 and 2018. Personal air samplers were used to monitor personal PM2.5 levels. Eight glucose and lipid metabolism parameters were quantified. We performed the linear mixed-effect models to investigate the relationships between PM2.5 and glucose and lipid metabolism parameters. Stratified analyses were further performed according to sex and body mass index (BMI). RESULTS: The concentration of PM2.5 was the highest in spring, with a median of 232 µg/m3 and the lowest in autumn (139 µg/m3). After adjusting for potential confounders, we found that for each twofold increase in PM2.5, the median of insulin concentration decreased by 5.89% (95% CI -10.91% to -0.58%; p<0.05), and ox-LDL increased by 6.43% (95% CI 2.21% to 10.82%; p<0.05). Stratified analyses indicated that the associations were more pronounced in females, overweight and obese participants. CONCLUSIONS: Exposure to high PM2.5 may have deleterious effects on glucose and lipid metabolism. Females, overweight and obese participants are more vulnerable.

Association between prenatal rare earth elements exposure and premature rupture of membranes: Results from a birth cohort study.

BACKGROUND: The widespread exploitation and application of rare earth elements (REE) have led to the risk of human exposure and might result in the adverse health effect on pregnant women. However, no epidemiological studies have explored the associations between prenatal REE exposure and premature rupture of membranes (PROM). OBJECTIVE: We aimed to investigate the associations of maternal urinary REE levels with the risk of PROM. METHODS: A total of 4897 mother-newborn pairs were recruited from a birth cohort study in Wuhan, China. Urinary concentrations of REE were measured by inductively coupled plasma mass spectrometry (ICP-MS). The associations of prenatal REE exposure with PROM were evaluated using logistic regression models. False discovery rate (FDR) was applied to adjust for multiple testing. Weighted quantile sum (WQS) regression was used to estimate the association of urinary REE mixture with PROM. RESULTS: With one unit increase (µg/g creatinine) in natural log-transformed urinary REE levels (Ce, Yb, La, Pr, Nd, Eu, Gd, Dy, Ho, Er, Tm), the adjusted ORs (95% CIs) for the PROM were from 1.143 (1.078, 1.211) to 1.317 (1.223, 1.419), and the associations were still observed after FDR adjustment (all PFDRs < 0.05). The associations were stronger among male infants than female infants. Furthermore, the urinary REE mixture was also associated with the risk of PROM, a quartile increase in the WQS index of REE resulted in ORs (95% CI) for the PROM of 1.494 (1.356, 1.645) in the adjusted model. CONCLUSIONS: Our findings suggested that prenatal exposure to REE (Ce, Yb, La, Pr, Nd, Eu, Gd, Dy, Ho, Er, and Tm) and REE mixture were associated with the increased risk of PROM. Further studies from different populations are needed to confirm the associations and to explore the mechanisms.

Association between early-term birth and delayed neurodevelopment at the age of 2 years: results from a cohort study in China.

A growing body of evidence indicates that early-term births (37-38 weeks of gestational age) have an increased risk of short-term and long-term complications. Here, we sought to explore the association between early-term births and the risk of delayed neurodevelopment at age 2 years. Pregnant women and their live singleton birth were recruited from a single tertiary hospital between October 2013 and February 2017. Mental and Psychomotor Development Indexes (MDI and PDI) were assessed using the Bayley Scales of Infant Development (BSID). Delayed neurodevelopment was defined as scores of PDI or MDI less than -1SD relative to the mean score of the study population. In total, 1678 full-term infants and 727 early-term infants were assessed when they were 2 years old. After adjustment for potential confounders, early-term birth was related to 43% increased odds of neurodevelopmental delay in the PDI domain as compared with full-term birth (OR: 1.43; 95% CI: 1.12, 1.82). The observed associations were more prominent among those infants born by cesarean (OR: 1.44; 95% CI: 1.03, 2.00) and among males (OR: 1.66; 95% CI: 1.20, 2.28). No statistical difference in the MDI domain was found between early-term and full-term births.Conclusions: Our findings suggest that early-term birth was associated with increased odds of delayed neurodevelopment in the PDI domain as measured by BSID assessments at age 2 years. Health professionals should be aware of the influence of early-term birth on the risk of delayed neurodevelopment. What is Known: • Evidence indicates that early-term births have an increased risk of short-term and long-term complications. • The association between early-term births and delayed neurodevelopment at their early childhood has not been widely studied. What is New: • Early-term birth was associated with increased odds of delayed neurodevelopment in PDI domain as measured by BSID assessments at age 2 years. • The observed associations were more prominent among infants born by cesarean section and among male infants.

Association of BPA exposure during pregnancy with risk of preterm birth and changes in gestational age: A meta-analysis and systematic review.

The associations of bisphenol A exposure during pregnancy with risk of preterm birth (PTB) and changes in gestational age have remained controversial. To conduct the meta-analysis, the relevant studies were searched through PubMed, OVID, and Web of Science from inception through June 17, 2020. Data were independently extracted and analyzed using odds ratio (OR) or regression coefficient (ß) and their 95% confidence intervals (CIs). We identified 668 references and included 7 studies for preterm birth and 9 studies for gestational age. The included studies reported that the median or geometric mean (GM) of maternal urinary BPA ranged from 0.48 to 6.44 ng/ml. The meta-analysis estimated OR to be 1.36 (95% CI: 1.03, 1.69) for preterm birth associated with maternal urinary BPA exposure during pregnancy. In the subgroup analysis based on BPA exposure level, a significant association was observed between preterm birth and higher BPA exposure among the populations had BPA median or GM concentrations higher than 2.16 ng/ml (OR: 1.92; 95% CI: 1.38, 2.47). In the subgroup analyses by maternal urinary BPA exposure assessed in different trimesters, a significant association of preterm birth was only observed with BPA assessed in the third trimester (OR: 1.62; 95% CI: 1.15, 2.09). In addition, higher maternal urinary BPA exposure during pregnancy was associated with decreased gestational age by 0.50 (-0.87, -0.13) days, and the subgroup analyses also showed that only BPA exposure in the third trimester was associated with decreased gestational age by 1.36 (-2.21, -0.52) days. This meta-analysis demonstrated that higher BPA exposure was associated with an increased risk of preterm birth and decreased length of gestational age, and suggested that BPA exposure in the third trimester of pregnancy may be a critical susceptible period of preterm birth.