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.

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.

Associations of glyphosate exposure and serum sex steroid hormones among 6-19-year-old children and adolescents.

Glyphosate, ranked as one of the most widely used herbicides in the world, has raised concerns about its potential disruptive effects on sex hormones. However, limited human evidence was available, especially for children and adolescents. The present study aimed to examine the associations between exposure to glyphosate and sex hormones among participants aged 6-19 years, utilizing data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2016. Children and adolescents who had available data on urinary glyphosate, serum sex steroid hormones, including testosterone (TT), estradiol (E2) and sex hormone binding globulin (SHBG), and covariates were selected. Additionally, the ratio of TT to E2 (TT/E2) and the free androgen index (FAI), which was calculated using TT/SHBG, were also included as sex hormone indicators. Survey regression statistical modeling was used to examine the associations between urinary glyphosate concentration and sex hormone indicators by age and sex group. Among the 964 participants, 83.71% had been exposed to glyphosate (>lower limit of detection). The survey regression revealed a marginally negative association between urinary glyphosate and E2 in the overall population, while this association was more pronounced in adolescents with a significant trend. In further sex-stratified analyses among adolescents, a significant decrease in E2, FAI, and TT (p trend <0.05) was observed in female adolescents for the highest quartile of urinary glyphosate compared to the lowest quartile. However, no similar association was observed among male adolescents. Our findings suggest that exposure to glyphosate at the current level may decrease the levels of sex steroids in adolescents, particularly female adolescents. Considering the cross-sectional study design, further research is needed to confirm our findings.

Prenatal phthalate exposure and fetal penile length and width.

BACKGROUND: Phthalates are endocrine-disrupting chemicals with anti-androgenic qualities and studies reported associations between prenatal phthalate exposure and infant genitalia. This study investigated whether increased prenatal phthalate exposure is associated with decreased fetal penile measures. METHODS: Data was from the New York University Children's Health and Environment Study (2016-2019). Maternal urinary concentrations of 16 phthalate metabolites were quantified at <18 weeks gestation as a proxy for fetal exposure (n = 334 male pregnancies). We retrospectively measured penile length and width using ultrasounds conducted 18-24 weeks gestation (n = 173 fetuses). Associations of maternal urinary levels of phthalates with fetal penile length and width were determined using linear regression models. RESULTS: 57.2% of women were Hispanic, 31.8% Non-Hispanic White, 6.4% Asian, 2.3% Non-Hispanic Black, and 2.3% multiple races. Mean maternal age was 32 years (standard deviation [SD] = 5.7). Mean penile length was 7.13 mm (SD = 1.47) and width was 6.16 mm (SD = 0.87). An inverse relationship was observed between maternal levels of mono-ethyl phthalate and fetal penile length, and mono-(7-carboxy-n-heptyl) phthalate and penile width, though estimates were small and not significant when considering correction for multiple comparisons. CONCLUSIONS: In our cohort we found no clinically meaningful associations between early pregnancy phthalate exposure and fetal penile length or width. IMPACT: First-trimester phthalate metabolites were assessed in pregnant women in New York City. Penile length and width were retrospectively measured on clinically assessed ultrasounds conducted ≥18 weeks and <24 weeks of gestation. In this cohort, no clinically meaningful associations were observed between first-trimester prenatal phthalate exposure and fetal penile length. This study contributes to the limited but growing research on the impact of prenatal phthalate exposure on male fetal genital development. The results emphasize that there may not be a clear association between prenatal phthalate exposure and fetal penile length and width, and further research on this topic may be required.

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.

Determinants of phthalate exposures in pregnant women in New York City.

Previous studies have provided data on determinants of phthalates in pregnant women, but results were disparate across regions. We aimed to identify the food groups and demographic factors that predict phthalate exposure in an urban contemporary pregnancy cohort in the US. The study included 450 pregnant women from the New York University Children's Health and Environment Study in New York City. Urinary concentrations of 22 phthalate metabolites, including metabolites of di-2-ethylhexylphthalate (DEHP), were determined at three time points across pregnancy by liquid chromatography coupled with tandem mass spectrometry. The Diet History Questionnaire II was completed by pregnant women at mid-pregnancy to assess dietary information. Linear mixed models were fitted to examine determinants of urinary phthalate metabolite concentrations. Using partial-linear single-index (PLSI) models, we assessed the major contributors, among ten food groups, to phthalate exposure. Metabolites of DEHP and its ortho-phthalate replacement, diisononyl phthalate (DiNP), were found in >90% of the samples. The sum of creatinine-adjusted DiNP metabolite concentrations was higher in older and single women and in samples collected in summer. Hispanic and non-Hispanic Black women had lower urinary concentrations of summed metabolites of di-n-octyl phthalate (DnOP), but higher concentrations of low molecular weight phthalates compared with non-Hispanic White women. Each doubling of grain products consumed was associated with a 20.9% increase in ∑DiNP concentrations (95%CI: 4.5, 39.9). PLSI models revealed that intake of dried beans and peas was the main dietary factor contributing to urinary ∑DEHP, ∑DiNP, and ∑DnOP levels, with contribution proportions of 76.3%, 35.8%, and 27.4%, respectively. Urinary metabolite levels of phthalates in pregnant women in NYC varied by age, marital status, seasonality, race/ethnicity, and diet. These results lend insight into the major determinants of phthalates levels, and may be used to identify exposure sources and guide interventions to reduce exposures in susceptible populations.

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.

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.

[Automatic epileptic seizure detection algorithm based on dual density dual tree complex wavelet transform].

It is very important for epilepsy treatment to distinguish epileptic seizure and non-seizure. In this study, an automatic seizure detection algorithm based on dual density dual tree complex wavelet transform (DD-DT CWT) for intracranial electroencephalogram (iEEG) was proposed. The experimental data were collected from 15 719 competition data set up by the National Institutes of Health (NINDS) in Kaggle. The processed database consisted of 55 023 seizure epochs and 501 990 non-seizure epochs. Each epoch was 1 second long and contained 174 sampling points. Firstly, the signal was resampled. Then, DD-DT CWT was used for EEG signal processing. Four kinds of features include wavelet entropy, variance, energy and mean value were extracted from the signal. Finally, these features were sent to least squares-support vector machine (LS-SVM) for learning and classification. The appropriate decomposition level was selected by comparing the experimental results under different wavelet decomposition levels. The experimental results showed that the features selected in this paper were different between seizure and non-seizure. Among the eight patients, the average accuracy of three-level decomposition classification was 91.98%, the sensitivity was 90.15%, and the specificity was 93.81%. The work of this paper shows that our algorithm has excellent performance in the two classification of EEG signals of epileptic patients, and can detect the seizure period automatically and efficiently.

Characterization and pathogenicity of extracellular serine protease MAP3292c from Mycobacterium avium subsp. paratuberculosis.

Serine protease is the virulence factor of many pathogens. However, there are no prevailing data available for serine protease as a virulence factor derived from Mycobacterium avium subsp. paratuberculosis (MAP). The MAP3292c gene from MAP, the predicted serine protease, was expressed in Escherichia coli and characterized by biochemical methods. MAP3292c protein efficiently hydrolyzed casein at optimal temperature and pH of 41 °C and 9.0, respectively. Furthermore, divalent metal ions of Ca2+ significantly promoted the protease activity of MAP3292c, and MAP3292c had autocleavage activity between serine 86 and asparagine 87. Site-directed mutagenesis studies showed that the serine 238 residue had catalytic roles in MAP3292c. Furthermore, a BALB/c mouse model confirmed that MAP3292c significantly promoted the survival of Mycobacterium smegmatis in vivo; caused damage to the liver, spleen, and lung; and promoted the release of inflammatory cytokines IL-1ß, IL-6, and TNF-α in mice. Finally, we confirmed that MAP3292c was relevant to mycobacterial pathogenicity.

Association between phthalate exposure and blood pressure during pregnancy.

BACKGROUND: Phthalates are endocrine disrupting chemicals (EDCs) that pose a serious hazard to the human health. Many epidemiological studies revealed a relationship between phthalates exposure and blood pressure in general population, while the relationship in pregnant women remains unknown. OBJECTIVES: Aimed to elucidate whether phthalate exposure is associated with blood pressure among pregnant women. METHODS: This study included 636 participants from Wuhan, China. Urine samples were conducted repeatedly in three trimesters, and 9 phthalates were measured in these samples. After each urine was sampled, all the participants completed blood pressure measurements. Associations between repeated measurements of phthalate concentration and blood pressure were evaluated by using generalized estimating equations. Stratified analysis by fetus gender was conducted. RESULTS: Among the pregnant women with male fetuses, mono-i-butyl phthalate (MiBP) exposed in the 1st trimester was associated with the increased diastolic blood pressure (DBP) measured in the 2nd trimester, while the environmental risk score (ERS) measured in the 1st and 2nd trimester was positively associated with systolic blood pressure (SBP) and DBP in the 2nd trimester. No significant relationships were observed among all the population or pregnant women with female fetuses. CONCLUSIONS: Exposure to higher levels of MiBP may be related to increased blood pressure during pregnancy in pregnant women with male fetuses.

PE17 protein from Mycobacterium tuberculosis enhances Mycobacterium smegmatis survival in macrophages and pathogenicity in mice.

The capacity of Mycobacterium tuberculosis to survive and cause disease is strongly correlated with its ability to escape multiple defense strategies in hosts. In particular, M. tuberculosis has the remarkable capacity to survive within the hostile environment of macrophages. Here, we found that the PE17 (Rv1646) protein promoted intracellular survival of M. smegmatis in peritoneal macrophages from mice. Further experiments confirmed that the recombinant PE17 protein was localized in the cell wall of M. smegmatis. Results from the macrophage infection model showed that PE17 significantly downregulated pro-inflammatory cytokines (interleukin-6, interleukin-12, and tumer necrosis factor-α) secretion from macrophages induced by M. smegmatis and promoted macrophage necrosis. Furthermore, a C57BL/6 mouse infection model confirmed that PE17 significantly prolonged the survival of M. smegmatis in vivo and aggravated lesions in organs of infected mice. Moreover, persistent high levels of interferon-γ and interleukin-1ß in infected mice indicated that the bacteria were not easily removed in vivo. Overall, our present results suggested that the PE17 may act as an important pathogenic factor in M. tuberculosis.

Variations, Determinants, and Coexposure Patterns of Personal Care Product Chemicals among Chinese Pregnant Women: A Longitudinal Study.

Exposure to mixtures of personal care product chemicals (PCPCs) is commonplace among the Chinese population; yet, limited data are available on the variations, determinants, and coexposure patterns of PCPCs, particularly among pregnant women at multiple time points during gestation. Here, we measured concentrations of 11 most common PCPCs (five parabens, five benzophenones, and triclosan) in 2823 urine samples collected from 941 pregnant women over three trimesters. Based on the quantification results, we calculated the intraclass correlation coefficient (ICC) to assess within-person variability of targeted compounds, applied linear mixed mode models to explore associations between urinary concentrations of PCPCs and exposure-related factors, and used percentile analysis to evaluate exposure to specific or multiple chemicals at one or three trimesters. Seven targeted compounds: methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), 4-hydroxybenzophenone (4-OH-BP), 2,4-dihydroxybenzophenone (BP-1), 2-hydroxy-4-methoxybenzophenone (BP-3), and triclosan (TCS) were detected in over 66% of samples. The median urinary concentrations (ng/mL) of MeP, EtP, PrP, 4-OH-BP, BP-1, BP-3, and TCS were 15.44, 0.49, 0.61, 0.16, 0.25, 0.53, and 0.48, respectively. We observed that benzophenones (ICC: 0.46-0.55) and triclosan (ICC: 0.50) were less variable than parabens (ICC: 0.35-0.40). Urinary levels of parabens were related to physical activity frequency; urinary levels of benzophenones were associated with the refurbishment of homes and household income, and urinary levels of triclosan were contingent upon the personal basic information (prepregnancy body mass index and age). Notably, higher levels of benzophenones and triclosan but lower paraben levels were observed in summer than in winter. Both coexposure to high percentiles of multiple pollutants at one trimester and exposure to one pollutant at high-dose through three trimesters were rare in the study population. Our findings suggest that these exposure-related factors should be taken into consideration, and health risks should be assessed on mixtures of pollutants in future epidemiological studies.

Association of in utero hexachlorocyclohexane exposure with gestational age.

As endocrine disrupting chemicals, hexachlorocyclohexane (HCH) isomers were reported to impair the intrauterine growth. Although the findings of HCHs with preterm birth were well established, the associations with gestational age were limited. In the present study, we examined whether exposure to HCHs would influence gestational age. The study population included 1028 pregnant women and their offspring who were born in 2014-2015 from a birth cohort in Wuhan, China. Associations of the cord serum HCH levels with gestational age were estimated using generalized linear models. We found higher HCH levels in pregnant women, who were elder, had higher body mass index (BMI) before pregnancy, received higher education, or were exposed to smoking passively. For term birth, the 3rd tertiles of α-HCH and γ-HCH were significantly associated with shorter gestational age [crude ß = -1.017, confidence interval (CI): - 2.017, - 0.018 for α-HCH, crude ß = -1.068, CI: - 2.067, - 0.070 for γ-HCH], and relationships were similar after adjusted by covariates. Stratified analysis showed positive associations between α-HCH and gestational age for mothers younger than 25 years old (adjusted ß = 0.610, CI: 0.061, 1.158), while showing negative relationships for mothers elder than 35 years old (adjusted ß = -1.365, CI: -2.414, -0.317). In summary, our results indicated cord serum levels of HCHs were associated with gestational age at birth.

Maternal exposure to fine particulate matter and the risk of fetal distress.

Prenatal life exposure to fine particulate matter (aerodynamic diameter less than or equal to 2.5 µm, PM2.5) has been linked with increased risk of adverse fetal development and birth outcomes in previous studies. However, to our knowledge, no study has investigated the association of maternal PM2.5 with the risk of fetal distress, which is a harmful fetal status and may lead to fetal brain damage, even fetal death. Therefore, we conducted a study to determine the association between maternal PM2.5 and fetal distress among 7835 mother-infant pairs from a birth cohort, in Wuhan, China, 2013-2015. The individual daily PM2.5 level was assessed using land use regression model. We evaluated the association of maternal PM2.5 level over the whole pregnancy with fetal distress by logistic regression model, and estimated the risk between PM2.5 exposure in specific trimester and fetal distress using generalized estimating equations. We observed that per 10 µg/m3 change of maternal PM2.5 level over the whole pregnancy was associated with 25% increased risk of fetal distress (95% confidence interval: 1.09-1.44). Further, we found PM2.5 level in the 2nd trimester, but not in the 1st and 3rd trimesters, was associated with fetal distress. Stratified analyses indicated that the association was only significant among infants who were born in cold seasons. Our study suggested that PM2.5 exposure during the whole pregnancy exhibited significant associations with the risk of fetal distress, and exposure in the 2nd trimester maybe the susceptible window. Further stratified analyses indicated that birth season is a possible modifier in the association.

Novel Chlorinated Polyfluorinated Ether Sulfonates and Legacy Per-/Polyfluoroalkyl Substances: Placental Transfer and Relationship with Serum Albumin and Glomerular Filtration Rate.

Per- and polyfluoroalkyl substances (PFASs) may cross the placental barrier and lead to fetal exposure. However, little is known about the factors that influence maternal-fetal transfer of these chemicals. PFAS concentrations were analyzed in 100 paired samples of human maternal sera collected in each trimester and cord sera at delivery; these samples were collected in Wuhan, China, 2014. Linear regression was used to estimate associations of transfer efficiencies with factors. Chlorinated polyfluorinated ether sulfonates (Cl-PFAESs, 6:2 and 8:2) were frequently detected (>99%) in maternal and cord sera. A significant decline in PFAS levels during the three trimesters was observed. A U-shape trend for transfer efficiency with increasing chain length was observed for both carboxylates and sulfonates. Higher transfer efficiencies of PFASs were associated with advancing maternal age, higher education, and lower glomerular filtration rate (GFR). Cord serum albumin was a positive factors for higher transfer efficiency (increased 1.1-4.1% per 1g/L albumin), whereas maternal serum albumin tended to reduce transfer efficiency (decreased 2.4-4.3% per 1g/L albumin). Our results suggest that exposure to Cl-PFAESs may be widespread in China. The transfer efficiencies among different PFASs were structure-dependent. Physiological factors (e.g., GFR and serum albumin) were observed for the first time to play critical roles in PFAS placental transfer.

Associations between maternal urinary rare earth elements during pregnancy and birth weight-for-gestational age: Roles of cord blood vitamin D levels.

Prenatal exposure to rare earth elements (REEs) may contribute to adverse birth outcomes in previous studies. Cord blood vitamin D has been suggested to modify or mediate the effects of environmental exposures. However, none has investigated these roles of cord blood vitamin D in the associations of prenatal exposure to REEs with fetal growth. Maternal trimester-specific urinary concentrations of 13 REEs, cord blood total 25-hydroxyvitamin D at delivery, and birth weight (BW)-for-gestational age (GA) were determined in 710 mother-newborn pairs from Wuhan, China. Higher maternal average urinary concentrations of europium (Eu), gadolinium (Gd), dysprosium (Dy), holmium (Ho), erbium (Er), and ytterbium (Yb) across three trimesters, either individually or jointly, were significantly associated with lower BW-for-GA Z-scores and higher odds of small for gestational age (SGA) [ß = -0.092; 95 % confidence interval (CI): -0.149, -0.035 for BW-for-GA Z-scores, and odds ratio = 1.60; 95 % CI: 1.14, 2.24 for SGA involved in each unit increase in weighted quantile sum index of REEs mixture]. When stratified by cord blood vitamin D levels, the associations mentioned above persisted in participants with relatively low vitamin D levels (<13.94 µg/L, the first tertile of distribution), but not among those with relatively high levels (≥13.94 µg/L) (all p-values for interaction < 0.05). The mediation analyses taking account of exposure-mediator interaction showed that the relationships between REEs (as individual and mixture) exposure and lower BW-for-GA were partly mediated through decreasing cord blood vitamin D levels. The proportions mediated by cord blood vitamin D levels were 24.48 % for BW-for-GA Z-scores and 29.05 % for SGA corresponding to the REEs mixture exposure. Conclusively, our study revealed that prenatal exposures to Eu, Gd, Dy, Ho, Er, and Yb were related to fetal growth restriction. Cord blood vitamin D might alleviate toxic effects of these REEs and its reduction might partly mediate REE-induced fetal growth restriction.

Associations of intrauterine exposure to manganese with fetal and early-childhood growth: a prospective prenatal cohort study.

Prenatal manganese (Mn) exposure may be related to poor birth outcomes; however, there are few relevant epidemiological reports on the effects of intrauterine Mn levels on intrauterine fetal and early childhood growth. From 2013 to 2016, 2082 pairs of mothers and infants were recruited in Wuhan, China, who provided an entire set of urine samples during their first, second, and third trimesters. Fetal head circumference (HC), abdominal circumference (AC), femoral length (FL), and estimated fetal weight (EFW) were obtained by ultrasound at the 16, 24, and 31 weeks of pregnancy. When the children were born, 6 months old, 12 months old, and 24 months old, their weight, height, weight-for-height, and BMI were measured. We used generalized linear models, generalized estimated equations, and restricted cubic spline curves (RCS) to investigate the linear and nonlinear relationships between antenatal Mn levels and fetal and early childhood growth. In all fetuses, Mn exposure during the 1st and 2nd gestation was associated with decreased fetal AC, FL, and EFW at 24 weeks (e.g., for each doubling of urinary Mn concentrations during the 1st and 2nd gestation, the SD score of EFW at 24 weeks decreased by - 4.16% (95% CI, - 6.22%, - 2.10%) and - 3.78% (95% CI, - 5.86%, - 1.70%)). Mn concentrations in the highest tertile group of the 1st and 2nd gestation were related to decreased fetus growth parameters compared to the lowest tertile group. For each doubling of the average Mn concentrations during pregnancy, the z-scores of weight, weight-for-height, and BMI at 12 months decreased, with percentage changes of - 2.93% (95% CI, - 5.08%, - 0.79%), - 3.25% (95% CI, - 5.56%, - 0.94%), and - 3.09% (95% CI, - 5.44%, - 0.73%). In the RCS model, we found a reverse U-shaped association between 1st trimester Mn concentration and fetal FL at 16 weeks and HC at 31 weeks in male fetuses and a non-linear association between mean Mn concentration during pregnancy and girls' weight-for-height and BMI at 6 months. Intrauterine exposure to Mn may be related to restricted growth in the fetus and early childhood, especially in fetuses at 24 weeks of gestation and children at 12 months of age. Also, meaningful curvilinear relationships were found in the sex stratification.