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.

Intrauterine and early postnatal exposures to submicron particulate matter and childhood allergic rhinitis: A multicity cross-sectional study in China.

BACKGROUND: Airborne particulate matter pollution has been linked to occurrence of childhood allergic rhinitis (AR). However, the relationships between exposure to particulate matter with an aerodynamic diameter ≤1 µm (PM1) during early life (in utero and first year of life) and the onset of childhood AR remain largely unknown. This study aims to investigate potential associations of in utero and first-year exposures to size-segregated PMs, including PM1, PM1-2.5, PM2.5, PM2.5-10, and PM10, with childhood AR. METHODS: We investigated 29286 preschool children aged 3-6 years in 7 Chinese major cities during 2019-2020 as the Phase II of the China Children, Families, Health Study. Machine learning-based space-time models were utilized to estimate early-life residential exposure to PM1, PM2.5, and PM10 at 1 × 1-km resolutions. The concentrations of PM1-2.5 and PM2.5-10 were calculated by subtracting PM1 from PM2.5 and PM2.5 from PM10, respectively. Multiple mixed-effects logistic models were used to assess the odds ratios (ORs) and 95% confidence intervals (CIs) of childhood AR associated with per 10-µg/m3 increase in exposure to particulate air pollution during in utero period and the first year of life. RESULTS: Among the 29286 children surveyed (mean ± standard deviation, 4.9 ± 0.9 years), 3652 (12.5%) were reported to be diagnosed with AR. Average PM1 concentrations during in utero period and the first year since birth were 36.3 ± 8.6 µg/m3 and 33.1 ± 6.9 µg/m3, respectively. Exposure to PM1 and PM2.5 during pregnancy and the first year of life was associated with an increased risk of AR in children, and the OR estimates were higher for each 10-µg/m3 increase in PM1 than for PM2.5 (e.g., 1.132 [95% CI: 1.022-1.254] vs. 1.079 [95% CI: 1.014-1.149] in pregnancy; 1.151 [95% CI: 1.014-1.306] vs. 1.095 [95% CI: 1.008-1.189] in the first year of life). No associations were observed between AR and both pre- and post-natal exposure to PM1-2.5, indicating that PM1 rather than PM1-2.5 contributed to the association between PM2.5 and childhood AR. In trimester-stratified analysis, childhood AR was only found to be associated with exposure to PM1 (OR = 1.077, 95% CI: 1.027-1.128), PM2.5 (OR = 1.048, 95% CI: 1.018-1.078), and PM10 (OR = 1.032, 95% CI: 1.007-1.058) during the third trimester of pregnancy. Subgroup analysis suggested stronger PM-AR associations among younger (<5 years old) and winter-born children. CONCLUSIONS: Prenatal and postnatal exposures to ambient PM1 and PM2.5 were associated with an increased risk of childhood AR, and PM2.5-related hazards could be predominantly attributed to PM1. These findings highlighted public health significance of formulating air quality guideline for ambient PM1 in mitigating children's AR burden caused by particulate air pollution.

Modification of Food Allergy on the Associations between Early Life Exposure to Size-Specific Particulate Matter and Childhood Allergic Rhinitis.

Previous studies have reported the association between particulate matter (PM) and childhood allergic rhinitis (AR). However, it is unclear whether food allergy (FA) modifies the PM-AR association. We aimed at evaluating the effect of the modification of FA on PM-AR association in preschool children. We adopted a cross-sectional study and conducted a questionnaire survey among preschool children aged 3-6 years in 7 cities in China from June 2019 to June 2020 to collect information on AR and FA. We used a combination of multilevel logistic regression and restricted cubic spline functions to quantitatively assess whether FA modifies the associations between size-specific PM exposure (1 × 1 km) and the risk of AR. The adjusted odds ratios (ORs) for AR among the children with FA as per a 10 µg/m3 increase in early life PM1, PM2.5, and PM10 were significantly higher than the corresponding ORs among the children without FA [e.g., OR: 1.58, 95% CI: (1.32, 1.90) vs 1.29, 95% CI: (1.18, 1.41), per 10 µg/m3 increase in PM1]. The interactions between FA and size-specific PM exposure and their effects on AR were statistically significant (all p-int < 0.001). FA, as an important part of the allergic disease progression, may modify the PM-AR association in preschool children.

The association between adverse ergonomic factors and work-related musculoskeletal symptoms among medical staff in China: a cross-sectional study.

We investigated the prevalence of work-related musculoskeletal symptoms (WMSs) among medical staff and evaluated the associations of different levels of adverse ergonomic factors with WMSs. A total of 6099 Chinese medical staff were asked to complete a self-reported questionnaire to assess the prevalence and risk factors of WMSs from June 2018 to December 2020. A prevalence rate of 57.5% was observed for WMSs among overall medical staffs, which mainly affected the neck (41.7%) and shoulder (33.5%). 'Keeping sitting for long hours very frequently' (OR = 1.26, 95% CI: 1.04, 1.53) was positively associated with WMSs in doctors, while 'keeping sitting for long hours occasionally' (OR = 0.91, 95% CI: 0.85, 0.97) was identified as a protective factor of WMSs in nurses. The associations of adverse ergonomic factors, organisational factors, and environmental factors with WMSs were different among medical staff in different positions.Practitioner summary: We conducted a multi-city study concerning the risk factors of WMSs by carrying out a face-to-face one-to-multiple questionnaire survey among medical staff in China. As a risk factor of WMSs in medical staff, adverse ergonomic factors should be paid more attention by the standard setting department and policy makers.Abbreviations: WMSDs: work-related musculoskeletal disorders; WMSs: work-related musculoskeletal symptoms; MSDs: musculoskeletal disorders; NMQ: Nordic Musculoskeletal Questionnaires; DMQ: Dutch Musculoskeletal Questionnaires; NIOSH: National Institute for Occupational Safety and Health; ORs: odds ratios.

Associations of Early-Life Exposure to Submicron Particulate Matter With Childhood Asthma and Wheeze in China.

Importance: Exposure to particulate matter (PM) has been associated with childhood asthma and wheeze. However, the specific associations between asthma and PM with an aerodynamic equivalent diameter of 1 µm or less (ie, PM1), which is a contributor to PM2.5 and potentially more toxic than PM2.5, remain unclear. Objective: To investigate the association of early-life (prenatal and first year) exposure to size-segregated PM, including PM1, PM1-2.5, PM2.5, PM2.5-10, and PM10, with childhood asthma and wheeze. Design, Setting, and Participants: This cross-sectional study was based on a questionnaire administered between June 2019 and June 2020 to caregivers of children aged 3 to 6 years in 7 Chinese cities (Wuhan, Changsha, Taiyuan, Nanjing, Shanghai, Chongqing, and Urumqi) as the second phase of the China, Children, Homes, Health study. Exposures: Exposure to PM1, PM1-2.5, PM2.5, PM2.5-10, and PM10 during the prenatal period and first year of life. Main Outcomes and Measures: The main outcomes were caregiver-reported childhood asthma and wheeze. A machine learning-based space-time model was applied to estimate early-life PM1, PM2.5, and PM10 exposure at 1 × 1-km resolution. Concentrations of PM1-2.5 and PM2.5-10 were calculated by subtracting PM1 from PM2.5 and PM2.5 from PM10, respectively. Multilevel (city and child) logistic regression models were applied to assess associations. Results: Of 29 418 children whose caregivers completed the survey (15 320 boys [52.1%]; mean [SD] age, 4.9 [0.9] years), 2524 (8.6%) ever had wheeze and 1161 (3.9%) were diagnosed with asthma. Among all children, 18 514 (62.9%) were breastfed for more than 6 months and 787 (2.7%) had parental history of atopy. A total of 22 250 children (75.6%) had a mother with an educational level of university or above. Of the 25 422 children for whom information about cigarette smoking exposure was collected, 576 (2.3%) had a mother who was a current or former smoker during pregnancy and 7525 (29.7%) had passive household cigarette smoke exposure in early life. Early-life PM1, PM2.5, and PM10 exposure were significantly associated with increased risk of childhood asthma, with higher estimates per 10-µg/m3 increase in PM1 (OR, 1.55; 95% CI, 1.27-1.89) than in PM2.5 (OR, 1.14; 95% CI, 1.03-1.26) and PM10 (OR, 1.11; 95% CI, 1.02-1.20). No association was observed between asthma and PM1-2.5 exposure, suggesting that PM1 rather than PM1-2.5 contributed to the association between PM2.5 and childhood asthma. There were significant associations between childhood wheeze and early-life PM1 exposure (OR, 1.23; 95% CI, 1.07-1.41) and PM2.5 exposure (OR, 1.08; 95% CI, 1.01-1.16) per 10-µg/m3 increase in PM1 and PM2.5, respectively. Conclusions and Relevance: In this cross-sectional study, higher estimates were observed for the association between PM with smaller particles, such as PM1, vs PM with larger particles and childhood asthma. The results suggest that the association between PM2.5 and childhood asthma was mainly attributable to PM1.

Prenatal metal mixture exposure and birth weight: A two-stage analysis in two prospective cohort studies.

The understanding of the impact of prenatal exposure to metal mixtures on birth weight is limited. We aimed to identify metal mixture components associated with birth weight and to determine additional pairwise interactions between metals showing such associations. Concentrations of 18 metals were measured using inductively coupled plasma mass spectrometry in urine samples collected in the 3rd trimester from a prenatal cohort (discovery; n = 1849) and the Healthy Baby Cohort (replication; n = 7255) in Wuhan, China. In the discovery set, we used two penalized regression models, i.e., elastic net regression for main effects and a lasso for hierarchical interactions, to identify important mixture components associated with birth weight, which were then replicated. We observed that 8 of the 18 measured metals were retained by elastic net regression, with five metals (vanadium, manganese, iron, cesium, and barium) showing negative associations with Z-scores for birth weight and three metals (cobalt, zinc, and strontium) showing positive associations. In replication set, associations remained significant for vanadium (ß = -0.035; 95% confidence interval [CI], -0.059 to -0.010), cobalt (ß = 0.073; 95% CI, 0.049 to 0.097), and zinc (ß = 0.040; 95% CI, 0.016 to 0.065) after Bonferroni correction. We additionally identified and replicated a single pairwise interaction between iron and copper exposure on birth weight (P < 0.001). Using a two-stage analysis, we identified and replicated individual metals and additional pairwise interactions-associated birth weight. The approach could be used in other studies estimating the effect of complex mixtures on human health.

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.

Associations of prenatal exposure to vanadium with early-childhood growth: A prospective prenatal cohort study.

Prenatal vanadium exposure is reported to be associated with restricted fetal growth and adverse birth outcomes. However, trimester-specific vanadium exposure in relation to early-childhood growth still remains unclear. A total of 1873 Chinese mother-infant pairs from whom a complete series of maternal urinary samples were collected over three stages of pregnancy were included from 2014 to 2016. The urinary concentrations of vanadium were analyzed. Children's anthropometric parameters were measured at birth, 6, 12 and 24 months. In boys, each doubling increase in vanadium concentrations at middle pregnancy was inversely associated with weight-for-length [- 9.07% (-17.21%, -0.93%)] and BMI z-score [- 9.66% (-18.05%, -1.28%)] at 24 months. Moreover, vanadium exposure at late pregnancy was negatively associated with weight [- 9.85% (-16.42%, -3.28%)], weight-for-length [- 11.00% (-18.40%, -3.60%)], and BMI z-scores [- 11.05% (-18.67%, -3.42%)] at 24 months in boys. However, the negative associations were not observed in girls, and we found evidence for sex difference (FDR p for interaction=0.01, 0.01 and 0.03 for weight, weight-for-length and BMI z-scores, respectively). Prenatal vanadium exposure may have an adverse effect on early-childhood growth, and the middle and late pregnancy could be windows of vulnerability for the adverse effects of vanadium exposure on growth development.

Multiple metal exposure and platelet counts during pregnancy: A repeated measure study.

BACKGROUND: Evidence from animal and in vitro studies suggest that some metals interfere with normal platelet counts (PLT). However, limited human studies have investigated the association of metals and PLT, a marker of hematologic and hemostatic, particularly in susceptible populations such as pregnant women. OBJECTIVES: Our purpose was to investigate the associations of repeated measures of 13 urinary metals with PLT during pregnancy. METHODS: The present study involved 3911 pregnant women participating in a prospective cohort study in Wuhan, China, from 2013 to 2016. We measured 13 metals in urine and PLT in blood samples collected in the first, second, and third trimester (median = 13, 24, and 35 weeks of gestation, respectively). Mixed linear models and general linear models were applied to analyze the associations between multiple metals and PLT during pregnancy. The odds ratio (OR) for gestational thrombocytopenia was examined using generalized estimating equations. RESULTS: After adjusting for other metals and covariates, the repeated measure analyses showed that decreased levels of PLT were associated with a 10-fold increase in urinary concentration of cadmium (Cd) [percent difference (%Δ) = -5.02, 95%CI = -9.53, -0.29], manganese (Mn) [percent difference (%Δ) = -4.63, 95%CI = -7.50, -1.67], and arsenic (As) [percent difference (%Δ) = -4.56, 95%CI = -8.11, -0.86]. Cross-sectional analyses by trimesters revealed that Cd was inversely associated with PLT through the three trimesters. In addition, Cd was associated with an increased OR of 1.80 (95%CI: 1.26, 2.56), 1.65 (95%CI: 1.05, 2.59), 1.54 (95%CI: 1.02, 2.33) for gestational thrombocytopenia in the first, second, and third trimester, respectively. CONCLUSIONS: Our study suggested an association of Cd, Mn, and As with decreased PLT during pregnancy. Particularly, Cd may increase the risk of gestational thrombocytopenia.

Epidemiological and Clinical Characteristics of COVID-19 in Adolescents and Young Adults.

BACKGROUND: Adolescents and young adults might play a key role in the worldwide spread of Coronavirus Disease 2019 (COVID-19) because they are more likely to be involved in overseas study, business, work, and travel. However, the epidemiological and clinical characteristics remain unknown. METHODS: We collected demographic, epidemiological, and clinical data from 46 confirmed COVID-19 patients aged 10 to 35 years from the Chongqing Three Gorges Central Hospital. Several key epidemiological parameters, asymptomatic cases, transmission to family members, and clinical characteristics at admission and during treatment were summarized. RESULTS: Of 46 confirmed patients, 14 patients (30.4%) were aged between 10 and 24 years, and 24 (52.2%) patients were male. The estimated mean incubation period was 6.6 days (95% confidence interval [CI] 4.4-9.6). The median serial interval was 1.9 days (95% CI 0.4-6.2). Three of the asymptomatic cases showed transmission to their family members. Only one patient was identified as a severe case at admission. The common symptoms at admission were dry cough (34, 81.0%) and fever (29, 69.1%). Nearly 60% of the patients showed ground-glass opacity on chest computed tomography. Three patients developed acute kidney injury during treatment. Most of the patients (78.3%) recovered and were discharged by the end of the follow-up. CONCLUSIONS: This single-center study with a relatively small sample size showed that adolescent and young adult patients with COVID-19 had a long incubation period and a short serial interval. The transmission occurred from asymptomatic cases to family members. Fewer patients developed complications during treatment.

Associations of Trimester-Specific Exposure to Bisphenols with Size at Birth: A Chinese Prenatal Cohort Study.

BACKGROUND: Bisphenol A (BPA) is an endocrine disruptor that affects fetal growth in experimental studies. Bisphenol F (BPF) and bisphenol S (BPS), which have been substituted for BPA in some consumer products, have also shown endocrine-disrupting effects in experimental models. However, the effects of BPF and BPS on fetal growth in humans are unknown. OBJECTIVES: Our goal was to investigate trimester-specific associations of urinary concentrations of BPA, BPF, and BPS with size at birth. METHODS: The present study included 845 pregnant women from Wuhan, China (2013-2015), who provided one urine sample in each of the first, second, and third trimesters. Linear regressions with generalized estimating equations were applied to estimate trimester-specific associations of urinary bisphenol concentrations with birth weight, birth length, and ponderal index. Linear mixed-effects models were used to identify potential critical windows of susceptibility to bisphenols by comparing the exposure patterns of newborns in the 10th percentile of each birth anthropometric measurement to that of those in the 90th percentile. RESULTS: Medians (25th-75th percentiles) of urinary concentrations of BPA, BPF, and BPS were 1.40 (0.19-3.85), 0.65 (0.34-1.39), and 0.38 (0.13-1.11) ng/mL, respectively. Urinary BPA concentrations in different trimesters were inversely, but not significantly, associated with birth weight and ponderal index. Urinary concentrations of BPF and BPS during some trimesters were associated with significantly lower birth weight, birth length, or ponderal index, with significant trend p-values (ptrend<0.05) across quartiles of BPF and BPS concentrations. The observed associations were unchanged after additionally adjusting for other bisphenols. In addition, newborns in the 10th percentile of each birth anthropometry measure had higher BPF and BPS exposures during pregnancy than newborns in the 90th percentile of each outcome. CONCLUSIONS: Prenatal exposure to BPF and BPS was inversely associated with size at birth in this cohort. Replication in other populations is needed. https://doi.org/10.1289/EHP4664.

Exposure Assessment of Bisphenols in Chinese Women during Pregnancy: A Longitudinal Study.

Bisphenol S (BPS) and bisphenol F (BPF) are increasingly used in manufacturing consumer products to replace the use of bisphenol A (BPA), but exposure data are limited, particularly among pregnant women. Here, we measured BPA, BPS, and BPF levels in urine samples, collected from 941 pregnant women over three trimesters. We examined the correlations, coexposure patterns, variability, and predictors of bisphenols using Spearman's correlation coefficient, percentile analysis, intraclass correlation coefficient, and linear mixed models, respectively. We assessed health risks using average concentrations of bisphenols over three trimesters. The three bisphenols were detected in more than 50% of samples, among which BPA was the predominant one. Cashiers, office workers, teachers, and salespersons had elevated urinary BPS concentrations, while healthcare workers had relatively higher BPA concentrations. About 15 participants had potential health risks induced by exposure to bisphenol mixtures. These findings indicate that exposure to multiple bisphenols at low levels is common over three trimesters. Multiple measurements of urinary BPA and BPS concentrations are needed for more accurate evaluation of the exposure levels during pregnancy, while urinary BPF concentrations during pregnancy are moderately reliable. Occupational exposure should be taken into consideration in future demographic studies.

Variations of phthalate exposure and metabolism over three trimesters.

Maternal exposure to phthalates may cause some adverse health effects on both mother and fetus, but variations of phthalate exposure and metabolism during pregnancy have not been thoroughly characterized. A total of 946 participants were selected from a cohort study conducted in Wuhan between 2014 and 2015 through which they had provided a complete set of urine samples at three trimesters. Eight phthalate metabolites were analyzed in 2838 urine samples. Based on urinary concentrations, various parameters (i.e. phthalate metabolite concentrations, ratios of metabolites of bis(2-ethylhexyl) phthalate (DEHP) in DEHP, and percentages of individual metabolites in total phthalates) were compared over three visits. We observed that levels of phthalate metabolites showed a U-shaped trend across three trimesters. The significant variations in the ratios of DEHP metabolites indicated that the efficiency in metabolizing DEHP declined during pregnancy and less recent exposure occurred in mid-pregnancy. The changes of percentages of individual compound in total phthalates suggested the inconsistent pattern over trimesters. This longitudinal study found that the exposure pattern, exposure timing and metabolic susceptibility varied by trimesters, which suggests that urine samples should be collected at multiple time points and mothers should be especially careful in the early pregnancy.

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.

Repeated Measurements of Paraben Exposure during Pregnancy in Relation to Fetal and Early Childhood Growth.

Parabens are potential endocrine disruptors with short half-lives in the human body. To date, few epidemiological studies regarding repeated paraben measurements during pregnancy associated with fetal and childhood growth have been conducted. Within a Chinese prenatal cohort, 850 mother-infant pairs from whom a complete set of maternal urine samples were acquired during three trimesters were included, and the levels of five parabens were measured. We assessed the associations of both average and trimester-specific urinary paraben levels with weight and height z-scores at birth, 6 months, 1, and 2 years of age. In all infants, each doubling increase in average ethyl paraben (EtP) was associated with -2.82% (95% CI: -5.11%, -0.53%) decrease in weight z-score at birth, whereas no significant age-specific associations were identified. After stratifying by sex, we further observed age-specific association of average EtP with -3.96% (95% CI: -7.03%, -0.89%) and -3.38% (95% CI: 6.72%, -0.03%) reduction in weight z-scores at 1 and 2 years in males, respectively. Third-trimester EtP was negatively associated with weight z-scores at birth, 1 and 2 years in males. Our results suggested negative associations between prenatal paraben exposure and fetal and childhood growth, and the third trimester may be the window of susceptibility.

Maternal urinary benzophenones and infant birth size: Identifying critical windows of exposure.

Benzophenones (BPs) are widely used as ultraviolet absorbers and fragrance retention agents. Evidences from animal studies have suggested that exposure to BPs may affect fetal growth, but human data is limited and no study is concerning critical windows of BPs exposure throughout pregnancy in relation to fetal growth. We aimed to investigate the associations of prenatal exposure to BPs with birth size and examine the critical exposure windows of fetus development. We measured BPs (including 2,4-dihydroxybenzophenone (BP-1), 2-hydroxy-4-methoxybenzophenone (BP-3) and 4-hydroxybenzophenone (4-OH-BP)) in maternal urine samples collected in the first, second, and third trimester from 847 mothers recruited in Wuhan, China. The general estimation equations were used to analyze the relationships between maternal exposure to BPs levels and birth size. In all newborns, we found each log unit increase in maternal urinary concentrations of BP-1 and 4-OH-BP in the 1st trimester were associated with decreases in birth length by 0.06 cm (95% confidence interval (CI): -0.11, -0.01) and 0.08 cm (95% CI: -0.15, -0.01), respectively, but only the association with BP-1 in the boys remained significant in the stratified analysis by infant sex. In girls, urinary concentrations of BP-1 and BP-3 in the 3rd trimester were associated with decreased birth weight (adjusted ß = -27.99 g, 95% CI: -50.66, -5.31 and -19.75 g, 95% CI: -37.31, -2.19, respectively) and length (adjusted ß = -0.08 cm, 95% CI: -0.17, 0.00 and -0.08 cm, 95% CI: -0.15, -0.02) (p for interaction = 0.04). Our findings indicate that maternal urinary levels of BPs in the early and late periods during pregnancy may have impacts on delayed fetal growth, and the effects were more pronounced in girls.

Urinary metabolomics reveals novel interactions between metal exposure and amino acid metabolic stress during pregnancy.

Pregnant women are a unique group undergoing profound structural modifications in uterus, breast, adipose tissue and extracellular fluids. Amino acid metabolic stress is a unique physical process that occurs during pregnancy. Metals constitute a fundamental part of the maternal body and have a universal effect on amino acid metabolism. However, the exact interaction between metals and amino acid metabolism during pregnancy is unknown. The aim of the present study was to determine the correlations of metals with amino acid metabolic intermediates in the urine of 232 healthy pregnant women in their first, second and third trimesters during normal pregnancy. Sixteen metals in the urine of 232 healthy pregnant women in their first, second and third trimesters were quantified using inductively coupled plasma mass spectrometry (ICP-MS). An ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometer (UPLC-QTOFMS)-based metabolomics approach was conducted to detect intermediate products involved in amino acid metabolism during the entire pregnancy period. A panel regression model was established to investigate the relationship between urine metals and amino acid metabolism. Seven metals-cadmium, cobalt, copper, cesium, manganese, thallium and vanadium-showed significant association with amino acid metabolic intermediates, including 2-oxoarginine, 3-indoleacetonitrile, indole, indole-5,6-quinone, N2-succinyl-l-glutamic acid 5-semialdehyde, N-methyltryptamine and N-succinyl-l,l-2,6-diaminopimelate, in the healthy pregnant women. These findings indicated that exposure to cadmium, cobalt, copper, cesium, manganese, thallium and vanadium significantly affected the metabolic status of tryptophan, arginine, proline, tyrosine and lysine metabolism in the maternal body during normal pregnancy.

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

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

The association of repeated measurements of prenatal exposure to triclosan with fetal and early-childhood growth.

BACKGROUND: Triclosan (TCS) is known to possess endocrine disrupting properties and metabolize rapidly in the human body. Human data concerning repeated measurements of TCS throughout pregnancy in relation to fetal and childhood growth are sparse. OBJECTIVES: We investigated the associations between multiple measurements of maternal urinary concentrations of TCS during pregnancy and fetal and early-childhood growth. METHODS: The study population included 850 mother-infant pairs who participated in a prenatal cohort established between 2014 and 2015 in Wuhan. Prenatal TCS exposure was measured in a complete series of urine samples collected at the first, second and third trimesters. General linear models and generalized estimating equation models were applied to evaluate the associations of the averaged maternal urinary concentrations of TCS over trimesters and trimester-specific urinary TCS with the z-scores of estimated fetal weight, head circumference, abdominal circumference, and femur length at 16, 24, and 31 gestational weeks, weight and length at birth, and weight and height at 0.5, 1, and 2 years of age. RESULTS: In overall infants, we did not observe any significant association of the averaged maternal urinary concentrations of TCS over trimesters with ultrasound parameters and size at birth. However, a positive association of borderline statistical significance was found between averaged prenatal TCS exposure and the third-trimester estimated fetal weight z-score in girls in sex-stratified analyses (ß = 0.054, 95% CI: -0.005, 0.113, p = 0.07). Moreover, averaged prenatal TCS exposure was positively associated with 2 year-old weight z-score among total infants (ß = 0.046, 95% CI: 0.005, 0.087). After stratifying by sex, the same association was observed in girls with more prominent estimation (ß = 0.062, 95% CI: 0.000, 0.124), whereas the association weakened and became not significant in boys (ß = 0.033, 95% CI: -0.024, 0.089). TCS exposure at 1st and 2nd-trimester were positively associated with weight z-score at 2 years, in both overall and female infants. CONCLUSIONS: Prenatal exposure to triclosan was associated with elevated third-trimester estimated fetal weight and 2 year-old weight z-score in girls, and the early and middle stage of pregnancy may be the windows of vulnerability. Apart from these findings, we did not find strong evidence for prenatal triclosan exposure in relation to fetal and early-childhood growth.