The seasonal cycle and variability of sea level in the South China Sea

The spatial and temporal characteristics of the seasonal sea level cycle in the South China Sea (SCS) and its forcing mechanisms are investigated using tide gauge records and satellite altimetry observations along with steric and meteorological data. The coastal mean annual amplitude of the seasonal cycle varies between zero and 24 cm, reaching a maximum between July and January. The maximum mean semiannual amplitude is 7 cm, peaking between March and June. Along the coast, the seasonal cycle accounts for up to 92% of the mean monthly sea level variability. Atmospheric pressure explains a significant portion of the seasonal cycle with dominant annual signals in the northern SCS, the Gulf of Thailand and the north-western Philippines Sea. The wind forcing is dominant on the shelf areas of the SCS and the Gulf of Thailand where a simple barotropic model forced by the local wind shows annual amplitudes of up to 27 cm. In the deep basin of the SCS, the Philippines Sea and the shallow Malacca Strait, the steric component is the major contributor with the maximum annual amplitudes reaching 15 cm. Significant variability in the seasonal cycle is found on a year-to-year basis. The annual and semiannual amplitudes vary by up to 63% and 45% of the maximum values, 15 cm and 11 cm, respectively. On average, stepwise regression analysis of contribution of different forcing factors accounts for 66% of the temporal variability of the annual cycle. The zonal wind was found to exert considerable influence in the Malacca Strait

Prenatal phthalate exposures and child temperament at 12 and 24 months

Introduction Gestational phthalate exposures have been adversely associated with attention, externalizing, and internalizing behaviors in childhood. Early childhood temperament may be a marker of later behavioral patterns. We therefore sought to determine whether gestational phthalate exposures were associated with infant and toddler temperament. Methods The Mount Sinai Children's Environmental Health Study is a prospective cohort study of children born between May 1998 and July 2001 in New York City (N = 404). Phthalate metabolites were measured in spot urine samples collected from pregnant women in their third trimester. Child temperament was assessed by parental report at 12-months using the Infant Behavior Questionnaire (IBQ) (N = 204) and at 24-months using the Toddler Behavior Assessment Questionnaire (TBAQ) (N = 279). We used multiple linear regression to evaluate associations between urinary phthalate metabolites and eleven temperament domains. Results Phthalate biomarker concentrations were weakly associated with lower gross motor activity levels as well as higher duration of orienting at the 12-month assessment. Mono(3-carboxypropyl) phthalate (MCPP), monobenzyl phthalate (MBzP) and the sum of metabolites of di(2-ethylhexyl) phthalate (∑DEHP) were associated with lower levels of smiling and laughing at 12 months. At 24-months, social fear and lower pleasure was linked to higher concentrations of MCPP and MBzP, and higher ∑DEHP was weakly associated with increased anger levels at 24-months. Conclusions Though we observed some weak associations between biomarkers of prenatal exposure to phthalates and temperament at 12- and 24-months, overall phthalates biomarkers were not strongly associated with alterations in temperament

Prenatal exposure to per- and polyfluoroalkyl substances and infant growth and adiposity: the Healthy Start Study

Background: Prenatal exposures to certain per- and polyfluoroalkyl substances (PFAS) have been linked to lower weight and adiposity at birth but greater weight and adiposity in childhood. We hypothesized that faster growth in early infancy may be associated with maternal PFAS concentrations. Methods: Among 415 mother-infant pairs in a longitudinal cohort study, we estimated associations between maternal pregnancy serum concentrations of six PFAS and offspring weight and adiposity at ~5 months of age, and growth in early infancy. Linear and logistic regression models were adjusted for potential confounders including maternal pre-pregnancy body mass index. Effect modification by infant sex was evaluated. We evaluated potential confounding by correlated exposures via multipollutant linear regression and elastic net penalized regression. Results: Associations between maternal PFAS concentrations and infant weight and adiposity differed by offspring sex. In male infants, maternal perfluorooctanoate and perfluorononanoate were positively associated with adiposity, with percent fat mass increases of 1.5–1.7% per ln-ng/mL increase in PFAS (median adiposity at ~5 months: 24.6%). Maternal perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were associated with lower weight-for-age z-score among female infants only (−0.26 SD per ln-ng/mL PFOS, 95% CI −0.43, −0.10; −0.17 SD per ln-ng/mL PFHxS, 95% CI −0.33, −0.01). In analyses pooled by sex, 2-(N-methyl-perfluorooctane sulfonamido) acetate above vs. below the limit of detection was associated with greater odds of rapid growth in weight-for-age (odds ratio [OR] 2.2, 95% CI 1.1, 4.3) and weight-for-length (OR 3.3, 95% CI 1.8, 6.2). Multipollutant models generally confirmed the results and strengthened some associations. Discussion: We observed sex- and chemical-specific associations between maternal serum PFAS concentrations and infant weight and adiposity. Multipollutant models suggested confounding by correlated PFAS with opposing effects. Although maternal PFAS concentrations are inversely associated with infant weight and adiposity at birth, rapid gain may occur in infancy, particularly in fat mass

Associations of prenatal environmental phenol and phthalate biomarkers with respiratory and allergic diseases among children aged 6 and 7 years

Background: Prenatal environmental phenol and phthalate exposures may alter immune or inflammatory responses leading to respiratory and allergic disease. Objectives: We estimated associations of prenatal environmental phenol and phthalate biomarkers with respiratory and allergic outcomes among children in the Mount Sinai Children's Environmental Health Study. Methods: We quantified urinary biomarkers of benzophenone-3, bisphenol A, paradichlorobenzene (as 2,5-dichlorophenol), triclosan, and 10 phthalate metabolites in third trimester maternal samples and assessed asthma, wheeze, and atopic skin conditions via parent questionnaires at ages 6 and 7 years (n = 164 children with 240 observations). We used logistic regression to estimate covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) per standard deviation difference in natural log biomarker concentrations and examined effect measure modification by child's sex. Results: Associations of prenatal 2,5-dichlorophenol (all outcomes) and bisphenol A (asthma outcomes) were modified by child's sex, with increased odds of outcomes among boys but not girls. Among boys, ORs for asthma diagnosis per standard deviation difference in biomarker concentration were 3.00 (95% CI: 1.36, 6.59) for 2,5-dichlorophenol and 3.04 (95% CI: 1.38, 6.68) for bisphenol A. Wheeze in the past 12 months was inversely associated with low molecular weight phthalate metabolites among girls only (OR: 0.27, 95% CI: 0.13, 0.59) and with benzophenone-3 among all children (OR: 0.65, 95% CI: 0.44, 0.96). Conclusions: Prenatal bisphenol A and paradichlorobenzene exposures were associated with pediatric respiratory outcomes among boys. Future studies may shed light on biological mechanisms and potential sexually-dimorphic effects of select phenols and phthalates on respiratory disease development

Prenatal phthalate exposure and performance on the Neonatal Behavioral Assessment Scale in a multiethnic birth cohort

We investigated the relationship between prenatal maternal urinary concentrations of phthalate metabolites and neonatal behavior in their 295 children enrolled in a multiethnic birth cohort between 1998 and 2002 at the Mount Sinai School of Medicine in New York City. Trained examiners administered the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) to children within 5 days of delivery. We measured metabolites of 7 phthalate esters in maternal urine that was collected between 25 and 40 weeks' gestation. All but two phthalate metabolites were over 95% detectable. We summed metabolites on a molar basis into low and high molecular weight phthalates. We hypothesized the existence of sex-specific effects from phthalate exposure a priori given the hormonal activity of these chemicals. Overall we found few associations between individual phthalate metabolites or their molar sums and most of the BNBAS domains. However, we observed significant sex-phthalate metabolite interactions (p < 0.10) for the Orientation and Motor domains and the overall Quality of Alertness score. Among girls, there was a significant linear decline in adjusted mean Orientation score with increasing urinary concentrations of high molecular weight phthalate metabolites (B = -0.37, p = 0.02). Likewise, there was a strong linear decline in their adjusted mean Quality of Alertness score (B = -0.48, p < 0.01). In addition, boys and girls demonstrated opposite patterns of association between low and high molecular weight phthalate metabolite concentrations and motor performance, with some indication of improved motor performance with increasing concentration of low molecular weight phthalate metabolites among boys. This is the first study to report an association between prenatal phthalate exposure and neurological effects in humans or animals, and as such requires replication

Response to “Comment on ‘optimal exposure biomarkers for nonpersistent chemicals in environmental epidemiology’”

We appreciate the opportunity to respond to the letter from Stahlhut et al. regarding our Brief Communication. We stressed the importance of biospecimen integrity and the potential danger of unrecognized contamination of convenience samples, particularly with ubiquitous environmental chemicals such as bisphenol A (BPA) and phthalates

Prenatal exposure to per-and polyfluoroalkyl substances, umbilical cord blood DNA methylation, and cardio-metabolic indicators in newborns: The healthy start study

BACKGROUND: Per-and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals widely detected in women of reproductive age. Prenatal PFAS exposure is associated with adverse health outcomes in children. We hypothesized that DNA methylation changes may result from prenatal PFAS exposure and may be linked to offspring cardio-metabolic phenotype. OBJECTIVES: We estimated associations of prenatal PFAS with DNA methylation in umbilical cord blood. We evaluated associations of methylation at selected sites with neonatal cardio-metabolic indicators. METHODS: Among 583 mother–infant pairs in a prospective cohort, five PFAS were quantified in maternal serum (median 27 wk of gestation). Umbilical cord blood DNA methylation was evaluated using the Illumina HumanMethylation450 array. Differentially methylated positions (DMPs) were evaluated at a false discovery rate (FDR) <0:05 and differentially methylated regions (DMRs) were identified using comb-p (Šidák-adjusted p <0:05). We estimated associations between methylation at candidate DMPs and DMR sites and the following outcomes: newborn weight, adiposity, and cord blood glucose, insulin, lipids, and leptin. RESULTS: Maternal serum PFAS concentrations were below the median for females in the U.S. general population. Moderate to high pairwise correla-tions were observed between PFAS concentrations (q =0:28 − 0:76). Methylation at one DMP (cg18587484), annotated to the gene TJAP1, was associated with perfluorooctanoate (PFOA) at FDR < 0:05. Comb-p detected between 4 and 15 DMRs for each PFAS. Associated genes, some common across multiple PFAS, were implicated in growth (RPTOR), lipid homeostasis (PON1, PON3, CIDEB, NR1H2), inflammation and immune activity (RASL11B, RNF39), among other functions. There was suggestive evidence that two PFAS-associated loci (cg09093485, cg09637273) were associated with cord blood triglycerides and birth weight, respectively (FDR < 0:1). DISCUSSION: DNA methylation in umbilical cord blood was associated with maternal serum PFAS concentrations during pregnancy, suggesting potential associations with offspring growth, metabolism, and immune function. Future research should explore whether DNA methylation changes mediate associations between prenatal PFAS exposures and child health outcomes. https://doi.org/10.1289/EHP6888

Longitudinal association of biomarkers of pesticide exposure with cardiovascular disease risk factors in youth with diabetes

Background: Cardiovascular disease (CVD) is the leading cause of death among individuals with diabetes, but little is known about the role of exposures to environmental chemicals such as pesticides in the early development of CVD risk in this population. Objectives: To describe changes over time in concentrations of pesticide biomarkers among youth with diabetes in the United States and to estimate the longitudinal association between these concentrations and established risk factors for CVD. Methods: Pesticide biomarkers were quantified in urine and serum samples from 87 youth with diabetes participating in the multi-center SEARCH cohort study. Samples were obtained around the time of diagnosis (baseline visit, between 2006 and 2010) and, on average, 5.4 years later (follow-up visit, between 2012 and 2015). We calculated geometric mean (95% CI) pesticide biomarker concentrations. Eight CVD risk factors were measured at these two time points: body mass index (BMI) z-score, HbA1c, insulin sensitivity, fasting C-peptide (FCP), LDL cholesterol, HDL cholesterol, total cholesterol, and triglycerides. Linear regression models were used to estimate the associations between each pesticide biomarker at baseline and each CVD risk factor at follow-up, adjusting for baseline health outcome, elapsed time between baseline and follow up, sex, age, race/ethnicity, and diabetes type. Results: Participants were, on average, 14.2 years old at their baseline visit, and most were diagnosed with type 1 diabetes (57.5%). 4-nitrophenol, 3-phenoxybenzoic acid, 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloro-2-pyridinol, 2,2-bis(4-chlorophenyl)-1,1-dichloroethene, and hexachlorobenzene were detected in a majority of participants at both time points. Participants in the highest quartile of 2,4-D and 4-nitrophenol at baseline had HbA1c levels at follow-up that were 1.05 percentage points (95% CI: −0.40, 2.51) and 1.27 percentage points (0.22, 2.75) higher, respectively, than participants in the lowest quartile of these pesticide biomarkers at baseline. These participants also had lower log FCP levels (indicating reduced beta-cell function) compared to participants in the lowest quartile at baseline: beta (95% CI) for log FCP of −0.64 (−1.17, −0.11) for 2,4-D and −0.39 (−0.96, 0.18) for 4-nitrophenol. In other words, participants in the highest quartile of 2,4-D had a 47.3% lower FCP level compared to participants in the lowest quartile, and those in the highest quartile of 4-nitrophenol had a 32.3% lower FCP level than those in the lowest quartile. Participants with trans-nonachlor concentrations in the highest quartile at baseline had HbA1c levels that were 1.45 percentage points (−0.11, 3.01) higher and log FCP levels that were −0.28 (−0.84, 0.28) lower than participants in the lowest quartile at baseline, that is to say, participants in the highest quartile of trans-nonachlor had a 24.4% lower FCP level than those in the lowest quartile. While not all of these results were statistically significant, potentially due to the small same size, clinically, there appears to be quantitative differences. No associations were observed between any pesticide biomarker at baseline with BMI z-score or insulin sensitivity at follow-up. Conclusions: Exposure to select pesticides may be associated with impaired beta-cell function and poorer glycemic control among youth with diabetes

Associations between Prenatal Urinary Biomarkers of Phthalate Exposure and Preterm Birth: A Pooled Study of 16 US Cohorts

Importance: Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth. Objective: To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US. Design, Setting, and Participants: Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included. Exposures: Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated. Main Outcomes and Measures: Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth. Results: The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively. Conclusions and Relevance: Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery