BACKGROUND:Previous studies have suggested that prenatal exposure to organophosphate flame retardants (OPFRs) may have adverse effect on early neurodevelopment, but limited data are available in China, and the overall effects of OPFRs mixture are still unclear. OBJECTIVE:This study aimed to investigate the association between prenatal exposure to OPFR metabolites mixture and the neurodevelopment of 1-year-old infants. METHODS:A total of 270 mother-infant pairs were recruited from the Laizhou Wan (Bay) Birth Cohort in China. Ten OPFR metabolites were measured in maternal urine. Neurodevelopment of 1-year-old infants was assessed using the Gesell Developmental Schedules (GDS) and presented by the developmental quotient (DQ) score. Multivariate linear regression and weighted quantile sum (WQS) regression models were conducted to estimate the association of prenatal exposure to seven individual OPFR metabolites and their mixture with infant neurodevelopment. RESULTS:The positive rates of seven OPFR metabolites in the urine of pregnant women were greater than 70% with the median concentration ranged within 0.13-3.53 μg/g creatinine. The multivariate linear regression model showed significant negative associations between bis (1-chloro-2-propyl) phosphate (BCIPP), din-butyl phosphate (DnBP), and total OPFR metabolites exposure and neurodevelopment in all infants. Results from the WQS model consistently revealed that the OPFR metabolites mixture was inversely associated with infant neurodevelopment. Each quartile increased in the seven OPFR metabolites mixture was associated with a 1.59 decrease (95% CI: 2.96, -0.21) in gross motor DQ scores, a 1.41 decrease (95% CI: 2.38, -0.43) in adaptive DQ scores, and a 1.08 decrease (95% CI: 2.15, -0.02) in social DQ scores, among which BCIPP, bis (1, 3-dichloro-2-propyl) phosphate (BDCIPP) and DnBP were the main contributors. CONCLUSION:Prenatal exposure to a mixture of OPFRs was negatively associated with early infant neurodevelopment, particularly in gross motor, adaptive, and social domains.

Background: Organophosphate flame retardants (OPFRs) are widely used as flame retardants and plasticizers. Laboratory evidence has suggested that maternal OPFR exposure may adversely affect fetal growth, but the epidemiological data are limited. Objectives: To investigate the association of maternal OPFR exposure with neonatal anthropometric measures.Methods: This study included 354 mother-newborn pairs from the Laizhou Wan Birth Cohort (LWBC), China. Ten OPFR metabolites were measured in maternal urine samples collected before delivery. Neonatal anthropometric data was collected from medical records and standardized into z-scores using the WHO standards (2007), including the weight-for-age (WAZ), length-for-age (LAZ), body mass index-for-age (BMIZ), weight-for-length (WLZ), and head circumference-for-age z-score (HCZ). Multiple linear regression and weighted quantile sum (WQS) regression were used to estimate the associations of individual OPFR metabolites and their mixtures with neonatal anthropometrics, respectively. Stratified analysis by sex was performed.Results: The detection rates of BCEP, DPHP, BCIPP, BDCIPP, BBOEP, DnBP and DiBP were above 60%, with median concentrations ranging from 0.14 to 3.60 & mu;g/g creatinine. Most OPFR metabolites (i.e., BCIPP, BDCIPP, DiBP, DnBP, or BBOEP) were associated with decreased offspring WAZ and HCZ. When using WQS analysis, the OPFR metabolite mixture was inversely associated with the WAZ, BMIZ and HCZ, whereas DnBP had the highest weights. After stratified by gender, the negative associations were more pronounced among males.Conclusions: Maternal OPFR exposure was negatively associated with offspring WAZ, BMIZ, and HCZ, and males seemed to be more vulnerable to the developmental toxicity of certain OPFRs.

BACKGROUND:Bisphenol A (BPA) exposure has been linked to adverse childhood neurodevelopment, but little is known about whether BPA substitutes exposures are also related to childhood neurodevelopment.OBJECTIVES:To investigate the associations of exposure to BPA and its substitutes with infant neurodevelopment at 12 months.METHODS:A total of 420 infants at 12 months were included from the Laizhou Wan (Bay) Birth Cohort in Shandong, China. Urinary concentrations of BPA and its substitutes including bisphenol S (BPS), bisphenol B (BPB), bisphenol AF (BPAF), bisphenol AP (BPAP), bisphenol P (BPP) and bisphenol Z (BPZ) were measured. Developmental quotient (DQ) scores based on the Gesell Development Schedules (GDS) were used to evaluate infant neurodevelopment. The multivariable linear regression and weighted quantile sum (WQS) regression were applied to estimate the associations of exposure to individual bisphenols and their mixtures with DQ scores, respectively. Sex-stratified analyses were also performed.RESULTS:BPA was detected in most infants (89.05%) and had the highest median concentration (0.709 ng/mL) among all bisphenols. BPA substitutes except BPZ were ubiquitous in infants' urine samples (>70%), and BPS showed the highest median concentration (0.064 ng/mL) followed by BPAP (0.036 ng/mL), BPAF (0.028 ng/mL), BPP (0.015 ng/mL) and BPB (0.013 ng/mL). In multivariable linear regression, only BPAF exposure was inversely associated with social DQ scores among all infants (β = -0.334; 95% CI: -0.650, -0.019). After sex stratification, this inverse association was significant in girls (β = -0.605; 95% CI: -1.030, -0.180). Besides, BPA exposure was negatively related to gross motor DQ scores in boys (β = -1.061; 95% CI: -2.078, -0.045). WQS analyses confirmed these results.CONCLUSIONS:Our study suggests that bisphenol exposure during infancy may be associated with poor infant neurodevelopment, and BPAF as a commonly used BPA substitute contributing the most to this adverse association deserves more attention.

Organophosphate flame retardants (OPFRs) and organophosphate pesticides (OPPs), pertaining to organophosphate esters, are ubiquitous in environment and have been verified to pose noticeable risks to human health. To evaluate human exposures to OPFRs and OPPs, a fast and sensitive approach based on a solid phase extraction (SPE) followed by the ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) detection has been developed for the simultaneous analysis of multiple organophosphorus metabolites in urine. The method allows the identification and quantification of ten metabolites of the most common OPFRs and all six dialkylphosphates (DAPs) of OPPs concerning the population exposure characteristics. The method provided good linearities (R2 = 0.998-0.999), satisfactory method detection limits (MDLs) (0.030-1.129 ng/mL) and only needed a small volume (200 μL) of urine. Recovery rates ranged 73.4-127.1% at three spiking levels (2, 10 and 25 ng/mL urine), with both intra- and inter-day precision less than 14%. The good correlations for DAPs in a cross-validation test with a previous gas chromatography-mass spectrometry (GC-MS) method and a good inter-laboratory agreement for several OPFR metabolites in a standard reference material (SRM 3673) re-enforced the precision and validity of our method. Finally, the established method was successfully applied to analyze 16 organophosphorus metabolites in 35 Chinese children's urine samples. Overall, by validating the method's sensitivity, accuracy, precision, reproducibility, etc., data reliability and robustness were ensured; and the satisfactory pilot application on real urine samples demonstrated feasibility and acceptability of this method for being implemented in large population-based studies.

In this study, we investigated the emission and fate of 9 organophosphate esters (OPEs) from a natural environment chamber, in which three environment matrices (i.e., air, dust, and window film samples) as well as three decoration materials (i.e., laminate flooring, latex paint, and nonwoven paper) were collected within gradient variation of room temperature and relative humidity. ΣAlkyl-OPEs and ΣCl-OPEs were the predominant classes in the three environment matrices, accounting - on average - for 98.7%, 99.8% and 99.3% of ΣOPEs in indoor dust, air and window film, respectively. TBOEP was the most abundant OPE in air, dust, and laminate flooring, respectively, while tris (2-chloro-isopropyl) phosphate (TCIPP) and tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) in nonwoven paper and latex paint, respectively. The results showed that higher room temperature expedited the emission of OPEs to indoor air. However, the room temperature and relative humidity had no effect on the levels of OPEs in dust. The OPEs equilibrium time in indoor environment may be dependent on room temperature and relative humidity. The area specific emission rates (SERs) of the three materials were calculated, and an optimal expression based on the concept of mass balance model was constructed, preliminarily revealing a general relationship between OPEs source and sink effects in indoor environment.

Although evidence suggests that prenatal exposure to polybrominated diphenyl ethers (PBDEs) alter offspring's physical growth, most studies rely upon physical growth at a single timepoint, and little is known regarding their longitudinal effects over time. In the current study, we determined the associations between prenatal PBDEs exposure and child physical growth by following up 207 mother-child pairs from the Laizhou Wan Birth Cohort (LWBC) from pregnancy until the children were seven years old. Child physical growth including weight, height, and body mass index (BMI) was assessed at birth, and at one, two and seven years of age. Prenatal exposure to PBDEs was quantified by measuring eight PBDE congeners (BDE-28, BDE-47, BDE-85, BDE-99, BDE-100, BDE-153, BDE-154, and BDE-183) in maternal serum samples collected upon hospital admission for delivery. Linear mixed models were applied to examine the associations between prenatal PBDEs exposure and repeated measures of child physical growth, and to determine whether these associations were modified by child's sex. Our findings indicated that BDE-28, BDE-85, BDE-153, BDE-183, and Σ7PBDEs were positively associated with child weight z-score; and that BDE-28, BDE-47, BDE-85, BDE-99, BDE-153, and Σ7PBDEs were positively associated with child height z-score. In addition, these associations were modified by the child's sex as reflected by pronounced positive associations among boys, while negative associations were noted among girls. In conclusion, our findings indicated the sex-specific associations between prenatal PBDE exposures and child physical growth during the first seven years of life.