| Benzophenones(BPs)are widely used in sunscreens,cosmetics,skin care products and other personal care products.The widespread application results in exposure to BPs in the general population through dermal absorption,ingestion,or inhalation.Existing studies have shown that BPs compounds belong to environmental endocrine disrupting chemicals(EDCs),which can interfere with the hormone system homeostasis.Therefore,BP exposure may affect the reproductive system,neural system,growth and development,etc.As a sensitive population,pregnant women are more susceptible to environmental chemicals such as BPs.In addition,BPs can be detected in pregnant women's urine,blood,amniotic fluid and placenta,suggesting that BPs may cross the placental barrier and enter the fetal environment,thus,probably influence the fetal development due to their potential toxicity.In addition,prenatal environmental exposure plays a decisive role in the lifetime health and disease status.At present,there are some epidemiological studies which explored the relationships between gestational BP exposure and the health outcomes of pregnant women and children,such as gestational weight gain and birth outcomes,but the results are inconsistent.One possible explanation would be attributed to the different time points of the assessments of BP exposure.In view of the short half-life of BPs,the exposure assessment at a single time point may not accurately reflect the exposure over the course of pregnancy.The study of BP concentrations at multiple points may help to evaluate the adverse effects of BP exposure and whether there is a critical exposure window of BPs on maternal and infant health.Based on a large prospective birth cohort,we have collected materal urine samples in 1st,2nd and 3rd trimesters during pregnancy.Ultra-high performance liquid chromatography-tandem mass spectrometer(UPLC-MS/MS)was used to detect the maternal urinary BPs levels.Then,we assessed the relationships between maternal urinary BPs levels and gestational weight gain,birth outcomes [gestational age,birth weight,birth length,ponderal index(PI)],and early childhood growth and development(weight and height z-score and PI),and explored the critical exposure windows.This study might provide epidemiological evidence for the effects of BPs on maternal and child health.Part 1: The relationships between repeated urinary levels of BPs during pregnancy and gestational weight gainObjective: To explore the relationships between urinary levels of BPs in three trimesters of pregnancy and gestational weight gain.Methods: Based on a prospective birth cohort,847 pregnant women were recruited from the children's medical care center of wuhan children's hospital during 2014-2015.Urine samples were collected when the pregnant women came to the hospital for prenatal care in first(13.0?±?1.1 weeks),second(23.6?±?3.2 weeks)and third trimester(35.9?±?3.4 weeks).UPLC-MS/MS was used to detect the maternal urinary 2,4-dihydroxybenzophenone(BP-1),2-hydroxy-4-methoxybenzophenone(BP-3)and 4-hydroxybenzophenone(4-OH-BP)levels.Gestational weight gain was calculated by pre-pregnancy weight(kg)and prenatal weight(kg).The weight difference beween gestational weight gain and birth weight was also caculated as net gestational weight gain for sensitively analysis.We assessed the relationships between urinary levels of BPs in the three trimesters of pregnancy and gestational weight gain and net gestational weight gain by Generalized Estimating Equations(GEEs),and explored the critical exposure windows.Result: After adjusting for the urinary specific gravity,the urinary concentrations of BP-1,BP-3 and 4-OH-BP were 0.20-0.33 ng/m L,0.44-0.72 ng/m L and 0.15-0.17 ng/m L,respectively.The pearson coefficients between BPs ranged from 0.19 to 0.76(P < 0.01).The ICCs for BP-1,BP-3 and 4-OH-BP concentrations in maternal urine ranged 0.55?0.63,0.49?0.58 and 0.43?0.51,respectively.The urinary concentration of 4-OH-BP in 1st trimester was positively associated with gestational weight gain(? = 0.24 kg,95% CI: 0.01,0.47).Among pregnant women who carried a male fetus,4-OH-BP in 1st trimester was positively associated with gestational weight gain(? = 0.36 kg,95% CI: 0.04,0.68).In addition,4-OH-BP(? = 0.25 kg,95% CI: 0.02,0.48)and BP Sum levels(? = 0.20 kg,95% CI: 0.03,0.38)in 1st trimester was also positively associated with net gestational weight gain in sensitive analysis,and the associations were more significant in pregnant women with male infants.Conclusion: BPs exposure in early pregnancy was positively correlated with pregnancy weight gain,particularly for pregnant women who carried a male fetus.Part 2: The associations between repeated maternal urinary levels of BPs during pregnancy and birth outcomesObjective: To explore the effects of urinary BPs levels in the three trimesters of pregnancy on birth outcomes(birth weight,birth length,gestational age and Ponderal index(PI)),and to explore the critical exposure windows.Methods: The study population was the same as the first part.UPLC-MS/MS was used to detect the BP levels.The birth weight,length and gestational week of the newborn were obtained from the medical record system of Wuhan maternal and child health hospital.PI was calculated by birth weight and body length.GEEs model was used to evaluate the relationships between BP levels in three trimesters and neonatal birth weight,body length,PI and gestational week,respectively.Result: The mean birth weight,birth length,PI and gestational week of the newborn was 3318.1 ± 409.9 g,50.2 ± 1.5 cm,26.1 ± 2.1 kg/m3 and 39.4 ± 1.2 weeks,respectively.In the total populations,for each log unit increase in the urinary BP-1 and 4-OH-BP levels in 1st trimester,the birth length decreased by 0.06 cm(95% CI:-0.11,-0.01)and 0.08 cm(95% CI:-0.15,-0.01),respectively.However,no association was observed between BP concentration and birth weight.After stratification by infant sex,the BP-1 level was negatively associated with birth length in male infants.In female intants,maternal urinary BP-1 and BP-3 levels in 3rd trimester were associated with decreased birth weight(? =-27.99 g,95% CI:-50.66,-5.31 and-19.75 g,95% CI:-37.31,-2.19)and birth length(? =-0.08 cm,95% CI:-0.17,0.00 and-0.08 cm,95% CI:-0.15,-0.02).In addition,we also obseved a significant sex interaction between BP-3 exposure level and birth length(p interaction = 0.04).Conclusion: Maternal urinary BPs levels in early and late pregnancy were negatively associated with birth weight and birth length,especially in female newborns.Part 3: The relationships between repeated maternal BPs levels of pregnancy and early childhood growth and developmentObjective: To investigate the relationships between prenatal BP exposure and early childhood growth and development.Methods: In this part,the children that were included in the second part were followed up.The weight(kg)and height(cm)data of the children in the early stage(1 month,6 months,1 year and 2 years old)were collected,and the z-score of weight and height was calculated using the child growth standards published by the world health organization.PI was also caculated by the weight and height of the children.The relationships between urinary BPs concentration and early childhood weight and height z-score and PI were evaluated by GEEs and mixed effect model.Result: The range of weight and height z score and PI in early-childhood(1 month,6 months,1 year and 2 years)was 0.1-0.7 and 0.2-0.5 and 18.4-27.3 kg/m3,respectively.Among the total children,the average level of 4-OH-BP during pregnancy was negatively associated with height z-score of 1-month children(? =-0.07,95% CI:-0.13,-0.01).In the associations of trimester-specific BPs levels with early-child growth and development,the maternal urinary BP-1 concentration in the 1st trimester was negatively associated with height z-score of 6-month children(? =-0.04,95% CI:-0.07,0.00);4-OH-BP level in 2nd trimester was negatively associated with the z-score of height at 1 month children(? =-0.05,95% CI:-0.10,0.00)and weight at 6 months children(? =-0.06,95% CI:-0.11,-0.01).In addition,urinary 4-OH-BP concentration in the 2nd trimester was negatively correlated with PI of 1-year old children(?=-0.13 kg/m3,95% CI:-0.24,-0.01).Conclusion: Maternal urinary BPs levels were associated with a decrease in early-childhood weight and length z-score,suggesting that prenatal BPs exposure may have adverse effects on infant growth and development. |
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