The Associations Of Maternal Urinary Benzophenones Levels With Gestational Weight Gain, Birth Outcomes, And Early-childhood Growth

Benzophenones?BPs?are used in sunscreens,cosmetics,skin care products and other personal care products.BPs can be absorbed by the general population through the skin,digestive and respiratory tract and so on.Existing studies have shown thatBPs compounds belong to environmental endocrine disrupting chemicals?EDCs?,which can interfere with the hormone system homeostasis.Therefore,BPs exposure may affect the reproductive system,neural system,child 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,breast milk,amniotic fluid and placenta,suggesting that BPs may cross the placental barrier,thereby affecting the growth and development of fetus.Adverse factors experienced in early life can affect the growth and development of embryo,and these adverse effects can last lifetime.Currently,only a few epidemiological studies have explored the relationships between gestational BPs exposure and maternal or child health,such as birth outcomes,early-childhood growth and development.However,the results are inconsistent.Existing research only using urine of single point to assess the relationship between gestational exposure and outcomes.In view of the short half-life of BPs in vivo,the exposure assessment at a single time point may only reflect the recent exposure level.The collection of multiple time point samples can assess the exposure level of BPs during the whole pregnancy,so as to better clarify the relationships between BPs exposure during pregnancy and maternal and child health.This study relied on a large prospective birth cohort,and Ultra-high performance liquid chromatography-tandem mass spectrometer?UPLC-MS/MS?was used to detect the maternal urinary BPs levels in 1st,2nd and 3rd trimesters.Then,we assessed the relationships between gestational BPs exposure 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 will provide epidemiological evidence for the effect of BPs on maternal and child health.Part 1:The relationships between repeated urinary BPs levels during pregnancy and gestational weight gainObjective:To explore the relationships between urinary BPs levels in three trimesters?early,middle and late?of pregnancy and gestational weight gain.Methods:Based on the large prospective birth cohort,this studyselected 847pregnant women recruited from the children's medical care center of wuhan children's hospital during 2014-2015,andurine samples were collected when the pregnant women came to the hospital for prenatal care in first?13.0?±?1.1 weeks?,second?23.6?±?3.2weeks?and third trimester?35.9?±?3.4 weeks?.UPLC-MS/MS was used to detect the maternalurinary2,4-dihydroxybenzophenone?BP-1?,2-hydroxy-4-methoxybenzophenone?BP-3?and 4-hydroxybenzophenone?4-OH-BP?levels.In addition,the gestational weight gain was calculated by pre-pregnancy weight?kg?and prenatal weight?kg?,and the net gestational weight gain was calculated by gestational weight gain and birth weight.We assessed the relationships between urinary BPs levels in the three trimesters of pregnancy and gestational weight gain and net gestational weight gainby Generalized Estimating Equations?GEEs?,and explored the critical exposure windows.Result:After adjusting for the urinary specific gravity,the concentration of BP-1,BP-3 and 4-OH-BP was 0.20-0.33 ng/mL,0.44-0.72 ng/mL and 0.15-0.17 ng/mL,respectively,The pearson coefficients between BPs ranged from 0.19 to 0.76,and were statistically significant?P<0.01?.The ICCs ranges of BP-1,BP-3 and 4-OH-BP concentrations in maternal urine were 0.55?0.63,0.49?0.58 and 0.43?0.51,respectively.In the total populations,urinary 4-OH-BP level in 1st trimester was positively associated with gestational weight gain??=0.24,95%CI:0.24,0.01?.Among pregnant women who carried a male fetus,4-OH-BP level in 1st trimester remained positively associated with gestational weight gain??=0.36,95%CI:0.36,0.04?.In addition,4-OH-BP??=0.25,95%CI:0.02,0.48?and BP Sum levels??=0.20,95%CI:0.03,0.38?in 1st trimester was also positively associated with net gestational weight gain,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 BPs levels during pregnancy and birth outcomesObjective:To explore the effects of urinary BPs levels in the three trimesters of pregnancyon birth outcomes?birth weight,birth length,gestational age and PI?,and to explore the critical exposure windows.Methods:The study populations were the same as the first part.UPLC-MS/MS was used to detect the BPs 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 is calculated by birth weight and body length.GEEs model was used to evaluate the relationships between BPs 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 kg,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 and4-OH-BP levels in 1st trimester,the birth length decreased by 0.06cm?95%CI:-0.11,-0.01?and 0.08 cm?95%CI:-0.15,-0.01?,respectively.However,no association was observed between BPs 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??=-27.99g,95%CI:-50.66,-5.31 and-19.75g,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 observed a significant sex interaction between BP-3exposure 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 BPs levels in the three trimesters of pregnancy?early,middle and late?and early childhood growth and development.Methods:In this part,the subjects 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,1year 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.The calculation of PI is the same as the second part.The relationships between urinary BPs concentration and early childhood weight and height z-score and PI was 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?was0.1?0.7 and 0.2?0.5 and 18.4?27.3 kg/m³,respectively.In the total populations,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 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?.The partial negative association was more pronounced in boys.In addition,urinary 4-OH-BP concentration in the 2nd trimester was negatively correlated with ponderal index of 1-year old children??=-0.13,95%CI:-0.24,0.01?.Conclusion:Maternal urinary BPs levels were associated with a decrease in early-childhood weight and length z-score and ponderal index,suggesting that prenatal BPs exposure may have adverse effects on infant growth and development.