| Telomeres consist of non-coding repetitive sequences of DNA（TTAGGG）and nucleoproteins that together form “cap” at the end of chromosomes and maintain genomic stability and integrity of chromosomes.Telomere length（TL）shortens with each cell division and thus serves as a marker of biological aging.Once telomeres reach a critical length,cellular apoptosis or senescence is triggered.Extensive epidemiological studies have reported that shorter TL was associated with aging-related diseases.The natural telomeres attrition in relation to aging might be accelerated by other factors.Studies suggested that TL in adulthood was determined by newborn TL and subsequent attrition.Telomere attrition rates are higher in early life than those in later life.Thus,factor that influence initial or newborn TL may be an important determinant of lifetime health,and newborn TL may be a potential biomarker of risk of lifetime disease.However,studies on TL have been mainly conducted in adults,studies regarding on newborn TL were limited.Environmental factors during in utero life that influence the variability of newborn TL are largely unidentified.Therefore,we explored the maternal exposure to phthalate metabolites and air pollution(PM2.5,PM10,NO2,SO2,and CO)during three trimesters,and identified potential critical window of vulnerability to exposure to phthalate metabolites and air pollution on newborn TL in a birth cohort study.The main content are as follows:Part Ⅰ.Associations between prenatal exposure to phthalates andnewborn telomere lengthObjectives: Phthalates are a common class of endocrine-disrupting chemicals that are widely found in the environment.Previous studies reported that exposure to phthalates was associated with increased oxidative stress and inflammation among pregnant women,both of which are potential mechanisms for telomere length（TL）shortening.To date,few studies have investigated the associations between prenatal exposure phthalates and newborn TL.The aim of our study was to explore the associations between the concentration of urinary phthalate metabolites in three trimesters and newborn TL.Methods: A total of 762 mother-newborn pairs were recruited from a prospective birth cohort study conducted between November 2013 and March 2015 at the Wuhan Children’s Hospital（Wuhan Maternal and Child Healthcare Hospital）in Wuhan city,Hubei province,China.We obtained information on demographic characteristics,and lifestyle of pregnant women,and clincial data through questionnaires and medical records.Spot urine samples of pregnant women during three trimesters and newborn cord blood were collected.Relative cord blood TL was measured using quantitative real-time polymerase chain reaction.We measured seven phthalate metabolites in urine samples using solid phase extraction coupled with ultra-performance liquid chromatographytandem mass spectrometry（UPLC-MS/MS）,including MEP,MECPP,MEHHP,MEOHP,MBP,MBZP,and MEHP.Multiple informant models were applied to estimate the associations between prenatal exposure to phthalates and cord blood TL and to evaluate potential windows of vulnerability.We also explored the dose-response relationships between urinary phthalate metabolites during three trimesters and newborn TL using restricted cubic spline.Results: After adjustment for maternal age,pre-pregnancy BMI,parity,maternal educational level,passive smoking during pregnancy,gestational diabetes mellitus,hypertensive disorders of pregnancy,infant sex,birth weight,and gestational age,each doubling of MECPP,MEHHP,MEOHP,（50）LMW,and（50）DEHP were associated with 2.28%（95% CI:-4.12%,-0.42%）,2.46%（95% CI:-4.32%,-0.58%）,2.83%（95% CI:-4.69%,-0.93%）,2.11%（95% CI:-3.18%,-0.38%）,and 3.22（95% CI:-5.22%,-1.16%）decrease in cord blood TL,respectively.Compared with urinary MEP,MECPP,MEHHP,MEOHP,MBP,（50）LMW,and（50）DEHP during the first trimester in the lowest quartile,those in the highest quartile were related to 11.22%（95% CI:-18.03%,-3.83%）,11.33%（95% CI:-18.12%,-3.96%）,9.22%（95% CI:-16.18%,-16.8%）,11.66%（95% CI:-18.45%,-4.32%）,8.08%（95% CI:-15.13%,-0.45%）,11.94%（95% CI:-18.68%,-4.64%）,and 11.93（95% CI:-18.69%,-4.60%）shorter in cord blood TL,respectively（all Ptrend <0.05）.Results from the spline analyses suggested linear relationships between maternal urinary MEP,MECPP,MEHHP,MEOHP,MBP,（50）LMW,and（50）DEHP during first trimester and cord blood TL(all Poverall < 0.05,Pnonlinear >0.05).In the stratified analyses,the inverse associations between maternal urinary MECPP,MEHHP,（50）LMW,and（50）DEHP were more evident among female infants,mothers ≥28 years,and mothers with pre-pregnancy BMI<24 kg/m2.Conclusion: Maternal exposure to phthalate metabolites during the first trimester were associated with shorter newborn TL.Our results,if confirmed in other population,suggests that prenatal exposure to phthalates may increase the risk of future chronic disease or death by shortening newborn TL and provided evidence for the hypothesis of “Developmental Origins of Health and Disease”Part Ⅱ.Associations between prenatal exposure to air pollution andnewborn telomere lengthObjectives: Air pollution is one of the greatest environmental challenge for human health.Extensive epidemiological studies have explored the association between exposure to air pollution and telomere length（TL）in adults.However,studies regarding the association between exposure to air pollution and newborn TL were limited.The initial TL shortening at birth may predict chronic diseases in later life.Highlighting the factors that influence initial or newborn TL may provide more evidence for taking appropriate interventions to prevent adult disease.We aimed to explore the association between prenatal exposure to air pollution and newborn TL.Methods: A total of 762 mother-newborn pairs were recruited at the Wuhan Children’s Hospital（Wuhan Maternal and Child Healthcare Hospital）in Wuhan city,Hubei province,China between November 2013 and March 2015.Information on demographic characteristics and lifestyle behaviors of pregnant women were collected through questionnaires and medical records.Relative cord blood TL was assessed using quantitative real-time polymerase chain reaction.Spatial-temporal land use regression（LUR）models were used to predict maternal exposure to PM2.5,PM10,SO2,NO2,and CO at mothers’ residential addresses during pregnancy.Multiple informant models were used to explore the trimester-specific associations between maternal air pollution exposure and cord blood TL,and evaluate potential windows of vulnerability.Dose-response relationships between air pollution during three trimesters and newborn TL were estimated using restricted cubic spline.Results: After adjustment for maternal age,pre-pregnancy BMI,parity,educational level,passive smoking during pregnancy,gestational diabetes mellitus,hypertensive disorders in pregnancy,birth weight,gestational age,infant sex,and season at delivery,a 10 mg/m3 increase in PM2.5,PM10,SO2,and a 100 mg/m3 increase in CO during the third trimester were associated with 3.71%（95% CI:-6.06%,-1.30%）,3.24%（95% CI:-5.29%,-1.14%）,11.07%（95% CI:-18.86%,-2.53%）,and 3.67%（95% CI:-6.27%,-1.00%）shorter cord blood TL,respectively.Compared with those in the lowest quartile,maternal exposure to PM2.5,PM10,and SO2 during the third trimester in the highest quartile were associated with 17.13%（95% CI:-27.55%,-5.22%）,18.69%（95% CI:-27.96%,-8.22%）,and 18.16%（95% CI:-29.01%,-5.66%）decrease in cord blood TL,respectively（all Ptrend < 0.05）.No significant association was observed between NO2 exposure during three trimesters and cord blood TL.Results from the spline analyses suggested linear relationships between maternal exposure to PM10,SO2,and CO during the third trimester and cord blood TL(all Poverall < 0.05,Pnonlinear>0.05).In contrast,the association between maternal exposure to PM2.5 during the third trimester and cord blood TL was nonlinear,with a reverse J-shaped relationship(Pnonlinear= 0.016).In the stratified analysis,the inverse associations between exposure to PM2.5,PM10,SO2,and CO during the third trimester and cord blood TL were more evident in male infants,mothers≥ 28 years,and mothers with pre-pregnancy BMI<24 kg/m2.Conclusion: Maternal exposures to PM2.5,PM10,SO2,and CO during the third trimester were associated with shorter TL in newborns,particularly in male infants,older and non-obese mothers.Our results suggests that air pollution may cause long-term adverse health outcomes by shortening newborn TL. |
