Associations Of Ambient Particulate Matter Exposures During Pregnancy With Gestational Weight Gain,gestational Diabetes Mellitus And Infant Growth

The latest Global Burden of Disease Study(GBD 2019)have evaluated 87 risk factors that might contribute to the burden of disease in 204 countries and territories during 1990 to 2019.The findings of GBD 2019 revealed that the greatest increase in the risk exposure was for ambient particulate matter.Ambient particulate matter(PM)is the mixture of solid particles and liquid particles which has been derived from traffic emissions,industrial emissions,coal burning,biomass burning,soil dust and so on.The chemical compositions of particulate matter are complex and embrace water-soluble inorganic ions,heavy metal and organic matters.The size of ambient particulate matter varies from a few nanometers to tens of microns.It is easier for particulate matters with smaller sizes and lager specific surface areas to absorb toxic and hazardous substances.PMs could deposit in different regions of respiratory tract including nasal cavity,trachea,bronchus and alveoli.A fraction of the particles could further penetrate through the air-blood barrier,enter into the circulation and travel to remote organs and tissues,posing a big threat on human health.In vivo and in vitro experimentations have put forward several possible mechanisms of adverse health impacts attributed to ambient particulate matters,including genotoxicity,oxidative stress,and inflammation response.Compared to the general population,pregnant women and fetus are more sensitive to the adverse effects of ambient particulates during pregnancy.Population-based studies have indicated the possible impacts of ambient particulate matter exposures on obesity,whereas epidemiological evidences among special populations,for example pregnant women,are rare.With regard to the impacts of ambient particulate matters on maternal blood glucose levels and gestational diabetes mellitus,the results are inconclusive.More researches are needed in combination with the specific conditions of different regions,different populations,and different exposure characteristics.Ambient particulate matters could exert their effects directly on fetal growth by penetrating through the placental barrier,or indirectly on development programming of fetus by affecting maternal health or placental function.Studies exploring the relationships between ambient particulate matters during pregnancy and infant growth are limited,and the conclusions are inconsistent.In addition,epidemiological evidences have indicated that infant growth might be affected by gestational weight gain and maternal plasm glucose.However,no study has examined whether gestational weight gain or maternal glucose homeostasis could play a mediating role in the associations between ambient particulate matter exposures during pregnancy and infant growth.Given all this,taking advantage of an ongoing prospective birth cohort,impacts of ambient particulate matter exposures during pregnancy on gestational weight gain,as well as gestational diabetes mellitus and maternal glucose levels,were assessed in the first and second parts of the study.Potential effect modifiers in the associations were explored.In addition,associations of particulate matter exposures during pregnancy with birth weight and infant growth were estimated in the third part of the study.In combination with the prior results,mediation analyses were performed to explore the potential mediating effects of gestational weight gain and maternal glucose homeostasis in above associations.Part 1 The relationships between ambient particulate matter during pregnancy and gestational weight gainObjectives:To evaluate the relationships between ambient particulate matter(PM)exposures during pregnancy and maternal total gestational weight gain(GWG),as well as inadequate/excessive GWG,and further to investigate the potential effect modification by some variables,including ambient temperature.Methods:Based on a prospective birth cohort conducted at the Wuhan Women and Children Medical and Healthcare Center,7606 participants were included in our study during 2013 and 2015.Spatial-temporal land-use regression models were applied to evaluate the exposure levels of ambient PM_2.5and PM₁₀ for each participant during pregnancy.General estimating equations(GEE)with linear link function and GEEs with Poisson link function were employed to explore the associations of trimester-specific PM_2.5and PM₁₀ exposures with total GWG and inadequate/excessive GWG,respectively.Generalized linear models(GLM)and modified Poisson regression models were used to investigate the relationships between ambient PM exposures during the whole pregnancy and total GWG and inadequate/excessive GWG,respectively.Several stratified analyses were conducted to explore the possible effect modifiers in the associations between ambient PM exposures and total GWG.Results:Of all the 7606 participants,the mean GWG was 16.68 kg,931(12.24%)had inadequate GWG and 4326(56.88%)had excessive GWG.With each 10?g/m³increase in PM_2.5 exposure levels during the first,second,third trimester and the whole pregnancy,increased total GWG were observed[1^st trimester:0.103 kg(95%CI:0.044,0.162),2^nd trimester:0.162 kg(95%CI:0.102,0.222),3^rd trimester:0.143 kg(95%CI:0.086,0.201),entire pregnancy:0.215 kg(95%CI:0.137,0.294)],respectively.Increased risks of excessive GWG for every 10?g/m³ increase in PM_2.5exposure concentrations were found during the first trimester(RR=1.014,95%CI:1.002,1.025),the second trimester(RR=1.019,95%CI:1.007,1.030),the third trimester(RR=1.013,95%CI:1.002,1.023),and the whole pregnancy(RR=1.024,95%CI:1.009,1.039).Elevated GWG were also observed with each 10?g/m³ increase of PM₁₀during the second trimester[0.066 kg(95%CI:0.013,0.118)],the third trimester[0.088 kg(95%CI:0.035,0.142)]and the whole pregnancy[0.114 kg kg(95%CI:0.037,0.191)].No significant associations were found between ambient PM₁₀ exposures and inadequate/excessive GWG.Significant effect modifications by ambient temperature were found in the relationships between first trimester ambient PM exposures and total GWG(P for interaction<0.05).Conclusion:Ambient PM exposures during pregnancy were observed to be associated with increased total GWG.Increased risks of excessive GWG were found to be related with elevated PM_2.5 exposure levels.The results of stratified analysis showed that the impacts of first trimester PM exposures on total GWG were modified by ambient temperature.The results suggest that ambient PM might cause adverse health effect on mothers and their offsprings by increasing maternal weight gain during pregnancy.In addition,more researches are needed to clarify the impacts of air pollution on gestational weight gain and explore more potential effect modifiers.Part 2 Associations of exposure to ambient particulate matter during pregnancy with gestational diabetes mellitusObjectives:To assess the associations of ambient PM exposures during pregnancy with GDM as well as maternal glucose levels,and further to explore the potential effect modifiers which might modify the relationships between ambient PM and GDM.Methods:4736 pregnant women were enrolled in this study based on the research subjects of the first part.GEEs were performed to evaluate the impacts of PM exposures during each trimester on maternal glucose levels and the risk of GDM.The associations of PM_2.5 and PM₁₀ exposures during the whole study period with GDM and maternal glucose levels were estimated using modified Poisson regression model and GLMs,respectively.We conducted several stratified analyses to explore the potential effect modification in the associations between ambient particulate matters and GDM by pre-pregnancy BMI,maternal age,parity,iron supplementation during pregnancy,season of oral glucose tolerance test(OGTT)and maternal ABO blood group.Results:Among all the 4736 participants,388(8.19%)had GDM.Increased risks of GDM for each 10?g/m³ increase in PM_2.5levels were observed during the first trimester(RR=1.079,95%CI:1.019,1.142)and the whole study period(RR=1.133,95%CI:1.039,1.235),but not the second trimester(RR=1.060,95%CI:0.988,1.138).Exposure to PM_2.5 was found to be positively associated with elevated fasting glucose level during the first trimester(0.138 mg/d L,95%CI:0.002,0.274,per 10?g/m³increase in PM_2.5),the second trimester(0.415 mg/d L,95%CI:0.261,0.569)and the whole study period(0.472 mg/d L,95%CI:0.271,0.673).With each 10?g/m³increase in PM₁₀ exposures during pregnancy,no significant changes of GDM incidence and maternal glucose levels were found.Stratified analysis indicated that the impacts of PM_2.5 exposures during the first trimester and the whole study period on GDM were more pronounced among pregnant women with pre-pregnancy BMI<24 kg/m²,age?30,primiparity,iron supplementation during pregnancy,blood group A,and women who had taken OGTT in warm seasons(spring and summer).First trimester PM₁₀exposures were also observed to be significant positively associated with GDM for women who had taken OGTT during warm seasons.Significant effect modification by OGTT season was found in the association of first trimester PM_2.5 exposure and GDM.Conclusion:Our study enriched the epidemiological evidence linking PM_2.5exposures during pregnancy to increased risk of GDM and elevated maternal glucose levels.First trimester might be the susceptible time window in the impacts of PM_2.5 on GDM.Among women with lower pre-pregnancy BMI?older age?blood group A,women who was primiparous,as well as women who had taken iron supplementation during pregnancy and taken with an OGTT during warm seasons,the impacts of PM_2.5on GDM were stronger.Our study suggests that environmental factors such as season might play a role in the associations between air pollution and GDM,more researches in different regions are needed to explore the potential effect modifiers in the associations.Part 3 Associations of exposure to ambient particulate matter during pregnancy with birth weight and infant growth:Potential mediating roles of gestational weight gain and maternal blood glucoseObjectives:To explore the associations of ambient PM exposures with birth weight and infant growth,and further to investigate whether the associations could be mediated by gestational weight gain and maternal blood glucose.Methods:The subjects in this research were the same with that of the first part.During the follow-up of the newborns,the anthropometric measurements of weight and height of infants aged 1-24 months were collected.According to the z-score standardized method,weight-for-length(WFL)z scores and BMI-for-age z scores were calculated for infants.Macrosomia has been defined as birth weight greater than 4000g,and the overweight and obesity(OWOB)of infants has been defined as BMI z scores greater than 1.GEEs were employed to estimate the associations of trimester-specific PM exposures with birth weight and macrosomia.GLMs and Logistic regressions were used to evaluate the impacts of PM exposures during the whole pregnancy on birth weight and macrosomia.GEEs and GLMs were applied to investigate the associations of PM exposures during each trimester and the whole pregnancy with WFL z scores and BMI z scores of infants aged 1 month,12months and 24 months,respectively.Mixed linear regressions were used to evaluate the average impacts of PM exposures on WFL z scores and BMI z scores of infants aged 1-24 months.GEEs and modified Poisson regressions were employed to estimate the effects of ambient PM exposures during each trimester and the entire pregnancy on OWOB of infants at three time points(1month,12 months and 24 months).In addition,mediation analyses were performed to explore the potential mediating roles of gestational weight gain and maternal blood glucose in the above associations.Results:The average birth weight of the newborns was 3291.14 g and the incidence of macrosomia was 5.13%.Among infants aged 1 month,12 months and 24months,the average WFL z scores were 0.32,0.69,0.27;the average BMI z scores were 0.36,0.62 and 0.26;and the incidence of OWOB were 24.96%,31.66%and18.87%,respectively.PM_2.5 exposures in each trimester and the whole pregnancy were associated with increased birth weight.Increased risks of macrosomia were associated with higher exposure levels of PM_2.5 during the latter two trimesters and the entire pregnancy.Significant associations were also observed between PM₁₀ exposures and birth weight in the third trimester and the entire pregnancy,but null associations were found between PM₁₀ exposures and macrosomia.Elevated PM_2.5 exposures during each trimester and the whole pregnancy were associated with increased WFL z scores,BMI z scores and the incidences of OWOB in infants aged 1 month.Increased PM₁₀ exposure levels during the latter two trimesters and the entire pregnancy were also related with the growth of infants aged 1 month.For infants aged 12 months,significant negative associations were observed between first trimester PM exposures and BMI z scores as well as OWOB incidences,while significant positive associations were found between third trimester PM exposures and BMI z scores as well as OWOB incidences.First trimester PM_2.5 exposures were negatively associated with BMI z scores and the incidences of OWOB for infants aged 24 months,but no significant relationships were found between PM₁₀ exposures and infant growth.In the analyses of the average impacts of PM exposures on infants aged 1-24 months,significant positive associations between PM_2.5 exposures during each trimester and WFL z scores and BMI z scores were observed.First trimester PM₁₀ exposures were negatively associated with WFL z scores of infants,while third trimester PM₁₀ exposures were found to be positively associated WFL z scores and BMI z scores of infants.The results of mediation analyses showed that gestational weight gain played a mediation role in the relationships between PM exposures during pregnancy and birth weight and macrosomia.In addition,the impacts of first trimester PM_2.5 exposures on birth weight and macrosomia were also mediated by maternal fasting glucose.For infants aged 1 month,12 months and 24 months,significant indirect effects by gestational weight gain were found in the associations of PM_2.5 exposures during each trimester with WFL z scores,BMI z scores,and the incidences of OWOB of infants.In addition,in the associations of PM₁₀ exposures during the latter two trimesters and the whole pregnancy with the growth of infants aged 1 and 12 months,the mediation effect by gestational weight gain were found.Significant indirect effects by gestational weight gain were also observed in the associations of PM₁₀ exposures during the third trimester and the entire pregnancy with the growth of infants aged 24 months.In addition,maternal fasting glucose was observed to play a mediation role in the associations between second trimester PM_2.5 exposures and the growth of infants aged 1 month.Since no significant relationships were observed between maternal fasting glucose and the growth of infants aged 12 months and 24 months,mediation analyses were not conducted.Conclusion:Ambient PM exposures,especially for PM_2.5,were positively associated with birth weight,and might lead to macrosomia.There existed differences with respect to the impacts of PM exposures during different trimesters on the growth of infants at different ages.For instance,first trimester PM_2.5 exposures were positively associated with BMI z scores in infants aged 1 month,while negatively associated with BMI z scores for infants aged 12 and 24 months.Second and third trimester PM_2.5exposures were found to be positively associated with BMI z scores in infants aged 1and 12 months,but not in infants aged 24 month.The results of mediation analyses depicted that gestational weight gain might play a mediation role in the associations of ambient PM exposures during pregnancy with birth weight and infant growth.In addition,significant indirect effects by maternal fasting glucose were observed in the associations of PM_2.5 exposures with birth weight and the growth of infants aged 1month.This study could only provide some epidemiological clues,experimental researches are called for in future studies to further explore the potential mechanisms.