Associations Of Air Pollution Exposure During Pregnancy And Residential Greenness With Fetal Growth

Normal fetal growth is a key component of a healthy pregnancy,and it influences the long-term health of the offspring.Recent studies have increasingly used prenatal ultrasound measurements as direct estimates of intrauterine fetal growth to identify environmental factors that may interfere with fetal growth.Air pollution is a well-known,ubiquitous environmental risk factor,and is highly relevant to public health.In recent years,an increasing number of studies have reported an association between increased concentrations of ambient air pollution during pregnancy and poor intrauterine fetal growth using prenatal ultrasound measurements.However,there is inconsistency in the strength of the reported effects,and the associated critical exposure periods.Most studies have considered only single time points that may fail to fully elucidate patterns of growth changes in utero.In addition,maternal thyroid hormones are critical for fetal development and growth,and its homeostasis is vulnerable to environmental disruptors.It’s necessary to investigate whether the maternal thyroid hormones disruption by air pollution exposure has an adverse impact on fetal growth or not.Moreover,evidence is accumulating that urban greenness is associated with improved health conditions.Recent studies have reported that greenness may improve health conditions by reducing air pollution levels.However,evidence regarding the association between residential greenness and fetal growth is limited,with the underlying mechanisms and interactions with air pollution exposure remaining unclear.Based on a prospective birth cohort study in Wuhan,we aimed to evaluate the association between prenatal exposure to air pollution and fetal biometry at different stages of pregnancy,and to identify critical exposure windows.We also investigated the effect of air pollutant exposure on fetal growth traj ectories using a group-based traj ectory modeling approach.In addition,we studied the impact of air pollution exposure on maternal thyroid function during early pregnancy and their mediating role on fetal growth.Finally,we explored protective associations by residential greenness on fetal growth,and explored the interplay between air pollution,residential greenness,and fetal growth.Part 1 Associations between prenatal exposure to air pollution and fetal growthObjectives:We examined the association between prenatal exposure to air pollution and fetal biometry at different stages of pregnancy,and identifying critical exposure windows.We also investigated the effect of air pollution exposure on fetal growth trajectories.Methods:The present study was based on a prospective birth cohort in Wuhan from 2013 to 2016.A total of 4283 eligible women were included.Ultrasound measurements of pregnant women at 16,24,31 and 38 weeks of gestation were collected to provide fetal growth parameters including biparietal diameter(BPD),abdominal circumference(AC),femur length(FL)and estimated fetal weight(EFW).We calculated gestational age-adjusted standard deviation scores(SDS)for all fetal growth parameters using generalized additive models for location scale and shape(GAMLSS)based on location,scale and shape parameters.The inverse distance weighted(IDW)method was used to estimate exposure to air pollution.Multiple informant model,linear regression model and group-based traj ectory modelling(GBTM)were used to investigate the prenatal exposure to air pollution and fetal biometry at different stages of pregnancy.Results:After adjusting for potential confounders,an interquartile range(IQR)increase in PM2.5,PM10,NO2,SO2 and CO during weeks 1-16 was associated with-0.13～-0.09 decrease in AC SDS and-0.11～-0.07 decrease in EFW SDS at 16 weeks.The same exposure was also inversely associated with reduced SDS of FL at 16 weeks,BPD,FL,and EFW at 24 weeks,as well as AC at 38 weeks.Exposure to air pollution during weeks 24-31 was associated with-0.08～-0.03 decrease in SDS for AC and EFW at 38 weeks.There was little significant association between air pollutant exposure and fetal growth parameters at week 31.Using GBTM,we have identified five trajectory groups for BPD,FL,and EFW,and four groups for AC.Exposure to PM2.5 and SO2 significantly increased the risk of "small"trajectory for BPD.Exposure to PM2.5,PM10,NO2,SO2 and CO during weeks 1-16 was significantly negatively associated with "large" trajectories for AC and EFW.Conclusion:Our study supports an adverse impact of prenatal exposure to air pollution on fetal growth.The critical windows of exposure are in early pregnancy.Exposure to air pollution during weeks 1-16 was significantly associated with fetal growth trajectories.Part 2 Mediating roles of maternal thyroids hormones in the effects of prenatal air pollution exposure on fetal growthObjectives:We aimed to evaluate the association between air pollution exposure and maternal thyroid function,and investigate the potential mediating roles of maternal thyroids hormones in the effects of prenatal air pollution exposure on fetal growth.Methods:A total of 2413 pregnant women were included in this study based on the study population from Part 1.The levels of maternal thyroid hormones(FT4,FT3 and TSH)during early pregnancy(13.3±1.lweeks)were obtained from the electronic medical records in the study hospital.Multiple linear regressions,mixed linear regression models and mediation analysis were used to examine the relationship between air pollution,maternal thyroid parameters and fetal growth indicators.Results:After adjusting for potential confounders,an IQR increase in PM2.5,PM1O,NO2,SO2 and CO during weeks 0-16 was associated with 0.21%-0.31%increase in maternal FT4.Maternal FT4 level was associated with-0.28(95%Cl:-0.44,-0.11)and-0.41(95%Cl:-0.55,-0.28)decreased in SDS for AC and EFW during 16-38 weeks.The mediation analysis clarified that the maternal FT4 level explained 23.88%,24.30%and 39.55%of the associations between prenatal NO2,SO2 and CO exposure with fetal AC at 16 weeks,respectively(P<0.05).Conclusion:Our results suggest that exposure to air pollution during weeks 0-16 may interfere with maternal thyroid function during early pregnancy.Maternal FT4 may play a mediating role between exposure to gaseous pollutants and fetal growth.Part 3 Associations between residential greenness and fetal growthObjectives:We aimed to explore associations between residential greenness with fetal growth parameters,and explored the interplay between air pollution,residential greenness,and fetal growth.Methods:The study population in this part was the same with Part I.We defined residential surrounding greenness as average of satellite-based Normalized Difference Vegetation Index(NDVI)derived from Landsat-8 OLI image data in buffers of 250 m,500 m,1000 m and 2000m around each maternal home address.Multiple linear regression models and mixed linear models were used to examine the associations of residential greenness and fetal growth indicators.We conducted stratified analyses to assess effect modification considering fetal sex,maternal age,individual and area socioeconomic status(SES)indicators and air pollution exposure.Results:After adjusting for potential confounders,an IQR increase in NDVI within 250 m was associated with 0.05(95%Cl:0.01,0.10)、0.06(95%Cl:0.01,0.12)and 0.08(95%Cl:0.02,0.13)increase in BPD,AC and EFW SD scores at 16 weeks,respectively.Significant effect modifications by fetal sex and SES were found in the relationships between NDVI and fetal growth(P-interaction<0.05).We observed no interaction between NDVI and air pollution on fetal growth.NDVI within 250 and 2000m buffer areas were positively associated with the "large"trajectory for BPD(OR=1.25,95%Cl:1.02,1.53;OR=1.56,95%Cl:1.09,2.22).There’s no significant association between NDVI with AC,FL or EFW trajectories.Conclusion:This study identified protective associations by residential greenness on fetal growth,especially in early gestation.We also reported the positive association between residential greenness and "large" traj ectory for BPD.More studies are needed to validate these associations considering different types of greenness indicators,potential effect modifiers and mediators,and further explore the potential mechanisms.