The Role Of Cortisol In The Association Between Air Pollutant Exposure During Pregnancy And Fetal Growth

ObjectiveBased on the Maternal＆Infants Health in Hefei（MIH-Hefei）cohort study,we examined the associations between air pollutant exposure during pregnancy,maternal and cord blood cortisol levels,and fetal growth,and identified critical exposure windows for adverse effects of air pollution.Then,we further explored the role of cortisol in the association between air pollutant exposure and fetal growth.MethodsFrom March 2015 to December 2020,pregnant women who get an antenatal examination in the second trimester were recruited from 3 hospitals in Hefei city and followed up until delivery.Finally,a total of 7,419 maternal and infant pairs were recruited in the study.Demographic characteristics,health status,and lifestyle information were collected through questionnaires.Ultrasound measures during pregnancy（gestational age,bi-parietal diameter,abdominal circumference,and femur length）and delivery information（delivery mode,gestational age,delivery date,infant sex,birth weight,circumference,and length）were obtained from electronic medical records.We use gestational age-standardized Z scores of ultrasound measures and gestational age-and sex-standardized Z scores of neonatal anthropometric parameters to assess fetal growth.Maternal blood samples before delivery and cord blood samples after delivery were collected,and 2,296 pairs of maternal and infant blood samples were randomly selected for plasma cortisol concentration detection.We obtained daily mean concentrations of PM_2.5and PM₁₀,SO₂,and CO measured at regional monitoring stations by the Hefei City Ecology and Environment Bureau.Multivariate linear regression models were used to examine the associations between air pollutant exposure during pregnancy,maternal and cord blood cortisol levels,and fetal growth.Then,we conducted a mediation analysis to investigate the role of cortisol in the association between air pollutant exposure and fetal growth.ResultsAmong the 7419 maternal and infant pairs included in the study,the average gestational age of pregnant women was（28.6±4.2）years old,and the average pre-pregnancy BMI was（21.5±3.0）kg/m~2.Among newborns,the mean of birth weight,head circumference,and length was（3403.6±453.9）g,（33.9±1.5）cm,and（50.1±2.0）cm.The average exposure concentrations of PM_2.5,PM₁₀,SO₂and CO during entire pregnancy were（53.8±10.3）μg/m~3,（82.6±11.1）μg/m~3,（11.7±3.8）μg/m~3and（0.9±0.1）mg/m~3,respectively.The average concentration of all pollutant exposure was highest in early pregnancy.Multivariate linear regression models analysis results showed that there were significant negative associations between air pollutant exposure levels in the first trimester and ultrasound measures indexes in late pregnancy.An IQR increase in PM_2.5,PM₁₀,SO₂and CO exposure in the first trimester were significantly associated with reductions in bi-parietal diameter Z score of-0.080（95%CI:-0.128,-0.031）,-0.066（95%CI:-0.113,-0.019）,-0.070（95%CI:-0.120,-0.021）and-0.081（95%CI:-0.122,-0.039）,respectively.Exposure to air pollutants was also significantly associated with reduced fetal abdominal circumference and femur length.Moreover,we found that the Z score of bi-parietal diameter was significantly reduced with exposure to PM_2.5（β=-0.060,95%CI:-0.104,-0.016）,PM₁₀（β=-0.065,95%CI:-0.107,-0.022）,and SO₂（β=-0.054,95%CI:-0.102,-0.006）in the second trimester.Exposure to air pollutants during pregnancy is inversely associated with neonatal anthropometric parameters.After adjusting for confounding factors,we found that PM_2.5and PM₁₀exposure in early,middle,and entire pregnancy significantly were associated with reductions in the Z score of both birth weight and length apart from the head circumference.The Z score of birth weight（β=-0.053,95%CI:-0.090,-0.016）and head circumference（β=-0.053,95%CI:-0.102,-0.004）reduced with the increase in SO₂exposure in the first trimester.Furthermore,CO exposure in the first trimester was significantly associated with reductions in the Z score of birth weight（β=-0.049,95%CI:-0.080,-0.019）,length（β=-0.044,95%CI:-0.076,-0.013）and head circumference（β=-0.042,95%CI:-0.082,-0.002）.However,no significant associations were observed between any air pollutants in the third trimester and neonatal anthropometric parameters.We examined the association between air pollutant exposure during pregnancy and cortisol levels.Multivariate linear regression models analysis results showed that PM_2.5（β=0.082,95%CI:0.029,0.135）,PM₁₀（β=0.086,95%CI:0.036,0.136）,SO₂（β=0.086,95%CI:0.028,0.144）,and CO（β=0.063,95%CI:0.017,0.109）exposure in the first trimester were significantly associated with the increase in cord blood cortisol levels.Furthermore,air pollutant exposure in the first trimester was positively associated with the ratio of cord to maternal blood cortisol levels significantly.Nevertheless,there was no significant association between maternal cortisol levels and neonatal anthropometric parameters.We further found that the increase in cord blood cortisol levels was significantly associated with reductions in Z score of birth weight（β=-0.17,95%CI:-0.23,-0.10）,birth length（β=-0.09,95%CI:-0.16,-0.03）,and birth head circumference（β=-0.33,95%CI:-0.42,-0.25）,respectively.Stratified analysis results showed that compared to low-medium levels,there was greater association between air pollutant exposure（except for CO）and neonatal anthropometric parameters at high levels of cord blood cortisol.Linear regression analysis results showed that the principal component scores of air pollutant exposure in early pregnancy was inversely correlated with the total Z score of neonatal anthropometric parameters（β=-0.073,95%CI:-0.135,-0.011）,and significantly positively associated with cord blood cortisol levels（β=0.029,95%CI:0.011,0.046）.In addition,cord blood cortisol levels were inversely correlated with the total Z score of neonatal anthropometric parameters（β=-0.601,95%CI:-0.778,-0.423）.Mediation analysis results showed that the association of the principal component scores of air pollutants exposure during pregnancy and the total Z score of neonatal anthropometric parameters mediated by cord blood cortisol was 20.62%.ConclusionsThis study suggested that exposure to air pollutant during pregnancy could reduce fetal growth by increasing cord blood cortisol levels.The critical window of air pollutant exposure was in the first trimester.