Association Between Air Pollutants And Meteorological Factors Exposure During Early Pregnancy And Congenital Limb Defects

Objective:To assess the association between air pollutants(CO,NO₂,SO₂,PM_2.5,PM₁₀and O₃)exposure during the first trimester of pregnancy and congenital limb defects（CLDs）,and further to detect the interactive effects of air pollutants with temperature and air humidity.Methods:This is a case-control study.Perinatal infants of CLDs in Changsha with the conception date falls between 2015 and 2018 were enrolled from the hospital based birth defect monitoring（HBBDM）system of Hunan Province as cases.Health infants in Changsha from the electronic medical records（EMR）system of Maternal and Child Health Care Hospital of Hunan Province were matched 1:10 to the cases by year of conception as controls.Information of mothers and perinatal infants were abstracted.Data on daily air pollutants and meteorological factors from 2015 to 2018 were obtained from local national monitoring stations.Individual daily exposure levels of air pollutants and meteorological factors during early pregnancy were estimated using the nearest monitoring station approach and city-wide average approach,respectively.According to the distribution of daily average temperature and relative humidity of Changsha during 2015 and 2018,the 25^thpercentile and 75^thpercentile of temperature were chosen to divide individual monthly temperature exposure into low,normal and high levels,the 50^thpercentile of relative humidity was chosen to divide individual monthly humidity exposure into reference and high levels for further analysis.Multivariate logistic regression models were built to evaluate the monthly effects of air pollutants on overall CLDs and subtypes during the first trimester of pregnancy.The interactive effects of air pollutants with meteorological factors were assessed by including interaction items in the models.Results:A total of 972 cases of CLDs and 9720 controls were enrolled in the study.According to regression analysis,increase in CO,NO₂,SO₂and O₃were associated with elevated risk of CLDs,of which NO₂（a ORs ranging from 1.126 to 1.264）and SO₂（a ORs ranging from1.373 to 2.489）exposure were consistently associated with overall CLDs and all subtypes during the first trimester of pregnancy.Positive associations between CO and O₃exposure and CLDs were observed to distribute in different months and subtypes,with a ORs ranging from1.024 to1.061.Interaction analysis showed synergistic effects of NO₂and SO₂in combination with both low and high temperature exposure.Low temperature exposure also acted synergistically with PM₁₀and O₃.Additionally,high humidity exposure showed synergistic effects with NO₂and SO₂,but antagonistic effects with CO and O₃.Conclusions:The risk of CLDs increased with increasing CO,NO₂,SO₂and O₃exposure levels during the first trimester of pregnancy.Both low and high temperature,as well as high humidity exposure may enhance the effects of NO₂and SO₂,and low temperature exposure may enhance the effects of PM₁₀and O₃.The study suggested that environmental policies and practices should be formulated and implemented to decrease air pollutant emissions and improve meteorological conditions.Additionally,pregnant women should be suggested to reduce outdoor time when the air quality is poor,especially when ambient temperature is higher or lower than what is comfortable,or when the air is excessively humid.