Modification of the effects of nitrogen dioxide and sulfur dioxide on congenital limb defects by meteorological conditions
Authors: Jiang Wen , Liu Zhiyu , Ni Bin , Xie Wanqin , Zhou Haiyan , Li Xingli 
Published: July 2021

Abstract

STUDY QUESTION
Can meteorological conditions modify the associations between NO2 and SO2 exposure and congenital limb defects (CLDs) during the first trimester of pregnancy?

SUMMARY ANSWER
Increases in NO2 and SO2 exposure were consistently associated with higher risks of CLDs during the first trimester of pregnancy; both low- and high-temperature exposure and high air humidity act synergistically with the two air pollutants on CLDs.

WHAT IS KNOWN ALREADY
Animal studies have indicated air pollutants are associated with CLDs, but corresponding epidemiological studies are limited with equivocal conclusions. Meteorological conditions are closely connected to the generation, diffusion, distribution and even chemical toxicity of air pollutants.

STUDY DESIGN, SIZE, DURATION
This case–control study included 972 cases of CLDs and 9720 controls in Changsha, China during 2015–2018.

PARTICIPANTS/MATERIALS, SETTING, METHODS
Cases from the hospital based monitoring system for birth defects (including polydactyly, syndactyly, limb shortening, and clubfoot) and healthy controls from the electronic medical records system were studied. Complete data on daily average NO2 and SO2 concentrations and meteorological variables were obtained from local monitoring stations to estimate monthly individual exposures during the first trimester of pregnancy, using the nearest monitoring station approach for NO2 and SO2 concentrations, and the city-wide average approach for temperature and relative humidity, respectively. The 25th and 75th percentiles of daily mean temperature, as well as the 50th percentile of daily mean relative humidity during the study period were used to classify high- and low-temperature exposure, and high humidity exposure based on existing evidence and local climate characteristics. Multivariate logistic regression models were used to estimate the independent effects per 10 μg/m3 increase in NO2 and SO2 on CLDs, and the attribute proportions of interaction (API) were used to quantify the additive joint effects of air pollutants with meteorological conditions after including a cross product interaction term in the regression models.

MAIN RESULTS AND THE ROLE OF CHANCE
NO2 and SO2 exposures during the first trimester of pregnancy were consistently and positively associated with overall CLDs and subtypes, with adjusted odd ratios (aORs) ranging from 1.13 to 1.27 for NO2, and from 1.37 to 2.49 for SO2. The effect estimates were generally observed to be the strongest in the first month and then attenuated in the second and third months of pregnancy. Synergistic effects of both low and high temperature in combination with NO2 (with APIs ranging from 0.07 to 0.38) and SO2 (with APIs ranging from 0.18 to 0.51) appeared in the first trimester of pregnancy. Several significant modifying effects by high humidity were also observed, especially for SO2 (with APIs ranging from 0.13 to 0.38). Neither NO2 nor SO2 showed an interactive effect with season of conception.

LIMITATIONS, REASONS FOR CAUTION
The methods used to estimate individual exposure levels of air pollutants and meteorological factors may lead to the misclassification bias because of the lack of information on maternal activity patterns and residential mobility during pregnancy. Moreover, we were unable to consider several potentially confounding factors, including socioeconomic status, maternal nutrient levels, alcohol use and smoking during early pregnancy due to unavailable data, although previous studies have suggested limited change to the results after when including these factors in the analysis.

WIDER IMPLICATIONS OF THE FINDINGS
The findings are helpful for understanding the combined effects of air pollution and meteorological conditions on birth defects. Environmental policies and practices should be formulated and implemented to decrease air pollutant emissions and improve meteorological conditions to reduce their harmful effects on pregnancy. 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 it is excessively humid.

STUDY FUNDING/COMPETING INTEREST(S)
The study is funded by Major Scientific and Technological Projects for Collaborative Prevention and Control of Birth Defects in Hunan Province (2019SK1012), Major Research and Development Projects in Hunan Province (2018SK2060) and Scientific and Technological Department Projects in Hunan Province (2017SK50802). There are no competing interests.

TRIAL REGISTRATION NUMBER
N/A.