Maternal Exposure To Ambient Carbon Monoxide And Risk Of Preeclampsia

Objectives:To explore whether maternal exposure to ambient Carbon Monoxide (CO) has impact on risk of development of preeclampsia (PE), to explore the association between maternal exposure to CO, PE, and fetal growth, and to explore whether socioeconomic status (SES) can modify the CO-PE association. Findings from current study will facilitate future studies help understanding the mechanism by which exposure to environmental CO decreases the incidence of PE and will lead to the development of novel therapeutics to prevent or mitigate the impact of the disease.Methods:The2004-2009provincial birth record system from BORN Ontario (formerly Ontario perinatal surveillance system-OPSS) was used as the study population database. Ambient CO data was maintained by the Ontario Ministry of Environment and was retrieved from the Air Quality Ontario website. Ambient CO database was linked with perinatal database by postal code of mother’s residence. To ensure the accuracy and precision of exposure measurement, only women whose residence was within10km from the closest monitoring station were included. Date on the CO records was matched temporally to the date of pregnancy calculated by date of birth and length of gestation. Maternal exposure to ambient CO during pregnancy was estimated by average (median) CO concentration of the monitoring station located in the residential area of the mother during the entire pregnancy, and was used as the exposure variable in the study.Median family income and percentage of having a university degree among adult population aged from25to64years at postal code level were used as neighborhood level SES variables to adjust for potential confounders and to explore the potential effect modification on the association between environmental CO exposure and risk of PE.Women who had a multiple gestation, a stillbirth or those whose information on PE or exposure measure or birth date or gestational age were missing were excluded from the study. Baby’s date of birth, mother’s date of birth and postal codes were deleted from the research file after the record linkage, for the protection of privacy and confidentiality.Study subjects were divided into four groups according to quartiles of CO concentration based on maternal residence. Adjusted odds ratio (aOR) and95%confidence interval (CI), estimated by multilevel logistic regression model using SAS GLIMMIX procedure, were used to estimate the independent effect of CO on PE, with the lowest quartile of CO concentration as the reference. After stratifying study subjects by SES strata, the multi-level logistic regression analysis was repeated to further assess potential effect modification on the association between maternal exposure to environmental CO and PE. A multiple linear regression model was used to assess the association between measures of maternal exposure to CO, PE and z-score of birth weight for gestational age (BWGA).All analyses were conducted using SAS v.9.2(SAS Inc., Cary, NC, USA). The study was approved by Central South University, the Ottawa Hospital and the Children’s Hospital of Eastern Ontario Research Ethics Boards.Results:A total of23monitoring stations had CO measurements during the study period, with average CO concentration of0.25ppm (lowest0.18ppm and highest0.58ppm).The final analyses included127,370eligible study subjects, of whom,2,186(1.72%) had a diagnosis of PE. Advanced maternal age, primiparity, lower SES, and maternal health problems were associated with an increased risk of developing PE. On the other hand, maternal cigarette smoking was associated with lower risk of developing PE.The risk of developing PE was inversely associated with maternal environmental CO concentration, with a clear linear dose-response relationship:rates of PE were2.25%,1.96%,1.58%, and1.35%, respectively, in the first, second, third, and fourth quartile of CO concentration. The inverse association between CO concentration and PE risk remained the same after adjustment for several confounding factors and across populations with different SES.Among quartiles of maternal exposure to CO, mean B WGA z-score was lower in highest quartile than in lowest quartile (-0.07vs.-0.006; p <0.05). Moreover, the z-score was lower in smokers than non-smokers (-0.14vs.-0.02;p<0.001). Similarly, the z-score was lower in PE women than women without PE (-0.25vs.-0.04;p<0.001).Linear regression analysis showed that maternal exposure to CO and PE were each associated with lower z-scores of birth weight for gestational age (β=-0.022;p<0.001, and β=-0.246; p<0.001, respectively). On the other hand, for women with PE, the association between CO and BWGA z-score was positive, but not to a statistically significant extent (β=0.032; p=0.122). In model2, smoking and PE were also associated with lower z-score of BWGA(β=-0.117;p<0.001, and β=-0.228; p<0.001, respectively), and interaction term for smoking and PE was positive after adjusting for confounders, although not statistically significant (β=0.023; p=0.735).Conclusion:Maternal exposure to moderate ambient CO is associated independently with a decreased risk of preeclampsia. The association between CO and PE remained the same among different exposure windows and across different SES subgroup. Maternal exposure to environmental CO also seems to protect against PE related fetal growth.