UC Irvine

Hypertensive disorders in pregnancy (HDP) are a leading cause of maternal and fetal morbidity and mortality world-wide. According to a recent CDC report, HDP have increased by 3% in 2019, implicating an association with environmental etiology. There are numerous reports of adverse health effects caused by fine particulate matter (PM2.5), particularly on respiratory and cardiovascular health; however, their effects on changed CVS dynamic during pregnancy and associated HDP is unclear yet. Basic pathophysiology of HDP is largely unknown as of today. Since HDP is a cluster of different conditions including milder to severe variety, associations with air pollutants to both mild and severe categories of HDP examined separately will shed light on pathophysiology of HDP spectrum. Such understanding will help to develop preventive measures to reduce environmental contributor to HDP and HDP related unwanted pregnancy outcomes.

The associations between pollution and mild and severe categories of HDP are understudied in literature. Most of the existing studies are based on taking HDP as an umbrella diagnosis outcome, and results of these studies are ambiguous regarding the associations between air pollution and HDP. This is the first large study to examine the relationship between ambient air pollution with gestational hypertension (GH) and preeclampsia- eclampsia (PE-E) separately with personal exposure data of PM2.5 total mass and its constituents. This is a retrospective cohort study with an extensive literature review on patient population of Southern California Kaiser Permanente (KPSC) that includes 15 hospitals and 234 medical offices across Southern California with personal exposure data from residential addresses using fine-resolution geoscience-derived models’ data for PM2.5 total mass and its constituents for the period of 2008 to 2017. Data on demographic characteristics, including race, smoking status, insurance type, income category, residential history, medical records, birth records for maternal age, first pregnancy status, and individual lifestyle were collected from KPSC electronic health record (EHR) system. Information on gestational hypertension (GH), preeclampsia (PE) and eclampsia (E) were collected from the EHR using International Classification of Disease 9th and 10th revision (ICD-9 and ICD-10) codes for diagnosis. The descriptive statistics of selected demographic and pregnancy characteristics and air pollution levels were conducted that showed a total of 431,800 cases, with a prevalence of 4.7% (n= 20310) for GH, 5.3% (n=22,678) for preeclampsia and 0.1% (n=313) for eclampsia. There were no significant age differences between GH group and PE-E group. Prevalence of both GH and PE-E were highest among Hispanic mothers (44.1% and 54.1%, respectively), followed by non-Hispanic White mothers (34.6% and 21.1%, respectively). There were no significant differences in the prevalence of either of the conditions based on mothers’ education level, household income, smoking status, and season of conception. Prevalence of both the conditions were higher in primiparous women than respective controls [GH: 53.7% (non-GH: 40.8%) and PE-E: 56.6% (non-PE-E: 40.3%)]. Additionally, while the prevalence of both the conditions were less among underweight [GH: 0.9% (non-GH: 2.6%), PE-E:1.5%, (non-PE-E: 2.5%)] and normal body mass index (BMI) [GH: 22.9% (non-GH: 44.9%), PE:27.5%, (non-PE-E: 43.7% )] mothers than non-cases, there was no differences in the prevalence of either GH or PE-E among overweight mothers and higher prevalence of both the conditions among obese mothers [GH: 21.3% (non-GH: 14.5%), PE-E:21%, (non-PE-E: 14.8%)]. Associations between air pollution exposures during entire pregnancy and the risk of GH and PE-E was estimated by multivariate Cox regression analysis. Positive associations were observed between PE-E and black carbon, PM2.5 total mass and organic matter [Hazard Ratio (HR):1.12, CI:1.07-1.16, HR: 1.06, CI:1.03-1.08 and HR:1.06, CI:1.03-1.08 respectively]. Sensitivity analysis was conducted after further adjusting the model for pre-pregnancy Body Mass Index (BMI), primiparity and season, results consistent with that of the base model were observed for both GH and PE-E groups. To investigate whether differences in the associations among different race/ethnicity, pre-pregnancy BMI categories, mothers of different smoking habits and mothers from different economic condition exist, stratified analysis was conducted by race/ethnicity, maternal pre-pregnancy BMI, mother’s smoking status and house-hold income categories. It was observed that slightly low risks of PE-E are associated with exposures to sulphate among White mothers with significant heterogenicity (Cochrane p value: 0.04), but for the GH group, maximum negative associations were observed among Asian American mothers in exposure to most of the pollutants with significant heterogenicity (Cochrane p value: <0.01). There were no significant differences in the risks of PE-E among mothers of different BMI categories; However, the GH group shows most negative associations to exposure ammonium in underweight mothers and to exposure to PM2.5 total mass, nitrate, organic matter and black carbon in the groups of normal body weight category, all with significant heterogenicity (Cochrane p value <0.05). For smoking subgroup analysis, the current smoker category shows no significant associations of risks in exposure to any of the pollutants (Cochrane p value: <.05). For the GH group, negative associations are observed in exposure to black carbon most among current smoker mothers, followed by past and never smoker pregnant women. For the subgroup analysis of house-hold income, highest risk of PE-E is seen among mothers with household income than $43,667 in exposure to black carbon with significant heterogenicity (Cochrane p value: <.01); while in the GH group, upper economic condition mothers (household income > $71, 591) were seen to be most protective of risk of developing GH in exposure to black carbon (Cochrane p value: <.01). This study shows that exposure to air pollution with PM2.5 total mass and two of its constituents, black carbon and organic matter, increases risks to develop severe forms of HDP, while there is no statistically significant association with milder HDP.