NTP monograph on the systematic review of traffic-related air pollution and hypertensive disorders of pregnancy.

Introduction: Traffic-related air pollution (TRAP) contributes significantly to ambient air pollution, especially in urban settings. Air pollution has been established as a risk factor for hypertension and cardiovascular disease in adults, but this effect is less studied in other susceptible populations. There is increasing evidence that air pollution may adversely affect hypertensive disorders of pregnancy (e.g., gestational hypertension, preeclampsia, eclampsia).

Objective: Because reports indicate that air pollution may be linked to hypertensive disorders, the National Toxicology Program (NTP) conducted a systematic review to evaluate whether exposure to TRAP during pregnancy is associated with hypertensive disorders of pregnancy.

Methods: A systematic review protocol was developed and utilized for this evaluation that followed the Office of Health Assessment and Translation approach for conducting literature-based health assessments. This evaluation considered a range of traffic-related air pollutant measurements (e.g., fine particulate matter [PM2.5]) and traffic measures (e.g., proximity to major roads) in the literature search. Confidence ratings and level-of-evidence conclusions were developed for bodies of evidence for a given exposure measure when there was sufficient evidence (i.e., more than three studies). Changes in blood pressure during pregnancy, gestational hypertension, preeclampsia, eclampsia, or hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) syndrome were considered as measures of hypertension. Hazard conclusions were developed using a two-step process. First, confidence ratings were developed for individual air pollutants (e.g., PM2.5, nitrogen oxides [NOx]) and traffic measures (traffic density and proximity to major roads). Overall hazard conclusions were then developed for TRAP, considering the combined bodies of evidence across different individual measures of traffic-related pollutants.

Results and evidence synthesis: The literature search and screening process identified 18 relevant epidemiological studies and one relevant animal study (from 344 potentially relevant references) that met the objective and the inclusion criteria. The human bodies of evidence for traffic-related PM2.5 and NO2 present a consistent pattern of findings that exposure to these pollutants is associated with the development of hypertensive disorders of pregnancy. There is a similar pattern of findings, but a smaller effect size, for bodies of evidence that residing in high-traffic density regions or in close proximity to major roads are associated with developing hypertensive disorders during pregnancy. There is a moderate level of evidence in the combined human body of evidence based primarily on the TRAP air pollutant studies with support from the traffic measures studies. There is an inadequate level of evidence in the animal body of evidence due to the lack of experimental animal studies identified for these measures. Evidence for other traffic-related pollutants that were identified (i.e., carbon monoxide [CO], black carbon [BC], and elemental carbon [EC]), including one animal study for CO, were few in number or provided inconsistent results across studies, and level-of-evidence conclusions were not reached.

Discussion and conclusion: NTP concludes that exposure to TRAP is presumed to be a hazard to pregnant women for developing hypertensive disorders of pregnancy. This conclusion was based on moderate confidence and moderate level of evidence in the combined body of evidence from human studies reporting on multiple measures of TRAP exposure (traffic-related PM2.5 and NO2) with support from studies on traffic measures (residing in high-traffic density regions or in close proximity to major roads during pregnancy). (This section of the abstract has been abridged.).