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).
The effect of TRAP was consistent across bodies of evidence for individual TRAP components and was supported by meta-analyses for individual traffic-related metrics (i.e., PM2.5 and NO2) and supported by studies that evaluated traffic measures. The collective evidence across the air pollutant measurements and traffic measurements shows consistency in the direction of effect across multiple populations and geographic locations, strengthening the confidence in the association between combined TRAP exposure (versus exposure to the individual TRAP components) and hypertensive disorders of pregnancy. Many of the studies evaluated only one TRAP component, and those that evaluated more than one component still found significant associations between the individual components and hypertensive disorders of pregnancy after statistically accounting for other exposures, although the effect size may have been reduced by controlling for other TRAP measures.
In addition to consistency across bodies of evidence, mechanistic data evaluating single pollutants indicate that the individual PM2.5 and NO2 exposures can act independently to affect different pathways (e.g., vascular inflammation and oxidative stress) that lead to increased blood pressure. Because TRAP comprises multiple pollutants, the likelihood of being exposed simultaneously to multiple TRAP components is high. The independent mechanisms by which these TRAP exposures can elevate blood pressure—combined with evidence of an association between increased TRAP exposure and development of hypertensive disorders of pregnancy (supported by meta-analyses)—increase support for the moderate level of evidence that multiple TRAP components can act on blood pressure parameters during pregnancy to lead to hypertension. Therefore, the combined body of evidence is considered robust due to the greater number of studies, the multiple mechanisms by which the individual components can affect blood pressure, and the greater likelihood of exposure to multiple components of TRAP. Taken together, these factors demonstrate a moderate level of evidence that exposure to TRAP is associated with the development of hypertensive disorders of pregnancy and support a conclusion of presumed to be a hazard to pregnant women.
Overall, based on the body of evidence for the combined TRAP exposure, the available evidence supports that exposure to TRAP during pregnancy increases the likelihood of developing hypertensive disorders of pregnancy. Because of the recognized relationship between maternal blood pressure status and the effect of hypertension during pregnancy on fetal and infant health outcomes, hypertensive disorders of pregnancy associated with TRAP exposure may have significant adverse health effects in the developing offspring.
National Toxicology Program (NTP). 2019. NTP monograph on the systematic review of traffic-related air pollution and hypertensive disorders of pregnancy. Research Triangle Park, NC: National Toxicology Program. NTP Monograph 07. https://doi.org/10.22427/NTP-MGRAPH-7