In 2013 965,000 deaths due to preterm birth occurred world-wide. Preterm birth, birth before 37 weeks of gestation, puts a newborn at serious risk of postnatal death. An infant that lives is at increased risk of long-term chronic physical and neurological disabilities. The economic costs of preterm births to society are tremendous. It has been estimated based on 2005 data that the cost of preterm birth is $26.2 billion ($51,600 per preterm infant) in the U.S. These births are more prevalent among women of lower income status and from racial and ethnic minorities. The preterm birth rate in the U.S. declined from 12.8% in 2006 to 11.4% in 2013 and now is 9.98%. We still have a long way to go to meet 5.5% by 2030, a goal set by the March of Dimes.
The causes of preterm birth are myriad. They include spontaneous preterm births as well as preterm birth induced because of maternal medical conditions such as severe preeclampsia, severe heart and renal disease, brain tumors and other cancers. Other causes are unhealthy conditions of the fetus, such as severe growth restriction that could led to fetal death. Doctors for decades have searched for the underlying pathophysiology of preterm birth. Despite extensive efforts medical science still does not understand all the mechanisms leading to prematurity.
Recent studies report strong associations of maternal exposure to outdoor air pollution and preterm birth. These epidemiologic studies are difficult to conduct and there have been conflicting results due to small sample sizes, misclassification of pollution exposure, and the fact that air pollution does not contain the same chemicals and particles across many geographical areas. However, a large number of studies from many parts of the world are linking outdoor air pollution and preterm birth. Edward McCabe, MD. PhD, Chief Medical Officer for the March of Dimes has this to say: “While epidemiologic studies cannot demonstrate causation between air pollution and preterm birth or that the association is with these particular small particles, we cannot ignore the weight of the evidence.”
A certain percentage of preterm births is attributed to maternal exposure to fine particulate matter (PM 2.5). PM 2.5 are particles including the droplets they contain with a total mass with an aerodynamic diameter of 2.5μm. These are small particles indeed, only one-thirteenth the width of a human hair. Because they are so small they can penetrate deep into the lung airways. PM2.5 contain a complex mixture of different chemicals. These particles are emitted by industrial factories, oil refineries, diesel fuel, cooking fuels, wood smoke, and by natural chemical reactions occurring in the atmosphere and from dust storms. Chemicals such as ammonium nitrate and ammonium chloride are often in the mix of PM2.5 pollution. Ozone (O3) formed during warm weather near the earth’s surface and PM 10 (particles with a total aerodynamic mass of 10μm) have also been reported to be associated with preterm birth. Recently, exposure to ozone in the last week of pregnancy was found to be associated with stillbirth. These pollutants are not good for anyone’s health and there are many studies showing their effects on children and adults as well as causing serious lung and other disease.
In Western countries the upper levels of reported air pollution exposure are relatively low, a fact that contributes to less confidence in results. However, in Asia the upper limits of pollutant exposure are much greater. Recently, a study of a cohort of 95,911 live births in Wuhan, China during 2011-2013 reported increases in the risk of preterm birth with each 5μg/m increase in PM 2.5 and PM 10 concentration in the ambient air. Increased preterm birth with each 100μg/m increase in carbon monoxide and 10μg/m in ozone concentration was also found. While it was not possible to determine exact times during pregnancy when exposures were most critical, the strongest risk for preterm birth for PM2.5, PM10 and carbon monoxide was in the second trimester while the highest risk for preterm birth associated with ozone was in the third trimester.
One of the most powerful studies indicating that air pollution is associated with preterm birth is research comparing birth outcomes for Utah mothers within and outside the Utah Valley before, during and after the closing of the Utah Valley Steel Mill. The mill was closed between August 1986 and September 1987. Mothers who were pregnant during the time of the mill closure were less likely to deliver preterm infants than those who were pregnant before or after the closure of the mill. This natural experiment is important as it helps to reduce concerns about confounding factors and exposure misclassification.
Scientists at New York University estimate that the costs of preterm birth due to air pollution in the United States are $4.33 billion (based on 2010 data). They calculated that an estimated 3.32% or 15,808 of all preterm births are due to PM2.5 pollution. $760 million of the $4.33 billion is attributable to the cost of medical care. The Campion Fund is currently most active in two states, North Carolina and Utah and our interest was kindled regarding the cost of preterm births in these two states. In NC the preterm birth medical costs attributable to air pollution are $31.6 million and total costs are $181 million. The costs in Utah are lower but they are still considerable. The medical care costs are $4.65 million and total costs are $26.5 million.
It is thought that maternal exposure to fine particle air pollution causes placental inflammation and intrauterine inflammation as well as oxidative stress, blood coagulation, endothelial dysfunction and changed hemodynamic responses. All of these responses are recognized as playing a role in the initiation of preterm delivery. It is especially intriguing that scientists postulate that epigenetic processes may be involved. Epigenetics involve changes in gene expression by mechanisms that do not modify underlying DNA structure. These mechanisms are DNA methylation, histone modifications and expression of noncoding RNA. Published studies suggest that fine particle air pollution may trigger these mechanisms. Exploration of a connection between epigenetics and preterm birth has been the focus of recent studies using cord blood, placental and myometrial tissue. While these studies are not conclusive they suggest the need for future research. Animal models of preterm birth are not feasible because most animal species do not as a rule have spontaneous preterm births and furthermore, both placentation and parturition are different in non-human primates and rodents. Epigenetics provides mechanisms that effect pathways that could be changed or mitigated by air pollution leading to preterm birth. Studies designed to elucidate a link between epigenetics and air pollution could lead to new insights into the cause of preterm birth.
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