Fetal Exposure to Environmental Contaminants May Underlie CHD

From Medscape Medical News

Environmental Link to Congenital Heart Disease Strengthened

Brian Hoyle

May 2, 2011(Denver, Colorado) — Maternal exposure to compounds present in crude oil, cleaning agents, and stain removers has been linked to an increased risk for congenital heart disease (CHD) in a study presented here at the Pediatric Academic Societies and Asian Society for Pediatric Research 2011 Annual Meeting.

CHD "is a major cause of childhood death and life-long health problems, so identifying risk factors contributing to CHD is important to public health. Environmental causes of CHD have been suspected, and animal studies have linked certain chemicals to CHD as potential teratogens, but the link has remained unproven," Gail McCarver, MD, professor of pediatrics at the Medical College of Wisconsin and Children's Research Institute, Milwaukee, told Medscape Medical News.

To probe whether human exposure to a battery of volatile organic compounds and halogens increased the risk for CHD, Dr. McCarver and her colleagues tested meconium as a means of assessing fetal exposure to the solvents.

"Meconium monitoring is an established and valid means of assessment of fetal exposure," Dr. McCarver noted in an interview with Medscape Medical News.

Meconium from 135 newborns diagnosed with CHD and 432 newborns without CHD, as determined by echocardiography, was examined for 17 compounds using gas chromatography–mass spectrometry for volatile organic compounds and gas chromatography–electron capture detector for halogens.

Both techniques were exquisitely sensitive, with detection limits in the parts-per-trillion range.

Infants of diabetic mothers and infants identified with chromosomal abnormalities linked to CHD were excluded from the study. Demographic data, information concerning family history of CHD, and maternal history of the use of tobacco, alcohol, illicit drugs, and vitamins were collected. Mothers and infants were genotyped for 2 genes implicated in CHD: ADH, which encodes alcohol dehydrogenase, and CYP2E1, which encodes cytochrome P450 2E1.

The infants with CHD were significantly more likely to be smaller at birth, born at an earlier gestational age, white, have a family history of CHD, and born to a woman who smoked tobacco (P < .05 for all).

Of the 567 infants, 82% had detectable levels of 1 or more of the examined solvents. Infants with CHD more often displayed fetal exposure to ethylbenzene (P < .001), meta/ortho/para-xylene (P < .001), benzene (P < .01), tetrachloroethylene (P < .05), and dichloroethylene (P < .05).

When the data were examined on the basis of race, fetal exposure to ethyl benzene (a component of crude oil) and the inhaled vapors of vehicle emissions, gasoline, and cigarette smoke increased the risk for CHD 4-fold in white infants, but not in black infants.
Exposure to trichloroethylene (a common degreasing chemical that is a component of a variety of cleaners and spot removers) increased CHD risk 2-fold in white infants and 8-fold in black infants.

Maternal obesity; tobacco smoking; the use of alcohol, illicit drugs, or vitamins; exposure to other solvents; and presence/absence of ADH and CYP2E1 were not significant CHD risk factors.

The association between ethylbenzene and CHD — described by Dr. McCarver as "novel and important for public health" — might explain previous reports linking smoking during pregnancy and CHD, and might heighten public health concerns about events such as the recent oil spill in the Gulf of Mexico.

"This is the first report that exposure to ethyl benzene, a compound present in crude oil, is associated with CHD. This association is troubling, particularly concerning recent oil spills," Dr. McCarver told Medscape Medical News.

The data also implicate tetrachloroethylene as a teratogen and strengthen the validity of the noninvasive examination of meconium as a means of analyzing fetal exposure to environmental compounds.

"This is valuable work. But it could, perhaps, be a whole bunch more insightful if we had more of a history of maternal exposure and its relation to pregnancy. This would allow a more accurate assessment of exposure as a causal factor," Robert Geller, MD, from Emory University School of Medicine, Atlanta, Georgia, told Medscape Medical News.

Data gathered throughout pregnancy are limited at present, Dr. Geller added.
Dr. McCarver and Dr. Geller have disclosed no relevant financial relationships.

Pediatric Academic Societies (PAS) and Asian Society for Pediatric Research 2011 Annual Meeting: Abstract 1150.1. Presented April 30, 2011.