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Published online September 1, 2008
PEDIATRICS Vol. 122 No. 3 September 2008, pp. 479-485 (doi:10.1542/peds.2007-2313)
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ARTICLE

Heritability of Bronchopulmonary Dysplasia, Defined According to the Consensus Statement of the National Institutes of Health

Pascal M. Lavoie, MD, PhD, FRCPCa,b, Chandra Pham, RNb, Kerry L. Jang, PhDc

a Department of Pediatrics, Division of Neonatology
c Department of Psychiatry, University of British Columbia, Vancouver, Canada
b Neonatal Program, Children's and Women's Health Centre of British Columbia, Vancouver, Canada

OBJECTIVE. The goal was to determine the magnitude of genetic effects on susceptibility and risk factors for bronchopulmonary dysplasia by using the clinically validated National Institutes of Health consensus definition as a demonstrated proxy for long-term respiratory and neurodevelopmental outcomes in extremely low birth weight infants.

METHODS. We analyzed clinical data from twin pairs born at ≤30 completed weeks of gestation in British Columbia, Canada, between 1993 and 2006. Differences in correlations between monozygotic and dizygotic twin pairs and model-fitting approaches were used to quantify the relative contributions of genetic, shared environmental, and nonshared environmental effects.

RESULTS. Among 318 twins of known zygosity, monozygotic twin pair similarities were greater than those observed for dizygotic pairs, which suggests significant heritability for bronchopulmonary dysplasia. Model-fitting analyses confirmed that genetic effects accounted for 82% and 79% of the observed variance in bronchopulmonary dysplasia susceptibility, defined on the basis of the need for supplemental oxygen at 36 weeks or the National Institutes of Health consensus definition, respectively. Variations in rates of hemodynamically significant patent ductus arteriosus were largely accounted for by genetic effects, whereas the observed variability in susceptibility to blood-borne bacterial infections was largely attributable to environmental factors, both common and unique to each infant.

CONCLUSIONS. Susceptibility to bronchopulmonary dysplasia and persistence of patent ductus arteriosus are both significantly heritable. Our study strengthens the case for investigating genetic risk stratification markers useful for predicting the most significant long-term respiratory and neurodevelopmental consequences of bronchopulmonary dysplasia in premature neonates.

Key Words: bronchopulmonary dysplasia • infant • premature • twin study • heritability • patent ductus arteriosus

Abbreviations: RDS—respiratory distress syndrome • BPD—bronchopulmonary dysplasia • NICHD—National Institute of Child Health and Human Development • PMA—postmenstrual age • PDA—patent ductus arteriosus

Accepted Dec 13, 2007.


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