Role of Genetic Susceptibility in the Development of Bronchopulmonary Dysplasia.

OBJECTIVE

To assess heritable contributions to bronchopulmonary dysplasia (BPD) risk in a twin cohort restricted to gestational age at birth <29 weeks.

STUDY

DESIGN

A total of 250 twin pairs (192 dichorionic, 58 monochorionic) born <29 weeks gestational age with known BPD status were identified. Three statistical methods applicable to twin cohorts (χ2 test, intraclass correlations [ICCs], and ACE modeling [additive genetic or A, common environmental or C, and unique environmental or E components]) were applied. Heritability was estimated as percent variability from A. Identical methods were applied to a subcohort defined by zygosity and to an independent validation cohort.

RESULTS

χ2 analyses comparing whether neither, 1, or both of monochorionic (23, 19, 16) and dichorionic (88, 56, 48) twin pairs developed BPD revealed no difference. Although there was similarity in BPD outcome within both monochorionic and dichorionic twin pairs by ICC (monochorionic ICC = 0.34, 95% CI [0.08, 0.55]; dichorionic ICC = 0.39, 95% CI [0.25, 0.51]), monochorionic twins were not more likely than dichorionic twins to have the same outcome (P = .70). ACE modeling revealed no contribution of heritability to BPD risk (% A = 0.0%, 95% CI [0.0%, 43.1%]). Validation and zygosity based cohort results were similar.

CONCLUSIONS

Our analysis suggests that heritability is not a major contributor to BPD risk in preterm infants <29 weeks gestational age.