Role of Genetic Susceptibility in the Development of Bronchopulmonary Dysplasia

J Pediatr. 2018 Dec:203:234-241.e2. doi: 10.1016/j.jpeds.2018.07.099. Epub 2018 Oct 1.

Abstract

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.

Keywords: ACE modeling; bronchopulmonary dysplasia; disease risk; extremely low gestational age newborns; genetics; heritability; twin study.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Boston
  • Bronchopulmonary Dysplasia / diagnosis
  • Bronchopulmonary Dysplasia / epidemiology
  • Bronchopulmonary Dysplasia / genetics*
  • Cause of Death*
  • Cohort Studies
  • Databases, Factual
  • Female
  • Genetic Predisposition to Disease / epidemiology*
  • Gestational Age
  • Humans
  • Infant, Extremely Premature*
  • Infant, Newborn
  • Male
  • Pregnancy
  • Pregnancy, Twin
  • Prevalence
  • Retrospective Studies
  • Risk Assessment
  • Survival Rate
  • Twin Studies as Topic*
  • Twins, Dizygotic
  • Twins, Monozygotic