Published online January 26, 2009
PEDIATRICS Vol. 123 No. 2 February 2009, pp. 669-673 (doi:10.1542/peds.2008-1117)

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bhandari, V. Articles by Zhang, H. Search for Related Content PubMed PubMed Citation Articles by Bhandari, V. Articles by Zhang, H. Related Collections Heart & Blood Vessels Related AAP Red Book topics: Yersinia enterocolitica and... Social Bookmarking                         What's this?

ARTICLE

Genetic Contribution to Patent Ductus Arteriosus in the Premature Newborn

Vineet Bhandari, MD, DM^a, Gongfu Zhou, PhD^b, Matthew J. Bizzarro, MD^a, Catalin Buhimschi, MD^c, Naveed Hussain, MD^d, Jeffrey R. Gruen, MD^a,e,f,g and Heping Zhang, PhD^b

Departments of ^a Pediatrics
^b Epidemiology and Public Health
^c Obstetrics and Gynecology
^e Genetics
^f Investigative Medicine
^g Yale Child Health Research Center, Yale University School of Medicine, New Haven, Connecticut
^d Division of Neonatology, University of Connecticut Health Center, Farmington, Connecticut

BACKGROUND. The most common congenital heart disease in the newborn population, patent ductus arteriosus, accounts for significant morbidity in preterm newborns. In addition to prematurity and environmental factors, we hypothesized that genetic factors play a significant role in this condition.

OBJECTIVE. The objective of this study was to quantify the contribution of genetic factors to the variance in liability for patent ductus arteriosus in premature newborns.

PATIENTS AND METHODS. A retrospective study (1991–2006) from 2 centers was performed by using zygosity data from premature twins born at 36 weeks' gestational age and surviving beyond 36 weeks' postmenstrual age. Patent ductus arteriosus was diagnosed by echocardiography at each center. Mixed-effects logistic regression was used to assess the effect of specific covariates. Latent variable probit modeling was then performed to estimate the heritability of patent ductus arteriosus, and mixed-effects probit modeling was used to quantify the genetic component.

RESULTS. We obtained data from 333 dizygotic twin pairs and 99 monozygotic twin pairs from 2 centers (Yale University and University of Connecticut). Data on chorioamnionitis, antenatal steroids, gestational age, body weight, gender, respiratory distress syndrome, patent ductus arteriosus, necrotizing enterocolitis, oxygen supplementation, and bronchopulmonary dysplasia were comparable between monozygotic and dizygotic twins. We found that gestational age, respiratory distress syndrome, and institution were significant covariates for patent ductus arteriosus. After controlling for specific covariates, genetic factors or the shared environment accounted for 76.1% of the variance in liability for patent ductus arteriosus.

CONCLUSIONS. Preterm patent ductus arteriosus is highly familial (contributed to by genetic and environmental factors), with the effect being mainly environmental, after controlling for known confounders.

---

Key Words: neonate • patent ductus arteriosus • twins • genetic

Abbreviations: PDA—patent ductus arteriosus • RDS—respiratory distress syndrome • NEC—necrotizing enterocolitis • BPD—bronchopulmonary dysplasia • MELR—mixed-effects logistic regression • GA—gestational age • BW—birth weight • INST—treating institution • OR—odds ratio • CI—confidence interval

---

Accepted Jun 4, 2008.

CiteULike    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?