BACKGROUND: Intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia remain significant causes of morbidity and mortality in preterm newborns. OBJECTIVES: Our goal was to assess the familial and genetic susceptibility to intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia. METHODS: Mixed-effects logistic-regression and latent variable probit model analysis were used to assess the contribution of several covariates in a multicenter retrospective study of 450 twin pairs born at < or =32 weeks of gestation. To determine the genetic contribution, concordance rates in a subset of 252 monozygotic and dizygotic twin pairs were compared. RESULTS: The study population had a mean gestational age of 29 weeks and birth weight of 1286 g. After controlling for effects of covariates, the twin data showed that 41.3%, 51.9%, and 65.2%, respectively, of the variances in liability for intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia could be accounted for by genetic and shared environmental factors. Among the 63 monozygotic twin pairs, the observed concordance for bronchopulmonary dysplasia was significantly higher than the expected concordance; 12 of 18 monozygotic twin pairs with > or =1 affected member had both members affected versus 3.69 expected. After controlling for covariates, genetic factors accounted for 53% of the variance in liability for bronchopulmonary dysplasia. CONCLUSIONS: Twin analyses show that intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia are familial in origin. These data demonstrate, for the first time, the significant genetic susceptibility for bronchopulmonary dysplasia in preterm infants.
BACKGROUND: Intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia remain significant causes of morbidity and mortality in preterm newborns. OBJECTIVES: Our goal was to assess the familial and genetic susceptibility to intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia. METHODS: Mixed-effects logistic-regression and latent variable probit model analysis were used to assess the contribution of several covariates in a multicenter retrospective study of 450 twin pairs born at < or =32 weeks of gestation. To determine the genetic contribution, concordance rates in a subset of 252 monozygotic and dizygotic twin pairs were compared. RESULTS: The study population had a mean gestational age of 29 weeks and birth weight of 1286 g. After controlling for effects of covariates, the twin data showed that 41.3%, 51.9%, and 65.2%, respectively, of the variances in liability for intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia could be accounted for by genetic and shared environmental factors. Among the 63 monozygotic twin pairs, the observed concordance for bronchopulmonary dysplasia was significantly higher than the expected concordance; 12 of 18 monozygotic twin pairs with > or =1 affected member had both members affected versus 3.69 expected. After controlling for covariates, genetic factors accounted for 53% of the variance in liability for bronchopulmonary dysplasia. CONCLUSIONS: Twin analyses show that intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia are familial in origin. These data demonstrate, for the first time, the significant genetic susceptibility for bronchopulmonary dysplasia in preterm infants.
Authors: Alice Hadchouel; Xavier Durrmeyer; Emmanuelle Bouzigon; Roberto Incitti; Johanna Huusko; Pierre-Henri Jarreau; Richard Lenclen; Florence Demenais; Marie-Laure Franco-Montoya; Inès Layouni; Juliana Patkai; Jacques Bourbon; Mikko Hallman; Claude Danan; Christophe Delacourt Journal: Am J Respir Crit Care Med Date: 2011-08-11 Impact factor: 21.405
Authors: Joseph M Collaco; Lewis H Romer; Bridget D Stuart; John D Coulson; Allen D Everett; Edward E Lawson; Joel I Brenner; Anna T Brown; Melanie K Nies; Priya Sekar; Lawrence M Nogee; Sharon A McGrath-Morrow Journal: Pediatr Pulmonol Date: 2012-07-06
Authors: Anne Hilgendorff; Irwin Reiss; Harald Ehrhardt; Oliver Eickelberg; Cristina M Alvira Journal: Am J Respir Cell Mol Biol Date: 2014-02 Impact factor: 6.914
Authors: Hui Wang; Krystal R St Julien; David K Stevenson; Thomas J Hoffmann; John S Witte; Laura C Lazzeroni; Mark A Krasnow; Cecele C Quaintance; John W Oehlert; Laura L Jelliffe-Pawlowski; Jeffrey B Gould; Gary M Shaw; Hugh M O'Brodovich Journal: Pediatrics Date: 2013-07-29 Impact factor: 7.124
Authors: Nansi S Boghossian; Grier P Page; Edward F Bell; Barbara J Stoll; Jeffrey C Murray; C Michael Cotten; Seetha Shankaran; Michele C Walsh; Abbot R Laptook; Nancy S Newman; Ellen C Hale; Scott A McDonald; Abhik Das; Rosemary D Higgins Journal: J Pediatr Date: 2013-01-13 Impact factor: 4.406
Authors: Minseok Seo; Weiliang Qiu; William Bailey; Gerard J Criner; Mark T Dransfield; Anne L Fuhlbrigge; John J Reilly; Mary Beth Scholand; Peter Castaldi; Robert Chase; Margaret Parker; Aabida Saferali; Jeong H Yun; James D Crapo; Michael H Cho; Terri H Beaty; Edwin K Silverman; Craig P Hersh Journal: J Mol Med (Berl) Date: 2018-10-23 Impact factor: 4.599