Carol L Shen1, Qunyuan Zhang2, Julia Meyer Hudson1, F Sessions Cole1, Jennifer A Wambach3. 1. Division of Newborn Medicine, Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO. 2. Center for Genome Sciences and Systems Biology, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO. 3. Division of Newborn Medicine, Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, MO. Electronic address: Wambach_j@kids.wustl.edu.
Abstract
OBJECTIVE: To determine the genetic contribution to risk for respiratory distress syndrome (RDS) among moderately preterm, late preterm, and term infants (estimated gestational age ≥32 weeks) of African- and European-descent. STUDY DESIGN: We reviewed clinical records for 524 consecutive twin pairs ≥32 weeks gestation. We identified pairs in which at least 1 twin had RDS (n = 225) and compared the concordance of RDS between monozygotic and dizygotic twins. Using mixed-effects logistic regression, we identified covariates that increased disease risk. We performed additive genetic, common environmental, and residual effects modeling to estimate genetic variance and used the ratio of genetic variance to total variance to estimate genetic contribution to RDS disease risk. RESULTS: Monozygotic twins were more concordant for RDS than dizygotic twins (P = .0040). Estimated gestational age, European-descent, male sex, delivery by cesarean, and 5-minute Apgar score each independently increased risk for RDS. After adjusting for these covariates, genetic effects accounted for 58% (P = .0002) of the RDS disease risk variance for all twin pairs. CONCLUSIONS: In addition to environmental factors, genetic factors may contribute to RDS risk among moderately preterm, late preterm, and term infants. Discovery of risk alleles may be important for prediction and management of RDS risk.
OBJECTIVE: To determine the genetic contribution to risk for respiratory distress syndrome (RDS) among moderately preterm, late preterm, and term infants (estimated gestational age ≥32 weeks) of African- and European-descent. STUDY DESIGN: We reviewed clinical records for 524 consecutive twin pairs ≥32 weeks gestation. We identified pairs in which at least 1 twin had RDS (n = 225) and compared the concordance of RDS between monozygotic and dizygotic twins. Using mixed-effects logistic regression, we identified covariates that increased disease risk. We performed additive genetic, common environmental, and residual effects modeling to estimate genetic variance and used the ratio of genetic variance to total variance to estimate genetic contribution to RDS disease risk. RESULTS: Monozygotic twins were more concordant for RDS than dizygotic twins (P = .0040). Estimated gestational age, European-descent, male sex, delivery by cesarean, and 5-minute Apgar score each independently increased risk for RDS. After adjusting for these covariates, genetic effects accounted for 58% (P = .0002) of the RDS disease risk variance for all twin pairs. CONCLUSIONS: In addition to environmental factors, genetic factors may contribute to RDS risk among moderately preterm, late preterm, and term infants. Discovery of risk alleles may be important for prediction and management of RDS risk.
Authors: Alan T N Tita; Mark B Landon; Catherine Y Spong; Yinglei Lai; Kenneth J Leveno; Michael W Varner; Atef H Moawad; Steve N Caritis; Paul J Meis; Ronald J Wapner; Yoram Sorokin; Menachem Miodovnik; Marshall Carpenter; Alan M Peaceman; Mary J O'Sullivan; Baha M Sibai; Oded Langer; John M Thorp; Susan M Ramin; Brian M Mercer Journal: N Engl J Med Date: 2009-01-08 Impact factor: 91.245
Authors: Caryn St Clair; Errol R Norwitz; Karlijn Woensdregt; Michael Cackovic; Julia A Shaw; Herbert Malkus; Richard A Ehrenkranz; Jessica L Illuzzi Journal: Am J Perinatol Date: 2008-09-04 Impact factor: 1.862