Kristi L Watterberg1, Michele C Walsh1, Lei Li1, Sanjay Chawla1, Carl T D'Angio1, Ronald N Goldberg1, Susan R Hintz1, Matthew M Laughon1, Bradley A Yoder1, Kathleen A Kennedy1, Georgia E McDavid1, Conra Backstrom-Lacy1, Abhik Das1, Margaret M Crawford1, Martin Keszler1, Gregory M Sokol1, Brenda B Poindexter1, Namasivayam Ambalavanan1, Anna Maria Hibbs1, William E Truog1, Barbara Schmidt1, Myra H Wyckoff1, Amir M Khan1, Meena Garg1, Patricia R Chess1, Anne M Reynolds1, Mohannad Moallem1, Edward F Bell1, Lauritz R Meyer1, Ravi M Patel1, Krisa P Van Meurs1, C Michael Cotten1, Elisabeth C McGowan1, Abbey C Hines1, Stephanie Merhar1, Myriam Peralta-Carcelen1, Deanne E Wilson-Costello1, Howard W Kilbride1, Sara B DeMauro1, Roy J Heyne1, Ricardo A Mosquera1, Girija Natarajan1, Isabell B Purdy1, Jean R Lowe1, Nathalie L Maitre1, Heidi M Harmon1, Laurie A Hogden1, Ira Adams-Chapman1, Sarah Winter1, William F Malcolm1, Rosemary D Higgins1. 1. From the University of New Mexico Health Sciences Center, Albuquerque (K.L.W., C.B.-L., J.R.L.); the Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland (M.C.W., A.M.H., D.E.W.-C.), Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati (B.B.P., S.M.), and the Department of Pediatrics, Nationwide Children's Hospital, Ohio State University College of Medicine, Columbus (M.M., N.L.M.) - all in Ohio; the Social, Statistical, and Environmental Sciences Unit, RTI International, Research Triangle Park (L.L.), the Department of Pediatrics, Duke University, Durham (R.N.G., C.M.C., W.F.M.), and the Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill (M.M.L.) - all in North Carolina; the Department of Pediatrics, Wayne State University (S.C., G.N.), and the Department of Pediatrics, Central Michigan University (S.C.) - both in Detroit; the University of Rochester School of Medicine and Dentistry, Rochester (C.T.D., P.R.C.), and the Department of Pediatrics, University of Buffalo Women's and Children's Hospital of Buffalo, Buffalo (A.M.R.) - both in New York; the Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto (S.R.H., K.P.V.M.), and the Department of Pediatrics, University of California, Los Angeles, Los Angeles (M.G., I.B.P.) - both in California; the Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City (B.A.Y., S.W.); the Department of Pediatrics, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston (K.A.K., G.E.M., A.M.K., R.A.M.), and the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas (M.H.W., R.J.H.) - both in Texas; the Social, Statistical, and Environmental Sciences Unit, RTI International, Rockville (A.D., M.M.C.), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda (R.D.H.) - both in Maryland; the Department of Pediatrics, Women and Infants Hospital, Brown University, Providence, RI (M.K., E.C.M.); the Department of Pediatrics, Indiana University School of Medicine, Indianapolis (G.M.S., A.C.H.); Emory University School of Medicine, Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta (B.B.P., R.M.P., N.L.M., I.A.-C.); the Division of Neonatology, University of Alabama at Birmingham, Birmingham (N.A., M.P.-C.); the Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO (W.E.T., H.W.K.); the Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia (B.S., S.B.D.); the Department of Pediatrics, University of Iowa, Iowa City (E.F.B., H.M.H.); the Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls (L.R.M., L.A.H.); and the College of Health and Human Services, George Mason University, Fairfax, VA (R.D.H.).
Abstract
BACKGROUND: Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown. METHODS: We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age. RESULTS: We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups. CONCLUSIONS: In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.).
BACKGROUND: Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown. METHODS: We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age. RESULTS: We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups. CONCLUSIONS: In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.).
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