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N Engl J Med. 2015 Jan 22;372(4):331-40. doi: 10.1056/NEJMoa1403489.

Causes and timing of death in extremely premature infants from 2000 through 2011.

Collaborators (154)

Jobe AH, Caplan MS, Oh W, Hensman AM, Basso K, Fanaroff AA, Truog WE, Gauldin C, Schibler K, Donovan EF, Alexander B, Bridges K, Grisby C, Mersmann MW, Mincey HL, Hessling J, Jackson L, Kirker K, Fischer EE, Muthig G, Goldberg RN, Cotten C, Auten KJ, Fisher KA, Lohmeyer MB, Grimes S, Foy KA, Carlton DP, Wright LL, McClure EM, Archer SW, Poindexter BB, Lemons JA, Herron DE, Miller LC, Wilson LD, Nelin LD, Jadcherla SR, Fortney CA, Parikh NA, Clifford B, Daubenmire A, Leonhart K, Stein M, Wishloff E, Gantz MG, Poole W, Wallace D, Auman JO, Crawford M, Hastings BK, Huitema CM, Zaterka-Baxter KM, Stevenson DK, Adams MM, Ahlfors CE, Palmquist AW, Proud MS, Stebbins RD, Frantz ID 3rd, MacKinnon BL, Nylen E, Furey A, Ambalavanan N, Collins MV, Cosby SS, Devaskar U, Garg M, Chanlaw T, Geller R, Finer NN, Rasmussen MR, Wozniak PR, Arnell K, Bridge R, Demetrio C, Rich W, Johnson KJ, Campbell DB, Widness JA, Ellsbury DL, Colaizy TT, Bauer CR, Duara S, Everett-Thomas R, Worth AM, Watterberg KL, Papile LA, Ohls RK, Lacy CB, Montman RA, Schmidt B, Kirpalani H, DeMauro SB, Chaudhary AS, Abbasi S, Mancini T, Cucinotta D, D'Angio CT, Phelps DL, Guillet R, Lakshminrusimha S, Reubens LJ, Burnell E, Rowan M, Horihan CA, Wadkins HI, Reynolds AM, Wynn K, Korones SB, Hudson T, Rosenfeld CR, Salhab WA, Brion LP, Burchfield P, Guzman A, Hensley G, Leps MH, Madison S, Miller NA, Vasil DM, Torres LE, Chen L, Tyson JE, Kennedy KA, Akpa EG, Orekoya PA, Harris BF, Franco CI, Lis AE, Martin S, McDavid GE, Tate PL, Simmons MC, Faix RG, Yoder BA, Bird K, Burnett J, Jensen JJ, Osborne KA, Spencer C, Weaver-Lewis K, O'Shea T, Peters NJ, Bara R, Johnson ME, Sawaya K, Ehrenkranz RA, Jacobs H, Cervone P, Gettner P, Konstantino M, Poulsen J, Taft J.

Author information

From the Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta (R.M.P., E.C.H., B.J.S.); the Social, Statistical, and Environmental Sciences Unit, RTI International, Research Triangle Park, NC (S.K.); the Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland (M.C.W., N.S.N.), and Department of Pediatrics, Nationwide Children's Hospital-Ohio State University, Columbus (P.J.S.); the Department of Pediatrics, University of Iowa, Iowa City (E.F.B.); the Division of Neonatology, University of Alabama at Birmingham, Birmingham (W.A.C.); the Department of Pediatrics, Women and Infants Hospital, Brown University, Providence, RI (A.R.L.); the Department of Pediatrics, Wayne State University School of Medicine, Detroit (S.S.); the Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, CA (K.P.V.M., M.B.B.); and the Social, Statistical, and Environmental Sciences Unit, RTI International, Rockville (A.D.), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda (R.D.H.) - both in Maryland.



Understanding the causes and timing of death in extremely premature infants may guide research efforts and inform the counseling of families.


We analyzed prospectively collected data on 6075 deaths among 22,248 live births, with gestational ages of 22 0/7 to 28 6/7 weeks, among infants born in study hospitals within the National Institute of Child Health and Human Development Neonatal Research Network. We compared overall and cause-specific in-hospital mortality across three periods from 2000 through 2011, with adjustment for baseline differences.


The number of deaths per 1000 live births was 275 (95% confidence interval [CI], 264 to 285) from 2000 through 2003 and 285 (95% CI, 275 to 295) from 2004 through 2007; the number decreased to 258 (95% CI, 248 to 268) in the 2008-2011 period (P=0.003 for the comparison across three periods). There were fewer pulmonary-related deaths attributed to the respiratory distress syndrome and bronchopulmonary dysplasia in 2008-2011 than in 2000-2003 and 2004-2007 (68 [95% CI, 63 to 74] vs. 83 [95% CI, 77 to 90] and 84 [95% CI, 78 to 90] per 1000 live births, respectively; P=0.002). Similarly, in 2008-2011, as compared with 2000-2003, there were decreases in deaths attributed to immaturity (P=0.05) and deaths complicated by infection (P=0.04) or central nervous system injury (P<0.001); however, there were increases in deaths attributed to necrotizing enterocolitis (30 [95% CI, 27 to 34] vs. 23 [95% CI, 20 to 27], P=0.03). Overall, 40.4% of deaths occurred within 12 hours after birth, and 17.3% occurred after 28 days.


We found that from 2000 through 2011, overall mortality declined among extremely premature infants. Deaths related to pulmonary causes, immaturity, infection, and central nervous system injury decreased, while necrotizing enterocolitis-related deaths increased. (Funded by the National Institutes of Health.).

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