Outcomes of Preterm Infants Born at 22 to 23 Weeks’ Gestation in 11 International Neonatal Networks
Tetsuya Isayama, Mikael Norman, Satoshi Kusuda, Brian Reichman, Liisa Lehtonen, Kei Lui, Mark Adams, Michael Torres, Luca Filippi, Malcolm Battin, Ruth Guinsburg, Neena Modi, Stellan Håkansson, Gil Klinger, Maria Fernanda Branco de Almeida, Kjell Helenius, Dirk Bassler, Yichen Su, Prakesh S. Shah, International Network for Evaluation of Outcomes (iNeo) Investigators, Kei Lui, Scott Morris, Peter R. Schmidt, Manbir Chauhan, Anjali Dhawan, Larissa Korostenski, Mary Sharp, Tobias Strunk, Jacqueline Stack, Pita Birch, Tori Oliver, Lucy Cooke, Dan Casalaz, Jim Holberton, Alice Stewart, Rod W. Hunt, Kenneth Tan, Lyn Downe, Michael Stewart, Andrew Berry, Leah Hickey, Mantho Kgosiemang, Laura de Godoy Rousseff Prado, Tony De Paoli, Naomi Spotswood, Srinivas Bolisetty, Eveline Staub, Mark Greenhalgh, Pieter Koorts, Risha Bhatia, Bron Hennebry, Hari Ravindranathan, Hazel Carlisle, Nadia Badawi, Himanshu Popat, Gary Alcock, Jonathan Davis, Melissa Luig, Michael J. Stark, Margaret Broom, Georgina Chambers, Natalie Merida, Bronwyn Dixon, Brian A. Darlow, Jason Wister, Kristin O’Connor, Mariam J. Buksh, Malcolm Battin, Jutta van den Boom, Angelica Allermo-Fletcher, Helen Miller, David Barker, Claire S. Jacobs, José Maria de Andrade Lopes, Ruth Guinsburg, Maria Fernanda Branco de Almeida, Fábio Carmona, Jamil Pedro de Siqueira Caldas, Sérgio Tadeu Martins Marba, Lígia Maria Suppo de Souza Rugolo, Walusa Assad Gonçalves‐Ferri, Maria Albertina Santiago Rego, Regina Vieira Cavalcanti da Silva, Daniela Marques de Lima Mota Ferreira, Renato S. Procianoy, Nathalia Moura de Mello e Silva, Milton Harumi Miyoshi, Jorge Hecker Luz, Juliana Paula Ferraz dos Santos, José Luiz Muniz Bandeira Duarte, L. Ferrari, Marynéa Silva do Vale, Edna Maria de Albuquerque Diniz, Vera Lúcia Jornada Krebs, Jucille Meneses, Silvia Cwajg, José Mariano Alves Junior, Maurício Obal Colvero, Marc Beltempo, Prakesh S. Shah
Abstract
Importance: Postnatal intensive care for preterm infants born at 22 to 23 weeks' gestation is increasing, although survival rates remain low. Information on outcomes for multiple countries or regions can be important for research, benchmarking, quality improvement, and parental counseling. Objective: To evaluate survival and major morbidities and their between-network variations in infants born at 22 to 23 weeks' gestation in 11 neonatal networks participating in the International Network for Evaluation of Outcomes (iNeo) in neonates in 12 countries or regions. Design, Setting, and Participants: International registry-based cohort study of infants born at 22 to 23 weeks' gestation from January 1, 2015, through December 31, 2021, without major congenital anomalies who were admitted for neonatal intensive care in 11 national or regional neonatal consortia. Data analysis was performed from December 2, 2023, to June 15, 2025. Exposures: Neonatal consortium and gestational age at birth. Main Outcomes and Measures: Survival to neonatal intensive care unit discharge, major neonatal morbidities, and survival without any major morbidities. Results: A total of 5019 neonates were included (1084 of 4636 neonates [23%] with a maternal age >35 years; 2641 of 5017 neonates [53%] male); among them, 846 neonates were born at 22 weeks' gestation and 4173 were born at 23 weeks' gestation. Variations between contributing networks for perinatal management at 22 and 23 weeks' gestation, respectively, include any antenatal steroids (ranges of 18%-83% and 57%-98%), cesarean birth (0%-42% and 5%-73%), and outborn (0%-26% and 0%-22%). Significant variations between contributing networks for adjusted probabilities of outcomes at 22 and 23 weeks' gestation, respectively, include survival to discharge (95% CIs of 9%-64% and 16%-80%; P < .001), grade 3 or 4 periventricular hemorrhage (PVH) or periventricular leukomalacia (PVL) (severe PVH or PVL: 24%-65% and 18%-56%; P < .001), survival without severe PVH or PVL (7%-53% and 9%-69%; P < .001), treated retinopathy of prematurity among survivors (32%-57% [P = .008] and 16%-48% [P < .001]), bronchopulmonary dysplasia among survivors (for 23 weeks only: 64%-88%; P < .001), and necrotizing enterocolitis (for 23 weeks only: 6%-28%; P < .001). Standardized incidence ratios showed significant differences in survival and major morbidities in some networks compared with a reference population from all other networks. Conclusions: Substantial international variations were identified in outcomes for infants born at 22 to 23 weeks' gestation who were admitted to 11 neonatal networks in the 12 countries or regions. The variations can be due to differences in systems, care practices, attitudes, and culture; however, identification of variation can help focus efforts toward research aimed at understanding the causal determinants of variation.