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Neonatal outcomes of extremely preterm twins by sex pairing: an international cohort study
  1. Luigi Gagliardi1,
  2. Franca Rusconi2,
  3. Brian Reichman3,
  4. Mark Adams4,
  5. Neena Modi5,
  6. Liisa Lehtonen6,
  7. Satoshi Kusuda7,
  8. Maximo Vento8,
  9. Brian A Darlow9,
  10. Dirk Bassler4,
  11. Tetsuya Isayama10,
  12. Mikael Norman11,12,
  13. Stellan Håkansson13,
  14. Shoo K Lee14,15,16,
  15. Kei Lui17,
  16. Junmin Yang16,
  17. Prakeshkumar Shah14,15
  18. the International Network for Evaluating Outcomes of Neonates (iNeo) Investigators
  1. 1Division of Neonatology and Pediatrics, Ospedale Versilia, Viareggio, Azienda USL Toscana Nord Ovest, Italy
  2. 2Unit of Epidemiology, Anna Meyer Children's University Hospital and Regional Health Agency, Florence, Italy
  3. 3Gertner Institute for Epidemiology and Health Policy Research, Sheba Medical Center, Tel Hashomer, Israel
  4. 4Department of Neonatology, University Hospital Zurich and University of Zurich, Zurich, Switzerland
  5. 5UK Neonatal Collaborative, Neonatal Data Analysis Unit, Section of Neonatal Medicine, Department of Medicine, Imperial College London, London, UK
  6. 6Department of Pediatrics and Adolescent Medicine, Turku University Hospital and Department of Clinical Medicine, University of Turku0, Turku, Finland
  7. 7Neonatal Research Network Japan, Maternal and Perinatal Center, Tokyo Women's Medical University, Tokyo, Japan
  8. 8Division of Neonatology, Health Research Institute La Fe, Valencia, Spain
  9. 9Department of Paediatrics, University of Otago Christchurch, Canterbury, New Zealand
  10. 10Division of Neonatology, National Center for Child Health and Development, Tokyo, Japan
  11. 11Department of Neonatal Medicine, Karolinska University Hospital, Stockholm, Sweden
  12. 12Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
  13. 13Department of Clinical Science/Pediatrics, Umea University, Umea, Sweden
  14. 14Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada
  15. 15Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
  16. 16Maternal-infant Care Research Centre, Mount Sinai Hospital, Toronto, Ontario, Canada
  17. 17Royal Hospital for Women, National Perinatal Epidemiology and Statistic Unit, 0, Randwick, New South Wales, Australia
  1. Correspondence to Dr Luigi Gagliardi, Neonatology and Paediatrics, Ospedale Versilia, Lido di Camaiore 55041, Toscana, Italy; l.gagliardi{at}neonatalnet.org

Abstract

Objective Infant boys have worse outcomes than girls. In twins, the ‘male disadvantage’ has been reported to extend to female co-twins via a ‘masculinising’ effect. We studied the association between sex pairing and neonatal outcomes in extremely preterm twins.

Design Retrospective cohort study

Setting Eleven countries participating in the International Network for Evaluating Outcomes of Neonates.

Patients Liveborn twins admitted at 23–29 weeks’ gestation in 2007–2015.

Main outcome measures We examined in-hospital mortality, grades 3/4 intraventricular haemorrhage or cystic periventricular leukomalacia (IVH/PVL), bronchopulmonary dysplasia (BPD), retinopathy of prematurity requiring treatment and a composite outcome (mortality or any of the outcomes above).

Results Among 20 924 twins, 38% were from male-male pairs, 32% were from female-female pairs and 30% were sex discordant. We had no information on chorionicity. Girls with a male co-twin had lower odds of mortality, IVH/PVL and the composite outcome than girl-girl pairs (reference group): adjusted OR (aOR) (95% CI) 0.79 (0.68 to 0.92), 0.83 (0.72 to 0.96) and 0.88 (0.79 to 0.98), respectively. Boys with a female co-twin also had lower odds of mortality: aOR 0.86 (0.74 to 0.99). Boys from male-male pairs had highest odds of BPD and composite outcome: aOR 1.38 (1.24 to 1.52) and 1.27 (1.16 to 1.39), respectively.

Conclusions Sex-related disparities in outcomes exist in extremely preterm twins, with girls having lower risks than boys and opposite-sex pairs having lower risks than same-sex pairs. Our results may help clinicians in assessing risk in this large segment of extremely preterm infants.

  • mortality
  • multiple births
  • neonatology
  • twins
  • outcomes research
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Footnotes

  • Twitter @NeenaModi1

  • Collaborators Contributing International Network for Evaluating Outcomes of Neonates (iNeo) Investigators. Australian and New Zealand Neonatal Network (ANZNN): Kei Lui* Chair of ANZNN. Flinders Medical Centre, SA: Peter Marshall. Gold Coast University Hospital, QLD: Peter Schmidt. Blacktown District Hospital, NSW: Anjali Dhawan*. John Hunter Children’s Hospital, NSW: Paul Craven, Koert de Waal*. King Edward Memorial and Perth Children’s Hospitals, WA: Karen Simmer, Andy Gill*, Jane Pillow*. Liverpool Hospital, NSW: Jacqueline Stack. Mater Mothers' Hospital, QLD: Pita Birch, Neonatal Retrieval Service, QLD: Lucy Cooke*. Mercy Hospital for Women, VIC: Dan Casalaz, Jim Holberton*. Monash Medical Centre, VIC: Alice Stewart. Nepean Hospital, NSW: Lyn Downe. Newborn Emergency Transport Service (VIC): Michael Stewart. NSW Pregnancy and Newborn Services Network: Barbara Bajuk*. NSW Newborn & Paediatric Emergency Transport Service: Andrew Berry. Royal Children's Hospital, VIC: Rod Hunt. Royal Darwin Hospital, NT: Charles Kilburn. Royal Hobart Hospital, Tasmania: Tony De Paoli. Royal Hospital for Women, NSW: Kei Lui*, Srinivas Bolisetty. Royal North Shore Hospital, NSW: Mary Paradisis. Royal Prince Alfred Hospital, NSW: Ingrid Rieger. Royal Brisbane and Women's Hospital, QLD: Pieter Koorts. Royal Women's Hospital, VIC: Carl Kuschel, Lex Doyle. Sydney Children's Hospital, NSW: Andrew Numa. The Canberra Hospital, ACT: Hazel Carlisle. The Children's Hospital at Westmead, NSW: Nadia Badawi, Alison Loughran-Fowlds. The Townsville Hospital, QLD: Guan Koh. Western Australia Neonatal Transport Service: Jonathan Davis. Westmead Hospital, NSW: Melissa Luig. Women's & Children's Hospital, SA: Chad Andersen*. National Perinatal Epidemiology and Statistics Unit, University of New South Wales: Georgina Chambers*. New Zealand: Christchurch Women's Hospital: Nicola Austin, Adrienne Lynn. University of Otago, Christchurch: Brian Darlow. Dunedin Hospital: Liza Edmonds. Middlemore Hospital: Lindsay Mildenhall. Auckland City Hospital: Mariam Buksh, Malcolm Battin*. North Shore and Waitakere Hospitals: Jutta van den Boom*. Waikato Hospital: David Bourchier. Wellington Women's Hospital: Vaughan Richardson, Fiona Dineen*. Singapore: KK Women's and Children's Hospital, Singapore: Victor Samuel Rajadurai*. Hong Kong: Prince of Wales Hospital: Simon Lam. United Christian Hospital: Genevieve Fung. *Denotes the ANZNN Executive Committee: Canadian Neonatal Network (CNN): Prakesh S Shah, MD, MSc (Director, Canadian Neonatal Network and site investigator), Mount Sinai Hospital, Toronto, Ontario; Adele Harrison, MD, MBChB, Victoria General Hospital, Victoria, British Columbia; Anne Synnes, MDCM, MHSC, and Joseph Ting, MD, B.C. Women’s Hospital and Health Centre, Vancouver, British Columbia; Zenon Cieslak, MD, Royal Columbian Hospital, New Westminster, British Columbia; Rebecca Sherlock, MD, Surrey Memorial Hospital, Surrey, British Columbia; Wendy Yee, MD, Foothills Medical Centre, Calgary, Alberta; Khalid Aziz, MBBS, MA, MEd, and Jennifer Toye, MD, Royal Alexandra Hospital, Edmonton, Alberta; Carlos Fajardo, MD, Alberta Children’s Hospital, Calgary, Alberta; Zarin Kalapesi, MD, Regina General Hospital, Regina, Saskatchewan; Koravangattu Sankaran, MD, MBBS, and Sibasis Daspal, MD, Royal University Hospital, Saskatoon, Saskatchewan; Mary Seshia, MBChB, Winnipeg Health Sciences Centre, Winnipeg, Manitoba; Ruben Alvaro, MD, St. Boniface General Hospital, Winnipeg, Manitoba; Amit Mukerji, MD, Hamilton Health Sciences Centre, Hamilton, Ontario; Orlando Da Silva, MD, MSc, London Health Sciences Centre, London, Ontario; Chuks Nwaesei, MD, Windsor Regional Hospital, Windsor, Ontario; Kyong-Soon Lee, MD, MSc, Hospital for Sick Children, Toronto, Ontario; Michael Dunn, MD, Sunnybrook Health Sciences Centre, Toronto, Ontario; Brigitte Lemyre, MD, Children’s Hospital of Eastern Ontario and Ottawa General Hospital, Ottawa, Ontario; Kimberly Dow, MD, Kingston General Hospital, Kingston, Ontario; Ermelinda Pelausa, MD, Jewish General Hospital, Montréal, Québec; Keith Barrington, MBChB, Hôpital Sainte-Justine, Montréal, Québec; Christine Drolet, MD, and Bruno Piedboeuf, MD, Centre Hospitalier Universitaire de Québec, Sainte Foy Québec; Martine Claveau, MSc, LLM, NNP, and Marc Beltempo, MD, McGill University Health Centre, Montréal, Québec; Valerie Bertelle, MD, and Edith Masse, MD, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec; Roderick Canning, MD, Moncton Hospital, Moncton, New Brunswick; Hala Makary, MD, Dr Everett Chalmers Hospital, Fredericton, New Brunswick; Cecil Ojah, MBBS, and Luis Monterrosa, MD, Saint John Regional Hospital, Saint John, New Brunswick; Akhil Deshpandey, MBBS, MRCPI, Janeway Children’s Health and Rehabilitation Centre, St. John’s, Newfoundland; Jehier Afifi, MB BCh, MSc, IWK Health Centre, Halifax, Nova Scotia; Andrzej Kajetanowicz, MD, Cape Breton Regional Hospital, Sydney, Nova Scotia; Shoo K Lee, MBBS, PhD (Chairman, Canadian Neonatal Network), Mount Sinai Hospital, Toronto, Ontario. Finnish Medical Birth Register (FinMBR): Sture Andersson, MD, Helsinki University Hospital, Helsinki; Liisa Lehtonen, MD, Turku University Hospital, Turku; Outi Tammela, MD, Tampere University Hospital, Tampere; Ulla Sankilampi, MD, Kuopio University Hospital, Kuopio; Timo Saarela, MD, Oulu University Hospital, Oulu. Israel Neonatal Network (INN): Eli Heymann, MD, Assaf Harofeh Medical Center, Tzrifin; Shmuel Zangen, MD, Barzilai Medical Center, Ashkelon; Tatyana Smolkin, MD, Baruch Padeh Medical Center, Poriya; Francis Mimouni, MD, Bikur Cholim Hospital, Jerusalem; David Bader, MD, Bnai Zion Medical Center, Haifa; Avi Rothschild, MD, Carmel Medical Center, Haifa; Zipora Strauss, Chaim Sheba Medical Center, Ramat Gan; Clari Felszer, MD, Emek Medical Center, Afula; Hussam Omari, MD, French Saint Vincent de Paul Hospital, Nazareth; Smadar Even Tov-Friedman, MD, Hadassah University Hospital-Ein Karem, Jerusalem; Benjamin Bar-Oz, MD, Hadassah University Hospital-Har Hazofim, Jerusalem; Michael Feldman, MD, Hillel Yaffe Medical Center, Hadera; Nizar Saad, MD, Holy Family (Italian) Hospital, Nazareth; Orna Flidel-Rimon, MD, Kaplan Medical Center, Rehovot; Meir Weisbrod, MD, Laniado Hospital, Netanya; Daniel Lubin, MD, Mayanei Hayeshua Medical Center, Bnei Brak; Ita Litmanovitz, MD, Meir Medical Center, Kfar Saba; Amir Kugelman, MD, Rambam Medical Center; Eric Shinwell, MD, Rivka Ziv Medical Center, Safed; Gil Klinger, MD, Schneider Children’s Medical Center of Israel, Rabin Medical Center (Beilinson Campus), Petah Tikva; Yousif Nijim, MD, Scottish (EMMS) Hospital, Nazareth; Alona Bin-Nun, MD, Shaare-Zedek Medical Center, Jerusalem; Agneta Golan, MD, Soroka Medical Center, Beersheba; Dror Mandel, MD, Sourasky Medical Center, Tel Aviv; Vered Fleisher-Sheffer, MD,Western Galilee Medical Center, Nahariya; David Kohelet, MD, Wolfson Medical Center, Holon; Lev Bakhrakh, MD, Yoseftal Hospital, Eilat. Neonatal Research Network Japan (NRNJ): Satoshi Hattori, MD, Sapporo City Hospital, Sapporo, Hokkaido; Masaru Shirai, MD, Asahikawa Kosei Hospital, Asahikawa, Hokkaido; Toru Ishioka, MD, Engaru Kosei Hospital, Engaru, Hokkaido; Toshihiko Mori, MD, NTT East Sappro Hospital, Sapporo, Hokkaido; Takasuke Amizuka, MD, Aomori Prefecture Central Hospital, Aomori, Aomori; Toru Huchimukai, MD, Iwate Prefecture Ohfunato Hospital, Ofunato, Iwate; Hiroshi Yoshida, MD, Tsuruoka City Shonai Hospital, Tsuruoka, Yamagata; Ayako Sasaki, MD, Yamagata University, Yamagata, Yamagata; Junichi Shimizu, MD, Tsuchiura Kyodo Hospital, Tsuchiura, Ibaraki; Toshihiko Nakamura, MD, National Nishisaitama Central Hospital, Tokorozawa, Saitama; Mami Maruyama, MD, Jichi Medical University Saitame Medical Center, Omiya, Saitama; Hiroshi Matsumoto, MD, Asahi Central Hospital, Asahi, Chiba; Shinichi Hosokawa, MD, National International Medical Center, Shinjuku, Tokyo; Atsuko Taki, MD, Tokyo Medical and Dental University, Bunkyo, Tokyo; Machiko Nakagawa, MD, Saint Luku Hospital, Chuo, Tokyo; Kyone Ko, MD, Sanikukai Hospital, Sumida, Tokyo; Azusa Uozumi, MD, Odawara City Hospital, Odawara, Kanagawa; Setsuko Nakata, MD, Iida City Hospital, Iida, Nagano; Akira Shimazaki, MD, National Shinshu Ueda Medical Center, Ueda, Nagano; Tatsuya Yoda, MD, Saku General Hospital, Saku, Nagano; Osamu Numata, MD, Nagaoka Red Cross Hospital, Nagaoka, Niigata; Hiroaki Imamura, MD, Koseiren Takaoka Hospital, Takaoka, Toyama; Azusa Kobayashi, MD, Kanazawa Medical University, Kanazawa, Kanazawa; Shuko Tokuriki, MD, Fukui University, Fukui, Japan; Yasushi Uchida, MD, National Nagara Medical Center, Nagara, Gifu; Takahiro Arai, MD, Takayama Red Cross Hospital, Takayama, Gifu; Mitsuhiro Ito, MD, Fujieda City Hospital, Fujieda, Shizuoka; Kuniko Ieda, MD, Koritsu Tosei Hospital, Toyota, Aichi; Toshiyuki Ono, MD, Komaki City Hospital, Komaki, Aichi; Masashi Hayashi, MD, Okazaki City Hospital, Okazaki, Aichi; Kanemasa Maki, MD, Yokkaichi City Hospital, Yokkaichi, MieToru Yamakawa, MD, Japan Baptist Hospital, Kyoto, Japan; Masahiko Kawai, MD, Kyoto University, Kyoto, Japan; Noriko Fujii, MD, Fukuchiyama City Hospital, Fukuchiyama, Kyoto, Japan; Kozue Shiomi, MD, Kyoto City Hospital, Kyoto, Japan; Koji Nozaki, MD, Mitubishi Kyoto Hospital, Kyoto, Japan; Hiroshi Wada, MD, Yodogawa Christian Hospital, Osaka, Japan; Taho Kim, MD, Osaka City Sumiyoshi Hospital, Osaka, Japan; Yasuyuki Tokunaga, MD, Toyonaka City Hospital, Toyonaka, Osaka, Japan; Yasuyuki Tokunaga, MD, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan; Akihiro Takatera, MD, Chifune Hospital, Osaka, Japan; Toshio Oshima, MD, Bell Land General Hospital, Sakai, Osaka, Japan; Hiroshi Sumida, MD, Rinku General Hospital, Izumisano, Osaka, Japan; Yae Michinomae, MD, Yao City Hospital, Yao, Osaka, Japan; Yoshio Kusumoto, MD, Osaka General Medical Center, Osaka, Japan; Seiji Yoshimoto, MD, Kobe Children's Hospital, Kobe, Hyogo, Japan; Takeshi Morisawa, MD, Kakogawa City Hospital, Kakogawa, Hyogo, Japan; Tamaki Ohashi, MD, Hyogo Prefectural Awaji Hospital, Sumoto, Hyogo, Japan; Yukihiro Takahashi, MD, Nara Prefecture Medical University, Kashiwara, Nara, Japan; Moriharu Sugimoto, MD, Tsuyama Central Hospital, Tsuyama, Okayama, Japan; Noriaki Ono, MD, Hiroshima University, Hiroshima, Japan; Shinichiro Miyagawa, MD, National Kure Medical Center, Kure, Hiroshima, Japan; Takahiko Saijo, MD, Tokushima University, Tokushima, Japan; Takashi Yamagami, MD, Tokushima City Hospital, Tokushima, Japan; Kosuke Koyano, MD, Kagawa University, Kida, Kagawa, Japan; Shoko Kobayashi, MD, Shikoku Medical Center for Children and Adults, Zentsuji, Kagawa, Japan; Takeshi Kanda, MD, National Kyushu Medical Center, Fukuoka, Japan; Yoshihiro Sakemi, MD, National Kokura Medical Center, Kitakyushu, Fukuoka, Japan; Mikio Aoki, MD, National Nagasaki Medical Center, Nagasaki, Japan; Koichi Iida, MD, Oita Prefectural Hospital, Oita, Japan; Mitsushi Goshi, MD, Nakatsu City Hospital, Nakatsu, Oita, Japan; Yuko Maruyama, MD, Imakyure General Hospital, Kagoshima, Japan. Spanish Neonatal Network (SEN1500): Alejandro Avila-Alvarez, MD, and José Luis Fernandez-Trisac, MD, Complexo Hospitalario Universitario De A Coruña, A Coruña; Mª Luz Couce Pico, MD, and María José Fernández Seara, MD, Hospital Clínico Universitario de Santiago, Santiago de Compostela; Andrés Martínez Gutiérrez, MD, Complejo Hospitalario Albacete, Albacete; Carolina Vizcaíno, MD, Hospital General Universitario de Elche, Alicante; Miriam Salvador Iglesias, MD, and Honorio Sánchez Zaplana, MD, Hospital General Universitario de Alicante, Alicante; Belén Fernández Colomer, MD, and José Enrique García López, MD, Hospital Universitario Central de Asturias, Oviedo, Asturias; Rafael García Mozo, MD, and M Teresa González Martínez, MD, Hospital Universitario de Cabueñes, Gijón, Asturias; Mª Dolores Muro Sebastián, MD, and Marta Balart Carbonell, MD, Clínica Corachán, Barcelona; Joan Badia Barnusell, MD, and Mònica Domingo Puiggròs, MD, Corporacio Parc Taulí, Sabadell, Barcelona; Josep Figueras Aloy, MD, and Francesc Botet Mussons, MD, Hospital Clínic de Barcelona, Barcelona; Israel Anquela Sanz, MD, Hospitalario De Granollers, Granollers; Gemma Ginovart Galiana, MD, H De La Santa Creu I Sant Pau, Barcelona; W Coroleu, MD, Hospital Universitari Germans Trias I Pujol, Badalona; Martin Iriondo, MD, Hospital Sant Joan de Déu Barcelona, Esplugues de Llobregat, Barcelona; Laura Castells Vilella, MD, Hospital General de Cataluña, Barcelona; Roser Porta, MD, Institute Dexeus, Barcelona; Xavier Demestre, MD, and Silvia Martínez Nadal, MD, Scias-Hospital Barcelona, Barcelona; Cristina de Frutos Martínez, MD, Hospital Universitario de Burgos, Burgos; María Jesús López Cuesta, MD, H San Pedro de Alcántara, Cáceres; Dolores Esquivel Mora, MD, and Joaquín Ortiz Tardío, MD, Hospital Jerez, Cádiz; Isabel Benavente, MD, and Almudena Alonso, MD, Hospital Universitario Puerta Del Mar, Cádiz; Ramón Aguilera Olmos, MD, Hospital General de Castellón, Castellón; Miguel A García Cabezas, MD, and Mª Dolores Martínez Jiménez, MD, Hospital General Universitario de Ciudad Real, Ciudad Real; Mª Pilar Jaraba Caballero, MD, and Mª Dolores Ordoñez Díaz, MD, Hospital Universitario Reina Sofía, Córdoba; Alberto Trujillo Fagundo, MD, and Lluis Mayol Canals, MD, Hospital Universitari de Girona Dr Josep Trueta, Girona; Fermín García-Muñoz Rodrigo, MD, and Lourdes Urquía Martí, MD, HMI Las Palmas, Las Palmas, Gran Canaria; María Fernanda Moreno Galdo, MD, and José Antonio Hurtado Suazo, MD, Hospital Universitario Virgen De Las Nieves, Granada; Eduardo Narbona López, and José Uberos Fernández, MD, Hospital Universitario San Cecilio, Granada; Miguel A Cortajarena Altuna, MD, and Oihana Muga Zuriarrain Hospital, MD, Donostia, Gipuzkoa; David Mora Navarro, MD, Hospital Juan Ramón Jiménez, Huelva; María Teresa Domínguez, MD, Hospital Costa De La Luz, Huelva; Mª Yolanda Ruiz del Prado, MD, and Inés Esteban Díez, MD, Hospital San Pedro, Logroño, La Rioja; María Teresa Palau Benavides, MD, and Santiago Lapeña, MD, Hospital de León, León, León; Teresa Prada, MD, Hospital del Bierzo, Ponferrada, León; Eduard Soler Mir, MD, Hospital Arnau De Vilanova, Lleida; Araceli Corredera Sánchez, MD, Enrique Criado Vega, MD, Náyade del Prado, MD, and Cristina Fernández, MD, Hospital Clínico San Carlos, Madrid; Lucía Cabanillas Vilaplana, MD, and Irene Cuadrado Pérez, MD, Hospital Universitario De Getafe, Madrid; Luisa López Gómez, MD, Hospital De La Zarzuela, Madrid; Laura Domingo Comeche, MD, Hospital Universitario de Fuenlabrada, Fuenlabrada, Madrid; Isabel Llana Martín, MD, Hospital Madrid-Torrelodones, Madrid, Madrid; Carmen González Armengod, MD, and Carmen Muñoz Labián, MD, Hospital Universitario Puerta De Hierro, Majadahonda, Madrid; Mª José Santos Muñoz, MD, Hospital Severo Ochoa, Leganés, Madrid; Dorotea Blanco Bravo, MD, and Vicente Pérez, MD, Hospital Gregorio Marañón, Madrid; Mª Dolores Elorza Fernández, MD, Celia Díaz González, MD, and Susana Ares Segura, MD, HU La Paz, Madrid; Manuela López Azorín, MD, Hospital Universitario Quirónsalud Madrid, Madrid; Ana Belén Jimenez MD, Hospital Universitario Fundación Jiménez Díaz, Madrid; Tomás Sánchez-Tamayo, MD, and Elías Tapia Moreno, MD, Hospital Carlos Haya, Málaga; María González, MD, and José Enrique Sánchez Martínez, MD, Hospital Parque San Antonio De Málaga, Málaga; José María Lloreda García, MD, Hospital Universitario Santa Lucia De Cartagena, Murcia; Concepción Goñi Orayen, MD, Hospital Virgen Del Camino De Pamplona, Pamplona, Navarra; Javier Vilas González, MD, Complexo Hospitalario Pontevedra, Pontevedra; María Suárez Albo, MD, and Eva González Colmenero, MD, Hospital Xeral De Vigo, Pontevedra; Elena Pilar Gutiérrez González, MD, and Beatriz Vacas del Arco, MD, Hospital Universitario de Salamanca, Salamanca; Josefina Márquez Fernández, MD, and Laura Acosta Gordillo, MD, Hospital Valme, Sevilla; Mercedes Granero Asensio, MD, Hospital Virgen De La Macarena, Sevilla; Carmen Macías Díaz, MD, Hospital Universitario Virgen Del Rocío, Sevilla; Mar Albújar, MD, Hospital Universitari de Tarragona Joan XXIII, Tarragona; Pedro Fuster Jorge. MD, Hospital Universitario De Canarias, San Cristóbal de La Laguna, Santa Cruz de Tenerife; Sabina Romero, MD, and Mónica Rivero Falero, MD, Hospital Universitario Nuestra Señora De Candelaria, Santa Cruz de Tenerife; Ana Belén Escobar Izquierdo, Hospital Virgen De La Salud, Toledo; Javier Estañ Capell, MD, Hospital Clinico Universitario De Valencia, Valencia; Mª Isabel Izquierdo Macián, MD, Hospital Universitari La Fe, Valencia; Mª Mar Montejo Vicente, MD, and Raquel Izquierdo Caballero, MD, Hospital Universitario Río Hortega, Valladolid; Mª Mercedes Martínez, MD, and Aintzane Euba, MD, Hospital de Txagorritxu, Vitoria-Gasteiz; Amaya Rodríguez Serna, MD, and Juan María López de Heredia Goya, MD, Hospital de Cruces, Baracaldo; Alberto Pérez Legorburu, MD, and Ana Gutiérrez Amorós, MD, Hospital Universitario de Basurto, Bilbao; Víctor Manuel Marugán Isabel, MD, and Natalio Hernández González, MD, Hospital Virgen De La Concha—Complejo Asistencial De Zamora, Zamora; Segundo Rite Gracia, MD, Hospital Miguel Servet, Zaragoza; Mª Purificación Ventura Faci, MD, and Mª Pilar Samper Villagrasa, MD, Hospital Clínico Universitario Lozano Blesa, Zaragoza. Swedish Neonatal Quality (SNQ Register): Jiri Kofron, MD, Södra Älvsborgs Sjukhus, Borås; Katarina Strand Brodd, MD, Mälarsjukhuset, Eskilstuna; Andreas Odlind, MD, Falu Lasarett, Falun; Lars Alberg, MD, Gällivare Sjukhus, Gällivare; Sofia Arwehed, MD, Gävle Sjukhus, Gävle; Ola Hafström, MD, SU/Östra, Göteborg; Anna Kasemo, MD, Länssjukhuset, Halmstad; Karin Nederman, MD, Helsingborgs Lasarett, Helsingborg; Lars Åhman, MD, Hudiksvalls Sjukhus, Hudiksvall; Fredrik Ingemarsson, MD, Länssjukhuset Ryhov, Jönköping; Henrik Petersson, MD, Länssjukhuset, Kalmar; Pernilla Thurn, MD, Blekingesjukhuset, Karlskrona; Eva Albinsson, MD, Centralsjukhuset, Karlstad; Bo Selander, MD, Centralsjukhuset, Kristianstad; Thomas Abrahamsson, MD, Universitetssjukhuset, Linköping; Ingela Heimdahl, MD, Sunderby sjukhus, Luleå; Kristbjorg Sveinsdottir, MD, Skånes Universitetssjukhus, Malmö/Lund; Erik Wejryd, MD, Vrinnevisjukhuset, Norrköping; Anna Hedlund, MD, Skellefteå Lasarett, Skellefteå; Maria Katarina Söderberg, MD, Kärnsjukhuset Skaraborg, Skövde; Lars Navér, MD, Karolinska Sjukhuset, Stockholm; Thomas Brune, MD, Södersjuhuset, Stockholm; Jens Bäckström, MD, Länssjukhuset, Sundsvall; Johan Robinson, MD, Norra Älvsborgs Länssjukhus, Trollhättan; Aijaz Farooqi, MD, Norrlands Universitetssjukhus, Umeå; Erik Normann, MD, Akademiska Barnsjukhuset, Uppsala; Magnus Fredriksson, MD, Visby Lasarett, Visby; Anders Palm, MD, Västerviks Sjukhus, Västervik; Urban Rosenqvist, MD, Centrallasarettet, Västerås; Bengt Walde, MD, Centrallasarettet, Växjö; Cecilia Hagman, MD, Lasarettet, Ystad; Andreas Ohlin, MD, Universitetssjukhuset, Örebro; Rein Florell, MD, Örnsköldsviks Sjukhus, Örnsköldsvik; Agneta Smedsaas-Löfvenberg, MD, Östersunds Sjukhus, Östersund. Swiss Neonatal Network (SwissNeoNet): Mark Adams, PhD (Network coordinator), University Hospital Zurich; Philipp Meyer, MD, and Rachel Kusche, MD, Cantonal Hospital, Children's Clinic, Aarau; Sven Schulzke, MD, University Children's Hospital, Basel; Mathias Nelle, MD, University Hospital, Berne; Bendicht Wagner, MD, University Hospital, Berne; Thomas Riedel, MD, Children's Hospital, Chur; Grégoire Kaczala, MD, Cantonal Hospital, Fribourg; Riccardo E. Pfister, MD, University Hospital (HUG), Geneva; Jean-François Tolsa, MD, and Matthias Roth, MD, University Hospital (CHUV), Lausanne; Martin Stocker, MD, Children's Hospital, Lucerne; Bernhard Laubscher, MD, Cantonal Hospital, Neuchatel; Andreas Malzacher, MD, Cantonal Hospital, St. Gallen; John P Micallef, MD, Children's Hospital, St. Gallen; Lukas Hegi, MD, Cantonal Hospital, Winterthur; Dirk Bassler, MD, and Romaine Arlettaz, MD, University Hospital (USZ), Zurich; Vera Bernet, MD, University Children's Hospital, Zurich. Tuscany Neonatal Network (TIN Toscane online): Carlo Dani, MD, Careggi University Hospital, Florence; Patrizio Fiorini, MD, Anna Meyer Children’s University Hospital, Florence; Paolo Ghirri, MD, University Hospital of Pisa, Pisa; Barbara Tomasini, MD, University Hospital of Siena, Siena; Marco Pezzati, MD, San Giovanni di Dio Hospital, Florence; Pier Luigi Vasarri, MD, Santo Stefano Hospital, Prato; Marco Martini, MD, San Donato Hospital, Arezzo, all in Italy. United Kingdom Neonatal Collaborative (UKNC): Anita Mittal, MBChB, Bedford Hospital, Bedford, Bedfordshire; Jonathan Kefas, MBChB, Lister Hospital, Stevenage, Hertfordshire; Anand Kamalanathan, MBChB, Arrowe Park Hospital, Wirral, Merseyside; Jayachandran, MBChB, Leighton Hospital, Crewe, Cheshire; Bill Yoxall, MBChB, Liverpool Women's Hospital, Liverpool, Merseyside; Tim McBride, MBChB, Ormskirk District General Hospital, Ormskirk, Lancashire; Delyth Webb, MBChB, Warrington Hospital, Warrington, Cheshire; Ross Garr, MBChB, Whiston Hospital, Prescot, Merseyside; Ahmed Hassan, MBChB, Broomfield Hospital, Chelmsford, Essex; Priyadarshan Ambadkar, MBChB, James Paget Hospital, Gorleston, Norfolk; Mark Dyke, MBChB, Norfolk & Norwich University Hospital, Norwich, Norfolk; Katharine McDevitt, MBChB, Peterborough City Hospital, Peterborough, Cambridgeshire; Glynis Rewitzky, MBChB, Queen Elizabeth Hospital, King's Lynn, Birmingham, West Midlands; Angela D'Amore, MBChB, Rosie Maternity Hospital, Addenbrookes, Cambridge, Cambridgeshire; Nagesh Panasa, MBChB, North Manchester General Hospital, Manchester, Greater Manchester; Paul Settle, MBChB, Royal Bolton Hospital, Bolton, Lancashire; Natasha Maddock, MBChB, Royal Oldham Hospital, Manchester, Greater Manchester; Ngozi Edi-Osagie, MBChB, St. Mary's Hospital, Manchester, Greater Manchester; Christos Zipitis, MBChB, The Robert Albert Edward Infirmary, Wrightington, Greater Manchester; Carrie Heal, MBChB, Stepping Hill Hospital, Stockport, Cheshire; Jacqeline Birch, MBChB, Tameside General Hospital, Ashton-under-Lyne, Lancashire; Abdul Hasib, MBChB, Darent Valley Hospital, Dartford, Kent; Aung Soe, MBChB, Medway Maritime Hospital, Gillingham, Kent; Niraj Kumar, MBChB, Queen Elizabeth The Queen Mother Hospital, Margate, Kent; Hamudi Kisat, MBChB, Tunbridge Wells Hospital, Tunbridge Wells, Kent; Vimal Vasu, MBChB, William Harvey Hospital, Ashford, Kent; Meera Lama, MBChB, Lancashire Women & Newborn Centre, Burnley, Lancashire; Richa Gupta, MBChB, Royal Preston Hospital, Preston, Lancashire; Chris Rawlingson, MBChB, Victoria Hospital, Blackpool, Blackpool, Lancashire; Tim Wickham, MBChB, Barnet Hospital, Barnet, Hertfordshire; Marice Theron, MBChB, The Royal Free Hospital, Hampstead, London; Giles Kendall, MBChB, University College Hospital, Fitzrovia, London; Aashish Gupta, MBChB, Basildon Hospital, Basildon, Essex; Narendra Aladangady, MBChB, Homerton Hospital, Hackney, London; Imdad Ali, MBChB, Newham General Hospital, Newham, London; Lesley Alsford, MBChB, North Middlesex University Hospital, Edmonton, London; Wilson Lopez, MBChB, Queen's Hospital, Romford, Essex; Vadivelam Murthy, MBChB, The Royal London Hospital, Whitechapel, London; Caroline Sullivan, MBChB, Whipps Cross University Hospital, Whipps Cross, London; Mark Thomas, MBChB, Chelsea & Westminster Hospital, Chelsea, London; Tristan Bate, MBChB, Hillingdon Hospital, Hillingdon, London; Sunit Godambe, MBChB, Queen Charlotte's Hospital, East Acton, London; Sunit Godambe, MBChB, St. Mary's Hospital, Westminister, London; Timothy Watts, MBChB, Guy's & St Thomas’ Hospital, Lambeth, London; Jauro Kuna, MBChB, University Hospital Lewisham, Lewisham, London; John Chang, MBChB, Croydon University Hospital, Croydon, Surrey; Vinay Pai, MBChB, Kingston Hospital, Kingston, London; Charlotte Huddy, MBChB, St George's Hospital, Wandsworth, London; Salim Yasin, MBChB, St. Helier Hospital, Merton, London; Richard Nicholl, MBChB, Northwick Park Hospital, Brent, London; Poornima Pandey, MBChB, Kettering General Hospital, Kettering, Northhamptonshire; Jonathan Cusack, MBChB, Leicester General Hospital, Leicester, Leicestershire; Venkatesh Kairamkonda, MBChB, Leicester Royal Infirmary, Leicester, Leicestershire; Dominic Muogbo, MBChB, Queen's Hospital, Burton upon Trent, Burton upon Trent, Staffordshire; Liza Harry, MBChB, Alexandra Hospital, Redditch, Worcestershire; Phil Simmons, MBChB, Birmingham Heartlands Hospital, Birmingham, West Midlands; Julie Nycyk, MBChB, City Hospital, Birmingham, West Midlands; Phil Simmons, MBChB, Good Hope Hospital, Birmingham, West Midlands; Andrew Gallagher, MBChB, Worcestershire Royal Hospital, Worcester, Worcestershire; Tilly Pillay, MBChB, New Cross Hospital, Wolverhampton, West Midlands; Sanjeev Deshpande, MBChB, Royal Shrewsbury Hospital, Shrewsbury, Shropshire; Mahadevan, MBChB, Russells Hall Hospital, Dudley, West Midlands; Alison Moore, MBChB, University Hospital of North Staffordshire, Hartshill, Staffordshire; Simon Clark, MBChB, The Jessop Wing, Sheffield, South Yorkshire; Mehdi Garbash, MBChB, Darlington Memorial Hospital, Darlington, County Durham; Mithilesh Lal, MBChB, James Cook University Hospital, Middlesborough, North Yorkshire; Majd Abu-Harb, MBChB, Sunderland Royal Hospital, Sunderland, Tyne and Wear; Mehdi Garbash, MBChB, University Hospital of North Durham, Durham, UK; Alex Allwood, MBChB, Derriford Hospital, Plymouth, Devon; Michael Selter, MBChB, North Devon District Hospital, Barnstaple, Devon; Paul Munyard, MBChB, Royal Cornwall Hospital, Truro, Cornwall; David Bartle, MBChB, Royal Devon & Exeter Hospital, Exeter, Devon; Siba Paul, MBChB, Torbay Hospital, Torquay, Devon; Graham Whincup, MBChB, Conquest Hospital, St. Leonards-on-sea, East Sussex; Abdus Mallik, MBChB, Frimley Park Hospital, Frimley, Surrey; Philip Amess, MBChB, Princess Royal Hospital, Telford, Shropshire; Charles Godden, MBChB, Royal Surrey County Hospital, Guildford, Surrey; Philip Amess, MBChB, Royal Sussex County Hospital, Brighton, East Sussex; Peter Reynolds, MBChB, St. Peter's Hospital, Chertsey, Surrey; Indranil Misra, MBChB, Milton Keynes Foundation Trust Hospital, Milton Keynes, Buckinghamshire; Peter De Halpert, MBChB, Royal Berkshire Hospital, Reading, Berkshire; Sanjay Salgia, MBChB, Stoke Mandeville Hospital, Aylesbury, Buckinghamshire; Rekha Sanghavi, MBChB, Wexham Park Hospital, Slough, Berkshire; Ruth Wigfield, MBChB, Basingstoke & North Hampshire Hospital, Basingstoke, Hampshire; Abby Deketelaere, MBChB, Dorset County Hospital, Dorchester, Dorset; Minesh Khashu, MBChB, Poole Hospital NHS Foundation Trust, Poole, Dorset; Michael Hall, MBChB, Princess Anne Hospital, Southampton, Hampshire; Charlotte Groves, MBChB, Queen Alexandra Hospital, Portsmouth, Hampshire; Nick Brown, MBChB, Salisbury District Hospital, Salisbury, Wiltshire; Nick Brennan, MBChB, St. Richard's Hospital, Chichester, West Sussex; Katia Vamvakiti, MBChB, Worthing Hospital, Worthing, West Sussex; John McIntyre, MBChB, Royal Derby Hospital, Derby, Derbyshire; Simon Pirie, MBChB, Gloucestershire Royal Hospital, Gloucester, Gloucestershire; Stephen Jones, MBChB, Royal United Hospital, Avon, Somerset; Paul Mannix, MBChB, Southmead Hospital, Westbury on Trym, Bristol; Pamela Cairns, MBChB, St. Michael's Hospital, Bristol, Bristol; Megan Eaton, MBChB, Yeovil District Hospital, Yeovil, Somerset; Karin Schwarz, MBChB, Calderdale Royal Hospital, Halifax, West Yorkshire; David Gibson, MBChB, Pinderfields General Hospital, Dewsbury, West Yorkshire; Lawrence Miall, MBChB, Leeds Neonatal Service, Leeds, Yorkshire; David Gibson, MBChB, Pinderfields General Hospital, Wakefield, West Yorkshire; Krishnamurthy, MBChB, Walsall Manor Hospital, Walsall, West Midlands.

  • Contributors LG conceptualised and designed the study; acquired, analysed and interpreted data; drafted the manuscript and supervised the study. FR helped conceptualise and design the study, acquired and interpreted data, suggested analyses, reviewed and revised the manuscript for important intellectual content and supervised the study. PS conceptualised and designed the study; acquired, analysed and interpreted data; reviewed and revised the manuscript for important intellectual content; provided administrative, technical and material support and supervised the study. JY acquired and managed data, performed statistical analyses and reviewed and revised the manuscript for important intellectual content. BR, MA, NM, LL, SK, MV, BAD, DB, TI, MN, SH, SKL and KL acquired, analysed and interpreted data and reviewed and revised the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work in ensuring that questions related to its accuracy or integrity are appropriately investigated and resolved.

  • Funding iNeo has been supported by the Canadian Institutes of Health Research (APR-126340 to PSS). The Australian and New Zealand Neonatal Network is predominantly funded by membership contributions from participating centers. The Canadian Neonatal Network is supported by a team grant from the Canadian Institutes of Health Research (CTP 87518), by the Ontario Ministry of Health and Long-Term Care, and by the participating centers. The Finnish Medical Birth Register is governmentally funded and kept by the National Institute for Health and Welfare (THL). The Israel Neonatal Network very low birth weight infant database is partially funded by the Israel Center for Disease Control and the Ministry of Health. The Neonatal Research Network Japan is partly funded by a Health Labour Sciences Research Grant from the Ministry of Health, Labour and Welfare of Japan. The Spanish Neonatal Network is supported by funds from the Spanish Neonatal Society (SENeo). The Swedish Neonatal Quality Register is funded by the Swedish Government (Ministry of Health and Social Affairs), the body of regional health care providers and the participating units. The Swiss Neonatal Network is partially funded by participating units in the form of membership fees. The Tuscany Neonatal Network is funded by the Tuscany Region. The United Kingdom Neonatal Collaborative receives no core funding. This research was also supported by Instituto de Investigación Sanitaria Carlos III (Ministry of Science, Innovation and Universities, Kingdom of Spain) (FIS17/0131 to MV); and RETICS funded by the PN 2018-2021 (Spain), ISCIII-Sub-Directorate General for Research Assessment and Promotion, and the European Regional Development Fund (ERDF) (RD16/0022).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval Each participating network obtained research ethics review and approval for primary data collection from their local institutional review board. Separate data sharing agreements were obtained from each network’s Executive Committee and the iNeo Coordinating Centre at Mount Sinai Hospital, Toronto, Canada. Specific approval for this project was granted by the Mount Sinai Hospital Research Ethics Board (approval number: 18–0318 C) and by the iNeo Steering Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement No data are available. Data transfer agreements from the individual participating networks require that data not be made available to anyone else: data are thus housed only at the study coordinating centre and not available for public access.

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