Neonatal Outcomes in Very Preterm Infants With Severe Congenital Heart Defects: An International Cohort Study
Authors: Norman Mikael , Håkansson Stellan , Kusuda Satoshi , Vento Maximo , Lehtonen Liisa , Reichman Brian , Darlow Brian A. , Adams Mark , Bassler Dirk , Isayama Tetsuya , Rusconi Franca , Lee Shoo , Lui Kei , Yang Junmin , Shah Prakesh S. , Lui Kei , Marshall Peter , Schmidt Peter , Dhawan Anjali , Craven Paul , de Waal Koert , Simmer Karen , Gill Andy , Pillow Jane , Stack Jacqueline , Birch Pita , Cooke Lucy , Casalaz Dan , Holberton Jim , Stewart Alice , Downe Lyn , Stewart Michael , Bajuk Barbara , Berry Andrew , Hunt Rod , Kilburn Charles , De Paoli Tony , Lui Kei , Bolisetty Srinivas , Paradisis Mary , Rieger Ingrid , Koorts Pieter , Kuschel Carl , Doyle Lex , Numa Andrew , Carlisle Hazel , Badawi Nadia , Loughran‐Fowlds Alison , Koh Guan , Davis Jonathan , Luig Melissa , Andersen Chad , Chambers Georgina , Austin Nicola , Lynn Adrienne , Darlow Brian , Edmonds Liza , Mildenhall Lindsay , Buksh Mariam , Battin Malcolm , van den Boom Jutta , Bourchier David , Richardson Vaughan , Dineen Fiona , Rajadurai Victor Samuel , Lam Simon , Fung Genevieve , Shah Prakesh S. , Harrison Adele , Synnes Anne , Ting Joseph , Cieslak Zenon , Sherlock Rebecca , Yee Wendy , Aziz Khalid , Toye Jennifer , Fajardo Carlos , Kalapesi Zarin , Sankaran Koravangattu , Daspal Sibasis , Seshia Mary , Alvaro Ruben , Mukerji Amit , Da Silva Orlando , Nwaesei Chuks , Lee Kyong‐Soon , Dunn Michael , Lemyre Brigitte , Dow Kimberly , Pelausa Ermelinda , Barrington Keith , Drolet Christine , Piedboeuf Bruno , Claveau Martine , Beltempo Marc , Bertelle Valerie , Masse Edith , Canning Roderick , Makary Hala , Ojah Cecil , Monterrosa Luis , Deshpandey Akhil , Afifi Jehier , Kajetanowicz Andrzej , Lee Shoo K. , Andersson Sture , Lehtonen Liisa , Tammela Outi , Sankilampi Ulla , Saarela Timo , Heymann Eli , Zangen Shmuel , Smolkin Tatyana , Mimouni Francis , Bader David , Rothschild Avi , Strauss Zipora , Felszer Clari , Omari Hussam , Tov‐Friedman Smadar Even , Bar‐Oz Benjamin , Feldman Michael , Saad Nizar , Flidel‐Rimon Orna , Weisbrod Meir , Lubin Daniel , Litmanovitz Ita , Kugelman Amir , Shinwell Eric , Klinger Gil , Nijim Yousif , Bin‐Nun Alona , Golan Agneta , Mandel Dror , Fleisher‐Sheffer Vered , Kohelet David , Bakhrakh Lev , Hattori Satoshi , Shirai Masaru , Ishioka Toru , Mori Toshihiko , Amizuka Takasuke , Huchimukai Toru , Yoshida Hiroshi , Sasaki Ayako , Shimizu Junichi , Nakamura Toshihiko , Maruyama Mami , Matsumoto Hiroshi , Hosokawa Shinichi , Taki Atsuko , Nakagawa Machiko , Ko Kyone , Uozumi Azusa , Nakata Setsuko , Shimazaki Akira , Yoda Tatsuya , Numata Osamu , Imamura Hiroaki , Kobayashi Azusa , Tokuriki Shuko , Uchida Yasushi , Arai Takahiro , Ito Mitsuhiro , Ieda Kuniko , Ono Toshiyuki , Hayashi Masashi , Maki Kanemasa , Yamakawa MieToru , Kawai Masahiko , Fujii Noriko , Shiomi Kozue , Nozaki Koji , Wada Hiroshi , Kim Taho , Tokunaga Yasuyuki , Takatera Akihiro , Oshima Toshio , Sumida Hiroshi , Michinomae Yae , Kusumoto Yoshio , Yoshimoto Seiji , Morisawa Takeshi , Ohashi Tamaki , Takahashi Yukihiro , Sugimoto Moriharu , Ono Noriaki , Miyagawa Shinichiro , Saijo Takahiko , Yamagami Takashi , Koyano Kosuke , Kobayashi Shoko , Kanda Takeshi , Sakemi Yoshihiro , Aoki Mikio , Iida Koichi , Goshi Mitsushi , Maruyama Yuko , Avila‐Alvarez Alejandro , Fernandez‐Trisac José Luis , Pico Mª Luz Couce , Fernández Seara María José , Gutiérrez Andrés Martínez , Vizcaíno Carolina , Salvador Iglesias Miriam , Zaplana Honorio Sánchez , Fernández Colomer Belén , García López José Enrique , Mozo Rafael García , Martínez M. Teresa González , Muro Sebastián Mª Dolores , Carbonell Marta Balart , Barnusell Joan Badia , Puiggròs Mònica Domingo , Taulí Corporacio Parc , Aloy Josep Figueras , Mussons Francesc Botet , Sanz Israel Anquela , Galiana Gemma Ginovart , De La Santa H. , Coroleu W. , Iriondo Martin , Castells Vilella Laura , Porta Roser , Demestre Xavier , Martínez Nadal Silvia , de Frutos Martínez Cristina , López Cuesta María Jesús , Mora Dolores Esquivel , Tardío Joaquín Ortiz , Benavente Isabel , Alonso Almudena , Aguilera Olmos Ramón , García Cabezas Miguel A. , Martínez Jiménez Mª Dolores , Jaraba Caballero Mª Pilar , Ordoñez Díaz Mª Dolores , Fagundo Alberto Trujillo , Canals Lluis Mayol , Rodrigo Fermín García‐Muñoz , Martí Lourdes Urquía , Galdo María Fernanda Moreno , Suazo José Antonio Hurtado , López Eduardo Narbona , Fernández José Uberos , Cortajarena Altuna Miguel A. , Muga Zuriarrain Oihana , Mora Navarro David , Domínguez María Teresa , del Prado Mª Yolanda Ruiz , Díez Inés Esteban , Palau Benavides María Teresa , Lapeña Santiago , Prada Teresa , Mir Eduard Soler , Sánchez Araceli Corredera , Vega Enrique Criado , del Prado Náyade , Fernández Cristina , Vilaplana Lucía Cabanillas , Pérez Irene Cuadrado , Gómez Luisa López , Comeche Laura Domingo , Martín Isabel Llana , González Armengod Carmen , Labián Carmen Muñoz , Santos Muñoz Mª José , Bravo Dorotea Blanco , Pérez Vicente , Fernández Mª Dolores Elorza , González Celia Díaz , Segura Susana Ares , Azorín Manuela López , MD Ana Belén Jimenez , Sánchez‐Tamayo Tomás , Moreno Elías Tapia , González María , Sánchez Martínez José Enrique , Lloreda García José María , Orayen Concepción Goñi , González Javier Vilas , Albo María Suárez , Colmenero Eva González , Gutiérrez González Elena Pilar , Vacas del Arco Beatriz , Fernández Josefina Márquez , Gordillo Laura Acosta , Asensio Mercedes Granero , Díaz Carmen Macías , Albújar Mar , Fuster Jorge Pedro , Romero Sabina , Falero Mónica Rivero , Escobar Izquierdo Ana Belén , Estañ Capell Javier , Izquierdo Macián Mª Isabel , Montejo Vicente Mª Mar , Caballero Raquel Izquierdo , Martínez Mª Mercedes , Euba Aintzane , Serna Amaya Rodríguez , de Heredia Goya Juan María López , Legorburu Alberto Pérez , Amorós Ana Gutiérrez , Isabel Víctor Manuel Marugán , González Natalio Hernández , Gracia Segundo Rite , Faci Mª Purificación Ventura , Villagrasa Mª Pilar Samper , Kofron Jiri , Strand Brodd Katarina , Odlind Andreas , Alberg Lars , Arwehed Sofia , Hafström Ola , Kasemo Anna , Nederman Karin , Åhman Lars , Ingemarsson Fredrik , Petersson Henrik , Thurn Pernilla , Albinsson Eva , Selander Bo , Abrahamsson Thomas , Heimdahl Ingela , Sveinsdottir Kristbjorg , Wejryd Erik , Hedlund Anna , Söderberg Maria Katarina , Navér Lars , Brune Thomas , Bäckström Jens , Robinson Johan , Farooqi Aijaz , Normann Erik , Fredriksson Magnus , Palm Anders , Rosenqvist Urban , Walde Bengt , Hagman Cecilia , Ohlin Andreas , Florell Rein , Smedsaas‐Löfvenberg Agneta , Adams Mark , Meyer Philipp , Kusche Rachel , Schulzke Sven , Nelle Mathias , Wagner Bendicht , Riedel Thomas , Kaczala Grégoire , Pfister Riccardo E. , Tolsa Jean‐François , Roth Matthias , Stocker Martin , Laubscher Bernhard , Malzacher Andreas , Micallef John P. , Hegi Lukas , Bassler Dirk , Arlettaz Romaine , Bernet Vera , Dani Carlo , Fiorini Patrizio , Ghirri Paolo , Tomasini Barbara 
Published: February 2020

Background

Very preterm infants are at high risk of death or severe morbidity. The objective was to determine the significance of severe congenital heart defects (
CHDs
) for these risks.

Methods and Results

This cohort study included infants from 10 countries born from 2007–2015 at 24 to 31 weeks’ gestation with birth weights <1500 g. Severe
CHDs
were defined by
International Classification of Diseases, Ninth Revision
(
ICD‐9
) and
Tenth
(
ICD‐10
) codes and categorized as those compromising systemic output, causing sustained cyanosis, or resulting in congestive heart failure. The primary outcome was in‐hospital mortality. Secondary outcomes were neonatal brain injury, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity. Adjusted and propensity score–matched odds ratios (
ORs
) were calculated. Analyses were stratified by type of
CHD
, gestational age, and network. A total of 609 (0.77%) infants had severe
CHD
and 76 371 without any malformation served as controls. The mean gestational age and birth weight were 27.8 weeks and 1018 g, respectively. The mortality rate was 18.6% in infants with
CHD
and 8.9% in controls (propensity score–matched
OR
, 2.30; 95%
CI
, 1.61–3.27). Severe
CHD
was not associated with neonatal brain injury, necrotizing enterocolitis, or retinopathy of prematurity, whereas the
OR
for bronchopulmonary dysplasia increased. Mortality was higher in all types, with the highest propensity score–matched
OR
(4.96; 95% CI, 2.11–11.7) for
CHD
causing congestive heart failure. While mortality did not differ between groups at <27 weeks’ gestational age, adjusted
OR
for mortality in infants with CHD increased to 10.9 (95% CI, 5.76–20.70) at 31 weeks’ gestational age. Rates of
CHD
and mortality differed significantly between networks.

Conclusions

Severe
CHD
is associated with significantly increased mortality in very preterm infants.