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Original Investigation
September 2018

Association of Maternal Diabetes With Neonatal Outcomes of Very Preterm and Very Low-Birth-Weight Infants: An International Cohort Study

Author Affiliations
  • 1Department of Medicine, Clinical Epidemiology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
  • 2Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
  • 3Department of Pediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada
  • 4Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
  • 5Maternal-Infant Care Research Centre, Mount Sinai Hospital, Toronto, Ontario, Canada
  • 6Unit of Epidemiology Meyer Children’s University Hospital and Regional Health Agency, Florence, Italy
  • 7Israel Neonatal Network, Gertner Institute for Epidemiology and Health Policy Research, Tel Hashomer, Israel
  • 8Neonatal Data Analysis Unit, Section of Neonatal Medicine, Department of Medicine, Imperial College London, Chelsea and Westminster campus, London, England
  • 9Division of Neonatology, National Center for Child Health and Development, Tokyo, Japan
  • 10Turku University Hospital and University of Turku, Finland
  • 11Department of Clinical Science/Pediatrics, Umeå University, Umeå, Sweden
  • 12Department of Pediatrics, McGill University Health Centre, Montreal, Québec, Canada
  • 13Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
  • 14Department of Neonatal Medicine, Karolinska University Hospital, Stockholm, Sweden
JAMA Pediatr. 2018;172(9):867-875. doi:10.1001/jamapediatrics.2018.1811
Key Points

Question  Does maternal diabetes, a strong risk factor for very preterm birth, have an association with risks of in-hospital mortality or severe neonatal morbidity in very preterm infants?

Findings  In this international cohort study of singleton infants born very preterm, the risk of in-hospital mortality or severe neonatal morbidity for infants who were born to mothers with diabetes was not significantly different from the risk of infants who were born to mothers without diabetes.

Meaning  Maternal diabetes is not associated with an excess risk of in-hospital mortality or severe morbidity in infants born very preterm in high-income countries.


Importance  Diabetes in pregnancy is associated with a 2-times to 3-times higher rate of very preterm birth than in women without diabetes. Very preterm infants are at high risk of death and severe morbidity. The association of maternal diabetes with these risks is unclear.

Objective  To determine the associations between maternal diabetes and in-hospital mortality, as well as neonatal morbidity in very preterm infants with a birth weight of less than 1500 g.

Design, Setting, Participants  This retrospective cohort study was conducted at 7 national networks in high-income countries that are part of the International Neonatal Network for Evaluating Outcomes in Neonates and used prospectively collected data on 76 360 very preterm, singleton infants without malformations born between January 1, 2007, and December 31, 2015, at 24 to 31 weeks’ gestation with birth weights of less than 1500 g, 3280 (4.3%) of whom were born to diabetic mothers.

Exposures  Any type of diabetes during pregnancy.

Main Outcomes and Measures  The primary outcome was in-hospital mortality. The secondary outcomes were severe neonatal morbidities, including intraventricular hemorrhages of grade 3 to 4, cystic periventricular leukomalacia, retinopathy of prematurity needing treatment and bronchopulmonary dysplasia, and other morbidities, including respiratory distress, treated patent ductus arteriosus, and necrotizing enterocolitis. Odds ratios (ORs) with 95% confidence intervals were estimated, adjusted for potential confounders, and stratified by gestational age (GA), sex, and network.

Results  The mean (SD) birth weight of offspring born to mothers with diabetes was significantly higher at 1081 (262) g than in offspring born to mothers without diabetes (mean [SD] birth weight, 1027 [270] g). Mothers with diabetes were older and had more hypertensive disorders, antenatal steroid treatments, and deliveries by cesarean delivery than mothers without diabetes. Infants of mothers with diabetes were born at a later GA than infants of mothers without diabetes. In-hospital mortality (6.6% vs 8.3%) and the composite of mortality and severe morbidity (31.6% vs 40.6%) were lower in infants of mothers with diabetes. However, in adjusted analyses, no significant differences in in-hospital mortality (adjusted OR, 1.16 (95% CI, 0.97-1.39) or the composite of mortality and severe morbidity (adjusted OR, 0.99 (95% CI, 0.88-1.10) were observed. With few exceptions, outcomes of infants born to mothers with and without diabetes were similar regardless of infant sex, GA, or country of birth.

Conclusions and Relevance  In high-resource settings, maternal diabetes is not associated with an increased risk of in-hospital mortality or severe morbidity in very preterm infants with a birth weight of fewer than 1500 g.