Long-Term Outcomes after Early Neonatal Hyperglycemia in VLBW Infants: A Systematic Review

Megan E. Paulsen, Sarah Jane Brown, Katherine M. Satrom, Johannah M. Scheurer, Sara E. Ramel, Raghavendra B. Rao

Research output: Contribution to journalReview articlepeer-review


INTRODUCTION: Long-term effects of early hyperglycemia in VLBW infants are poorly characterized. The objective of this study was to systematically review the effect of early hyperglycemia on growth, metabolic health, and neurodevelopment after neonatal intensive care unit discharge in VLBW infants.

METHODS: The systematic review was conducted in accordance with the PRISMA guidelines. A study protocol was registered in PROSPERO (CRD42019123335). Data sources included Ovid MEDLINE, Embase, Cochrane Library, CINAHL, and Scopus. Selected studies included infants with a blood glucose concentration >150 mg/dL (8.3 mmol/L) during the first 28 days of life, a gestational age (GA) <32 weeks, and/or a birth weight <1,500 g and longitudinal data on growth, metabolic health, or neurodevelopment outcomes. The GRADE system was used to assess quality of evidence.

RESULTS: Eight studies (n = 987 infants) reported long-term outcomes from 4-month corrected GA to 7 years old. Most studies compared long-term outcomes of preterm infants with and without hyperglycemia. Two studies addressed outcomes related to interventions following early hyperglycemia. Some studies found differences in growth, metabolic health, and neurodevelopment outcomes between VLBW preterm infants with hyperglycemia and without hyperglycemia, while other studies found no differences between groups. The overall graded quality of evidence was low.

CONCLUSIONS: Well-designed randomized controlled and prospective studies are necessary to determine the effect of early hyperglycemia and its treatment on later metabolic and neurodevelopmental outcomes in VLBW infants. Authors propose a potential study design for standardizing the assessment of long-term metabolic and neurodevelopmental outcomes following early hyperglycemia in preterm infants.

Original languageEnglish (US)
Number of pages13
Issue number5
Early online dateAug 19 2021
StatePublished - Aug 19 2021

Bibliographical note

Funding Information:
Dr. Paulsen was supported by the National Institute of Health Building Interdisciplinary Research Careers in Women’s Health grant HD055887. The NIH had no role in the design and conduct of the study.

Publisher Copyright:
© 2021 S. Karger AG, Basel.


  • Glucose
  • Insulin
  • Metabolic
  • Neonatal intensive care unit
  • Neurodevelopment
  • Preterm infant
  • Prognosis

PubMed: MeSH publication types

  • Systematic Review


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