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

Abstract

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> Eight studies (<i>n</i> = 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. <b><i>Conclusions:</i></b> 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.

Neonatal Hyperglycemia and Neurodevelopmental Outcomes in Preterm Infants: A Review

“…Our findings agree with other recent reviews on the subject [ 35 , 36 ]: while hyperglycemia negatively impacts short-term clinical outcomes in preterm infants [ 15 ], more uncertainties remain about the impact of hyperglycemia on long-term outcomes. The variable definition of a glucose threshold for hyperglycemia in this population contributes to conclusions drawn on this topic.…”

“…The variable definition of a glucose threshold for hyperglycemia in this population contributes to conclusions drawn on this topic. Paulsen et al [ 36 ] underlined the critical need for well-designed studies that could provide stronger evidence on this topic. Unlike Paulsen et al [ 36 ], we focused only on neurological outcome, and we used stricter criteria, excluding studies without a control group.…”

“…Paulsen et al [ 36 ] underlined the critical need for well-designed studies that could provide stronger evidence on this topic. Unlike Paulsen et al [ 36 ], we focused only on neurological outcome, and we used stricter criteria, excluding studies without a control group. Our review includes two more recent studies with larger sample sizes: 533 patients in Zamir at al.…”

Risk Factors and Outcomes of Hyperglycemia in Low Birth Weight Infants: A Prospective Observational Study

“…Later, Beardsall et al (25) revealed that although early elective insulin therapy reduces hyperglycemia, it dramatically raises the risk of hypoglycemia and mortality by the first 28 days of life, raising doubts about its effectiveness in the prevention and treatment of hyperglycemia in premature infants. More recently, the long-term effects of early hyperglycemia in VLBW infants did not yield reliable advice for how to address the condition (26) .…”

Early Hyperglycemia in Very Preterm Infants Is Associated with Reduced White Matter Volume and Worse Cognitive and Motor Outcomes at 2.5 Years

“…Although several studies have demonstrated the risks associated with hyperglycemia, insulin treatment has not been associated with clear benefits [14]. Little is known about the long-term consequences of hyperglycemia in surviving VPT infants, although available data indicate an increased risk for adverse outcomes [15, 16]. Furthermore, since most studies have focused on extremely low birth weight or extremely preterm (EPT) infants, i.e., with a gestational age (GA) <28 weeks, less is known about potential effects of hyperglycemia in more mature VPT infants (GA <28–31 weeks).…”