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Original Investigation |

Early Enhanced Parenteral Nutrition, Hyperglycemia, and Death Among Extremely Low-Birth-Weight Infants

Hans Jorgen Stensvold, MD1,2; Kenneth Strommen, MD1; Astri M. Lang, MD, PhD1; Tore G. Abrahamsen, MD, PhD3,4; Eline Kjorsvik Steen, BSc5; Are H. Pripp, PhD6; Arild E. Ronnestad, MD, PhD1,2
[+] Author Affiliations
1Women and Children’s Division, Department of Neonatology, Oslo University Hospital Rikshospitalet, Oslo, Norway
2Norwegian Neonatal Network, Oslo University Hospital Rikshospitalet, Oslo, Norway
3Women and Children’s Division, Department of Pediatrics, Oslo University Hospital, Oslo, Norway
4Faculty of Medicine, University of Oslo, Oslo, Norway
5Medical student at the Faculty of Medicine, University of Oslo, Oslo, Norway
6Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway
JAMA Pediatr. 2015;169(11):1003-1010. doi:10.1001/jamapediatrics.2015.1667.
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Importance  Efforts to optimize early parenteral nutrition (PN) in extremely low-birth-weight (ELBW) infants to promote growth and development may increase hyperglycemia risk. Recent studies have identified an association between early hyperglycemia and adverse outcomes in ELBW infants.

Objectives  To examine the prevalence of early hyperglycemia and clinical outcomes among ELBW infants before (2002-2005) and after (2006-2011) the implementation of an early enhanced PN protocol and to assess the independent effects of early enhanced PN and early hyperglycemia on mortality.

Design, Setting, and Participants  Observational cohort study in a level III neonatal intensive care unit. Prospectively collected clinical data in the neonatal intensive care unit’s medical database, nutritional information, and blood glucose levels were merged for analysis. All ELBW infants born between January 1, 2002, and December 31, 2011, without lethal malformations and still alive at 12 hours of life were eligible for inclusion in the study.

Main Outcomes and Measures  Mortality was the main outcome measure. Severe hyperglycemia was defined as 2 consecutive blood glucose levels exceeding 216 mg/dL at least 3 hours apart. A multivariable logistic regression model was applied to determine the independent effects of early enhanced PN and hyperglycemia on mortality.

Results  In total, 343 infants were included in the study, 129 in a historical comparison group before the enhanced PN protocol and 214 in the early enhanced PN group. Baseline characteristics were similar between the study groups. After the introduction of early enhanced PN, the prevalence of severe hyperglycemia during the first week of life was higher in the early enhanced PN group (11.6% [15 of 129] vs 41.6% [89 of 214], P < .001), as was the mortality (10.9% [14 of 129] vs 24.3% [52 of 214], P = .003). When adjusting for background characteristics, treatment, and nutritional data, early severe hyperglycemia remained a strong independent risk factor for death (odds ratio, 4.68; 95% CI, 1.82-12.03), together with gestational age (odds ratio, 0.62; 95% CI, 0.49-0.79).

Conclusions and Relevance  The implementation of an enhanced PN protocol was correlated with an increased prevalence of severe hyperglycemia and higher mortality. In the multivariable analysis, an enhanced PN regimen per se was not predictive of mortality, whereas early severe hyperglycemia remained strongly predictive of death. To avoid detrimental effects on outcomes in ELBW infants, the optimal composition of early PN to avoid postnatal growth failure must be carefully balanced against hyperglycemia risk.

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Figure.
Total Carbohydrate Intake, Intravenous Glucose Infusion Rate, Calorie Intake, and Proportion of Infants With Severe Hyperglycemia Each Day During the First Week of Life

In D, severe hyperglycemia was defined as 2 consecutive blood glucose levels exceeding 216 mg/dL at least 3 hours apart. To convert glucose level to millimoles per liter, multiply by 0.0555.

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