Hypoglycemia and HIE

Initial hypoglycemia and neonatal brain injury in term infants with severe fetal acidemia. Salhab WA, Wyckoff MH, Laptook A, Perlman JM. Pediatrics 2004;114:361-66.

Objective. To determine the potential contribution of initial hypoglycemia to the development of neonatal brain injury in term infants with severe fetal acidemia.

Methods. A retrospective chart review was conducted of 185 term infants who were admitted to the neonatal intensive care unit with an umbilical arterial pH <7.00. Short-term neurologic outcome measures include death as a consequence of severe encephalopathy and evidence of moderate to severe encephalopathy with or without seizures. Hypoglycemia was defined as an initial blood glucose < or =40 mg/dL.

Results. Forty-one (22%) infants developed an abnormal neurologic outcome, including 14 (34%) with severe hypoxic ischemic encephalopathy who died, 24 (59%) with moderate to severe hypoxic ischemic encephalopathy, and 3 (7%) with seizures. Twenty-seven (14.5%) of the 185 infants had an initial blood sugar < or =40 mg/dL. Fifteen (56%) of 27 infants with a blood sugar < or =40 mg/dL versus 26 (16%) of 158 infants with a blood sugar >40 mg/dL had an abnormal neurologic outcome (odds ratio [OR]: 6.3; 95% confidence interval [CI]: 2.6-15.3). Infants with abnormal outcomes and a blood sugar < or =40 mg/dL versus >40 mg/dL had a higher pH (6.86 +/- 0.07 vs. 6.75 +/- 0.09), a lesser base deficit (-19 +/- 4 vs. -23.8 +/- 4 mEq/L), and lower mean arterial blood pressure (34 +/- 10 vs. 45 +/- 14 mm Hg), respectively. There was no difference between groups in the proportion of infants who required cardiopulmonary resuscitation (7 [46%] vs. 15 [57%]) and those with a 5-minute Apgar score <5 (11 [73%] vs. 22 [85%]). By multivariate logistic analysis, 4 variables were significantly associated with abnormal outcome: initial blood glucose < or =40 mg/dL versus >40 mg/dL (OR: 18.5; 95% CI: 3.1-111.9), cord arterial pH < or =6.90 versus >6.90 (OR: 9.8; 95% CI: 2.1-44.7), a 5-minute Apgar score < or =5 versus >5 (OR: 6.4; 95% CI: 1.7-24.5), and the requirement for intubation with or without cardiopulmonary resuscitation versus neither (OR: 4.7; 95% CI: 1.2-17.9).

Conclusion. Initial hypoglycemia is an important risk factor for perinatal brain injury, particularly in depressed term infants who require resuscitation and have severe fetal acidemia. It remains unclear, however, whether earlier detection of hypoglycemia, such as in the delivery room, in this population could modify subsequent neurologic outcome.

Commentary: Oxygen and glucose are both vital substrates for brain metabolism, so it is not surprising that this retrospective study documented poorer short-term neurological outcomes in asphyxiated infants with initial hypoglycemia as opposed to normoglycemia. One might hazard that the initial blood sugar level (in the absence of maternal diabetes) correlates with the cumulative asphyxial insult. Although this paper does not document details of resuscitation, I would guess (given that the average cord pH of all infants was < 6.9) that venous access was achieved rapidly and glucose boluses were administered early. For these reasons, I am skeptical that a trial of early glucose therapy for asphyxiated infants could be designed to demonstrate a clinical benefit. Nonetheless, this study behooves us to consider glucose to be on a par with oxygen and bicarbonate as therapies for the asphyxiated infant. - MLH

Date: 29 Oct 2004
Time: 10:37:03

the assumption that severely acidaemic infants with HIE should be considered in need of glucose could be harmful if the infant has shown an adequate stress reaction and had a stress response causing elevated glucose levels. This reaction was reported in Dawes' the early work on birth asphyxia. We have always advised checking blood glucose before giving bolus glucose in early resuscitation. There might also be a need to consider non-glucose substrate utilization by the brain before attributing outcomes to hypoglycaemia

UserName: Una MacFadyen
Institution: Stilring Royal Infirmaty
telephone: 01786 434000
email: una.macfadyen@fvah.scot.nhs.uk

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