AAP Sets Guidelines for Neonatal Hypoglycemia

Janis C. Kelly

March 01, 2011

March 1, 2011 — The American Academy of Pediatrics (AAP) Committee on Fetus and Newborn has waged an opinion on neonatal hypoglycemia and produced a "practical guide and algorithm for the screening and subsequent management of neonatal hypoglycemia." The guidelines recommend against routine glucose monitoring except for "high-risk" infants.

The AAP guideline, reported in the March issue of Pediatrics by David H. Adamkin, MD, and colleagues, includes which infants to screen, when to screen, laboratory data, clinical signs, and management.

Dr. Adamkin told Medscape Medical News, "We have no previous guidelines, so this represents the first document on the subject with some guidance provided in a very controversial area. This algorithm will provide some guidance in an area of medicine where evidence is lacking. The point is that babies will be screened, and hopefully managed, to prevent any symptoms from developing. Those with symptoms will be treated promptly."

Dr. Adamkin is professor of pediatrics, director of the Division of Neonatal Medicine, director of the Neonatal Fellowship Program, and director of Neonatal Nutrition Research at the University of Louisville, Kentucky.

William W. Hay, Jr, MD, told Medscape Medical News that the report "does represent the state of the art, as there is very little science." Dr. Hay is professor of pediatrics; codirector, Colorado Clinical Translational Sciences Institute; director, Child and Maternal Health Research; director of the Neonatal Clinical Research Center; and scientific director of the Perinatal Research Center at the University of Colorado in Denver.

The process of weighing the evidence and writing the guidelines was far from smooth or simple.

"I was surprised at the degree of uncertainty and contentiousness that not only the topic had, but the experts and other stakeholders had as we tried to develop these recommendations," Dr. Adamkin said.

No Simple Cut-Off for Safe vs Unsafe Glucose Levels

The AAP paper notes that "there has been no substantial evidence-based progress in defining what constitutes clinically important [neonatal hypoglycemia (NH)], particularly regarding how it relates to brain injury, and that monitoring for, preventing, and treating NH remain largely empirical." Other medical conditions are also a complicating factor, as are differences between infants who are breastfed and those who are not.

Clinically significant NH is the result of an imbalance between glucose supply and other fuels such as ketone bodies, which are released from fat. Blood glucose concentrations often dip to 30 mg/dL within 1 to 2 hours after birth in healthy neonates, but they typically return to more than 45 mg/dL with normal feeding within 12 hours.

According to the guidelines, the infants at highest risk for clinically significant NH are small for gestational age, large for gestational age, born to mothers who have diabetes, or late-preterm. Routine screening and monitoring of blood glucose is recommended only for infants who have these risk factors or who have clinical manifestations of NH such as jitteriness, cyanosis, seizures, an apneic episode, tachypnea, weak or high-pitched cry, floppiness, or lethargy, poor feeding, or eye-rolling.

The guidelines call for immediate intravenous glucose for infants who are symptomatic and have glucose levels lower than 40 mg/dL.

For asymptomatic at-risk infants, the initial feed should be within 1 hour of birth, with glucose screening 30 minutes after the first feed. Because there is no point-of-care screening method reliable enough to be used as the sole method for screening for NH, the blood or plasma glucose concentration must be confirmed by laboratory testing ordered stat.

If NH is suspected, the plasma or blood glucose level should be determined by a laboratory enzymatic method such as glucose oxidase, hexokinase, or dehydrogenase.

Dr. Adamkin and colleagues wrote, "A long delay in processing the specimen can result in a falsely low concentration as erythrocytes in the sample metabolize the glucose in the plasma. This problem can be avoided by transporting the blood in tubes that contain a glycolytic inhibitor such as fluoride."

Early Treatment for Better Safety Margin

The guidelines warn that despite the lack of hard evidence that rapid treatment will prevent neurological damage, "[t]reatment of suspected NH should not be postponed while waiting for laboratory confirmation."

If the initial screen is lower than 25 mg/dL, the guidelines call for feeding and checking again in 1 hour. If the level remains lower than 25 mg/dL, intravenous glucose is called for. If it is 26 to 40 mg/dL, the guidelines call for refeeding and/or intravenous glucose as needed. The target glucose level is 45 mg/dL or higher before routine feeds. The recommended glucose dose is a minibolus 200 mg/kg (dextrose 10% at 2 mL/kg) and/or intravenous infusion at 5 to 8 mg/kg per minute (80 - 100 mL/kg/day).

During the 4 to 24 hours after birth, feeds should be continued every 2 to 3 hours, with glucose screening taking place before each feed. If a screen shows less than 35 mg/dL, the guideline is to feed and check again in 1 hour. If the glucose levels remain lower than 35 mg/dL, the guideline calls for intravenous glucose. If the level is 35 to 45 mg/dL, the guideline calls for refeeding with intravenous glucose as needed to reach the target.

The screening schedule varies slightly. Late preterm (34- to 36-week) infants and small-for-gestational-age infants should be fed every 2 to 3 hours and screened before each feeding for at least the first 24 hours after birth. Infants born to mothers with diabetes and large-for-gestational-age infants with 34 weeks' gestation or more should be screened for the first 12 hours after birth.

At-risk infants should maintain normal plasma glucose on a routine diet for at least 3 feed–fast periods before discharge.

The authors note that plasma glucose levels tend to be lower in breastfed infants, whereas ketone body concentrations tend to be higher than in formula-fed infants. They suggest that breastfed infants might tolerate lower plasma glucose because of the increased ketone concentrations.

Hyperinsulinemic hypoglycemia is described as "the most common cause of severe persistent hypoglycemia in the newborn period" and calls for measurement of blood insulin and glucose at a time when bedside blood glucose is less than 40 mg/dL, as well as endocrinology consult.

Finally, the guidelines stress that managing neonatal hypoglycemia should "not unnecessarily disrupt the mother-infant relationship and breastfeeding."

Dr. Hay said that the recommendations reinforce the conclusions of the National Institute of Child Health and Human Development Workshop on Neonatal Hypoglycemia, which have largely already become standard of care. "So I would not expect this report to change practice, and I would only expect lawyers to really be interested in it, trying as they do to find yet another wrinkle to support their cause," he said.

The guidelines process also threw into sharp focus the gaps in knowledge regarding management of neonatal hypoglycemia. "We need evidence on outcomes of hypoglycemia and on the use of alternative fuels in these patients that may protect them even when they are hypoglycemic," Dr. Adamkin said.

Pediatric endocrinologist Stuart Weinzimer, MD, who reviewed the study for Medscape Medical News, said that new guidelines are likely both to increase clinicians' awareness of and testing for neonatal hypoglycemia and to generate important data clarifying what is "normal."

"Any kind of standardization that will get people to test more is a good thing, since testing is not routinely done. The testing is not difficult, and can even be done using a home blood glucose monitor. I am concerned that the limit for hypoglycemia set by the guidelines for 4 to 24 hours of age (<35 mg/dL) might be too low. The fact that these levels are common in babies does not mean that they are normal, and this points up the lack of data in this area," Dr. Weinzimer said.

"One thing we do know is that unrecognized persistent neonatal hypoglycemia can be very dangerous and can cause irreversible brain damage, although it is transient in most babies. I think these first guidelines will increase awareness, lead to more testing, and encourage more aggressive management of persistent neonatal hypoglycemia," Dr. Weinzimer added. He is associate professor of pediatrics at the Yale School of Medicine in New Haven, Connecticut.

The report is the property of AAP and was not commercially solicited or supported. Dr. Adamkin, the other members of the AAP Committee on Fetus and Newborn, and Dr. Weinzimer have disclosed no relevant financial relationships. Dr. Hay serves as an advisor to the AAP Committee on Fetus and Newborn.

Pediatrics. 2011;127:575-579. Abstract


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