AAP 新生儿血糖监测指南

DOI: 10.1542/peds.2010-3851 2011;127;575-579; originally published online Feb 28, 2011; Pediatrics Committee on Fetus and Newborn Postnatal Glucose Homeostasis in Late-Preterm and Term Infants http://www.pediatrics.org/cgi/content/full/127/3/575 located on the World Wide Web at: The online version of this article, along with updated information and services, is rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275. Grove Village, Illinois, 60007. Copyright © 2011 by the American Academy of Pediatrics. All and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk publication, it has been published continuously since 1948. PEDIATRICS is owned, published, PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly by on March 1, 2011 www.pediatrics.orgDownloaded from Clinical Report—Postnatal Glucose Homeostasis in Late-Preterm and Term Infants abstract This report provides a practical guide and algorithm for the screening and subsequent management of neonatal hypoglycemia. Current evi- dence does not support a specific concentration of glucose that can discriminate normal from abnormal or can potentially result in acute or chronic irreversible neurologic damage. Early identification of the at-risk infant and institution of prophylactic measures to prevent neo- natal hypoglycemia are recommended as a pragmatic approach de- spite the absence of a consistent definition of hypoglycemia in the literature. Pediatrics 2011;127:575–579 INTRODUCTION This clinical report provides a practical guide for the screening and subsequentmanagement of neonatal hypoglycemia (NH) in at-risk late- preterm (34–366⁄7 weeks’ gestational age) and term infants. An expert panel convened by the National Institutes of Health in 2008 concluded that there has been no substantial evidence-based progress in defining what constitutes clinically important NH, particularly regarding how it relates to brain injury, and that monitoring for, preventing, and treat- ing NH remain largely empirical.1 In addition, the simultaneous occur- rence of othermedical conditions that are associatedwith brain injury, such as hypoxia-ischemia or infection, could alone, or in concert with NH, adversely affect the brain.2–5 For these reasons, this report does not identify any specific value or range of plasma glucose concentra- tions that potentially could result in brain injury. Instead, it is a prag- matic approach to a controversial issue for which evidence is lacking but guidance is needed. BACKGROUND Blood glucose concentrations as low as 30 mg/dL are common in healthy neonates by 1 to 2 hours after birth; these low concentrations, seen in all mammalian newborns, usually are transient, asymptomatic, and considered to be part of normal adaptation to postnatal life.6–8 Most neonates compensate for “physiologic” hypoglycemia by produc- ing alternative fuels including ketone bodies, which are released from fat. Clinically significant NH reflects an imbalance between supply and use of glucose and alternative fuels and may result from a multitude of disturbed regulatory mechanisms. A rational definition of NH must account for the fact that acute symptoms and long-term neurologic sequelae occur within a continuum of low plasma glucose values of varied duration and severity. David H. Adamkin, MD and COMMITTEE ON FETUS AND NEWBORN KEY WORDS newborn, glucose, neonatal hypoglycemia, late-preterm infant ABBREVIATIONS NH—neonatal hypoglycemia D10W—dextrose 10% in water This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors. All authors have filed conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American Academy of Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of this publication. The guidance in this report does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate. www.pediatrics.org/cgi/doi/10.1542/peds.2010-3851 doi:10.1542/peds.2010-3851 All clinical reports from the American Academy of Pediatrics automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time. PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). Copyright © 2011 by the American Academy of Pediatrics FROM THE AMERICAN ACADEMY OF PEDIATRICS Guidance for the Clinician in Rendering Pediatric Care PEDIATRICS Volume 127, Number 3, March 2011 575 by on March 1, 2011 www.pediatrics.orgDownloaded from The authors of several literature re- views have concluded that there is not a specific plasma glucose concentra- tion or duration of hypoglycemia that can predict permanent neurologic in- jury in high-risk infants.3,9,10 Data that have linked plasma glucose concentra- tionwith adverse long-termneurologic outcomes are confounded by variable definitions of hypoglycemia and its du- ration (seldom reported), the omis- sion of control groups, the possible in- clusion of infants with confounding conditions, and the small number of asymptomatic infants who were fol- lowed.3,11,12 In addition, there is no sin- gle concentration or range of plasma glucose concentrations that is associ- ated with clinical signs. Therefore, there is no consensus regarding when screening should be performed and which concentration of glucose re- quires therapeutic intervention in the asymptomatic infant. The generally adopted plasma glucose concentra- tion that defines NH for all infants (�47 mg/dL) is without rigorous sci- entific justification.1,3,4,9,12 WHICH INFANTS TO SCREEN Because plasma glucose homeostasis requires glucogenesis and ketogene- sis to maintain normal rates of fuel use,13 NH most commonly occurs in in- fants with impaired glucogenesis and/or ketogenesis,14,15 which may oc- cur with excessive insulin production, altered counterregulatory hormone production, an inadequate substrate supply,14–16 or a disorder of fatty acid oxidation.15 NH occurs most commonly in infants who are small for gesta- tional age, infants born to mothers who have diabetes, and late-preterm infants. It remains controversial whether otherwise normal infants who are large for gestational age are at risk of NH, largely because it is diffi- cult to exclude maternal diabetes or maternal hyperglycemia (prediabe- tes) with standard glucose-tolerance tests. A large number of additional maternal and fetal conditions may also place in- fants at risk of NH. Clinical signs are common with these conditions, and it is likely that patients with such a con- dition are already being monitored and that plasma glucose analyses are being performed.13,17 Therefore, for practicality, “at risk” in the manage- ment approach outlined in Fig 1 in- cludes only infants who are small for gestational age, infants who are large for gestational age, infants who were born to mothers who have diabetes, and late-preterm infants. Routine screening andmonitoring of blood glu- cose concentration is not needed in healthy term newborn infants after an entirely normal pregnancy and deliv- ery. Blood glucose concentration should only be measured in term in- fants who have clinical manifestations or who are known to be at risk. Plasma or blood glucose concentration should bemeasured as soon as possible (min- utes, not hours) in any infant whoman- ifests clinical signs (see “Clinical Signs”) compatible with a low blood glucose concentration (ie, the symp- tomatic infant). Breastfed term infants have lower con- centrations of plasma glucose but higher concentrations of ketone bodies than do formula-fed infants.13,17 It is pos- tulated that breastfed infants tolerate lower plasma glucose concentrations withoutanyclinicalmanifestationsorse- quelae of NH because of the increased ketone concentrations.8,12–14 WHEN TO SCREEN Neonatal glucose concentrations de- crease after birth, to as low as 30 mg/dL during the first 1 to 2 hours af- ter birth, and then increase to higher and relatively more stable concentra- tions, generally above 45 mg/dL by 12 hours after birth.6,7 Data on the optimal timing and intervals for glucose screening are limited. It is controver- sial whether to screen the asymptom- atic at-risk infant for NH during this FIGURE 1 Screening for and management of postnatal glucose homeostasis in late-preterm (LPT 34–366⁄7 weeks) and term small-for-gestational age (SGA) infants and infants who were born to mothers with diabetes (IDM)/large-for-gestational age (LGA) infants. LPT and SGA (screen 0–24 hours), IDM and LGA �34 weeks (screen 0–12 hours). IV indicates intravenous. 576 FROM THE AMERICAN ACADEMY OF PEDIATRICS by on March 1, 2011 www.pediatrics.orgDownloaded from normal physiologic nadir. No studies have demonstrated harm from a few hours of asymptomatic hypoglycemia during this normal postnatal period of establishing “physiologic glucose homeostasis.”9 Infants born to mothers with diabetes may develop asymptomatic NH as early as 1 hour after birth18 and usually by 12 hours of age.18 In contrast, infants who are large for gestational age or small for gestational age may develop low plasma glucose concentrations at as early as 3 hours of age,19 and these infantsmay be at risk of NH for up to 10 days after birth.20 Therefore, at-risk in- fants should be screened for NH with a frequency and duration related to risk factors specific to the individual in- fant.5 Screening the asymptomatic at- risk infant can be performed within the first hours of birth and continued throughmultiple feed-fast cycles. Late- preterm infants and infants who are small for gestational age should be fed every 2 to 3 hours and screened before each feeding for at least the first 24 hours. After 24 hours, repeated screening before feedings should be continued if plasma glucose concen- trations remain lower than 45 mg/dL. LABORATORY DATA When NH is suspected, the plasma or blood glucose concentration must be determined immediately by using one of the laboratory enzymatic methods (eg, glucose oxidase, hexokinase, or dehydrogenase method). Plasma blood glucose values tend to be ap- proximately 10% to 18% higher than whole-blood values because of the higher water content of plasma.21,22 Although a laboratory determination is the most accurate method of measur- ing the glucose concentration, the re- sults may not be available quickly enough for rapid diagnosis of NH, which thereby delays the initiation of treatment.23 Bedside reagent test-strip glucose analyzers can be used if the test is performed carefully and the cli- nician is aware of the limited accuracy of these devices. Rapid measurement methods available at the bedside in- clude the handheld reflectance color- imeter and electrode methods. The blood sample is usually obtained from a warmed heel. Test-strip results demonstrate a rea- sonable correlation with actual plasma glucose concentrations, but the variation from the actual level may be as much as 10 to 20 mg/dL.24–27 Un- fortunately, this variation is greatest at low glucose concentrations. There is no point-of-care method that is suffi- ciently reliable and accurate in the low range of blood glucose to allow it to be used as the sole method for screening for NH. Because of limitations with “rapid” bedside methods, the blood or plasma glucose concentration must be con- firmed by laboratory testing ordered stat. 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. Screening of the at-risk infant for NH and institution of prophylactic measures to prevent prolonged or symptomatic NH is a reasonable goal. Treatment of sus- pected NH should not be postponed while waiting for laboratory confirma- tion. However, there is no evidence to show that such rapid treatment will mit- igate neurologic sequelae. CLINICAL SIGNS The clinical signs of NH are not specific and include a wide range of local or generalized manifestations that are common in sick neonates.12,13,17 These signs include jitteriness, cyanosis, sei- zures, apneic episodes, tachypnea, weak or high-pitched cry, floppiness or lethargy, poor feeding, and eye-rolling. It is important to screen for other pos- sible underlying disorders (eg, infec- tion) as well as hypoglycemia. Such signs usually subside quickly with nor- malization of glucose supply and plasma concentration.9,13 Coma and seizures may occur with prolonged NH (plasma or blood glucose concentra- tions lower than 10 mg/dL range) and repetitive hypoglycemia. The more se- rious signs (eg, seizure activity) usu- ally occur late in severe and pro- tracted cases of hypoglycemia and are not easily or rapidly reversed with glu- cose replacement and normalization of plasma glucose concentrations.28–30 Development of clinical signs may be ameliorated by the presence of alter- native substrates.31 Because avoidance and treatment of cerebral energy deficiency is the prin- cipal concern, greatest attention should be paid to neurologic signs. To attribute signs and symptoms to NH, Cornblath et al12 have suggested that the Whipple triad be fulfilled: (1) a low blood glucose concentration; (2) signs consistent with NH; and (3) resolution of signs and symptoms after restoring blood glucose concentrations to nor- mal values.12 MANAGEMENT Any approach tomanagement needs to account for the overall metabolic and physiologic status of the infant and should not unnecessarily disrupt the mother-infant relationship and breast- feeding. The definition of a plasma glu- cose concentration at which interven- tion is indicated needs to be tailored to the clinical situation and the particular characteristics of a given infant. For example, further investigation and im- mediate intravenous glucose treat- ment might be instituted for an infant with clinical signs and a plasma glu- cose concentration of less than 40 mg/ FROM THE AMERICAN ACADEMY OF PEDIATRICS PEDIATRICS Volume 127, Number 3, March 2011 577 by on March 1, 2011 www.pediatrics.orgDownloaded from dL, whereas an at-risk but asymptom- atic term formula-fed infant may only require an increased frequency of feeding and would receive intravenous glucose only if the glucose values de- creased to less than 25 mg/dL (birth to 4 hours of age) or 35 mg/dL (4–24 hours of age).32 Follow-up glucose con- centrations and clinical evaluation must always be obtained to ensure that postnatal glucose homeostasis is achieved and maintained. Because severe, prolonged, symptom- atic hypoglycemia may result in neuro- nal injury,27,28,32 prompt intervention is necessary for infants who manifest clinical signs and symptoms. A reason- able (although arbitrary) cutoff for treating symptomatic infants is 40mg/ dL. This value is higher than the physi- ologic nadir and higher than concen- trations usually associated with clinical signs. A plasma sample for a laboratory glucose determination needs to be obtained just before giving an intravenous “minibolus” of glucose (200mg of glucose per kg, 2mL/kg dex- trose 10% in water [D10W], intrave- nously) and/or starting a continuous infusion of glucose (D10W at 80–100 mL/kg per day). A reasonable goal is to maintain plasma glucose concentra- tions in symptomatic infants between 40 and 50 mg/dL. Figure 1 is a guideline for the screen- ing and management of NH in late- preterm infants and term infants who were born to mothers with diabetes, small for gestational age, or large for gestational age. In developing a prag- matic approach to the asymptomatic at-risk infant during the first 24 hours after birth, mode of feeding, risk fac- tors, and hours of age were consid- ered. This strategy is based on the fol- lowing observations from Cornblath and Ichord13: (1) almost all infants with proven symptomatic NH during the first hours of life have plasma glucose concentrations lower than 20 to 25 mg/dL; (2) persistent or recurrent NH syndromes present with equally low plasma glucose concentrations; and (3) little or no evidence exists to indi- cate that asymptomatic NH at any con- centration of plasma glucose in the first days of life results in any adverse sequelae in growth or neurologic development.13 Figure 1 is divided into 2 time periods (birth to 4 hours and 4–12 hours) and accounts for the changing values of glucose that occur over the first 12 hours after birth. The recommended values for intervention are intended to provide a margin of safety over con- centrations of glucose associated with clinical signs. The intervention recom- mendations also provide a range of values over which the clinician can de- cide to refeed or provide intravenous glucose. The target glucose concentra- tion is greater than 45 mg/dL before each feeding. At-risk infants should be fed by 1 hour of age and screened 30 minutes after the feeding. This recom- mendation is consistent with that of the World Health Organization. Gavage feeding may be considered in infants who are not nippling well. Glucose screening should continue until 12 hours of age for infants born to moth- ers with diabetes and those who are large for gestational age and maintain plasma glucose concentrations of greater than 40 mg/dL. Late-preterm infants and infants who are small for gestational age require glucose moni- toring for at least 24 hours after birth, because they may be more vulnerable to low glucose concentrations, espe- cially if regular feedings or intrave- nous fluids are not yet established.20 If inadequate postnatal glucose ho- meostasis is documented, the clinician must be certain that the infant can maintain normal plasma glucose con- centrations on a routine diet for a rea- sonably extended period (through at least 3 feed-fast periods) before dis- charge. It is recommended that the at- risk asymptomatic infant who has glu- cose concentrations of less than 25 mg/dL (birth to 4 hours of age) or less than 35 mg/dL (4–24 hours of age) be refed and that the glucose value be re- checked 1 hour after refeeding. Subse- quent concentrations lower than 25 mg/dL, or lower than 35mg/dL, respec- tively, after attempts to refeed, neces- sitate treatment with intravenous glu- cose. Persistent hypoglycemia can be treated with aminibolus (200mg/kg [2 mL/kg] D10W) and/or intravenous infu- sion of D10W at 5 to 8mg/kg perminute, 80 to 100 mL/kg per day; the goal is to achieve a plasma glucose concentra- tion of 40 to 50 mg/dL (higher concen- trations will only stimulate further in- sulin secretion). If it is not possible to maintain blood glucose concentra- tions of greater than 45 mg/dL after 24 hours of using this rate of glucose in- fusion, consideration should be given to the possibility of hyperinsulinemic hypoglycemia, which is the most com- mon cause of severe persistent hypo- glycemia in the newborn period. A blood sample should be sent for mea- surement of insulin along with a glu- cose concentration at the time when a bedside blood glucose concentration is less than 40 mg/dL, and an endocri- nologist should be consulted. SUMMARY Current evidence does not support a specific concentration of glucose that can discriminate euglycemia from hy- poglycemia or can predict that acute or chronic irreversible neurologic damage will result. Therefore, similar to the Canadian Paediatric Society guidelines, a significantly low concen- tration of glucose in plasma should be reliably established and treated to re- store glucose values to a normal phys- iologic range.5 Recognizing infants at risk of disturbances in postnatal glu- cose homeostasis and providing a margin of safety by early measures to 5