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ABM Clinical Protocol #1: Guidelines for Blood Glucose Monitoring and Treatment of Hypoglycemia in Term and Late-Preterm Neonates, Revised 2014
Abstract
A central goal of The Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient .
Purpose
To provide guidance in the first hours/days of life to:
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Prevent clinically significant hypoglycemia in infants
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Appropriately monitor blood glucose levels in at-risk term and late-preterm infants
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Manage documented hypoglycemia in infants
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Establish and preserve maternal milk supply during medically necessary supplementation for hypoglycemia or during separation of mother and baby
Background
Physiology
The term “hypoglycemia” refers to a low blood glucose concentration. Clinically significant neonatal hypoglycemia reflects an imbalance between the supply and utilization of glucose and alternative fuels and may result from several disturbed regulatory mechanisms. Transient hypoglycemia in the first hours after birth is common, occurring in almost all mammalian newborns. In healthy, term human infants, even if early enteral feeding is withheld, this phenomenon is self-limited, without clinical signs, and considered to be part of adaptation to postnatal life, as glucose levels spontaneously rise with in the first 24 hours after birth (for some, it is even longer but still physiological). Most neonates compensate for this “physiological” low blood glucose with endogenous fuel production through gluconeogenesis, glycogenolysis, and ketogenesis, collectively called “counter-regulation.” Even in those situations where low blood glucose concentrations do develop secondary to prolonged intervals (>8 hours) between breastfeeding, a marked ketogenic response occurs. The enhanced capability of the neonatal brain to utilize ketone bodies provides glucose-sparing fuel to the brain, protecting neurological function. The compensatory provision of alternate fuels constitutes a normal adaptive response to transiently low nutrient intake during the establishment of breastfeeding, resulting in most breastfed infants tolerating lower plasma glucose levels without any significant clinical manifestations or sequelae.
No studies have shown that treating transiently low blood glucose levels results in better short-term or long-term outcomes compared with no treatment, and in fact there is no evidence at all that hypoglycemic infants with no clinical signs benefit from treatment. Increases in neurodevelopmental abnormalities have been found in infants who have hypoglycemia associated with abnormal clinical signs, especially those with severe, persistent hyperinsulinemic hypoglycemia. Rozance and Hay have delineated the conditions that should be present before considering that long-term neurologic impairment might be related to neonatal hypoglycemia. Transient, single, brief periods of hypoglycemia are unlikely to cause permanent neurologic damage. Therefore, the monitoring of blood glucose concentrations in healthy, term, appropriately grown neonates is unnecessary and potentially harmful to parental well-being and the successful establishment of breastfeeding.
Definition of hypoglycemia
The definition of hypoglycemia in the newborn infant has remained controversial because of a lack of significant correlation among plasma glucose concentration, clinical signs, and long-term sequelae. An expert panel convened in 2008 by the U.S. National Institutes of Health concluded that there has been no substantial evidence-based progress in defining what constitutes clinically important neonatal hypoglycemia, particularly regarding how it relates to brain injury. Multiple reviews have concluded that there is no specific plasma or blood glucose concentration or duration of low blood glucose level that can be linked to either clinical signs or permanent neurologic injury. In addition, blood glucose test results vary enormously with the source of the blood sample, the assay method, and whether whole blood, plasma, or serum glucose concentration is determined. Plasma or serum glucose concentrations are 10–15% higher than in whole blood.
Breastfed, formula-fed, and mixed-fed infants follow the same pattern of glucose values, with an initial fall in glucose level over the first 2 hours of life, followed by a gradual rise in glucose level over the next 96 hours, whether fed or not. Artificially fed infants tend to have slightly higher levels of glucose and lower levels of ketone bodies than breastfed infants.
The incidence of “hypoglycemia” varies with the definition. Many authors have suggested numeric definitions of hypoglycemia, usually between 30 and 50 mg/dL (1.7–2.8 mmol/L) and varying by postnatal age. There is no scientific justification for the value of < 47 mg/dL (2.6 mmol/L) that has been adopted by some clinicians. Cornblath et al. summarized the problem as follows:
Significant hypoglycemia is not and cannot be defined as a single number that can be applied universally to every individual patient. Rather, it is characterized by a value(s) that is unique to each individual and varies with both their state of physiologic maturity and the influence of pathology.
A meta-analysis of studies published from 1986 to 1994 looked at low plasma glucose thresholds in term healthy newborns who were mostly mixed fed (breastfed and formula-fed) or formula-fed. It presented statistical ranges of low thresholds for plasma glucose level based on hours after birth in healthy term infants ( Table 1 ). The authors specifically noted that given the known lower plasma glucose levels in healthy term breastfed infants as compared with formula-fed infants, the low thresholds for exclusively breastfed infants might even be lower. Table 1 gives recommendations for this timed threshold approach.
Table 1
Population Low Thresholds: Plasma Glucose Level
| Hour(s) after birth | ≤5 th percentile plasma glucose level |
|---|---|
| 1–2 (nadir) | 28 mg/dL (1.6 mmol/L) |
| 3–47 | 40 mg/dL (2.2/mmol/L) |
| 48–72 | 48 mg/dL (2.7 mmol/L) |
This information is translated into guidelines for clinical intervention by the operational treatment guidance of Cornblath et al. As they stated, an operational threshold is that concentration of plasma or whole blood glucose at which clinicians should consider intervention, based on the evidence currently available in the literature ( Table 2 ). It needs to be underscored that the therapeutic objective (45 mg/dL [2.5 mmol/L]) is different from the operational threshold for intervention (36 mg/dL [2.0 mmol/L]), which is different from the population low thresholds in normal babies with no clinical signs or risk factors who do not need to be treated ( Table 1 ). The higher therapeutic goal was chosen to include a significant margin of safety in the absence of data evaluating the correlation between glucose levels in this range and long-term outcome in full-term infants.
Table 2
Operational Thresholds for Treatment of Plasma Glucose Levels
| Infant | Plan/PGL | Treatment |
|---|---|---|
| Infant with clinical signs | If <45 mg/dL (2.5 mmol/L) | Clinical interventions to increase blood glucose concentration |
| Infants with risk factors a | Initiate glucose monitoring as soon as possible after birth, within 2–3 hours after birth and before feeding, or at any time there are abnormal signs. | Clinical interventions to increase blood glucose concentration: at very low glucose concentration (20–25 mg/dL, 1.1–1.4 mmol/L), intravenous glucose infusion to raise plasma glucose levels to >45 mg/dL (2.5 mmol/L) is indicated. |
| If plasma glucose concentration is <36 mg/dL (2.0 mmol/L), close surveillance should be maintained. Intervention is recommended if plasma glucose remains below this level, does not increase after a feed, or if abnormal clinical signs develop. |
PGL , plasma glucose level.
a See Table 3 .
Given this information, it is clear that routine monitoring of blood glucose in healthy term infants is not only unnecessary, but is instead potentially harmful to the establishment of a healthy mother–infant relationship and successful breastfeeding patterns. This recommendation has been supported by the World Health Organization, the American Academy of Pediatrics, the U.S. National Institutes of Health, and the National Childbirth Trust of the United Kingdom. These organizations all conclude that (1) early and exclusive breastfeeding is safe to meet the nutritional needs of healthy term infants and that (2) healthy term infants do not develop clinically significant hypoglycemia simply as a result of a time-limited duration of underfeeding.
Testing methods
Bedside glucose reagent test strips are inexpensive and practical but are not reliable, with significant variance from true blood glucose levels, especially at low glucose concentrations. Bedside glucose tests may be used for screening, but laboratory levels sent STAT (immediate determination, without delay) (e.g., glucose oxidase, hexokinase, or dehydrogenase method) must confirm results before a diagnosis of hypoglycemia can be made, especially in infants with no clinical signs. Other bedside rapid measurement methods such as reflectance colorimetry and electrode methods may be more accurate. Continuous subcutaneous glucose monitoring, as is used in diabetic patients, has been used experimentally in neonates with good correlation with laboratory glucose values but is not currently recommended for screening.
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