Definition Of Neonatal Hypoglycaemia Research Articles

New approaches to screening and management of neonatal hypoglycemia based on improved understanding of the molecular mechanism of hypoglycemia.

For the past 70 years, controversy about hypoglycemia in newborn infants has focused on a numerical "definition of neonatal hypoglycemia", without regard to its mechanism. This ignores the purpose of screening newborns for hypoglycemia, which is to identify those with pathological forms of hypoglycemia and to prevent hypoglycemic brain injury. Recent clinical and basic research indicates that the three major forms of neonatal hypoglycemia are caused by hyperinsulinism (recognizing also that other rare hormonal or metabolic conditions may also present during this time frame). These include transitional hypoglycemia, which affects all normal newborns in the first few days after birth; perinatal stress-induced hypoglycemia in high-risk newborns, which afflicts ∼1 in 1,200 newborns; and genetic forms of congenital hyperinsulinism which afflict ∼1 in 10,000-40,000 newborns. (1) Transitional hyperinsulinism in normal newborns reflects persistence of the low glucose threshold for insulin secretion during fetal life into the first few postnatal days. Recent data indicate that the underlying mechanism is decreased trafficking of ATP-sensitive potassium channels to the beta-cell plasma membrane, likely a result of the hypoxemic state of fetal life. (2) Perinatal stress-induced hyperinsulinism in high-risk infants appears to reflect an exaggeration of this normal low fetal glucose threshold for insulin release due to more severe and prolonged exposure to perinatal hypoxemia. (3) Genetic hyperinsulinism, in contrast, reflects permanent genetic defects in various steps controlling beta-cell insulin release, such as inactivating mutations of the K ATP-channel genes. The purpose of this report is to review our current knowledge of these three major forms of neonatal hyperinsulinism as a foundation for the diagnosis and management of hypoglycemia in newborn infants. This includes selection of appropriate interventions based on underlying disease mechanism; combined monitoring of both plasma glucose and ketone levels to improve screening for infants with persistent forms of hypoglycemia; and ultimately to ensure that infants at risk of persistent hyperinsulinemic hypoglycemia are recognized prior to discharge from the nursery.

Glucose levels in first 3 days and neurodevelopmental outcome at 1 year in low birth weight infants: A cohort study

Background: Definition of neonatal hypoglycemia is still controversial. Objective: To find the effect of blood glucose (BG) levels in the first 3 days of life, on developmental outcome at 1 year in low birth weight neonates <2000 g. Methods: A prospective cohort study was conducted in tertiary level neonatal intensive care unit and follow-up clinic in south India. Intramural neonates admitted from September 2009 to August 2010 were enrolled. Perinatal and neonatal variables were recorded. Respiratory support, fluids, and feeding management were based on the standard protocols. BG was measured within 2 h, then 6 hourly for 72 h by glucometerand BG <50 mg% was analyzed by hexokinase method. Infants were followed until 1 year corrected age and development age (DA) assessed by Developmental Assessment Scales for Indian Infants (DASII). Motor and mental DA at various BG levels were compared. Composite outcome of motor or mental developmental delay; or cerebral palsy or hearing impairment or visual impairment was analyzed, and logistic regression analysis was performed. Results: The mean birth weight and gestation of the study group (n=129) was 1493 g and 32.5 weeks. The 10th centile of BG in the first 72 h was 51 mg%. BG below 10th centile was seen in 60 infants. The mean motor and mental DA of the infants by DASII assessment at 1 year was 11.3 and 11.5 months, respectively. The motor DA and mental DA were significantly higher until 50 mg% lowest BG level, and positive correlation was seen (r=0.26 motor, 0.2 mental DA). Mean BG level, the presence of symptoms; number of episodes or small for gestation did not influence the DA. The adjusted odds for poor composite outcome when BG was below 51 mg% is 2.83 (0.65-12.3). Conclusion: Even though high-risk neonates with BG <51 mg% have a lower motor DA and mental DA at 1 year, than neonates with BG >50 mg%; other morbidities do determine their composite outcome.

Definition of neonatal hypoglycaemia: time for a rethink?

In 1989, I commenced a research project to investigate the processes of metabolic adaptation after birth. One aspect was to investigate the endocrine and metabolic responses to neonatal hypoglycaemia.1 ,2...

Neonatal glucose metabolism in offspring of mothers with varying degrees of hyperglycemia during pregnancy

The definition of neonatal hypoglycemia is controversial. Operational thresholds of blood glucose values at which intervention should be considered have been proposed. IDM and GDM infants frequently exhibit a pronounced drop of plasma glucose immediately after birth. This exaggerated physiological decline of glucose is transient and is seldom accompanied by suppressed lipolysis or clinical symptoms. It is generally attributed to hyperinsulinism elicited by maternal hyperglycemia. Alternative substrates for CNS i.e. lactate and astrocyte glycogen may explain lack of symptoms. Similarly low glucose values later on may cause clinical symptoms. Glucose production rates vary from attenuated to normal likely reflecting differences in maternal glycemic control. The HAPO study of around 25,000 non-diabetic pregnancies revealed strong associations between glucose values (75g OGTT) and increased fetal size and hyperinsulinemia at birth - findings adding strong support to the maternal hyperglycemia - fetal hypinsulinism theory. Mothers with the highest fasting glucose had infants with the highest frequency of clinical neonatal hypoglycaemia (4,6%).

Survey of the definition and screening of neonatal hypoglycaemia in Australia.

To determine the approach to identifying neonatal hypoglycaemia and the definition of neonatal hypoglycaemia used by neonatal paediatricians in Australian Level 3 neonatal intensive care units (NICU). A questionnaire was sent to the 101 neonatal paediatricians in the 22 Level 3 NICU in Australia asking their method of screening for, and definition of, neonatal hypoglycaemia. Responses were received from 70 neonatal paediatricians, including all 22 directors. A bedside glucose meter is used in 19 of 22 NICU to screen for hypoglycaemia, whilst one NICU uses a glucose analyzer and another NICU uses a visual colour comparison method. One NICU does not screen, but has blood glucose measured in a satellite laboratory. If the screening method suggests hypoglycaemia, 62 of 63 neonatal paediatricians proceed to blood glucose determination in a laboratory, mostly using plasma samples. Based on the laboratory measurement, the definition of neonatal hypoglycaemia ranged from < 1.1 to 3.0 mmol/L. The majority of neonatal paediatricians in Australian NICU screen for neonatal hypoglycaemia using a bedside glucose meter. There is a wide range in the definition of neonatal hypoglycaemia from < 1.1 to 3.0 mmol/L.

Definition of neonatal hypoglycaemia in 1986 and 1992: is there a change? : T.H.H.G. Koh and S.K. Vong, Department of Neonatology, Children's Hospital, Sydney, Australia 2050 (Australia) and Department of Pharmacy, Chase Farm Hospital, London (UK)

Definition of neonatal hypoglycaemia in 1986 and 1992: is there a change? : T.H.H.G. Koh and S.K. Vong, Department of Neonatology, Children's Hospital, Sydney, Australia 2050 (Australia) and Department of Pharmacy, Chase Farm Hospital, London (UK)

13 THE METABOLIC ADAPTATION OF HEALTHY TERM INFANTS IN THE FIRST POSTNATAL WEEK

In the light of recent controversy regarding the definition of neonatal hypoglycaemia, it is important to document blood glucose (BG) levels of healthy neonates in relation to other metabolic fuels. A cross sectional study was performed, taking pre-feed samples from 149 infants in the first seven days. The overall mean BG concentration for the week was 3-67 mmol/l (range 1.50-6.18 mmol/l). The widest range of values was seen on the first day. 14% of all infants studied had BG levels ≤ 2.6 mmol/l, with all but two such low levels occurring within the first three days. The maximum mean ketone body levels were found on days 2 and 3 (max. level 2.568 mmol/l). The ketone body: glucose ratio is low on the first day, despite low blood glucose levels, indicating an immaturity of counterregulatory ketogenesis. The ratio rises to a maximum on the second postnatal day. We conclude that a significant number of infants has low blood glucose levels in the first postnatal week, with an early immaturity of ketogenic response. Longitudinal studies of neonatal metabolic adaptation are required, as well as studies to establish the relationship between metabolic adaptation and neurological function.