Failure to detect preterm infants at risk of hypoglycemia before discharge

doi:10.1016/S0022-3476(99)70210-6

The Journal of Pediatrics

Volume 134, Issue 4, April 1999, Pages 499-502

https://doi.org/10.1016/S0022-3476(99)70210-6 Get rights and content

Abstract

In a series of 79 consecutive preterm infants who were ready for discharge, 14 (18%) infants were unable to maintain normal concentrations of blood glucose. This finding suggests that a significant number of preterm infants are at risk of hypoglycemia at home if a feed is omitted or delayed. (J Pediatr 1999;134:499-502)

Section snippets

EXPERIMENTAL SUBJECTS

Consecutive preterm infants who were 25 to 36 weeks’ gestation (n = 79), admitted to a level III nursery, and survived to discharge home were recruited. At the time of discharge home all infants were receiving regular feeds every 4 hours. Blood glucose and lactate concentrations were measured 4 hours from the start of the last feed. The scheduled feed was omitted, and blood glucose and lactate concentrations were measured 2 and 4 hours later. Insulin, glucagon, corticotropin, cortisol, human

METHODS

All blood glucose and lactate measurements were determined immediately on site with a Yellow Springs Instruments analyzer. Hypoglycemia was defined as a blood glucose measurement of <2.6 mmol/L (47 mg/dL). Severe hypoglycemia was defined as a blood glucose <2.2 mmol/L (40 mg/dL) and persistent if 2 such results were recorded. Hormonal and metabolite assays were done in the Department of Biochemical Medicine of Ninewells Hospital. Acetoacetate and β-hydroxybutyrate concentrations were measured

RESULTS

The infants were subdivided into groups: (1) infants who remained normoglycemic (n = 65, 82.3%), (2) infants who were transiently hypoglycemic (n = 9, 11.4%), lowest blood glucose values 2.42 ± 0.06 mmol/L, n = 9, and (3) infants who had severe and persistent hypoglycemia (n = 5, 6.3%) (Table).

Table. Characteristics of infant study groups

Empty Cell	Normoglycemia (n = 65)	Transient hypoglycemia (n = 9)	Severe persistent hypoglycemia (n = 5)
At birth
M/F	40:25	2:7	4:1
Gestational age (wk)	32.3 ± 0.3	32.3 ± 0.9	32.0 ±

DISCUSSION

Hypoglycemia is common in newborn preterm infants. For the first few days blood glucose concentrations are routinely measured, and glucose is given to achieve normoglycemia.9, 13, 14 Subsequently, many infants are given parenteral feeding or continuous or frequent bolus nasogastric milk feeds (usually hourly). Thereafter, it is not normal practice to routinely measure blood glucose concentrations, and most infants will advance to an increased reliance on enteral nutrition and a progression from

Acknowledgements

We thank Mrs Pamela Houston for excellent technical assistance and Ian Hanning and Callum Fraser, Department of Biochemical Medicine, for advice.

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(1992)

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Cited by (42)

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2018, Volpe's Neurology of the Newborn
Retrospective evaluation of a national guideline to prevent neonatal hypoglycemia
2017, Pediatrics and Neonatology
Citation Excerpt :
No evidence of an increase in hypoglycemia was observed after the guideline introduction, suggesting that the uniform incidence decrease was not due to methodological bias. The overall population incidence of neonatal hypoglycemia, according to discharge diagnosis, was 8.4%, which was within previously reported incidences of 5–15%.2,7,8,16,17,25,26 Our estimate had the advantage of being based on a large population birth cohort, but the disadvantage of being based predominantly on discharge diagnoses and glucose measurements obtained with different methods.
Hypoglycemia is common in neonates and may cause adverse neurological outcomes. Guidelines should aim to prevent repeated hypoglycemic episodes in risk groups, but they are not usually stratified according to the severity of hypoglycemia risk, which may lead to inappropriate and redundant interventions. We evaluated the effect of a national prevention guideline stratified according to mild, moderate, and severe risks of hypoglycemia.
From national registers, a population cohort of 22,725 neonates was identified retrospectively before and after implementation of a national guideline. Of these, 1900 had World Health Organization International Classification of Diseases 10 discharge diagnoses of hypoglycemia. Diagnoses indicating hypoglycemia risk [small/large for gestational age (SGA/LGA), asphyxia, prematurity, maternal insulin-treated diabetes mellitus] were recorded. Neonatal ward files were evaluated to validate hypoglycemia diagnoses. Adjusted odds ratios (aORs) were calculated, adjusting for sex, parity, SGA, LGA, preterm birth, and asphyxia, where relevant.
Primiparity and male sex were associated independently with hypoglycemia diagnosis [aORs, 1.29 (1.17–1.42) and 1.14 (1.03–1.26), respectively]. Overall incidence of hypoglycemia at discharge decreased from 9.4% to 5.5% after guideline implementation [aOR_change, 0.57 (0.50–0.64)]. Overall incidence of validated hypoglycemia decreased from 2.1% to 1.2% [aOR 0.59 (0.46–0.77), p < 0.001]. By risk group, the hypoglycemia incidence decreased from 30.5% to 18.6% [aOR 0.52 (0.36–0.75)] among SGA neonates, from 25.8% to 16.4% [aOR 0.57 (0.42–0.76)] among preterm infants, and from 27.4% to 16.6% [aOR 0.63 (0.34–0.83)] among those with asphyxia. LGA neonates showed a decreased incidence in obstetric wards only. No significant change was observed for the diabetes group.
Stratification of hypoglycemia risk in a hypoglycemia prevention guideline was followed by decreased estimated hypoglycemia incidence, but no causative conclusion could be drawn. Prospective studies with risk stratification for hypoglycemia prevention are encouraged.
Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children
2015, Journal of Pediatrics
Citation Excerpt :
Because of the difficulty in distinguishing a suspected persistent hypoglycemia disorder from transitional neonatal glucose concentrations during the first 48 hours of life, we suggest delaying diagnostic evaluations until 2-3 days after birth. Some neonates can be identified by various clinical features as being at high risk for severe hypoglycemia during the first 48 hours after delivery,16,26 and a subset of those neonates are also at increased risk for persistent hypoglycemia beyond 48 hours of life (Table).27-30 These include not only the rare infants with genetic hypoglycemia disorders, such as congenital hyperinsulinism or hypopituitarism,31 but also those with relatively more common prolonged neonatal hyperinsulinism (also referred to as perinatal stress hyperinsulinism) associated with birth asphyxia, intrauterine growth restriction, or toxemia.27,28,30
Instability of glucose values in very preterm babies at term postmenstrual age
2014, Journal of Pediatrics
Citation Excerpt :
Previous studies have shown a high prevalence (up to 36%) of hypoglycemia in very premature babies during their first days of life, whether using intermittent capillary24 or continuous interstitial glucose monitoring.12 Some reports also find low glucose values whether by intermittent or continuous methods in about one-third of VPT babies about 5 weeks old, just after transitioning to full enteral feedings,13,25 if challenged by a fasting period at the time of discharge.14 Our data suggests that hypoglycemia is not restricted to the first weeks after birth, but persists in time, at least up until term-equivalent age, when these patients are usually discharged.
To determine if very preterm (VPT) babies are capable of maintaining glucose levels within normal ranges at or near term postmenstrual age.
Glucose levels were intermittently or continuously monitored during 48 hours in a cohort of 60 VPT infants near hospital discharge. Hypoglycemic (≤45 mg/dL, 2.5 mmol/L) and hyperglycemic (≥140 mg/dL or 7.8 mmol/L, severe if ≥180 mg/dL or 10 mmol/L) episodes were considered relevant if they lasted longer than 30 minutes. Feeding regimes followed current practice.
With intermittent capillary, 2 hypoglycemic values and another 3 that were abnormally high were detected. With continuous monitoring, 6 babies (10.0%) had isolated hypoglycemia ≤45 mg/dL (2.5 mmol/L) (3 of them reaching 40 mg/dL, 2.2 mmol/L), 14 (23.3%) had isolated hyperglycemia, and 8 (13.3%) had episodes of both. The mean duration of hypoglycemia per patient was 2.8 ± 2.9 hours and 4.68 ± 4.35 hours in the case of hyperglycemia, with 12 infants becoming severely hyperglycemic. Of the 12 severely hyperglycemic patients, 5 also developed severe hypoglycemia. No specific characteristics identified the hypoglycemic babies. A history of intrauterine growth restriction (P = .037) and female sex (P = .063) seemed to increase the risk of severe hyperglycemia.
VPT infants continue to have abnormal glucose values, especially hyperglycemia, by the time of hospital discharge. No specific factors identify babies at higher risk for hypoglycemia, and intrauterine growth restriction and female sex seemed to predispose to hyperglycemia.
Incidence of neonatal hypoglycemia in babies identified as at risk
2012, Journal of Pediatrics
Citation Excerpt :
Nevertheless, in those whom we did continue to monitor, over one-third of hypoglycemic babies had their first episode after 3 normal blood glucose measurements, and 6% had a first hypoglycemic episode after 24 hours of age. Previous authors have also shown that hypoglycemic episodes can occur long after the first 48 hours in preterm babies,2,10 suggesting that there may have been others whose first hypoglycemic episode occurred after monitoring was discontinued. Once again, the significance of any such episodes for long-term neurologic outcome remains uncertain.
Routine blood glucose screening is recommended for babies at risk of neonatal hypoglycemia. However, the incidence of hypoglycemia in those screened is not well described. We sought to determine the incidence of hypoglycemia in babies identified as being at risk, and also to determine differences in incidence between at risk groups.
Infants (n = 514) were recruited who were born in a tertiary hospital, ≥35 weeks gestation and identified as at risk of hypoglycemia (small, large, infant of a diabetic, late-preterm, and other). Blood glucose screening used a standard protocol and a glucose oxidase method of glucose measurement in the first 48 hours after birth.
One-half of the babies (260/514, 51%) became hypoglycemic (<2.6 mM), 97 (19%) had severe hypoglycemia (≤2.0 mM), and 98 (19%) had more than 1 episode. The mean duration of an episode was 1.4 hours. Most episodes (315/390, 81%) occurred in the first 24 hours. The median number of blood glucose measurements for each baby was 9 (range 1-22). The incidence and timing of hypoglycemia was similar in all at risk groups, but babies with a total of 3 risk factors were more likely to have severe hypoglycemia.
Hypoglycemia is common amongst babies recommended for routine blood glucose screening. We found no evidence that screening protocols should differ in different at risk groups, but multiple risk factors may increase severity. The significance of these hypoglycemic episodes for long-term outcome remains undetermined.
Neonatal hypoglycemia - Answers, but more questions
2012, Journal of Pediatrics

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^☆: Supported by grants from the Scottish Home and Health Department (A.B., R.H.), Wellcome Trust (R.H.), Tenovus (Scotland) (R.H., A.B.), Research Trust for Metabolic Diseases in Children (A.B.), Paediatric Metabolic Research Trust (R.H.), and the Northwood Charitable Trust (A.B.). Dr Burchell was a Lister Institute Research Fellow.

^☆☆: Reprint requests: Robert Hume, FRCPEdin, Department of Obstetrics and Gynaecology, University of Dundee, Ninewells Hospital & Medical School, Dundee, DD1 9SY, Scotland.

^★: 0022-3476/99/$8.00 + 0 9/22/97127

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Failure to detect preterm infants at risk of hypoglycemia before discharge☆,☆☆,★

Abstract

Section snippets

EXPERIMENTAL SUBJECTS

METHODS

RESULTS

DISCUSSION

Acknowledgements

Fine tuning of blood glucose concentrations

TIBS

The molecular basis of the type 1 glycogen storage diseases

Bioessays

Adverse neurodevelopmental outcome of moderate neonatal hypoglycaemia

BMJ

The endoplasmic reticulum glucose-6-phosphatase proteins

Mol Membr Biol

The ontogeny of the human hepatic glucose-6-phosphatase proteins

Clin Chem

Abnormal expression of glucose-6-phosphatase in preterm infants

Arch Dis Child

Impairment of the activity of the microsomal glucose-6-phosphatase system in premature infants

Acta Paediatr