Note to my readers: The quality of the Neonatal Hypoglycemia Guidelines vary greatly. (See Table 1 below for a ranking of all the guidelines analyzed.) Therefore, I have linked to the highest rated guideline:
Queensland Newborn Hypoglycemia Guideline [29 pagePDF]
Today, I review, link to, and excerpt from JAMA Pediatrics‘ “Infants Eligible for Neonatal Hypoglycemia Screening A Systematic Review”. [PubMed Abstract] [Full-Text HTML] [Full-Text PDF]. JAMA Pediatr. 2023 Oct 2;177(11):1187–1196. doi: 10.1001/jamapediatrics.2023.3957
All that follows is from the above resource.
Strengths and LimitationsStrengths of this study include the use of a validated tool for critical appraisal of clinical practice guidelines and the size and ethnic diversity of the cohort studied. Limitations of this study include that this is a retrospective observational study of a single tertiary center, which as a referral center for women with high-risk pregnancies, may affect the generalizability of results to other populations. The maternity database does not collect data on all factors that contribute to hypoglycemia screening eligibility; therefore, the true proportion of at-risk infants is likely to be higher than estimated.
ConclusionsOver one-quarter of infants are eligible for hypoglycemia screening. Practice guidelines providing recommendations for clinical care are of variable quality with a lack of consensus regarding definitions for infants at risk for hypoglycemia. Further research is required to understand transitional hypoglycemia and long-term outcomes in these groups.
Key Points
Question What is the proportion of infants eligible for neonatal hypoglycemia screening?
Findings In this review of 18 clinical practice guidelines for neonatal hypoglycemia screening, the Queensland Clinical Guideline: Hypoglycaemia–newborn was identified as the highest-scoring guideline. In this 15-year cohort study of 101 372 eligible infants, the proportion of infants eligible for hypoglycemia screening was 26.3%.
Meaning One-quarter of well infants are eligible for hypoglycemia screening. .
AbstractImportance Neonatal hypoglycemia is common, occurring in up to 50% of infants at risk for hypoglycemia (infant of diabetic mother [IDM], small for gestational age [SGA], large for gestational age [LGA], and preterm) and is associated with long-term neurodevelopmental impairment. Guidelines recommend screening infants at risk of hypoglycemia. The proportion of infants who require screening for neonatal hypoglycemia is unknown.
Objective To determine the proportion of infants eligible for neonatal hypoglycemia screening using criteria from the highest-scoring critically appraised clinical guideline.
Design, Setting, and Participants This systematic review of the literature was conducted to identify clinical practice guidelines for neonatal hypoglycemia and took place at a tertiary maternity hospital in Auckland, New Zealand. Eligible guidelines were critically appraised using the Appraisal of Guidelines for Research and Evaluation II tool. Using screening criteria extracted from the highest-scoring guideline, the proportion of infants eligible for neonatal hypoglycemia screening was determined in a retrospective observational cohort study of infants born January 1, 2004, to December 31, 2018. Data were analyzed by logistic regression. Infant participants were included if gestational age was 35 weeks or more, birth weight was 2000 g or more, and they were not admitted to a neonatal intensive care unit less than 1 hour after birth. The data were analyzed from November 2022 through February 2023. A total of 101 372 infants met the inclusion criteria.
Exposure Risk factors for neonatal hypoglycemia.
Main Outcome Proportion of infants eligible for neonatal hypoglycemia screening.
Results The study team screened 2366 abstracts and 18 guidelines met inclusion criteria for appraisal. There was variability in the assessed quality of guidelines and a lack of consensus between screening criteria. The highest-scoring guideline defined screening criteria as: IDM, preterm (less than 37 weeks’ gestation), SGA (less than 10th percentile), birth weight of less than 2500 g or more than 4500 g, LGA (more than 90th percentile), or gestational age more than 42 weeks. A total of 101 372 infants met criteria for inclusion in the cohort study; median (IQR) gestational age was 39 (38-40) weeks and 51% were male. The overall proportion of infants eligible for screening was 26.3%. There was an increase in the proportion of eligible infants from 25.6% to 28.5% over 15 years, which was not statistically significant after adjustment for maternal age, body mass index, ethnicity, and multiple pregnancy (odds ratio, 0.99; 95% CI, 0.93-1.03; change in proportion per year).
Conclusion A systematic review found that practice guidelines providing recommendations for clinical care of neonatal hypoglycemia were of variable quality with is a lack of consensus regarding definitions for infants at risk for hypoglycemia. In the cohort study, one-quarter of infants were eligible for hypoglycemia screening. Further research is required to identify which infants may benefit from neonatal hypoglycemia screening.
IntroductionNeonatal hypoglycemia is a common metabolic abnormality in the newborn period with up to 50% of at-risk infants developing low blood glucose concentrations.1,2 It is well recognized that severe and prolonged hypoglycemia is associated with neurologic injury and long-term neurodevelopmental sequelae.3 The effects of mild, asymptomatic, or transitional hypoglycemia on long-term neurodevelopmental outcomes remain less certain. There is an association between hypoglycemia and an increased risk of neurodevelopmental impairments in childhood, including impaired visual-motor processing and executive functioning in early childhood, and reductions in literacy and numeracy skills in mid-childhood.4–7 However, recently reported follow-up studies have not shown differences in academic performance at 9 to 10 years of age in at-risk infants exposed to hypoglycemia compared with those without hypoglycemia.4 Multiple maternal and infant factors are associated with neonatal hypoglycemia due to impaired metabolic transition following birth. Prematurity, small for gestational age (SGA), large for gestational age (LGA), and infants of mothers with diabetes (IDM) are the most commonly identified risk factors.5–7 Hypoglycemia is commonly asymptomatic or associated with nonspecific clinical signs2 and clinical practice guidelines were developed to provide recommendations for early identification and screening of infants at risk for hypoglycemia.8 However, there remains a paucity of high-quality evidence to inform best practice with screening and management recommendations often formed from expert opinion.2,9,10 There is a lack of consensus between guidelines with how at-risk infants are defined and there remains uncertainty about which infants are most at risk of impaired metabolic transition and potential neurodevelopmental consequences.11
Current screening practices for neonatal hypoglycemia are not without potential risks and challenges.12 Screening for neonatal hypoglycemia fails to meet some of the universal principles for an effective screening test and there is a lack of high-quality evidence that screening improves long-term neurodevelopmental outcomes.2,11,13,14 Infants are exposed to repeated painful blood tests and screening practices that may disrupt establishment of breastfeeding.15 Commonly used point-of-care glucometers that do not use gold standard enzymatic analysis may be inaccurate in detecting hypoglycemia in neonates,2,11,12,16 while research using blinded continuous glucose monitors has shown that undetected episodes of hypoglycemia are common with current screening practices.16,17 There is also an association between a rapid rise in interstitial glucose concentrations following intravenous dextrose boluses and poorer long-term neurodevelopmental outcomes, suggesting that treatment of hypoglycemia may also not be without potential risks.17–19
The proportion of healthy infants who are at risk for hypoglycemia, and therefore eligible for hypoglycemia screening, has not previously been determined. The aim of this study was to determine the proportion of infants eligible for hypoglycemia screening.
Across all guidelines, IDM, SGA, and prematurity were recommended as screening criteria, although definitions varied between guidelines. LGA infants were recommended for screening in 12 guidelines (eTable 1 in Supplement 1). The highest-scoring guideline was the Queensland Clinical Guideline: Hypoglycaemia–newborn36 (Table 1), which had an overall rating score of 88%. It scored highly across all domains, with all domain scores more than 80%. This guideline defined hypoglycemia screening criteria as preterm, less than 37 weeks’ gestation; SGA, less than 10th percentile; birth weight, less than 2500 g or more than 4500 g; LGA, more than 90th percentile; gestational age of 42 weeks; and maternal diabetes (IDM), with additional criteria, such as asphyxia or maternal medications (eTable 1 in Supplement 1).
Retrospective Observational Cohort StudyA total of 112 344 infants (20 weeks’ gestation or more) were born at ACH during the study period; 101 372 met the inclusion criteria for analysis (eFigure in Supplement 1). Baseline characteristics for the patient population eligible for screening against those not meeting screening eligibility criteria are shown in Table 2.
The proportion of infants who were eligible for screening based on criteria from the Queensland Clinical Guideline was 26.3%. There was an increase in the proportion of infants eligible from 25.6% in 2004 to 28.5% in 2018 (Figure 2), which was not statistically significant after adjustment for maternal age, BMI, ethnicity, and multiple pregnancy (odds ratio [OR], 0.99; 95% CI, 0.93-1.03; change in proportion per year).
Figure 2. Eligibility of Infants Born in Auckland City Hospital for Neonatal Hypoglycemia Screening
Table 3. Infants Eligible for Screening by Clinical Practice Guideline
There were significant differences in eligibility for hypoglycemia screening based on ethnicity with infants of Indian (37.8%) and Pacific (32.1%) mothers most likely to be eligible for screening and infants from all non-European ethnic groups more likely to be eligible for screening compared with infants of European mothers (29.7% v 22.3%; OR, 1.47; 95% CI, 1.43-1.51; P < .001). Maternal diabetes as a risk factor for eligibility was more common in infants of Asian (44.8%), Indian (45.1%), and Pacific women (35.1%), compared with European women (19.2%). SGA was also more common in infants of Asian (29.8%) and Indian women (40.1%) , while LGA as an independent risk factor for screening eligibility was most common among infants of European (36.6%) and Pacific women (37.4%) (eTable 2 in Supplement 1).
DiscussionWe conducted a systematic review and critically appraised clinical practice guidelines that provide recommendations on screening for neonatal hypoglycemia and identified the Queensland Clinical Guideline: Hypoglycaemia–newborn guideline as the highest-scoring clinical guideline. Based on the criteria from this guideline, we determined in a large retrospective cohort study that at least one-quarter of all infants meet the criteria for screening for neonatal hypoglycemia and that the proportion of infants eligible is increasing over time.
To our knowledge, this study is the first of its nature to determine the proportion of infants eligible for neonatal hypoglycemia screening, using critically appraised clinical practice guidelines. A previous single-center European, 2-year retrospective audit of 1017 births identified eligibility for screening as 13.4% based on criteria adapted from the American Academy of Pediatrics Guideline.26,42 In our study, with a large and ethnically diverse population, we determined that at least one-quarter of infants typically cared for in a postnatal ward setting were defined as at risk for neonatal hypoglycemia, based on screening eligibility criteria extracted from the highest-scoring clinical guideline. This is likely an underestimate of the true proportion, as the guideline includes additional criteria for screening eligibility, such as maternal drug therapy, that were not able to be determined from data collected by the maternity database. Targeted screening is based on risk factors for transient hypoglycemia, eg, infants of mothers with diabetes, which will not reliably detect infants with genetic causes of hypoglycemia, such as fatty acid oxidation disorders, which are not associated with prematurity or birth weight. However, the most common genetic cause of persistent hypoglycemia is congenital hyperinsulinism and many, although not all, infants with this condition will be LGA and will meet the neonatal hypoglycemia screening criteria.43
There was a statistically significant increase in the annual proportion of infants eligible for hypoglycemia screening over the 15-year study period associated with an increase in maternal diabetes as a risk factor for eligibility over time. This is consistent with evidence of the increasing burden of gestational diabetes and type 2 diabetes in the community, particularly in non-European populations in New Zealand,23,44 which has been associated worldwide with factors including the obesity epidemic and advancing maternal age.45,46
Emphasis added to the paragraph below:
While guidelines varied in assessed quality, even the most robust clinical practice guideline can only be as good as the strength of the evidence that forms the basis for guideline recommendations. Moreover, higher ratings by the AGREE II tool confirm that best practices were followed during guideline development but they do not necessarily mean that better clinical outcomes are achieved. While most guidelines performed well in communicating their key recommendations, establishing links between recommendations and an evidence base was a common challenge. Screening criteria were variably defined, leading to significant variability in eligibility for screening depending on guideline criteria used. These issues reflect the ongoing challenges presented by a lack of evidence available regarding which infants are most at risk of hypoglycemia and who will benefit most from screening and treatment to improve long-term neurodevelopmental outcomes.11
While IDM, SGA, and preterm infants were included as risk factors across all guidelines with variable definitions, LGA infants were included as an independent risk factor in only two-thirds of guidelines and were specifically excluded from routine screening in some guidelines. LGA infants (independent of IDM) were the second largest group of infants eligible for screening after IDM in this population. Traditionally, LGA infants have been screened for hypoglycemia to identify those infants where there may be undiagnosed diabetes or rare metabolic disorders contributing to macrosomia.8,47 While hypoglycemia was previously thought to be a common occurrence in LGA infants, there is a lack of evidence on the effect of hypoglycemia on neurodevelopmental outcomes in otherwise healthy LGA infants who have transitional hypoglycemia.8,48,49 Additionally, recent evidence has shown that asymptomatic transitional hypoglycemia occurs in 40% of healthy, term appropriately grown infants.50 Further research is required to understand which infants are most at risk of impaired metabolic transition in the newborn period, rather than just detecting those with low blood glucose concentrations and to understand who will benefit most from screening and interventions with respect to protecting and improving long-term neurodevelopmental outcomes.11
Current screening practices for neonatal hypoglycemia balance potential benefits and challenges of screening tests and treatment strategies. Ongoing research continues into the role of alternative strategies to improve detection of asymptomatic hypoglycemia and the effect of treatment, such as continuous interstitial glucose monitors or noninvasive glucose monitoring systems; however, these are not yet available in routine clinical practice.9,51,52 Prevention of hypoglycemia in at-risk populations with prophylactic buccal dextrose gel 200 mg/kg is a safe, cost-effective, and noninvasive treatment to reduce the risk of hypoglycemia in at-risk infants.24,53,54 The current study is informative about the growing population of infants considered at risk for hypoglycemia that may benefit from prophylactic strategies if they are determined to have long-term benefits. However, recent follow-up data from the hPOD trial have shown no significant difference in neurosensory outcomes at 2 years in at-risk infants randomized to receive prophylactic dextrose gel.55
This study has also demonstrated that there are significant differences in screening eligibility between ethnic groups with infants of Indian mothers most likely to be eligible for screening, predominately due to IDM and SGA. While some differences between ethnic groups were attributable to differences in maternal diabetes diagnosis rates, with diabetes and obesity recognized to be more common in Māori and Pasifika populations in New Zealand,44 there were also differences in eligibility due to LGA and SGA criteria. This may reflect a limitation of using population-based percentile charts, such as the Fenton growth charts, due to the lack of a comparable percentile charts based on New Zealand data. These have been generated from predominately Western population data from developed countries and their use in infants from other ethnic backgrounds may not be representative, as it has been recognized that there are ethnic differences in size at birth.21,56–58
