Cord glucose: A normal reference and a potential of an ideal universal screening tool for pathological hyperinsulinism

Julie Siersbaek; Hansen Rasmus Soegaard; Mads Nybo; Christesen henrik thybo

FC14.2

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ESPE Abstracts (2024) 98 FC14.2

ESPE2024 Free Communications Fetal and Neonatal Endocrinology (6 abstracts)

Cord glucose: A normal reference and a potential of an ideal universal screening tool for pathological hyperinsulinism.

Julie Siersbaek ¹ , Rasmus Soegaard Hansen ² , Mads Nybo ² & henrik thybo Christesen ^1,3,4

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¹Hans Christian Andersen Children's Hospital, ODense University Hospital, Odense, Denmark. ²Dept. Biochemistry, Odense University Hospital, Odense, Denmark. ³Clinical Institute, University of Southern Denmark, Odense, Denmark. ⁴Odense Pancreas Center, Odense University Hospital, Odense, Denmark

Background: Normal neonates exhibit a transitional state of physiological hyperinsulinism (HI) during the first 2-3 days of life as an adaption from the fetal state. Prolonged, pathological HI can cause irreversible cerebral damage, if not avoided by early diagnosis and prompt treatment. We hypothesized that umbilical cord blood glucose, included in routine cord gas analysis, can be used as an ideal screening tool for pathological HI. We first aimed to establish normal values for venous and arterial cord glucose and the difference (delta glucose) and second; to apply the first diagnostic performance test of cord glucose as a screening tool for pathological HI.

Methods: From cord blood gas analyses routinely analyzed within a few minutes after birth, we extracted data on cord venous and arterial glucose. Exclusion criteria for the normal controls standard reference were; pre/post/multiple birth; birthweight outside +/-2SD; asphyxia; maternal diabetes or medication; missing cord glucoses and delta cord pH <0.02; and neonatal disease. Neonatal hypoglycemia was defined as plasma glucose <2.5mmol/L (45 mg/mL) age 2 hours to 2 days, or <3.2mmol/L (57.5 mg/mL) from day 3. Cases with pathological HI were identified through a laboratory search of neonates <100 days with serum insulin measurements ≥18pmol/L (2.6mU/L; reference range 18-174pmol/L; 2.6-25mU/L) and simultaneous hypoglycemia as defined.

Results: We identified 133 normal controls and 4 cases with pathological HI. The cases were diagnosed day 1-7 with plasma glucose 2.0-2.6mmol/L and simultaneous insulin of 21-481pmol/L. Cases were treated with diazoxide and iv glucose until clinical remission age 6-45 days. Cases had lower cord venous, arterial and delta (v-a) glucose compared to controls, Table. By receiver operating curve analyses, arterial cord glucose had the best, and an excellent, diagnostic performance of with an area under the curve of 0.9596 and an optimal cut-off of 3.5mmol/L (65 mg/dL).

Table 1
	Healthy	Hyperinsulinism	P
Venous Glucose, mmol/L, mean (range)	5.81 (3.4-9.2)	3.85 (3.4-4.8)	0.0019
Arterial Glucose, mmol/L, mean (range)	4.72 (2.5-7.9)	2.15 (0.6-3.5)	<0.0001
Delta Glucose, mmol/L, mean (range)	1.08 (0-3.6)	1.7 (1.1-2.8)	0.0365

Discussion: In this pilot, low arterial cord glucose (cut-off 3.5mmol/L) had an excellent diagnostic performance in predicting pathological HI. More cases should be collected, especially with severe congenital HI. Sick controls references, i.e. at-risk neonates without presenting hypoglycemia (small for gestational age, maternal diabetes, late preterms) should be established. Cord glucose holds potential as an ideal universal screening tool for pathological HI to prevent brain damage.