Epinephrine Responses to Hypoglycemia on the First Postnatal Day: Keep Testing Serum Glucose!

Author Type(s)

Faculty, Resident/Fellow

Document Type

Abstract

Publication Date

2022

DOI

10.1136/jim-2022-ERM.109

Journal Title

Journal of Investigative Medicine

Department

Pediatrics

Abstract

Purpose of Study Catecholamines are rapid responding neurohumoral signals that provide a survival advantage aiding in adaptation to common postnatal stressors such as hypoglycemia. Our previous preclinical studies showed that antibioticinduced gut dysbiosis results in prolonged sympathoadrenal hyporesponsiveness (LaGamma, Neurobio Stress;2021, doi.org/ 10.1016/j.ynstr.2021.100376). To characterize this phenomenon in humans, we sought to identify a metric for baseline responsiveness before gut colonization. Epinephrine responses to hypoglycemia on the first postnatal day would fulfill this goal. Methods Used All urine samples (cumulative index of interval Epi release) were obtained in our regional level IV NICU within 24h after birth. Samples were collected in cotton sponges, acidified with 0.01 M HCL (1:1 v/v) and stored at - 80°C until analyzed. Samples were run in duplicate batches of 16 to minimize variability (Rocky Mountain Dx, CO). Spot urine measurements were normalized to urine creatinine [Epi/ Cr (ng/ml) ratio]. The protocol was approved by our NYMC IRB. Summary of Results Samples from 21 patients at gestational age median= 27wks (25%-75%'ile: 24,32) and weight of 780g (620, 1475) were analyzed. We defined abnormal urinary Epi/cr ratio values as exceeding 3 SEM for the entire patient population (2.1 ± 0.5; or £ 0. 6 ng/ml ratio). Hypoglycemia < 55 mg/dl was detected in 12 patients, where 42% (5/12) failed to respond by increasing Epi levels into the normal range. In contrast, 58% (7/12) responded with a 383% increase in Epi/cr to 2.9 (0.7- 3.4; p=0.003) consistent with a responsive sympathoadrenal axis. Cumulative risk (CR) (i.,e. ≥1 recognized risk factors for hypoglycemia: preterm, SGA, PEC, low APGARs) was identified in 46% (22/48) of all hypoglycemic patients but, did not differ from the euglycemic cohort: 44% (16/36). Non-responders were more likely to have CR exposure when compared to responders [65% (13/ 20) vs 32% (9/28), p= 0.04]. Unexpectedly, presence of ≥1 recognized risk factors correlated with an inability to respond to hypoglycemia. Conclusions Clinicians cannot determine at-risk newborns by physical or perinatal history alone. As the brain is dependent on this substrate, our results underscore the need for early and frequent measures of serum glucose to ensure adequate supply. Factors (e.g. fermentation products of gut flora; Giri, Ped Res 85:57, 2019) that determines early functional maturation of the sympathoadrenal system remain to be further elucidated. (Table Presented).

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