Iatrogenic Fetal Hypoglycemia Following Tight Peripartum Glucose Control in Diabetic Mothers: A Hypothesis and a Case Report

Abstract

Current management of diabetes in pregnancy includes prompt normalization of glucose prior to delivery in women with poorly controlled diabetes. While the benefits of glucose control throughout pregnancy are well-documented, the benefits of rapid glucose normalization prior to delivery are borderline. There is a lack of information on the fetal effects of this practice. There is a concern that a rapid decrease in maternal glucose level could cause hypoglycemia in the fetus, developing in the same manner as in a newborn infant of a mother with diabetes.

This case highlights a 37 week infant of a mother with poorly controlled diabetes, whose mother's glucose was normalized with intravenous insulin 24 hours before delivery. The infant's arterial cord blood glucose was 2.1 mmol/L, indicative of hypoglycemia, and it required neonatal intensive care unit admission. Current guidelines emphasize tight peripartum glycemic control but overlook potential fetal hypoglycemia before birth. This case suggests fetal hypoglycemia may precede neonatal hypoglycemia, with similar risks but limited diagnostic opportunities. Further research is needed to evaluate fetal outcomes of stringent glycemic control and to establish early cord blood glucose monitoring to improve the identification and management of hypoglycemia in this vulnerable population.

Keywords

cord blood glucose - fetal blood glucose - hypoglycemia - infant of diabetic mother - infant - newborn - peripartum period

Case Report

Infants born to mothers with diabetes (IDMs) frequently experience hypoglycemia soon after birth, a condition that can lead to brain injury, especially if left untreated. IDMs experience cessation of excessive glucose supply following birth. Due to beta-cell hyperplasia and hyperinsulinemia developed during fetal life and downregulated gluconeogenesis, the glucose levels in IDM rapidly drop after birth. The brain is primarily affected by hypoglycemia due to its dependence on glucose as an exclusive energy source.

The fetal benefits of glucose control throughout pregnancy are supported by robust research data. Some mothers never achieve diabetes control during pregnancy. In mothers with poorly controlled diabetes in pregnancy, tight peripartum control of glucose, usually with intravenous insulin,[1] is recommended. This is a common practice despite contentious conclusions in a systematic review[2] and calls for less aggressive management prior to expected labor.[3] There is no research or even concern regarding adverse fetal effects following rapid normalization of maternal glucose levels. However, it is plausible that following fast maternal glucose normalization, the fetal glucose metabolism becomes similar to that upon birth: rapid decrease of glucose supply coupled with hyperinsulinemia and insufficient gluconeogenesis, leading to fetal hypoglycemia. Fetal hypoglycemia is expected to result in the same consequences as in a neonate but in a setting with no diagnostic opportunities and few to no options for intervention if it is suspected.

The literature lacks data regarding the fetal effects of stringent peripartum glycemic control. The studies of peripartum glucose control were focused on neonatal hypoglycemia and followed current recommendations for neonatal glucose testing. It was tested an hour or later following birth, when the fetal hypoglycemia may have subsided.[4] In a single study reporting umbilical cord glucose levels in IDMs, the details of maternal glycemic control are unclear.[5]

We report a case of an infant born at the 37th week of pregnancy to a mother with poorly controlled type 2 diabetes throughout pregnancy. The mother's glucose level was normalized with an intravenous insulin drip within 24 hours prior to cesarean section delivery. The fetal whole blood glucose level, tested in the arterial cord blood immediately after birth, was 2.1 mmol/L—significantly below the 5th percentile for normal newborns (3.5 mmol/L)[6] and the World Health Organization neonatal hypoglycemia treatment threshold (2.6 mmol/L). Because of hypoglycemia and mild transitory tachypnea of the newborn, the infant was admitted to the neonatal intensive care unit (NICU). The tachypnea resolved within a few hours. The hypoglycemia was successfully managed with intravenous dextrose once, followed by feeding. The infant had to receive supplemental feeding via an orogastric tube for the first week of life and was discharged on the 8th day of life. No neurological abnormalities were noted during the NICU stay. There is no follow up data.

This case highlights the potential for fetal hypoglycemia following the rapid normalization of glucose levels in a diabetic mother. It is prudent to infer that in the patient presented here, fetal hypoglycemia was more severe immediately following normalization of maternal glucose than it was at birth. In this patient, the fetal beta cell hyperplasia was moderate, considering moderately elevated maternal hemoglobin HbA_1c (7.9%) and mean glucose (9.8 mmol/L) prior to the labor. In the situations of severe fetal beta-isle hyperplasia and/or maternal iatrogenic hypoglycemia, the fetal hypoglycemia is anticipated to be more profound.

Fetal hypoglycemia might elucidate the recent findings of typical hypoglycemic brain damage in children with no history of neonatal hypoglycemia.[7]

This hypothesis, supported by observation, suggests a need for a thorough clinical study to evaluate the fetal, neonatal, and long-term consequences of tight peripartum glycemic control. Additionally, early glucose monitoring in cord blood might facilitate the timely identification and treatment of hypoglycemia in this subgroup of IDM.

Conflict of Interest

None declared.

Discloser

The author does not have any other affiliations outside of the University of Oklahoma Health Sciences Center.

Note

The author is the only author of the submitted manuscript.

Ethical approval

The collection of the patient's data was approved by the University of Oklahoma Health Sciences Center IRB, IRB #: 17488. The author was conforming to the Declaration of Helsinki.

• References

• 1 American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 201: pregestational diabetes mellitus. Obstet Gynecol 2018; 132 (06) e228-e248
• 2 Yamamoto JM, Benham J, Mohammad K, Donovan LE, Wood S. Intrapartum glycaemic control and neonatal hypoglycaemia in pregnancies complicated by diabetes: a systematic review. Diabet Med 2018; 35 (02) 173-183
• 3 Barrett HL, Morris J, McElduff A. Watchful waiting: a management protocol for maternal glycaemia in the peripartum period. Aust N Z J Obstet Gynaecol 2009; 49 (02) 162-167
• 4 Bitar G, Bravo R, Pedroza C. et al. Permissive intrapartum glucose control: an equivalence randomized control trial (PERMIT). Am J Obstet Gynecol 2024; 231 (03) 355.e1-355.e11
• 5 Wang Y, Liu H, Zhang L. et al. Umbilical artery cord blood glucose predicted hypoglycemia in gestational diabetes mellitus and other at-risk newborns. BMC Endocr Disord 2023; 23 (01) 277
• 6 Heck LJ, Erenberg A. Serum glucose levels in term neonates during the first 48 hours of life. J Pediatr 1987; 110 (01) 119-122
• 7 Worth C, Gokul PR, Ramsden K. et al. Brain magnetic resonance imaging review suggests unrecognised hypoglycaemia in childhood. Front Endocrinol (Lausanne) 2024; 15: 1338980

Publication History

Article published online:
11 April 2025