By Ahizechukwu C. Eke, MD, PhD, MPH
Associate Professor of Maternal Fetal Medicine, Division of Maternal Fetal Medicine, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore
SYNOPSIS: This study demonstrated an increased risk of neonatal hypoglycemia in neonates born to patients with diabetes as the result of maternal hyperglycemia in labor. However, strict intrapartum maternal glycemic control appeared to be associated with a reduced risk of neonatal hypoglycemia only in patients with gestational diabetes on medication, but not for other diabetes subtypes.
SOURCE: Anwer TZ, Aguayo R, Modest AM, Collier ARY. Reexamining intrapartum glucose control in patients with diabetes and risk of neonatal hypoglycemia. J Perinatol 2021;41:2754-2760.
Pregestational and gestational diabetes are important causes of maternal morbidity and common causes of neonatal hypoglycemia.1 Gestational diabetes mellitus (GDM) is defined by the World Health Organization (WHO) as “carbohydrate intolerance resulting in hyperglycemia of variable severity with onset or first recognition during pregnancy.”2 Pregestational diabetes is defined as carbohydrate intolerance predating pregnancy. In both forms of diabetes, there is a continuum of maternal and fetal risk with hyperglycemia during pregnancy, and, therefore, optimal glycemic control is imperative.3,4
Tight glycemic monitoring and control during labor in women with diabetes in pregnancy has been hypothesized to decrease the risk of fetal complications, such as acidemia, hypoglycemia, and admission to the neonatal intensive care unit.4,5 Although tight glucose control during labor is a common practice, there is little evidence to support this practice. In addition, the optimal frequency of glucose monitoring during labor has not been established, especially in women with gestational diabetes. Based on these research gaps, Anwer and colleagues designed this study to better understand the relationship between maternal intrapartum glycemic control and neonatal hypoglycemia in women with pregestational diabetes and gestational diabetes to determine whether this relationship differed by maternal diabetes type.5
The study was a retrospective cohort study of live births complicated by maternal gestational or pregestational diabetes at a single academic teaching hospital in Boston between January 2017 and June 2019.5 Inclusion criteria included all singleton pregnancies that resulted in live births with a history of gestational or pregestational diabetes. Women were excluded if they had multifetal gestations, intrauterine fetal demise, and previable birth (< 24 weeks gestational age). GDM was diagnosed using the Carpenter-Coustan criteria (two or more elevated values on the 100-g, three-hour oral glucose tolerance test) or a 50-g, one-hour oral glucose tolerance test ≥ 200 mg/dL.5 GDM controlled with diet and lifestyle changes alone was classified as diet-controlled GDM (GDMA1), whereas GDM requiring medications (insulin or glyburide) was classified as GDM on medication (GDMA2). The diagnosis of pregestational diabetes was established by an elevated hemoglobin A1c ≥ 6.5%, as defined by the American Diabetes Association, or by a history of diabetes diagnosis or treatment prior to pregnancy.5
The primary outcome was neonatal hypoglycemia, defined as capillary glucose < 45 mg/dL within the first hour of life. Secondary outcomes included neonatal hypoglycemia two to 24 hours after birth, and neonatal intensive care unit (NICU) admission, irrespective of indication. Secondary analyses included evaluating outcomes between each diabetes type and between pregestational diabetes and GDM subgroups. A total sample size of 832 participants was needed to detect a 12% difference in neonatal hypoglycemia (from 27% neonatal hypoglycemic rate in people with pregestational diabetes to 15% rate of neonatal hypoglycemia in the GDM group based on prior studies), assuming 80% power, and a type 1 error rate of 5%.
During the study period, 853 participants who met inclusion criteria were identified as having gestational diabetes (79.6%, 679 women) or pregestational diabetes (20.4%, 174 women). The primary outcome was observed in 64 out of 154 (41.6%) neonates born to women with hyperglycemia during labor compared to 202 of 699 (28.9%) neonates born to women who were euglycemic. This was not a statistically significant difference (relative risk [RR], 1.1; 95% confidence interval [CI], 0.88-1.4). Among patients with maternal euglycemia during labor, the incidence of neonatal hypoglycemia at one hour of life was higher in those with pregestational diabetes (73.8% in type 1 diabetes mellitus and 42.3% in type 2 diabetes mellitus) compared to patients with GDM (14.3% in GDMA1 and 40.5% in GDMA2). The incidence of neonatal hypoglycemia two to 24 hours post-delivery did not differ based on maternal glycemic control during labor. Neonates of women with hyperglycemia during labor were more likely to be admitted into the NICU, but this was not statistically significant (RR, 1.3; 95% CI, 0.95-1.2). In a subgroup analysis to evaluate if the relationship of maternal hyperglycemia and neonatal hypoglycemia or NICU admission was modified by the type of maternal diabetes, maternal hyperglycemia was only associated with an increased risk (1.6-fold increase) in neonatal hypoglycemia at one hour of life in patients with GDM on medication (RR, 1.8; 95% CI, 1.1-2.7).
COMMENTARY
Hypoglycemia remains the most important metabolic complication in babies of mothers with diabetes because neonatal hypoglycemia can result in adverse neurologic outcomes and therefore must be avoided.6 Hence, it is common practice to evaluate neonatal blood sugars and commence early oral feeds immediately following vaginal or cesarean delivery in people with diabetes to counteract the effects of rebound hypoglycemia from maternal diabetes. Several factors can be responsible for neonatal hypoglycemia in mothers with diabetes, but the most critical factor is the mean peripartum maternal plasma glucose concentrations, especially during the active phase of labor, four to six hours prior to delivery.7,8 Hence, maintenance of maternal euglycemic concentrations during labor is important.
Maternal glucose typically is monitored every two to four hours during the latent phase of labor and every one to two hours during the active phase of labor. Insulin therapy usually is commenced when maternal blood glucose exceeds 120 mg/dL during the active phase of labor. A combined regular/rapid-acting insulin and glucose infusions typically are used to maintain euglycemic levels during labor. The finding by Anwer and colleagues that maternal hyperglycemia was only associated with an increased risk in neonatal hypoglycemia at one hour of life in patients with GDM receiving medications suggests greater fetal sensitivity to transient maternal glucose elevation in the context of GDM in contrast to pregestational diabetes.5 This finding needs to be validated in future prospective studies and randomized trials before it can be generalized.
The American College of Obstetricians and Gynecologists and the American College of Endocrinology continue to recommend tight glycemic monitoring and control in patients with diabetes during labor, with maintenance of blood glucose between 70 mg/dL and 110 mg/dL (mean, 100 mg/dL) to prevent fetal hypoglycemia and optimize neonatal outcomes. This goal is the same irrespective of whether the patient has pregestational or gestational diabetes mellitus.9
REFERENCES
- Dervisoglu P, Kosecik M, Kumbasar S. Effects of gestational and pregestational diabetes mellitus on the foetal heart: A cross-sectional study. J Obstet Gynaecol 2018;38:408-412.
- [No authors listed]. Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy: A World Health Organization guideline. Diabetes Res Clin Pract 2014;103:341-363.
- HAPO Study Cooperative Research Group; Metzger BE, Lowe LP, Dyer AR, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:
1991-2002.
- Metzger BE, Coustan DR, Trimble ER. Hyperglycemia and adverse pregnancy outcomes. Clin Chem 2019;65:937-938.
- Anwer TZ, Aguayo R, Modest AM, Collier ARY. Reexamining intrapartum glucose control in patients with diabetes and risk of neonatal hypoglycemia. J Perinatol 2021;41:2754-2760.
- Mitanchez D, Yzydorczyk C, Simeoni U. What neonatal complications should the pediatrician be aware of in case of maternal gestational diabetes? World J Diabetes 2015;6:734-743.
- Miyakoshi K, Tanaka M, Saisho Y, et al. Pancreatic beta-cell function and fetal growth in gestational impaired glucose tolerance. Acta Obstet Gynecol Scand 2010;89:769-775.
- Iafusco D, Stoppoloni F, Salvia G, et al. Use of real time continuous glucose monitoring and intravenous insulin in type 1 diabetic mothers to prevent respiratory distress and hypoglycaemia in infants. BMC Pregnancy Childbirth 2008;8:23.
- American College of Obstetricians and Gynecologists’ Committee on Practice Bulletines–Obstetrics. ACOG Practice Bulletin No. 201: Pregestational diabetes mellitus. Obstet Gynecol 2018;132:e228-e248.
