Adverse Pregnancy Outcomes in Nondiabetic Patients with an Elevated Early Pregnancy HbA1c

Abstract

Objective This study aimed to evaluate the impact of elevated early hemoglobin A1c (HbA1c) values on perinatal outcomes in patients without a diagnosis of diabetes or gestational diabetes.

Study Design This is a retrospective study of patients with a singleton pregnancy who underwent universal HbA1c screening in early pregnancy at an urban tertiary care center between December 1, 2016, and December 31, 2018. Patients with pregestational diabetes mellitus (DM) and gestational DM (GDM) were excluded from analysis. The exposure of interest was HbA1c of 5.7 to 6.4% as measured on routine prenatal bloodwork at or during 16 weeks' gestation. The following pregnancy outcomes were assessed: preterm delivery <37 weeks, hypertensive disorders of pregnancy, shoulder dystocia, macrosomia (birth weight >4,000 g), small or large for gestational age neonate, operative vaginal delivery, third- or fourth-degree lacerations, cesarean delivery, neonatal intensive care unit (NICU) admission, neonatal hypoglycemia, and neonatal hyperbilirubinemia. Multivariable regression was performed to assess the relationship between HbA1c and selected adverse outcomes while controlling for potential confounders

Results Of the 2,621 patients who met inclusion criteria, 334 (12.7%) had an elevated HbA1c of 5.7 to 6.4%. Patients with an elevated HbA1c were more likely to be older, Black, multiparous, publically insured, obese, or have chronic hypertension than patients with normal HbA1c values. In the unadjusted analysis, patients with an elevated HbA1c were less likely to deliver at term (84.7 vs. 92.4%, p = 0.006), but more likely to undergo cesarean section (32.8 vs. 27.6%, p = 0.038), develop hypertensive disorders of pregnancy (31.9 vs. 23.2%, p = 0.001), or deliver a macrosomic infant (10.5 vs. 6.8%, p = 0.016) than those with a normal A1c. After adjusting for race, body mass index, insurance status, nulliparity, and age, however, only the relationship between HbA1c and spontaneous preterm birth remained significant (adjusted odds ratio [aOR] = 1.76, 95% confidence interval [CI]: 1.01–3.07).

Conclusion In our urban population, an elevated early HbA1c was associated with spontaneous preterm birth in nondiabetic patients

Key Points

• In nondiabetic patients, early pregnancy HbA1c was associated with selected adverse outcomes.

• Rates of preterm birth, pregnancy-induced hypertension, cesarean section, and macrosomia were higher in patients with an elevated HbA1c.

• The relationship between early pregnancy HbA1c and spontaneous preterm birth remained significant after adjustment.

Keywords

HbA1c - preterm birth - adverse outcomes - glucose tolerance

• 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 Hughes RC, Moore MP, Gullam JE, Mohamed K, Rowan J. An early pregnancy HbA1c >/=5.9% (41 mmol/mol) is optimal for detecting diabetes and identifies women at increased risk of adverse pregnancy outcomes. Diabetes Care 2014; 37: 2953-2959
• 3 Mañé L, Flores-Le Roux JA, Gómez N. et al. Association of first-trimester HbA1c levels with adverse pregnancy outcomes in different ethnic groups. Diabetes Res Clin Pract 2019; 150: 202-210
• 4 Osmundson SS, Zhao BS, Kunz L. et al. First trimester hemoglobin A1c prediction of gestational diabetes. Am J Perinatol 2016; 33 (10) 977-982
• 5 Chen L, Pocobelli G, Yu O. et al. Early pregnancy hemoglobin A1C and pregnancy outcomes: a population-based study. Am J Perinatol 2019; 36 (10) 1045-1053
• 6 Rasmussen KV, Nielsen KK, Pedersen ML. No association between early maternal HbA1c and offspring birthweight among women without pre-existing diabetes in Greenland. Int J Circumpolar Health 2020; 79 (01) 1702798
• 7 American Diabetes Association. 14. management of diabetes in pregnancy: Standards of Medical Care in Diabetes-2019. Diabetes Care 2019; 42 (Suppl. 01) S165-S172
• 8 American Diabetes Association. 2. classification and diagnosis of diabetes: Standards of Medical Care in Diabetes-2018. Diabetes Care 2018; 41 (Suppl. 01) S13-S27
• 9 ACOG Practice Bulletin No. 202: gestational hypertension and preeclampsia. Obstet Gynecol 2019; 133: 1
• 10 Lowe LP, Metzger BE, Dyer AR. et al; HAPO Study Cooperative Research Group. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: associations of maternal A1C and glucose with pregnancy outcomes. Diabetes Care 2012; 35 (03) 574-580