The association between maternal HbA1c and adverse outcomes in gestational diabetes

**Background:** The role of HbA1c in gestational diabetes mellitus (GDM) remains unclear, especially in Asian populations. While HbA1c is established for diabetes diagnosis and monitoring, its utility for predicting adverse pregnancy outcomes in GDM is not well-defined, and most evidence comes from Caucasian cohorts. This study aimed to investigate the association between HbA1c levels at GDM diagnosis and adverse outcomes, considering maternal age, pre-pregnancy BMI, and gestational weight gain (GWG) in Chinese women.

**Methods:** This retrospective study included 2048 women with GDM and singleton live births who received prenatal care and delivered at the Women’s Hospital, School of Medicine, Zhejiang University from 1-July-2017 to 30-June-2018. GDM was diagnosed by 75g OGTT at 24–28 weeks using IADPSG criteria. HbA1c was measured by HPLC (HLC-723G8), NGSP-certified. Women with pre-existing diabetes, chronic diseases, autoimmune diseases, or tumors were excluded. HbA1c was categorized by quartiles: ≤5.0% (31 mmol/mol; n=755), 5.1–5.4% (32–36 mmol/mol; n=942), and ≥5.5% (37 mmol/mol; n=351). Pre-pregnancy BMI was classified by Chinese criteria (underweight <18.5, normal 18.5–23.9, overweight 24.0–27.9, obese ≥28.0 kg/m²). GWG was categorized per IOM 2009 guidelines as inadequate, adequate, or excessive. Logistic regression was used to assess associations, with two-sided p<0.05 considered significant.

**Key Results:** Compared to women with HbA1c ≤5.0%, those with HbA1c ≥5.5% had significantly higher adjusted odds of macrosomia (aOR 2.63, 95%CI 1.61–4.31), PIH (aOR 2.56, 95%CI 1.57–4.19), preterm birth (aOR 1.64, 95%CI 1.05–2.55), and primary C-section (aOR 1.49, 95%CI 1.09–2.03). Women with HbA1c 5.1–5.4% had significantly increased risk of PIH (aOR 1.91, 95%CI 1.24–2.94). Associations varied by subgroup: In women aged ≤29 years, HbA1c ≥5.5% was associated with primary C-section (aOR 2.35, 95%CI 1.22–4.53) and PIH (aOR 3.53, 95%CI 1.34–9.30). In women aged ≥35 years, HbA1c ≥5.5% was associated with macrosomia (aOR 5.52, 95%CI 2.00–15.24) and PIH (aOR 2.56, 95%CI 1.13–5.78). Among pre-pregnancy normal-weight women, HbA1c ≥5.5% was associated with preterm birth (aOR 2.21, 95%CI 1.29–3.78), macrosomia (aOR 2.92, 95%CI 1.52–5.61), PIH (aOR 2.72, 95%CI 1.36–5.45), and primary C-section (aOR 1.51, 95%CI 1.01–2.25). In underweight women, HbA1c 5.1–5.4% was associated with primary C-section (aOR 2.58, 95%CI 1.26–5.26). Women with inadequate GWG and HbA1c ≥5.5% had increased risk of macrosomia (aOR 4.71, 95%CI 1.52–14.58); those with excess GWG and HbA1c ≥5.5% also had increased macrosomia risk (aOR 3.27, 95%CI 1.39–7.71). Women with adequate GWG and HbA1c ≥5.5% had increased PIH risk (aOR 3.42, 95%CI 1.48–7.88). No significant association was found between HbA1c and LGA.

**Clinical Implications:** This study demonstrates that HbA1c at GDM diagnosis is significantly associated with major adverse outcomes in Chinese women, even at levels below the ADA-recommended cutoff of 6.0%. The findings highlight the importance of considering maternal age, pre-pregnancy BMI, and GWG when using HbA1c for risk stratification. The authors recommend strict counseling and follow-up for women with HbA1c 5.1–5.4% and ≥5.5% at 24–28 weeks, particularly those with normal or underweight pre-pregnancy BMI. Limitations include the single-center retrospective design, relatively small sample size, and lack of data on nutrition and lifestyle factors. Further multi-center studies are needed to establish optimal HbA1c cutoffs for Chinese and other Asian populations.