Study finds preconception hypoglycemia tied to adverse pregnancy outcomes

Study finds preconception hypoglycemia tied to adverse pregnancy outcomes | Image Credit: © fotoduets - stock.adobe.com.

Women with low blood glucose levels prior to pregnancy may face a higher risk of adverse pregnancy outcomes, according to findings from a large retrospective study published July 29 in PLOS Medicine.^1,2

Researchers analyzed data from nearly 4.9 million Chinese women and found that preconception hypoglycemia was associated with an increased risk of preterm birth, low birth weight, small for gestational age, and birth defects—even in women without pre-existing diabetes.

The study, led by Hanbin Wu of the Chinese University of Hong Kong in collaboration with China’s National Research Institute for Family Planning, evaluated participants in the National Free Preconception Checkup Project between 2013 and 2016. All women were aged 20 to 49 years and conceived within one year of enrollment.

Of the total study population, 239,128 women (4.91%) had fasting plasma glucose (FPG) levels below 3.9 mmol/L at the preconception visit, classifying them as hypoglycemic per American Diabetes Association criteria.

Compared with women with normal FPG levels (3.9–<5.6 mmol/L), those with hypoglycemia were generally younger, more likely to be underweight, and had a higher prevalence of anemia. The adjusted analyses accounted for a broad range of confounders, including maternal age, BMI, parity, region, smoking status, chronic disease, and prior adverse pregnancy history.

Women with preconception hypoglycemia had significantly higher odds of several outcomes:

• Preterm birth: 10% higher risk (adjusted OR, 1.10; 95% CI, 1.08–1.12; P<.001)
• Low birth weight: 8% higher risk (OR, 1.08; 95% CI, 1.03–1.12; P=.001)
• Small for gestational age: 7% higher risk (OR, 1.07; 95% CI, 1.05–1.08; P<.001)
• Birth defects: 21% higher risk (OR, 1.21; 95% CI, 1.06–1.37; P=.004)

However, hypoglycemia was also linked to a modest reduction in several outcomes:

• Medical abortion: 6% lower risk (OR, 0.94; 95% CI, 0.91–0.98; P=.002)
• Miscarriage or early stillbirth: 5% lower risk (OR, 0.95; 95% CI, 0.92–0.97; P<.001)
• Macrosomia: 12% lower risk (OR, 0.88; 95% CI, 0.86–0.90; P<.001)
• Large for gestational age: 12% lower risk (OR, 0.88; 95% CI, 0.86–0.89; P<.001)

Outcomes were consistent across multiple sensitivity analyses, including those excluding women with prior adverse pregnancy outcomes or diabetes diagnoses.

The researchers also assessed the interaction between preconception BMI and hypoglycemia. Among underweight women, hypoglycemia was associated with a higher risk of miscarriage or early stillbirth. In contrast, overweight women with hypoglycemia showed a reduced risk of macrosomia and large-for-gestational-age infants.

“In addition to paying attention to women with preconception hyperglycemia, our findings call for increased concern for women with hypoglycemia in preconception glycemic screening,” the authors wrote. “These findings emphasize the importance of preconception examination in preventing and managing reproductive health risks for all women planning to conceive.”

The study has several limitations. It included only Chinese women, which may limit generalizability, and relied on a single fasting glucose measurement without HbA_1c data. The authors also noted the potential for unmeasured confounding factors, such as gestational complications or post-screening interventions.

Still, the authors suggest that these findings support the potential benefit of adding hypoglycemia screening to preconception care. “Comprehensive screening and coordinated interventions for abnormal FPG prior to and during pregnancy… is crucial for advancing the intervention window and mitigating the risk of adverse pregnancy outcomes,” they wrote.

References:

1. PLOS. Low pre-pregnancy blood sugar linked with higher risk of preterm birth, other risks. Eurekalert. July 29, 2025, Accessed August 1, 2025. https://www.eurekalert.org/news-releases/1091937
2. Wu H, Yang Y, Zhao C, Lyu X, Li J, Lei J, et al. (2025) Preconception hypoglycemia and adverse pregnancy outcomes in Chinese women aged 20–49 years: A retrospective cohort study in China. PLoS Med 22(7): e1004667. https://doi.org/10.1371/journal.pmed.1004667