Preconception HbA1C Unrelated to Pregnancy Loss in Women Without Diabetes

Disappointed african-american girl getting unexpected result from pregnancy test
Elevated glycated hemoglobin (HbA1C) levels in women with diabetes have been linked to pregnancy loss. Researchers investigated if this was the case for women without diabetes.

Glycated hemoglobin (HbA1C) levels were not associated with live birth or pregnancy success among women without diabetes or other metabolic disorders but who did have a history of pregnancy loss. These findings were published in F&S Reports.

Investigators at the National Institutes of Health sourced data from the prospective cohort, Effects of Aspirin in Gestation and Reproduction (EAGeR), between 2006 and 2012 at 4 clinical sites throughout the United States. Women (N=1194) who were attempting to conceive spontaneously and had a history of pregnancy loss were followed for 6 months to assess pregnancy success.

The study participants were aged 28.7±4.8 years, body mass index (BMI) was 26.2±6.5 kg/m2, waist-to-hip ratio was 0.81±0.07, 94.7% were White, 67% had 1 previous pregnancy loss, and 33% had 2 pregnancy losses. More than 600 women (53.9%) had  pregnancy loss £4 months before the study, 46.5% had no previous live births, and 87.6% did not smoke in the year before the study.

Stratified by low (n=442), intermediate (n=372), and high (n=380) tertiles of HbA1C, women with high HbA1C  levels were slightly older (29.5±5.0 years) compared with 28.7±4.8 years in the low percentile group, had higher BMI (P <.0001), greater waist-to-hip ratios (P <.0001), and fewer were White (P <.0001). They were also more likely to have had a pregnancy loss 12 months or more before the study,

smoked during the previous year (P =.009), had higher glucose (P <.0001), fasting glucose (P <.0001), fasting insulin (P =.002), and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) scores (P =.001).

Compared with the intermediate tertile, no significant trends were observed among the high and low tertile cohorts in relation to fecundity on the basis of HbA1C, fasting glucose, fasting insulin, or HOMA-IR scores. Similarly, tertiles of HbA1C were not related with human chorionic gonadotropin (hCG)-detected pregnancy, clinical pregnancy, live birth, early pregnancy loss, or clinical loss.

A continuous model found an association between higher HbA1C and reduced fecundity (fecundability odds ratio [FOR], 0.74; 95% CI, 0.57-0.96; P <.05), lower odds of an hCG-detected pregnancy (FOR, 0.85; 95% CI, 0.77-0.95; P <.01), and clinical pregnancy (FOR, 0.84; 95% CI, 0.74-0.96). However, these associations were no longer significant after adjusting for age, ethnicity, smoking, BMI, and aspirin exposure.

The investigators acknowledged several limitations of the study, including that the majority of the participants were White women of higher socioeconomic class, so results may not be generalizable.

“We found no relationship between preconception [HbA1c] in women without known metabolic disease and fecundability, live birth, and pregnancy loss,” the investigators concluded. “The association between [HbA1c] and fecundability was influenced by BMI, a strong risk factor for both diabetes and infertility.” 

In light of their findings, the investigators said they support guidelines from the American College of Obstetricians and Gynecologists and the American Society of Reproductive Medicine to measure HbA1c  only in women who are diabetic or who otherwise meet the criteria for diabetes screening based on other risk factors, such as an elevated BMI.


Zolton JR, Sjaarda LA, Mumford SL, et al. Preconception hemoglobin A1c in healthy women is not associated with fecundability or pregnancy loss. F&S Reports.  Published online January 22, 2022. doi:10.1016/j.xfre.2022.01.002