Hemoglobin A1C Screening in Early Gestational Diabetes
With no clear standards for A1C screening in early pregnancy, researchers focus on establishing useful guidelines
Gestational diabetes (GD) is a common complication in pregnancy, and in the US, up to 15 percent of pregnant women develop GD.1 But sometimes, women can have pre-existing diabetes and not know it, in which case the challenge often becomes distinguishing between pre-existing diabetes and GD.
In both cases, diabetes in pregnancy is associated with maternal and fetal complications, including preeclampsia, metabolic dysfunctions, and higher rates of NICU admissions.2 Diabetes screening in early pregnancy aims to identify women at risk of complications so they can make healthy lifestyle changes or begin treatment with medications; however, there are no set standards for early GD screening in the US.
Historically, pregnant women with risk factors for diabetes are tested for GD in the second or third trimester of pregnancy using a two-step approach: a glucose challenge test followed by an oral glucose tolerance test.3 But when a woman has never been tested for diabetes, testing for GD later in pregnancy can make it difficult to distinguish between pre-existing diabetes and GD.
Part of the problem is that in the US, a pregnant woman’s first prenatal appointment may be the first time she sees a doctor. “Many women are showing up pregnant with clear risk factors for insulin resistance and diabetes, but they were not screened before pregnancy,” says Dr. Kartik Venkatesh, a high-risk obstetrician at Ohio State Wexner Medical Center. “The dilemma is, how do you diagnose diabetes in early pregnancy? Do you need to go through a two-step process like the way we diagnose gestational diabetes later in pregnancy, or can you actually use an A1C [test] in pregnancy?”
Hemoglobin A1C tests
Recommended by the International Expert Committee in 2009, the A1C test is a blood test now commonly used for diabetes screening and monitoring in non-pregnant people.4 In the blood, glucose can bind to the hemoglobin A molecule in red blood cells for up to 120 days. Thus, an A1C test measures the percentage of hemoglobin A bound with glucose, known as glycated hemoglobin (A1C), over the past two to three months. According to the committee, an A1C measure of more than or equal to 6.5 percent is indicative of diabetes, while a range between 6 percent and 6.4 percent is considered prediabetes, meaning a person is at high risk of developing diabetes.4
The traditional two-step approach to testing can be difficult for pregnant women, as the test is time-consuming and requires women to fast and drink a nauseating sugary liquid. In contrast, the A1C test can be added to the usual prenatal blood panel.
Because of the complications associated with diabetes in pregnancy, the American College of Obstetricians and Gynecologists, the American Diabetes Association (ADA), and the International Association of Diabetes and Pregnancy Study Groups (IADPSG) all recommend early diabetes screening in pregnant women with risk factors for diabetes.3,5–7 However, there are no established A1C guidelines in early pregnancy.
Early GD screening
In terms of screening for early GD, it is unclear which test performs best. Currently, the ADA and IADPSG allow use of A1C for testing and screening, but the ADA does not recommend using A1C alone.3
“Diabetes screening in early pregnancy aims to identify women at risk of complications so they can make healthy lifestyle changes or begin treatment with medications; however, there are no set standards for early GD screening in the US.”
To investigate diagnosing early GD using A1C, Venkatesh and colleagues conducted a retrospective study using the medical records of 243 high-risk women who had had both an A1C and a two-step test before or during the second trimester.8 They found that early A1C screening was somewhat predictive of early GD, where women who had GD had higher median A1C values compared to women without GD. Based on their data, the A1C cutoff value that best balanced the sensitivity and specificity of the test was 5.6 percent, similar to previous research.9
Likewise, a retrospective analysis of electronic medical records from over 7,000 pregnant women at Kaiser Permanente Washington compared the outcome of women with A1C values between 5.7 percent and 6.5 percent to those with normal levels below 5.7 percent.10 “We were really interested in these women with borderline scores in the prediabetes range, where they're not normal, but they're not diabetic,” says Dr. Sascha Dublin, an internal medicine doctor and epidemiologist who studies women’s health and is the senior author of the study. “We wanted to see if there was evidence that women with prediabetes are at high risk for adverse pregnancy outcomes—meaning that there might be a need for some kind of intervention.”
Dublin's team found that 48 percent of women with A1C levels within the prediabetic range developed GD, compared to only 11 percent of women with normal levels, meaning that pregnant women with an A1C between 5.7 percent and 6.5 percent were almost three times more likely to develop GD compared to women with normal A1C. However, they did not find any other statistically significant difference in outcomes between the two groups, suggesting that prediabetic women may not need treatment.
Interestingly, Dublin, along with Dr. Lu Chen, a postdoctoral fellow at the time and first author of the study, also found that women who were within the prediabetic range gained significantly less weight during pregnancy compared to the women with normal A1C. Dublin has one idea why: “Maybe [prediabetic women] were motivated to eat healthy and exercise more and control their weight gain, and that was how they ended up with outcomes that were about as good as the women who went into pregnancy with a normal A1C.”
In that way, A1C screening may have helped. But without a randomized controlled trial, there is no way to know for certain, Dublin adds.
Does early screening change outcomes?
Other studies have also found that A1C levels within the prediabetic range are associated with a higher risk of GD.11,12 But does early identification of women at high risk of GD change outcomes? One study set out to answer this question and found that in 913 high-risk women with a BMI over 30, early GD screening with A1C did not improve outcomes.13
Another issue around using A1C tests in pregnancy is rapid red blood cell turnover.14 “In early pregnancy, particularly in the first and second trimesters, women’s red blood cell turnover is increased because they're building up their red cell volume,” says Dr. Kimberly Vesco, an OB-GYN at Kaiser Permanente Northwest. Since high red blood cell turnover can interfere with A1C results, A1C may not be the best test for early GD screening, she says.
Vesco’s center is part of a consortium funded by the National Institute of Diabetes and Digestive and Kidney Diseases to study glycemia in pregnancy, but it will be several years before the results are published.
Pregnancy as a window into health
"When a woman has never been tested for diabetes, testing for GD later in pregnancy can make it difficult to distinguish between pre-existing diabetes and GD."
With increasing rates of obesity and diabetes, as well as increasing age in pregnancy, more and more women are at risk of GD.
“One could certainly argue there is inherent value to use pregnancy as a window into overall health,” says Venkatesh.
“It's a time that's been great to motivate [women] to do anything they can to make their lifestyle healthier,” says Dublin. “And that may help protect [them] from future diabetes, and it may protect their baby from a variety of risks.”
*NOVEMBER 3, 2020: This article has been updated to reflect that Dr. Lu Chen was first author of the Kaiser Permanente Washington study.
1. DeSisto, Carla L et al. “Prevalence estimates of gestational diabetes mellitus in the United States, Pregnancy Risk Assessment Monitoring System (PRAMS), 2007-2010.” Preventing Chronic Disease vol. 11 E104.
2. “Gestational Diabetes.” ACOG, www.acog.org/patient-resources/faqs/pregnancy/gestational-diabetes.
3. Committee on Practice Bulletins—Obstetrics. “ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus.” Obstetrics and Gynecology vol. 131,2 (2018): e49-e64.
4. International Expert Committee. “International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes.”Diabetes Care vol. 32,7 (2009): 1327-34.
5. American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Obstetrics. “ACOG practice bulletin No. 201: Pregestational diabetes mellitus.” Obstetrics and Gynecology vol. 132,6 (2018): e228-e248.
6. International Association of Diabetes and Pregnancy Study Groups Consensus Panel et al. “International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy.” Diabetes Care vol. 33,3 (2010): 676-82.
7. American Diabetes Association. “2. Classification and diagnosis of diabetes.” Diabetes Care vol. 40,Suppl 1 (2017): S11-S24.
8. Battarbee, Ashley N et al. “Hemoglobin A1c and early gestational diabetes.” Journal of Women's Health (2002), 10.1089/ jwh.2019.8203.
9. O'Connor, Catherine et al. “Trimester-specific reference intervals for haemoglobin A1c (HbA1c) in pregnancy.” Clinical Chemistry and Laboratory Medicine vol. 50,5 905-9.
10. Chen, Lu et al. “Early pregnancy hemoglobin A1C and pregnancy outcomes: A population-based study.” American Journal of Perinatology vol. 36,10 (2019): 1045-1053.
11. Fong, Alex et al. “Use of hemoglobin A1c as an early predictor of gestational diabetes mellitus.” American Journal of Obstetrics and Gynecology vol. 211,6 (2014): 641.e1-7.
12. Osmundson, Sarah S et al. “First Trimester Hemoglobin A1c Prediction of Gestational Diabetes.” American Journal of Perinatology vol. 33,10 (2016): 977-82.
13. Champion, Macie L et al. “71: Early gestational diabetes screening based on ACOG guidelines.” American Journal of Obstetrics and Gynecology vol. 222,1 (2020): S60-S61.
14. Lurie, S, and Y Mamet. “Red blood cell survival and kinetics during pregnancy.” European Journal of Obstetrics, Gynecology, and Reproductive Biology vol. 93,2 (2000): 185-92.