Ho, Y.-R. et al. Associations of mid-pregnancy HbA1c with gestational diabetes and risk of adverse pregnancy outcomes in high-risk Taiwanese women. PLoS One 12, e0177563 (2017). Another important finding of our study with biological relevance was that with increasing levels of HbA1c, GDM risk increased significantly and in a linear fashion.
Its current application in pregnancy has been limited to screening for overt type 2 diabetes and it remains unclear if it has utility for GDM screening. We observed that HbA1c provided a clinically meaningful improvement in GDM prediction over conventional high-risk factors with a 0.06-point improvement in the AUC. At the suggested ‘optimal’ cutpoint of 5.1% (32 mmol/mol), the sensitivity remained relatively low at 47% and the specificity was moderately high at 79%.
Pract. 133, 85–91 (2017). Longitudinal trajectories of the mean HbA1c levels across gestation were plotted by visit according to GDM status. Differences between GDM cases and controls were tested using linear mixed models. HbA1c was measured in blood collected at enrollment, visit 1, 2 and 4 in all GDM cases and one of the two matched controls.
Increased third-trimester HbA1c levels are associated with an increased risk of preeclampsia (3,13), macrosomia (1), and stillbirth (2), leading to speculations that the target for HbA1c in pregnancy should be even lower than outside pregnancy to prevent adverse events. 8.
Unlike the OGTT, the HBA1C test is equipped to tell if a woman has been a diabetic even before conception. This is because HBA1C provides the average concentration of blood glucose during the weeks previous to testing. So the HBA1C test when done at the time of first visit, especially when the OGTT value is abnormal, can help in distinguishing the true GDM cases from the other. Routine monitoring of fetal wellbeing (using methods such as fetal umbilical artery Doppler recording, fetal heart rate recording and biophysical profile testing) before 38 weeks is not recommended in pregnant women with diabetes, unless there is a risk of fetal growth restriction. Do not routinely offer continuous glucose monitoring to pregnant women with diabetes.
For women who were diagnosed with gestational diabetes and whose blood glucose levels returned to normal after the birth, do not routinely offer a 75 g 2-hour OGTT. These considerations highlight the need to carefully review glycemic control goals during pregnancy. Although HbA1c reference intervals for the general population are well established, they are not clearly defined in Mexican pregnant women.
The glucose values in OGTT were significantly higher in the T3 group than the T2 group. Pregestational diabetes refers to any type of diabetes diagnosed before a pregnancy.
Worth et al.  reported a significant increase among T1, T2, and T3 groups. Versantvoort et al.  reported a small decrease in HbA1c levels during T1 (5.4%), compared with T2 (5.5%), and T3 (5.8%). They also suggested a correlation between HbA1c levels during T1 and T2 and the birth weight percentile . However, Hartland et al. , O’Kane et al. , Hanson et al. , and Günter et al. , Hiramatsu et al.  reported a significant decrease in HbA1c in T2, which is similar to our findings.
This study aimed to comprehensively examine of HbA1c across pregnancy and its relation with GDM. The first aim was to profile the physiological variation in HbA1c across gestation and examine for differences in women with and without GDM. The second aim of this study was to prospectively evaluate the association between HbA1c levels measured in the first trimester and subsequent risk for GDM diagnosis. The third exploratory aim of this study was to evaluate the predictive utility of using first trimester HbA1c to predict GDM and potentially identify an ideal cut-off for GDM screening in the first trimester. A few prior studies have examined if HbA1c measured in the first trimester is useful for early predication of GDM3,4,5,6; however, these studies have been among high-risk populations only4,5, evaluated an HbA1c threshold only of 5.7% (39 mmol/mol), corresponding to prediabetes outside of pregnancy6, or used GDM diagnosed in the first trimester only as the outcome3.
A key limitation of our study was that we were unable to account for the presence of hemoglobinopathy or iron deficiency, which would have impacted the accuracy of HbA1c assessment. Nonetheless, investigation and active management of iron deficiency is a routine component of antenatal care at our institution. We also acknowledge that the early GDM cohort was preselected, and thus, it is possible the data may not be representative of all with early onset GDM.
Other studies have focused primarily on HbA1c measured in the second trimester or at the time of GDM diagnosis7,8,9. Thus, research remains limited on HbA1c measured in the first trimester and its relation with GDM among a population based sample.
Our study included a sufficient number of women to detect significant differences, and the importance of using a DCCT-aligned HbA1c method has been addressed in a consensus statement (8). The nonpregnant control group consisted of 145 healthy women aged 30 years who were investigated as a part of the population survey Inter 99 (15). All had a normal OGTT. If your HbA1c levels are high, it may be a sign of diabetes, a chronic condition that can cause serious health problems, including heart disease, kidney disease, and nerve damage.
First, the low sensitivity at higher HbA1c levels suggests that HbA1c may not be a good substitute for a second trimester OGTT, which tests the acute response to the glucose challenge and how women respond to the increased insulin resistant environment of late pregnancy. However, more importantly, the high specificity at 5.7% (39 mmol/mol) suggests that with this threshold few low-risk women, who otherwise would not receive early screening, would be incorrectly diagnosed by an elevated first trimester HbA1c level. This presents a unique opportunity for earlier interventions in these women which would be ideal as GDM is associated with adverse pregnancy outcomes such as macrosomia23. While it is plausible that with an earlier intervention these risks might be minimized, future studies evaluating early intervention based on elevated first trimester HbA1c are essential to determine its utility.
5. 5. Benaiges, D.
This optimal cutpoint maximizes the effectiveness of the test, but may not be ideal for the sole purpose of GDM diagnosis given that we have existing diagnostics based on the OGTT and the purpose of measuring HbA1c would only be an earlier diagnosis. Nonetheless, at a cutpoint of 5.7% (39 mmol/mol), the current cutpoint for prediabetes outside of pregnancy, the sensitivity was 21%, but the specificity was very high at 95%, which is very similar to estimates reported in a prior study of 13% and 94%, respectively6. There are two important things to note from our findings.
However, we applied leave-one-out cross-validation to avoid overfitting the model. Nonetheless, inferences regarding GDM diagnostics based on the ROC curves can only be treated as preliminary and require replication. In addition, the controls were matched to the GDM cases according to their age and race-ethnicity. While the matching was appropriately accounted for in our methods and the 6-point AUC difference between the models with and without HbA1c is valid, the overall AUC statistics are likely underestimated as the matching factors of age, race/ethnicity, which are strong risk factors for GDM, are not contributing to the AUC.
Because HbA1c reflects glucose levels in the prior two to three months, we interpret these results to suggest that hyperglycemia even within women without pre-pregnancy diabetes may be relevant for the development of GDM. This finding is in line with prior studies on preconception diet which have observed substantial increased risks for GDM with poor dietary quality, further supporting the hypothesis that preconception improvements in glucose function may aid in GDM prevention24.
If you have diabetes, the American Diabetes Association recommends keeping your HbA1c levels below 7%. Your health care provider may have other recommendations for you, depending on your overall health, age, weight, and other factors. If you already have diabetes, an HbA1c test can help monitor your condition and glucose levels. A hemoglobin A1c (HbA1c) test measures the amount of blood sugar (glucose) attached to hemoglobin. Hemoglobin is the part of your red blood cells that carries oxygen from your lungs to the rest of your body.
At visit 2 (24–29 weeks), 90.3% of the blood draws were within the targeted range. No blood was collected at visit 3.
At enrollment (8–13 gestational weeks), 99.7% of the blood draws were within the targeted range. At visit 1 (16–22 weeks), 91.0% of the blood draws were within the targeted range. At visit 2 (24–29 weeks), 90.3% of the blood draws were within the targeted range. No blood was collected at visit 3.
& 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 37, 2953–2959 (2014). One limitation of our study was that the sample size was somewhat small at 321 participants (107 women with GDM and 214 matched controls), however, this was based on the larger underlying cohort of women from across the United States providing adequate power to address the research question. Nonetheless, the sample size did preclude us from creating training and confirmation datasets for our predication models.
Gestational diabetes mellitus (GDM) refers to diabetes diagnosed in the second trimester (T2) or third trimester (T3) of pregnancy that is not clearly overt diabetes . The International Diabetes Federation estimated a global prevalence of 16.9% for hyperglycemia in pregnancy in 2013 .
Strict glycemic control is essential to minimize the maternal and fetal morbidity and mortality of pregnancies complicated by diabetes (1–3). In addition to home blood glucose measurement, which may not always reflect the true average blood glucose level (4), HbA1c is a useful parameter in metabolic regulation (5–8). Thus, supplementation with HbA1c, as is common outside pregnancy, seems appropriate. The hemoglobin A1c done early in pregnancy may be a convenient and effective way to identify women with pre-existing type 2 diabetes or who are at greater risk of worse pregnancy outcomes.
Second, we estimated the value of using HbA1c for prediction of GDM above and beyond conventional high-risk factors (i.e., maternal age, race-ethnicity, pre-pregnancy overweight or obesity, family history of diabetes, GDM in a prior pregnancy, and nulliparity). Finally, studying the fourth group of 159 women helped bring out the importance of knowing the truly normal women.
Levels of 6.5% or higher mean you have diabetes. All pregnant women should undergo screening for diabetes and prediabetes at initial appointment and also later in their pregnancy. If you are planning to become pregnant, you should be offered an HbA1c measurement on a monthly basis to help monitor your blood glucose control.
22. 22. Hiramatsu, Y., Shimizu, I., Omori, Y. & Nakabayashi, M. Determination of reference intervals of glycated albumin and hemoglobin A1c in healthy pregnant Japanese women and analysis of their time courses and influencing factors during pregnancy.
The strengths of our study include the large numbers of subjects and a multiethnic cohort likely to be translatable to different populations. The prospectively collected standardized data, the well-validated and standardized treatment intervention, and the single laboratory measuring HbA1c provide for a robust investigational data set. 6.
Women who are already diabetic but become aware of their disease at the time of pregnancy cannot be classified as having gestational diabetes. The study showed that 7% of women diagnosed with gestational diabetes were already diabetic at the time of first visit and were misdiagnosed with gestational diabetes, when they had diabetes.
The sugar in your blood is called glucose. When glucose builds up in your blood, it binds to the hemoglobin in your red blood cells. The A1c test measures how much glucose is bound. People who have diabetes need this test regularly to see if their levels are staying within range.
20. Catalano, P. M., Huston, L., Amini, S. B. & Kalhan, S. C. Longitudinal changes in glucose metabolism during pregnancy in obese women with normal glucose tolerance and gestational diabetes mellitus. Am. J. Obstet.
At visit 4 (34–37 weeks), 89.2% of the blood draws were within the targeted range. Home Diagnostics, offers a complete portfolio of blood glucose monitoring systems to meet the testing needs of every person with diabetes.
cData are presented by study visit. At enrollment (8–13 gestational weeks), 99.7% of the blood draws were within the targeted range. At visit 1 (16–22 weeks), 91.0% of the blood draws were within the targeted range.
Several authors have demonstrated that the measurement of HbA1c is a useful parameter in glycemic control [20, 21, 30]; Therefore, we suggest that these results be considered when determining treatment goals in Mexican women with diabetes during pregnancy, however studies among diabetic women using this reference value for HbA1c are needed. From the results of the study it was concluded that, in a multiethnic population, an early HbA1c ≥5.9% measurement identifies women at high risk for poorer pregnancy outcomes independently of GDM diagnosis later in pregnancy. Further studies are required to establish cutoff points adapted to each ethnic group and to assess whether early detection and treatment are of benefit.
Recent evidence has also shown that, despite optimal preconception control and unplanned pregnancies with good glycemic control in early pregnancy with optimal HbA1c levels, the development of complications associated with diabetes cannot always be prevented [13, 14]. The reference range of HbA1C in healthy Mexican pregnant women during pregnancy was 4.4% to 5.6%. We suggest as upper limits of HbA1c value ≤5.6%, 5.5%, and 5.7% for T1, T2, and T3, respectively among Mexican pregnant women.
An HbA1c test shows what the average amount of glucose attached to hemoglobin has been over the past three months. It's a three-month average because that's typically how long a red blood cell lives. For people without diabetes, the normal range for the hemoglobin A1c level is between 4% and 5.6%. Hemoglobin A1c levels between 5.7% and 6.4% mean you have a higher chance of getting diabetes.
While our findings are similar to other studies, such as Nielsen et. al who reported that levels decreased between two measurements from early to later in pregnancy21, we provide longitudinal data across pregnancy to show the complete pattern in each trimester. Another study observed similar patterns across pregnancy, but each time point was based only on cross sectional measurements with one observation per participant22. In this prospective study among women without pre-existing medical conditions, we systematically examined HbA1c measured across pregnancy starting in the first trimester and its relation with GDM risk.