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Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

Stefanie N. Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, USA. Department of Nutritional Sciences, School of Health Professions, Rutgers University, Newark, NJ, USA.

Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. You can also search for this author in PubMed Google Scholar. analyzed the data and wrote the paper. developed the study concept and supervised the study.

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Subjects Epidemiology Gestational diabetes Predictive markers. Abstract We aimed to examine the prospective association between first trimester HbA 1c and gestational diabetes GDM and explore the utility of HbA 1c for prediction of GDM.

Introduction Gestational diabetes GDM is a common pregnancy complication associated with adverse maternal and fetal outcomes including an increased risk for type 2 diabetes and cardiovascular disease later in life in mothers and an increased risk for macrosomia and obesity in offspring 1.

Blood Collection Blood specimens were collected in all participants following a standardized protocol at enrollment at 8—13 gestational weeks and at three additional study visits targeted at weeks 16—22 fasting , 24—29, and 34— Covariates All women underwent a screening ultrasound at enrollment to confirm accurate dating of the pregnancy by last menstrual period, which was then used to calculate gestational weeks at each subsequent visit.

HbA 1c Profile Across Pregnancy Longitudinal trajectories of the mean HbA 1c levels across gestation were plotted by visit according to GDM status. Prospective Association between HbA 1c and GDM Risk We examined the prospective association between HbA 1c measured in the first trimester and GDM risk as well as the change between HbA 1c in the first and second trimesters and GDM risk.

First Trimester HbA 1c and GDM Prediction We used a receiver-operating-characteristic ROC curves to evaluate the predictive ability of HbA 1c for GDM diagnosis. Results The participant characteristics of the women with and without GDM are shown in Table 1.

Table 1 Baseline characteristics among women who developed gestational diabetes GDM and non-GDM controls, NICHD Fetal Growth Studies- Singletons — Full size table. Figure 1. Full size image. Table 2 Odds of gestational diabetes GDM according to HbA 1c level at 8—13 weeks and the change in HbA 1c from 8—13 weeks and 16—22 and 24—29 weeks, NICHD Fetal Growth Studies- Singletons — Table 3 Sensitivity and specificity of HbA 1c at 8—13 weeks gestation and gestational diabetes diagnosis, NICHD Fetal Growth Studies-Singletons — Discussion In this prospective study among women without pre-existing medical conditions, we systematically examined HbA 1c measured across pregnancy starting in the first trimester and its relation with GDM risk.

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Article PubMed CAS Google Scholar Thériault, S. Article PubMed CAS Google Scholar Grewal, J. Article PubMed Central Google Scholar American Diabetes Association. Article PubMed CAS Google Scholar Stone, M.

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Article PubMed CAS Google Scholar Download references. Acknowledgements This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural funding and included American Recovery and Reinvestment Act funding via contract numbers HHSNC, HHSNI, HHSN, HHSNIC, HHSNC, HHSNC, HHSNC, HHSNC, and HHSNZ.

Author information Authors and Affiliations Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA Stefanie N.

Tsai Department of Nutritional Sciences, School of Health Professions, Rutgers University, Newark, NJ, USA Shristi Rawal Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Paul S.

Albert Authors Stefanie N. Hinkle View author publications. View author publications. Ethics declarations Competing Interests The authors declare no competing interests. Additional information Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material. Supplementary Figure S1. GDM was diagnosed by the International Association of Diabetes and Pregnancy Study Groups IADPSG criteria using a one-step g, 2-h OGTT. The results indicated a first-trimester HbA1c level of 5. In another study, the OGTT and HbA1c tests were performed in pregnant women at 24—28 weeks of gestation.

The cut-off point of the HbA1c level was 5. In Korean women, the HbA1c level at a cut-off point of 5. We further attempted to salvage a positive outlook on the use of mid-pregnancy HbA1c levels.

A further objective was to determine whether a combination of maternal age, the g, 1-h GCT and the mid-pregnancy HbA1c level would reduce the need for a subsequent g, 3-h OGTT. Thus, we concluded that the mid-pregnancy HbA1c level could not replace a two-step diagnostic approach to identify GDM.

However, a recent study reported that mid-pregnancy HbA1c may potentially reduce the number of OGTTs. It appears different criteria the Carpenter-Coustan criteria using a two-step diagnostic approach vs. the IADPSG criteria using a one-step g, 2-h OGTT for GDM diagnosis affect the results.

Further comparison studies are required. Our findings demonstrated that the mid-pregnancy HbA1c level was associated with various adverse pregnancy outcomes in a continuous fashion. These outcomes included gestational hypertension or preeclampsia, preterm delivery, NICU admission, low birth weight, and macrosomia.

The results provided supporting evidence for recent reports that the HbA1c level during pregnancy was associated with adverse pregnancy outcomes [ 14 — 16 ]. Thus, the mid-pregnancy HbA1c level may be used as a prognostic biomarker for adverse pregnancy outcomes.

In addition, compared with the women with HbA1c levels of 4. Similar J-shaped relationships have been identified for HbA1c levels and cardiovascular, cancer and all-cause mortality in patients with diabetes in the Ludwigshafen Risk and Cardiovascular Health study [ 23 ].

For adults without overt diabetes, a J-shaped relationship was also identified between the HbA1c levels and all-cause mortality in the Atherosclerosis Risk in Communities ARIC study and in a New Zealand linkage study [ 24 , 25 ].

However, there have been limited studies regarding this relationship in pregnant women. We hypothesized that low HbA1c levels measured at GDM diagnosis may potentially reflect a chronic, consuming physiopathological condition, which may lead to adverse pregnancy outcomes.

Additional studies are required to confirm these results and determine the potential mechanisms that may underlie this association [ 26 , 27 ]. The strength of the study was the assessment of the clinical usefulness of a mid-pregnancy HbA1c measurement as a replacement for the OGTT in pregnancy using a relatively large population over a 7-year period.

In Taiwan, the NHI provided 10 prenatal examinations by obstetrician gynecologists for pregnant women. Our study was based on the prenatal visit service of the NHI, which may refine the HbA1c measurement in this study and the diagnosis of GDM.

Nevertheless, because of the single-center non-randomized design, we should be cautious regarding the generalizability. Additional, large-scale, multi-center, randomized control design studies are required.

However, it lacked adequate sensitivity and specificity to replace a two-step diagnostic approach for GDM. The current study was a single-center prospective study; thus, additional, randomized control design studies are required.

GCT, glucose challenge test; HbA1c, hemoglobin A1c; GDM, gestational diabetes mellitus; OGTT, oral glucose tolerance test. HbA1c, hemoglobin A1c; BMI, body mass index; GCT, glucose challenge test; OGTT, oral glucose tolerance test; GDM, gestational diabetes mellitus; NICU, neonatal intensive care unit.

Continuous variables are presented as the median 25thth and were analyzed using the Wilcoxon rank sum test. b Caesarean as a result of prolonged labor, macrosomia, or cephalopelvic disproportion, with the exclusion of elective caesarean sections and caesarean sections scheduled because of a previous cesarean section, placenta previa, and malposition or malpresentation of fetus.

c Only includes vaginal deliveries. HbA1c, hemoglobin A1c; BMI, body mass index. Continuous variables are presented as the mean ± SD or median 25thth and were analyzed using analysis of variance ANOVA or the Kruskal-Wallis test, as appropriate. Conceptualization: YRH PW MCL CPY YHY.

Data curation: PW MCL. Formal analysis: MCL. Investigation: YRH PW MCL YHY. Methodology: YRH PW MCL YHY. Project administration: CPY YHY. Resources: PW YHY. Software: MCL YHY. Supervision: PW CPY YHY.

Validation: YRH STT YHY. Visualization: MCL YHY. Writing — original draft: YRH MCL YHY. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Article Authors Metrics Comments Media Coverage Reader Comments Figures.

Methods This prospective study enrolled 1, pregnant Taiwanese women. Results An ROC curve demonstrated that the optimal mid-pregnancy HbA1c cut-off point to predict GDM, as diagnosed by the Carpenter-Coustan criteria using a two-step approach, was 5.

Conclusions The mid-pregnancy HbA1c level was associated with various adverse pregnancy outcomes in high-risk Taiwanese women. Funding: The authors received no specific funding for this work. Introduction For the previous 30 years, investigators have attempted to determine whether the glycated hemoglobin A1c HbA1c level during pregnancy may be used as a screening or diagnostic test for gestational diabetes GDM [ 1 — 3 ].

Research design and methods Study participants This prospective study enrolled all pregnant women without overt diabetes and with positive g, 1-h GCT results who subsequently underwent a g, 3-h OGTT at the outpatient clinics of the Ditmanson Medical Foundation Chia-Yi Christian Hospital DMF-CYCH between March and September Download: PPT.

Two-step diagnostic approach for GDM As a result of the health policy and National Health Insurance NHI coverage, most non-diabetic pregnant women in Taiwan were administered a g, 1-h GCT at 24—28 weeks of gestation. Fig 2.

Gestational week of GDM screening using a two-step diagnostic approach and time frame for receiving the HbA1c test. HbA1c measurement and classification HbA1c was measured at the time the g, 3-h OGTT was performed. Statistical analysis Continuous variables are descriptively expressed as the mean ± standard deviation SD and were analyzed using analysis of variance ANOVA ; alternatively, they are expressed as the median 25thth and were analyzed using non-parametric tests the Kruskal-Wallis test or the Wilcoxon rank-sum test when the data were not normally distributed.

Results The study enrolled 3, pregnant women without overt diabetes and with positive g, 1-h GCT results who subsequently underwent the g, 3-h OGTT and delivered at DMF-CYCH during the study period.

Fig 3. ROC curve indicates the sensitivity and specificity of HbA1c levels for detecting GDM. Table 2. Discussion In this study, we determined that the optimal cut-off point of the HbA1c level with maximal sensitivity and specificity to predict GDM was 5.

Supporting information. S1 Fig. Proposed algorithm for avoiding g OGTTs. s TIF. S1 File. The analysis data. s XLS. S1 Table. Differences in the maternal characteristics, glucose levels, and pregnancy outcomes between the HbA1c and non-HbA1c groups.

s DOC. S2 Table. Associations between maternal characteristics and HbA1c. Author Contributions Conceptualization: YRH PW MCL CPY YHY. References 1.

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Am J Obstet Gynecol. Artal R, Mosley GM, Dorey FJ. Glycohemoglobin as a screening test for gestational diabetes. Rajput R, Yogesh Y, Rajput M, Nanda S. Utility of HbA1c for diagnosis of gestational diabetes mellitus. Diabetes Res Clin Pract. Moses RG. HbA1c and the diagnosis of gestational diabetes mellitus—a test whose time has not yet come.

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Does First-Trimester Hemoglobin A1C Predict Gestational Diabetes and Fetal Outcome?