HbA1c levels are significantly lower in early and late pregnancy
Open accessAbstract
S trict glycemic control is essential tominimize the maternal and fetalmorbidity and mortality of pregnan-cies complicated by diabetes (1–3). In addition to home blood glucose measure-ment, 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 preg-nancy, seems appropriate. Before pregnancy, the target for met-abolic control in women with diabetes is HbA1c values near the normal range (9). However, the upper normal range of HbA1c during normal pregnancy is only sparsely investigated with different meth-ods (10), mainly in late pregnancy (5,6,11,12), and reference ranges are gen-erally established from the nonpregnant state (4). Increased third-trimester HbA1c levels are associated with an increased risk of preeclampsia (3,13), macroso-mia (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. There is a need to establish the refer-ence range of HbA1c during normal preg-nancy with an internationally recognized Diabetes Control and Complications Trial (DCCT)-aligned method. In this study, we evaluated the normal upper range of HbA1c in early and late pregnancy. RESEARCH DESIGN AND METHODS — From our antenatal clinic, we randomly selected 100 healthy pregnant women without previous gesta-tional diabetes (early pregnancy group). All subjects had a random capillary blood glucose level 7.0 mmol/l at their first antenatal visit at approximately week 14 (range 8–17), and none developed gesta-tional diabetes. A selective screening based on risk factors for gestational dia-betes was used (14). A late pregnancy group was estab-lished of 98 healthy pregnant women in week 33 (range 28–37), who, as part of another study (14), had a normal 75-g oral glucose tolerance test (OGTT). HbA1c was measured on the same day as the OGTT. The nonpregnant control group con-sisted 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.
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The HAPO study showed that increasing glycemia is associated with more neonatal adverse outcomes such as macrosomia, neonatal hypoglycemia, and cesarean delivery.
“The HAPO study showed that increasing glycemia is associated with increased neonatal adverse outcomes such as macrosomia, neonatal hypoglycemia, and cesarean delivery.64,115–119”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [119]
The introduction (section “S,” page not given) says higher third-trimester HbA1c is associated with increased risk of macrosomia. It does not discuss the HAPO study or report associations with neonatal hypoglycemia or cesarean delivery; the Methods and Results instead address HbA1c reference ranges in pregnancy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredA1C levels fall during normal pregnancy due to physiological increases in red blood cell turnover.
“Due to physiological increases in red blood cell turnover, A1C levels fall during normal pregnancy (41,42).”
From 15. Management of Diabetes in Pregnancy: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [41]
The Results report lower HbA1c in early and late pregnancy than in nonpregnant women. The paper proposes that a likely shorter erythrocyte lifespan may contribute, but it also identifies lower fasting glucose as a possible explanation and does not establish increased red blood cell turnover as the cause. (LLM, conf=0.86)
Experimental — accuracy not yet measuredUsing the standardized report, clinicians can address glucose variability or use GMI to discuss discrepancies between CGM-derived glucose exposure and laboratory-measured A1C.
“Using the standardized report the clinician can also address glucose variability (e.g., %CV metric) (75) or use glucose management indicator (GMI) metric (43) to discuss the possible discrepancies noted in glucose exposure derived from CGM data versus the individual's laboratory-measured A1C (40; 76).”
From Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range (2019) · cites this paper as [40]
The Results (page not provided) suggest that a shorter erythrocyte lifespan in pregnancy can lower HbA1c, supporting a possible difference between measured glucose exposure and laboratory A1C. The paper does not examine CGM-derived exposure, GMI, or using a standardized report to discuss discrepancies. (LLM, conf=0.78)
Experimental — accuracy not yet measuredThe A1C test can at times fail to accurately reflect mean glucose even when anemia, hemoglobinopathies, iron deficiency, and pregnancy are not present.
“Importantly, as reported by Beck and colleagues, the A1C test can at times fail to accurately reflect mean glucose even when none of these conditions are present (40).”
From Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range (2019) · cites this paper as [40]
The Results report lower HbA1c during pregnancy than in nonpregnant controls, and the discussion considers pregnancy-related changes in glucose and erythrocyte lifespan. The paper does not address whether A1C can misrepresent mean glucose when pregnancy, anemia, hemoglobinopathies, and iron deficiency are absent; searches for that claim and for Beck found no supporting passage. (LLM, conf=0.77)
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References 20 · Cited by 331
- Authors
- Nielsen, L. R., Ekbom, P., Damm, P., Glümer, C., Frandsen, M. M., Jensen, D. M., & Mathiesen, E. R.
- Affiliations
- Department of Endocrinology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark
- Copenhagen University Hospital (DK)
- Steno Diabetes Center, Copenhagen, Denmark
- Steno Diabetes Center Copenhagen (DK)
- Odense University Hospital (DK)
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2004-05-01
- Volume
- 27
- Issue
- 5
- Pages
- 1200-1201
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2011185825
- Cited by
- 331
- References
- 20
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 20 · 2023: 23 · 2022: 24 · 2021: 26 · 2020: 23 · 2019: 13 · 2018: 23 · 2017: 19 · 2016: 17 · 2015: 14 · 2014: 7 · 2013: 12 · 2012: 15
- FWCI
- 6.23
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Keywords
- HbA1c, pregnancy, reference values, glycemic control, gestational diabetes mellitus, early pregnancy, late pregnancy, capillary blood glucose, oral glucose tolerance test, preeclampsia, macrosomia, stillbirth
- MeSH terms
- Blood Glucose, Female, Glycated Hemoglobin, Humans, Pregnancy, Pregnancy Trimester, First, Pregnancy Trimester, Second, Pregnancy Trimester, Third, Reference Values
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