Use of maternal GHb concentration to estimate the risk of congenital anomalies in the offspring of women with prepregnancy diabetes
Open accessAbstract
OBJECTIVE— We sought to determine the absolute risk of having a congenital anomaly in relation to periconceptional GHb concentration among women with prepregnancy diabetes. RESEARCH DESIGN AND METHODS— Two reviewers independently retrieved all cohort studies through a systematic literature search between January 1985 and May 2006. For each study, the absolute risk of having a pregnancy affected by a major or minor structural anomaly (diagnosed either antenatally or up to 28 days after conception) was calculated according to the number of SDs of GHb above the mean for nondiabetic, nonpregnant control subjects. A multilevel logistic-normal model was used to pool the data, which were expressed in tabular and graphic formats. RESULTS— In seven cohort studies, there were 117 anomalies among 1,977 pregnancies. At a periconceptional GHb concentration 0 SD above normal, the absolute risk of a pregnancy affected by a congenital anomaly was ∼2% (95% CI 0.0–4.4). At 2 SD above normal, the risk was 3% (0.4–6.1), and at 8 SD it was ∼10% (2.3–17.8). For each 1-SD unit increase in GHb, the associated risk of a congenital malformation increased by an odds ratio of 1.2 (95% CI 1.1–1.4). The risk in relation to A1C followed the same pattern. CONCLUSIONS— Using data from a limited number of published studies, a practical aid was developed to optimize use of the GHb and A1C concentrations for estimating the absolute risk of a congenital anomaly in the offspring of women with prepregnancy diabetes.
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Increased risk of diabetic embryopathy, especially anencephaly, microcephaly, congenital heart disease, renal anomalies, and caudal regression, is directly proportional to elevations in A1C during the first 10 weeks of pregnancy.
“Observational studies show an increased risk of diabetic embryopathy, especially anencephaly, microcephaly, congenital heart disease, renal anomalies, and caudal regression, directly proportional to elevations in A1C during the first 10 weeks of pregnancy (3).”
From 15. Management of Diabetes in Pregnancy: <i>Standards of Care in Diabetes—2024</i> (2024) · cites this paper as [3]
The Implications and Other research sections report that higher periconceptional GHb/A1C is associated with greater congenital-anomaly risk, including cardiac and central nervous system anomalies. But the paper describes a curvilinear—not directly proportional—risk increase. Its Literature search section defines the measurement period as extending from before conception through 16 weeks’ gestation, not specifically the first 10 weeks, and its Congenital anomalies section does not establish increased risk for each named defect. (LLM, conf=0.90)
Experimental — accuracy not yet measuredOverall, studies show that treatment including a basal insulin regimen gives better glycemic control than sliding-scale insulin alone.
“Overall, studies have shown that treatment including a basal insulin regimen resulted in better glycemic control compared with sliding-scale insulin alone.92,107–109”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [108]
The Implications and Statistical analysis passages (page numbers unavailable) address maternal GHb, glycemic control, and congenital-anomaly risk. Searches for basal insulin and sliding-scale insulin found no passage comparing those treatment regimens, so our copy does not verify the attributed claim. (LLM, conf=0.75)
Experimental — accuracy not yet measuredIn an RCT, the basal-plus approach gave glycemic control similar to standard basal-bolus and can be an effective option when insulin needs are low, oral intake is reduced, or surgery is planned.
“The basal-plus approach in an RCT resulted in similar glycemic control compared with a standard basal-bolus regime108 and can be an effective alternative with low insulin requirements, decreased oral intake, or when undergoing surgery.1266,1353”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [108]
The Statistical analysis and Implications sections address periconceptional GHb and congenital-anomaly risk, not inpatient insulin regimens. Searches for basal-plus versus basal-bolus treatment and for low insulin needs, reduced oral intake, or surgery found no passage addressing the attributed claim. Page numbers were unavailable in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredRCTs showed that a basal prandial regimen with insulin analogs improved glycemic control and reduced hospital complications in general medical and surgical T2D patients compared with sliding-scale regular insulin alone.
“RCTs have shown that treatment with a basal prandial regimen using insulin analogs improved glycemic control with fewer hospital complications in general medical and surgical persons with T2D compared with sliding-scale regular insulin alone.92,107,108,1333–1336”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [108]
The paper’s Statistical analysis and Results section describes a meta-analysis of prospective cohort studies on maternal GHb and congenital anomalies, not randomized trials in hospitalized patients. Searches for basal-prandial insulin, sliding-scale insulin, and medical or surgical inpatients found no passage addressing the claimed treatment comparison or hospital complications. Page numbers were not available in our copy. (LLM, conf=0.78)
Experimental — accuracy not yet measuredThe risk of congenital anomaly progressively rises with the degree of periconceptional HbA1C elevation.
“It has been reported (16, 18) that the risk progressively rises in concert with the degree of periconceptional HbA1C elevation”
From Diabetes and Pregnancy: An Endocrine Society Clinical Practice Guideline (2013) · cites this paper as [16]
Maternal hyperglycemia in the first few weeks of pregnancy increases the risk of fetal malformations.
“Maternal hyperglycemia in the first few weeks of pregnancy increases the risk of fetal malformations, spontaneous abortions, and perinatal mortality (14–18).”
From Diabetes and Pregnancy: An Endocrine Society Clinical Practice Guideline (2013) · cites this paper as [16]
Maternal hyperglycemia in the first few weeks of pregnancy increases the risk of perinatal mortality.
“Maternal hyperglycemia in the first few weeks of pregnancy increases the risk of fetal malformations, spontaneous abortions, and perinatal mortality (14–18).”
From Diabetes and Pregnancy: An Endocrine Society Clinical Practice Guideline (2013) · cites this paper as [16]
Maternal hyperglycemia in the first few weeks of pregnancy increases the risk of spontaneous abortions.
“Maternal hyperglycemia in the first few weeks of pregnancy increases the risk of fetal malformations, spontaneous abortions, and perinatal mortality (14–18).”
From Diabetes and Pregnancy: An Endocrine Society Clinical Practice Guideline (2013) · cites this paper as [16]
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- Authors
- Guerin, A., Nisenbaum, R., & Ray, J. G.
- Affiliations
- Western University (CA)
- St. Michael's Hospital (CA)
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2007-07-01
- Volume
- 30
- Issue
- 7
- Pages
- 1920-1925
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2123539063
- Cited by
- 215
- References
- 32
- Citations by year
- 2026: 5 · 2025: 15 · 2024: 14 · 2023: 12 · 2022: 14 · 2021: 19 · 2020: 15 · 2019: 15 · 2018: 15 · 2017: 10 · 2016: 12 · 2015: 11 · 2014: 6 · 2013: 13 · 2012: 8
- FWCI
- 8.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Health Sciences › Medicine › Surgery › Congenital Anomalies and Fetal Surgery
- Keywords
- HbA1c, congenital malformations, structural malformations, periconceptional period, maternal glycemic control, risk estimation, pregnancy outcomes
- MeSH terms
- Congenital Abnormalities, Adult, Female, Glycated Hemoglobin, Hemoglobins, Humans, Hyperglycemia, Pregnancy, Pregnancy in Diabetics, Cohort Studies, Risk Assessment, Diabetes Complications
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