Use of Maternal Glycosylated Hemoglobin Concentration to Estimate the Risk of Congenital Anomalies in the Offspring of Women with Pre-Pregnancy Diabetes Mellitus
- Andrea Guerin, Bsc1,
- Rosane Nisenbaum, PhD2 and
- Joel G Ray, MD, MSc, FRCPC (rayj{at}smh.toronto.on.ca)3
- 1Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario
- 2Center for Research on Inner City Health St. Michael's Hospital, Toronto, Ontario
- 3Departments of Medicine, Obstetrics and Gynecology and Health Policy Management and Evaluation, and the Divisions of General Internal Medicine and Endocrinology and Metabolism, St. Michael's Hospital, University of Toronto, Toronto, Ontario
Abstract
Objective: To determine the absolute risk of having a congenital anomaly in relation to periconceptional glycosylated hemoglobin concentration (GHb) among women with pre-pregnancy diabetes mellitus (DM).
Research design and methods: Two reviewers independently retrieved all cohort studies through a systematic literature search between 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 standard deviations (SD) of GHb above the mean for non-diabetic, non-pregnant controls. 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 1977 pregnancies. At a periconceptional GHb concentration 0 SD above normal the absolute risk of a pregnancy affected by a congenital anomaly was about 2% (95% confidence interval [CI] 0.0-4.4). At 2 SD above normal, the risk was 3% (95% CI 0.4-6.1), and at 8 SD it was approximately 10% (95% CI 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 HbA1c 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 HbA1c concentration for estimating the absolute risk of a congenital anomaly in the offspring of women with pre-pregnancy DM.
Conclusions: The offspring of women with pre-pregnancy diabetes mellitus (DM) are at increased risk of having a structural congenital anomaly <1-3>. It is hypothesized that hyperglycemia exerts a teratogenic effect on the developing fetus <4>. There is a positive association between poor glycemic control in the periconception period and the risk of such anomalies <1, 6-10>.
Footnotes
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- Received February 9, 2007.
- Accepted March 22, 2007.
- Copyright © 2007 American Diabetes Association
