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Major malformations in infants of IDDM women. Vasculopathy and early first-trimester poor glycemic control
M Miodovnik1, F Mimouni, P S Dignan
1Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Ohio 45267-0526.
Insights
Congenital malformations (CMs) in infants of diabetic mothers (IDMs) may be linked to maternal health factors. Poor glycemic control and high insulin needs in diabetic pregnancies are associated with increased CM risk.
Area of Science:
- Perinatology
- Endocrinology
- Medical Genetics
Background:
- Animal and in vitro studies suggest environmental glucose, ketone, or insulin levels impact congenital malformations (CMs) in infants of diabetic mothers (IDMs).
- Transplacental passage of antibody-bound insulin is known in humans, but the pathophysiology of CMs in insulin-dependent diabetes mellitus (IDDM) pregnancies remains debated.
Purpose of the Study:
- To investigate the association between CMs in IDMs and maternal factors including vasculopathy, first-trimester glycemic control, White class, and insulin requirements.
Main Methods:
- A cohort of 165 first pregnancies of women with IDDM was studied between 1978 and 1986.
- Maternal glycemic control was monitored weekly via blood glucose and HbA1 levels, alongside insulin requirements and weight.
- Infants underwent systematic examinations by neonatologists and geneticists/dysmorphologists.
Main Results:
- In this cohort, 7.9% of infants of diabetic mothers (IDMs) had major congenital malformations (CMs).
- The study aimed for specific glycemic targets: fasting blood glucose <100 mg/dl and 90-min postprandial blood glucose <140 mg/dl.
Conclusions:
- Maternal vasculopathy, poor first-trimester glycemic control (hyper- and/or hypoglycemia), advanced White class, and high insulin requirements are hypothesized to be associated with CMs in IDMs.
- Further research is needed to confirm these associations and elucidate the precise mechanisms.
Abstract:
From animal and in vitro studies, it has been suggested that high environmental glucose, ketone, or insulin concentrations and low glucose or insulin concentrations may be etiologic factors for congenital malformations (CMs) in infants of diabetic mothers (IDMs). Transplacental passage of antibody-bound insulin has been demonstrated in humans. Controversy exists regarding the pathophysiology of CMs in human insulin-dependent diabetes mellitus (IDDM) pregnancies. We hypothesized that CMs in IDMs are associated with maternal vasculopathy, poor first-trimester glycemic control (i.e., hyper- and/or hypoglycemia), advanced White class, and high insulin requirements. We studied 165 first pregnancies of women with IDDM from 1978 to 1986. The goals of glucose control were a fasting blood glucose of less than 100 mg/dl and a 90-min postprandial blood glucose of less than 140 mg/dl. Insulin requirements, body weight, and pre- and postprandial blood glucose were recorded at weekly clinic visits. Maternal blood HbA1 was measured on entry and every 4 wk to confirm that adequate glycemic control was achieved. Women who enrolled in the project were interviewed during gestation by a geneticist/dysmorphologist who obtained genetic and environmental histories using a standard questionnaire. All live-born infants and stillbirths were examined. Each live-born infant was assessed systematically by two independent examiners, a neonatologist and a geneticist/dysmorphologist; examination with standardized checklists was performed in the newborn nursery as soon after birth as was practical. In first pregnancies in the study, there were 13 IDMs with major CMs (7.9%).(ABSTRACT TRUNCATED AT 250 WORDS)