NATIONAL CHILDREN’S STUDY CORE HYPOTHESIS

Impaired glucose metabolism during organogenesis is associated with an increased risk for major structural congenital malformations. Maternal and fetal genetic susceptibilities, and maternal environmental exposures and lifestyle factors modulate the impact of impaired maternal glucose metabolism on the developing fetus. II. Public Health Significance Prevalence Each year in the United States, about 150,000 babies are born with a major birth defect—about 3 % of all live births.1 Impairments in glucose metabolism during pregnancy are associated with an increased risk of birth defects; thus, infants of women with Type I2, Type II and gestational diabetics have a greater risk of having a birth defect.3 The risk of birth defects among these infants is estimated at 3-5 times higher than for non-diabetic mothers, and increases as glycemic control worsens. The most common related malformations include cardiac, neural tube defects and musculoskeletal anomalies, which are all induced before the seventh week of gestation.4;5 Studies have demonstrated that women who are obese, but have not been diagnosed with diabetes, are also at an increased risk for birth defects such as those observed in diabetic embryopathy.3;6-8 It has been suggested that the underlying mechanism involved in this phenomenon is poor glycemic control, albeit not as diagnosed diabetes. Over the past four decades the incidence of diabetes among women of childbearing age has increased.9 In a recent article in The Lancet, it was stated that among individuals aged 30-39 years of age, the prevalence of Type II diabetes has increased by 70 % and is expected to doubl