Risk of Congenital Defects with Maternal Obesity and Diabetes

Abstract

Source: Moore LL, Singer MR, Bradlee ML, et al. A prospective study of the risk of congenital defects associated with maternal obesity and diabetes mellitus. Epidemiology. 2000;11:689–694.Between 1984 and 1987, the authors enrolled a cohort of 22,951 women from over 100 obstetrics practices who underwent 2nd trimester amniocentesis or α-fetoprotein screening in a prospective study to determine whether obesity and/or diabetes increased the risk of non-chromosomal congenital birth defects. Patients were categorized according to Body Mass Index (BMI) and the presence of diabetes (either type 1 or type 2). Congenital defects were assigned to the following 6 categories: craniofacial, musculoskeletal, urogenital, cardiovascular, neural tube, and other neurological defects. Defects due to birth trauma, infection, chromosomal and single gene abnormalities were excluded. Prevalence ratios were calculated for the effects of obesity and diabetes using multiple logistic regression analysis to adjust for confounding variables of maternal age, education, 1st trimester cigarette smoking, alcohol intake, and mean folate and retinol intake during the 3rd through 8th weeks of pregnancy. These potential confounders did not differ between those with and without diabetes or between those categorized as obese (>28 kg/m2) and non-obese with the exception of a somewhat older age distribution noted in the diabetic group.When compared to women without diabetes or obesity, obese women without diabetes had no higher risk of having a baby with a major defect (Prevalence Ratio [PR]=.95; 95% CI, .62–1.5). When compared to women without diabetes or obesity, women with either diabetes or gestational diabetes who were not obese had no higher risk of having a baby with a major defect (PR=.98; 95% CI, .43–2.2). However, when compared to women without diabetes or obesity, the pregnancies of women who were both obese and diabetic were 3.1 times more likely (95% CI, 1.2–7.6) to result in a baby with a defect and 7 times more likely to have a baby with craniofacial or musculoskeletal defects (95% CI, 2.1–22.7).This paper supports the conclusion that there are a growing number of serious complications associated with obesity, in this case congenital defects in offspring of mothers with obesity and diabetes. A very large prospective study by Calle et al concluded that the risk of death from all causes including cancer increased throughout the range of moderate and severe obesity for all age groups.1 The association of diabetes and increasing BMI is well known and documented2 but the surprising aspect of the above study is that diabetes and obesity seem to be synergistic factors contributing to the development of congenital defects. Why obesity would make the outcome in diabetic pregnancies worse is perplexing. The authors do not offer any plausible explanation other than age and nutrition but could not find any support for these possible factors in their own data. The issue of diabetic control and its potential relationship to the prevalence of congenital defects could have been a factor as it may be possible that diabetic control worsens as weight increases. Since the degree of control was not evaluated as a variable, this study cannot answer whether improved control in those patients with diabetes will lower the rate of congenital defects in their offspring.Selection bias might also have influenced the results of this study since women were included only if they were perceived as “at risk” (referred for amniocentesis, or α-fetoprotein screen). It is also important to note that the data analyzed in this study were collected in the mid-1980s, and practice patterns related to the optimal control of diabetes and criteria for diagnosis of gestational diabetes have changed since that time. Nonetheless, the large number of patients in this cohort makes the data compelling.The fact that obesity without diabetes did not increase the relative risk of congenital abnormalities is an important observation, though unexplained. It is also important for families and practitioners to recognize that diabetes or gestational diabetes without obesity does not significantly increase the overall incidence of congenital defects. The pregnancies associated with an increased risk of congenital defects were those where the mothers had both diabetes and obesity. A significant take-home message from this article is that control of obesity prior to conception, especially in diabetic women, might carry great benefits for the fetus. Initiating control of obesity as soon as a diabetic knows she is pregnant, or when a woman develops gestational diabetes, may have general clinical benefit. However, these actions are not guaranteed to prevent congenital anomalies, which occur in the first 8 weeks of the pregnancy. Given the current epidemic of obesity in the United States and disturbing trends of increased obesity3 and development of type 2 diabetes among children and adolescents,4 the implications of this study regarding the prevalence of birth defects should concern us all.