Pregestational maternal diabetes was associated with an increased risk of a major congenital anomaly, but obesity itself was not, a cross-sectional study found.
In a multivariable logistic model, the major contributor to a rising rate of congenital anomalies was maternal pregestational diabetes (OR 3.8, 95% CI 2.1 to 6.6), according to Joseph R. Biggio, Jr., MD, and colleagues from the University of Alabama at Birmingham.
“Because hyperglycemia is a major contributor to developmental malformations, interventions to address obesity and identify women at risk for diabetes and hyperglycemia should be considered in efforts to reduce the occurrence of congenital anomalies,” they wrote in the February issue of Obstetrics & Gynecology.
Maternal obesity has been linked with numerous problems, including preeclampsia, gestational diabetes, fetal and neonatal death, and birth trauma, but scientists have disagreed over whether it also contributes to the risk of fetal malformations, the researchers noted.
To help settle the issue, Biggio and colleagues used a perinatal database in their university health system that included all women with singletons delivered between 1991 and 2004.
They divided the cohort into three time periods — 1991 to 1994, 1995 to 1999, and 2000 to 2004, with a total of 41,902 pregnancies.
For their primary analysis, they defined maternal obesity as a first prenatal visit weight greater than 200 lb, because during the earlier epochs many women did not have body mass index (BMI) calculated. For their secondary analyses they used BMI greater than 29 kg/m2 as the criterion for obesity.
In each epoch, there were increases in mean maternal weight, mean BMI, the proportion of women weighing more than 200 lb, the proportion with a BMI greater than 29 kg/m2, and the prevalence of pregestational diabetes (P<0.001 for all).
Univariable analysis determined that the rate of major anomalies, particularly involving the cardiac and pulmonary systems, also increased during each time period.
But there was no independent association between congenital anomalies and maternal obesity using either definition, during any of the three time periods or during the study overall.
Although no direct association was seen between congenital malformations and maternal obesity, the investigators reported that the proportion of anomalies that could be attributed to obesity increased from 0% to 23% during the overall study period.
The proportion of anomalies that could be attributed to diabetes ranged from 58% to 76%.
Moreover, for obese women with diabetes the proportion of anomalies attributed to diabetes increased sharply, from 48% in the first epoch to 74% in the third epoch.
In contrast, for the obstetric population as a whole, the population-attributable risk of congenital malformation related to obesity rose from near zero in the first epoch to 6.1% in the third epoch, while that related to diabetes increased from 3.3% to 9.2%, the investigators reported.
During the course of the study there was a nearly 15-lb increase in maternal weight and a 30% increase in the proportion of women whose BMI exceeded 29 kg/m2.
There also was a nearly twofold increase in the rate of major anomalies — and a 250% increase in the prevalence of diabetes.
The authors observed that there has been much interest in the effects of maternal obesity on birth defects.
Although the pathophysiologic basis for this possible association have not been identified, hypotheses have included increased serum insulin, lower levels of folic acid, chronic hypoxia, and increased inflammatory mediators.
“Our study provides evidence that the defects may not be due solely to the maternal obesity per se but may be due to undiagnosed diabetes,” the investigators wrote.
From a public health standpoint, the study findings suggest that efforts to reduce the prevalence of congenital anomalies should be focused less on obesity and aimed more closely at correcting hyperglycemia.
“If euglycemia could be achieved before pregnancy, or at least embryogenesis and organogenesis, the majority of these anomalies could potentially be avoided,” they observed.
They also suggested that even women of normal weight, but with other diabetes risk factors, could benefit from closer attention to glycemic control.
A weakness of the study was the fact that detailed data on glycemic control was not available in the perinatal database, “and therefore we cannot comment on the association between glycemic control and anomaly rates,” the investigators wrote.
The study was supported in part by the National Institute of Child Health and Human Development.
The authors did not report any potential conflicts of interest.