Fetal Anomalies in Obese Women
The rate of obesity in adult women in the United States is 35.3%. In addition to the decrement in overall health and well-being caused by obesity, a multitude of adverse pregnancy outcomes have been consistently associated with maternal obesity. Maternal obesity increases the risk for gestational diabetes, preeclampsia, fetal death, macrosomia, infection, cesarean delivery, thromboembolic events, surgical complications, early neonatal death, and birth trauma. Whether maternal obesity is associated with an increased risk of fetal malformations remains controversial, with case–control and cohort studies often yielding contrary results.
We undertook the present investigation to estimate whether the increase in the prevalence of obesity in our obstetric population was associated with a corresponding increase in the prevalence of major congenital anomalies and, if so, to evaluate whether other factors, particularly diabetes, could be contributory.
OBJECTIVE: To examine temporal changes in maternal weight and the association with major structural anomalies and other factors, such as diabetes, in our primary obstetric population.
METHODS: We conducted a serial, cross-sectional study using a perinatal database to identify all women with singletons who delivered in our system from 1991 to 2004. Three 5-year time epochs were defined to compare patient cohorts. Maternal weight, body mass index (BMI), diabetes status, incidence of major anomalies, and demographic data were compared. Multiple logistic regression was performed to estimate factors contributing to anomaly rates.
RESULTS: A total of 41,902 pregnancies were included. In each time epoch, there was an increase in the mean maternal weight, the mean BMI, the proportion of women weighing in excess of 200 lb, the proportion with a BMI higher than 29, the prevalence of pregestational diabetes, and the prevalence of major anomalies (all P
<.001). There was no significant independent association between maternal obesity and the presence of a major anomaly. In a multivariable logistic model, the major factor contributing to the increasing rate of congenital anomalies was the prevalence of pregestational diabetes (odds ratio 3.8, 95% confidence interval 2.1–6.6). The population-attributable risk of anomalies related to obesity increased from essentially 0% in 1991–1994 to 6.1% in 2000–2004, whereas that related to diabetes increased from 3.3% to 9.2% during the same time periods.
CONCLUSION: Although the prevalence of maternal obesity and anomaly have increased, maternal weight alone was not associated with an increase in congenital anomalies. Instead, diabetes was significantly associated with the increase in the rate of anomalies seen in our population. Identification of maternal weight as a risk factor in epidemiologic studies may be a surrogate for pregestational diabetes.
MATERIALS AND METHODS
This study was approved by the University of Alabama Institutional Review Board. We used a computerized perinatal database to identify women who received prenatal care within the University of Alabama maternity care system from 1991 to 2004. We defined three time epochs—1991–1994, 1995–1999, and 2000–2004—to compare patient cohorts in a serial, cross-sectional fashion. In addition to data routinely available in our perinatal database, computerized records of prenatal ultrasound examinations on each patient were linked to the perinatal database to enhance the identification of infants with congenital anomalies. Our perinatal database has been in operation since 1979 and contains almost 1,000 coded antepartum, intrapartum, and postpartum items per patient. Immediately after delivery, physicians record the intrapartum and postpartum data on standardized forms. All antepartum data from the patient’s clinical chart are entered by dedicated personnel, and these data are subjected to scheduled audit. Neonatal outcome data are derived directly from the infant discharge summary and diagnoses and incorporated into the database. Our current ultrasound database has been in operation since 1991 and includes fields for sonographic findings and diagnoses. This database can be reliably linked to the perinatal database using a medical record number, a unique perinatal care number, and date of birth.
Major congenital anomalies were defined as defects requiring medical or surgical intervention in the neonatal period as well as defects with the potential for significant physical or neurologic morbidity. The analysis was limited to patients delivering after 20 weeks to avoid potential failed ascertainment of anomalies in early second-trimester pregnancy losses or terminations. Women who terminated pregnancies because of prenatally diagnosed major congenital anomalies after 20 weeks of gestation were included in this cohort. All anomalies on terminated fetuses were confirmed after delivery either by gross examination of the abortus or by autopsy. All neonates diagnosed with a major congenital anomaly prenatally or in whom a major defect was diagnosed by the examining pediatrician or neonatologist before discharge or death were considered to have a major anomaly.
We investigated an association between obesity and the presence of any anomaly involving single organ systems (central nervous, cardiovascular, pulmonary, genitourinary, and musculoskeletal) and ventral wall defects. This analysis was limited to singleton gestations to minimize the effect of any temporal changes in multiple gestations and their effect on anomaly rates. Women who delivered at or beyond 20 weeks of gestation and received primary prenatal care in our system were eligible for inclusion in this analysis regardless of the time of antenatal care initiation.
Body mass index (BMI) was calculated from the maternal weight at the first visit and the maternal height from self-report. In the early time periods, up to 30% of patients did not have a height recorded. We therefore used a first prenatal visit weight in excess of 200 lb as our primary definition of obesity so as to include patients without a recorded height. Among women with a weight of at least 200 lb, only those with a height of at least 5 ft 9 in would have a BMI less than 29 kg/m2. As previously reported by our group, in our patient population, this height represents the 99th percentile, so our 200-lb threshold perforce includes few women with a BMI less than 29 kg/m2. In secondary analyses, we used Institute of Medicine criteria for obesity: BMI of more than 29.0 kg/m2. Women were considered to have pregestational diabetes if they had a diagnosis of medically treated diabetes predating pregnancy, or if they demonstrated evidence of glucose intolerance and were treated medically before 20 weeks of gestation. Because variation in practice patterns during the time studied made it difficult to accurately ascertain whether a woman had insulin-dependent or non–insulin-dependent diabetes mellitus, we collected data on the White classification and the proportion of women diagnosed with diabetes after the initiation of prenatal care but before 20 weeks of gestation. Throughout the time course of this study, our standard management policy was to place women with pregestational diabetes on split-mix regular and intermediate-acting insulin injections once pregnancy was recognized. Women were instructed to check pattern blood sugars with glucose goals of less than 105 mg/dL fasting and less than 120 mg/dL preprandial.
Comparisons between time epochs were made using analysis of variance for continuous variables and the x2 test for proportions. Multiple logistic regression was performed to examine the independent effect of maternal obesity, hypertension, pregestational diabetes, maternal age, parity, and race on the prevalence of congenital anomalies. A relative risk and 95% confidence interval (CI) for major congenital anomalies in obese women was calculated for each time epoch. Data were analyzed with SAS v9.1 (SAS Institute, Cary, NC). Statistical significance was defined at the ?=.05 level.
With the increase in the rate of obesity over the past two decades, we suspected that there might be a concomitant escalation in the rate of pregestational diabetes. Given the association between poorly controlled maternal diabetes and fetal anomalies, we examined the magnitude of the effect of diabetes on anomaly rates in the face of increasing prevalence of obesity by considering the etiologic fraction and the population-attributable risk for obesity and pregestational diabetes. The etiologic fraction, also known as the proportion of the attributable risk among the exposed, was calculated to estimate the proportion of anomalies due to obesity or pregestational diabetes. It is derived by dividing the difference in the incidence rates between exposed and unexposed groups by the incidence rate of the exposed group. The population-attributable risk estimates the proportion of all cases in the population that arise because of the exposure and is calculated by dividing the difference between the incidence in the total population and the incidence in the nonexposed by the incidence in the total population. It serves as a measure of the impact of the exposure on the population as a whole and represents the proportion of outcomes that could be eliminated in the population if it were possible to eliminate the exposure.
A total of 41,902 singleton gestations were included in this analysis. Over the three 5-year epochs of this study, there was an increase in the proportion of patients receiving care in our health system who were Hispanic (1.3%, 4.2%, and 17.0%, respectively; P<.001). Because these patients were underrepresented during the earlier epochs, we limited our analysis to whites and African Americans. Key demographic data are displayed in Table 1. In each subsequent time epoch, there was an increase in the mean maternal weight, the mean BMI, the proportion of women weighing in excess of 200 lb, the proportion with a BMI greater than 29, and the prevalence of pregestational diabetes (P<.001). In univariable analysis, the rate of major anomalies increased at each time period with the greatest relative increases in the cardiac and pulmonary systems (Table 2).
During each time period, there was no significant independent association between maternal obesity by either definition and the presence of a major congenital anomaly (Table 2). Moreover, even considering the entire time course of the study as one unit, obesity was not independently associated with an increase in the risk of major congenital anomalies. The adjusted odds ratio (OR) (95% CI) for major anomalies using the 200-lb threshold was 0.9 (0.6–1.3), and for BMI greater than 29, it was 1.3 (0.3–5.1).
In both obese and normal-weight women, the prevalence of pregestational diabetes increased across time periods (Table 3). In a multivariable logistic model, the major factor contributing to the increasing rate of congenital anomalies was the prevalence of pregestational diabetes (OR 3.8, CI 2.1–6.6; Table 4).
Although there was no direct association between maternal obesity and major congenital anomalies, the proportion of anomalies in obese women related to obesity increased from 0 to 23% during the time course of our study (Table 3). Among women with diabetes, the fraction of anomalies attributable to diabetes ranged from 58% to 76% during the time periods studied. In women with obesity and diabetes, the proportion of anomalies related to diabetes increased dramatically from 48% in 1991–1994 to 74% in 2000–2004. For our obstetric population as a whole, the population-attributable risk of anomalies related to obesity increased from essentially 0% in 1991–1994 to 6.1% in 2000–2004, whereas that related to diabetes increased from 3.3% to 9.2% during the same time periods (Table 3).