About one third of Americans are currently classified as obese.1,2 At least 22% of women of reproductive age,3 and 54% of women aged 20–39 years4 are either overweight or obese. More disturbingly is the recent observation of a persistent surge in the proportion of women that are extremely obese.5–9 While the relationship between obesity in general and poor birth outcomes has been fairly well-articulated,10–12 data on the effect of extreme obesity on birth outcomes remain sparse.13 Because considering obesity as a homogeneous entity would lead to misinterpretation of individual and population risk profiles,9 it is important to estimate the magnitude of these risks across population subsets of obese women. In this study, we set out to estimate the risk for stillbirth among three generally accepted obesity subtypes based on severity,9,14 and driven by the following working hypotheses:
- High maternal body mass index (BMI) impairs fetal well-being and leads to in utero fetal demise.
- The relationship between high maternal BMI and fetal death shows a positive correlation, and is dose dependent. This implies that the level of stillbirth increases as maternal BMI rises.
- Among obese gravidas, black–white disparity in fetal death is further widened with rising BMI.
MATERIALS AND METHODS
This analysis was conducted using the Missouri maternally linked cohort data files covering the period 1978 through 1997 inclusive. The data source contains information on both live birth and fetal death for each sibling and provides a platform for a longitudinal study of birth outcomes for each pregnancy. In this dataset, siblings are linked to their biologic mothers using unique identifiers. The methods and algorithm used in linking birth data into sibships and the process of validation have been described in detail previously.15 The Missouri vital record system is a reliable one that has been adopted as the criterion standard to validate U.S. national datasets that involve matching and linking procedures.16
For the purpose of our study, we selected singleton pregnancies within the gestational age range of 20–44 weeks. Body mass index (weight [in kilograms] divided by height [in meters2]) was used to define maternal prepregnancy weight groups. Height, measured at the first prenatal visit, and prepregnant weight, as reported at the first prenatal visit, were used to calculate prepregnant BMI.17 Based on previously published reports,9,14 we assigned women to the following BMI-based categories: normal (18.5–24.9), class I obesity (30.0–34.9), class 2 obesity (35.0–39.9) and extreme obesity (40 or higher). Because we were interested in the effect of excess fat storage on stillbirth, we excluded underweight mothers. We have used the word “toxic” in this paper to refer to the harmful effects of excess fat storage.
Information on maternal characteristics for each woman was considered to evaluate any differences in sociodemographic features: maternal age (categorized as younger than 35 or 35 or older), marital status (married or unmarried), educational status (less than 12 years or 12 years or more), cigarette smoking during pregnancy (yes or no), and adequacy of prenatal care (adequate or inadequate) between obese and nonobese mothers. Adequacy of prenatal care was assessed using the revised graduated index algorithm, which has been found to be more accurate than several others, especially in describing the level of prenatal care utilization among groups that are high risk.18,19 This index assesses the adequacy of care based on the trimester prenatal care began, number of visits, and the gestational age of the infant at birth.
We performed crude frequency comparisons for the presence of common obstetric complications, namely, anemia, type-1 diabetes, other types of diabetes mellitus, chronic hypertension, preeclampsia, eclampsia, abruptio placenta, and placenta previa. The documentation of these morbidities on birth certificates became official beginning in 1989 in the United States. For this reason, comparison was only restricted to the period 1989 through 1997.
The outcome of interest was stillbirth, which we defined as in utero fetal death at 20 or more weeks of gestation. Gestational age was computed in weeks as the interval between the last menstrual period and the date of delivery of the fetus. We subsequently used this time scale in the estimation of hazard ratios.
Stillbirth rates were computed by dividing the number of stillbirths by the sum of live births and stillbirths and multiplying by 1,000. Chi-square test was used to evaluate differences in sociodemographic characteristics and maternal pregnancy complications between the two groups. We tested for trend in stillbirth across gradations of BMI using χ2 test for trend.20 Using normal-weight, white women (18.5–24.9) as a reference, we used the Cox proportional hazards regression models to generate risk estimates after confirming the nonviolation of the proportionality assumption. The following factors were loaded and retained in the model based on biologic plausibility and the literature: maternal race, age, educational achievement, marital status, smoking habits during pregnancy, adequacy of prenatal care received, fetal gender, and year of birth. We also identified mothers with repeat pregnancies and ran models that adjusted for correlations within sibling clusters. Since the results we obtained from the Cox proportional hazards regression model were similar to one that adjusted for intracluster correlations, we report the former in this article.
All tests of hypothesis were two-tailed with a type 1 error rate fixed at 5%. SAS 9.1 (SAS Institute, Cary, NC) was used to perform all analyses. This study was approved by the Office of the Institutional Review Board at the University of Medicine & Dentistry of New Jersey (IRB reference number: 5547).
Records covering 1,577,082 births were available for analysis. We sequentially excluded multiple births (38,981 or 2.4%), pregnancies before 20 weeks or beyond 44 weeks of gestation (76,305 or 4.8%) and records for which BMI could not be computed either because of missing values (29,092 or 1.8%) or implausible values (2 individuals). After these exclusions, a total of 1,413,953 mother–fetus pairs were analyzed. About 9.5% of the mothers (n=134,527) had a BMI greater than 30 and were classified as obese (12.8% among blacks and 8.9% among whites). Of these, class I obesity was the most frequent (83,254 or 5.9%) followed by class II obesity (33,364 or 2.3%), and extreme obesity was found in 17,909 mothers (1.3%).
Differences between obese and nonobese mothers are summarized in Table 1. Obese gravidas were more likely to be older, multiparous, and black. The level of high school education and above was slightly higher among obese mothers. The level of adequate prenatal care received was also higher among obese gravidas. Nonobese mothers were, however, more likely to be married and to smoke during pregnancy.
Table 2 displays the prevalence of common medical and obstetric complications among mothers in the study. Medical complications traditionally known to be associated with high BMI were documented in greater frequency among obese mothers. Of the obstetric complications preeclampsia and eclampsia were more common among obese mothers while placental abruption and placenta previa were slightly higher in nonobese mothers. The prevalence of anemia was also slightly more likely among nonobese mothers.
Overall, 8,240 cases of stillbirth were registered over the entire study period. Of these, 7,091 (86.1%) were among nonobese mothers, yielding a stillbirth rate of 5.5 per 1,000. The crude stillbirth rate was significantly higher among obese mothers (8.5 per 1,000; P<.01). The 1,149 cases of stillbirth among obese mothers comprised 649 (stillbirth rate of 7.8 per 1,000) among mothers with class 1 obesity, 290 (stillbirth rate of 8.7 per 1,000) among gravidas with class II obesity, and 210 cases (stillbirth rate of 11.7 per 1,000) among mothers that were extremely obese.
The results of the association among obesity, obesity subtypes, and stillbirth are as shown in Table 3. The adjusted hazard ratios were not different from the crude estimates. The likelihood of stillbirth was 50% greater if a mother was obese compared with norma-weight mothers. The level of in utero fetal survival compromise correlated with the amount of maternal fat burden in a dose-dependent fashion. The greatest threat to in utero fetal survival was among women that were extremely obese who showed more than 100% higher likelihood for stillbirth compared with normal-weight women (Table 3).
Of the total number of stillbirths among obese mothers (1,149), 320 or 28% (stillbirth rate 11.4 in 1,000) occurred among black obese gravidas while 829 or 72% (stillbirth rate 7.8 in 1,000) were among white obese mothers. The absolute risk difference for obesity-associated stillbirth was on average 50% greater among blacks as compared to whites (Table 4). In both racial groups, the risk for stillbirth increased progressively with increase in BMI in a dose-effect pattern (P<.01). However, black–white disparity in obesity-related stillbirth remained persistent to the disadvantage of blacks regardless of the obesity subtype (Table 4).
We found a 40% increased likelihood for stillbirth among obese compared with nonobese mothers, a finding that supports our first hypothesis which posits that high maternal BMI impairs fetal survival in utero. This finding is in accord with previous studies on the risk of stillbirth among obese mothers11,12,21 or abnormal pregnancy weight gain.10 It is pertinent to point out the difference in magnitude of risk detected in our study compared with results published from Nordic countries.10,11 Whereas, we observed an overall 40% increased risk for stillbirth among women obese women in the United States, studies from Nordic states have reported a more than twofold elevated risk. An important factor that could have contributed to the risk difference is the definition of stillbirth. In the United States, the official definition of stillbirth is fetal death at and beyond 20 weeks of gestation, a definition applied in this study, while stillbirth as reported in the Nordic studies was based on a cutoff at 28 weeks of gestation. Since obesity-related fetal death increases with gestational age,21 the variation in definition of stillbirth could have accounted for the lower risk levels reported by us and other investigators.12
Our second hypothesis proposed a progressive rise in stillbirth with increase in maternal BMI. The reasoning behind this assumption is that, if abnormal body fat storage in the mother is toxic to the developing fetus, then the higher the dose of the toxin the more pronounced one would expect the effect to be. We observed an increase in the risk for stillbirth from 40% for class I obesity to around 100% for extreme obesity. The literature is deficient in studies that specifically address the effect of morbid acquisition of body mass and stillbirth. A recent and relatively rare population-based study by Cedergen13 found a similar lethal dose-effect of increasing BMI on fetal survival in utero based on 28 cases of stillbirth recorded among 3,386 morbidly obese gravidas. One obvious merit of our study is its pronounced power, because our analysis is based on approximately 10 times the number of stillbirth reported by Cedergen13 among extremely obese mothers. Our findings therefore add and strengthen currently sparse information on morbid obesity and stillbirth in general.
A third specific aim of our study tests the hypothesis that, among obese gravidas, black–white disparity in fetal mortality is further widened with rising BMI. Our analysis showed that the increase in excess maternal fat storage was more lethal to black than white fetuses. The absolute black–white risk difference in stillbirth rose from 30% for class I obesity to 50% for extreme obesity. These racial differences could probably be explained by variation in the incidence of obesity-related morbidities across the two racial groups. Obesity is associated with hypertension and diabetes in a dose-effect fashion.9 Previous investigators have found a fivefold increase in risk of stillbirth with placental dysfunction. A plausible explanation for the widening racial gap in utero mortality as BMI increases is a higher-than-expected rate of placental dysfunction among obese blacks because black women have higher rates of hypertension, which often go undiagnosed.22 An important limitation of our results is our inability to explore this pathway due to the blunted sensitivity of the instrument used in collecting information on maternal morbidity during pregnancy as previously reported by us.23 In addition, routine collection of data on pregnancy-related complications started only in 1989 in the United States, almost a decade after the commencement of this study. Nevertheless, it is recommendable that future research examines the reason for the linkage between racial background and lethality of rising BMI on the fetus, as this could potentially improve our understanding of obesity-related in utero fetal death. Strategies to reduce black–white disparities in birth outcomes should consider targeting obese, black women.
An important shortcoming of our data is the long period of follow-up of these women which spanned over 20 years. Different infant cohorts were aggregated and analyzed together. Because these infants were exposed to varying obstetric practices across the period of study, our findings might have been affected by this cohort effect. However, by controlling for year of birth in computing adjusted hazard estimates, the influence of this potential source of bias on our results must have been minimized considerably.
A strength in this study is that it is population-wide, and the results are, therefore, minimally affected by selection biases (eg, referrals), a source of concern in data derived from individual health facilities. The advantage is that the findings are reasonably generalizable. Another merit of this work is that it adds new data to a domain that is still poorly understood and under-researched. Nevertheless, our findings should not be regarded as definite but rather as impetus for more refined studies that will potentially offer answers to many questions emanating from these preliminary results.
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