During the previous two decades, the prevalence of obesity has been rising continuously in the United States, especially among women1. It is estimated that between 1986 and 2000, the prevalence of obesity, defined as a body mass index (BMI) of 30 or more, has doubled, and that of morbid or extreme obesity has quadrupled.2 As a result of these substantial increases in BMI and the strong association between obesity and years of life lost,3 some have predicted that the steady rise in life expectancy that characterized the past century may come to a stop in the 21st century.4
Absent in the ongoing national debate on the impact of the obesity epidemic on longevity is the effect of maternal obesity on survival chances of their offspring; in other words, if obesity decreases the life expectancy of women, does it also affect early survival among infants born to these women? Currently, information on the association between obesity and neonatal survival is sparse, and the few studies that have addressed the topic come from Scandinavian populations,5,6 a highly homogeneous constellation. Risk estimates from these countries may not find practical application in the racially and ethnically diverse population of the United States. The paucity of United States-specific, population-wide data on the impact of maternal obesity on early survival of neonates probably has retarded progress in knowledge and the momentum for intervention strategies that could target obese women during pregnancy.
To narrow this gap in applicable knowledge that could potentially inform policy, we sought to estimate the effect of maternal obesity on neonatal survival using a data source that has consistently obtained prepregnancy BMI indices (height and weight) as well as infant survival for almost two decades. Although the main objective of the article is broadly on maternal obesity, we also examined the gradations of obesity as well as obesity-related black-white disparity in neonatal survival. This approach is more informative given the fact that the obesity epidemic has disproportionately affected black females and that risk profiles vary across gradations of severity of obesity.7
MATERIALS AND METHODS
We used the Missouri maternally linked cohort data files covering the period from1978 through 1997 inclusive. In this dataset, siblings are linked to their biological 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.8 The Missouri vital record system is a reliable one that has been adopted as “gold standard” to validate U.S. national datasets that involve matching and linking procedures.9
For the purpose of our study, we selected singleton live births 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 prepregnancy weight, as reported at the first prenatal visit, were used to calculate prepregnancy BMI.10 Based on previously published reports,7,11 we assigned women to the following BMI-based categories: normal (18.5–24.9), class I obesity (30.0–34.9), class II obesity (35.0–39.9), and morbid/extreme obesity (40 or higher). Because we were interested in the effect of excess fat storage on neonatal survival, we excluded underweight women.
Information on maternal characteristics for each woman was considered to evaluate any differences in sociodemographic features between obese and nonobese mothers: race (categorized as black or white), maternal age (categorized as less than 35 years or 35 years or more), 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). 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.12,13 This index assesses the adequacy of care based on the trimester prenatal care began, the 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, insulin-dependent diabetes mellitus (IDDM), other types of diabetes mellitus, chronic hypertension, preeclampsia, eclampsia, abruptio placenta, and placenta previa. The documentation of these morbidities on birth certificates became official in 1989 in the United States. For this reason, comparison was restricted only to the period 1989 through 1997.
The outcome of interest was neonatal mortality, which we defined as death occurring between the day of birth (day 0) and 27 days after birth (day 27). We further subdivided neonatal mortality into early neonatal (from day 0 to day 6) and late neonatal (from day 7 to day 27) mortality.
Neonatal mortality rates were computed by dividing the number of neonatal deaths by the number of total live births and multiplying by 1000. The χ2 test was used to evaluate differences in sociodemographic characteristics and maternal pregnancy complications between the two groups. We applied χ2 for trend to assess a dose-response relationship between severity of maternal obesity and neonatal mortality.14 We used the Cox Proportional Hazards Regression models to generate risk estimates after confirming the nonviolation of the proportionality assumption. We confirmed this by plotting the log-negative-log of the Kaplan-Meier estimates of the survival function versus the log of time.15 The results were parallel. Adjusted hazards ratios were derived by loading all variables considered to be potential confounders onto the model. These variables were selected based on biological plausibility and the literature. Because the dataset also contains successive pregnancies, we identified sibling clusters and adjusted for intracluster correlation by means of the Robust Sandwich Estimator.16
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 South Florida.
A total of 1,577,082 births were available for analysis. We sequentially excluded multiple births (38,981 or 2.5%), pregnancies before 20 weeks or beyond 44 weeks of gestation (76,305 or 4.8%), and records for which BMI could not be computed because of either missing or implausible values (29,093 or 1.8%). We also excluded fetal deaths (8,318 or 0.5%) and restricted the analysis to live births. Finally, we limited the dataset to records containing black and white mother-infant pairs, totaling 1,405,698.
Approximately 9.5% (n=133,376) of mothers were categorized as obese based on a BMI greater than 30 (12.8% among black mothers and 8.9% among white mothers; P<.01). Of these, class I obesity was the most frequent (82,603 or 5.9%), followed by class II obesity (33,074 or 2.3%); extreme/morbid obesity was found in 17,699 mothers (1.3%). A comparison of the distribution of the three classes of obesity indicated a preponderance of black mothers in all obesity subclasses: class I (7.5% versus 5.6%; P<.01), class II (3.2% versus 2.2%; P<.01), and extreme/morbid obesity (2.1% versus 1.1%; P<.01).
A comparison of obese and nonobese pregnant women with respect to selected sociodemographic characteristics is presented in Table 1. Obese women were older, multiparous, and more likely to receive adequate prenatal care than nonobese women. On the other hand, nonobese women were more likely to be married and to be smokers during pregnancy. Fewer than 15% of nonobese women were of black race compared with nearly 21% of obese women. Small but statistically significant differences were observed in the level of educational attainment between the two groups, to the advantage of obese women.
Table 2 presents the prevalence of common medical and obstetric complications among the pregnant women in the study. The data were available only beginning in 1989, the date the United States officially started collecting routine information on these variables. Complications typically associated with high BMI, such as chronic hypertension, IDDM, and other forms of diabetes, occurred more frequently in obese pregnant women. The level of chronic hypertension was six times as likely among obese pregnant women compared with their nonobese counterparts; the level of IDDM and other forms of diabetes was three times as likely. Preeclampsia and eclampsia were also more common among obese pregnant women, occurring at twice the frequency of nonobese pregnant women. By contrast, anemia, placental abruption, and placenta previa occurred with slightly higher frequency in nonobese pregnant women.
Overall, 7,622 cases of neonatal death were recorded for the entire study period. Infants of nonobese mothers comprised 88.8% of cases (n=6,770), yielding a neonatal death rate of 5.3 per 1000 versus 6.4 per 1000 among obese mothers (P<.01). More than 80% of neonatal deaths occurred within 6 days postpartum (early neonatal death). Of the 6,152 early neonatal deaths, 696 occurred among obese mothers, resulting in a rate of 5.2 per 1000 compared with 4.3 per 1000 among nonobese mothers. The rate of late neonatal death was 1.2 per 1000 and 1.0 per 1000 among obese and nonobese women, respectively. The rates of total, early, and late neonatal death increased with rising BMI, as shown in Figure 1. It is noteworthy that the prevalence of obesity among pregnant women increased almost 200-fold within the 20-year period of study, from 6.0% to 16.4%. For each of the years under study, the rate of neonatal mortality was greater among obese women except for the years 1984 and 1992.
The absolute risk estimates for neonatal mortality (rate/1000) in Figure 1 provide a framework for determining the absolute impact of obesity on neonatal mortality in terms of the number needed to treat to prevent one case of neonatal mortality among the various classes of obese individuals. These estimates demonstrate decreasing number needed to treat with ascending obesity subclass: class I (1,667), class II (588), and morbid obesity (455).
Results of the association between obesity and period of neonatal death are shown in Table 3. The likelihood of neonatal death and early neonatal death was 20% greater if a woman was obese compared with nonobese women. In addition, the risk of neonatal death and early neonatal death increased with greater levels of maternal obesity, displaying a clear dose-response pattern. No significant risk differences were detected in late neonatal deaths between obese and nonobese women. Because low gestational age at birth could be a likely mediating factor for neonatal mortality, we further examined the role of preterm birth by loading the variable coding for this information into the adjusted model. The results remained the same for neonatal (adjusted hazards ratio 1.2; 95% confidence interval [CI] 1.1–1.2), early neonatal (adjusted hazards ratio 1.2; 95% CI 1.1–1.2), and late neonatal (adjusted hazards ratio 1.1; 95% CI 0.9–1.3) death.
We present in Table 4 results of the association between obesity severity subclasses and neonatal mortality stratified by race. The findings demonstrate clearly that the elevated risk of neonatal mortality among newborns of obese mothers was confined to blacks only. Neonates born to obese white women had risk levels for neonatal mortality similar to those born to nonobese women regardless of the degree of severity of the obesity. By contrast, neonates of black women had significantly elevated risks for neonatal death that increased in a monotonic fashion with increasing BMI. These contrasting results for white and black neonates also were confirmed in the early and late neonatal periods. Because the higher frequency of obesity-associated medical complications (eg, diabetes and chronic hypertension) could to some degree explain our findings, we sought to delineate the association of high BMI and neonatal mortality by race independent of these complications. We did this by restricting our analyses to the years 1989 to 1997 inclusive, the period during which these complications were reported on vital records. The results we obtained were similar to those in Table 4.
In this large, population-based study, we examined the relationship between morbid obesity and neonatal survival among black and white women. We found a positive association between excessive maternal BMI and neonatal mortality after adjusting for several confounding factors. These findings are in agreement with the relatively few studies on maternal obesity and neonatal mortality.5,6 Unique to our study is the incremental rise in neonatal mortality with increase in maternal body fat storage, with a peak in risk among infants born to morbidly obese mothers. Our results also demonstrate that the elevated risk associated with maternal obesity is limited to the early neonatal period; both obese and nonobese pregnant women had comparable risks for late neonatal mortality.
The hallmark of the results of this study is the disparity in obesity-related neonatal mortality observed between black and white neonates. The elevated risk for neonatal mortality among obese women was noted only among neonates of black mothers. Interestingly, although overall estimation did not find elevated risk for late neonatal mortality among obese women, race-specific analyses revealed that neonates born to black women had an elevated risk for mortality as compared with those born to nonobese women regardless of the neonatal period. These neonatal period-specific mortality risks were also worse among heavier black mothers. This finding has implications in defining areas of intervention to reduce the persistent black-white disparity in neonatal and infant mortality in the United States. This becomes all the more interesting and feasible because obesity is a modifiable condition, and targeting obese black women to reduce weight in the preconception period could be a useful and reasonable primary prevention strategy to curtail the excess neonatal mortality risks in blacks.
A possible explanation for the black-white disparity in neonatal mortality among obese pregnant women is differences in access to care. One postulate is that obese white women have the advantage of better prenatal care compared with black women, and this is reflected in optimal fetal growth and development associated with levels of neonatal survival comparable with those of neonates of nonobese mothers. However, when we adjusted for the adequacy of prenatal care received, the disparity still persisted, indicating that obesity-associated black-white disparity in neonatal mortality is independent of access to prenatal care. Nonetheless, we cannot dismiss access to care as a factor because the adequacy of prenatal care index does not take into account the quality of care received. Future research on this topic may need to investigate black-white differences in access and quality of care received by neonates of obese mothers.
The results of this study showed a higher frequency of diabetes, chronic hypertension, and preeclampsia among obese women for those years for which data were officially available in the United States. The contribution of these complications to adverse outcomes in the neonate as reported in the literature remains unclear. Although some authors report that diabetes and hypertensive disorders might partially explain the association between maternal BMI and adverse pregnancy outcomes,17,18 others do not.5,6 Our findings are consistent with those of the latter group, which further confirms our findings that high BMI is an independent risk factor for neonatal mortality among blacks but not whites.
An important shortcoming of our data is the long period of follow-up of these women, which spanned almost 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. Another limitation of the dataset is our inability to separate black and white non-Hispanics from Hispanics because of the nondifferentiation of ethnicity across this categorization in many of the records.
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 an impetus for more refined studies that will potentially offer answers to many questions emanating from these preliminary results. The finding that neonates of obese blacks and not those of obese whites are at greater risk for neonatal mortality is new and warrants further investigation.
In summary, our study found maternal obesity to be an independent risk factor for neonatal mortality among blacks but not whites. The results suggest a possible avenue for targeting interventions that aims to reduce the black-white disparity in infant survival, a problem that has been persistent for decades in the United States.
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