1. Obesity and Extreme Obesity: New Insights into the Black-White Disparity in Neonatal Mortality Hamisu M. Salihu, MD, PhD Department of Epidemiology and Biostatistics & Department of Obstetrics and Gynecology University of South Florida

2. Co-Authors: Amina P. Alio, PhD Council on African American Affairs, Washington, DC Roneé E. Wilson, MPH Department of Epidemiology and Biostatistics, University of South Florida Russell S. Kirby, PhD Department of Maternal and Child Health, University of Alabama at Birmingham, Birmingham, AL Greg R. Alexander, ScD Department of Pediatrics, University of South Florida

3. Introduction During the past two decades, the prevalence of obesity has been rising continuously in the United States, especially among women 1 Between 1986 to 2000 the prevalence of obesity, defined as body mass index (BMI) ≥30, doubled, while that of morbid or extreme obesity quadrupled 2

4. Introduction As a result of the increases in BMI and the strong association between obesity and years of life lost 3, some authors have predicted that the steady increase in life expectancy that marked the 20th century may halt in the 21st century 4 Absent in the ongoing debate on the impact of obesity on longevity is any discussion of the effect of maternal obesity on survival chances of the offspring Absent in the ongoing debate on the impact of obesity on longevity is any discussion of the effect of maternal obesity on survival chances of the offspring

5. Introduction Information on the association between obesity and neonatal survival is scant Risk estimates in the published literature are derived from highly homogenous populations –May not have practical application in the racially/ethnically diverse populace of the United States

6. Objectives To determine the impact of maternal obesity on neonatal survival To examine gradations of obesity as well as obesity-related black-white disparity in neonatal survival

7. Materials and Methods Missouri maternally linked cohort data files were used covering the period from 1978 through 1997 Singleton live births within the gestational age range of 20-44 weeks were selected Body mass index [weight (in kilograms) divided by height (in metres 2 )] was used to define maternal pre-pregnancy weight groups

8. Materials and Methods Women were assigned 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) –Class III (morbid/extreme obesity) (≥40) Underweight mothers were excluded

9. Materials and Methods Differences between obese and non-obese mothers in socio-demographic features were examined using the following characteristics: –Race (categorized as black or white) –Maternal age (categorized as < 35 or ≥35 years) –Marital status (married or unmarried) –Educational status (<12 or ≥12 years) –Cigarette smoking during pregnancy (yes or no) –Adequacy of prenatal care (adequate or inadequate) assessed using the revised graduated index algorithm based on the trimester prenatal care began, number of visits, and the gestational age of the infant at birth

10. Materials and Methods Documentation of certain morbidities on United States birth certificates did not become official until 1989 Thus, comparison of the following complications was restricted to the period 1989 through 1997: –Anemia –Insulin-dependent diabetes mellitus –Other types of diabetes mellitus –Chronic hypertension –Pre-eclampsia –Eclampsia –Abruptio placenta –Placenta previa

11. Materials and Methods The outcome of interest was neonatal mortality –defined as death occurring from the day of birth (day 0) to 27 days after birth (day 27) –further subdivided into: early neonatal mortality (from day 0 to day 6) late neonatal mortality (from day 7 to day 27)

12. Statistical Analysis Neonatal mortality rates were computed by dividing the number of neonatal deaths by total live births and multiplying by 1000 Chi-square test was used to determine differences in socio-demographic characteristics and maternal pregnancy complications between obese and non-obese mothers Chi-square for trend was applied to assess a dose-response relationship between severity of maternal obesity and neonatal mortality

13. Statistical Analysis Cox Proportional Hazards Regression models were used to generate risk estimates after confirming the non-violation of the proportionality assumption Adjusted hazards ratios were derived by loading all variables considered to be potential confounders into the model The Robust Sandwich estimator was used to adjust for intracluster correlation because the dataset contained successive pregnancies 5

14. Statistical Analysis All tests of hypothesis were two-tailed with a type 1 error rate fixed at 5% SAS version 9.1 (SAS Institute, Cary, NC) was used to perform all analyses Study was approved by the Office of the Institutional Review Board at the University of South Florida.

15. RESULTS

16. Results Prevalence of Obesity = 9.5% –12.8% and 8.9 % among black and white mothers respectively; p <0.01 Class I obesity - 82,603 or 5.9% Class II obesity - 33,074 or 2.3% Class III obesity - 17,699 or 1.3%

17. Results Black preponderance regardless of obesity subclass: –Class I (7.5% versus 5.6%; p <0.01) –Class II (3.2% versus 2.2%; p <0.01) –Class III (2.1% versus 1.1%; p <0.01)

18. Comparison of obese and non-obese mothers by selected socio-demographic characteristics, Missouri, 1978-1997 Obese (N=133,376) % Non-Obese (N=1,272,322) % P-value Maternal Age ≥ 35 years10.06.4<0.01 Parity Multiparous67.057.2<0.01 Race Black White 20.7 79.3 14.8 85.2 <0.01 Education ≥ 12 years80.979.2<0.01 Married Yes73.175.9<0.01 Smoking Yes22.326.2<0.01 Adequate Prenatal Care Yes43.439.6<0.01

19. Prevalence of common obstetric complications among obese and non-obese women, Missouri, 1989-1997 Obese (N=80,044) % Non-Obese (N= 545,491) % p-value Anemia Yes899 (1.1)7513 (1.4)<0.01 Insulin-dependent diabetes Yes 1308 (1.6)2068 (0.4)<0.01 Other forms of diabetes Yes3773 (4.7)7906 (1.5)<0.01 Chronic hypertension Yes2402 (3.0)2607 (0.5)<0.01 Pre-eclampsia Yes6728 (8.4)18,721 (3.4)<0.01 Eclampsia Yes151 (0.2)489 (0.1)<0.01 Placental abruption Yes494 (0.6)4171 (0.8)<0.01 Placental previa Yes264 (0.3)2113 (0.4)<0.01

20. Rates of neonatal, early, and late neonatal death by obesity subclass

21. Risk of neonatal, early and late neonatal death among obese mothers by obesity subclass Adjusted hazard ratio (95% Confidence Interval) *Neonatal*Early neonatalLate neonatal Normal weight (BMI =18.5 – 24.9) 1.0 Overall obesity1.2 (1.1-1.2)1.2 (1.1-1.3)1.1 (0.9-1.3) Class I obesity (BMI =30 – 34.9) 1.1 (1.0-1.2) 0.9 (0.8-1.2) Class II obesity (BMI =35 – 39.9) 1.2 (1.1-1.4) 1.3 (1.0-1.8) Class III obesity (BMI ≥40) 1.3 (1.1-1.5) 1.3 (0.9-1.9) *P value for trend < 0.01 Note: Adjusted hazard ratios were obtained after controlling for the effects of maternal race, age, educational achievement, marital status, smoking habits during pregnancy, adequacy of prenatal care received, fetal gender and year of birth.

22. Black-White disparity risk for neonatal, early and late neonatal mortality associated with obesity [normal weight white mothers (18.5-24.9) are the referent category] NeonatalEarlyLate Adjusted hazard ratio (95% Confidence Interval) *BlackWhite*BlackWhite*BlackWhite Overall Obesity1.8 (1.6-2.0) 1.0 (0.9-1.1) 1.8 (1.6-2.0) 1.0 (0.9-1.1) 1.6 (1.2-2.1) 0.9 (0.8-1.2) Class I 1.6 (1.3-1.8) 0.9 (0.8-1.1) 1.6 (1.3-1.9) 1.0 (0.9-1.1) 1.5 (1.0-2.1) 0.8 (0.6-1.0) Class II 1.9 (1.5-2.4) 1.1 (0.9-1.3) 2.0 (1.5-2.5) 1.1 (0.9-1.3) 1.6 (1.0-2.8) 1.2 (0.9-1.8) Class III 2.0 (1.4-2.4) 1.1 (0.9-1.4) 1.9 (1.4-2.5) 1.1 (0.8-1.4) 1.9 (1.0-3.4) 1.1 (0.7-1.9) *P for trend < 0.01; N = number of deaths Note: Adjusted hazard ratios were obtained after controlling for the effects of maternal age, educational achievement, marital status, smoking habits during pregnancy, adequacy of prenatal care received, fetal gender and year of birth.

23. Summary We found an association between maternal obesity and neonatal mortality The positive association restricted only to obese black mothers. White obese mothers did not show an association The higher the gradation of obesity the more pronounced the black-white risk differential for neonatal mortality Early rather than late neonatal death appears to be the major contributor to the preponderance of neonatal deaths among obese black mothers

24. Discussion A potential explanation for the black-white disparity is differences in access to care However, after adjusting for the adequacy of prenatal care received, the disparity still persisted –indicating that the obesity-associated black-white disparity in neonatal mortality is independent of access to prenatal care Nonetheless, access to care cannot be dismissed as a factor, because the adequacy of prenatal care index does not take into account the quality of care received

25. Discussion Results showed a higher frequency of diabetes, chronic hypertension and pre-eclampsia among obese women for those years for which data were officially available in the United States Contribution of these complications to adverse outcomes on the infant as reported in the literature remains unclear However, our findings did not indicate that diabetes and hypertensive disorders might partially explain the association between maternal BMI and adverse pregnancy outcomes

26. Limitations Long period of follow-up which spanned almost 20 years –Different infant cohorts were aggregated and analyzed together –Exposure to varying obstetric practices across the period of study, thus the findings might have been impacted 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 was minimized considerably Inability to separate black and white non-Hispanics from Hispanics because of the non-differentiation of ethnicity across this categorization in many of the records

27. Strengths Population-wide study –Therefore, the results are minimally affected by selection biases (e.g., referrals, etc), a source of concern in data derived from individual health facilities –The findings are reasonably generalizable This work adds new data to a domain that is still poorly understood and under-researched

28. Public Health Implications The findings of this study have considerable implications in defining areas of intervention to reduce the persistent black-white disparity in neonatal and infant mortality in the United States Since obesity is a modifiable condition, targeting obese black women to reduce weight in the pre- conceptional period could be a useful and reasonable primary prevention strategy to curtail the excess neonatal mortality risks in blacks

29. THANKS

30. References 1. Sturm R. Increases in clinically severe obesity in the United States, 1986-2000. Arch Intern Med 2003;163:2146-2148 2. Ferraro KF, Thorpe RJ, Jr, Wilkinson JA. The life course of severe obesity: does childhood overweight matter? J Gerontol B Psychol Sci Soc Sci. 2003;58:S110-S119 3. Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB. Years of life lost due to obesity. JAMA 2003;289:187-193 4. Olshansky SJ, Passaro DJ, Hershow RC et al. A potential decline in life expectancy in the United States in the 21st century. N Engl J Med 2005;352:1138-1145 5.Lin DY, Wei LJ. The robust inference for the Cox proportional hazards model. J Am Stat Assoc 1989;84:1074-1078

31. Acknowledgements This work was supported through a Young Clinical Scientist Award to Dr. Hamisu Salihu by the Flight Attendant Medical Research Institute (FAMRI). The funding agency did not play any role in any aspect of the study. The rest of the authors have no financial or conflict of interest disclosures to make. We thank the Missouri Department of Health and Senior Services for providing the data files used in this study.

32. Contact Information Hamisu Salihu, MD, PhD COPH 13201 Bruce B. Downs Blvd., MDC 56 Tampa, Florida 33612-3805 Tel: (205) 910-8720 / Fax: (813) 974-4719 E-mail: hamisu.salihu@gmail.com