1. 1 A Closer Look at Prematurity and Infant Death: Variation in Receipt of Antenatal Corticosteroids, Massachusetts 2004-2008 Lizzie Harvey, MPH CDC/CSTE Applied Epidemiology Fellow Massachusetts Department of Public Health June 6, 2012

2. Prematurity Preterm: < 37 weeks gestation US: 1 in 8 births are premature –$26 billion/year

3. Consequences of Prematurity Chronic problems –Intellectual disabilities –Cerebral palsy –Breathing and respiratory problems –Vision and hearing loss –Feeding and digestive problems Prematurity is one of the leading causes of infant death

4. Burden of Prematurity, US 2005-06

5. Burden of Prematurity, MA 2008 68.8% of MA infant deaths were due to conditions originating in the perinatal period

6. Causes of Preterm Infant Death The primary cause of preterm infant death is respiratory distress syndrome (RDS)

7. RDS is Preventable Administration of antenatal corticosteroids (ANC) can improve infant outcomes is associated with –Decreased RDS –Decreased intraventricular hemorrhage –Decreased mortality

8. ACOG Recommendation

9. Study Question: Are there differences in antenatal corticosteroid (ANC) administration and outcomes among infants in MA who were eligible for treatment?

10. Methods Linked birth-infant death data in MA from 2004-2008 in Pregnancy to Early Life Longitudinal (PELL) data system Eligibility criteria: –24-34 weeks GA –Level III Hospitals Frequency distributions and multivariate logistic regression models were used to assess risk controlling for covariates

11. Methods Gestational age (GA): combination of clinical estimate (CE) and calculated age based on the last menstrual period (LMP) –Used LMP when the CE was within 2 weeks of LMP –Used CE in all other cases

12. Methods Exposure and outcome criteria: –Steroid for Neonatal Pulmonary Maturity: “Glucocorticoid administered to mother 24-48 hours prior to premature delivery at 28-32 weeks. The administration of the steroid augments the maturation of the fetal respiratory system” –Infant death: Death < 1 year of age

13. Results 397,704 Births 11,895 24-34 wks GA 6.9% 171,719 Level III 43.2%

14. Demographics Characteristic Race %N (11,895) Hispanic14.41712 NH White62.37415 NH Black14.41718 Asian/PI6.0715 AI/Other2.8327 Unknown0.18 Maternal Age <20 years6.2742 20-34 years64.37644 35+ years29.53509 Plurality Singleton63.37533 Twins31.53752 Triplets+5.1610 Gestational Age 24-27 weeks11.71397 28-30 weeks17.62098 31-34 weeks70.628400 Mode of Delivery %N Vaginal38.14534 VBAC1.9229 Primary C-section47.65659 Repeat C-section12.41471 Missing0.022 Prenatal Care Inadequate1.4162 Intermediate1.5177 Adequate5.8691 Adequate Plus88.510526 Missing2.9339 Payer Source Private61.17270 Public37.14414 Self-pay0.6679 Free Care1.11132 Mother's Birthplace US70.78411 PR3.4408 Foreign25.93074

15. Outcomes of Interest 397,704 Births 11,895 24-34 wks GA 6.9% 1886 Yes ANC 15.9% 10,009 No ANC 84.1% 171,719 Level III 43.2% Less than 1 out of every 6 eligible infants received ANC

16. P=0.0039 % ANC administration by year, Level III hospitals, MA 2004-2008

17. ANC Variation Characteristic% ANC% No ANCp Race Hispanic11.089.0<0.0001 NH White17.182.9 NH Black14.485.6 Asian/PI14.582.5 AI/Other17.182.9 Unknown12.687.5 Maternal Age <20 years8.591.5<0.0001 20-34 years16.084.1 35+ years17.288.8 Plurality Singleton13.386.7<0.0001 Twins19.580.5 Triplets+24.875.3 Gestational Age 24-27 weeks24.675.4<0.0001 28-30 weeks23.476.6 31-34 weeks12.587.5 Characteristic% ANC% No ANCp Mode of Delivery Vaginal10.989.1<0.0001 VBAC17.982.1 Primary C-section19.480.6 Repeat C-section17.182.9 Missing0.0100.0 Prenatal Care Inadequate10.289.4<0.0001 >Adequate16.383.7 Missing5.394.7 Payer Source Private17.682.4<0.0001 Public13.186.8 Self-pay17.782.3 Free Care9.990.2 Mother's Birthplace US16.283.90.0018 PR9.690.4 Foreign15.984.1

18. Adjusted Odds of Receiving ANC

19. % ANC Administration by Gestational Age

20. Distribution of Level III Hospitals

21. P<0.0001 ANC Administration by Hospital, Level III Hospitals, MA ANC Eligible Infants, 2004-2008

22. Outcomes of Interest 397,704 Births 11,895 24-34 wks GA 6.9% 1886 Yes ANC 15.9% 10,009 No ANC 84.1% 1806 Alive 95.8% 80 Dead 4.2% 385 Dead 3.2% 9624 Alive 96.15% 171,719 Level III 43.2%

23. Variation in Infant Death among ANC Recipients Characteristic% Dead% Alive @1p Race Hispanic6.493.70.29 NH White3.796.3 NH Black6.194.0 Asian/PIN/A AI/OtherN/A UnknownN/A Maternal Age <20 yearsN/A 0.11 20-34 years4.995.1 35+ years2.897.2 Plurality Singleton4.695.40.73 Twins3.896.2 Triplets+4.096.0 Gestational Age 24-27 weeks14.485.8<0.0001 28-30 weeks3.396.7 31-34 weeks1.498.6 Characteristic% Dead% Alive@1p Mode of Delivery Vaginal3.896.20.66 VBACN/A Primary C-section4.595.5 Repeat C-section3.696.4 Prenatal Care InadequateN/A 0.87 >Adequate4.395.7 MissingN/A Payer Source Private3.596.50.04 Public5.594.5 Self-payN/A Free CareN/A Mother's Birthplace US4.395.70.87 PRN/A Foreign4.395.7 N/A=<5 infant deaths in category

24. Odds of Death among ANC Recipients CharacteristicUnadjusted OR (95% CI) Adjusted OR (95% CI) Race Hispanic Non-Hispanic White Non-Hispanic Black API AI/Other 1.76 (0.92-3.38) Ref 1.67 (0.92-3.04) 0.64 (0.20-2.08) 1.47 (0.44-4.87) 2.22 (0.96-5.08) Ref 1.24 (0.62-2.46) 0.61 (0.16-2.28) 1.36 (0.35-5.26) Maternal Age <20 years 20-34 years 35+ years 0.97 (0.29-3.17) Ref 0.56 (0.32-0.97) 0.97 (0.26-3.59) Ref 0.67 (0.38-1.20) Plurality Singletons Twins Triplets+ Ref 0.83 (0.51-1.34) 0.86 (0.36-2.05) Ref 0.94 (0.56-1.58) 0.79 (0.32-1.98) Gestational Age 24-27 weeks 28-30 weeks 31-34 weeks 11.47 (6.34-20.75) 2.33 (1.14-4.75) Ref 11.72 (6.39-21.5) 2.36 (1.15-4.84) Ref CharacteristicUnadjusted OR (95% CI) Adjusted OR (95% CI) Delivery Method Vaginal VBAC Primary C-section Repeat C-section 0.85 (0.50-1.46) 1.69 (0.50-5.66) Ref 0.79 (0.38-1.64) 0.84 (0.47-1.51) 2.68 (0.71-10.05) Ref 0.90 (0.42-1.92) Prenatal Care Adequate Inadequate Ref 0.64 (0.09-1.74) Ref 0.59 (0.07-4.64) Payer Private Public Self-care Free care Ref 1.61 (1.01-2.55) 2.11 (0.27-16.49) 4.99 (1.08-23.18) Ref 1.27 (0.73-2.21) 2.73 (0.32-23.92) 2.88 (0.55-15.02) Nativity US born PR Foreign born Ref 0.77 (0.28-2.09) 1.00 (0.85-1.19) Ref 0.89 (0.73-1.07) 1.02 (0.98-1.07)

25. % Infant Deaths by Gestational Age among ANC Recipients

26. Outcomes of Interest 397,704 Births 11,895 24-34 wks GA 6.9% 1886 Yes ANC 15.9% 10,009 No ANC 84.1% 1806 Alive 95.8% 80 Dead 4.2% 385 Dead 3.2% 9624 Alive 96.8% 171,719 Level III 43.2%

27. No difference between preterm-related causes of death by ANC receipt in infant deaths p=0.93 Differences in Cause of Death

28. Congenital malformations more prevalent in non-ANC infant cause of death p=0.008 Differences in Congenital Malformations

29. More infants who did NOT received ANC died within the first 24 hours of life p=0.0043 Differences in Time of Death

30. % Infant Deaths by Gestation and ANC Receipt

31. Notes: Hospital 1 had no recorded ANC administration data and therefore no ANC infant death data Hospitals 3 and 4: ANC infant death data suppressed due to <5 deaths Between variation: ANC Admin p=<0.0001; ANC infant death p=0.0038; No ANC infant death p=0.023 Within variation: Only 2 hospitals had significant differences between the two death categories (Hospital #2 : p=0.0043; Hospital #6: p=0.028) ANC Administration and Infant Deaths by Hospital

32. Limitations Administrative data –No ICD-9 code association with ANC receipt –Differences in BC guidelines and ACOG recommendations Discrepancy with medical records: –2008 (22-<30 weeks GA or <=1500g): 83.9% –Comparable data: 23.5%

33. Conclusions Higher rates of steroid use among lower gestational ages Higher rates of early death among infants not receiving steroids Possible trend that hospitals with lower steroid rates have higher mortality rates

34. Next Steps Examine data quality –Chart review with 1 hospital –1 year of data –Compare BC steroid status to hospital records Scenario 1: Data quality is poor –Definition on BC –Educate hospital registrars Scenario 2: Data is reliable –Dig deeper into sources of variations

35. Acknowledgements Hafsatou Diop, MD, MPH Xiaohui Cui, PhD Milton Kotelchuck, PhD, MPH Munish Gupta, MD, MPH Angela Nannini, PhD Maria Vu, MPH Emily Lu, MPH Karin Downs, RN, MPH CDC/CSTE Fellowship

36. References CDC Premature Birth: –http://www.cdc.gov/Features/PrematureBirth/http://www.cdc.gov/Features/PrematureBirth/ IOM Report: –National Research Council. Preterm Birth: Causes, Consequences, and Prevention. Washington, DC: The National Academies Press, 2007. ACOG recommendations: –http://www.acog.org/~/media/Committee%20Opinions/Committee%20on%20Obs tetric%20Practice/co475.pdf?dmc=1&ts=20120426T1750113547http://www.acog.org/~/media/Committee%20Opinions/Committee%20on%20Obs tetric%20Practice/co475.pdf?dmc=1&ts=20120426T1750113547 PELL Data System: –https://sph.bu.edu/index.php/Maternal-a-Child-Health/Pregnancy-to-Early-Life- Longitudinal-Linkage-bPELLb/menu-id-452.htmlhttps://sph.bu.edu/index.php/Maternal-a-Child-Health/Pregnancy-to-Early-Life- Longitudinal-Linkage-bPELLb/menu-id-452.html MA Death Statistics: –http://www.mass.gov/eohhs/docs/dph/research-epi/death-report-08.pdfhttp://www.mass.gov/eohhs/docs/dph/research-epi/death-report-08.pdf Preterm-related cause of death ICD classifications: –Mathews TJ, MacDorman MF. Infant mortality statistics from the 2004 period linked birth/infant death data set. National vital statistics reports; vol 55 no 15. Hyattsville, MD: National Center for Health Statistics. 2007. Antenatal Steroid Organization: –http://daybeforebirth.org/index.htmlhttp://daybeforebirth.org/index.html

37. Thank you Contact Information: Lizzie.Harvey@gmail.com Hafsatou.Diop@state.ma.us Lizzie.Harvey@gmail.com Hafsatou.Diop@state.ma.us