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A Closer Look at Prematurity and Infant Death: Variation in Receipt of Antenatal Corticosteroids, Massachusetts 2004-2008

Lizzie Harvey, MPHCDC/CSTE Applied Epidemiology FellowMassachusetts Department of Public HealthJune 6, 2012

Prematurity

• Preterm: < 37 weeks gestation

• US: 1 in 8 births are premature– $26 billion/year

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

Burden of Prematurity, US 2005-06

Burden of Prematurity, MA 2008

68.8% of MA infant deaths were due to conditions originating in the perinatal period

Causes of Preterm Infant Death

• The primary cause of preterm infant death is respiratory distress syndrome (RDS)

RDS is Preventable

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

ACOG Recommendation

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

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

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

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

Results397,704 Births

11,895 24-34 wks GA

6.9%

171,719 Level III

43.2%

DemographicsCharacteristic

Race % N (11,895)

Hispanic 14.4 1712

NH White 62.3 7415

NH Black 14.4 1718

Asian/PI 6.0 715

AI/Other 2.8 327

Unknown 0.1 8

Maternal Age

<20 years 6.2 742

20-34 years 64.3 7644

35+ years 29.5 3509

Plurality

Singleton 63.3 7533

Twins 31.5 3752

Triplets+ 5.1 610

Gestational Age

24-27 weeks 11.7 1397

28-30 weeks 17.6 2098

31-34 weeks 70.62 8400

Mode of Delivery % N

Vaginal 38.1 4534

VBAC 1.9 229

Primary C-section 47.6 5659

Repeat C-section 12.4 1471

Missing 0.02 2

Prenatal Care

Inadequate 1.4 162

Intermediate 1.5 177

Adequate 5.8 691

Adequate Plus 88.5 10526

Missing 2.9 339

Payer Source

Private 61.1 7270

Public 37.1 4414

Self-pay 0.66 79

Free Care 1.11 132

Mother's Birthplace

US 70.7 8411

PR 3.4 408

Foreign 25.9 3074

Outcomes of Interest397,704 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

P=0.0039

% ANC administration by year, Level III hospitals, MA 2004-2008

ANC VariationCharacteristic % ANC % No ANC p

Race

Hispanic 11.0 89.0 <0.0001

NH White 17.1 82.9

NH Black 14.4 85.6

Asian/PI 14.5 82.5

AI/Other 17.1 82.9

Unknown 12.6 87.5

Maternal Age

<20 years 8.5 91.5 <0.0001

20-34 years 16.0 84.1

35+ years 17.2 88.8

Plurality

Singleton 13.3 86.7 <0.0001

Twins 19.5 80.5

Triplets+ 24.8 75.3

Gestational Age

24-27 weeks 24.6 75.4 <0.0001

28-30 weeks 23.4 76.6

31-34 weeks 12.5 87.5

Characteristic % ANC % No ANC p

Mode of Delivery

Vaginal 10.9 89.1 <0.0001

VBAC 17.9 82.1

Primary C-section 19.4 80.6

Repeat C-section 17.1 82.9

Missing 0.0 100.0

Prenatal Care

Inadequate 10.2 89.4 <0.0001

>Adequate 16.3 83.7

Missing 5.3 94.7

Payer Source

Private 17.6 82.4 <0.0001

Public 13.1 86.8

Self-pay 17.7 82.3

Free Care 9.9 90.2

Mother's Birthplace

US 16.2 83.9 0.0018

PR 9.6 90.4

Foreign 15.9 84.1

Adjusted Odds of Receiving ANC

% ANC Administration by Gestational Age

®v®v®v®v

®v

®v®v

®v®v

Distribution of Level III Hospitals

P<0.0001

ANC Administration by Hospital, Level III Hospitals,

MA ANC Eligible Infants, 2004-2008

Outcomes of Interest397,704 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%

Variation in Infant Deathamong ANC Recipients

Characteristic % Dead % Alive @1 p

Race

Hispanic 6.4 93.7 0.29

NH White 3.7 96.3

NH Black 6.1 94.0

Asian/PI N/A N/A

AI/Other N/A N/A

Unknown N/A N/A

Maternal Age

<20 years N/A N/A 0.11

20-34 years 4.9 95.1

35+ years 2.8 97.2

Plurality

Singleton 4.6 95.4 0.73

Twins 3.8 96.2

Triplets+ 4.0 96.0

Gestational Age

24-27 weeks 14.4 85.8 <0.0001

28-30 weeks 3.3 96.7

31-34 weeks 1.4 98.6

Characteristic % Dead % Alive@1 p

Mode of Delivery

Vaginal 3.8 96.2 0.66

VBAC N/A N/A

Primary C-section 4.5 95.5

Repeat C-section 3.6 96.4

Prenatal Care

Inadequate N/A N/A 0.87

>Adequate 4.3 95.7

Missing N/A N/A

Payer Source

Private 3.5 96.5 0.04

Public 5.5 94.5

Self-pay N/A N/A

Free Care N/A N/A

Mother's Birthplace

US 4.3 95.7 0.87

PR N/A N/A

Foreign 4.3 95.7

N/A=<5 infant deaths in category

Odds of Death among ANC Recipients

Characteristic Unadjusted 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

Characteristic Unadjusted 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)

% Infant Deaths by Gestational Age among ANC Recipients

Outcomes of Interest397,704 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%

No difference between preterm-related causes of death by ANC receipt in infant deaths

p=0.93

Differences in Cause of Death

Congenital malformations more prevalent in non-ANC infant cause of death p=0.008

Differences in Congenital Malformations

More infants who did NOT received ANC died within the first 24 hours of life

p=0.0043

Differences in Time of Death

% Infant Deaths by Gestation and ANC Receipt

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

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%

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

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

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

References• CDC Premature Birth:

– 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

%20Obstetric%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.html

• MA Death Statistics:– http://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.html

Thank you

Contact Information:Lizzie.Harvey@gmail.com

Hafsatou.Diop@state.ma.us