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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
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