1. Short-term costs of preeclampsia to the United States healthcare system
Warren Stevens, PhD1; Tiffany Shih, PhD1; Devin Incerti, PhD1; Thanh G.N. Ton, PhD1; Henry C. Lee, MD2; Desi Peneva, MS1; George A. Macones, MD3; Baha M. Sibai, MD4; Anupam B. Jena, MD5
1 Precision Health Economics
2 Division of Neonatal & Developmental Medicine, Stanford University, Lucile Packard Children's Hospital
3 Division of Maternal-Fetal Medicine, Washington University School of Medicine, Obstetrics and Gynecology
4 Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Texas Medical School at Houston
5 Department of Health Care Policy, Harvard Medical School; and Massachusetts General Hospital
Stevens, W., Shih, T., Incerti, D. et al. AJOG 2017

2. Background
Preeclampsia is among the top 6 causes of maternal mortality, maternal morbidity, and adverse neonatal outcomes in the U.S. and globally.
U.S. preeclampsia incidence has risen over the last three decades from 2.4% to 3.8% of pregnancies, outstripping the growth rate for diabetes, ischemic heart failure, Alzheimer’s disease, obesity, and chronic kidney disease.
Pregnancies complicated by preeclampsia are associated with both substantial maternal and neonatal complications.
The full health and economic burden of preeclampsia on both mothers and infants during the first year after delivery remains unclear.
Stevens, W., Shih, T., Incerti, D. et al. AJOG 2017

3. Objective
Our primary objective was to estimate health care costs for mothers with preeclampsia and their infants in the US within the first 12 months after delivery in 2012.
We estimated the economic burden in terms of costs attributable to preeclampsia alone.
Stevens, W., Shih, T., Incerti, D. et al. AJOG 2017

4. Methods: Datasets Assessed and Chosen
Overarching Criteria for Datasets
Nationally representative of U.S.
Longitudinal follow-up
Gestational age data available
Linked data on mothers and infants
Cost and outcome data available
Accessible to researchers
Athena HealthCare California Maternal Quality Care Collaborative (CMQCC) California Office of Statewide Health Planning and Development (California OSHPD) California Perinatal Quality Care Collaborative (CPQCC) Child Health Development Study (CHDS): Danish Birth Cohort Early Childhood Longitudinal Study Birth Cohort (National Center for Education Statistics) European Birth Cohorts (many) Extremely Low Gestational Age Newborns (ELGAN) Geisinger (MedMining) & Quintiles Healthcare Cost and Utilization Project (HCUP) HealthCore (WellPoint Anthem) Henry Ford Health Systems Kaiser Permanente of Northern California (KPNC) Maternal Fetal Medicine Units Network (MFMU) National Bureau of Economic Research / National Center for Health Statistics National Perinatal Collaborative Project (PCP):
National Survey of Family Growth (NSFG)
Neonatal Research Network (NRN)
NIAID Birth Cohorts (40+ cohorts)
Pediatrix Center for Research, Education, and Quality (CREQ)
Pharmetrics IMS
Pharmetrics Plus
Preeclampsia International Network
Preeclampsia Foundation
Pregnancy to Early Life Longitudinal System (PELL)
Premier Perinatal Safety Initiative
Regenstrief Institute
Optum Stork
Optum Touchstone
Truven Marketscan
UK Millennium Cohort Study (UK MCS)
Vermont Oxford Network (VON)
Stevens, W., Shih, T., Incerti, D. et al. AJOG 2017

5. Methods: Outcomes Maternal Outcomes Infant Outcomes Eclamptic seizure
Myocardial infarction
Cerebrovascular accidents & transient ischemic attacks
Thrombocytopenia
Acute renal failure
Disseminated intravascular coagulation
Pulmonary edema
Hemorrhage
Deep venous thrombosis
Pulmonary embolism
Death
Infant Outcomes
Fetal distress
Respiratory distress syndrome
Bronchopulmonary dysplasia
Retinopathy of prematurity stage >3
Necrotizing enterocolitis Bell’s grade ≥2
Intraventricular hemorrhage stage ≥3
Cystic periventricular leukomalacia
Sepsis
Meningitis
Seizures
Death
Stevens, W., Shih, T., Incerti, D. et al. AJOG 2017

6. Methods: Cost analysis schematic
Stage I: Develop a dataset of maternal covariates, health outcomes, and nationally-corrected predicted costs of mothers (infants)
(1)
Estimate a model of maternal (infant) costs as a function of maternal covariates
and health outcomes
Data: Claims
(2)
Apply claims-based model to predict costs in a representative dataset of maternal covariates and maternal (infant) outcomes
Data: OSHPD
(3)
Correct costs predicted in (2) for national generalizability
Data: Factors from claims data + HCUP  OSHPD
Stage 2: Estimate national burden of preeclampsia
(4)
Use dataset from Stage I to estimate nationally-representative relationship between preeclampsia and maternal costs (gestational age and infant costs)
Data: Stage I dataset
(5)
Estimate marginal impact of preeclampsia on individual maternal (infant) costs based on results of (4)
(6)
Multiply marginal impacts of preeclampsia from (5) by preeclampsia prevalence
(for infants, calculations conducted by gestational age)
Data: Results from (5) + preeclampsia rates from OSHPD + NCHS birth counts
Note: OSHPD = Office of Statewide Health Planning and Development; HCUP = Healthcare Cost and Utilization Project; NCHS = National Center for Health Statistics
Stevens, W., Shih, T., Incerti, D. et al. AJOG 2017

7. Results: Preeclampsia is associated with adverse infant and maternal outcomes
Predicted probability of adverse maternal and infant outcomes for pregnancies with and without preeclampsia
Stevens, W., Shih, T., Incerti, D. et al. AJOG 2017

8. Without covariate adjustment With covariate adjustment
Results: Preeclampsia is associated with earlier gestational age at delivery by approximately 1.7 weeks
Without covariate adjustment
With covariate adjustment
Change in gestational age (weeks) associated with preeclampsia SE
P-value
-2.1
(0.01)
<.0001
-1.7
Stevens, W., Shih, T., Incerti, D. et al. AJOG 2017

9. Mothers with preeclampsia Thrombocyto-penia (%)
Number of adverse maternal outcomes in US within 12 months of delivery among mothers with preeclampsia by gestational age, using California Office of Statewide Health Planning and Development combined with Natality data from National Center for Health Statistics
GA, weeks
Mothers with preeclampsia
ARF (%)
CVA or TIA (%)
MI (%)
Seizures (%)
Thrombocyto-penia (%)
Hemorrhage (%)
DIC (%)
Death (%)
Total events
<28
3,605
122 (3.4)
7 (0.2)
232 (6.4)
352 (9.8)
95 (2.6)
4 (0.1)
941
28-33
23,624
700 (3.0)
102 (0.4)
17 (0.1)
1,231 (5.2)
1,374 (5.8)
417 (1.8)
41 (0.2)
4,581
34-36
41,856
576 (1.4)
91 (0.2)
11 (0.03)
1,790 (4.3)
2,475 (5.9)
474 (1.1)
14 (0.03)
6,006
37+
87,595
389 (0.5)
131 (0.1)
398 (0.5)
3,052 (3.5)
5,288 (6.0)
637 (0.7)
13 (0.01)
9,931
Total
156,681
1,796 (1.1)
331 (0.2)
49 (0.03)
1,795 (1.1)
6,306 (4.0)
9,489 (6.1)
1,622 (1.0)
72 (0.1)
21,460
Note: ARF = acute renal failure, CVA/TIA = cerebrovascular and transient ischemic accidents, MI = myocardial infarction, DIC = disseminated intravascular coagulation
Stevens, W., Shih, T., Incerti, D. et al. AJOG 2017

10. Adverse outcomes in US within 12 months of delivery among infants born to mothers with preeclampsia in 2012, by gestational age
GA, weeks
Born to mothers with PE
Fetal distress (%)
RDS
(%)
ROP
NEC
IVH
PVL
BPD
Sepsis
Seizures
Death
Total
<28
3,605
83 (2.3)
2,256 (62.6)
965 (26.8)
304 (8.4)
693 (19.2)
79 (2.2)
1,030 (28.6)
1,287 (35.7)
42 (1.2)
1,413 (39.2)
8,151
28-33
23,624
635 (2.7)
9,753 (41.3)
920 (3.9)
582 (2.5)
1,398 (5.9)
127 (0.5)
981 (4.2)
4,783 (20.3)
213 (0.9)
642 (2.7)
20,035
34-36
41,856
444 (1.1)
2,225 (5.2)
18 (0.04)
75 (0.2)
118 (0.3)
10 (0.02)
79 (0.2)
1,949 (4.7)
171 (0.4)
179 (0.4)
5,268
37+
87,595
2,439 (2.8)
376 (0.4)
14 (0.02)
15 (0.02)
27 (0.03)
4 (0.00)
99 (0.1)
1,954 (2.2)
173 (0.2)
5,106
156,681
3,601 (2.6)
14,611 (10.9)
1,918 (1.4)
976(0.7)
2,236 (1.7)
220 (0.2)
2,189 (1.6)
9,974 (7.4)
430 (0.3)
2,407 (1.8)
38,561
Note: RDS = respiratory distress syndrome, ROP = retinopathy of prematurity, NEC = necrotizing enterocolitis, IVH = intraventricular hemorrhage, PVL = cystic periventricular leukomalacia, BPD = bronchopulmonary dysplasia
Stevens, W., Shih, T., Incerti, D. et al. AJOG 2017

11. Results: Total costs for preeclampsia pregnancies
Estimated unit and total health care cost for preeclampsia patients in the U.S., by gestational age at birth using California Office of Statewide Health Planning and Development and commercial claims data
<28 weeks
28-33 weeks
34-36 weeks
37+ weeks
All
(3,604)
(23,624)
(41,856)
(87,596)
(156,680)
Maternal cost per birth
$29,131
$24,063
$19,692
$17,021
$19,075
Infant cost per birth
$282,570
$59,803
$11,112
$6,013
$21,847
Combined cost per birth
$311,701
$83,866
$30,804
$23,035
$40,922
Total health care cost
$1.2B
$2.0B
$1.3B
$6.4B
% of total cost due to infant cost
91%
71%
36%
26%
Stevens, W., Shih, T., Incerti, D. et al. AJOG 2017

12. Results: Maternal cost burden of preeclampsia
Preeclampsia is associated with a $6,583 increase in maternal costs
Summed across an estimated 156,680 preeclampsia births in the U.S. in 2012, this study estimated a total maternal cost burden of $1.03 billion
Stevens, W., Shih, T., Incerti, D. et al. AJOG 2017

13. Results: Infant cost burden of preeclampsia
If infants born to mothers with preeclampsia could have birth delayed by 2 weeks, mean costs would be estimated to decrease by $8,108 per birth
Summed across an estimated 141,830 preterm preeclampsia births between 23 and 36 weeks gestational age, this study implies a total maternal cost burden of $1.15 billion
Effects vary by gestational age
Mean decrease in costs for infants born two weeks later by gestational age
Stevens, W., Shih, T., Incerti, D. et al. AJOG 2017

14. Limitations
Administrative databases and birth certificates have inherent limitations
ICD-9 coding can be inaccurate
Information on preeclampsia status is not available on birth certificates
Potential misclassification of hypertension, chronic hypertension, diabetes, number of prenatal visits
Prediction models are limited by
Stochastic uncertainty
Capturing geographic variation in sampling weights only accounts for variability of maternal characteristics obtained from birth certificates
Cost data were not directly available in the California database
Cost estimations were based on imputed costs using claims data
Problems with under diagnosis or coding errors likely lead to an underestimation of burden, especially at low gestational age
Stevens, W., Shih, T., Incerti, D. et al. AJOG 2017

15. Conclusions
Preeclampsia is associated with increased risk of adverse maternal and infant outcomes in the 12 months after delivery
Preeclampsia is associated with earlier gestational age of 1.7 weeks in the U.S.
The total U.S. healthcare cost burden of preeclampsia is estimated to be $2.2 billion per year
$1.03 billion for mothers
$1.15 billion for infants (which varies considerably by gestational age)
Little is known about long-term consequences of preterm births
Stevens, W., Shih, T., Incerti, D. et al. AJOG 2017