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

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

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

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): 1950-1970 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): 1959-1974 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

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

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

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

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

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

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

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

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

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

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

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