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D
A Systematic Review of Costs Associated with Preterm Birth

John A. F. Zupancic1

The costs of prematurity have been the subject of close scrutiny for more than 2 decades. During that time, there have been dramatic advances in therapeutic interventions, improvements in mortality, and significant inflation in medical care costs. Although the neonatal intensive care phase is most prominent in discussions of these costs, the sequelae of prematurity constitute a chronic disease with significant long-term implications. This appendix has two parts: the first examines the literature on costs associated with the initial hospitalization for prematurity, whereas the second examines longer-term economic factors.

To evaluate the quality and applicability of cost-of-illness studies, it is important to have agreed-upon definitions of certain technical terms. There are, for example, several different categories of cost that might be important to stakeholders. Direct medical costs arise from resources directly consumed by patients. In the context of this review of costs of initial hospitalization, these include costs for the hospital bed and support services (“accommodation”), ancillary services (pharmacy, radiology, laboratory, and respiratory care services), and professional fees. In contrast to these direct costs, overhead costs are those expenses that are incurred in running the institution but that are not directly attributable to a particular patient.

1

John A. F. Zupancic MD, ScD, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.



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Preterm Birth: Causes, Consequences, and Prevention D A Systematic Review of Costs Associated with Preterm Birth John A. F. Zupancic1 The costs of prematurity have been the subject of close scrutiny for more than 2 decades. During that time, there have been dramatic advances in therapeutic interventions, improvements in mortality, and significant inflation in medical care costs. Although the neonatal intensive care phase is most prominent in discussions of these costs, the sequelae of prematurity constitute a chronic disease with significant long-term implications. This appendix has two parts: the first examines the literature on costs associated with the initial hospitalization for prematurity, whereas the second examines longer-term economic factors. To evaluate the quality and applicability of cost-of-illness studies, it is important to have agreed-upon definitions of certain technical terms. There are, for example, several different categories of cost that might be important to stakeholders. Direct medical costs arise from resources directly consumed by patients. In the context of this review of costs of initial hospitalization, these include costs for the hospital bed and support services (“accommodation”), ancillary services (pharmacy, radiology, laboratory, and respiratory care services), and professional fees. In contrast to these direct costs, overhead costs are those expenses that are incurred in running the institution but that are not directly attributable to a particular patient. 1 John A. F. Zupancic MD, ScD, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.

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Preterm Birth: Causes, Consequences, and Prevention These include overhead expenditures for housekeeping, administration, and the physical plant. Costs to patients include nonmedical direct costs (such as the cost of transportation to the hospital, meals, and child care for other siblings). Finally, there are costs related to lost productivity, also referred to as indirect costs. In the short run, these are the lost contributions of labor by the parents; in the long run, they also include reduced work alternatives for the patient. The particular choice of which costs to include is dependent on the perspective of the stakeholder who will be using the information. For example, hospital administrators will be most interested in the direct medical costs that affect hospital financial operations and less interested in wage losses by parents. However, in valuing the financial burden of prematurity to society, it is vitally important to understand the full extent of costs, regardless of the individuals to whom they accrue. In the absence of such information, policy makers may make decisions that appear to be fiscally desirable but in fact simply shift costs to another, unmeasured facet of care. Studies that measure costs on their own without reference to the effectiveness of an intervention are known as “cost-of-illness studies.” When costs are combined into a single metric with a measure of effectiveness, such as life years saved, the study is referred to as a “cost-effectiveness analysis.” When patient preferences for particular outcomes are used as the measure of effectiveness, as they are in quality-adjusted life years, the study is a known as a “cost-utility analysis.” Both cost-effectiveness and cost-utility analyses express costs and effects as a ratio measure. In contrast, cost-benefit analyses measure effects in monetary terms and subtract this value from the cost of the intervention to determine value for money. METHODS Population Description Although much attention has been focused on infants at the borderline of viability, the large volume of children at higher gestational ages may drive the overall financial impact of prematurity. Therefore, broad inclusion criteria were maintained for the review and encompass children in the following categories: (a) premature, defined as birth at less than 37 weeks of gestational age, and (b) low birth weight, defined as a birth weight of less than 2,500 grams. Although the assessment of efficiency is a critical component of technology assessment, the focus of this appendix is on the absolute financial burden of prematurity and low birth weight rather than on the value for money of treatment modalities. Therefore, only costing studies are included and cost-effectiveness, cost-utility, and cost-benefit studies are excluded,

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Preterm Birth: Causes, Consequences, and Prevention except when the population measurement of pertinent costs was a central component. In some cases cost descriptions of cohorts alongside trials of efficacy of therapeutic interventions are included, but these are restricted to control groups to optimize external validity. Two factors have significant impacts on the generalizability of the findings from economic studies. First, the therapies offered in the field of neonatal intensive care and their resulting outcomes have changed substantially in the past 2 decades. In the late 1980s, there was a dramatic decrease in the rate of mortality because of prematurity with the introduction of surfactant replacement therapy, a therapy subsequently shown repeatedly to have important cost implications. Because the underlying structure of care has changed, this problem is difficult to overcome. For the review of short-run costs, therefore only studies reporting on cohorts after 1990 are included to optimize the external validity of the results and avoid bias against lower birth weight in incremental cost comparisons. Since follow-up care of infants following discharge has changed to a lesser degree, reports of long-run costs are included if the cohort was born after 1980. In a few cases, cohorts were assembled with patients from before and after 1980; these studies are included if >50 percent of the cohort met the inclusion date criterion. Similarly, substantial effort has been made to assess the costs of neonatal intensive care in other countries. In some cases, as in the United Kingdom, Europe, and Canada, health care delivery and financing may have certain similarities that allow extrapolation of the results to the U.S. population. However, studies from middle-income and developing countries were excluded on the grounds that both outcomes and health care delivery cost structures are too different to interpret the applicability of the results in the U.S. context. Data Sources and Search Strategies The following databases were searched for candidate articles: Medline (1990 to 2005), electronic abstracts from the annual meetings of the Society for Pediatric Research (1998 to 2005), Econlit (1990 to 2005), and the Proquest dissertation and theses full-text index (1990 to 2005). The Science citation index was searched for articles citing any of the first authors of included studies. The bibliographies of other systematic or informal reviews were scanned (1–7). The websites of organizations known to be involved in similar research were also scanned; these included the websites of the March of Dimes, the Alan Guttmacher Institute, and the Centers for Disease Control and Prevention. The search strategies were intentionally broad to ensure optimal sensitivity. The intersection of the exploded MeSH headings “infant, newborn” and “costs and cost analysis” was used for Medline

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Preterm Birth: Causes, Consequences, and Prevention searches. For other databases, the keywords “econom*” OR “cost*” AND “infant” were used. The titles and abstracts of the articles retrieved with these strategies were manually screened to determine whether they met the inclusion criteria described above. Cost Projections Cost estimates were inflated to 2005 constant dollars by using both the medical component of the consumer price index (8) and the hospital producer price index (9). Currencies were converted to U.S. dollars by using purchasing power parities (10). Per-patient estimates of cost were projected to the U.S. birth cohort by multiplying by the number of infants in a given gestational age or birth weight category, according to the 2002 natality file of the National Center for Vital Statistics (11). State-level population cost estimates were projected to the U.S. birth cohort by dividing by the ratio of the state’s birth cohort to the total number of births nationally for 2002 (the most recent year for which such statistics were available). YIELD OF SEARCH STRATEGY The manual screening of titles and abstracts from the initial literature searches yielded 170 articles. Of these, the majority were eliminated because they were review articles or economic evaluations of interventional studies, were based on data from middle-income or developing countries, were studies at the neonatal intensive care unit level not stratified by birth weight or gestational age, or had cohort dates prior to 1990 for short-run cost reports or 1980 for long-run cost reports. Descriptions and methodological assessment of the short-run (12–27) and the long-run (15, 27–41) cost studies retrieved are shown in Tables D-1 and D-2, respectively. METHODOLOGICAL LIMITATIONS OF STUDIES RETRIEVED Studies of Initial Hospitalization The methodological quality of the short-run cost studies since 1990 was variable. Only five of the reports involved the collection of data alongside prospective research projects (12, 16, 23, 24, 27), whereas the remainder were retrospective analyses of administrative and clinical data collected for other purposes. In some cases, particularly those analyses involving statelevel data in California, there was a preexisting process for checking the integrity of data through reabstraction (18, 25). However, the accuracy of the smaller secondary data sets was not reported in the publications.

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Preterm Birth: Causes, Consequences, and Prevention TABLE D-1A Studies of Costs During Initial Hospitalization Paper Date of Cohort Location of Cohort Type of Cohort Sample Size Currency Currency Date Adams (13) 1996 US Convenience sample Total: 12,125 Normal preterm: 456 Extreme preterm: 513 Normal full term: 9,179 USD Not specified Brazier (14) Not specified UK Hospital-specific 38 UK pounds Not specified Chollet (15) 1989-1991 US Convenience sample Total: 58,904 Normal preterm: 946 Extreme preterm: 986 Normal full term: 44,041 USD Not specified Doyle (16) 1997 Australia Geographic (state) 233 Australian dollar 1997 Giacoia (17) 1983-1984 US Hospital-specific 167 USD Not specified Gilbert (18) 1996 California Geographic (state) 25-38 weeks: 147,224 500-3000 grams: 458,366 USD Not specified Kilpatrick (19) 1990-1994 California Hospital-specific 138 USD Not specified

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Preterm Birth: Causes, Consequences, and Prevention Luke (20) 1991-1992 Illinois Hospital-specific Twins: 111 Singletons: 106 USD Not specified Marbella (21) 1989-1994 Wisconsin Geographic (state) Premature: 26,668 Full term: 368,955 USD Not specified McLoughlin (22) Not specified UK Hospital-specific 109 UK pounds Not specified Rogowski (23) 1993-1994 US 25self-selected hospitals 3,288 USD 1994 Rogowski (24) 1997-1998 US 29 hospitals in QI collaborative 6,797 USD 1998 Schmitt (25) 2000 California Geographic (state) 518,697 USD 2003 St John (26) 1989-1992 Alabama Hospital-specific 958 USD Not specified Tommiska (27) 1996-1997 Finland Geographic (regional hospital) <1000 g: 105 Euro 1997 Victorian Infant Collaborative Study Group (12) 1991-1992 Australia Geographic (state) 429 Australian dollar 1992

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Preterm Birth: Causes, Consequences, and Prevention TABLE D-1B Studies of Costs During Initial Hospitalization Paper Gestational Age Birth Weight Costs Included Cost vs Charges Data Sources Uncertainty Adams (13) Not specified (premature and extreme preterm defined by ICD9) Not specified Hospital; professional Paid claims Claims database Not specified Brazier (14) Not specified Not Specified Travel Costs Parent interview Not specified Chollet (15) All All Hospital; professional Billed charges Claims database Not specified Doyle (16) Not specified 500-999 grams Hospital Cost(ventilator and non-ventilator days, inflated from 1987 values) Prospective research database Sensitivity analysis Giacoia (17) Not specified All Travel Costs Parent interview Statistical Gilbert (18) 25-38 weeks 500-3000 grams Hospital CCR (hospital-specific) State-level linked vital statistics and discharge records Not specified Kilpatrick (19) 24-26 weeks Not specified Hospital CCR (hospital-specific) Hospital chart review and billing database Not specified Luke (20) All All Hospital Not specified Hospital bills; hospital chart Statistical

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Preterm Birth: Causes, Consequences, and Prevention Marbella (21) Not specified (premature defined as all prematurity-related DRG) All Hospital Charges State-level linked vital statistics and discharge records Not specified McLoughlin (22) 22-37 <2500 g Travel Costs Parent interview Not specified Rogowski (23) Not specified 501-1,500 grams Hospital CCR (department-specific) Hospital financial data Not specified Rogowski (24) Not specified 501-1,500 Hospital CCR (department-specific) Hospital financial data Not specified Schmitt (25) All All Hospital CCR (hospital-specific) State-level linked vital statistics and discharge records Statistical St John (26) 24-32 vs 33-42 Not specified Hospital; professionl CCR (hospital-specific) Hospital chart review and billing database Not specified Tommiska (27) ≥22weeks <1000 grams Hospital; nonmedical direct; productivity losses Cost (derivation not specified) Hospital cost database and national ELBW registry; familyquestionnaire at 2 years Statistical and sensitivity analysis Victorian Infant Collaborative Study Group (12) Not specified 500-999 grams Hospital Cost (ventilator and nonventilator days, inflated from 1987 values) Prospective research database Sensitivity analysis

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Preterm Birth: Causes, Consequences, and Prevention TABLE D-2A Studies of Costs Following Discharge from Initial Hospitalization Paper Date of Cohort Location of Cohort Type of Cohort Sample Size Currency Currency Date Broyles (28) 1988-1996 Texas Hospital-specific 388 (control group of RCT) USD 1997 Chaikand (29) 1987-1988 US National 6,788 USD 1989-1990 Chollet (15) 1989-1991 US Convenience sample Total: 58,904 Normal preterm: 946 Extreme preterm: 986 Normal full term: 44,041 USD Not specified Gennaro (30) 1990-1994 US Hospital-specific 224 USD Not specified Lewit (31) 1988 US National 35,000 USD 1988 McCormick (32) 1983-1984 Pennsylvania Hospital-specific VLBW: 32 Controls: 34 USD Notspecified Medstat (41) 2001 US Convenience sample Total: 28,958 All preterm: 3,214 Normal full term: 15,795 USD 2004 Petrou (33) 1970-1993 UK Geographic (regional) >37weeks: 226,120 32-36 weeks: 11,728 28-31 weeks: 1,346 <28weeks: 500 UK Pounds 1998-1999

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Preterm Birth: Causes, Consequences, and Prevention Petrou (34) 1978-1988 UK Geographic (regional) >37weeks: 90,236 32-36 weeks: 4,485 28-31 weeks: 596 <28weeks: 241 UK Pounds 1998-1999 Pharaoh (35) 1979-1981 UK Geographic (regional) 109 UK Pounds 1984 Rogowski (36) 1986-1987 California Geographic (state) Inception: 887 Survived: 591 USD 1987 Rolnick (37) 1993, 1995 Minnesota Hospital-specific (single health plan) 2500-4499: 1203=1500-2499: 38 USD Notspecified Roth (38) 1990-1991 Florida Geographic (state) 120,533 USD 2001 Stevenson (39) 1980-1981 UK Geographic (regional) Total: 641 <1,000: 20 1,000-1,500: 153 1,501-2,000: 468 UK Pounds 1979 Stevenson (40) 1980-1981 UK Geographic (regional) Total: 52 <1,000: 9 1,000-1,500: 25 1,501-2,000: 18 UK Pounds 1979 Tommiska (27) 1996-1997 Finland Geographic (regional hospital) <1000 g: 105 >36weeks: 75 Euro 1997

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Preterm Birth: Causes, Consequences, and Prevention TABLE D-2B Studies of Costs Following Discharge from Initial Hospitalization Paper Gestational Age Birth Weight Costs Included Cost vs Charges Data Sources Uncertainty Discounting Broyles (28) Not specified <1000 or <1,500 and ventilated except drugs Hospital; outpatient CCR (department-specific) Prospective research database Statistical 3% Chaikand (29) Not specified <2,500 Education Costs NCHS Child Health Supplement to National Health Interview Survey Statistical 2% Chollet (15) All All Hospital; professional Billed charges Claims database Not specified Not specified Gennaro (30) Not specified <2,500 Wages; transportation; unreimbursed med Costs Interviews Statistical Not specified Lewit (31) All All Hospital; education Charges National Medical Expenditure Survey Not specified Not specified McCormick (32) Not specified <1,500 Hospital; outpatient MD; transportation; childcare Charges Diary; interviews Statistical Not specified

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Preterm Birth: Causes, Consequences, and Prevention TABLE D-5 Direct Medical Expenses Following Discharge from the Initial Hospitalization Paper Time Horizon Rehospitalization (cost) Outpatient MD, Drug and Other (cost) Broyles (28) 1 year adjusted age <1,500: 6,982 <1,500: 2,931 Chollet (15)a 2 years (1 year detail) Not separated from initial hospitalization Normal preterm: 4,463 Extreme preterm: 6,329 Normal full-term: 2,243 Other preterm: 4,195 Lewit (31) 15 years of age <1,500 <1 year (not separated from initial hospitalization) 3-5 years: 290 6-10 years: 470 N/A McCormick (32) 1 year of age <1,500: 8,250 Term: 900 MD visits 1,500: 564 Term: 232 Other Outpatient: <1,500: 1,311 Term: 63 Medstat (41) 1 year of age Preterm: 35,034 Normal full-term: 1,210 Preterm: 6,576 Normal full-term: 1,620 Petrou (33) 5 years of age Year 1: >37 weeks: 297 32-36 weeks: 2,016 28-31 weeks: 7,272 <28 weeks: 10,630 Total (inc birth hosp): >37 weeks: 1,333 32-36 weeks: 4,378 28-31 weeks: 14,059 <28 weeks: 13,639 N/A Petrou (34) 10 years of age Including birth hosp: >37 weeks: 1,659 32-36 weeks:7,394 28-31 weeks:17,751 <28 weeks: 17,820 N/A

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Preterm Birth: Causes, Consequences, and Prevention Post-Discharge Total Rehospitalization (mean or median) Rehospitalization (mean total days) Rehospitalization (LOS) Outpatient Visits (Clinic, MD, ER) <1,500: 9,913 <1,500: 0.7 <1,500: 7.6 N/A <1,500: Clinic: 6.4 ER: 1.9 Total: 8.2 Not separated from initial hospitalization N/A N/A N/A N/A <1,500 <1 year (not separated from initial hospitalization) 3-5 years: 290 6-10 years: 470 N/A N/A N/A N/A <1,500: 10,139 Term: 1,179 N/A N/A N/A <1,500: 18.5 Term: 9.3 Preterm: 41,611 Normal full-term: 2,831 Preterm: 1.3 Normal full-term: 1.1 N/A Preterm: 16.8 Normal full-term: 2.3 Preterm: 8.9 Normal full-term: 5.9 Year 1: >37 weeks: 297 32-36 weeks: 2,016 28-31 weeks: 7,272 <28 weeks: 10,630 Total (inc birth hosp): >37 weeks: 1,333 32-36 weeks: 4,378 28-31 weeks: 14,059 <28 weeks: 13,639 >37 weeks: 2 32-36 weeks: 2 28-31 weeks: 1 <28 weeks: 1 >37 weeks: 6.3 32-36 weeks: 16.2 28-31 weeks: 48.7 <28 weeks: 49 N/A N/A Including birth hosp: >37 weeks: 1,659 32-36 weeks: 7,394 28-31 weeks: 17,751 <28 weeks: 17,820 >37 weeks: 0.75 32-36 weeks: 1.48 28-31 weeks: 2.54 <28 weeks: 1.9 Including birth hosp: >37 weeks: 6.2 32-36 weeks: 18 28-31 weeks: 58.2 <28 weeks: 59.2 N/A N/A

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Preterm Birth: Causes, Consequences, and Prevention Paper Time Horizon Rehospitalization (cost) Outpatient MD, Drug and Other (cost) Pharaoh (35) 4 years of age N/A N/A Rogowski (36) 1 year of age <1,000: 12,800 <1,500: 5,290 <1,500: 870 Rolnick (37) 1 year postdischarge N/A N/A Stevenson (39)c 8-9 years of age <1,000: 421 1,001-1,500: 433 1,501-2,000: 270 <1,000: 876 1,001-1,500: 793 1,501-2,000: 430 Stevenson (40)d 8-9 years of age <1,000: 1,861 1,001-1,500: 1,439 1,501-2,000: 570 <1,000: 1,617 1,001-1,500: 1,447 1,501-2,000: 1,149 Tommiska (27)e 2 years of age Year 1: <1,000: 12,185 control: 225 Year 2: <1,000: 2,575 control: 195 Year 1: <1,000: 1,995 control: 295 Year 2: <1,000: 1,420 control: 315 aMothers and infants combined bCalculated from data in article cPer infant with no disability dPer infant with disability eTotal cost includes nonmedical (See Tables D-5 and D-6) with a range of 54 to 60 percent of the costs in the non-U.S. studies and 70 to 86 percent of the costs in the U.S. cohorts. Petrou examined factors associated with higher rehospitalization costs (33). These included maternal conditions, such as hospitalization, age >35 or <20 years, or smoking; perinatal factors, such as instrumental delivery or delivery complications; demographic factors, such as lower socioeconomic status; and prematurity.

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Preterm Birth: Causes, Consequences, and Prevention Postdischarge Total Rehospitalization (mean or median) Rehospitalization (mean total days) Rehospitalization (LOS) Outpatient Visits (Clinic, MD, ER) <1,500: 2,620b N/A N/A N/A N/A <1,500: 6,160 <1,000: 1.8 1,000-1,249: 1.9 1,250-1,499: 2.1 <1,500: 5.5 <1,000: 13.6 1000-1,249: 9.6 1,250-1,499: 9.8 N/A 2,500-4,499: 2,919 1,000-2,500: 5,938 N/A N/A N/A N/A <1,000: 1,297 1,001-1,500: 1,226 1,501-2,000: 699 N/A N/A N/A N/A <1,000: 3,475 1,001-1,500: 2,886 1,501-2,000: 1,719 N/A N/A N/A N/A Year 1: <1,000: 20,390 control: 1,415 Year 2: <1,000: 13,955 control: 1,205 Year 1: <1,000: 1.8 control: 0.1 Year 2: <1,000:1.0 control: 0.1 Year 1: <1,000: 8.4 control: 0.3 Year 2: <1,000: 4.2 control: 0.4 N/A Year 1: <1,000: 7.1 control: 2.9 Year 2: <1,000: 6.5 control: 3.8 Educational Costs Details of studies assessing educational costs are given in Table D-6. As noted above, the assessment of educational costs was inconsistent with respect to both the study methodology and the age at the time of the assessment. After controlling for medical, economic, and social factors, Chaikind and Corman found a 49 percent relative risk for special education placement in low-birth-weight infants (29). This translated to a net present value

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Preterm Birth: Causes, Consequences, and Prevention TABLE D-6 Educational Expenditures Following Discharge from Initial Hospitalization Paper Pre-School Age School Age Chaikand (29) N/A <2500 Age 6-15: 1,240 (370.8 million total/yr) Lewit (31) <1500 Preschool: 290 <1500 Age 6-10: Special Ed 150 Age 6-15: Grade Rep 45 Pharaoh (35) N/A <1,500: 4,211 Roth (38) N/A Kindergarten <1,000: 6979 1,000-1,499: 5,740 1,500-2,499: 4,870 >2,500: 4,375 Tommiska (27) “Special Day Care” Year 1: <1,000: 0 control: 0 Year 2: <1,000: 1,285 control: 0 N/A Clements Early intervention (0-3 years cumulative) <28 weeks: 7,182 28-30 weeks: 5254 31-33 weeks: 2,654 34-36 weeks: 1,321 37-39 weeks: 770 >40 weeks: 613 N/A of $1,240 (in 1988 U.S. dollars) per low birth weight infant, or $370 million per year for special education costs alone. Roth et al. found that infants with birth weights of <1,000 grams had kindergarten costs 60 percent higher than those for normal birth weight controls (38). However, the authors noted that low levels of maternal education and poverty accounted for more than three quarters of the total excess costs of kindergarten, whereas low birth weight accounted for only 1 percent of the total excess costs because of the relative numbers of children with these predisposing conditions. Early intervention costs may also be significant. A recent study of statelevel data in Massachusetts assessed costs from birth to age 3 years for early

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Preterm Birth: Causes, Consequences, and Prevention intervention services by gestational age. Infants born at less than 28 weeks of gestation had early intervention costs of $7,182 (in 2003 U.S. dollars), whereas the early intervention costs were $613 for those delivered at 40 weeks of gestation or more (53). Direct Nonmedical Costs and Lost Productivity Table D-7 shows the costs associated with postdischarge parental out-of-pocket expenses and lost productivity. Tommiska et al. documented firstyear parental wage losses of €5,990 for infants with birth weights of <1,000 grams, whereas the loss was €880 for controls. These costs increased to €8,175 in the second year for the parents of children born with low birth weights (27). Similar data are not available for the United States. SUMMARY OF COST STUDIES FOR PREMATURITY Several themes emerged from this systematic review of cost-of-illness studies: Most studies had significant methodological limitations. These included a reliance on administrative data sets without adequate checks on data validity, small sample sizes and possible selection bias, a lack of quantification of uncertainty through the use of descriptive statistics or sensitivity analysis, the use of charges or inadequately described costing, the lack of a control group, and a failure to discount appropriately for longer studies. All cost estimates in the literature omitted at least some potentially important components of costs and are therefore likely to underestimate true resource use. These omissions included professional fees, hospital costs for transferred infants, costs for nonsurviving infants, and out-of-pocket costs for parents. There is almost no information on the lost earnings of parents and no information on the productivity losses of the infants themselves. Maternal costs for the delivery hospitalization and the costs of antenatal admissions were omitted by most studies. The analysis of infants and mothers separately risks both an underestimation of the costs of prematurity and the possibility of missed shifting of costs between the two groups. Very few studies have addressed educational costs, and these do not provide adequate information across the spectrum of school age and disability. Most authors did not disaggregate costs into their components, making it problematic to target the sources and predictors of high costs. Studies confirmed the previously noted inverse relationship of maternal, neonatal, and postdischarge costs with birth weight and gestational age.

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Preterm Birth: Causes, Consequences, and Prevention TABLE D-7 Out-of-Pocket Expenses and Lost Productivity Following Discharge from Initial Hospitalization Paper Parental Wages Lost Productivity of Child Child Care Other Travel Tommiska (27) Year 1: <1,000: 5,990 control: 880 Year 2: <1,000: 8,175 control: 595 N/A N/A “Home Aid” Year 1: <1,000: 0 control: 0 Year 2: <1,000: 255 control: 85 Year 1: <1,000: 75 control: 15 Year 2: <1,000: 85 control: 15 McCormick (32) N/A N/A <1,500: 563 Term: 1,082 N/A <1,500: 180 Term: 23 Gennaro (30) N/A N/A N/A Non-reimbursed Health <2,500: 69 Total Out of Pocket <2,500: 445 N/A

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Preterm Birth: Causes, Consequences, and Prevention Although the per-patient cost for moderately preterm infants is lower than that for extremely preterm infants, the larger numbers of these infants results in population costs of similar magnitudes in both groups. This has important implications for the setting of policy, as interventions that ameliorate moderate prematurity may be as cost-effective as the more difficult interventions that would eliminate extreme prematurity. The time horizon for economic follow-up is inadequate. Very few studies have followed infants beyond 5 years, and none have documented the implications of prematurity in young adulthood, despite the availability of appropriate cohorts. Most of the studies with longer time horizons or more comprehensive methods of cost ascertainment have been from countries other than the United States. The appropriateness of generalizing these cost estimates to the United States is uncertain. RECOMMENDATIONS FOR POLICY AND FURTHER RESEARCH The findings summarized above have direct implications for policy and research: Because policy makers are likely to accept the dollar estimates of the costs of illness without adequately assessing the quality of the underlying studies, it is important that the peer review process identify the more significant methodological limitations, such as the use of unadjusted charges or the lack of assessment of uncertainty. In light of the prominence of the economic implications on health policy decision making for this population, it is essential that a U.S. study with a societal perspective be performed. This should include a comprehensive assessment of productivity losses and parental out-of-pocket expenditures in the U.S. context. Studies with longer time horizons should be undertaken and should preferably use an incidence approach rather than a prevalence approach to costing. At a minimum, these should extend well into school age. The implications of prematurity as young adults enter the work force should be examined, as should lifetime labor force implications. Because of the interactions between socioeconomic status and outcome, costing studies should include specific analyses of the increased burden on particular racial and ethnic populations. The focus of short-run costing studies should be shifted toward a perinatal perspective, in which the unit of analysis is the maternal-infant dyad. This is now feasible with improved data linkage. Attention should be directed toward the economic implications of moderate prematurity, in addition to extreme prematurity.

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