Trends in Hospitalization for PediatricPulmonary HypertensionBryan G. Maxwell, MD, MPHa, Melanie K. Nies, MDb, Chinwe C. Ajuba-Iwuji, MDa, John D. Coulson, MDb, Lewis H. Romer, MDa,b,c,d

abstractBACKGROUND AND OBJECTIVES: Pulmonary hypertension (PH) has been associated with substantialmorbidity and mortality in children, but existing analyses of inpatient care are limited to smallsingle-institution series or focused registries representative of selected patient subgroups. Weexamined US national data on pediatric PH hospitalizations to determine trends in volume,demographics, procedures performed during admission, and resource utilization.

METHODS: Retrospective cohort study using a national administrative database of pediatrichospital discharges: the Kids’ Inpatient Database.

RESULTS: Children with PH accounted for 0.13% of the 43 million pediatric hospitalizations inthe United States between 1997 and 2012, and discharges demonstrated an increasing trendover the study period (P , .0001). Cumulative, inflation-adjusted national hospital charges forPH hospitalizations rose (P = .0003) from $926 million in 1997 to $3.12 billion in 2012.Patients with PH without associated congenital heart disease (CHD) comprised an increasingand majority (56.4%) proportion over the study period (P , .0001), children withoutassociated CHD admitted at urban teaching hospitals comprised the fastest-growing subgroup.In-hospital, all-cause mortality was high (5.9%) in children with PH, but demonstrateda decreasing trend (P , .0001).

CONCLUSIONS: Morbidity and mortality of pediatric PH continue to represent substantial andgrowing health care burdens. Shifts in case mix toward PH not associated with CHD,toward noncardiac procedures, and toward care in urban teaching hospitals willincrease pressure to manage resource utilization in this small but growing patient groupand to improve expertise and define excellence in PH care across a wide range of clinicalsettings.

WHAT’S KNOWN ON THIS SUBJECT: Althoughexisting analyses of inpatient pediatricpulmonary hypertension (PH) care haveestablished an association with substantialmorbidity and mortality, these investigationshave been limited to small single-institutionseries or focused registries representative ofselected patient subgroups.

WHAT THIS STUDY ADDS: This study provides thefirst contemporary, national trend analysis ofinpatient care for children with PH. Pediatric PHis associated with a rapidly increasing numberof hospital discharges and magnitude ofresource utilization, and the makeup of thispopulation is changing.

Departments of aAnesthesiology and Critical Care Medicine, bPediatrics, cBiomedical Engineering, and dCellBiology, Johns Hopkins University School of Medicine, Baltimore, Maryland

Dr Maxwell conceptualized and designed the study, carried out the initial analyses, drafted theinitial manuscript, and reviewed and revised the manuscript; Drs Nies, Ajuba-Iwuji, and Coulsonprovided input about study design and data analysis/interpretation, and critically reviewed themanuscript; Dr Romer helped conceptualize and design the study, reviewed and refined dataanalysis and interpretation, and reviewed and revised the manuscript; and all authors approved thefinal manuscript as submitted.

www.pediatrics.org/cgi/doi/10.1542/peds.2014-3834

DOI: 10.1542/peds.2014-3834

Accepted for publication May 13, 2015

Address correspondence to Bryan G. Maxwell, MD, MPH, Department of Anesthesiology and CriticalCare Medicine, Johns Hopkins University School of Medicine, 1800 Orleans St, Zayed 6208P,Baltimore, MD 21287. E-mail: bmaxwell@jhu.edu.

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2015 by the American Academy of Pediatrics

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Pediatric pulmonary hypertension(PH) is a severe and often chroniccondition1,2 associated withsignificantly reduced quality of life forpatients, parents, and caregivers.3 Ittypically requires lifelong care and isassociated with a significant burdenof health care costs.4 Nearly all PHtherapies are used off-label inchildren because evidence for theiruse is available only from adult datathat have been extrapolated to thepediatric population. Assessingtreatment efficacy is furthercomplicated by heterogeneity ofpatient subsets and by the challengesof establishing clinical endpoints thatare appropriate to children. Forinstance, surrogate clinical endpointsused in adults with PH, such as a6-minute-walk test, are morechallenging to standardize andvalidate in the pediatric population.The gold standard in adult andpediatric PH diagnosis, invasivetesting via cardiac catheterization, isresource intensive, requires anexperienced center, is complicated bythe lack of a uniformly acceptedpediatric protocol,5 and involves therisk of repeated exposures to generalanesthesia.6

Despite improved treatment, itappears from the limited outcomedata that are available that morbidityand mortality from pediatric PHremain high: 5-year survival has beenestimated at 74% and 64% in UnitedStates (REVEAL7) and UnitedKingdom (UK PulmonaryHypertension Service for Children8)registries, respectively. Neitherregistry shows a significant survivaldifference between idiopathic PH andPH that is associated with congenitalheart disease (CHD), although theestimate of 5-year survival in the UKgroup of children with PH associatedwith CHD is as low as 57%.

The heterogeneity of pediatric PH hasinhibited inclusive, broadassessments of hospitalizationoutcomes, trends, and associatedresource allocation. Existing insights

and information from registries7–9

have defined PH as a pressing healthcare issue,10 but although important,these studies have limitations. Thelandmark work by Haworth andHislop8 from the UK registry providesdata from a hub-and-spoke model ofregional centers of expertise withina national referral program. Groups inthe Netherlands11,12 and Spain13

have focused on broad capture of themany individual diagnostic groupsthat contribute to the growingproblem of pediatric PH. However,these analyses capture selectedpatient subsets and/or draw fromregional centers of expertise that mayhave specific diagnostic criteria forinclusion, and therefore may notreflect patterns of PH care seen inbroader clinical practice at thepopulation level.14

Despite the suggestion that thispopulation is growing, few recognizedPH centers for children exist in theUnited States, and to date, no currentpublished national US data exist onvolume or trends in pediatric PHhospitalizations. A more robustunderstanding of the development ofpediatric PH as a growing health carepriority in the United States is neededto work toward the critical goal ofregistry development15 that willunderpin PH subtype differentiationand clinical trials, as well as to guidepublic policy and resource allocation.

We sought to use an established,nationally representativeadministrative database to examinepediatric hospitalizations in theUnited States involving childrendiagnosed with PH, in an effort toinform providers and policymakerswith insights regarding shiftingdemographics and unmet needs thatmay guide system and policyimprovements. Specifically, we soughtto assess the hypothesis that PHhospitalizations have become morecommon, with shifts in patientdemographics, in the balance of PHassociated with CHD compared withPH without associated CHD, in

procedures performed duringadmission, and in overall resourceutilization.

METHODS

This study was exempt frominstitutional review board reviewbecause it uses data that aredeidentified and publicly available.Administrative records wereextracted from discharge datasets for1997 to 2012 from the Kids’ InpatientDatabase (KID), part of theHealthcare Cost and UtilizationProject (HCUP) of the Agency forHealthcare Research and Quality.KID is the largest publicly availabledatabase of inpatient pediatric care inthe United States. Datasets arereleased every third year and includerecords for a sample of dischargesfrom all nonfederal, nonrehabilitationhospitals in states that participate inHCUP.

KID is designed with sample weightsthat facilitate nationallyrepresentative estimates; theseweights adjust for growth inparticipation from 1997, when 2521hospitals in 22 participating statessubmitted 1.9 million recordsreflective of 6.66 million nationaldischarges, to 2012, when4179 hospitals in 44 states submitted3.2 million records reflective of6.68 million national discharges. KIDcontains limited data on eachinpatient encounter, but its size andsampling frame facilitate the analysisof rare clinical events at a nationallevel.

Diagnostic, comorbidity, andprocedural information was based onHCUP-supplied InternationalClassification of Diseases, NinthRevision, Clinical Modification (ICD-9-CM)codes. Pulmonary hypertensionwas identified (416.3) and dividedbased on the presence or absence ofCHD (745.3, 746.3, and 747.1–4)into 2 subgroups for analysis: PHassociated with CHD (hereafter “CHDgroup”) and PH without associated

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CHD (hereafter “non-CHD group”).The performance of surgicalprocedures was identified based onpreviously described ICD-9 volume3 procedure codes for cardiac16 andnoncardiac17 operations. Post hocreclassification as part of the CHDgroup was performed for a smallnumber (0.8%) of admission recordsthat did not contain a CHD diagnosiscode but contained a cardiac surgicalprocedure code that would haveoccurred only in a patient with CHD(eg, “repair of total anomalouspulmonary venous connection”).

A composite comorbidity point scorewas calculated based on the vanWalraven modification18 of theElixhauser comorbidity measure,19

which is the basis of the dedicatedcomorbidity variables included inHCUP databases. Procedure codesalso were used to identify theperformance of procedures that wereviewed by the multidisciplinaryauthor group as clinically relevant toeither the diagnosis or sequelae ofpediatric PH and that reliably couldbe identified by procedure codes:cardiac catheterization (37.23,38.23), MRI (88.91–88.97),tracheostomy (31.1, 31.2),hemodialysis or peritoneal dialysis(39.95, 54.93, 54.98, or V45.11), andextracorporeal membraneoxygenation (ECMO; 39.65, 39.66).

Beginning in 2012, freestandingchildren’s hospitals were identifieddirectly in KID (variableKID_STRATUM=9999). For previousyears, we reconstructed thisclassification based on the NationalAssociation of Children’s Hospitalsand Related Institutionsclassifications, provided in KID(variable NACHTYPE=1 or 2).

Discharge sample weights were usedto create national estimates withinthe KID sampling frame. Primaryoutcome measures included inpatientlength of stay (variable LOS), totalinpatient hospital charges (variableTOTCHG), and in-hospital mortality(variable DIED). Secondary outcome

measures included respiratory failure(518.53, 518.83, 770.84, 799.1, andV46.1–2) and discharge disposition(routine home discharge, home withhome health or nursing, or to a long-term care/skilled nursing facility).

Hospital charges were indexed toinflation and to the broadly risingcosts of medical care by adjusting allvalues to 2012 dollars by using theBureau of Labor Statistics ConsumerPrice Index subindex specific toinpatient hospital services.20

Statistical Analysis

Because the sampling frame of KIDrequires the use of advancedtechniques (facilitated by PROCSURVEYMEANS in SAS [SAS Institute,Cary, NC]) to estimate variance,continuous variables are presented asmeans 6 SE. Discrete variables arepresented as number (percentage).Intergroup comparisons were carriedout using the Mann-Whitney-Wilcoxon test for continuousvariables and Fisher’s exact test orthe Pearson x2 test for categoricalvariables, as appropriate. Odds ratioswere calculated for intergroupdiscrete outcome comparisons; forPH versus non-PH comparisons, thenon-PH cohort is the reference group.For CHD versus non-CHD subgroupswithin the PH population, the non-CHD cohort is the reference group.

Trends over time were examined bymonth of hospital admission by usinga seasonal Mann-Kendall test fortrend, a nonparametric test todetermine the presence and directionof a trend over time21 that accountsfor seasonal variability, as inpatientpediatric care might involve seasonalfluctuations due to patterns ofwinter illness, surgical scheduling inrelation to school calendars, andother similar factors. Records withmissing data for the month ofadmission (7.2% of all records in the1997–2012 KID datasets) wereexcluded from trend analyses only;these records were included for allnontrend and descriptive analyses.

A predetermined a of 0.05 was usedas the threshold of statisticalsignificance. Trend analyses wereperformed by using R (R 3.1.3; The RFoundation for Statistical Computing,Vienna, Austria). All other analyseswere performed by using SAS (SAS9.4; SAS Institute, Cary, NC).

RESULTS

Children with PH accounted for 56 678discharges nationwide between 1997and 2012, which represents 0.13% ofthe estimated 43.0 million totalpediatric discharges reflected in KID.

Cumulative, inflation-adjusted nationalhospital charges for PHhospitalizations rose from $926million in 1997 (totaled annually) to$3.12 billion in 2012 (P = .0003,Fig 1A). This increase was associatedwith increasing trends among PHdischarges during the study period inaverage total charges perhospitalization (P, .0001, Fig 1B) andlength of stay (P , .0001). Thenumber of discharges for PH increasedin absolute terms and as a proportionof all pediatric discharges (P , .0001for both, Fig 2). The increase in PHdischarges was most pronouncedduring the period 2006 to 2012.

Table 1 shows demographiccharacteristics of hospitalized childrenwith PH compared with the referencepopulation of all pediatric inpatients.Children with PH were younger, hada greater average comorbidity score,and were more commonly admitted tourban teaching hospitals andchildren’s hospitals. A minority of PHhospitalizations (33.9%) occurred inchildren’s hospitals, although thisproportion was higher than in non-PHhospitalizations (7.8%, P , .0001,Table 1). No significant trend wasobserved in average age of PHdischarges during the study period(P = .13). Table 2 shows theprocedural and outcomecharacteristics of discharges forchildren with PH compared with allpediatric discharges.

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Among PH discharges, the CHD groupaccounted for 43.6% overall (n = 24706).This proportion demonstrateda decreasing trend over the studyperiod (P , .0001, Fig 3) relative tothe non-CHD group (n = 31 972; 56.4%).Figure 4 demonstrates that the increase

in PH hospitalizations over the studyperiod largely was driven by growth inhospitalizations at urban teachinghospitals, as hospitalizations at urbanteaching hospitals increased more thanthose in other settings. Within urbanteaching hospitals, growth in the

non-CHD group outpaced that of theCHD group.

Table 3 shows demographiccharacteristics of the 2 PH subgroupswith and without associated CHD.Compared with the non-CHD group,children in the CHD group wereyounger and had lower baselinecomorbidity scores. Table 4 showsprocedural and outcomecharacteristics of PH dischargesamong the CHD and non-CHD groups.Children in the CHD group were morelikely to undergo cardiaccatheterization, cardiac andnoncardiac surgery, and ECMO, andhad longer lengths of stay and greatertotal hospital charges.

During the study period, there wasa decreasing trend in the proportionof PH discharges that involved cardiacsurgical procedures (P , .0001,Fig 5). There was also an increasingtrend in the proportion of PHdischarges that involved noncardiacsurgical procedures: from 3.6% inJanuary 1997 to 12.0% in December2012 (P , .0001, Fig 5).

Mortality occurred in n = 3332 PHdischarges (5.9% of these dischargesoverall). The pattern was one of steadyimprovement, as the incidence ofin-hospital mortality decreased from11.3% in January 1997 to 6.6% inDecember 2009 (P , .0001, Fig 6).Mortality was slightly higher in the CHDgroup than the non-CHD group (6.5%vs 5.4% of discharges, P , .0001).

Mortality among patients undergoingnoncardiac surgery was substantiallyhigher in PH patients than in theaggregate of all KID discharges (9.3% vs1.0%, crude odds ratio [OR] 10.64, 95%confidence interval [CI] 9.71–11.67,P , .0001) and was higher in the CHDgroup of patients with PH than in thenon-CHD group (11.5% vs 7.3%, crudeOR 1.66, 95% CI 1.38–2.00], P, .0001).

DISCUSSION

The principal findings of this studyare that hospitalizations of childrenwith PH account for an increasing

FIGURE 1Hospital charges. Cumulative, inflation-adjusted national hospital charges for PH admissions (A) andaverage hospital charges per PH admission (B) are shown by month, in triennial years (increasingtrend, P , .0001 for both).

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proportion of all pediatrichospitalizations (1 in 1000 dischargesat the beginning of the study periodcompared with 1 in 500 discharges

by its end), with a dramatic increasein resource utilization associated withinpatient pediatric PH care,particularly from 2006 to the present.

These trends appear to have resultedfrom a combination of greaternumbers of hospitalizations, longerlengths of stay, and increasing totalhospital charges.

The increased number of thesechildren admitted to urbanteaching hospitals largely accountsfor the increase in discharges. Therelative case mix shifted during thestudy period, with the non-CHDgroup comprising a majority andgrowing share of the overallpopulation of pediatric PHdischarges. All-cause, in-hospitalmortality among children with PHremained high, but it declinedsignificantly during this period anddiffered only slightly between CHDand non-CHD groups.

Administrative data providea limited opportunity to elucidatethe etiologies of these trends.However, our study period doescoincide with an era of significantimprovement in neonatology careand outcomes, as well as in thedetection and medical managementof chronic PH, particularly that inchildren without CHD.22,23 Improvedsurvival of infants withbronchopulmonary dysplasia and theemergence of pulmonary vasodilatortherapy may explain both thedecrease in observed mortality perhospitalization as well as the relativeincrease in the non-CHD group ofchildren admitted with PH. Thesetrends also may relate to increasingsuccess in the early surgicaltreatment of CHD with a focus onprevention of PH.

Compared with the index populationof pediatric discharges, dischargesfor children with PH werecharacterized by a younger andconsiderably sicker population(Table 1) that had a substantiallylonger average length of stay, greaterhospital charges, a greater need forselected diagnostic and therapeuticprocedures, a higher rate ofrespiratory failure and nonroutinedischarges, and a substantially

FIGURE 2PH Admissions. Monthly volume (in triennial years) of PH admissions in absolute numbers (bluebars, increasing trend, P , .0001) and as a proportion of all pediatric admissions (orange line,increasing trend, P , .0001).

TABLE 1 Demographic Characteristics of Patients With PH Compared With All Pediatric Admissions

PH All KID P

n = 56 678 n = 42 961 763

Age, y 5.4 6 0.10 7.3 6 0.002 ,.0001Age category, y ,.0001Birth admission 5130 (11.9) 14 116 325 (32.9),1, readmitted since birth 16 285 (37.8) 5 592 830 (13.0)1–4 6709 (15.6) 3 876 399 (9.0)5–9 2397 (5.6) 2 294 807 (5.3)$10 12 616 (29.2) 17 081 402 (39.8)

Gender ,.0001Boys 21 950 (50.9) 21 401 544 (49.8)Girls 21 187 (49.1) 21 560 219 (50.2)

Race ,.0001White 16 077 (37.3) 17 572 152 (40.9)Black 7362 (17.1) 6 003 610 (14.0)Hispanic 7360 (17.1) 7 898 972 (18.4)Asian 1296 (3.0) 1 081 801 (2.5)Other/Missing 11 042 (25.6) 10 405 228 (24.2)

van Walraven comorbidity score 4.1 6 0.01 0.6 6 0.001 ,.0001Congenital heart disease 24 706 (43.6) 1 154 794 (2.7) ,.0001Payer ,.0001Medicare 331 (0.8) 137 454 (0.3)Medicaid 21 266 (49.3) 19 783 184 (46.0)Private insurance 17 887 (41.5) 19 264 192 (44.8)Self-pay/other 3653 (8.5) 3 776 933 (8.8)

Hospital setting ,.0001Rural 1046 (2.4) 3 911 689 (10.8)Urban, nonteaching 6524 (15.1) 12 990 582 (35.8)Urban, teaching 35 567 (82.5) 19 384 270 (53.4)

Children’s hospital 19 227 (33.9) 3 370 577 (7.8) ,.0001

Values are number (percentage) or mean 6 SE, as appropriate.

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higher in-hospital mortality rate(Table 2). These findings are notsurprising, but they provide clear,quantitative delineation of themorbidity and mortality associatedwith pediatric PH.

The non-CHD group had a higherproportion of children who wereAfrican American, which may reflectPH from prematurity-related chroniclung disease due to the higherincidence of prematurity in theAfrican American population.24

Resource utilization was greater inthe CHD group, with longer lengths ofstay and greater average hospitalcharges compared with the non-CHDgroup. We suspect, but cannot prove,that the greater resource utilizationobserved in the CHD group is due toa larger number of surgicalprocedures.

We observed a decreasing trend overthe study period in the proportion ofdischarges that involved cardiacsurgery, likely because of the

concomitant growth of the non-CHDgroup. We also observed anincreasing trend in the proportionof discharges that involvednoncardiac surgery. It isencouraging that these trends wereassociated with a decreasing trendin all-cause mortality. Noncardiacsurgery has been associated withsubstantial risk of mortality inchildren with PH in previousanalyses,6,25,26 and this remainsevident from the 9.3% incidence ofmortality in the current analysisamong children who requireda noncardiac operation.

Important limitations to this studyexist as a result of structural featuresof the KID database. First, it isimportant to note that KID isa database of discharges, so thisanalysis does not providelongitudinal data on patients with PHover time or on outpatient care. Nomechanism allows for connectingmultiple admissions records fora single child. This also means thatthe observed decrease in theproportion of PH discharges endingin mortality does not necessarilydemonstrate a true decrease in theincidence of PH mortality. This trendalso could reflect more frequenthospitalizations earlier in the diseasecourse, with or without relatedchanges in the duration of survival orthe proportion eventuallyexperiencing mortality. Similarly,trends in hospital charges and lengthof stay per admission could reflecta change in the type or acuity ofhospital admissions. Thus,cumulative national charges for allPH discharges provide the bestreflection of the overall trend in thecollective resource utilizationassociated with PH-related inpatientcare.

A second limitation of the currentstudy is that ICD-9-CM codes do notpermit accurate identification ofsubgroups of patients with PH ina way that is consistent with themost current schemata for

TABLE 2 Procedural and Outcome Characteristics of PH Admissions Compared With All PediatricAdmissions

PH All KID P OR 95% CI

n = 56 678 n = 42 961 763

Procedures during admissionCardiac MRI 783 (1.4) 268 039 (0.6) ,.0001 2.23 (2.08–2.39)Cardiac catheterization 6291 (11.1) 115 481 (0.3) ,.0001 46.32 45.10–47.58Noncardiac surgery 5441 (9.6) 3 190 658 (7.4) ,.0001 1.32 1.29–1.36Cardiac surgery 9484 (16.7) 236 414 (0.6) ,.0001 36.32 35.51–37.14Tracheostomy 967 (1.7) 45 989 (0.1) ,.0001 16.20 15.19–17.27Dialysis 865 (1.5) 76 083 (0.2) ,.0001 8.74 8.17–9.35ECMO 1123 (2.0) 15 078 (0.04) ,.0001 57.58 54.16–61.21

Respiratory failure 14 315 (25.3) 771 845 (1.8) ,.0001 18.47 18.12–18.83Length of stay, d 15.6 6 0.29 4.8 6 0.003 ,.0001 — —

Total hospital charges, $ 171 376 6 4717 26 846 6 20 ,.0001 — —

Discharge disposition ,.0001Home, routine 43 328 (76.4) 39 912 226 (92.0) — —

Home with home health 6556 (11.6) 1 451 729 (3.4) — —

SNF/subacute/long-term care 6794 (12.0) 1 597 808 (3.7) — —

Mortality 3332 (5.9) 245 084 (0.6) ,.0001 10.89 10.51–11.28

Values are number (percentage) or mean 6 SE, as appropriate.SNF, skilled nursing facility; —, not applicable.

FIGURE 3Case mix. Proportion of admissions accounted for by patients with PH associated with CHD, bymonth, in triennial years (decreasing trend; P , .0001).

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categorizing PH. Early attempts toclassify PH as “primary” or“secondary” have been refined over

the past 2 decades through multipleiterations of World HealthOrganization classifications defined

at international consensus symposiain 1998 (Evian, France),27 2003(Venice, Italy),28 2008 (Dana Point,CA),29 and 2013 (Nice, France)30 toreflect progress in understanding thepathophysiology of PH and identifysubgroups of patients with PH whoshare meaningful aspects of theirdisease process. Unfortunately,administrative analyses cannotcapture these clinical distinctions,because ICD-9 coding has not beenmodified to reflect theserefinements. However, we do believethat it is both clinically meaningfuland operationally reliable to identifyPH associated with CHD. Wetherefore designed our analysis touse only this subclassification withinthe entirety of PH admissions, asprevious registries have done.7,8 Weshould note that our post hocreclassification of patients otherwisebelonging to the non-CHD group onthe basis of cardiac surgicalprocedure codes that should reliablyidentify them as patients with CHDwas likely imperfect, and someclassification error may persist.A small proportion of the non-CHDgroup may represent patients withCHD who simply lack a correct CHDdiagnosis code; this would tend tobias the comparison between CHDand non-CHD discharges toward thenull.

Lack of granularity about PHsubtypes and residual classificationerror are limitations of the use of anadministrative database and must beweighed against the advantages ofa large, national analysis. Similarly,a limitation of retrospective studies,such as this one, is that they rely onexisting practices of diagnosing PHand do not offer a mechanism forusing gold standard (eg,echocardiographic or catheterization-based) diagnostic criteria forinclusion.

We should note that we did not usethe persistent PH of the newborndiagnosis code (747.83, “persistentfetal circulation”) as an inclusion

FIGURE 4Location of care. Monthly admissions (in triennial years) by hospital setting and presence of CHD. Darkblue bars, non-CHD group, urban teaching hospitals; light blue bars, CHD group, urban teaching hospitals;green bars, non-CHD group, urban nonteaching hospitals; purple bars, CHD group, urban nonteachinghospitals; orange bars, non-CHD group, rural hospitals; red bars, CHD group, rural hospitals.

TABLE 3 Characteristics of Admissions in Patients With PH Associated with CHD and Patients WithPH Not Associated With CHD

PH With CHD PH Without CHD P

n = 24 706 n = 31 972

Age, y 3.3 6 0.09 7.0 6 0.13 ,.0001Age category, y ,.0001Birth admission 2346 (9.5) 4104 (12.8),1, readmitted since birth 12 975 (52.5) 7953 (24.9)1–4 4269 (17.3) 6073 (19.0)5–9 1430 (5.8) 2048 (6.4)$10 3686 (14.9) 11 794 (36.9)

Gender ,.0001Boys 12 589 (51.0) 16 914 (52.9)Girls 12 117 (49.0) 15 058 (47.1)

Race ,.0001White 9821 (39.8) 11 739 (36.7)Black 3281 (13.3) 7159 (22.4)Hispanic 4736 (19.2) 5137 (16.1)Asian 843 (3.4) 965 (3.0)Other/Missing 6025 (24.4) 6972 (21.8)

van Walraven comorbidity score 3.5 6 0.10 4.6 6 0.09 ,.0001Payer ,.0001Medicare 72 (0.3) 390 (1.2)Medicaid 12 473 (50.5) 16 357 (51.2)Private insurance 9935 (40.2) 12 639 (39.5)Self-pay/other 2226 (9.0) 2286 (8.1)

Hospital setting ,.0001Rural 315 (1.3) 903 (2.8)Urban, nonteaching 2597 (10.5) 4960 (15.5)

Urban, teaching 21 794 (88.2) 26 109 (81.7)Children’s hospital 9808 (39.7) 9384 (29.4) ,.0001

Values are number (percentage) or mean 6 SE, as appropriate.

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criterion for our patient cohort, as wesuspect patients with that diagnosisalone differed in important ways fromour population of interest. Thisdecision was in keeping with otherprevious analyses of pediatric PH,including the UK registry.8 Patientswith a persistent PH of the newborndiagnosis code were included only inthe event of a separate PH diagnosiscode (416.3).

A third issue is that total hospitalcharges reported in KID representglobal charges for entire hospitalstays. This precludes knowledge ofthe individual contributors toresource utilization (eg, medicationcosts, tests, supplies, procedures) orthe degree to which the contributionof PH was direct or indirect. Also, thecomplex relationships betweenhospital charges, hospital costs,

insurance reimbursement, andpatient copayments complicate theextrapolation of these results to anestimation of the true societal cost ofinpatient pediatric PH care. However,hospital charges are useful foranalysis of resource utilization trends,allow for aggregation of data at thenational level, and give the bestavailable sense of the magnitude ofresource utilization devoted to thispatient population. We attempted tominimize the effect of any broaderincreases in the cost of medical careduring the study period by adjustingfor inflation to 2012 dollars by usinga subindex of the Consumer PriceIndex that applies specifically toinpatient hospital care; increases inaverage total hospital charges that wereport are therefore abovebackground trends of increasing costsof hospitalization, and not just abovethe economy-wide inflation.

Fourth, KID provides data onlytriennially, and its sampling framedoes change slightly from year toyear. Discharge weights adjust toproduce national estimates for eachyear, and we also attempted toaddress this limitation by ensuringthat the ICD-9 codes used to identifyPH discharges did not changesignificantly during the studyperiod.31 It remains possible thatshifts in awareness of PH in certainpatient subgroups (eg, preterminfants with bronchopulmonarydysplasia) have contributed to theincrease in the number of pediatrichospitalizations associated with PH.Also, it should be noted that allfigures showing trends havea nonhomogeneous time axis becauseKID provides triennial data (ie, thereare gaps between available datasetyears). Therefore, the figures provideinformation as to the nature anddirection of trends over the studyperiod, but should not be interpretedto provide precise quantitative trendinformation (eg, the slope of a line) orbe used to interpolate or extrapolatethese trends. As such, we have limitedour trend analyses to time-ordered

TABLE 4 Procedural and Outcome Characteristics of Admissions for Patients With PH AssociatedWith CHD and Patients With PH Not Associated With CHD

PH With CHD PH Without CHD P OR 95% CI

n = 24 706 n = 31 972

Procedures during admissionCardiac MRI 351 (1.4) 432 (1.4) .48 1.05 0.91–1.21Cardiac catheterization 4080 (16.5) 2211 (7.0) ,.0001 2.66 2.52–2.81Noncardiac surgery 2539 (10.3) 2902 (9.1) ,.0001 1.15 1.08–1.21Cardiac surgery 8327 (33.7) 1157 (3.6) ,.0001 13.54 12.70–14.44Tracheostomy 424 (1.7) 543 (1.7) .88 1.01 0.89–1.15Dialysis 330 (1.3) 535 (1.7) .001 0.80 0.69–0.91ECMO 1011 (4.1) 112 (0.4) ,.0001 12.14 9.98–14.76

Respiratory failure 7145 (28.9) 7456 (23.3) ,.0001 1.34 1.28–1.39Length of stay, d 17.7 6 0.43 14.0 6 0.29 ,.0001 — —

Total hospital charges, $ 214 581 6 6783 137 152 6 3869 ,.0001 — —

Discharge disposition ,.0001Home, routine 19 118 (77.4) 24 210 (75.7) — —

Home with home health 2882 (11.7) 3674 (11.5) — —

SNF/subacute/long-term care 2706 (11.0) 4088 (12.8) — —

Mortality 1599 (6.5) 1727 (5.4) ,.0001 1.21 1.13–1.30

Values are number (percentage) or mean 6 SE, as appropriate.SNF, skilled nursing facility; —, not applicable.

FIGURE 5Surgical procedures. Proportion of PH admissions that involved a cardiac surgical procedure (greenbars, decreasing trend, P = .0056) or a noncardiac surgical procedure (orange bars, increasingtrend, P , .0001), by month, in triennial years.

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tests and have not used linearregression to assess the slopes of anytrends or extrapolate trends into thefuture.

Last, trend analyses reported herewere limited by a small amount ofmissing data (7.2% of all records didnot include the month of admission,only the year). However, we believethe benefit of greater datagranularity outweighs thedisadvantages of this limitation, asuse of admission year alone wouldsignificantly limit the power of trendanalyses and would prohibit anyadjustment for seasonal fluctuationsthat are particularly important inpediatrics. Sensitivity analysesrevealed that the small number of

missing records did not change theresults of nontrend analyses,including descriptive data orcomparisons between the PH groupand all KID discharges or betweenPH subgroups.

Despite these limitations, the currentstudy is useful in demonstrating theburgeoning number and nature ofpediatric PH hospitalizations and theimplications of these trends forresource utilization and publicpolicy.

CONCLUSIONS

This study highlights the substantialand growing health care burden thatpediatric PH represents, while also

documenting the declining trajectoryof morbidity and mortalityassociated with inpatient PH care.These results have practice andpolicy implications at theinstitutional, state, and nationallevels, particularly in the face ofincreasing pressure to restrain costswhile caring for a population withincreasingly complex medical needs.

Our finding that most children werenot cared for in dedicated children’shospitals further underscores theneed for increased awareness of PHamong providers. Additionally,accelerated efforts are needed tofoster multidisciplinary collaboration,to build consensus on standardizedtreatment protocols, strengthen theevidence base that supports clinicalguidelines, and to define requisiteexpertise for clinical excellence inpediatric PH care across a wide rangeof settings.

ABBREVIATIONS

CHD: congenital heart diseaseCI: confidence intervalECMO: extracorporeal membrane

oxygenationICD-9-CM: International

Classification ofDiseases, Ninth Revision,Clinical Modification

KID: Kids’ Inpatient DatabaseHCUP: Healthcare Cost and

Utilization ProjectOR: odds ratioPH: pulmonary hypertension

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

COMPANION PAPER: A companion to this article can be found on page 392, and online at www.pediatrics.org/cgi/doi/10.1542/peds.2015-1697.

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Lewis H. RomerBryan G. Maxwell, Melanie K. Nies, Chinwe C. Ajuba-Iwuji, John D. Coulson and

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