Cost of different approaches the respiratory distress syndrome · for diagnosing respiratory distress syndrome were as follows: tachypnoea (more than 60 breaths/minute), substernal

Archives ofDisease in Childhood 1991; 66: 757-764

ARCHIVES OF

DISEASE IN

CHILDHOODThe Journal of the British Paoediatric Association

ORIGINAL ARTICLES

Cost implications of different approaches to theprevention of respiratory distress syndrome

Miranda Mugford, James Piercy, Iain Chalmers

AbstractBecause the incidence of both neonatal respir-atory distress syndrome and neonatal mortal-ity can be reduced by giving corticosteroids towomen expected to deliver preterm and bygiving surfactant to babies at high risk ofdeveloping hyaline membrane disease, wehave considered what effects the adoption ofone or both of these preventive policies wouldhave on the costs of neonatal care. We haveestimated the effects of treatment from over-views of the relevant controlled trials, andestimated costs from observations of care atone neonatal unit. Our results suggest that ifeither of these policies is adopted for allbabies under 35 weeks' gestation at a drugcost of £150 or less/baby, the overall costs ofcare would be reduced by between 1 and 10%.The cost per survivor would be reduced by upto 16% even if the drug cost were to be as highas £550/baby. If the policies were to beadopted only for babies under 31 weeks' ges-tation, both policies would result in a reduc-tion in cost of between 5 and 16%/survivor,although the increased survival resulting fromthe policies would lead to an increase in over-all costs for babies of less then 31 weeks' ges-tation of between 7 and 32%.

National PerinatalEpidemiology Unit,Radcliffe Infirmary,Oxford OX2 6HEMiranda MugfordJames PiercyIain ChalmersCorrespondence to:Mrs Mugford.Accepted 18 January 1991

Although neonatal intensive care is more costeffective than many other widely accepted com-

ponents of health care,' it is one of the mostcostly parts of the perinatal health services.21-3The costs of caring for babies who require arti-ficial ventilation are particularly high,3 '3 and a

high proportion of these babies have respiratorydistress syndrome. Interventions that reducethe incidence of respiratory distress syndromeare clearly desirable because they reduce morbi-dity and mortality. In addition, however, theymay reduce the costs of neonatal intensive care

both for the health services and for those usingthem.There is now strong evidence that the inci-

dence of respiratory distress syndrome can be

reduced by at least two prophylactic policies:giving corticosteroids to women who areexpected to deliver preterm, and giving surfac-tant to babies judged to be at high risk ofdeveloping respiratory distress syndrome. Weare not the first to draw attention to the poten-tial economic benefits of these forms of prophy-laxis. The potential cost saving from using ante-natal corticosteroids was noted in a leading art-icle in the Journal of Pediatrics in 1984,'4 and itwas estimated in one of the controlled trials ofantenatal corticosteroids that prophylaxis hadmore than halved subsequent hospital chargesin the group that had received the drugs.'5 Theeconomic consequences of adopting early treat-ment with surfactant are less certain, because itis clear that the market cost of surfactant willbe considerable. Although some of the availableestimates suggest that savings are unlikely to beas dramatic as with antenatal corticosteroids,16giving surfactant early to immature infants maynevertheless be cost effective.'7

In this paper we present estimates of thelikely effects of introducing each of theseprophylactic strategies on health service costs.

Materials and methodsOur aims were to derive estimates from over-views of controlled trials of the effects of the twopolicies on respiratory distress syndrome andmortality; to observe the costs of care for pre-term babies in a unit where mothers did not (atthe time of the study) routinely receive steroidsas a prophylactic measure against respiratorydistress syndrome, and where babies were notgiven surfactant; and, using these two sourcesof data, to predict the expected effect on costs ofintroducing different policies for prevention ofrespiratory distress syndrome in that unit.

ASSESSMENT OF EFFECTS OF INTERVENTIONS TOREDUCE THE INCIDENCE OF RESPIRATORYDISTRESS SYNDROMEPrenatal administration of corticosteroidsEstimates of the effects of corticosteroids on the

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Mugford, Piercy, Chalmers

incidence of respiratory distress syndrome andearly neonatal death were derived from ananalysis of 12 trials of prenatal corticosteroidsincorporated in the overview reported by Crow-ley and her colleagues.'8 These trials togetherincluded a total of 3266 babies judged prenatallyto have been at increased risk of developingrespiratory distress syndrome. Although theentry criteria for these trials differed in somedetails, most of the babies studied were between24 and 34 weeks' gestational age at birth.

Early postnatal administration of surfactantEstimates of the effects of prophylactic surfac-tant were derived from overviews reported bySoll.'9 20 The trials included babies of between24 and 34 weeks' gestation (or who were inequivalent birthweight categories). The esti-mate of the effect of surfactant on the incidenceof respiratory distress syndrome was based ondata derived from the 1491 babies who partici-pated in the 10 trials in which this outcome wasreported. The estimate of the effect on the riskof death before discharge from hospital wasbased on data derived from 1924 babies whoparticipated in a total of 14 trials.The methods used in creating the overviews

have been described more fully elsewhere.2'Estimates of the effects of the two interventionswere derived using a modification of theMantel-Haenszel method,22 and have beenexpressed as summary odds ratios with their95% confidence intervals (CI).

ESTIMATION OF COSTSOur costing study was carried out at the neona-tal unit of the John Radcliffe Maternity Hospi-tal, Oxford. The aim of this part of the studywas to estimate the difference in costs of neona-tal care for babies with and without respiratorydistress syndrome who survived to be dis-charged, and also for those who died. Thesecosts were estimated for babies admitted to theunit during the first half of 1989. The criteriafor diagnosing respiratory distress syndromewere as follows: tachypnoea (more than 60breaths/minute), substernal and intercostalrecession; grunting, disease increasing in sever-ity over 24-36 hours, and clinical diagnosis sup-ported by radiological appearances.To estimate the costs of treating respiratory

distress syndrome, we estimated the cost at eachof the levels of care from detailed review of thetreatment of eight babies admitted during theperiod with a range of gestational ages. Four ofthese babies, with gestational ages of 28, 32, 34,and 36 weeks, met the diagnostic criteria forrespiratory distress syndrome. We then selectedthe casenotes of four control babies, who weredischarged from hospital at about the sametime, but who had not developed respiratorydistress syndrome and were as close in gestatio-nal age as we could find (30, 30, 32, and 36weeks).

Procedures noted in the case records werecosted by observation of care in the neonatalunit. One of us (JP) made detailed observationsof the staffing, equipment, and clinical proce-

dures used in the care of newborns in the unitduring the two months of July and August1989. We obtained administrative data aboutthe costs of services provided to the neonatalunit by the pharmacy, and by the departmentsof pathology, radiology, and physiotherapy.Overhead costs were for ward overheads, anddid not include any element for capital value ofthe building. Details of the costing methods aregiven elsewhere.23 From these data we usedsimple algebra to calculate average costs/day ofcare for three levels of care experienced by theeight babies in the detailed study: babies hav-ing intermittent positive pressure ventilation(IPPV), babies given oxygen without IPPV, andbabies receiving other special care.The expected cost of care for the 70 babies

with gestational ages of less than 35 weeksadmitted to the unit between 1 January and 30June 1989 were calculated from data about theaverage length of stay at each of these levels ofcare, together with cost data from our observa-tions about the costs of different levels of care.These costs were tabulated by diagnosis ofrespiratory distress syndrome, by whether thebaby survived to be discharged or not, and bygestational age. To avoid the problem ofmeasuring the use of resources in more than onehospital, we studied only babies born withinthe John Radcliffe Maternity Hospital and nottransferred elsewhere.The costs of steroids and surfactant were esti-

mated after discussion with pharmacists and cli-nical staff. Giving steroids is likely to add rela-tively little to the cost of care, as a womanadmitted to hospital with threatened pretermdelivery is likely to receive a high level of obstet-ric and midwifery care whether or not she isgiven these drugs, thus the marginal cost islikely to be the cost of the drug and the mat-erials needed to give it. The additional cost ofgiving surfactant to infants at high risk ofdeveloping respiratory distress syndrome is alsolikely to be low, because it is likely that con-tinuous paediatric medical care would anywaybe required at this stage in the life of thesebabies. The drug cost/dose is considerablyhigher than that for corticosteroids. For thisstudy we calculated expected costs based onhigh and low estimates of its cost.

All estimates of financial costs have beenbased on 1989 prices. The estimated value ofcapital equipment used was calculated usingthe method now recommended for NHSaccounts, using straight line depreciation overseven years, with an added annual fixed interestcharge of 6%.

ESTIMATING THE LIKELY IMPACT OF INTRODUCINGMEASURES TO PREVENT RESPIRATORY DISTRESSSYNDROME AT THE JOHN RADCLIFFE MATERNITYHOSPITALData were collected from routine sources aboutall the babies of less than 35 weeks' gestationwho were born between 1 January and 30 June1989 and admitted to the neonatal unit. Theseprovided information about whether babies haddeveloped respiratory distress syndrome, andwhether they had survived to be discharged. To

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Cost implications ofdifferent approaches to the prevention ofrespiratory distress syndrome

assess the proportion of babies that mighthave benefited from antenatal corticosteroids,further data about the length of time betweenthe mothers' admission and their delivery werecollected from the labour ward delivery book.To assess the likely impact of adopting each

of these prophylactic strategies on the incidenceof respiratory distress syndrome and death inthis cohort, we calculated expected numbers byapplying the typical odds ratios derived fromthe trial overviews to the observed odds ofoccurrence of the two outcomes, using the for-mula:

R=NRoT/(N-R&)1+ [ROT/(N-R0)]

Where: RK=expected number with particularoutcome with prophylactic intervention; N=total number of babies; Ro=observed numberof babies with particular outcome without theprophylactic intervention; and T=typical oddsratio for the effect of the prophylactic interven-tion.

ResultsEFFECTIVENESS OF PROPHYLACTICCORTICOSTEROIDS AND SURFACTANTTable 1 shows typical odds ratios and 95% CIfor the effects of prenatal corticosteroids andearly postnatal surfactant on respiratory distresssyndrome and on mortality. The 95% CI for

Table I Effect ofprophylaxis with antenatal corticosteroidsand early surfactant administration on respiratory distresssyndrome and mortality

No of No of Typical 95% CItrials babies odds

ratio

Antenatal corticosteroids:"Respiratory distresssyndrome 12 3266 0-49 0-41 to 0-60

Early neonataldeath 12 3266 0 59 047 to 075

Early postnatal surfactant administration:9 20Respiratory distresssyndrome 10 1491 0-61 0-49 to 0-75

Death beforedischarge 14 1924 0 55 043 to 070

the typical odds ratio (the ratio between theodds for the intervention and control popula-tions) for antenatal corticosteroid administationis between 0-41 and 0-60, which means that theprophylaxis is likely to reduce the odds ofrespiratory distress syndrome by between about60 and 40%. The reduction in the odds ofrespiratory distress syndrome likely to followearly administration of surfactant lies betweenabout 50 and 25%, because the confidence inter-val for the typical odds ratio is between 0-49 and0-75. Both prophylactic regimens are alsoassociated with a significant and clinicallyimportant reduction in the risk of death. Theavailable data on longer term effects are reassur-

ing for corticosteroids but not yet available forsurfactant. 8

COSTS OF RESPIRATORY DISTRESS SYNDROME

The detailed costs of caring for babies with andwithout respiratory distress syndrome withcomparable gestational ages are shown in table2. The mean cost of caring for the four babieswith respiratory distress syndrome (£6554/baby) was about twice that for the four controlswith similar gestational ages who did notdevelop respiratory distress syndrome (£3265/baby). A breakdown of the costs shows that thelargest absolute difference in costs is for nursingand equipment costs. Although they accountedfor a smaller part of the total costs, however,relative differences in costs were greatest forbiochemistry, radiology, oxygen, and phar-macy.From these data we estimated the costs/day of

care at each of the three prespecified levels ofcare to be as follows: with IPPV, £272; withoxygen but no IPPV, £118; and for other care inthe unit, £102. Based on these costs, table 3shows, for the 70 babies included in our study,the costs by gestational age group, survival todischarge, and diagnosis of respiratory distresssyndrome. Whether or not they had respiratorydistress syndrome, babies who died hadreceived intensive care throughout their stay inthe neonatal unit. Table 3 shows that the aver-

age cost of care for surviving babies under 31

Table 2 Differences in detailed cost (£ sterling) of care for four babies with and four without respiratory distress syndromematched for gestational age

Mean costlcase at 1989 prices Ratio of costs ofcare for those with

Babies with respiratory Babies without respiratory respiratory distressdistress syndrome distress syndrome matched syndrome:those

for gestational age without

Staff:Nursing 2736-53 1608-73 1-7:1Medical 962-39 498-24 19:1Physiotherapy 32-45 24 61 1-3:1

Depreciation and running costs ofequipment, including ultrasound 1172-08 560 44 2 1:1

Pathology:Biochemistry 227-19 46 25 4-9:1Haematology 117-00 57 00 2-1:1Microbiology 96-00 37 12 2-6:1

Radiology (including staff and equipment) 388 80 43 20 9 0:1Disposable supplies 276-28 158-95 1-7:1Oxygen 88 50 2-25 39-3:1Pharmacy (including blood products and

total parenteral nutrition) 199-65 29 20 6-8:1Overheads (including all ancillary and

support services) 250 57 191-14 1-3:1

Total cost/case 6554-00 3265-00 2 0:1

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Table 3 Numbers of babies* and costs of care by gestation, development of respiratory distress syndrome, and outcome

With respiratory distress syndrome Without respiratory distress syndrome

Total Died Survived Total Died Survived

Estimated cost per baby(£, 1989 prices)

Gestational age (completed weeks):<31 6385 1844 10100 47% 0 479631-34 3872 0 3872 2408 2227 2418

Total <35 weeks 5667 1844 7478 2635 2227 2649No of babiesGestational age (completed weeks):<31 20 9 11 4 0 431-34 8 0 8 38 2 36

Total <35 weeks 28 9 19 42 2 40

'Babies less than 35 weeks' gestation admitted to the John Radcliffe Maternity Hospital neonatal unit between 1 January and 30June 1989.

weeks' gestation with respiratory distress syn-

drome was more than twice that for those whodid not develop respiratory distress syndrome.For babies of 31 to 34 weeks' gestation the costis 60% higher for those with respiratory distresssyndrome.

Costs of antenatal corticosteroids are between£5 and £11/woman treated. In our calculationswe have assumed the cost is £7-50. The costs ofmost surfactant preparations are not yet known.The costs of a course of artificial lung expandingcompound (ALEC) are between £700 and £800.Another artificial surfactant preparation,'Exosurf', has recently been given a productlicence for sale in the United States and is being

Table 4 Numbers with different outcomes and costs of pregestation

marketed at $450/10 ml vial (Wellcome, perso-nal communication). Our calculations in thispaper have used the two extreme values of £100and £1000/baby treated.

IMPLICATIONS OF ADOPTING DIFFERENT

STRATEGIES TO PREVENT RESPIRATORY DISTRESS

SYNDROMEOf the 70 babies with a gestational age of lessthan 35 weeks' admitted to the neonatal unitduring the first six months of 1989, 28 (40%)had a diagnosis of respiratory distress syn-drome. Eleven babies died before dischargefrom hospital. Tables 4 and 5 show, for babies

vention of respiratory distress syndrome: babies <35 weeks'

Policy No of babies Cost of Cost of Total costlbaby Total costlsurvivorneonatal prevention

Survived Died care (£)* (£) £ Percentage £ Percentagechange change

With Without compared comparedrespiratory respiratory with withdistress distress no policy no policysyndrome syndrome

(1) No antenatal corticosteroidor surfactant 19 40 11 269 085 0 3844 0 4561 0

(2) With antenatalcorticosteroids 12-8 48-7 8 5 240 985 525 3450 -10 3927 -14

(3) With prophylactic surfactant:(A) At £100 16 48 5 5-5 258 646 7000 3795 -1 4119 -10(B) At £1000 16 48 5 5-5 258 646 70 000 4695 +22 5095 +12

(4) Antenatal corticosteroidsand surfactant for thosedelivered within 6 hours ofmother's admission:(A) At £100 12-4 50 6 7 240 157 1870 3458 -10 3842 -16(B) At £1000 12-4 50 6 7 240 157 16 594 3668 -5 4075 -10

*Excludes cost of any preventive treatment (corticosteroid or surfactant).

Table S Numbers with different outcomes and costs of prevention of respiratory distress syndrome: babies <31 weeks'gestation

Policy No of babies Cost of Cost of Total costlbaby 7otal costlsurvivorneonatal prevention

Survived Died care (£)* (£) £ Percentage £ Percentagechange change

With Without compared comparedrespiratory respiratory with withdistress distress no policy no policysyndrome syndrome

(1) No antenatal corticosteroidor surfactant 11 4 9 146 880 0 6120 0 9792 0

(2) With antenatalcorticosteroids 11-4 6-2 6-4 156 841 180 6542 +7 8912 -9

(3) With prophylactic surfactant:(A) At £100 12-1 8-9 3 170426 2400 7201 +18 8230 -16(B) At £1000 12-1 8-9 3 170426 24000 8101 +32 9258 -5

(4) Antenatal corticosteroidsand surfactant for thosedelivered within 6 hoursof mother's admission:(A) At £100 11-7 6-7 5 6 160 630 880 6730 +10 8778 -10(B) At £1000 11-7 6-7 56 160630 7180 6992 -14 9120 -7

*Excludes cost of any preventive treatment (corticosteroid or surfactant).

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Babies born alive at<35 weeks' gestation(n=70)

Delivered within

6 hours of admission(n=1 6)

RDS | RDS(n=7) (n=9)

Discharged Died Discharged Died

alive (n=3 alive (n=n=4)

(n=9)

Delivered more than

6 hours after admission(n=54)

RDS No RDS(n=21 ) (n=33)

Discharged Died Discharged Died

alive (n=6 alive (n=2

Figure I Observed number ofbabies <35 weeks' gestation with different outcomes. RDS, respiratory distress syndrome.


No prophylaxis Antenatal corticosteroids

Delivered within Delivered more than6 hours of admission 6 hours after admission

(n=16) (n=54)

RDS No RDS RDS No RDSI(r=7) | |(n=9) | (n=12 8)1 (n=41 2)1

Discharged Di d Discharged Died Discharged d d Discharged Died

alive ie=3 alive(n=

aliveDied)

alive15

| (n=4) || (=) (n=9) (=) | (n=8-8) || (=) (n=;39-7) (n15

Figure 2 Estimated numbers ofbabies with different outcomes with a policy ofgiving antenatal corticosteroids. RDS,respiratory distress syndrome.

under 35 weeks' and under 31 weeks' gestation,respectively, the estimated costs for these 70babies, firstly given the care that they experi-enced (care policy 1), and then for each of threepolicies for the prevention of respiratory dis-tress syndrome (care policies 2, 3, and 4). Foreach policy including use of prophylactic surfac-tant, separate estimates are made for the upperand lower costs of surfactant.Of the 70 babies, 16 were delivered within six

hours of the mother's admission to hospital.Even if the mothers of these babies had beeneligible to receive antenatal corticosteroids, we

have assumed that the babies would not havebenefited, but we have included the costs ofgiving corticosteroids to their mothers.

Figure 1 shows the observed numbers ofbabies with particular outcomes. Figures 2, 3,and 4 show the estimated numbers with diff-erent outcomes for three different policies ofprevention of respiratory distress syndrome:firstly, use of antenatal corticosteroids for those

likely to benefit; secondly, use of early prophy-lactic surfactant for all babies; and thirdly, useof corticosteroids for those likely to benefit,

Babies born alive.at<35 weeks' gestation(n=70)

Prophylactic surfactant

RDS No RDS(n=20-2) |(n=49-8)|

Discharged Died Discharged Diedalive (n=-421 alive n1-3

Figure 3 Estimated numbers ofbabies with differentoutcomes with a policy ofearly surfactant administration.RDS, respiratory distress syndrome.

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Prophylactic surfactant

RDS No RDS(n=5-1 ) (n=10-9)

Discharged Died Discharged Diedalive (n= I5 alive (n=

(n=3 6) [jn7j=J )

Antenatal corticosteroids

Delivered more than6 hours after admission

(n=54)

|RDS No|RDSI[(n=12-8) (n=41-2)

Discharged Died Discharged Diedalive (n=4)I I alive (n=I 5)(n=8-8L2r(n=L39171

Figure 4 Estimated numbers ofbabies with different outcomes with a policy ofgiving antenatal corticosteroids combined withearly surfactant administration for those babies delivered within six hours ofmother's admission. RDS, respiratory distresssyndrome.

together with early prophylactic surfactant forthose who were unlikely to have benefited fromcorticosteroids. The expected costs arising fromadopting each of these different policies for allbabies under 35 weeks' gestation, and fromadopting them only for babies under 31 weeks'gestation, are given in tables 4 and 5.The cost of caring for the 70 babies of less

than 35 weeks' gestation was estimated to havebeen £269 085. We estimate that the use ofantenatal corticosteroids for women with gesta-tions up to 35 weeks (policy 2 in table 4) wouldhave reduced the number of cases of respiratorydistress syndrome by 28%, and the number ofdeaths by 22%. Given these changes, we esti-mate that the costs of caring for the wholecohort of 70 babies would have been reducedfrom £269 085 to £240 985, which means areduction in the average cost/baby by 10%; thecost/survivor would have been reduced from£4561 to £3927, a reduction of 14%. Appliedonly to mothers of babies with gestational agesof less than 31 weeks (table 5), prenatal admi-nistration of corticosteroids (policy 2 in table 5)would increase total costs by 7% because of thegreater cost of caring for babies of this gesta-tional age who would have survived, but thispolicy would have reduced the cost/survivor by9%.We estimate that early administration of sur-

factant to babies of less than 35 weeks' gestation(policies 3A and 3B in tables 4 and 5) wouldhave reduced the number of cases of respiratorydistress syndrome by 28%, and the number ofdeaths by half. The only difference betweenpolicies 3A and 3B is the cost of surfactant(costs of prevention in tables 4 and 5). Theeffectiveness is the same, and so the expectedcosts of neonatal care are the same. If the cost ofsurfactant were to be only £100/baby, theoverall costs for the cohort of 70 babies wouldhave decreased from £269 085 to £265 646, thatis by 1%, and the cost/survivor would have beenreduced from £4561 to £4119, a reduction of10%. If the cost of surfactant were to be as

much as £1000/baby, the overall costs for thecohort of 70 babies would have increased from£269 085 to £328 646-that is by 220/o-and thecost/survivor would have increased by 12%. Ifthe policy were applied only to babies of lessthan 31 weeks' gestation (table 5), the total costof care would have been increased by between18 and 32%, depending on the cost of surfac-tant, but the cost/survivor would have beenreduced by 5%, even at the higher cost ofsurfactant.

If antenatal corticosteroids had been used inall the women whose babies were likely tobenefit and surfactant had been restricted to theremaining babies (policies 4A and 4B in tables 4and 5) we estimate that, in the case of gestationsof up to 35 weeks, the number of cases of respir-atory distress syndrome and the number ofdeaths would both have been reduced by 36%.Once again, the two policies (4A and 4B) differonly in the costs of surfactant. At the lower endof the range of possible costs of surfactant(policy 4A in table 5), the costs of caring for thecohort of 70 babies would have been reducedfrom £269 085 to £242 027, that is by 10%. Thecost/survivor would have been reduced by 16%.At the higher end of the range of possible costsof surfactant (policy 4B in table 5), the costs ofcaring for the cohort of 70 babies would stillhave been reduced by 5% and the cost/survivorby 10%. Applied only to babies of under 31weeks' gestation (table 5), this policy wouldhave increased total costs by between 10 and14%, but the cost/survivor would have beenreduced by at least 7%.

DiscussionThe data we have used to assess the effects ofprophylactic corticosteroids and surfactant werederived from controlled trials involving sub-stantial numbers of babies, so our estimates ofthe effects ofthese policies on respiratory distresssyndrome and death are likely to be secure.Furthermore, the trials incorporated in the

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overviews were conducted in a wide range otsettings and so the results are likely to be widelyapplicable.

Although based on small numbers of babiesstudied in one neonatal intensive care nursery,our estimate that the cost of caring for babieswith respiratory distress syndrome is double thecost of caring for babies of similar gestationalage without respiratory distress syndrome isconsistent with previous estimates. A study con-ducted in United States found that hospitalcharges for babies who had had respiratory dis-.tress syndrome were more than twice those forbabies who had not developed respiratory dis-tress syndrome, a difference which was largelyaccounted for by the increased need for assistedventilation for those with respiratory distresssyndrome.3 These findings are consistent withthose of a recent Irish study,'4 and are reflectedin differences in reimbursement used by Medi-care in the United States for babies with andwithout respiratory complications of prematur-ity.24 The costs/day that we have calculatedfor different levels of care are low in comparisonto costs estimated by Ryan et al in Leeds.'°Several factors may explain this: we excludedoutborn babies, who had higher costs in theLeeds study; secondly, the Leeds studyincluded babies having operations and ourstudy did not; and, thirdly, the overhead costsincluded in our study were much lower thanthose in the Leeds study. Our estimated averagetreatment costs are comparable with morerecent data from a study of very preterm babiesentered into a trial of surfactant treatment inBelfast, where the average cost/case was £5888.25Although the absolute costs of caring for babieswith respiratory distress syndrome may varysubstantially among health care settings, theratio of costs within centres for babies ofcomparable gestations with and without respira-tory distress syndrome (about 2:1) seems not todiffer widely.The organisation of care at the neonatal unit

that we studied, where babies are moved to adifferent part of the unit when they are weanedfrom the ventilator and do not need intensivecare, made it relatively straightforward for us toestimate the additional costs for babies receivingventilation. This method could not be appliedin those units where all care, at whatever level,is given to the baby in the same place. To esti-mate costs in such circumstances would requireeither more intensive work study or the use ofsome algorithm for allocation of costs betweenlevels of care.We estimated that there would have been a

10% reduction in the costs of caring for babiesborn at less than 35 weeks' gestation if antenatalcorticosteroids had been used to prevent respir-atory distress syndrome. Data from the rando-mised trials in which resource consequenceswere estimated suggest that our estimate may beconservative.'5 26 In our calculations we as-sumed that corticosteroids would have affectedonly the incidence of respiratory distress syn-drome, yet the available evidence suggests thatthe incidence of both necrotising enterocolitisand periventricular haemorrhage would alsohave been reduced. 9 We also assumed that the

cost of treating respiratory distress syndromewas the same whether or not those babies whohad respiratory distress syndrome had beengiven any of the possible preventive interven-tions. This also seems to be a conservativeassumption in the light of evidence from thosetrials that have recorded data on severity of dis-ease and need for ventilation.About 3% of live births are at gestations of

less than 35 weeks (S Cole, personal com-munication). If the costs of care and incidenceof respiratory distress syndrome at this hospitalare typical, the costs of care for babies of under35 weeks' gestation born in England and Walesin 1989 would have been around £80m. If, asseems likely, antenatal corticosteroids are notwidely used by British obstetricians for the pre-vention of respiratory distress syndrome, thepotential reduction in neonatal costs could be asmuch as £8m in a year in England and Wales,which is more than 1% of the total amount esti-mated to have been spent on the maternityservices.27We estimate that routine early administration

of surfactant to babies born before 35 weeks'gestation would result in a 4% reduction in thecosts of subsequent care. A detailed analysis ofhospital charges based on two consecutive trialsof the prophylactic use of calf lung surfactantshowed that the total cost of neonatal care,excluding the cost of surfactant, was similar forbabies receiving surfactant and for those whodid not. 6 The overall cost of such a policy willdepend on the unit cost of surfactant. Our esti-mates indicate that the policy would result inoverall net savings if the cost/baby of surfactantis £150 or less. Above this price there would notbe overall savings, although the cost/survivorwould still be reduced up to a surfactant cost/baby of £550. Our estimates suggest that res-tricting early administration of surfactant tobabies born at less than 31 weeks' gestationwould increase overall costs while reducing thecost/survivor. Analyses of data collected withina controlled trial conducted in Canada haveshown that the cost of caring for babies whoreceived surfactant were 27% lower than thecost of caring for control babies.'7 The differ-ence in average cost/patient was estimated tohave been $C1O 000, which would certainlyoutweight the likely costs of surfactant.

Although our analyses have not assumed thatthere would be an additional benefit to babies ofreceiving both corticosteroids and surfactant,there is some evidence to suggest that this addi-tive effect may exist.28 29 This too, therefore,may have led us to underestimate the cost effec-tiveness of these policies.Our estimates of the changes in costs arising

from policies to reduce the incidence of respira-tory distress syndrome were based on relativelysmall numbers of cases observed in a particularunit. Others may wish to apply the approach weadopted to data derived from their own units.Furthermore, it may turn out to be preferableon cost and other grounds to withhold surfac-tant until clear evidence has emerged that thebaby concerned has begun to develop the signsof respiratory distress syndrome. A report of arecent analysis of babies who had already

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764 Mugford, Piercy, Chalmers

developed severe respiratory distress syndromeand had been entered into a randomised trial ofsurfactant treatment concluded that surfactantreduced the cost/survivor. Taking account ofsubsequent neonatal morbidity, the use of sur-factant treatment was found to reduce the costof achieving a quality adjusted life year by£710.25 The relative merits of early surfactantprophylaxis compared with surfactant treat-ment of babies who have already developedrespiratory distress syndrome is currently beingassessed in a number of controlled trials.30 In atleast two trials the relative costs of the alterna-tive approaches will be assessed.3' 32

We are grateful to the staff at the John Radcliffe neonatal unit,and particularly to Caroline Pepys, Andrew Wilkinson, and PeterHope, for their help and advice. We also thank the staff of otherJohn Radcliffe Hospital departments who supplied us with infor-mation. The work could not have been done without the effortsof those who synthesised the results of the relevant controlledtrials, particularly Patricia Crowley, Marc Keirse, and RogerSoll. We also thank Mary Ellen Avery, Henry Halliday, AllenMerritt, Charles Normand, Andrew Shennan, Alec Turnbull,and our colleagues in the National Perinatal Epidemiology Unitfor their helpful comments on drafts of this paper. The paper isbased on work done by James Piercy as a project for an MSc inhealth economics at the University of York. The National Peri-natal Epidemiology Unit is funded by the Department of Health.

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9 Sandhu B, Cooke RWI, Stevenson RC, Pharoah POD. Costof neonatal intensive care for very low birthweight infants.Lancet 1986;i:600-3.

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11 Marshall PB, Halls HJ, James SL, Grivell AR, Goldstein A,Berry MN. The cost of intensive and special care of thenewborn. Med J Aust 1989;150:568-74.

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13 Connolly M, Fox G, U(Connor G(, Cl(arke T, Matthews T.Cost of neonatal intensive and special care. ir Med 7 1989;89:34-6.

14 Avery ME. The argument for prenatal administration ofdexamethasone to prevent respiratory distress syndrome.J Pediatr 1984;104:240.

15 Morales WJ, Diebel D, Lazar A, Zadrozny D. The effect ofantenatal dexamethasone administration on the preventionof respiratory distress syndrome in preterm gestations withpremature rupture of the membranes. Am J Obstet Gynecol1986;154:591-5.

16 Maniscalco WM, Kendig JW, Shapiro DL. Surfactantreplacement therapy: impact on hospital charges for pre-mature infants with respiratory distress syndrome. Pedia-trics 1989;83:1-6.

17 Shennan A, Dunn M, Possmayer F. Cost-effectiveness ofsingle dose surfactant prophylaxis in infants of less than 30weeks' gestation. Pediatr Res 1989;25:231A.

18 Crowley P, Chalmers I, Keirse MJNC. The effects of corti-costeroid administration before preterm delivery: anoverview of the evidence from controlled trials. BrJ ObstetGynaecol 1990;97:11-25.

19 Soil RF. Prophylactic administration of natural surfactantextract. Record No 5207. In: Chalmers I, ed. Oxford data-base of perinatal trials. Version 1.1, disk issue 3, February1990.

20 Soll RF. Prophylactic administration of synthetic surfactant.Record No 5253. In: Chalmers I, ed. Oxford Database ofPerinatal Trials. Version 1.1, disk issue 3, February 1990.

21 Chalmers I, Hetherington J, Elbourne D, Keirse MJNC,Enkin M. Materials and methods used in synthesisingevidence to evaluate the effects of care during pregnancyand childbirth. In: Chalmers I, Enkin M, Keirse MJNC,eds. Effective care in pregnancy and childbirth. Oxford:Oxford University Press, 1989:39-65.

22 Yusuf S, Peto R, Lewis J, Collins R, Sleight P. Beta-blockadeduring and after myocardial infarction, an overview of therandomised controlled trials. Prog Cardiovasc Dis 1985;27:336-71.

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25 Tubman TRJ, Normand C, Halliday H. Cost of surfactantreplacement for severe neonatal respiratory distresssyndrome: results of a randomised trial. BMJ 1990;301:842-5.

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27 Comptroller and Auditor General. National Audit Office reporton the maternity services. London: HMSO, 1990.

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Cost of different approaches the respiratory distress syndrome · for diagnosing respiratory distress syndrome were as follows: tachypnoea (more than 60 breaths/minute), substernal