Hypoplastic Left Heart Syndrome: Natural History in a Geographically Defined Population

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METHODS

This study is part of a larger investigation of

surgical repair of congenital heart defects in

child-hood and subsequent morbidity and mortality. For

Hypoplastic

Left Heart

Syndrome:

Natural

History

in a Geographically

Defined

Population

Cynthia

D. Morris,

PhD,

MPH;

Jacquelyn

Outcalt;

and

Victor

D. Menashe,

MD

From the Division of Cardiology, Department of Medicine, and Department of Pediatrics, Oregon Health Sciences University, Portland

ABSTRACT. Advances in surgical treatment of hypoplas-tic left heart syndrome with the Norwood procedure and cardiac transplantation have made essential the under-standing of the natural history of hypoplastic left heart syndrome. In a geographically defined population, we ascertained the prevalence of hypoplastic left heart

syn-drome in children born in Oregon from 1971 through

1986. Clinical and anatomic data were extracted from the charts of the 98 affected children and the survival rate was calculated. Hypoplastic left heart syndrome occurred in 0.162 per 1000 live births in Oregon during this period.

No syndrome complex was prevalent and 84% were free

of other congenital malformations. However, there was an increased occurrence of congenital heart defects in first-degree relatives of probands with hypoplastic left heart syndrome. Of the affected children 15 ± 4% died on the first day of life, 70 ± 5% died within the first week, and 91 ± 3% died within 30 days. No secular change in survival occurred during the study. Palliation with the

Norwood procedure was performed in 20 children.

Al-though survival was significantly improved with this sur-gery (P = .01), the effect was observed principally through

30 days of life and only one of these children remains alive. Hypoplastic left heart syndrome is a lethal congen-ital heart defect in children and poses management and ethical dilemmas. Pediatrics 1990;85:977-983; hypoplastic left heart syndrome, Norwood procedure, cardiac trans-plantation, congenital heart defects.

Ethical and medical management of hypoplastic

left heart syndrome (HLHS), an uncommon

con-genital anomaly, has become the subject of

contro-versy. This syndrome describes infants with a

con-tinuum of anomalies, including underdevelopment

of the left ventricle, aorta, aortic arch, and mitral

valve. The spectrum of defects ranges in severity

from aortic and mitral atresia with a vestigial left

ventricle to a small left ventricle with aortic

hypo-plasia.

Introduction of surgical palliation for HLHS has

offered some hope to neonates with these defects.

Although considered by many to be experimental,

the Norwood procedure as a first stage of surgical

management is performed in a number of pediatric

centers.’ More recently, Bailey and colleagues,2’3

proposed cardiac transplantation as definitive

treatment for this syndrome. Innovations to

im-prove the survival of children with HLHS were

propelled by its relatively high prevalence as a cause

of death among newborns with congenital heart

defects and the reportedly low association of

extra-cardiac anomalies.4’5

A high neonatal mortality rate has consistently

been reported by all studies of the natural history

of HLHS.69 In 1985, Noonan and Nadas7 reported

that of 101 infants with HLHS observed in a 9-year

period in Boston, 16% died within the first 72 hours

of life and 65% died in the first 35 days of life. More

recently, a retrospective analysis of 54 children

whose cardiac specimens were located in a

pathol-ogy museum demonstrated 80% mortality in the

first week; by 1 month, 95% had died.8

Because of renewed interest in HLHS due to

advances in surgical palliation, understanding the

natural history and clinical profile of this syndrome

has become more important. The purpose of this

investigation was to review the morbidity and

mor-tality with changing medical and surgical therapy

of infants with HLHS in a geographically defined

population.

Received for publication Nov 14,

1988;

accepted Jul 17, 1989. Reprint requests to (C.D.M.) Division of Cardiology L462, Ore-gon Health Sciences University, Portland, OR 97201.

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978 HYPOPLASTIC LEFT HEART SYNDROME

this purpose, a population-based registry has been

formed of all children with definitive repair of eight

common congenital heart defects. In the present

study, we have assessed the occurrence of HLHS

defined as left ventricular hypoplasia occurring in

conjunction with left heart obstruction, aortic valve

malformation, and/or aortic arch hypoplasia, often

with mitral stenosis or atresia. This diagnosis was

made by clinical examination and

echocardiogra-phy, augmented by autopsy or by surgical

proce-dune.

Medical records departments at all Oregon

hos-pitals with pediatric or obstetric facilities were

sun-veyed to identify cases. Five neonatal intensive care

facilities service Oregon and few, if any, patients are transferred out of state. All children discovered

were referred to one of these five facilities for the

diagnosis of HLHS. Despite attempts to identify

children who died of HLHS before referral to a

neonatal facility, none was identified. No stillborn

infants with HLHS were discovered during this

period, nor were any therapeutic abortions of

fe-tuses with HLHS recognized.

The search ofthe computerized records at Oregon

hospitals included any child coded to have complex

congenital heart disease or any recognizable

com-ponent of the syndrome, including hypoplastic left

ventricle, aortic stenosis, aortic arch hypoplasia, or

coanctation. Approximately 250 charts were

re-viewed to determine 98 cases of HLHS.

The following information was collected from

charts: anatomic components of HLHS; dates of

birth, appearance of symptoms, diagnosis, and

death; clinical presentation; events and illnesses

during pregnancy; occurrence of heart defects in

first-degree relatives; method of diagnosis of HLHS (autopsy, cardiac catheterization, echocardiogram,

or clinical examination); and presence of other

con-genital malformations. Follow-up to death or the

date the child was last known to be alive was

collected for all individuals. In the majority of cases,

death occurred while the child was in the hospital;

if the child died outside the hospital, the death

certificate was obtained and the child’s physician

contacted to confirm the information. For the two

survivors, their physicians were contacted to obtain

current follow-up information. No contact was

in-itiated with the infants’ parents. Oregon vital

sta-tistics for birth records were used to calculate the

rate of occurrence of HLHS by county and year of

birth in this defined cohort.

Survival, estimated by the Kaplan-Meier

method, was defined as elapsed time from birth to

death or the date the child was last known to be

alive. The Mantel-Cox statistic was used to

com-pare survival. Univariate analysis of discrete and

continuous variables was performed by

x2 and

two-sample t statistics, respectively. Birth weight was

analyzed and compared by computation of z scores

using a series of normal newborns in Oregon as a

control population and using the means and

stand-and deviations by weeks of gestation.’#{176} Each

pa-tient’s birth weight was displayed as the number of

standard deviations above or below the mean

con-trol birth weight for the appropriate gestational age.

RESULTS

Between 1971 and 1986, 98 children were born

with HLHS in Oregon (0.162 per 1000 live births).

During the first 5 years of the study (1971 through

1975) 16 children were born with HLHS, compared

with 39 born during the last 5 years (1982 through

1986). The increased number of cases by year

di-rectly parallels the increased utilization of

echocar-diography to make the diagnosis of HLHS during

this period. There was no significant difference in

the rate of occurrence by county in Oregon or by

month of birth.

Of the 98 children with HLHS, 54 were males

and 44 females. These infants had a mean birth

weight of 3338 ± 538 g and were born at an average

of 40 weeks’ gestation. Only 7% of the cohort was

born prematurely (<37 weeks’ gestation). Of these

children 34% were first born, 29% were second

born, 25% were third born, and 12% were fourth or

greater in order. The birth weight distribution of

these children was compared with the distribution

of birth weights by weeks of gestation in Oregon by

computation of z scores.8 The average of the z scores

was -0.07, which represents the number of

stand-and deviations from expected. Therefore, birth

weights of these children with HLHS did not differ

from the expected birth weight distribution of

Or-egon.

The clinical diagnosis of HLHS was confirmed

by autopsy in 58 (59%) and by surgery in 8 (8%).

In 33% of the infants, the diagnosis was confirmed

by cardiac catheterization and/or echocardiography

and no autopsy was performed. All children in this

study had hypoplastic left ventricle with aortic

stenosis, hypoplastic aortic arch, and aortic or

mi-tral atresia. A patent foramen ovale was identified

in less than half of the cohort, but the size could

not be analyzed from the autopsy notes. One third

of the cohort had a hypoplastic left atrium in

ad-dition to a hypoplastic left ventricle. Other defects

associated infrequently with HLHS included

pul-monic stenosis, discrete coarctation of the aorta,

mitral stenosis, hypoplastic mitral valve, mitral

atresia, double outlet right ventricle, atrioventric-ular canal, and dextrocardia.

The prevalence of extracardiac malformations

at Viet Nam:AAP Sponsored on September 7, 2020

www.aappublications.org/news

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-

With Norwood palliation

----

Without Norwood palliation

Days of Life

and chromosomal anomalies was determined from

clinical examination augmented by autopsy in 59%

of the cohort of which 72% were unrestricted

au-topsies. A cytogenetic examination was performed

in 12% of the cohort. Genetic anomalies discovered

in this cohort were tnisomy 18, a balanced

chro-mosome 3:7 translocation, 7q3 monosomy, and the

Noonan syndrome. Seven other children had

con-genital malformations, including fused labia and

imperforate anus, annular pancreas and megacolon,

polysplenia, microcystic kidney disease,

microce-phaly, hydronephrosis, and hypospadias. Of these

seven children, four had no apparent chromosomal disorder; in three, chromosomes were not assessed.

The majority (89%) appeared free from congenital

malformations other than HLHS.

Hypoplastic left heart syndrome occurred in two

female siblings, and both children are included in

this cohort. Three other probands had siblings with congenital heart defects: endocardial fibroelastosis,

coanctation of the aorta, and one undetermined

defect.

The initial clinical presentation in these children

with HLHS frequently included tachypnea,

cy-anosis, congestive heart failure, tachycardia, and

renal failure. These children were first noted to be ill at a median of 1 day old, with a range of minutes

after birth to 121 days. Diagnosis of HLHS was

made at a median of 4 days, with a range from 7

days before birth, as diagnosed by fetal

ultrasonog-raphy, to 121 days of life. On average, there was a

gap of 1.1 days from the first appearance of

symp-toms to the diagnosis of HLHS.

Of the 98 children with HLHS, 96 have died and

2 remain alive through 1987 at 21 and 24 months

of age. Overall survival to day 1 was 85 ± 4%; to

day 2, 64 ± 5%; to day 3, 46 ± 5%; to day 7, 30 ±

5%; and to day 30, 9 ± 3%. The greatest risk of

dying came on day 3, as evidenced by the hazard

rate of33 ± 8%.

During the course of the study, there was no

significant variation in survival rates by year.

Al-though the 30-day survival is somewhat greater in

children born since 1984 (17 ± 9%) compared with

those born between 1971 and 1974 (0%), 1975 and

1979 (4 ± 4%), and 1980 and 1984 (12 ± 5%), this

difference is not noted after 30 days and apparently

relates to the increased use of the Norwood

proce-dune for palliation.

A number ofpneoperative variables, including sex

and treatment with prostaglandin E,, were analyzed as potential predictors of longer survival. Overall,

females tended to live longer than males (P = .11);

however, this was due principally to a difference in

7-day survival (males, 22 ± 6% vs females, 39 ±

7%) as 30-day survival was similar (males, 7 ± 4%

vs females, 11 ± 5%). At the end of the study, 1

male and 1 female with HLHS remain alive.

Pros-taglandin E1 was given to 37 neonates to inhibit

physiologic closure of the ductus, but it had no

influence on survival as demonstrated by 7-day

survival of 30 ± 8% in neonates who received

pros-taglandin and 30 ± 6% who did not. In all but 4 of

the children who received prostaglandin, the

infu-sion was given until the day of death or surgery.

The infusion was discontinued in 4 cases to allow

death at home in accordance with the parents’

wishes.

The first stage of the Norwood procedure was

performed on 20 patients in this cohort. Surgery

was performed from within hours of birth to 2 years

of age but at a median of 4 days of age. Infants with

HLHS who survived the first days of life were more

likely to undergo Norwood palliation as shown by

greater survival from birth (Fig 1). Ofthese children

45% died during surgery and 75% within one day

of surgery. Two children survived long-term and

subsequently had a Blalock shunt; 1 of these

chil-dren died subsequently, 2.6 years after the initial

surgery. As shown by 30-day survival (Fig 1) and

overall survival (Fig 2), the Norwood procedure was

associated with a significant but temporary

im-provement in survival (P = .01), However, through

1987, 1 child undergoing the Norwood procedure

remains alive at 21 months of age and 1 child

without Norwood palliation also remains alive at

24 months of age.

DISCUSSION

Hypoplastic left heart syndrome comprises 15%

of all neonatal congenital heart defect deaths in the

0

Fig 1. Thirty-day survival of infants with hypoplastic left heart syndrome who underwent Norwood palliation vs survival of those who did not. Infants who underwent Norwood palliation demonstrated improved survival

im-mediately after birth despite surgery at a median of 4

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1.00

-

With Norwood palliation

----

Without Norwood palliation

100 200 300 400 500 600 700 800 900 1000 Days of Life

980 HYPOPLASTIC LEFT HEART SYNDROME

,0 t

0

a

0.

Fig 2. Overall survival of infants with hypoplastic left

heart syndrome who underwent Norwood palliation vs

survival of those who did not. The Norwood procedure is associated with a statistically significant (P = .01)

im-provement in survival as compared with natural survival.

first month of life;” however, it is a rare defect and accounts for less than 1 % of all cyanotic congenital heart disease.’2 In this geographically defined

pop-ulation, we found that the birth prevalence of

HLHS was 0.162 per 1000 live births. This is

con-sonant with the estimate in another geographically

defined survey, the New England Infant Cardiac

Registry, which found a birth prevalence of HLHS

of 0.163 pen 1000. In a summary by Ferencz et al,’3

this prevalence in live births ranged from 0.053 to

0.247 per 1000. Based on estimates from our study,

approximately 620 infants were born with HLHS

in the United States in 1987.

Although we attempted to identify children who

died within 24 hours of birth with suspected cardiac disease before referral to a neonatal facility, it is

possible that some children with HLHS were not

identified if an autopsy was not performed.

Simi-larly, it is possible that we missed stillborn infants

and spontaneously aborted fetuses with HLHS. In

the New England regional study, autopsies were

performed on 77% of all patients with HLHS; in

24% of these, the syndrome was discovered during

autopsy.6 In our experience, this occurred rarely.

With recent advances in echocardiographic

diag-nosis of congenital defects, it is likely that fewer

diagnoses of HLHS are missed premortem. Because

these children are critically ill, and because of

im-proved diagnostic methodology, the diagnosis is

made early, usually within 1 day of the occurrence of symptoms.

The occurrence of HLHS in males exceeds that

in females. In previous studies, 60% to 70% of

children with HLHS were male,8’9”4”5 and in this

study 55% were male. These proportions are

con-cordant with increased occurrence of all left

yen-tnicular outflow obstruction (aortic stenosis,

supra-valvular aortic stenosis, and coarctation of the

aorta) in males.

The occurrence of heart defects in prior-born

siblings and the recognition of HLHS in two female

siblings in this cohort suggests a genetic risk,

al-though the pattern of inheritance is unclear. The

lack of routine cytogenetic or genetic evaluation of

children in this cohort limits our ability to draw

conclusions about the occurrence of chromosomal

anomalies with HLHS as it is likely that some

genetic disorders were undetected. A number of

genetic and chromosomal syndromes have been

re-corded to occur with HLHS, including the Turner

syndrome; chromosome 17-18 deletions6; tnisomy

13, 18, and 2116; monosomy 2q’6; isochnomosome

Xq syndrome and mosaicism for 46xy/45xy-20’7;

the Holt-Oram, Apert, and Smith-Lemli-Opitz

syndromes’6; and the Noonan syndrome,

chromo-some 3:7 translocation, and 7q3 monosomy noted

in this study.

Shokeir’8 postulated that the pattern of genetic

occurrence suggested autosomal recessive

inherit-ance, perhaps because consanguinity was present

in five of nine sibships in the study. Although in a

subsequent study Brownell and Shokeir’9 concluded

that inheritance was probably multifactonial, the

possibility of autosomal recessive inheritance could

not be excluded. A population-based study by

Boughman and co-workers2#{176} reported a 13.5%

pre-currence rate of congenital heart defects in 38

sib-lings of 50 probands with HLHS; all precurrent

defects were related morphogenetically to HLHS.

These authors could not conclude the pattern of

inheritance from their data but could not reject the

possibility of an autosomal recessive mode. In one

previous series of 11 patients,2’ one set of twins

with HLHS was found in addition to three other

patients with family members who had congenital

heart defects, including coarctation and cyanotic

congenital heart disease. In our series, two siblings

had HLHS, and three other siblings had congenital

heart defects. The possibility of a rare mode of

autosomal recessive inheritance of HLHS may exist

in addition to the more common mode of

multifac-tonal inheritance. Additional research will be

re-quired to define the recurrence risks in offspring

and the pattern of inheritance.

Surgical management of HLHS has been

encour-aged because of a “very low rate of associated

ex-tracardiac malformations.”5 In this study,

extracar-diac malformations were present in 1 1 % of the

cohort. However, in previous series, this prevalence

has been consistently greater, occurring in 12%,6

although more commonly it occurs in 24% to 37%

(5)

of the cohort.7’’6’22’23 Natowicz et al’6 tabulated

autopsy findings in 83 children with HLHS for an

1 1-year period, with subsequent review by a

genet-icist; 11% had a chnomosomal abnormality, 5% had

a single-gene abnormality, and an additional 12%

had a major extracardiac anomaly unassociated

with a chromosomal defect. No specific system or

tract was dominant in the prevalence of extracar-diac anomalies.

Several factors are important in determining the

prevalence of extracardiac and genetic anomalies.

These include the proportion of infants with

unre-stnicted autopsies and genetic or cytogenetic

eval-uation, as well as the nature of the cohort under

study. The prevalence of anomalies in children with

HLHS is underestimated in this study as 41% of

the children were not autopsied. The higher

pro-portion of anomalies (28%) in series in which all

children were autopsied’6 may be due in part to a

selection bias; specifically, children with obvious or

suspected extracardiac or genetic anomalies may be

autopsied more often because of either physician or

parental request. However, the true prevalence of

extracardiac malformations in HLHS as

deter-mined by clinical and autopsy studies is probably close to this latter estimate, 28%.

Cardiac defects associated with HLHS include

mitral valve atresia in the minority; mitral valve

hypoplasia or mitral stenosis coincident with the

left heart obstruction of a hypoplastic left ventricle; and aortic atresia, hypoplastic aorta, or coarctation of the aorta. Because of the retrospective nature of this study, we were unable to systematically deter-mine sizes of the mitral and aortic orifices and the

size of the left ventricle from the autopsy notes.

However, with this study as with others, if a large

ventricular septal defect was present, the left

yen-tnicular hypoplasia tended to be milder.5”2 When

considering palliative surgery, it is important to

note that other congenital heart defects, including atnioventniculan canal, double outlet left ventricle,

endocandial fibroelastosis, as well as anomalous

arteries and a secundum atnial septal defect, can

occur coincident with HLHS.

The majority of children with HLHS die during

the first week of life and the greatest risk of dying

occurs on the third day of life. Although long

sur-viva! with HLHS has been reported in a previous

autopsy series, survival past 1 year of age is rare and occurred in only three children in this cohort;

two of these three died before 2 years of age.

Sun-vival often depends on a patent ductus arteniosus

and adequate pulmonary venous return through a

patent foramen ovale or an atrial septal defect. The right to left ductal shunt from the pulmonary artery

to the aorta becomes dependent on sustained

pul-monary vascular resistance and right ventricular

function. Deaths occurring in the first few days are

commonly due to closure or constriction of the

ductus arteniosus with a resultant decrease in

sys-temic perfusion. In healthy term infants, 81% have

ductal closure within the first 72 hours of life.24 In

children with HLHS who have duct-dependent

blood flow, the greatest risk of death, which occurs

on day 3, may be due to the process of ductal

closure. However, with continuation of ductal

shunting, death in infants usually results from

congestive heart failure and poor decompression of

the left atrium, which leads to pulmonary

hyperten-sion and right ventricular failure. In some children,

poor aortic and coronary perfusion results from a

small patent ductus arteriosus and a significant

pressure gradient between the main pulmonary

ar-teny and the aorta. With no ventricular septal defect

and with aortic atresia on mitral valve atresia, the

lack of egress of blood from the left ventricle results in atrophy of the myocardium, fibroelastosis, large

myocardial sinusoids, and vacuolization of the

sub-endocardium.25 Commonly at autopsy, evidence of

generalized systemic underperfusion is seen with

pathologic changes in the liver, pancreas, and

ad-renal glands.

In our study, we were unable to detect any specific

components of the HLHS complex that predicted

survival. This may be due to the lack of

standardi-zation of autopsies in this retrospective series.

Other investigators have noted better survival in

children with mitral stenosis or mitral atresia with

HLHS in the absence of aortic arch disease7 or in

children with a large atrial septal defect or

ventric-ular septal defect; the latter allows better

de-compression of the left ventricle and left atrium

and better mixing of blood in the right ventricle.”

Data from a pediatric cardiology museum indicated

that right ventricular wall thickness predicted

sun-vival as did a large on restrictive interatnial

com-munication, a relatively large ascending aorta,

in-creased left atrial thickness, higher pulmonary

vas-cular resistance, and/or a large patent ductus

arteniosus.8 Good right ventricular function and

some physiologic restriction of pulmonary blood

flow also was essential for longer survival.

Over the course of the 16 years of observation,

from 1971 through 1986, there was no significant

change in survival. Changes in efforts to prolong

life, such as with prostaglandin E1 infusion, had

little effect in this series. While similar to a series

reported by Hastreiter and co-workers,25 the

pres-ent study differs from a report by Moodie et al.26 In

the latter series, 1 1 infants were treated with pros-taglandin E, before palliative surgery. Three of the

children who underwent surgery were found to have

myocardial infarctions that occurred before

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in-982 HYPOPLASTIC LEFT HEART SYNDROME

farcts played a major role in mortality and were

thought to be very possibly due to prostaglandin E,

administered through an umbilical catheter in

chil-dren with HLHS. This does not occur in children

with other congenital heart defects.

Therapeutic options for HLHS are controversial

and offer difficult ethical considerations. The

Nor-wood procedure is the first of two staged surgical

procedures for “correction” of HLHS.5’27 Pigott and

colleaguestm recently reported a 29% operative

mor-tality and a late mortality of 11% in a cohort of 104

patients, although actuarial analysis of survival was

not performed. This represents a substantial

ad-vance in reduction of operative mortality for the

initial palliation, although it must be noted that the

subsequent Fontan operation has a 36% operative

mortality. Cardiac transplantation as proposed by

Bailey and co-workers2’3 offers an uncertain future

to these infants with respect to rejection and

com-plications of immunosuppression. In our cohort, the

first stage of the Norwood procedure was performed

on 20 children. Although their early survival was

prolonged significantly, it is difficult to separate

this from a so-called “survival bias”; this group had

somewhat better survival during the first week of

life as compared with those with no surgical

pallia-tion. No significant predictor of successful

pallia-tion with the Norwood procedure, including right

ventricular wall thickness, right ventricular

short-ening, size of the ascending aorta, distal aortic arch

anatomy, or atnial septal anatomy, has been

iden-tified.29 Early operative deaths have been most

corn-monly associated with inadequate ventilation and

postoperative hemorrhage, and late deaths with

obstruction of the aortic arch.

The options available to families of children with

HLHS present a dilemma. All choices (doing

noth-ing, cardiac transplantation, or Norwood

proce-dure) present high mortality and morbidity. Opting

for no surgery usually guarantees an early demise.

Similarly, the Norwood procedure has a more

van-able but generally high mortality and morbidity.

Cardiac transplantation has limited access, but

even where performed, there is a high mortality

rate among patients awaiting a donor heart.

Re-ports of survival after cardiac transplantation

gen-erally relate a favorable functional state as well as

good growth and development.3 Currently at our

institution, only the first two options are available

(no surgery or the Norwood procedure). With these

difficult choices, we make no specific

recommen-dations to parents but inform them of the

alterna-tives and help them to make the choice with which

they feel the greatest comfort. After making their

decision, the family needs continued support with

the infant’s demise or with after-hospital care.

ACKNOWLEDGMENTS

This study was funded by grants from the National

Institutes of Health (R23 HL36856 and R29 HL39052)

and from the March of Dimes and the American Heart

Association, Oregon Affiliate.

We dedicate this paper to Tamara A. McAllister, who

provided technical support for this study. Ms McAllister died in 1989, after submission of this manuscript.

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26. Moodie DS, Gill CC, Sterba R, et al. The hypoplastic left

heart syndrome: evidence of preoperative myocardial and hepatic infarction in spite of prostaglandin therapy. Ann

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27. Norwood WI, Lang P, Hansen DD. Physiologic repair of aortic atresia-hypoplastic left heart syndrome. N EngI J

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PROFITING FROM DISEASE

Beware

muddled

emotions

about

“excessive”

prices

for

drugs.

An AIDS sufferer dies a horrible death, too poor to buy the drug that might

prolong his life. A manufacturer counts handsome

profits

from its sales of an

AIDS treatment, and lectures its critics on the economics ofthe pharmaceuticals

business. There could hardly be a more one-sided battle for public opinion.

Pressure from America’s AIDS lobby has helped to force Britain’s Weilcome to

cut the price of its AZT treatment from $10,000 to $3,000 per patient per year

since the drug was launched in 1987. This has alerted Congress to larger

possibilities, and a campaign is now on to curb the “excessive” profits earned

by the drugs industry as a whole. Sadly, if this campaign succeeds, the biggest

losers may be the very people in whose name it is being waged...

Despite the failings of the global drugs market, competition. . .is the best way

to bring new, cheap drugs into existence. But street marchers and populist

congressmen should remember that competition cannot work without profit.

Around 150 anti-AIDS drugs have been investigated. Many ofthem have already

turned out to be ineffective or toxic; more will be rejected in due course. If

companies are to risk the losses that such abortive quests entail, they must be

allowed to make money-and in amounts that seem large by the standards of

less risky businesses-when they get it right.

Profiting from disease. The Economist. January 27, 1990:17-18.

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1990;85;977

Pediatrics

Cynthia D. Morris, Jacquelyn Outcalt and Victor D. Menashe

Population