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Issues

in State

Newborn

Screening

Programs

These are heady times for newborn screening.

Ar-tides in the medical literature and speakers at grand rounds urge us to test babies for disorders, including cystic fibrosis,’ biotinidase deficiency,2 and

medium-chain acyl coenzyme A dehydrogenase deficiency.3

States are expanding the batteries of tests they

per-form. My own state of Tennessee just began testing

neonates for galactosemia this year. And this is no

doubt just the beginning. New techniques are being

developed that will make it possible to look for a host of genetic characteristics using microscopic amounts

of blood. We soon may be able to discern many

conditions and characteristics of our children.

These developments, as exciting as they are, also

raise numerous concerns. Some of the problems can

be viewed as technical, such as determining how to

ensure that usable samples are obtained for all

appro-priate newborns, and that tests are performed and

interpreted correctly. These issues were addressed in

great detail earlier this year by the American Academy of Pediatrics’ Committee on Genetics, in its statement

focused on screening for phenylketonuria (PKU),

con-genital hypothyroidism, and sickle cell anemia.4 The

Committee was particularly careful to remind

pedia-tricians that these are screening and not diagnostic tests. As such, they are not foolproof, and pediatri-cians should not be inappropriately reassured by nor-mal screening test results when symptomatic children appear in their practices.

The Committee on Genetics’ new statement is the

best source available on many of the practical

prob-lems that arise in newborn screening and points out

many ways in which pediatricians can help to make

these programs more effective. The statement can

also serve as a jumping-off point for a discussion of

the social, ethical, and legal implications of these

programs, topics that were beyond the scope of the

Committee’s project. These issues have recently

ree-merged as subjects of thoughtful analysis. A group of

scientists, lawyers, and policymakers from around the

world met to discuss the subject a few years ago and

issued a series of recommendations.5 Neil Holtzman

offered a more critical view of these practices in an

editorial last year.6 Yet we need to take an even

broader approach to newborn screening. While

screening is performed throughout medicine,

espe-cially in pediatrics, the facts that newborn screening is uniquely a function of the state and that its results

can affect children and parents in a variety of ways

raise special concerns about how states make

deci-sions to adopt new tests. The power of the new

genetics to delineate much more clearly the genetic

contributions to dysfunction adds urgency to this

Received for publication Mar 23, 1992; accepted May 20, 1992.

Reprint requests to (E.W.C.) I)ivision of General Pediatrics, Suite 3963, The vanderbilt Clinic, Nashville, TN 37232-5577.

PEDIATRICS (ISSN 0031 4005). Copyright © 1992 by the American

Acad-emy of Pediatrics.

inquiry. The information that will be made available

by these emerging technologies has implications not

only for therapeutic intervention but also for broader social issues, such as insurance coverage and privacy. These consequences are not hypothetical; instead they directly affect children and their families.

IMPACT ON CHILDREN

When we look at the effects of newborn screening

on children, it is easiest to focus on the undeniable

benefits that newborns with diseases such as PKU

and congenital hypothyroidism can receive from early

detection and treatment.7’8 Yet newborn screening

also entails substantial costs, some of which are

in-herent in the screening process.9 All abnormal test

results trigger diagnostic and sometimes therapeutic

cascades with their economic costs, anxiety, and

ia-trogenic side effects. In addition, when screening tests

are designed to avoid missing individuals affected by

relatively uncommon disorders, the tests almost

al-ways generate a significant number of false-positive results. In newborn screening, many states report that

between 1% and 3% of newborns receive

false-posi-tive results, and in some states the rate is even

higher.’#{176} In New Jersey, for example, for every

neo-nate who is found to have PKU, 20 others are false

positives on their initial screen. False positives may be particularly costly in the setting of newborn screen-ing.” Newborns who receive results that inaccurately

suggest the presence of disease not only undergo

further testing, with its risks and costs, but there is

also a growing body of evidence to suggest that

identifying a child as ill in the newborn period, even if incorrectly and only for a brief time, can have

long-term effects on the parent-child relationship and on

the child’s subsequent psychological development.’2

‘5 These costs rarely receive the same sort of consid-eration that is given to the benefits of screening for affected babies, and there has been very little research

directed either at assessing the extent of these

Se-quelae or at ameliorating these problems.

There are two reasons why this systematic neglect

of many of the costs of screening for children is

increasingly problematic. First, efforts to increase de-tection of children who are truly positive for PKU and

congenital hypothyroidism by increasing the number

of children tested and by modifying cutoff levels to

ensure that no false negatives occur inevitably result

in labeling even more children as false positives.

Second, there is tremendous pressure to expand the

number of conditions sought in newborn screening

batteries. The Committee on Genetics, in its recent

statement,4 acknowledges this trend but could be read

as sending mixed messages. In this statement, the

Committee points out that some of the proposed

screening programs are discussed in its 1989

“New-born Screening Fact Sheets”6 but quickly says that

these new programs are beyond the scope of its

present statement. Later, however, the Committee

mentions that some states screen for galactosemia,

maple syrup urine disease, and congenital adrenal

hyperplasia, diseases that are “potentially

life-threat-ening in the immediate neonatal period.4’347 The

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symptoms of these disorders that may appear before the test results come back and points out the impor-tance of early referral to regional treatment centers.

Since children with these disorders become

sympto-matic so early, the Committee might have concluded

that newborn screening is not the optimal way to

detect these affected children. The absence of such a

statement may reflect a judgment that newborn

screening for these conditions can be justified as a

fail-safe mechanism for lapses in clinical and parental vigilance.

It is important, however, that we not add more and

more tests whenever it is asserted that early detection

would help affected children. We should address

head-on the propriety of expanded screening, taking

into account all the benefits and costs. For the poten-tially life-threatening disorders discussed by the Corn-mittee, the real issue is whether there is sufficient benefit to early detection. Screening for congenital adrenal hyperplasia seems to pass this test.’7 By

con-trast, the President’s Commission almost 10 years ago

pointed out the difficult ethical problems posed by

early detection of maple syrup urine disease because,

in its view, the best that could be achieved by very

costly treatment was preservation of affected

chil-dren’s lives for a “few, very burdened years.”8

0th-ers, however, contend that the prognosis for some

children with maple syrup disease can be improved

by early diagnosis.’9

Even more troubling is the pressure to screen for

serious disorders for which early detection confers

little, questionable, or no benefit to the child or for which there are insufficient data. In some instances, both in the United States and abroad, the technolog-ical imperative has prevailed. Colorado has mandated screening newborns for cystic fibrosis”#{176} even though there is no consensus that detection in the neonatal

period improves long-term outcome.6’2024 Even more

striking, a number of countries screen newborn boys

for Duchenne muscular dystrophy, a lethal disorder

for which there is no truly effective treatment.2527

Several writers have suggested that these programs

are beneficial to affected children because diagnosis

in the newborn period avoids the parental anxiety

that otherwise may result when there is a delay

between the child’s onset of symptoms and

diagno-sis.28-29 No one has determined, however, whether

the benefits to the child of avoiding parental

uncer-tainty exceed the impact on the child’s bonding with

the parents when serious disease is diagnosed in the

newborn period. Some have also argued that it is

particularly appropriate to screen for serious disorders

for which there is little or no treatment because the

detection of one child enables the parents to avoid

having other affected children.29 It is difficult to see, however, how the first child is made better off by the parents’ altered procreation.

At the other end of the spectrum, some provinces

in Canada screen newborns for a number of disorders that are not associated with substantial morbidity, such as histidinemia, Hartnup disease, and dicarbox-ylic aminoaciduria.’#{176}’3#{176} Melancon admits that many

of these parents were worried when they were

in-formed of their children’s diagnoses, but he praises

these programs, defending “our right to search and

know . . .“ and arguing that the greater understanding

of the natural history of these metabolic

derange-ments is beneficial for “the scientific community and society.”3#{176} These benefits hardly seem worth the price to the families. And there are frequent calls to screen for new disorders, often before there is sufficient

evidence that early detection improves the outcome

of affected children. To name just a few, some

com-mentators have advocated screening for

medium-chain acyl coenzyme A dehydrogenase deficiency,

citing evidence that this disorder may be associated

with sudden infant death, while others suggest that

more needs to be known about this disorder.3’3133

Even more dramatically, an article in the New York

Times last year suggested that newborns should be

tested for long QT syndrome when the linkage of the

gene responsible for the disorder had first been

re-ported only a few days earlier.34’35 We can only

antic-ipate that there will be more and more pressure to

test newborns as the new genetic technologies make

it possible to look for more conditions using smaller

and smaller amounts of blood. If we accept the

invi-tation to test newborns for more and more conditions,

there will be more and more parents who receive

false-positive test results about the children, the

psy-chological and economic cost of which will loom

particularly large when the benefits of early detection of affected children are not clear.

The potential adverse impact of expanded testing

on children is exacerbated by the fact that early

diagnosis does not necessarily mean that the child

will be provided or have access to treatment. Few

legislatures have enacted programs to provide the

special dietary supplements needed for children with

metabolic disorders.3638 Even parents with traditional health insurance often find that their children’s

treat-ment is not covered, since few state leislatures

re-quire insurers to provide such coverage.3 “ Although

many states ultimately provide some assistance,’#{176} these efforts do not always fill in the gaps. As a result,

children often fall through the cracks, and many

parents tell stories about the difficulties they face in

obtaining care for their children. As a result, the

premise on which newborn screening is based, that

the early diagnosis of disease will lead to a better

outcome, is not always fulfilled because of gaps in

access to treatment that arise from geographic, social, and economic factors.

Yet another problem posed for children by

new-born screening is that it will soon be possible to

identify individuals from their heel-stick blood spots

using analytic techniques that are currently being

developed. DNA fingerprinting, which is increasingly gaining acceptance in the area of forensics, is only a

crude forebear of what is to come.42 These new

tech-niques obviously can be applied to blood samples no

matter how obtained, but since newborn screening is

done on virtually all babies born in this country and

the samples are obtained by the state, particular pri-vacy concerns are at issue and have not been totally

resolved. The possibility of state-run DNA banks

means that we must consider such practical issues as

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a specified period of time, who else can have access

to these cards, and whether the state should or must

go back and test old samples when new tests become

available43’44 as well as more fundamental problems such as defining the extent to which individuals have the right not to be identified by the state.

The role of parents in deciding about this type of

testing is by no means clear even though, in our

country, parents are typically viewed as the primary

guardians of their children’s health. As such, one

would suppose as an initial proposition that they

should be the ones to decide whether their children

should be screened. In fact, there is little consensus about the appropriate role of parents in the

decision-making process. Even though the Committee on

Screening for Inborn Errors of Metabolism working

under the direction of the National Academy of

Sci-ences said in 1975 that parents should be allowed to

decide whether or not to participate,45 few states

actually require in statutes or regulations that parents

consent to screening.46’47 Some commentators have

argued forcefully that parents should not be allowed

to refuse screening for diseases that would cause

serious and irreversible harm if treatment were not

begun in the newborn period.’8’4849 The Committee

on Genetics’ emphasis on ensuring that samples be

obtained from all children suggests that it, too,

be-lieves that parents have relatively little role to play. Indeed, the reality that newborn screening is almost exclusively a function of the state, a relative rarity in the practice of medicine, implies that legislators and state health officials were convinced early on, perhaps as we shall see below for reasons that are not entirely laudable or valid, that all children should be tested.

Even if seeking consent were not required, parents

at least ought to be informed about what is being

done to their children. As a practical matter, however, even this often does not occur. In many states, parents are given no information at all, and in others, parents

are given a pamphlet to read in the immediate

post-partum period, a time when new parents are

dis-tracted. At most, parents seem to know that their

babies were given a “retardation test.” Thus, current practice demonstrates relatively little respect for

par-ents’ roles as decision makers for and as people who

are particularly interested in their children’s well-being.

IMPACT ON PARENTS

Parents are also affected directly by newborn

screening in a variety of ways. As already mentioned,

an abnormal test result may alter the parent’s

rela-tionship with the child. If the diagnosis is correct, the child’s health care needs can also affect the parent’s

future employment. Parents whose insurance does

provide coverage for therapy at the time that the

condition is diagnosed face “job lock,” the ofttimes

almost insurmountable barrier to changing jobs that

results because the insurance supplied by a new

em-ployer has exclusions or waiting periods for prior

existing conditions. This problem may be addressed

in part by regulations and technical assistance

pro-mulgated under the Americans with Disability Act.50

53 Ultimately, however, there is not likely to be a

complete solution to the dilemma of “job lock” as long

as employer-based health insurance remains the norm

in this country.

To this point, the effects on parents are simply

those that accompany the diagnosis of any serious

illness in a child. Newborn screening, however, has

even broader implications than most other diagnostic

procedures because so many of the disorders that are

sought are genetic in origin. Finding an affected child

almost always implies either that the parents have an

increased chance of having more affected children in

future pregnancies or that there has been nonpatern-ity.

Although it is commonly said that all genetic

infor-mation revealed by newborn screening should be

provided to parents,4 this does not always happen,

often because the responsible state agencies have

inadequate resources.54’55 The appropriate response

to the reality that many parents are not counseled

depends on the reasons why parents are being told.

If allowing parents the opportunity to make more

informed reproductive decisions is the goal, then

more resources should be devoted to finding parents

whenever newborn screening reveals them to be at

increased risk of having a child with a significant

genetic disorder in the future and then permitting

these parents to decide for themselves whether or not

they want this information. While many will elect to

learn about the implications of their particular genetic traits, others will want to refuse this information. Both choices must be respected if procreative

auton-omy is to be protected. Some people do not believe

that it is appropriate to take steps, whether they be

prenatal diagnosis and selective abortion or the use

of donated eggs or sperm, to avoid having a child

with genetic disease.5 Others have come to see the

state as punitive toward their having children and so

view the offer of genetic counseling as yet another

intrusion.58 Still others worry that their health insur-ance may be affected if they are both carriers for the same deleterious genetic trait. There is already

evi-dence that the last of these fears is not totally

un-founded,59 although a survey of insurers soon to be

released by the Office of Technology Assessment

should provide more insight into the extent to which this fear is realistic. Despite the likelihood that some

people will refuse to learn about their chances of

having a child with a genetic disorder in future

preg-nancies, the decision about whether or not to be

informed is one that should be made by the

individ-uals at risk and not foreclosed by the state’s failure to present the choice.

A different course of action may be required,

how-ever, if the goal is something more than enhancing

autonomy in matters of procreation. Some state

offi-cials view deterring the birth of future affected

chil-dren as a proper goal of the genetic counseling that

accompanies newborn screening.6#{176} On a much

broader scale, a growing number of people are talking

about “responsible” childbearing, the idea that it is

somehow wrong to have a child with a genetic

dis-order or birth defect if the birth could have been

avoided.61’62 If these goals are given any credence,

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less freedom to refuse genetic information or perhaps less choice about having children than is permitted

now. Thus, it is critical that we reexamine what has

been termed the “benefit beyond the target” and ask

again whether the state has any legitimate interest in influencing couples’ decisions about procreation.54

ROLE OF THE STATE

We should consider again the truly remarkable

nature of the state’s involvement. Newborn screening is the only test that the state offers to, and for the

most part requires from, all its citizens. It is now

generally acknowledged that the primary impetus for

state involvement was political advocacy by the

de-veloper of the initial test for PKU and by groups of

parents of retarded children who believed that

phy-sicians were not adopting the test quickly

enough.45’63’64 The establishment of state-run

new-born screening was supported by the perception that

early diagnosis of metabolic disease would actually

cost the state less in the long run. By contrast, physi-cian acceptance and the availability of third-party

reimbursement ordinarily determine the

incorpora-tion of new diagnostic tests and therapy into practice. While there are many reasons to criticize the propriety

of relying on physicians and insurers to determine

the diffusion of new technology, one still needs to

look carefully at a case such as this one, where the

decision-making process is so different from that

nor-mally observed in medicine. It also appears to be

more difficult to undo the inappropriate adoption of

new tests in a state-run system. The history of medi-cine is replete with instances in which new diagnostic

and therapeutic modalities became widely used, only

later to be rejected when their lack of efficacy or even

harmfulness became clear. By contrast, there is only

one instance in which a legislature initially required

testing for a certain disorder and later deleted that

provision from its statute.65’66 With all these

difficul-ties, it is striking is that we simply do not know

whether the decisions that are made about newborn

screening in a political/administrative system and the potential ability of state-run programs to ensure more uniform testing and follow-up actually lead to better

results for children than would occur were newborn

screening simply another aspect of routine medical

practice. If the answer is no, then it is difficult to justify treating newborn screening so differently from other aspects of medicine.

In the short term we do need to improve our present

newborn screening programs to avoid as many errors

as possible in obtaining and processing samples and

in interpreting results. We cannot be content,

how-ever, simply with fixing technical problems. There is

growing pressure to screen newborns for more and

more conditions, and in many instances, the tests

seem particularly attractive because they cost only a

few cents per child to perform. If we are to respond

appropriately to this technological imperative, we

must reexamine the goals of these programs and the

premises that underlie them, pay attention to all the

costs of screening for both children and adults as well as the benefits, and ask again about the appropriate

roles of the state and parents as well as physicians in this process.

Taking this broader view, I suggest the following: #{149}Newborn screening is appropriate only when the

benefits to affected children of early diagnosis are

significant in relation to the costs of testing as well as the costs that will be incurred by children who receive false-positive test results. This balance weighs more heavily in favor of screening when the state ensures that all children with the disorders sought will receive appropriate treatment, especially when there is little

or no out-of-pocket cost to the parents. Screening is

not appropriate when affected children can derive no

substantial benefit from early detection.

#{149}Allnewborn screening programs should be

eval-uated on a regular basis, preferably by a body

inde-pendent of the laboratory that is performing the

testing. The evaluation should assess not only such

technical matters as the sensitivity and specificity of testing but also such issues as whether early detection of affected children actually improves their long-term prognosis and the effect of false-positive test results on children and their families. It is particularly

im-portant that no new tests be incorporated into

new-born screening programs without pilot testing and a

similar evaluation. The importance of ongoing

eval-uation and reassessment means that statutory

schemes in which legislatures define which disorders

are to be sought in newborns may be unduly rigid.

#{149}Onceit has been determined which diseases are

the appropriate targets of screening, parents are

en-titled to know what their children are being tested for

and to decide whether or not their children should be

screened. Information found in the course of newborn screening that may be relevant to future procreation

by the parents must be offered to them. In most

jurisdictions, the physician who diagnoses a genetic disorder in a child and does not tell the parents about

their chance of having another child with the same

disease may well face a successful lawsuit if the

parents later have another affected child.6769 The

state should be no different. At the same time, parents

should be informed about the reasons why they might

not want genetic counseling, and their decisions about

whether to receive counseling about procreation must

be respected.

Adherence to these principles will ensure that

chil-dren receive appropriate screening and that parents

receive information that maximizes their autonomy

in matters of procreation. It will also resolve the

problems posed by the extraordinary role of the state

in newborn screening and make clear the roles of

physicians and the state.

ACKNOWLEDGMENTS

Dr Clayton is a Charles E. Culpeper Foundation Scholar in

Medical Humanities.

1 thankJay Clayton, Gerald B. Hickson, MD, and John A. Phillips

Ill, MD, for their insightful comments on earlier drafts.

ELLEN WRIGHT CLAYTON, MD, JD

Division of General Pediatrics

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54. Crover R, Newman 5, Wethers D, Anyane-Yeboa K, Pass K. Newborn

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Steroids,

Chronic

Lung

Disease,

and

Retinopathy

of Prematurity

ABBREVIATIONS. CLD, chronic lung disease; ROP, retinopathy

of prematurity; BPD, bronchopulmonary dysplasia.

This issue of Pediatrics contains two conflicting, retrospective observational studies concerning the

re-lation between steroid therapy for chronic lung

dis-ease (CLD) and the need for cryotherapy for severe

retinopathy of prematurity (ROP). Batton et al’ noted

that more infants treated with dexamethasone for

CLD needed cryotherapy for ROP, whereas Sobel

and Philip2 found that steroid therapy for CLD did

not affect the number of infants who needed

cryo-therapy for ROP. In fact, Sobel and Philip suggest

that prolonged (>24 days) treatment with steroids

may actually reduce the likelihood that ROP will

reach “thresholdS criteria for cryotherapy. Are these reports really contradictory? Does steroid therapy for

CLD influence the development of severe ROP and

affect an infant’s need for cryotherapy? Will steroid

therapy for CLD risk exchanging one complication

for another?

Chronic lung disease, also referred to as broncho-pulmonary dysplasia (BPD), is a chronic respiratory disease of infants that is characterized by the persist-ence of clinical features of respiratory distress and a

need for supplemental inspiratory oxygen beyond the

first month of life, in conjunction with an abnormal

chest radiograph.3 Chronic lung disease is a major

cause of mortality and long-term morbidity in infants.

It most commonly occurs in very low birth weight

infants, especially in those with birth weights

10OO

g, following treatment for respiratory distress

syn-drome; these are the same infants at greatest risk of

developing severe ROP and of requiring cryotherapy. Since the mid-1970s, anecdotal reports of

cortico-steroid therapy have appeared which claim that

ste-roids are beneficial in the treatment of CLD, reducing the need for ventilatory assistance and supplemental inspiratory oxyen.3’4 During recent years several con-trolled trials5’ evaluating the effect of

dexametha-sone therapy on infants with CLD have been

per-formed. In addition, steroids have been evaluated as

an interdictive 52 for infants who were

considered to be at high risk of developing CLD. In

those studies, dexamethasone had been initiated

be-tween 2 and 4 weeks of age in ventilatory- and/or

oxygen-dependent infants with abnormal chest

radio-PEDIATRICS (ISSN 0031 4005). Copyright © 1992 by the American

Acad-emy of Pediatrics.

graphs, and the hypothesis of whether steroid therapy

altered the progression toward CLD by facilitating

extubation and reducing the need for supplemental

inspiratory oxygen was tested. Even though the

din-ical trials5’2 are not similar enough to permit a meta-analysis,3 the majority of them indicate a beneficMl effect of corticosteroid therapy in CLD; specifically,

dexamethasone therapy facilitates weaning from

pos-itive pressure mechanical ventilation and extubation.

Although concerns about complications such as

sep-sis, hypertension, and suppression of the hypothal-amic-pituitary-adrenal axis persist, currently available data suggest that the risk of infection is not increased and that hypertension and adrenocortical suppression

are self-limited.3 Furthermore, while questions such

as who should be treated with steroids for CLD, when should treatment be started, what is the best

thera-peutic regimen, and how long should treatment be

continued remain to be resolved, the potential

bene-fits of steroid therapy for CLD have appeared to

outweigh the risks. However, as steroid use for CLD

becomes more widespread, clinicians must remain

vigilant for the development of adverse events.

Batton et al’ should therefore be commended for

their vigilance and for searching for factors that might explain why the percentage of their neonatal intensive

care unit’s inborn survivors with gestational ages

between 23 and 26 weeks who required cryotherapy

for severe ROP had increased yearly between 1988

and 1990. Although exposure to dexamethasone

treatment for CLD correlated strongly with the need

for cryotherapy, the report does not demonstrate a

cause-and-effect relationship. Specifically, while in-fants were considered candidates for steroid therapy only if they remained ventilator dependent at 21 days

of age, only 9 of 36 infants requiring mechanical

ventilation beyond 21 days of age were treated with

dexamethasone. Steroid therapy was started at 22 to

70 days of age and was continued for a mean of 38

days (range 32 to 45 days), reflecting the fact that

steroid use for CLD varied according to the attending neonatologist’s preference. Nine of those 36 infants

required cryotherapy; 7 of the 9 were treated with

steroids.

Sobel and Philip2 retrospectively reviewed their

patient data to determine whether the wider use of

dexamethasone in the treatment of infants with CLD

affected the number of infants needing cryotherapy for threshold ROP. Overall, no effect was identified.

Dexamethasone was supposedly only used in infants

with BPD. However, since the indication, dosage, age

at initiation, and length of treatment were at the

discretion of the attending neonatologist, steroid

ther-apy was started between 10 and 68 days of age and

was continued for up to 252 days (mean duration was

47 days in those infants who did not require

cryo-therapy and 16 days in those who did). Twenty-three

of 48 infants with BPD and birth weights <1000 g

were treated with steroids; 6 of those infants required cryotherapy compared with 5 of the 25 non-steroid-treated infants. (In fact, if the 3 infants treated for <5 days are discounted, then only 4 of 20 steroid-treated infants had cryotherapy.) Focusing on the 30 infants

who were also 26 weeks gestational age revealed

that 6 of the 1 6 steroid-treated infants required at Viet Nam:AAP Sponsored on September 1, 2020

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1992;90;641

Pediatrics

ELLEN WRIGHT CLAYTON

Issues in State Newborn Screening Programs

Services

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1992;90;641

Pediatrics

ELLEN WRIGHT CLAYTON

Issues in State Newborn Screening Programs

http://pediatrics.aappublications.org/content/90/4/641

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The online version of this article, along with updated information and services, is located on

American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

References

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