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
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
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,
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
REFERENCES
1. Hammond KB, Abman SH, Sokol RJ, Accurso FJ. Efficacy of statewide
neonatal screening for cystic fibrosis by assay of trypsinogen concentra-tions. N Engi IMed. 1991;325:769-774
2. Wolf B, Heard CS. Screening for biotinidase deficiency in newborns: worldwide experience. Pediatrics. 1990;85:51 2-517
3. Roe C. Sudden Infant Death: New Answers to an Old Problem. Pediatric
Grand Rounds, Vanderbilt University Medical Center, Nashville, TN,
February 4, 1992
4. American Academy of Pediatrics, Committee on Genetics. Issues in
newborn screening. Pediatrics. 1992;89:345-349
5. Knoppers BM, Laberge CM, edo. Genetic Screening: From Newborns to
DNA Typing. New York, NY: Excerpta Medica; 1990
6. Holtzman NA. What drives neonatal screening programs? N Engi IMed.
1991;325:802-804
7. Azen CC, Koch R, Friedman EG, et al. Intellectual development in
12-year old children treated with phenylketonuria. AJDC. 1991;145:35-39
8. New England Congenital Hypothyroidism Collaborative. Elementary
school performance of children with congenital hypothyroidism. J
Pe-diatr. 1990;1 16:27-32
9. Clayton EW. Screening and treatment of newborns. Houston: Lau’ Rev.
1992;29:85- T48
10. Illinois Dept of Public Health. Newborn Screening: An Overview of
Newborn Screening Programs in the United States and Canada. Spring-field, IL: 1990
I I. Annas C. Mandatory PKU screening: the other side of the looking glass. Am JPublic Health. 1982;72:1401-1403
I 2. Fyro K, Bodegard C. Four-year follow-up of psychological reactions to false positive screening tests for congenital hypothyroidism. Acta Pae-diatr Scand. 1987;76:107-114
13. Schild S. Psychological issues in genetic counseling in phenylketonuria.
In: Kessler 5, ed. Genetic Counseling: Psychological Dimensions. New
York, NY: Academic Press; 1979:135-152
14. Thelin T, McNeil TF, Aspegren-Jannson E, Sveger T. Identifying children at high somatic risk: parents’ long-term emotional adjustment to their
children’s alpha I antitrypsin deficiency. Acta Psychiatr Scand.
1985;72:323-330
15. Vetrone P, Leuzza V. Zazzara V, Antonozzi I. Psychological effects on parents of children with early detected phenylketonuria. I Inherited Metab Dis. 1989;12:345-346
16. American Academy of Pediatrics, Coanmittee on Genetics. Newborn
screening fact sheets. Pediatrics. 1989;83:449-464
1 7. Thompson R, Seargeant L, Winter JSD. Screening for congenital adrenal
hyperplasia: Distribution of 1 7a-hydroxyprogesterone concentrations in neonatal blood spot specimens. IPediatr. 1989;1 14:400-404
I 8. President’s Commission for the Study of Ethical Problems in Medicine
and Biomedical and Behavioral Research. Screening and Counseling for
Genetic Covaditions: The Ethical, Social, and Legal Implications of Genetic Screening, Counseling, and Educations Programs. Washington, DC: US Government Printing Office; 1983
19. Kaplan P. Mazur A, Field M, et al. Intellectual outcome in children with maple syrup urine disease. /Pediatr. 1991;1 19:46-50
20. Chatfield 5, Owen C, Ryley HC, et al. Neonatal screening for cystic
fibrosis in Wales and the West Midlands: clinical assessment after five years of screening. Arch Dis Child. 1991;66:29-33
21. Dankert-Roelse JE, teMeerman Ci, Martijn A, tenKate LP, Knol K.
Survival and clinical outcome in patients with cystic fibrosis, with or without neonatal screening. I Pediatr. 1989;114:362-367
22. Karem E, Lynch A. Screening for cystic fibrosis: ethical and social issues.
Am Rev Respir Dis. 1991;143:457-460
23. teMeerman Ci, Dankert-Roelse JE. Pros and cons of neonatal screening for cystic fibrosis. Adv Exp Med. Biol, 1991;290:83-92
24. Wesley AW, Smith PA, Elliott RB. Experience with neonatal screening for cystic fibrosis in New Zealand using measurement of immunoreactive trypsinogen. Aust PaediatrJ. 1989;25:151-155
25. Greenberg CR, Jacobs HK, Halliday W, Wrogemann K. Three years’
experience with neonatal screening for Ducherune/Becker muscular dys-trophy: gene analysis, gene expression, and phenotype prediction. Am I
Med Genet. 1991;39:68-75
26. Plauchu H, Dorche C, Cordier MP, Cuibaud P. Robert JM. Duchenne
muscular dystrophy: neonatal screening and prenatal diagnosis. Lancet.
1989;1:669
27. Worton RC. Does research success in Duchenne-Becker muscular
dys-trophy now warrant neonatal mass screening? The perspective of a
molecular biologist. In: Knoppers BM, Laberge CM, eds. Genetic
Screen-ing: From Newborns to DNA Typing. New York, NY: Excerpta Medica;
1990:197-202
28. Al-Jader LN, Goodchild MC, Ryley HC, Harper PS. Attitudes of parents of cystic fibrosis children towards neonatal screening and antenatal diagnosis. Clin Genet. 1990;38:460-465
29. Firth MA, Wilkinson EJ. Screening the newborn for Duchenne muscular dystrophy: parents’ views. Br Med J.1983;286:1933-1934
30. Melan#{231}on SB. Ethical implications in diagnosis and treatment of non-disease (DIS-) phenotypes issuing from screening programs. In:
Knop-pers BM, Laberge CM, eds. Genetic Screening: From Newborns to DNA
Typing. New York, NY: Excerpta Medica; 1990:33-39
31. Medium chain acyl CoA dehydrogenase deficiency. Lancet.
1991;338:544-545. Editorial
32. Blakemore A, Singleton H, Pollit R, et al. Frequency of the C985 MCAD mutation in the general population. Lancet. 1991;337:298-299
33, Pollit Ri. Disorders of mitochondrial beta-oxidation, prenatal and
post-natal diagnosis and their relevance to Reye’s syndrome and sudden
infant death. JInherited Metab Dis. 1989;12(suppl 1):215-230
34. Angler M. Cenetic marker found for a heart disorder that kills the young.
New York Times. May 14, 1991:C3
35. Keating M, Atkinson D, Dunn C, Timothy K, Vincent CM, Leppert M.
Linkage of a cardiac arrhythmia, the long QT syndrome, and the Harvey ras-1 gene. Science. 199 1 ;252:704-706
36. Alaska Stat §18.15.200; 1990 37. Cal Health & Safety Code 341; 1991
38. Minn Stat Ann §144.128(1); 1990
39. Mass Cen Laws Ann ch 175, §47C, 176A, §88, 176B, §4C; West 1991
40. Mont Rev Code Ann §33-22-131 & 33-31-102; 1990
41. Wash Rev Code Ann §48.20.520, 48.21.300, 48.44.440, & 48.46.510; 1990
42. Office of Technology Assessment. Genetic Witness. Washington, DC: US
Government Printing Office; 1990
43, Andrews LB. Medical Genetics: A Legal Frontier. Chicago, IL: American Bar Foundation; 1987
44, Pelias MZ. Duty to disclose in medical genetics: a legal perspective. Am IMed Genet. 1991;39:347-354
45, Committee on Screening for Inborn Errors of Metabolism. Genetic Screen-ing: Programs, Principles, and Research. Washington, DC: National Acad-emy of Sciences; 1975
46. Md Code Ann 13-102; 1991
47. Wyo Stat §35-4-801(c); 1991
48. Acuff KL, Faden RR. A history of prenatal and newborn screening
programs: lessons for the future. In: Faden RR, Celler C, Powers M,
eds. AIDS, Women, and the Next Generation: Towards a Morally Acceptable Policy for HIV Testing of Pregnant Women and Newborns. New York, NY: Oxford; 1991:59-93
49. Fletcher JC, Wertz DC. Ethics, law, and medical genetics: after the
human genome is mapped. Emory Law 1.1990;39:747-810
50. 42 USCA §12101-12213; West Supp 1991 51. 29 CFR §1630.8; 1991
52. EEOC issues more guidance on new Disabilities Act. US Law Week.
February 4, 1992;60:2478-2479
53. Rothstein MA. Genetic discrimination in employment and the Americans with Disabilities Act. Houston Law Rev. 1992;29:23-84
54. Crover R, Newman 5, Wethers D, Anyane-Yeboa K, Pass K. Newborn
screening for hemoglobinopathies: the benefit beyond the target. Am
Public Health. 1986;76:1236-1237
55. Hurst D. Northern California’s experience. Pediatrics. 1989;83:868-871 56. Kenen RH. A look at prenatal diagnosis within the context of changing
parental and reproductive norms. In: Holmes HB, Hoskins BB, Cross M,
eds. The Custom-Made Child? Women-Centered Perspectives. Clifton, NJ: Humana Press; 1981:67-73
57, Rothman BK. The Tentative Pregvaancy. New York, NY: Penguin; 1987
58. Diaz-Barrios V. New York’s experience. Pediatrics. 1989;83:872-875 59. Lippman A. Prenatal genetic testing and screening: constructing needs
and reinforcing inequities. Am JLaw Med. 1991;17:15-50
60. Cunningham CC. Balancing the individual’s rights to privacy against
the need for information to protect and advance public health. In:
Knoppers BM, Laberge CM, eds. Genetic Screening: From Newborns to
DNA Typing. New York, NY: Excerpta Medica. 1990:205-215
61. Robertson JA. Procreative liberty and the control of conception. preg-nancy, and childbirth. Va Law Rev. 1983;69:405-464
62. Shaw MW. Conditional prospective rights of the fetus. ILeg Med (Chic).
1984;5:63-1 16
64. Reilly PR. Genetics, Law, arid Society. Cambridge. MA: Harvard University Press; 1977
65. 1980 Mass Acts 455, §1
66. 1986 Mass Acts 137, 2
67. Blake v Crux, 108 Idaho 253, 698 P2d 315; 1984
68. Schroeder v Perkel, 87 NJ 53, 432 A2d 834; 1981
69. Becker v Schwartz, 46 NY2d 401, 386 NE2d 807, 413 NYS2d 895; 1976
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