Intrauterine Growth as Estimated From Liveborn Birth-Weight Data at 24 to 42

Weeks of Gestation , by Lula O. Lubchenco et al,Pediatrics, 1963;32:793800

Frank R. Greer
Pediatrics 1998;102;237

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 1998 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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Present Significance

When diagnosed in the neonatal period and

treated adequately, infants homozygous for mutations at the PAH locus grow up with near normal
cognitive function. However, evaluation of the first
generation of patients with PKU to reach adulthood
reveals the need for improvement in screening, treatment, and follow up; corresponding new guidelines
have appeared.8 Meanwhile it has become apparent
that all hyperphenylalaninemia is not classic phenylketonuria; a small fraction of patients have disorders of tetrahydrobiopterin synthesis or recycling
that require additional diagnostic procedures in the
screening program and specific forms of treatment
for affected patients.9 It also has been recognized that
maternal hyperphenylalaninemia10 puts the fetus at
risk for microcephaly, impaired cognitive development, and congenital anomalies, all of which can be
avoided by careful treatment, preconception and intrapartum, of the mother. The expanding circles of
awareness about these new problems are additional legacies of the Guthrie test.
In November 1990, investigators from around the
world convened in Paris, France, to discuss some of
the emerging issues in PKU. Mutation analysis had
become feasible, thanks to the availability and generous distribution by the Houston group of a probe
hybridizing to the PAH gene.11 It would become
apparent that many mutations had occurred at the
human PAH locus, that some were prevalent and
most were rare, and that they were distributed nonrandomly in human populations according to political, ethnic, and geographic identity. A consortium
was formed in 1991 (it now comprises 88 investigators in 28 countries), and a PAH gene mutation
database was established. PAHdb (http://www.
mcgill.ca/pahdb) has since become a prototype for
locus-specific mutation databases,12 linked to the corresponding entry in the online version of McKusicks
catalogs of Mendelian Inheritance in Man (OMIM

261600). PAHdb contains records (on December 31,

1997) of more than 340 different mutations by state,
accompanied by a vast array of descriptors of those
mutations. PAHdb illustrates what is happening at
the interface between genomics (which is producing
results in the Human Genome Project), genetics
(which is the study of human genetic variation), and
medical genetics (where the associated diseases are
addressed). Together, a remarkable legacy of concepts, data, and techniques has descended from the
test developed by Guthrie and Susi, described in
Pediatrics in 1963.
REFERENCES
1. Penrose LS. Phenylketonuria. A problem in eugenics. Lancet. 1946;1:
949 953
2. Bickel H, Gerrard J, Hickman EM. Influence of phenylalanine intake on
the chemistry and behaviour of a phenylketonuric child. Acta Paediatr.
1954;43:64 77
3. Woolf LI, Griffiths R, Moncrieff A. Treatment of phenylketonuria with
a diet low in phenylalanine. Br Med J. 1955;1:57 64
4. Armstrong MD, Tyler FH. Studies on phenylketonuria. I. Restriction of
phenylalanine intake in phenylketonuria. J Clin Invest. 1955;34:565580
5. Scriver CR, Rosenberg LE. Amino Acid Metabolism and Its Disorders.
Philadelphia, PA: WB Saunders Co; 1973:104 107
6. National Academy of Sciences. Committee for the Study of Inborn
Errors of Metabolism, Division of Medical Sciences, Assembly of Life
Sciences. Genetic Screening. Programs, Principles and Research. Washington, DC: National Academy of Sciences; 1975
7. Institute of Medicine. In: Andrews LB, Fullarton JE, Holtzman NA,
Motulsky AG, eds. Assessing Genetic Risks. Implications for Health and
Social Policy. Washington, DC: National Academy Press; 1994
8. Medical Research Council Working Party on Phenylketonuria. Recommendations on the dietary management of phenylketonuria. Arch Dis
Child. 1993;68:426 427
9. Blau N, Thony B, Heizmann CW, Dhondt JA. Tetrahydrobiopterin
deficiency: from phenotype to genotype. Pteridines. 1993;4:110
10. Lenke RR, Levy HL. Maternal phenylketonuria and hyperphenylalaninemia. An international survey of untreated and treated pregnancies.
N Engl J Med. 1980;303:12021208
11. Woo SLC, Lidsky AS, Guttler F, Chandra T, Robson KJH. Cloned
human phenylalanine hydroxylase gene allows prenatal diagnosis and
carrier detection of classical phenylketonuria. Nature. 1983;306:151155
12. Nowacki P, Byck S, Prevost L, Scriver CR. The PAH Mutation Analysis
Consortium database: update 1996. Nucl Acids Res. 1997;25:139 142

COMMENTARY
Intrauterine Growth as Estimated From Liveborn Birth-Weight Data at 24
to 42 Weeks of Gestation, by Lula O. Lubchenco et al, Pediatrics,
1963;32:793 800
Comments by Frank R. Greer, MD
ABSTRACT OF ORIGINAL ARTICLE. Data on the
birth weights of 5,635 live-born Caucasian infants at 24 to
From the Department of Pediatrics, University of Wisconsin, Madison,
Wisconsin.
Received for publication Mar 19, 1998; accepted Mar 19, 1998.
Address correspondence to: Frank R. Greer, MD, Wisconsin Perinatal Center, Meriter Hospital, 202 S Park St, Madison, WI 53715.
PEDIATRICS (ISSN 0031 4005). Copyright 1998 by the American Academy of Pediatrics.

42 weeks gestation are presented. All infants were born

from July 1948 to January 1961. Data from infants born at
greater than 36 weeks gestation after 1955 are excluded
because of the large number of infants. The socioeconomic stratum represented by this population is defined
as medically indigent or part-pay. The median weights of
Colorado babies (3230 g) were found to be lower at 40
weeks gestation that the national median (3340 g).
Weight curves in the form of percentiles are generated
from the data. These curves can be used as standards for

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237

Fig 1. The weights of liveborn Caucasian infants at gestational ages from 24

to 42 weeks are graphed as percentiles.

determining the adequacy of weight gain of individual

infants which may be done either at the time of birth, or
after birth in relation to extrauterine environmental factors.
COMMENTARY

he work described in this landmark publication by Lubchenco and colleagues is still

used by every practitioner caring for newborn infants even today.1 For those of us who
began our pediatric training after 1970, the Lubchenco growth curves, supplied in a convenient
tablet form to most newborn nurseries by a US
formula manufacturer, were a part of every newborn infant work-up. Most of us took these for
granted and paid scant attention to the previous
generation of newborn infant care providers who
spoke of the days when the definition of a premature infant was any newborn with a birth weight
,2500 g. This definition was recommended by
both the American Academy of Pediatrics and the
World Health Assembly.2,3 Todays use of serial
perinatal ultrasound dating of the fetus makes
these good old days seem even more remote.
Pediatricians attend deliveries with little suspense
concerning the questions of gestational age and
fetal growth. Yet it was this article that pointed out
the importance of fetal growth and its potential
relationship to both the immediate well-being and
the long-range outcome of the newborn. It made
possible a more precise definition of prematurity
and the widespread adoption of the terms small
for gestational age, large for gestational age,
intrauterine growth retardation, and fetal dys-

238

maturity. It also established the basis for screening

infants with birth weights greater than the 90th
percentile or less than the 10th percentile for potential medical problems.
To be sure, the Lubchenco curves (see Fig 1)
were established in the mile-high city of Denver,
CO, and subsequently, it was shown that these
curves overestimated the number of infants greater
than the 90th percentile (and underestimated those
less than the 10th percentile) in cities at lower
altitudes, which included most of the United
States. The study also was criticized for including
only a relatively indigent population. However,
other growth curves quickly followed, most notably those of Babson4 and Usher.5 The Denver population included a large Hispanic population that
accounted for 30% of the births, but the authors
noted that there were no differences in birth
weights between Hispanic and other Caucasian
infants. Of note, the database excluded infants of
Negro, Oriental, and Indian ethnicity. Finally,
the growth curves did include twin deliveries,
even though the authors pointed out that after 34
weeks gestation, twins fell from the 50% to the
15% by 42 weeks gestation. They also described
separate curves for males and females, although
the ;100 g weight difference between sexes was
small enough that a combined curve for both sexes
generally was adopted in the United States.
Just 2 years earlier, Joseph Warkany and colleagues6 had pointed out in a lengthy publication
that intrauterine growth retardation was a syndrome of sorts, with significant effects on long-

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term outcome. According to Warkany: The unsatisfactoriness of our knowledge in this area is due,
to a great extent, to the false label attached to these
children, whose records are pooled with those of
the prematures. The lack of separation of the 2
types of children underweight at birth has led to a
neglect of observations and recordings necessary
for a better knowledge of this field. Indeed a
study in 1965 showed that there were as many
term as preterm infants born weighing ,2500 g in
the United States, and that the majority of preterm
infants were actually born with a birth weight
of .2500 g.7 Building on these reports and the
Lubchenco fetal growth curves, Battaglia and
Lubchenco8 then proposed the well known classification system of large for gestational age, small
for gestational age, and appropriate for gestational
age for determining at-risk infants for various
medical problems, initially focusing on increased
mortality rate8 and hypoglycemia.9 Usher10 and
Farr11,12 went on to begin the description of the
physical characteristics differentiating premature
and small for gestational age infants that also remain in wide use today.
After 35 years, the observations made by Lub-

chenco remain a keystone in the practice of neonatology. This work is truly a landmark in its field.
REFERENCES
1. Lubchenco LO, Hansman C, Dressler M, Boyd E. Intrauterine growth as
estimated from liveborn birth-weigh data at 24 to 42 weeks of gestation.
Pediatrics. 1963;32:793 800
2. Parmelee AH. Management of the Newborn. Chicago, IL: The Year Book
Publishers, Inc; 1952;135
3. Silverman WA. Dunhams Premature Infants. 3rd ed. New York, NY: Paul
B. Hoeber; 1961:1
4. Babson SG, Behrman RE, Lessel R. Fetal growth: Liveborn birth weights for
gestational age of white middle-class infants. Pediatrics. 1970;45:937944
5. Usher R, McLean F. Intrauterine growth of live born Caucasian infants
at sea level: standards obtained from measurements of infants born
between 25 and 44 weeks of gestation. J Pediatr. 1969;74:901910
6. Warkany J, Monroe BB, Sutherland BS. Intrauterine growth retardation.
Am J Dis Child. 1961;102:249 279
7. Jerushalmy J, van de Berg BJ, Erhardt CL, Jacobziner H. Birth weight
and gestation as indices of immaturity. Am J Dis Child. 1965;109:4357
8. Battaglia FC, Lubchenco LO. A practical classification of newborn infants by weight and gestational age. J Pediatr. 1967;71:159 163
9. Lubchenco LO, Bard H. Incidence of hypoglycemia in newborn infants
classified by birth weight and gestational age. Pediatrics. 1971;47:831838
10. Usher R. Judgement of fetal age. II. Clinical significance of gestational
age and an objective method for its assessment. Pediatr Clin N Am.
1966;13:835 848
11. Farr V. The value of some external characteristics in the assessment of
gestational age at birth. Dev Med Child Neurol. 1966;8:657 660
12. Farr V. The definition of some external characteristics used in the
assessment of gestational age in the newborn. Dev Med Child Neurol.
1966;8:507511

COMMENTARY
Reactions to the Threatened Loss of a Child: A Vulnerable Child Syndrome,
by Morris Green, MD, and Albert A. Solnit, MD, Pediatrics, 1964;34:58 66
Comments by Jack P. Shonkoff, MD
ABSTRACT OF ORIGINAL ARTICLE. This report describes a constellation of clinical features found in 25
children with a history of an illness or accident from
which they recovered, despite their parents anticipation
of a fatal outcome. The paper proposes the hypothesis
that children who are expected by their parents to die
prematurely often react with a disturbance in psychosocial development that is rooted in the parent-child relationship, which the authors characterize as a vulnerable
child syndrome. The essential features of the proposed
syndrome include difficulty with separation, infantile
behavior, bodily overconcerns, and school underachievement. The paper provides an overview of predisposing
factors and determinants of the presenting symptoms,

From the Heller Graduate School, Brandeis University, Waltham, Massachusetts.

Received for publication Mar 19, 1998; accepted Mar 19, 1998.
Address correspondence to: Jack P. Shonkoff, MD, Heller Graduate School,
Brandeis University, Box 9110, Mailstop 035, Waltham, MA 02254-9110.
PEDIATRICS (ISSN 0031 4005). Copyright 1998 by the American Academy of Pediatrics.

along with suggestions for both clinical management and

primary prevention.
COMMENTARY

his classic paper by Green and Solnit illustrates

the essence of the behavioral developmental
dimension of clinical pediatrics. Its brilliance is
reflected in both its seminal creativity and its enduring salience over more than 3 decades. Its relevance
for the practicing pediatrician remains vital to this
day, and its message is particularly compelling in
view of the challenges facing our highly dynamic
health care system. Its implications for the academic
community are similarly worthy of serious reflection.
The core contribution of this paper is the extent to
which it provides a rich conceptual framework for
the assessment and management of a cluster of
bread and butter clinical concerns that permeate
the worlds of primary and tertiary care pediatrics.
The symptomatology that captured the attention of

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239

Intrauterine Growth as Estimated From Liveborn Birth-Weight Data at 24 to 42

Weeks of Gestation , by Lula O. Lubchenco et al,Pediatrics, 1963;32:793800
Frank R. Greer
Pediatrics 1998;102;237
Updated Information &
Services

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1/237.full.html

References

This article cites 10 articles, 3 of which can be accessed free

at:
http://pediatrics.aappublications.org/content/102/Supplement_
1/237.full.html#ref-list-1

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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned, published, and
trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk Grove
Village, Illinois, 60007. Copyright 1998 by the American Academy of Pediatrics. All rights
reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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