PEDIATRICS
August 2000
EDITORIALS
Vitamin D–deficient rickets: The reemergence of a
once-conquered disease
At the end of the 19th century, rickets
was a major scourge of children in de-
veloped countries; 80% of infants
under the age of 2 years at Infants
Hospital in Boston in 1898 had physi-
cal stigmata of rickets.1 In the 1897
edition of his textbook, Holt drew at-
tention to the very high frequency of
its occurrence in dark-skinned infants,
stating that he found it “almost invari-
ably.”2
See related article, p. 153.
When Mellanby3 established the an-
tirachitic effect of cod liver oil in 1918,
the presence of a vitamin was assumed
and the letter “D” was assigned be-
cause A, B, and C were already
known. By 1919, Huldschinsky4 had
shown that exposure to sunlight or ar-
tificial sources of ultraviolet light could
also prevent or cure rickets. Apprecia-
tion of the link between these two dis-
coveries followed years of research by
McCollum et al,5 Steenbock and
Black,6 DeLuca,7 Norman,8 Holick et
al,9 and others. By 1960, it was clear
that the effects ascribed to “vitamin D”
resulted from the synthesis of a hor-
mone dependent in part on the action
J Pediatr 2000;137:143-5.
Copyright © 2000 by Mosby, Inc.
0022-3476/2000/$12.00 + 0 9/18/109008
doi:10.1067/mpd.2000.109008
THE JOURNAL OF
Volume 137
of ultraviolet light on an endogenous
steroid precursor.
During the early decades of the 20th
century, the relative importance of diet
and environment in the genesis of in-
fantile rickets was debated at length. A
major advance occurred in 1925, with
the publication of a seminal study by
Eliot.10 This report detailed the results
of a demonstration project by the Unit-
ed States Children’s Bureau begun in
New Haven in 1923. The project was a
clinical trial of virtually unprecedented
complexity; 116 infants received cod
liver oil and regular sunlight exposure,
beginning within the first month of life.
Compliance was assessed by regular
home visits, and a physician performed
monthly physical examinations and ob-
tained standardized forearm radi-
ographs. An additional 100 children
with minimal sun exposure and lower
cod liver oil intake served as control
subjects. At the time of the report,
when children had been studied for 8
to 18 months, none of the treatment
group had “marked” rickets, and only
4.3% had “moderate” rickets. In con-
trast, about one third of the control
groups had marked or moderate dis-
ease. The author commented that it
was “uncommon” not to find rickets in
a “vigorous breast fed infant.”
Although this and other studies in the
early 20th century stressed the protec-
tive effect of cod liver oil, it was well
known that deficient sun exposure was
responsible for the prevalence of rickets
Number 2
in the developed world. Many authors
noted the rarity of the disorder in re-
gions where unobstructed sunlight was
freely available. It was assumed that a
combination of social factors—includ-
ing air pollution, urban architecture,
and limited opportunity to take infants
outside—was the proximate cause of in-
fantile rickets. Cod liver oil somehow
substituted for sun exposure.11
Soon after chemical studies had led
to the identification of the antirachitic
substance in fish oils, it was found that
irradiated ergosterol provided an effec-
tive, concentrated, and more easily ad-
ministered source of vitamin D.6 Sup-
plementation of formulas derived from
cow’s milk with vitamin D was nearly
universal by the 1930s, as was the pro-
vision of some form of vitamin D sup-
plement to human milk–fed infants. In-
fantile deficiency rickets, nearly
universal in urban America at the turn
of the century,2 had vanished within 50
years. Cone,12 in discussing the history
of rickets, commented that pediatric
house officers in the mid 20th century
might not see nutritional rickets during
their entire training period. A combi-
nation of basic research, clinical trials,
and public policy had apparently elim-
inated a crippling disease over the
course of a few decades.
By the late 1970s, however, there
was evidence that infantile vitamin D
deficiency rickets was reappearing. A
hospital survey identified several hun-
dred children with nutritional rickets,
143
 EDITORIALS
many of whom were reported to be re-
ceiving “long-term breast feeding.”13
Case reports and case series of infants
with vitamin D–deficient rickets began
to appear in the literature.14-19 In the
current issue of The Journal, Kreiter
et al20 in North Carolina present 30
very well documented cases occurring
over the past decade.
What could account for the reemer-
gence of a disorder once so nearly elim-
inated? A simple lack of recognition for
a few decades seems unlikely. Many
children with rickets develop severe,
pathognomonic orthopedic deformi-
ties,16 and a few become critically
ill with profound metabolic distur-
bances.21 To understand vitamin D–
deficient rickets today, one need only
consider the population of infants affect-
ed. As is the case with the patients of
Kreiter et al,20 rickets now chiefly affects
dark-skinned infants receiving human
milk without supplemental vitamin D.
The reappearance of rickets may be
an unintended consequence of an ad-
mirable health initiative: the promotion
of human milk feeding. Currently, only
about 15% of African American infants
even begin this optimal feeding
method.22 Only about a fifth of all
American infants are still human
milk–fed at 6 months of age.23 The
Healthy People 2000 initiative has set
a target of 75% of American infants
breast-feeding for at least 6 months. If
this goal is to be achieved, a major ef-
fort to increase the frequency and du-
ration of breast-feeding among African
Americans will be required. Strategies
to effect this have been reported.24 Un-
less this change is accompanied by pro-
vision of vitamin D supplementation to
replace that currently derived from
formula, an epidemic of rickets seems
inevitable. As Kreiter et al20 point
out, the group in which the greatest
potential for increased breast-feeding
(African Americans) exists is also that
most at risk. There is precedent for this
prediction in the high prevalence of
rickets among the children of Asian
immigrants in Great Britain.25
144
Although standard textbooks of infant
nutrition26,27 support the need for sup-
plements, such recommendations are not
always heeded. Some manuals intended
for nursing mothers, for example, sug-
gest that vitamin D supplementation is
unnecessary.28,29 One of these,29 an ac-
claimed reference, makes the clearly
incorrect claim that rickets does not
occur in the children of well-nourished
nursing mothers. Worse still, the Work-
group on Breast-feeding of the Ameri-
can Academy of Pediatrics recently
presented a position statement implying
that the need for supplemental vitamin
D in nursing infants was “not estab-
lished.”30 It was proposed that physi-
cians assess maternal vitamin D status
and the extent of potential outdoor time
available before making individual rec-
ommendations. When the safety and
feasibility of this approach were ques-
tioned,31 a spokesman for the Work-
group countered that additional research
on the subject was necessary.32
We do not believe that additional re-
search is required to support a practice
that nearly a century of experience has
shown to be safe, cheap, and effective.
The suggestion that supplementation be
restricted to the offspring of actually or
potentially deficient mothers30,32 is dou-
bly flawed. The cost of a single assay of
25-hydroxy-calciferol, the best objec-
tive measure of vitamin D sufficiency, is
prohibitive. In any case, maternal vita-
min D stores influence calcium metabo-
lism in infants only briefly during the
neonatal period. Basing supplementa-
tion advice on the complexion of the
mother or her infant would be impossi-
ble to incorporate into a usable practice
guideline. Similarly, the prescription of
regular sun exposure is not only diffi-
cult to quantitate but also may be in
conflict with other current health rec-
ommendations. The protocol of Eliot10
in the early 1920s, for example, called
for sufficient sunlight to induce redden-
ing, hardly appropriate advice today.
It is difficult to understand the origin
of the apparent objection to vitamin D
supplementation of nursing infants.
THE JOURNAL OF PEDIATRICS
AUGUST 2000
One factor may be the way in which it
is available. Most supplements used
today are in the form of drops contain-
ing vitamins A and C, as well as calcif-
erol. Such preparations date from the
days of evaporated milk formulas and
have no rationale today, as human milk
is an adequate source of these vita-
mins. The additional amounts so given
are superfluous but harmless.
A second objection may actually de-
rive from our very appropriate advoca-
cy for human milk as a “perfect food.”
For some, the need for supplementation
may imply nutritional inadequacy. As
emphasized above, however, calciferol is
in no sense a nutrient, but rather the
precursor of a steroid hormone that is
not naturally present in any infant food.
Classifying the antirachitic substance in
cod liver oil as a vitamin was an unfortu-
nate historical error that has become too
ingrained to correct. If one views calcif-
erol in this light, then it is not necessary
to consider human milk “deficient.” In-
stead, the provision of supplemental cal-
ciferol can be looked on as ensuring an
adequate substrate for a hormone whose
normal production has been adversely
affected by the realities of modern living
conditions. Human milk is, indeed, the
“perfect food” for infants. Unfortunate-
ly, neither it nor any unsupplemented
food or formula can prevent climate,
latitude, smog, economic factors, or reli-
gious practices from coming between in-
fants and sunshine.
Thomas R. Welch, MD
Division of Nephrology and Hypertension
Children’s Hospital Research Foundation
Cincinnati, OH 45229-3039
William H. Bergstrom, MD
The Department of Pediatrics
SUNY Upstate Medical University
Syracuse, NY 13210
Reginald C. Tsang, MBBS
The Bone Research Center
Children’s Hospital Research Foundation
Cincinnati, OH 45229-3039
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