ARTICLES
MILK
ALLERGY
I. Observations
on
Incidence
and
Symptoms
in
“Well”
Babies
By Kay D. Bachman, M.D., and Susan C. Dees, M.D.
Departnie’at of Pediatrics, Duke University School of Medicine
(Submitted November 8, 1956, accepted March 5, 1957.)
This stud was aided by a research grant from the Prescription Products Division, Borden Company, New York, New York.
I)r. Bachman was Borden Fellow in Pediatric Allergy. ADDRESS: (S.C.!).) I)urham, North Carolina.
393
Ped #{237}a!
rics
VOLUME 20 SEPTEMBER 1957 NUMBER 3
M
ANY pediatricians are impressed with the tlivergence of opinion on the subject of allergy to cow’s milk and its importance in the first few years of life. In order to clarify our OWn idea on milk allergy in this age group, we have col-lected and summarized chronologic records of diet and symptoms in infants receiving veII baby care in the period from 1954 to 1956. Similar information has been collected on presumably allergic infants referred tofor studies during the same 2-year period, and this will be the subject of the second portion of this report.
PLAN OF STUDY
Clinical Material
The group under consideration comprises consecutive, full-term, white and Negro
in-fants attending the Well Baby Clinic of Duke
Hospital, and infants simultaneously receiVillg
routine well baby care in the private practices
of two pediatricians. These pediatricians estab-lislied the vell-babv routine for the Hospital clinic, and therefore the general feeding prac-tices are essentially the same for the clinic
aIld private patients. Practically all of the
pri-vate patients were followed with a
consider-able degree of regularity for 2 ‘ears, but the clinic patients were seen primarily for illness during the second i-ear. The records of 403 infants who were followed in detail during their first 3 months were considered suitable for analysis for the presence of earl symptoms due to milk allergy. By 1 ear of age 360
pa-tients were still under observation. The distri-bution of patients in each category is shown in Table I.
In order to maintain the role of impartial observers and recorders, the authors prescribed
no diet, no treatment, and avoided using the
word allergy while interviewing mothers, and while examining anti testing these children.
Criteria for Milk Allergy
A part of the disagreement among
physi-cians regarding the incidence of milk allergy
may well arise from the different criteria used
in establishing this diagnosis. The apparent
production of symptoms after feeding cows
-
PATIENT1
2
3
4
5
6*
_
Crying,
“colic”
S
Diarrhea
S
5
Rash
S
S
S
Frequent
“colds”
S
5
Wheezing
S
Fic. 1. Symptoms in six infants allergic to cow’s milk.
TABLE I
CLASSIFICATION OF INFANTS IN
UNSELECTED SERIES
Age (ma)
0-3 3-6 6-9 9_1Oi
Number 403 38 365 360
Clinic
White
Negro
44 9
63 57 53 50
Private practice I
Privatepracticell
163 163 160 160
133 133 130 130
The number of patients at each age indicates the
number of each initial group still being followed.
cow’s milk only when ingestion of small amounts is regularly followed by (a) one of the recognized allergic manifestations such as eczema, hives, asthma, or noninfectious
rhini-tis, or (b) gastrointestinal symptoms or be-haviour patterns which are definitely abnormal in the setting in which they occur. Reactions of the (a) and (b) types should be reproducible on repeated exposures to milk made over a considerable period of time, and absent at periods when there is no contact with milk. A further requirement has been that no or-ganic or functional cause for symptoms could be detected. A positive skin test to milk was not considered obligatory to the diagnosis of milk allergy, and conversely no diagnosis rested on this finding alone. Skin testing was done on many of the children in this series. When a positive test to milk was present it was looked upon as one looks upon eosinophilia or a posi-tive family history, as helpful but not absolute
*SUSPECTED MILK ALLERGY
evidence that one is dealing with an allergic individual.
Feeding
In these 403 unselected babies, during the first month 99 were breast fed exclusively, 41 had breast milk plus evaporated milk supple-ment, and 263 had an evaporated milk for-mula. By the end of 1 month the diet in five had been changed to some type of modified evaporated milk, and in four to a soybean for-mula. After the first month, various other foods were added to the diet of so many infants that further tabulation of the formula changes alone did not prove worthwhile.
Incidence
RESULTS
On the basis of the criteria outlined for diagnosis of milk allergy, we found among the 403 unselected babies, 4 with allergy to cow’s milk, or 1%. If we subtract the 99 breast-fed infants from the total, the inci-dence among babies fed cow’s milk is 1.3% (4 in 304). Two additional infants developed rash which cleared when milk was discon-tinued, but as they were not subjected to repeated trial of cow’s milk, they are in-cluded only as suspected allergy.
Symptoms Due to Milk Sensitivity
per-Age (ma)
0-3 3-6 6-9 9-12 12-24
Total
Patients 403 382 365 360 296
Crying 50, 2 52
Gastrointestinal
Spitting Vomiting I)iarrhea
Mucus
Blood
15
2
2, 2
2
2
15
2
4
2
2
Skin
Minor rash
Eczema
hives
36 26
3#{176} 4 4
1 1 3
62
11
5
Respiratory
“Colds”
Wheezy
2 6 5 5 4
5 10 16,1 5 3 40
Boldface figures indicate milk allergy.
These figures refer to age at onset of symptoms. Some infants had multiple symptoms. Totals in each age column
indicate number remaining in series at each age; see Table I.
* Milk allergy suspected in two of these.
395
TABLE II
SYMPTOMS IN UNSELECTED BABIES RELATED TO AGE OF ONSET
mits no more than the statement that colicky crying of excessive degree, diarrhea, rash, frequent colds, and wheezing were encount-ered either alone or in various combinations. In each child the symptoms were present by 3 months, in most instances by 1 month of age. The gastrointestinal symptoms ceased to be a clinical problem beyond the third month, since by this time it was apparent that the infant was sensitive to cow’s milk and a substitute was fed. Subsequently, gastrointestinal, as well as other symptoms, recurred when attempts were made to re-introduce milk into the diet. By 15 months of age these four children were being fed cow’s milk, one, apparently tolerating milk with no symptoms, while one was asthmatic and two others were having symptoms sug-gestive that allergy to milk was still present.
Review of All Symptoms Recorded in Unselected Infants
In the unselected group, the infants were separated into “crying” and “non-crying” babies, since this study arose, in part, from
an interest in the role of colic0 as an ante-cedent to frank allergy. Among the 403 in-fants there were 52 “crying babies.” Of these supposedly “colicky” children, only two were found to be milk-sensitive (Table II). This agrees with the impression of many pediatricians that colic is only rarely due to or followed by milk allergy in a general infant population, but is in disagreement with the inference Martin2 drew from the allergic background of 60% of babies with colic. The feeding history during the first month shows that 14 of 52 “crying babies” and 85 of 351 “non-crying babies” were breast fed, so that the ratio of breast feed-ing to bottle feeding is about one in four in both crying and noncrying groups.
Referring again to Table II, the
gastro-#{176}As our definition of colic we have used
Bart-ram’s frequently quoted description’ of the young infant who shows excessive or prolonged crying
without obvious cause or illness, particularly when
this is accompanied by tenseness of the abdomen,
396
intestinal symptoms encountered in the well babies had all made their appearance dur-ing the first 3 months, and did not persist into older age groups. This was in contrast to the appearance and persistence of gastro-intestinal symptoms, when they were pres-ent, throughout the first 2 years in the infants from our allergy practice.
Wheezing was present at some time dur-ing the first 2 years in 40 of the unselected infants, in 32 instances this occurred during the first year, and in only 1 of the 40 could it be attributed to milk allergy. Infection seemed related to and responsible for most wheezing. Two of twenty-two infants who had persistent “colds,” nasal stuffiness, or obstruction were found to be allergic to milk.
Because the minor rashes all appeared during the first 6 months, the 62 infants who had this symptom were followed with par-ticular interest with the thought that this might represent or be the forerunner of an allergic rash. Poor hygiene of the skin was ultimately found to be the most likely cause for the short-lived minor eruptions. Only 11 patients with eczema were seen in the entire series. The only three established as due to sensitivity to milk appeared by 3 months of age.
One of the most impressive facts which emerges from the observations made on the series of unselected babies, is that so few of the symptoms recorded were actually due to milk sensitivity even though they could be considered as suspicious, early signs of allergy.
Skin Tests
Seventy-two infants were scratch tested with cow’s milk, bovine lactalbumin, casein and egg. Scratch tests were negative in 66 of the 72 babies, and no strongly positive reactions to any allergen were observed. No correlation was noted between positive tests and present or subsequent allergic symptoms. This is illustrated by the finding of only two children with symptoms among the six reacting positively. One of these regurgitated frequently at 6 weeks of age,
and the other infant had a minor short-lived rash not typical of eczema.
Among the 66 infants whose skin tests were negative, we found 1 with severe milk allergy, consisting of diarrhea with rash at 1 month, 1 with severe milk allergy before 1 month of age, 1 with wheezing during pneumonia at 2 months and croup at 2 years, 1 with mild rash at 2 months, 1 with colic for the first 3 months, and 25 with
minor symptoms which could not be estab-lished as allergic.
It is obvious that these results are in agreement with the generally accepted im-pression that skin tests cannot be relied upon to differentiate the very young allergic infant from his normal contemporary.
Stool Eosinophilia
Stool eosinophilia has been described as a useful diagnostic test for gastrointestinal allergy.35 With the hope that this would be a helpful objective screening test for early allergy to milk, stool smears were made at frequent intervals, starting from the newborn period and continuing through the first few months of life. Using Hansel’s stain, 156 children were followed with stool smears and only three positive smears were found. While these three proved to he from colicky babies, the infants did not subse-quently develop any allergic symptoms (Fig. 2). The eosinophils were scanty, and not in sheets as Nance#{176} described in his patients. We concluded from our observations that staining stools for eosinophils is not a prac-tical routine diagnostic test.
Family History
his-NEWBORNS
99000
90999
BABIES HAVING COLIC
NEG.
POS.
99091
OTHER “WELL BABIES”
30
12 3
999#{149}90
99909
90999
09900
00990
99900
OonUU
99
111
Each Symbol
Represents
Smears
on 3 Patients
Total 153 3
ARTICLES
397tory was positive in all. In the additional two suspected of allergy to milk the family history was positive in the mother of one child and sibling of the other.
DISCUSSION
The purpose of the present study has been to gather information on the incidence of allergy to cow’s milk in the first 2 years and is not primarily a study of the general incidence of allergy in infants. Sufficient time has not elapsed to establish the sig-nificance of the frequent colds and brief
clear-cut allergic symptoms, including those thought to be sensitive to milk.
No discussion of the incidence, symptoms and diagnosis of allergy to cow’s milk can rest solely on the results of one series of sev-eral hundred infants such as we have studied. Yet among the extensive literature on this subject only the recent report of Collins-Williams uses an approach and cri-teria sufficiently similar to ours to be com-parable in respect to incidence. In this au-thor’s private practice 9 of 3,000 nonallergic patients, or 0.3%, had clinical sensitivity to
Fic. 2. Occurrence of stool cosinophihia.
episodes of wheezing recorded during the first 2 years in these patients, but observa-tions of these children have shown that most of them have not developed frank allergy during the first 2 years of life, nor in the 6 to 12-month period since then to the present. Only one child had definite asthma before 2 years of age, and he was among those sensitive to milk. One other child has developed asthma during the sec-ond year. If one considers wheezing on any occasion however brief, or under any cir-cumstance, as asthma, then 10% of the group are “asthmatics.” Our own present opinion is that this implication is too sweeping. We plan to report in detail on the course of these children at a later date. The incidence of allergy in this series approaches 5% if one bases this on the 20 children who have
PEDIATRICS SEPTEMBER 1957
based on different types of clinical material, collected in different ways; for example, the Loveless series is a composite impression from many doctors, whose definition of milk allergy undoubtedly varies widely. Many of these and other reports on the incidence do not describe their data in sufficient detail to permit one to compare the portions of the material which are based on similar patients. In addition, we feel that one must not only limit and specify the ages compared, but that one should compare patients seen in the same years in order to eliminate variables of feeding and therapy. These factors are of equal importance to the inherent selection of a group of patients which is based on the type of people a doctor attracts, a point which Collins-Wil-hams emphasizes.6
SUMMARY
During two consecutive calendar years, a series of 403 babies receiving routine well-baby care were followed and records kept of all symptoms and illness occurring dur-ing their first 2 years of life.
Gastrointestinal disorders and eczematous rash were the symptoms most frequently en-countered which appeared to be due to allergy. Many minor digestive, skin and respiratory symptoms were recorded which did not prove to be allergic manifestations during the 2 years of observations.
Colic was present in 52 well babies, of whom 2 were sensitive to milk.
The incidence of allergy to cow’s milk in this series of infants was 4 in 403 or 1%.
Scratch tests were negative in 66 of 72 well babies tested, and no strongly positive reactions were observed. The allergens used were cow’s milk, bovine lactalbumin, casein and egg. No correlation could be made be-tween skin tests and clinical symptoms.
Three infants showed a few scattered eosinophils in the stool smear, among 156
from whom stool smears were made. These babies had colic but no symptoms sug-gestive of allergy later.
CONCLUSIONS
The incidence of allergy to cow’s milk is low (1%) in this well baby group.
Allergy at this age most frequently in-volves the gastrointestinal tract and the skin.
Colic, rashes, minor digestive and res-piratory symptoms were infrequent pre-allergic manifestations during the first 2 years of life in a series of 403 vell babies.
Skin tests and stool smears for eosinophils are not useful as routine screening tests for early detection of milk sensitivity.
There is a real need for improved methods of detection of, and precise cri-teria for the diagnosis of allergy to cow’s milk in infancy.
ACKNOWLEDGMENT
The authors thank their colleagues in the Department of Pediatrics, Duke University School of Medicine, for making their pa-tients available for this study.
REFERENCES
1. Bartram,
J.
B.: Colic, in Nelson, W. E., editor: Textbook of Pediatrics, 6th Ed. Philadelphia, Saunders, 1954, p. 119. 2. Martin, F.J.:
The colicky baby. Ann.Al-lergy, 12:700, 1954.
3. Neuhaus, H., and Schaub, C.: Uber die sogenannte Kuhmilchidiosvnkrasie bei Sauglingen. Ztschr. Kinderh., 7:310, 1913. Quoted by Meigs, C.: Review of the literature on the feeding and gastro-intestinal diseases of infants for the year 1913-14. Am.
J.
Dis. Child., 8:58, 1914. 4. Nance, F. D.: Stool eosinophilia ingastro-intestinal allergy of infancy.
J.
Pediat., 33:313, 1948.5. Rosenblum, A. H., and Rosenblum, P.: Gastrointestinal allergy in infancy. PEDI-ATRICS, 9:311, 1952.
6. Collins-Williams, C.: The incidence of
milk allergy in pediatric practice.
J.
Pediat., 48:39, 1956.7. Rackemann, F. C.: Quoted in Vaughan, W. T.: Practice of Allergy, 2nd Ed., revised by Black,
J.
H. St. Louis, Mosby, 1948, p. 407.ARTICLES
9. Loveless, M. H.: Milk allergy: A survey of its incidence; experiments with a masked ingestion test.
J.
Allergy, 21:489, 1950. 10. Clein, N. W.: Cow’s milk allergy inin-fants. Ann. Allergy, 9:195, 1951. 11. Claser,
J.:
Allergy in Childhood.Spring-field, Thomas, 1956, p. 445.
SUMMARIO IN INTERLINGUA
Allergia a Lacte. I. Observationes in
Re Incidentia e Symptomas in Babys
in “Bon” Stato de Sanitate
Le revista del stato de 403 non-seligite in-fantes blanc e negre al Clinica pro Patientes Visitante del Hospital Duke e in le practica
private de duo pediatros-omnes mantenite secundo un regime routinari pro babys in bon stato de sanitate e omnes vidite durante le periodo ab 1954 a 1956-revelava que allergia a lacte de vacca esseva presente in solmente quatro casos. Isto es un incidentia de 1 pro cento. Si nos exclude le 99 infantes qui esseva nutrite al pectore, le incidentia deveni 1,3 pro cento.
Crados excessive de critar in colica dolorose, diarrhea, eruptiones cutanee, rheumas de oc-currentia frequente, e respiration stridorose-individualmente o in combination-esseva
pre-sente al etate de tres menses o plus tosto in
omne le quatro demonstrate casos e in duo suspicite casos de allergia a lacte. Le minor symptomas digestive, cutanee, e respiratori que
esseva notate in multe infantes esseva demon-stratemente manifestationes ni de allergia ni de sensibilitate a lacte durante le duo annos del periodo de observation. Le cutireaction
esseva negative in 66 ex 72 casos testate, e nulle fortemente positive reactiones esseva
ob-servate contra le sequente allergenos: Lacte de vacca, lactalbumina bovin, caseina, o ovos.
Nulle correlation esseva trovate inter le cuti-reaction e le symptomas clinic.
Tres infantes monstrava sporadic eosinophi-los in le frottis fecal que esseva examinate in 156 casos. Iste tres infantes habeva colica sed nuhle symptomas in menses subsequente que haberea indicate he presentia de allergia. Gin-quanta-duo infantes del serie total habeva colica. Duo de istes esseva sensibile a lacte de vacca.
Le criterios usate in le presente studio pro le diagnose de allergia a lacte de vacca esseva le sequente: Le ingestion de parve quantitates de lacte de vacca es regularmente sequite per un del recognoscite manifestationes allergic o per symptomas gastrointestinal o modos de comportamento que es definitemente anormal in he situation in que illos occurre. Le symp-tomas debe reproducer se in repetite exposi-tiones. Illos debe esser absente quando nulle lacte de vacca es administrate, e illos non debe esser explicabile per ulle detegibile causa or-ganic o functional. Positivitate del reaction cutanee a lacte non esseva considerate como indispensabile pro he diagnose de allergia a lacte, e nulle diagnose esseva basate super iste constatation so!.
