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Macrocytic Anemia in Pregnant Women with Vitamin B Deficiency

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Macrocytic Anemia in Pregnant Women with Vitamin B Deficiency MACROCYTIC ANEMIA IN PREGNANT WOMEN WITH VITAMIN B DEFICIENCY Katharine O'Shea Elsom, Albert B. Sample J Clin Invest. 1937;16(3):463-474. https://doi.org/10.1172/JCI100871. Research Article Find the latest version: https://jci.me/100871/pdf MACROCYTIC ANEMIA IN PREGNANT WOMEN WITH VITAMIN B DEFICIENCY 1 By KATHARINE O'SHEA ELSOM 2 WITH THE TECHNICAL ASSISTANCE OF ALBERT B. SAMPLE (From the Gwstro-Intestinal Section of the Medical Clinic, Hospital of the University of Pennsylvania, Philadelphia) (Received for publication August 17, 1936) Recent observations of sprue (1), pernicious studied by Strauss and Castle would develop this anemia (2), tropical macrocytic anemia (3) and form of anemia when their habitually inadequate the pernicious anemia of pregnancy (4) have led diet was supplemented to bring it to the level of to the hypothesis that a dietary deficiency of vita- full caloric requirements and otherwise adequate min B 3 or some closely allied substance is re- conditions but without any attempt to supply de- sponsible both for the anemia and for the clinical ficiency of vitamin B. It may be noted that these manifestations of these diseases. Animal experi- patients admitted to an obstetrical clinic were sub- ments designed to test this hypothesis (5, 6, 7) sisting on a diet deficient in calories as well as have yielded results which vary with the species vitamins. Any resulting anemia under these cir- of animal employed. This and the fact that cumstances may be attributable to general nutri- macrocytic anemia does not occur in animals as tional deficiency or to vitamin inadequacy. It a spontaneous entity constitute limitations which was the purpose of this study to determine which made it seem desirable to study the problem in factor is significant. Every other known essen- human beings. The occurrence in pregnancy of tial was therefore added to the diet and such a syndrome which resembles pernicious anemia amounts of vitamin B as had been taken in the and the other macrocytic anemias in every im- previous diet continued to be given but no at- portant respect except that it is temporary sug- tempt was made to increase this factor, the im- gested that there may develop during that period portance or unimportance of taking which was a temporary deficiency of factors necessary to the object of the study. By careful clinical ob- prevent macrocytic anemia. If the assumption servation the early signs of vitamin B deficiency is correct that vitamin B is the responsible factor previously described in a report from this Clinic one would expect to encounter a high percentage (9) were sought and when detected were promptly of anemia of this type in women who, by force relieved by the administration of brewer's yeast of circumstances, were taking a diet during preg- or liver extract. The present communication is nancy which was deficient in vitamin B. Preg- a report of studies made chiefly upon the blood, nant patients taking poor diets have been observed gastric secretion and clinical manifestations of by Strauss and Castle (8) to develop macrocytic these women from the 4th month of pregnancy anemia late in pregnancy. The subjects of that to term. consumed deficient in many investigation diets METHODS OF STUDY substances, however, and it was impossible to be certain whether one alone of the missing factors The subjects of the study were selected from was responsible for the development of the among the patients attending the Outpatient Ma- anemia. It seemed desirable, therefore, to deter- ternity Clinics of this and the Pennsylvania Ly- mine whether pregnant women such as those ing-In Hospitals. Each subject was examined every 10 to 14 days at which time a detailed rec- 1Aided by a donation from Mr. Samuel S. Fels and ord was made of symptoms and physical observa- by a grant from the Faculty Research Committee of the tions. Blood was drawn without stasis from an University of Pennsylvania. antecubital vein. 2Justice M. Thompson Fellow in Gastro-enterology. manifestations of 8 The term vitamin B as used in this paper includes all Seven clinical phenomena, members of the vitamin B complex. Individual members vitamin B deficiency, recognizable from previous are referred to as vitamin B%, B%, etc. study (9) were watched for in particular. The 463 464 KATHARINE O SHEA ELSOM AND ALBERT B. SAMPLE changes were: alterations of the tongue, gastro- were made in duplicate from smears of blood intestinal symptoms, paresthesias, impaired vibra- stained immediately with brilliant cresyl blue, tory sense, susceptibility to fatigue, edema and 1000 cells being counted. Morphological changes tachycardia. The term "deficiency index" has in the cells were observed from smears of blood been used in the text to denote the number of prepared with Wright's stain. The infants were these phenomena manifested at any given time by examined and erythrocyte counts and hemoglobin each individual. The deficiency index ranges estimations were made at birth and at 1, 3 and 9 from 0 to 7. months of age. The acuity of perception of vibration was de- RESULTS termined with a C tuning fork (128 vibrations per second). A standard of reference was ob- Dietary requirements tained from normal persons who perceived a sense The 11 subjects of this report took diets so con- of vibration for 20 to 30 seconds when the fork, stant that the composition, the caloric and the vibrating at maximal intensity, was placed over protein values could be estimated with accuracy. TABLE I Chart showing articles composing the diets of Group I Vegetabes Cereals and starches Pastry and desserts Meat Beans (kidney) Cornmeal Bread Veal Potatoes Cream of wheat Crackers Lamb Turnips Cornflakes Cake Corned beef Corn (canned) Rice Pie: apple Frankfurters Beets Macaroni pear Spinach Spaghetti Puddings: cornstarch without Onions rice J milk Cabbage gelatine Rutabaga Candies Carrots Jellies Fats Seasonings, etc. Fruit Beverages Butter Chocolate Apples Tea Mayonnaise Cinnamon Pears Coffee Lard Molasses Grapes Grape juice Syrup Cocoanut Gingerale Honey, salt, etc. any bony prominence of the lower extremities. Eight subjects hereafter called Group I consumed Electrocardiograms and orthodiagrams were made throughout the period of observation a diet com- several times, as were also gastric analyses in posed of the articles shown in Table I. These which the rate and the acid content of the fasting foods were taken in amounts which supplied ap- secretion and the acid response to 50 cc. of 7 per proximately 50 calories and 1.5 grams of protein cent alcohol were determined. Titrations of acid per kilogram of body weight per day. The vita- were carried out in the usual way with 0.1 normal min B: calorie ratio of this diet was approx- NaOH, using Topfer's reagent and phenolph- imately 1.66. The vitamin B per calorie require- thalein as indicators. ment of these subjects at the beginning of the Erythrocyte counts were made in triplicate, us- observation, calculated from Cowgill's4 formula ing pipettes certified by the U. S. Bureau of (12), averaged 1.5 (Table II). Since the caloric Standards. Hemoglobin values were determined intake of these women remained essentially con- by the method of Stadie (10) which permits ac- stant throughout observation, their theoretical re- curate determination of hemoglobin concentration 4 Vitamin B to within 0.3 gram per 100 cc. of blood. Hemato- Calories B=.0000284 Weight grams. crit determinations were made in duplicate using Although the figure obtained by this formula of Cowgill's applies strictly to vitamin B1, it is used here as an index Wintrobe tubes. Mean corpuscular volume and of the concentration of other vitamin B fractions since, mean corpuscular hemoglobin were calculated in as far as is known, other fractions were present in the the usual fashion (11). Reticulocyte counts diet in approximately the same concentration as B1. MACROCYTIC ANEMIA IN PREGNANT WOMEN 465 TABLE II TABLE III The theoretical requirement of vitamin B per calorie,* the The theoretical requirement of vitamin B per calorie, the intake of vitamin B per caJorie ** and the deficiency intake of vitamin B per calorie and the deficiency index of subjects of Group I at various times index of subjects of Group II at various times during pregnancy during pregnancy Bning of period Appearanceofdefinite Final examination after of observation clinical phenomena administration of therapytt Beginning of period 8th to 9th Final ..of obsvation month examination Sub----____ - S3ub- Vitamin ____ __ n B: --_ _-- -- Vitamin D Vitamin Ject __ - num-nect Dy VitB Dar B D r ~ D. num- calorie D Vitamin Da Vitamin Da Vitamin D. D. D. ber raio '~: B: B: X B: D. preg-o Wora°ie 1t preg calorie L.t preg or~~~calricralorie Lt ther, D. 'o[ D. n preg- calorie . preg- calorie I. preg- calorie I. nerequiredZuZred requitd nancy ratio nancy ratio nancy ratio _____ required required required 1 82 1.8 0 238 2.0 7 271 2.1 2 35 2 102 1.5 0 264 1.6 4 280 1.6 2 16 1 3.4 59 1.3 0 220 1.5 0 273 1.5 0 3 112 1.5 0 234 1.7 6 269 1.7 1 35 2 2.5 125 1.5 0 224 1.7 0 273 1.8 0 4 96 1.3 0 233 1.6 5 277 1.6 1 44 3 2.3 120 1.5 0 246 1.9 3 267 1.9 0 5 107 1.6 0 249 1.9 5 277 2.0 3 28 6 96 1.5 0 249 1.8 3 277 1.8 0 28 Aver- 7 62 1.4 0 232 1.7 7 280 1.8 1 48 age 2.8 101 1.4 0 230 1.7 1 271 1.7 0 8 138 1.8 0 266 2.2 6 279 2.2 1 14 Aver- * 21 grams of brewer's yeast administered to this subject age 99 1.5 0 245 1.8 5 276 1.9 1 31 from the 253d to the 267th day of pregnancy increased to *From 10.2 the Vitamin B: calorie ratio of her diet during that B_ time.
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