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Hemorrhagic Disease of the Newborn

By Robert M. Green, M.D., Boston, and John B. Swift, Jr., M.D., Boston
(From the Clinic of the Boston Lying-In Hospital)

Boston Medical and Surgical Journal 164(13):454-456, March 30, 1911
Read before the Surgical Fortnightly Club, Boston, Feb. 21, 1911.

The subject of hemorrhagic disease in the newborn is one of particular interest, not only because its etiology is still uncertain, but because it is one of the serious emergencies of early infantile life, in the treatment of which important progress has been made in recent years. The disease was first described as a clinical entity in 1852 by Dr. Francis Minot, [1] of Boston. In 1891, Dr. Charles W. Townsend, [2] of Boston, published a valuable paper reviewing the literature of the subject since Minot's time and reporting a series of 32 cases from the clinic of the Boston Lying-In Hospital, together with 577 cases collected from other writers. From an analysis of these cases he reached the conclusions that the disease is probably due to an acute infection, that its mortality in all forms is about 75% and that its treatment is best directed towards mechanical control of the hemorrhage and maintenance of the strength of the patient. (In a subsequent paper [3] Dr. Townsend reported 18 additional cases; but we have confined ourselves to the first series for comparison.) Taking Dr. Townsend's original paper as a point of departure, it is out desire to report a further series of 51 cases from the clinic of the Boston Lying-In Hospital, and to discuss briefly the bearing of their statistics on the etiology and on the various methods of treatment of this disease which have been advanced during the past twenty years. For the privilege of consulting the records of the hospital and of observing some of the cases in the wards, we wish gratefully to acknowledge our indebtedness to the courtesy of the visiting physician and other members of the Boston Lying-In Hospital staff.

The 51 cases which form the basis of this paper occurred in the wards of the hospital from June 19, 1904, to April 1, 1910, a period of nearly six years. The total number of babies born in the hospital during this time was 4,455, showing a percentage incidence of 1.14% as against 0.57% in Dr. Townsend's series. We have presented these cases in tabular form, noting particularly the parity and the civil condition of the mother, the duration of labor, the fetal position and the complications of labor and puerperium, the date of delivery, the age of baby at onset of disease, the treatment and the result. We will next proceed to an analysis of these cases to determine the bearing, if any, of each of these factors on the problems of the disease.

Of the 51 mothers, 31 were primiparae, 20 were multiparae. It has been thought that firstborn children are more subject to the disease than those of subsequent pregnancies, chiefly because of the longer average period of labor to which they are subjected. The present figures would seem to bear out this assertion, but in reality we believe they do not, since this proportion is approximately the same as that of primiparae to multiparae in the entire clinic. In none of the multiparae of this series is there any record of hemorrhage in previous children. This fact would tend to controvert the theory that the disease is analogous to hemophilia, or in any way dependent on a hereditary dyscrasia.

Thirteen of the 51 mothers were single, 38 were married. This again would seem to bear out the supposition that illegitimate children are more subject to the disease; but again this is approximately the proportion of illegitimacy in the entire clinic.

The presentation of the fetus in every case was a vertex, but any series of 51 cases taken at random might well fail to include any other variety.

As stated above, it has been held that length of labor is an important predisposing factor in the production of the disease, from the exhaustion to which it subjects the fetus. The present statistics, however, would not seem to bear out this supposition. The longest labor of the series, it is true, ran to seventy hours, but this baby recovered, and of the 25 who died, 10 were born after less than twelve hours of labor. The average duration of labor for the entire series is fourteen hours thirty-seven minutes, which is only slightly above the general average for a large number of unselected cases.

Nine of the labors were forceps deliveries, again about the same percentage as of all cases in the clinic. One of the mothers had pneumonia at the time of delivery, one had mitral regurgitation, and one impending eclampsia. One mother was an epileptic. Three of the puerperia were complicated by slight uterine sepsis, two by mastitis, one by salpingitis, and one by scarlet fever. It does not seem that any of these complications or attendant circumstances could have had any bearing on the hemorrhagic condition.

The seasonal distribution of the cases seems, on the other hand, distinctly significant. Of the 51 cases, 39 occurred during the six months from November to April inclusive, and only 12 during the six months from May to October inclusive. This proportion, which is essentially the same as that of the seasonal incidence of such infections as impetigo, diphtheria, and bronchopneumonia, should confirm the theory of the infectious etiology of the disease, which is more prevalent during the months when ventilation is poorest and general resistance to infection is lowered.

Again it is instructive to observe that 33 of the cases occurred in distinct groups, after the manner of hospital infections. These groups are indicated in the table by brackets, including such cases as occurred closely enough together to admit of being due to a common infection. Of these groups, the most remarkable, and the only one amounting to a distinct epidemic, is the next to last, of 13 cases, when from Dec. 20 to the following March 20, there was not a single day when there was not in the hospital a baby who had, or had had, hemorrhagic disease.

The average age at onset for the entire series was three and one-half days. The average age at onset for the fatal cases was only slightly less, three and one-fifth days. The only two days that began after the tenth day recovered. The greatest age at onset among the fatal cases was nine days, but all the other fatal cases occurred under seven days. This would seem to indicate that after ten days the disease is infrequent and the prognosis good; that after a week, the prognosis is fairly good; but that under a week the prognosis is poor and the age at onset has no particular bearing on the prognosis.

The subject of the location of the hemorrhage raises at once the question of classification of types of the disease. Townsend tabulated his cases according to the source of the hemorrhage, and for the sake of comparison we have placed ours in a similar parallel table with his. It does not seem, however, that this method affords important information.

Comparative Tables of Sources of Bleeding in Hemorrhagic Cases

Sources

Townsend's
series

Green and
Swift's series

Total

Intestine

12

23

35

Stomach

12

7

19

Mouth

12

9

21

Nose

8

7

15

Navel

14

15

29

Ecchymoses of skin

11

14

25

Crack of skin

1

2

3

All of above sources

3

0

3

Meninges

0

2

2

Genito-urinary tract

0

3

3

Eyes

0

1

1

Navel alone

2

6

8

Gastro-intestinal tract alone

15

2

17

Stomach, mouth, and nose alone

7

2

9

Intestines alone

3

9

12

Ecchymoses alone

2

1

3

Clinically the cases arrange themselves in three distinct groups as follows: First, those in which the hemorrhage is principally from the umbilicus; second, those in which it is principally from the mucous or serous membranes; third, those characterized principally by the formation of subcutaneous purpuric patches or ecchymoses. These types we have designated respectively the umbilical, the sero-mucous and the purpuric, according to which form of hemorrhage predominates. The important bearing of this classification is on the prognosis. Grouped in this manner, the cases and their results in our series may be presented in the following table:

Classification of Hemorrhagic Cases

Clinical type

Recoveries

Deaths

Total

Umbilical

6

9

15

Sero-mucous

13

14

27

Purpuric

7

2

9

Total

26

25

51

It would appear from this that the mortality of the umbilical type is about 60%, and of the sero-mucous type about 50%, and that of the purpuric type about 22%. It remains to consider the various means of treatment employed and the results obtained from each.

The treatment of hemorrhagic disease may be local or general or both. When possible, its aim is to check the actual hemorrhage and prevent its recurrence by such measures as may increase the coagulability of the blood. The local agents employed are the same as those used to check hemorrhage under other conditions. Compression, adrenalin chloride and other astringents have been used, and sometimes seem of value in minimizing the amount of bleeding. In general, however, these agents are often as unsatisfactory as in other conditions. When the bleeding is from the gastro-intestinal tract, local application is impracticable, and the administration of paregoric to allay peristalsis seems to have little effect on bleeding. Attempts to check umbilical hemorrhage by pursestring suture are inadvisable, as the bleeding continues from the stitch-holes.

The general treatment of hemorrhagic disease may be grouped under three headings: First, the use of gelatine and calcium salts; second, the use of animal sera; third, the use of direct blood transfusion. It is instructive to consider these methods of treatment historically and with reference to results obtained.

At the time Dr. Townsend's paper was written, the treatment of hemorrhagic disease was essentially limited to local styptics and general supportive measures. Not long afterwards, the use of gelatine by mouth and rectum was advocated in hemophilia and cholemic hemorrhage, and was adopted in hemorrhagic disease of the newborn apparently with beneficial results. Dr. Townsend was enthusiastic in its use, and subsequently reported [4] a case in which it seemed of advantage. When the effect of Ca salts on the coagulability of blood was discovered, these also were employed in hemorrhagic disease. Until 1908 these measures constituted the routine treatment of the disease.

In 1908, however, Leary's experiments with normal rabbit serum suggested its employment in this condition, and accordingly its use was begun at the Boston Lying-In Hospital. It was given subcutaneously in 30 ccm. doses, repeated two or three times, in case the bleeding recurred after the first dose. Opinions differ as to the value of this treatment. Its numerical results are indicated by the accompanying table.

Table of Methods of Treatment and Results

Treatment

Recoveries

Deaths

Total

General supportive

2

4

6

Local hemostatic

2

5

7

Gelatine

9

4

13

Rabbit serum

12

10

22

None

1

2

3

Total

26

25

51

Finally, Crile's experiments in direct blood transfusion suggested its use also in hemorrhagic disease, and it was employed in one case (No. 36) of this series, after a dose of rabbit serum had failed to arrest bleeding. The transfusion was successful, but the patient died. This single case is, of course, inconclusive as to the therapeutic merits of this procedure. It has been followed by recovery in several cases, and in a recent article [5] Lespinasse and Fisher report its use in six collected cases with four recoveries, and speak enthusiastically in its favor as the ideal treatment. Without admitting this contention as proved, it seems that the method certainly deserves careful and extensive trial.

In the interpretation of the present series of cases there are to be taken into account several considerations which prevent its results from being conclusive or its percentages reliable indications, except in a general way. In the first place, there is some latitude of diagnosis; probably several cases included in the series were not really, and would not formerly have been considered, hemorrhagic disease. Second, the cases may be of various types and of varying degrees of severity, so that the apparent efficiency or inefficiency of any one method of treatment may depend not on its own merits, but on the type and severity of the cases treated by it. Third, in many cases several methods of treatment have been employed, so that in these cases neither recovery nor death can accurately be attributed to any one remedy.

Though all indications point to the probably infectious etiology of this disease, we believe that further study should be made of the microscopic blood picture in this condition, especially with reference to the platelet count. Research on this subject has already been undertaken by Dr. Swift, and its results will be presented in a later paper.

Conclusions

1. The parity and civil status of the mother, the fetal presentation, the duration of labor and the complications of labor and the puerperium are factors of no significance as predisposing or determining causes of hemorrhagic disease in the newborn.

2. The seasonal incidence and the occurrence of hospital cases in groups tend strongly to confirm the theory of the infectious etiology of the disease.

3. The earlier the onset of the disease, the worse its prognosis; after one week, the prognosis becomes relatively, and after ten days, absolutely, good.

4. Clinically the disease occurs in three fairly distinct types, the umbilical, the sero-mucous, and the purpuric, which have an approximate respective mortality of 60%, 50%, and 22%. The gross total mortality is about 50%.

5. The treatment should be directed toward local hemostasis and increase of coagulability of the blood. Gelatine and rabbit serum are agents of proved value. Quiet and isolation are indicated in every case. Blood transfusion is a promising procedure which deserves further trial. The ideal treatment has not yet been demonstrated.

References

1. Minot, F.: Am. Jour. Med. Sc., vol. xxiv (n.s.), p. 310.

2. Townsend, C. W.: Boston Med. and Surg. Jour., vol. cxxv, p. 218.

3. Idem.: Arch. Pediat., vol. xi, p. 559.

4. Idem.: Boston Med. and Surg. Jour., vol. clii, p. 638.

5. Lespinasse and Fisher: Surg., Gynec. and Obstet., vol. xii, p. 40.


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