Joseph Bolivar DeLee’s final published article, “The Use of Solution of Posterior Pituitary in Modern Obstetrics,” appeared in 1940 in the Journal of the American Medical Association. In this article, DeLee expressed concern as he had many times before over the use of procedures and drugs on women by unskilled hands, wondering if “we have been at fault in our application of the blessings of science.”
For example, DeLee never advocated for universal adoption of his prophylactic forceps operation. He repeated cautioned against its widespread use, expressing preference that some doctors handle labor expectantly and save the prophylactic forceps operation for specialists.
In this article, DeLee weighs in on many of the same problems that burden the practice of obstetrics today, including the danger of convenience inductions, medicolegal issues and lawsuits for iatrogenic injuries and the need for strict regulation of the claims of the pharmaceutical industry.
Scientists sometimes have an uneasy feeling of doubt whether their epoch making discoveries are really benefiting mankind and try to argue themselves into the conviction that they are improving the social order. Fosdick of the Rockefeller Foundation asks “Can man control the forces he has let loose?”
Carrel says that our stature is not adjusted to the environment which we have created and sometimes what the sciences have given to man has fallen into unsafe hands. Labor saving inventions, he says, have dislocated employment, stunted our mental and physical growth, interfered with improvement of the species which naturally results from the struggle for existence, invited the development of political tyranny, increased the number and magnified the power of death dealing machines, and so on.
Whether or not these charges are borne out in our general social existence, we medical men must admit that sometimes as practitioners, let us say from over enthusiasm or because we believe propaganda, we have been at fault in our application of the blessings of science—anesthesia, asepsis, surgical technic, hospitalization and medication.
The discovery of posterior pituitary’s effect on labor is credited to Henry Dale, who was working on the pharmacology of ergot extracts and found that posterior pituitary affects the smooth muscles of the uterus. According to the book “Drug Discovery: A History ,” the drug was being used by 1909 to hasten labor and “once the risk of rupture of the uterus had been recognized, the administration of extracts was generally restricted until after expulsion of the placenta…” DeLee expressed frustration with the unsubstantiated claims by pharmaceutical companies, who were quick to notice the “lusciousness of the world market with more than 40,000,000 births annually”:
Among these indictments solution of posterior pituitary has been singled out for this symposium. Rupture of the uterus, laceration of the cervix and dead babies follow in the train of its use all too often, yet it is being used more widely than ever. Many preparations of solution of posterior pituitary are on the market, and although they are supposed to be standardized in Vögtlin units they vary not a little in strength and, what is equally important, some of them contain an appreciable amount of protein, which may cause anaphylaxis.
Further, combinations of solution of posterior pituitary with hormones and/or drugs proprietaries under fantastic names—have enjoyed worldwide recommendation and use. Manufacturers have been quick to realize the lusciousness of a world market with more than 40,000,000 births annually, although many in the far countries are beyond the influence of seductive advertising.
It is claimed that these preparations are safer than straight solution of posterior pituitary, that they have virtues of their own which not only reduce the dangers of the oxytocic but also favorably influence labor; and obstetricians are importuned to administer these questionable drugs to all women for the purpose of hurrying delivery.
No convincing physiologic, experimental or clinical evidence has yet been presented to prove that thymophysin, pituthymin, thytuitary and the like are anything more than diluted solution of posterior pituitary or the drug in another guise (Nelson,1 Greenhill,2 Rucker, 3 E. L. King,4 Müller and del Campo, Asher’s laboratory in Berne).
It is significant that only one of these proprietaries has been submitted to the Council on Pharmacy and Chemistry of the American Medical Association and that one was refused approval, its claims not having been substantiated. Pharmaceutic firms advertise solution of posterior pituitary as an oxytocic for special indications but doctors the world over are using it so indiscriminately and the evils of such practice have become so notorious that it is time for the profession to take stock and see where it is going.
DeLee warned against the dangers of “streamlined labor” and the rise in demand for abnormally rapid labors by consumers and doctors alike.
There is an increasing demand among American women for “streamlined labor,” an unhealthy demand fostered by hysterical magazine and newspaper writers and, I regret to have to say, by not a small number of physicians. I have observed quite a number of their results, experienced many abnormally rapid labors, and learned that a streamlined labor can be as safe as a streamlined parachute.
What are the dangers resulting from injection of solution of posterior pituitary? One thinks they all would come from the increase in the violence of the uterine contractions. Most of them do, but solution of posterior pituitary has other evil qualities. It can cause shock which, though seldom fatal, is often ominous and may leave permanent after-effects in the brain. Shock acts like asphyxia. Solution of posterior pituitary upsets the hormone balance in the body. Therefore its use should be avoided in cases of dysthyroidism and diabetes, ergonovine being used instead. In patients with heart disease it may be used only post partum, but here too ergot is better. In cases of threatened eclampsia it is claimed, though I have not yet seen it, to cause convulsions. Indeed Schockaert reports postpartum eclampsia without premonitory symptoms with the use of solution of posterior pituitary.
Here the pure oxytocic principle of the gland is recommended, and the reasons given are that the whole extract, containing the pressor factor, reduces the flow of urine, raises the blood pressure and also directly causes fits. The latest experiments (Bradbury) cause surprise by showing that the pressor factor affects the uterus and is oxytocic—like the true oxytocic factor— which leaves us about where we were before. Perhaps we shall learn that solution of posterior pituitary causes other acute dyshormonisms, which may explain death in labor, the convulsions and anaphylaxis.
DeLee wondered how many deaths were never properly attributed to iatrogenic causes.
Anaphylaxis is not so rare. It shows itself as severe urticaria, violent general or local pruritus, edema of the eyes, face, glottis or lungs, and in some cases as severe shock. A sizable literature is accumulating (McMann and others). But the greatest dangers come out of the increase in the intensity and duration of the contractions of the uterus. These may reach a violence that will rupture the organ if the resistance to the advance of the projectile (the baby) is more than the strength of the wall of the exploding chamber (the uterus). How many cases of pituitary ruptures of the uterus occur will never be known? Either they are not reported at all or the women are buried—purposely without postmortem examinations—under another diagnosis. Many women should have the words solution of posterior pituitary put in their death certificates instead of postpartum hemorrhage, embolism, massive collapse of the lungs, anesthesia or shock.
McNeile in the early days of solution of posterior pituitary had no trouble in collecting sixteen cases of rupture of the uterus. Greenhill gathered twenty-three references from the literature (mostly older) thirty-eight giving cases (two from thymophysin, one from thytuitary) ; Dugger has unearthed three cases, possibly five, in Philadelphia, and all the men to whom I have written replied that they know of uterine ruptures from solution of posterior pituitary but cannot prove them, for reasons already stated. This year two ruptures occurred in Chicago hospitals, one from small doses of solution of posterior pituitary, doses usually considered safe.
I have seen pituitary blast the head through the cervix and the perineum, tearing both extensively, and if it happens when I give the drug it will happen when others give it, but I do not have to quote cases of evil results; the action of the oxytocic can be studied with a tokodynamometer, by looking at and feeling the uterus and by watching the effects on the baby. Of course we obstetricians are grateful to the physiologic research worker who has placed a scientific foundation under our clinical experience. Reynolds and Murphy have shown the actions of the uterus under the influence of solution of posterior pituitary, and those who really understand the mechanism of labor will need no admonition regarding the dangerous (for mother and child) potentialities of the drug. Forces may be set in motion which cannot be controlled.
It has been claimed that combinations of solution of posterior pituitary can be formed which contract the fundus while they relax the lower uterine segment and cervix—but I could not find in this claim an iota of scientific proof. The more rapid dilatation of the cervix is due to the drug strengthening the contractions which force the head, with or without the bag of waters, through the parts, thus canalizing the cervix quicker. One does not have to know much of the mechanism of labor to understand how such violence will destroy the whole internal pelvic architecture which supports the pelvic organs in a manner so admirably adapted to bear the stresses, strains, torques and pressures of the natural functions for which they are intended. Even normal labor puts this well balanced muscular, fascial and connective tissue framework to a severe test. Action of solution of posterior pituitary is ruthless in destroying it and the portals are thrown wide open for the entry of infection. Theory and practice agree, so that statistical proof is not necessary.
I will quote from a letter from a former resident of the Chicago Lying-in Hospital newly located in a large town: “My work is progressing by leaps and bounds. There is a lot of chance for educating people to accept prenatal care and I can spend fifty years repairing the damage done by the injudicious use of pituitary to force stronger labor on the women in the community.”
Solution of posterior pituitary can cause such violent labor pains, combined with powerful bearing down efforts, that the sudden overexertion causes cardiac death.
Uteri stimulated by solution of posterior pituitary not seldom suffer secondary atony with clot retention, thrombosis and embolism.
The effects on babies were not known.
As for the babies, solution of posterior pituitary is of equal if not of greater danger. There is so much ignorance as to the baby’s life processes in utero, and particularly during labor, that one is left with little but to theorize, which is especially true of the possible chemical and hormonal changes wrought in its system by the introduction of such a powerful drug. But one does not have to theorize about the physical effects of solution of posterior pituitary on the baby’s health and life. Those can be seen during labor and at autopsy.
It is known that during a normal labor pain the baby is exposed to augmented pressure from all sides; its gross blood pressure is raised and also there are in its body local fluctuations of pressure which, as the cervix opens, are progressively greater in the direction of the vagina.
This is because the resistance at the uterine outlet is diminished, and it is thus that the child is propelled into the external world. The baby’s head naturally receives the brunt of the fluctuations in pressure, as is so plainly evident from the caput succedaneum and the minute hemorrhages in the scalp, the periosteum and often in the subjacent dura and brain. The physics of the process can be seen and understood every time one squeezes a tube of tooth paste.
The molding of the head is another result of the mechanical forces of the uterus, and its safety for the fetus is only partly guaranteed by the slowness of its execution. Every strongly molded fetal head should be scrutinized at postmortem examination. One will be astonished at the dislocation and deformation of the bones, the distortion of the brain, the overstretched falx and tentorium, with even tiny dehiscences in them, and the minute and larger suggillations. Indeed, ruptures of the falx and/or tentorium are not so rare even in normal labor, and there is no doubt that these membranes occasionally tear and the child apparently recovers without threatening symptoms, i.e, while in the hospital.
Maternal blood pressure begins to be measured in labor:
The “hypodermic manometer” was developed by them at the University of Georgia School of Medicine: It has enabled us to measure the effective maternal blood pressure which supplies maternal blood to the placenta. We have recorded this effective pressure as well as the uterine pressure when pituitary preparations were given to three multiparous patients. Luckily no fatalities have occurred in these experimental studies.
“Pit to distress?”
Our results show that (1) intra-uterine asphyxia and (2) uterine tetany are real dangers associated with the use of pituitary preparations in the second stage of labor. In all three cases it reduced markedly the effective blood pressure to the placenta and produced incomplete uterine tetany which lasted from seven to twelve minutes. In one case intra-uterine asphyxia of the baby nearly occurred. The effective maternal placental blood pressure in this case averaged 85/50 mm. Hg between pains and 65/15 during pains. Pituitary extract reduced this to an average of 30/— 10 mm. Hg for ten minutes and it stayed low throughout the remainder of labor. At one time this effective pressure was reduced to 5/—25 mm. Hg (5 systolic and 25 mm. Hg below zero diastolic pressure).
This meant that the uterus was so contracted that maternal arterial blood not only could not enter the placenta, but that the uterus was actually squeezing blood from the placenta into the mother’s aorta as well as into the veins. The maternal blood supply to the placenta was stopped. The baby’s heart sounds became slow and faint and at one time we were not sure that we could hear them. Fortunately the uterine tetany subsided somewhat, the effective placental pressure gradually increased to nearly normal and the child’s heart sounds became louder and regular. What chemical changes go on in the brain, in the endocrine glands and in the fetal body are not known, but there is enough other information to make one realize that the brain is a very tender organ, that it bears the insults of the forces of labor poorly, and therefore that one should not augment the intensity of these forces without very good reason.
On the contrary, understanding and fearing their power one should rather reduce the forces to the minimum required for the delivery of the child. In this connection a recommendation by Dr. Rawlins of London 150 years ago is of interest. He forbade bearing down in the second stage of labor, insisting that the baby be born by the uterine action alone. He claimed that there were less perineal lacerations and fewer dead babies with this practice. A modern delivery room without “Bear down ! Bear down ! ! Bear down ! ! !” would be quite a curiosity. The harmful action of solution of posterior pituitary in normal labor is thus clear. Solution of posterior pituitary (1) strengthens the uterine power and prolongs its action, (2) shortens the diastolic rest periods and (3) increases the intra-uterine tension by raising the tonus of the muscle—in short, solution of posterior pituitary makes normal pains pathologic and exaggerates all their evil effects on both mother and baby.
DeLee managed to save a colleague from a lawsuit over a case of a six year old boy whose mother’s labor was induced and augmented by posterior pituitary, after the boy’s father approached DeLee for help with the case. Patient advocacy has come a long way.
A totally neglected aspect of the use of solution of posterior pituitary to hurry normal labor is the medicolegal one, but it was brought to my attention recently in a poignant manner: A father brought his spastic and idiotic 6 year old son to me, asking me to appear as expert witness in an action he proposed to bring against his doctor. The doctor had given solution of posterior pituitary to start and then to expedite labor so that he could go on his vacation. The labor was tumultuous, painful and spontaneous and the child suffered a cerebral hemorrhage, diagnosed by four of the city’s leading pediatricians and neurologists as birth injury. I had much trouble in saving the doctor from a lawsuit.
Inquiry of the Bureau of Legal Medicine and Legislation of the American Medical Association brought this reply from Dr. W. C. Woodward, condensed from a long exhaustive opinion:
As far as civil liability is concerned, the question would have to be decided by the testimony of experts in the community testifying as to whether such practice in the individual case represented “due diligence, ordinary knowledge and skill and best judgment”:
“To the foregoing may be added the statement that no professional standard anywhere or at any time could justify a physician in doing anything that would jeopardize the life and well being of mother or infant solely for the physician’s convenience. Moreover, consent by the father or mother, even with a thorough understanding of the matter, would not excuse a physician who deliberately induces and expedites labor solely for his own convenience, to the material danger of the mother and child.” Further, it would be necessary to prove cause and effect.
Experiments at the Chicago Lying-in Hospital:
At present at the Chicago Lying-in Hospital we are experimenting with ergonovine intravenously, injected as a routine when both shoulders have appeared, and we find that it is not to be recommended for general practice. It is useful, like solution of posterior pituitary, after operative delivery and when atonia uteri is feared.
DeLee concluded that posterior pituitary is a boon to science but should not be used without “scientific indication.”
Solution of posterior pituitary is one of the great boons that science has conferred on women, but it should not be used without a clear, generally accredited, scientific indication. It is now being supplanted by ergonovine in many places.