The use of twilight sleep and fetal apnea
Little’s observation of the association of cerebral palsy with obstetrical complications was repeated in the 1930’s under different circumstances. In that period, twilight sleep, using scopolamine, barbiturate and/or morphine, became a popular form of anesthesia during childbirth. In 1938, a neurosurgeon, Dr. Frederic Schreiber, published a study reviewing the doses of this obstetrical anesthetic in relation to the development of cerebral injury in the newborn1. He was looking back on children that he had seen in consultation because of brain injury, much as Little had done in his orthopedic practice. He compared two groups of children, 155 from complicated pregnancies with precipitate, breech, twin or premature delivery, and 345 from normal term deliveries. Then separately he looked at all infants as to whether they had suffered apnea at birth, after birth or both. Approximately two-thirds of infants with brain injury had apnea independently of the type of birth or the type of apnea. In the discussion of the paper, he noted that the expected incidence of apnea at birth was 2%. His conclusion that apnea was associated with neonatal brain injury was strong. Like Little, he found that it was the suffocation that was the problem.
- He had more difficulty demonstrating a relationship of apnea to anesthesia usage. The medical charts often had incomplete information on the anesthesia and/or analgesics given to the patients. Too few patients did not have anesthesia to compare to those with it. Only 7 of his patients were known to have received neither anesthesia and/or analgesics, and 2 of these patients had a history of birth apnea. In the group known to have anesthesia and analgesics, 33 of 86 had a history of birth apnea. The high incidence of infant apnea with obstetrical anesthesia use appeared to argue for a true association, but he was not comparing the incidence of apnea in an unselected population. The overwhelming majority of patients being delivered did not have brain injury in their children. Dr. Schreiber tried to bolster his case by showing an association of a higher dose of anesthesia with a higher risk of infant apnea. He gave drug doses a multiplier related to how many times above the recommended dose that a drug was given and if multiple drugs were given. Forty six mothers had a factor of 2 or less, and 76 had more than that with single outliers having factors of 9,10, and 11! He did not compare his findings to a large unselected population, but it seemed reasonable that infant apnea was related to the iatrogenic overdose of anesthesia.
- The discussion following the presentation of the study presented two sides. Dr. J.C. Litzenberg was positive. He states “Ever since I observed the extremely high percentages of asphyxiated babies at the Frieburg clinic, where Koenig and Gauss developed “twilight sleep”, I have been apprehensive of such extreme cases of apnea.…the question of relieving the pain of labor must be reevaluated, and the remote results and not only the immediate apparent results being kept in mind”. The other discussant, Dr. Charles E. Galloway took a different tact. He stated “…I feel that women in childbirth deserve to have as much pain relieved as possible with safety.” He believed that the high doses quoted in the paper led to increased infant mortality and brain damage. He interrogated 11 of his colleagues and concluded that “the consensus among the men treating such cases is that mental damage does not occur.” He excoriated the use of the high doses of drug and concluded that more study was needed. He states that “Since the world began, about 2% of the population has been born defective mentally and it may be that a baby is cyanotic at birth because it is mentally deficient”.
- Schreiber noted “ The fact they [mothers] are in labor does not protect them against the effects of toxic doses. The usual and most alarming effect is respiratory depression. If the mother must contend with drug-induced respiratory depression in addition to the natural exigencies of childbirth, the fetus must also, being dependent on the mother for its oxygen supply until actually born, suffer from the same respiratory depression and at the same time go through the intensely traumatic experience of being born.” The mothers like their infants were not receiving modern respiratory support. Even Dr. Galloway admits that “there have been only two maternal deaths among the patients receiving the drugs”. He does not say the deaths were due to the drugs, but they certainly could have been.
- From today’s perspective, it is hard to understand what was actually occurring to the brain damaged infants from mothers with twilight sleep. Were the infants apneic because they were anesthetized? How were those apneic infants treated? What was really meant by the later onset apnea? The answers have to be teased from the textbooks of medical practice at the time. They also have to be put in perspective of research on fetal asphyxia that would not occur until a decade or more after Dr. Schreiber’s paper. Like Dr. Little before him, Dr. Schreiber could accumulate insight not available to individual obstetricians. Unlike Dr. Little, his observations could be acted on. He did not show that the anesthesia caused brain injury, but only that its use led to apnea and brain injury. The understanding of the complex relationship between apnea and brain injury would become clearer with future studies in experimental animals. Dr. Schreiber’s view eventually won out and obstetrical anesthesia was abandoned.
- As an obstetrical resident in 1975, I still heard stories about the horrors of “twilight sleep” with mothers who were zombies and did not recall delivering their infants. The theory was that this damaged the mother-infant bond. Certainly as a pathologist, I have no insight into the psychology of childbirth. However, during my year as an intern in obstetrics at the peak of mothers going “natural”, I did experience the rooms full of women screaming with the pain of labor despite all the Lamaze training. Our medical repertoire of pain relief in that period was limited to intravenous Fentanyl, a short acting narcotic, and pudendal nerve block given vaginally with very long needles. These seemed to help only a little. Human labor may have been this painful for eons, but it seemed like a process that was in need of fixing. Epidural anesthesia was a novelty back then, but fortunately it eventually provided acceptable obstetrical anesthesia with the mother fully conscious.
Reference
- Schreiber F. Apnea of the newborn and associated cerebral injury A clinical and statistical study. JAMA 1938;111:1263-9.
obstetrical pathology 