History…and future of perinatal asphyxia research

14 Nov

I have added a history of perinatal asphyxia research to the placenta textbook. The association of birth asphyxia with cerebral palsy was first made by Dr. Little, a surgeon who developed a procedure to release the tendon in a spastic limb. The connection was not made by obstetricians not surprisingly because they were not in a position to accumulate the number of cases that Dr. Little saw in referral. It is hardly a novel idea that someone with a different perspective can provide a new insight into a problem outside their own special area of interest, but Dr. Little presents an archetypical example. Not nearly so dramatic, but I think pathology also has a useful perspective to offer obstetrics. For example, I have performed around 2000 perinatal autopsies, but an obstetrician will probably see far fewer than 100 such deaths in a lifetime. To me it is obvious that unexplained intrauterine asphyxia independent of labor is a major cause of intrauterine death. Yet, most obstetrical studies of stillbirth concentrate on risk factors but not on elucidating potential mechanisms of asphyxia. I will be presenting the evidence of the significance of asphyxia in stillbirth on the website, and hopefully I can interest someone.

Historically the most important insights inyo perinatal asphyxia were made by experimentalists. The foremost of these is Dr. Ron Myers. He inherited studies of asphyxia in which a healthy newborn monkey was totally asphyxiated at birth demonstrated a predictable course and onset of neurologic injury. Dr. Myers was also a neuropathologist which enabled him see that the neuronal lesions produced in the newborn monkey acute asphyxia experiments did not correspond to the devastating white and gray matter lesions seen in human cerebral palsy. More importantly he discovered the precise conditions under which the lesions of cerebral palsy can be produced in the fetal monkey. If the monkey has a partial or intermittent asphyxia prior to complete asphyxia, then there is injury to the endothelial blood brain barrier leading to cerebral edema and extensive brain necrosis. It is this one two punch that produces the devastating brain lesions seen with cerebral palsy. Clinically a fetus rescued from a sudden asphyxial event such as prolapsed cord or uterine rupture corresponds to the model producing only neuronal necrosis, and except in extreme prolongation of the asphyxia, will likely suffer less significant brain injury. On the other hand, the fetus with repetitive late decelerations who develops cardiovascular collapse is at risk of severe brain injury even if promptly rescued. The best prevention would be to reverse the mechanism causing fetal hypoxia before the severe asphyxia event. Research to that end would need to start by identifying the mechanisms. Of course some causes can be identified such as uterine tetany, maternal hypoxia, or placental abruption, but there is still a large unknown category.

In the monkey, Myers found numerous antecedent causes of the fetal acidosis including severe maternal stress, but he often manipulated the fetal monkey asphyxia by umbilical cord compression. Many other experimentalists have since used similar balloon cuffs around the umbilical cord to create patterns of partial, intermittent and complete asphyxia. Obviously balloon cuffs are not the natural cause of fetal asphyxia. There remains a role for obstetricians to discover the anatomic mechanisms underlying fetal asphyxia in many patients. It also wouldn’t hurt if research centers maintained and valued sheep physiologists with the expertise to test obstetrical hypotheses about the natural mechanisms of asphyxia. I believe understanding these asphyxia mechanisms is key to lowering Cesarean section rates, reducing cerebral palsy incidence, and preventing some stillbirths.

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