Early mythologies express a deep reverence for the mystery of birth. The stars, the mountains, and the oceans are all described as having been issued from some wonderful and hidden generative force. Human birth is in many ways equally mysterious. Modern science enables doctors to detect conception shortly after it has occurred and to visualize embryos moving in the womb, but most aspects of fetal development are invisible to the scientific eye. Injury occurring during the sensitive early stages of fetal growth may go undetected until well after a baby is born.
The events that comprise fetal brain development are perhaps the most scientifically elusive aspect of prenatal life. Although very little is known about the causes of brain injury during early development, chronic brain injury can result in a condition called cerebral palsy. According to the United Cerebral Palsy Organization, cerebral palsy affects over 500,000 children and adults in the United States alone with an annual cost well into the billions of dollars. While we cannot at present cure cerebral palsy, new research on placental screening may offer some insights into prevention, and might provide scientists with a clearer picture of fetal development.
Defining Cerebral Palsy
Neural damage occurring during early fetal development has the most obvious effects on muscle control. Cerebral palsy is a condition characterized by motor dysfunction – uncoordinated muscle movement, or palsy. This motor dysfunction can be grouped descriptively into three types: spastic palsy (stiff movement), athetoid palsy (uncontrolled, involuntary movement), and ataxic palsy (loss of balance). Individuals with cerebral palsy often exhibit some combination of these motor problems.
Cerebral palsy typically involves injury to multiple sites in the cortex, and so it is not necessarily limited to motor dysfunction. Concurrent problems may include a loss of general balance, difficulty with speech and hearing, impaired vision, learning disabilities, and seizures. The dysfunctions associated with cerebral palsy are difficult to diagnose in newborn infants because a baby may exhibit apparent neurologic abnormalities very early in life, yet ultimately develop normally. Consequently, cerebral palsy is almost never diagnosed before children are 6 months to 1 year of age. Once detected, cerebral palsy can be managed with a physical therapy regime, and though it cannot cure the condition, physical therapy can teach individuals effective coping strategies. While these coping strategies may minimize the effects of cerebral palsy on an individual’s life, the underlying condition neither regresses nor progress.
What Causes Cerebral Palsy
During early brain development, neurons form at an astonishing rate — about 250,000 neurons every minute during the peak phases. In fact, far more connections are formed in the brain of an infant than will be retained in adulthood. One advantage of this excess of neural growth is that the developing brain becomes tolerant of damage. A young brain has sufficient neural redundancy that injuries that would be catastrophic in an adult brain might have only a moderate effect on an infant.
Ironically, this tolerance for injury helps to explain why the pattern of trauma called cerebral palsy is found so predominantly in infants. Cerebral palsy is caused by sustained, chronic injury to the brain; though an infant’s brain is damaged by this type of injury, an adult brain would be unlikely to survive such an insult.
Cerebral palsy is associated with several different types of injury that can affect a developing infant’s brain. Indirect forms of injury include premature delivery and intrauterine infection, both resulting from maternal conditions (Grether, JK., Nelson, KB.). An infant’s brain can also be injured directly from infection mediated by a class of molecules called cytokines and from anoxia. Karen Nelson and her colleagues at the National Institutes of Health have described the role of cytokines in fetal brain injury (Nelson, KB., Dambrosia, JM., Grether, JK, et al). Cerebral palsy is most often correlated with anoxic injury, damage to brain tissue that results from oxygen starvation. Neural tissues might be deprived of oxygen for several reasons; premature birth may cause bleeding into the infant’s brain, awkward fetal positioning may block the baby’s airways, small blood clots can cause strokes, and the baby’s placenta can detach from the mother prematurely (in some cases because of infection and the production of cytokines). In each of these cases, cerebral palsy is most likely to result if the injury is repetitive or sustained and occurs before or during birth. Sudden, traumatic injury can also induce cerebral palsy, but these cases are rare.
Doctors in the United States have made aggressive, but unsuccessful, efforts to control the types of fetal injuries believed to result in cerebral palsy. These efforts have included very close monitoring of the fetus and its environment for abnormalities in heart rate, amniotic fluid composition, or fetal positioning. Any abnormality might prompt doctors to perform a caesarian section instead of a standard vaginal delivery. In fact, 20 to 25 percent of all deliveries in the United States are currently performed by caesarian section for this very reason, compared to just 5 percent of deliveries in, for example, Ireland. However, because cerebral palsy is the result of chronic injury to the brain before the time of delivery, caesarian section as a strategy for preventing cerebral palsy does not work. In point of fact, the frequency of cerebral palsy is approximately the same in United States as it is in Ireland, suggesting that new approaches to prevention of the condition are urgently needed.
New Research Techniques
The types of chronic prenatal brain injury that lead to cerebral palsy are often subtle and difficult to detect. A whole host of identified maternal risk factors exist, for example hypertension and smoking, but many cases of cerebral palsy are not correlated with these risk factors. The medical community remains frustrated in its attempts to either predict or to reduce the incidence of cerebral palsy in newborns.
New research conducted by Dr. Frederick Kraus at the St. John’s Mercy Medical Center in St. Louis suggests a better alternative for predicting, and eventually preventing, some of the causes of cerebral palsy. In the July 1999 issue of Human Pathology, (Kraus, Frederick T., Acheen, Viviana l.) Dr. Kraus and his colleagues report findings from their study of perinatal autopsies. They found that a significant number of infants who had tiny blood clots called thrombi in the fetal vessels of the placenta, also had such clots in their developing organs. The study showed that within the delicate tendrils of blood vessels supplying a fetus’s brain, these thrombi caused infarct, or stroke, resulting in cerebral
Blood Screening for Pregnant Mothers
During a recent interview, Dr. Kraus remarked that the placenta is “the baby’s most important organ before and until it is born.” He pointed out that traditionally, little attention is paid to the placenta as a source of insight into fetal development. Critics argue that since the placenta isn’t accessible until after a baby is born, any problems placental analysis can reveal are historical. Nonetheless, Dr. Kraus’s study shows that the placenta can reveal quite a lot about the conditions in which a fetus ultimately developed — in particular, that blood clots in the placenta are highly predictive of blood clots in the fetal brain.
“If you could identify clotting cases early, based on the mother’s medical history, you might be able to prevent cerebral palsy” Dr. Kraus said, “This requires screening mothers who are pregnant for coagulopathy (a blood clotting disorder). Right now, women with clotting disorders are normally not screened unless they have miscarriages because the testing is very expensive…If the link between thrombi and cerebral palsy can be established, then screening for coagulopathy becomes very important, and we could screen more affordably if we did it more often.”
Hope for Prevention
If Dr. Kraus is right, then studying placentas could provide the insight into cerebral palsy that the medical community has been looking for. He is now tracking a large group of liveborn infants whose placentas showed thrombi in the fetal circulation to determine what fraction of those infants ultimately develop cerebral palsy. If he finds a strong correlation between thrombi in the placenta and the development of cerebral palsy, Dr. Kraus’s research may offer hope to a significant population of women at risk for coagulopathies that could threaten their children.
Still, much work remains to be done, and preventing fetal brain injuries that result from blood clots represents just one approach to a larger story. Placental abruption (early detachment of the placenta from the uterus), neonatal cytokines, and blood clotting factors also have the potential to injure the developing brain. But Dr. Kraus’s study demonstrates that previously neglected sources of information such as a baby’s placenta can provide invaluable insights into prevention of developmental injury, and may allow medicine to further unveil the shrouded mysteries of prenatal life.
Ashish Ranpura earned his bachelor’s degree in neuroscience at Yale University, where he studied the cellular basis of learning and memory. He began his career in science journalism at National Public Radio’s “Science Friday,” and continues to be deeply interested in promoting public understanding of science. He is currently conducting research on cognitive development underlying number perception and arithmetical skills.
References:
Grether, J. K., & Nelson, K. B. (1997). Maternal infection and cerebral palsy in infants of normal birth weight. JAMA, 278, 207-211.
Kraus, F. T., & Acheen, V. I. (1999). Fetal thrombotic vasculopathy and cerebral palsy. Human Pathology, July.
Nelson, K. B., Dambrosia, J. M., Grether, J. K., et al. (1998). Neonatal cytokines and coagulation factors in children with cerebral palsy. Ann Neurol, 44, 665-675.
