William H. Clewell performed surgery on a hydrocephalic fetus by placing a shunt to allow the removal of fluid from the brain before birth, leading to more normal brain development.
In the late 1970’s and early 1980’s, fetal medicine was expanding in several fields. More treatment options for the fetus had been made possible over the previous decades as new techniques were developed for recognizing and managing anatomical and physiological problems. Fetal blood transfusions were begun in the 1950’s as a treatment for erythroblastosis fetalis, the destruction of fetal red blood cells by the immune system attack of an Rh-negative mother against her Rh-positive fetus. This allowed the birth of babies who would otherwise probably have died in utero. By the early 1980’s, fetal surgery also was being performed by opening the mother’s abdomen and uterus and operating on the fetus, usually after removing the affected portion of the fetus from the uterus. Such a major operation would nearly always necessitate a cesarean delivery later. Emphasis was placed on trying to develop techniques to correct abnormalities with the least invasiveness for both the mother and the fetus.
A major improvement in the recognition and treatment of fetal aberrations was the result of technological improvements in ultrasound imaging and the ability to interpret what was visualized by this process. Diagnosis of brain enlargement in the fetus by ultrasound became possible in the 1970’s. A fetus with hydrocephalus (literally “water in the head”) develops ventriculomegaly, or enlarged brain ventricles, the cavities that contain cerebrospinal fluid. This abnormality produces thinning of the cerebral lobes and skull enlargement that generally causes difficulties in normal delivery. Mental and physical retardation most often accompany the physical deformities of the head. Fluid buildup occurs as a result of blockage of the pathway by which cerebrospinal fluid normally enters the bloodstream. It was recognized that if another way could be found to drain off the excess cerebrospinal fluid, perhaps the head enlargement and cerebral thinning could be prevented, allowing for more typical development before birth.
In 1981, William H. Clewell and his team of physician-scientists developed a means of treating this problem by placement of a shunt in the head of an affected fetus, thereby allowing the excess fluid to drain into the surrounding amniotic fluid. At the time of this innovative treatment, Clewell had previous experience in treating fetuses, having transfused blood numerous times over the previous four years into fetuses that were affected by erythroblastosis fetalis. The precise placement of the transfusion needle into the fetal abdomen was possible with guidance by ultrasound.
The parents of the hydrocephalic fetus that Clewell treated by shunt placement had a previous son born with congenital hydrocephalus. This was caused by the presence of a defective X-linked gene for aqueductal stenosis, or narrowing of the passage by which fluid is normally removed from the brain. The second pregnancy was being carefully followed, and it was recognized that the male fetus definitely was affected at twenty-one weeks of gestation, about halfway through the pregnancy. The parents did not wish to consider an abortion and wanted treatment of the fetus to limit or prevent damage caused by the hydrocephalus.
Clewell and a team of two other obstetricians, two radiologists-ultrasonologists, a neurosurgeon, and a bioengineer were involved in this treatment. A miniature shunt was designed by John B. Newkirk, the bioengineer, to be placed in the skull of the fetus as a drainage route for excess fluid. It was constructed of medical-grade Silastic tubing with a valve that would limit the rate of outflow of cerebrospinal fluid and prevent backflow of amniotic fluid into the brain. The shunt was put into place in the fetal skull at twenty-three weeks of gestation, when the ultrasound measurements showed that ventriculomegaly was increasing.
Although this process was a surgical procedure, there was no need to open up the mother’s abdomen and uterus to treat the fetus. The shunt had been designed so that it could be passed into the fetal head through a blunt needle with a pointed stylet attached. The needle and stylet were clearly visible with ultrasound and could be guided indirectly by looking at the real-time images on the computer screen. It was thus possible to use local anesthesia to allow a small incision in the skin and abdominal fascia of the mother. The uterus was entered only with the needle, and the shunt was passed through the needle into the head of the fetus. The ventricles could be visualized clearly with ultrasound, and shunt placement was similar to that used in an infant, although this placement was done by looking at the screen rather than at the infant’s head to place the tubing. The needle and stylet were withdrawn, leaving the shunt correctly in place, as determined by ultrasound. The fetus showed no distress at the procedure, and only sporadic uterine contractions that soon stopped were produced as a result of the treatment. The process was much less invasive than surgery that would allow the fetal head to be seen directly for shunt placement, and the risk of fetal loss from surgery-induced premature birth was reduced.
As a result of the shunt placement, the size of the fetus’s ventricles decreased and cerebral thickness increased over several weeks. Measurements through thirty-two weeks of gestation showed that the shunt was performing as desired. Examination at thirty-four weeks, however, showed increased ventricular size, presumed to be the result of obstruction of the shunt. The mother was treated with a drug to induce maturation of the fetal lungs, because the normal time of delivery is about forty weeks. The baby was delivered at thirty-four weeks’ gestation by cesarean section. The shunt was found to be completely blocked by growth of tissue. The vigorous, active infant was examined soon after birth by ultrasound and computerized tomography (CAT scan), both of which confirmed the need for a shunt. The original prenatal shunt was removed, and a new shunt was put in place to divert fluid into the baby’s peritoneal cavity. When examined at thirteen weeks after birth, the child showed some physical delay, but by eighteen weeks, he showed improved strength and coordination and had learned to smile.
In the early 1980’s, there were numerous investigations dealing with the prenatal treatment of abnormal fetuses. The use of ultrasound was replacing fluoroscopy (X rays) as a means of visualizing the movement of structures within the body, particularly in the developing fetus. Technology was producing greater resolution in ultrasound, so more detail could be distinguished in earlier fetuses. Research in animal systems, particularly the fetal monkey and fetal lamb, was leading to greater familiarity with the development of hydrocephalus and possible ways to treat it. In these animal studies, however, it was common to pull the fetal head out of an incision in the uterus, both to induce hydrocephalus artificially and then later to treat it. Michael R. Harrison and a group at the University of California, San Francisco, were involved in these studies, placing shunts in lambs and monkeys with hydrocephalus induced by chemical treatment with a teratogen (an agent that causes developmental malformations). Maria Michejda and Gary D. Hodgen
A relatively noninvasive clinical treatment for hydrocephalus used before Clewell’s procedure involved repeatedly puncturing the fetal skull and brain to draw off fluid, a process called cephalocentesis. Jason C. Birnholz
Clewell’s procedure was recognized and referenced in numerous papers on prenatal hydrocephalus following his report of the process. The report did not appear to have had much effect on perinatal management of hydrocephalus, however, and there was no immediate increase in the use of the treatment. This resulted from the fact that many cases of recognizable prenatal hydrocephalus are accompanied by other abnormalities, and a simple treatment, such as shunting, can correct only the physical condition of ventricular enlargement.
While shunting can be important in certain cases, such as the X-linked hereditary condition of aqueductal stenosis in Clewell’s patient, it is not as useful in other forms of hydrocephalus. This point is illustrated in a case report by Frigoletto and colleagues in November, 1982, in which they used a shunt similar to Clewell’s to treat a fetus that had other anomalies as well as hydrocephalus. The baby died at five and one-half weeks of age of cardiac arrest, apparently caused by these other anomalies. Investigators recommended several conditions under which prenatal treatment for hydrocephalus would be advisable: when detection of hydrocephalus is too early to wait for birth and postnatal shunting; simple obstructive hydrocephalus, not associated with other major developmental problems of the brain or other systems; no chromosomal aberrations; progressive ventricular enlargement; and a team of physicians representing different disciplines involved in treatment.
Clewell and others reported on the evaluation and management of ventriculomegaly in 1985, describing the fetal surgery approach as experimental. They listed reasons to include or exclude a fetus from this treatment. Inclusion would be possible only if there were progressive ventricle enlargement and cerebral thinning, gestational age at shunting less than thirty-two weeks, a single fetus, and no other significant detectable abnormalities. Exclusion from consideration would occur in the case of twins, gestational age great enough that birth could soon occur and treatment could then take place, or the presence of other anomalies. Five pregnancies were discussed in this report in which shunts were placed. Two of the resulting children were normal at two and three years of age, two were severely retarded at three years, and the last fetus was electively aborted after the shunt was placed. These results suggest that, in some cases, the treatment completely corrects the effects of hydrocephalus. In another paper in 1985, Clewell and coauthors again stressed the poor prognosis for most hydrocephalus detected prenatally. Studies done by a team at Yale University Medical School, led by F. A. Chervenak
Additional severe abnormalities often are present in fetuses that show ventriculomegaly, even if the abnormalities are not detectable before birth. With early detection and fully informed decisions by parents, often the chosen course with fetal hydrocephalus is elective abortion. In a small number of cases, Clewell’s approach to prenatal treatment works very well, but in the majority of cases of ventriculomegaly, death or severe retardation occurs. Careful selection is necessary to determine which fetuses may benefit from this treatment.
The International Fetal Medicine and Surgery Society implemented a moratorium on shunting procedures for fetal hydrocephalus in 1985. However, improvements in fetal imaging and diagnosis has led some to call for reconsideration of this moratorium, since one of the problems with the shunts centered on poor selection of fetuses most likely to benefit from the procedure, and new knowledge provides a way to rectify this problem.
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Chervenak, Frank A., Glenn Isaacson, and John Lorber. Anomalies of the Fetal Head, Neck, and Spine: Ultrasound Diagnosis and Management. Philadelphia: W. B. Saunders, 1988. Written for the physician who deals with ultrasound and neurological disorders; provides much information to the lay reader as well. Covers the normal anatomy of the brain and spinal cord of the fetus, and shows how the anatomy is envisioned by the use of ultrasound. Includes photographs of neural structures as they develop at different stages of gestation. Discusses diagnosis and prognosis of fetal hydrocephalus, with a very brief mention of shunt placement for prenatal treatment. -
Clewell, William H., et al. “Placement of Ventriculo-Amniotic Shunt for Hydrocephalus in the Fetus.” New England Journal of Medicine 303 (October 15, 1981): 955. A very short communication that first announced the event. Written while the pregnancy was still in progress. -
_______. “A Surgical Approach to the Treatment of Fetal Hydrocephalus.” New England Journal of Medicine 306 (June 3, 1982): 1320-1325. Describes the team of physicians who developed and placed the shunt to treat fetal hydrocephalus as well as the shunt itself and the procedure of placement. Includes numerous sonograms to show reduction of fluid in the ventricles after shunt placement. A photograph shows the shunt still in place shortly after birth of the child. -
Frigoletto, Fredric D., Jr., Jason C. Birnholz, and Michael F. Green. “Antenatal Treatment of Hydrocephalus by VentriculoAmniotic Shunting.” Journal of the American Medical Association 248 (November 19, 1982): 2496-2497. A case report that briefly describes a shunt treatment that failed to work, followed by a second shunt on the same fetus that did allow fluid drainage. Includes recommendations for guidelines to be used in selecting cases for treatment. -
Harrison, Michael R., ed. The Unborn Patient: Parental Diagnosis and Treatment. 3d ed. Philadelphia: W. B. Saunders, 2001. A major resource covering prenatal anatomical and physiological disorders, although out of date for current methods. Discusses fetoscopy and fetal sampling methods, as well as congenital hydrocephalus. Includes numerous photographs and sonograms to show what could be seen in ultrasound observations of the affected fetuses. -
Harrison, Michael R., Mitchell S. Golbus, and Roy A. Filly. “Management of the Fetus with a Correctable Congenital Defect.” Journal of the American Medical Association 246 (August 14, 1981): 774-777. Contains a useful set of guidelines for assessing the means of management of congenital malformations of the fetus. Prenatal hydrocephalus is included in the group that may require intervention in utero, which may include the use of a catheter, or shunt. -
Levene, Malcolm I., et al. Fetal and Neonatal Neurology and Neurosurgery. 3d ed. London: Churchill Livingstone, 2001. A large volume that covers the subject in depth for physicians. Includes numerous chapters by various contributors on the normal and abnormal aspects of neurological development in the fetus and infant. A section on imaging shows how to interpret ultrasound images. A section on defects of the neural tube discusses diagnosis and management of hydrocephalus, and two chapters on fetal ventriculomegaly and infantile hydrocephalus are covered under neurosurgery. -
Michejda, Maria, and Gary D. Hodgen. “In Utero Diagnosis and Treatment of Non-human Primate Fetal Skeletal Anomalies: 1. Hydrocephalus.” Journal of the American Medical Association 246 (September 4, 1981): 1093-1097. Discusses research in the experimental production of fetal hydrocephalus in monkeys and the subsequent treatment of the disorder by placement of a screw-type shunt or vent to allow outflow of cerebrospinal fluid from the enlarged brain ventricles.
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