Before August 2003, Raquel, Nicole, Verônica, Gabriel, Lucas, Vitória and Gabriela would have been children running a serious risk of showing mental retardation and total or partial paralysis of the legs. These problems are the result of a malformation that can be identified by the doctors during pregnancy named myelomeningocele, which blocks the complete development of the spine and leaves the spinal medulla of the fetus exposed. In a surgery of an hour and a half, the obstetrician makes a cut like that of a cesarean into the womb and another of 9 centimeters into the maternal uterus. Then, through this opening, another doctor, a neurosurgeon, corrects the defect in the baby’s spine, which continues in the abdomen of the mother until birth.
Brazil is the second country, along with the United States, to carry out this type of operation, called open fetal surgery. Done for the first time in the country the year before last, the procedure is experimental: neither the Brazilian doctors nor the American doctors are certain that the benefits are greater than the risks. Two distinct teams, one from the State University of Campinas (Unicamp) and the other from the Federal University of Sao Paulo (Unifesp), have already carried out eight open fetal surgeries: six of the babies have been born and are well and one should be born this month. The other, the first to undergo this type of surgery in Brazil in 2002, died.
Even though the success has not been total, the results obtained up until now can well be considered promising. Complications exist, but are much milder than if the babies had undergone surgery to correct their spinal defect after birth, the only previous possible alternative treatment. Besides this correction of the spine, done on the same day as the delivery, the majority of these children would probably have needed further surgery, three days afterwards, to implant a permanent valve in the brain, destined to eliminate the accumulation in the cranium of liquid which bathes the central nervous system, the so called hydrocephalus, the main consequence of myelomeningocele, a common illness that affects one in every thousand children the equivalent of 300 babies per year only in the city of São Paulo.
Firm steps
At the Unifesp hospital, the team led by the obstetrician Antonio Fernandes Moron operated on six babies, of whom five have already been born. Four of them move their legs well and are free of hydrocephalus, which jeopardizes the development of the nervous system and can provoke mental retardation. The fifth baby showed a moderate level of hydrocephalus and has received a valve, according to the child neurosurgeon Sérgio Cavalheiro.
In themselves these results are an indicator of the viability of the technique, since 85% to 90% of the babies who are born with an open spine have hydrocephalus and require the implant of a drain in the brain to re-stabilize the normal circulation of this liquid, known as the cerebrospinal fluid. The placing of this drain in not without its problems: it reduces by 20% the child’s mental capacity, according to studies by Joseph Bruner, from Vanderbilt University, in the United States, the coordinator of one of the three American teams capable of treating babies inside the uterus.
In order to close the opening on the spine sooner, the fetal surgery diminished the exposure of the spinal medulla and of the nerves linked to the mobilization of the legs, to the liquid that surrounds the baby in the uterus the amniotic fluid, which, for unknown reasons, can damage the medulla and the nerves.
Thus, it is possible to reduce the risk of paralysis of these limbs. It is for this reason that Raquel, the first Brazilian baby born after open fetal surgery, may be able to walk without the need for any mechanical device. If she had undergone the surgery after birth, her chances of managing to move using a wheel chair would have been 45% and to walk without the help of a walker or crutches only 7%. “If the benefit is not total, at least the complications were mitigated “, says Moron, who, along with Carlos Almodin, from the Unifesp team, developed a Brazilian version of the reutilization of the trochanter, the equipment used to make the opening in the uterus, currently imported at a cost of up to US$ 500.
On March 1st Lucas was born in Campinas, four months after having been operated on by the team of obstetrician Ricardo Barini, of Unicamp. The first surgery performed by the group in December of 2002, was not successful: the placenta separated and the fetus died shortly after the delivery. In Lucas’s case, the surgery reduced the damage caused by the myelomeningocele and hindered the advance of hydrocephalus.
He was born during the 35th week of pregnancy, almost nine months, while the majority of children with this defective congenital are born very much more premature, around the 32nd week the risk of a premature delivery is one of the reasons that led the doctors to hesitate in carrying out open fetal surgery. “If the initial lesion had not been not corrected, Lucas would certainly never have moved his legs”, explains Lourenço Sbragia Neto, the team’s surgery coordinator. “Now we have the hope that he might even walk.”
Although pursuing the same objective, the two teams adopted distinct criteria for the selection of the babies who held the necessary requirements for the operation. The Unicamp group followed the norms established by the National Health Institutes (NIH) of the United States, which only recommends fetal surgery for myelomeningocele when the mother is healthy and is between the 19th and 25th week of her pregnancy (between the end of the fourth and the beginning of the sixth month). In the case of the baby, the lesion on the spine must be located between the first thoracic vertebra, at the height of the arms, and the first sacral, close to the waist.
“The improvement in hydrocephalus is small after the 25th week”, says Sbragia. “After this period it is better to wait until the baby is born before operating”, adds the researcher, who directs the fetal experimental surgery laboratory at Unicamp here, one of the ongoing studies deals with the inflammatory effect of the amniotic fluid upon spinal medulla of the fetus of rats.
In a study carried out with 104 children submitted to open fetal surgery and another 189 treated in a conventional manner, North American doctors at the Vanderbilt University and the Children’s Hospital of Philadelphia verified that the incidence of hydrocephalus is similar among the babies operated in the uterus after the 25th week of pregnancy and those submitted to surgery to correct the spine after birth.
Another conclusion: 75% of the fetuses operated within the mother’s abdomen after the 25th week needed the implant of a brain valve after birth, while only a half of those operated upon before the 25th week of pregnancy needed to go through the second surgery. This number rose to 85% among the babies who are only operated upon after birth. The Unifesp doctors carried out the surgery on the fetus of the maternal uterus up until the 27th week of pregnancy (the end of the sixth month).
Under evaluation
In the United States the National Health Institutes are funding a large-scale study, with a budget of US$ 25 million, destined to uncovering the doubts about which type of surgery before or after birth is the more efficient to correct myelomeningocele. The project entitled Management of Myelomeningocele Study (Moms) should, until August of 2008, evaluate the results presented by one hundred children who will go through correction of the spine in the uterus and a further one hundred operated after their delivery.
While the Moms results do not come out, better than attempting to minimize the damages caused by myelomeningocele is to prevent its appearance, associated to genetic defects and diet poor in folic acid which is found in vegetables and red meat. For this reason, doctors are telling women who want to have children that, two months before becoming pregnant, they should take supplementary doses of folic acid, in a preventative therapy that should last until the end of the third month of pregnancy. The extra consumption of folic acid avoids the recurrence of myelomeningocele in up to 72% of the cases of families who have already had a baby with a problem.
The Project
Morphological, Histological and Biochemical Evaluation of the fetuses of Sprague-Dowley Rats, Submitted to Experimental Intra-uterus Gastroschisis At Different Gestation Stages (nº 02/02563-8); Modality Regular Line of Research Project Assistance; Coordinator Lourenço Sbragia Neto Unicamp; Investment R$ 226,889.18
