Now that baby Lucas is calmly carrying on
with his life, surgeon talks about perspectives of fetal surgery


Inside the maternal sanctuary

LUIZ SUGIMOTO

O Professor Lourenço Sbragia Neto, who participated in the first successful surgery for a baby inside the womb at Unicamp, returned to the topic exactly on the day Lucas turned three months old. Now that the media spotlight has been turned off, the doctor addresses ethical issues surrounding the so-called open fetal surgery, the stage at which fetal medicine is in Brazil and the studies underway at the “Michael Harrison” Experimental Laboratory – which he has just been set up with resources from Fapesp – to improve techniques aimed at eliminating or mitigating congenital defects. Lucas was born on March 1st and had undergone an intrauterine intervention in December carried out by the fetal medicine and surgery team coordinated by obstetrician professor Ricardo Barini, due to a lumbar injury that would prevent the movement of his legs and compromise his mental functions.

“Making a normal baby is the desire of any pregnant woman”, highlighted Lourenço Sbragia in an editorial for the internal newspaper of the Faculty of Medical Sciences (FCM), in which he summarized the learning, achievements and hardships of the Fetal Medicine Group at Unicamp , including the impact of the loss of Valéria's baby, who died during the first intrauterine surgery performed by the team, due to placental abruption. In the article, the researcher highlights that scientific advances have allowed “entering the sanctuary of the maternal amniotic cavity and carrying out a series of fetal surgeries on humans carried out in the open, that is, opening the maternal uterus, operating on the fetus, closing the uterus and monitoring the pregnancy until resolution.”

This academic tone, however, will never be seen in personal contact with Lourenço Sbragia. So much informality surprises those who measure people only by their CV. Graduated from USP in Ribeirão Preto, the doctor chose pediatrics, which he studied for two years, followed by pediatric surgery for another five years; the master's degree was also obtained at USP, the doctorate at Unicamp and the post-doctorate in fetal surgery and neonatal surgery at the University of California San Francisco (UCSF), where he learned what he knows from professor Michael Harrison, who names the new laboratory and is considered “the father of fetal surgery”. “Thank the good Lord, I’m making progress”, he jokes. The abuse of slang and inflammatory statements, typical of young idealists, camouflage his age of 41 years. “You can’t imagine how desperate these mothers are, man!”

The professor refers to the anguish not only of pregnant women who learn about congenital defects in their babies, but also of those who are later advised against resorting to fetal surgery, as sometimes the risk is great for themselves or for the child that will surely be born. premature. “It is very difficult and embarrassing to notify families that the fetal operation will not be performed. It's like taking them off 'Schindler's list'. If, to improve the health of their babies even a little, we asked these mothers to jump from the Eiffel Tower, they would jump.”

Projects – Financing of R$ 226 thousand from Fapesp allowed the Experimental Laboratory to be equipped with a physical structure – computers, software, microscope and other equipment – ​​comparable to what Lourenço Sbragia had in the United States. “No complaints. But in terms of government support, for example, we are in prehistory and the Americans are on Mars. We are achieving relevant research thanks to the commitment of the students who work in the laboratory, a dedication that can only be justified by something that I would define as a 'craving' for science. It's a shame that these boys are not valued in Brazil; If they were abroad, they would burst the balloon”, protests the professor.

Experiments in the laboratory are carried out with rats. Roughly speaking, what is done is to produce congenital defects in fetuses, in order to operate on them and evaluate procedures and results. It may sound cruel to laypeople, but it was experiments like these that led to techniques that mitigated the effects of myelomeningocele (MM) in Lucas and six other babies operated on at Unifesp. MM, for those who didn't see the national news in March, is a malformation that prevents the spine from closing and leaves the spinal cord exposed, causing hydrocephalus which in 80% of cases leads to mental retardation, in addition to total or partial paralysis of the legs. .

Among the studies on this disease at the moment, Sbragia is guiding scientific initiation student Maria Weber Guimarães, who has a grant from Fapesp to formulate a new model of MM in rats: a huge number of measurements, dates, medications, etc. “Few groups in the world perform fetal surgery on such a small model”, explains the researcher, who in this work has the collaboration of professors Francesco Langone and Luis Violin, from the Institute of Biology.

Another associated project, with Professor Alberto Cliquet, an electronics engineer linked to the Department of Orthopedics, concerns a pacemaker for the development of the injured spinal cord. The idea is to implant a miniaturized neuron stimulator in the rat, which will be connected by wires to the fetus, with the hope that it will promote the growth of the neuron damaged by MM. “It sounds like a 'Mané' thing, but if this works perhaps we could, in the future, puncture the pregnant woman's uterus with a thin tube like a pen, implanting a neurotransmitter and promoting the growth of the compromised spinal nerves. Instead of performing fetal surgery, which is aggressive, we would place a chip in the baby's spine during pregnancy to minimize the neuronal damage caused by the defect. Logically, these are hypotheses that we are going to test”, explains Lourenço Sbragia.

Deadly hernia – There is a disease called congenital diaphragmatic hernia (CDH), which occurs in 1 in every two to three thousand births. The diaphragm, the muscle that separates the chest from the abdomen, has a hole, allowing the intestines to pass into the chest and ends up preventing lung growth. Even with prenatal diagnosis, 50% of babies born with CDH die. “The lung does not need to function inside the uterus, but if the umbilical cord is cut, the lung must expand. A beautiful, perfect baby dies because the lungs do not grow and do not carry out gas exchange properly. In developed countries there are special neonatology reference centers where routine treatment is possible, after birth, with a type of artificial lung called ECMO. It turns out that the treatment is very expensive. In Brazil, with rare exceptions, if a child is born with severe CDH, they die.”

An alternative being studied is the introduction, through intrauterine surgery, of a plastic microballoon into the baby's trachea, a technique called tracheo-occlusion. When the trachea is closed, the amniotic fluid produced in the lungs is prevented from escaping, which then expands and pushes the intestine downwards. Anderson Gonçalves and Alexandre Iscaife, scientific initiation students (Pibic/CNPq scholarship) who study lung development, managed to perform this tracheo-occlusion in 18 and a half day old rat fetuses. “The original work was started in the USA during postdoc with 19 and a half day old rats and was on the cover of the American Journal of Physiology. Here, with two medical students, we are achieving the procedure in 1 day less”, observes Sbragia.

Gastroschisis – Another line of research, which actually motivated the creation of the Experimental Laboratory, is aimed at gastroschisis, a congenital defect where the baby's abdominal wall, right next to the navel, does not close and the intestine protrudes outside. The incidence is 1 for every two thousand births; mortality is 10%, but morbidity is high. After birth, the baby must undergo surgery to return the intestine to the abdominal cavity. However, due to exposure of the intestines to amniotic fluid, inflammation of the loops occurs, which leads to delayed bowel movements. “As they have a bowel movement with each feeding, babies need to be hospitalized for an average of 45 days, with high hospital costs and a high rate of complications until intestinal functions return,” he adds.

The professor himself is responsible for studying the intestinal inflammatory process. A doctoral student, Willy França, researches the neuronal part of the affected intestine. Daniel Bittencourt, master's student, seeks the best intrauterine treatment, evaluating the use of corticosteroids, an anti-inflammatory widely used in obstetrics to mature the baby's lungs. In August, Roberto Teixeira will defend his doctoral thesis on intrauterine growth retardation in gastroschisis. “In research in Brazil, we have to go after it. Runner Zeferina Baudaia, who trained barefoot in the middle of the sugarcane field and ended up winning São Silvestre, is an inspiration,” he compares.

Fetal legislation – Lourenço Sbragia notes that in Brazil legislation allows abortion in cases of rape, high risk to maternal life and in cases judged individually in the event of fetuses with no hope of life, such as anencephalic ones or fetuses without a skull. “In developed countries, the law says that a woman has the supreme right to decide on the future of her pregnancy. In our country, without making any value judgment, during the pregnancy of a child with a congenital defect, which will result in a very serious future situation for the child, the family and society, the laws need to be clear and the health system must be prepared to support the malformed fetus. More in-depth ethical discussions and new legislation will be inevitable in the coming years, with regard to embryo cloning, stem cell implantation, fetal tissue bioengineering, invasive fetal treatments, fetal rights, maternal rights and government support in fetal medicine”, he warns .

From a political point of view, Lourenço Sbragia defends the creation of regional centers of excellence in the country, as is already the case in the northern hemisphere. He states that he sent to the Ministry of Health a project to create a nursery with ten ICU beds at the Center for Comprehensive Attention to Women's Health (Caism) at Unicamp, which would guarantee care in the region for malformed patients with prognosis and interventions. fetal. “We requested 1,5 million reais, an amount that would guarantee the creation of a structure for highly complex specialized care, but we received no return. We need to support these people. We just want to send these kids to school.”