Fetal therapy: Issues we face

he operation was relatively simple. Michael R Harrison, MD, T pediatric surgeon a t the Univer-

sity of California Hospitals and Clinics, San Francisco, inserted a catheter through an expectant mother’s abdo- men into a fetus’s bladder. The intent was to relieve hydronephrosis caused by a urinary obstruction. (See related arti- cle.) But the procedure opened up potential for a new type of surgery and raised complex questions for expectant par-

Intrauterine treatment is experimental and limited t o a few carefully selected conditions. “The only anatomic malformations that warrant consider-

= ents, physicians, and society. Fetal therapy Issues we face

Patricia ation are those that interfere with fetal organ development and that, if al- leviated, would allow normal fetal development to proceed,” Dr Harrison wrote in a recent artic1e.l Experts cau- tion that it is much too early to predict how widely these types of procedures might be used.

Investigation continues on a variety of other congenital malformations. Neural tube defects are a focus for study because they are among the most com- mon anomalies. Rates are estimated to be about 2 per 1,000 births in the US. Exact causes are still unknown. About two of every three cases of spina bifida, one of these defects, involves hydrocephalus. Fluid accummulates in the ventricular spaces of the fetus’s brain, causing irreversible brain damage. At birth, these children may be mentally handicapped and have severe physical handicaps.

At Brigham and Women’s Hospital and Harvard Medical School, Boston, physicians drained fluid from a fetus with hydrocephalus. From 25 t o 32 weeks’ gestation, they did a series of six cephalocenteses. The child was born by cesarean section at 34 weeks. The treatments had reduced the hydrocephalus, but there were other com-

Pa~erson

AORN Journal, March 1982, Vol35, No 4 663

plications, which the physicians found consistent with Becker’s muscular dys- trophy.2 They commented that serial cephalocentesis was not a definitive treatment, but it could be done without infection, adverse cardiovascular effect, intracranial hemorrhage, or apparent cerebral damage.3

A team at the University of Colorado Health Sciences Center, Denver, treated a fetus with congenital hydrocephalus, using a Silastic shunt they designed with a one-way valve. It was placed in the left lateral ventricle a t 23 weeks’ gestation in April 1981.4 Results of the procedure had not been published as of January.

Researchers a t the National Insti- tutes of Health (NIH) have been exper- imenting with treatments for hydrocephalus in rhesus monkey fetuses. They have also been working on intrauterine allogenic bone transplants and limb bud regeneration in the ani- mals.

For hydrocephalus, they have devised a one-way stainless steel valve that can be mounted in the fetal skull to drain off cerebrospinal fluid. It is called a hydro- cephalic antenatal vent for intrauterine treatment (HAVIT). The valve opens when the fluid pressure reaches a cer-

Techniques are promising but now experimental.

tain level. Experimental results have been encouraging. Compared with a control group that was not treated, more monkey infants with valves were alive, and they showed progressive physical dexterity and near normal growth ratese5

For mending other defects, the scien- t ists working with rhesus monkey fetuses found that crushed bone parti- cles in an agar-based medium aids clo- sure of fissures in the neural tube in cases of spina bifida. They believe this technique might eventually help in cor- recting some gross malformations in utero. In addition, the monkey fetuses have shown remarkable ability to re- generate severed fingers. This discov- ery may open paths leading to ways to correct problems of limb development.6

Although the prospects are exciting, Gary D Hodgen, one of the principal NIH researchers, is cautious. “As groups like ours begin to develop approaches to the in utero repair of fetal defects in nonhuman primates, it will be important to emphasize the tentative and experimental nature of the work,” said the chief of the Pregnancy Re- search Branch in the National Institute of Child Health and Human Develop- ment, Bethesda, Md. Nevertheless, he sees thatultimately “a great deal of disability and suffering will be pre- ~ e n t e d . ” ~

As physicians and scientists continue their tentative steps toward fetal treatment, questions arise. An immedi- ate concern is that, seeing headlines, expectant parents around the country may assume any fetal defect can be corrected. They may flock to medical cen- ters with false hopes, and inexperienced physicians may be tempted to try an unproven procedure. Articles in medical journals have one underlying theme-although the techniques are promising, they are presently limited to only a few conditions, and they are experimental.

Moreover, fetuses with one problem may have many. Dr Harrison points out the importance of thorough evaluation Yo avoid delivering a neonate with one corrected anomaly but other unrecog- nized disability or le thal abnor-

664 AORN Journal, March 1982, Vol35, No 4

malities.”* Since the field is experimental, it is critical to weigh benefits and risks.

What questions will the expectant parents face? In some cases, fetal treatment will offer a middle ground between abortion and birth of a seriously deformed child. There may be new and hopeful options, but there will also be difficult choices. In a phone interview,’ John C Fletcher outlined issues he sees for parents and society. An assistant for bioethics at the NIH’s Clinical Center, the world‘s largest research hospital, he is involved in the research review pro- cess. He advises physicians and scientists on the ethical implications of their studies. He wrote an editorial on the subject for the Journal of the American Medical Association (Aug 14, 1981).

What happens when a physician believes he can help the fetus, but the mother refuses to give her consent? Or what happens when the mother’s surgi- cal consent is ambiguous?

“I see conflicts developing as there is more opportunity for this type of therapy,” Fletcher commented. The situation becomes especially compli- cated when the fetus approaches viability in the third trimester. Physicians and hospitals often go to great lengths to save and treat premature infants. So- ciety gives a high priority to treating these tiny, fragile beings, judging from the elaborate and expensive care they receive. Fletcher believes this standard of care would probably be extended to fetuses who could be treated, even if their viability is marginal.

On the other hand, society also places high value on a pregnant woman’s right to self-determination. This was the con- clusion of the 1973 abortion decision, Roe u. Wade. The US Supreme Court said that, during the first trimester of pregnancy, the decision to abort is a matter for a woman and her physician. During the second trimester, states may

regulate the procedure to some extent because it becomes more risky. After viability, states may prohibit abortion, except when the mother’s life or health is in danger, because the government has an interest in protecting viable fetuses. In addition, the expectant mother is the one who must consent to the surgery, because the fetus is within her body.

“There is an apparent inconsistency in society encouraging fetal therapy and at the same time respecting par- ental choice,” Fletcher said. He believes these values are most likely to clash when the fetus is on the borderline of viability or when the proposed treatment is so new or the condition so complex that physicians cannot predict with certainty what the outcome would be.

Currently, Fletcher thinks it would be unwise to resolve these conflicts in favor of the fetus. “For the present, the most helpful attitude in the midst of such conflicts is to maximize choices, learn as much as possible, and stay within the existing legal guidelines on abortion,” he wrote in the JAMA editorial.

For a legal view of fetal and maternal rights, we called Leonard H Glantz, associate professor of health law at Boston

What are the mother‘s rights? Can she refuse a procedure?

University Medical School and associate director of the School of Public Health, Boston University. A lawyer, he specializes in law related to parents and children.

Since the fetus would be having surgery, could the child sue the physi-

AORN Journal, March 1982, Val 35, No 4 665

cian after birth if something went wrong? we asked. The answer is yes, Glantz said. Although prenatal procedures are new, the law in this area is actually well developed.

“It is the law essentially everywhere at this stage that if a child is injured in utero, and the child is then born alive and suffers as a result of that injury, the child can sue,” he explained. Courts are not much concerned a t this point whether the fetus has reached viability or not. In fact, a child may even have a cause of action if the injury occurred before he was conceived.

How is this possible? One recent case involved a 13-year-old woman who needed a blood transfusion and was transfused with blood of the wrong Rh type. She was not told about this, and seven or eight years later, she became pregnant. The child was born injured because of the Rh problem.

“The question is whether the child has a cause of action against the physician who originally did the transfusion,” Blantz said. “The court decided yes.

“I believe the court’s reasoning is right in this sense,” he continued. “The court said that the physician could have foreseen that transfusing the young

~ ~~

We are on the threshold of great discoveries.

woman with the wrong blood would in- jure a fetus or child. That was negli- gent.” Prenatal or preconception suits require that the child be born alive and suffer some harm from the injury that occurred.

What about the mother’s rights? Can

she refuse to have a prenatal procedure? Glantz finds the law in this area is not as clear and well developed. He told of a case in which a pregnant woman who was a Jehovah’s Witness needed to have a blood transfusion to save the life of the fetus. It may have been needed for her own life as well. The incident occurred before the 1973 abortion decision, and the court ordered the mother to be transfused. She walked away from the hospital, and no attempt was made to apprehend her or enforce the order.

“It seems to me the case is really wide open,” Glantz commented. “Depending on where she is in pregnancy, a woman would be entitled to abort the fetus. That would negate any court order, except in postviability situations where the state may have a law against abortion.

“If the mother chooses not to abort, that would be her choice. But it raises a very difficult question and one I don’t know can be answered. I believe that answer would have to do in large part with how invasive the procedure is.

“I would say that if the procedure could be done without any risk of injury to the mother-if someone could magi- cally wave a hand over her-then I don’t think the mother could object.” On the other hand, he noted that except for some transfusion cases, which are low risk, and a couple of lower court decisions, courts have not ordered noncon- senting competent adults to be treated.

“That’s a very tough question,” he concluded, “And it will be a new area of the law.”

Fletcher referred to a recent case in which a court did order a pregnant woman to have surgery. A morbidly obese woman in labor appeared at the University of Colorado Health Sciences Center in Denver. Hostile and comba- tive, she insisted on an abortion. She had received no prenatal care, so physicians could not tell how advanced the

666 AORN Journal, March 1982, Val 35, No 4

pregnancy was, but they believed she was near term.

The fetus showed signs of distress, and they determined a cesarean section should be performed. The patient re- fused to consent to surgery and wanted to leave the hospital. After the hospital attorney had interviewed her, the legal staff decided to go to court. Attorneys were appointed for mother and fetus. The judge ruled that the mother must have surgery. Fletcher noted this was the first time a woman had been legally coerced to have a c-~ection.~

Whether the parents could sue the physician if a prenatal procedure was not offered is also a difficult question to answer, Glantz believes.

“It seems to me that at this point, this is such a sophisticated and experimental form of care that it is very unlikely parents could bring an action,” he said. “But when it becomes a more ordinary kind of care, then I think one would be able to bring a malpractice suit. I t would be like when a child is sick and the physician does not offer the standard treatment the child needs.”

Further issues arise for society at large. Fletcher discussed the implications of doing research on fetuses and what priority society should give to fetal therapy.

The federal government has guidelines applying to all fetal research that it funds. Currently, these efforts are limited to two types: (1) research designed to meet the needs of a particular fetus, and (2) research with a minimal risk to the fetus that has the potential to develop important biomedical knowledge when there is no other means of obtaining this knowledge. Essentially, the risk must be no higher than every- day life. Local institutional review boards may approve research protocols that fall within these guidelines. Other proposals carrying more risk must be referred to the national level for consid-

eration and approval. Fletcher favors assigning a high

priority to fetal therapy because “the potential is so great.” “We should give a good bit of time to studying i t and should fund projects because of the chances of preventing costly disease,” he believes.

He referred to Hodgen’s research at NIH. Eventually, if he and his col- leagues continue to have good results with monkeys, the technique could be applied to humans. This would provide an ethical alternative to abortion in some cases of neural tube defects, even if the surgery were experimental, Fletcher said.

The procedure would also be inexpen- sive, compared with the tremendous cost of caring for these seriously handicapped children.

Maria Michejda, MD, an associate of Hodgen at NIH, described the cost of caring for children with neural tube defects in an interview with theJournaZ of the American Medical Association (Oct 2, 1981). In 1979, annual expenses for each child were about $60,000, totaling more than $200 million per year. This is money spent by state crippled children’s services and does not include spending by private agencies or the federal government. Contributions from the March of Dimes and visits by private physicians would have to be added as well. In contrast, costs of prenatal treatment would be limited to diagnostic tests, the brief, relatively simple surgery, and a short hospital stay.1°

Experts seem to agree we are on the threshold of great discoveries. Poten- tially, fetal therapy may do a great deal of good. With this progress will come more difficult decisions for expectant parents.

The techniques seem deceptively simple, but often defects will not be easy t o correct. Physicians do not know enough about the syndromes tha t

AORN Journal, March 1982, Vol35, No 4 667

accompany individual defects. They do n o t understand enough about t h e right t i m e to intervene, w h e n they can pre- v e n t d i s a b i l i t y . T h e y do n o t k n o w enough about t h e degree o f correction that i s needed to prevent f u r the r deteri- oration. They are learning.

In t h e meantime, there i s danger that some parents m a y have t h e i r hopes raised by what i s a tentat ive and exper imenta l procedure. Physicians w i l l have great responsibi l i ty b o t h for studying t h e potent ia l for fe ta l therapy and for educat ing t h e i r pat ients about what is possible and w h a t i s not. 0 Notes

1. Michael R Harrison, Mitchell S Golbus, Roy A Filly, "Management of the fetus with a correctable congenital defect," Journalof the American Medical Association 246 (Aug 14, 1981) 776.

2. Jason C Birnholz, Frederic D Frigoletto, "An- tenatal treatment of hydrocephalus," New England JournalofMedicine 304(April23,1981) 1021-1023.

3. Jason C Birnholz. Frederic D Frigoletto, correspondence, New €ng/and Journal of Medicine 305 (Aug 13, 1981) 403.

4. William H Clewell et al, correspondence, New England Journal of Medicine 305 (Oct 15, 1981) 955.

5. Maria Michejda, Gary D Hodgen, "In utero diagnosis and treatment of nonhuman primate fetal skeletal anomalies," Journal of the American Medi- cal Association 246 (Sept 4, 1981) 1093-1097.

6. Gary D Hodgen, "Antenatal diagnosis and treatment of fetal skeletal malformations,"Journalof fhe American Medical Association 246 (Sept 4, 1981) 1079- 1083.

7 . Ibid, 1079, 1083. 8 . Harrison, Golbus, Filly, "Management of the

fetus," 776. 9. Watson A Bowes, Jr, Brad Selgestad, "Fetal

versus maternal rights: Medical and legal perspec- tives," Obstetrics & Gynecology 58 (August 1981)

10. William R Barclay et al, "The ethics of in utero surgery," Journal ofthe American Medical Associa- tion 246 (Oct 2, 1981) 1554.

209-214.

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given to help readily identify exposed daughters. There are interviewing techniques for determining potentially exposed mothers and children.

A question-and-answer section is designed to answer questions most likely to be asked by exposed daughters. The importance of education and counseling services and adequate referral is highlighted. The booklet also contains a list of educational materials.

In 1971, the US Food and Drug Administration listed pregnancy as a contraindication for use of DES. Physicians at Massachusetts General Hospital, Boston, had observed an association between a rare type of cancer (vaginal or cervical clear cell adenocarcinoma) in a small number of young girls and prescription of DES for their mothers during pregnancy.

The booklet, Prenatal Diethylstilbestrol (LIES) Exposure: Recommendations of the Diethylstilbestrol Adenosis (DESA 0) Project for the Identification and Management of Exposed Individuals, may be ordered free of charge from the Office of Cancer Communications, Bldg 31, Rrn 10-A-21, Dept SC, NCI, Bethesda, Md 20205. Or you may call (800) 638-6694. Also available are new editions of Questions and Answers about DES .Exposure and a public alert brochure, Were You or Your Daughter or Son Born after 1940?

Pictures and step-by-step instructions are

668 AORN Journal, March 1982, Val 35, No 4

Documents

Fetal therapy: Issues we face