Some treatments done in the womb may cause seizures

When the Morrisons were expecting their second child, the young couple faced an anguishing dilemma.

Their first child, a girl born in 2002, had a condition known as congenital adrenal hyperplasia, or CAH, which can sometimes result in male-like genitals in female newborns. So when Mrs. Morrison became pregnant again, the couple was well aware the baby had a 1-in-8 chance of being born with the same disorder.

There were choices. They could treat the fetus with a powerful steroid that would most likely avert the possibility of the genitals becoming malformed. But the couple worried about doing this. There was little research on the long-term effects of treating a fetus with steroids, and statistically, there was a much greater chance that the baby wouldn't have the genital problem at all. So the fetus -- and mother -- could be taking powerful drugs for no reason.

The couple decided to forgo the steroid treatment. "It was touch-and-go, but in the end I couldn't expose the baby to the drugs," says Mrs. Morrison. When the baby arrived, it was a girl and, like her older sister, was born with swollen genitalia.

Early Intervention

Earlier genetic diagnosis has spurred new prenatal therapies.

• Steroids are commonly used to treat some fetal ailments.
• Specialized scopes are being tested for fixing underdeveloped lungs and other problems.
• Doctors hope stem cells will one day treat fetal disorders.

Doctors have long been able to use imaging technology to diagnose serious fetal problems, including anatomical deformities and irregular heartbeats, and sometimes even treat them in the womb. Now, thanks to rapid advances in prenatal genetic diagnosis, inherited disorders that may be invisible to imaging are also being found and treated.

Last year, the University of California San Francisco started a trial using steroids to treat a condition that causes abnormal lung tissue in a fetus. The condition previously could be tackled prenatally only with high-risk surgery. Some doctors are experimenting with an instrument called the fetoscope, an ultrasound-guided tube, to fix a fetal condition that leads to underdeveloped lungs. Doctors also are hoping that promising efforts at prenatally grafting stem cells in dogs will eventually pave the way for treating two human genetic disorders, sickle cell anemia and thalassemia.

As the number of conditions that can be addressed grows, more and more families and their doctors are facing tough tradeoffs that come with such interventions. Some considerations: How should the potential benefit for the fetus be weighed against any possible long-term consequences for the baby, and any risk posed to the mother? And, as it becomes possible to diagnose many more genetic disorders in the womb, should prenatal treatment be used only for life-threatening ailments or also for afflictions, such as ambiguous genitalia?

"A lot of what we do is not in a black-and-white zone but a gray one," says Alan Flake, pediatric surgeon at the Children's Hospital of Philadelphia and an expert in the field of prenatal medicine.

CAH is a genetic disorder that causes overproduction of male hormones in the womb. The severe form of the disease occurs in about one in 15,000 births, and CAH is one of the disorders many U.S. hospitals routinely screen newborns for. About 75% of the severe cases suffer from a potentially fatal form called salt-wasting CAH that can trigger vomiting and dehydration within the first weeks of life. Treatment typically involves taking steroids for life.

Both boys and girls can be afflicted with CAH, but girls can suffer an additional complication: External genitalia are "virilized," leading to an enlarged clitoris and fused labia that can in varying degrees appear male-like. Many parents choose to have their infant daughter's genitalia surgically reconstructed soon after birth. Without proper treatment, girls may later develop a deeper-than-normal voice and facial hair and may be infertile.

Doctors have used steroids to target CAH in the womb for about two decades, but the treatment is a lot more common today. Although administering steroids to a fetus doesn't prevent the disease, it can avert malformed genitalia in girls.

The Morrisons, who declined to let their first names be published, had their first daughter in 2002. Her genitalia were somewhat swollen, but the couple wasn't overly worried. When she was two weeks old, the girl fell seriously ill and had to be rushed to intensive care. The salt level in her body had dropped sharply, and she was at a high risk of seizures and organ failure. Diagnosed with CAH, she spent several days in the hospital but eventually pulled through.

In 2004, when Mrs. Morrison got pregnant again, her doctor mentioned a steroid called dexamethasone, or dex. He explained that if her second baby happened to be a CAH-affected girl, dex treatment would most likely prevent the development of affected genitalia.

It was a tough call. The dex only works if it's taken when the fetus is a few weeks' old, well before its sex can be determined. That means there's a 7-in-8 chance that a baby -- either because it's a boy or an unaffected girl -- won't need the drug but would in any case be exposed to it in the womb.

The steroid can also cause unpleasant side effects for the mother, including mood swings, weight gain and insomnia. More worrying is the lack of long-term research to indicate whether dex affects a child's physical and mental development in later life.

Doctors say that most mothers facing the possibility of CAH in an infant decide to take the steroid. "They don't want to have a baby with ambiguous genitalia. It's a pretty terrifying prospect if the baby is born and the doctor can't tell you whether it's a girl or a boy," says Maria New, professor of pediatrics at Mount Sinai School of Medicine in New York.

Backed by an National Institutes of Health grant, Dr. New is studying the long-term effects of dex on children who are now at least 12 years old. Though the study isn't complete, preliminary data indicate that children exposed to dex in the womb don't seem to suffer medical or psychological effects or confusion about what their sexuality is, Dr. New says. The study included about 100 subjects, more than half of whom were treated prenatally with dex.

Some experts caution about the use of dex in unborn babies who may not even need it. "It only treats the birth defect [of ambiguous genitalia in girls] and not the disease itself," says Kelly Leight, founder of CARES Foundation, an education and support group for CAH patients.

After the Morrisons' second daughter was born with affected genitalia as a result of CAH, the couple initially decided to have no more children. But a year later, Mrs. Morrison became pregnant for the third time, and the dex question loomed again. This time, Mrs. Morrison decided to take the steroids.

"Just because we could deal with it doesn't mean it would be fine for the child," says Mrs. Morrison. "She might grow up and ask why her mother didn't take the steroid when she could."

The dex caused side effects. Mrs. Morrison suffered bouts of crying and insomnia and found it hard to make simple decisions, symptoms she hadn't experienced in her other pregnancies.

In the 11th week of pregnancy, Mrs. Morrison went for chorionic villus sampling, a procedure that can reveal a baby's sex and CAH status. It showed that the baby was a girl and that she was free from the genetic disorder. Mrs. Morrison stopped taking the steroid treatments.

The Morrison girls are now 6, 3½ and 1½ years old. The older girls with CAH have not had surgery. The couple says they might consider this as the girls approach puberty if it is medically necessary. Otherwise, the parents say they will let the girls make their own decision about surgery when they become adults.

Write to Gautam Naik at gautam.naik@wsj.com