Prenatal Gene Tests Offer Answers

 

No prenatal test can guarantee a woman that her baby will be perfect, but gene testing can reassure some while preparing others for the birth of a child with serious medical problems.

When a woman has had five miscarriages and one of her two children is born with birth defects, she needs some answers, especially when she discovers she is pregnant again.

So the anxious mother made an appointment with Andrew F. Wagner, M.D., a geneticist and obstetrician-gynecologist in the maternal fetal section of the Department of Obstetrics and Gynecology. She wanted to learn whether genetics had caused the multiple miscarriages and whether anything could keep her from miscarrying again.

The weekend before her appointment, however, she miscarried for the sixth time. Fortunately, she kept her appointment at OU's Prenatal Diagnostic Center, where Wagner spends two days a week doing genetic counseling, screening and testing.

"We found something very obvious - lupus anticoagulant, which has nothing to do with the disease of lupus, and it's not hereditary," but is a cause of multiple miscarriages, Wagner said. "The woman had tears of joy at the end of her visit, mainly because someone could tell her why."

She also learned there are medications that could help her prevent a miscarriage. In about six weeks, she called back, pregnant and seeking a prescription.

This is one of Wagner's happier endings, but it's indicative of the nature of much of his practice.

"All of the screens and tests that we do are basically pieces of information to help families with planning, reassurance, decision making. Whatever they decide, we are totally fine with their decision," he said.

"That's one of the main tenets of genetics - to do non-directive counseling," he said. "I'm happy to help them have the information they need to make the decision that's best for them, the decision that's right for their lives, their values, their families."

Most of his patients are referrals, and most will deliver at age 35 or older. This means they have an increased risk of delivering a baby with Down syndrome and other chromosomal abnormalities.

His other patients, including those under 35, may have a family history of birth defects or they've already had a child with a chromosomal abnormality. Perhaps early screening has indicated they have an increased risk of delivering a baby with abnormalities.

"We're seeing a growing number of patients who want the First Trimester Screen, which is a way in early pregnancy - between the 11th and into the 13th week - to determine the risk of Down syndrome or chromosomal problems called Trisomy-18 or Trisomy-13," he said.

The First Trimester Screen uses history, blood test and a specific ultrasound to measure nuchal translucency, the clear space in tissue at the back of the fetal neck where a larger-than-usual amount of fluid collects in fetuses with abnormalities. Wagner is one of four at OU certified to perform this ultrasound.

"About 98 percent of the time, our patients have the genetics counseling with the ultrasound to follow," he said.

First trimester tests detect about 90 percent of Down syndrome, with a 5 percent false positive rate, Wagner said. Some patients decline further testing because of risks to the fetus or the mother - about a 1 percent pregnancy loss with amniocentesis and chorionic villus sampling, or CVS, a test that detects chromosomal abnormalities such as Down syndrome and other genetic disorders.

Other patients, however, see the more exact testing as vital to possible interventions, such as fetal surgery for spinabifida. Knowing what to expect allows them to prepare for a child with special needs and connect with support groups and resources. For some, the decision may be whether to carry the child to term.

He recalled a couple who recently came to him specifically for fetal CVS testing, which is available in Oklahoma only from Wagner and his OU colleague Andrew Elimian, M.D.

The woman had experienced one miscarriage and was again pregnant. Previous tests showed a translocation between chromosomes 13 and 14 in tissue from the earlier conception and that the mother also carried this translocation.

In a 13;14 translocation, there is higher risk of passing on a translocated chromosome, which could result in a fetus with an extra chromosome (trisomy 13 or 14), Wagner explained. All trisomy 14 conceptions and most trisomy 13 conceptions result in a miscarriage, he said.

CVS testing of the fetus enabled Wagner to tell the couple they were having a daughter with the same translocation as the mother. The baby will be fine, he said, although she, like her mother, will carry the risk of having an abnormal pregnancy.

"The mother and her husband were relieved."

Wagner completed his OB/GYN medical residency at Aurora Sinai Medical Center in Milwaukee and followed it with a fellowship in genetics at the University of Pittsburgh Medical Center.

"In Pittsburgh, people came in just for the tests. Here, that's rare, probably because people here are more likely to keep the pregnancy regardless of the outcome," Wagner said.

"However, preparing for a baby with special needs can be a primary reason for testing."

When the 14-story OU Children's Physicians Building opens this summer, it will offer convenient, multidisciplinary care for pregnant women who are carrying babies identified as having genetic anomalies.

"What we're planning will give them ‘one-stop shopping' so they can come in for just one day to meet with the pediatric surgeon and the neo-natologist and tour the neonatal intensive care unit.

"We can all work together to set up plans, know what to look out for, what to do if ‘X' happens and what it might mean for the surgical planning," he said. "When we get in the new building, it will be the perfect approach, since we'll be on the first floor, and the physicians we'll refer to will be on the floor above us."

When Wagner arrived at OU in 2005, he took a position that hadn't existed before and began serving a state unused to having the genetic testing options he could offer. "It has been a good move. I'm happy here in Oklahoma," he said.