As reported by The Hartford Courant, April 5, 2005.

New State Law Widens Scope of Newborn Blood Tests to Screen for More Disorders

By Rob Elder

When Mimi Rivard was expecting her second child at age 37, she and her husband, Andrew Roberts, wanted to be sure their baby would be healthy. Rivard had prenatal blood tests and an ultrasound. Because Roberts is Jewish, the couple also went to the trouble to rule out the remote possibility of Tay-Sachs disease.

Their son Andre was born late last fall, weighing a normal 7 pounds 13 ounces, and he seemed like a perfectly healthy newborn.

So his parents were shocked when they received a call from their pediatrician telling them their 5-day-old son had tested positive for galactosemia. "I was just terrified," says Rivard, whose next thought was: "What is it?"

Galactosemia is a rare disorder that affects about 1 in 50,000 newborns. These babies are unable to break down galactose, a form of sugar that is a component of lactose in milk products, including breast milk. Because children with galactosemia can't get rid of excess galactose, it builds up in the blood and can cause life-threatening infections and liver damage. If children survive the newborn period, they still can have chronic health problems, such as trouble with speech, poor coordination, cataracts or even mental retardation.

Andre, like almost every other baby born in Connecticut, had a small sample of blood pricked from his heel when he was still at St. Mary's Hospital in Waterbury. That blood was soaked into a filter paper card and sent to the state's newborn screening laboratory in Hartford to be tested.

Connecticut's newborn screening program, mandated for all babies unless parents object for religious reasons, began in 1964 with testing for two disorders - PKU and galactosemia. During the last four decades, the program gradually grew and, by 1997, covered eight genetic disorders, including sickle cell anemia.

But as of January 1, the program expanded dramatically, testing newborns for 42 disorders, using new technology called tandem mass spectrometry.

Dr. Kati Kelley, director of the state health department's laboratory, says Connecticut is one of the few states that has made the major investment of both time and money that the screening involves.

"And," she says, "I think that our system is working well."

Screening for 42 disorders does not cost parents much more than screening for eight. The newborn screening fee that all hospitals add to maternity patients' bills, which was $18 last year, rose to $28 under the expanded program.

Although neonatal genetic screening is internationally recognized as an important, preventive public health initiative, it varies widely from state to state. A child born in Connecticut is screened for 42 disorders, many of them very rare. Children born in Arkansas, Kansas and Kentucky are screened for just four.

More, however, is not necessarily better. Children who are diagnosed early can receive prompt treatment and may be spared serious complications or even death. But false positives are possible, and some children identified with a disorder may not require any treatment. Experts agree that too much testing can drive up public health costs - and add to parental stress. Dr. Robert Greenstein, director of the Division of Human Genetics at the University of Connecticut, has had to make many alarming phone calls, like the one Andre's parents received. "In essence, it is a call from a stranger about an esoteric condition that nobody has ever heard of, nor can they spell it."

Though the disorders are rare, a cost-benefit analysis reported by the journal Pediatrics in 2002 concluded that expanded screening makes economic sense. Because children who are identified early can have early intervention to prevent serious health problems, they are less likely to spend costly time in the hospital or intensive care.

When an infant screens positive for one of the disorders, he or she is referred to the University of Connecticut or Yale University for further care. Greenstein says that because of the expanded screening, referrals to UConn's genetics clinic are up by about 10 percent to 15 percent since January 1.

When Greenstein first called her, Rivard says, she was devastated to learn that she would have to stop breastfeeding. Andre was started on a soy-based formula, which he could metabolize without problems.

When Greenstein examined Andre at 6 days old, he appeared well. He was taking his soy formula and showed no signs of having the disease.

Kelley says genetic screening tests do not provide a definitive diagnosis.

"All of the tests that we do are screening tests, and the definition of a screening test is that you set your parameters so that you do not miss a possible case," she says. "When you do that, you always get false positives," or people who screen positive but don't actually have the disease.

Although Andre had tested positive for galactosemia, more in-depth genetic testing was necessary to verify the initial screening results. The cost of such follow-up testing varies, depending on which disorder is initially identified; it can cost hundreds of dollars but often is covered by insurance. Andre's parents decided to go ahead with the further tests.

"I didn't want to be in a situation of looking for something that wasn't there, in that steady state of waiting for the other shoe to drop," says Roberts. "He tripped - does he have a neurological disorder related to his

Andre remained on the galactose-free diet, and a few weeks after his initial visit with Greenstein, his parents received good news. Andre did not have classic galactosemia but an unusual variant in his DNA that is not likely to cause him long-term health problems. Rivard, who is a nurse, says she is glad she knows about Andre's unusual trait.

"Of course, you want to know. You want to know anything that puts your child in harm's way, especially if there is something that you can do about it."

She says it also may help with "future family planning, for the kids and for ourselves."

At his four-month checkup, Andre is doing well. He is a large, healthy child who laughs easily when his dad lifts his arms and comments "so big!" Andre has stayed on the restricted diet as a precaution but now is ready to begin incorporating milk and other foods with galactose.

Last month, a federal advisory committee on genetic diseases recommended that all babies in the United States be screened for 29 disorders, regardless of the state in which they are born. The report is available at http://mchb.hrsa.gov/screening, and the federal Health Resources and Services Administration is collecting public comment on it through early May.

Whether those recommendations are implemented nationwide likely will depend on the success of expanded programs such as Connecticut's.

Rob Elder of Middlefield is a fourth-year medical student at the University of Connecticut.