Seek to Reduce False Positives,
Improve Physician Education
and Follow-Up for Families
October 30, 2007; Page D1
The recent adoption of widespread screening of newborns for congenital health problems is saving thousands of lives every year, identifying potentially deadly conditions in time to begin treatment. But now, health-care professionals recognize that success has highlighted glitches in the system.
More screening has meant more potential for erroneous test results and misdiagnoses, causing needless angst for parents. Doctors and hospital officials, who must inform new parents about the screening process, are often ill-informed about the diseases that are screened for and how they are treated. And once a diagnosis is confirmed, families may get little follow-up as they struggle with the overwhelming rigors of caring for their sick infant.
To improve the screening process, health providers and government officials are starting to expand beyond the push for more screening to also address shortcomings in the entire system. Efforts include creating a national standard for assessing screening, in order to cut down on false positives. Genetics experts are developing an online map of specialists across the country to help families find treatment. And researchers and health officials are working to educate doctors about screening and create state registries to track the long-term impact of early diagnosis.
"We're trying to see the newborn screening as a system and not a lab test," says Rani Singh, associate professor and director of the Genetics Metabolic Nutrition Program at Emory University in Atlanta, which has been working in a collaborative of southern states to improve access to genetic services.
Newborn screening has grown exponentially over the past two years -- the result of years of effort by health experts and patient advocates. All 50 states now mandate the procedure, which involves pricking the heel of an infant before the baby leaves the hospital to obtain a few drops of blood for testing. As of July, nearly 90% of U.S. babies are tested for 21 of the 29 conditions recommended by the American College of Medical Genetics, compared with 38% in 2005, according to the March of Dimes.
The conditions, many of which are metabolic disorders that interfere with how the body breaks down and absorbs nutrients, are typically rare. With some, fewer than 1 in 10,000 are afflicted. But these conditions can have devastating consequences, including mental retardation, physical disabilities or even death within days of birth. Caught early, many of these diseases are treatable, and the children can live normal lives.
"Without a good screening program in place in a state, the rest doesn't happen," says Jennifer L. Howse, president of the March of Dimes.
Yet problems can arise from the outset. For one thing, even the most accurate screening tests will identify some children as false positives. The likelihood that a test correctly identifies a case ranges from 10% to 45%, depending on the test and what score a state uses as its cutoff to define abnormal, says Brad Therrell, director of the National Newborn Screening and Genetics Resource Center, an Austin, Texas-based agency.
Hayward Genetics Center at Tulane University in New Orleans, for example, sees about seven false positives for every one baby with a true metabolic defect, according to director Hans Andersson.
To help make test results more accurate, groups of genetic experts across the country -- separated into seven "regional collaboratives" -- are carrying out a project to figure out what test cutoff scores best distinguish the true cases while minimizing false positives. The effort, funded by the Department of Health and Human Service's Health Resources and Services Administration, aims to establish a uniform cutoff score for each condition. Currently, variations in states' standards and testing procedures mean that a child who tests positive in one state might have tested negative if he or she had been born in another state.
Also, a number of medical centers that conduct "second-tier" tests to check results are getting inquiries from around the country about expanding the use of such tests before informing pediatricians or parents, according to Michael Watson, executive director of the American College of Medical Genetics, the nonprofit that puts out recommendations for screening. Second-tier tests are used by a limited number of states, either through their own state lab or contracted out to another laboratory such as the Mayo Clinic, but there are no formal national recommendations for their use yet.
Uncertainty over screening results, including false positives, can have a significant impact on families. Even when parents are later told initial results were wrong, they may still worry about their baby's health. Parents continue to take these babies more frequently to the doctor and the emergency room, according to a study that Susan Waisbren, associate professor of psychiatry at Harvard Medical School, and colleagues published last year in JAMA, the Journal of the American Medical Association.
Many organizations, including the American College of Obstetrics, say they would like to get obstetricians more involved in educating parents earlier about newborn screening to head off unnecessary angst. ACOG's committee on genetics will be publishing an opinion at the end of the year urging obstetricians to be "proactive" and offer written, video or electronic materials to patients during pregnancy, says Anthony Gregg, chairman of the committee and associate professor at the University of South Carolina School of Medicine.
The aim is to convey the importance of screening results without creating undue panic -- since many conditions can be effectively treated. When Christena Neal of Hallsville, Texas, received a call from her pediatrician on a Friday afternoon last December, she says she fell apart. "I heard the panic in him, but he was trying to be calm," Ms. Neal said. Her three-week-old son Jesse David, the doctor said, had "something wrong with his blood."
"I hung up and started bawling," Ms. Neal said. "I was so afraid he would die."
Screening results indicated the boy -- nicknamed J.D. -- likely had the metabolic disorder known as MCAD (medium chain acyl CoA dehydrogenase deficiency), which prevents his body from breaking down certain kinds of fats for energy. Infants with this condition can die in just hours if they don't eat enough food that provides usable energy to keep their blood sugar normal. The Neals' pediatrician had never treated anyone with the condition before and had printed information about MCAD from the Internet.
Fortunately, J.D. was able to get an appointment with a specialist quickly, and was started on the treatment, a special low-fat formula, even before his diagnosis was confirmed. He is now a healthy 11-month-old.
J.D is a screening success story. Yet his family's journey illustrates how screening leads to a host of other struggles. Ms. Neal makes the hourlong trek with J.D. to the geneticist every three months, and she remains vigilant about feeding him like clockwork with nutritional supplements and special foods. She has had to rush him to the emergency room four times, and had to beseech a state senator in order to get Medicaid to cover the cost of his supplements.
To improve follow-up for children like J.D., HHS's Health Resources and Services Administration, the National Newborn Screening and Genetics Resource Center, and others would like to have states monitor patients' outcomes to better understand what happens if these rare conditions are caught early. A study of 35 states published this month in the Archives of Pediatrics and Adolescent Medicine found that less than one-third of states surveyed collect long-term follow-up data, and the follow-up information varies tremendously. But some states, including California, and 16 pediatric metabolic centers in several Midwestern states have begun collecting this information, and more are starting or looking to do so, according to Cynthia Cameron, director of the Region 4 Genetics Collaborative.
Another difficulty in the follow-up process is that many pediatricians and primary-care doctors aren't familiar with these rare and complex diseases. To help better inform doctors, the American College of Medical Genetics' Web site offers a series of so-called ACT Sheets, which walk them through what to do when a baby screens positive for a rare condition, according to executive director Dr. Watson.
The group is also developing an online map of genetic specialists across the country so parents and doctors can search for treatment in their area. Dr. Watson says the map will be launched within six months.
Write to Shirley S. Wang at firstname.lastname@example.org