In July 2005, the state of Missouri expanded its mandatory newborn screening program to include testing for 20 additional metabolic disorders and two hemoglobinopathies, bringing the total screenings to 27. According to Kathy Grange, MD, a medical geneticist at St. Louis Children’s Hospital (SLCH) and a member of the state’s newborn screening committee, this change is of major importance for several reasons.
“When not detected at birth, many of these diseases can result in severe, devastating illnesses that are preventable, sometimes by simple measures,” says Dr. Grange. “For instance, about one out of four children with medium-chain acyl-CoA dehydrogenase deficiency (MCAD) who presents during an acute illness without a prior diagnosis dies, and another 25 percent has permanent brain injury. However, when MCAD is identified early, parents know that if their baby can’t keep food down, they need to bring the infant to the hospital to get an IV containing glucose.”
Maple syrup urine disease (MSUD) has a similar prognosis—without treatment, an affected baby can present at a week or 10 days of age with overwhelming metabolic illness and severe neurologic problems that can result in brain injury or death. But with early diagnosis, a simple change in the baby’s diet can avoid serious illness and a poor outcome.
“Early identification also permits critical education for patients’ families about the diseases and how they are inherited,” says F. Sessions Cole, MD, director of newborn medicine at SLCH. “A good example is sickle cell disease. Infants with this disease have a greater susceptibility to lethal, acute bacterial infections caused by pneumococcus. When identified early, they can be started on prophylactic antibiotics and immunized against the pneumococcus. In addition, these affected infants’ families can be educated about the disease, its symptoms, its prevention and the genetic implications for the babies and for other family members.”
Expanded newborn screening by tandem mass spectrometry is a growing trend throughout the country. For instance, Illinois expanded its newborn screenings in July 2002, and Wisconsin and North Carolina’s programs have been in place long enough that their data are used by other states as a measure of effectiveness. The March of Dimes is a leader in the effort to develop a standard protocol for newborn screening throughout the United States.
“Right now, a baby born in one state may be screened for 25 or more diseases, while a baby born in a neighboring state is screened for only four. Imagine how parents feel knowing that if their babies with these rare disorders had been born in another state, they would be healthy or even alive,” says Dr. Grange. “By contrast, some countries, like Australia, have been doing expanded screening for newborns for years.”
The screening and notification procedure
To ensure the viability of its expanded program, the state is including several safeguards within the screening and notification process. First, the state laboratory is setting the cutoffs for reporting abnormal results at a point such that numerous false positives are not reported, but low enough to ensure identification of all babies who have the potential for having these diseases.
Another safety net is having a network of medical geneticists in place to follow-up on babies with abnormal results who need further evaluation. This network divides the state into regions:
• Region 1, Children’s Mercy Hospital, Kansas City, MO
• Region 2, University Hospitals and Clinics, Columbia, MO
• Region 3, St. Louis Children’s Hospital and Cardinal Glennon Children’s Hospital
Results of the screening usually are available within five to seven days. When the screening identifies a baby as potentially having one of the diseases, the infant’s pediatrician and the appropriate regional genetic center are notified via telephone and fax. Efforts commence to make sure the baby receives follow-up diagnostic testing.
“The state laboratory’s report includes an interpretation of whether the test indicates a high, moderate or low risk to the baby’s health. Depending upon the condition, a number of scenarios are possible. The worst case would be that the baby is admitted to the hospital immediately. But it also could be a matter of seeing the baby in the clinic for evaluation or having blood and urine specimens collected at the outpatient laboratory,” says Dr. Grange. “No matter what degree of risk for a disorder is indicated by the screening, the aim is to get the baby in for further evaluation and diagnostic testing as soon as possible.”
Because Missouri law mandates the screenings, private or public insurers must pay the $50 cost of the test.
A pilot project shows on-target results
In the first weeks of a pilot project testing the state’s expanded newborn screening, 8,700 infants were tested. Of those, 10 abnormal cases were identified. Follow-up evaluation determined that eight of those results were false positives, while one baby was identified as having phenylketonuria (PKU) and another having a urea cycle defect.
“This is right on target with what we predicted; namely, that about 10 to 20 percent of the babies identified with moderate to high risk abnormal results will actually have a disorder,” says Dr. Grange. “That becomes a significant number, especially to the families involved.”
Dr. Grange notes that members of the division of genetics and genomic medicine at SLCH are available to review patient cases with physicians 24 hours a day, seven days a week. “We have a newborn screening follow-up team experienced in providing evaluation and treatment for these rare, complex and potentially debilitating or fatal diseases,” she says. “Our skilled medical geneticists, metabolic dietitian and genetic counselors provide services to 1,600 to 2,000 patients and their families annually. In addition, we can call upon the in-house expertise of specialists from all fields of pediatric medicine as needed, and we have access to an excellent, on-site metabolic genetics laboratory.”
To review newborn screening test results with a SLCH medical geneticist and determine a plan of action, call the division of genetics and genomic medicine at 314.454.6093.