Newborn screenings: Search for standards creates more questions

Ability to test outpaces knowledge of conditions, in some cases

Newborns in every state are screened for disorders that, if undetected, could lead to disability or death; but while some states test for nine or more conditions, others test for only one or two. Now, efforts are being made to bring uniformity to testing nationwide and to determine what tests are the most crucial.

Among the issues being debated are whether tests that show disorders for which there are no treatments should be standard or should merely be available at families’ request.

"Over time, states were doing a small number of tests, and then it grew until some were doing eight or nine tests," says Mary Ann Baily, PhD, associate for ethics and health policy for The Hastings Center in Garrison, NY. "It turned into somewhat of a patchwork done by the states, and there has been some concern that we see more uniformity and more access."

Several factors determine screens

Because newborn screens, which began in most states with tests for thyroid function and phenylketonuria, have expanded in different states at different rates, there are no national newborn screening standards.

Consensus and uniformity in screening have been affected by state resources available for testing; each state’s interpretation of what conditions are treatable and warrant detection; the introduction and availability of new tests; and opinion of the public, legislators, and the medical community.

But the advent of tandem mass spectronomy suddenly meant states with the technology could test for hundreds of conditions — some that are treatable, some that are not, and some that are genetic mutations that geneticists aren’t even yet sure cause any problems.

"There are a whole set of disorders that can be identified, and some are lethal and the child will die, while others are not very well understood disorders for which there might be treatments that are untested," Baily explains. "So there’s a range of these disorders with various implications, but they don’t usually meet the standard for screening, which is that we know what [the disorder] is and we know what to do when we find it."

Because technology now allows testing for this broader spectrum of disorders, adding more tests is not difficult. In fact, while some states still test for fewer than 10 disorders, others now are testing for more than 40.

Baily says the quickly expanding possibilities for newborn genetic testing, and the ethical implications of some tests, put pressure on medical policy-makers to come up with guidance for standardizing testing.

Harley Ginsberg, MD, neonatologist at Ochsner Clinic Foundation in New Orleans, says the questions are difficult ones.

"Do you screen for a disease you can’t do anything for now?" he asks. "Do families want to know? Also, there’s a financial part that can’t be ignored. Not every state has the financial wherewithal to pay for these types of screenings, so you screen for the ones where the majority of abnormalities are detected."

Test results only part of picture

Baily says one big factor to consider when putting together a policy on screening newborns is the responsibility that comes when results of those screens are positive.

"Newborn screening is not just a test," she points out. "Screening means follow-up for those that test positive."

Baily says if the more than 4 million babies born in the United States each year are tested for 40 conditions, and several of those tests in each baby return with false positives, there have to be millions of follow-ups for those false positives.

Treatment and long-term follow-up are required for all the newborns whose positive results turn out to be true positives.

In a report released earlier this year, the American College of Medical Genetics (ACMG) recognized that "many states provide the programs necessary to ensure that screening and diagnosis will occur, but are limited in their ability to ensure long-term management, including the provision of the necessary treatment and services."

"It’s complicated and expensive," Baily says. "So that’s why you have to ask, when you talk about some of these rare conditions that we don’t know much about, Do I really know there will be a benefit to screening for this?’ And that takes evidence."

Ginsberg says delivering positive findings of lesser known conditions to parents carries a responsibility.

"The challenge is that if there is nothing we can do about a disease, then delivering this news to a parent could be a painful, scary endeavor," he explains. "If we are not sure that the abnormality causes clinical disease, then it’s even less helpful."

Ginsberg says he would like to see all newborns tested for diseases for which we have accepted, tested treatments, and to let families decide if they want tests run for less familiar diseases or conditions to which they may be ethnically or genetically prone.

"If the mother’s family has the gene for breast cancer, do you test [the baby]?" he asks. "Some families might want to know, and some might not."

Duane W. Superneau, MD, a geneticist with Genetic Services of Louisiana in Baton Rouge, says even conditions that are not curable have treatments — for example, while there is no treatment for Down syndrome, there are beneficial early interventions.

"That’s a common misconception, that there is no treatment," says Superneau. "With many of these conditions, you can maybe employ some therapies that can be helpful down the road, and the earlier you know, the better."

March of Dimes picks 29

The March of Dimes has endorsed screening all babies for 29 disorders for which effective treatment is available. (See table). The recommendation is based on endorsement of the ACMG report, which was commissioned by the U.S. Health Resources and Services Administration, urging screening for these disorders.

The 29 disorders can be grouped into five categories: amino acid metabolism disorders, organic acid metabolism disorders, fatty acid oxidation disorders, hemoglobinopathies, and other disorders.

As of June 1, 2005, 23 states were testing for at least 20 of the 29 disorders recommended in the ACMG report. Fifteen states and the District of Columbia test for fewer than 10.

The March of Dimes also urges states to provide test results for an additional 25 "reportable" conditions named in the ACMG report. There are reliable tests for those conditions, but no documented treatments, yet.

A newborn can’t consent to being tested for a genetic condition, so that decision falls to the parents. In the case of disorders for which there is a sure, sometimes lifesaving treatment, Ginsberg says, the choice is clear — the child’s health dictates the test should be done.

But when little is known about the condition and even less about how to treat it, or if the genetic markers can only indicate a risk of disease, such as breast cancer, which the child might never develop, should the tests be run and the results disclosed?

"You’re drawing blood from a baby, so the decision has been made for the baby," says Ginsberg. "Do you want to know the distant future, even if it might never develop?"

Baily says treatment of some potentially fatal conditions in newborns hinges on early detection, possibly before the conditions and screens can be thoroughly explained to parents, who are presumed to consent to the screenings unless they opt out for religious or other legally permitted reasons.

"There is a strong ethical argument [in medicine] that patients undergoing genetic testing should be able to consent to treatment, but that any well-informed newborn’ would want to be tested for life-threatening disorders," she says.

But besides parents, who else should — or might — learn of the results of genetic tests?

"It’s an issue that we will have to share this information with insurance companies who then may not insure someone who might not even develop the disease," Ginsberg says. "What if you find out you’re going to develop Parkinson’s disease at age 30 or 40 — do you have to share that with your life or health insurance company?"

Babies and their families may be left in a bind. If they deliberately withhold information about a disorder from an insurance company, they could be guilty of insurance fraud. On the other hand, if they disclose a health condition, they could face higher premiums or complete refusal of coverage.

The effects of that needlestick to the heel, Baily points out, "go far beyond just doing the tests."

"It’s very complex, with lots of ethical issues attached."

Sources

  • Mary Ann Baily, PhD, Associate for Ethics and Health Policy, The Hastings Center, Garrison, NY. Phone: (845) 424-4040. E-mail: bailym@thehastingscenter.org.
  • Harley Ginsberg, MD, Neonatologist, Ochsner Clinic Foundation, New Orleans. Phone: (540) 842-4109.
  • Duane W. Superneau, MD, Geneticist, Genetic Services of Louisiana, Baton Rouge. E-mail: duane. superneau@womans.org.
  • American College of Medical Genetics. "Newborn Screening: Toward a Uniform Screening Panel and System," final report, available at www.mchb.hrsa.gov/screening.
  • March of Dimes, White Plains, NY. Web site: www.marchofdimes.com.
  • The National Newborn Screening and Genetics Resource Center. Web site: www.genes-r-us.uthscsa.edu.