After seven years of unexplained infertility, Ann Najdek-Andrada finally had a son, a baby boy who seemed as perfect as she’d always imagined.
But that fantasy was shattered when Gianni was two weeks old. That’s when the call came saying the child had tested positive for cystic fibrosis — and that it would take nearly four months to find out for sure.
“After everything we’d been through, I was thinking to myself ‘Why does this have to happen?’” said the 34-year-old Mastic, N.Y., mom. “My husband even cried when I was explaining the whole thing to him.”
The weeks dragged by, with Najdek-Andrada juggling the care of a newborn with constant worry about his health.
“Absolutely, waiting was the worst part,” she said. “You’re living in uncertainty.”
When Gianni was finally old enough to have the sweat test that confirms CF, an inherited lung disease that can lead to disability and early death, the news was good. Gianni’s initial newborn screening test was actually a false positive, a kind of mistaken result experts say may affect as many as 200,000 babies in the U.S. each year.
"I was extremely relieved," his mother said.
Gianni Andrada was among some 4.1 million babies born in the U.S. in 2009, one of nearly all newborns who are screened for an ever-growing list of genetic problems aimed at detecting devastating disease before symptoms start.
Every year, between 4,000 and 5,000 infants are correctly identified as having serious genetic disorders, including some that would result in disability or death if they weren't flagged so treatment could begin.
When they’re correct, such tests are invaluable. But when they’re not — and they're not a lot — parents and kids can endure months of repeated tests, special sleeping schedules and stringent diets, plus lingering uncertainty and anxiety, health experts say.
Only 1 in 50 positive tests is true
Overall, perhaps only one in 50 of every “positive” newborn screening tests detects actual disease, estimates Dr. Philip M. Farrell, a professor of pediatrics and population health sciences at the University of Wisconsin School of Medicine and Public Health. But that average can vary widely.
On average, for every 10 positive screening tests for cystic fibrosis, one child will actually have the disease, Farrell said.
But for the disorder congenital adrenal hyperplasia — which can cause boys to enter puberty at age 2 or 3 — there are between 100 and 200 false positives for every child truly affected.
“In my opinion, it’s just tragic that parents have to suffer and think about their child having a chronic illness when the child is perfect healthy,” said Audrey Tluczek, an assistant professor and psychologist at the University of Wisconsin-Madison School of Nursing.
In Jennifer Allen’s case, for instance, she was told her 10-day-old daughter, Sophie, had tested positive for propionic acidemia, a potentially fatal disorder that required Allen to wake the baby on a strict schedule for careful feeding. For two weeks last fall, the 25-year-old mother of three from Ontario, Canada, lived with constant fear.
“There was all this pressure on me to keep her fed, to keep waking her up,” Allen recalled. “And then it came back she was perfectly healthy. It felt like a part of what I was supposed to enjoy with her as a newborn was taken away from me.”
Certainly, no one wants to miss sick babies, said Farrell, noting that the consequence of a false negative test "can be devastating." However, experts now say that tackling the problem of false positives must become as important as detecting disease in the first place.
“These families with false positive tests should be cared for and receive the kind of attention they deserve," Farrell said. "There needs to be more attention given to that, in my judgment.”
Dozens of conditions screened
Newborn screening has been conducted in the U.S. for more than four decades, starting with mass voluntary testing for phenylketonuria or PKU.
Today’s babies may be screened for dozens of disorders, including a uniform screening panel of 30 core treatable conditions, plus another 25 ailments without a standard treatments, according to the American College of Medical Genetics. States may also screen for additional conditions beyond the 55.
With a few drops of blood from a heel prick, a process called tandem mass spectrometry testing can identify multiple genetic defects at once. Computer analysis has made the process both fast and relatively inexpensive, allowing screening for problems from blood disorders such as sickle cell anemia to conditions such as congenital hypothyroidism.
But just because technology allows such testing doesn’t mean it’s done well — or consistently, noted Dr. Piero Rinaldo, a professor of laboratory medicine and pathology at the Mayo Clinic in Rochester, Minn.
He’s been working for years to improve a system in which newborn screening is conducted on a state-by-state basis, with widely ranging standards — and wildly varying outcomes for those who receive the results. The differences often depend on varied skills, plus political realities and resources. Some states, such as Minnesota, detect far more actual cases of disease with far fewer false positives than others, which may put some families at a disadvantage.
“To me, all children matter the same and they matter a lot,” Rinaldo said.
As it stands now, parents in one state might find that false positives rates are as low as 0.01 percent of all newborn tests, while parents a few states over may find as many as 1.52 percent of those tests are false alarms. In a hypothetical state with 100,000 live births, that’s the difference between 10 false positive results and more than 1,500 false positives.
Another measure, called the positive predictive value, or PPV, records the probability that a patient with a positive test result actually has the disorder in question.
Some states have a PPV of nearly 3 percent, which means that only 3 percent of the people who test positive for the disease actually have it, and 97 percent are false positives. In other states, the PPV is much better, above 50 percent. So far, only 28 states have been willing to report their results and then only anonymously, Rinaldo says.
Calculations aside, the impact of false positives on families can be huge, said Tluczek, the Wisconsin researcher. First, there’s the shock and anxiety that accompanies the initial finding. Then there’s the worry that pervades the waiting period for a confirmatory test, which can range from a few days to several months.
“For parents, even a day or two days wait, that can be like an eternity,” said Tluczek.
Lingering fears
Even after the diagnosis has been dismissed and the child proclaimed disease-free, the anxiety may linger. Some parents continue to wonder why the initial markers showed any problem, and secretly to worry that disease will emerge, after all. Some become wildly overprotective or find that stress infuses their family dynamics.
“They’re always waiting for that other shoe to drop, wondering whether my child will develop symptoms,” said Tluczek.
Experts like Rinaldo would like to see more consistent calculation, monitoring and lab-to-lab comparisons of newborn screening results, plus a second tier of DNA testing to weed out many false positives before parents are ever notified. So far, progress has been slow.
That's partly because in a field that’s rife with turf battles over how newborn tests will be conducted, who will do it, and how to pay for it, it’s a tough battle. Advocacy groups such as the Save Babies Through Screening Foundation Inc., abound.
Some critics object to raising the issue of false positives at all, saying that worries about anxiety are overstated, especially considering the potential devastation of a false negative test.
“Parents who are extremely anxious are in the extreme minority,” said Fred Lorey, acting director of the Genetic Disease Laboratory at the California Department of Public Health. “Compare that anxiety of the parent who finds out their kid is healthy vs. one whose child is missed.”
Take Korissa Olson, 41, of Brooklyn Park, Minn. She almost declined newborn screening when her son, Everett was born three years ago. Instead, hospital nurses convinced her to allow it — and the tests came back positive for galactosemia, a rare genetic disorder that can lead to cataracts, mental retardation and death if not detected and treated immediately. She had to wait two weeks for the condition to be confirmed, but in the meantime, treatment likely saved his life.
“I was actually hoping my son had a false positive,” she said. “I recognize and understand the pain they went through, but I really believe it is worth having the screening.”
Will concerns deter life-saving testing?
Olson also worries that any attention to the downsides of false positives might discourage parents to decline screening altogether.
Lorey urges expectant parents to pay attention to the information they receive about newborn screening and to educate themselves so false positives don’t come as a surprise. Tluczek advises doctors and other medical professionals to improve their communication skills to ensure that patients understand what a positive screening might mean – or not mean.
Although she values the goals of newborn tests, better information might have eased the worry about her son, said Ann Najdek-Andrada, the New York mom. When her second child, McKenzie, was born five months ago, she made sure to let everyone in her prenatal class know about the potential for false positive results from newborn screenings.
“It’s just something they should bring up,” she said. “There’s a lot of false positives, so don’t freak out until you have to freak out.”