Newborn babies who develop jaundice, a common liver problem that turns their skin and eyes yellow, are at greater risk for autism, according to Danish researchers who studied all children born in that country during a 10-year period.
Full-term babies born between 1994 and 2004 who were diagnosed with jaundice were 67 percent more likely to develop autism than those without jaundice, according to the study published in the latest issue of the journal Pediatrics.
Babies most at risk were those born to mothers who had had children previously, and those born in the darkest months of the year, October to March, said researchers at Aarhus University in Denmark.
“Yes, I was a bit surprised,” said Rikke Maimburg, the Danish epidemiologist who led the study that analyzed records from nearly 734,000 births. “We have previously found the connection in a smaller study … Now we find it again with sufficient statistical power.”
U.S. autism researchers and advocates found the population-based results surprising, too, but they said the findings should be interpreted with caution by the public, by parents of children with autism — and by parents of the millions of newborns who develop jaundice in the first few days of life.
“This study does not say that increased bilirubin caused autism,” said Dr. Susan Levy, a developmental pediatrician and autism expert at the Center for Autism Research at Children’s Hospital of Philadelphia. “That may be a little piece of it, but it’s not the whole thing.”
5 percent of babies treated for jaundice
Bilirubin is a yellowish pigment found in bile, a fluid produced by the liver. Jaundice occurs when bilirubin accumulates faster than a baby’s new liver can break it down to be excreted. Sixty percent of babies have some form of jaundice, and about 5 percent have to be treated for the condition with special phototherapy lights that help dissipate bilirubin. If left untreated, jaundice can cause a condition called kernicterus, which can cause brain damage, deafness, mental retardation and cerebral palsy.
Previous studies have investigated a possible link between jaundice and autism, the pervasive developmental disorder that now affects about 1 in 100 children in the United States. Parents on autism blogs routinely suggest that the liver trouble could have been a key to their children’s autism diagnoses.
But Alycia Halladay, director of research in the environmental services division for Autism Speaks, a leading autism advocacy agency, said this study should be interpreted with caution by those parents, too.
“It does show an elevated risk, but it’s not a biomarker for autism,” said Halladay. "For those parents with children who did have jaundice, it should not be a confirmation whatsoever that jaundice causes autism."
At best, the study suggests that jaundice should be considered, along with factors such as family history and autism in an older sibling, as a possible risk for autism, said Wendy Stone, director of the University of Washington Autism Center in Seattle. Eventually, the disorder may become part of a larger screening tool.
“It’s a long way before extrapolating to the individual child,” Stone said.
The Danish researchers analyzed medical records of 733,826 children born in Denmark over 10 years. Of those babies, 35,766, or nearly 5 percent, were documented as having jaundice. Of those, 1,721 children, or nearly 5 percent, developed a range of psychological disorders, including autism.
By comparison, of the 698,060 babies born without jaundice, only 1,019 developed a psychological disorder, or 0.1 percent. In Denmark, autism is usually diagnosed at about age 4 or 5, said Maimburg, the lead researcher.
Overall, the babies with jaundice were between 56 percent and 88 percent more likely to develop any kind of psychological development disorder and they were 67 percent more likely to develop infantile autism specifically, the study reported.
Risk disappears in warmer months
The most puzzling findings were that the risk of autism disappeared for firstborn babies, for those born before 40 weeks gestation and for babies born in the warmer months, April through September. Maimburg speculated that mothers who’ve already had children may have more antibodies that could be linked to future problems and that full-term babies might have a window of vulnerability in their liver function. Perhaps more daylight contributes to lower bilirubin levels or faster resolution of the liver condition, the study suggested. Maimburg is hoping for future funding to answer those questions.
This study is not the last word and any link between jaundice in newborns and autism will have to be explored more thoroughly, said Dr. Frederick Suchy, a professor of pediatrics and chief of pediatric hepatology at Mount Sinai Medical Center in New York, who reviewed the research.
That's partly because the Danish health records didn’t include key data, Suchy said. There was no record of the levels of bilirubin found in the children’s blood, or whether the children received phototherapy. Also, it's likely, but not certain, that the 5 percent of newborns recorded as being diagnosed with jaundice were only those with conditions serious enough to require phototherapy treatment.
(In Denmark, as elsewhere, about 60 percent of all babies develop some level of jaundice in the first days of life, and about 5 percent require treatment, Maimburg said.)
The findings also might be confounded by the rules of the Danish health system, which keep first-born babies in the hospital for up to three days — long enough to be diagnosed and treated for jaundice — while babies born to previous mothers are sent home shortly after delivery.
In any case, Suchy cautioned against a rush to blame a recent rise in apparent autism rates to the common liver disorder, which has remained steady. “I don’t think you can attribute the increase in autism to hyperbilirubinemia,” he said, using the formal name for jaundice.
Even Wendy Fournier, the mother of a child who had jaundice and later developed autism, said she’d need more convincing about the link. Fournier, who is president of the National Autism Association, wants to know what it is about the babies’ livers that makes them more prone to jaundice, and whether that mechanism may be behind the increased risk for autism.
“I think it’ll be taken with a grain of salt for now,” Fournier said. “I think it’s interesting, but it does raise a lot of questions.”