Neonatal Jaundice and Autism Risk

Objectives The goals were to study the association between neonatal jaundice and disorders of psychological development in a national, population-based cohort and to study whether gestational age, parity, and season of birth influenced that association.

Methods A population-based, follow-up study of all children born alive in Denmark between 1994 and 2004 (N = 733 826) was performed, with data collected from 4 national registers. Survival analysis was used to calculate hazard ratios (HRs).

Results Exposure to jaundice in neonates was associated with increased risk of disorders of psychological development for children born at term. The excess risk of developing a disorder in the spectrum of psychological development disorders after exposure to jaundice as a neonate was between 56% (HR: 1.56 [95% confidence interval [CI]: 1.05–2.30]) and 88% (HR: 1.88 [95% CI: 1.17–3.02]). The excess risk of infantile autism was 67% (HR: 1.67 [95% CI: 1.03–2.71]). This risk for infantile autism was higher if the child was conceived by a parous woman (HR: 2.71 [95% CI: 1.57–4.66]) or was born between October and March (HR: 2.21 [95% CI: 1.24–3.94]). The risk for infantile autism disappeared if the child was conceived by a primiparous woman (HR: 0.58 [95% CI: 0.18–1.83]) or was born between April and September (HR: 1.02 [95% CI: 0.41–2.50]). Similar risk patterns were found for the whole spectrum of autistic disorders.

Conclusions Neonatal jaundice in children born at term is associated with disorders of psychological development. Parity and season of birth seem to play important roles.

From press release:

Autism is more common in children who had jaundice at birth, a big Danish study found, but researchers cautioned they don't know how the two conditions might be related and that new parents shouldn't be alarmed.

Mild jaundice is fairly common and generally harmless. Severe, untreated jaundice is known to cause brain damage, but it's also rare and hasn't been proven to cause autism. It's possible that children genetically predisposed to autism might also be more vulnerable than others to jaundice.

But if autism and jaundice are related, the study doesn't answer whether one of the ailments might have caused the other, said Rikke Damkjaer Maimburg, the lead author and a researcher at Denmark's Aarhus University.

Maimburg and colleagues examined medical data on all 733,826 children born in Denmark between 1994 and 2004. The results were prepared for release online Monday in Pediatrics.

More than 35,000 newborns had jaundice, while autism was eventually diagnosed in 577 children. Among autistic children, almost 9 percent had jaundice as newborns, compared with 3 percent of other children.

Previous studies on a possible autism-jaundice link have produced conflicting results.

The new results shouldn't scare parents whose newborns are jaundiced, said Dr. Thomas Newman, a pediatrician and epidemiologist at the University of California at San Francisco who studied the same topic and found no link.

Mild jaundice can cause a yellowish-orange tinge to the skin and simply signals that newborns' livers aren't fully mature. Newborns are typically examined for jaundice before leaving the hospital, and it usually disappears within a week or two without treatment.

"Jaundice is almost always harmless," Newman said. "The evidence for an association (with autism) is weak and inconsistent and evidence for causality nonexistent."

The study lacked data on severity of jaundice, which involves having elevated levels of bilirubin in the body. Bilirubin is yellowish pigment created as the body recycles old red blood cells. It is processed by the liver; during pregnancy the mother's liver handles the job and sometimes newborns' livers take a while to kick in.

The autism-jaundice link was not seen in Danish children born prematurely. The authors said brain development near birth might be most vulnerable to high bilirubin levels, but that's only speculation.