A large study looking at the incidence of neonatal jaundice has found a strong correlation with subsequent development of neurodevelopmental disorders, including autism, in affected newborns.
Jaundice is a yellowing of the skin and whites of the eyes resulting from elevated levels of the blood pigment, bilirubin. It can result from increased production of bilirubin or reduced capacity of the liver to remove it from the bloodstream.
The study, conducted by Rikke Damkjær Maimburg and colleagues at Aarhus University in Denmark, found full-term infants presenting with jaundice at birth were much more likely to be diagnosed with a developmental disorder during childhood. The association did not hold true for children who were born prematurely, however.
Maimburg and colleagues had previously carried out a case-control study and found a nearly fourfold increased risk of autism among children who had neonatal jaundice. The current study was designed to explore this link further and involved analysing the birth records of all 733,826 children born in Denmark between 1994 and 2004. Of these children, 35,766 had been diagnosed with neonatal jaundice, while 1,721 were given a diagnosis of a developmental disorder during childhood.
The analysis revealed that jaundiced newborns were almost 90% more likely to subsequently present with a developmental disorder than neonates without jaundice. Furthermore, full-term newborns with jaundice had a 56% greater risk of the specific diagnosis of pervasive developmental disorder (PDD), a disorder on the autism spectrum.
Reporting their results in the journal Pediatrics, the researchers report that once children were grouped based on full-term and premature births, and factors such as maternal smoking, birth weight, and gender were controlled for, there emerged a statistically significant association between neonatal jaundice and developmental disorders for those born at full-term.
It is suspected that during foetal development the brain may be particularly susceptible to high concentrations of bilirubin, which is neurotoxic. Newborns with jaundice are exposed to elevated levels of bilirubin which may cause some degree of brain damage and result in developmental problems. To explain why full-term neonates with jaundice are at increased risk of developmental disorders while their preterm peers with jaundice are not, the Maimberg and colleagues say "The difference in risk for term and preterm children might suggest that brain development undergoes a sensitive period with special vulnerability to bilirubin exposure at ~40 weeks of gestation."
Another explanation might be that those born before 37 weeks are routinely kept in hospital and monitored for an extended period, so the jaundice would be detected and treated promptly, reducing exposure of the brain to bilirubin.
The study also revealed that risk was also increased for other disorders of psychological development, specifically disorders of speech and language and mixed developmental disorders. Additionally, the analysis of birth records showed that boys, infants with congenital malformations, and low-birthweight infants were more likely to be jaundiced at birth.
Since jaundice is a sign of reduced detoxification capacity it seems reasonable to speculate that along with bilirubin, infants affected may also be exposed to increased amounts of other neurotoxins passed to them by their mothers, or to which they are exposed during early childhood, and these could also contribute to the development of disorders such as autism.
The researchers conclude that "Additional evidence to distinguish the genetic and environmental components is needed to explain the association between neonatal jaundice and autistic disorders" and suggest that their results may have been underestimated due to data on neonatal jaundice obtained from the Danish National Hospital Register only reflecting the most severe cases.
Source: Maimburg RD Bech BH Væth M Møller-Madsen B Olsen J (2010) Neonatal jaundice, autism, and other disorders of psychological development Pediatrics 126:872-8