Published: October 11, 2010
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
Full-term neonates with jaundice are at greatly increased risk of later being diagnosed with a disorder of psychological development, a Danish study found.
Jaundiced newborns had an almost 90% higher likelihood of subsequently having any psychological developmental disorder compared with neonates without jaundice (HR 1.87, 95% CI 1.58 to 2.21, P=0.001), according to Rikke Damkjær Maimburg, PhD, of Aarhus University in Denmark, and colleagues.
Moreover, those born at term with jaundice had a 56% greater risk of the specific diagnosis of pervasive developmental disorder -- a disorder on the autism spectrum -- than those without jaundice (HR 1.56, 95% CI 1.05 to 2.30, P=0.028), the researchers reported in the November issue of Pediatrics
Neonatal jaundice typically is caused by increased bilirubin production and inadequate liver excretory function.
Exposure to high levels of bilirubin is neurotoxic in very young children and can be fatal or associated with permanent sequelae.
Recent research also has suggested that even moderate bilirubin exposure in very young children can be harmful, possibly leading to impairments in their development.
In an earlier case-control study, Maimburg and colleagues found a nearly fourfold increased risk of autism among children who had neonatal jaundice.
To further explore this link, along with other possible contributory factors, the Danish researchers conducted a population-based study that included all 733,826 children born in that country between 1994 and 2004, analyzing data from the Danish Medical Birth Register.
A total of 35,766 children had been diagnosed with neonatal jaundice, while 1,721 were given a diagnosis of a disorder of psychological development during childhood.
They found that jaundice was more common among boys, infants born preterm, infants with congenital malformations, and low-birthweight infants.
After stratification for term versus preterm birth, and adjustment for factors such as maternal smoking, birth weight, and gender, the association of neonatal jaundice and any disorder of psychological development was statistically significant for infants born at term (HR 1.29, 95% CI 1.06 to 1.56, P=0.011), the researchers reported.
In contrast, preterm infants were not at risk (HR 0.88, 95% CI 0.64 to 1.21, P=0.437).
"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," they observed.
Another possible explanation for the difference in risk between term and preterm infants is that those born before 37 weeks routinely are hospitalized, so the bilirubinemia would be detected and treated promptly.
Risks also were increased for certain specific subtypes of disorders of psychological development. The adjusted hazard ratio for disorders of speech and language was 1.56 (95% CI 1.01 to 2.40, P=0.46), while the hazard ratio for mixed developmental disorders was 1.88 (95% CI 1.17 to 3.02, P=0.009).
Further analysis of children born at term and exposed to bilirubin found other specific factors linked to autism:
- Birth between October and March, adjusted HR 1.97 (95% CI 1.23 to 3.17, P=0.005)
- Parous mother, adjusted HR 2.29 (95% CI 1.44 to 3.63, P=0.001)
Birth during the winter months, according to the researchers, may influence the development of neonatal jaundice because exposure to daylight helps decrease bilirubin levels.
"These results may reflect the different exposures to daylight but also the fact that children born in the winter period are more exposed to other contributing agents, such as infections," they wrote.
And as to why primiparous women were less likely to have jaundiced infants, possible reasons include their lower levels of antibodies and the fact that firstborn children in Denmark typically remain in the hospital for several days, and hyperbilirubinemia would be detected more quickly.
The researchers noted that their results may have been underestimated, because the data on neonatal jaundice were obtained from the Danish National Hospital Register and reflect only the severest cases.
"Additional evidence to distinguish the genetic and environmental components is needed to explain the association between neonatal jaundice and autistic disorders," they concluded.
Link to original article here: http://www.medpagetoday.com/Pediatrics/Autism/22663
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