December 14, 2023
Bilirubin is an orange-yellow pigment formed in the liver by the breakdown of hemoglobin and excreted in bile. Elevated levels in blood serum can cause jaundice, a yellowing of the skin, or whites of the eyes.
More than one in twenty Swedish newborns are treated for neonatal jaundice, which is particularly common among preterm babies. It is usually benign.
A team of Swedish researchers used e Swedish Medical Birth Register, which contains information on all children born in the country, to identify all 814,420 single births without birth defects between 1992 and 2000, and followed them until 2009. They then identified instances of neonatal jaundice and of ADHD through linked nationwide medical registers.
The team also identified a sub-sample of full siblings (384,290 children from 181,354 families) in order to control for shared familial traits.
In the unadjusted results, children with any kind of neonatal jaundice were 38% more likely to be diagnosed with ADHD. After adjustment for known confounding variables, two-thirds of the association disappeared, with a residual increased risk of 13%.
There are, however, two types of neonatal jaundice: hemolytic and non-hemolytic. Hemolytic jaundice is typically caused by the mother's immune system mistaking the fetus' red blood cells as a threat, and responding by attacking with antibodies, rupturing and destroying the cells.
The study found no association between hemolytic jaundice and ADHD, either in the raw results or after adjusting for known confounders. Unsurprisingly, there was also no association in the sibling comparison.
That meant that all the association was concentrated among children born with non-hemolytic jaundice, who in the crude results were 43% more likely to subsequently develop ADHD. Adjusting for known confounders again reduced the association by two-thirds, to 14%. But among siblings, that association vanished altogether. Children born with non-hemolytic jaundice were no more likely than their non-jaundiced siblings to develop ADHD.
The authors concluded that "neonatal jaundice is not likely a causal risk factor for ADHD."
Isabelle Le Ray, Chen Wang, Catarina Almqvist, PaulLichtenstein, Brian M. D'Onofrio, Stefan Johansson, Henrik Larsson, Mina A.Rosenqvist, "Neonatal jaundice, attention deficit hyperactivity disorder andfamilial effects: A Swedish register study with sibling analysis," ActaPaediatrica (2020), https://doi.org/10.1111/apa.15475.