Autism: What’s Jaundice Got to do with it?
Staff bloggers Alycia Halladay, Ph.D., Director of Environmental Sciences and Leanne Chukoskie, Ph.D., Assistant Director of Science Communication and Special Projects
A study published on Monday in Pediatrics revealed that newborns who experienced jaundice were at greater risk for a later diagnosis of autism spectrum disorders. Jaundice is a common condition where bilirubin is not properly excreted by the liver, builds up in the blood and leads to a slight yellow pigment of the skin. Bilirubin is a neurotoxin and it is well established that untreated severe jaundice can lead to brain damage and even death. Fortunately, despite the fact that jaundice is very common in newborns, it usually resolves with minimal or no intervention within a few days of birth.
Previous studies have investigated the potential for increased risk of ASD following jaundice with mixed conclusions. The advantage of this study is that the researchers used a large health registry database in Denmark including over 700,000 birth and associated developmental health records. The researchers looked at the development of 35,766 children diagnosed with perinatal jaundice (4.9% of the entire study population). They looked for children diagnosed with ASD as well as a broader definition of disorders of psychological development, which included speech delay. The risk of an ASD was found to be about 52% greater in children who experienced jaundice as newborns versus those who did not.
This may be an overestimate because factors such as season of birth, gestational age, parental age, gender, and the birth order of the child were not considered in this comparison. When these factors were considered, the overall risk increase was no longer statistically reliable. However an interesting pattern emerged from individually considering the factors.
Although preterm children typically experience a greater risk of autism by virtue of the challenges of prematurity, it is the full term babies that have an increased risk for ASD after exposure to jaundice. The authors speculate that there may be some unique window of vulnerability in brain development around 40 weeks gestational age that can explain this finding.
Another interesting relationship emerged from looking at cases from mothers who had previously had children versus those giving birth for the first time. Jaundice increased the risk for developing an ASD in children who were second or later born, but conveyed no increased risk for first born children. This effect is also a bit of a scientific mystery, however we do know that second and later-born children can be exposed to maternal antibodies that accumulate from previous pregnancies.
Lastly, the authors found that birth during the winter months was statistically associated with greater ASD risk than birth in the summer months. Exposure to daylight helps to break down bilirubin, so it is possible that individuals born in summer months, though diagnosed with jaundice had lower levels of bilirubin in their blood simply because they were exposed to more sunlight. The authors also note that sunlight is required for Vitamin D synthesis and low light levels in the winter may alter the body’s ability to as synthesize Vitamin D. Vitamin D deficiency is another autism risk factor under investigation. Autism Speaks is currently supporting a study examining how Vitamin D levels at birth and genes for the Vitamin D receptor are related to a later autism diagnosis.
In summary, it is important to note that although this paper brings many new considerations, it does not establish that jaundice causes autism. Instead, this paper reports on the risk of developing ASD after exposure to jaundice. This risk is significantly modified by several factors. Data from this study suggests that babies with jaundice who were born prior to 37 weeks gestation have little to no increased risk of ASD. However, the data also indicate a substantially elevated risk for full-term babies born to mothers with previous pregnancies and also full-term babies that were born during winter months. Hopefully, this and other information about medical conditions at birth will lead to the further development of screening tools to identify individuals at risk for a later autism diagnosis. Before that is done, scientists need to determine the mechanism by which jaundice may be contributing to the risk of developing ASD. Further research will been needed to determine whether bilirubin is itself an environmental risk factor, or if jaundice is a consequence of both genetic and environmental effects that elevate the risk of developing autism.