This past week, while supervising the neuropsychology rotation of our doctoral students, I asked a student to clarify on a report whether the birth weight of a patient was “below or at expectation” for his gestational age. I explained that in most cases, it is not whether the baby was born prematurely, but whether his weight was “normal” for the length of the pregnancy.  Sometimes, being premature itself is not a risk factor for specific neurodevelopmental disorders. What is important in predicting healthy development is whether the baby shows typical growth up to the day of the birth – even when the birth day is significantly before the full term date.

In the latest issue of the journal of the American Academy of Pediatrics there is a new epidemiological examination of the association between prematurity and autism that highlights the point I was making to my students. There are a number of studies that have found a link between prematurity and autism, in that premature babies are at greater risk for developing autism than full term babies. However, other studies have failed to replicate such findings. What could explain such discrepancy? One possibility is that it is not about being premature that increases the risk for autism, but instead such increased risk is due to complications and other factors associated with prematurity. If these variables have not been controlled similarly across studies then you will find studies providing conflicting results due to unknown, or uncontrolled, characteristics of the sample.

In the study published in Pediatrics, a Swedish team of researchers examined a population sample of 1,216 individuals with a autism spectrum diagnosis and over 6,000 non affected peers. These groups were similar in sex distribution, age, and most importantly: birth hospital. This is key, because it theoretically eliminates the possibility that any differences found between the groups are due to differences in the health services received during birth.  The authors first compared the risk for autism spectrum disorders associated with prematurity, and then examined whether specific neonatal complication factors could explain the observed risk.

Main finding:

  1. Being born at or before 31 weeks of gestation doubled the risk for developing an autism disorder  when compared to full term infants.
  2. Being born between 32 and 36 weeks of gestation increased the risk for an autism disorder by 55%.

However:

After adjusting (controlling) for neonatal complications and related factors, being born prematurely – even before 32 week gestation – DID NOT increase the risk of developing autism. That is, prematurity itself was not associated with autism once we take into account specific complications that are common among premature infants.

So what are the neonatal factors associated with autism risk?

While controlling for all neonatal and related factors:

  1. Low weight for gestational age was a risk factor for autism. Specifically, being small for gestational age increased the risk for developing autism by 86%.
  2. Having congenital malformations increased the risk by 106%
  3. Having intra-cranial bleeding, edema, or seizures increased the risk by 206%
  4. Having Hypoglycemia increased the risk for ASD by 120%

The following neonatal factors were NOT associated with an increased risk for autism: Jaundice, respiratory distress, infections, head and neck injuries during delivery, apgar score, being a twin, or being large for gestational age.

The results are consistent with other findings suggesting that “weight for gestational age” and related complications are more informative when estimating the probability of future neurodevelopmental disorders than simply being premature. This may also help explain why many premature babies don’t show any lasting effects, even when they are born severely premature (<32 weeks), while others have significant developmental complications  (autism, ADHD, learning disabilities) even when they are born only a few weeks premature.

Buchmayer, S., Johansson, S., Johansson, A., Hultman, C., Sparen, P., & Cnattingius, S. (2009). Can Association Between Preterm Birth and Autism be Explained by Maternal or Neonatal Morbidity? PEDIATRICS, 124 (5) DOI: 10.1542/peds.2008-3582
ResearchBlogging.org

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One Response to Autism and premature babies: some possible explanatory variables.

  1. RAJ says:

    How did the authors define low birth weight? Cutoffs for defining low birth weight babies may be arbitrary. Hack et al (2009) looked at the outcomes of Extremely Low Birth Weight (ELBW) for gestational age and found that ELBW is associated with increased risk for poor neurodevelopmental outcomes, including both autism and Asperger Syndrome.

    http://www.ncbi.nlm.nih.gov/pubmed/19322106?

    Unfavorable events in the prenatal, perinatal and neonatal period increase the risk for ASD and other neurodevelopmental problems.

    http://pediatrics.aappublications.org/cgi/content/abstract/107/4/e63

    The authors state the obvious:

    “Perhaps future research will confirm certain pre-, peri-, and neonatal associations that could be used to generate a high-risk historical profile with which to use in conjunction with currently employed diagnostic tools. This may, in turn, help to determine the reliability of a diagnosis of autism in younger children, leading to earlier intervention and assistance for an improved outcome in long-term functionality and quality of life”

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