How systematic reviews help us to advance research in neuropsychology
By Isabel Williams
A systematic review by some of our lab members was recently published in the journal of Child Psychiatry and Human Development [1]. A systematic review is a paper written after an exhaustive search of the relevant literature on a specific topic. All of the available, relevant studies are then gathered and their results are synthesised. This review sought to compare the findings of studies investigating predictors of autism spectrum disorder (ASD) in children born preterm. ASD is defined as expressing persistent, cross-contextual difficulties with social communication and interaction, which can range from mild to severe [2]. It is important to note that there is an ongoing debate surrounding the use of “person-first language” (i.e., people with autism) and “identity-first language” (i.e., autistic people) when talking about autism. For the purpose of our systematic review and this article, the term “people with ASD” was used to align with the most up to date edition of the Diagnostic and Statistical Manual of Mental Disorder (DSM-5). We identified a total of eleven relevant and eligible studies for our review.
What are the causes/risk factors for ASD?
While there is no one known cause of ASD, and no biological test for ASD, there has been a lot of research into the possible contributing factors. People with ASD have been found to have mutations in multiple different genes [3]. ASD is therefore thought to be moderately heritable [4], meaning that close relatives of someone with an ASD diagnosis are more likely to have ASD than a random member of the population. Structural brain differences – particularly in the frontal lobes – have been found in people with ASD, and have been linked to some of the typical ASD behavioural traits, such as difficulty with change in environment, as well as difficulty processing and responding to social cues and interactions [3]. Since genetics and early brain formation play a fundamental role in ASD, many of the risk factors for ASD that have been found are related to prenatal (before birth), perinatal (during birth) or postnatal (the first days or weeks after birth) factors. Therefore, studies investigating prenatal, perinatal and postnatal factors, such as premature birth, are crucial to our understanding of ASD.
Our research in the UCD Neuropsychology lab
In our recent systematic review we found that very few prenatal predictors were found to be risk factors for ASD, although one study found cervical-vaginal infections during pregnancy to be a potential predictor of ASD [5]. Many other factors such as prenatal steroid therapy, smoking in pregnancy, medication use and urinary tract infection were investigated, however none were found to be significantly related to ASD diagnosis. Despite multiple investigations into many perinatal factors including mode of delivery, birth asphyxia and duration of labour, no perinatal factors were found to significantly increase the risk of autism.
Most of the studies found links between ASD and postnatal factors, with most indicating that prematurity (infants born at less than 37 weeks [6]) was a significant predictor of ASD. Almost half of the studies found male sex to be a significant predictor of ASD development. However it is likely that this factor is not related to preterm births, as a higher proportion of males than females have an ASD diagnosis in the general population. Infants with low gestational age or who were born extremely preterm (EP; infants born at less than 28 weeks [6]) were found to be at a higher risk of developing autism. Some hypothesised reasons for this connection include that their immature brain and body are extremely vulnerable, their immune system may not be functioning as it should, and that EP infants may not have developed all of the neuroprotective factors necessary for typical brain development [7]. In relation to post-natal factors, two studies using EP births found that cognitive impairments in childhood was related to ASD diagnosis. One reason given for this connection by one author [7] were that being born preterm can alter the course of normal brain development, resulting in social difficulties. An alternative reason may be that infants who are born preterm are more likely to experience an abnormal or unnatural physical and psychosocial environment (such as long periods of time in the NICU) during a possible postnatal sensitive period for social development [7].
Overall, this review highlighted the limited, contradictory research that has been conducted pertaining to the potential predictors of ASD. The one consensus found among the studies is that infants who are born prematurely are at a higher risk of receiving an ASD diagnosis later in life. Although it is not clear how being born prematurely is linked with autism, this review suggests that there may be an increased need for ASD screening for children who were born preterm. This might help more people to receive an earlier diagnosis, and to access ASD therapies and resources that may be needed.
Systematic reviews such as this one are vital to our scientific understanding of a topic, as they can provide a broad picture of the existing research. Furthermore, they can be a great guide to practitioners and future researchers in the field alike!
If you would like to learn more about ASD, take a look at these great Irish websites with lots of resources below.
https://asiam.ie/about-autism/
References
1. Cogley, C., O’Reilly, H., Bramham, J., & Downes, M. (2020). A systematic review of the risk factors for autism spectrum disorder in children born preterm. Child Psychiatry and Human Development, 52(5), 841-855. https://doi.org/10.1007/s10578-020-01071-9
2. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). https://doi.org/10.1176/appi.books.9780890425596
3. Casanova, E. L., & Casanova, M. F. (2019). Defining autism: A guide to brain, biology, and behavior. Jessica Kingsley Publishers.
4. Yu, T., Chahrour, M., Coulter, M., Jiralerspong, S., Okamura-Ikeda, K., Ataman, B., Schmitz-Abe, K., Harmin, D., Adli, M., Malik, A., D’Gama, A., Lim, E., Sanders, S., Mochida, G., Partlow, J., Sunu, C., Felie, J., Rodriguez, J., Nasir, R., . . . Walsh, C. (2013). Using whole-exome sequencing to identify inherited causes of autism. Neuron (Cambridge, Mass.), 77(2), 259-273. https://doi.org/10.1016/j.neuron.2012.11.002
5. Joseph, R. M., Korzeniewski, S. J., Allred, E. N., O’Shea, T. M., Heeren, T., Frazier, J. A., Ware, J., Hirtz, D., Leviton, A., Kuban, K., Ware, J., Coster, T., Henson, B., Wilson, R., McGhee, K., Lee, P., Asgarian, A., Sadhwani, A., Perrin, E., . . . ELGAN Study Investigators. (2017). Extremely low gestational age and very low birthweight for gestational age are risk factors for autism spectrum disorder in a large cohort study of 10-year-old children born at 23-27 weeks’ gestation. American Journal of Obstetrics and Gynecology, 216(3), 304.e1-304.e16. https://doi.org/10.1016/j.ajog.2016.11.1009
6. World Health Organisation. (2022, November 14). Preterm birth. https://www.who.int/news-room/fact-sheets/detail/preterm-birth
7. Johnson, S., PhD, Hollis, Chris, PhD, MRCPsych, Kochhar, P., BSc, Hennessy, E., MSc, Wolke, D., PhD, & Marlow, Neil, DM, FMedSci. (2010). Autism spectrum disorders in extremely preterm children. The Journal of Pediatrics, 156(4), 525-531.e2. https://doi.org/10.1016/j.jpeds.2009.10.041