Saturday, 19 November 2016

Low gestational age is associated with risk for autism

The results published by Robert Joseph and colleagues [1] provide some blogging fodder today, observing that as part of the ELGAN (Extremely Low Gestational Age Newborns) Research Study, gestational age might matter when it comes to offspring risk of autism spectrum disorder (ASD).

Gestational age is a measure of how far along a pregnancy is but in the context of the Joseph study refers to premature birth or those "born at least 3 months early." Researchers included data for nearly 1000 children born extremely premature using a prospective (rather than retrospective) methodology who, at age 10, were "evaluated for ASD and ID [intellectual disability]." They also took into account various other 'pregnancy information' derived from both medical records and interviews with mums. This included instances of cervical-vaginal ‘infection’ among other things.

The results: over 90% of their cohort were assessed for autism/ASD and ID. Rates of ASD alone (without ID) were 3.2%. Some 3.8% of participants screened positive for autism and ID and 8.5% of participants presented with ID but not autism. Whilst these autism (with or without ID) rates might seem high, I'm not actually convinced that they are 'significantly higher' than that suggested in modern times (see here). The authors also noted that: "The lowest gestational age category (23-24 weeks) was associated with increased risk of ASD+/ID+... and ASD+/ID-."

Also: "Maternal report of presumed cervical-vaginal ‘infection’ during pregnancy was associated with increased risk of ASD+/ID+." The sorts of things included under the heading of cervical-vaginal infection were "bacterial infection (n = 4), bacterial vaginosis (n = 30), yeast infection (n = 62), mixed infection (n = 4) or other/unspecified infection (n=43; e.g., chlamydia, trichomonas or herpes, etc.)."

I agree with the authors that "low gestational age is associated with increased risk for ASD" and this research does seem to tally with other studies on this topic (see here for example). The one caveat I do want to make however is that the absolute numbers of children diagnosed with autism (with or without ID) were quite low (27 and 32 children respectively out of a total of 840) and somewhat dwarfed in comparison to those presenting with ID without autism (71 children out of 840). Still, preferential screening for autism and ID might be implied from these results; assuming that is, that the screening instrument in question is up to the job [2].

As to potential mechanisms of effect... well, it's rather difficult to pin any 'excess autism risk' to any one mechanism in light of the various factors that can accompany prematurity. Aside from the immaturity of various biological system associated with premature birth (including the brain), the obvious effect of a reduced birth weight is something to consider (see here). I am also interested in the idea that infection (using the term quite broadly) during pregnancy might also impact on offspring autism risk in light of other data (see here). Specific pathogens during pregnancy affecting offspring developmental risks have already made a mark on the peer-reviewed research literature (see here for example) and could provide a template for the processes pertinent to infection plus prematurity too.


[1] Joseph RM. et al. Extremely low gestational age and very low birth weight for gestational age are risk factors for ASD in a large cohort study of 10-year-old children born at 23-27 weeks gestation.  American Journal of Obstetrics and Gynecology. 2016. Aug 13.

[2] Kim SH. et al. Predictive Validity of the Modified Checklist for Autism in Toddlers (M-CHAT) Born Very Preterm. J Pediatr. 2016 Nov;178:101-107.e2.

---------- Joseph, R., Korzeniewski, S., Allred, E., O’Shea, T., Heeren, T., Frazier, J., Ware, J., Hirtz, D., Leviton, A., & Kuban, K. (2016). Extremely low gestational age and very low birth weight for gestational age are risk factors for ASD in a large cohort study of 10-year-old children born at 23-27 weeks gestation American Journal of Obstetrics and Gynecology DOI: 10.1016/j.ajog.2016.11.1009