Wednesday, April 11, 2018

Diagnosing autism in newborns: The 'wave' of the future?

Miron O, Beam AL, Kohane IS. Auditory brainstem response in infants and children with autism spectrum disorder: A meta-analysis of wave V. Autism Res. 2018 Feb;11(2):355-363.

Infants with autism spectrum disorder (ASD) were recently found to have prolonged auditory brainstem response (ABR); however, at older ages, findings are contradictory. We compared ABR differences between participants with ASD and controls with respect to age using a meta-analysis. Data sources included MEDLINE, EMBASE, Web of Science, Google Scholar, HOLLIS, and ScienceDirect from their inception to June 2016. The 25 studies that were included had a total of 1349 participants (727 participants with ASD and 622 controls) and an age range of 0-40 years. Prolongation of the absolute latency of wave V in ASD had a significant negative correlation with age (R2 = 0.23; P = 0.01). The 22 studies below age 18 years showed a significantly prolonged wave V in ASD (Standard Mean Difference = 0.6 [95% CI, 0.5-0.8]; P < 0.001). The 3 studies above 18 years of age showed a significantly shorter wave V in ASD (SMD = -0.6 [95% CI, -1.0 to -0.2]; P = 0.004). Prolonged ABR was consistent in infants and children with ASD, suggesting it can serve as an ASD biomarker at infancy. As the ABR is routinely used to screen infants for hearing impairment, the opportunity for replication studies is extensive. 

Our analysis of previous studies showed that infants and children with autism spectrum disorder (ASD) have a slower brain response to sound, while adults have a faster brain response to sound. This suggests that slower brain response in infants may predict ASD risk. Brain response to sound is routinely tested on newborns to screen hearing impairment, which has created large data sets to afford replication of these results.

Miron O, Ari-Even Roth D, Gabis LV, Henkin Y, Shefer S, Dinstein I, Geva R. Prolonged auditory brainstem responses in infants with autism. Autism Res. 2016 Jun;9(6):689-95.

Numerous studies have attempted to identify early physiological abnormalities in infants and toddlers who later develop autism spectrum disorder (ASD). One potential measure of early neurophysiology is the auditory brainstem response (ABR), which has been reported to exhibit prolonged latencies in children with ASD. We examined whether prolonged ABR latencies appear in infancy, before the onset of ASD symptoms, and irrespective of hearing thresholds. To determine how early in development these differences appear, we retrospectively examined clinical ABR recordings of infants who were later diagnosed with ASD. Of the 118 children in the participant pool, 48 were excluded due to elevated ABR thresholds, genetic aberrations, or old testing age, leaving a sample of 70 children: 30 of which were tested at 0-3 months, and 40 were tested at toddlerhood (1.5-3.5 years). In the infant group, the ABR wave-V was significantly prolonged in those who later developed ASD as compared with case-matched controls (n = 30). Classification of infants who later developed ASD and case-matched controls using this measure enabled accurate identification of ASD infants with 80% specificity and 70% sensitivity. In the group of toddlers with ASD, absolute and interpeak latencies were prolonged compared to clinical norms. Findings indicate that ABR latencies are significantly prolonged in infants who are later diagnosed with ASD irrespective of their hearing thresholds; suggesting that abnormal responses might be detected soon after birth. Further research is needed to determine if ABR might be a valid marker for ASD risk.

We used the test called the auditory brainstem response (ABR), which is done on every newborn to detect hearing impairment, and we modified it so that it also can detect autism. We accomplished this by looking back at databases, including thousands of brain tests, and checking which of these patients have autism today. We found that while children with hearing impairment do not have a stable response to this test, children with autism tend to have a delayed response. We found this to be a great predictor of autism and have published two studies about it.[1,2]

We are now trying to develop the test further so that it can be included with those hearing tests. Thus, we would turn those 4 million hearing tests that are done each year into 4 million autism tests. Our hope is that, together with other risk factors and eventually with more thorough and comprehensive behavioral diagnoses, this will allow earlier validation of autism, perhaps at age 2 or 3 years (now it is at 4 years), and earlier treatment with potentially better results….

When I first started learning about autism, everyone was focused on the prefrontal cortex, and the newer the cortex, the better. When I looked at the literature, I saw that there have been studies dating from the '70s. I have just published a meta-analysis that included these.[2] Dozens of studies were conducted with ABR and found this prolongation of response in children with autism. At some point, they understood the ABR so well that they started using it to screen for hearing impairment; they did not just use it for those children with problems. And now it is being used on every baby in most US hospitals. I thought that if this delayed response happens in children with autism, why don't we also check it in newborns and look for a correlation? And that proved to be successful. I definitely built on the work done by these earlier researchers, and I am very grateful for them, especially Professor Hildesheimer, who not only found the abnormality of autism in ABR for the first time but also invented the ABR device that we use. I am standing in their shadows…

This test is inexpensive, which is important to me. The baby comes to you, you give the click, and 5 minutes afterwards you know if the baby hears.

That is why this test is rapidly expanding to developing countries where autism is never diagnosed. If we can use this test to help detect autism in those countries, that would be phenomenal…

It seemed crazy at first to say that we were going to detect autism at birth, but I said to myself, if I am looking at existing data, I am wasting my time but not wasting anyone's money to check it. Thankfully, it turned out. Now with MIT Solve, we are trying to push it ahead to implementation. I am looking forward to helping. The test has already been done on 98% of the [newborn] population in the United States.

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