Clinical Context

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted behavior and deficits in social communication and interaction. Previous research showed prolonged auditory brainstem response (ABR) in children and adults with ASD.

Although ABR is a promising biomarker, it is unclear whether healthy newborns who later develop ASD also have ABR abnormalities. The current study addressed this question using ABR data from Universal Newborn Hearing Screening (UNHS).

Study Synopsis and Perspective

A commonly used newborn hearing test shows promise for early detection of ASD, according to one of the largest studies of its kind, published online October 31 in Autism Research.

The ABR test, performed on most newborns, represents "a huge untapped potential" to detect autism, lead author Oren Miron, research associate, Department of Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, and a PhD candidate at Ben Gurion University in Israel, told Medscape Medical News.

"The findings further reinforce our understanding that autism, in many cases, has a sensorial and auditory aspect," said Miron, adding that an adverse response to sound is one of the earliest behavioral signs of autism.

Early Intervention Critical

ASD affects an estimated 1 in 59 children. Early identification and intervention are critical for improving outcomes and decreasing the associated economic burden.

ABR, used for UNHS, uses surface electrodes to measure auditory nerve and brainstem responses to sound delivered through an earpiece at 35 decibels (dB) above normal hearing level (nHL) at 77 clicks/second in the right ear and 79 clicks/second in the left ear.

Previous studies identified abnormal ABR amplitude in children with ASD. However, it is unclear whether healthy newborns who later develop autism also show ABR differences vs those who do not.

UNHS data provided a larger, younger, healthier sample compared with previous studies (321 newborns later diagnosed with ASD; 138,844 controls). Mean ABR testing age was 1.76 vs 1.86 days; 76.95% vs 51.11% were male; neonatal intensive care unit admission rate was 7.79% vs 9.72%.

Brainstem Abnormalities?

When sound reaches the brain stem, it creates 5 consecutive waveforms: I, II, III, IV, and V.

Previous studies focused on wave V, which is easiest to detect. The current study used low-intensity sound, causing a weaker signal. To overcome this, the researchers focused on the negative drop (latency) after wave V (Vn), which is easier to detect, and on ABR phase, or the entire waveform.

ABR phase was prolonged in the ASD vs non-ASD group in the right (P<.001) and left (P=.021) ear. In the right but not left ear, Vn latency was significantly prolonged (P=.048) such that Vn might appear after 8 msec in normally developing children vs 8.5 to 9 msec in those with autism.

This is the first study to show Vn and phase abnormalities associated with ASD, suggesting anatomical abnormalities in the brainstem.

Present Before Birth?

The presence of ABR biomarkers of ASD in the first weeks after birth suggests it is likely present before birth in many of these children.

It is possible the ABR test could be modified to use lower intensities to detect not only hearing impairment but also autism risk, said Miron. "The test has been optimized to detect hearing impairment, and it does so brilliantly and it helps thousands of children. We want to do the same kind of optimization for autism."

The level of prolongation to detect ASD is still unclear. "I would think a lot of people would want to make it 1 standard deviation [SD], but it depends on a lot of factors, including, for example, whether a baby is preterm," he said.

More research and better accuracy and specificity are needed before the newborn hearing test is clinically useful. Miron noted that it is only one marker of autism, which could potentially be combined with other behavioral signs and genetic markers to facilitate earlier diagnosis and treatment and improve outcomes for patients with ASD.

Future research by his group will investigate whether the degree of auditory prolongation relates to autism severity and ASD subgroups including children with comorbid epilepsy.

Terrific, Clever Research

Commenting for Medscape Medical News, Jeremy Veenstra-VanderWeele, MD, professor, Child and Adolescent Psychiatry, Columbia University, called the study "terrific" and a "clever use" of an existing data set, showing "a difference between a large group of kids with autism and a large group of kids without," but more research is needed.

"[F]or this to be a screening test that could be broadly applied you would need to identify a cutoff where you'd think a child was at risk for autism, [but] there are no clear cutoffs," he said. "[Y]ou would have to establish sensitivity and specificity [and] look not just at the comparison of kids with autism and kids without but apply it in a predictive way in a second population."

The study authors and Dr Veenstra-VanderWeele have no relevant conflicts of interest.

Clinical Implications

• ASD vs non-ASD newborns had significantly prolonged ABR phase in both ears and Vn latency in the right but not left ear.
• Early detection of ASD risk could result in earlier diagnosis, allowing earlier treatments and better outcomes.
• Implications for the Health Care Team: Even if future studies are sufficiently accurate to detect ASD risk, clinicians should rule out hearing impairment and other diagnoses affecting ABR and should refer infants for a behavioral ASD diagnosis.

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