Deficits in Early Infancy May Point to Autism

Aug. 8, 2010— -- Certain developmental characteristics seen as early as 1 month of age in infants who need care in a neonatal intensive care unit (NICU) may help predict a later diagnosis of autism spectrum disorders (ASD), researchers found.

A study of more than 2,100 newborns requiring a NICU stay found that those infants later diagnosed with an ASD were more likely to have persistent neurobehavioral abnormalities observed at 1 month, according to Bernard Karmel of the New York State Institute for Basic Research in Developmental Disabilities in Staten Island, N.Y. and colleagues.

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These infants were also more likely to have a characteristic known as asymmetric visual tracking, as well as abnormal upper extremity tone, seen at 1 month compared with matched controls without ASD, the researchers reported in the August issue of the journal Pediatrics.

Additional deficits among infants who would subsequently receive an ASD diagnosis were also identified with testing through age 2.

"These patterns, although not in the social domain, have features that are consistent with behaviors that are associated with ASD in older children, leading us to speculate that they may be precursors to ASD, if not other developmental disorders," the researchers wrote.

The study does not confirm that the patterns observed are diagnostic for ASD, or would allow for earlier intervention in children with ASD, the researchers stressed.

Karmel and his colleagues proposed, however, "that the association of the behaviors described here with ASD in a medically compromised cohort might establish a group of infants to study prospectively to identify precursors to ASD, along with the more established strategy of study designs involving infant siblings of children with ASD."

Previous studies have found that rates of ASD are higher among children who required a stay in the NICU.

To identify early problems which may be more frequent in children who had spent time in a NICU and later developed an ASD, Karmel and his colleagues looked at data over an 11-year period among 2,197 babies who had spent time in a NICU and who participated in a prospective study of infant development.

Overall, 1.3 percent of that group eventually received an ASD diagnosis. These 28 children were matched by gender, gestational age, and birth year with 112 controls who did not have an ASD.

As generally noted in previous studies, children with an ASD diagnosis were four times more likely to be male and around 2 weeks younger at birth, "but their distribution of types and severity of CNS injury was similar to that in other NICU infants" after controlling for gestational age, the authors wrote.

Those babies who would eventually receive an ASD diagnosis were more likely to have persistent neurobehavioral abnormalities and higher rates of asymmetric visual tracking and abnormal upper extremity tone, seen as early as 1 month of age.

"We speculate that such deficits in tone, especially in combination with visual tracking errors, could result in suppression of manual exploration or in poor development of fine motor skills, gesturing, or joint attention," the researchers wrote.

By age 4 months, the affected children were more likely to have a visual preference for higher amounts of stimulation, much like newborns.

"Continuing higher attention to more stimulating events of infants with ASD at 4 months represents a lack of transition to more mature levels past the neonatal period, providing evidence for early atypical development, including the visual system," according to the researchers.

The "consequences of these very early sensory and motor signs may be an arrest in performance beginning as early as 7 to 10 months' postterm age such that cognitive and motor development as measured by standardized instruments is significantly slowed or suppressed," they wrote.

Indeed, the infants who were later diagnosed with an ASD had sharper declines in motor performance by 7 months and in mental performance by 10 months.

The authors acknowledged some limitations of the study, including the lack of investigation into social, communication, and language development, the small sample size, and the fact that not all children later determined to have an ASD received clinical diagnoses. The findings may therefore not be specific to all children with ASD and emphasize the need to replicate these retrospective findings with more directed prospective studies, they noted.

While autism is heterogeneous in cause, "our report helps to confirm a substantial prevalence of ASD in NICU graduates, making them important to study," the authors commented.

Whether the NICU graduates studied are typical of other ASD-affected infants who lack early medical issues is not clear, they added. "It also is not clear whether this group is emergent within the increasing cohort of surviving very tiny and preterm infants or identified through more recent changes in diagnostic criteria and better surveillance."

"Whether NICU graduates represent a different phenotype from other children with ASD requires additional confirmation, but, at the least, these findings support the view that studying this cohort prospectively may yield insights into underlying mechanisms and behavioral precursors to ASD," the authors concluded.