Incidental MRI Findings In Infants at Risk for Autism

Background: Infants with an older sibling with autism have a higher recurrence rate of developing the disorder than infants without familial autism.  These high-risk infants are also more likely to have other developmental delays than low-risk infants without a family history of autism.  Despite the growing use of MRI to study the brain development of infants at risk for autism, it is unclear whether high-risk infants exhibit clinically significant incidental MRI findings and whether the presence of neurological anomalies is associated with developmental delays.

Objectives: To evaluate the rate of incidental MRI findings in infants at risk for autism and its association with developmental delays.

Methods: High-resolution, T1-weighted structural MRI scans (voxel size=1 cubic mm) were acquired during natural sleep on 40 infants (n=28 high-risk, 12 low-risk) at either 6 or 9 months of age.  A board-certified pediatric neuroradiologist, blind to subject risk status, evaluated the scans for incidental findings (i.e. unexpected, asymptomatic brain abnormalities).  Motor and language function of each infant was assessed using the Mullen Scales of Early Learning (standardized mean for each scale=50, sd=10, scores<40 are considered delayed).

Results: We found a high incidence (41%) of high-risk infants with “benign extraaxial fluid” at 6 months.  Benign extraaxial fluid (BEAF) is characterized by an excess of cerebrospinal fluid in the subarachnoid space, which may be associated with head growth in the absence of corresponding brain growth.  The high-risk infants with extraaxial fluid had significantly lower Mullen scores at 6 months on fine motor, gross motor, and receptive language scales, relative to high-risk infants without extraaxial fluid [fine motor: BEAF M=38.6(sd=11.0), non-BEAF M=46.1(6.5), p<.05; gross motor: BEAF M=37.3(12.9), non-BEAF=45.7(10.3), p<.10; receptive language: BEAF M=37.7(9.7), non-BEAF M=44.2(8.6), p<.10].  57% of high-risk infants with BEAF were delayed in all three fine motor, gross motor, and receptive language scales, compared to 11% of infants without BEAF.

Conclusions: Infants at risk for autism have a high incidence of “benign extraaxial fluid” at 6 months of age, as indicated by a pediatric neuroradiologist.  Motor and language delays found in high-risk infants with extraaxial fluid call into question the “benign” nature of this finding.  This raises the potential of clinical MRI findings to serve as an early indication of general developmental delay in infants at risk for autism, although it is yet unclear how general delays will relate to autism symptoms in later development.  In addition, since extraaxial fluid occupies space that would otherwise contain cerebral cortex, head circumference may be an inaccurate proxy of brain volume in infants with this incidental finding.  If this finding is confirmed in a larger cohort of subjects, it should be considered when interpreting previous studies that used head circumference to report early brain overgrowth in autism.