Early medical and behavioral characteristics of NICU infants later classified with ASD

Abstract

Objectives: Recent evidence suggests higher prevalence of autism spectrum disorder (ASD) in NICU graduates. This aim of this study was to identify retrospectively early behaviors found more frequently in NICU infants who went on to develop ASD.

Methods: Twenty-eight NICU graduates who later received a diagnosis of ASD were compared with 2169 other NICU graduates recruited from 1994 to 2005. They differed in gender, gestational age, and birth cohort. These characteristics were used to draw a matched control sample (n=112) to determine which, if any, early behaviors discriminated subsequent ASD diagnosis. Behavioral testing at targeted ages (adjusted for gestation) included the Rapid Neonatal Neurobehavioral Assessment (hospital discharge, 1 month), Arousal-Modulated Attention (hospital discharge, 1 and 4 months), and Bayley Scales of Infant Development (multiple times, 4-25 months).

Results: At 1 month, children with ASD but not control children had persistent neurobehavioral abnormalities and higher incidences of asymmetric visual tracking and arm tone deficits. At 4 months, children with ASD had continued visual preference for higher amounts of stimulation than did control children, behaving more like newborns. Unlike control children, children with ASD had declining mental and motor performance by 7 to 10 months, resembling infants with severe central nervous system involvement.

Conclusions: Differences in specific behavior domains between NICU graduates who later receive a diagnosis of ASD and matched NICU control children may be identified in early infancy. Studies with this cohort may provide insights to help understand and detect early disabilities, including ASD.

FIGURE 1

Differences in recovery on RNNA from newborn (hospital discharge) to 1 month PTA. Reduction in mean number of RNNA abnormalities in control subjects versus children with ASD reflects improved performance in control subjects but not children with ASD across the neonatal period.

FIGURE 2

Differences in incidence of specific RNNA abnormalities at 1 month PTA. Higher percentage of children with ASD versus control subjects show visual asymmetry and hypertonicity or hypotonicity in upper extremity tone, which may be early precursors of ASD-associated visual function and motor deficits seen at older ages.

FIGURE 3

Differences in AModA stimulus preferences at 4 months’ PTA. Higher percentage looking to fastest (8 Hz) frequency in children with ASD versus control subjects, children with no CNS injury, and children with severe CNS injury (no differences among infants without ASD) indicates persistent preference for increased stimulation in ASD, more like newborns than 4-month-olds. Percentage looking plotted as a function of log_eHz to equalize stimulus intervals across Hz.

FIGURE 4

BSID-II MDI (A) and PDI (B) for children with ASD, control subjects, children with no CNS injury, and children with severe CNS injury across ages from 4 to 25 months’ PTA. Nonoverlapping 95% CIs indicate significant differences. A, MDI: Children with ASD versus control subjects and children with no CNS injury show a sharper decline in performance across age, with differences significant by 10 months’ PTA. Children with ASD start higher, similar to control subjects and children with no CNS injury, and end lower than children with severe CNS injury, but apparent crossover effect is not significant. B, PDI: Children with ASD versus control subjects and children with no CNS injury also show a sharper decline across age in performance (but less than for MDIs), with differences significant by 7 months’ PTA. Children with ASD start and end lower than control subjects and children with no CNS injury and are most similar to children with severe CNS injury throughout.