Evidence of Brain Overgrowth in the First Year of Life in Autism

TLDR

Autism typically manifests by 2–3 years of age, by which time the brain is already abnormally large. The study aimed to determine whether pathological brain overgrowth precedes the first clinical signs of ASD and whether the rate of overgrowth during the first year predicts neuroanatomical and clinical outcomes. Head circumference, body length, and weight were measured during the first year from medical records of 48 ASD children, with 15 having longitudinal data at birth, 1–2 months, 3–5 months, and 6–14 months, and outcomes were compared to national normative databases. Infants with ASD had a smaller head circumference at birth but then grew rapidly, exceeding normative growth by 1.67 SDs, with accelerated growth linked to larger cerebellar gray matter and cortical volumes and occurring in 59 % of autistic disorder cases versus 6 % of healthy infants, indicating early brain overgrowth as a potential warning signal.

Abstract

ContextAutism most commonly appears by 2 to 3 years of life, at which time the brain is already abnormally large. This raises the possibility that brain overgrowth begins much earlier, perhaps before the first clinically noticeable behavioral symptoms.ObjectivesTo determine whether pathological brain overgrowth precedes the first clinical signs of autism spectrum disorder (ASD) and whether the rate of overgrowth during the first year is related to neuroanatomical and clinical outcome in early childhood.Design, Setting, and ParticipantsHead circumference (HC), body length, and body weight measurements during the first year were obtained from the medical records of 48 children with ASD aged 2 to 5 years who had participated in magnetic resonance imaging studies. Of these children, 15 (longitudinal group) had measurements at 4 periods during infancy: birth, 1 to 2 months, 3 to 5 months, and 6 to 14 months; and 33 (partial HC data group) had measurements at birth and 6 to 14 months (n = 7), and at birth only (n = 28).Main Outcome MeasuresAge-related changes in infants with ASD who had multiple-age measurements, and the relationship of these changes to brain anatomy and clinical and diagnostic outcome at 2 to 5 years were evaluated by using 2 nationally recognized normative databases: cross-sectional normative data from a national survey and longitudinal data of individual growth.ResultsCompared with normative data of healthy infants, birth HC in infants with ASD was significantly smaller (z = –0.66, P<.001); after birth, HC increased 1.67 SDs and mean HC was at the 84th percentile by 6 to 14 months. Birth HC was related to cerebellar gray matter volume at 2 to 5 years, although the excessive increase in HC between birth and 6 to 14 months was related to greater cerebral cortex volume at 2 to 5 years. Within the ASD group, every child with autistic disorder had a greater increase in HC between birth and 6 to 14 months (mean [SD], 2.19 [0.98]) than infants with pervasive developmental disorder-not otherwise specified (0.58 [0.35]). Only 6% of the individual healthy infants in the longitudinal data showed accelerated HC growth trajectories (>2.0 SDs) from birth to 6 to 14 months; 59% of infants with autistic disorder showed these accelerated growth trajectories.ConclusionsThe clinical onset of autism appears to be preceded by 2 phases of brain growth abnormality: a reduced head size at birth and a sudden and excessive increase in head size between 1 to 2 months and 6 to 14 months. Abnormally accelerated rate of growth may serve as an early warning signal of risk for autism.