Pre-autism: What a paediatrician should know about early diagnosis of autism‎

Table 3 Neonatal and early infancy markers for the risks of autism

Marker	Details
Physical markers	Large or abnormal head sizes at birth and throughout early childhood
	Smaller head sizes in girls
	Long body lengths at birth
	Hypertelorism, anteriorly rotated ears, long back of the nose, abnormal shape of ‎the mouth, and facial asymmetries
	Abnormal motor development during the first year of life e.g., hypotonia, ‎hyperreflexia, poor movement quality, ‎head lag, delayed or missing major ‎motor development, and delayed milestones, such as sitting or crawling, or ‎‎prefer using one hand over the other
	Asymmetric visual tracking
	Reduced heart rate variability
	Enhanced pupillary light reflex during infancy‎
	More liable for sleep disturbances and gastrointestinal symptoms, such as ‎constipation, diarrhea, or gastroesophageal ‎‎reflux
Social & behavioural markers	Deficits in social behavior, specifically in joint attention, eye contact, orienting ‎to names, facial expressions, social smiles, attention, and tolerance of social ‎touch
	Atypical sensory processing, with hypersensitivity or hyposensitivity to touch, ‎sounds, or visual stimuli
	Dislike being touched and cuddled
	Lie in the bassinet constantly and cry when being held up
	Avoid eye contact or have difficulty following a person's gaze when directing ‎the infant's attention to something
	Reduced visual attention to social stimulation
	Impaired orienting to novel stimuli at the age of two months‎
	Reduced interest in social interaction or decreased responsiveness to social cues
	Lie on one of the extremes of being very low or very high needs
Immunological profile	Neonatal cord blood anti-brain antibodies, especially against both 39kDa and ‎‎73kDa proteins
	Abnormalities in the concentrations of total IgG and IgG 4
	Presence of anti-dopamine D2L receptors and anti-tubulin autoantibodies and ‎the ratio of the anti-dopamine D2L to D1 receptor antibodies
	Folate receptor-alpha autoantibodies
	High immunoglobulin A in the stool
Inflammatory profile	High neonatal C-reactive protein levels
	Decreased levels of α-2-macroglobulin, ferritin, and serum amyloid P
	High IL-1B, IL-4, IL-6, IL-8, interferon-gamma, eotaxin, and monocyte ‎chemotactic protein-1 levels
	Low transforming growth factor-β1 levels
Biochemical & metabolic profile	Low blood levels of Brain-derived neurotrophic factor
	Neonatal hyperbilirubinemia
Hormonal profile‎	Reduced neonatal CSF or plasma vasopressin concentration
	Low plasma or salivary oxytocin levels
	Reduced oxytocin receptor number
Brainstem function‎	Abnormal neonatal auditory brainstem responses

CSF: Cerebrospinal fluid; IgG: Immunoglobulin G; IL: Interleukin; kDa: Kilodalton.