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

Table 2 Antenatal markers for the risks of autism

Marker	Details
Genetic markers	Single-gene disorders: Fragile X syndrome (FMRI mutations), ‎neurofibromatosis (NF1), tuberous sclerosis complex (TSC1 and TSC2 ‎mutation), Dup15q syndrome, Rett syndrome (MeCP2 mutation), 16p11.2 ‎region deletions, SHANK3, NRXN1, CNTNAP2, and CHD8 genes mutations
	Chromosomal Disorders: Down syndrome, aberrations on the long arm of ‎Chromosome 15, and reciprocal chromosomal translocation between long ‎arms of chromosomes 4 and 14
	Messenger RNA (mRNA) and microRNA (miRNA) expression abnormality
	Abnormal DNA methylation patterns
Cytokines biomarkers	Abnormal profile of interleukin-6, tumor necrosis factor-alpha, interleukin-1 ‎receptor antagonist, TNF- α, Serpin E1, vascular cell adhesion molecule 1, ‎vascular endothelial growth factor D, Epidermal growth factor, Colony ‎Stimulating Factor 1, and 2
Autoantibodies biomarkers	The presence of circulating maternal autoantibodies, especially anti-brain ‎autoantibodies, during pregnancy
	Maternal autoantibody response against Collapsin Response Mediator Protein 1 ‎‎(CRMP1)
	Simultaneous reactivity against bands at 39 kDa and 73 kDa is associated with ‎early-onset autism.
Oxidative stress biomarkers	Maternal urinary levels of free 8-iso-prostaglandin F2α (8-iso-PGF2α)‎
Hormonal biomarkers	High prenatal testosterone levels
	Polycystic ovary syndrome
	Elevated levels of steroidogenic hormones (cortisol, androstenedione, testosterone, 17α-hydroxy-progesterone, and progesterone) in amniotic fluid
	Mid-pregnancy thyroid-stimulating hormone (inverse relationship)
Maternal nutritional biomarkers	Fetal levels of manganese and zinc
	Abnormal zinc-copper cycles (altered rhythmicity, shorter cycle duration, reduced regularity, and diminished complexity)
	Vitamin D deficiency
	Poor folic acid intake
Biophysical markers	Presence of multiple fetal abnormalities (especially cardiac, urinary, cranial, and ‎brain anomalies)‎
	Presence of a narrower head and a relatively broader ocular distance
	Altered prenatal brain growth
	Abnormal Kurjak's antenatal neurodevelopmental scoring test in the last ‎trimester
Radiological profile	Isolated ventriculomegaly
	Altered cortical development
	Enlarged insula ‎lobe
	Increased amygdala volume and fast growth rate

CHD8: Chromodomain helicase DNA binding protein 8; CNTNAP2‎: Contactin Associated Protein 2; Dup15q syndrome: Duplications of the portion of 15q11.2-13.1 chromosome; kDa: Kilodalton; MeCP2 mutation: Mutations of the methyl-CpG binding protein 2; NRXN1‎: Neurexin 1 RNA: Ribonucleic acid; SHANK3: SH3 and multiple ankyrin repeat domains 3; TNF-α: Tumor Necrosis Factor Alpha; TSC1: Tuberous sclerosis complex 1; TSC2: Tuberous sclerosis complex 2.