Prenatal conditions and ASD
Specific maternal illnesses, conditions and treatments can result in adverse neurodevelopmental outcomes in children [124]. Perinatal complications place an infant at significant risk for mental, neurological and behavioural disorders [125]. Maternal metabolic conditions may increase the risk of ASD. Maternal Type 2 diabetes, hypertension, and obesity have been identified as risk factors for ASD and other developmental disorders [124,126]. Prenatal factors such as advanced maternal (and paternal) age, bleeding or gestational diabetes have been associated with the risk of ASD [127,128]. An Australian study has linked an increased risk for the development of intellectual disabilities (which included ASD) with maternal asthma [124]. Another report observed that maternal asthma increased the risk of adverse fetal and maternal outcomes such as low birth weight, preeclampsia, hypertensive disorders and gestational diabetes [129]. A high rate of autoimmune diseases occurs in families with ASD indicating that immune dysfunction could combine with other environmental factors in the development of ASD [130]. Parental psychiatric history and prenatal environmental factors also contribute to an increased risk of developing ASD [131].
Prescriptions taken during the pregnancy, length of labour, viral infections, abnormal presentation during birth, and a low birth weight could also be factors that predict outcomes of infantile ASD [125]. Furthermore, the risk of ASD development in preterm babies who are small for their gestational weight is increased, whereas preterm babies who are large for their gestational weight have a reduced risk of ASD [132]. Foetal stress during delivery may also increase the risk of ASD [128]. Overall, epidemiological studies have identified factors including gestational diabetes, stress, infections and inflammatory disorders as prenatal risk factors for ASD. Many of these conditions are known to directly or indirectly elevate cortisol levels [133]. Taking oral corticosteroids during pregnancy confers increased risk of lower birth weight and congenital malformations [129]. Elevated prenatal cortisol is known to negatively affect the behaviour of newborn children with increased irritability, attention and temperament problems [134,135]. Excess plasma cortisol levels have been implicated in the aetiology of comorbid illnesses associated with ASD, such as depression, anxiety, dyspepsia and migraine [136,137] (see Table 1). Furthermore, elevations in plasma cortisol and platelet serotonin levels have been observed in schizophrenic patients [138]. Hence, there is evidence to indicate that excess cortisol levels co-exist with serotonin-selective pathologies.
Table 1  Clinical outcomes of tissue-specific glucocorticoid excess [139-142]

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