Evening salivary cortisol and alpha-amylase at 14months and neurodevelopment at 4years: Sex differences.

Stress system activity in early life can have long-term effects on neurodevelopment. The main aim of this study was to assess the association of child evening salivary cortisol and alpha-amylase basal levels at 14months of age with longer-term neuropsychological development at 4years in a low-risk population-based birth cohort derived from the INMA (Environment and Childhood) project in Spain. We included 186 parent-children pairs with information on both stress system activity and neurodevelopment. Both stress markers at 14months of age showed an association with neuropsychological development at 4years. Salivary cortisol showed a sex-specific pattern of association. In girls, cortisol levels at 14months were negatively associated with cognitive development [long-term declarative memory (β=-17.8, p=0.028; 95% CI=-33.2 to -2.5); executive function (β=-9.8, p=0.08; 95% CI=-21 to 1)] and gross motor development (β=-13; p=0.022; 95% CI=-24 to -2), whereas in boys cortisol levels were negatively associated with socioemotional development [autistic-like behaviours: Incidence Rate Ratio (IRR)=1.6, p=0.039; 95% CI=1.01 to 2.41]. Salivary alpha-amylase was positively associated with socioemotional development in boys only [social competence (β=2.11, p=0.013; 95% CI=0.47 to 3.72), autistic-like behaviours (IRR=0.93, p=0.042; 95% CI=0.87 to 0.99) and hyperactivity symptoms (IRR=0.81, p=0.021; 95% CI=0.69 to 0.97)]. These results suggest that stress system activity in early life is associated with longer-term neurodevelopment and that sex is an important factor in this relationship.