Neonatal levels of neurotrophic factors and risk of autism spectrum disorders

Abstract

To examine levels of 3 neurotrophic factors (NTFs): Brain derived neurotrophic factor (BDNF), Neurotrophin-4 (NT-4), and transforming growth factor-β (TGF-β) in dried blood spot samples of neonates diagnosed with autism spectrum disorders (ASD) later in life and frequency-matched controls. Biologic samples were retrieved from the Danish Newborn Screening Biobank. NTFs for 414 ASD cases and 820 controls were measured using Luminex technology. Associations were analyzed with continuous measures (Tobit regression) as well as dichotomized at the lower and upper 10th percentiles cutoff points derived from the controls' distributions (logistic regression). ASD cases were more likely to have BDNF levels falling in the lower 10th percentile (odds ratios [OR], 1.53 [95% confidence intervals (CI), 1.04-2.24], P-value = 0.03). Similar pattern was seen for TGF-β in females with ASD (OR, 2.36 [95% CI, 1.05-5.33], P-value = 0.04). For NT-4, however, ASD cases diagnosed with ICD-10 only were less likely to have levels in upper 10th percentile compared with controls (OR, 0.22 [95% CI, 0.05-0.98], P-value = 0.05). Results cautiously indicate decreased NTFs levels during neonatal period in ASD. This may contribute to the pathophysiology of ASD through impairments of neuroplasticity. Further research is required to confirm our results and to examine the potential therapeutic effects of NTFs in ASD.