Selective Hematological Profiles in Drug-Naïve Early Autism: Clinical and Developmental Correlates

Background/Objectives: Peripheral biomarkers for autism spectrum disorder (ASD) have shown mixed results in previous studies. In this study, complete blood count-derived immune-inflammatory markers, iron and micronutrient levels, and thyroid function were compared between drug-naïve preschoolers newly diagnosed with ASD and healthy controls. Additionally, the relationships between these markers, symptom severity, and developmental skills were examined. Methods: This retrospective case–control study included 62 children with ASD (aged 24–72 months) and 61 age-matched healthy controls. Symptom severity, behavioral traits, and developmental status were assessed using the Childhood Autism Rating Scale (CARS), Autism Behavior Checklist (ABC), and Denver II Developmental Screening Test (DDST), respectively. Composite inflammatory indices were calculated from hemogram data. Statistical analyses incorporated Holm–Bonferroni corrections for multiple comparisons and sex-stratified exploratory analyses of conditional associations using 95% bootstrap confidence intervals based on 5000 resamples. Results: Children with ASD demonstrated significantly lower mean corpuscular volume (MCV; d = 0.66, adj. p = 0.019), lower mean platelet volume (MPV; d = 0.58, adj. p = 0.034), and higher absolute lymphocyte counts (LYMPH; d = 1.10, adj. p = 0.019). Initial group differences in ferritin, serum iron, and transferrin saturation did not survive adjustment (adj. p > 0.05). Composite inflammatory indices were not significantly associated with clinical or developmental scores. Higher CARS and ABC scores correlated with lower personal–social and language scores on the DDST (p < 0.01). Furthermore, exploratory sex-stratified, conditional association analyses suggested preliminary basophil- and lymphocyte-related patterns in girls; however, these findings are strictly hypothesis-generating due to the small female sample size (n = 12). Conclusions: Newly diagnosed, drug-naïve preschoolers with ASD showed a distinct baseline blood profile, including lower MCV and MPV and higher lymphocyte counts. Clinical challenges were most evident in personal–social and language domains. While the primary diagnostic value of routine hemograms in this context appears limited, the exploratory sex-stratified basophil- and lymphocyte-related patterns require validation in adequately powered future cohorts.