Autoinflammatory periodic fever syndromes in preschoolers: neurodevelopmental, behavioral, and maternal psychosocial outcomes.
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome and familial Mediterranean fever (FMF) are the most common pediatric autoinflammatory syndromes, yet their developmental and psychosocial impacts during early childhood remain poorly understood. This cross-sectional study compared developmental and behavioral outcomes, parental mental health, and perceived child vulnerability in preschool-aged children diagnosed with PFAPA syndrome or FMF versus healthy controls. A total of 158 children aged 18-71 months (79 patients, 79 controls of similar age and sex) were recruited from a tertiary pediatric hospital in Turkiye. Development was evaluated using the Ages and Stages Questionnaire and Bayley Scales of Infant and Toddler Development, Third Edition. Behavioral functioning was assessed using the Child Behavior Checklist, while maternal depression, anxiety, and perception of child vulnerability were measured via the Patient Health Questionnaire-9, Beck Anxiety Inventory, and Child Vulnerability Scale. Children with periodic fever syndromes had significantly higher rates of developmental delay (p < 0.05) and lower cognitive, language, and motor scores than healthy peers (all p < 0.05). They also exhibited elevated internalizing and externalizing symptoms. Mothers of affected children reported higher perceptions of child vulnerability. Multivariable logistic regression identified male sex (OR 2.71, 95% CI 1.08-6.85), patient group status (OR 2.65, 95% CI 1.12-6.23), lack of preschool attendance (OR 6.58, 95% CI 2.26-19.19), and lower shared reading frequency (OR 0.76, 95% CI 0.65-0.89) as independent predictors of developmental delay. Among clinical factors, attack frequency was positively associated with internalizing problems. Preschool children with PFAPA syndrome and FMF may be at increased risk for early developmental and behavioral difficulties. These findings support the need for routine screening and integrated care approaches that address both child development and caregiver-relate d factors. • PFAPA syndrome and FMF are the most common childhood periodic fever syndromes associated with stress and reduced quality of life in both children and their families. • Although inflammation and psychosocial stress are known to affect early development, their impact in these syndromes remains largely unexplored. • Preschool children with PFAPA syndrome and FMF are at increased risk for developmental and behavioral difficulties, along with elevated maternal perceptions of child vulnerability. • This is the first study to systematically evaluate early developmental and psychosocial outcomes in these syndromes, identifying clinical and caregiving factors associated with increased risk.