Neurodevelopmental outcomes in Intrauterine Growth-Restricted children–an umbrella review

Objective: Optimal neurodevelopment during pregnancy is crucial for healthy brain functioning for a lifetime, which can prevent the risk of adverse outcomes like autism, Attention-deficit hyperactivity disorder (ADHD), mental health issues, or learning disabilities. Intrauterine Growth Restriction (IUGR) is one of the conditions leading to adverse neurodevelopmental outcomes in the newborn. This umbrella review aimed to synthesize the existing evidence on neurodevelopmental outcomes in children with IUGR and highlight critical knowledge gaps, emphasizing the need for long-term standardized studies. Methods: A systematic literature search was conducted across Medline/PubMed, Embase, and Scopus up to June 2025 as per the eligibility criteria, including systematic reviews on neurodevelopmental outcomes in IUGR children diagnosed as per the Delphi criteria. The extracted articles underwent study selection and data extraction processes, with discrepancies resolved by consensus. The eligible articles were synthesized qualitatively and presented. Results: Eight eligible studies were included in this review; two included meta-analyses, and six had only qualitative synthesis. Qualitative narrative synthesis was conducted for these eight studies. The included studies were of moderate quality and consistently reported that IUGR children exhibited significantly lower cognitive, motoric, and linguistic scores than their Appropriate for Gestational Age (AGA) peers. Some noted specific impairments included reduced Intelligence Quotient (IQ), fine and gross motor delays, and language comprehension deficits. While some studies showed insignificant differences in behavioral or language outcomes, others linked biomarkers like S100B, Neuron Specific Enolase (NSE), and tau proteins to substandard neurodevelopment. Adverse neurological outcomes and neurodevelopmental impairment were associated with IUGR. Protective brain-sparing effects might pose benefits early in life, which may not persist throughout. Conclusion: IUGR children are at an elevated risk for adverse neurodevelopmental outcomes, specifically in cognitive and motor domains. While language and behavioral findings vary, early life impairments are notable. The heterogeneity in the methodologies across the included primary studies highlights the need for standardized research, diagnostic criteria, and longitudinal studies to extract definitive conclusions. Extensive neurodevelopmental monitoring, timely interventions, and further exploration of predictive biomarkers are essential to optimize outcomes and mitigate long-term adverse effects in this vulnerable population.