Extrauterine Growth Restriction and its Association with Neurodevelopment in Very Premature Newborns: A Systematic Review with Meta-Analysis
DOI:
https://doi.org/10.14306/renhyd.30.1.2551Keywords:
Premature Birth, Growth, Neurodevelopmental Disorders, AnthropometryAbstract
Introduction: Preterm birth is a high-risk condition for adverse neurodevelopmental outcomes. Extrauterine growth restriction (EUGR) has been proposed as a potential predictor of these outcomes; however, the available evidence shows variable results depending on the anthropometric standards and definitions applied. The aim of this study was to evaluate the association between EUGR in weight and head circumference (HC) and neurodevelopmental impairment between 18 and 24 months of corrected age in very preterm infants.
Methods: A systematic review and meta-analysis of studies published from January 2016 to January 2026 was conducted using MEDLINE/PubMed, Web of Science, Scopus, ScienceDirect, and Springer Nature. Studies including very preterm infants (<32 weeks of gestational age) that evaluated the association between extrauterine growth restriction (EUGR) in weight and head circumference (decrease ≥1 ± 0.2 z-score according to INTERGROWTH-21st standards) and neurodevelopment using the Bayley II/III or Griffith scales were included. The meta-analysis was performed using DerSimonian–Laird random-effects models. Risk of bias was assessed using the ROBINS-E tool.
Results: Eight studies were included in the narrative synthesis and six in the meta-analysis, comprising a total of 6,286 infants assessed for weight and 3,747 for HC. EUGR defined by weight was associated with higher odds of neurodevelopmental impairment (OR = 1.7; 95% CI: 1.1–2.7), while EUGR defined by HC showed a comparable association (OR = 1.8; 95% CI: 1.0–3.3).
Conclusions: EUGR defined using INTERGROWTH-21st weight- and HC-for-age standards was associated with an increased risk of neurodevelopmental impairment between 18 and 24 months of corrected age. However, the limited number of available studies restricts the generalizability of these findings.
Funding: National Postgraduate Scholarship Program of the Secretariat of Science, Humanities, Technology and Innovation (SECIHTI), grant number 4042646.
Protocol publication: https://osf.io/j2exd/
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