Prenatal human brain development is not spared by IUGR: A systematic review

Intrauterine growth restriction (IUGR) is a severe condition in which the fetus fails to reach its genetically predetermined growth potential, impairing prenatal development and predisposing individuals to postnatal consequences that may persist into adulthood. Although fetal mechanisms such as the brain-sparing effect have been proposed to protect the brain against IUGR-related deficits, the extent of this protection remains unclear. To conduct a systematic review that demonstrates prenatal morphofunctional abnormalities in the brain of individuals with IUGR. A comprehensive literature search was performed in the MEDLINE/PubMed database using keywords and Boolean operators: IUGR AND newborn AND nervous system NOT review. Inclusion criteria used: free and full-text availability, publication date from January 1, 2013, to July 31, 2024, newborns (birth to 1 month), and both sexes. Exclusion criteria included studies of older infants, lack of focus on the central nervous system, multiple pregnancies, concurrent pathologies with IUGR, use of animal models, and review articles. The review protocol is registered with PROSPERO (ID: CRD42024542500). Seventeen studies were identified, totaling 2085 individuals. Of these, 1203 had some form of IUGR (early- or late-onset, symmetrical or asymmetrical, with or without circulatory centralization), whereas 882 were appropriate for gestational age (AGA) and served as controls. Across all studies, individuals with IUGR showed biometric, morphological, and/or cerebral vascular abnormalities, even when biparietal diameter or head circumference measurements were similar to those of AGA individuals. Prenatal human brain development is not spared by IUGR. •Prenatal brain development is compromised in all IUGR classifications.•Even with preserved BPD or HC measurements similar to AGA individuals, prenatal brain development is still affected by IUGR.•Centralization fails to protect the brain from IUGR, shown by blood-brain barrier disruption and reduced frontal lobe growth.•Head biometric measurements and circulatory centralization should not be interpreted as indicative of a brain-sparing effect.•A consensus is needed that IUGR does not spare the brain.