Molecular Pathways of Altered Brain Development in Fetuses Exposed to Hypoxia

Placental-related fetal growth restriction, resulting from placental dysfunction, impacts 3–5% of pregnancies and is linked to elevated risk of adverse neurodevelopmental outcomes. In response, the fetus employs a mechanism known as brain-sparing, redirecting blood flow to the cerebral circuit, for adequate supply to the brain. In this study we aimed to quantitatively evaluate disparities in gyrification and brain volumes among fetal growth restriction, small for gestational age and appropriate-for gestational-age fetuses. Additionally, we compared fetal growth restriction fetuses with and without brain-sparing. The study encompassed 106 fetuses: 35 fetal growth restriction (14 with and 21 without brain-sparing), 8 small for gestational age, and 63 appropriate for gestational age. Gyrification, supratentorial, and infratentorial brain volumes were automatically computed from T2-weighted magnetic resonance images, following semi-automatic brain segmentation. Fetal growth restriction fetuses exhibited significantly reduced gyrification and brain volumes compared to appropriate for gestational age (P < 0.001). Small for gestational age fetuses displayed significantly reduced gyrification (P = 0.038) and smaller supratentorial volume (P < 0.001) compared to appropriate for gestational age. Moreover, fetal growth restriction fetuses with BS demonstrated reduced gyrification compared to those without BS (P = 0.04), with no significant differences observed in brain volumes. These findings demonstrate that brain development is affected in fetuses with fetal growth restriction, more severely than in small for gestational age, and support the concept that vasodilatation of the fetal middle cerebral artery reflects more severe hypoxemia, affecting brain development.

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Long-Term Neurologic Consequences following Fetal Growth Restriction: The Impact on Brain Reserve

Shah,

Pereira,

Lodygensky

2024

Dev Neurosci

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Background: Fetal growth restriction (FGR) corresponds to the fetus’s inability to achieve an adequate weight gain based on genetic potential and gestational age. It is an important cause of morbidity and mortality. Summary: In this review we address the challenges of diagnosis and classification of FGR. We review how chronic fetal hypoxia impacts brain development. We describe recent advances on placental and fetal brain imaging using MRI and how they offer new non-invasive means to study growth restriction in humans. We go on to review the impact of FGR on brain integrity in the neonatal period, later childhood, and adulthood and review available therapies. Key Messages: Fetal growth restriction consequences are not limited to the perinatal period. We hypothesize that impaired brain reserve, as defined by structure and size, may predict some concerning epidemiological data of impaired cognitive outcomes and dementia with aging in this group of patients.

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Molecular Pathways of Altered Brain Development in Fetuses Exposed to Hypoxia

Cited by 4 publications

References 94 publications

The Influence of Maternal Hypoxia and Buspirone during Pregnancy on Cognitive Abilities and a Stress Response in Adult Male Offspring

The Influence of Maternal Hypoxia and Buspirone during Pregnancy on Cognitive Abilities and a Stress Response in Adult Male Offspring

Reduced gyrification in fetal growth restriction with prenatal magnetic resonance images

Long-Term Neurologic Consequences following Fetal Growth Restriction: The Impact on Brain Reserve

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