ArticleThe Journal of thoracic and cardiovascular surgery2019
Chronic intrauterine hypoxia alters neurodevelopment in fetal sheep.
Article in The Journal of thoracic and cardiovascular surgery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Meta-regression of sulcal patterns, clinical and environmental factors on neurodevelopmental outcomes in participants with multiple CHD types.Cerebral cortex (New York, N.Y. : 1991) · 2024Pooled it
- Understanding physiological adaptations of pregnancy to the chronic hypoxia of high altitude to inform obstetrical and neonatal care.Physiological reviews · 2026Review
- The Sooner, the Better: Neuroprotective Strategies in Fetuses With Congenital Heart Disease.Prenatal diagnosis · 2026Review
- Artificial Womb Technology for Extremely Premature Neonates: Preclinical Neurodevelopmental Outcomes.Children (Basel, Switzerland) · 2025Review
- Neurodevelopment in congenital heart disease: a review of antenatal mechanisms and therapeutic potentials.Pediatric research · 2025Review
- Molecular and Biochemical Mechanisms of Cardiomyopathy Development Following Prenatal Hypoxia-Focus on the NO System.Antioxidants (Basel, Switzerland) · 2025Review
- Experimental Impact of Increasing Circuit Resistance in the Artificial Womb.Prenatal diagnosis · 2025Article
- Chronic Hypoxia in an EXTrauterine Environment for Neonatal Development Impairs Lung Development.American journal of respiratory cell and molecular biology · 2025Article
- Artificial womb technology - A more physiologic solution to treating extreme prematurity.European journal of obstetrics & gynecology and reproductive biology: X · 2025Review
- Unique model of chronic hypoxia in fetal lambs demonstrates abnormal contrast-enhanced ultrasound brain perfusion.Pediatric research · 2025Article
- Extrauterine support of pre-term lambs achieves similar transcriptomic profiling to late pre-term lamb brains.Scientific reports · 2024Article
- The brain of fetuses with congenital diaphragmatic hernia shows signs of hypoxic injury with loss of progenitor cells, neurons, and oligodendrocytes.Scientific reports · 2024Article
- Article
- A fetal wound healing program after intrauterine bile duct injury may contribute to biliary atresia.Journal of hepatology · 2023Article
- Biological and structural phenotypes associated with neurodevelopmental outcomes in congenital heart disease.Translational pediatrics · 2023Review
- Fetal Brain Development in Congenital Heart Disease.The Canadian journal of cardiology · 2023Review
- Antenatal and neonatal factors and morphology of the optic nerve head in the Northern Finland birth cohort.Acta ophthalmologica · 2022Article
- Article
- In Utero MRI Identifies Impaired Second Trimester Subplate Growth in Fetuses with Congenital Heart Disease.Cerebral cortex (New York, N.Y. : 1991) · 2022Article
- Chronic hypoxemia induces mitochondrial respiratory complex gene expression in the fetal sheep brain.JTCVS open · 2022Article
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17 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveWe tested the hypothesis that chronic fetal hypoxia, at a severity present in many types of congenital heart disease, would lead to abnormal neurodevelopment.
methodsEight mid-gestation fetal sheep were cannulated onto a pumpless extracorporeal oxygenator via the umbilical vessels and supported in a fluid-filled environment for 22 ± 2 days under normoxic or hypoxic conditions. Total parenteral nutrition was provided. Control fetuses (n = 7) were harvested at gestational age 133 ± 4 days. At necropsy, brains were fixed for histopathology. Neurons were quantified in white matter tracts, and the thickness of the external granular layer of the cerebellum was measured to assess neuronal migration. Capillary density and myelination were quantified in white matter. Data were analyzed with unpaired Student t tests or 1-way analysis of variance, as appropriate.
resultsOxygen delivery was reduced in hypoxic fetuses (15.6 ± 1.8 mL/kg/min vs 24.3 ± 2.3 mL/kg/min, P < .01), but umbilical blood flow and caloric delivery were not different between the 2 groups. Compared with normoxic and control animals, hypoxic fetuses had reduced neuronal density and increased external granular layer thickness. Compared with normoxic and control animals, hypoxic fetuses had increased capillary density in white matter. Cortical myelin integrity score was lower in the hypoxic group compared with normoxic and control animals. There was a significant negative correlation between myelin integrity and capillary density.
conclusionsChronic fetal hypoxia leads to white matter hyper-vascularity, decreased neuronal density, and impaired myelination, similar to the neuropathologic findings observed in children with congenital heart disease. These findings support the hypothesis that fetal hypoxia, even in the setting of normal caloric delivery, impairs neurodevelopment.
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