Reduced fetal cerebral oxygen consumption is associated with smaller brain size in fetuses with congenital heart disease
Open accessAbstract
Background—: Fetal hypoxia has been implicated in the abnormal brain development seen in newborns with congenital heart disease (CHD). New magnetic resonance imaging technology now offers the potential to investigate the relationship between fetal hemodynamics and brain dysmaturation. Methods and Results—: We measured fetal brain size, oxygen saturation, and blood flow in the major vessels of the fetal circulation in 30 late-gestation fetuses with CHD and 30 normal controls using phase-contrast magnetic resonance imaging and T2 mapping. Fetal hemodynamic parameters were calculated from a combination of magnetic resonance imaging flow and oximetry data and fetal hemoglobin concentrations estimated from population averages. In fetuses with CHD, reductions in umbilical vein oxygen content ( P <0.001) and failure of the normal streaming of oxygenated blood from the placenta to the ascending aorta were associated with a mean reduction in ascending aortic saturation of 10% ( P <0.001), whereas cerebral blood flow and cerebral oxygen extraction were no different from those in controls. This accounted for the mean 15% reduction in cerebral oxygen delivery ( P =0.08) and 32% reduction cerebral V o 2 in CHD fetuses ( P <0.001), which were associated with a 13% reduction in fetal brain volume ( P <0.001). Fetal brain size correlated with ascending aortic oxygen saturation and cerebral V o 2 ( r =0.37, P =0.004). Conclusions—: This study supports a direct link between reduced cerebral oxygenation and impaired brain growth in fetuses with CHD and raises the possibility that in utero brain development could be improved with maternal oxygen therapy.
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In fetuses and neonates with critical CHD, chronically decreased oxygen and nutrient delivery disturbs optimal cerebral development, resulting in slower brain growth with delayed maturation when compared with healthy controls.
“In fetuses and neonates with critical CHD, chronically decreased oxygen and nutrient delivery disturbs optimal cerebral development, resulting in slower brain growth with delayed maturation when compared with healthy controls.9,10”
From Perioperative neonatal brain injury is associated with worse school-age neurodevelopment in children with critical congenital heart disease (2018) · cites this paper as [10]
The Methods and Results report lower cerebral oxygen consumption and smaller brain volume in fetuses with CHD than in controls. The Background also describes delayed maturation in affected fetuses and newborns. But the Discussion says reduced nutritional content was suspected, not measured, and acknowledges other possible explanations for the findings; the claim presents decreased oxygen and nutrient delivery as an established cause across both fetuses and neonates. (LLM, conf=0.86)
Experimental — accuracy not yet measuredChildren with tetralogy of Fallot have reduced oxygen delivery and oxygen consumption.
“Children with TOF have reduced oxygen delivery and oxygen consumption (36)”
From Changes in Cortical Thickness Are Associated With Cognitive Ability in Postoperative School-Aged Children With Tetralogy of Fallot (2020) · cites this paper as [36]
The Results report lower cerebral oxygen consumption in the TOF subgroup of fetuses. They do not report significantly reduced cerebral oxygen delivery for that subgroup, and the study examined fetuses rather than children after birth. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAll studies of fetal and neonatal brain volumes show significant reductions in total brain volume, white matter, and cortical gray matter in congenital heart disease compared with controls.
“All studies of fetal and neonatal brain volumes (Table I) show significant reductions in total brain volume, white matter, and cortical gray matter (CGM) in CHD when compared with controls.28,30,33,34”
From Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease (2017) · cites this paper as [28]
In late gestation, fetuses with either left or right outflow tract obstruction have a 10% lower oxygen saturation of blood supplied to the brain than healthy fetuses.
“In late gestation, 10% reduction in oxygen saturation of blood supplied to the brain is seen in fetuses (n=30) with either left or right outflow tract obstruction when compared with healthy fetuses.28”
From Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease (2017) · cites this paper as [28]
Reduced oxygen delivery and oxygen consumption to the brain are associated with decreased total brain volume, and this is most severe in hypoplastic left heart syndrome compared with biventricular pathology.
“Also, reduction in oxygen delivery and oxygen consumption to the brain is associated with decreased total brain volume, 28 which is most severe in HLHS when compared with biventricular pathology.”
From Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease (2017) · cites this paper as [28]
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“Children with TOF have reduced oxygen delivery and oxygen consumption (36), to which the cerebral cortex is especially vulnerable (25).”
BackgroundMoscatelli, S., Leo, I., Lisignoli, V., Boyle, S., Bucciarelli-Ducci, C., Secinaro, A., & Montanaro, C. (2023) · Children · doi:10.3390/children10050763 · Cited by 6 · see citing works
- Authors
- Sun, L., Macgowan, C. K., Sled, J. G., Yoo, S.-J., Manlhiot, C., Porayette, P., Grosse-Wortmann, L., Jaeggi, E., McCrindle, B. W., Kingdom, J., Hickey, E., Miller, S., & Seed, M.
- Affiliations
- Mount Sinai Hospital (CA)
- From Department of Ultrasound, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (L.S.); Division of Pediatric Cardiology, Department of Pediatrics (L.S., S.-J.Y., C.M., P.P., L.G.-W., E.J., B.W.M., M.S.), Department of Physiology and Experimental Medicine (C.K.M., J.G.S.), Department of Diagnostic Imaging (S.-J.Y., L.G.-W., M.S.), Department of Cardiovascular Surgery (E.H.), and Department of Pediatric Neurology (S.M.),...
- ORCID
- Venue
- Circulation
- Published
- 2015-04-14
- Volume
- 131
- Issue
- 15
- Pages
- 1313-1323
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC4398654
- OpenAlex
- W2002403913
- Cited by
- 533
- References
- 34
- Citations by year
- 2026: 36 · 2025: 53 · 2024: 43 · 2023: 47 · 2022: 62 · 2021: 47 · 2020: 48 · 2019: 51 · 2018: 48 · 2017: 45 · 2016: 38 · 2015: 13 · 2013: 1
- FWCI
- 37.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (U01HL068270)
- Topics
- Health Sciences › Medicine › Epidemiology › Congenital Heart Disease Studies
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- congenital heart disease, fetal hypoxia, fetal hemodynamics, cerebral blood flow, cerebral oxygen extraction, fetal brain development, fetal brain volume
- MeSH terms
- Adult, Brain, Cerebrovascular Circulation, Cross-Sectional Studies, Female, Fetus, Heart Defects, Congenital, Hemodynamics, Humans, Magnetic Resonance Imaging, Organ Size, Oximetry, Oxygen Consumption, Pregnancy, Pregnancy Trimester, Third, Prospective Studies, Regional Blood Flow, Case-Control Studies
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