Physiological correlates of intellectual function in children with sickle cell disease: Hypoxaemia, hyperaemia and brain infarction
Open accessAbstract
Lowered intelligence relative to controls is evident by mid-childhood in children with sickle cell disease. There is consensus that brain infarct contributes to this deficit, but the subtle lowering of IQ in children with normal MRI scans might be accounted for by chronic systemic complications leading to insufficient oxygen delivery to the brain. We investigated the relationship between daytime oxyhaemoglobin saturation (SpO2), cerebral blood flow velocity (CBFV) and intellectual function (IQ) using path-analysis in 30 adolescents with sickle cell disease (mean age 17.4 years, SD 4.2). Initial analyses revealed that the association between SpO2 and Full Scale IQ (FSIQ) was fully mediated by increased CBFV, whereby SpO2 was negatively correlated with CBFV and CBFV was negatively correlated with FSIQ, i.e. decreases in oxygen saturation are associated with increases in velocity, and increased velocity is associated with lowered IQ scores. The mediated relationship suggests that lowered IQ may be a function of abnormal oxygen delivery to the brain. Further analyses showed that the association between CBFV and IQ was significant for verbal but not for performance IQ. The pathophysiology characteristic of SCD can interfere with brain function and constrain intellectual development, even in the absence of an infarct. This supports the hypothesis that lowered intellectual function is partly explained by chronic hypoxia, and has wider implications for our understanding of SCD pathophysiology.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The text we found for this paper looks like another document, so the self-check wasn’t run.
Cites
Cerebrovascular accidents in sickle cell disease: rates and risk factors.
(1998) · PubMed · doi:10.1182/blood.v91.1.288 · Cited by 1,694 · see citing works
Structural Equation Modeling with EQS and EQS/WINDOWS: Basic Concepts, Applications, and Programming
Byrne, B. M. (1994) · Medical Entomology and Zoology · Cited by 1,499 · see citing works
Serjeant, G. R. (1997) · The Lancet · doi:10.1016/s0140-6736(97)07330-3 · Cited by 760 · see citing works
Chugani, H. T., & Phelps, M. E. (1986) · Science · doi:10.1126/science.3945811 · Cited by 663 · see citing works
The Use of Transcranial Ultrasonography to Predict Stroke in Sickle Cell Disease
Adams, R. J., McKie, V. C., Nichols, F. T., Carl, E., Zhang, D.-L., McKie, K., Figueroa, R., Litaker, M. S., Thompson, W. O., & Hess, D. C. (1992) · New England Journal of Medicine · doi:10.1056/nejm199202273260905 · Cited by 654 · see citing works
A Critical Period of Brain Development: Studies of Cerebral Glucose Utilization with PET
Chugani, H. T. (1998) · Preventive Medicine · doi:10.1006/pmed.1998.0274 · Cited by 590 · see citing works
Stroke in a cohort of patients with homozygous sickle cell disease
Balkaran, B., Char, G., Morris, J. S., Thomas, P. W., Serjeant, B. E., & Serjeant, G. R. (1992) · The Journal of Pediatrics · doi:10.1016/s0022-3476(05)80897-2 · Cited by 419 · see citing works
Long‐term stroke risk in children with sickle cell disease screened with transcranial doppler
Adams, R. J., McKie, V. C., Carl, E., Nichols, F. T., Perry, R. E., Brock, K., McKie, K., Figueroa, R., Litaker, M. S., Weiner, S. J., et al. (1997) · Annals of Neurology · doi:10.1002/ana.410420505 · Cited by 394 · see citing works
Armstrong, F. D., Rj, T., Wang, W., Zimmerman, R. A., Pegelow, C. H., Miller, S., Moser, F. G., Bello, J. A., Hurtig, A., & Vass, K. (1996) · PubMed · Cited by 361 · see citing works
Pegelow, C. H. (2002) · Blood · doi:10.1182/blood.v99.8.3014 · Cited by 349 · see citing works
Cognitive Functioning and Brain Magnetic Resonance Imaging in Children With Sickle Cell Disease
Armstrong, F. D., Thompson, R. J., Wang, W. C., Zimmerman, R. D., Pegelow, C. H., Miller, S., Moser, F. G., Bello, J. A., & Hurtig, A. (1996) · PEDIATRICS · doi:10.1542/peds.97.6.864 · Cited by 332 · see citing works
Wang, W. C., Enos, L. E., Gallagher, D. M., Thompson, R. J., Guarini, L., Vichinsky, E. P., Wright, E., Zimmerman, R. D., & Armstrong, F. D. (2001) · The Journal of Pediatrics · doi:10.1067/mpd.2001.116935 · Cited by 301 · see citing works
Iron Deficiency and Cognitive Function
Pollitt, E. (1993) · Annual Review of Nutrition · doi:10.1146/annurev.nu.13.070193.002513 · Cited by 288 · see citing works
Nocturnal hypoxaemia and central-nervous-system events in sickle-cell disease
Kirkham, F. J., Hewes, D. K. M., Prengler, M., Wade, A. M., Lane, R., & Evans, J. P. M. (2001) · The Lancet · doi:10.1016/s0140-6736(00)04821-2 · Cited by 258 · see citing works
Self-citationBernaudin, F., Verlhac, S., Fréard, F., Roudot‐Thoraval, F., Benkerrou, M., Thuret, I., Mardini, R., Vannier, J., Ploix, E., Romero, M., et al. (2000) · Journal of Child Neurology · doi:10.1177/088307380001500510 · Cited by 246 · see citing works
Cognitive Functioning in Children With Sickle Cell Disease: A Meta-Analysis
Schatz, J. C. (2002) · Journal of Pediatric Psychology · doi:10.1093/jpepsy/27.8.739 · Cited by 234 · see citing works
Psychological complications in sickle cell disease
Anie, K. (2005) · British Journal of Haematology · doi:10.1111/j.1365-2141.2005.05500.x · Cited by 206 · see citing works
Hypoxaemia in sickle cell disease: biomarker modulation and relevance to pathophysiology
Setty, Y. B. N., Stuart, M. J., Dampier, C., Brodecki, D., & Allen, J. L. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14689-2 · Cited by 191 · see citing works
Sickle cell disease: The neurological complications
Prengler, M., Pavlakis, S. G., Prohovnik, I., & Adams, R. J. (2002) · Annals of Neurology · doi:10.1002/ana.10192 · Cited by 169 · see citing works
Self-citationSteen, R. G., Miles, M. A., Helton, K. J., Strawn, S., Wang, W. C., Xiong, X., & Mulhern, R. K. (2003) · PubMed Central · Cited by 143 · see citing works
Neurocognitive Functioning and Magnetic Resonance Imaging in Children With Sickle Cell Disease
Brown, R. T., Davis, P. C., Lambert, R. G. W., Hsu, L. L.-Y., Hopkins, K. L., & Eckman, J. R. (2000) · Journal of Pediatric Psychology · doi:10.1093/jpepsy/25.7.503 · Cited by 135 · see citing works
Buchanan, G. R., DeBaun, M. R., Quinn, C. T., & Steinberg, M. H. (2004) · Hematology · doi:10.1182/asheducation-2004.1.35 · Cited by 129 · see citing works
Sleep related upper airway obstruction and hypoxaemia in sickle cell disease.
Samuels, M. P., Stebbens, V. A., Davies, S. C., Picton‐Jones, E., & Southall, D. P. (1992) · Archives of Disease in Childhood · doi:10.1136/adc.67.7.925 · Cited by 127 · see citing works
Cognitive Deficits in Children With Sickle Cell Disease
Steen, R. G., Fineberg-Buchner, C., Hankins, G., Weiss, L., Prifitera, A., & Mulhern, R. K. (2005) · Journal of Child Neurology · doi:10.1177/08830738050200020301 · Cited by 125 · see citing works
Neuropsychologic Impairment in Children With Sickle Cell Anemia
Swift, A. V., Cohen, M. J., Hynd, G. W., Wisenbaker, J. M., McKie, K., Makari, G. S., & McKie, V. C. (1989) · PEDIATRICS · doi:10.1542/peds.84.6.1077 · Cited by 108 · see citing works
Prepubertal Growth and Skeletal Maturation in Children With Sickle Cell Disease
Stevens, M. C. G., Maude, G. H., Cupidore, L., et al. (1986) · PEDIATRICS · doi:10.1542/peds.78.1.124 · Cited by 107 · see citing works
Cognitive and Academic Functioning in Children With Sickle-Cell Disease
Brown, R. T., Buchanan, I. D., Doepke, K. J., Eckman, J. R., Baldwin, K., Goonan, B., & Schoenherr, S. J. (1993) · Journal of Clinical Child Psychology · doi:10.1207/s15374424jccp2202_7 · Cited by 107 · see citing works
RACKOFF, W. R., KUNKEL, N. C., Silber, J. H., Asakura, T., & Ohene‐Frempong, K. (1993) · Blood · doi:10.1182/blood.v81.12.3422.3422 · Cited by 104 · see citing works
Cognitive deficits associated with frontal‐lobe infarction in children with sickle cell disease
Watkins, K. E., Hewes, D. E. M., Connelly, A., Kendall, B. E., Kingsley, D. P. E., Evans, J. P. M., Gadian, D. G., Vargha‐Khadem, F., & Kirkham, F. J. (1998) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.1998.tb15412.x · Cited by 98 · see citing works
Self-citationNeuropsychologic effects of stroke in children with sickle cell anemia
Craft, S., Schatz, J. C., Glauser, T. A., Lee, B. J., & DeBaun, M. R. (1993) · The Journal of Pediatrics · doi:10.1016/s0022-3476(05)80844-3 · Cited by 95 · see citing works
Kral, M. C., Brown, R. T., Nietert, P. J., Abboud, M. R., Jackson, S. M., & Hynd, G. W. (2003) · PEDIATRICS · doi:10.1542/peds.112.2.324 · Cited by 94 · see citing works
Noll, R. B. (2001) · Journal of Pediatric Psychology · doi:10.1093/jpepsy/26.2.69 · Cited by 92 · see citing works
Neurologic Complications of Sickle Cell Disease
Pavlakis, S. G., Prohovnik, I., Piomelli, S., & Vivo, D. C. D. (1989) · Advances in Pediatrics · doi:10.1016/s0065-3101(24)00141-5 · Cited by 90 · see citing works
Subtle Neuropsychological Deficits in Children With Sickle Cell Disease
Wasserman, A. L., Wilimas, J. A., Fairclough, D. L., Mulhern, R. K., & Wang, W. C. (1991) · Journal of Pediatric Hematology/Oncology · doi:10.1097/00043426-199121000-00004 · Cited by 89 · see citing works
Quinn, C. T., & Ahmad, N. (2005) · British Journal of Haematology · doi:10.1111/j.1365-2141.2005.05738.x · Cited by 85 · see citing works
Detecting white matter injury in sickle cell disease using voxel‐based morphometry
Baldeweg, T., Hogan, A. M., Saunders, D. E., Telfer, P. T., Gadian, D. G., Vargha‐Khadem, F., & Kirkham, F. J. (2006) · Annals of Neurology · doi:10.1002/ana.20790 · Cited by 85 · see citing works
Self-citationIntelligence After Stroke in Childhood: Review of the Literature and Suggestions for Future Research
Hogan, A. M., Kirkham, F. J., & Isaacs, E. (2000) · Journal of Child Neurology · doi:10.1177/088307380001500509 · Cited by 81 · see citing works
Self-citationLesion Burden and Cognitive Morbidity in Children With Sickle Cell Disease
Schatz, J. C., White, D. A., Moinuddin, A., Armstrong, M. M., & DeBaun, M. R. (2002) · Journal of Child Neurology · doi:10.1177/08830738020170122401 · Cited by 78 · see citing works
Thompson, R. J. (2002) · Journal of Pediatric Psychology · doi:10.1093/jpepsy/28.1.59 · Cited by 76 · see citing works
Neuropsychological Impairment in Children With Sickle Cell Anemia and Cerebrovascular Accidents
Cohen, M. J., Branch, W. B., McKie, V. C., & Adams, R. J. (1994) · Clinical Pediatrics · doi:10.1177/000992289403300902 · Cited by 72 · see citing works
Functional outcomes of children with sickle-cell disease affected by stroke.
Hariman, L. M., Griffith, E. R., Hurtig, A. L., & Keehn, M. (1991) · PubMed · Cited by 71 · see citing works
Pulse oximetry in a cohort study of sickle cell disease
Homi, J., LEVEE, L., Higgs, D. R., et al. (1997) · Clinical & Laboratory Haematology · doi:10.1046/j.1365-2257.1997.00215.x · Cited by 65 · see citing works
Steen, R. G., Reddick, W. E., Mulhern, R. K., Langston, J. W., Ogg, R. J., Bieberich, A. A., Kingsley, P. B., & Wang, W. C. (1998) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.1880080304 · Cited by 61 · see citing works
Factors associated with lowered intelligence in homozygous sickle cell disease.
Knight, S., Singhal, A., Thomas, P., & Serjeant, G. R. (1995) · Archives of Disease in Childhood · doi:10.1136/adc.73.4.316 · Cited by 56 · see citing works
PATHOPHYSIOLOGY OF SICKLE CELL ANEMIA
Bookchin, R. M., & Lew, V. L. (1996) · Hematology/Oncology Clinics of North America · doi:10.1016/s0889-8588(05)70397-x · Cited by 55 · see citing works
Intellectual decline in children with moyamoya and sickle cell anaemia
Hogan, A. M., Kirkham, F. J., Isaacs, E., Wade, A. M., & Vargha‐Khadem, F. (2005) · Developmental Medicine & Child Neurology · doi:10.1017/s001216220500174x · Cited by 53 · see citing works
Self-citationGrueneich, R. (2004) · Journal of Pediatric Psychology · doi:10.1093/jpepsy/jsh012 · Cited by 51 · see citing works
Growth and Development in Children with Sickle-Cell Trait
Kramer, M. S., Rooks, Y., & Pearson, H. A. (1978) · New England Journal of Medicine · doi:10.1056/nejm197809282991303 · Cited by 50 · see citing works
Transcranial Doppler ultrasonography and executive dysfunction in children with sickle cell disease.
Kral, M., & Brown, R. T. (2004) · Journal of Pediatric Psychology · doi:10.1093/jpepsy/jsh020 · Cited by 50 · see citing works
Psychological and Electroencephalographic Study in School Children with Iron Deficiency
Otero, G., Aguirre, D. M., Porcayo, R., & Fernández, T. (1999) · International Journal of Neuroscience · doi:10.3109/00207459908994318 · Cited by 49 · see citing works
Central nervous system abnormalities in asymptomatic young patients with Sβ‐thalassemia
Zafeiriou, D., Prengler, M., Gombakis, N., Kouskouras, K., Economou, M. P., Kardoulas, A., Tsantali, C., Dimitriadis, A., Athanasiou, M. A., & Kirkham, F. J. (2004) · Annals of Neurology · doi:10.1002/ana.20104 · Cited by 39 · see citing works
Self-citationSteen, R. G., Langston, J. W., Ogg, R. J., Manci, E. A., Mulhern, R. K., & Wang, W. C. (1998) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/s1052-3057(98)80019-0 · Cited by 38 · see citing works
Middle cerebral artery blood velocity and cerebral blood flow in sickle cell disease.
Brass, L. M., Prohovnik, I., Pavlakis, S. G., DeVivo, D. C., Piomelli, S., & Mohr, J. P. (1991) · Stroke · doi:10.1161/01.str.22.1.27 · Cited by 38 · see citing works
Adams, R. J., Aaslid, R., Gammal, T. A. M. E., Nichols, F. T., & McKie, V. C. (1988) · Stroke · doi:10.1161/01.str.19.4.518 · Cited by 38 · see citing works
Social Information Processing and Magnetic Resonance Imaging in Children With Sickle Cell Disease
Boni, L. C. (2001) · Journal of Pediatric Psychology · doi:10.1093/jpepsy/26.5.309 · Cited by 35 · see citing works
Steen, R. G., Langston, J. W., Ogg, R. J., Xiong, X., Ye, Z., & Wang, W. C. (1999) · Magnetic Resonance Imaging · doi:10.1016/s0730-725x(98)00204-5 · Cited by 30 · see citing works
McCormack, M. K., Scarr‐Salapatek, S., Polesky, H. F., et al. (1975) · PEDIATRICS · doi:10.1542/peds.56.6.1021 · Cited by 25 · see citing works
Growth, behaviour, and educational achievement of Jamaican children with sickle-cell trait.
Ashcroft, M. T., Desai, P., Richardson, S. A., et al. (1976) · BMJ · doi:10.1136/bmj.1.6022.1371 · Cited by 23 · see citing works
Steen, R. G., Reddick, W. E., Glass, J. O., & Wang, W. C. (1998) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/s1052-3057(98)80051-7 · Cited by 19 · see citing works
Heverly, L. L. (1986) · Archives of Clinical Neuropsychology · doi:10.1016/0887-6177(86)90013-2 · Cited by 18 · see citing works
Intellectual decline in children with moyamoya and sickle cell anaemia
Hogan, A., Kirkham, F. J., Isaacs, E. B., et al. (2005) · Developmental Medicine & Child Neurology · doi:10.1111/j.1469-8749.2005.tb01088.x · Cited by 15 · see citing works
Self-citationHeverly, L. L., Isaac, W., & Hynd, G. W. (1986) · Archives of Clinical Neuropsychology · doi:10.1093/arclin/1.2.139 · Cited by 14 · see citing works
Sleep related upper airway obstruction and hypoxaemia in sickle cell disease.
D'Aloya, N. (1993) · Archives of Disease in Childhood · doi:10.1136/adc.68.5.715-a · Cited by 12 · see citing works
Quantitative MR imaging of children with sickle cell disease: Striking T1 elevation in the thalamus
Steen, R. G., Langston, J. W., Reddick, W. E., Ogg, R. J., Chen, G., & Wang, W. C. (1996) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.1880060140 · Cited by 11 · see citing works
Perceptual-Motor Dysfunction in Children with Sickle Cell Trait
Flick, G. L., & Duncan, C. (1973) · Perceptual and Motor Skills · doi:10.2466/pms.1973.36.1.234 · Cited by 10 · see citing works
Audit of screening for congenital hypothyroidism.
Torrance, M. E., Bantock, H. M., & Freeman, M. (1993) · Archives of Disease in Childhood · doi:10.1136/adc.68.5.715 · Cited by 4 · see citing works
Bridges between nutrition, neuroscience, and behavior
Pollitt, E., & Read, M. S. (1985) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/42.2.348 · Cited by 3 · see citing works
Haemorrhagic shock encephalopathy or near miss sudden infant death syndrome?
Samuels, M. P., & Southall, D. P. (1993) · Archives of Disease in Childhood · doi:10.1136/adc.68.4.526-a · Cited by 2 · see citing works
Bridges between nutrition, neuroscience, and behavior
Pollitt, E., & Read, M. (1985) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/42.2.348a · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Rees, D. C., Williams, T. N., & Gladwin, M. T. (2010) · The Lancet · doi:10.1016/s0140-6736(10)61029-x · Cited by 2,504 · see citing works
Tardy, A.-L., Pouteau, E., Marquez, D., Yilmaz, C., & Scholey, A. (2020) · Nutrients · doi:10.3390/nu12010228 · Cited by 541 · see citing works
Vichinsky, E. P. (2010) · JAMA · doi:10.1001/jama.2010.562 · Cited by 296 · see citing works
- Authors
- Hogan, A. M., Pit‐ten Cate, I. M., Vargha‐Khadem, F., Prengler, M., & Kirkham, F. J.
- Affiliations
- University of Southampton (GB)
- University College London (GB)
- Southampton General Hospital (GB)
- Corresponding author
- Hogan, Alexandra M.
- Venue
- Developmental Science
- Publisher
- Wiley
- Published
- 2006-06-06
- Volume
- 9
- Issue
- 4
- Pages
- 379-387
- ISSN
- 1363-755X (ISSN-L)
- 1467-7687
- OpenAlex
- W1973245875
- Cited by
- 101
- References
- 69
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 8 · 2020: 9 · 2019: 9 · 2018: 4 · 2017: 5 · 2016: 7 · 2015: 10 · 2014: 6 · 2013: 7 · 2012: 7
- FWCI
- 0.36
- Type
- journal article
- Language
- en
- Open access
- green
- orbilu.uni.lu
- Licence
- Locations
- Developmental Science (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion, cc-by-nc-sa)
- Funders
- Wellcome Trust
- Action Medical Research
- LEO Fondet
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal Health and Biochemistry
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- sickle cell disease, intellectual functioning, IQ, cerebral blood flow velocity, hypoxemia, cerebral infarction, adolescents, verbal IQ, performance IQ, chronic hypoxia
- MeSH terms
- Adolescent, Adult, Anemia, Sickle Cell, Hypoxia, Child, Child, Preschool, Humans, Hyperemia, Infant, Intelligence, Intelligence Tests, Magnetic Resonance Imaging, Oxygen, Time Factors, Brain Infarction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
