The contribution of hepcidin as a regulator of iron metabolism & erythropoiesis on the severity o... more The contribution of hepcidin as a regulator of iron metabolism & erythropoiesis on the severity of anemia in sickle cell disease (SCD) remains poorly characterized, especially in Sub-Saharan African populations. The aims of the study were to determine if hepcidin is associated with severity of steady-state anemia in SCD and to investigate factors associated with hepcidin and anemia in SCD. Archived samples from 199 Tanzanian children, 56% boys aged 3-18 with laboratory-confirmed SCD were analysed based on recorded averaged steady-state hemoglobin (ASSH) quartiles (lowest vs. highest). Univariable and multivariable logistic regression was used to assess associations with ASSH quartiles. In univariable analysis, hepcidin <5·5 ng/mL was associated with increased odds of being in the lowest ASSH quartile (OR 2·20; 95%CI 1·2-3·93) but which was limited to girls (OR 4·85, 95%CI 1·79-13·09, p = .046 for interaction). In multivariable analyses including either reticulocyte percentage or ...
Exposure to environmental tobacco smoke (ETS) is an important modifiable risk factor for child ho... more Exposure to environmental tobacco smoke (ETS) is an important modifiable risk factor for child hospitalization, although its contribution is not well documented in countries where ETS due to maternal tobacco smoking is negligible. We conducted a birth cohort study of 1999 neonates between May 2009 and May 2010 in Nha Trang, Vietnam, to evaluate paternal tobacco smoking as a risk factor for infectious and non-infectious diseases. Hospitalizations during a 24-month observation period were identified using hospital records. The effect of paternal exposure during pregnancy and infancy on infectious disease incidence was evaluated using Poisson regression models. In total, 35.6% of 1624 children who attended follow-up visits required at least one hospitalization by 2 years of age, and the most common reason for hospitalization was lower respiratory tract infection (LRTI). Paternal tobacco smoking independently increased the risk of LRTI 1.76-fold (95% CI: 1.24-2.51) after adjusting for p...
Fetal hemoglobin (HbF, α2γ2) is a major contributor to the remarkable phenotypic heterogeneity of... more Fetal hemoglobin (HbF, α2γ2) is a major contributor to the remarkable phenotypic heterogeneity of sickle cell anemia (SCA). Genetic variation at 3 principal loci (HBB cluster on chromosome 11p, HBS1L-MYB region on chromosome 6q, and BCL11A on chromosome 2p) have been shown to influence HbF levels and disease severity in β-thalassemia and SCA. Previous studies in SCA, however, have been restricted to populations from the African diaspora, which include multiple genealogies. We have investigated the influence of these 3 loci on HbF levels in sickle cell patients from Tanzania and in a small group of African British sickle patients. All 3 loci have a significant impact on the trait in both patient groups. The results suggest the presence of HBS1L-MYB variants affecting HbF in patients who are not tracked well by European-derived markers, such as rs9399137. Additional loci may be identified through independent genome-wide association studies in African populations.
Anemia affects most pregnant African women and is predominantly due to iron deficiency, but anten... more Anemia affects most pregnant African women and is predominantly due to iron deficiency, but antenatal iron supplementation has uncertain health benefits and can increase the malaria burden. To measure the effect of antenatal iron supplementation on maternal Plasmodium infection risk, maternal iron status, and neonatal outcomes. Randomized placebo-controlled trial conducted October 2011 through April 2013 in a malaria endemic area among 470 rural Kenyan women aged 15 to 45 years with singleton pregnancies, gestational age of 13 to 23 weeks, and hemoglobin concentration of 9 g/dL or greater. All women received 5.7 mg iron/day through flour fortification during intervention, and usual intermittent preventive treatment against malaria was given. Supervised daily supplementation with 60 mg of elemental iron (as ferrous fumarate, n = 237 women) or placebo (n = 233) from randomization until 1 month postpartum. Primary outcome was maternal Plasmodium infection at birth. Predefined secondary...
The contribution of hepcidin as a regulator of iron metabolism & erythropoiesis on the severity o... more The contribution of hepcidin as a regulator of iron metabolism & erythropoiesis on the severity of anemia in sickle cell disease (SCD) remains poorly characterized, especially in Sub-Saharan African populations. The aims of the study were to determine if hepcidin is associated with severity of steady-state anemia in SCD and to investigate factors associated with hepcidin and anemia in SCD. Archived samples from 199 Tanzanian children, 56% boys aged 3-18 with laboratory-confirmed SCD were analysed based on recorded averaged steady-state hemoglobin (ASSH) quartiles (lowest vs. highest). Univariable and multivariable logistic regression was used to assess associations with ASSH quartiles. In univariable analysis, hepcidin <5·5 ng/mL was associated with increased odds of being in the lowest ASSH quartile (OR 2·20; 95%CI 1·2-3·93) but which was limited to girls (OR 4·85, 95%CI 1·79-13·09, p = .046 for interaction). In multivariable analyses including either reticulocyte percentage or ...
Exposure to environmental tobacco smoke (ETS) is an important modifiable risk factor for child ho... more Exposure to environmental tobacco smoke (ETS) is an important modifiable risk factor for child hospitalization, although its contribution is not well documented in countries where ETS due to maternal tobacco smoking is negligible. We conducted a birth cohort study of 1999 neonates between May 2009 and May 2010 in Nha Trang, Vietnam, to evaluate paternal tobacco smoking as a risk factor for infectious and non-infectious diseases. Hospitalizations during a 24-month observation period were identified using hospital records. The effect of paternal exposure during pregnancy and infancy on infectious disease incidence was evaluated using Poisson regression models. In total, 35.6% of 1624 children who attended follow-up visits required at least one hospitalization by 2 years of age, and the most common reason for hospitalization was lower respiratory tract infection (LRTI). Paternal tobacco smoking independently increased the risk of LRTI 1.76-fold (95% CI: 1.24-2.51) after adjusting for p...
Fetal hemoglobin (HbF, α2γ2) is a major contributor to the remarkable phenotypic heterogeneity of... more Fetal hemoglobin (HbF, α2γ2) is a major contributor to the remarkable phenotypic heterogeneity of sickle cell anemia (SCA). Genetic variation at 3 principal loci (HBB cluster on chromosome 11p, HBS1L-MYB region on chromosome 6q, and BCL11A on chromosome 2p) have been shown to influence HbF levels and disease severity in β-thalassemia and SCA. Previous studies in SCA, however, have been restricted to populations from the African diaspora, which include multiple genealogies. We have investigated the influence of these 3 loci on HbF levels in sickle cell patients from Tanzania and in a small group of African British sickle patients. All 3 loci have a significant impact on the trait in both patient groups. The results suggest the presence of HBS1L-MYB variants affecting HbF in patients who are not tracked well by European-derived markers, such as rs9399137. Additional loci may be identified through independent genome-wide association studies in African populations.
Anemia affects most pregnant African women and is predominantly due to iron deficiency, but anten... more Anemia affects most pregnant African women and is predominantly due to iron deficiency, but antenatal iron supplementation has uncertain health benefits and can increase the malaria burden. To measure the effect of antenatal iron supplementation on maternal Plasmodium infection risk, maternal iron status, and neonatal outcomes. Randomized placebo-controlled trial conducted October 2011 through April 2013 in a malaria endemic area among 470 rural Kenyan women aged 15 to 45 years with singleton pregnancies, gestational age of 13 to 23 weeks, and hemoglobin concentration of 9 g/dL or greater. All women received 5.7 mg iron/day through flour fortification during intervention, and usual intermittent preventive treatment against malaria was given. Supervised daily supplementation with 60 mg of elemental iron (as ferrous fumarate, n = 237 women) or placebo (n = 233) from randomization until 1 month postpartum. Primary outcome was maternal Plasmodium infection at birth. Predefined secondary...
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Papers by Sharon Cox