Maternal Sickle Cell Trait and Fetal Hypoxia

Manzar, Shabih

doi:10.1055/s-2000-13444

Cited by 16 publications

(11 citation statements)

References 13 publications

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“…Finally, NRBC enumeration in CB, particularly in related conditions and when NRBC count is elevated, could lead clinicians to further investigate its possible causes, such as sickle cell disease for which elevated number of circulating NRBC in the CB of neonates born to mothers with sickle cell trait has been described. 14 In conclusion, the flow cytometric method we used provides a simple, quick, and easily reproducible tool for measurement of NRBCs and improves QC of CB units.…”

Section: Discussionmentioning

confidence: 87%

“…Moreover, including NRBC counts in CB QC before freezing could help to explain in part the poor TNC recovery or viability sometimes observed at thawing, especially for CB units with many NRBCs. Finally, NRBC enumeration in CB, particularly in related conditions and when NRBC count is elevated, could lead clinicians to further investigate its possible causes, such as sickle cell disease for which elevated number of circulating NRBC in the CB of neonates born to mothers with sickle cell trait has been described 14 …”

Section: Discussionmentioning

confidence: 99%

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Prospective flow cytometric evaluation of nucleated red blood cells in cord blood units and relationship with nucleated and CD34+ cell quantification

et al. 2006

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Prospective flow cytometric evaluation of nucleated red blood cells in cord blood units and relationship with nucleated and CD34+ cell quantification

et al. 2006

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“…Risk factors including placental insufficiency, decreased utero-placental blood flow, as well as neonatal pulmonary and/or cardiac dysfunction can compromise neonatal oxygenation, thus affecting the development and growth of the brain [3,4]. Neuroinflammation, characterized by microglial activation, has been reported to play an important role in the hypoxic injuries in the neonatal brain [5,6].…”

Section: Introductionmentioning

confidence: 99%

Toll-like receptor 4 mediates microglial activation and production of inflammatory mediators in neonatal rat brain following hypoxia: role of TLR4 in hypoxic microglia

Yao

Kan

et al. 2013

J Neuroinflammation

249

177

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BackgroundHypoxia induces microglial activation which causes damage to the developing brain. Microglia derived inflammatory mediators may contribute to this process. Toll-like receptor 4 (TLR4) has been reported to induce microglial activation and cytokines production in brain injuries; however, its role in hypoxic injury remains uncertain. We investigate here TLR4 expression and its roles in neuroinflammation in neonatal rats following hypoxic injury.MethodsOne day old Wistar rats were subjected to hypoxia for 2 h. Primary cultured microglia and BV-2 cells were subjected to hypoxia for different durations. TLR4 expression in microglia was determined by RT-PCR, western blot and immunofluorescence staining. Small interfering RNA (siRNA) transfection and antibody neutralization were employed to downregulate TLR4 in BV-2 and primary culture. mRNA and protein expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and inducible nitric oxide synthase (iNOS) was assessed. Reactive oxygen species (ROS), nitric oxide (NO) and NF-κB levels were determined by flow cytometry, colorimetric and ELISA assays respectively. Hypoxia-inducible factor-1 alpha (HIF-1α) mRNA and protein expression was quantified and where necessary, the protein expression was depleted by antibody neutralization. In vivo inhibition of TLR4 with CLI-095 injection was carried out followed by investigation of inflammatory mediators expression via double immunofluorescence staining.ResultsTLR4 immunofluorescence and protein expression in the corpus callosum and cerebellum in neonatal microglia were markedly enhanced post-hypoxia. In vitro, TLR4 protein expression was significantly increased in both primary microglia and BV-2 cells post-hypoxia. TLR4 neutralization in primary cultured microglia attenuated the hypoxia-induced expression of TNF-α, IL-1β and iNOS. siRNA knockdown of TLR4 reduced hypoxia-induced upregulation of TNF-α, IL-1β, iNOS, ROS and NO in BV-2 cells. TLR4 downregulation-mediated inhibition of inflammatory cytokines in primary microglia and BV-2 cells was accompanied by the suppression of NF-κB activation. Furthermore, HIF-1α antibody neutralization attenuated the increase of TLR4 expression in hypoxic BV-2 cells. TLR4 inhibition in vivo attenuated the immunoexpression of TNF-α, IL-1β and iNOS on microglia post-hypoxia.ConclusionActivated microglia TLR4 expression mediated neuroinflammation via a NF-κB signaling pathway in response to hypoxia. Hence, microglia TLR4 presents as a potential therapeutic target for neonatal hypoxia brain injuries.

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“…In a retrospective case-control study, Manzar showed that 9 of 20 infants born to SCT mothers had occasional or increased number of circulating nucleated red blood cells, a marker of fetal asphyxia, 12,13 in their cord blood compared with none in normal controls. 14 Furthermore, histopathological examination of the placenta of SCT pregnancies showed sickling in the intervillous space and decidual vessels, suggesting hypoxia at the maternal and fetal blood interface. 3 These studies support the concern of small infants in SCT pregnancies expressed by some authors.…”

Section: Introductionmentioning

confidence: 99%

Birthweights in sickle cell trait pregnancies

Tan

Seed

Oteng‐Ntim

2008

BJOG

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Objectives Available evidence on the effect of sickle cell trait (SCT) on birthweight is conflicting, not gestational age specific, and does not account for maternal and infant factors. The objectives of this study are to determine the contemporary mean birthweight, mean customised birthweight centile, and to analyse the risk of small-for-gestational-age (SGA) and large-forgestational-age (LGA) babies in SCT pregnancies.Design Large retrospective cohort study.Setting London hospital. Methods All qualifying pregnancies were identified on Terra Nova Healthware. Birthweight centiles of these cases were computed with Gardosi customised bulk centile calculator using collected data on maternal height, weight, ethnicity and parity, and the infant's gender, gestational age and birthweight. Birthweight and birthweight centiles of SCT and pregnancies with no haemoglobinopathy (control) were compared. Statistical analysis was performed using Stata version 9.2.Main outcome measures Birthweight and birthweight centiles.Results Five hundred and five SCT and 16 320 controls were analysed. The mean birthweight of SCT pregnancies was 3223 g, 57 g lower than controls (P = 0.024). However, its mean birthweight centile was 49.0% similar to that of controls' 47.5% (P = 0.320). There is an apparent risk of LGA babies in SCT pregnancies, but logistic regression analysis suggests that the odds are related to being an older non-white parturient and a male infant rather than SCT status.Conclusions SCT is not a risk factor for SGA or LGA infants.Keywords Birthweight, birthweight centile, customised birthweight centile, large for gestational age, sickle cell trait, small for gestational age.

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Maternal Sickle Cell Trait and Fetal Hypoxia

Cited by 16 publications

References 13 publications

Prospective flow cytometric evaluation of nucleated red blood cells in cord blood units and relationship with nucleated and CD34+ cell quantification

Prospective flow cytometric evaluation of nucleated red blood cells in cord blood units and relationship with nucleated and CD34+ cell quantification

Toll-like receptor 4 mediates microglial activation and production of inflammatory mediators in neonatal rat brain following hypoxia: role of TLR4 in hypoxic microglia

Birthweights in sickle cell trait pregnancies

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