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Iron stores in pregnant women with sickle cell disease: a systematic review.

ABSTRACT: BACKGROUND:Gradual improvements in the management of sickle cell disease (SCD), have led to an increase in the number of women with SCD who reach the age of procreation. However, evidence on the iron status of pregnant women with sickle cell disease (PWSCD) remains inconclusive. We conducted the first systematic review on the prevalence, determinants and maternal/foetal outcomes of iron deficiency anaemia among PWSCD. METHODS:We searched MEDLINE, EMBASE, Global Health, Africa Index Medicus, the Cochrane library databases and reference lists of retrieved publications for studies describing the iron status of PWSCD. The literature search was done over a period of 1?month, with no language or date restrictions applied. Data were extracted on a Microsoft excel sheet. Two authors assessed all included studies for methodological quality and risk of bias. RESULTS:A total of 710 reports were identified for title and article screening. Five retained studies were conducted before or during the 90s and included 67 participants. After quality assessment, the observational studies were designated to have a "fair" quality assessment while the randomised control trial had an "unclear" quality assessment. The prevalence of iron deficiency anaemia among PWSCD varied by study design and diagnostic method. The overall prevalence ranged from 6.67-83.33%. None of the studies provided evidence on factors associated with iron deficiency anaemia and the randomized trial reported no difference in outcomes between PWSCD who had iron supplementation and those who did not. CONCLUSION:Evidence on factors associated with iron deficiency anaemia among PWSCD and maternal/foetal outcomes in PWSCD who have iron deficiency anaemia is poor. The studies included in this review suggests that iron deficiency anaemia may be highly prevalent in PWSCD but due to the very small sample sizes and varied study designs, this evidence is inconclusive. The review shows that there is a need for more studies with robust designs and adequate sample sizes to assess the disease burden of iron deficiency anaemia in PWSCD.

SUBMITTER: Aroke D

PROVIDER: S-EPMC7566031 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Iron stores in pregnant women with sickle cell disease: a systematic review.

Aroke Desmond D Kadia Benjamin Momo BM Njim Tsi T

BMC pregnancy and childbirth 20201016 1

<h4>Background</h4>Gradual improvements in the management of sickle cell disease (SCD), have led to an increase in the number of women with SCD who reach the age of procreation. However, evidence on the iron status of pregnant women with sickle cell disease (PWSCD) remains inconclusive. We conducted the first systematic review on the prevalence, determinants and maternal/foetal outcomes of iron deficiency anaemia among PWSCD.<h4>Methods</h4>We searched MEDLINE, EMBASE, Global Health, Africa Inde ...[more]

PMID: 33066749

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Project description:Pregnancy in Sickle Cell Disease (SCD) women is associated to increased risk of clinical and obstetrical complications. Placentas from SCD pregnancies can present increased abnormal findings, which may lead to placental insufficiency, favoring adverse perinatal outcome. These placental abnormalities are well known and reported, however little is known about the molecular mechanisms, such as epigenetics. Thus, our aim was to evaluate the DNA methylation profile in placentas from women with SCD (HbSS and HbSC genotypes), compared to uncomplicated controls (HbAA). We included in this study 11 pregnant women with HbSS, 11 with HbSC and 21 with HbAA genotypes. Illumina Methylation EPIC BeadChip was used to assess the whole placental DNA methylation. Pyrosequencing was used for array data validation and qRT-PCR was applied for gene expression analysis. Our results showed high frequency of hypermethylated CpGs sites in HbSS and HbSC groups with 73.5% and 76.2% respectively, when compared with the control group. Differentially methylated regions (DMRs) also showed an increased hypermethylation status for the HbSS (89%) and HbSC (86%) groups, when compared with the control group methylation data. DMRs were selected for methylation validation (4 DMRs-HbSS and 3 DMRs the HbSC groups) and after analyses three were validated in the HbSS group, and none in the HbSC group. The gene expression analysis showed differential expression for the PTGFR (-2.97-fold) and GPR56 (3.0-fold) genes in the HbSS group, and for the SPOCK1 (-2.40-fold) and ADCY4 (1.80-fold) genes in the HbSC group. Taken together, these data strongly suggest that SCD (HbSS and HbSC genotypes) can alter placental DNA methylation and lead to gene expression changes. These changes possibly contribute to abnormal placental development and could impact in the clinical course, especially for the fetus, possibly leading to increased risk of abortion, fetal growth restriction (FGR), stillbirth, small for gestational age newborns and prematurity.

Project description:Background and aimsChildren with sickle cell disease (SCD) have an increased risk of multiple hemotransfusions and this can predispose them to elevated iron stores. The objectives of the study were to determine the extent of elevated iron stores and the associated risk factors in a population of steady-state SCD children in Ghana.MethodsThis cross-sectional study was conducted at the pediatric sickle cell clinic at the Komfo Anokye Teaching Hospital. Complete blood count and serum ferritin assay were performed for (n = 178) steady-state SCD children. Descriptive and multivariate logistic regression analysis were performed. Elevated iron stores were defined as serum ferritin levels >300 ng/ml. Statistical significance was considered at p < 0.05.ResultsThe mean (standard deviation) age of the participants was 9.61 (±4.34) years, and 51% of them were males. About 17% of SCD children had elevated iron stores and receiving at least three hemotransfusions during the last 12 months was strongly associated with elevated iron stores (p < 0.001). History of chronic hemotransfusion increased the odds of having elevated iron store (adjusted odds ratio [aOR] = 11.41; 95% confidence interval [CI] = 3.11-30.85; p < 0.001) but SCD patients on hydroxyurea treatment had reduced-odds of having elevated iron stores (aOR = 0.18; 95% CI = 0.06-0.602; p = 0.006). Moreover, red blood cell (Coef. = -0.84; 95% CI = -0.37, -1.32; p = 0.001), hemoglobin (Coef. = -0.83; 95% CI = -0.05, -1.61; p = 0.04), hematocrit (Coef. = -0.85; 95% CI = -0.08, -1.63; p = 0.03), mean cell volume (Coef. = 0.02; 95% CI = 0.01, 0.03; p = 0.001) and mean cell hemoglobin (Coef. = 0.04; 95% CI = 0.01, 0.07; p = 0.002) could significantly predict serum ferritin levels.ConclusionThe magnitude of elevated iron stores was high among children with SCD in steady-state. Red cell indices could provide invaluable information regarding the risk of elevated iron stores. SCD children who have a history of chronic hemotransfusion or had received at least three hemotransfusions in a year should be monitored for elevated iron stores.

Project description:BackgroundSickle cell disease (SCD) is an inherited autosomal recessive disorder caused by the replacement of normal haemoglobin (HbA) by mutant Hb (sickle Hb, HbS). The sickle-shaped red blood cells lead to haemolysis and vaso-occlusion. Especially in the first years of life, patients with SCD are at high risk of life-threatening complications. SCD prevalence shows large regional variations; the disease predominantly occurs in sub-Saharan Africa. We aimed to systematically assess the evidence on the benefit of newborn screening for SCD followed by an earlier treatment start.MethodsWe systematically searched bibliographic databases (MEDLINE, EMBASE, Cochrane Databases, and the Health Technology Assessment Database), trial registries, and other sources to identify systematic reviews and randomised controlled trials (RCTs) or non-randomised trials on newborn screening for SCD. The last search was in 07/2020. Two reviewers independently reviewed abstracts and full-text articles and assessed the risk of bias of the studies included. Data were extracted by one person and checked by another. As meta-analyses were not possible, a qualitative summary of results was performed.ResultsWe identified 1 eligible study with direct evidence: a Jamaican retrospective study evaluating newborn screening for SCD followed by preventive measures (prevention of infections and education of parents). The study included 500 patients with SCD (intervention group, 395; historical control group, 105). Although the results showed a high risk of bias, the difference between the intervention and the control group was very large: mortality in children decreased by a factor of about 10 in the first 5 years of life (0.02% in the intervention group vs. 0.19% in the control group, odds ratio 0.09; 95% confidence interval [0.04; 0.22], p < 0.001).ConclusionThe results are based on a single retrospective study including historical controls. However, the decrease of mortality by a factor of 10 is unlikely to be explained by bias alone. Therefore, in terms of mortality, data from this single retrospective study included in our systematic review suggest a benefit of newborn screening for SCD (followed by preventive measures) versus no newborn screening for SCD (weak certainty of conclusions).

Project description:Background/Objectives: Sickle cell disease (SCD) impacts about 100,000 people in the US. SCD increases the risk of cholelithiasis and microvascular ischemia, which could increase the risk of acute pancreatitis (AP). Abdominal pain is a common presenting symptom of AP and sickle cell vaso-occlusive crisis. The purpose of our systematic review is to estimate the prevalence and determine the severity of AP in individuals with SCD compared to the general population. Methods: Multiple electronic databases were searched. We included studies that included children and adults (population) and addressed the association of SCD (exposure) with AP (outcome) compared to the same population without SCD (control). Two authors screened titles and abstracts independently, and data were abstracted in duplication from included studies. We registered this protocol in PROSPERO-CRD42023422397. Results: Out of 296 studies screened from multiple electronic databases, we identified 33 studies. These studies included 17 case reports, one case series, and 15 retrospective cohort studies, and 18 studies included children. Eight of the AP case reports were in patients with HbSS genotype, two with sickle beta thalassemia, and one with HbSoArab, and in six case reports, a genotype was not specified. Complications were reported in 11 cases-respiratory complication (in at least four cases), splenic complications (three cases), pancreatic pseudocyst (two cases) and death from AP (one case). Of the four AP cases in the case series, three had HbSS genotype, and two cases had complications and severe pancreatitis. AP prevalence in SCD was estimated to be 2% and 7% in two retrospective studies, but they lacked a comparison group. In retrospective studies that evaluated the etiology of AP in children, biliary disease caused mostly by SCD was present in approximately 12% and 34%, respectively. Conclusions: Data on the prevalence of AP in individuals with SCD are limited. Prospectively designed studies aiming to proactively evaluate AP in individuals with SCD who present with abdominal pain are needed to improve timely diagnosis of AP in SCD and outcomes.

Project description:BACKGROUND:Despite the supplementation of iron-folic acid is the recommended strategy during the antenatal period; iron deficiency anemia is the commonest hematologic complication during pregnancy. Therefore, this systematic review and meta-analysis aimed to assess the level of adherence to iron-folic acid supplementation and its associated factors among pregnant women in Ethiopia. METHODS:Systematic review and meta-analysis guideline was followed for this study. Different online databases were used for the review: PubMed, HINARI, EMBASE, Google Scholar and African Journals Online. Different searching terms were applied based on the adapted PICO principles to achieve and access all the essential articles. The data were entered and analyzed using Microsoft Excel and Stata 11 software respectively. RESULTS:Fifteen studies were included in this systematic review and meta-analysis with a total of 5808 pregnant women. The overall pooled prevalence of adherence to iron-folic acid supplementation among pregnant women in Ethiopia was 41.38% (95% CI: 33.09, 49.67). Having secondary and above educational status of the women (AOR:2.68,95%CI:1.25, 5.74), having an early registration of antenatal care follow-up (?16?weeks) (AOR:2.54,95%CI:1.99, 3.24), having anemia complication during current pregnancy (AOR:3.01,95%CI:1.88, 4.81), having good knowledge of iron-folic acid supplementation (AOR: 2.96, 95%CI:1.76, 4.99), having four times or more antenatal care follow up (AOR:3.66, 95%CI:2.81, 4.77), getting health education about benefit of iron and folic acid (AOR:2.62,95%CI:1.46,4.72), and having good knowledge about anemia (AOR:2.99,95%CI:2.32, 3.85) were associated risk factors for adherence to iron-folic acid supplementation. CONCLUSION:The overall pooled prevalence adherence of IFAS among pregnant women was lower than the WHO recommendations. Educational status, early registration of ANC, anemia in the current pregnancy, good knowledge of IFAS, number of ANC visits, good knowledge of anemia and receiving health education about the benefit of IFAS were factors associated with the adherence of IFAS among pregnant women in Ethiopia. This finding is important to design strategic policies and to prevent anemia and congenital anomaly resulted from inadequate intake of iron and folic acid.

Dataset Information

Iron stores in pregnant women with sickle cell disease: a systematic review.

Publications

Iron stores in pregnant women with sickle cell disease: a systematic review.

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