Iron stores in pregnant women with sickle cell disease: a protocol for a systematic review and meta-analysis

IntroductionSickle cell disease (SCD) is the most common inherited disease worldwide. The greatest disease burden is seen in sub-Saharan Africa. Early diagnosis and improved care of people living with SCD have led to an increase in the number of women with SCD reaching the reproductive age. Iron deficiency anaemia remains the most common cause of anaemia in pregnancy, affecting 51%–63% of pregnancies in Africa. However, the unavailability of guidelines on supplementation of iron in this pregnant subpopulation often leaves clinicians in a fix. We propose to conduct the first systematic review and possibly a meta-analysis on the prevalence, associated factors and maternal/fetal outcomes of iron deficiency anaemia among pregnant women with SCD.Methods and analysisWe will search the following electronic databases for studies on the iron status of pregnant women with SCD: PubMed, MEDLINE, EMBASE, Google Scholar, African Journals Online, African Index Medicus, Popline and the Cochrane Library. After the selection of eligible studies from the search output, review of full text, data extraction and data synthesis will be performed. Studies obtained from the review shall be evaluated for quality, risk of bias and heterogeneity. Appropriate statistical methods shall be used to pool prevalence estimates for matching studies globally and in subpopulations. This protocol has been reported as per the 2015 guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols.Ethics and disseminationThere is no requirement for ethical approval as the proposed study will use published data. The findings of this study will be published in a peer-reviewed journal and will be presented at conferences.Trial registration numberCRD42018109803.

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

BMC Pregnancy and Childbirth ◽

10.1186/s12884-020-03326-8 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Desmond Aroke ◽

Benjamin Momo Kadia ◽

Tsi Njim

Keyword(s):

Systematic Review ◽

Sickle Cell Disease ◽

Iron Deficiency ◽

Quality Assessment ◽

Sickle Cell ◽

Iron Deficiency Anaemia ◽

Iron Status ◽

Cell Disease ◽

Deficiency Anaemia ◽

Factors Associated

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.

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Adverse maternal and perinatal outcomes in pregnant women with sickle cell disease: systematic review and meta-analysis

Blood ◽

10.1182/blood-2014-11-607317 ◽

2015 ◽

Vol 125 (21) ◽

pp. 3316-3325 ◽

Cited By ~ 84

Author(s):

E. Oteng-Ntim ◽

D. Meeks ◽

P. T. Seed ◽

L. Webster ◽

J. Howard ◽

...

Keyword(s):

Systematic Review ◽

Sickle Cell Disease ◽

Pregnant Women ◽

Sickle Cell ◽

Meta Analysis ◽

Perinatal Outcomes ◽

Cell Disease

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IRON-DEFICIENCY ANÆMIA AND SICKLE-CELL DISEASE : A HYPOTHESIS

The Lancet ◽

10.1016/s0140-6736(73)93163-2 ◽

1973 ◽

Vol 302 (7823) ◽

pp. 260-261 ◽

Cited By ~ 15

Author(s):

ThomasL. Lincoln ◽

Jerome Aroesty ◽

Paul Morrison

Keyword(s):

Sickle Cell Disease ◽

Iron Deficiency ◽

Sickle Cell ◽

Iron Deficiency Anaemia ◽

Cell Disease ◽

Deficiency Anaemia

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Iron deficiency anaemia in Jamaican children, aged 1-5 years, with sickle cell disease

West Indian Medical Journal ◽

10.1590/s0043-31442005000500004 ◽

2005 ◽

Vol 54 (5) ◽

Cited By ~ 5

Author(s):

L King ◽

M Reid ◽

TE Forrester

Keyword(s):

Sickle Cell Disease ◽

Iron Deficiency ◽

Sickle Cell ◽

Iron Deficiency Anaemia ◽

Cell Disease ◽

Deficiency Anaemia

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Iron preparations for women of reproductive age with iron deficiency anaemia in pregnancy (FRIDA): a systematic review and network meta-analysis

The Lancet Haematology ◽

10.1016/s2352-3026(21)00137-x ◽

2021 ◽

Vol 8 (7) ◽

pp. e503-e512

Author(s):

Ewelina Rogozińska ◽

Jahnavi Daru ◽

Marios Nicolaides ◽

Carmen Amezcua-Prieto ◽

Susan Robinson ◽

...

Keyword(s):

Systematic Review ◽

Iron Deficiency ◽

Iron Deficiency Anaemia ◽

Meta Analysis ◽

Reproductive Age ◽

Women Of Reproductive Age ◽

Deficiency Anaemia ◽

Anaemia In Pregnancy ◽

In Pregnancy

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Systematic review to investigate the safety of induction and augmentation of labour among pregnant women with iron-deficiency anaemia

BMJ Open ◽

10.1136/bmjopen-2018-021793 ◽

2018 ◽

Vol 8 (12) ◽

pp. e021793 ◽

Cited By ~ 1

Author(s):

Kathryn Bunch ◽

Nia Roberts ◽

Marian Knight ◽

Manisha Nair

Keyword(s):

Systematic Review ◽

Iron Deficiency ◽

Pregnant Women ◽

Iron Deficiency Anaemia ◽

Case Reports ◽

Case Series ◽

Severe Anaemia ◽

Risk Of Bias ◽

Deficiency Anaemia ◽

Increased Risk

ObjectiveTo conduct a systematic review to investigate the safety of induction and/or augmentation of labour compared with spontaneous-onset normal labour among pregnant women with iron-deficiency anaemia.DesignSystematic review.SettingStudies from all countries, worldwide.PopulationPregnant women with iron-deficiency anaemia at labour and delivery.InterventionAny intervention related to induction and/or augmentation of labour.Outcome measuresPrimary: Postpartum haemorrhage (PPH), heart failure and maternal death. Secondary: Emergency caesarean section, hysterectomy, admission to intensive care unit.MethodWe searched 10 databases, including Medline and Embase, from database inception to 1 October 2018. We included all study designs except cross-sectional studies without a comparator group, case reports, case series, ecological studies, and expert opinion. The searches were conducted by a healthcare librarian and two authors independently screened and reviewed the studies. We used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approachto ascertain risk of bias and conducted a narrative synthesis.ResultsWe identified 3217 journal articles, 223 conference papers, 45 dissertations and 218 registered trials. Ten articles were included for full-text review and only one was found to fulfil the eligibility criteria. This was a retrospective cohort study from India, which showed that pregnant women with moderate and severe anaemia could have an increased risk of PPH if they underwent induction and/or augmentation of labour, but the evidence was weak (graded as ‘high risk of bias’).ConclusionThe best approach is to prevent anaemia, but a large number of women in low-to-middle-income countries present with severe anaemia during labour. In such women, appropriate peripartum management could prevent complications and death. Our review showed that at present we do not know if induction and augmentation of labour is safe in pregnant women with iron-deficiency anaemia and further research is required.PROSPERO registration numberCRD42015032421.

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Efficacy of Allogeneic Hematopoietic Cell Transplantation (HCT) in Sickle Cell Disease: Results of a Systematic Review/Meta-Analysis

Blood ◽

10.1182/blood-2019-124955 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2106-2106

Author(s):

Madiha Iqbal ◽

Tea Reljic ◽

Ernesto Ayala ◽

Hemant S. Murthy ◽

Ambuj Kumar ◽

...

Keyword(s):

Systematic Review ◽

Sickle Cell Disease ◽

Clinical Outcomes ◽

Sickle Cell ◽

Pediatric Patients ◽

Medical Literature ◽

Meta Analysis ◽

Adult Patients ◽

Cell Disease ◽

Allogeneic Hct

Background: Sickle cell disease (SCD) is an inherited hemoglobinopathy which affects over 300,000 children born each year worldwide. In spite of improvement in supportive care in recent years, there is still a lack of effective treatment options. SCD leads to debilitating and cyclic episodes of erythrocyte sickling with progressive organ injury, contributing to lifetime morbidity and shortened life expectancy. Allogeneic HCT (allo-HCT) is a potentially curative therapy for SCD because engraftment is associated with resolution of the clinical phenotype of the disease and abrogation of its complications. Medical literature on allo-HCT for SCD is largely limited to children. Recent studies have evaluated the efficacy of allo-HCT in the adult population. Here, we conduct a systematic review/meta-analysis to assess the totality of evidence pertaining to the efficacy (or lack thereof) of allo-HCT in children and adults. Materials and methods: We performed a comprehensive search of the medical literature using PubMed/Medline, EMBASE and Cochrane library on July 3rd, 2019. We extracted data on clinical outcomes related to benefits (overall [OS] and disease free/event free survival [EFS/DFS]) and harms (non-relapse mortality [NRM] and graft failure [GF]), independently by two authors. Our search strategy identified 1001 references but only 30 studies (n= 1995 patients) were included in this systematic review/meta-analysis. We also performed a sub analysis on clinical outcomes for studies that included only pediatric patients (defined as <18 years) and those in patients ≥18 years of age. Results: Median age for patients enrolled in all the studies was at 10 years. Recurrent veno-occlusive crises represented the most common indication for allo-HCT followed by acute chest syndrome and stroke; nevertheless, most patients had more than one indication. Matched related donors (MRD) were the most common donor source (93%). Bone marrow was the most common source of hematopoietic stem cells (77%). Majority of patients underwent conditioning with myeloablative regimens (77%). Pooled OS rates (n=29 studies, 1681 patients) after allogeneic HCT was 95% (95%CI=93-96%) with low heterogeneity (I2=6.4%) among included studies (Figure 1). Pooled EFS/DFS rates (n=29 studies, 1894 patients) post-allografting was 90% (95%CI=87-93%) with moderate heterogeneity (I2=54%). Pooled NRM rates from 30 studies (1995 patients) was 4% (95%CI=2-6%) with low heterogeneity (I2=29.4%). Pooled GF rates from 28 studies (1851 patients) was 4% (95%CI=2-6%) with moderate heterogeneity (I2=55%). A subset analysis specifically for pediatric patients (n= 11 studies, 1009 patients, median age at 9.7 years) showed a pooled OS rate of 96% (95%CI=94-97%) with low heterogeneity (I2=0%); and for adult patients (n=3 studies, 51 patients, median age at 33.4 years) the pooled OS was 94% (95%CI=80-100%) with moderate heterogeneity (I2=52%). Pooled EFS/DFS for pediatric patients (n= 11 studies, 1009 patients) was at 89 %( 95%CI=84-93%) with moderate heterogeneity (I2=55.1%); and for adult patients (n=2 studies, 30 patients) was at 95% (95%CI=83-100%) with high heterogeneity (I2=96.5%). Pooled NRM from 10 studies with pediatric patients (281 patients) was at 6 % (95%CI=3-10%) with low heterogeneity (I2=0%); and from 3 studies with adult patients (51 patients) was at 1% (95%CI=0-7%) with low heterogeneity (I2=15.1%). Pooled GF from 10 studies with pediatric patients (281 patients) was at 3 % (95%CI=1-7%) with moderate heterogeneity (I2=40%); and from 2 studies with adult patients (30 patients) was at 5% (95%CI=0-17%) with high heterogeneity (I2=95.4%). Conclusions: The results of our systematic review/meta-analysis show excellent OS, EFS/DFS in children and adults undergoing allo-HCT with pooled OS rates exceeding 90%. The main limitation to offering an allo-HCT in SCD remains the availability of a suitable donor as 85% of patients meeting criteria do not have a MRD. We anticipate that with emergence of haploidentical transplantation the number of allo-HCT will increase in the future. GF remains a significant concern in this population and future studies should focus on novel immune suppression strategies to help reduce GF. Disclosures Kharfan-Dabaja: Pharmacyclics: Consultancy; Daiichi Sankyo: Consultancy.

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