A meta-analysis of ferric carboxymaltose versus other intravenous iron preparations for the management of iron deficiency anemia during pregnancy.

Objective: We conducted a meta-analysis of randomized clinical trials evaluating the clinical effects of ferric carboxymaltose therapy compared to other intravenous iron in improving hemoglobin and serum ferritin in pregnant women. We also assessed the safety of ferric carboxymaltose vs. other intravenous iron. Data source: EMBASE, PubMed, and Web of Science were searched for trials related to ferric carboxymaltose in pregnant women, published between 2005 and 2021. We also reviewed articles from google scholar. The keywords "ferric carboxymaltose," "FCM," "intravenous," "randomized," "pregnancy," "quality of life," and "neonatal outcomes" were used to search the literature. The search was limited to pregnant women. Selection of studies: Studies related to ferric carboxymaltose in pregnancy were scanned. Observational studies, review articles, and case reports were excluded. Randomized studies in pregnant women involving ferric carboxymaltose and other intravenous iron formulations were shortlisted. Of 256 studies, nine randomized control trials were selected. Data collection: Two reviewers independently extracted data from nine selected trials. Data synthesis: The final effect size for increase in hemoglobin after treatment was significant for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 0.89g/dl [95% confidence interval 0.27,1.51]). The final effect size for the increase in ferritin after treatment was more for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 22.53µg/L [-7.26, 52.33]). No serious adverse events were reported with ferric carboxymaltose or other intravenous iron. Conclusion: Ferric carboxymaltose demonstrated better efficacy than other intravenous iron in increasing hemoglobin and ferritin levels in treating iron deficiency anemia in pregnant women.

The Experience of Anaemia and Ingesting Oral Iron Supplementation in Pregnancy: A Qualitative Study.

INTRODUCTION: The objective of this study was to understand the experience of iron deficiency anaemia requiring oral iron in pregnancy and the factors affecting compliance with oral iron supplementation. Participants' understanding regarding the possible consequences of anaemia in pregnancy was also explored. Feedback on a proposed randomised controlled trial of daily versus alternate day oral iron in pregnancy was sought. MATERIALS & METHODS: Following ethical approval, fourteen semi-structured one-to-one interviews were carried out using an interview tool with open-ended questions. Recruitment was carried out through social media and from an antenatal out-patient setting. Interviews were audio-recorded, transcribed and analysed thematically. RESULTS: Fatigue emerged as a predominant and troubling symptom. Awareness was often highlighted through friends/family and from healthcare professionals, particularly in first pregnancies. Knowledge surrounding the potential short-term and long-term adverse consequences of untreated anaemia however was limited. Gastro-intestinal side-effects, a previous experience of poor tolerance and forgetfulness all negatively impacted compliance with oral iron supplementation in pregnancy. Routine, a perceived improvement in fatigue with supplementation and reduced dose frequency recurred as themes which positively affected compliance. Pregnancy as a motivating factor recurred as a theme in analysis. The role of diet was felt to be important. Knowledge of iron-rich foods and absorption aids and inhibitors was good, but practice on optimal ingestion of oral iron supplementation varied. Feedback on trial acceptability was positive with the benefit of extra supportive care noted. Incorporating study visits with routine care was advised in view of time constraints. This area of research was perceived as important. CONCLUSION: In order to successfully reduce the rates of iron deficiency anaemia in pregnancy, it is crucial that all factors affecting compliance with oral iron are considered. Providing women with the important information on the possible consequences of sub optimally treated anaemia may help to improve this public health issue.

Current obstetric outcomes in Jamaican women with sickle hemoglobinopathy - a balance of risks for aspirin?

OBJECTIVES: Sickle cell disease (SCD) occurs in 2.8 % of our Jamaican antenatal population with homozygous HbSS being most associated with adverse maternal and perinatal outcomes. METHODS: A retrospective comparative analysis of HbSS, HbSC and HbSßThal pregnancy outcomes at the University Hospital of the West Indies (UHWI) between January 2012 and December 2022 was conducted. RESULTS: Of 120 patients (138 pregnancies), obesity occurred in 36 % (20/56) of the 'non-HbSS' group, i.e. HbSßThal (55 %, 5/9) and HbSC (32 %, 15/47) combined vs. 9.7 % of the HbSS (8/82). HbSS patients had more crises requiring transfusions, acute chest syndrome (ACS), maternal 'near-misses' (OR=10.7, 95 % 3.5-32.3; p<0.001), hospitalizations (OR 7.6, 95 % CI 3.4-16.9; p<0.001), low birth weight (LBW) neonates (OR 3.1, 1.1-8.9; p=0.037) and preterm birth (OR=2.6, 1.2-5.8; p=0.018) compared to HbSC and HbSßThal. Low dose aspirin was prescribed in 43 %. Logistic regression showed those NOT on aspirin (n=76) had more miscarriages (22 v. 2 %), were LESS likely to have a live birth (75 v. 95 % (0.2, 0.04-0.57, p=0.005)), but surprisingly had fewer painful crises (28 v. 46 % (0.5, 0.03-0.9, p=0.03)). CONCLUSIONS: HbSS women had a 10-fold excess of maternal near-misses. Additional research may further clarify the effects of aspirin on pregnancy outcomes as related to SCD genotypes.

Clinical outcome post treatment of anemia in pregnancy with intravenous versus oral iron therapy: a systematic review and meta-analysis.

Oral iron therapy is often the most common way of treating anaemia; however intravenous iron is considered effective due to rapid iron replenishment. We have dearth of evidence on clinical outcomes post treatment of anaemia. We have searched studies published in English in PubMed, Cochrane, Scopus, ProQuest, and Google Scholar. Our study analysed the clinical outcomes amongst neonates and mother and the adverse events post treatment and assessed the mean change in maternal haemoglobin concentration in both the groups. Forest plots for the clinical outcomes are presented. From a total of 370 studies, 34 Randomized and quasi experimental studies comparing clinical outcomes post-treatment of anaemia in pregnancy were included for quantitative evidence synthesis. Pooled results of maternal clinical outcomes using random effect model [OR: 0.79 (95% CI 0.66; 0.95); 10 outcomes; 17 studies] showed statistically significant difference among both the groups [Moderate quality evidence]; however no significant difference [OR: 0.99 (95% CI 0.86; 1.14); 7 outcomes; 8 studies] have been observed for neonatal complications [Low quality evidence]. The study found that pregnant women receiving IV iron were significantly less likely to experience adverse events as compared with those receiving oral iron [OR 0.39;  (95% CI 0.26-0.60)]; 34 studies; 13,909 women; [Low quality evidence]. Findings from meta-regression analysis showed that IV iron is more likely to reduce maternal complications by 21% compared to oral iron. Increase in odds of adverse maternal outcomes was observed due to increase in gestational age and publication year but no effect for the type of drug used. IV iron increases Hb more and at a higher pace than oral iron. Intravenous iron is more likely to avert adverse maternal outcomes and adverse reactions. However, there is no conclusive evidence on its effectiveness on individual maternal outcome or neonatal outcome/s. Protocol registered with PROSPERO CRD42022368346).

Successful management of refractory immune-mediated thrombotic thrombocytopenic purpura during pregnancy and delivery using the anti-VWF nanobody caplacizumab.

Pregnancy is a potential trigger of acute thrombotic thrombocytopenic purpura (TTP). The management of pregnancy-associated immune-mediated TTP (iTTP) can be challenging, especially when it is refractory to standard treatment. Caplacizumab, a nanobody to von Willebrand factor (VWF) blocking its A1 domain, is a valuable new therapeutic option. Its use is, however, not approved during pregnancy and breastfeeding. We describe the successful off-label administration of caplacizumab during pregnancy and delivery in a patient with refractory iTTP. The favourable outcome without significant thrombotic or haemorrhagic complications indicates that caplacizumab may be an effective and safe treatment option in refractory iTTP during pregnancy.

Assessment-based management of placenta-mediated pregnancy complications: Pragmatism until a precision medicine approach evolves.

The management of pregnant women with thrombophilia and a history of gestational vascular complications remains debatable. Treatment of the latter is often based on clinical outcome rather than disease mechanism. While the use of venous thromboembolism prophylaxis in pregnancy is recommended for those at increased risk, the ability of anticoagulant and/or antiplatelet agents to lower the risk of placenta-mediated complications in this clinical setting remains controversial. The available guidelines are inconsistent in some situations, which reflects the limited evidence base. This review critically discusses risk assessment models (RAMs) and management strategies of women with thrombophilia and pregnancy complications, using clinical vignettes. RAMs, taking into account obstetric and thrombotic history as well as thrombophilia status, could drive a precision medicine approach, based on disease mechanism, and guide individual therapeutic interventions in high-risk clinical settings.

Association of lupus anticoagulants with risk factors for obstetric complications and adverse gestational outcome.

BACKGROUND: Lupus anticoagulant (LA) may be a cause of poor obstetric outcome. OBJECTIVE: To search the association of LA with risk factors for obstetric complications and adverse gestational outcome. METHODS: This retrospective cohort was consisted of 2 groups of pregnancies with poor obstetric history; 1) LA (+) gestations (Study Group, n= 20) and 2) LA (-) gestations (Control Group, 78). All patients were admitted to a special antenatal care program and were examined in terms of risk factors for thrombotic events, placenta-related obstetric complications, and poor gestational outcomes. Patients were administered low-dose low-molecular-weight heparin (LMWH), low-dose salicylic acid and low-dose corticosteroid (if necessary) within the framework of a prophylaxis protocol in addition to their already existing medications. RESULTS: We have shown that adverse gestational outcome was 1.7-fold more frequent in LA (+) pregnancies with poor obstetric history (p= 0.039, 70% vs. 41%). Higher rates of autoimmune diseases and hereditary thrombophilia were observed among LA (+) patients compared to LA (-) gestations (35% vs. 10.3%, p< 0.012 and 55% vs. 19.2%, p< 0.003, respectively). To identify the effectiveness of low-dose LMWH prophylaxis protocol, we compared gestational outcomes and demonstrated that the miscarriage rate was significantly decreased to half in current pregnancies compared to the previous gestations (73.6% vs. 35%, p= 0.003). CONCLUSIONS: Autoimmune diseases and hereditary thrombophilia are more frequent in LA (+) pregnancies, and these women are prone to obstetric problems. Low-dose LMWH and salicylic acid prophylaxis are critical in the management of LA (+) pregnant women.

Thrombocytopenia in pregnancy.

Hematologists are often consulted for thrombocytopenia in pregnancy, especially when there is a concern for a non-pregnancy-specific etiology or an insufficient platelet count for the hemostatic challenges of delivery. The severity of thrombocytopenia and trimester of onset can help guide the differential diagnosis. Hematologists need to be aware of the typical signs of preeclampsia with severe features and other hypertensive disorders of pregnancy to help distinguish these conditions, which typically resolve with delivery, from other thrombotic microangiopathies (TMAs) (eg, thrombotic thrombocytopenic purpura or complement-mediated TMA). Patients with chronic thrombocytopenic conditions, such as immune thrombocytopenia, should receive counseling on the safety and efficacy of various medications during pregnancy. The management of pregnant patients with chronic immune thrombocytopenia who are refractory to first-line treatments is an area that warrants further research. This review uses a case-based approach to discuss recent updates in diagnosing and managing thrombocytopenia in pregnancy.

The incidence, complications, and treatment of iron deficiency in pregnancy.

Iron deficiency and/or iron deficiency anemia (IDA) complicate nearly 50% of pregnancies globally, negatively impacting both maternal and fetal outcomes. Iron deficiency can cause a range of symptoms that range from aggravating to debilitating including fatigue, poor quality of life, pagophagia, and restless leg syndrome. Iron deficiency and IDA are also associated with maternal complications including preterm labor, increased rates of cesarean delivery, postpartum hemorrhage, and maternal death. Fetal complications include increased rates of low birth weight and small for gestational age newborns. Prenatal maternal anemia has also been associated with autism spectrum disorders in the neonate, although causation is not established. Deficiency in the newborn is associated with compromised memory, processing, and bonding, with some of these deficits persisting into adulthood. Despite the prevalence and consequences associated with iron deficiency in pregnancy, data show that it is routinely undertreated. Due to the physiologic changes of pregnancy, all pregnant individuals should receive oral iron supplementation. However, the bioavailability of oral iron is poor and it is often ineffective at preventing and treating iron deficiency. Likewise, it frequently causes gastrointestinal symptoms that can worsen the quality of life in pregnancy. Intravenous iron formulations administered in a single or multiple dose series are now available. There is increasing data suggesting that newer intravenous formulations are safe and effective in the second and third trimesters and should be strongly considered in pregnant individuals without optimal response to oral iron repletion.

Screening, Treatment, and Monitoring of Iron Deficiency Anemia in Pregnancy and Postpartum.

Iron deficiency anemia is the most prevalent form of anemia worldwide. In the United States, clinicians routinely screen for iron deficiency anemia upon initiation of prenatal care, at the start of the third trimester, and prior to birth. Treatment of iron deficiency anemia generally begins with oral supplementation of elemental iron, which is associated with adverse gastrointestinal effects. These adverse effects can decrease adherence, leading to subtherapeutic treatment. Newer evidence highlights the benefits of early screening for iron deficiency before the onset of anemia, as well as the use of intravenous iron to expedite the treatment of iron deficiency anemia. More research is needed on the potential consequences of over-supplementation and iron deficiency without anemia to guide treatment. This article reviews the evidence for best practices for screening, treatment, and continued monitoring of iron deficiency anemia during pregnancy and postpartum. Maternal, fetal, and neonatal implications are reviewed, as well as the risks and benefits of treatment options. Finally, an evidence-based algorithm is proposed to guide clinicians on continued monitoring after treatment.

Effectiveness of Health Information Package Program on Knowledge and Compliance among Pregnant Women with Anemia: A Randomized Controlled Trial.

Despite the availability of iron supplements during pregnancy for all pregnant women receiving antenatal care in Saudi Arabia, anemia remains to be a global public health concern leading to adverse maternal, fetal, and neonatal effects. We aimed to evaluate the effectiveness of the Health Information Package Program on the knowledge anemic pregnant women had about anemia, their compliance with iron and folic acid supplementation, and their hemoglobin levels. A single-blind randomized controlled trial was carried out in accordance with the Consolidated Standards of Reporting Trials (CONSORT) guidelines between January and May 2021. Pregnant women (n = 196) aged 18-45 years old and diagnosed with anemia during the first trimester of their pregnancy were randomly assigned into two groups: the intervention group (Health Information Package Program plus routine care, n = 98) and the control group (routine care only, n = 98). Knowledge, the ability to select appropriate food, and hemoglobin levels were assessed at baseline and after three months, while compliance with iron and folic acid supplementation was also measured at the end of three months. This study indicated that the post-education mean knowledge score, food selection ability score, compliance rate, and hemoglobin level were significantly higher for the intervention group than for the control group. The Health Information Package Program with regular follow-ups using the WhatsApp platform was an effective educational intervention for anemic pregnant women.

Desiderosmia: a manifestation of iron deficiency in pregnancy.

A pregnant woman in her 20s presented with an excessive desire to smell a specific household cleaning product. She was found to have severe iron deficiency anaemia and her symptoms resolved following intravenous iron supplementation. She described symptoms of fatigue, shortness of breath and olfactory cravings. The specific scent could not be replicated with other smells and the woman had to significantly modify her lifestyle to accommodate the excessive desire. She had a similar experience during her prior pregnancy which resolved after the correction of severe iron deficiency anaemia. This unique symptom has been described as desiderosmia: iron deficiency manifesting as olfactory cravings. This underappreciated but useful symptom is defined as a separate entity to pica, as there is an absence of desire to ingest the product. Desiderosmia can harm mother and baby through inhalation of potentially harmful fumes; hence, women who describe this symptom should be assessed for iron deficiency anaemia.

Applying reflective multicriteria decision analysis to understand the value of therapeutic alternatives in the management of gestational and peripartum anaemia in Spain.

BACKGROUND: The objective of the FeminFER project was to assess the value of ferric carboxymaltose following a multicriteria decision analysis in obstetrics and gynaecology in Spain. METHODS: Ferric carboxymaltose (FCM) and ferrous sulphate were evaluated using the EVIDEM framework. Ten stakeholders participated to collect different perspectives. The framework was adapted considering evidence retrieved with a PICO-S search strategy and grey literature. Criteria/subcriteria were weighted by level of relevance and an evidence-based decision-making exercise was developed in each criterion; weights and scores were combined to obtain the value of intervention relative to each criterion/subcriterion, that were further combined into the Modulated Relative Benefit-Risk Balance (MRBRB). RESULTS: The most important criterion favouring FCM was Compared Efficacy/Effectiveness (0.183 ± 0.07), followed by Patient Preferences (0.059 ± 0.10). Only Direct medical costs criterion favoured FS (-0.003 ± 0.03). MRBRB favoured FCM; 0.45 ± 0.19; in a scale from -1 to + 1. CONCLUSIONS: In conclusion, considering the several criteria involved in the decision-making process, participants agreed with the use of FCM according to its MRBRB.

Is every other day iron supplementation effective for the treatment of the iron deficiency anemia in pregnancy?

AIM: To understand if every other day iron supplementation may be as effective as daily iron intake in anemic pregnant women. METHODS: This case-control study was conducted at a tertiary hospital in Turkey. The study randomly categorized women into two groups as daily intake (n = 124) vs every other day intake (n = 140) of 100 mg daily oral ferrous fumarate. The numbers of women recruited from the study were 13 and 34 in two groups. Thus, for analysis, there were 111 women in the daily group and 106 women in the other group. The current study obtained hemoglobin (Hb) and ferritin levels two times to evaluate the effects of treatment, noting initial levels before drug administration, and a second blood sample was obtained after two months. Two groups were compared according to the increase in Hb and ferritin levels. The study asked the women whether they experienced gastrointestinal side effects. RESULTS: The ferritin levels increased 4.9 ± 4.2 ng/mL in the daily intake group and 3.9 ± 2.9 ng/mL in every other day group (p = .215). The Hb increased 1.4 ± 0.7 g/dL in the daily intake group and 1.6 ± 0.6 g/dL in the other group (p = .021). Gastrointestinal side effects appeared in 47 (17.8%) out of 264 women. The rate of gastrointestinal side effect was lower in every other day group (41.4% vs 15.1%, p = .0057). CONCLUSION: Every other day iron supplementation is as effective as daily intake for treating iron deficiency anemia with lesser gastrointestinal side effects during pregnancy.