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).

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.

Reproductive Failure and Thrombophilia: Not Enough Evidence for a Tight Bond.

OBJECTIVES: The role of hereditary thrombophilia in reproductive failure (RF) is strongly debatable. In this retrospective single-center study, we analyzed pregnancy outcome in 175 women screened for thrombophilia after at least one event of RF. RESULTS: The prevalence of thrombophilia in our cohort was 33.4%. Pregnancy survival curves were not different according to severity (log-rank, p = 0.302) or type of thrombophilia (log-rank, p = 0.532). In total, 81.7% of 175 subsequent pregnancies were proceeded with LMWH. Concomitant use of ASA was prescribed in 75 pregnancies according to physician choice. The primary endpoint was live birth rate (LBR) that succeeded in 152/175 next pregnancies (86.8%) and late obstetric complications (LOBC) which occurred in 17/175 next pregnancies (9.8%). In logistic regression analysis, neither the severity nor the type of thrombophilia was important for any pregnancy outcome (LBR or LOBC). Considering therapeutic interventions, the use of LMWH ± ASA was not related to LBR or LOBC. The only factor inversely related to LBR was age above the cutoff value of 35.5 years (p = 0.049). CONCLUSIONS: Incidence of thrombophilia is increased among women with RF, but the severity or type of thrombophilia is not related to pregnancy outcome.

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.

Rebound of platelet count in a patient with type 2 calreticulin-mutant essential thrombocythemia in the postpartum period: A case report.

INTRODUCTION: Essential thrombocythemia (ET) is an uncommon myeloproliferative neoplasm. It is more common in females; 20% of them are below 40 years old. The optimal management of ET during pregnancy and postpartum periods is still not well established. PATIENT CONCERN: We report a case of a young lady with type 2 calreticulin-mutant ET who developed a marked rebound in her platelet count (reaching 2030 × 103/µL) 2 weeks after premature delivery of her baby (24th week of gestation). She was on Pegylated Interferon alfa 2-a during pregnancy (her platelet was around 500 × 103/µL during the second trimester), but she had stopped it on her own from the 20th week of gestation. DIAGNOSIS: Postpartum rebound of platelet count due to medication non-compliance. INTERVENTION AND OUTCOME: We resumed her regular Pegylated Interferon, and subsequently, her platelet count reduced dramatically within 4 weeks to an acceptable level (684 × 103 /µL). CONCLUSION: The guideline is still not well-established regarding the optimal approach for postpartum rebound of platelet count in patients with ET. It is still unclear if the platelet count will fall spontaneously without intervention after the rebound phase. Further research is required to establish the optimal management of ET during the postpartum phase. This case emphasizes the importance of platelet count follow-up during the postpartum period and outlines our management approach in such cases.

Oral Iron Supplementation in Pregnancy: Current Recommendations and Evidence-Based Medicine.

OBJECTIVE: To review the evidence about universal iron supplementation in pregnancy to prevent maternal anemia. METHODS: Bibliographic research of randomized and controlled clinical trials, meta-analyses, systematic reviews, and clinical guidelines, published between August 2009 and August 2019, using the MeSH terms: iron; therapeutic use; pregnancy; anemia, prevention and control. RESULTS: We included six clinical guidelines, three meta-analyses and one randomized controlled clinical trial. DISCUSSION: Most articles point to the improvement of hematological parameters and reduction of maternal anemia risk, with supplementary iron. However, they do not correlate this improvement in pregnant women without previous anemia with the eventual improvement of clinical parameters. CONCLUSION: Universal iron supplementation in pregnancy is controversial, so we attribute a SORT C recommendation strength.

OBJETIVO: Rever a evidência sobre a necessidade de suplementação universal de ferro na gravidez para prevenção de anemia materna. MéTODOS: Pesquisa bibliográfica de ensaios clínicos aleatorizados e controlados, metanálises, revisões sistemáticas e normas de orientação clínica, publicados entre agosto de 2009 e agosto de 2019, utilizando os termos MeSH: iron, terapêuticas use; pregnancy; anemia, preventivos and control. RESULTADOS: Incluímos seis normas de orientação clínica, três metanálises e um ensaio clínico randomizado e controlado. DISCUSSãO: A maioria dos artigos aponta para a melhoria dos parâmetros hematológicos e redução do risco de anemia materna por meio da suplementação com ferro. Todavia, eles não correlacionam a melhoria destes parâmetros em grávidas sem anemia prévia com a eventual melhoria de parâmetros clínicos. CONCLUSõES: A suplementação universal com ferro na gravidez é controversa, pelo que atribuímos uma força de recomendação SORT C.

Iron Deficiency Anemia in Pregnancy.

Anemia is defined as a low red blood cell count, a low hematocrit, or a low hemoglobin concentration. In pregnancy, a hemoglobin concentration of less than 11.0 g/dL in the first trimester and less than 10.5 or 11.0 g/dL in the second or third trimester (depending on the guideline used) is considered anemia. Anemia is the most common hematologic abnormality in pregnancy. Maternal anemia is associated with adverse fetal, neonatal and childhood outcomes, but causality is not established. Maternal anemia increases the likelihood of transfusion at delivery. Besides hemodilution, iron deficiency is the most common cause of anemia in pregnancy. The American College of Obstetricians and Gynecologists recommends screening for anemia with a complete blood count in the first trimester and again at 24 0/7 to 28 6/7 weeks of gestation. Mild anemia, with a hemoglobin of 10.0 g/dL or higher and a mildly low or normal mean corpuscular volume (MCV) is likely iron deficiency anemia. A trial of oral iron can be both diagnostic and therapeutic. Mild anemia with a very low MCV, macrocytic anemia, moderate anemia (hemoglobin 7.0-9.9 g/dL) or severe anemia (hemoglobin 4.0-6.9 g/dL) requires further investigation. Once a diagnosis of iron deficiency anemia is confirmed, first-line treatment is oral iron. New evidence suggests that intermittent dosing is as effective as daily or twice-daily dosing with fewer side effects. For patients with iron deficiency anemia who cannot tolerate, cannot absorb, or do not respond to oral iron, intravenous iron is preferred. With contemporary formulations, allergic reactions are rare.

Oral Iron Supplementation in Pregnancy: Current Recommendations and Evidence-Based Medicine Suplementação oral de ferro na gravidez: recomendações atuais e medicina baseada na evidência

Abstract Objective To review the evidence about universal iron supplementation in pregnancy to prevent maternal anemia. Methods Bibliographic research of randomized and controlled clinical trials, meta-analyses, systematic reviews, and clinical guidelines, published between August 2009 and August 2019, using the MeSH terms: iron; therapeutic use; pregnancy; anemia, prevention and control. Results We included six clinical guidelines, three meta-analyses and one randomized controlled clinical trial. Discussion Most articles point to the improvement of hematological parameters and reduction of maternal anemia risk, with supplementary iron. However, they do not correlate this improvement in pregnant women without previous anemia with the eventual improvement of clinical parameters. Conclusion Universal iron supplementation in pregnancy is controversial, so we attribute a SORT C recommendation strength.

Resumo Objetivo Rever a evidência sobre a necessidade de suplementação universal de ferro na gravidez para prevenção de anemia materna. Métodos Pesquisa bibliográfica de ensaios clínicos aleatorizados e controlados, metanálises, revisões sistemáticas e normas de orientação clínica, publicados entre agosto de 2009 e agosto de 2019, utilizando os termos MeSH: iron, terapêuticas use; pregnancy; anemia, preventivos and control. Resultados Incluímos seis normas de orientação clínica, três metanálises e um ensaio clínico randomizado e controlado. Discussão A maioria dos artigos aponta para a melhoria dos parâmetros hematológicos e redução do risco de anemia materna por meio da suplementação com ferro. Conclusões A suplementação universal com ferro na gravidez é controversa, pelo que atribuímos uma força de recomendação SORT C.

Eltrombopag treatment for severe immune thrombocytopenia during pregnancy: a case report.

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia (platelet count <100 × 109/l) in the absence of other causes or disorders associated. The incidence of ITP in pregnancy is one to two cases per 1000 gestations. ITP could be diagnosed before or during pregnancy; sometimes a relapse of a previously diagnosed ITP can occur. Intravenous immune globulins (IVIg) and corticosteroids are the standard frontline therapy because of their well known safety profile either for the mother or for the neonate. Treatments for refractory patients are limited by potential fetal risk. We report the case of a patient with ITP along pregnancy, refractory to corticosteroids and IVIg, successfully treated with, the thrombopoietin receptor agonist (TPO-RA) eltrombopag. Patient received this compound for almost the whole pregnancy and in particular for the whole first trimester, without any complication for the mother and the neonate. Although transient administration of TPO-RAs in pregnancy seems to be well tolerated, their use during the whole gestation is still controversial; this is the reason of the description of this case, which did not show any complications, and thus it could add useful information on this field.

A randomized controlled trial comparing the efficacy, tolerability, and cost of oral iron preparations in iron-deficiency anemia in pregnancy.

OBJECTIVE: To evaluate the efficacy, tolerability, and cost of four commonly prescribed oral iron preparations: ferrous sulfate (FS), ferrous fumarate (FF), ferrous ascorbate (FA), and carbonyl iron (CI) in the treatment of iron-deficiency anemia (IDA) in pregnant women. METHODS: It was a prospective, randomized, open-label, blinded endpoint (PROBE) design with four parallel active control groups: FS, FF, FA, CI. The primary outcome was the proportion of participants becoming non-anemic (Hb ≥ 11 g%) at the end of the study period. The secondary outcomes were the proportion of participants achieving normal red blood corpuscular indices such as mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration; the proportion of participants achieving normal iron indices such as serum iron, serum ferritin, total iron-binding capacity, and transferrin saturation; and comparison of incidence of any adverse events between treatment groups and comparison of costs of individual drug therapy between treatment groups. RESULTS: One hundred and twenty patients were randomized to four different groups (n = 30). The results of the present study show that all the four iron salts at the dose of 200 mg elemental iron per day were equally effective in improving hemoglobin concentration and other hematological parameters. The adverse effects were more common in the FF group (56.7%). The pharmacoeconomic analysis showed that all the drugs are equally cost-effective. CONCLUSION: To conclude from the results of the present study, it can be said that FS, FF, FA, and CI are equally effective in treating IDA and they can be prescribed interchangeably.