Patient Blood Management in Pregnancy.

Background: Patient blood management (PBM) is a multidisciplinary and patient-centered treatment approach, comprising the detection and treatment of anemia, the minimization of blood loss, and the rational use of allogeneic transfusions. Pregnancy, delivery, and the puerperium are associated with increased rates of iron deficiency and anemia, which correlates with worse maternal and fetal outcomes and places pregnant women at increased risk of obstetric hemorrhage. Summary: Early screening for iron deficiency before the onset of anemia, as well as the use of oral and intravenous iron to treat iron deficiency anemia, has been shown to be beneficial. Anemia in pregnancy and the puerperium should be treated according to a staged regimen, administering either iron alone or in combination with an off-label use of human recombinant erythropoietin in selected patients. This regimen should be tailored to the needs of each individual patient. Postpartum hemorrhage (PPH) accounts for up to one-third of maternal deaths in both developing and developed countries. Bleeding complications should be anticipated and blood loss reduced by interdisciplinary preventive measures and individually tailored care. It is recommended that facilities have a PPH algorithm, primarily focusing on prevention through use of uterotonics, but also incorporating early diagnosis of the cause of bleeding, optimization of hemostatic conditions, timely administration of tranexamic acid, and integration of point-of-care tests to support the guided substitution of coagulation factors, alongside standard laboratory tests. Additionally, cell salvage has proven beneficial and should be considered for various indications in obstetrics including hematologic disturbances, as well as various forms of placental disorders. Key Message: This article reviews PBM in pregnancy, delivery, and the puerperium. The concept comprises early screening and treatment of anemia and iron deficiency, a transfusion and coagulation algorithm during delivery, as well as cell salvage.

Endogenous oestradiol and progesterone as predictors of oncogenic human papillomavirus (HPV) persistence.

BACKGROUND: High-risk human papillomavirus (HR-HPV) is the main aetiological factor for the development of cervical cancer. While nearly 70% of HR-HPV infections are cleared within 12 months, in the remainder of women they persist and can progress into cervical cancer. Oestradiol and progesterone have been shown to be involved in the development and progression of cervical cancer. The objective of this study was to investigate, for the first time, whether diurnal oestradiol and progesterone are also involved in HR-HPV persistence - before cervical cancer develops. METHODS: A total of N = 39 women between 18 and 31 years of age were investigated. All were nulliparous and regular users of combined oral contraceptives. Presence of HR-HPV was determined by cervical swabs. Salivary oestradiol and progesterone were measured upon awakening and at 11 am, 2 pm, and 5 pm. All HR-HPV positive women were re-tested in terms of HR-HPV status 12 months later. RESULTS: HR-HPV positive women had significantly higher morning (p = .007, partial eta2 = .221) and daily oestradiol levels (p < .001, partial eta2 = .442) when compared to HR-HPV negative women. In addition, those with persistent HR-HPV 12 months later had significantly elevated morning (p = .005, partial eta2 = .534) and daily (p = .027, partial eta2 = .346) oestradiol. Progesterone was found to be unrelated to HR-HPV. CONCLUSIONS: Oestradiol was positively linked to HR-HPV presence and persistence. Provided that these findings are replicated, regular monitoring of oestradiol levels may prove useful in identifying women who are at risk of developing cervical cancer.

Is stress related to the presence and persistence of oncogenic human papillomavirus infection in young women?

BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) is the most important risk factor for the development of cervical cancer, but factors contributing to HR-HPV persistence are incompletely understood. The objective of this study was to test for associations of chronic stress and two aspects of diurnal cortisol secretion (i.e., the cortisol awakening response [CAR] and total cortisol output over the day [AUCgday]) with HR-HPV status at baseline and 12 months later (follow-up). METHODS: We evaluated 188 women (25 ± 3 years) at baseline. Follow-up investigation was restricted to HR-HPV infected women at baseline. Of the initial 48 HR-HPV positive participants, 42 completed the follow-up (16 HR-HPV positive and 26 HR-HPV negative). At baseline and follow-up, we determined HR-HPV status in cervical smears, assessed chronic stress, and repeatedly measured salivary cortisol over the day. At baseline, we analyzed salivary cortisol only in a subgroup of 90 participants (45 HR-HPV negative and 45 HR-HPV positive). RESULTS: At baseline, higher chronic stress (excessive demands at work: p = .022, chronic worrying: p = .032), and a higher CAR (p = .014) were related to baseline HR-HPV positivity. At follow-up, there was a statistical trend for a positive association between the CAR and HR-HPV positivity (p = .062). Neither the CAR nor the AUCgday mediated the associations between chronic stress and HR-HPV status. CONCLUSIONS: Our findings suggest that both chronic stress and diurnal cortisol are related to the presence of HR-HPV infection and may thus play a role in HPV-associated cervical carcinogenesis.

Patient blood management (PBM) in pregnancy and childbirth: literature review and expert opinion.

PURPOSE: Patient blood management [PBM] has been acknowledged and successfully introduced in a wide range of medical specialities, where blood transfusions are an important issue, including anaesthesiology, orthopaedic surgery, cardiac surgery, or traumatology. Although pregnancy and obstetrics have been recognized as a major field of potential haemorrhage and necessity of blood transfusions, there is still little awareness among obstetricians regarding the importance of PBM in this area. This review, therefore, summarizes the importance of PBM in obstetrics and the current evidence on this topic. METHOD: We review the current literature and summarize the current evidence of PBM in pregnant women and postpartum with a focus on postpartum haemorrhage (PPH) using PubMed as literature source. The literature was reviewed and analysed and conclusions were made by the Swiss PBM in obstetrics working group of experts in a consensus meeting. RESULTS: PBM comprises a series of measures to maintain an adequate haemoglobin level, improve haemostasis and reduce bleeding, aiming to improve patient outcomes. Despite the fact that the WHO has recommended PBM early 2010, the majority of hospitals are in need of guidelines to apply PBM in daily practice. PBM demonstrated a reduction in morbidity, mortality, and costs for patients undergoing surgery or medical interventions with a high bleeding potential. All pregnant women have a significant risk for PPH. Risk factors do exist; however, 60% of women who experience PPH do not have a pre-existing risk factor. Patient blood management in obstetrics must, therefore, not only be focused on women with identified risk factor for PPH, but on all pregnant women. Due to the risk of PPH, which is inherent to every pregnancy, PBM is of particular importance in obstetrics. Although so far, there is no clear guideline how to implement PBM in obstetrics, there are some simple, effective measures to reduce anaemia and the necessity of transfusions in women giving birth and thereby improving clinical outcome and avoiding complications. CONCLUSION: PBM in obstetrics is based on three main pillars: diagnostic and/or therapeutic interventions during pregnancy, during delivery and in the postpartum phase. These three main pillars should be kept in mind by all professionals taking care of pregnant women, including obstetricians, general practitioners, midwifes, and anaesthesiologists, to improve pregnancy outcome and optimize resources.

Safety and efficacy of intravenous iron administration for uterine bleeding or postpartum anaemia: a narrative review.

The management of iron deficiency anaemia (IDA) consists of oral or intravenous administration of iron supplements. The aim of this narrative review is to summarise information regarding the treatment of IDA in women who have postpartum anaemia or uterine bleeding with intravenous (IV) or oral iron supplements. Fourteen randomised control studies comparing IV to oral iron treatment for IDA in 2913 women with uterine bleeding or postpartum haemorrhage are included. All reviewed studies suggest that IV iron administration is important in treating the IDA in such women and in improving their physical performance and quality of life. Comparisons among intravenous iron supplements show advantages of ferric carboxymaltose over others in time of reaching desired haemoglobin and ferritin values and in adverse reactions. Despite the limitation that the above evidence emerges from not systematically collected data, our review highlights that new forms of IV iron supplements seem safe and efficient in treating IDA.

Ferric carboxymaltose vs. oral iron in the treatment of pregnant women with iron deficiency anemia: an international, open-label, randomized controlled trial (FER-ASAP).

OBJECTIVE: To compare the efficacy and safety of intravenous ferric carboxymaltose (FCM) with first-line oral ferrous sulfate (FS) in pregnant women with iron deficiency anemia (IDA). MATERIALS AND METHODS: Pregnant women (n=252; gestational weeks 16-33) with IDA were randomized 1:1 to FCM (1000-1500 mg iron) or FS (200 mg iron/day) for 12 weeks. The primary objective was to compare efficacy; secondary objectives included safety and quality of life. RESULTS: Hemoglobin (Hb) levels improved at comparable rates across both treatments; however, significantly more women achieved anemia correction with FCM vs. FS [Hb ≥11.0 g/dL; 84% vs. 70%; odds ratio (OR): 2.06, 95% confidence interval (CI): 1.07, 3.97; P=0.031] and within a shorter time frame (median 3.4 vs. 4.3 weeks). FCM treatment significantly improved vitality (P=0.025) and social functioning (P=0.049) prior to delivery. Treatment-related adverse events were experienced by 14 (FCM; 11%) and 19 (FS; 15%) women, with markedly higher rates of gastrointestinal disorders reported with FS (16 women) than with FCM (3 women). Newborn characteristics were similar across treatments. CONCLUSIONS: During late-stage pregnancy, FCM may be a more appropriate option than first-line oral iron for rapid and effective anemia correction, with additional benefits for vitality and social functioning.

RhEPO improves time to exhaustion by non-hematopoietic factors in humans.

PURPOSE: Erythropoietin (EPO) controls red cell volume (RCV) and plasma volume (PV). Therefore, injecting recombinant human EPO (rhEPO) increases RCV and most likely reduces PV. RhEPO-induced endurance improvements are explained by an increase in blood oxygen (O2) transport capacity, which increases maximum O2 uptake ([Formula: see text]O2max). However, it is debatable whether increased RCV or [Formula: see text]O2max are the main reasons for the prolongation of the time to exhaustion (t lim) at submaximal intensity. We hypothesized that high rhEPO doses in particular contracts PV such that the improvement in t lim is not as strong as at lower doses while [Formula: see text]O2max increases in a dose-dependent manner. METHODS: We investigated the effects of different doses of rhEPO given during 4 weeks [placebo (P), low (L), medium (M), and high (H) dosage] on RCV, PV, [Formula: see text]O2max and t lim in 40 subjects. RESULTS: While RCV increased in a dose-dependent manner, PV decreased independent of the rhEPO dose. The improvements in t lim (P +21.4 ± 23.8%; L +16.7 ± 29.8%; M +44.8 ± 62.7%; H +69.7 ± 73.4%) depended on the applied doses (R (2) = 0.89) and clearly exceeded the dose-independent [Formula: see text]O2max increases (P -1.7 ± 3.2%; L +2.6 ± 6.8%; M +5.7 ± 5.1 %; H +5.6 ± 4.3 %) after 4 weeks of rhEPO administration. Furthermore, the absolute t lim was not related (R (2) ≈ 0) to RCV or to [Formula: see text]O2max. CONCLUSIONS: We conclude that a contraction in PV does not negatively affect t lim and that rhEPO improves t lim by additional, non-hematopoietic factors.

High-resolution chromosomal microarrays in prenatal diagnosis significantly increase diagnostic power.

OBJECTIVE: The objective of this study was to determine for the first time the reliability and the diagnostic power of high-resolution microarray testing in routine prenatal diagnostics. METHODS: We applied high-resolution chromosomal microarray testing in 464 cytogenetically normal prenatal samples with any indication for invasive testing. RESULTS: High-resolution testing revealed a diagnostic yield of 6.9% and 1.6% in cases of fetal ultrasound anomalies and cases of advanced maternal age (AMA), respectively, which is similar to previous studies using low-resolution microarrays. In three (0.6%) additional cases with an indication of AMA, an aberration in susceptibility risk loci was detected. Moreover, one case (0.2%) showed an X-linked aberration in a female fetus, a finding relevant for future family planning. We found the rate of cases, in which the parents had to be tested for interpretation of unreported copy number variants (3.7%), and the rate of remaining variants of unknown significance (0.4%) acceptably low. Of note, these findings did not cause termination of pregnancy after expert genetic counseling. The 0.4% rate of confined placental mosaicism was similar to that observed by conventional karyotyping and notably involved a case of placental microdeletion. CONCLUSION: High-resolution prenatal microarray testing is a reliable technique that increases diagnostic yield by at least 17.3% when compared with conventional karyotyping, without an increase in the frequency of variants of uncertain significance.

Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration.

This is the first study to investigate the efficacy of intravenous iron in treating fatigue in nonanemic patients with low serum ferritin concentration. In a randomized, double-blinded, placebo-controlled study, 90 premenopausal women presenting with fatigue, serum ferritin ≤ 50 ng/mL, and hemoglobin ≥ 120 g/L were randomized to receive either 800 mg of intravenous iron (III)-hydroxide sucrose or intravenous placebo. Fatigue and serum iron status were assessed at baseline and after 6 and 12 weeks. Median fatigue at baseline was 4.5 (on a 0-10 scale). Fatigue decreased during the initial 6 weeks by 1.1 in the iron group compared with 0.7 in the placebo group (P = .07). Efficacy of iron was bound to depleted iron stores: In patients with baseline serum ferritin ≤ 15 ng/mL, fatigue decreased by 1.8 in the iron group compared with 0.4 in the placebo group (P = .005), and 82% of iron-treated compared with 47% of placebo-treated patients reported improved fatigue (P = .03). Drug-associated adverse events were observed in 21% of iron-treated patients and in 7% of placebo-treated patients (P = .05); none of these events was serious. Intravenous administration of iron improved fatigue in iron-deficient, nonanemic women with a good safety and tolerability profile. The efficacy of intravenous iron was bound to a serum ferritin concentration ≤ 15 ng/mL. This study was registered at the International Standard Randomized Controlled Trial Number Register (www.isrctn.org) as ISRCTN78430425.

Endothelial Progenitor Cell-Based in vitro Pre-Endothelialization of Human Cell-Derived Biomimetic Regenerative Matrices for Next-Generation Transcatheter Heart Valves Applications.

Hemocompatibility of cardiovascular implants represents a major clinical challenge and, to date, optimal antithrombotic properties are lacking. Next-generation tissue-engineered heart valves (TEHVs) made from human-cell-derived tissue-engineered extracellular matrices (hTEMs) demonstrated their recellularization capacity in vivo and may represent promising candidates to avoid antithrombotic therapy. To further enhance their hemocompatibility, we tested hTEMs pre-endothelialization potential using human-blood-derived endothelial-colony-forming cells (ECFCs) and umbilical vein cells (control), cultured under static and dynamic orbital conditions, with either FBS or hPL. ECFCs performance was assessed via scratch assay, thereby recapitulating the surface damages occurring in transcatheter valves during crimping procedures. Our study demonstrated: feasibility to form a confluent and functional endothelium on hTEMs with expression of endothelium-specific markers; ECFCs migration and confluency restoration after crimping tests; hPL-induced formation of neo-microvessel-like structures; feasibility to pre-endothelialize hTEMs-based TEHVs and ECFCs retention on their surface after crimping. Our findings may stimulate new avenues towards next-generation pre-endothelialized implants with enhanced hemocompatibility, being beneficial for selected high-risk patients.

Expert recommendations for the diagnosis and treatment of iron-deficiency anemia during pregnancy and the postpartum period in the Asia-Pacific region.

Anemia during pregnancy and the postpartum period is commonly caused by iron deficiency and is a significant worldwide issue with severe consequences for both mother and developing fetus. From a worldwide perspective, iron-deficiency anemia (IDA) during pregnancy is highest in the Asia-Pacific region; however, there has been little guidance in this region for safe and effective treatment. An expert panel was convened to develop a concise and informative set of recommendations for the treatment of IDA in pregnant and postpartum women in the Asia-Pacific region. This manuscript provides these recommendations and aims to reduce the morbidity and mortality associated with IDA in pregnant and postpartum women in the Asia-Pacific region. The consensus recommendations define anemia as a hemoglobin (Hb) level <10.5 g/dL during pregnancy and <10 g/dL during the postpartum period, and provide cut-off Hb levels to initiate therapy with oral iron, intravenous iron or red blood cell transfusion.

Iron sucrose with and without recombinant erythropoietin for the treatment of severe postpartum anemia: a prospective, randomized, open-label study.

AIM: Postpartum anemia is a common problem in obstetrics. Depending on the severity of anemia, it can cause a wide range of symptoms. Obstetrical management should be focused on avoiding blood transfusion in young and otherwise healthy women. The aim of this study was to examine the effectiveness of recombinant human erythropoietin (rhEPO) combined with iron sucrose compared to iron sucrose alone in patients with severe postpartum anemia. METHODS: A prospective randomized study was conducted in women with severe postpartum anemia (Hb < 8.5 g/dL). The first group received 200 mg iron sucrose intravenously daily on days 1-4. The second group received 200 mg iron sucrose plus 10.000E rhEPO in the same regimen. Twenty women were enrolled in each group. The follow-up period was two weeks. RESULTS: Baseline Hb was 7.1 g/dL and 7.5 g/dL, respectively, depending on the subgroup. Hemoglobin values increased close to normal values within two weeks in both groups treated with iron sucrose alone or in combination with rhEPO (10.5 g/dL, 10.7 g/dL, respectively). CONCLUSION: In general, iron sucrose alone is a sufficient anemia therapy agent. A subgroup of patients (i.e. with a more pronounced inflammatory response after cesarean section) may benefit from additional rhEPO therapy. Despite being severely anemic, none of our patients required transfusion. Iron sucrose as well as rhEPO was very well tolerated. The benefit of the therapy lies in the avoidance of allogenic blood transfusions with their potential side effects. In cases of severe anemia after operative delivery, additional rhEPO therapy can result in a faster Hb increase and, therefore, faster recovery.

Questions and answers on iron deficiency treatment selection and the use of intravenous iron in routine clinical practice.

Iron deficiency is a common cause of morbidity and can arise as a consequence or complication from many diseases. The use of intravenous iron has increased significantly in the last decade, but concerns remain about indications and administration. Modern intravenous iron preparations can facilitate rapid iron repletion in one or two doses, both for absolute iron deficiency and, in the presence of inflammation, functional iron deficiency, where oral iron therapy is ineffective or has not worked. A multidisciplinary team of experts experienced in iron deficiency undertook a consensus review to support healthcare professionals with practical advice on managing iron deficiency in gastrointestinal, renal and cardiac disease, as well as; pregnancy, heavy menstrual bleeding, and surgery. We explain how intravenous iron may work where oral iron has not. We provide context on how and when intravenous iron should be administered, and informed opinion on potential benefits balanced with potential side-effects. We propose how intravenous iron side-effects can be anticipated in terms of what they may be and when they may occur. The aim of this consensus is to provide a practical basis for educating and preparing staff and patients on when and how iron infusions can be administered safely and efficiently. Key messages Iron deficiency treatment selection is driven by several factors, including the presence of inflammation, the time available for iron replenishment, and the anticipated risk of side-effects or intolerance. Intravenous iron preparations are indicated for the treatment of iron deficiency when oral preparations are ineffective or cannot be used, and therefore have applicability in a wide range of clinical contexts, including chronic inflammatory conditions, perioperative settings, and disorders associated with chronic blood loss. Adverse events occurring with intravenous iron can be anticipated according to when they typically occur, which provides a basis for educating and preparing staff and patients on how iron infusions can be administered safely and efficiently.

Diagnosis and treatment of iron-deficiency anaemia during pregnancy and postpartum.

INTRODUCTION: Iron-deficiency anaemia during pregnancy and postpartum occurs frequently and may lead to severe maternal and foetal complications. New treatment regimens include intravenous iron administration in particular clinical situations. The aim of the study was to determine optimal diagnostic and therapeutic approaches to iron-deficiency anaemia during pregnancy and postpartum. METHODS: The evidence from data available from published studies and recommendations regarding diagnosis and treatment were reviewed. As conclusions, recommendations are given by an expert panel. RESULTS: During pregnancy, oral iron therapy is given as first-line treatment. In cases with lack of efficacy, unwarranted side effects or very low haemoglobin values, intravenous iron treatment with iron carboxymaltose is a preferable alternative, although data regarding safety are limited. In the postpartum period, haemoglobin values less than 95 g/L are treated ideally by intravenous carboxymaltose, leading to more rapid haemoglobin recovery. CONCLUSION: New intravenous iron preparations such as iron carboxymaltose have an excellent efficacy, side effect profile and advantages as compared to oral iron preparations for particular clinical indications.

Iron Sucrose: A Wealth of Experience in Treating Iron Deficiency.

Iron deficiency and iron-deficiency anemia are associated with increased morbidity and mortality in a wide range of conditions. In many patient populations, this can be treated effectively with oral iron supplementation; but in patients who are unable to take or who do not respond to oral iron therapy, intravenous iron administration is recommended. Furthermore, in certain conditions, such as end-stage kidney disease, chronic heart failure, and inflammatory bowel disease, intravenous iron administration has become first-line treatment. One of the first available intravenous iron preparations is iron sucrose (Venofer®), a nanomedicine that has been used clinically since 1949. Treatment with iron sucrose is particularly beneficial owing to its ability to rapidly increase hemoglobin, ferritin, and transferrin saturation levels, with an acceptable safety profile. Recently, important new data relating to the use of iron sucrose, including the findings from the landmark PIVOTAL trial in patients with end-stage kidney disease, have been reported. Several years ago, a number of iron sucrose similars became available, although there have been concerns about the clinical appropriateness of substituting the original iron sucrose with an iron sucrose similar because of differences in efficacy and safety. This is a result of the complex and unique physicochemical properties of nanomedicines such as iron sucrose, which make copying the molecule difficult and problematic. In this review, we summarize the evidence accumulated during 70 years of clinical experience with iron sucrose in terms of efficacy, safety, and cost-effectiveness.

Genome-wide non-invasive prenatal testing in single- and multiple-pregnancies at any risk: Identification of maternal polymorphisms to reduce the number of unnecessary invasive confirmation testing.

OBJECTIVE: Non-invasive prenatal testing by targeted or genome-wide copy number profiling (cnNIPT) has the potential to outperform standard NIPT targeting the common trisomies 13, 18, and 21, only. Nevertheless, prospective results and outcome data on cnNIPT are still scarce and there is increasing evidence for maternal copy number variants (CNVs) interfering with results of both, standard and cnNIPT. STUDY DESIGN: We assessed the performance of cnNIPT in 3053 prospective and 116 retrospective cases with special consideration of maternal CNVs in singleton and multiple gestational pregnancies at any risk, as well as comprehensive follow-up. RESULTS: A result was achieved in 2998 (98.2%) of total prospective cases (89.2% analyzed genome-wide). Confirmed fetal chromosomal abnormalities were detected in 45 (1.5%) cases, of which five (11%) would have remained undetected in standard NIPTs. Additionally, we observed 4 likely fetal trisomies without follow-up and a likely phenotype associated placental partial trisomy 16. Moreover, we observed clinically relevant confirmed maternal CNVs in 9 (0.3%) cases and likely maternal clonal hematopoiesis in 3 (0.1%). For common fetal trisomies we prospectively observed a very high sensitivity (100% [95% CI: 91.96-100%]) and specificity (>99.9% [95% CI: 99.8-100%]), and positive predictive value (PPV) (97.8% [95% CI: 86.1-99.7%]), but our retrospective control cases demonstrated that due to cases of fetal restricted mosaicism the true sensitivity of NIPT is lower. After showing that 97.3% of small CNVs prospectively observed in 8.3% of genome-wide tests were mostly benign maternal variants, sensitivity (75.0% [95% CI: 19.4%-99.4%]), specificity (99.7% [99.5%-99.9%]) and PPV (30.0% [14.5%-52.1%]) for relevant fetal CNVs were relatively high, too. Maternal autoimmune disorders and medication, such as dalteparin, seem to impair assay quality. CONCLUSION: When maternal CNVs are recognized as such, cnNIPT showed a very high sensitivity, specificity and PPV for common trisomies in single and multiple pregnancies at any risk and very good values genome-wide. We found that the resolution for segmental aberrations is generally comparable to standard karyotyping, and exceeds the latter if the fetal fraction is above 10%, which allows detection of the 2.5 Mb 22q11.2 microdeletion associated with the velocardiofacial syndrome, even if the mother is not a carrier.

Selective use of recombinant human erythropoietin in pregnant patients with severe anemia or nonresponsive to iron sucrose alone.

OBJECTIVE: To evaluate the effectiveness of a stepwise use of recombinant human erythropoietin (rhEPO) in pregnant patients with severe anemia or nonresponsive to intravenously administered iron only. METHODS: All subjects had iron deficiency anemia, i.e., a hemoglobin (Hb) level <10.0 g/dl and ferritin < or =15 microg/l. Patients with an Hb level > or =9.0 g/dl and <10.0 g/dl received 200 mg iron sucrose intravenously twice weekly. If response to therapy was poor, patients additionally received 10,000 U rhEPO twice weekly. Patients with an Hb level <9.0 g/dl primarily received iron sucrose and rhEPO likewise. RESULTS: Of the 84 patients, 59 had a baseline Hb level between 9.0 and 9.9 g/dl, of whom 32 responded poorly, thus receiving additional rhEPO. Twenty-five patients had a baseline Hb level <9.0 g/dl. The overall Hb level after therapy was 11.0 g/dl (+/-0.5, range 10.0-12.6 g/dl). Mean duration of therapy was 3.5 weeks (7 infusions). CONCLUSION: This study shows an effective treatment regimen for patients with various degrees of anemia in pregnancy. Iron sucrose is a safe and effective treatment option. In cases of severe iron deficiency anemia or poor response to parenteral iron therapy additional administration of rhEPO might be considered. However, the mechanism for not responding to intravenous iron therapy despite iron deficiency anemia still remains unclear to a large extent.

Prenatally fabricated autologous human living heart valves based on amniotic fluid derived progenitor cells as single cell source.

BACKGROUND: A novel concept providing prenatally tissue engineered human autologous heart valves based on routinely obtained fetal amniotic fluid progenitors as single cell source is introduced. METHODS AND RESULTS: Fetal human amniotic progenitors were isolated from routinely sampled amniotic fluid and sorted using CD133 magnetic beads. After expansion and differentiation, cell phenotypes of CD133- and CD133+ cells were analyzed by immunohistochemistry and flowcytometry. After characterization, CD133- derived cells were seeded onto heart valve leaflet scaffolds (n=18) fabricated from rapidly biodegradable polymers, conditioned in a pulse duplicator system, and subsequently coated with CD133+ derived cells. After in vitro maturation, opening and closing behavior of leaflets was investigated. Neo-tissues were analyzed by histology, immunohistochemistry, and scanning electron microscopy (SEM). Extracellular matrix (ECM) elements and cell numbers were quantified biochemically. Mechanical properties were assessed by tensile testing. CD133- derived cells demonstrated characteristics of mesenchymal progenitors expressing CD44 and CD105. Differentiated CD133+ cells showed features of functional endothelial cells by eNOS and CD141 expression. Engineered heart valve leaflets demonstrated endothelialized tissue formation with production of ECM elements (GAG 80%, HYP 5%, cell number 100% of native values). SEM showed intact endothelial surfaces. Opening and closing behavior was sufficient under half of systemic conditions. CONCLUSIONS: The use of amniotic fluid as single cell source is a promising low-risk approach enabling the prenatal fabrication of heart valves ready to use at birth. These living replacements with the potential of growth, remodeling, and regeneration may realize the early repair of congenital malformations.

Comparative efficacy and safety of intravenous ferric carboxymaltose in the treatment of postpartum iron deficiency anemia.

OBJECTIVES: To compare the safety and efficacy of iron carboxymaltose with ferrous sulfate to treat iron deficiency anemia in the post partum. METHODS: Patients were randomized (2:1 ratio) to receive iron carboxymaltose (up to 3 weekly doses of 1000 mg maximum, applied in 15 min; n=227) or ferrous sulfate (100 mg twice daily, 12 weeks; n=117). Changes in hemoglobin and iron stores up to week 12 were analyzed. RESULTS: Iron carboxymaltose was as effective as oral iron sulfate in changing hemoglobin, despite the much shorter treatment period (2 weeks vs 12 weeks). Ferritin levels were significantly higher. Except for injection site burning, iron carboxymaltose was better tolerated than ferrous sulfate, mainly concerning gastrointestinal side effects. There were no safety concerns identified in breast-fed infants. CONCLUSION: Parenteral iron carboxymaltose is a safe and effective treatment option for postpartum anemia, with advantages of a shorter treatment period, better compliance, rapid normalization of iron storages, and lower incidence of gastrointestinal side effects.