Prevalence and determinants of anaemia among pregnant women in a high malaria transmission setting: a cross-sectional study in rural Burkina Faso.

Introduction: anemia, the commonest nutritional deficiency disorder among pregnant women in sub-Saharan Africa, is associated with severe peripartum complications. Its regular monitoring is necessary to timely inform clinical and preventive decision-making. The aim of this study was to assess the prevalence and determinants of anemia among pregnant women in rural areas of Burkina Faso. Methods: between August 2019 and March 2020, a cross-sectional study was conducted to collect maternal sociodemographic, gynaeco-obstetric, and medical characteristics by face-to-face interview or by review of antenatal care books. In addition, maternal malaria was diagnosed by standard microscopy and the hemoglobin levels (Hb) measured by spectrophotometry. The proportion of anaemia (Hb<11.0 g/dL), moderate (7.0

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.

Pregnancy and sickle cell disease: an overview of complications and suggested perinatal care.

INTRODUCTION: Pregnancy in women with sickle cell disease (SCD) has been identified as high risk owing to increased incidence of materno-fetal complications across various studies and reports. These complications include consequences related to the underlying hemoglobinopathy; chronic anemia/associated inflammation, and pregnancy related including the risk for thromboembolism, bleeding and maternal mortality. Outcomes of neonates born to women with SCD has been suboptimal over the years with recent improvement due to strict monitoring, preventive and therapeutic measures. Much is yet to be unraveled regarding the optimal management of women with SCD during pregnancy, identifying target hemoglobin, delivery mode or timing among others. AREAS COVERED: This review includes a summary of available data of the maternal and fetal outcomes; in addition to current recommendations for monitoring and management of women with SCD during pregnancy. EXPERT OPINION: To have a successful pregnancy, women should be closely monitored, and interventions provided as needed to guarantee adequate management of anemia, as well as prevention, diagnosis and management of disease. They should also be educated regarding their reproductive health, emphasizing that pregnancy is possible, and achieving optimal results depends on providing adequate care in a health care facility with expertise in high-risk pregnancies and SCD.

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.

Prevalence and aetiologies of anaemia among first trimester pregnant women in Sri Lanka; the need for revisiting the current control strategies.

BACKGROUND: The Sustainable development goals, which focus strongly on equity, aim to end all forms of malnutrition by 2030. However, a significant cause of intergenerational transfer of malnutrition, anaemia in pregnancy, is still a challenge. It is especially so in the low- and middle-income settings where possible context-specific aetiologies leading to anaemia have been poorly explored. This study explores the prevalence of etiological factors significantly contributing to anaemia in pregnancy in Sri Lanka, a lower-middle-income country with a high prevalence of malnutrition albeit robust public health infrastructure. METHODS: All first-trimester pregnant women registered in the public maternal care programme in the Anuradhapura district from July to September 2019 were invited to participate in Rajarata Pregnancy Cohort (RaPCo). After a full blood count analysis, high-performance liquid chromatography, peripheral blood film examination, serum B12 and folate levels were performed in anaemic participants, guided by an algorithm based on the red cell indices in the full blood count. In addition, serum ferritin was tested in a random subsample of 213 participants. Anaemic women in this subsample underwent B12 and folate testing. RESULTS: Among 3127 participants, 14.4% (95%CI 13.2-15.7, n = 451) were anaemic. Haemoglobin ranged between 7.4 to 19.6 g/dl. 331(10.6%) had mild anaemia. Haemoglobin ≥13 g/dl was observed in 39(12.7%). Microcytic, normochromic-normocytic, hypochromic-normocytic and macrocytic anaemia was observed in 243(54%), 114(25.3%), 80(17.8%) and two (0.4%) of full blood counts in anaemic women, respectively. Microcytic anaemia with a red cell count ≥5 * 106 /µl demonstrated a 100% positive predictive value for minor haemoglobinopathies. Minor hemoglobinopathies were present in at least 23.3%(n = 105) of anaemic pregnant women. Prevalence of iron deficiency, B12 deficiency and Southeast Asian ovalocytosis among the anaemic was 41.9% (95%CI 26.4-59.2), 23.8% (95%CI 10.6-45.1) and 0.9% (95%CI 0.3-2.3%), respectively. Folate deficiency was not observed. CONCLUSION: Even though iron deficiency remains the primary cause, minor hemoglobinopathies, B 12 deficiency and other aetiologies substantially contribute to anaemia in pregnancy in this study population. Public health interventions, including screening for minor hemoglobinopathies and multiple micronutrient supplementation in pregnancy, should be considered in the national programme for areas where these problems have been identified.

Risk factors for severe neonatal thrombocytopenia in cases of maternal immune thrombocytopenia.

AIM: Maternal immune thrombocytopenia (ITP) may induce neonatal thrombocytopenia (nTP), which carries a risk of neonatal haemorrhagic complications. Some risk factors for nTP have reached consensus such as maternal splenectomy and previous severe nTP, while others such as maternal platelet count have not. METHODS: We conducted a retrospective cohort study in a university hospital, including 145 neonates of mothers with ITP. We assessed the risk of severe nTP and bleeding complications. RESULTS: Severe nTP in the first 24 h after birth was more common in case of maternal splenectomy (OR = 4.4) and a previous severe nTP (OR = 46.9). Severe nTP at nadir (lowest platelet count during the initial postnatal days) was more frequent in cases of a previous neonate with severe nTP (OR = 42), maternal treatment during pregnancy (OR = 2.4) and a low maternal platelet count during pregnancy or at delivery. These risk factors were not significantly associated with an increased risk of neonatal haemorrhagic complications. CONCLUSION: In our population, we confirm the risk of severe nTP in case of maternal splenectomy or previous nTP. By monitoring the platelet count to its nadir, we identified three additional risk factors: maternal treatment during pregnancy and low maternal platelet count during pregnancy or low maternal platelet count at delivery.

Iron parameters in pregnant women with beta-thalassaemia minor combined with iron deficiency anaemia compared to pregnant women with iron deficiency anaemia alone demonstrate the safety of iron supplementation in beta-thalassaemia minor during pregnancy.

In patients with beta-thalassaemia intermedia or major, hepcidin induces iron overload by continuously promoting iron absorption. There have been no studies in pregnant women with beta-thalassaemia minor combined with iron deficiency anaemia (IDA), examining whether hepcidin is inhibited by GDF15, as may occur in patients with beta-thalassaemia intermedia or major, or whether the iron metabolism characteristics and the effect of iron supplementation are consistent with simple IDA in pregnancy. We compared and analysed routine blood parameters, iron metabolism parameters, the GDF15 levels, and the hepcidin levels among four groups, namely the beta-thalassaemia (ß) + IDA, ß, IDA, and normal groups. In addition, the ß + IDA and IDA groups received iron supplementation for four weeks. We found no statistically significant correlation between hepcidin and GDF15 in any group, but a positive correlation was observed between hepcidin and ferritin. After iron supplementation, the routine blood parameters and iron metabolism parameters in the ß + IDA group were improved, and the hepcidin content was significantly increased. These results suggest that in pregnant women with beta-thalassaemia minor, hepcidin functions normally to maintain iron homeostasis, and that iron supplementation is effective and safe.

Associations between Serum Aflatoxin-B1 and Anemia in Pregnant Women: Evidence from Guangxi Zhuang Birth Cohort in China.

Aflatoxin B1 (AFB1) is a common toxic mycotoxin and is detectable in pregnant women. Animal studies have revealed that AFB1 caused the lysis of erythrocytes and a decrease in hemoglobin. We conducted a prospective cohort study in Guangxi, China, in order to evaluate the association between AFB1 exposure and anemia in pregnant women during the entire pregnancy. A total of 616 pregnant women from the Guangxi Zhuang Birth Cohort were included in the study. Serum AFB1-albumin (AFB1-ALB) adduct levels were measured. The effect of AFB1-ALB adducts on hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were analyzed by using multivariable linear regression. The risks of anemia from AFB1-ALB adduct exposure were assessed by multivariable logistic regression. We found that the AFB1-ALB adduct was significantly associated with a decrease in Hb (ß = -4.99, 95% CI: -8.42, -1.30), MCV (ß = -4.58, 95% CI: -7.23, -1.94), MCH (ß = -1.86, 95% CI: -2.87, -0.85), and MCHC (ß = -5.23, 95% CI: -8.28, -2.17) in the first trimester with the third tertile of AFB1-ALB adducts when compared with the first tertile. Furthermore, the third tertile of the AFB1-ALB adduct significantly increased the risk of anemia by 2.90 times than compared to the first tertile in the first trimester (OR = 3.90, 95% CI: 1.67, 9.14). A significant positive does-response relationship existed between AFB1-ALB adduct levels and anemia risk (Ptrend = 0.001). When dividing anemia types, we only found that the third tertile of AFB1-ALB adduct increased the risk of microcytic hypochromic anemia (MHA) in the first trimester (OR = 14.37, 95% CI: 3.08, 67.02) and second trimester (OR = 4.75, 95% CI: 1.96, 11.51). These findings demonstrate the correlation between maternal AFB1 exposure during early pregnancy and risk of anemia, especially MHA, and during different trimesters in Southern China. More efforts should be made to diminish AFB1 exposure for pregnant women.

Laboratory approach to investigation of anemia in pregnancy.

Anemia is a global health problem in all age groups. According to World Health Organization (WHO), approximately 40% of pregnant women are anemic. Iron deficiency anemia (IDA) due to nutritional deficiency is the most common cause. The incidence of IDA varies worldwide depending on the socioeconomic status, but it remains the leading cause even in developed countries. Physiologic anemia of pregnancy due to relatively higher expansion of blood volume in comparison with elevated red blood cell mass also occurs frequently. Complete blood count (CBC) in the first trimester is recommended for all pregnant women to screen for anemia. The screening of pregnant women for IDA in absence of anemia is still debatable. If IDA is suspected, ferritin level of <30 ng/ml is diagnostic. Iron supplementation is recommended for all pregnant women to compensate the increased demand.

High and Low Haemoglobin Levels in Early Pregnancy Are Associated to a Higher Risk of Miscarriage: A Population-Based Cohort Study.

To evaluate whether women with anaemia or high haemoglobin (Hb) in early pregnancy would be at higher risk of miscarriage, this population-based cohort study involved 9453 women whose pregnancies were monitored at primary care centres between 2007 and 2012. The computerised clinical histories were used to collect: Hb measurements (up to 14 weeks of gestation), miscarriage before or by 24 weeks of gestation, and other maternal characteristics. The relation between anaemia (Hb < 110 g/L), normal Hb (110-140 g/L, reference), and high Hb concentrations (≥140 g/L) with miscarriage were expressed as adjusted OR with 95%CI. Restricted cubic spline models were applied to evaluate the dose-response relationships. A total of 520 (5.5%) women were recorded as having a miscarriage. The rate of miscarriage in anaemia, normal Hb, and high Hb concentrations was 8.4%, 5.1%, and 10.2%, respectively. Compared with women with normal Hb at the first trimester, the multivariable-adjusted OR for miscarriage was 2.11 (95%CI, 1.38-3.21) for women with anaemia and 1.83 (95%CI, 1.29-2.58) for women with high Hb. Hb concentrations showed a U-shaped association with miscarriage, with the lowest incidence among women with Hb of 120-130 g/L. These data highlight the importance of considering anaemia and high Hb levels in early pregnancy as harmful indicators for miscarriage.

Maternal and neonatal bleeding complications in relation to peripartum management in hemophilia carriers: A systematic review.

Currently, there is no consensus on the optimal management to prevent postpartum hemorrhage (PPH) in hemophilia carriers. We aimed to evaluate peripartum management strategies in relation to maternal and neonatal bleeding outcomes by performing an extensive database search up to August 2020. Seventeen case-reports/series and 11 cohort studies were identified of overall 'poor' quality describing 502 deliveries. The PPH incidence in the individual patient data was 63%; 44% for those women receiving prophylaxis to correct coagulation and 77% for those without (OR 0.23, CI 0.09-0.58) and in cohort data 20.3% (26.8% (11/41) vs. 19.4% (55/284) (OR: 1.53, 95% CI: 0.72-3.24), respectively. Peripartum management strategies mostly consisted of clotting factor concentrates, rarely of desmopressin or plasma. Tranexamic acid appears promising in preventing secondary PPH, but was not used consistently. Neonatal bleeding was described in 6 affected male neonates, mostly after instrumental delivery or emergency CS, but insufficient information was provided to reliably investigate neonatal outcome in relation to management. The high PPH risk seems apparent, at most mildly attenuated by prophylactic treatment. Prospective cohort studies are needed to determine the optimal perinatal management in hemophilia.

Efficacy and safety of the long-acting C5 inhibitor ravulizumab in patients with atypical hemolytic uremic syndrome triggered by pregnancy: a subgroup analysis.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) triggered by pregnancy is a rare disease caused by dysregulation of the alternative complement pathway that occurs in approximately 1 in 25,000 pregnancies. The 311 phase 3 trial (NCT02949128) showed that ravulizumab, a long-acting C5 inhibitor obtained through selective modifications to eculizumab, is efficacious in inhibiting complement-mediated thrombotic microangiopathy (TMA) in patients with aHUS. In this analysis, we report outcomes in a subgroup of patients from the 311 study who developed TMA postpartum. METHODS: This was a phase 3, multicenter trial evaluating efficacy and safety of ravulizumab in adults (≥18 years of age) with aHUS naïve to complement inhibitor treatment. The primary endpoint was complete TMA response (simultaneous platelet count normalization [≥150 × 109/L], lactate dehydrogenase normalization [≤246 U/L] and 25% improvement in serum creatinine) through the 183-day initial evaluation period. Additional efficacy endpoints included time to complete TMA response, hematologic normalization, and dialysis requirement status. RESULTS: Eight patients presenting with TMA postpartum (median age of 37.7 [range; 22.1-45.2] years) were diagnosed with aHUS and received ≥1 dose of ravulizumab. Five patients (63%) were on dialysis at baseline. Complete TMA response was achieved in 7/8 patients (87.5%) in a median time of 31.5 days. Hematologic normalization was observed in all patients. All patients on dialysis at baseline discontinued dialysis within 21 days after treatment with ravulizumab. All patients showed continued improvements in the estimated glomerular filtration rate from baseline to Day 183. Three possible treatment-related adverse events were observed in 2 patients (arthralgia and nasopharyngitis [both non-severe]; urinary tract infection). No deaths or meningococcal infections occurred. CONCLUSIONS: Treatment with ravulizumab provided immediate and complete C5 inhibition, resulting in rapid clinical and laboratory improvements and complete TMA response through 183 days in patients with aHUS triggered by pregnancy. The safety profile observed in this subset of patients analysed is consistent with the 311 study investigating ravulizumab in patients with aHUS naïve to complement treatment. TRIAL REGISTRATION: Clinical trial identifier: NCT02949128 .

Pregnancy and non-pregnancy related immune thrombotic thrombocytopenic purpura in women of reproductive age.

Pregnancy is a precipitating factor for immune thrombotic thrombocytopenic purpura (iTTP). We compared the clinical course and outcomes of iTTP in women of reproductive age, between those with pregnancy- and non-pregnancy-related iTTP. A review of all reproductive-aged women diagnosed with iTTP during 2010-2019 in seven university hospitals in Israel. Of 42 cases of iTTP, 12 (28.6%) were pregnancy-related. At presentation, the laboratory profiles did not differ significantly between those with pregnancy- and non-pregnancy-related iTTP, including hemoglobin (median 8.4 vs 8.0 g/dL), platelet count (12.5 vs. 11.5 X 109/L); and levels of bilirubin (1.23 vs. 1.82 mg/dL), lactate dehydrogenase (1615 vs. 1701 U/L), creatinine (0.61 vs. 0.79 mg/dL) and anti-ADAMTS13 antibodies titer (75 vs. 82 U/mL). The proportions of women with renal, neurologic, or hepatic involvement were similar between the groups. Cardiac involvement was more common among those with pregnancy-related disease (25.0% vs. 3.3%, P = 0.06). The median number of courses of plasma-exchange therapy was 11 for both groups. All the women were treated with parenteral corticosteroids and the rate of adjunctive treatments did not differ between the groups (P = 0.30). Four women (one-third) with pregnancy-related disease had preeclampsia. Two women (16.7%) with pregnancy-related iTTP died during the acute episode (P = 0.07); no deaths were observed in the non-pregnancy-related group. Among reproductive-aged women with iTTP, most clinical and laboratory profiles were similar between those with pregnancy- and non-pregnancy-related disease. However, the higher rates of cardiac involvement and mortality among women with pregnancy-related iTTP highlight its challenging management.

Treatment of severe thrombocytopenia associated with systemic lupus erythematosus in pregnancy with eltrombopag: A case report and literature review.

WHAT IS KNOWN AND OBJECTIVE: Severe thrombocytopenia associated with systemic lupus erythematosus (SLE) in pregnancy is infrequent. Its occurrence can lead to serious adverse pregnancy consequences and perinatal complications. The thrombopoietin (TPO) analogue eltrombopag has been successfully used in the treatment of autoimmune thrombocytopenia, but its safety and efficacy in severe thrombocytopenia during pregnancy remain unclear. CASE SUMMARY: We report a 33-year-old woman with SLE at 29 + 3 weeks gestational age who developed severe thrombocytopenia with complaints of epistaxis, gum bleeding and haematuresis. Most conventional treatments including glucocorticoids, intravenous immunoglobulin (IVIG) and cyclosporine did not elevate her platelets, but eltrombopag worked well and her platelet count gradually recovered, allowing her to deliver a healthy baby at 36 + 3 weeks gestational age. WHAT IS NEW AND CONCLUSION: This suggests that eltrombopag in combination with glucocorticoids has a good safety and efficacy profile in pregnant patients with SLE complicated by severe thrombocytopenia.

Bleeding and thrombotic risk in pregnant women with Fontan physiology.

BACKGROUND/OBJECTIVES: Pregnancy may potentiate the inherent hypercoagulability of the Fontan circulation, thereby amplifying adverse events. This study sought to evaluate thrombosis and bleeding risk in pregnant women with a Fontan. METHODS: We performed a retrospective observational cohort study across 13 international centres and recorded data on thrombotic and bleeding events, antithrombotic therapies and pre-pregnancy thrombotic risk factors. RESULTS: We analysed 84 women with Fontan physiology undergoing 108 pregnancies, average gestation 33±5 weeks. The most common antithrombotic therapy in pregnancy was aspirin (ASA, 47 pregnancies (43.5%)). Heparin (unfractionated (UFH) or low molecular weight (LMWH)) was prescribed in 32 pregnancies (30%) and vitamin K antagonist (VKA) in 10 pregnancies (9%). Three pregnancies were complicated by thrombotic events (2.8%). Thirty-eight pregnancies (35%) were complicated by bleeding, of which 5 (13%) were severe. Most bleeds were obstetric, occurring antepartum (45%) and postpartum (42%). The use of therapeutic heparin (OR 15.6, 95% CI 1.88 to 129, p=0.006), VKA (OR 11.7, 95% CI 1.06 to 130, p=0.032) or any combination of anticoagulation medication (OR 13.0, 95% CI 1.13 to 150, p=0.032) were significantly associated with bleeding events, while ASA (OR 5.41, 95% CI 0.73 to 40.4, p=0.067) and prophylactic heparin were not (OR 4.68, 95% CI 0.488 to 44.9, p=0.096). CONCLUSIONS: Current antithrombotic strategies appear effective at attenuating thrombotic risk in pregnant women with a Fontan. However, this comes with high (>30%) bleeding risk, of which 13% are life threatening. Achieving haemostatic balance is challenging in pregnant women with a Fontan, necessitating individualised risk-adjusted counselling and therapeutic approaches that are monitored during the course of pregnancy.

Carriers of haemophilia: pregnancy, childbirth and postpartum.

Management of haemophilia carrier women during labour and postpartum is yet to be standardized. Pregnancy was accompanied by a marked rise in factor VIII levels compared with only a small rise in factor IX levels. After delivery, a carrier's factor level drops down to prepregnancy levels, which increases the chance of postpartum haemorrhage. Availability of management guideline and care provided in a multidisciplinary approach can help to minimize bleeding complications in carriers of haemophilia and their newborns.

Less common hemorrhagic coagulopathies in women.

Congenital coagulopathies are a group of hereditary conditions associated with significant hemorrhagic complications. Women with congenital coagulopathies tend to experience higher bleeding rates resulting from physiological processes and pregnancy and delivery. In these women, it is essential to recognize the symptoms and work in a coordinated way between hematologists and gynecologists.