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.

Iron deficiency during pregnancy and lactation modifies the fatty acid composition of the brain of neonatal rats.

Iron deficiency is common in pregnant and lactating women and is associated with reduced cognitive development of the offspring. Since iron affects lipid metabolism, the availability of fatty acids, particularly the polyunsaturated fatty acids required for early neural development, was investigated in the offspring of female rats fed iron-deficient diets during gestation and lactation. Subsequent to the dams giving birth, one group of iron-deficient dams was recuperated by feeding an iron-replete diet. Dams and neonates were killed on postnatal days 1, 3 and 10, and the fatty acid composition of brain and stomach contents was assessed by gas chromatography. Changes in the fatty acid profile on day 3 became more pronounced on day 10 with a decrease in the proportion of saturated fatty acids and a compensatory increase in monounsaturated fatty acids. Long-chain polyunsaturated fatty acids in the n-6 family were reduced, but there was no change in the n-3 family. The fatty acid profiles of neonatal brain and stomach contents were similar, suggesting that the change in milk composition may be related to the changes in the neonatal brain. When the dams were fed an iron-sufficient diet at birth, the effects of iron deficiency on the fatty acid composition of lipids in both dam's milk and neonates' brains were reduced. This study showed an interaction between maternal iron status and fatty acid composition of the offspring's brain and suggests that these effects can be reduced by iron repletion of the dam's diet at birth.

Auditory brainstem response in full-term neonates born to mothers with iron deficiency anemia: relation to disease severity.

Background: Iron is crucial for fetal brain development; however, there are insufficient data regarding the effects of maternal iron deficiency anemia (IDA) on auditory neural maturation.Aim: We evaluated the effect of maternal IDA on auditory brainstem response (ABR) in full-term neonates.Methods: Out of 223 pregnant women, 50 were diagnosed as having IDA and 50 healthy mothers were enrolled as controls. ABR test was done for the studied neonates within 48 hours after birth and at 3 months.Results: We found that hemoglobin and iron profile were lower in neonates born to anemic mothers compared with controls. Of 100 neonates screened for ABR, 25 failed the test (all of them were born to anemic mothers). The majority of neonates who failed the screening ABR test (88%) had latent iron deficiency (cord blood ferritin 11-75 µg/L). After 3 months, 85 neonates underwent diagnostic ABR test which revealed significantly prolonged interpeak latencies I-III, III-V, and I-V among neonates born to IDA mothers compared with the control group. Within the IDA group, all interpeak latencies were more prolonged in neonates with latent iron deficiency and in those born to mothers with serum ferritin <15 µg/L. Logistic regression analysis showed that maternal hemoglobin and mean corpuscular volume could predict neonatal ABR results.Conclusions: IDA during late pregnancy adversely affects cord blood iron and hearing status. ABR results are closely related to the severity of maternal and neonatal iron status. Antenatal screening of pregnant mothers is needed to improve fetal iron status and prevent abnormal auditory maturation.

Acquired amegakaryocytic thrombocytopenia as a rare cause of thrombocytopenia during pregnancy.

A rare case of acquired amegakaryocytic thrombocytopenia (AATP) in a 35-year-old woman who presented with anaemia and thrombocytopenia at 22 weeks gestation. The first diagnostic impression was of an evolving aplastic anaemia; however, the patient was simultaneously diagnosed with severe vitamin B12 deficiency in the setting of vegetarianism. Once the cyanocobalamin deficiency was corrected, a repeat bone marrow biopsy revealed an isolated depletion of megakaryocytes, which suggested the diagnosis of AATP. Supportive care was provided for her anaemia and thrombocytopenia and she delivered a healthy baby girl with a normal platelet count. The patient was subsequently started on romiplostim with steady improvement in her platelet counts. This rare AATP case presentation highlights the importance of a well-structured diagnostic approach to thrombocytopenia during pregnancy and supports the successful use of thrombopoietin agonists for the management of AATP.

Gender differences in determinants of iron-deficiency anemia: a population-based study conducted in four European countries.

Iron-deficiency anemia (IDA) was the main condition contributing to higher rates of years lived with disabilities in women in 2016. To date, few studies have investigated gender differences in determinants of IDA in Europe. The aim of the present study was to evaluate the determinants of IDA among females and males in four European countries. IDA determinants were estimated using multivariable Cox regression based on information gathered from national primary care databases, namely Italy (for years 2002-2013), Belgium, Germany, and Spain (for years 2007-2012). Adjusted hazard ratios (aHR) with 95% confidence intervals (CIs) were estimated. Age was significantly associated with IDA in females of childbearing age in all four countries, as well as pregnancy, for which the aHR ranged from 1.20 (95% CI 1.15-1.25) in Italy to 1.88 (95% CI 1.53-2.31) in Germany. In males, the aHR increased with age starting from the 65-69 age group. Menometrorrhagia was associated with IDA in Germany (aHR 2.71, 95% CI 1.96-3.73), Italy (aHR 1.80, 95% CI 1.60-2.03), and Spain (aHR 1.52, 95% CI 1.31-1.76). A greater risk for women with alopecia was also observed. Weakness and headache indicated a higher risk in both men and women. Patients with diseases characterized by blood loss or gastrointestinal malabsorption were also at significantly increased risk. Physicians should encourage women of childbearing age to adhere to dietary recommendations regarding iron intake and regularly prescribe screening of iron status. Upper and lower gastrointestinal investigations should be recommended for patients with a confirmed diagnosis of IDA.

A systematic literature review of the relation between iron status/anemia in pregnancy and offspring neurodevelopment.

BACKGROUND: The fetal brain starts developing early and animal studies have suggested that iron plays several roles for the development, but results from epidemiological studies investigating associations between gestational iron and offspring neurodevelopment are inconsistent. OBJECTIVE: To systematically examine results from observational studies and RCTs on gestational iron and offspring neurodevelopment, with focus on the importance of four domains: iron status indicators, exposure timing, neurodevelopmental outcomes, and offspring age. METHODS: PRISMA guidelines were followed. Embase, PsychInfo, Scopus, and The Cochrane library were searched in September 2017 and February 2018. Overall, 3307 articles were identified and 108 retrieved for full-text assessment. Pre-specified eligibility criteria were used to select studies and 27 articles were included;19 observational and 8 RCTs. RESULTS: Iron status in pregnancy was associated with offspring behavior, cognition, and academic achievement. The direction of associations with behavioral outcomes were unclear and the conclusions related to cognition and academic achievement were based on few studies, only. Little evidence was found for associations with motor development. Observed associations were shown to persist beyond infancy into adolescence, and results depended on iron status indicator type but not on the timing of exposure. CONCLUSION: We conclude that there is some evidence that low pregnancy iron, possibly particularly in the 3rd trimester, may be associated with adverse offspring neurodevelopment. As most previous research used Hemoglobin, inferring results to iron deficiency should be done with caution. No conclusions could be reached regarding associations beyond early childhood, and supplementation with iron during pregnancy did not seem to influence offspring neurodevelopment.

Impact of maternal iron deficiency on the auditory functions in the young and adult guinea pig.

OBJECTIVES: The aim of this study was to evaluate the hearing function in the guinea pig offspring at post-natal day (PNd) 24 and PNd84 born from dams suffering from iron deficiency during pregnancy and lactation by using the auditory brainstem response (ABR). METHOD: Female guinea pigs (n = 24 per dietary group) were fed an iron sufficient (IS) diet (114 mg/kg) or an iron deficient (ID) diet (11.7 mg/kg) during the gestation and lactation periods. Pups in both groups were weaned at PNd9 and given the IS diet. The hematocrit level was measured at every trimester of pregnancy and at the day of sacrifice in dams and at PNd24 and PNd84 in pups. The animal body weight was measured on every second day until the day of sacrifice. The ABR was used in pups to measure the hearing threshold using a broad range of stimulus intensities and latency at 100 and 80 dB in response to 2, 4, 8, 16, and 32 kHz tone pips at PNd24 and 84. RESULTS AND DISCUSSION: No significant difference between dietary groups was measured in hearing threshold and absolute latencies in pups at PNd24 and PNd84. Although the ID offspring (n = 16) did not differ in brainstem transmission times (BTTs) at 80 dB compare to the IS siblings (n = 25) at PNd24, they showed significant delayed inter-peak latency (IPL) I-IV at 100 dB suggesting a delayed BTT. At PNd84, the latency of all peaks including IPL I-IV at 80 and 100 dB significantly decreased and was also similar in pups from both dietary groups suggesting a better brain maturation. This is the first study investigating the long-term impact of maternal iron deficiency on the auditory functions in the guinea pig offspring during early development to adulthood.

Do pregnancies reduce iron overload in HFE hemochromatosis women? results from an observational prospective study.

BACKGROUND: HFE hemochromatosis is an inborn error of iron metabolism linked to a defect in the regulation of hepcidin synthesis. This autosomal recessive disease typically manifests later in women than men. Although it is commonly stated that pregnancy is, with menses, one of the factors that offsets iron accumulation in women, no epidemiological study has yet supported this hypothesis. The aim of our study was to evaluate the influence of pregnancy on expression of the predominant HFE p.[Cys282Tyr];[Cys282Tyr] genotype. METHODS: One hundred and forty p.Cys282Tyr homozygous women enrolled in a phlebotomy program between 2004 and 2011 at a blood centre in western Brittany (France) were included in the study. After checking whether the disease expression was delayed in women than in men in our study, the association between pregnancy and iron overload was assessed using multivariable regression analysis. RESULTS: Our study confirms that women with HFE hemochromatosis were diagnosed later than men cared for during the same period (52.6 vs. 47.4 y., P < 0.001). Compared to no pregnancy, having at least one pregnancy was not associated with lower iron markers. In contrast, the amount of iron removed by phlebotomies appeared significantly higher in women who had at least one pregnancy (eß = 1.50, P = 0.047). This relationship disappeared after adjustment for confounding factors (eß = 1.35, P = 0.088). CONCLUSIONS: Our study shows that pregnancy status has no impact on iron markers level, and is not in favour of pregnancy being a protective factor in progressive iron accumulation. Our results are consistent with recent experimental data suggesting that the difference in disease expression observed between men and women may be explained by other factors such as hormones.

Effect of maternal iron deficiency anemia on fetal neural development.

OBJECTIVE: Perinatal iron deficiency may have deleterious consequences on fetal neural development. The present study was conducted to determine the effect of maternal iron deficiency anemia (IDA) on fetal hippocampal morphogenesis and production of brain-derived neurotrophic factor (BDNF). STUDY DESIGN: Seventy term, singleton neonates born to mothers with IDA (hemoglobin <110g/L and serum ferritin <12 µg/L) formed the study group. Twenty gestational age-matched neonates born to healthy mothers without IDA (hemoglobin ≥110 g/L and serum ferritin >12 µg/L) served as controls. Maternal and fetal inflammatory conditions, infections and neonates with perinatal asphyxia were excluded. Cord blood BDNF concentrations were estimated by enzyme-linked immunosorbent assay. Volumetric analysis of hippocampus (right, left and combined, corrected for total intracranial volume) was done by cranial magnetic resonance imaging on days 3-5 of life. RESULTS: In the study group, 24 mothers had mild (hemoglobin 100.0-109.0 g/L), 24 had moderate (hemoglobin 70.0-99.0 g/L), and 22 had severe (hemoglobin <70.0 g/L) anemia. Both hippocampal volumes and serum BDNF concentrations of neonates born to iron-deficient mothers were significantly reduced compared to controls. A progressive decline in hippocampal volumes and BDNF concentrations was observed with increasing severity of maternal anemia. Pearson correlation showed significant correlations among maternal and cord blood hemoglobin, iron indices, hippocampal volumes and BDNF concentrations. CONCLUSIONS: Maternal IDA adversely affects hippocampal morphogenesis and fetal production of BDNF. The degree of affection is proportional to the severity of maternal anemia.

Iron deficiency anemia in pregnant women.

Screening for iron deficiency anemia (IDA) in all pregnant women is recommended. IDA is a prevalent cause of nutritional deficiency anemia, and oral iron is the first line of treatment. Other treatments include parenteral iron or blood transfusion(s). Untreated IDA in pregnancy can result in complications for the mother and fetus.

Anesthetic management of spontaneous cervical epidural hematoma during pregnancy: a case report.

BACKGROUND: Spontaneous spinal epidural hematoma during pregnancy is a quite rare event requiring emergent decompressive surgery in the majority of cases to prevent permanent neurological damage. Therefore, there is little data in the literature regarding anesthetic management of cervical localization during pregnancy. The potential for difficult airway management with the patient under general anesthesia is one of the major concerns that needs to be addressed to prevent further cord compression. Anesthetic management should also include measures to maintain the mean arterial pressure to improve spinal cord perfusion. Furthermore, spine surgery in pregnant patients needs special consideration in terms of positioning and in the postoperative period. CASE PRESENTATION: We present a case of a 35-year-old white woman at 21 weeks of gestation with a spontaneous cervical epidural hematoma. Fiberoptic bronchoscope-guided nasal intubation was a safe option to ensure a higher rate of successful endotracheal intubation while minimizing the risk of aggravating the injury. Her care posed other multiples challenges that required a multidisciplinary team approach. CONCLUSIONS: The case of our patient serves as a reminder of this rare condition and its implications regarding anesthesia.

Pregnancy complicated with agranulocytosis.

RATIONALE: Pregnancy is a complicated physiological process. Physiological leukocytosis often takes place and it is primarily related to the increased circulation of neutrophils, especially during the last trimester of pregnancy. Noncongenital agranulocytosis during pregnancy is rare and reported only occasionally, while in most of the cases, the agranulocytosis has already occurred prior to pregnancy or induced by identified factors such as antibiotics, antithyroid agents, or cytotoxic agents. Gestation-induced agranulocytosis has not been reported, so we present a case of gestation-induced agranulocytosis in this article. PATIENTS CONCERN: In this case, we present a Chinese woman (aged 25) in her 38th week of the first gestation who had the complication of agranulocytosis. No abnormality was detected in regular examinations before pregnancy and in the first trimester. Since the last trimester of pregnancy, the patient began to suffer from agranulocytosis and intermittent fever, the maximum being temperature 38.8°C. At admission, the neutrophil granulocytes were 0.17 × 10 L and the bone marrow biopsy showed that agranulocytosis was detected, but the levels of red blood cell and megalokaryocyte were normal. In addition, antinuclear antibodies were detected at a dilution of 1:40, but anti-dsDNA, antiphospholipid antibody, and neutrophil granulocyte antibody were negative. DIAGNOSES: The patient was empirically treated as having pneumonia. INTERVENTIONS: We tried to use granulocyte colony-stimulating factor, γ-globulin, glucocorticoids, antibiotics, and antifungi agents to treat the patient, but her symptoms were not alleviated until the patient had a cesarean section. OUTCOMES: After 24 hours of cesarean section, the temperature and neutrophil granulocyte returned to normal. After a year of follow-up, we found that the patient and the baby were healthy. LESSONS: Agranulocytosis during pregnancy seems to be associated with immunosuppression induced by immunoregulations and termination of pregnancy may be effective for refractory pregnancy complicated with agranulocytosis, but further studies are needed to confirm this.

Haematological malignancies in pregnancy: An overview with an emphasis on thrombotic risks.

With increase of maternal age, the incidence of haematological malignancies during pregnancy is rising and posing diagnostic and treatment challenges. Lymphoma is the fourth most common malignancy diagnosed in pregnancy; Hodgkin lymphoma is more frequent in pregnant women than non-Hodgkin lymphoma (NHL). The proportion of highly aggressive lymphomas in pregnant women is significantly higher than in non-pregnant women of reproductive age. Reproductive organ involvement is observed in almost half of pregnant women with NHL. The association of acute leukaemia and pregnancy is infrequent and it is assumed that pregnancy does not accelerate the disease course. Both cancer and pregnancy induce a procoagulant state which can lead to maternal venous thromboembolism (VTE) and placental occlusion. Pregnancy in woman with myeloproliferative neoplasms (MPN) promotes thrombotic environment, associating with an augmented risk of placental thrombosis, intrauterine growth retardation or loss and maternal thrombotic events.Haematological malignancies during pregnancy often require urgent diagnosis and management and are associated with potential adverse fetal outcomes. Most chemotherapeutic agents are teratogenic and should be avoided during the first trimester. Their use during the second and third trimesters may cause intrauterine growth restriction, premature birth and intrauterine fetal death. All chemotherapeutic drugs should be administered only after a detailed discussion with the patient and with close fetal monitoring. Chemotherapy and biological agents might also augment thrombotic risk. Guidelines for VTE prophylaxis in pregnant women with hematologic malignancies, apart from MPN, are currently unavailable, and therefore, clinical judgment should be made in each case.

Perinatal Iron Deficiency-Induced Hypothyroxinemia Impairs Early Brain Development Regardless of Normal Iron Levels in the Neonatal Brain.

BACKGROUND: Both perinatal hypothyroxinemia and perinatal iron deficiency (ID) are associated with poor neurodevelopment in offspring. Iron is an important component of thyroid peroxidase, a key enzyme in the synthesis of thyroid hormone. The authors' previous study demonstrated that perinatal ID can lead to maternal hypothyroxinemia during pregnancy. The goal of this study was to determine whether perinatal ID-associated hypothyroxinemia can cause brain defects prior to neonatal brain iron depletion. METHODS: Two rat models were established to imitate the two common types of maternal ID (mild ID with anemia [ID + A] and ID without anemia [ID - A]), and iron limitation was initiated two weeks before pregnancy. Maternal and neonatal thyroid hormones in serum were analyzed at postnatal day (P) 0 and P10. Neonatal thyroid hormone, as well as mRNA expression of some thyroid hormone-responsive genes in the cerebral cortex and hippocampus, were measured at P10. Serum iron and brain iron concentrations were analyzed by inductively coupled plasma mass spectrometry. Liver iron concentration was determined using graphite furnace atomic absorption spectroscopy. Hemoglobin was analyzed with an automated blood coagulation analyzer. Surface righting reflex and vibrissae-evoked forelimb placing were measured to assess the sensorimotor behaviors. RESULTS: It was found that pre-pregnant mild ID resulted in maternal hypothyroxinemia, which lasted from gestation day 13 to P10. Pre-pregnant mild ID decreased the neonatal brain total triiodothyronine level at P10. Consistent with a low total triiodothyronine level, the mRNA expression of some thyroid hormone-responsive genes (Mbp, RC3, and Srg1) were significantly reduced in the neonatal cerebral cortex and hippocampus in both ID rat models at P10. Furthermore, ID rat pups at P10 showed retarded sensorimotor skills. No significant difference was found between the control and the ID pups in terms of iron concentrations in the neonatal brain at P10. CONCLUSIONS: This study demonstrates that perinatal ID-associated hypothyroxinemia is sufficient to impair early brain development, regardless of whether the neonatal brain iron level is normal, and monitoring thyroid hormone level is indicated in ID pregnant women.

Shedding Light on Inherited Thrombophilias: The Impact on Pregnancy.

Physiologic changes of pregnancy result in a hypercoagulable state, placing the risk for venous thromboembolic events at 1 in 1600 births. Venous thromboembolic events are one of the leading causes of maternal mortality. A correlation among venous thromboembolic events, pregnancy complications, and inherited thrombophilia continues to be investigated. This article primarily focuses on the impact of inherited thrombophilias on pregnancy, labor, and birth and yet also addresses acquired thrombophilia. Prophylactic and therapeutic perinatal anticoagulation are lifesaving and pregnancy-sparing interventions. Interprofessional management of these high-risk pregnancies allows for increased surveillance to reduce perinatal morbidity and mortality.

[Anemia in obstetrics and gynecological surgery]. / Anemia en obstetricia y cirugía ginecológica.

Iron deficiency is more common in women due to uterine bleeding, which affects them throughout their fertile life. Additionally, iron needs increase physiologically during pregnancy and breastfeeding. Pregnant women therefore constitute one of the risk groups for iron deficiency. During the postpartum period, iron deficiency is the most common cause of anemia. Longer hospital stays and greater susceptibility to infections are potential consequences of postpartum anemia.

The impact of maternal iron deficiency and iron deficiency anemia on child's health.

Iron deficiency anemia is extremely common, particularly in the developing world, reaching a state of global epidemic. Iron deficiency during pregnancy is one of the leading causes of anemia in infants and young children. Many women go through the entire pregnancy without attaining the minimum required intake of iron. This review aims to determine the impact of maternal iron deficiency and iron deficiency anemia on infants and young children. Extensive literature review revealed that iron deficiency is a global nutritional problem affecting up to 52% of pregnant women. Many of these women are symptomatic. Lack of proper weight gain during pregnancy is an important predictor of iron deficiency.

Thrombocytopenia.

Thrombocytopenia is defined as a platelet count less than 150,000/µL. It can be the result of decreased platelet production, sequestration of the platelets, or increased destruction of the platelets. The clinical presentation may vary from an incidental finding to obvious bleeding. Causes of thrombocytopenia include infections, malignancy, liver disease, autoimmune disorders, disseminated intravascular coagulation, pregnancy, medications, and coagulation disorders. Treatment is determined by the underlying cause of the thrombocytopenia. This article discusses the evaluation and management of common causes of thrombocytopenia.