Outcomes of haemoglobin Bart's hydrops fetalis following intrauterine transfusion in Ontario, Canada.

OBJECTIVES: With improved access to intrauterine transfusion (IUT), more fetuses with haemoglobin Bart's hydrops fetalis (HBHF; homozygous α0-thalassaemia) will survive. DESIGN: To evaluate the long-term outcome of affected fetuses with and without IUT in Ontario, Canada, we retrospectively collected data on IUTs and pregnancy outcomes in all cases of HBHF, from 1989 to 2014. Clinical outcome and neurocognitive profiles of long-term survivors were also collected and compared with data from 24 patients with transfusion-dependent ß-thalassaemia (TDT-ß). RESULTS: Of the 99 affected pregnancies (93 prenatally diagnosed), 68 resulted in miscarriage or elective termination of pregnancy. Twelve mothers (12%) continued their pregnancies without IUT, and none of those newborns survived the first week of life. All 13 fetuses that received IUT(s) were live-born, but 3 died due to severe hydrops at birth and 1 died due to infection. The remaining nine survivors, in comparison with TDT-ß patients, had earlier iron overload requiring iron chelation therapy. Endocrinopathies and short stature were more frequent in these patients. Neurocognitive outcome was not significantly affected in five patients who were assessed, and none were diagnosed with intellectual impairment. In three patients, MRI studies demonstrated brain white matter changes in keeping with 'silent' ischaemic infarcts. CONCLUSIONS: In patients with HBHF, IUT is associated with improved survival. While acceptable neurocognitive outcome can be expected, these patients have more clinical complications compared with their TDT-ß counterparts. The clinical and neurocognitive outcomes of HBHF should be discussed in detail when counselling and offering IUT for patients.

Isolated hypoplasia of the abdominal wall associated with fetal parvovirus B19 infection.

We report a rare case of a preterm infant with a diagnosis of hydrops fetalis, associated with parvovirus B19 infection. At birth, the infant had severe ascites. She recovered and was discharged in later good condition. In follow-up at 10 years of age, she still had severe isolated hypoplasia of the abdominal muscles. Isolated hypoplasia of the abdominal muscles after parvovirus B19 infection appears to be a separate entity, which should be differentiated from other abdominal wall anomalies.

Dietary fatty acids fine-tune Piezo1 mechanical response.

Mechanosensitive ion channels rely on membrane composition to transduce physical stimuli into electrical signals. The Piezo1 channel mediates mechanoelectrical transduction and regulates crucial physiological processes, including vascular architecture and remodeling, cell migration, and erythrocyte volume. The identity of the membrane components that modulate Piezo1 function remain largely unknown. Using lipid profiling analyses, we here identify dietary fatty acids that tune Piezo1 mechanical response. We find that margaric acid, a saturated fatty acid present in dairy products and fish, inhibits Piezo1 activation and polyunsaturated fatty acids (PUFAs), present in fish oils, modulate channel inactivation. Force measurements reveal that margaric acid increases membrane bending stiffness, whereas PUFAs decrease it. We use fatty acid supplementation to abrogate the phenotype of gain-of-function Piezo1 mutations causing human dehydrated hereditary stomatocytosis. Beyond Piezo1, our findings demonstrate that cell-intrinsic lipid profile and changes in the fatty acid metabolism can dictate the cell's response to mechanical cues.

Inherited or acquired modifiers of iron status may dramatically affect the phenotype in dehydrated hereditary stomatocytosis.

Severe iron overload is frequent in dehydrated hereditary stomatocytosis (DHSt) despite well-compensated hemolysis and no or little transfusion requirement. We investigated 4 patients with proven DHSt, in whom the degree of hemolysis was closely related to iron status. Genetic modifiers increasing iron stores (HFE:pCys282Tyr, HAMP:c-153C>T mutations) were accompanied with high liver iron concentrations and increased hemolysis, whereas therapeutic phlebotomies alleviated the hemolytic phenotype. There were no manifestations of hemolysis in one patient with low iron stores. Hemolysis reappeared when iron supplementation was given. The search for genetic or acquired modifiers of iron status and the modulation of iron stores may help in the management of these patients.

Anti-M induced severe haemolytic disease of foetus and newborn in a Malay woman with recurrent pregnancy loss.

Haemolytic disease of the foetus and newborn (HDFN) is caused by maternal red blood cells (RBC) alloimmunisation resulted from incompatibility of maternal and foetal RBCs. However, only a few HDFN attributed to anti-M were reported, varying from asymptomatic to severe anaemia with hydrops foetalis and even intrauterine death. A case of severe HDFN due to anti-M alloantibody from an alloimmunized grandmultiparous Malay woman with recurrent pregnancy loss is reported here. The newborn was delivered with severe and prolonged anaemia which required frequent RBC transfusions, intensive phototherapy and intravenous immunoglobulin administration. Although anti-M is rarely known to cause severe HDFN, a careful serological work-up and close assessment of foetal well-being is important, similar to the management of RhD HDFN. Alloimmunisation with anti-M type can lead to severe HDFN and even foetal loss.

[Difficulties of the care of public antigen alloimmunization]. / Difficultés de la prise en charge de l'allo-immunisation anti-public.

Alloimmunization against high-frequency erythrocyte antigens is a problematic situation in terms of laboratory diagnosis, transfusion and obstetrical management. We report the case of a pregnant woman alloimmunized against public Ag. We detail the difficulties of alloantibody (Ab) identification and transfusion management of the deliveries. A 29-year-old pregnant woman was hospitalized in gynecology and obstetrics departments at 36 weeks of gestation for assessment of hydrops fetalis. Antibody identification test revealed the presence of a pan-reactive antibody. Investigations realized in CNRGS (Paris) concluded in anti-GE2+anti-RH3+autoantibody. The red cell phenotype was GE: -2,3. A therapeutic interruption of the pregnancy was indicated. A program of autologous transfusion was organized with withdrawal of 2 units of blood. The 2nd pregnancy took place normally. Before delivery, an autologous blood reserve consisting of 2 red cell packs and 2 fresh frozen plasma was withdrawn and transfused after delivery. The management of anti-public alloimmunization poses several problems. The first one is of diagnostic nature with, on the one hand, the difficulty of Ab identification by the available red cell panels and, on the other hand, the possible presence of alloantibodies of transfusional or obstetric interest masked by anti-public Ab. The second is represented by transfusional care of these patients. In the absence of a national reserve of frozen rare blood, the autologous transfusion remains the only alternative. However, it can answer only a limited number of indications and only in case of moderate blood loss.

Anti-M antibodies as a cause of intrauterine fetal death and neonatal hyperbilirubinaemia.

A preterm male infant (35 weeks), appropriate for gestational age with birth weight of 2.20 kg was born to a 28-year G2 P0 mother. The mother's blood group was A positive and the father's was B positive. Her first pregnancy was an intrauterine fetal death due to immune hydrops. The mother's blood was positive for indirect Coomb's test with 1:32 dilution and anti-M antibodies. This pregnancy was induced at 35 weeks of gestation. Investigations from the cord blood revealed A positive blood group, positive direct Coomb's test, haematocrit of 41.4%, cord reticulocyte count of 5.3% and total serum bilirubin (TSB) of 2.7 mg/dL. Phototherapy was started at 27 h of life for visible jaundice. In view of progressive pallor and a sudden rise of bilirubin, the infant was subjected to exchange transfusion on day 5 of life. The transfusion was given with O negative and anti-M antibodies negative donor blood. Total serum bilirubin (TSB) prior to exchange transfusion was 28 mg/dL and packed cell volume (PCV) was 21%. Phototherapy was continued for a total duration of 8 days.

Sobrecarga de ferro em adolescente com xerocitose: a importância da ressonância nuclear magnética / Iron overload in a teenager with xerocytosis: the importance of nuclear magnetic resonance imaging

Relatar um caso de sobrecarga de ferro secundária à xerocitose, uma doença rara, em uma adolescente, diagnosticada por meio de ressonância magnética em T2*. Relatamos o caso de uma paciente sintomática com xerocitose, nível de ferritina de 350ng/mL e sobrecarga de ferro cardíaca significativa. Ela foi diagnosticada por ressonância magnética em T2* e recebeu terapia de quelação. Análise por ectacitometria confirmou o diagnóstico de xerocitose hereditária. Na sequência, a ressonância magnética em T2* demonstrou resolução completa da sobrecarga de ferro em vários órgãos e novo ecocardiograma revelou resolução completa das alterações cardíacas anteriores. A paciente permanece em terapia de quelação. Xerocitose é uma desordem genética autossômica dominante rara, caracterizada por estomatocitose desidratada. O paciente pode apresentar fadiga intensa e sobrecarga de ferro. Sugerimos o uso regular de ressonância magnética em T2* para o diagnóstico e controle da resposta à quelação de ferro em xerocitose e acreditamos que o exame pode ser útil também em outras anemias hemolíticas que necessitam de transfusões.

To report a case of iron overload secondary to xerocytosis, a rare disease in a teenager, diagnosed, by T2* magnetic resonance imaging. We report the case of a symptomatic patient with xerocytosis, a ferritin level of 350ng/mL and a significant cardiac iron overload. She was diagnosed by T2* magnetic resonance imaging and received chelation therapy Ektacytometric analysis confirmed the diagnosis of hereditary xerocytosis. Subsequent T2* magnetic resonance imaging demonstrated complete resolution of the iron overload in various organs, as a new echocardiography revealed a complete resolution of previous cardiac alterations. The patient remains in chelation therapy. Xerocytosis is a rare autosomal dominant genetic disorder characterized by dehydrated stomatocytosis. The patient may present with intense fatigue and iron overload. We suggest the regular use of T2* magnetic resonance imaging for the diagnosis and control of the response to iron chelation in xerocytosis, and we believe it can be used also in other hemolytic anemia requiring transfusions.

Nonimmune hydrops fetalis caused by G6PD deficiency hemolytic crisis and congenital dyserythropoietic anemia.

We present a case of a female neonate who had a nonimmune hydrops fetalis and severe hemolytic anemia due to a rare combination of glucose-6-phosphate dehydrogenase (G6PD) deficiency and congenital dyserythropoietic anemia. We conclude that in severe cases with persistent anemia one should search after delivery for a second reason other than G6PD deficiency alone.

Iron overload in a teenager with xerocytosis: the importance of nuclear magnetic resonance imaging.

To report a case of iron overload secondary to xerocytosis, a rare disease in a teenager, diagnosed, by T2* magnetic resonance imaging. We report the case of a symptomatic patient with xerocytosis, a ferritin level of 350ng/mL and a significant cardiac iron overload. She was diagnosed by T2* magnetic resonance imaging and received chelation therapy Ektacytometric analysis confirmed the diagnosis of hereditary xerocytosis. Subsequent T2* magnetic resonance imaging demonstrated complete resolution of the iron overload in various organs, as a new echocardiography revealed a complete resolution of previous cardiac alterations. The patient remains in chelation therapy. Xerocytosis is a rare autosomal dominant genetic disorder characterized by dehydrated stomatocytosis. The patient may present with intense fatigue and iron overload. We suggest the regular use of T2* magnetic resonance imaging for the diagnosis and control of the response to iron chelation in xerocytosis, and we believe it can be used also in other hemolytic anemia requiring transfusions.

Neonatal outcome of fetuses receiving intrauterine transfusion for severe hydrops complicated by Rhesus hemolytic disease.

OBJECTIVE: To evaluate neonatal outcomes among a homogeneous group of fetuses with severe hydrops treated with intrauterine transfusion (IUT). METHODS: In a prospective study at Dokuz Eylul University School of Medicine, Izmir, Turkey, outcomes were compared for 35 IUTs carried out between 2005 and 2010 in 19 pregnancies that were complicated by Rhesus D hemolytic disease with severely hydropic fetuses. RESULTS: There was no correlation between the number of IUTs and the duration of phototherapy or number of exchange transfusions. After delivery, 36% (7/19) of neonates tested positive in a direct Coombs test and their requirement for exchange transfusion was higher than that of neonates who tested negative. The neonatal survival rate was 73.7%. Admission to the neonatal intensive care unit was 78%, and the median duration of neonatal unit stay was 4 days (range, 1-77 days). Only 1 newborn had hearing impairment. CONCLUSION: IUT is a unique, gold standard treatment for severely hydropic fetuses. When treated optimally with IUT, fetuses with severe hydrops showed no increased risk of neurodevelopmental abnormalities. Factors affecting the survival of hydropic fetuses after IUT, and whether the number of IUTs performed affects the number of exchange transfusions required remain unclear.

Potential reproductive toxicity of Largehead Atractylodes Rhizome, the most commonly used Chinese medicine for threatened miscarriage.

BACKGROUND: Largehead Atractylodes Rhizome (LAR) is the most commonly used Chinese medicine to prevent early pregnancy loss due to threatened miscarriage. However, its safety profile during pregnancy is still not available. Here we aimed to identify the potential adverse effects of LAR on embryo-fetal development as well as prenatal and post-natal growth. METHODS: Pregnant mice, rats and rabbits were orally administered with LAR extracts in various doses (from 1×, 2×, 3× and up to 6× clinical doses) at different gestational periods (implantation, gastrulation, organogenesis, maturation and whole gestation). Maternal effects on weight loss, implantation failure and fetal resorption and perinatal effects on developmental delay, growth restriction and congenital malformations were studied. RESULTS: In mice, with early LAR exposure, a significant decrease in fetal growth parameters and a significant increase in post-implantation loss were identified. With late LAR exposure, significant increases in gestational duration as well as prenatal and post-natal mortality were found. At high clinical doses, congenital skeletal malformations were recorded. In rabbits, fetal resorption, hydrops fetalis and short ear anomaly were observed. No significant adverse effects were found in rats. CONCLUSIONS: Potential reproductive toxicity of LAR in pregnant animals was identified within the clinical dose. Caution should be taken in clinical applications of LAR during pregnancy.

Type 1 Bland Sutton colonic atresia complicated by fetalis hydrops in a premature neonate.

Colonic atresia (CA) is an unusual cause of neonatal intestinal obstruction where a section of the colon has failed to form, leading to blockage or absence. A premature baby was delivered at 32 weeks of gestation via caesarian section following fetal distress. She was grossly oedematous and diagnosed with severe fetalis hydrops secondary to anaemia. She was resuscitated and stabilized. On the sixth day of life, the neonate's abdomen became severely distended with billous vomiting and failure to pass meconium. We suspected intestinal obstruction and performed an omnipaque enema which revealed dilated small bowel loops and a bowel atresia. Exploratory laparotomy confirmed a Type 1 Bland Sutton CA with mucosal web. An end colostomy was successfully performed and uneventful. In our case report, we describe a rare occurrence of postnatally diagnosed CA, complicated by fetalis hydrops and anaemia.

Giant placental chorioangioma: a rare cause of fetal hydrops.

Giant choriangiomas are rare placental tumours, associated with a high prevalence of pregnancy complications and a poor perinatal outcome. Neonatal consequences include severe microangiopathic haemolytic anaemia, thrombocytopaenia and hydrops. The associated high perinatal death rate (30-40%) has led to a number of prenatal therapeutic interventions with limited success in most cases. The authors present a case of non-immune fetal hydrops caused by a giant chorioangioma, diagnosed at 27 weeks of gestational age. Despite tocolytic therapy, the baby was born prematurely (28 weeks of gestational age) and required transfusion of blood derivatives, intensive phototherapy and exchange transfusion. She had an uncomplicated recovery and was discharged home in the second month of life. The authors emphasise the need to consider chorioangioma as a cause of non-immune fetal hydrops and microangiopathic haemolytic anaemia.

In utero development of symmetric thalamic and brainstem necrosis in a preterm hydropic stillborn.

Focal and symmetric necrotic lesions of the brainstem are thought to result from fetal hypotension or cardiac arrest in the perinatal period and thus occur in the course of postnatal intensive care rather than in utero. Here, we report for the first time on brainstem necrosis in a preterm stillborn demonstrating that brainstem necrosis occurs already in utero. The preterm stillborn of 28 weeks gestation of a mother that suffered from HELLP-syndrome was severely affected by a fetal hydrops with bilateral pleural effusions and lung hypoplasia. Bilateral tegmental brainstem necrosis and thalamic lesions were detected.

Management of red cell alloimmunized pregnancies using conventional methods compared with that of middle cerebral artery peak systolic velocity.

The aim of this retrospective study was to find out the effect of change in the management of red cell alloimmunized pregnancies from conventional method of amniocentesis to the Doppler assessment of middle cerebral artery peak systolic velocity (MCA-PSV). There were 29 alloimmunized pregnancies affected by red cell antibodies. Ten cases were managed by amniocentesis and another 19 were managed by MCA-PSV measurements. The antenatal management and perinatal outcome of both groups are presented. This study suggests that the non-invasive monitoring should be the method of choice to monitor alloimmunized pregnancies.

[Perinatal management and neurological outcome of newborns hospitalized with Rhesus hemolytic disease]. / Prise en charge périnatale et devenir neurologique à moyen terme des nouveau-nés hospitalisés pour maladie hémolytique par immunisation anti-D.

OBJECTIVES: To evaluate perinatal management and neurological outcome in a group of infants born with Rhesus fetomaternal allo-immunization. PATIENTS AND METHODS: Between 1 January and 31 December 2005, all newborns admitted to neonatal unit of Rouen tertiary centre for Rhesus hemolytic disease were included in a retrospective study and divided in two groups. The newborns who were treated with intrauterine transfusion are in the group 1 and those who needed only postnatal treatment in the group 2. In each case, were considered antenatal management (ultrasonographic data, middle cerebral artery peak systolic velocity, intrauterine transfusion), postnatal treatment (phototherapy, exchange transfusion, transfusion requirements) and neurological outcome. RESULTS: Among 42 cases of Rhesus allo-immunization observed in six years, 28 newborns (67%) were admitted for neonatal cares. No case of fetal hydrops was noted. But 16/28 (57%) were preterm with a median term of 35 weeks gestation (32-36 weeks). In group 1 of six infants who had received intrauterine transfusion (IUT), only one (17%) needed postnatal exchange transfusion, and all six received one to three blood transfusions after their birth. In group 2 of 22 infants who did not receive IUT, 6/22 (27%) needed postnatal exchange and 18/22 (82%) of them received one to four blood transfusions. Phototherapy duration and albumin requirements were similar in both groups. Three deaths occurred, one due to necrotizing enterocolitis and the other two later on due to sudden infant death and fulminant meningococcemia. Neurological outcome of the remaining 25 children was normal. DISCUSSION AND CONCLUSION: Rhesus alloimmunization remain a situation at risk. Neonatal clinical presentation is less severe than previously described due to improvement in antenatal management. Infants required less postnatal exchange transfusion when they received intrauterine transfusion but more frequent blood transfusions.

Rhesus haemolytic disease of the newborn: Postnatal management, associated morbidity and long-term outcome.

Rhesus haemolytic disease of the newborn can lead to complications such as hyperbilirubinaemia, kernicterus and anaemia. Postnatal management consists mainly of intensive phototherapy, exchange transfusion and blood transfusion. During the last decades, significant progress in prenatal care strategies for patients with Rhesus haemolytic disease has occurred. New prenatal management options have led to a remarkable reduction in perinatal mortality. As a result of the increase in perinatal survival, attention is now shifting towards short-term and long-term morbidity. This review focuses on the management of neonatal and paediatric complications associated with Rhesus haemolytic disease, discusses postnatal treatment options and summarizes the results of studies on short-term and long-term outcome.