RESUMO
BACKGROUND: The objective of this study is to examine the hypothesis that cystic hygroma (CH) with normal karyotype can manifest as a Mendelian inherited trait, and that a genetic similitude with hereditary lymphedema exists. To reach this goal, we investigated the prevalence of genetic variants in angiogenesis and lymphangiogenesis genes in a cohort of euploid fetuses with CH that almost resolved before delivery. A short review of cases from literature is also reported. METHODS AND RESULTS: Five fetuses were screened using a next-generation sequencing approach by targeting 33 genes known to be associated with vascular and lymphatic malformations. The genetic evaluation revealed two novel variants in KDR and KRIT1 genes. CONCLUSION: A review of the literature to date revealed that an association exists between CH and hereditary lymphedema and, similar to lymphedema, CH can be inherited in autosomal recessive and autosomal dominant manner, with the latter most likely associated with a better prognosis. About KDR and KRIT1 genes, no other similar associations are reported in the literature and caution is needed in their interpretation. In conclusion, we thought that a genetic test for the outcome of familial CH could be of enormous prognostic value.
Assuntos
Neoplasias de Cabeça e Pescoço/genética , Padrões de Herança , Proteína KRIT1/genética , Linfangioma Cístico/genética , Linfedema/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Feminino , Feto , Expressão Gênica , Testes Genéticos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cariotipagem , Linfangiogênese/genética , Linfangioma Cístico/diagnóstico por imagem , Linfangioma Cístico/patologia , Linfedema/diagnóstico por imagem , Linfedema/patologia , Masculino , Modelos Genéticos , Mutação , Neovascularização Patológica/diagnóstico , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Prognóstico , UltrassonografiaRESUMO
INTRODUCTION: Megacystis is a condition of abnormal enlarged fetal bladder for gestational age, which is usually associated with urological malformations that may constitute a life-threatening condition for the baby. OBJECTIVE: The purpose of this study was to assess the prognostic and etiological criteria of fetal megacystis and to describe the neonatal outcome in a large series collected in a single tertiary center. STUDY DESIGN: A retrospective observational study was conducted between 2008 and 2012. We reviewed all consecutive cases of fetal megacystis diagnosed during routine ultrasound (US) screening. The following data were collected and analyzed: maternal age, gestational age at diagnosis, prenatal ultrasonographic details of the urinary system, extra-urinary ultrasonographic anomalies, fetal karyotype, pregnancy outcome, postnatal diagnosis, and medical/surgical follow-up. RESULTS: Of the 25 fetuses included in this study, 76% were males. The mean gestational age (GA) at diagnosis was 23.1 ± 7.5 weeks (range 12-34), among them only four (16%) were diagnosed during the first trimester. Associated urological malformations were detected in 92% (n = 23) of the cases, while other malformations were detected in 36% (n = 9). Oligohydramnios or anyhydramnios were observed in 52% (n = 13) of the cases. Twelve (48%) fetuses were considered as having poor prognosis for renal function. Vesicocentesis with or without vesico-amniotic infusion were performed in 28% (n = 7) of the cases. Pregnancy outcome was surprisingly good, with only one case of prenatal death and survival rate of 96% (n = 24) of liveborn babies. Posterior urethral valve (PUV) (n = 9, 36%) was the most common etiology of the fetal megacystis, followed by persistent urogenital sinus (n = 2, 8%), Prune belly syndrome (n = 2, 8%) and bilateral vescico-ureteral reflux (VUR) (n = 2, 8%). Surgical or endoscopic procedures were performed in 75% (n = 18) of the cases. Six (24%) newborns presented with moderate/severe respiratory distress that requested invasive assisted ventilation. Three cases (n = 3, 12%) of perinatal death were observed due to severe impaired renal function. After a median follow-up of 29 months renal function was good in 79% (n = 19) of the cases. CONCLUSIONS: Fetal megacystis may underline a wide range of associated pathologies with the highest prevalence of urinary malformation. Optimal counseling of the involved parents requires a multidisciplinary approach to allow the best management during the pregnancy and the perinatal period. Despite the high risk of renal failure, lung hypoplasia, and severe associated anomalies, the outcome of fetuses with megacystis could be improved thanks to an appropriate perinatal diagnosis and neonatal management.
Assuntos
Duodeno/anormalidades , Doenças Fetais/diagnóstico por imagem , Centros de Atenção Terciária , Ultrassonografia Pré-Natal , Bexiga Urinária/anormalidades , Duodeno/diagnóstico por imagem , Feminino , Doenças Fetais/etiologia , Doenças Fetais/terapia , Humanos , Recém-Nascido , Masculino , Gravidez , Prognóstico , Estudos Retrospectivos , Bexiga Urinária/diagnóstico por imagemRESUMO
The ultrasonographic detection of renal anomalies may modify obstetric management and facilitate pediatric care of the newborn. We performed prenatal differential diagnosis of an isolated unilateral cystic renal mass (71 × 74 × 82 mm) in a pregnant woman at 26 weeks of gestation. No other abnormalities were detected by ultrasonography, except for polyhydramnios. Repeated percutaneous cyst aspirations were required because of the increasing risk of vital organ damage. Postnatal nephroureterectomy was performed. Anatomopathologic analysis led to the diagnosis of segmental renal dysplasia, which could not be included in any of the four groups of Potter's classification of cystic renal dysplasia.
Assuntos
Rim/anormalidades , Adulto , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Rim/diagnóstico por imagem , Rim/cirurgia , Doenças Renais Císticas/congênito , Doenças Renais Císticas/diagnóstico por imagem , Doenças Renais Císticas/terapia , Masculino , Nefrectomia , Gravidez , Sucção , Ultrassonografia Pré-Natal , Ureter/cirurgiaRESUMO
OBJECTIVE: The purpose of this study is to define the role of foetal magnetic resonance imaging (MRI) in evaluating cerebral ischaemic-haemorrhagic lesions and the extension of parenchymal injuries. STUDY DESIGN: From September 2006 to September 2010, 271 foetal MRI have been performed on cases referred to us for ultrasound suspect of brain abnormalities or cytomegalovirus infection and Toxoplasma serum conversion. Foetal MRI was performed with a 1.5-T magnet system without mother sedation. RESULTS: Foetal MRI detected ischaemic-haemorrhagic lesions in 14 of 271 foetuses, consisting of 5% incidence. MRI confirmed the diagnosis in three of 14 cases with ultrasonography (US) suspect of ischaemic-haemorrhagic lesions associated with ventriculomegaly. In one of 14 cases with US findings of cerebellar haemorrhage, MRI confirmed the diagnosis and provided additional information regarding the parenchymal ischaemic injury. In eight of 14 cases with US suspect of ventriculomegaly (3), corpus callosum agenesis (2), hypoplasia of cerebellar vermis (1), holoprosencephaly (1) and spina bifida (1), MRI detected ischaemic and haemorrhagic lesions unidentified at US examination. In two of 14 foetuses with US suspect of intracerebral space-occupying lesion, MRI modified the diagnosis to extra-axial haematoma associated with dural sinus malformation. Results were compared with post-mortem findings or afterbirth imaging follow-up. CONCLUSIONS: Foetal MRI is an additional imaging modality in the diagnosis of cerebral ischemic-haemorrhagic lesions, and it is useful in providing further information on the extension of the parenchymal injury and associated abnormalities, thus improving delivery management.
Assuntos
Isquemia Encefálica/embriologia , Hemorragia Cerebral/embriologia , Doenças Fetais/diagnóstico , Imageamento por Ressonância Magnética , Diagnóstico Pré-Natal/métodos , Anormalidades Múltiplas , Adulto , Agenesia do Corpo Caloso/diagnóstico , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/patologia , Doenças Cerebelares/diagnóstico , Cerebelo/anormalidades , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/patologia , Infecções por Citomegalovirus/diagnóstico , Anormalidades do Olho/diagnóstico , Feminino , Doenças Fetais/patologia , Idade Gestacional , Holoprosencefalia/diagnóstico , Humanos , Doenças Renais Císticas/diagnóstico , Gravidez , Retina/anormalidades , Disrafismo Espinal/diagnósticoRESUMO
OBJECTIVE: To show the validity of prenatal invasive surgical intervention when a fetal ovarian cyst is diagnosed, compared to a wait and see attitude, in order to avoid possible prenatal and postnatal complications. PATIENTS: Fourteen cases of intra-abdominal cysts monitored in our center between April 2005 and November 2010. All cases were first diagnosed in the third trimester, and were monitored for the remainder of the pregnancy and after delivery (2 months-3 years postnatally). SURGICAL INTERVENTION: Upon maternal and fetal cutaneous anesthesia performed trans-amniotically, the cystic fluid (mean contents 43.85 cc, DS 46.27) was extracted for cytological, biochemical, and hormonal examination. RESULTS: Thirteen cases of intra-abdominal cysts (92.8%) were fetal ovarian cysts. Ninety-two percent of pregnancies bearing such a condition were successfully concluded (nâ=â12). Sixty-nine percent concluded in vaginal delivery (nâ=â9). None experienced maternal and/or fetal complications. Every drained cyst had an estradiol concentration higher than 10,000 pg/ml. CONCLUSIONS: The aspiration of ovarian cysts exceeding a 40 mm diameter, performed as early as possible, allows a good longitudinal treatment of this fetal affection, thus avoiding torsion, tissue necrosis, and invasive postnatal surgery, as well as giving hope of future gestational capability to the fetus/newborn.
Assuntos
Terapias Fetais/métodos , Cistos Ovarianos/cirurgia , Doenças Ovarianas/cirurgia , Adulto , Feminino , Humanos , Cistos Ovarianos/diagnóstico por imagem , Doenças Ovarianas/diagnóstico por imagem , Gravidez , Reprodutibilidade dos Testes , Ultrassonografia Pré-NatalRESUMO
The majority of neonates with Rh-isoimmunization develops late anemia between the second and the sixth week of life. We report the effectiveness of recombinant human erythropoietin (rHuEPO) in preventing late anemia in 25 intrauterine and nonintrauterine-transfused neonates. The neonates were treated from 11+/-4 days after birth to 26+/-14 days (400 U/kg/d of rHuEpo, administered subcutaneously). During rHuEpo therapy, vitamin E, calcium folinate, and iron maltose were administered intramuscularly on a daily basis. Hematocrit, platelet, and neutrophil counts did not differ significantly before and after 21-days therapy. However, average values for reticulocyte showed a significant increase. The hematocrit values in the non-intrauterine transfusion (IUT) group increased progressively from the beginning to the end of the treatment, whereas that in the IUT group remained stable. Reticulocyte count increased during treatment in both groups, but it was significantly elevated in the non-IUT group only. Moreover, we observed that only neonates transfused with IUTs needed transfusions before and after treatment. This study suggests the effectiveness of rHuEpo therapy in the treatment of neonates with Rh-isoimmunization and it highlights how IUTs decrease the neonatal response efficacy. Larger, better if multicentric, randomized controlled trial are needed to definitely state whether rHuEPO safely decreases the incidence of late onset anemia.
Assuntos
Anemia/etiologia , Anemia/prevenção & controle , Transfusão de Sangue Intrauterina , Transfusão de Sangue , Eritropoetina/uso terapêutico , Isoimunização Rh/complicações , Estudos de Coortes , Feminino , Idade Gestacional , Hematócrito , Humanos , Recém-Nascido , Masculino , Gravidez , Proteínas Recombinantes , Taxa de Sobrevida , Resultado do TratamentoRESUMO
We evaluated the possibility of prolonged chimerism formation in fetus and lamb, following human cord blood-selected CD133+ hemopoietic stem cell (HSC) transplantation into the celomic cavity of ewes at a pre-immune fetal age (44-45 days of pregnancy). Nineteen ewes were injected with HSC and 5 controls with a saline solution. By PCR, HLA-DQ alpha 1 and 6 human microsatellites (CODIS) were used for HSC traceability. FISH analysis was performed with 8 human DNA probes from different chromosomes, to confirm chromosomal integrity, nuclear DNA localization and donor DNA identification. Immunological staining for revealing HLA-DQ alpha 1 expression demonstrated multilineage engraftment. Both HLA-DQ alpha 1 and microsatellites were detected in different tissues of 3 available aborted fetuses, to a lesser extent in 11 lambs tested at 2-months, but not 12-months after birth. Although only 1 fetus of siblings of each sheep was injected, all siblings revealed positive engraftments. Microsatellite analysis showed evidence of human allele segregation in different tissues of individual fetuses and lambs. FISH analysis confirmed chimerism and the presence of human chromosomes. Non-detection of some human gene sequences in different chromosomes and random finding of allele segregation for some human heterozygous microsatellites were found in different tissues of individual animals. Controls born from un-transplanted ewes never revealed any human DNA sequences nor HLADQ alpha 1 expression.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Quimeras de Transplante , Animais , Sequência de Bases , Cromossomos Humanos/genética , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Primers do DNA/genética , Feminino , Idade Gestacional , Sobrevivência de Enxerto/genética , Sobrevivência de Enxerto/imunologia , Antígenos HLA-DQ/metabolismo , Cadeias alfa de HLA-DQ , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Repetições de Microssatélites , Cavidade Peritoneal , Reação em Cadeia da Polimerase , Gravidez , Quimeras de Transplante/genética , Quimeras de Transplante/imunologiaRESUMO
Preterm labor is one of the most important factors limiting the advancement of fetal surgery programs. While prostaglandins (PGs) have long been indicated as the key factor in the initiation of labor in humans, there is significant evidence showing that the chorionic membrane acts as a powerful barrier between the decidua/myometrium and amniotic PGs during normal pregnancy. After either open or endoscopic fetal surgery the imperfect, non-hermetical closure of the chorion permits leakage of PGs from the amnionic sac, allowing them to reach the decidua and myometrium. The surgical wound in the chorionic barrier could be the major factor involved in preterm labor and delivery after human fetal surgery.
Assuntos
Córion/metabolismo , Fetoscopia/efeitos adversos , Feto/cirurgia , Trabalho de Parto Prematuro/metabolismo , Complicações Infecciosas na Gravidez/metabolismo , Prostaglandinas/metabolismo , Líquido Amniótico/metabolismo , Córion/cirurgia , Citocinas/metabolismo , Feminino , Humanos , Trabalho de Parto Prematuro/etiologia , Trabalho de Parto Prematuro/fisiopatologia , Gravidez , Complicações Infecciosas na Gravidez/fisiopatologia , Prostaglandina-Endoperóxido Sintases/metabolismo , Contração UterinaRESUMO
The intracoelomic route for in utero hematopoietic stem cell transplantation has been evaluated in pre-immune fetal sheep and the engraftment characteristics defined. Twelve ovine fetuses (gestational ages: 40-45 days) received intracoelomic transplants of human CD3-depleted (50 x 10(6) per lamb) or CD34-selected (1-2 x 10(5) per lamb) cord blood hematopoietic stem cells. Engraftment was evaluated from cell suspension of the liver, spleen, bone marrow and thymus by flow cytometry, cloning assays and polymerase chain reaction (PCR) analysis for human beta(2)-microglobulin gene. The engraftment of liver samples was also evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR), fluorescent in situ hybridization (FISH) and immunohistochemistry. Four fetuses (33%) aborted shortly after intracoelomic transplantation and were not evaluable for engraftment. Engraftment was detected in 4 fetuses obtained from cesarean delivery on day 70 after transplantation of CD3-depleted cord blood cells. The degree of engraftment in these 4 fetuses ranged from 6 to 22% in the different organs (as revealed by antigenic analysis of human CD45 with flow cytometry). Three fetuses obtained after cesarean section at 102 (No. 435184) and 105 (Nos 915293, 037568) days and 1 fetus delivered at term, which received CD34-selected cord blood cells, had human engraftment with 10, 32, 20 and 10% CD45+ cells in bone marrow, respectively. A further check of human chimerism was done at 1 year after birth of the fetus delivered at term and 7.6% of bone marrow chimerism was detected. In 6 out of 8 fetuses evaluable for human engraftment, chimerism was confirmed by PCR analysis for human beta(2)-microglobulin which also identified human cells in brain, spinal cord, heart, lung and skeletal muscle. On liver samples, FISH and RT-PCR confirmed the xenograft of human cells and the immunohistochemical analysis detected human markers of hematopoietic and hepatic lineage of differentiation. This preliminary study indicates that intracoelomic transplantation of human hematopoietic stem cells in fetal lambs is feasible and effective in terms of hematopoietic engraftment.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Feto/cirurgia , Animais , Antígenos CD34/análise , Coleta de Amostras Sanguíneas , Feminino , Citometria de Fluxo , Células-Tronco Hematopoéticas/imunologia , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Antígenos Comuns de Leucócito/análise , Gravidez , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ovinos/embriologia , Transplante HeterólogoRESUMO
The intracelomic route for in utero hematopoietic stem cell transplantation was evaluated in preimmune fetal sheep and the engraftment characteristics were defined. Twelve twin ovine fetuses (gestational age: 40-45 days) received intracelomic transplants of human CD3-depleted (50 x 10(6) per lamb) or CD34-selected (1-2 x 10(5) per lamb) cord blood hematopoietic stem cells. Engraftment was evaluated from cell suspensions of the liver, spleen, bone marrow, and thymus by flow cytometry, cloning assays, and polymerase chain reaction (PCR) analyses of human beta2-microglobulin. Four fetuses (33%) aborted shortly after intracelomic transplantation and were not evaluable for engraftment. Engraftment was detected in four fetuses obtained from cesarean delivery on day 70 after transplantation of CD3-depleted cord blood cells. The degrees of engraftment in these four fetuses ranged from 6%-22% in the different organs (as revealed by antigenic analysis of human CD45 with flow cytometry). Three fetuses obtained after cesarean section at 102 (no. 435184) and 105 (no. 915293, no. 037568) days and one fetus delivered at term that received CD34-selected cord blood cells had human engraftment with 10%, 32%, 20%, and 10% CD45(+) cells in bone marrow, respectively. In six of eight fetuses evaluable for human engraftment, chimerism was confirmed by PCR analysis for human beta2-microglobulin, which also identified human cells in brain, spinal cord, heart, lung, and skeletal muscle. This preliminary study indicates that intracelomic transplantation of human hematopoietic stem cells in fetal lambs is feasible and effective in terms of hematopoietic engraftment.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Animais , Antígenos CD34/análise , Células da Medula Óssea/imunologia , Feminino , Feto/cirurgia , Citometria de Fluxo , Idade Gestacional , Células-Tronco Hematopoéticas/fisiologia , Humanos , Antígenos Comuns de Leucócito/análise , Gravidez , OvinosRESUMO
It is well known that nitric oxide (NO), the most important vasodilator agent, plays an important role in lowering vascular resistance in the human umbilical-placental circulation and that its deficiency is related to the pathogenesis of pre-eclamptic disorder. Besides it has recently been demonstrated that human hemoglobin (HbA) is able to transport nitric oxide, as S-nitrosohemoglobin (SNO-Hb), from the arterial to the venous blood. In the present study we examine the functional properties of the adult and fetal nitrosated hemoglobins to see if the double transport of oxygen and NO may influence the fetal oxygenation and the relation between maternal and fetal blood. Our results show that S-nitrosation significantly increases the oxygen affinity of the adult Hb (HbA) with respect to native protein (no-nitrosated) while the functional properties of HbF are less influenced. The oxygen affinity modification, found for SNO-HbA, was ascribed to the nitrosation of cysteine beta 93: really, the same residue is also present in the gamma chains of fetal hemoglobin, while the increase of affinity is less evidenced; hence, it is probable that the 39 aminoacidic substitutions between beta and gamma chains allay the effects of S-nitrosation. As regards the physiological modulators (protons, chloride ions, 2,3-diphosphoglyceric acid, and temperature), they influence the oxygen affinity of the two hemoglobins S-nitrosated, in equal mode with respect to the native forms determining the same variation on the oxygen affinity. Hence, our results evidence the fact that the NO release by SNO-HbA "in vivo" would be limited to regions of extremely low oxygen tension (such as hypoxic regions), while in fetus, SNO-HbF would unload nitric oxide and oxygen at pressure values close to normal.
Assuntos
Sangue/metabolismo , Hemoglobina Fetal/metabolismo , Óxido Nítrico/farmacologia , Oxigênio/metabolismo , Hemoglobina A/metabolismo , Hemoglobinas/química , Hemoglobinas/metabolismo , Humanos , Modelos Biológicos , Modelos Moleculares , Nitrogênio/metabolismo , Pressão , Temperatura , Cordão Umbilical/metabolismoRESUMO
AIMS: The authors compare their experience of 17 cases of sacrococcygeal teratoma (SCT) with the literature in an attempt to clarify the natural history of this tumor and to identify factors related to its prognosis and management. METHODS: The obstetrical, neonatal and surgical data were analyzed for 17 cases of SCT observed between July 1985 and December 1998. RESULTS: Three fetuses died in utero or shortly after birth. In the remaining 14, the tumors were removed. Twelve of the infants are currently tumor-free, with good sphincter control and lower-limb function. The remaining two died: one had a malignant tumor, and the other had a recurrence of an embryonal carcinoma. Recurrent tumors (mature histotypes) were also removed from two of the 12 patients who survived. CONCLUSIONS: Benign SCTs generally have favorable prognosis. Negative prognostic factors for SCT include solid tumors, those detected early in pregnancy, malignant histotypes, polyhydramnios, placentomegaly, and fetal hydrops.