Morphological characterization of the nasopalatine region in human fetuses and its association to pathologies

The nasopalatine region is composed of structures such as the vomeronasal organ and nasopalatine duct. The nasopalatine duct may provide the communication of the mouth to the nasal cavity in human fetuses and can be obliterated in an adult human. Knowledge on the development of the nasopalatine region and nasopalatine duct in humans is necessary for understanding the morphology and etiopathogenesis of lesions that occur in this region. Objective: The aim of the present study was to describe the morphological aspects of the nasopalatine region in human fetuses and correlate these aspects with the development of pathologies in this region. Material and Methods: Five human fetuses with no facial or palatine abnormalities were used for the acquisition of specimens from the nasopalatine region. After demineralization, the specimens were histologically processed. Histological cuts were stained with methylene blue to orient the cutting plane and hematoxylin-eosin for the descriptive histological analysis. Results: The age of the fetuses was 8.00, 8.25, 9.00 and 9.25 weeks, and it was not possible to determine the age in the last one. The incisive canal was observed in all specimens as an opening delimited laterally by the periosteum and connecting oral and nasal cavity. The nasopalatine duct is an epithelial structure with the greatest morphological variation, with either unilateral or bilateral occurrence and total patent, partial patent and islet forms. The vomeronasal organ is a bilateral epithelized structure located alongside the nasal septum above the incisive canal in all the fetuses. Conclusions: The incisive canal, nasopalatine duct and vomeronasal organ are distinct anatomic structures. The development of nasopalatine duct cysts may occur in all forms of the nasopalatine duct.

Fetal venous Doppler in pregnancies with placental dysfunction and correlation with pH at birth

Objectives: To determine the correlation between ph at birth and venous Doppler parameters in pregnancies with placental dysfunction. Methods: This was a prospective cohort study of 58 pregnancies with the diagnosis of placental dysfunction between 26 and 34 weeks of gestation. Inclusion criteria were singleton pregnancies, abnormal umbilical artery (UA) Doppler, fetal growth restriction diagnosed by estimated fetal weight <10th centile for gestational age, intact membranes, and absence of fetal congenital abnormalities. The Doppler measurements were the following: UA pulsatility index (PI), ductus venosus (DV) pulsatility index for veins (PIV), intra-abdominal umbilical vein (UV) time-averaged maximum velocity (TAMxV) and blood flow and left portal vein (LPV) time-averaged maximum velocity (TAMxV) and blood flow. All Doppler parameters were transformed into z-scores (SD values from the mean) according to normative references. Results: The UA pH at birth showed a negative significant correlation with the DV-PIV (p = 0.004) and the DV-PIV z-score (p = 0.004), while LPV TAMxV (p = 0.004), LPV TAMxV z-score (p = 0.002), LPV blood flow (p = 0.01), LPV blood flow normalized (p = 0.04) and UV blood flow (p = 0.04) positively correlated with pH at birth. Multiple regression analysis was performed and the DV-PIV z-score was the variable that independently correlated with pH at birth (p = 0.002). Conclusions: the present results suggest that changes in fetal venous blood flow, mainly DV and LPV are useful in the management of cases with early onset placental insufficiency and that venous Doppler parameters correlate with pH at birth.

Predicting pH at birth in pregnancies with abnormal pulsatility index and positive end-diastolic velocity in the umbilical artery

Objectives: To identify potential associations between fetal surveillance tests and acidosis at birth in pregnancies with abnormal but positive end-diastolic velocity in the umbilical artery. Methods: A prospective case-control study [group 1: pH < 7.2; group 2: pH >= 7.2] including 46 fetuses with abnormal but positive end-diastolic velocity in the umbilical artery was conducted between February 2007 and March 2009. Outcome variables were evaluated by univariate analysis and compared between the two groups. Clinically relevant and statistically significant variables were analyzed by logistic regression. Results: Abnormal nonstress test, presence of deceleration, and absent fetal breathing movements were statistically significant. Logistic regression analysis revealed that fetal heart rate (FHR) deceleration in the nonstress test is the only predictor of fetal acidosis at birth (p = 0.024; OR = 8.2; 95% CI: 1.2-52). Conclusions: In fetuses with positive end-diastolic flow velocity, acute variables of the antenatal surveillance tests are correlated with acidosis at birth and FHR deceleration in the nonstress test is the only predictor of fetal acidosis.

Comparison between multiplanar and rendering modes in the assessment of fetal atrioventricular valve areas by 3D/4D ultrasonography

Objective: To compare the agreement of multiplanar and rendering modes in the assessment fetal atrioventricular valves (mitral and tricuspid) areas by three-dimensional (3D) ultrasonography using the software spatio-temporal image correlation (STIC). Methods: We conducted a prospective cross-sectional study with normal pregnant women, with single fetuses, between 18-33 weeks. To measure the areas, we used the plan of four-chamber view. In the case of multiplanar, the plane was rotated on the axis "Z" form the heart to position at 9h. For rendering, the green line (region of interest - ROI) was placed from the atria of the heart perpendicular to the crux. The agreement was assessed by a Bland-Altman (limits of agreement) using the relative difference between the measures: ((rendering mode) - (multiplanar mode)) / (average). Results: 328 fetuses were evaluated. We have not identified the occurrence of systematic error between methods: the average relative difference was 1.62% (-2.07% to 5.32%, confidence interval 95%) in the mitral and 1.77% (- 1.08% to 4.62%) in the tricuspid valve. The limits of agreement between methods were -65.26% to 68.51% for the mitral and -49.91% to 53.45% for the tricuspid. Conclusions: There was no systematic error between modes and thus the observed values for the area of fetal atrioventricular valves can be used for comparisons needs to be corrected. However, relatively large variations may be observed when repeating the measurement area by different modes.

Three-Dimensional Ultrasonographic Assessment of Fetal Total Lung Volume as a Prognostic Factor in Primary Pleural Effusion

Objectives-The purpose of this study was to predict perinatal outcomes using fetal total lung volumes assessed by 3-dimensional ultrasonography (3DUS) in primary pleural effusion. Methods-Between July 2005 and July 2010, total lung volumes were prospectively estimated in fetuses with primary pleural effusion by 3DUS using virtual organ computer-aided analysis software. The first and last US examinations were considered in the analysis. The observed/expected total lung volumes were calculated. Main outcomes were perinatal death (up to 28 days of life) and respiratory morbidity (orotracheal intubation with mechanical respiratory support >48 hours). Results-Twelve of 19 fetuses (63.2%) survived. Among the survivors, 7 (58.3%) had severe respiratory morbidity. The observed/expected total lung volume at the last US examination before birth was significantly associated with perinatal death (P < .01) and respiratory morbidity (P < .01) as well as fetal hydrops (P < .01) and bilateral effusion (P = .01). Conclusions-Fetal total lung volumes may be useful for the prediction of perinatal outcomes in primary pleural effusion.

Near-Term Fetal Hypoxia-Ischemia in Rabbits MRI Can Predict Muscle Tone Abnormalities and Deep Brain Injury

Background and Purpose-The pattern of antenatal brain injury varies with gestational age at the time of insult. Deep brain nuclei are often injured at older gestational ages. Having previously shown postnatal hypertonia after preterm fetal rabbit hypoxia-ischemia, the objective of this study was to investigate the causal relationship between the dynamic regional pattern of brain injury on MRI and the evolution of muscle tone in the near-term rabbit fetus. Methods-Serial MRI was performed on New Zealand white rabbit fetuses to determine equipotency of fetal hypoxia-ischemia during uterine ischemia comparing 29 days gestation (E29, 92% gestation) with E22 and E25. E29 postnatal kits at 4, 24, and 72 hours after hypoxia-ischemia underwent T2- and diffusion-weighted imaging. Quantitative assessments of tone were made serially using a torque apparatus in addition to clinical assessments. Results-Based on the brain apparent diffusion coefficient, 32 minutes of uterine ischemia was selected for E29 fetuses. At E30, 58% of the survivors manifested hind limb hypotonia. By E32, 71% of the hypotonic kits developed dystonic hypertonia. Marked and persistent apparent diffusion coefficient reduction in the basal ganglia, thalamus, and brain stem was predictive of these motor deficits. Conclusions-MRI observation of deep brain injury 6 to 24 hours after near-term hypoxia-ischemia predicts dystonic hypertonia postnatally. Torque-displacement measurements indicate that motor deficits in rabbits progressed from initial hypotonia to hypertonia, similar to human cerebral palsy, but in a compressed timeframe. The presence of deep brain injury and quantitative shift from hypo-to hypertonia may identify patients at risk for developing cerebral palsy. (Stroke. 2012;43:2757-2763.)

Mesenchymal stem cells with rhBMP-2 inhibits the growth of canine osteosarcoma cells

Background: The bone morphogenetic proteins (BMPs) belong to a unique group of proteins that includes the growth factor TGF-beta. BMPs play important roles in cell differentiation, cell proliferation, and inhibition of cell growth. They also participate in the maturation of several cell types, depending on the microenvironment and interactions with other regulatory factors. Depending on their concentration gradient, the BMPs can attract various types of cells and act as chemotactic, mitogenic, or differentiation agents. BMPs can interfere with cell proliferation and the formation of cartilage and bone. In addition, BMPs can induce the differentiation of mesenchymal progenitor cells into various cell types, including chondroblasts and osteoblasts. The aim of this study was to analyze the effects of treatment with rhBMP-2 on the proliferation of canine mesenchymal stem cells (cMSCs) and the tumor suppression properties of rhBMP-2 in canine osteocarcoma (OST) cells. Osteosarcoma cell lines were isolated from biopsies and excisions of animals with osteosarcoma and were characterized by the Laboratory of Biochemistry and Biophysics, Butantan Institute. The mesenchymal stem cells were derived from the bone marrow of canine fetuses (cMSCs) and belong to the University of Sao Paulo, College of Veterinary Medicine (FMVZ-USP) stem cell bank. After expansion, the cells were cultured in a 12-well Transwell system; cells were treated with bone marrow mesenchymal stem cells associated with rhBMP2. Expression of the intracytoplasmic and nuclear markers such as Caspase-3, Bax, Bad, Bcl-2, Ki-67, p53, Oct3/4, Nanog, Stro-1 were performed by flow citometry. Results: We evaluated the regenerative potential of in vitro treatment with rhBMP-2 and found that both osteogenic induction and tumor regression occur in stem cells from canine bone marrow. rhBMP-2 inhibits the proliferation capacity of OST cells by mechanisms of apoptosis and tumor suppression mediated by p53. Conclusion: We propose that rhBMP-2 has great therapeutic potential in bone marrow cells by serving as a tumor suppressor to increase p53 and the pro-apoptotic proteins Bad and Bax, as well as by increasing the activity of phosphorylated caspase 3. Study design: Canine bone marrow mesenchymal stem cells associated with rhBMP2 in canine osteosarcoma treatment: "in vitro" study

Postnatal longitudinal evaluation of children diagnosed with prenatal hydronephrosis: insights in natural history and referral pattern

Objectives Clinical significance and management of prenatal hydronephrosis (PNH) are sources of debate. Existing studies are flawed with biased cohorts or inconsistent follow-up. We aimed to evaluate the incidence of pathology in a large cohort of PNH and assess the biases and outcomes of this population. Methods We reviewed 1034 charts of fetuses with PNH. Records of delivered offspring were reviewed at a pediatric center and analyzed with respect to prenatal and postnatal pathology and management. Results Prenatal resolution of hydronephrosis occurred in 24.7% of pregnancies. On first postnatal ultrasound, some degree of dilatation was present in 80%, 88% and 95% of mild, moderate and severe PNH cases, respectively. At the end of follow-up, hydronephrosis persisted in 10%, 25% and 72% of children, respectively. Incidence of vesicoureteral reflux did not correlate with severity of PNH. Children with postnatal workup had more severe PNH than those without. Conclusions Despite prenatal resolution totalizing 25%, pelvic dilatation persisted on first postnatal imaging in most cases, thus justifying postnatal ultrasound evaluation. Whereas most mild cases resolved spontaneously, a quarter of moderate and more than half of severe cases required surgery. Patients with postnatal imaging and referral had more severe PNH, which could result in overestimation of pathology. (c) 2012 John Wiley & Sons, Ltd.

Derivation and characterization of progenitor stem cells from canine allantois and amniotic fluids at the third trimester of gestation

Fetal tissues are frequently discarded before (amniocentesis) or after birth, which both facilitates stem cell access and helps to overcome ethical concerns. In the present study, we aimed to isolate and characterize stem cells from the allantoic and amniotic fluids (ALF; AMF) of third trimester canine fetuses. This gestation age has not been previously explored for stem cells isolation. The gestational age, cell culture conditions and method of isolation used in this study allowed for the establishment and efficient expansion of ALF and AMF cells. We showed that the majority of ALF and ALF cells express the stem cell markers, such as vimentin, nestin and cytokeratin 18 (CK18). Under appropriate culture conditions AMF derived cells can undergo differentiation into osteogenic, adipogenic, chondrogenic and neuron-like lineages. ALF derived cells showed adipogenic, and chondrogenic potential. Therefore, ALF and AMF cells derived at the third gestation trimester can be qualified as progenitor stem cells, accordingly referred as (alantoic fluid progenitor/stem) ALF PS cells and (amniotic fluid progenitor/stem) AMF PS cells. (C) 2012 Elsevier Ltd. All rights reserved.

Effects of daily intake of zidovudine-stavudine on rat pregnancy outcome: biological essay

Purpose: To evaluate the effects at term of a highly active antiretroviral drug association when administered for the whole period of rat pregnancy. Methods: Forty pregnant rats weighing about 200 g were randomly divided into four groups: a control group (Ctr = drug vehicle control, n = 10) and three experimental groups. which were treated with an oral solution of zidovudine-stavudine (Exp1x = 10/1 mg/kg b.w., n = 10; Exp3x = 30/3 mg/kg b.w., n = 10; Exp9x = 90/9 mg/kg b.w., n = 10) from "day 0" up to the 20th day of pregnancy. Maternal body weights were recorded at the start of the experiment and on the 7th, 14th and 20th day thereafter. At term (20th day) the rats were anesthetized and submitted to hysterotomy. Implantations, reabsorptions, living fetuses, placentae and intrauterine deaths were looked for and recorded. The collected fetuses and placentae were weighed and the concepts were examined by a stereoscopic microscope looking for external malformations. Results: No significant alterations due to the antiretroviral drug treatment could be detected regarding the number of implantations, fetuses, placentae, absorptions and malformations nor regarding maternal and fetal mortality. Conclusions: Administration of the association zidovudine/stavudine for the whole period of rat pregnancy did not interfere with the maternal, fetal and placental weight gain as well as abnormalities detectable by the employed methodology.

Fetal Pulmonary Response After Fetoscopic Tracheal Occlusion for Severe Isolated Congenital Diaphragmatic Hernia

OBJECTIVE: To estimate the response in lung growth and vascularity after fetal endoscopic tracheal occlusion for severe congenital diaphragmatic hernia in the prediction of neonatal survival. METHODS: Between January 2006 and December 2010, fetal lung parameters (observed-to-expected lung-to-head ratio; observed-to-expected lung volume; and contralateral lung vascularization index) were evaluated before fetal tracheal occlusion and were evaluated longitudinally every 2 weeks in 72 fetuses with severe isolated congenital diaphragmatic hernia. Thirty-five fetuses underwent fetal endoscopic tracheal occlusion and 37 cases did not. RESULTS: Survival rate was significantly higher in the fetal endoscopic tracheal occlusion group (54.3%) than in the no fetal endoscopic tracheal occlusion group (5.4%, P<.01). Fetal endoscopic tracheal occlusion resulted in a significant improvement in fetal lung size and pulmonary vascularity when compared with fetuses that did not go to the fetal intervention (increase of the observed-to-expected lung-to-head ratio, observed-to-expected total lung volume, and contralateral pulmonary vascularization index 56.2% compared with 0.3%, 37.9% compared with 0.1%, and 98.6% compared with 0.0%, respectively; P<.01). Receiver operating characteristic curves indicated that the observed-to-expected total fetal lung volume was the single best predictor of neonatal survival before fetal endoscopic tracheal occlusion (cutoff 0.23, area under the curve [AUC] 0.88, relative risk 5.3, 95% confidence interval [CI] 1.4-19.7). However, the contralateral lung vascularization index at 4 weeks after fetal endoscopic tracheal occlusion was more accurate in the prediction of neonatal outcome (cutoff 24.0%, AUC 0.98, relative risk 9.9, 95% CI 1.5-66.9) with the combination of observed-to-expected lung volumes and contralateral lung vascularization index at 4 weeks being the best predictor of outcome (AUC 0.98, relative risk 16.6, 95% CI 2.5-112.3). CONCLUSION: Fetal endoscopic tracheal occlusion improves survival rate by increasing the lung size and pulmonary vascularity in fetuses with severe congenital diaphragmatic hernia. The pulmonary response after fetal endoscopic tracheal occlusion can be used to predict neonatal survival. (Obstet Gynecol 2012; 119: 93-101) DOI: 10.1097/AOG.0b013e31823d3aea

Análise dos resultados maternos e fetais dos procedimentos invasivos genéticos fetais: um estudo exploratório em Hospital Universitário

OBJETIVO: Caracterizar as indicações das gestantes que procuraram o serviço de Medicina Fetal do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo para realização de procedimentos invasivos diagnósticos e avaliar os resultados dos cariótipos fetais e de suas gestações. MÉTODOS: Estudo observacional retrospectivo das gestantes que realizaram biópsia de vilo corial (BVC), amniocentese e cordocentese no período de fevereiro de 2005 a dezembro de 2009. Não foram incluídos outros procedimentos diagnósticos ou procedimentos terapêuticos. O resultado da gestação foi obtido através de consulta de prontuário eletrônico e/ou físico e/ou contato telefônico. RESULTADOS: Foram realizados 713 procedimentos (113 BVC, 340 amniocenteses e 260 cordocenteses). A principal indicação para a realização dos procedimentos invasivos foi a presença de alterações estruturais nos fetos, seguido por valores aumentados da translucência nucal e pela idade materna avançada. O cariótipo fetal esteve alterado em 186 casos (26,1%). A trissomia do cromossomo 18 foi a aneuploidia mais comum, seguida pela trissomia do 21, a monossomia do X e a trissomia do cromossomo 13. Ocorreram 4,9% de abortamento, 25,7% de natimortos e 13% de neomortos. Oito gestantes optaram pela interrupção judicial, e 99% das gestantes cujos fetos não apresentavam malformação e que apresentavam cariótipo fetal normal tiveram nativivos.

Distribuição do nervo ibular comum em fetos de equinos e descrição anatômica de pontos para bloqueio anestésico

Analisou-se a distribuição do nervo fibular comum em 30 fetos de equinos, sem raça definida, provenientes do acervo do Laboratório de Anatomia Animal da Faculdade de Medicina Veterinária da Universidade Federal de Uberlândia, que foram injetados e conservados em solução aquosa de formaldeído a 10%. Contatou-se que o referido nervo deriva do isquiático, divide-se em nervos fibulares superficial e profundo, distribuindo-se para os músculos extensores lateral e longo do dedo, fibular terceiro e tibial cranial. Traçando-se uma linha imaginária na região médio-lateral da tuberosidade do osso tíbia, o nervo fibular comum pode ser bloqueado em sua parte proximal, no terço caudal, entre o tendão de inserção do músculo bíceps femoral e a face lateral do músculo gastrocnêmio lateral (terço médio); e o nervo fibular profundo, na parte proximal da tíbia, crânio-distalmente ao fibular comum. O bloqueio do nervo fibular superficial pode ser realizado em duas regiões da tíbia: na proximal, considerando-se a linha imaginária, distalmente ao ponto citado para o fibular comum e caudalmente ao descrito para o fibular profundo; e na distal, na face lateral da articulação tíbio-társica, entre os tendões de inserção dos músculos extensores lateral e longo do dedo.

Percutaneous laser ablation under ultrasound guidance for fetal hyperechogenic microcystic lung lesions with hydrops: a single center cohort and a literature review

Objective To evaluate the perinatal outcomes in hydropic fetuses with congenital microcystic pulmonary lesions that underwent percutaneous, invasive, laser therapy. Method This retrospective study reviews the literature and our experience between 2004 and 2010. Characteristics of the cystic lung lesions, liquor volume (presence of polyhydramnios or not), localization of ablation (vascular vs interstitial) and gestational age at which the procedure was performed were related to outcome (survival). Results In total, 16 fetuses with congenital lung lesions underwent invasive percutaneous laser ablation, seven performed in our center and nine published cases. Survival rate was higher in fetuses with a subsequent postnatal diagnosis of bronchopulmonary sequestration (87.5%) compared with congenital adenomatoid malformation (28.6%; p?=?0.04). The technique of vascular ablation was more successful (100%) than interstitial ablation (25.0%, p?<?0.01). Conclusion Percutaneous vascular laser ablation seems to be effective for bronchopulmonary sequestration in hydropic fetuses. Outcomes were worst following interstitial ablation for microcystic congenital adenomatoid with hydrops. (C) 2012 John Wiley & Sons, Ltd.

Linear and nonlinear measures of fetal heart rate patterns evaluated on very short fetal magnetocardiograms

We analyzed the effectiveness of linear short- and long-term variability time domain parameters, an index of sympatho-vagal balance (SDNN/RMSSD) and entropy in differentiating fetal heart rate patterns (fHRPs) on the fetal heart rate (fHR) series of 5, 3 and 2 min duration reconstructed from 46 fetal magnetocardiograms. Gestational age (GA) varied from 21 to 38 weeks. FHRPs were classified based on the fHR standard deviation. In sleep states, we observed that vagal influence increased with GA, and entropy significantly increased (decreased) with GA (SDNN/RMSSD), demonstrating that a prevalence of vagal activity with autonomous nervous system maturation may be associated with increased sleep state complexity. In active wakefulness, we observed a significant negative (positive) correlation of short-term (long-term) variability parameters with SDNN/RMSSD. ANOVA statistics demonstrated that long-term irregularity and standard deviation of normal-to-normal beat intervals (SDNN) best differentiated among fHRPs. Our results confirm that short-and long-term variability parameters are useful to differentiate between quiet and active states, and that entropy improves the characterization of sleep states. All measures differentiated fHRPs more effectively on very short HR series, as a result of the fMCG high temporal resolution and of the intrinsic timescales of the events that originate the different fHRPs.