Clinical phenotype and genetic analysis of a fetus with Glutaracidemia type II C / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical phenotype and genetic variants of a fetus with Glutaracidemia type II C (GA II C).@*METHODS@#Clinical data of a 32-year-old pregnant woman and her fetus with GA II C diagnosed at the Third Affiliated Hospital of Zhengzhou University in December 2021 due to the enlargement and enhanced echo of the kidneys and oligohydramnios fluid at 17 weeks were analyzed retrospectively. Amniotic fluid sample of the fetus and peripheral blood samples of the couple were collected for whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Copy number variation (CNV) was detected by using low-coverage whole genome sequencing (CNV-seq).@*RESULTS@#At 18 weeks' gestation, ultrasound revealed that the fetus had enlargement and enhanced echo of the kidneys along with no echo of renal parenchymal tubular fissure and oligohydramnios. MRI at 22 weeks' gestation confirmed that both kidneys were enlarged with uniformly increased abnormal T2 signal and decreased DWI signal. The volume of both lungs was small, with slightly higher T2 signal. No CNV was detected in the fetus. WES revealed that the fetus has harbored compound heterozygous variants of the ETFDH gene, namely c.1285+1G＞A and c.343_344delTC, which were inherited from its father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+PM2_Supporting+PS3_Supporting; PVS1+PM2_Supporting+PM3).@*CONCLUSION@#The c.1285+1G＞A and c.343_344delTC compound heterozygous variants of the ETFDH gene probably underlay the disease in this fetus. Type II C glutaric acidemia may manifest as bilateral kidney enlargement with enhanced echo and oligohydramnios. Discovery of the c.343_344delTC has enriched the spectrum of ETFDH gene variants.

Analysis of clinical phenotype and pathogenic variant of a fetus with Cornelia de Lange syndrome type II / 中华医学遗传学杂志

OBJECTIVE@#To explore the prenatal ultrasonographic features and genetic basis for an abortus suspected for type II Cornelia de Lange syndrome (CdLS2).@*METHODS@#A fetus diagnosed with CdLS2 at the Shengjing Hospital Affiliated to China Medical University on September 3, 2019 was selected as the study subject. Clinical data of the fetus and family history was collected. Following induced labor, whole exome sequencing was carried out on the abortus. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#Prenatal ultrasonography (33 weeks of pregnancy) has revealed multiple anomalies in the fetus, which included slightly widened cavity of septum pellucidum, blurred corpus callosum, slightly reduced frontal lobe volume, thin cortex, fusion of lateral ventricles, polyhydramnios, small stomach bubble, and digestive tract atresia. Whole exome sequencing has revealed a heterozygous c.2076delA (p.Lys692Asnfs*27) frameshifting variant in the SMC1A gene, which was found in neither parent and was rated as pathogenic based on the guidelines of American College of Medical Genetics and Genomics (ACMG).@*CONCLUSION@#The CdLS2 in this fetus may be attributed to the c.2076delA variant of the SMC1A gene. Above finding has provided a basis for genetic counseling and assessment of reproductive risk for this family.

Comparison of results of prenatal diagnosis by different techniques for fetuses with increased nuchal translucency / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of chromosomal microarray analysis (CMA) and trio-whole exome sequencing (trio-WES) for fetuses with increased nuchal translucency (NT) thickness.@*METHODS@#Sixty two pregnant women who had visited Urumqi Maternal and Child Care Health Hospital between June 2018 and June 2020 for NT ≥ 3.0 mm at 11 ~ 13+6 gestational weeks were selected as study subjects. Relevant clinical data were collected. The patients were divided into 3.0 ~ ＜3.5 mm (n = 33) and ≥3.5 mm groups (n = 29). Chromosome karyotyping analysis and chromosomal microarray analysis were carried out. And trio-WES analysis was performed on 15 samples with NT thickening but negative CMA results. The distribution and incidence of chromosomal abnormalities in the two groups were compared by using chi-square test.@*RESULTS@#The median age of the pregnant women was 29 years old (22 ~ 41 years old), the median thickness of NT was 3.4 mm (3.0 ~ 9.1 mm), and the median gestational age at the detection was 13+4 weeks (11+5 ~ 13+6 weeks). Chromosome karyotyping analysis has detected 12 cases of aneuploidies and 1 case of derivative chromosome. The detection rate was 20.97% (13/62). CMA has detected 12 cases of aneuploidies, 1 case of pathogenic CNV and 5 cases of variant of uncertain significance (VUS), with a detection rate of 29.03% (18/62). The aneuploidy rate for the NT ≥ 3.5 mm group was higher than that for the 3.0 ≤ NT < 3.5 mm group [3.03% (1/33) vs. 41.38% (12/29), χ² = 13.698, P < 0.001]. There was no statistically significant difference between the two groups in the detection rate of fetal pathogenic CNV and VUS (χ² = 0.028, P > 0.05). Trio-WES analysis of 15 samples with negative CMA result and no structural abnormality has identified 6 heterozygous variants, including SOS1: c.3542C>T (p.A1181V) and c.3817C>G (p.L1273V), COL2A1: c.436C>T (p.P146S) and c.3700G>A (p.D1234N), LZTR1: c.1496T>C (p.V499A), and BRAF: c.64G>A (p.D22N), respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), all of the variants were rated as VUS.@*CONCLUSION@#NT thickening can indicate chromosome abnormality, and CMA and trio-WES may be used for the prenatal diagnosis.

Prenatal diagnosis and genetic analysis of three fetuses with duodenal atresia or stenosis / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for three fetuses with duodenal atresia or stenosis detected by ultrasonography.@*METHODS@#Clinical data of three fetuses identified at the Women's Hospital Affiliated to Zhejiang University School of Medicine between January 2021 and August 2022 were collected. Umbilical cord blood and amniotic fluid samples of the fetuses and peripheral blood samples of their parents were collected and subjected to G-banded chromosomal karyotyping and single nucleotide polymorphism array (SNP array) analysis.@*RESULTS@#Prenatal ultrasound of the three fetuses revealed duodenal atresia or stenosis. No karyotypic abnormality was detected, whilst SNP array has identified 1.4 ~ 1.9 Mb duplications at 17q12 in all of them, which were all predicted to be pathogenic copy number variations (CNVs).@*CONCLUSION@#The 17q12 duplications probably underlay the duodenal atresia and stenosis in these fetuses, and chromosomal CNVs should be considered in duodenal atresia and stenosis.

Clinical features and genetic analysis of two fetuses with ring chromosome 21 mosaicism / 中华医学遗传学杂志

OBJECTIVE@#To investigate the perinatal clinical phenotype and genetic characteristics of two fetuses with ring chromosome 21 mosaicisms.@*METHODS@#Two fetuses who were diagnosed at the Xiamen Maternal and Child Health Care Hospital in November 2021 were selected as the study subjects. Clinical data of the two fetuses were collected. Conventional G-banded karyotyping and chromosomal microarray analysis (CMA) were carried out for the fetuses and their parents.@*RESULTS@#Prenatal ultrasonography of fetus 1 has revealed absence of nasal bone, ventricular septal defect, persistent left superior vena cava, and mild tricuspid regurgitation. Chromosomal karyotyping was 46,X?,dic r(21;21)(p12q22;q22p12)[41]/45,X?,-21[9]. CMA has revealed a 30.00 Mb quadruplication at 21q11.2q22.3 and a 3.00 Mb deletion at 21q22.3. For fetus 2, ultrasonography has revealed pointed echo of the nasal bone. The fetus was found to have a karyotype of 46,X?,r(21)(p12q22)[83]/45,X?,-21[14]/46,X?,dic r(21;21)(p12q22;q22p12)[3]. CMA has revealed a 5.10 Mb quadruplication at 21q22.12q22.3 and a 2.30 Mb deletion at 21q22.3.@*CONCLUSION@#The perinatal phenotype of the two fetuses with ring chromosome 21 mosaicisms is related to the duplication of chromosomal segments near the breakpoints of the chromosomal deletions. The combined chromosomal karyotyping and CMA has enabled prenatal diagnosis and genetic counseling for these families.

Prevalence and clinical significance of fetal tricuspid regurgitation during the third trimester of pregnancy / Prevalência e significado clínico da regurgitação tricúspide em fetos no terceiro trimestre da gestação

Abstract Objectives: the aim of this study was to determine the prevalence of fetal tricuspid valve regurgitation (TR) during the third trimester of low-risk pregnancies and to assess its clinical significance on neonates. Methods: this is a cross-sectional study including 330 singleton fetuses referred for routine fetal echocardiography during 3rd trimester in a fetal medicine center in Recife, Brazil. The presence and degree of tricuspid regurgitation were analyzed. Whenever TR was identified on fetal echocardiography, postnatal data, including the results of postnatal echocardiography were reviewed. Results: the prevalence of tricuspid regurgitation was 10.0% (n=33) in the study population. Regarding regurgitation degree, 90.9% (n=30) presented mild regurgitation and none presented important TR. Postnatal data was obtained from 21 neonates. Twenty of them were discharged without any complications, and one presented respiratory distress due to prematurity. Transthoracic echocardiography was performed in 66.7% (n=14) of the neonates and it was normal in 92.9% (n=13) of them. One neonate, 7.1%, persisted with tricuspid regurgitation, but had no other findings. Conclusions: tricuspid regurgitation in fetuses with normal cardiac anatomy during the 3rd trimester is a common condition in low-risk pregnancies, and is not associated with cardiac abnormalities or need for neonatal intervention.

Resumo Objetivos: determinar a prevalência da regurgitação tricúspide (RT) em fetos no terceiro trimestre de gestações de baixo risco e investigar sua repercussão clínica nos recémnascidos. Métodos: trata-se de um estudo transversal incluindo 330 fetos encaminhados para realização de ecocardiograma fetal de rotina no terceiro trimestre da gestação num centro de medicina fetal em Recife, Brasil. A presença e o grau de insuficiência tricúspide foram estudados. Quando RT estava presente ao ecocardiograma fetal dados pós-natais, incluindo ecocardiograma, também foram analisados. Resultados: a prevalência de RT foi de 10,0% na população estudada, sendo que 90,9% (n=30) dos casos foram classificados como RT leve, e nenhum caso de RT importante foi identificado. Foram obtidos dados pós-natais de 21 recém-nascidos. Destes, 20 receberam alta hospitalar sem nenhuma complicação, enquanto 1 apresentou desconforto respiratório associado à prematuridade. Ecocardiograma transtorácico foi realizado em 66.7% (n=14) dos recém-nascidos avaliados, e foi normal em 92.9% (n=13) deles. Apenas 1 recém-nascido, 7.1%, persistiu com RT mas sem outros achados significativos. Conclusões: a RT em fetos com anatomia cardíaca normal é comum no terceiro trimestre de gestações de baixo risco e não parece associar-se a anomalias cardíacas ou necessidade de intervenção no período neonatal.

Application of whole exome sequencing technology in fetuses with congenital structural abnormalities / 中华医学遗传学杂志

OBJECTIVE@#To investigate the application value of whole exome sequencing technology in fetuses with congenital structural abnormalities.@*METHODS@#The chromosomal abnormalities of 1147 families were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in late pregnancy or after birth were reanalyzed. Subgroups were divided according to the organs involved and whether single malformation or not. The gene regulatory network map was drawn by using string database and Cytoscape software. Fisher exact probability method was used to compare the difference of the diagnostic rate of pathogenic genes among the groups.@*RESULTS@#A total of 160 fetal cases received positive molecular diagnosed, involving 178 variant sites of 125 pathogenic genes, including 8 cases (4.9%, 8/163) by data reanalysis, and the overall positive diagnosis rate was 13.9%. Diagnostic rate was highest in the group of skeletal malformation (31.5%, 39/124) and lowest in that with thoracic malformation (0, 0/32). The gene clusters of fetal edema and intrauterine growth restriction were independent, and were not associated with the major structural malformations. The probability of each parent carrying the same recessive gene variant was 0.03 (39/1146) and 0.08 (4/53) with positive family history.@*CONCLUSION@#For fetuses with congenital structural abnormalities that are negative for conventional genetic tests, 13.9% of phenotypic associated pathogenic/likely pathogenic genetic variants can be detected by whole exome sequencing technology. Its application value for prenatal diagnosis varies in fetus with different organs involved. Reanalysis of sequencing data for cases with new phenotypes in late pregnancy or after birth can further improve the molecular diagnosis rate. Further investigations are needed to explore the related genetic mechanisms.

Aortic isthmus doppler velocimetry in fetuses with intrauterine growth restriction: A literature review / Dopplervelocimetria do istmo aórtico em fetos com crescimento intrauterino restrito: Uma revisão da literatura

Abstract Intrauterine growth restriction (IUGR) is associated with poor perinatal prognosis and a higher risk of stillbirth, neonatal death, and cerebral palsy. Its detection and the evaluation of its severity by new Doppler velocimetric parameters, such as aortic isthmus (AoI), are of great relevance for obstetrical practice. The AoI is a vascular segment that represents a point of communication between the right and left fetal circulations. It is considered to be a functional arterial shunt that reflects the relationship between the systemic and cerebral impedances, and has recently been proposed as a tool to detect the status of hemodynamic balance and prognosis of IUGR in fetuses. In the present review, we noticed that in healthy fetuses, the AoI net flow is always antegrade, but in fetuses with IUGR the deterioration of placental function leads to progressive reduction in its flow until it becomes mostly retrograde; this point is associated with a drastic reduction in oxygen delivery to the brain. The more impaired the AoI flow is, the greater is the risk of impairment in the Doppler velocimetry of other vessels; and the alterations of the AoI Doppler seem to precede other indicators of severe hypoxemia. Although there seems to be an association between the presence of retrograde flow in the AoI and the risk of long-term neurologic disability, its role in the prediction of perinatal morbi-mortality remains unclear. The AoI Doppler seems to be a promising tool in the management of fetuses with IUGR, but more studies are needed to investigate its employment in clinical practice.

Resumo O crescimento intrauterino restrito (CIUR) está associado a um prognóstico perinatal adverso, com maior risco de óbito intrauterino e neonatal, bem como de paralisia cerebral. Assim, sua detecção e a determinação de sua gravidade por novos parâmetros Dopplervelocimétricos, como o istmo aórtico (IAo), são de fundamental importância na prática obstétrica. O IAo é um segmento vascular que representa um ponto de comunicação entre os sistemas circulatórios fetais esquerdo e direito. É considerado um shunt arterial funcional, capaz de refletir a relação entre as impedâncias dos circuitos cerebral e sistêmico, e foi proposto como uma ferramenta para detecção do status do equilíbrio hemodinâmico e do prognóstico de fetos com CIUR. Na presente revisão, observou-se que, em fetos saudáveis, o fluxo predominante no IAo é sempre anterógrado; mas em fetos com CIUR a deterioração do estágio de insuficiência placentária acarreta reduções progressivas no fluxo ístmico até este apresentar sentido predominantemente retrógrado e levar a uma drástica redução no aporte de oxigênio ao sistema nervoso central. Quanto mais alterado estiver o fluxo no IAo, maior a chance de haver alteração na Dopplervelocimetria de outros vasos; e as alterações no Doppler do IAo parecem preceder outros indicadores de hipoxemia severa. Embora o fluxo retrógrado no IAo pareça se correlacionar com maior risco de alteração no desenvolvimento neurológico a longo prazo, ainda não está claro o seu papel na predição de morbimortalidade perinatal. O Doppler do IAo parece ser um parâmetro promissor no manejo do CIUR; entretanto, mais estudos são necessários para avaliar seu emprego na prática clínica.

Pubic arch angle measurement by transperineal ultrasonography: a prospective cross-sectional study / Medida do ângulo do arco púbico por ultrassonografia transperineal: um estudo prospectivo transversal

Abstract Objective To evaluate the ability of the pubic arch angle (PAA) as measured by transperineal ultrasonography during labor to predict the delivery type and cephalic pole disengagement mode. Methods The present prospective cross-sectional study included 221 women in singleton-gestational labor ≥ 37 weeks with cephalic fetuses who underwent PAA measurement using transperineal ultrasonography. These measurements were correlated with the delivery type, cephalic pole disengagement mode, and fetal and maternal characteristics. Results Out of the subjects, 153 (69.2%) had spontaneous vaginal delivery, 7 (3.2%) gave birth by forceps, and 61 (27.6%) delivered by cesarean section. For the analysis, deliveries were divided into two groups: vaginal and surgical (forceps and cesarean). The mean PAA was 102 ± 7.5º (range, 79.3-117.7º). No statistically significant difference was observed in delivery type (102.6 ± 7.2º versus 100.8 ± 7.9º, p = 0.105). The occipitoanterior position was seen in 94.1% of the fetuses and the occipitoposterior position in 5.8%. A narrower PAA was found in the group of surgical deliveries (97.9 ± 9.6º versus 102.6 ± 7.3º, p = 0.049). Multivariate regression analysis showed that PAA was a predictive variable for the occurrence of head disengagement in occipital varieties after birth (odds ratio, 0.9; 95% confidence interval, 0.82-0.99; p = 0.026). Conclusion Ultrasonographic measurement of the PAA was not a predictor of delivery type, but was associated with the persistence of occipital varieties after birth.

Resumo Objetivo Avaliar a medida do ângulo do arco púbico (AAP) por ultrassonografia transperineal durante trabalho de parto em predizer tipo de parto e modo de desprendimento do polo cefálico. Métodos Um estudo prospectivo transversal foi conduzido com 221 mulheres em trabalho de parto com gestação única ≥ 37 semanas, com fetos em apresentação cefálica, foram submetidas à avaliação ultrassonográfica por via transperineal para aferição do AAP. Correlações com tipo de parto, modo de desprendimento do polo cefálico e características fetais e maternas foram realizadas. Resultados Um total de 153 (69,2%) mulheres apresentaram parto vaginal espontâneo, 7 (3,2%) parto a fórceps e 61 (27,6%) parto cesárea. Para fins de análise, dividiu-se os partos em dois grupos: partos vaginais e cirúrgicos (fórceps e cesáreas). A média do AAP foi 102 ± 7,5º (variação: 79,3-117,7º). Não foi observada significância estatística do AAP em relação ao tipo de parto (102,6 ± 7,2º versus 100,8 ± 7,9º; p = 0,105). Um total de 94,1% dos fetos desprenderam em variedade de posição occipito anterior e 5,8% em occipito posterior. Encontrou-se AAP mais estreitado no grupo de partos cirúrgicos (97,9 ± 9,6º versus 102,6 ± 7,3º; p = 0,049). A análise de regressão multivariada demonstrou que AAP foi uma variável de proteção para a ocorrência de desprendimento da cabeça em variedades occipito posteriores ao nascimento (odds ratio [OR]= 0,9; índice de confiança (IC) 95%: 0,82-0,99; p = 0,026). Conclusão A medida ultrassonográfica do AAP não foi preditora do tipo de parto, porém demonstrou associação com persistência de variedades occipito posteriores ao nascimento.

Frequency of congenital anomalies in the Brazilian midwest and the association with maternal risk factors: case-control study / Frequência das anomalias congênitas no centro-oeste brasileiro e a associação com fatores de risco materno: estudo caso-controle

Abstract Objective To evaluate the frequency of structural congenital anomalies (CAs) in the midwest of Brazil and its association with maternal risk factors. Methods This was a prospective, observational, case-control study based on a hospital population. Pregnant women attended at a fetal medicine service in Brazil were analyzed in the period from October 2014 to February 2016.A total of 357 pregnant women were included, 223 of whom had fetuses with structural anomalies (group case), and 134 of whom had structurally normal fetuses (control group). The clinical history was made previous to prenatal consultation, and the diagnosis of the structural CA was performed through ultrasound. Results A frequency of 64.27% (n = 223) of pregnant women with fetuses with structural anomalies was observed. The most frequent structural CAs were those of the central nervous system (30.94%), followed by anomalies of the genitourinary system (23.80%), and, finally, by multiple CAs (16.60%). The background of previous children with CAs (odds ratio [OR]: 3.85; p = 0.022), family history (OR: 6.03; p = < 0.001), and consanguinity between the progenitors (OR: 4.43; p = 0.034) influenced the occurrence of structural CA. Conclusion The most frequent CAs are those of the central nervous system, followed by those of the genitourinary system, and then multiple anomalies. The maternal risk factors that may have influenced the occurrence of structural CA were previous children with CA, family history, and consanguinity among the parents.

Resumo Objetivo Avaliar a frequência de anomalias congênitas (ACs) estruturais no centro-oeste brasileiro e a associação com fatores de risco maternos. Métodos Estudo prospectivo, observacional, caso-controle, baseado em uma população hospitalar. Foram analisadas gestantes atendidas em um serviço de medicina fetal no Brasil, no período de outubro de 2014 a fevereiro de 2016. Foram analisadas 357 gestantes, dentre as quais 223 tiveram fetos com ACs estruturais (grupo controle) e 134 tiveram fetos estruturalmente normais (grupo controle). A história clínica foi feita antes da consulta de pré-natal, e o diagnóstico da AC estrutural foi realizado por ultrassonografia. Resultados Observou-se uma frequência de 64,27% (n = 223) de gestantes com fetos com ACs estruturais. As ACs estruturais mais frequentes foram as do sistema nervoso central (30,94%), seguidas das anomalias do sistema gênito-urinário (23,80%), e, por fim, das ACs múltiplas (16,60%). Antecedentes de crianças com AC (razão de probabiliade [RP]: 3,85; p = 0,022), antecedentes familiares (RP: 6,03; p = < 0,001), e consanguinidade entre os grupos progenitores (RP: 4,43; p = 0,034) influenciaram a ocorrência de AC estrutural. Conclusão As ACs mais frequentes foram as do sistema nervoso central, as do sistema gênito-urinário, e as ACs múltiplas. Os fatores de risco maternos que podem ter influenciado a ocorrência de AC estrutural foram antecedentes de crianças com AC, história familiar, e a consanguinidade entre os pais.

Prenatal diagnosis and genetic analysis of 17 fetuses with skeletal dysplasia / 中华医学遗传学杂志

OBJECTIVE@#To explore strategies of prenatal genetic testing for fetuses featuring abnormal skeletal development.@*METHODS@#Clinical data of 17 fetuses with skeletal dysplasia was collected. The results of genetic testing and outcome of pregnancy were analyzed.@*RESULTS@#For 12 fetuses, the femur-to-foot length ratio was less than 0.9. Thirteen fetuses had a positive finding by genetic testing. One fetus was diagnosed with chromosomal aneuploidy, three were diagnosed with microdeletion/microduplications, and nine were diagnosed with hereditary bone diseases due to pathological variants of FGFR3, COL1A2, GPX4 or ALPL genes.@*CONCLUSION@#For fetuses with skeletal dysplasia characterized by short femur, in addition to chromosomal karyotyping and microarray analysis, sequencing of FGFR3 and other bone disease-related genes can improve the diagnostic rate.

Fetal structural anomalies diagnosed during the first, second and third trimesters of pregnancy using ultrasonography: a retrospective cohort study

ABSTRACT BACKGROUND: The prevalence of congenital abnormalities in general populations is approximately 3-5%. One of the most important applications of obstetric ultrasound is in detection of fetal structural defects. OBJECTIVE: To assess fetal structural anomalies diagnosed using ultrasound in the three trimesters of pregnancy. DESIGN AND SETTING: Retrospective cohort study at the Mário Palmério University Hospital of the University of Uberaba (Universidade de Uberaba, UNIUBE), from March 2014 to December 2016. METHODS: Ultrasound data at gestational weeks 11-13 + 6, 20-24 and 32-36 were recorded to identify fetal anomalies in each trimester and in the postnatal period. The primary outcome measurements were sensitivity, specificity, positive predictive value and negative predictive value for detection of fetal anomalies and their prevalence. RESULTS: The prevalence of anomalies detected using ultrasound was 2.95% in the prenatal period and 7.24% in the postnatal period. The fetal anomalies most frequently diagnosed using ultrasound in the three trimesters were genitourinary tract anomalies, with a prevalence of 27.8%. Cardiac anomalies were diagnosed more often in the postnatal period, accounting for 51.0% of all cases. High specificity, negative predictive value and accuracy of ultrasound were observed in all three trimesters of pregnancy. CONCLUSION: Ultrasound is safe and has utility for detecting fetal anomalies that are associated with high rates of morbidity and mortality. However, the low sensitivity of ultrasound for detecting fetal anomalies in unselected populations limits its utility for providing reassurance to examiners and to pregnant women with normal results.

Tumores cardiacos primarios fetales: revisión de la literatura / Primary fetal cardiac tumors: review of the literature

Los tumores cardiacos primarios fetales representan una entidad de baja incidencia en la práctica clínica. La gran mayoría corresponde a lesiones benignas, siendo el rabdomioma el tipo más común. Si bien, es frecuente la regresión espontánea de este tipo de lesiones durante el embarazo, los tumores cardiacos fetales pueden asociarse a complicaciones como obstrucción del flujo cardíaco, insuficiencia valvular, arritmias, insuficiencia cardíaca e hidrops fetal, pudiendo conducir incluso a la muerte fetal. El mayor desarrollo de técnicas imagenológicas ha permitido un aumento en el número y precisión de los diagnósticos prenatales de tumores cardiacos, generando al mismo tiempo, nuevos desafíos y alternativas en relación al abordaje terapéutico. El objetivo del presente artículo de revisión es exponer la evidencia actual en relación al diagnóstico prenatal, manejo, complicaciones y condiciones asociadas de los tumores cardiacos fetales más frecuentes.

Fetal primary cardiac tumors represent a low incidence entity in clinical practice. The vast majority corresponds to benign lesions, with rhabdomyoma being the most common type. Although spontaneous regression of this type of lesions during pregnancy is frequent, fetal cardiac tumors can be associated with complications such as obstruction of cardiac flow, valvular insufficiency, arrhythmias, heart failure and fetal hydrops, which can even lead to fetal death. The greater development of imaging techniques has allowed an increase in the number and precision of prenatal diagnoses of cardiac tumors, generating at the same time, new challenges and alternatives in relation to the therapeutic approach. The objective of this review article is to present the current evidence regarding the prenatal diagnosis, management, complications and associated condition s of the most frequent fetal cardiac tumors.

Lithopedion in a geriatric patient

Abstract Lithopedion (lithos = rock and paidion = child) is a rare condition that only occurs in 1.5 to 1.8% of extrauterine pregnancies and in 0.00045% of all pregnancies. It consists of an ectopic pregnancy in which the fetus dies but cannot be reabsorbed by the mother's body, which then coats it in a calcium-rich substance.We present the case of a 77-year-old woman with an incidental diagnosis of a lithopedion, which had been retained in her left pelvis for presumably 40 years.

Diagnóstico prenatal y manejo quirúrgico posnatal exitoso de quiste ovárico fetal / Prenatal diagnosis and successful postnatal surgical management of fetal ovarian cyst

Los quistes ováricos fetales son el tumor abdominal más frecuente en las recién nacidas. Es la tercera causa de quistes intrabdominales, después de los de sistemas renal y gastrointestinal. Se puede sospechar su presencia en la ecografía cuando se observa una tumoración de aspecto quístico de estructura regular localizado en la parte inferior y lateral del abdomen, del tracto intestinal o urinario en un feto femenino sin anomalías. Presentan complicaciones agudas y a largo plazo. La más frecuente es la torsión anexial que presenta dificultades diagnósticas en la etapa neonatal. El diagnóstico prenatal es fundamental para el manejo oportuno de las pacientes. Existen diferentes alternativas terapéuticas donde la cirugía mínimamente invasiva y conservadora juega un importante rol. El objetivo del trabajo es demostrar que el diagnóstico temprano de los tumores fetales interviene en el resultado exitoso. Se presenta el caso de una paciente de 37 años primigesta, a la que durante la evaluación ecográfica; se observó la presencia de una tumoración de apariencia blanda en la parte inferior derecha del abdomen correspondiente a un quiste ovárico fetal claramente identificado y separado de la vejiga fetal. La paciente fue sometida a cesárea en la que se obtuvo una recién nacida femenina. Dos días después, la neonata fue intervenida quirúrgicamente por mínimo acceso y se resolvió exitosamente gracias a un manejo multidisciplinario(AU)

Fetal ovarian cysts are the most frequent abdominal tumor in newborns. It is the third cause of intra-abdominal cysts, after those of renal and gastrointestinal systems. Its presence can be suspected on ultrasound when a cystic-like tumor of regular structure located in the lower and lateral part of the abdomen, intestinal tract or urinary tract is observed in a female fetus with no anomalies. They present acute and long-term complications. The most frequent is adnexal torsion that presents diagnostic difficulties in the neonatal stage. Prenatal diagnosis is essential for the timely management. There are different therapeutic alternatives where minimally invasive and conservative surgery are important. The objective of the work is to demonstrate that the early diagnosis of fetal tumors intervenes in the successful outcome. We present the case of a 37-year-old primiparous patient, who had a soft-appearing tumor in the lower right part of the abdomen observed by ultrasound. This corresponded to a clearly identified fetal ovarian cyst and it was separated from the fetal bladder. The patient underwent cesarean section in which a female newborn was obtained. Two days later, the neonatal was minimal-access surgically treated successfully thanks to multidisciplinary management(AU)

Presumed Zika virus-related congenital brain malformations: the spectrum of CT and MRI findings in fetuses and newborns / Malformações congênitas do encéfalo presumivelmente relacionadas ao Zika vírus: espectro de achados de RM e TC em fetos e neonatos

ABSTRACT The new epidemic of Zika virus infection raises grave concerns, especially with the increasingly-recognized link between emerging cases of microcephaly and this infectious disease. Besides small cranial dimensions, there are striking morphologic anomalies in the fetal brain. Key anomalies include cortical developmental malformations and a peculiar distribution of pathologic calcifications. These potentially indicate a new pattern of congenital central nervous system infection. Methods: Eight women underwent fetal MRI. Four infants also underwent postnatal CT. Five of the women underwent amniocentesis. Results: All neonates were born with microcephaly. On fetal MRI, ventriculomegaly, marked reduction of white matter thickness, severe sylvian fissure simplification, abnormal sulcation, and diffuse volumetric loss of cerebellar hemispheres were consistently seen. On postnatal CT, diffuse subcortical and basal ganglia calcifications were observed. The Zika virus was detected in two amniocenteses by polymerase chain reaction assays. Conclusion: We hope to assist the medical community in recognizing the spectrum of encephalic changes related to congenital Zika virus infection.

RESUMO Os novos casos epidêmicos de infecção pelo vírus Zika suscitam grande preocupação, sobretudo com o crescente reconhecimento da ligação entre casos emergentes de microcefalia e esta doença infecciosa. Além da cabeça de pequenas dimensões, existem profundas alterações morfológicas no encéfalo fetal. Anomalias mais típicas incluem malformações do desenvolvimento cortical e uma distribuição peculiar de calcificações patológicas. Estes dados potencialmente indicam um novo padrão de infecção congênita do sistema nervoso central. Métodos: Oito mulheres foram submetidas a RM fetal. Quatro crianças também realizaram TC pós-natal. Cinco mulheres foram submetidas a amniocentese. Resultados: Todos os neonatos nasceram com microcefalia. Na RM fetal, ventriculomegalia, acentuada redução da espessura da substância branca, acentuada simplificação da fissura sylviana, sulcação anormal e redução volumétrica difusa dos hemisférios cerebelares foram constantes. Na TC pós-natal, calcificações difusas subcorticais e nos núcleos da base foram observadas. O vírus Zika foi detectado por PCR em duas amniocenteses. Conclusão: Esperamos dar suporte à comunidade médica em reconhecer este padrão de imagem potencialmente específico.

Intrauterine thrombosis of umbilical artery - case report / Trombose intrauterina de artéria umbilical - relato de caso

ABSTRACT: CONTEXT: Umbilical cord thrombosis is related to greater fetal and perinatal morbidity and mortality. It is usually associated with umbilical cord abnormalities that lead to mechanical compression with consequent vascular ectasia. Its correct diagnosis and clinical management remains a challenge that has not yet been resolved. CASE REPORT: This study reports a case of umbilical artery thrombosis that occurred in the second half of a pregnancy. The umbilical cord was long, thin and overly twisted and the fetus presented severe intrauterine growth restriction. The clinical and histopathological findings from this case are described. CONCLUSIONS: This case report emphasizes the difficulty in diagnosing and clinically managing abnormalities of intrauterine life with a high chance of perinatal complications.

RESUMO: CONTEXTO: A trombose do cordão umbilical está relacionada com o aumento da morbimortalidade fetal e perinatal. É geralmente associada a alterações do cordão umbilical que levam à compressão mecânica com consequente ectasia vascular. Seu correto diagnóstico e manejo clínico é um desafio que não está ainda bem esclarecido. RELATO DE CASO: Neste relato se descreve caso de trombose da artéria umbilical de ocorrência na segunda metade da gravidez associada a cordão umbilical longo, fino, excessivamente retorcido, associado a feto com restrição de crescimento intrauterino grave. São descritos seus achados clínicos e histopatológicos correlacionados. CONCLUSÃO: Este relato de caso reforça a dificuldade diagnóstica e de manejo clínico em alteração da vida intrauterina com grande possibilidade de complicações perinatais.

Ultrasonographic evaluation of hG-CSF transgenic goat conceptus / Avaliação ultrassonográfica de conceptos transgênicos para o hG-CSF

The objective of this study was to evaluate the development of transgenic (T) goat embryos and fetuses for human Granulocyte Colony Stimulating Factor (hG-CSF) by ultrasonography. Four pregnancies in non-transgenic (NT) goats were obtained after fertilization (either fixed-time artificial insemination or natural mating) using the T male for hG-CSF. Ultrasound examinations were carried out at 30, 40 (transrectal via), 50, 60, 90 and 120 days of pregnancy (transabdominal via). Some parameters were observed such as morphology, organogenesis and formation of skeletal fetuses, viability with cardiac activity and fetuses movements. Measurements were taken of the crown-rump length, diameter of embryonic vesicle, thorax, abdomen, umbilical cord and placentomes. After parturition, DNA testing was conducted in all offspring and 4 T and 2 NT kids were identified. The conceptus started their differentiation at 40 days. The heart was detected in all examinations and the heart chambers were assessed at 50 days. Gastric compartments, liver and kidneys were observed at 60 days, the same period that all bony structures were visualized. Average values of all evaluated parameters had a gradual increase with the progression of pregnancy. T and NT goat embryos and fetuses had a similar growth and all remained viable throughout the experimental period.

O objetivo deste estudo foi avaliar o desenvolvimento de embriões e fetos transgênicos (T) para o Fator Estimulante de Colôniasde Granulócitos humano (hG-CSF) por ultrassonografia. Quatro gestações em cabras não transgênicas (NT) foram obtidas pos fecundação (inseminação artificial em tempo fixo ou monta controlada) utilizando o bode T para o hG-CSF. Exames ultrassonográficos foram realizados aos 30, 40 (via transretal), 50, 60, 90 e 120 dias de gestação (via transabdominal). Alguns parâmetros foram observados como morfologia, organogênese e formação do esqueleto fetal, viabilidade por meio de atividade cardíaca e movimento fetal. As seguintes mensurações foram realizadas: comprimento crânio caudal, diâmetro da vesícula embrionária, do tórax, do abdomen, do cordão umbilical e dos placentomas. Após o parto, o exame por PCR foi conduzido em todas as crias e 4 T e 2NT foram identificadas. O concepto iniciou sua diferenciação aos 40 dias. O coração foi detectado em todos os exames e as câmeras cardíacas foram identificadas aos 50 dias. Compartimentos gástricos, fígado e rins foram observados aos 60 dias, o mesmo período que todas as estruturas ósseas foram visualizadas. Valores médios de todos os parâmetros avaliados tiveram um aumento gradual com o avanço da gestação. Embriões e fetos T e NT tiveram um crescimento similar e todos permaneceram viáveis durante o período experimental.

Ecocardiografía fetal en el diagnóstico de malformaciones congénitas cardiacas / Fetal echocardiography as a diagnostic test of congenital heart malformations

Introducción: las cardiopatías congénitas (CC) son los defectos congénitos graves más frecuentes y una de las tres principales causas de mortalidad prenatal y perinatal. Objetivos: determinar la sensibilidad y especificidad de la ecocardiografía fetal prenatal como prueba diagnóstica de CC. Metodología: se realizó un estudio observacional, analítico de prueba diagnóstica, temporalmente retrospectivo, en mujeres de 15 y 47 años, gestantes del tercer trimestre y sus recién nacidos, internadas en la Cátedra y Servicio de Ginecología y Obstetricia, FCM-UNA, desde enero del 2006 a diciembre del 2012. Todos fueron sometidos a estudios ecococardiográficos con el ecógrafo General Electric® modelo P5 con sonda convexa C3 multifrecuencia. Resultados: se encontraron 36 casos (43,3%) de cardiopatía congénita diagnosticada por ecocardiografía fetal y 47 casos (56,6%) de cardiopatía diagnosticada por ecocardiografía en recién nacidos. Las CC más frecuentes fueron la comunicación interventricular y la comunicación interauricular. Al comparar el diagnóstico prenatal (presencia o ausencia de anomalías) con el diagnóstico postnatal (gold standard), se encontró una sensibilidad de 83,7% (IC 95% 71,5-95,9) y especificidad de 100% (IC 95% 98,7-100), respectivamente. Conclusiones: la ecocardiografía prenatal tiene una sensibilidad de 83,7% y especificidad de 100%.

Introduction: congenital heart disease (CHD ) are the most common serious birth defects and one of the three leading causes of prenatal and perinatal mortality. Objectives: To determine the sensitivity and specificity of prenatal fetal echocardiography as a diagnostic test. Method: we conducted an observational analitic study of diagnostic test, temporarily retrospective, in women aged 15 to 47 years, pregnant women in the third trimester and infants hospitalized in the Gynecology and Obstetrics Department, FCM- UNA, since January 2006 to December 2012. All patients underwent ultrasound studies with a General Electric® model C3 P5 multifrequency convex probe ecocardiograph. Results: we found 36 cases (43.3%) of congenital heart disease diagnosed by fetal echocardiography and 47 cases (56.6%) of cardiac disease diagnosed by echocardiography in neonates. The most frequent CHD were interventricular and interauricular communication. Comparing prenatal diagnosis (presence or absence of anomalies) with postnatal diagnosis (gold standard) we found a sensitivity of 83.7% (95% CI 71.5 to 95.9) and specificity of 100% (95% CI 98.7 to 100), respectively. Conclusions: prenatal echocardiography has a sensitivity of 83.7% and specificity of 100%.