Clinical phenotype and genetic analysis of a fetus with Cardiac valvular dysplasia type 1 / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus with Cardiac valvular dysplasia type 1 (CVDP1).@*METHODS@#A CVDP1 fetus identified at the Ningbo Women and Children's Hospital on July 7, 2022 was selected as the study subject. Clinical data of the fetus was collected. The fetus and its parents were subjected to trio-whole exome sequencing (trio-WES), and candidate variants were verified by Sanger sequencing.@*RESULTS@#The fetus had exhibited generalized edema, complex cardiac malformation, abdominal effusion, and enhanced intestinal and renal parenchymal echoes. Trio-WES revealed that it has harbored compound heterozygous variants of the PLD1 gene, namely c.2977C>T (p.R993*) and c.1460G>A (p.W487*), which were respectively inherited from its father and mother. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.2977C>T (p.R993*) variant was evaluated to be likely pathogenic (PVS1_Moderate+PM2_Supporting+PM3+PP4), whilst the c.1460G>A (p.W487*) variant was evaluated to be pathogenic (PVS1+PM2_Supporting+PP4).@*CONCLUSION@#The c.2977C>T (p.R993*) and c.1460G>A (p.W487*) compound heterozygous variants of the PLD1 gene probably underlay the CVDP1 in the fetus. Above discovery has enriched the mutational spectrum of the PLD1 gene and provided a guidance for genetic counseling and prenatal diagnosis in this family.

Clinical characteristics and genetic counseling for a three-generation Chinese pedigree with recurrent fetal Kabuki syndrome due to variant of KDM6A gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a pregnant woman with a history of adverse pregnancy outcomes.@*METHODS@#A woman with an adverse history of pregnancies including one fetal demise and two induced abortions due to fetal diaphragmatic hernia and complex cardiac anomalies was selected as the study subject. Muscle tissue from the induced abortus was subjected to whole exome sequencing, and candidate variant was verified by Sanger sequencing of the couple and other family members.@*RESULTS@#Genetic sequencing revealed that the fetus has harbored a frameshift variant of the KDM6A gene (NM_001291415.2), namely c.1228_1229del (p.Gln410GlufsTer2), which was inherited from the woman and her mother. The variant was unreported previously, and the woman was found to have short stature, sparse eyebrows in the outer third, peculiar facial features, but normal intelligence in addition with female congenital genital malformation, like incomplete vaginal septum, double cervix, double uterus, and unilateral ovary absence. mostly similar phenotypes observed in her mother.@*CONCLUSION@#The hemizygous c.1228_1229del variant of the KDM6A gene probably underlay the abnormalities in the fetus. All findings have enabled genetic counseling for this family featuring X-linked inheritance, and the woman had given birth to a healthy girl with appropriate prevention and intervention.

Resultado a largo plazo de una serie de fetos con agenesia aislada del septum pellucidum / Long-term postnatal outcome of fetuses with isolated agenesis of the septum pellucidum

Objetivo: Reportar el resultado a largo plazo de una serie de fetos con agenesia del septum pellucidum aislada (ASP), con medición de su quiasma óptico mediante neurosonografía fetal (NSG). Método: Se incluyeron todas las pacientes con ASP y NSG evaluadas desde el año 2008 a la fecha y con seguimiento hasta su edad escolar. En todos los casos se consignaron los datos clínicos de NSG y de resonancia magnética (RM), cuando esta se realizó. Se entrevistó telefónicamente a los padres. Resultados: Nueve pacientes cumplieron los criterios: cuatro con displasia septo-óptica (DSO) (rango de seguimiento: 5-14 años) y cinco sin DSO (rango de seguimiento: 7-10 años). Un décimo caso se excluyó por tener solo 6 meses de seguimiento. Ninguna de las ASP tuvo otra anomalía detectada en su seguimiento. Ninguno de los casos con DSO tuvo alteración del tamaño de su quiasma óptico en la NSG ni anormalidad en la vía óptica en la RM. Conclusiones: En nuestra población, el riesgo residual de DSO frente a ASP es del 44,4%. En el seguimiento, nuestra definición de ASP por NSG no tuvo falsos negativos con relación a otras anomalías de aparición posnatal, a excepción de la DSO.

Objective: To report the long-term outcome of a series of fetuses with isolated septum pellucidum agenesis (ASP) with measurement of their optic chiasm by fetal neurosonography (NSG). Method: All patients with ASP and NSG evaluated from 2008 to date and with follow-up until their school age were included. In all cases, clinical, NSG and magnetic resonance imaging (MRI) data were recorded. Parents were interviewed by telephone. Results: Nine patients met the criteria: four with septo-optic dysplasia (SOD) (follow-up range: 5-14 years) and five without SOD (follow-up range: 7-10 years). A tenth case was excluded because only 6 months of follow-up. None of the ASP cases had another anomaly detected in their follow-up. None of the cases with DSO had anomaly of the size of their optic chiasm on NSG or abnormality in the optical pathway in the MRI. Conclusions: In our population, the residual risk of DSO versus ASP is 44.4%. At follow-up, our NSG definition of ASP had no false negatives in relation to other postnatal-onset anomalies, except for SOD.

É preciso um pacto para erradicar a sífilis congênita no Estado do Rio de Janeiro / A pact is needed to eradicate congenital syphilis in the State of Rio de Janeiro

Os números mostram que os municípios do Rio de Janeiro não têm conseguido diagnosticar precisamente ou tratado adequadamente suas gestantes, resultando na infecção e mortes de bebês. A transmissão vertical é de 70 a 100% dos casos, com morte de 40% doas fetos. A sífilis congênita é a mais antiga infecção congênita e a primeira pandemia com tratamento disponível no SUS, mas persiste por falta de diagnóstico e tratamento oportuno. Os casos de sífilis congênita atesta que falta qualidade às consultas. É preciso implementar esse pacto de ações na comissão Intergestores Bipartite do Rio de Janeiro: cabe à Secretaria de Estado articular com os secretários municipais o delineamento da política pública e sua implementação. (AU)

Revisión Exploratoria: Comunicación de la Articulación Temporomandibular y del Oído Medio en Fetos y Niños / Exploratory Review: Temporomandibular Joint and Middle Ear Communication in Fetuses and Infants

La Articulación temporomandibular (ATM) cumple funciones importantes para la vida; su adecuado funcionamiento se puede alterar por trastornos temporomandibulares (TTM). La sintomatología de los TTM es variada, entre ellos se encuentra dolor en los músculos masticatorios, ruidos articulares y con menos frecuencia algunos pacientes refieren síntomas auditivos, lo que sugiere la existencia de una relación entre la ATM y el oído medio; sin embargo, esta relación no es clara. En consecuencia, el presente estudio tiene como propósito realizar una revisión de literatura para identificar los aspectos conocidos, desconocidos y controvertidos sobre la relación entre la ATM y el oído medio en niños y fetos. Se efectuó una búsqueda de la literatura en bases de datos utilizando los operadores booleanos (AND/OR) y los términos clave en inglés y en español. Se identificaron inicialmente 1080 artículos, se eliminaron los artículos duplicados y se aplicaron los criterios de inclusión y exclusión. Finalmente, se seleccionaron un total de 14 artículos que se revisaron a texto completo. Los estudios encontrados se enfocan en el desarrollo histoembriológico de la ATM y cómo ese desarrollo se da en conjunto con los componentes del oído medio. Adicionalmente, se identificaron investigaciones sobre el origen, la morfología y función del ligamento discomaleolar, el ligamento esfenomandibular y la fisura petrotimpánica como estructuras que conectan la ATM y el oído medio, pero los resultados han sido controvertidos. Se concluye que son necesarios más estudios para determinar cualquier relación anatómica y fisiológica que pueda existir entre la ATM y el sistema auditivo en fetos y niños.

SUMMARY: The temporomandibular joint (TMJ) has important functions for life; its proper functioning can be altered by temporomandibular disorders (TMD). The symptomatology of TMD is varied, including pain in the masticatory muscles, joint noises and less frequently some patients report auditory symptoms, suggesting the existence of a relationship between the TMJ and the middle ear; however, this relationship is not clear. Consequently, the present study aims to conduct a literature review to identify the known, unknown and controversial aspects of the relationship between TMJ and the middle ear in children and fetuses. A literature search was performed in databases using Boolean operators (AND/ OR) and key terms in English and Spanish. A total of 1080 articles were initially identified; duplicate articles were eliminated and inclusion and exclusion criteria were applied. Finally, a total of 14 articles were selected and reviewed in full text. The studies found focus on the histoembryological development of the TMJ and how that development occurs in conjunction with the middle ear components. Additionally, research on the origin, morphology, and function of the discomalleolar ligament, sphenomandibular ligament, and petrotympanic fissure as structures connecting the TMJ and middle ear was identified, but the results have been controversial. It is concluded that further studies are necessary to determine any anatomical and physiological relationship that may exist between the TMJ and the auditory system in fetuses and children.

Dissecação anatômica como estratégia para o estudo do sistema neural em fetos humanos / Anatomic dissection as a strategy for the study of the neural system in fetuses / Disección anatómica como estrategia para el estudio del sistema neural en fetos

Esse trabalho busca relatar o processo de confecção de peças anatômicas para o ensino da anatomia humana a partir de material cadavérico fetal. Os discentes do curso de medicina da Universidade Federal do Paraná (UFPR) ­ Campus Toledo participaram do programa de voluntariado acadêmico e deram atenção especial aos aspectos técnicos do processo de dissecação, bem como a experiência subjetiva desse procedimento como ferramenta de aprendizado ativo. O procedimento foi realizado na sala de preparação de cadáver da UFPR ­ Campus Toledo, utilizando instrumental de dissecação e cadáveres humanos fetais com 20, 17 e 14 semanas de idade gestacional, direcionado de modo a expor as partes constituintes do sistema neural. Foram confeccionadas peças de cérebro, cerebelo, tronco encefálico, medula espinal, nervos espinais e suas estruturas associadas. Os voluntários envolvidos foram capazes de produzir material de estudo de qualidade através da dissecação e fortalecer seu conhecimento em anatomia humana e aptidão manual. Também foi dada atenção à importância e às limitações do processo de dissecação como estratégia de aprendizado em cursos da área de saúde. pôde ser observado que a dissecação pode fazer parte de uma formação completa e bem estruturada dos discentes, que por sua vez irão integrar a sociedade e a academia. Além disso, a exposição da topografia neural fetal pode servir de referencial para posteriores estudos que venham a utilizar essas informações.

This work aims to report the confection process of anatomic pieces for teaching human anatomy from fetal cadaveric material. The students of the medicine course of Universidade Federal do Paraná (UFPR) ­ Campus Toledo, took part in the academic volunteer program and paid special attention to the technical aspects of the dissection process, as well as the subjective experience of this procedure as an active learning tool. The procedure was performed at the cadaver preparation room of the UFPR ­ Campus Toledo, using dissection tools and human fetal corpses of 20, 17 and 14 weeks of gestational ages, directed so as to expose the constituent parts of the neural system. Pieces of the brain, cerebellum, brainstem, spinal cord, spinal nerves, and its associated structures were made. The involved voluntaries were able to produce quality study material through dissection, and strengthen their knowledge in human anatomy and manual skill. Attention was also given to the importance and limitations of the dissection process as a learning strategy in health courses. it was observed that dissection can be part of a complete and well-structured training of students, who in turn will integrate society and academia. In addition, the exposure of fetal neural topography can serve as a reference for further studies that use this information

Este trabajo tiene como objetivo relatar el proceso de confección de piezas anatómicas para la enseñanza de la anatomía humana a partir de material cadavérico fetal. Los alumnos del curso de medicina de la Universidade Federal do Paraná (UFPR) - Campus Toledo, participaron del programa de voluntariado académico y prestaron especial atención a los aspectos técnicos del proceso de disección, así como a la vivencia subjetiva de este procedimiento como herramienta de aprendizaje activo. El procedimiento fue realizado en la sala de preparación de cadáveres de la UFPR - Campus Toledo, utilizando herramientas de disección y cadáveres de fetos humanos de 20, 17 y 14 semanas de edad gestacional, dirigidos de forma a exponer las partes constitutivas del sistema neural. Se realizaron piezas del cerebro, cerebelo, tronco encefálico, médula espinal, nervios espinales y sus estructuras asociadas. Los voluntarios participantes pudieron elaborar material de estudio de calidad mediante la disección y reforzar sus conocimientos de anatomía humana y habilidad manual. También se prestó atención a la importancia y las limitaciones del proceso de disección como estrategia de aprendizaje en los cursos de salud. Se observó que la disección puede formar parte de una formación completa y bien estructurada de los estudiantes, que a su vez integrarán la sociedad y el mundo académico. Además, la exposición de la topografía neural fetal puede servir de referencia para estudios posteriores que utilicen esta información.

Fisiología respiratoria: el pulmón al momento de nacer / Respiratory Physiology - the lung at the moment of birth

La adaptación fisiológica de los recién nacidos de la vida intrauterina a la extrauterina incluye cambios fisiológicos complejos. Para que se complete con éxito la transición fetal a neonatal, los recién nacidos deben lograr el aclaramiento de líquido pulmonar, la generación de CRF e inicio de la respiración, para permitir el intercambio de gases y la oxigenación de los tejidos. En este artículo se describen estos mecanismos, algunas bases del desarrollo pulmonar y de la circulación fetal; y las medidas que se requieren para asistir al recién nacido cuando no logran completar esta transición espontáneamente, lo que ocurre en el 5 al 10 % de los casos.

The physiological adaptation of newborns from intrauterine to extrauterine life includes complex physiological changes. For the fetal to neonatal transition to be successfully completed, neonates must achieve lung fluid clearance, FRC generation, and initiation of respiration to allow gas exchange and tissue oxygenation. This article describes these mechanisms, some bases of lung development and fetal circulation; and the measures required to assist the newborn, when they fail to complete this transition spontaneously, which occurs in the 5 to 10% of cases.

Saúde mental e abortamento voluntário na audiência pública da ADPF442/STF / Mental health and voluntary abortion in the public hearing of ADPF442/STF / Salud mental y aborto voluntario en la audiencia pública del ADPF442/STF

O estudo teve como objetivo identificar os argumentos da estratégia de persuasão dos discursos apresentados na audiência pública sobre a Arguição de Descumprimento de Preceito Fundamental-ADPF 442, realizada em 2018, cujo propósito era discutir sobre a interrupção voluntária da gravidez até a 12ª semana. Para tal, foi realizada uma pesquisa de abordagem qualitativa, analítico-descritiva e documental. O objeto de análise foi o registro da audiência, apresentado em vídeo, disponibilizado na plataforma digital YouTube, e em ata lavrada pelo STF, ambos de acesso público. A partir de uma análise do discurso, identificou-se os argumentos utilizados na estratégia de persuasão, que foram sistematizados em quatro categorias de argumentos para cada um dos dois grupos identificados: o grupo pró e o grupo contra a descriminalização do aborto. As três primeiras categorias, Saúde mental, Direito e Saúde pública, mesmo com diferenças na forma de apresentar o argumento, se repetem nos dois grupos. Todavia, a quarta categoria, Pressupostos, se diferenciou. No grupo pró descriminalização do aborto, apresentou-se como Pressupostos filosóficos e científicos, e no grupo contra, como Pressupostos morais. Por fim, a defesa da saúde mental das mulheres foi o principal argumento numa forma de humanizar o sofrimento vivido pelas que desejam abortar e não encontram o suporte do Estado para assegurar sua dignidade, cidadania e efetiva igualdade, garantidas constitucionalmente.(AU)

The study aimed to identify the arguments of the persuasion strategy of the speeches presented at the public hearing on the Action Against the Violation of Constitutional Fundamental Rights -ADPF 442, held in 2018, whose purpose was to discuss the voluntary interruption of pregnancy until the 12th week. To this end, a qualitative, analytical-descriptive, and documentary research was carried out. The object of analysis was the video recording of the hearing available on the YouTube platform, and in minutes drawn up by the STF, both of which are public. Based on a discourse analysis, the arguments used in the persuasion strategy were identified, which were systematized into four categories of arguments for each of the two identified groups: the group for and the group against the decriminalization of abortion. The first three categories, Mental Health, Law and Public Health, even with differences in the way of presenting the argument, are repeated in both groups. However, the fourth category, Assumptions, differed. In the group for the decriminalization of abortion, it was presented as Philosophical and Scientific Assumptions, whereas the group against, as Moral Assumptions. Finally, the defense of women's mental health was the main argument in a way of humanizing the suffering experienced by those who wish to have an abortion and do not find the support of the State to guarantee their dignity, citizenship, and effective equality, constitutionally guaranteed.(AU)

El estudio tuvo como objetivo identificar los argumentos de la estrategia de persuasión de los discursos presentados en la audiencia pública sobre el Argumento por Incumplimiento de un Percepto Fundamental -ADPF 442, realizada en 2018, con el objetivo de discutir la interrupción voluntaria del embarazo hasta la 12.ª semana. Para ello, se llevó a cabo una investigación cualitativa, analítico-descriptiva y documental. El objeto de análisis fue la grabación de la audiencia, que está disponible en la plataforma digital YouTube, y actas levantadas por el Supremo Tribunal Federal -STF, ambas de acceso público. A partir de un análisis del discurso se identificaron los argumentos utilizados en la estrategia de persuasión, los cuales se sistematizaron en cuatro categorías de argumentos para cada uno de los dos grupos identificados: el grupo pro y el grupo en contra de la despenalización del aborto. Las tres primeras categorías ("salud mental", "derecho" y "salud pública") aún con diferencias en la forma de presentar el argumento se repiten en ambos grupos. Pero difiere la cuarta categoría "supuestos". En el grupo a favor de la despenalización del aborto se presentó como "supuestos filosóficos y científicos", y en el grupo en contra, como "supuestos morales". Finalmente, la defensa de la salud mental de las mujeres fue el principal argumento en un intento por humanizar el sufrimiento que viven aquellas que desean abortar y no encuentran el apoyo del Estado para garantizar su dignidad, ciudadanía e igualdad efectiva, preconizadas por la Constitución.(AU)

Índice de massa corpórea de recém-nascidos de gestações de baixo risco segundo idade gestacional e sexo / Newborns' body mass index from low-risk pregnancies according to gestational age and sex

O estado nutricional e o crescimento alcançado pelo recém-nascido tem sido utilizados como marcador/indicador de riscos de morbimortalidade precoce e até de problemas em idades mais avançadas. Como consequência o Indice de Massa Corpórea (IMC) pode ser instrumento útil para esta finalidade. O objetivo foi analisar o IMC de recém-nascidos de 34 a 41 semanas completas de idade gestacional (IG) de gestações de baixo risco. Trata-se de um estudo descritivo, analítico e quantitativo, desenvolvido a partir do banco de dados do projeto "Características biométricas ao nascimento, de filhos de mulheres adultas jovens, em um município de elevado índice de desenvolvimento humano". Foram incluídos no estudo todos os RN nascidos vivos no período de maio de 2015 e março de 2018 no Hospital Universitário de Taubaté, filhos de mulheres sem morbidade, que apresentavam em seus registros: a data do parto, idade e/ou data de nascimento materna, tipo de gestação, tipo de parto, IG, sexo, peso, comprimento e perímetro craniano ao nascimento. Foram excluídos os recém-nascidos de gestações gemelares, portadores de malformações ou outras morbidades. Também foram excluídos os que apresentavam valores extremos, acima de 3 desvios padrão em relação à média ou dados inconsistentes no arquivo. Realizaram-se análises de tendência central e dispersão dos valores, além das correlações entre IG e o peso do RN, e o comprimento do RN, e análise da correlação entre IG e o IMC do RN, sempre por sexo. Além disso, foram feitas comparações entre a evolução dos valores estimados de IMC por IG e sexo e os valores publicados por Olsen et.al (2015), Brock et.al (2008) e Davidson et.al (2011) e das tendências de evolução do IMC segundo a classificação ao nascimento em: pequenos para a idade gestacional (PIG), adequados para a IG (AIG) e grandes para a IG (GIG). Dos 6.321 nascidos no período, 6.138 preencheram os critérios de inclusão, destes 3.074 (50,1%) eram do sexo masculino. Metade da população de estudo nasceu entre 38 e 40 semanas de IG, com peso AIG, comprimento entre 46,5cm e 49 cm. A prevalência de partos vaginais foi de 60,1%. A descrição dos valores de IMC, mostrou um crescimento compatível com a evolução da idade gestacional tanto para recém-nascidos do sexo masculino quanto feminino. O comportamento do IMC ao nascimento, tanto em valor absoluto quando em escore-z, mostrou diferenças entre os três grupos de classificação da adequação dos RN, com os maiores valores observados entre os GIG e os menores para os PIG, tanto em meninos quanto em meninas, segundo IG. A tendência de evolução de acordo com a IG dos valores estimados de IMC foi semelhante com a tendência dos outros autores, embora em patamares de valores absolutos distintos. A interpretação destes resultados aponta a necessidade de se desenvolver novas pesquisas para estudar o comportamento do IMC, particularmente no Brasil, para verificar se resultados do IMC semelhantes são observados também em outras cidades/Estados/regiões e confirmar o possível papel do crescimento em comprimento na produção de valores de IMC aparentemente favoráveis. Além disso é também de interesse verificar uma possível influência intergeracional nos valores de crescimento do comprimento intraútero, no nosso meio.

The nutritional status and growth of the newborn (NB) have been used as a marker/indicator of morbidity and mortality risks that may occur at more advanced ages. This study aimed to analyze NBs' body mass index (BMI) born between 33 and 41 completed weeks of gestational age (GA) of low-risk pregnancies. This descriptive, analytical, quantitative, and retrospective study was developed from the project's database "Biometric characteristics at birth, of children of young adult women, in a municipality with a high human development index". All NBs born alive from single pregnancies from adult women and were born between May 2015 and March 2018 at the University Hospital of Taubaté, who presented in their records at least the date of delivery, maternal age and/or maternal date of birth, type of pregnancy, type of delivery, gestational age (GA), sex, weight at birth, and length at birth were included in the study. Analysis of the correlation between GA and NB weight by sex was carried out by calculating the correlation coefficient and its respective significance. As well as the correlation between GA and NB length by sex and analysis of the correlation between GA and BMI of the NB by sex. Additionally, graphic comparisons were made with the evolution of BMI by GI and sex and the values published by researchers Olsen et al. (2015), Brock et al. (2008), and Davidson et al. (2011) and BMI evolution trends according to the classification at birth in small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). In the study period, 6.321 children were born, and 6,138 met the inclusion criteria, being 3,074 males and 3.064 females. Half of the study population was born between 38 and 40 weeks of gestation, with AGA birth weight, a length between 46.5cm and 49 cm, and a prevalence of 60.1% of vaginal deliveries. The description of BMI values showed growth compatible with the evolution of GA for both male and female NBs. The behavior of BMI at birth, both in absolute value and in z-scores, showed that there was a difference between the three groups for classifying the adequacy of NBs proposed by Battaglia and Lubchenco (1967), with the highest values observed among the LGA and the smallest for SGA, both for boys and girls at different GAs. The interpretation of these results also opens some perspectives for the development of new research, particularly in Brazil, to verify whether similar BMI results are also observed in other cities/states/regions, in addition to demonstrating a possible intergenerational influence and confirming the potential role of growth in length in producing favorable BMI values.

Analysis of the maternal and fetal adverse outcomes of 154 pregnant women with cesarean section in the second stage of labor / 中华妇产科杂志

Objective: To investigate the perinatal maternal and fetal adverse outcomes of cesarean section in the different duration of the second stage of labor. Methods: A retrospective cohort study was conducted on the clinical data of 154 pregnant women with singleton head pregnancy who underwent cesarean section at different times of the second stage of labor due to maternal and fetal factors in the First Affiliated Hospital of Nanjing Medical University from January 1, 2019 to December 31, 2021. According to the duration of the second stage of labor, they were divided into <2 h group (54 cases), 2-<3 h group (61 cases), and ≥3 h group (39 cases). The general data of pregnant women and neonates, preoperative maternal and neonatal conditions related to labor stages, surgical indications, surgical procedures, and perioperative maternal and neonatal adverse outcomes were compared among the three groups. Results: (1) General Information: there were no significant differences in maternal age, gravidity and parity, proportion of primipara, gestational age at delivery, body mass index before delivery, pregnancy complications, labor analgesia rate and the duration of the first stage of labor among the three groups (all P>0.05). The differences of the gender composition, birth weight and incidence of macrosomia of the three groups were also not statistically significant (all P>0.05). (2) Maternal and fetal status and surgical indications: the incidence of intrapartum fever and type Ⅱ and Ⅲ fetal heart rate monitoring in the <2 h group were higher than those in the 2-<3 h group and the ≥3 h group, and the preoperative fetal head position in the ≥3 h group was lower than that in the 2-<3 h group, with statistically significant differences (all P<0.05). The proportion of cesarean section due to "fetal distress" was 40.7% (22/54) in the <2 h group, which was higher than that in the 2-<3 h group (4.9%, 3/61) and the ≥3 h group (2.6%, 1/39). The proportions of surgical indication of "relative cephalo-pelvic disproportion" were 98.4% (60/61) and 94.9% (37/39) in the 2-<3 h group and ≥3 h group, respectively, and the surgical indication of "fetal head descent arrest" were 41.0% (25/61) and 59.0% (23/39), respectively. Compared with <2 h group [63.0% (34/54), 13.0% (7/54)], the differences were statistically significant (all P<0.05). There were no significant difference in surgical indications between 2-<3 h group and ≥3 h group (all P>0.05). (3) Intraoperative conditions and perioperative complications of cesarean section: the puerperal morbidity rate of <2 h group was 37.0% (20/54), which was higher than those of 2-<3 h group (18.0%, 11/61) and ≥3 h group (7.7%, 3/39), the difference was statistically significant (P<0.05). There were no significant differences in operation time, intraoperative blood loss, incidence of fetal head inlay, uterine incision tear, modified B-Lynch suture for uterine atony, postpartum hemorrhage, perioperative blood transfusion, preoperative hemoglobin (Hb) level, perioperative Hb change, and postoperative hospital stay among the three groups (all P>0.05). (4) Adverse neonatal outcomes: non-hemolytic neonatal hyperbilirubinemia in ≥3 h group was 35.9% (14/39), which was significantly higher than that in <2 h group (13.0%, 7/54; P<0.05). Among the neonates admitted to neonatal intensive care unit (NICU) within 1 week after birth, the proportion of neonates admitted to NICU due to neonatal hyperbilirubinemia in ≥3 h group (15/19) was significantly higher than that in <2 h group (9/17) and 2-<3 h group (10/19), and the differences were statistically significant (all P<0.05). However, there was no significant difference between the <2 h group and the 2-<3 h group (P>0.05). There was no perinatal death in the three groups. Conclusions: The rate of puerperal morbidity is higher in patients who were transferred to cesarean section within 2 hours of the second stage of labor. In the early stage of the second stage of labor, the monitoring of fetal heart rate and amniotic fluid characteristics should be strengthened, especially the presence or absence of prenatal fever. In good maternal and neonatal conditions, conversion to cesarean section after 2 hours of the second stage of labor does not significantly increase the incidence of serious adverse maternal and neonatal outcomes. For the second stage of labor more than 3 hours before cesarean section, it is necessary to strengthen the monitoring of neonatal bilirubin.

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.

Study of a fetus with confined placental mosaicism for trisomy 2 in conjunct with fetal uniparental disomy and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To carry out genetic analysis for a fetus with confined placental mosaicism (CPM) for trisomy 2 (T2) in conjunct with fetal uniparental disomy (UPD).@*METHODS@#Amniocentesis and chromosomal karyotyping was carried out for a pregnant woman with a high risk for chromosome 2 anomalies indicated by non-invasive prenatal testing (NIPT). Single nucleotide polymorphism array (SNP-array) and trio-whole exome sequencing (Trio-WES) were carried out. Ultrasonography was used to closely monitor the fetal growth. Multifocal sampling of the placenta was performed after delivery for copy number variation sequencing (CNV-seq).@*RESULTS@#The fetus was found to have a normal chromosomal karyotype. SNP-array has revealed multiple regions with loss of heterozygosity (LOH) on chromosome 2. Trio-WES confirmed the presence of maternal UPD for chromosome 2. Ultrasonography has revealed intrauterine growth restriction and oligohydramnios. Intrauterine fetal demise had occurred at 23+4 weeks of gestation. Pathological examination had failed to find salient visceral abnormality. The placenta was proved to contain complete T2 by CNV-seq.@*CONCLUSION@#T2 CPM can cause false positive result for NIPT and may be complicated with fetal UPD, leading to adverse obstetric outcomes such as intrauterine growth restriction, oligohydramnios and intrauterine fetal demise.

Genetic analysis of a fetus with mosaicism Y chromosome aberration / 中华医学遗传学杂志

OBJECTIVE@#To carry out prenatal diagnosis for a fetus with mosaicism Yq deletion.@*METHODS@#A fetus with high risk of sex chromosomes indicated by non-invasive prenatal testing (NIPT) at Tianjin Medical University General Hospital in July 2021 was selected as the study subject. Prenatal diagnosis of the fetus was performed with combined G-banded chromosomal karyotyping, fluorescence in situ hybridization (FISH), copy number variation sequencing (CNV-seq), real-time fluorescence PCR (QF-PCR), and ultrasound examination.@*RESULTS@#Analysis of the amniocytes at 23 gestational weeks had yielded a 45,X karyotype. However, FISH had shown signals of Y chromosome. Re-examination by cordocentesis had shown a mosaicism of 46,X,+mar[33]/45,X[17]. FISH showed that 69% of the cells had contained Y chromosome signals. The result of CNV-seq was seq[19]del(Y)(q11.1q12)(mos) chrY: g.13200001_ 28820000del (mosaicism rate = 64%), which suggested mosaicism for a Yq deletion, which encompassed the azoospermia factor (AZF) region. Deletion of the AZF region was verified by QF-PCR. The fetal karyotype was ultimately determined as mos46,X,del(Y)(q11.1)[33]/45,X[17]. Although ultrasound examination had shown no abnormality in the fetus, the couple had opted to terminate the pregnancy, and the induced fetus had a normal male appearance.@*CONCLUSION@#The combined use of multiple techniques is beneficial for accurate and rapid prenatal diagnosis. For fetuses with mosaicism chromosomal abnormalities, it may be difficult to accurately predict the postnatal phenotype. It is therefore necessary to further explore their genotype-phenotype correlation in order to provide better guidance upon genetic counseling.

Prenatal diagnosis of a case with Schuurs-Hoeijmakers syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus with multiple malformations.@*METHODS@#Clinical data of the fetus was collected, Amniotic fluid sample of the fetus was subjected to conventional G-banded karyotyping, low-depth whole genome copy number variants detection and whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing of the fetus and its parents.@*RESULTS@#Prenatal ultrasound scan at 21+5 gestational weeks had revealed increased nuchal thickness (9.0 mm), enhanced echos of bilateral renal parenchyma, seroperitoneum, left pleural effusion and right displacement of the heart. The mother had a previous history of terminated pregnancy for multiple fetal anomalies. No abnormality was found by conventional karyotyping and CNV analysis, though WES revealed that the fetus has harbored a de novo heterozygous c.607C>T (p.Arg203Trp) variant of the ACS1 gene (NM_018026.3), and the result was validated by Sanger sequencing.@*CONCLUSION@#Through WES and prenatal ultrasonography, the fetus was diagnosed with Schuurs-Hoeijmakers syndrome due to the heterozygous c.607C>T (p.Arg203Trp) variant of the PACS1 gene (NM_018026.3). For fetuses with multiple malformations, WES can help to reveal the genetic etiology when CNV result is negative.

Genetic analysis of two families with Short-rib thoracic dysplasia type 3 / 中华医学遗传学杂志

OBJECTIVE@#To explore the pathogenic variants and clinical classification of two fetuses with Short-rib thoracic dysplasia with or without polydactyly (SRTD).@*METHODS@#With informed consent obtained, the phenotypic characteristics of the fetuses were comprehensively examined, and genomic DNA was extracted from fetal skin tissue and peripheral blood samples of the parents with conventional phenol-chloroform method. Whole exome sequencing (WES) was carried out on both fetuses, and the candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was analyzed using bioinformatic software VarCards, and the impact of the variants on the protein structure was predicted with Swiss-Pdb-viewer.@*RESULTS@#Both fetuses were found to harbor compound heterozygous variants of the DYNC2H1 gene, including c.515C>A (p.Pro172Gln) and c.5983G>A (p.Ala1995Thr) in fetus 1, and c.5920G>T (pGly1974) and c.9908T>C (p.He3303Thr) in fetus 2. The parents of both fetuses were heterozygous carriers.@*CONCLUSION@#The compound heterozygous variants of the DYNC2H1 gene probably underlay the SRTD3 in the two fetuses.

Clinical and genetic analysis of a rare fetus with Protein C deficiency due to compound heterozygous variants of PROC gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology for a fetus with hydrocephalus and intraventricular hemorrhage.@*METHODS@#Trio whole exome sequencing was carried out. Candidate variants were verified by Sanger sequencing of the fetus and its parents.@*RESULTS@#The fetus was found to harbor c.818G>A (p.W273X) and c.833T>C (p.L278P) compound heterozygous variants of the PROC gene, which were respectively inherited from its mother and father. Based on the guidelines of the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be likely pathogenic (PVS1_Strong+PM2_Supporting+PP4; PM2_Supporting+PM3+PP1+PP3+PP4).@*CONCLUSION@#The fetus was diagnosed with Protein C deficiency due to the c.818G>A (p.W273X) and c.833T>C (p.L278P) compound heterozygous variants of the PROC gene. Above finding has enriched the spectrum of PROC gene variants and enabled genetic counseling and prenatal diagnosis for the family.

Analysis of a fetus with multiple malformations due to a hemizygous variant of FANCB gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus with limb abnormality and cardiac malformation.@*METHODS@#Clinical data of a fetus diagnosed at the Shandong Provincial Maternal and Child Health Care Hospital on April 30th, 2021 was collected. Whole exome sequencing (WES) was carried out, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. X-inactivation analysis was carried out for the female members of its family.@*RESULTS@#The fetus was found to have meningoencephalocele, absence of bilateral radii, cleft lip, abnormal great arteries, and single umbilical artery at the gestational age of 11+ weeks. Sequencing revealed that the fetus has harbored a hemizygous c.1162del (p.Y388Tfs*7) variant of the FANCB gene, which was maternally inherited. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and ClinGen, the variant was classified as pathogenic (PVS1+PM2_Supporting+PP4). X-inactivation analysis has revealed complete skewed X-inactivation in the pregnant woman and her mother.@*CONCLUSION@#The hemizygous c.1162del (p.Y388Tfs*7) variant of the FANCB gene probably underlay the multiple malformations in this fetus.