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.

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)

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.

Amelioration potential of Moringa oleifera extracts against sodium arsenate induced embryotoxicity and genotoxicity in mouse (Mus musculus) / Potencial de melhoria de extratos de Moringa oleifera contra embriotoxicidade e genotoxicidade induzida por arseniato de sódio em camundongos (Mus musculus)

Previous studies have suggested that arsenic crosses the placenta and affects the fetus development. The study under consideration aims to show comparative ameliorative effect of Moringa oleifera leaf and flower extracts against sodium arsenate induced fetus toxicity of mice. Pregnant mice (N=44) were kept in lab and divided into eleven group from (A to K) and were orally administered the doses 6 mg/kg, 12 mg/kg for sodium arsenate, 150 mg/kg and 300 mg/kg for Moringa oleifera leaf extracts (MOLE) and 150 mg/kg and 300 mg/kg for Moringa oleifera flower extracts (MOFE) comparing with control. The investigation revealed evident reduction in the fetuses weight, hind limb, fore limb, tail and snout length, crown rump and head circumferences well as malformations in tail, feet, arms, legs, skin and eyes in the negative control group (only administered with sodium arsenate). Co-administration of sodium arsenate with MOLE and MOFE ameliorate the reversed effect of sodium arsenate on the shape, length, body weight and DNA damage of fetus significantly at 95% confidence interval. However, Moringa oleifera leaf extract showed more significant results in comparison to Moringa oleifera flower extract. Hence concluded that Moringa oleifera leaf extract ameliorated the embryo toxic effects of sodium arsenate and can be used against environmental teratogens.

Estudos anteriores sugeriram que o arsênio atravessa a placenta e afeta o desenvolvimento do feto. O estudo em consideração visa mostrar o efeito melhorador comparativo de extratos de folhas e flores de Moringa oleifera contra a toxicidade fetal induzida por arseniato de sódio em camundongos. Camundongos grávidas (N = 44) foram mantidos em laboratório e divididos em 11 grupos (de A a K) e foram administrados por via oral nas doses de 6 mg/kg, 12 mg/kg para arseniato de sódio, 150 mg/kg e 300 mg/kg para extratos de folhas de Moringa oleifera (MOLE) e 150 mg/kg e 300 mg/kg para extratos de flores de Moringa oleifera (MOFE) em comparação com o controle. A investigação revelou redução evidente no peso do feto, membro posterior, membro anterior, comprimento da cauda e focinho, coroa, nádega e circunferência da cabeça, bem como malformações na cauda, pés, braços, pernas, pele e olhos no grupo de controle negativo (apenas administrado com arseniato de sódio). A coadministração de arseniato de sódio com MOLE e MOFE melhora significativamente o efeito reverso do arseniato de sódio na forma, comprimento, peso corporal e dano ao DNA do feto, com intervalo de confiança de 95%. No entanto, o extrato da folha da Moringa oleifera apresentou resultados mais significativos em comparação ao extrato da flor da Moringa oleifera. Portanto, concluiu que o extrato da folha de Moringa oleifera melhorou os efeitos tóxicos do arseniato de sódio para o embrião e pode ser usado contra teratógenos ambientais.

Clinical characteristics of cardiac defects fetuses and the impact of multi-disciplinary team cooperation approach on the pregnancy decision making / 中华妇产科杂志

Objective: To analysis the clinical characteristics of 400 fetuses with heart defects and the impactors of pregnancy decision making, and explore the influence of a multi-disciplinary team (MDT) cooperation approach on it. Methods: Clinical data of 400 fetuses with abnormal cardiac structure diagnosed at Peking University First Hospital from January 2012 to June 2021 were collected, which were divided into 4 groups according to the characteristics of fetal heart defects and the presence of extracardiac abnormalities or not: single cardiac defects without extracardiac abnormalities (122 cases), multiple cardiac defects without extracardiac abnormalities (100 cases), single cardiac defects with extracardiac abnormalities (115 cases), and multiple cardiac defects with extracardiac abnormalities (63 cases). The types of fetal cardiac structural abnormalities and genetic test results, and the detection rate of pathogenic genetic abnormalities, MDT consultation and management situation, and pregnancy decision of fetuses in each group were retrospectively analyzed. A logistics regression was used to analyze the influencing factors of fetal heart defects pregnancy decision. Results: (1) Among the 400 fetal heart defects, the four most common major types were ventricular septal defect 96 (24.0%, 96/400), tetralogy of Fallot 52 (13.0%, 52/400), coarctation of the aorta 34 (8.5%, 34/400), and atrioventricular septal defect 26 (6.5%, 26/400). (2) Among the 204 fetuses undergoing genetic examination, 44 (21.6%, 44/204) pathogenic genetic abnormalities were detected. (3) Detection rate of pathogenic genetic abnormalities (39.3%, 24/61) and pregnancy termination rate (86.1%, 99/115) in the single cardiac defects with extracardiac abnormalities group were significantly higher than those in the single cardiac defects without extracardiac abnormalities group [15.1% (8/53), 44.3% (54/122), respectively] and the multiple cardiac defects without extracardiac abnormalities group [6.1% (3/49), 70.0% (70/100), respectively, both P<0.05], and the pregnancy termination rate in the multiple cardiac defects without extracardiac abnormalities group and the multiple cardiac defects with extracardiac abnormalities group (82.5%,52/63) were significantly higher than that of the single cardiac abnormalities without extracardiac abnormalities group (both P<0.05). (4) After adjusting for age, gravity, parity and performed prenatal diagnosis, maternal age, the diagnosis of gestational age, prognosis grades, co-existence of extracardiac abnormalities, presence of pathogenic genetic abnormalities, and receiving MDT consultation and management were still independent influencing factors of termination of pregnancy of fetuses with cardiac defects (all P<0.05). A total of 29 (7.2%, 29/400) fetal cardiac defects received MDT consultation and management, and compared with those without MDT management, the pregnancy termination rate in the multiple cardiac defects without extracardiac abnormalities group [74.2%(66/89) vs 4/11] and the multiple cardiac defects with extracardiac abnormalities group [87.9%(51/58) vs 1/5] were lower, the differences were statistically significant respectively (all P<0.05). Conclusions: Maternal age, diagnosed gestational age, severity of cardiac defects, extracardiac abnormalities, pathogenic genetic abnormalities and MDT counseling and management are the influencing factors of fetal heart defects pregnancy decision. MDT cooperation approach influences pregnancy decision-making and should be recommended for the management of fetal cardiac defect to reduce unnecessary termination of pregnancy and improve pregnancy outcomes.

Retrospective Analysis of Irregular Antibodies Causing Hemolytic Disease of the Fetus and Newborn in Jiangxi Province / 中国实验血液学杂志

OBJECTIVE@#To analyze the characteristics of antibody-specific distribution, laboratory detection results of hemolytic disease of the fetus and neonatal(HDFN) caused by irregular blood group antibodies other than ABO, and its correlation with the clinical situation.@*METHODS@#The non-ABO-HDFN cases in our hospital from October 2012 to December 2021 were selected as the research objects, and the cases diagnosed with ABO-HDFN in the same period were randomly selected as the control group, and the data of antibody specific distribution, total bilirubin, direct antibodies, maternal history, age of the children, the presence or absence of combined ABO-HDFN, and whether to exchange/transfuse blood were retrospectively analyzed. The characteristics of non-ABO-HDFN in Jiangxi province were analyzed.@*RESULTS@#The detection rate of non-ABO-HDFN in Jiangxi province increased. Among 187 non ABO-HDFN cases, the highest percentage of Rh-HDFN was detected (94.6%). Compared with the control group of ABO-HDFN, the non-ABO-HDFN had higher mean integral value of direct antibody, higher peak total bilirubin, and longer duration. Anti-M-HDFN may have severe disease but the direct antibody weak positive/negative, it was easy missed in clinical and delayed the treatment. There is no correlation between the specificity of irregular antibodies, the sex of the child, the mother's previous childbirth history, the presence or absence of combined ABO-HDFN and the need for blood exchange/transfusion(P>0.05).@*CONCLUSION@#The irregular antibodies of causing non ABO-HDFN in Jiangxi area are mainly Rh blood group system, followed by MNS blood group system. Understanding the characteristics of HDFN disease, serological features and the correlation with clinical indexes will help to detect and treat non ABO-HDFN in time and reduce the risk of complications.

Genetic analysis of a pregnant woman with moderate intellectual disability due to variant of DLG4 gene / 中华医学遗传学杂志

OBJECTIVE@#To carry out genetic testing and prenatal diagnosis for a woman featuring moderate intellectual disability (ID).@*METHODS@#The patient had presented at the First Affiliated Hospital of Zhengzhou University on April 28, 2021. With informed consent, peripheral blood and amniotic fluid samples were collected for the extraction of genomic DNA. Pathogenic copy number variations (CNVs) were detected with CNV-seq, and single gene variants were detected by whole exome sequencing (WES) and Sanger sequencing. Candidate variant was verified by Sanger sequencing, and CNV-seq and multiplex ligation-dependent probe amplification (MLPA) were used to detect fetal CNVs.@*RESULTS@#The 23-year-old woman had moderate ID, sideway walking, and unstable holding. Ultrasonography at 18+3 weeks' gestation had revealed no fetal abnormality. No pathogenic CNV was detected in the woman by CNV-Seq, while WES revealed that she has harbored a heterozygous c.1675C>T (p.Arg559*) variant of the DLG4 gene, which was verified by Sanger sequencing. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PVS1+PM2_supporting). Sanger sequencing has confirmed that the fetus has inherited this variant, and CNV-Seq also revealed that that fetus has harbored a 0.1 Mb heterozygous deletion at Xp21.1, which has encompassed the DMD gene, and the result was verified by MLPA.@*CONCLUSION@#The heterozygous c.1675C>T variant of the DLG4 gene probably underlay the mental retardation in this woman, and her fetus was found to harbor the same variant in addition with deletion of the DMD gene, which may predispose to ID type 62.

Analysis of genome copy number variations in fetuses with isolated ventricular septal defect and a literature review / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of copy number variation sequencing (CNV-seq) for revealing the genetic etiology of fetuses with isolated ventricular septal defect (VSD).@*METHODS@#From December 2017 to December 2020, 69 fetuses with isolated VSD were identified at the First Affiliated Hospital of Zhengzhou University. Meanwhile, 839 similar prenatal cases were selected from public databases including Wanfang data, Wanfang Medicine, and China National Knowledge Infrastructure (CNKI) by using keywords such as "Ventricular septal defect", "Copy number variation", and "Prenatal". A total of 908 fetuses with isolated VSD were analyzed. CNV-seq was carried out for 69 fetuses.@*RESULTS@#Among the 908 fetuses, 33 (3.63%) were found to harbor pathogenic CNVs, which included 11 chromosomal aneuploidies (1.21%) and 22 pathogenic CNVs (2.42%). The pathogenic CNVs have involved 12 genetic syndromes, with those known to involve the heart development including 5 cases of 22q11.21 deletion syndrome, 2 cases of 4q terminal deletion syndrome, and 1 case of 9q subtelomere deletion syndrome. The outcome of pregnancies for 15 fetuses with pathogenic CNVs was known, of which 12 were terminated, and 3 had spontaneous closure of the ventricular septum after birth, but 1 of them had other abnormalities.@*CONCLUSION@#Fetuses with isolated VSD have a relatively high risk for chromosomal abnormalities, for which CNV-seq should be recommended.

Analysis of a fetus with unbalanced translocation derived from a balanced t(6;14) maternal translocation / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic characteristics of a fetus with a high risk by maternal serum screening during the second trimester.@*METHODS@#Genetic counseling was provided to the pregnant woman on March 22, 2020 at Henan Provincial People's Hospital. G-banded chromosomal karyotyping and array comparative genomic hybridization (aCGH) were carried out on the amniotic fluid sample and peripheral blood samples from the couple.@*RESULTS@#The fetus and the pregnant woman were respectively found to have a 46,XX,der(6)t(6;14)(q27;q31.2) and 46,XX,t(6;14)(q27;q31.2) karyotype, whilst the husband was found to have a normal karyotype. aCGH analysis has identified a 6.64 Mb deletion at 6q26q27 and a 19.98 Mb duplication at 14q31.3q32.33 in the fetus, both of which were predicted to be pathogenic copy number variations. No copy number variation was found in the couple.@*CONCLUSION@#The unbalanced chromosome abnormalities in the fetus have probably derived from the balanced translocation carried by the pregnant woman. aCGH can help to determine the types of fetal chromosome abnormalities and site of chromosomal breakage, which may facilitate the prediction of fetal outcome and choice for subsequent pregnancies.

Value of chromosomal microarray analysis for the diagnosis of fetuses with anomalies of central nervous system / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of chromosomal microarray analysis (CMA) for the diagnosis of fetuses with anomalies of the central nervous system (CNS) and summarize the outcome of the pregnancies and follow-up.@*METHODS@#A total of 636 fetuses from June 2014 to December 2020 who were referred to the Prenatal Diagnosis Center of Nanjing Drum Tower Hospital due to abnormal CNS prompted by ultrasound were selected as the research subjects. Based on the ultrasound findings, the fetuses were divided into ventricular dilatation group (n = 441), choroid plexus cyst group (n = 41), enlarged posterior fossa group (n = 42), holoprosencephaly group (n = 15), corpus callosum hypoplasia group (n = 22), and other anomaly group (n = 75). Meanwhile, they were also divided into isolated (n = 504) and non-isolated (n = 132) groups based on the presence of additional abnormalities. Prenatal samples (amniotic fluid/chorionic villi/umbilical cord blood) or abortus tissue were collected for the extraction of genomic DNA and CMA assay. Outcome of the pregnancies and postnatal follow-up were summarized and subjected to statistical analysis.@*RESULTS@#In total 636 fetuses with CNS anomalies (including 89 abortus tissues) were included, and 547 cases were followed up. The overall detection rate of CMA was 11.48% (73/636). The detection rates for the holoprosencephaly group, ACC group, choroid plexus cyst group, enlarged posterior fossa group, ventricular dilatation group and other anomaly group were 80% (12/15), 31.82% (7/22), 19.51% (8/41), 14.29% (6/42), 7.48% (33/441) and 9.33% (7/75), respectively. Compared with the isolated CNS anomaly group, the detection rate for the non-isolated CNS anomaly group was significantly higher (6.35% vs. 31.06%) (32/504 vs. 41/132) (χ² = 62.867, P < 0.001). Follow up showed that, for 52 fetuses with abnormal CMA results, 51 couples have opted induced labor, whilst 1 was delivered at full term with normal growth and development. Of the 434 fetuses with normal CMA results, 377 were delivered at full term (6 had developmental delay), and 57 couples had opted induced labor. The rate of adverse pregnancy outcome for non-isolated CNS abnormal fetuses was significantly higher than that of isolated CNS abnormal fetuses (26.56% vs. 10.54%) (17/64 vs. 39/370) (χ² = 12.463, P < 0.001).@*CONCLUSION@#Fetuses with CNS anomaly should be tested with CMA to determine the genetic cause. Most fetuses with negative CMA result have a good prognosis, but there is still a possibility for a abnormal neurological phenotype. Fetuses with CNS abnormalities in conjunct with other structural abnormalities are at increased risk for adverse pregnancy outcomes.

Clinical application and evaluation of health economics for non-invasive prenatal testing of fetuses in Tianjin / 中华医学遗传学杂志

OBJECTIVE@#To assess the clinical efficacy and health economic value of non-invasive prenatal testing (NIPT) for the prenatal screening of common fetal chromosomal aneuploidies.@*METHODS@#10 612 pregnant women from October 2017 to December 2019 presented at the antenatal screening clinic of the General Hospital of Tianjin Medical University were selected as the study subjects. Results of NIPT and invasive prenatal diagnosis and follow-up outcome for the 10 612 pregnant women were retrospectively analyzed and compared. Meanwhile, NIPT data for two periods were analyzed for assessing the health economic value of NIPT as the second- or first-tier screening strategy for the prenatal diagnosis of fetal trisomies 21, 18 and 13.@*RESULTS@#The NIPT was successful in 10 528 (99.72%) subjects, with the sensitivity for fetal trisomies 21, 18 and 13 being 100%, 92.86% and 100%, and the positive predictive value (PPV) being 89.74%, 61.90% and 44.44%, respectively. The PPV of NIPT for sex chromosome aneuploidies was 34.21%. Except for one false negative case of trisomy 18, the negative predictive value for trisomy 21, trisomy 13 and other chromosomal abnormalities were 100%. For pregnant women with high risk by serological screening, advanced maternal age or abnormal ultrasound soft markers, NIPT has yielded a significantly increased high risk ratio. There was no statistical difference in the PPV of NIPT among pregnant women from each subgroup. NIPT would have higher health economic value as a second-tier screening until 2019, while compared to 2015 ~ 2017, its incremental cost-effectiveness ratio as a first-tier screening had declined clearly.@*CONCLUSION@#The screening efficacy of NIPT for trisomies 21, 18 and 13 for a mixed population is significantly better than conventional serological screening, but it is relatively low for sex chromosomal abnormalities. NIPT can also be recommended for populations with relatively high risks along with detailed pre- and post-test genetic counselling. From the perspective of health economics, except for open neural tube defects, it is possible for NIPT to replace the conventional serological screening in the future as its cost continues to decrease.

Prenatal diagnosis for a fetus with 5p deletion syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a fetus with club foot detected upon mid-pregnancy ultrasonography.@*METHODS@#Amniotic fluid of the fetus and peripheral blood samples of its parents were collected and subjected to G-banding karyotype analysis and copy number variation sequencing (CNV-seq). The result was verified by fluorescence in situ hybridization (FISH).@*RESULTS@#The fetus and its parents all had a normal karyotype. CNV-seq analysis revealed that the fetus has harbored a 23.12 Mb on chromosome 5 and a 21.46 Mb duplication on chromosome 7. FISH assay has verified that its mother has carried a cryptic t(5;7)(p14.3;q33) translocation.@*CONCLUSION@#CNV-seq combined with FISH can effectively detect cryptic chromosome aberrations, and can help to reduce severe birth defects and provide a basis for prenatal genetic counseling.

Fetal electrocardiogram signal extraction and analysis method combining fast independent component analysis algorithm and convolutional neural network / 生物医学工程学杂志

Fetal electrocardiogram (ECG) signals provide important clinical information for early diagnosis and intervention of fetal abnormalities. In this paper, we propose a new method for fetal ECG signal extraction and analysis. Firstly, an improved fast independent component analysis method and singular value decomposition algorithm are combined to extract high-quality fetal ECG signals and solve the waveform missing problem. Secondly, a novel convolutional neural network model is applied to identify the QRS complex waves of fetal ECG signals and effectively solve the waveform overlap problem. Finally, high quality extraction of fetal ECG signals and intelligent recognition of fetal QRS complex waves are achieved. The method proposed in this paper was validated with the data from the PhysioNet computing in cardiology challenge 2013 database of the Complex Physiological Signals Research Resource Network. The results show that the average sensitivity and positive prediction values of the extraction algorithm are 98.21% and 99.52%, respectively, and the average sensitivity and positive prediction values of the QRS complex waves recognition algorithm are 94.14% and 95.80%, respectively, which are better than those of other research results. In conclusion, the algorithm and model proposed in this paper have some practical significance and may provide a theoretical basis for clinical medical decision making in the future.

Mediation effect of resilience on pregnancy stress and prenatal depression in pregnant women / 中南大学学报(医学版)

OBJECTIVES@#Pregnancy stress is the psychological confusion or threat caused by various stress events and adverse factors during pregnancy. Pregnant women exposed to many stressors, they will be easy to produce bad mood and prenatal depression if they cannot adapt to their own changes. Prenatal depression is one of the major global public health problems, with a higher incidence in developing countries and a negative impact on the health of pregnant women and fetus. Resilience refers to pregnant women using their own positive psychological capital, can self-emotional adjustment and improve their ability to adapt to the response state. A better level of resilience can enable pregnant women to face various negative and adaptive problems positively. This study aims to investigate the relationship between pregnancy stress, resilience and prenatal depression through a mental health survey of pregnant women.@*METHODS@#A total of 750 pregnant women in a Grade A tertiary hospital in Urumqi were investigated by self-designed demographic questionnaire, Pregnancy Pressure Scale (PPS) and Patient Health Questionnaire-9 (PHQ-9), Connor-Davidson Resilience Scale (CD-RISC), and the levels of stress during pregnancy, prenatal depression and resilience were analyzed. Pearson correlation analysis was used to explore the correlation between the three. Bootstrap mediation effect test was used to test the mediation effect relationship among the three. If the mediation effect was confirmed, AMOS software was used to establish the mediation effect structural equation model to analyze the mediation effect among the three.@*RESULTS@#Among 750 respondents, 709 (94.53%) had mild or above pregnancy pressure, 459 (61.20%) had mild or above depressive symptoms and 241 (32.13%) had a good or above level of resilience. Pearson correlation analysis showed that prenatal depression was significantly positively correlated with pregnancy stress (P<0.01), prenatal depression and pregnancy stress were significantly negatively correlated with resilience (all P<0.01). Mediation effect test analysis showed that all the pathways were statistically significant (P<0.01). Mediation effect of resilience between pregnancy stress and prenatal depression was significantly found (95% CI 0.022-0.068, P<0.001). Pregnancy pressure negatively affected resilience (β=-0.38, P<0.01), and resilience negatively affected prenatal depression (β=-0.10, P<0.01). The mediation effect of resilience was 6.5%.@*CONCLUSIONS@#Pregnant women's pregnancy pressure, resilience and prenatal depression are significantly correlated, and the mediation variable resilience plays a partial mediating role in the impact of pregnancy pressure on prenatal depression. Pregnant women can reduce the incidence of prenatal depression and promote their physical and mental health by exercising their resilience.

Analysis of COL1A1 and COL1A2 gene variants in two fetuses with osteogenesis imperfecta / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis of two fetuses with an osteogenesis imperfecta (OI) phenotype.@*METHODS@#Two fetuses diagnosed at the Affiliated Hospital of Weifang Medical College respectively on June 11, 2021 and October 16, 2021 were selected as the study subjects. Clinical data of the fetuses were collected. Amniotic fluid samples of the fetuses and peripheral blood samples of their pedigree members were collected for the extraction of genomic DNA. Whole exome sequencing (WES) and Sanger sequencing were carried out to identify the candidate variants. Minigene splicing reporter analysis was used to validate the variant which may affect the pre-mRNA splicing.@*RESULTS@#For fetus 1, ultrasonography at 17+6 weeks of gestation had revealed shortening of bilateral humerus and femurs by more than two weeks, in addition with multiple fractures and angular deformities of long bones. WES revealed that fetus 1 had harbored a heterozygous c.3949_3950insGGCATGT (p.N1317Rfs*114) variant in exon 49 of the COL1A1 gene (NM_000088.4). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as a pathogenic variant (PVS1+PS2+PM2_Supporting) for disrupting the downstream open reading frame resulting in premature translational termination, being de novo in origin, and lacking records in the population and disease databases.For fetus 2, ultrasonography at 23 weeks of gestation also revealed shortening of bilateral humerus and femurs by one and four weeks, respectively, in addition with bending of bilateral femurs, tibias and fibulas. Fetus 2 had harbored a heterozygous c.1557+3A>G variant in intron 26 of the COL1A2 gene (NM_000089.4). Minigene experiment showed that it has induced skipping of exon 26 from the COL1A2 mRNA transcript, resulting in an in-frame deletion (c.1504_1557del) of the COL1A2 mRNA transcript. The variant was inherited from its father and had been previously reported in a family with OI type 4. It was therefore classified as a pathogenic variant (PS3+PM1+PM2_Supporting+PP3+PP5).@*CONCLUSION@#The c.3949_3950insGGCATGT (p.N1317Rfs*114) variant in the COL1A1 gene and c.1557+3A>G variant in the COL1A2 gene probably underlay the disease in the two fetuses. Above findings not only have enriched the mutational spectrum of OI, but also shed light on the correlation between its genotype and phenotype and provided a basis for genetic counseling and prenatal diagnosis for the affected pedigrees.

Genetic analysis of a Chinese family affected with α-dystroglycanopathy due to variant of B3GALNT2 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with recurrent fetal hydrocephalus.@*METHODS@#A couple who had presented at the Affiliated Hospital of Putian College on March 3, 2021 was selected as the study subject. Following elective abortion, fetal tissue and peripheral blood samples were respectively obtained from the abortus and the couple, and were subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing.@*RESULTS@#The fetus was found to harbor compound heterozygous variants of the B3GALNT2 gene, namely c.261-2A>G and c.536T>C (p.Leu179Pro), which were inherited from its father and mother, respectively.According to the guidelines of American College of Medical Genetics and Genomics, both variants were classified as pathogenic (PVS1+PM2_Supporting; PM3+PM2_Supporting+PP3+PP4).@*CONCLUSION@#The compound heterozygous variants of the B3GALNT2 gene probably underlay the α-dystroglycanopathy in this fetus. Above results have provided a basis for genetic counseling of this pedigree.