Desarrollo embriológico e importancia clínica de la membrana amniótica: revisión narrativa de literatura / Embryological development and clinical significance of the amniotic membrane: narrative literature review

La membrana amniótica (MA), ubicada en el lado interno de la placenta fetal, ha sido objeto de múltiples investigaciones para intentar dilucidar su papel embriológico y su potencial celular terapéutico. Actualmente las limitaciones del estudio en fetos humanos hacen que parte de su funcionamiento sea una incógnita, sin embargo algunos estudios clínicos y básicos nos dan luz sobre su papel en la médica moderna. Se realizó una revisión bibliográfica de la literatura desde 1960 hasta 2022, empleando bases de datos como PubMed, SciELO y Scopus, siendo incluidos un total de 50 artículos y dos textos de embriología. El objetivo de esta revisión narrativa fue sintetizar la información sobre la angiogénesis y su importancia clínica. La información recopilada permitió evidenciar que las propiedades de curación de la piel del feto se deben a factores intrínsecos del feto, y a que las células epiteliales amnióticas humanas poseen una diferenciación similar a las células madre embrionarias, con la capacidad de diferenciación similar al de las células mesenquimales, resaltando su importancia clínica por sus características regenerativas. En conclusión, el desarrollo embrionario humano sigue siendo relativamente inexplicable, pero su conocimiento ha permitido grandes avances, que podrían ser útiles en terapias de regeneración, reparación de tejidos y órganos lesionados.

The amniotic membrane, located on the inner side of the fetal placenta, has been the subject of multiple investigations to try to elucidate its embryological role and its therapeutic cellular potential. Currently, the limitations of the study in human fetuses mean that part of its functioning is unknown, however, some clinical and basic studies shed light on its role in modern medicine. A bibliographic review of the literature was carried out from 1960 to 2022, using databases such as PubMed, SciELO and Scopus, including a total of 50 articles and two embryology texts. The objective of this narrative review was to synthesize information on angiogenesis and its clinical importance. The information collected made it possible to show that the healing properties of the fetal skin are due to intrinsic factors of the fetus, and that human amniotic epithelial cells have a differentiation similar to embryonic stem cells, with the differentiation capacity similar to that of mesenchymal cells, highlighting their clinical importance due to their regenerative characteristics. In conclusion, human embryonic development remains relatively inexplicable, but its knowledge has allowed great advances, which could be useful in regeneration therapies, repair of injured tissues and organs.

Análise dos efeitos em fetos expostos à hiperêmese gravídica durante a gravidez / Analysis of the effects on fetuses exposed to hyperemesis gravidarum during pregnancy

INTRODUÇÃO: De etiologia desconhecida, a hiperêmese gravídica é um quadro caracterizado por vômitos persistentes, perda de 5% ou mais do peso, cetonúria, hipocalemia e desidratação. Acredita-se que a gonadotrofina coriônica humana (hCG) provoque aumento das náuseas e vômitos por meio de seu estímulo à produção de estrogênio pelo ovário, provocando a exacerbação dos sintomas do "enjoo matinal". OBJETIVO: Logo, essa revisão narrativa tem como objetivo analisar as repercussões fetais do quadro de hiperêmese gravídica. MÉTODOS: Foram realizadas buscas em Sistema Online de Busca e Análise de Literatura Médica - MEDLINE®. Sendo utilizadas os Medical Subject Headings (MeSh terms) e seus sinônimos: "hyperemesis gravidarum", "fetal risks", sendo selecionados ao todo 13 artigos. RESULTADOS: Os estudos demonstraram que a hiperêmese gravídica pode trazer malefícios para mãe e feto. A gestante pode apresentar distúrbios eletrolíticos, encefalopatia de Wernicke, fraqueza muscular, disfunções emocionais como depressão, ansiedade e estresse pós-traumático. DISCUSSÃO: Os estudos revelaram que a patologia pode estar relacionada ao risco aumentado para desfechos adversos no nascimento, como baixo peso ao nascer, nascimento prematuro e pequena estatura para idade gestacional. Ademais, alguns estudos relataram os riscos prejudiciais no neurodesenvolvimento do recém-nascido, como problemas psicológicos e comportamentais na idade adulta, redução à sensibilidade à insulina, e comorbidades (obesidade e doenças cardiovasculares) além de distúrbios de desenvolvimento neuropsicomotor. CONCLUSÃO: Gestantes que apresentam o quadro de hiperêmese gravídica devem ser regularmente acompanhadas com consultas entre 1 a 2 semanas, conforme a gravidade do caso e o mais precocemente possível tratadas, a fim de evitar maiores complicações tanto maternas quanto fetais.

INTRODUCTION: Of unknown etiology, hyperemesis gravidarum is a condition characterized by persistent vomiting, 5% or more weight loss, ketonuria, hypokalemia and dehydration. Human chorionic gonadotropin (hCG) is believed to cause increased nausea and vomiting through its stimulation of estrogen production by the ovary, causing exacerbation of "morning sickness" symptoms. OBJECTIVE: Thus, this narrative review aims to analyze the fetal repercussions of hyperemesis gravidarum. METHODS: Searches were performed in the Online Medical Literature Analysis and Search System - MEDLINE®. The Medical Subject Headings (MeSh terms) and their synonyms were used: "hyperemesis gravidarum", "fetal risks", being selected a total of 13 articles. RESULTS: The studies showed that hyperemesis gravidarum can bring harm to mother and fetus. The pregnant woman may present electrolyte disturbances, Wernicke's encephalopathy, muscle weakness, emotional dysfunctions such as depression, anxiety, and post-traumatic stress. DISCUSSION: The studies revealed that hyperemesis gravidarum may be associated with increased risk of adverse outcomes. Furthermore, some studies reported harmful risks in neurodevelopment of the newborn, such as psychological and behavioral problems in adulthood, reduced sensitivity to insulin, and comorbidities (obesity and cardiovascular diseases) and neurodevelopmental disorders. CONCLUSION: Pregnant women who present with hyperemesis gravidarum should be followed up with consultations between 1 to 2 weeks, according to the severity of the case and treated as early as possible in order to avoid further complications both maternal and fetal.

Trauma e gestação / Trauma and pregnancy

A incidência de trauma durante a gestação é de 6% a 8% (formas graves de trauma: 3%-6%). Das gestantes que necessitam de internação por causa de um trauma, 60% evoluem para o parto. As gestantes têm 1,6 vez mais chances de morrer numa situação de trauma. As alterações anatômicas e fisiológicas da gestação interferem nas repercussões e na abordagem do trauma. A violência doméstica representa o mecanismo mais comum de trauma para a gestante e desencadeia várias complicações obstétricas, devendo ser, idealmente, identificada no pré-natal. No acidente automobilístico, atenção especial deve ser dada ao diagnóstico de descolamento prematuro de placenta (DPP). O ultrassom na sala de trauma possibilita ação na assistência ao trauma e também, como mecanismo rápido, informações necessárias sobre o feto e a gestação (FAST fetal). A maioria dos exames de imagem necessários para a boa assistência ao trauma não representa agravos à gestação. O pré-natal tem papel importante na prevenção dos traumas na gestação. A ação conjunta do cirurgião do trauma e do obstetra é recomendada no atendimento da gestante traumatizada, principalmente nos casos graves e em gestantes acima de 20-24 semanas

Relación entre biometría fetal, producto de acumulación de los lípidos y condición trófica al nacer / Relationship between fetal biometry, lipid accumulation product and the trophic condition at birth

Fundamento: Las alteraciones del estado nutricional materno generalmente se relacionan con desviaciones del crecimiento fetal, que pueden detectarse por los parámetros biofísicos fetales e identifican la posible condición trófica al nacer. Objetivo: Determinar la posible relación entre los parámetros biométricos fetales, la condición trófica al nacer y el producto de acumulación de los lípidos. Metodología: Se realizó un estudio transversal en el Policlínico Chiqui Gómez Lubian del municipio Santa Clara, durante el año 2019, en una población de 253 gestantes normopeso supuestamente sanas al inicio de la gestación. La muestra no probabilística fue de 144 gestantes. Las variables de estudio fueron: producto de acumulación de los lípidos, biometría fetal y condición trófica al nacer. Se utilizaron métodos teóricos, empíricos y estadísticos. Resultados: En el segundo trimestre ningún parámetro biométrico coincidió con la condición al nacer de pequeño, mientras que para el grande coincidieron las circunferencias cefálica y abdominal. En el tercer trimestre la longitud del fémur y la circunferencia abdominal coinciden en la identificación del pequeño y del grande. El PAL se correlacionó con la circunferencia abdominal del tercer trimestre y con el peso al nacer; presentando mayor frecuencia de valores en el tercer tertil para los nacimientos grandes. Conclusiones: La circunferencia abdominal fue el parámetro biométrico con mayor coincidencia con la condición trófica al nacer, la que se asoció con valores en el tercer tertil del PAL para la detección de nacimientos grandes, relacionándose el fenotipo normopeso metabólicamente obeso con el crecimiento fetal por exceso.

Background: Maternal nutritional status disorders are usually related to fetal growth deviations, which can be detected by fetal biophysical parameters and identify the possible trophic condition at birth. Objective: To determine the possible relationship between fetal biometric parameters, the birth trophic state and lipid accumulation product. Methodology: A cross-sectional study was conducted at the Chiqui Gómez Lubian Polyclinic in Santa Clara municipality, during 2019, in a population of 253 normal-weight pregnant women who were apparently healthy at the beginning of their gestation. The non-probability sample was made up of 144 pregnant women. Study variables were: lipid accumulation product, fetal biometry and trophic condition at birth. Theoretical, empirical and statistical methods were used. Results: In the second trimester, none of the biometric parameters matched the condition at birth as a small child, while in the large one the head and abdominal circumferences matched. In the third trimester, femoral length and abdominal circumference coincide in identifying the small one and the large one. LAP correlated with third trimester abdominal circumference and birth weight, presenting higher frequency of values in the third tertile for large births. Conclusions: Abdominal circumference was the biometric parameter with the highest coincidence with trophic condition at birth, associated with values in the third tertile of the LAP for detecting large births, relating the metabolically obese normal weight phenotype with excessive fetal growth.

Manejo de Disminución de Movimientos Fetales en pacientes del Área de Urgencias Obstétricas / Management of Decreased Fetal Movements in patients in the Obstetric Emergency Area

Los movimientos fetales son uno de los primeros signos de vitalidad fetal. Durante la gestación, éstos van apareciendo progresivamente. La adecuada adquisición y mantenimiento de los mismos durante la gestación indica un correcto desarrollo neuromuscular, así como de bienestar fetal1. La percepción materna de una Disminución de los Movimientos Fetales (DMF) constituye un motivo de consulta frecuente en los Servicios de Urgencias Obstétricas; toda paciente embarazada debe vigilar los movimientos fetales, mediante un conteo subjetivo de los movimientos del feto, a partir de las 24 semanas de gestación. La DMF constituye el 5 ­ 15% de motivos de consulta en los servicios de Urgencias en el tercer trimestre del embarazo. Hasta un 25% de fetos que presentan una DMF presentarán alguna complicación perinatal (malformaciones, retraso de crecimiento, parto prematuro, hemorragia fetomaterna, y éxitus fetal) incluso en población de bajo riesgo. El manejo inadecuado de la DMF representa un 10-15% de las muertes evitables a término1-3. Es por esto que ninguna paciente que consulte por Disminución de Movimientos Fetales debe ser dada de alta sin asegurarse del adecuado bienestar fetal.

Fetal movements are one of the first signs of fetal vitality. During gestation, they appear progressively. Adequate acquisition and maintenance of fetal movements during gestation indicates correct neuromuscular development, as well as fetal well-being1. Maternal perception of decreased fetal movements (DMP) is a frequent reason for consultation in Obstetric Emergency Departments; every pregnant patient should monitor fetal movements by subjectively counting fetal movements, starting at 24 weeks of gestation. FMD constitutes 5-15% of the reasons for consultation in the emergency department in the third trimester of pregnancy. Up to 25% of fetuses with FMD will present some perinatal complication (malformations, growth retardation, premature delivery, fetomaternal hemorrhage, and fetal death) even in low-risk populations. Inadequate management of FMD accounts for 10-15% of preventable deaths at term1-3. This is why no patient who consults for decreased fetal movements should be discharged without ensuring adequate fetal well-being.

Association of maternal isolated thyroid peroxidase antibody positive in the first trimester with fetal growth / 北京大学学报(医学版)

OBJECTIVE@#To investigate the association of isolated thyroid peroxidase antibody (TPOAb) positive in the first trimester with fetal growth.@*METHODS@#A total of 16 446 pregnant women were included in the birth cohort study, whose last menstrual period was between May 2016 and April 2019 and with singleton pregnancy. Maternal serum samples were collected when they firstly came for prenatal care in the first trimester. The pregnant women were consecutively seen and followed in the hospital and the information of pregnant women was extracted from the electronic medical information system. The pregnant women were divided into isolated TPOAb positive group (n=1 654) and euthyroid group (n=14 792). Three fetal ultrasound examinations were scheduled during the routine prenatal visits at the hospital and were performed by trained sonographers. All fetal growth indicators were quantified as gestational age- and gender- adjusted standard deviation score (Z-score) using the generalized additive models for location, scale and shape (GAMLSS). Fetal growth indicators included estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), femur length (FL) and head circumference (HC). Fetal growth restriction (FGR) was defined as AC or EFW Z-score＜3rd centile based on clinical consensus. Generalized estimating equation (GEE) analysis was applied to assess the association of maternal isolated TPOAb positive with fetal growth. The generalized linear model was further used to analyze the association between isolated TPOAb positive and fetal growth indicator at different gestational ages when the fetal growth indicator was significantly associated with isolated TPOAb positive in the GEE mo-del.@*RESULTS@#The median gestational age at three ultrasound measurements was 23.6 (23.3, 24.1), 30.3 (29.7, 30.9), 37.3 (37.0, 37.7) weeks, respectively. The BPD Z-score was higher in isolated TPOAb positive women, compared with the euthyroid pregnant women after adjustment (β=0.057, 95%CI: 0.014-0.100, P=0.009). The generalized linear model showed the BPD Z-score was higher in the isolated TPOAb positive women at the end of 21-25 weeks (β=0.052, 95%CI: 0.001-0.103, P=0.044), 29-32 weeks (β=0.055, 95%CI: 0.004-0.107, P=0.035) and 36-40 weeks (β=0.068, 95%CI: 0.011-0.125, P=0.020), compared with the euthyroid pregnant women. There was no difference in other fetal growth indicators (EFW, AC, FL and HC) and FGR between the isolated TPOAb positive and euthyroid pregnant women.@*CONCLUSION@#The BPD Z-score was slightly increased in the isolated TPOAb positive pregnant women in the first trimester, while other fetal growth indicators were not changed. The reproducibility and practical significance of this result need to be confirmed.

Association between maternal plasma one-carbon biomarkers during pregnancy and fetal growth in twin pregnancies / 中华妇产科杂志

Objective: To characterize the relationship between the levels of plasma methyl donor and related metabolites (including choline, betaine, methionine, dimethylglycine and homocysteine) and fetal growth in twin pregnancies. Methods: A hospital-based cohort study was used to collect clinical data of 92 pregnant women with twin pregnancies and their fetuses who were admitted to Peking University Third Hospital from March 2017 to January 2018. Fasting blood was collected from the pregnant women with twin pregnancies (median gestational age: 18.9 weeks). The levels of methyl donors and related metabolites in plasma were quantitatively analyzed by high-performance liquid chromatography combined with mass spectrometry. The generalized estimation equation was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and neonatal outcomes of twins, and the generalized additive mixed model was used to analyze the relationship between maternal plasma methyl donors and related metabolites levels and fetal growth ultrasound indicators. Results: (1) General clinical data: of the 92 women with twin pregnancies, 66 cases (72%) were dichorionic diamniotic (DCDA) twin pregnancies, and 26 cases (28%) were monochorionic diamniotic (MCDA) twin pregnancies. The comparison of the levels of five plasma methyl donors and related metabolites in twin pregnancies with different basic characteristics showed that the median levels of plasma choline and betaine in pregnant women ≥35 years old were higher than those in pregnant women <35 years old, and the differences were statistically significant (all P<0.05). (2) Correlation between plasma methyl donor and related metabolites levels and neonatal growth indicators: after adjusting for confounding factors, plasma homocysteine level in pregnant women with twins was significantly negatively correlated with neonatal birth weight (β=-47.9, 95%CI:-94.3- -1.6; P=0.043). Elevated methionine level was significantly associated with decreased risks of small for gestational age infants (SGA; OR=0.5, 95%CI: 0.3-0.9; P=0.021) and low birth weight infants (OR=0.6, 95%CI: 0.4-0.9; P=0.020). Increased homocysteine level was associated with increased risks of SGA (OR=1.5, 95%CI: 1.0-2.2; P=0.029) and inconsistent growth in twin fetuses (OR=1.9, 95%CI: 1.0-3.7; P=0.049). (3) Correlation between the levels of plasma methyl donors and related metabolites and intrauterine growth indicators of twins pregnancies: for every 1 standard deviation increase in plasma choline level in pregnant women with twin pregnancies, fetal head circumference, abdominal circumference, femoral length and estimated fetal weight in the second trimester increased by 1.9 mm, 2.6 mm, 0.5 mm and 20.1 g, respectively, and biparietal diameter, abdominal circumference and estimated fetal weight increased by 0.7 mm, 3.0 mm and 38.4 g in the third trimester, respectively, and the differences were statistically significant (all P<0.05). (4) Relationship between plasma methyl donor and related metabolites levels in pregnant women with different chorionicity and neonatal birth weight and length: the negative correlation between plasma homocysteine level and neonatal birth weight was mainly found in DCDA twin pregnancy (β=-65.9, 95%CI:-110.6- -21.1; P=0.004). The levels of choline, betaine and dimethylglycine in plasma of MCDA twin pregnancy were significantly correlated with the birth weight and length of newborns (all P<0.05). Conclusion: Homocysteine level is associated with low birth weight in twins, methionine is associated with decreased risk of SGA, and choline is associated with fetal growth in the second and third trimesters of pregnancy.

Avaliação da etapa final do sinal insulínico, via inflamatória, estresse oxidativo, mecanismo epigenético por metilação do DNA e expressão de GLUT4 no músculo gastrocnêmio de ratos adultos, proles de ratas com periodontite apical / Assessment of insulin signaling and inflammatory pathways in skeletal muscle and adipose tissues of adult rats, offspring of the rats with periapical lesion

A programação fetal sugere que estímulos adversos quando aplicados durante o início do desenvolvimento fetal podem alterar o metabolismo da prole, aumentando o risco de doenças na sua vida adulta. A metilação do DNA é um dos mecanismos epigenéticos envolvida nesta programação e regula a expressão gênica. Estudos anteriores verificaram que a periodontite apical (AP) materna em ratas promove em sua prole adulta: resistência insulínica (RI), alteração na etapa inicial do sinal insulínico (SI) no músculo gastrocnêmio (MG) e aumento na concentração plasmática de fator de necrose tumoral-α (TNF-α). O TNF-α pode ativar o fator de transcrição nuclear kappa B (NF-kB) que diminui a expressão gênica do transportador de glicose GLUT4. Nesse contexto, mais estudos são necessários para investigar se as alterações no SI observadas em ratos adultos, proles de ratas com AP também estão presentes na continuidade da cascata insulínica. Ademais, sabendo-se que o estresse oxidativo tem sido implicado como fator contribuinte tanto para o início quanto para a progressão do diabetes, torna-se fundamental verificar o grau de estresse oxidativo tecidual nesta prole adulta. Em vista disso, os objetivos deste estudo foram avaliar a RI, estresse oxidativo, etapa final do SI e via inflamatória no MG de ratos adultos, proles de ratas com AP. Para tanto, as 21 ratas Wistar (2 meses de idade) foram distribuídas em 3 grupos: 1) ratas controle; 2) ratas com 1 AP induzida em 1º molar superior direito; 3) ratas com 4 APs induzidas em 1os e 2os molares superiores e inferiores do lado direito. A AP foi induzida empregandose broca em aço carbono dotada de esfera de 0,1 mm na extremidade. Após 30 dias da exposição pulpar, as ratas de todos os grupos foram colocadas para acasalamento. Quando os filhotes machos de todas as ratas completaram 75 dias de idade, foram realizadas as seguintes análises plasmáticas: 1) glicemia; 2) insulinemia; 3) RI. Ademais, foram realizados os seguintes experimentos no MG: 1) grau de fosforilação em serina/treonina da Akt, após o estímulo insulínico; 2) conteúdo proteico de GLUT4; 3) grau de metilação do DNA na região promotora do gene do GLUT4; 4) expressão gênica do GLUT4 e TNF-α; 5) conteúdo proteico de TNF-α e PGC-1α; 6) grau de fosforilação de NF-kB p50 e NF-kB p65; 7) estresse oxidativo (superóxido dismutase ­ SOD e espécies reativas ao tiobarbitúrico ­ TBARS). A análise estatística foi realizada pela análise de variância, seguida do teste de Tukey. O nível de significância adotado foi de 5%. Os resultados mostraram que AP materna (tanto 1 foco de infecção como 4 focos de infecções) promoveu hiperinsulinemia, RI e diminuição na atividade antioxidante da SOD e na concentração de TBARS no MG de sua prole adulta. Entretanto, somente a AP materna em quatro dentes promoveu aumento na massa corpórea, na ingestão alimentar e no grau de fosforilação das subunidades p50 e p65 do NF-kB no MG de proles adultas. Ademais, houve diminuição no grau de fosforilação em serina e treonina da Akt (após estímulo insulínico) e na expressão gênica e conteúdo proteico de GLUT4 no MG em proles adultas de ratas com 4APs. A AP materna não promoveu alteração na glicemia de jejum, conteúdo de PGC-1α, grau de metilação do DNA na região promotora do gene do GLUT4 e expressão gênica e conteúdo proteico de TNF-α no MG de proles adultas. Esses resultados revelam o impacto que a AP materna tem em longo prazo na predisposição às alterações metabólicas na fase adulta da prole. Isso reforça a importância que a manutenção da saúde bucal materna tem sobre a saúde geral da prole(AU)

Fetal programming suggests that adverse stimuli when applied during early fetal development may alter metabolism of offspring, increasing the risk of disease in adulthood. DNA methylation is one of the epigenetic mechanisms involved in this programming and regulates gene expression. Previous studies have shown that maternal apical periodontitis (AP) in rats promotes in their adult offspring: insulin resistance (IR), alteration in the initial steps of the insulin signaling (IS) in the gastrocnemius muscle (GM) and increase in plasma concentration of tumor necrosis factor-α (TNF-α). TNF-α can activate nuclear transcription factor kappa B (NF-kB) thus decreasing gene expression of the GLUT4 glucose transporter. In this context, more studies are needed to investigate whether changes in IS observed in adult rats, offspring of rats with AP are also present in the continuity of the insulin cascade. In addition, since oxidative stress has been implicated as a contributing factor for both the onset and progression of diabetes, it is essential to verify the degree of tissue oxidative stress in this adult offspring. Therefore, the aims of this study were to evaluate IR, oxidative stress, final steps of IS and inflammatory pathway in the GM of adult rats, offspring of rats with AP. For this purpose, 21 female Wistar rats (2 months of age) were distributed into three groups: 1) control rats (CN); 2) group with one AP induced in the upper right first molar (1AP); 3) group with four APs induced in the first and second upper and lower right molars (4AP). AP was induced using a surgical round bur measuring 0.1 mm in diameter. After 30 days of pulp exposure, female rats of all groups were placed for mating. Pregnant rats were separated into individual cages. When the male offspring of all rats reached 75 days of age, the following plasma analyzes were performed: 1) glycemia; 2) insulinemia; 3) IR. Furthermore, the following analyzes were performed in the GM: 1) Akt serine/threonine phosphorylation status, after insulin stimulation; 2) GLUT4 content; 3) degree of DNA methylation in the proximal promoter region of the GLUT4 gene; 4) GLUT4 and TNF- α gene expression; 5) TNF-α and PGC-1α content; 6) p50 and p65 subunits of NF-kB phosphorylation status; 7) oxidative stress (superoxide dismutase ­ SOD and thiobarbiturate reactive species ­ TBARS). Statistical analyzes were performed by analysis of variance, followed by the Tukey test. The level of significance adopted was 5%. Results showed that maternal AP (both 1 infection focus and 4 infection focus) promoted hyperinsulinemia, IR and decrease in SOD antioxidant activity and TBARS concentration in the GM of their adult offspring. However, only maternal AP in four teeth promoted an increase in body weight, food intake and p50 and p65 subunits of NF-kB phosphorylation status in the GM of adult offspring. Furthermore, there was a decrease in Akt serine and threonine phosphorylation status (after insulin stimulation) and in gene expression and protein content of GLUT4 in the GM in adult offspring of rats with 4APs. Maternal AP did not change fasting glycemia, PGC-1α content, degree of DNA methylation in the proximal promoter region of GLUT4, gene expression and protein content of TNF-α in the GM of adult offspring. These results demonstrate that maternal AP is associated with IR and promotes important alterations in IS and inflammation pathways in adult offspring. This reinforces the importance of maternal oral health on the overall health of offspring(AU)

Desempeño predictivo de los criterios diagnósticos de restricción de crecimiento fetal para resultados adversos perinatales en un hospital de Popayán, Colombia / Predictive performance of fetal growth restriction criteria for adverse perinatal outcomes in a hospital in Popayán, Colombia

Objetivos: determinar el desempeño predictivo de la definición de retardo de crecimiento fetal (RCF) de ultrasonografía de la Sociedad de Medicina Materno Fetal (SMMF), consenso Delphi (CD) y Medicina Fetal de Barcelona (MFB) respecto a resultados adversos perinatales en cada una, e identificar si hay asociación entre diagnóstico de RCF y resultados adversos perinatales. Materiales y métodos: se realizó un estudio de cohorte retrospectiva. Se incluyeron gestantes con embarazo único de 24 a 36 semanas con 6 días, quienes fueron atendidas en la unidad de medicina materna fetal con evaluación ecográfica de crecimiento fetal y atención de parto en una institución hospitalaria pública de referencia ubicada en Popayán, Colombia. Se excluyeron embarazos con hallazgos ecográficos de anomalías congénitas. Muestreo por conveniencia. Se midieron variables sociodemográficas y clínicas de las gestantes al ingreso, la edad gestacional, el diagnóstico de RCF y el resultado adverso perinatal compuesto. Se analizó la capacidad predictiva de tres criterios diagnósticos de restricción de crecimiento fetal para malos resultados perinatales y la asociación entre el diagnóstico de RCF y mal resultado periantal. Resultados: se incluyeron 228 gestantes, cuya edad media fue de 26,8 años, la prevalencia de RCF según los tres criterios fue de 3,95 %, 16,6 % y 21,9 % para CD, MFB y SMMF respectivamente. Ningún criterio aportó área bajo la curva aceptable para predicción de resultado neonatal adverso compuesto, el diagnóstico de RCF por CD y SMMF se asoció a resultados adversos perinatales con RR de 2,6 (IC 95 %: 1,5-4,3) y 1,57 (IC 95 %: 1,01-2,44), respectivamente. No se encontró asociación por MFB RR: 1,32 (IC 95 %: 0,8-2,1). Conclusiones: ante un resultado positivo para RCF, el método Delphi se asocia de manera más importante a los resultados perinatales adversos.Los tres métodos tienen una muy alta proporción de falsos negativos en la predicción de mal resultado perinatal. Se requieren estudios prospectivos que reduzcan los sesgos de medición y datos ausentes.

Objectives: To determine the predictive performance of fetal growth restriction by Maternal Fetal Medicine Society (MFMS) definition of ultrasound, the Delphi consensus (DC) and the Barcelona Fetal Medicine (BFM) criteria for adverse perinatal outcomes, and to identify whether there is an association between the diagnosis of fetal growth restriction (FGR) and adverse perinatal outcomes. Material and methods: A retrospective cohort study was conducted including women with singleton pregnancies between 24 and 36 weeks of gestation seen at the maternal fetal medicine unit for ultrasound assessment of fetal growth and delivery care in a public referral hospital in Popayán, Colombia. Pregnancies with ultrasound findings of congenital abnormalities were excluded. Convenience sampling was used. Sociodemographic and clinical variables were measured on admission; additional variables were gestational age, FGR diagnosis and adverse composite perinatal outcome. The predictive ability of three fetal growth restriction diagnostic criteria for poor perinatal outcomes was analyzed and asociation between FGR and adverse perinatlal outcomes. Results: Overall, 228 pregnant women with a mean age of 26.8 years were included; FGR prevalence according to the three criteria was 3.95 %, 16.6 % and 21.9 % for DC, BFM and MFMS, respectively. None of the criteria resulted in an acceptable area under the curve for the prediction of the composite adverse neonatal outcome; FGR diagnosis by DC and MFMS were associated with adverse perinatal outcomes with a RR of 2.6 (95 % CI: 1.5-4.3) and 1.57 (95 % CI: 1.01-2.44) respectively. No association was found for BFM RR: 1.32 (95 % CI: 0.8-2.1). Conclusions: Given a positive result for FGR, the Delphi method is significantly associated with adverse perinatal outcomes. The proportion of false negative results for a poor perinatal outcome is high for the three methods. Prospective studies that reduce measurement and attrition bias are required.

Referencias locales de valores de variables biométricas fetales por trimestre de gestación / Local references of values of fetal biometric variables in each trimester of pregnancy

RESUMEN Introducción: Las tablas de crecimiento y la ecografía de rutina son el estándar de oro para valorar adecuadamente al feto. Se consideran óptimas y adecuadas las tablas de biometría fetal que se crean con datos propios de cada población con el fin de usarlas como referencia, para identificar oportunamente malformaciones, o desviaciones del crecimiento. Objetivo: Identificar desviaciones de la norma de incremento en variables biométricas: diámetro biparietal, circunferencia cefálica, circunferencia abdominal y longitud del fémur. Métodos: Se realizó una investigación con diseño analítico longitudinal retrospectivo en la provincia Villa Clara, en el período comprendido entre enero de 2013 a diciembre de 2017. La población de estudio estuvo conformada por 6050 gestantes. La selección de la muestra se realizó a través de un muestreo no probabilístico intencional por criterios y quedó constituida por 3910 gestantes. Se obtuvieron datos de libros de registros de consultas de genética de áreas de salud seleccionadas. Se utilizaron medidas de resumen para variables cuantitativas, medias y percentiles (10, 50 y 90). Resultados: En el diámetro biparietal, la circunferencia cefálica y longitud del fémur, los valores reales obtenidos fueron inferiores a Hadlock en la mayoría de las semanas; la circunferencia abdominal cambió el comportamiento que llevaban las variables, ya que en esta predominaron los valores superiores entre los reales obtenidos, sobre todo en el percentil 10. Conclusiones: Los percentiles bajos de todas las variables en las primeras semanas, presentaron valores superiores a los de la tabla de Hadlock, pero en la circunferencia abdominal fetal, la muestra local tiene valores superiores mayoritarios a través de las semanas.

ABSTRACT Introduction: growth charts and routine ultrasound are the gold standard to adequately assess the fetus. Fetal biometry tables, created with data from each population, are considered optimal and appropriate in order to use them as a reference and to timely identify malformations or growth deviations. Objective: to identify deviations from the increase norm in the following biometric variables: biparietal diameter, head circumference, abdominal circumference and femur length. Methods: a retrospective, longitudinal and analytical study was conducted in Villa Clara province between January 2013 and December 2017. The study population consisted of 6050 pregnant women. The selection of the sample was carried out through an intentional non-probabilistic sampling and was made up of 3910 pregnant women who meet the criteria established for the study. Data were obtained from genetic consultation record books from selected health areas. Summary measures were used for quantitative variables, means and percentiles (10, 50 and 90). Results: the real values obtained in the biparietal diameter, head circumference and femur length were lower than Hadlock in most weeks; abdominal circumference changed the behavior of the variables, since in this the superior values prevailed between the real ones obtained, mainly in the10th percentile. Conclusions: low percentiles of all variables in the first weeks had higher values than those of the Hadlock table, but in the fetal abdominal circumference, the local sample had higher values throughout the weeks.

Gene-environment interactions related to maternal exposure to environmental and lifestyle-related chemicals during pregnancy and the resulting adverse fetal growth: a review

BACKGROUND@#There are only limited numbers of reviews on the association of maternal-child genetic polymorphisms and environmental and lifestyle-related chemical exposure during pregnancy with adverse fetal growth. Thus, this article aims to review: (1) the effect of associations between the above highlighted factors on adverse fetal growth and (2) recent birth cohort studies regarding environmental health risks.@*METHODS@#Based on a search of the PubMed database through August 2021, 68 epidemiological studies on gene-environment interactions, focusing on the association between environmental and lifestyle-related chemical exposure and adverse fetal growth was identified. Moreover, we also reviewed recent worldwide birth cohort studies regarding environmental health risks.@*RESULTS@#Thirty studies examined gene-smoking associations with adverse fetal growth. Sixteen maternal genes significantly modified the association between maternal smoking and adverse fetal growth. Two genes significantly related with this association were detected in infants. Moreover, the maternal genes that significantly interacted with maternal smoking during pregnancy were cytochrome P450 1A1 (CYP1A1), X-ray repair cross-complementing protein 3 (XRCC3), interleukin 6 (IL6), interleukin 1 beta (IL1B), human leukocyte antigen (HLA) DQ alpha 1 (HLA-DQA1), HLA DQ beta 1 (HLA-DQB1), and nicotinic acetylcholine receptor. Fetal genes that had significant interactions with maternal smoking during pregnancy were glutathione S-transferase theta 1 (GSTT1) and fat mass and obesity-associated protein (FTO). Thirty-eight studies examined the association between chemical exposures and adverse fetal growth. In 62 of the 68 epidemiological studies (91.2%), a significant association was found with adverse fetal growth. Across the studies, there was a wide variation in the analytical methods used, especially with respect to the genetic polymorphisms of interest, environmental and lifestyle-related chemicals examined, and the study design used to estimate the gene-environment interactions. It was also found that a consistently increasing number of European and worldwide large-scale birth cohort studies on environmental health risks have been conducted since approximately 1996.@*CONCLUSION@#There is some evidence to suggest the importance of gene-environment interactions on adverse fetal growth. The current knowledge on gene-environment interactions will help guide future studies on the combined effects of maternal-child genetic polymorphisms and exposure to environmental and lifestyle-related chemicals during pregnancy.

Prediction of birth weight in pregnancy with gestational diabetes mellitus using an artificial neural network / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Gestational diabetes mellitus (GDM) is common during pregnancy, with the prevalence reaching as high as 31.0% in some European regions (McIntyre et al., 2019). Dysfunction of the glucose metabolism in pregnancy can influence fetal growth via alteration of the intrauterine environment, resulting in an increased risk of abnormal offspring birth weight (McIntyre et al., 2019). Infants with abnormal birth weight will be faced with increased risks of neonatal complications in the perinatal period and chronic non-communicable diseases in childhood and adulthood (Mitanchez et al., 2015; McIntyre et al., 2019). Therefore, accurate estimation of birth weight for neonates from women with GDM is crucial for more sensible perinatal decision-making and improvement of perinatal outcomes. Timely antenatal intervention, with reference to accurately estimated fetal weight, may also decrease the risks of adverse long-term diseases.

Investigation of teratogenic effects of letrozole on fetal bone development / Investigación de los efectos teratogénicos de letrozol en el desarrollo óseo fetal

SUMMARY: Letrozole is mainly used for the treatment of unexplained infertility, breast cancer and polycystic ovarian syndrome, with secondary use in ovarian stimulation. In cases of unexpected or unknown pregnancy during the use of letrozole, letrozole may cause a teratogenic effect on the fetus. In this reason, in this study, we aimed to determine the effect of letrozole on fetal bone development. In this study, 32 pregnant Wistar albino rats were used. The rats were divided into four groups: Control (saline) and high; 0.3 mg/kg, medium; 0.03 mg/kg, low; 0.003 mg/ kg letrozole. Saline and letrozole were administered in 100 mL solutions by intraperitonaly from day 11 to day 15 of pregnancy. The skeletal system development of fetuses was examined with double skeletal staining, immunohistochemical staining methods and mineral density scanning electron microscopy. A total of 100 fetuses from female rats, 25 in each group, were included in the study. As a result of that, ossification rates were observed to decrease depending on the dose of letrozole in the forelimb limb (scapula, humerus, radius, ulna) and hindlimb (femur, tibia, fibula) limb bones. As a result of the statistical analysis, a statistically significant decrease was found in the ossification rates of all bones between the control group and low, medium, high letrozole groups (p<0.001). Exposure to letrozole during pregnancy adversely affected ossification and bone growth. However, the teratogenic effects of letrozole are unclear. Therefore, it needs to be investigated more extensively.

RESUMEN: Letrozol se usa principalmente para el tratamiento de la infertilidad inexplicable, el cáncer de mama y el síndrome de ovario poliquístico, con estimulación ovárica de uso secundario. En casos de embarazo inesperado o desconocido durante el uso de letrozol, puede causar un efecto teratogénico en el feto. Por esta razón, en este estudio, nuestro objetivo fue determinar el efecto de letrozol en el desarrollo óseo fetal. Se utilizaron 32 ratas albinas Wistar preñadas las cuales se distribuyeron en cuatro grupos: Control (solución salina) y alta; 0,3 mg/kg, medio; 0,03 mg/kg, bajo; 0,003 mg/kg de letrozol. Se administró solución salina y letrozol en soluciones de 100 mL por vía intraperitoneal desde el día 11 hasta el día 15 de la preñez. El desarrollo del sistema esquelético de los fetos se examinó con tinción esquelética doble, métodos de tinción inmunohistoquímica y microscopía electrónica de barrido de densidad mineral. Se incluyeron en el estudio un total de 100 fetos de ratas hembra, 25 en cada grupo. Como resultado, se observó que las tasas de osificación disminuían dependiendo de la dosis de letrozol en los huesos de los miembros torácicos (escápula, húmero, radio, ulna) y de las miembros pélvicos (fémur, tibia, fíbula). Se encontró una disminución estadísticamente significativa en las tasas de osificación de todos los huesos entre el grupo control y los grupos de letrozol bajo, medio y alto (p<0,001). La exposición a letrozol durante la preñez afectó negativamente la osificación y el crecimiento óseo. Sin embargo, los efectos teratogénicos del letrozol no están claros por lo que debe ser investigado más extensamente.

Relato de Caso: arco aórtico a direita com Divertículo de Kommerell / Case Report: aortic arch to the right with Kommerell's Diverticulum

RESUMO O divertículo de Kommerell é uma alteração rara que ocorre mais comumente com arco aórtico à esquerda e origem anômala de artéria subclávia direita (0,5%-2,0%). Em geral é assintomático, com sintomas relacionados a cardiopatias congênitas quando presentes. PALAVRA-CHAVE: Ultrassonagrafia pré-natal, desenvolvimento fetal, anormalidades congênitas

ABSTRACT Kommerell's diverticulum is a rare disorder that most commonly occurs with a left aortic arch and anomalous origin of the right subclavian artery (0.5%- 2.0%). It is usually asymptomatic, with symptoms related to congenital heart disease when present. KEYWORDS: Prenatal ultrasonography, fetal development, congenital abnormalities

Nutritional research and fetal programming: parental nutrition influences the structure and function of the organs / Investigación nutricional y programación fetal: la nutrición parental influye en la estructura y función de los órganos

SUMMARY: Rodents are animals extensively used in biomedical and nutrition research, a necessary step before the research in humans. The composition and type of administration of the experimental diets are relevant and should be thought, considering each type of animal used in the research. It is particularly important to consider, among others, the metabolic differences between species and food needs in macro- and micronutrients to avoid possible bias. The American Institute of Nutrition (AIN) made recommendations for rodents, adapted to the period of growth (AIN-93G), which are pivotal in fetal programming studies. The experiments can be compared among different studies and better translated into humans, considering these limitations in the nutrition of parents and offspring. The review addresses different compositions of experimental food for rodents during development with the ability to induce fetal programming in the offspring and chronic diseases in adulthood due to the nutrition of the mother and father. The 'developmental origins of health and disease' (DOHaD) concept due to maternal nutrition is commented considering the protein restriction, vitamin D restriction, obesity, and intake of fructose or fish-oil. The 'paternal origins of health and disease transmission' (POHaD), because of the nutritional state of the father, were also analyzed in the review, primarily considering the obesity of the father. The review proposes some diet compositions to experimental research considering varied nutritional situations, hoping to assist young researchers or researches not familiar with experimental diet manipulations in the elaboration of the projects.

RESUMEN: Los roedores son animales utilizados frecuentemente en la investigación biomédica y nutricional, un paso necesario antes de la investigación en humanos. La composición y el tipo de administración de las dietas experimentales son relevantes y se debe considerar cada tipo de animal utilizado en los estudios. Es particularmente importante considerar las diferencias metabólicas entre las especies y las necesidades alimentarias de macro y micronutrientes para evitar posibles sesgos. El Instituto Americano de Nutrición (AIN) estableció recomendaciones para los roedores, adaptadas al período de crecimiento (AIN-93G), que son fundamentales en los estudios de programación fetal. Los experimentos se pueden comparar entre diferentes estudios y aplicar en humanos, considerando estas limitaciones en la nutrición de padres e hijos. La revisión aborda diferentes composiciones de alimentos para estudios experimentales en roedores durante su desarrollo, con la capacidad de inducir programación fetal en la descendencia y enfermedades crónicas en la adultez, considerando la nutrición de los padres. El concepto de 'orígenes del desarrollo de la salud y la enfermedad' (DOHaD) debido a la nutrición materna se comenta considerando la restricción de proteínas, la restricción de vitamina D, la obesidad y la ingesta de fructosa o aceite de pescado. Los 'orígenes paternos de la salud y transmisión de enfermedades' (POHaD), debido al estado nutricional del padre, también fueron analizados considerando principalmente la obesidad del padre. La revisión propone algunas composiciones dietéticas a la investigación experimental considerando situaciones nutricionales variadas, con la esperanza de ayudar a jóvenes investigadores o investigadores no familiarizados con las manipulaciones experimentales de la dieta en la elaboración de los proyectos.

Placental mechanisms underlying the effects of maternal stress on the fetal development / 生理学报

Placenta is the only link between the pregnant woman and fetus, and the basis for maintaining the normal pregnancy process and fetal development. Maternal stress is the maternal physiological and psychological changes caused by various factors, characterized by the increased level of glucocorticoid, which affects the hypothalamic-pituitary-target gland axis and regulates the expression of target genes. Maternal stress also changes the weight, metabolism and nutrient transportation of the placenta, which will substantially influence the development of fetus. This paper will firstly summarize the characteristics of maternal stress and its influence on offspring. Then, the changes in the body under maternal stress will be described. Finally, we will clarify the proven mechanisms underlying maternal stress and raise some important problems that have not been clarified in this area. The study of maternal stress on fetus and its underlying mechanisms will serve as theoretical basis for the diagnosis and treatment of the stress-related pregnant diseases and disorders.

Development of fetal growth charts in twins stratified by chorionicity and mode of conception: a retrospective cohort study in China / 中华医学杂志(英文版)

BACKGROUND@#Twin pregnancies continue to increase worldwide; however, the current clinical prenatal evaluation for the intrauterine growth of twins still relies on the growth standards of singletons. We attempted to establish a set of fetal biometric references for Chinese twin pregnancies, stratified by chorionicity and conception mode as spontaneously conceived monochorionic diamniotic (SC-MCDA), spontaneously conceived dichorionic diamniotic (SC-DCDA), and assisted reproductive technology dichorionic diamniotic (ART-DCDA) twins.@*METHODS@#From 2016 to 2019, the ultrasonographic fetal biometric measurements were longitudinally collected in pregnant women, including fetal weight, biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length. The linear mixed models were used to test the difference of growth patterns between groups, and the growth curve of each biometric parameter was modeled by a generalized additive model for location scale and shape.@*RESULTS@#A total of 929 twin pregnant women and 2019 singleton pregnant women, met the inclusion criteria. Among twin pregnancies, 148 were SC-MCDA, 215 were SC-DCDA, and 566 were ART-DCDA twins. Overall, SC-DCDA twins grew faster than SC-MCDA twins, while slower than ART-DCDA twins (all P < 0.05), and all of the three groups showed significant differences comparing with singletons, especially during the third trimester. Hence, the customized fetal growth charts of each fetal biometric parameter were, respectively, constructed for SC-MCDA, SC-DCDA, and ART-DCDA twins.@*CONCLUSIONS@#The fetal biometric trajectories demonstrated characteristic patterns according to chorionicity and conception mode. To fill the gap, we modeled fetal biometric parameters for Chinese SC-MCDA, SC-DCDA, and ART-DCDA twin pregnancies, hoping to provide a reference for the further establishment of fetal growth reference values for Chinese twin fetuses.

Gestational echobiometry in brachycephalic bitches using high-definition ultrasonography / Ecobiometria gestacional em cadelas braquicefálicas utilizando ultrassonografia de alta-definição

The objective of the present study was to obtain echobiometric values for the most important canine maternal-fetal tissues using high-definition ultrasonography (HDUS) trying to update the formulas for predicting gestational age. Twelve healthy bitches of brachycephalic breeds weighing 7-13kg and aged one to four years were included. The fetuses were analyzed every day using conventional and high-definition ultrasonography from the eighth day after artificial insemination until the day of delivery, using the ACUSON S2000/SIEMENS ultrasound equipment and specific software. Embryonic and fetal structures; diameter of the embryonic vesicle; length of the embryo; biparietal diameter, abdominal length and kidney height; length of the femur, humerus, scapula, radius, and tibia; thickening of the stomach wall; adrenal length; and cardiac size were measured. These variables were correlated with gestational and adjusted tested according to regression models. The results obtained (P<0.001) for: lateral diameter of the gestational sac (R2=81.8%); length of the embryo (R2=85.7%); biparietal (R2=99.1%) and abdominal diameter (R2=97.2%); thickness of the gastric wall (R2=86.9%); length of the femur (R2=96.6%), radius (R2=97.5%), humerus (R2=96.5%), scapula (R2=95.8%) and tibia (R2=97.3%); kidney length (R2=95.8%) and height (R2=96.0%); adrenal length (R2=89.6%); heart length (R2=93.0%) and height (R2=91.5%) of the canine fetuses showed significant correlation with gestational days. This allowed monitoring fetal growth and estimation of age with high accuracy in different gestational periods.(AU)

O objetivo do presente estudo foi obter valores ecobiométricos para os tecidos materno-fetais caninos, usando a ultrassonografia de alta definição (HDUS), desenvolvendo fórmulas para prever a idade gestacional das cadelas. Doze cadelas saudáveis de raças braquicefálicas pesando 7-13kg e com idades entre um e quatro anos foram incluídas. Os fetos foram analisados diariamente com ultrassonografia convencional e de alta definição, do oitavo dia após a inseminação artificial até o dia do parto, utilizando o equipamento de ultrassom ACUSON S2000/SIEMENS e software específico. Estruturas embrionárias e fetais; diâmetro da vesícula embrionária; comprimento do embrião; diâmetro biparietal, comprimento abdominal e altura renal; comprimento do fêmur, úmero, escápula, rádio e tíbia; espessamento da parede do estômago; comprimento adrenal; e tamanho cardíaco foram medidos. Essas variáveis foram correlacionadas com o teste gestacional e ajustado de acordo com os modelos de regressão. Os resultados obtidos (P<0,001) para: diâmetro lateral do saco gestacional (R2=81,8%); comprimento do embrião (R2=85,7%); diâmetro biparietal (R2=99,1%) e abdominal (R2=97,2%); espessura da parede gástrica (R2=86,9%); comprimento do fêmur (R2=96,6%), rádio (R2=97,5%), úmero (R2=96,5%), escápula (R2=95,8%) e tíbia (R2=97,3%); comprimento do rim (R2=95,8%) e altura (R2=96,0%); comprimento adrenal (R2=89,6%); o comprimento do coração (R2=93,0%) e a altura (R2=91,5%) dos fetos caninos apresentaram correlação significativa com os dias gestacionais. Isso permitiu monitorar o crescimento fetal e estimar a idade com alta precisão em diferentes períodos gestacionais.(AU)