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.

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.

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.

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)

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.

Complicaciones cardiovasculares en relación con la programación fetal / Cardiovascular complications related to fetal programming

Introducción: la programación fetal ofrece nuevas perspectivas sobre el origen de las enfermedades cardiovasculares, relacionando su aparición con factores perinatales. Objetivo: exponer evidencia que vincule las alteraciones gestacionales con las enfermedades cardiovasculares en la vida adulta del feto. Metodología: búsqueda en las bases de datos EBSCO, COCHRANE, MEDLINE, PROQUEST y SciELO de los artículos de revisión e investigaciones originales en inglés publicados en los últimos diez años. Se utilizaron términos MeSH para búsqueda controlada y se evaluaron los estudios con STROBE y PRISMA según correspondía. Resultados: los hallazgos sugieren que nacer con menos de 2600 k guarda relación con diabetes mellitus (OR de 1.607 IC 95% 1.324-1.951), hipertensión arterial (OR de 1.15 IC 95% 1.043-1.288) y menor función endotelial (1.94+0.37 vs 2.68+0.41, p: 0.0001) en la adultez. La prematuridad se asocia con mayores presiones arteriales sistólicas (4.2 mmHg IC 95%; 2.8 - 5.7 p 0.001) y diastólicas (2.6 mmHg IC 95%; 1.2-4.0; p 0.001). Las alteraciones nutricionales maternas y la diabetes gestacional aumentan el riesgo de síndrome metabólico (OR 1.2 IC 95% 0.9-1.7) y sobrepeso en la edad escolar (OR 1.81 IC 95% 1.18 - 2.86). Conclusión: los resultados adversos en la gestación están relacionados con el desarrollo de enfermedades cardiovasculares en la vida adulta del feto expuesto.

Introduction: fetal programming offers new perspectives on the origin of cardiovascular diseases, relating their appearance with perinatal factors. Objective: to show the evidence associating gestational alterations with cardiovascular diseases in the offspring in adult life. Methodology: an EBSCO, COCHRANE, MEDLINE, PROQUEST and SciELO databases search of original review and research articles published in English in the last ten years was conducted. MeSH terms were used to perform a controlled search. The studies were analyzed accordingly using the STROBE and PRISMA reporting guidelines. Results:The findings suggest that a birth weight of less than 2600 kg is related with diabetes mellitus (OR = 1.607, 95% CI 1.324 to 1.951), hypertension (OR = 1.15, 95% CI 1.043 to 1.288) and impaired endothelial function (1.94+0.37 vs 2.68+0.41, p: 0.0001) in adulthood. Prematurity is related with higher systolic blood pressure (4.2 mmHg 95% CI; 2.8 to 5.7 p 0.001) and diastolic blood pressure (2.6 mmHg 95% CI; 1.2 to 4.0; p 0.001). Maternal nutritional alterations and gestational diabetes increase the risk of metabolic syndrome (OR = 1.2 95% CI 0.9 to 1.7) and overweight in school-age (OR = 1.81 95% CI 1.18 to 2.86). Conclusion: adverse results during pregnancy are related with the development of cardiovascular diseases in the exposed fetus in adult life.

Exposição à sífilis na gestação e suas consequências perinatais e no neurodesenvolvimento infantil / Exposure to syphilis during pregnancy and its perinatal and neurodevelopmental consequences for children

Objetivo: Descrever os possíveis acometimentos perinatais e no neurodesenvolvimento infantil entre crianças expostas à sífilis durante a gestação comparadas com crianças que não foram expostas à sífilis. Métodos: Trata-se de um estudo retrospectivo de caso controle. Houve aprovação do comitê de ética da instituição. Foram incluídas crianças nascidas de mulheres que tiveram resultado positivo para sífilis durante a gestação, sem outra infecção congênita associada. Para cada caso, foram selecionados dois controles pareados pelo mês de nascimento e sexo, e que não apresentavam nenhuma doença tipo TORCH ou arboviroses. Dados sociodemográficos, socioeconômicos e de saúde maternos e dados de saúde do recém-nascido foram coletados por análise de prontuário. Foi utilizado o teste estatístico de qui-quadrado, e valor de p < 0,05 foi considerado significante, sendo calculada a razão de chances (OR) bruta e seus respectivos intervalos de 95% de confiança. Resultados: Após a aplicação de critérios de inclusão e exclusão, foram analisados 29 casos de exposição fetal de sífilis durante gravidez pareados com 58 controles. O estudo observou que no grupo do caso havia mulheres mais jovens e com menor escolaridade. Em relação às alterações fetais, não encontramos mudanças estruturais. Foram encontradas alterações motoras em quatro crianças do grupo exposto à sífilis na gravidez, mas que não persistiram. Até 1 ano de vida, as crianças estavam sem qualquer tipo de alteração. Conclusões: A população de mulheres mais vulnerável a adquirir infecções sexualmente transmissíveis parece ainda ser a mais jovem e com menos escolaridade. Ser exposto à sífilis durante a gravidez não aumentou o risco para atrasos de desenvolvimento provavelmente pelo tratamento adequado.

Objective: To describe the possible perinatal and child neurodevelopmental involvement among children exposed to syphilis during pregnancy compared with children who were not exposed to syphilis. Methods: This is a retrospective case-control study. It was previously approved by the institution's ethics committee research. Children born to women who tested positive for syphilis during pregnancy, without another associated congenital infection, were included. For each case, two controls were selected, matched by month of birth and sex, and who did not present TORCH syndrome or arboviruses. Sociodemographic, socioeconomic, and maternal and newborn health data were collected in the medical record. The chi-square statistical test was used, a p-value of < 0.05 was considered significant and crude odds ratio (OR) and their respective 95% confidence intervals were calculated. Results: After applying the inclusion and exclusion criteria, 29 cases of fetal syphilis exposure during pregnancy were analyzed and matched with 58 controls. The study found that in the case group the women were younger with less education. Regarding fetal alterations, we did not find structural changes. The study encountered motor changes in four children from the group exposed to syphilis during pregnancy, which did not persist. Up to 1 year of life, the children were without any type of alterations. Conclusions: The population of women most vulnerable to acquire sexually transmitted infections still seems to be the youngest and less educated. Being exposed to syphilis during pregnancy did not increase the risk for developmental delays, probably due to adequate treatment.

Exposure to wood smoke pollution during pre-gestational period of rat has effects on placenta volume and fetus size / La exposición a la contaminación por humo de leña durante el período pregestacional de la rata tiene efectos sobre el volumen de la placenta y el tamaño del feto

SUMMARY: Studies in humans showed that prenatal exposure to urban air pollution (AP) influences fetal development, and increases the incidence of adverse pregnancy outcomes and some diseases in postnatal life. However, most of these were performed in environments where the main source of environmental particulate matters (PM) emission is diesel combustion by motor vehicles and industries, thereby ignoring the effects produced by wood smoke pollution. We hypothesized that morphological changes in the placenta could contribute to the reduction in fetal size associated with different periods of exposure to AP produced by wood smoke pollution prior to and during pregnancy. The objective of the study was to investigate the quantitative effects of long-term exposure to environmental levels of wood smoke pollution on the macroscopic and microscopic morphology of the placenta in rats. To test this, pregnant rats were exposed during pregestational and gestational periods to wood smoke pollution in indoor and outdoor environments. At 19 days of gestation, the placentas were obtained by caesarean and were prepared for histological, planimetric and stereological analysis. The volume and proportions of the placental compartments were estimated. In addition, stereological estimators in fetal capillaries were calculated in the labyrinth region. Crown rump length, fetus weight and litter weight were influenced by pregestational and gestational exposure periods. Exposure to wood smoke pollution during pregestational period has significant effect on the volume of the placenta, and consequently on fetal height. In conclusion, this study demonstrated that long-term outdoor exposure to wood smoke pollution from residential heating affects fetal health, decreasing the absolute volume of the entire placenta and the placental interface between the mother and fetus, decreasing the total volume of blood vessels present in the labyrinth region ofthe placenta and affecting the size of the fetus.

RESUMEN: Estudios en humanos demostraron que la exposición prenatal a la polución del aire urbano influye en el desarrollo fetal y aumenta la incidencia de resultados adversos de la gestación y algunas enfermedades postnatales. Sin embargo, la mayoría de ellos fueron realizados en entornos donde la principal fuente de emisión de material particulado, fue la combustión de petróleo por vehículos a motor e industrias, ignorando los efectos producidos por el humo de leña producido por la calefacción intradomiciliaria. Hipotetizamos respecto a que los cambios de la placenta contribuirían a la disminución del tamaño fetal relacionado a los períodos de exposición al humo de leña durante los periodos pregestacional y gestacional. El objetivo del estudio fue investigar los efectos cuantitativos de la exposición al humo de leña sobre la morfología macroscópica y microscópica en placenta de ratas. Para probar esto, ratas preñadas fueron expuestas durante los períodos pregestacional y gestacional a la contaminación por humo de leña en ambientes interiores y exteriores. A los 19 días de gestación, las placentas fueron obtenidas por cesárea y fueron preparadas para un análisis histológico, planimétrico y estereológico. Fue estimado el volumen absoluto y las proporciones de los compartimentos placentarios. Además, fueron calculados estimadores estereológicos en capilares fetales del laberinto y trofoblasto. La longitud, el peso del feto y el peso de la camada fueron influenciados por los períodos de exposición pregestacional y gestacional. La exposición a la contaminación por humo de leñá durante el período pregestacional tuvo un efecto significativo en el volumen de la placenta y, en consecuencia, en la altura del feto. En conclusión, este estudio demostró que la exposición a largo plazo al humo de leña afecta la salud del feto, disminuyendo el volumen absoluto de la placenta, además, afecta la interfaz placentaria entre la madre y feto, disminuyendo el volumen total de vasos sanguíneos presentes en la región del laberinto placentario y por consecuente afectando el tamaño del feto.