Estereología en placentas procedentes de gestaciones gemelares / Stereology in placentas from twin pregnancies

Introducción: La disfunción placentaria origina complicaciones fetales; de manera más frecuente, la restricción del crecimiento intrauterino y la preclampsia. Objetivo: Identificar el patrón estereológico en placentas gemelares, y su relación con la corionicidad y el peso del recién nacido. Métodos: Se realizó un estudio descriptivo en una muestra de 16 gestantes gemelares, 25 placentas y 32 recién nacidos. Se estudiaron las variables peso del recién nacido, número de vellosidades, superficie vellositaria total, área vellositaria, área de nodos, densidad óptica de fibrina en la superficie vellositaria y densidad óptica de fibrina alrededor del vaso. Resultados: Existió relación directa entre el número de vellosidades y la superficie vellositaria total. En las placentas monocoriónicas hubo predominio de recién nacidos bajo peso. Se percibe una diferencia en los resultados de área, según el tipo placentario y la región topográfica. En las placentas monocoriales se observó mayor área, tanto de la vellosidad placentaria como en los nodos sincitiales, siendo el área de la vellosidad mayor en la periferia placentaria, y el área de nodos sincitiales en la región 4 cm del cordón umbilical. Conclusiones: La estereología microscópica a nivel pericordón, a 4 cm del cordón y en la periferia del disco placentario, arrojó diferencias significativas para el área de la vellosidad y la densidad óptica de fibrina en la superficie de la vellosidad. Los valores promedio para el área de nodos sincitiales y la densidad óptica de fibrina alrededor del vaso no mostraron diferencias estadísticamente significativas. Es la corionicidad un predictor del bajo peso al nacer(AU)

Introduction: Placental dysfunction causes fetal complications; more frequently, intrauterine growth restriction and preeclampsia. Objective: To identify the stereological pattern in twin placentas, and its relationship with chorionicity and weight of the newborn. Methods: A descriptive study was carried out in a sample of 16 women with twin pregnancy, 25 placentas and 32 newborns. The variables weight of the newborn, number of villi, total villous surface, villous area, node area, optical density of fibrin on the villous surface and optical density of fibrin around the vessel were studied. Results: There was a direct relationship between the number of villi and the total villous surface. In monochorionic placentas there was a predominance of low birth weight newborns. A difference is observed in the area results according to the placental type and the topographic region. In monochorionic placentas, a greater area was observed, both in the placental villus and in the syncytial nodes, with the villus area being greater in the placental periphery and the area of syncytial nodes in the region 4 cm from the umbilical cord. Conclusions: Microscopic stereology at the perichordal level, 4 cm from the cord and at the periphery of the placental disc showed significant differences for the villus area and fibrin optical density on the villus surface. The average values for the area of syncytial nodes and the optical density of fibrin around the vessel did not show statistically significant differences. Chorionicity is a predictor of low birth weight(AU)

Fetal thymus in growth-restricted fetuses due to placental insufficiency.

OBJECTIVE: The aim of this study was to assess fetal thymus size by ultrasound in growth-restricted fetuses due to placental insufficiency and compare to high-risk and low-risk pregnancy fetuses with normal placental function. METHODS: This is a nested case-control study of pregnant women followed up at a university hospital (July 2012 to July 2013). In all, 30 pregnant women presenting small fetuses for gestational age (estimated fetal weight p95) were compared to 30 high-risk and 30 low-risk pregnancies presenting normal Doppler indices. The thymus transverse diameter and perimeter were converted into zeta score according to the normal values for gestational age. Head circumference and femur length were used to calculate ratios. RESULTS: Fetal thymus were significantly lower in pregnancies with placental insufficiency when compared to high-risk and low-risk pregnancies presenting, respectively, transverse diameter zeta score (-0.69±0.83 vs. 0.49±1.13 vs. 0.83±0.85, p<0.001) and P zeta score (-0.73±0.68 vs. 0.45±0.96 vs. 0.26±0.89, p<0.001). There was also a significant difference (p<0.05) in the ratios among the groups: pregnancies with placental insufficiency (TD/HC=0.10, P/FL=1.32, and P/HC=0.26), high-risk pregnancies (TD/HC=0.11, P/FL=1.40, and P/HC=0.30), and control group (DT/HC=0.11, P/FL=1.45, and P/HC=0.31). CONCLUSION: Fetal thymus size is reduced in growth-restricted fetuses due to placental insufficiency, suggesting fetal response as a consequence of the adverse environment.

Ductus venosus as a marker of fetal growth in first trimester in a population of Colombian pregnant women / Ductus venoso como marcador de crecimiento fetal en primer trimestre en una población de gestantes colombianas

Abstract Objectives: to evaluate the relationship between the ductus venosus (DV) and the variables of fetal growth in the first trimester in a Colombian pregnant population. Methods: a descriptive cross-sectional study was carried out with secondary data obtained from a multicenter study.526 patients were included between weeks 11 and 14 for gestational ultrasound follow-up attended in three health care institutions in Bogotá, Colombia, between May 2014 and October 2018. A bivariate descriptive analysis was carried out where the relationship between the characteristics of the DV in the first trimester and ultrasound findings. Results: the flow wave of the DV in the first trimester was normal in the entire sample, with a pulsatility index of the ductus venosus (DVPI) of 0.96±0.18. In addition, a negative correlation was found between the crown-rump length (CRL) and the DVPI (p<0.05). Conclusion: there is a relationship between the DVPI regarding the CRL, indicating an interest in this early marker in relation to fetal growth alterations; however, more studies are required to determine the usefulness of this variable with respect to fetal growth.

Resumen Objetivos: evaluar la relación entre el ductus venoso (DV) y las variables del crecimiento fetal en primer trimestre en una población de gestantes colombianas. Métodos: se realizó un estudio transversal descriptivo con datos secundarios obtenidos de un estudio multicéntrico. Se incluyeron 526 pacientes entre las semanas 11 a 14 para seguimiento ecográfico gestacional atendidas en tres instituciones prestadoras de salud en Bogotá, Colombia, entre mayo del 2014 y octubre del 2018. Se realizó un análisis descriptivo bivariado donde se evaluó la relación entre las características del DV en primer trimestre y los hallazgos ecográficos. Resultados: la onda de flujo del DV en primer trimestre fue normal en la totalidad de la muestra, con un índice medio de pulsatilidad del ductus venoso (IPDV) de 0,96±0.18. Se encontró una correlación negativa entre la longitud cefalocaudal (LCC) y el IPDV (p<0.05). Conclusión: existe una relación entre el IPDV respecto a la LCC, señalando un interés de este marcador temprano en relación con las alteraciones del crecimiento fetal, sin embargo, se requieren más estudios para determinar la utilidad entre esta variable respecto al crecimiento fetal

Prognostic factors and perinatal outcomes in early-onset intrauterine growth restriction due to placental insufficiency.

OBJECTIVE: To determine the principal prognostic factors and neonatal outcomes associated with perinatal death in cases of early-onset intrauterine growth restriction (IUGR) due to placental insufficiency and to define the cutoff point for the risk of perinatal death. METHODS: A retrospective cohort study conducted with 198 pregnant women with a diagnosis of early-onset IUGR (as detected before the 32nd week of gestational age). The association between the dependent variable (perinatal death) and the independent variables was investigated using a multivariate logistic regression model. The area under the receiver operating characteristic (ROC) curve was calculated to determine the sensitivity and specificity of the adjusted model. A significance level of 5% was established for the entire statistical analysis. RESULTS: Perinatal deaths occurred in 89 (44.9%) of the 198 fetuses with early-onset IUGR. Birthweight <800 grams (OR: 14.73; 95%CI: 4.13-52.54; p < .001), postnatal need for mechanical ventilation (OR: 24.56; 95%CI: 5.58-108.08; p < .001) and postnatal use of an oxygen hood (OR: 0.09; 95%CI: 0.02-0.39; p = .001) remained significantly associated with neonatal death in the multivariate model. The sensitivity, specificity, positive and negative predictive values for birthweight <800 grams and need for mechanical ventilation as predictors of death were, respectively, 84%, 91%, 88%, 88% and 93%, 71%, 60% and 96%, while the values for use of an oxygen hood were, respectively, 15%, 62%, 15% and 62%. CONCLUSION: The principal determinants of perinatal death in fetuses with early-onset IUGR were birthweight <800 grams, gestational age at delivery <30 weeks and postnatal need for mechanical ventilation as risk factors while postnatal use of an oxygen hood was found to constitute a protective factor.

Doppler Ultrasound of the Umbilical Artery: Clinical Application / Ultrassonografia Doppler da artéria umbilical: Aplicação clínica

Abstract Objective To provide a survey of relevant literature on umbilical artery Doppler ultrasound use in clinical practice, technical considerations and limitations, and future perspectives. Methods Literature searches were conducted in PubMed and Medline, restricted to articles written in English. Additionally, the references of all analyzed studies were searched to obtain necessary information. Results The use of this technique as a routine surveillance method is only recommended for high-risk pregnancies with impaired placentation. Meta-analyses of randomized trials have established that obstetric management guided by umbilical artery Doppler findings can improve perinatal mortality and morbidity. The values of the indices of Umbilical artery Doppler decrease with advancing gestational age; however, a lack of consensus on reference ranges prevails. Conclusion Important clinical decisions are based on the information obtained with umbilical artery Doppler ultrasound. Future efforts in research are imperative to overcome the current limitations of the technique.

Resumo Objetivo Compilar informação relevante proveniente da literatura atual sobre a ultrassonografia Doppler das artérias umbilicais (AUs) na prática clínica, considerações e limitações técnicas e perspectivas futuras. Métodos A pesquisa bibliográfica foi realizada nos bancos de dados PubMed e Medline e restringiu-se a artigos escritos na língua inglesa. Recorreu-se também à bibliografia dos artigos selecionados, quando necessário, para obter informação relevante. Resultados A utilização desta técnica como método de vigilância de rotina está apenas recomendada emgravidezes de alto risco comdisfunção placentar.Metanálises de estudos randomizados mostraram que o seguimento obstétrico baseado nos achados do Doppler da artéria umbilical pode melhorar a mortalidade e a morbilidade perinatal. É consensual que os valores dos índices Doppler da AU decrescem com o avanço da idade gestacional. No entanto, há ainda muita incerteza quanto aos valores de referência. Conclusão As informações obtidas através da AU Doppler US são a base para muitas decisões clínicas importantes. Trabalhos de investigação nesta área são essenciais para tentar colmatar atuais limitações da técnica.

Doppler abnormalities and perinatal outcomes in pregnant women with early-onset fetal growth restriction.

OBJECTIVE: To compare Doppler alterations and perinatal outcomes in pregnant women who evolved with early- and late-onset fetal growth restriction (FGR). METHODS: A retrospective, observational cohort study with pregnant women who evolved with FGR treated between January 2018 and April 2019, in which all live births from singleton pregnancies, over 24 weeks, with FGR ultrasound diagnosis and under 2700 g weight were included in the study. RESULTS: Pregnancies with early-onset FGR were more associated with hypertensive disorders (p = .00) and placental vascular insufficiency, resulting in a high degree of umbilical artery Doppler involvement (p = .00) in a short period of pregnancy and higher rates of adverse perinatal outcomes (p = .00). The time of prenatal follow-up of early- and late-onset FGR cases was similar, but the degree of prematurity of the former made the evolution more unfavorable. CONCLUSION: Early-onset FGR had a lower prevalence but was associated with higher maternal and fetal morbidity and mortality than late-onset FGR.

Doppler de arteria umbilical en fetos con síndrome de Down / Umbilical artery Doppler in fetuses with Down syndrome

INTRODUCCIÓN: La aneuploidía más común entre los recién nacidos vivos es el síndrome de Down (SD). En estos niños el crecimiento está disminuido, con una frecuencia del 25% de restricción del crecimiento intrauterino, pero no se ha establecido el papel de la insuficiencia placentaria. El objetivo es estudiar la resistencia placentaria a través del Doppler de arteria umbilical con índice de pulsatilidad (IP) y el tiempo medio de desaceleración (t/2), y el posible efecto de la insuficiencia placentaria en fetos con SD. MÉTODO: Se realizó Doppler en la arteria umbilical en 78 fetos con SD, se midieron el IP y el t/2, y se compararon los resultados con los pesos de nacimiento. RESULTADOS: Se estudiaron 78 fetos con SD con 214 mediciones Doppler. El t/2 y el IP estaban alterados en el 71,5% y el 65% de las mediciones, respectivamente. La incidencia de t/2 alterado aumenta con la edad gestacional desde un 28,6% a las 15-20 semanas hasta un 89,3% sobre las 36 semanas (p < 0,01); cifras similares se observan para el IP. La clasificación de los pesos fue: 64% adecuados, 12% grandes y 24% pequeños para la edad gestacional. La última medición de t/2 antes del parto era normal en el 17% y estaba alterada en el 83%. En el caso del IP, los valores fueron normales en el 27% y anormales en el 73%. El peso de nacimiento, la edad gestacional y el porcentaje de niños adecuados para la edad gestacional eran significativamente mayores en el grupo con Doppler normal que en el grupo con Doppler alterado. El z-score del t/2 estaba marcadamente alterado (−2.23), pero el del peso de nacimiento solo estaba algo disminuido (−0,39). La mortalidad perinatal fue del 10%, significativamente mayor cuando el flujo diastólico era ausente o reverso. CONCLUSIONES: El estudio demuestra que los fetos con SD tienen una alta incidencia de alteración del Doppler umbilical para el IP y el t/2, lo cual sugiere una insuficiencia placentaria grave. Este deterioro parece iniciarse hacia el final del segundo trimestre y aumenta con la edad gestacional. Sin embargo, en estos fetos, la insuficiencia placentaria produce una ligera caída en el crecimiento fetal. Como hipótesis general pensamos que en los fetos con SD hay datos claros de insuficiencia placentaria, pero habría algún factor que les protegería de una restricción grave del crecimiento.

INTRODUCTION: The most common aneuploidy in live newborns is Down syndrome (DS), in these children growth is decreased, with a frequency of 25-36% of fetal growth restriction (FGR); however, it is not established the role of placental insufficiency. The objective is to study the Doppler of the umbilical artery with pulsatility index (PI) and half peak systolic velocity (hPSV) deceleration time and the possible role of placental insufficiency in fetuses with DS. METHOD: Doppler was performed in fetuses with DS, the umbilical artery and IP and hPSV were measured, and the results were compared with birth weights. RESULTS: 78 fetuses with DS were studied with 214 Doppler measurements. hPSV and the IP were altered in 71.5% and 65% of the measurements; the incidence of abnormal hPSV increases with gestational age from 28.6% between 15 to 20 weeks, to 89.3% over 36 weeks (p < 0.01), similar figures are observed with respect to the PI. The weight classification was: 24% of FGR, 12% of great for age and 64% of adequate for gestational age (AGA). The last measurement of hPSV before delivery was normal in 17% of the fetuses and was abnormal in 83%, in the case of PI the normal and abnormal values were 27 and 73%, respectively. Birth weight, gestational age, and the percentage of AGA children were significantly higher in the normal Doppler group than in the abnormal Doppler group. The hPSV z-score was markedly altered (−2.23), but the birth weight z-score is slightly decreased (−0.39). Perinatal mortality is 10% and is significantly higher when diastolic flow is absent or reverse. CONCLUSIONS: The study shows that DS fetuses have a high incidence of abnormal umbilical Doppler measured with IP and hPSV, which suggests severe placental insufficiency, this deterioration seems to start towards the end of the second trimester and increases with gestational age. However, in these fetuses, placental insufficiency causes a discrete drop in fetal growth. As a general hypothesis, we think that there is clear evidence of placental insufficiency in fetuses with DS, but there would be some factor that would protect these fetuses from severe growth restriction.

Pregnancy loss due to amnionitis in anglo-arabian mare-Case report.

The amnion is a layer of the foetal membrane that has mechanical protection function and allows expansion and growth. The diseases that affect amnion have rarely been reported in horses. Amnionitis and funiculitis have been implicated as components of abortions as observed in abortions caused by the mare reproductive loss syndrome. Here, we report an abortion at 240-day gestation of a 7-year-old Anglo-Arabian mare with a history of previous stillbirth. Blood samples from both mare and foetus were collected for serological testing. Fragments from the placenta were taken for macroscopic and histopathological examinations. The results of these tests ruled out leptospirosis and concluded that the cause of the abortion was non-infectious chronic amnionitis. Moreover, the decreased vascularization in the placenta was consistent with placental insufficiency. This case highlights the importance of monthly ultrasound monitoring in equine pregnancy in order to diagnose placental insufficiency. The study also confirmed the efficiency of the histopathological examination for the definitive diagnosis of placental inflammation and for the study of foetal vascularization to rule out placental insufficiency in equine reproduction.

Predictors of perinatal outcome in early-onset fetal growth restriction: A study from an emerging economy country.

OBJECTIVE: To identify antenatal predictors of adverse perinatal outcomes in a population of preterm fetuses with early placental insufficiency diagnosed by Doppler abnormalities. METHOD: In this cross-sectional study of a cohort of singleton pregnant women diagnosed with early placental insufficiency, relationships between perinatal variables (arterial and venous Doppler, gestational age, birth weight, oligohydramnios, estimated fetal weight, and fetal weight z-scores) and major neonatal complications were analyzed by logistic regression. RESULTS: Two hundred sixty-five women were delivered, between 24 and 33 weeks gestation. The overall frequency of intact survival was 57.9% (n = 154). Gestational age thresholds for best prediction of survival was 27 + 6 weeks and for intact survival was 29 + 0 weeks gestation. Fetal weight and absent/reversed ductus venosus a-wave were the main predictors of survival in the regression model. When fetal weight was substituted for fetal weight z-score, ductus venosus abnormal Doppler predicted mortality and absent or reversed umbilical artery diastolic velocities predicted intact survival. CONCLUSIONS: This study illustrates the impact of gestational age and fetal weight on perinatal outcomes in early placental insufficiency, with well-defined thresholds. Gestational age and fetal weight, or a combination of fetal weight z-scores and fetal Doppler parameters, were the best predictors of intact survival in our sample.

Pulmonary Vein Flow Impedance: An Early Predictor of Cardiac Dysfunction in Intrauterine Growth Restriction.

INTRODUCTION: In intrauterine growth restriction (IUGR), increased uteroplacental vascular impedance contributes to preferential flow to left ventricle (LV), with consequent alteration of its compliance and increased left atrial (LA) pressure. Pulmonary vein pulsatility index (PVPI) reflects the increased impedance to LA filling and could be used as a cardiac monitoring parameter in IUGR. MATERIAL AND METHODS: A total of 27 IUGR fetuses (group 1), 28 fetuses with appropriate growth for gestational age from hypertensive mothers (group 2), and 28 controls (group 3) were studied. Pulsatility indices (PIs) of pulmonary veins and ductus venosus were calculated by Doppler echocardiography. Obstetric ultrasound was used to assess the PIs of uterine, umbilical, and middle cerebral arteries. Statistical analysis used analysis of variance, post-hoc Tukey, and Pearson's tests. RESULTS: Mean PVPI was higher in IUGR group (1.27 ± 0.39) when compared to groups 2 (1.02 ± 0.37; p = 0.01) and 3 (0.75 ± 0.12; p < 0.001). In group 2, moderate correlation between PVPI and ductus venosus pulsatility index (DVPI) was found but not between PVPI and cerebroplacental ratio (CPR). DISCUSSION: Higher PVPI in IUGR reflects decreased LV compliance and altered LA dynamics. As LV dysfunction precedes right ventricle, our results suggest that PVPI could be an early echocardiographic parameter of fetal diastolic function in IUGR.

A história obstétrica de gestantes com trombofilias hereditárias / Obstetric history of pregnant women with hereditary thrombophilias

Introdução: A doença tromboembólica venosa e as complicações obstétricas resultantes do tromboembolismo placentário são as principais causas de morbidade e mortalidade materna e fetal. Pode-se dizer que a gravidez é um fator independente para o desenvolvimento de trombose, já que seu risco é de 5 a 6 vezes maior em mulheres grávidas quando comparadas a não grávidas, sendo mais elevado após o parto. Métodos: Trata-se de uma coorte histórica, onde foram estudadas pacientes atendidas no Serviço de Obstetrícia da Universidade Federal de Juiz de Fora (expostos=n=70 pacientes) e na Faculdade de Medicina de Barbacena (não expostos=n=74 pacientes). As pacientes foram divididas em dois grupos: Grupo 1 = pacientes com alguma trombofilia identificada (expostos) através das dosagens de proteína S, proteína C, homocisteína, antitrombina III, mutação da MTHFR, mutação da protrombina e do fator V de Leiden; e Grupo 2 = pacientes do serviço de baixo risco obstétrico. Resultados: Houve associação entre trombofilia e aborto prévio, bem como trombofilia e morte fetal prévia (p<0,05). O tipo de trombofilia que foi associada a abortamento prévio foi o déficit da proteína S. A mutação da MTHFR foi associada aos antecedentes de HELLP síndrome (p=0,03; x2 =4,2) e de pré-eclâmpsia (p=0,03; X2 =4,5) quando em homozigotia mutante. A homozigotia para a MTHFR foi também associada às médias de homocisteína, de forma que as homozigotas eram aquelas que apresentavam a maior dosagem de homocisteína (p=0,01; X2 =5,8; X= 27,2 ± 41,2 vs. 12,62 ± 19,0). Conclusão: As trombofilias hereditárias podem estar associadas a mau desfecho obstétrico e devem ser valorizadas na clínica obstétrica. (AU)

Introduction: Venous thromboembolic disease and obstetric complications resulting from placental thromboembolism are the main causes of maternal and fetal morbidity and mortality. Pregnancy is considered an independent factor for the development of thrombosis, as its risk is 5 to 6 times greater in pregnant women when compared to non-pregnant women, being even higher after childbirth. Methods: This historical cohort included patients seen at the Obstetrics Service of Federal University of Juiz de Fora (exposed patients, n = 70) and at the School of Medicine of Barbacena (unexposed patients, n = 74). The patients were divided into two groups: Group 1 consisted of patients with some thrombophilia identified through measurement of protein S, protein C, homocysteine, antithrombin III, MTHFR mutation, prothrombin and factor V Leiden mutations; and Group 2 consisted of patients from the low obstetric risk service. Results: There was an association between thrombophilia and previous abortion, as well as thrombophilia and previous fetal death (p < 0.05). MTHFR mutation was associated with history of HELLP syndrome (p = 0.03; x2 = 4.2) and preeclampsia (p = 0.03; x2 = 4.5) when in homozygous mutation. Homozygous MTHFR was also associated with mean homocysteine levels, so that homozygotes were those with highest homocysteine levels (p = 0.01; x2 = 5.8; x = 27.2 ± 41.2 vs. 12.62 ± 19.0). Conclusions: Hereditary thrombophilias may be associated with poor obstetric outcome and should be valued at clinical obstetrics. (AU)

Avaliação do padrão de restrição do crescimento fetal em gestantes infectadas pelo vírus Zika / Evaluation of the pattern of fetal growth restriction in pregnant women infected with Zika virus

O foco principal desta Dissertação é a caracterização da restrição de crescimento em fetos expostos à infecção pelo vírus Zika (ZIKV) durante a gestação. A população de estudo é formada por mulheres com gestações únicas e testes moleculares positivos para a infecção pelo ZIKV detectados durante a gestação e que foram acompanhadas no IFF entre janeiro de 2016 e março de 2017. Optamos por dividir em dois grupos: fetos de crescimento normal e fetos com crescimento restrito e em faixas de idade gestacional para facilitar a interpretação; o critério diagnóstico para a restrição de crescimento foi a medida da circunferência abdominal abaixo do percentil 10 para a idade gestacional. As variáveis biométricas fetais foram reclassificadas em Z-scores conforme a idade gestacional e, juntamente com as variáveis Dopplervelocimétricas, foram analisadas comparando-se os dois grupos, utilizando o teste t-Student. Observamos que em todas as faixas analisadas, houve diferença significativa entre os parâmetros biométricos, principalmente as circunferências cefálica e abdominal, o fêmur apresentou menor discrepância entre grupos. Na avaliação Dopplervelocimétrica, destacou-se a diferença no índice de pulsatilidade da artéria umbilical. Por fim, descrevemos as malformações congênitas mais frequentes no grupo de fetos restritos, como microcefalia, ventriculomegalia, calcificações intracranianas e artrogripose. Os achados deste estudo sugerem que o vírus Zika interfere no crescimento fetal de uma forma mais seletiva, prejudicando apenas parcialmente o crescimento de ossos longos, e que também promove algum grau de insuficiência placentária, o que explicaria o aumento na resistência ao fluxo sanguíneo umbilical neste grupo de fetos acometidos.

The main focus of this Dissertation is the characterization of growth restriction in fetuses exposed to Zika virus infection during pregnancy. The study population consists of women with singleton pregnancies and positive molecular tests for ZIKV infection detected during pregnancy and who were followed at Instituto Fernandes Figueira between January, 2016 and March, 2017. Then, they were divided into two groups: fetuses with adequate growth and fetuses with restricted growth and we stratified them in gestational age strata to facilitate interpretation; the diagnostic criterion for the growth restriction was the abdominal circumference below the 10th percentile for gestational age. Fetal biometric variables were reclassified into Z-scores according to gestational age and, along with Dopplervelocimetric variables, they were analyzed by comparing the two groups using Student's t-test. We observed that in all analyzed strata, there was significant difference between biometric parameters, especially head and abdominal circumferences, femur length displayed lower discrepancy between groups. On Dopplervelocimetric evaluation, we highlight the difference in the umbilical artery pulsatility index. Finally, we describe the most frequent congenital malformations in the group of restricted fetuses, such as microcephaly, ventriculomegaly, intracranial calcifications and arthrogryposis. The findings of this study suggest that the Zika virus interferes in fetal growth in a more selective form, partially harming femoral growth, and that it also promotes some degree of placental insufficiency, which could explain the increase in umbilical blood flow resistance in the group of affected fetuses.

As consequências da restrição de crescimento intrauterino na estrutura e fluxo sanguíneo cerebral: uma revisão da literatura / The consequences of fetal growth restriction on brain structure and blood flow: a review

A Restrição de Crescimento Fetal (RCF) é definida como uma incapacidade do feto em alcançar seu potencial de crescimento, afeta 5-10% das gestações e está associada à alta morbimortalidade fetal e neonatal, principalmente a danos neurológicos. O objetivo dessa revisão foi levantar os estudos sobre a alteração cerebral nos fetos com RCF que possam estar relacionados aos danos neurológicos pós-natais já estabelecidos. Nesses fetos, há um crescimento desigual das estruturas cerebrais e reconhece-se que, na dependência de hipoxemia crônica e privação de nutrientes provocados pela insuficiência placentária, o feto tende a preferenciar o fluxo sanguíneo para o cérebro em detrimento de outros órgãos. Os resultados dessa revisão sugerem que o efeito protetor do aumento da perfusão sanguínea cerebral é diferente em cada estágio de deterioração fetal, propondo uma ordem hierárquica na proteção das diferentes funções/áreas cerebrais, e quanto mais severo esse acometimento, maiores mudanças estruturais cerebrais o feto apresentará.(AU)

Fetal growth restriction is defined as an inability of the fetus to reach its growth potential, affects 5-10% of pregnancies and is associated with high fetal and neonatal morbidity and mortality, mainly neurological damage. The aim of this review was to investigate brain alterations in fetus with fetal growth restriction that may be related to the already established postnatal neurological damage. In these fetus there is an uneven growth of the brain structures and it is recognized that in dependence on chronic hypoxemia and nutrient deprivation caused by placental insufficiency, the fetus tends to prefer the blood flow to the brain in detriment of other organs. The results of this review suggest that the protective effect of increased cerebral blood perfusion is different at each stage of fetal deterioration, proposing a hierarchical order in the protection of the different brain functions / areas and more severe this involvement, bigger structural changes the fetus will present.(AU)

¿Se relaciona la obesidad en el embarazo con muerte fetal por insuficiencia placentaria? / Is obesity in pregnancy related to fetal death due to placental insufficiency?

Se presentan 4 casos de muerte fetal en pacientes obesas con embarazos de término, con hallazgos placentarios variados, que sugieren insuficiencia placentaria, que podrían estar asociados a la obesidad. Esta afirmación se basa en evidencias recientes que demuestran que la obesidad por intermedio de la disminución de los mediadores como apelina, leptina, reguladores del tono vascular placentario y de otros reguladores de la angiogénesis, alteran la función placentaria especialmente en embarazos de término y podrían estar implicados con inadecuado crecimiento fetal y con resultados adversos asociados con la obesidad. Comunicamos un mecanismo inusualmente descrito relacionado posiblemente con la obesidad y con resultado desfavorable del embarazo.

We present 4 cases of fetal death in obese pregnant women with term pregnancies, with several placental findings suggesting placental insufficiency, that could be associated with obesity. According to recent evidence obesity could be associated with inadequate fetal growth and adverse outcomes especially at term pregnancies, through the decrease of mediators such as apelin, leptin, regulators of placental vascular tone and other regulators of angiogenesis altering placental function. We report a rarely described mechanism possibly related to obesity and unfavorable outcome of pregnancy.

Fetal growth standards in gastroschisis: Reference values for ultrasound measurements.

OBJECTIVES: The objectives of this study were to create growth curves based on ultrasonography biometric parameters of fetuses with gastroschisis, comparing them with normal growth standards, and to analyze umbilical artery (UA) Doppler velocimetry patterns. METHODS: A cohort study of 72 fetuses with gastroschisis, at gestational ages between 14 and 39 weeks was designed. Mean and standard deviation were calculated, with the 5th, 10th, 50th, 90th, and 95th centiles being established for biometric parameters according to gestational age. Curves were obtained, comparing with normal reference via the Mann-Whitney test. UA Doppler velocimetry patterns were obtained. RESULTS: A total of 434 examinations were performed, and centiles were established for biparietal diameter, head circumference, abdominal circumference, femur length, and estimated fetal weight. A significant difference was observed between the gastroschisis measurements when compared to control, with all curves shifted downwards. Abdominal circumference was the parameter presenting the largest difference. Estimated fetal weight was also lower, with mean difference of 256.3 ± 166.8 g for the 50th centile (P < .0001). UA Doppler velocimetry was normal in 97.5%. CONCLUSIONS: Fetuses with gastroschisis show symmetrical growth deficits in the second and third trimesters, with normal UA Doppler velocimetry. These results reinforce the hypothesis that they are constitutionally smaller, yet not restricted because of placental insufficiency.

Revealed versus concealed criteria for placental insufficiency in an unselected obstetric population in late pregnancy (RATIO37): randomised controlled trial study protocol.

INTRODUCTION: Fetal growth restriction (FGR) affects 5%-10% of all pregnancies, contributing to 30%-50% of stillbirths. Unfortunately, growth restriction often is not detected antenatally. The last weeks of pregnancy are critical for preventing stillbirth among babies with FGR because there is a pronounced increase in stillbirths among growth-restricted fetuses after 37 weeks of pregnancy. Here we present a protocol (V.1, 23 May 2016) for the RATIO37 trial, which evaluates an integrated strategy for accurately selecting at-risk fetuses for delivery at term. The protocol is based on the combination of fetal biometry and cerebroplacental ratio (CPR). The primary objective is to reduce stillbirth rates. The secondary aims are to detect low birth weights and adverse perinatal outcomes. METHODS AND ANALYSIS: The study is designed as multicentre (Spain, Chile, Mexico,Czech Republic and Israel), open-label, randomised trial with parallel groups. Singleton pregnancies will be invited to participate after routine second-trimester ultrasound scan (19+0-22+6 weeks of gestation), and participants will be randomly allocated to receive revealed or concealed CPR evaluation. Then, a routine ultrasound and Doppler scan will be performed at 36+0-37+6 weeks. Sociodemographic and clinical data will be collected at enrolment. Ultrasound and Doppler variables will be recorded at 36+0-37+6 weeks of pregnancy. Perinatal outcomes will be recorded after delivery. Univariate (with estimated effect size and its 95% CI) and multivariate (mixed-effects logistic regression) comparisons between groups will be performed. ETHICS AND DISSEMINATION: The study will be conducted in accordance with the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 23May 2016. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT02907242; pre-results.

Fetal growth restriction: current knowledge.

BACKGROUND: Fetal growth restriction (FGR) is a condition that affects 5-10% of pregnancies and is the second most common cause of perinatal mortality. This review presents the most recent knowledge on FGR and focuses on the etiology, classification, prediction, diagnosis, and management of the condition, as well as on its neurological complications. METHODS: The Pubmed, SCOPUS, and Embase databases were searched using the term "fetal growth restriction". RESULTS: Fetal growth restriction (FGR) may be classified as early or late depending on the time of diagnosis. Early FGR (<32 weeks) is associated with substantial alterations in placental implantation with elevated hypoxia, which requires cardiovascular adaptation. Perinatal morbidity and mortality rates are high. Late FGR (≥32 weeks) presents with slight deficiencies in placentation, which leads to mild hypoxia and requires little cardiovascular adaptation. Perinatal morbidity and mortality rates are lower. The diagnosis of FGR may be clinical; however, an arterial and venous Doppler ultrasound examination is essential for diagnosis and follow-up. There are currently no treatments to control FGR; the time at which pregnancy is interrupted is of vital importance for protecting both the mother and fetus. CONCLUSION: Early diagnosis of FGR is very important, because it enables the identification of the etiology of the condition and adequate monitoring of the fetal status, thereby minimizing risks of premature birth and intrauterine hypoxia.

Effects of transcutaneous electrical nerve stimulation on fetal and placental development in an experimental model of placental insufficiency.

OBJECTIVE: To elucidate the effects of transcutaneous electrical nerve stimulation (TENS) in pregnancies with placental insufficiency. METHODS: Pregnant rats were subjected to uterine artery ligation and to TENS according to the following groups: ligated stimulated (LS); ligated non-stimulated (LN), control stimulated (CS); and control non-stimulated (CN). Fetal external measurements, such as crown-rump length (CRL), fronto-occipital distance (FOD), thoracic ventral-dorsal (TVDD) and abdominal ventral-dorsal (AVDD) distances were analyzed together with the area occupied by fetal internal organs. Glucose transporter 1 (GLUT-1) expression was evaluated by immunohistochemistry in fetal organs. Thickness of junctional, labyrinth and intermediate placental zones was analyzed by morphometric evaluation in HE-stained slides, and placental hypoxia-inducible factor 1 alfa expression was measured by real-time polymerase chain reaction. RESULTS: In LN and CS groups compared to the CN group, CRL was reduced (27.51/28.95 versus 30.16 mm), as well as FOD (6.63/6.63 versus 7.36 mm), AVDD (7.38/8.00 versus 8.61 mm) and TVDD (6.46/6.87 versus 7.23 mm). Brain GLUT-1 expression was higher in LS (1.3%) and CS (1.8%). The area occupied by placental vessels in the labyrinth zone (29.67 ± 3.51 versus 20.83 ± 7.63) and intermediate zone (26.46 ± 10.21 versus 10.86 ± 8.94) was larger in the LS group than in the LN group. CONCLUSIONS: Our results suggest a negative effect of TENS on placental development, thus compromising the maintenance of adequate blood flow to the fetus.

Comparison between transdermal nitroglycerin and sildenafil citrate in intrauterine growth restriction: effects on uterine, umbilical and fetal middle cerebral artery pulsatility indices.

OBJECTIVES: To evaluate the effects of transdermal nitroglycerin (GTN) and sildenafil citrate on Doppler velocity waveforms of the uterine (UtA), umbilical (UA) and fetal middle cerebral (MCA) arteries in pregnancies with intrauterine growth restriction (IUGR). METHODS: This was a prospective study of 35 singleton pregnancies (gestational age, 24-31 weeks) with IUGR and abnormal UtA and UA Doppler waveforms. We compared maternal arterial blood pressure and Z-scores of the pulsatility index (PI) of UtA, UA and fetal MCA before and after application of a transdermal GTN patch (average dose, 0.4 mg/h), oral sildenafil citrate (50 mg) or placebo. Statistical analysis was performed by ANOVA for paired samples. RESULTS: There was a significant decrease in UtA-PI after application of GTN (21.0%) and sildenafil citrate (20.4%). A significant reduction in UA-PI was also observed for both GTN (19.1%) and sildenafil citrate (18.2%). There was no difference in UtA- and UA-PI when the GTN and sildenafil groups were compared. No changes in Doppler velocimetry were observed in the placebo group and no significant change in MCA-PI was observed in any group. Maternal arterial blood pressure decreased with administration of both GTN and sildenafil citrate in those with pre-eclampsia. CONCLUSION: The use of transdermal GTN or sildenafil citrate in pregnancies with IUGR is associated with a significant reduction in both UtA and UA Doppler PI, as well as maternal arterial blood pressure. Neither drug affected the MCA-PI. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.