Aortic isthmus doppler velocimetry in fetuses with intrauterine growth restriction: A literature review / Dopplervelocimetria do istmo aórtico em fetos com crescimento intrauterino restrito: Uma revisão da literatura

Abstract Intrauterine growth restriction (IUGR) is associated with poor perinatal prognosis and a higher risk of stillbirth, neonatal death, and cerebral palsy. Its detection and the evaluation of its severity by new Doppler velocimetric parameters, such as aortic isthmus (AoI), are of great relevance for obstetrical practice. The AoI is a vascular segment that represents a point of communication between the right and left fetal circulations. It is considered to be a functional arterial shunt that reflects the relationship between the systemic and cerebral impedances, and has recently been proposed as a tool to detect the status of hemodynamic balance and prognosis of IUGR in fetuses. In the present review, we noticed that in healthy fetuses, the AoI net flow is always antegrade, but in fetuses with IUGR the deterioration of placental function leads to progressive reduction in its flow until it becomes mostly retrograde; this point is associated with a drastic reduction in oxygen delivery to the brain. The more impaired the AoI flow is, the greater is the risk of impairment in the Doppler velocimetry of other vessels; and the alterations of the AoI Doppler seem to precede other indicators of severe hypoxemia. Although there seems to be an association between the presence of retrograde flow in the AoI and the risk of long-term neurologic disability, its role in the prediction of perinatal morbi-mortality remains unclear. The AoI Doppler seems to be a promising tool in the management of fetuses with IUGR, but more studies are needed to investigate its employment in clinical practice.

Resumo O crescimento intrauterino restrito (CIUR) está associado a um prognóstico perinatal adverso, com maior risco de óbito intrauterino e neonatal, bem como de paralisia cerebral. Assim, sua detecção e a determinação de sua gravidade por novos parâmetros Dopplervelocimétricos, como o istmo aórtico (IAo), são de fundamental importância na prática obstétrica. O IAo é um segmento vascular que representa um ponto de comunicação entre os sistemas circulatórios fetais esquerdo e direito. É considerado um shunt arterial funcional, capaz de refletir a relação entre as impedâncias dos circuitos cerebral e sistêmico, e foi proposto como uma ferramenta para detecção do status do equilíbrio hemodinâmico e do prognóstico de fetos com CIUR. Na presente revisão, observou-se que, em fetos saudáveis, o fluxo predominante no IAo é sempre anterógrado; mas em fetos com CIUR a deterioração do estágio de insuficiência placentária acarreta reduções progressivas no fluxo ístmico até este apresentar sentido predominantemente retrógrado e levar a uma drástica redução no aporte de oxigênio ao sistema nervoso central. Quanto mais alterado estiver o fluxo no IAo, maior a chance de haver alteração na Dopplervelocimetria de outros vasos; e as alterações no Doppler do IAo parecem preceder outros indicadores de hipoxemia severa. Embora o fluxo retrógrado no IAo pareça se correlacionar com maior risco de alteração no desenvolvimento neurológico a longo prazo, ainda não está claro o seu papel na predição de morbimortalidade perinatal. O Doppler do IAo parece ser um parâmetro promissor no manejo do CIUR; entretanto, mais estudos são necessários para avaliar seu emprego na prática clínica.

Modelo predictivo de restricción del crecimiento intrauterino usando doppler de arterias uterinas y edad materna / Predictive model of intrauterine growth restriction using uterine artery doppler and maternal age

INTRODUCCIÓN: La restricción del crecimiento intrauterino representa una importante morbimortalidad perinatal y cuya detección es variable según modelos clínicos y características propias en cada población. OBJETIVO: Evaluar si el Doppler de arterias uterinas y la edad materna conforman un modelo clínico con capacidad predictiva de restricción del crecimiento intrauterino en una amplia muestra de población peruana. MATERIALES Y MÉTODOS: Estudio observacional, analítico, de prueba diagnóstica. Participaron 1344 gestantes atendidas en un centro de referencia nacional materno perinatal Nivel III en Perú entre 2010-2018. La muestra fue seleccionada aleatoriamente y dividida en: muestra de entrenamiento y muestra para validación del mejor modelo clínico obtenido. Se usó análisis multivariado, medición de la capacidad diagnóstica y predictiva. RESULTADOS: El modelo clínico formado por el índice de pulsatilidad promedio mayor al percentil 95 de la arteria uterina y la edad materna mayor a 35 años conformo el modelo con el menor indicador de penalidad de Akaike en comparación con los otros modelos clínicos elaborados en el presente estudio, el índice de Youden fue 0.53. El área bajo la curva ROC fue de 0.75. Se obtuvo una sensibilidad de 71.5%, especificidad 72.1%, valor predictivo positivo 65.8%, valor predictivo negativo 91.2%. CONCLUSIONES: El uso del índice de pulsatilidad promedio de la arteria uterina asociado a la edad materna contribuyen a la formación de un modelo para discriminar RCIU; sin embargo, requiere de otros factores que permitan ajustar el modelo para una mayor tasa de detección.

INTRODUCTION: Intrauterine growth restriction represents an important perinatal morbimortality and its detection varies according to clinical models and characteristics of each population. OBJECTIVES: To evaluate if uterine artery Doppler and maternal age conform a clinical model with predictive capacity of intrauterine growth restriction in a wide sample of Peruvian population. MATERIALS AND METHOD: Observational, analytical, diagnostic test study. A total of 1344 pregnant women attended a national maternal perinatal reference center Level III in Peru between 2010-2018. The sample was randomly selected and divided: training sample and validation sample. In the analysis, multivariate analysis and measurement of diagnostic and predictive capabilities were applied. RESULTS: The clinical model formed by the average pulsatility index greater than the 95th percentile of the uterine artery and maternal age greater than 35 years made up the model with the lowest Akaike's penalty indicator compared to the other clinical models developed in the present study, Youden's index was 0.53. The area under the ROC curve 0.75. Sensitivity 71.5%, specificity 72.1%, positive predictive value 65.8%, negative predictive value 91.2%. CONCLUSIONS: The use of the average pulsatility index of the uterine artery associated with maternal age contributes to the formation of a model to discriminate IUGR; however, it requires other factors to adjust the model for a higher detection rate.

Restricción de crecimiento aumenta el riesgo de displasia broncopulmonar, muerte y sepsis en gemelos de 30 o menos semanas de gestación / Growth restriction increases the risk of bronchopulmonary dysplasia, death, and sepsis in twins of 30 weeks or less of gestation

INTRODUCCIÓN: Múltiples factores influyen en el riesgo de morbimortalidad del prematuro con restricción del crecimiento intrauterino (RCIU). La comparación de gemelos con crecimiento intrauterino discordante permite evaluar su efecto, excluyendo factores maternos y manejo prenatal. Nuestro objetivo fue evaluar el efecto de la RCIU sobre la morbilidad aguda, crónica y mortalidad, en parejas de recién nacidos gemelares prematuros extremos. PACIENTES Y MÉTODO: Gemelos menores de 1500 g y 30 semanas de gestación, de la Red Neocosur. Se realizaron análisis separados de pares de gemelos concordantes, discordantes leves y severos, evaluando el efecto de la RCIU sobre morbi-mortalidad. Se realizó análisis multivariado para establecer magnitud del efecto. RESULTADOS: 459 pares de gemelos, 227 concordantes, 110 discordantes leves y 122 severos. Entre los concordantes solo hubo diferencia en uso de oxígeno a las 36 semanas. En discordantes leves, el menor tuvo menos enfermedad de membrana hialina y requirió menos dosis de surfactante, pero tuvo un mayor riesgo de Displasia broncopulmonar (DBP) o muerte. En discordantes severos, el menor presentó mayor mortalidad, sepsis, utilización y permanencia en ventilación mecánica, pese a menor frecuencia de enfermedad de membrana hialina. En regresión múltiple, el riesgo combinado de DBP o muerte fue mayor en gemelo menor y discordante severo. CONCLUSIÓN: En gemelos discordantes, la patología respiratoria aguda fue más frecuente en el gemelo mayor, aunque el riesgo de DBP o muerte fue mayor en el gemelo con RCIU.

INTRODUCTION: Multiple factors influence the risk of morbidity and mortality of premature infants with intrauterine growth restriction (IUGR). The comparison of twins with different intrauterine growth allows evaluating the effect of the restriction, excluding maternal factors and prenatal mana gement. Our objective was to assess the effect of IUGR on acute and chronic morbidity, and mortality of extreme preterm twins. PATIENTS AND METHOD: Twins weighing less than 1500 grams and gesta tion equal to or less than 30 weeks, of the Neocosur Network. Separate analyses were performed on concordant twin pairs, and on mild and severe discordant twins, evaluating the effect of IUGR on morbidity and mortality. A multivariate analysis was performed in order to establish the impact of this effect. RESULTS: 459 twin pairs, 227 concordant twins, 110 of mild discordance, and 122 of severe discordance. Among the concordant ones, there was only a difference in oxygen uptake at 36 weeks. In those of mild discordance, the smaller twin presented a lower frequency of hyaline membrane disease and required fewer doses of surfactant, but had a higher risk of bronchopulmonary dysplasia (BPD) or death. In severe discordant twins, the smaller one presented higher mortality, sepsis, use and permanence in mechanical ventilation, despite the lower frequency of hyaline membrane disease. In multiple regression analysis, the combined risk of BPD or death was higher in the smaller twin and of severe discordance. CONCLUSION: In discordant twins, the acute respiratory pathology was more frequent in the larger one, although the risk of BPD or death was higher in the one with IUGR.

Is willingness to exercise programmed in utero? Reviewing sedentary behavior and the benefits of physical activity in intrauterine growth restricted individuals / A vontade de se exercitar é programada ainda no útero? Análise do comportamento sedentário e dos benefícios da atividade física em indivíduos com crescimento intrauterino restrito

Abstract Objective: The literature suggests that a fetus will adapt to surrounding adversities by optimizing its use of energy to improve survival, ultimately leading to the programming of the individual's energy intake and expenditure. While recent reviews focused on the fetal programming of energy intake and food preferences, there is also some evidence that fetal adversity is associated with diminished physical activity levels. Therefore, we aimed to review (a) the evidence for an association between being born with intrauterine growth restriction and sedentarism over the life-course and (b) the potential benefits of physical activity over cardiometabolic risk factors for this population. Sources: PubMed, Scielo, Scopus and Embase. Summary of findings: Most clinical studies that used objective measures found no association between intrauterine growth restriction and physical activity levels, while most studies that used self-reported questionnaires revealed such relationships, particularly leisure time physical activity. Experimental studies support the existence of fetal programming of physical activity, and show that exposure to exercise during IUGR individuals' life improves metabolic outcomes but less effect was seen on muscle architecture or function. Conclusions: Alterations in muscle strength and metabolism, as well as altered aerobic performance, may predispose IUGR individuals to be spontaneously less physically active, suggesting that this population may be an important target for preventive interventions. Although very heterogeneous, the different studies allow us to infer that physical activity may have beneficial effects especially for individuals that are more vulnerable to metabolic modifications such as those with IUGR.

Resumo Objetivo: A literatura sugere que um feto se adaptará às adversidades externas ao aprimorar seu gasto energético para melhorar a sobrevida, o que leva, em última instância, à programação do consumo e gasto energético do indivíduo. Apesar de análises recentes terem focado na programação fetal do consumo energético e preferências alimentares, ainda há alguma comprovação de que as adversidades fetais estão associadas aos baixos níveis de atividade física. Portanto, visamos a analisar: a) a comprovação de uma associação entre nascer com restrição de crescimento intrauterino (RCIU) e sedentarismo durante o curso de vida e b) os possíveis benefícios da atividade física sobre os fatores de risco cardiometabólico dessa população. Fontes: PubMed, Scielo, Scopus e Embase. Resumo dos achados: A maior parte dos estudos clínicos que usaram medidas objetivas não constatou associação entre RCIU e os níveis de atividade física, ao passo que a maior parte dos estudos que usaram questionários de autorrelato revelou essas relações, principalmente no que diz respeito à atividade física de lazer. Estudos experimentais corroboram a existência de programação fetal de atividade física e mostram que a exposição a exercícios durante a vida de indivíduos com RCIU melhora os resultados metabólicos, porém menos efeito foi visto sobre a arquitetura ou função muscular. Conclusões: Alterações na força muscular e no metabolismo, bem como o desempenho aeróbico alterado, podem predispor indivíduos com RCIU a serem espontaneamente menos ativos fisicamente, sugere que essa população pode ser um importante alvo de intervenções preventivas. Apesar de muito heterogêneos, os diferentes estudos nos possibilitam deduzir que a atividade física pode ter efeitos benéficos principalmente em indivíduos mais vulneráveis a modificações metabólicas, como aqueles com RCIU.

Papel do Doppler do ducto venoso na restrição de crescimento intrauterino / Ductus venosus Doppler assessment in intrauterine growth restriction

Objetivo: O crescimento intrauterino restrito (CIUR) por insuficiência placentária persiste como grande desafio obstétrico. A interrupção da gestação representa a única estratégia de condução e baseia-se na predição de desfechos adversos. O Doppler tem valor reconhecido na avaliação seriada das alterações circulatórias nesses fetos, em geral sequenciais e proporcionais à gravidade do insulto hipóxico. Este estudo objetiva revisar as evidências do papel do Doppler de ducto venoso (DV) na predição de morbimortalidade perinatal em gestações complicadas por CIUR placentário grave e precoce. Métodos: Realizou-se revisão narrativa, com busca de artigos publicados nos últimos 10 anos nas bases Medline/PubMed, Lilacs e Scielo, sendo encontradas 132 referências. Pesquisas com animais e gestações múltiplas foram excluídas. Dos 115 artigos selecionados, 34 foram excluídos por inadequação ao tema. A revisão baseou-se nas demais 81 referências, além de trabalhos de reconhecida relevância no tema. Resultados: Estudos demonstram evidência consistente do papel do Doppler de DV na avaliação de fetos com CIUR, com bom valor preditivo para acidemia fetal e desfecho perinatal adverso. As principais estratégias de monitorização se baseiam na combinação do Doppler de vasos arteriais/venosos e parâmetros biofísicos, mas o Doppler de DV seria o melhor parâmetro isolado para predição de comprometimento fetal grave. Conclusão: A incorporação do Doppler de DV na monitorização de fetos com CIUR grave e precoce é capaz de predizer desfechos perinatais críticos. A avaliação de múltiplos vasos fetais parece aumentar a acurácia, porém não há evidência para embasar a definição de protocolos para o manejo clínico.(AU)

Objective: Intrauterine growth restriction (IUGR) due to early onset placental insufficiency remains to be a great challenge in obstetrical practice. Delivery is still the only available strategy of management, and timing such intervention depends on prediction of adverse outcomes. Dopplervelocimetry studies have recognized value in the evaluation of the sequential hemodynamic changes that are stablished in the arterial and venous circulation of these fetuses, which correlate with the severity of hypoxemic insult. This study aims to review evidence on ductus venosus (DV) Doppler`s role as a predictor of perinatal outcome in pregnancies complicated by severe early onset IUGR. Methods: A Medline/PubMed, Lilacs and Scielo search was performed to identify original articles and systematic reviews published in the last 10 years. Eighty-one references were included in this review, in addition to other papers of recognized relevance in the subject. Results: Studies demonstrate consistent evidence on DV Doppler`s role in the longitudinal evaluation of IUGR fetuses, with adequate predictive value for fetal acidemia and adverse outcome. Monitoring strategies are usually based on a combination of arterial and venous Doppler assessment, in addition to biophysical parameters, but DV Doppler seems to be the best single parameter for prediction of severe fetal compromise. Conclusion: Monitoring of fetuses with severe early-onset IUGR through DV Doppler is able to predict critical perinatal outcomes. Evaluation of multiple fetal vessels seems to increase accuracy of prediction, but to this moment there is not enough evidence to recommend protocols of management.(AU)

Hipofosfemia en recién nacidos prematuros: un trastorno bimodal / Hypophosphatemia in preterm infants: a bimodal disorder

Las estrategias nutricionales para prematuros extremos con alto aporte de proteínas, han mostrado alteraciones metabólicas con hipofosfemia precoz, especialmente en el grupo de pacientes con restricción de crecimiento intrauterino (Rein). También se presenta hipofosfemia tardía, característica de la enfermedad metabólica ósea. En este artículo se revisan y actualizan conceptos en relación a la fisiopatología del metabolismo del fósforo en recién nacidos prematuros y uso de parenterales precoces en el contexto de enfermedad metabólica ósea. Los artículos fueron identificados en base de datos electrónicas como Pubmed y Rima. Fueron incluidos artículos en inglés y español. Fueron filtrados por título y resumen. La literatura actual propone diversas estrategias de nutrición precoz que permitan asegurar una adecuada cantidad de nutrientes para continuar con el crecimiento y desarrollo extrauterino. En pacientes con nutrición parenteral pero con diferentes aportes de fósforo, o relación calcio: fósforo inadecuada, a mayor contenido de aminoácidos, se presenta hipofosfemia, hipercalcemia, hipomagnesemia, hipokalemia e hiperglicemia, especialmente en casos de Rein. Estas alteraciones se asocian a prolongación de ventilación mecánica, mayor riesgo de displasia broncopulmonar y aumento de sepsis tardía. La hipofosfemia tardía, descrita ya hace muchos años, se presenta con normocalcemia y aumento de fosfatasas alcalinas, en la enfermedad metabólica ósea del prematuro, con alteración de la mineralización en distintos grados, secundaria a un inadecuado aporte de este mineral para los altos requerimientos de estos pacientes. Esta presentación de hipofosfemia precoz y tardía en el prematuro alerta sobre el control oportuno de fosfemia para ajustar el aporte nutricional. En el prematuro con nutrición parenteral precoz, el control en conjunto con la calcemia en la primera semana de vida, especialmente en Rein, permite tratar la hipofosfemia y prevenir sus complicaciones. En hipofosfemia tardía, el seguimiento semanal o quincenal desde las 4 semanas a los prematuros con riesgo, permite lograr un aporte óptimo de minerales.

New nutritional approaches to treat extreme premature babies have demonstrated relevant eviden ce of metabolic disturbances with early hypophosphatemia, especially in patients with intrauterine growth restriction (IUGR). They have shown late hypophosphatemia, as well, which is characteristic in the metabolic bone disease. A sytematic search of literature describing metabolic disturbances of phosphorus in preterm newborns is presented, related to the use of early parenteral nutrition and also in the context of metabolic bone disease. The articles were gathered from electronic data bases, such as PubMed and Rima. We include articles in english and spanish which were selected by titles and abstracts. Several strategies for early nutrition have been proposed in order to ensure an adequate amount of nutrients to accomplish the development and growth of preterm babies. Patients with parenteral nutrition support with different doses of phosphate, or inadequate calcium phosphate relation, or an increased amino acid content, may present hypophosphatemia, hypercalcemia, hy pomagnesemia, hypokalemia and hyperglycemia, all of these are additionally noteworthy in the pre sence of intrauterine growth restriction. Furthermore, said alterations are associated with prolonged mechanical ventilation, as well as bronchopulmonary dysplasia and increase in late onset sepsis. The late hypophosphatemia, described several years ago, arises as normocalcemia and as an increment of alkaline phosphatases in the metabolic bone disease in preterm babies, and also with an inadequate mineralization in different grades, secondary to an inadequate supply due to high nutritional requi rements in these patients. When early or late hypophosphatemia appears in preterm babies, it shall require timely control of phosphemia and will need to adjust the nutritional intake in order to correct it. In case of preterm babies with early parenteral nutrition it will also need a control of calcemia in the first week of birth, especially if those belonging to the IUGR group. Adjustment must be made along with metabolic follow up, as well. In late hypophosphatemia, a weekly or every two weeks fo llow up will be a must for all preterm babies in risk and they should be given supplements to get an optimum mineral supply.

Función gonadal en niños y adolescentes nacidos con restricción del crecimiento intrauterino / Gonadal function in children and adolescents born with restriction of intrauterine growth

Los niños con restricción del crecimiento intrauterino (RCIU) presentan en la vida posnatal una serie de alteraciones metabólicas y hormonales, y tienen predisposición al desarrollo de obesidad, hipertensión arterial, enfermedad cardiovascular, resistencia a la insulina y diabetes tipo 2. La exposición a un ambiente intrauterino desfavorable en fases críticas del desarrollo puede tener un efecto deletéreo sobre la gónada en formación. Se realizó una revisión bibliográfica y puesta al día sobre la posible asociación entre RCIU y alteraciones de la función gonadal en niños y adolescentes de ambos sexos. Para facilitar la actualización, se dividió por etapas en: 1, prenatal; 2, posnatal y prepuberal; 3, puberal, y 4, adulta. La mayoría de los niños que nacen muy prematuros o con muy bajo peso al nacer hacen una transición sin obstáculos desde la infancia a la edad adulta con respecto a la salud reproductiva. Sin embargo, en los varones se puede observar criptorquidia, hipospadias, cáncer testicular y menor fertilidad, y en las niñas, pubertad y menarca temprana, hiperandrogenismo y síndrome de ovario poliquístico. Existen datos controvertidos y se necesitan más estudios para aclarar la relación entre el RCIU y la función hipotálamo-hipófiso-gonadal.

Low birth weight due to intrauterine growth restriction (IUGR) is associated with an increased risk of obesity, hypertension, cardiovascular disease, insulin resistance, and type 2 diabetes during postnatal life. Exposure to an unfavourable intrauterine environment in critical phases of development may have a deleterious effect on the forming gonad. The objective was to carry out a bibliographic review and update on the possible association between IUGR and alterations of gonadal function in children and adolescents of both sexes. To facilitate the update, this was divided into stages: 1, prenatal; 2, postnatal and pre-pubertal; 3, puberal, and 4, adult. Most children born preterm or with low birth weight make a normal transition from childhood to adulthood with respect to reproductive health. However, cryptorchidism, hypospadias, testicular cancer and lower fertility could be observed in boys, and early puberty and menarche, hyperandrogenism and polycystic ovarian syndrome in girls. However, the data are controversial, and further studies are needed to clarify the relationship between IUGR and pituitary gonadal function.

Placental weight and birth weight to placental weight ratio in monochorionic and dichorionic growth-restricted and non-growth-restricted twins

OBJECTIVE: The aim of the present study was to compare the placental weight and birth weight/placental weight ratio for intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. METHODS: This was a retrospective analysis of placentas from twin pregnancies. Placental weight and the birth weight/placental weight ratio were compared in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins. The association between cord insertion type and placental lesions in intrauterine growth-restricted and non-intrauterine growth-restricted monochorionic and dichorionic twins was also investigated. RESULTS: A total of 105 monochorionic (intrauterine growth restriction=40; non-intrauterine growth restriction=65) and 219 dichorionic (intrauterine growth restriction=57; non-intrauterine growth restriction=162) placentas were analyzed. A significantly lower placental weight was observed in intrauterine growth-restricted monochorionic (p=0.022) and dichorionic (p<0.001) twins compared to non-intrauterine growth-restricted twins. There was no difference in the birth weight/placental weight ratio between the intrauterine growth restriction and non-intrauterine growth restriction groups for either monochorionic (p=0.36) or dichorionic (p=0.68) twins. Placental weight and the birth weight/placental weight ratio were not associated with cord insertion type or with placental lesions. CONCLUSION: Low placental weight, and consequently reduced functional mass, appears to be involved in fetal growth restriction in monochorionic and dichorionic twins. The mechanism by which low placental weight influences the birth weight/placental weight ratio in intrauterine growth-restricted monochorionic and dichorionic twins needs to be determined in larger prospective studies.

Comparative analysis of two different models of swimming applied to pregnant rats born small for pregnant age

ABSTRACT The aim of this study was to compare two models of swimming applied to pregnant rats born small for pregnancy age (SPA). Diabetes was chemically induced in adult female rats to develop an inadequate intrauterine environment, leading to birth of a SPA offspring. In adulthood, the female SPA rats were mated and submitted to different swimming programs. The exercise program 1 (Ex1) consisted of swimming for 15 minutes, followed by 15 minutes of rest and another 15 minutes of swimming, 3 days a week before and during pregnancy. Another program (Ex2) was applied during 60 minutes uninterrupted a day, 6 days/week during pregnancy. The pregnant rats presented no interference on body weight and glycemia. The rats submitted to Ex2 model showed decreased insulin and blood glucose levels by oral glucose tolerance test, and reduction in area under curve values. The offspring from dams submitted to both exercise protocols presented an increased rate of newborns SPA. However, the offspring from Ex2 dams showed percentage twice higher of newborns SPA than Ex1 offspring. Our data suggests that continuous exercise of 60 min/day ameliorated the enhanced peripheral insulin sensitivity in growth-restricted females. However, this protocol employed at pregnancy leads to intrauterine growth restriction.

O papel do DOPPLER da artéria cerebral média nos fetos com Crescimento Restrito Tardio / The role of middle cerebral artery Doppler in late onset fetal growth restriction

Ocrescimento intrauterino restrito (CIUR) é uma inibição patológica do crescimento fetal, acometendo 5-10% das gestações e está associado ao aumento da morbimortalidade perinatal. Este estudo tem como objetivo realizar uma revisão não sistemática sobre os eventos adversos perinatais dos fetos com CIUR tardio e alteração seletiva do Doppler da artéria cerebral média (ACM). A pesquisa bibliográfica foi realizada através da base de dados do PubMed, obtendo um total de 25 referências, que serviram de base para o presente artigo. Conclui-se que a artéria cerebral média possui valor particular na identificação e predição de resultados adversos nestes fetos, os quais possuem risco aumentado de desenvolvimento neurológico anormal ao nascimento e aos dois anos de idade.(AU)

Intrauterine growth restriction (IUGR) is a pathological inhibition of the fetal growth that affects 5-10% of pregnancies and it is associated with an increase of perinatal morbidity and mortality. This study aims to conduct a non-systematic review of perinatal adverse events of fetuses with late-onset IUGR and selective changes in middle cerebral artery (MCA) Doppler. A literature search was performed using the PubMed database. A total of 25 references, which were the basis for this article was obtained. It concludes the middle cerebral artery has a particular value in the identification and prediction of adverse outcomes in these fetuses, which has an increased risk of abnormal neurological performance at birth and at two years of age.(AU)

Restricción selectiva del crecimiento intrauterino en la gestación gemelar monocorial: diagnóstico y manejo / Selective intrauterine growth restriction in monochorionic-diamniotic twins: diagnosis and management

La Restricción Selectiva del Crecimiento Intrauterino se produce en 10 a 19% de los gemelos monocoriónicos, y se asocia con un aumento importante de la mortalidad y la morbilidad perinatal. La evolución clínica está dada en gran parte por la presencia de anastomosis vaculares y la distribución placentaria asimétrica. Se propuso una clasificación en tres tipos según el Doppler de la arteria umbilical del gemelo más pequeño, la que sé que se correlaciona con distintos comportamientos clínicos y características de la placenta, lo que ayuda en el asesoramiento y conducta obstétrica. Los del tipo I tienen un pronóstico favorable por el resultado perinatal satisfactorio por lo que se recomienda un seguimiento cercano por ecografía y Doppler. Los de tipo II tienen un mal pronóstico y el tipo III un pronóstico intermedio e impredecible. En estos dos últimos se puede realizar un manejo expectante hasta que se observe deterioro del feto pequeño, considerando la posibilidad de la coagulación con láser o la oclusión del cordón (feticidio selectivo). Ambas conductas aparentemente aumentan las posibilidades de supervivencia del feto de peso normal.

Selective intrauterine growth restriction occurs in 10-19% of monochorionic twins, and is associated with increased mortality important and perinatal morbidity. The clinical course is given largely by the presence of placental vascular anastomosis and asymmetric distribution. It classified into three types according to the proposed Doppler umbilical artery smaller twin, the one that correlates with different clinical behaviors and characteristics of the placenta, which helps in counseling and obstetric conduct. The type I have a favorable prognosis for satisfactory perinatal outcome so closely monitored by ultrasound and Doppler is recommended. The type II has a poor prognosis and type III intermediate and unpredictable prognosis. In these last two you can make an expectant management until deterioration of the small fetus is observed, considering laser coagulation or cord occlusion (selective feticide). Both behaviors appear to increase the chances of survival of the fetus of normal weight.

Resultados perinatales en fetos con flujo umbilical diastólico ausente / Perinatal outcome in fetuses with absent end diastolic umbilical flow

Objetivo: Estudiar los resultados perinatales de fetos diagnosticados con flujo umbilical ausente en diástole en el Hospital Universitario de Canarias, España. Métodos: Estudio retrospectivo de gestantes con Doppler fetal umbilical con flujo diastólico ausente entre 2004 y 2011, excluyendo embarazos gemelares. Las variables estudiadas fueron: edad y enfermedades maternas, edad gestacional al diagnóstico y parto, vía de parto, Apgar y estado del recién nacido. Resultados: Se recogieron 57 casos. Hubo un 43 por ciento de gestantes hipertensas y 19 por ciento de diabéticas. La edad gestacional media al diagnóstico fue de 30+4 semanas. En el 89% de los casos se observó redistribución del flujo y en el 21 por ciento el Doppler umbilical fue reverso. El 28 por ciento se acompañó de oligoamnios y en el 26 por ciento el peso fetal estimado inferior al percentil 3. Hubo 3 muertes fetales. En el 80 por ciento de los casos la vía de parto fue por cesárea. La supervivencia fue del 83 por ciento con una tasa de mortalidad perinatal del 17 por ciento. En el seguimiento entre 1 y 6 años encontramos un 35 por ciento de niños sin secuelas. Conclusiones: En nuestra serie, el Doppler con flujo umbilical ausente en diástole se relaciona con alto riesgo de morbimortalidad perinatal. El 65 por ciento de los niños tendrán secuelas de algún tipo en el seguimiento entre 1 a 6 años. El momento óptimo para la extracción fetal debe ser individualizado y resuelto junto con el consejo pediátrico y participación de los padres.

Objective: To determine the perinatal outcome in fetal growth restriction were umbilical artery Doppler end diastolic flow was absent. Methods: A retrospective study performed at the Canary Islands University Hospital. All consecutive cases between 2004 and 2011 were included. We excluded twin pregnancies. Data was abstracted for maternal age, gestational age at diagnosis and delivery, mode of delivery, Apgar and perinatal adverse outcomes. Results: Fifty seven patients were included. Forty three percent had a pregnancy complicated by hypertension and 19 percent diabetes. Mean gestational age at diagnosis was 30+4 weeks. We found 89 percent and 21 percent absent umbilical artery end diastolic flow and reverse flow respectively. Oligohydramnios was seen in 28 percent of the cases. Fetal weight was below the third percentile in 26 percent of the cases. Fetal demise occurred in 3 cases. Mode of delivery was cesarean section in 80 percent of the cases. We found a rate of 17 percent perinatal mortality. At 1 to 6 years follow up 35 percent of the children had no sequelae. Conclusion: Absent end diastolic umbilical flow is associated with a high risk of perinatal mortality. Up to 65 percent of the children will show some type of sequelae. The optimal gestational date for fetal extraction should be individualized after multidisciplinary counseling.

Aspectos relevantes de la restricción del crecimiento intrauterino / Highlights on Intrauterine Growth Restriction

Introducción: la restricción del crecimiento intrauterino (RCIU) es una afección caracterizada por una limitación del potencial del crecimiento fetal de causa heterogénea y manifestaciones variables. Su importancia no solo radica en lo que significa en la morbilidad y la mortalidad infantil, sino también, en que estos niños tienen habitualmente múltiples problemas posteriores. Objetivos: precisar la incidencia, así como la frecuencia con que se asociaron diversos factores de riesgo y otras situaciones habitualmente relacionadas con este problema de salud. Precisar incidencia de la restricción del crecimiento intrauterino. Identificar diagnóstico y seguimiento oportunos por área y consulta del nivel secundario. Métodos: se realizó un estudio descriptivo, retrospectivo y de corte longitudinal, sobre un total de 133 gestantes con restricción del crecimiento intrauterino, atendidas en el Hospital Materno Infantil 10 de Octubre, entre el 1º de enero y el 31 de julio de 2011. Resultados: el 7,7 porciento de los nacidos fueron pequeños para su edad gestacional. La altura uterina se presentó disminuida solo en el 26,3 porciento de nuestros casos. El peso deficiente al inicio del embarazo (32,5 porciento), así como la insuficiente ganancia de peso durante la gestación (61,2 porciento) fueron situaciones frecuentes. Pocos casos habían sido seguidos en consulta de RCIU hospitalaria (10 porciento), se hizo el diagnóstico al nacimiento. Conclusiones: la sensibilidad de la medición de la altura uterina y del ultrasonido fueron bajas para contribuir a la sospecha de esta entidad

Introduction:the intrauterine growth restriction (IUGR) is a condition characterized by limited fetal growth potential due to heterogeneous causes and it has variable manifestations. Its importance lies not only in what it means in morbidity and mortality, but also that these children usually have multiple problems further. Objectives: to determine the incidence and frequency of associated risk factors and other conditions commonly associated with this health problem, to determine incidence of intrauterine growth restriction, to identify appropriate diagnosis and follow-up strategies by area and secondary consultation. Methods: we conducted a descriptive, retrospective and longitudinal section study of 133 pregnant women with IUGR, who were assisted at the Teaching Maternal and Child Hospital Diez de Octubre, from January 1st to July 31st, 2011. Results: 7.7 percent of the infants were small for their gestational age. The uterine height decreased in only 26.3 percent of our cases. The underweight in early pregnancy (32.5 percent) and insufficient weight gain during pregnancy (61.2 percent)were frequent situations. Few cases have been followed up in IUGR hospital consultation (10 percent)and were diagnosed at birth. Conclusions: The sensitivity of the uterine height measurement and ultrasound were low to support the suspicion of this entity

A restrição do crescimento fetal influencia a composição corporal na idade escolar? / Does fetal growth restriction influence body composition at school age?

OBJETIVO: Verificar a influência do baixo peso de crianças nascidas a termo sobre a composição corporal na idade escolar. MÉTODO: Este estudo consistiu de um corte transversal aninhado em uma coorte de 375 crianças recrutadas ao nascimento em 1993-1994 no estado de Pernambuco. Aos 8 anos de idade, 213 crianças tiveram a composição corporal avaliada através da mensuração da espessura das pregas cutâneas tricipital e subescapular e da circunferência do braço. A regressão linear multivariada foi utilizada para identificar a influência do baixo peso ao nascer, das condições socioeconômicas, do estado nutricional materno e morbidade da criança na prega cutânea tricipital. RESULTADOS: As médias das pregas cutâneas tricipital e subescapular, da circunferência do braço e das áreas muscular e de gordura do braço foram menores nas crianças nascidas com baixo peso em relação às nascidas com peso adequado; no entanto, essas diferenças não foram estatisticamente significantes. Na análise de regressão linear multivariada, as variáveis socioeconômicas explicaram o maior percentual da variação da prega cutânea tricipital (12,3 por cento), especialmente a renda familiar per capita (9,1 por cento), seguida da ocorrência de anemia e da hospitalização anterior, que juntas explicaram 5,6 por cento, e do índice de massa corporal materna, que contribuiu com 2,4 por cento dessa variação. O baixo peso ao nascer não influenciou no depósito de gordura subcutânea tricipital nessa faixa etária. CONCLUSÃO: Os fatores socioeconômicos e a morbidade anterior da criança apresentaram uma maior influência na composição corporal de escolares nascidos a termo em detrimento do baixo peso ao nascer.

OBJECTIVE: To assess the influence of low birth weight in full-term infants on body composition at school age. METHOD: This is a cross-sectional study nested in a cohort of 375 infants recruited at birth between 1993 and 1994 in the state of Pernambuco, Brazil. At 8 years of age, the body composition of 213 children from this cohort was assessed by measurement of triceps and subscapular skinfold thickness and mid upper arm circumference. Multivariable linear regression analysis was used to identify the influence of low birth weight, socioeconomic condition, maternal nutritional status, and child morbidity on triceps skinfold thickness. RESULTS: Mean triceps and subscapular skinfold thickness, mid upper arm circumference, and upper arm muscle and fat areas were lower in children born at term with low weight than in those with appropriate birth weight. However, these differences were not statistically significant. Multivariable linear regression analysis showed that the relative majority of variance in triceps skinfold thickness (12.3 percent) was explained by socioeconomic variables, particularly per capita family income (9.1 percent), followed by anemia and past hospitalization (which, together, explained 5.6 percent of variance) and maternal body mass index, which contributed toward 2.4 percent of this variance. Low birth weight had no influence on triceps subcutaneous fat deposition in this age group. CONCLUSION: Socioeconomic factors and a history of morbidity had a greater influence on body composition than low birth weight in schoolchildren born at term.

Evaluación de la función cardiovascular en fetos con restricción de crecimiento / Cardiac function in fetus with growth restriction

Objective: To evaluate longitudinal changes in the cardiac function parameters in relation to the hemodynamic worsening in growth restricted (IUGR) fetuses. Methods: The cardiac function was serially studied in a cohort of 46 IUGR fetuses below 32 weeks of gestation by 2-D and Doppler ultrasound parameters. IUGR was defined as an estimated fetal weight below the 10th percentile with a Doppler pulsatility index (PI) in the umbilical artery (UA) above 2 standard deviations of the mean. Longitudinal changes, perinatal deaths and survivors were evaluated. Results: All cardiac parameters were significantly different in IUGR fetuses. Aortic isthmus blood flow index (IFI) and Modified myocardial performance index (Mod-MPI) showed the clearest longitudinal changes and temporal deterioration. Conclusions: IFI and Mod-MPI showed consistent longitudinal changes in IUGR fetuses. These 2 markers could be added to the DV to evaluate the fetal deterioration and indicate the optimal time of delivery.

Objetivo: Evaluar cambios longitudinales de los parámetros de función cardíaca en relación al agravamiento hemodinámico en fetos con restricción del crecimiento intrauterino (RCIU). Métodos: La función cardíaca fue estudiada en una cohorte de 46 fetos RCIU con menos de 32 semanas de gestación con parámetros 2-D y ultrasonografía Doppler. Se definió RCIU como un peso fetal estimado bajo el percentil 10 asociado a un índice de pulsatilidad (IP) al Doppler de la arteria umbilical (AU) por debajo de dos desviaciones estándar del promedio. Se evaluaron cambios longitudinales, mortalidad y sobrevida perinatal. Resultados: Todos los parámetros tuvieron diferencias estadísticamente significativas en fetos RCIU. El índice de velocidad de flujo del istmo aórtico (IFI) y el índice de función miocárdico modificado (IFM-mod) mostraron los más evidentes cambios longitudinales y deterioro en el tiempo. Conclusiones: El IFI y el IFM-mod mostraron consistentes cambios longitudinales en fetos RCIU. Estos dos marcadores podrían ser usados junto a la medición del ductus venoso para evaluar el deterioro fetal y la indicación óptima del momento del parto.

Prevalencia del retardo del crecimiento intrauterino en pacientes atendidos en el Hospital Tipo I de Coloncito Estado Táchira en el período entre enero-diciembre 2006 / Prevalence of the intrauterine growth retardation in patients attention at the Hospital of Type I Coloncito Táchira state in the period january-december 2006

El presente es un trabajo cuyo objeto fue caracterizar el Retardo del Crecimiento Intrauterino "RCIU" en pacientes atendidos en el Hospital tipo I de Coloncito entre enero-diciembre 2006, determinando su prevalencia, el tipo más frecuente y los factores de riesgo maternos existentes. Mediante un diseño descriptivo con abordaje longitudinal retrospectivo, con el 100 por ciento de la muestra que representó 362 historias. Se obtuvo que el RCIU tiene una prevalencia de 4,7 por ciento y que de éstos el 82,34 por ciento fue de tipo simétrico; además el factor de riesgo materno que destacó fue el mal control prenatal "CPN" con 42,54 por ciento. Demostrándose así que el RCIU de tipo simétrico tiene una alta prevalencia en nuestra zona y por tal motivo se recomienda buscar medidas para reforzar el CPN, y así recibir el diagnóstico y tratamiento oportuno.

Blood pressure and kidney size in term newborns with intrauterine growth restriction

CONTEXT AND OBJECTIVE: Low birth weight is associated with higher blood pressure in childhood and adulthood. The aim of this study was to investigate the influence of intrauterine growth restriction (IUGR) on newborn systolic blood pressure (SBP). DESIGN AND SETTING: Prospective comparative study at Neonatal and Intensive in Clinical Pediatrics Division, Maternity Hospital in Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. METHODS: 35 newborns with IUGR and 35 without IUGR were compared. Healthy term newborns without malformations, with Apgar score at fifth minute > 6 were included. Birth weight, kidney weight/birth weight ratio, kidney weight (ultrasound scan), plasma renin activity (PRA) and SBP evolution were analyzed during the first month of life (on 1st, 3rd, 7th and 30th days). RESULTS: SBP evolution, kidney weight/birth weight ratio and PRA did not differ between the two groups. In newborns with IUGR, SBP presented positive correlations with birth weight (r = 0.387 p = 0.026) and BMI (r = 0.412 p = 0.017) on the 7th day of life. Positive correlations with birth weight (r = 0.440 p = 0.01) and birth length (r = 0.386 p = 0.026) were also seen on the 30th day. There was an inverse correlation on the 7th day between SBP and kidney weight/birth weight ratio (r = -0.420 p = 0.014), but this did not persist to the end of the month. CONCLUSIONS: IUGR seems not to have any influence on SBP, PRA or kidney weight among term newborns during their first month of life.

CONTEXTO E OBJETIVO: O baixo peso ao nascimento está associado à pressão arterial mais elevada na criança e no adulto. O objetivo foi avaliar a influência do retardo do crescimento intra-uterino (RCIU) na pressão arterial sistólica de recém-nascidos (PAS). TIPO DE ESTUDO E LOCAL: Estudo prospectivo, realizado no berçário anexo à maternidade, Instituto da Criança, Hospital das Clínicas da Universidade de São Paulo. MÉTODOS: 35 recém-nascidos (RN) com RCIU e 35 RN sem RCIU foram avaliados em um estudo prospectivo. Os critérios de inclusão foram: recém-nascidos no termo, saudáveis, sem malformações e índice de Apgar de quinto minuto > 6. Parâmetros antropométricos (peso ao nascimento, relação comprimento renal/peso ao nascimento), dimensões renais (pela ultra-sonografia), dosagem da atividade da renina plasmática (ARP) e a evolução da PAS foram analisadas durante o primeiro mês de vida (no 1°, 3°, 7° e 30° dias de vida). RESULTADOS: A evolução da PAS, relação peso renal/peso ao nascimento e ARP não apresentaram diferença entre os dois grupos. Em recém-nascidos com CIUR, a correlação entre PAS e PN (r = 0,387 p = 0,026) e IMC (r = 0,412 p = 0,017) foi positiva no 7° dia de vida. No 30° dia de vida, a correlação com PN (r = 0,440 p = 0,01) e comprimento ao nascimento (r = 0,386 p = 0,026) também foi positiva. Houve correlação negativa entre a PAS do 7° dia e a relação peso do rim/peso ao nascimento (r = - 0,420 p = 0,014), porém, esta correlação não persistiu ao longo do primeiro mês de vida. CONCLUSÕES: RCIU parece não influenciar a PAS, a atividade de renina plasmática ou o peso renal em recém-nascidos no termo durante o primeiro mês de vida.

Comparison of perinatal outcome of growth-restricted fetuses with normal and abnormal umbilical artery Doppler waveforms.

AIMS: To evaluate the role of umbilical artery Doppler in growth- restricted fetuses. MATERIALS AND METHODS: In a prospective observational study, 70 pregnant women with growth-restricted fetuses confirmed by ultrasound, were followed up with Doppler studies of the umbilical artery. The study group consisted of 35 women, where the Doppler waveform in the umbilical artery was compromised (either absent end diastolic flow [AEDF] or reversed end diastolic flow [REDF]). These were compared with an equal number of controls, where growth- restricted fetuses had normal doppler waveforms. Outcome measures were evaluated in both groups and analyzed. RESULTS: The periods of gestation at delivery were 27.2 +/- 3.5 weeks in group 1 and 37 +/- 3.3 weeks in-group II, respectively. Perinatal morbidity and mortality was significantly increased in the group with compromised umbilical artery blood group. Birth weight in group I was 742 +/- 126 grams and in group II was 1680 +/- 259 grams. This difference was statistically significant (P=0.0001). In comparison to AEDF, REDF fetuses had more morbidities. Perinatal mortality was also significantly increased in this group (P=0.001). CONCLUSION: Umbilical artery Doppler should be used in the management of growth-restricted fetuses. In those fetuses in normal Doppler, pregnancy can be prolonged. REDF is an indication for termination of pregnancy.

Small for gestation and growth hormone therapy.

3 to 10% of neonates are born small for gestation (SGA). This usually occurs because of intrauterine growth retardation (IUGR). After birth most SGA infants show good catch-up growth and normalize their height and weight. About 10% of them continue to remain short (<-2SD) and do not achieve normal adult height, resulting in psychosocial problems. The mechanism of short stature in these children is poorly understood. Infants who do not show catch-up growth usually have an alteration in the GH-IGF-I axis. Diagnostic and management criteria for short stature in SGA were ill-defined in the past. Growth hormone (GH) therapy for improving height in these children has been approved by the FDA. GH therapy leads to growth acceleration and normalization of height during childhood. Long term GH treatment normalizes adult height above -2 SDS in 85% children, and 98% achieve an adult height within their target height range. GH therapy is safe in SGA children, but it is important to monitor for side effects.