Abstract The first aim of this study was to investigate the relationship between Doppler ultrasonographic parameters and biochemical markers of human fetal cardiac dysfunction and myocardial cell damage in pregnancies complicated by placental insufficiency and/or fetal growth restriction. Our second aim was to examine fetal central and peripheral hemodynamic characteristics associated with retrograde aortic isthmus net blood flow. Fetuses with significant myocardial cell damage (cTnT > 0.10 ng/ml) had increased pulsatility in the blood velocity waveforms of ductus venosus, left hepatic vein and inferior vena cava, and had more often atrial pulsations in the umbilical vein. Their umbilical artery NT-proANP concentrations were higher than in fetuses without myocardial cell damage. The proportion of left ventricular cardiac output of the combined cardiac output was greater and the corresponding proportion of the right ventricle was less than in fetuses with only increased NT-proANP levels ( > 1145 pmol/l). Tricuspid regurgitation was present more often and the right ventricular fractional shortening was less in fetuses with myocardial cell damage than in fetuses with normal umbilical artery cTnT levels. In fetuses with placental insufficiency and/or growth restriction (n = 48), umbilical artery NT-proANP concentrations showed a significant positive correlation with ductus venosus, left hepatic vein and inferior vena cava pulsatility index values for veins. Fetuses with placental insufficiency and antegrade aortic isthmus net blood flow demonstrated a shift in their right ventricular cardiac output from the pulmonary to the systemic circulation, and foramen ovale volume blood flow made up the majority of the left ventricular cardiac output. Fetuses with retrograde aortic isthmus net blood flow failed to demonstrate these changes, and they had signs of increased left atrial pressure. In addition, right ventricular fractional shortening was decreased and the pulsatility in the ductus venosus blood velocity waveforms was increased. In conclusion, human fetal myocardial cell damage was associated with a rise in systemic venous pressure, a change in the distribution of cardiac output towards the left ventricle and a rise in right ventricular afterload. Fetuses with retrograde aortic isthmus net blood flow failed to rearrange the distribution of the cardiac output and they had signs of increased left atrial pressure. In addition, right ventricular afterload and pulsatility in the ductus venosus blood velocity waveforms were increased.

Introdução: O istmo aórtico (IAo) fetal é um pequeno segmento vascular localizado entre a origem da artéria subclávia esquerda e a extremidade aórtica do canal arterial, que reflete o equilíbrio entre a impedância ao fluxo no território cerebral e na circulação fetal periférica. Considerado o único shunt arterial verdadeiro entre os sistemas vasculares direito e esquerdo, seu fluxo alterado se associa a resultados perinatais adversos, incluindo aumento da mortalidade fetal e morbidade neurológica, especialmente em fetos com insuficiência placentária e restrição de crescimento. Justificativa: Não há protocolo mundial estabelecido definindo conduta clínica baseada na avaliação Doppler do istmo aórtico fetal, havendo espaço para que sua análise seja incorporada como justificativa para indicação do parto e proteção contra injúrias perinatais. Entretanto, implementar novas medidas à prática clínica requer a demonstração de quão confiáveis e reprodutíveis são os resultados obtidos, o que contribui para a garantia de qualidade em sua utilização. Objetivos: Estimar a reprodutibilidade intra e interobservador do índice de pulsatilidade do istmo da aorta fetal (IAo-IP) no terceiro trimestre de gestação (32 a 36+6 semanas), e determinar qual das aquisições, longitudinal ou transversal, produz medidas com melhores confiabilidade e concordância. Métodos: Estudo observacional (transversal) para o qual foram convidadas a participar gestantes no terceiro trimestre de gestação (32 a 36+6 semanas) que preenchiam os critérios de elegibilidade. O IAo-IP foi obtido por dois observadores, que utilizaram os planos longitudinal e transversal para as aquisições, realizadas de forma completamente independente, sem que tivessem conhecimento dos valores das próprias medidas, tampouco das medidas do outro observador. Os dados foram apresentados como média ± DP (desvio-padrão), mediana, mínimo e máximo; A reprodutibilidade foi avaliada pelo coeficiente de correlação intraclasse (ICC). Resultados: As principais características das 49 gestantes foram: média de idade de 26.3 ± 4.7 anos, variando entre 18 e 40 anos, com média da idade gestacional de 33.6 ± 1.5 semanas e índice de massa corporal de 27.9 ± 4.5 Kg/m2. Os resultados dos IP obtidos do estudo Doppler espectral do istmo aórtico fetal pela via longitudinal, demonstraram uma média de 2.75 ± 0.46 para o observador A, 2.53 ± 0.38 para o observador B, e 2.74 ± 0.58 para a segunda medida do observador A. Para a via transversal, as médias foram de 2.75 ± 0.46 para o observador A, 2.53 ± 0.38 para o observador B, e 2.74 ± 0.58 para a segunda medida do observador A. A avaliação Doppler do istmo aórtico fetal no plano longitudinal apresentou ICC de 0.25 na comparação entre os observadores (interobservador), e de 0.42 para a análise intraobservador. No plano transversal, os coeficientes obtidos foram de 0.18 e 0.43 respectivamente para as análises inter-observador e intraobservador. Conclusões: Embora o papel do istmo aórtico na hemodinâmica fetal esteja bem estabelecido, o presente estudo demonstrou que sua reprodutibilidade no terceirotrimestre (32 a 36+6 semanas) é fraca, logo, a medida do IAo-IP deve ser interpretada com cautela, desencorajando seu emprego na prática clínica. Os estudos que examinam aperfeiçoamentos técnicos para melhorar a sua reprodutibilidade devem ser incentivados / Introduction: The fetal aortic isthmus (AoI) is a small vessel located between the origin of the left subclavian artery and the aortic extremity of the arterial ductus, which reflects the balance between the impedance of the brain and systemic circulation of the fetus. Known as the only arterial shunt regarding both right and left vascular systems, its abnormal flow is associated to adverse perinatal outcomes, including high fetal mortality and neurological morbidity, especially among placental insufficiency and growth-restricted fetuses. Rationale: There is no established global protocol defining clinical management based on the Doppler evaluation of the fetal aortic isthmus, allowing its analysis to be incorporated as a reason to indicate delivery and protection against perinatal injury. However, implementation of new methods to clinical practice requires demonstration of how reliable and reproducible the results are, which contributes to quality assurance in their use. Objectives: To estimate the intra and interobserver reproducibility of the fetal aortic isthmus pulsatility index (IAo-PI) in the third trimester of gestation (32 to 36+6 weeks), and to determine which of both longitudinal and transversal acquisitions show better reliability and agreement. Methods: Observational (cross-sectional) study in which were invited to participate pregnant women in the third trimester of gestation (32 to 36+6 weeks) who met the eligibility criteria. The AoI-PI was obtained by two observers, who used the longitudinal and transverse plans for the acquisitions, performing independent acquisitions and blinded analysis. Data were presented as mean ± SD (standard deviation), median, minimum and maximum. The reproducibility was evaluated by the intraclass correlation coefficient (ICC). Results: The main characteristics of the 49 pregnant women were: mean age of 26.3 ± 4.7 years, ranging from 18 to 40 years, with mean gestational age of 33.6 ± 1.5 weeks and body mass index of 27.9 ± 4.5 kg/m2. The results of the PI obtained from the spectral Doppler evaluation of the fetal aortic isthmus, regarding the longitudinal plane, have demonstrated an average of 2.75 ± 0.46 for observer A, 2.53 ± 0.38 for observer B, and 2.74 ± 0.58 for the second measurement of observer A. For the transversal plane the mean values were 2.75 ± 0.46 for the observer A, 2.53 ± 0.38 for the observer B, and 2.74 ± 0.58 for the second measurement of the observer A. The Doppler evaluation of the fetal aortic isthmus in the longitudinal plane has shown a ICC of 0.25 in the comparison between the observers (interobserver), and 0.42 for the intraobserver analysis. In the transversal plane, the coefficients obtained were 0.18 and 0.43 respectively for the interobserver and intraobserver analysis. Conclusions: Although the role of the aortic isthmus in fetal hemodynamics is well established, the present study have reported that its reproducibility in the third trimester (32 to 36+6 weeks) is very poor, so the measurement of the AoI-PI should be interpreted with caution, discouraging its use in clinical practice. Studiesexamining technical amendments to improve its reproducibility should be encouraged