Luiz Henrique Nicoloso

New insights on fetal ductal constriction: role of maternal ingestion of polyphenol-rich foods

Fetal ductus arteriosus constriction is a clinical disorder that occurs as a result of inhibition of the prostaglandin synthesis pathway, and has long been associated to maternal intake of nonsteroidal anitiinflammatory drugs in late pregnancy. As a consequence of an increased right ventricular pressure, with tricuspid regurgitation and heart failure, there is a risk for the development of neonatal pulmonary artery hypertension. This artcile reviews the basic knowledge of the mechanisms involved in this important disorder. Clinical and experimental evidence that maternal consumption of polyphenol-rich substances, such as herbal teas, orange and grape juice, chocolate, and others, may interfere with fetal ductus arteriosus dynamics are discussed. Preventive measures to avoid fetal ductal constriction in the third trimester of pregnancy are discussed, including the possible need to change maternal dietary orientation, aiming to limit ingestion of foods with high concentrations of polyphenol-rich substances.

Estudo do encurtamento global do átrio esquerdo em fetos de mães diabéticas

OBJECTIVE: To test the hypothesis that left atrial shortening fraction is lower in fetuses of diabetic mothers than in fetuses of mothers with no systemic disease. METHODS: Forty-two fetuses of mothers with previous diabetes or gestational diabetes and 39 healthy fetuses of mothers with no systemic disease (controls) underwent echocardiographic examination. Their gestational ages ranged from 25 weeks to term. The left atrial shortening fraction was obtained with the following formula: (left atrial maximum diameter - left atrial minimum diameter)/left atrial maximum diameter. Data were compared using the Student t test, with an alpha level of 0.05. RESULTS: Mean left atrial shortening fractions in fetuses of diabetic mothers and in those in the control group were 0.39±0.15 and 0.51±0.11, respectively. This difference was significant with P < 0.001. CONCLUSION: Left atrial dynamics, with a reduction in global left atrial shortening, is increased in fetuses of diabetic mothers. We speculate that this parameter may be useful in assessing fetal left ventricular diastolic function.

Pulsatilidade venosa pulmonar em fetos de mães diabéticas: estudo doppler-ecocardiográfico pré-natal

OBJECTIVE To verify the hypothesis that the pulmonary vein pulsatility index is higher in fetuses of diabetic mothers than it is in normal fetuses of nondiabetic mothers. METHODS Twenty-four fetuses of mothers with either gestational or previous diabetes (cases), and 25 normal fetuses of mothers without systemic disease (control) were examined. Fetuses were examined through prenatal Doppler and color flow mapping. The pulmonary vein pulsatility index was obtained by placing the pulsed Doppler sample volume over the right superior pulmonary vein and applying the formula (systolic velocity - presystolic velocity)/mean velocity. RESULTS The mean gestational age of the study fetuses was 30.3 2.7 weeks, and gestational age of the controls was 29 3.3 weeks, with no significant difference in gestational age between groups (p=0.14). Fetuses of diabetic mothers had a mean pulmonary vein pulsatility index of 1.6 1, and those of the control group had an index of 0.86 0.27. CONCLUSION Fetuses of diabetic mothers had pulmonary vein pulsatility indexes (parameter easily obtained through Doppler echocardiography that may be related to fetal diastolic function) higher than those in fetuses of mothers with normal glycemia.

Left atrial shortening fraction in fetuses with and without myocardial hypertrophy in diabetic pregnancies

To test the hypothesis that, in diabetic pregnancies, left atrial shortening fraction (LASF) is decreased in fetuses with myocardial hypertrophy, compared to those without hypertrophy and to fetuses of non‐diabetic mothers.

Fluxo no ducto venoso e hipertrofia miocárdica em fetos de mães diabéticas

OBJECTIVE To test the hypothesis that the pulsatility index of ductus venosus (PIDV) is greater in the fetuses of diabetic mothers (FDM) with myocardial hypertrophy (MH) than in the FDM with no MH and in the control fetuses of nondiabetic mothers (FNDM). Comparing the results with mitral and tricuspid diastolic peak flows. METHODS The cross-sectional study included fetuses with gestational ages ranging from 20 weeks to term, divided into the following 3 groups: 56 FDM with MH (group I), 36 FDM with no MH (group II), and 53 FNDM (group III, control). The Doppler echocardiogram assessed the PIDV through the ratio (systolic velocity - presystolic velocity)/mean velocity. The mitral and tricuspid E and A waves were also assessed. RESULTS The mean PIDV in groups I, II, and III were 1.13 +/- 0.64, 0.84 +/- 0.38, and 0.61 +/- 0.17, respectively. Using ANOVA and the Tukey test, a statistically significant difference was found in the 3 groups (P = 0.015 between groups I and II; P < 0.001 between groups I and III; and P = 0.017 between groups II and III). The mean mitral E wave was significantly greater in group I (0.39 +/- 0.12 m/s) than in groups II (0.32 +/- 0.08 m/s) (P = 0.024) and III (0.32 +/- 0.08 m/s) (P = 0.023). The mean tricuspid E wave was also greater in group I (0.43 +/- 0.1 m/s) than in group III (0.35 +/- 0.10 m/s) (P = 0.031). CONCLUSION The PIDV is significantly greater in FDM with MH than in FDM with no MH and in FNDM. Because the PIDV may represent modifications in ventricular compliance, this index may be a more sensitive parameter for assessing fetal diastolic function.

Dynamics of the Pulmonary Venous Flow in the Fetus and Its Association With Vascular Diameter

Background—The usual positioning of the Doppler sample volume to assess fetal pulmonary vein flow is in the distal portion of the vein, where the vessel diameter is maximal. This study was performed to test the association of the pulmonary vein pulsatility index (PVPI) with the vessel diameter. Methods and Results—Twenty-three normal fetuses (mean gestational age, 28.6±5.3 weeks) were studied by Doppler echocardiography. Pulmonary right upper vein flow was assessed adjacent to the venoatrial junction (“distal” position) and in the middle of the vein (“proximal” position). The vessel diameter was measured by 2D echocardiography with power Doppler, and the PVPI was obtained by the ratio (maximal velocity [systolic or diastolic peak]−minimal velocity [presystolic peak])/mean velocity. The statistical analysis used t test and exponential correlation studies. Mean distal diameter was 0.33±0.10 cm (0.11 to 0.57 cm), and mean proximal diameter was 0.16±0.08 cm (0.11 to 0.25 cm) (P <0.0001). Mean distal PVPI was 0.84±0.21 (0.59 to 1.38), and mean proximal PVPI was 2.09±0.59 (1.23 to 3.11) (P <0.0001). Exponential inverse correlation between pulmonary vein diameter and pulsatility index was highly significant (P <0.0001), with a determination coefficient of 0.439. Conclusions—In the normal fetus, the pulmonary venous flow pulsatility decreases from the lung to the heart, and this parameter is inversely correlated to the diameter of the pulmonary vein, which increases from its proximal to its distal portion. This study emphasizes the importance of the correct positioning of the Doppler sample volume, adjacent to the venoatrial junction, to assess pulmonary venous flow dynamics.

Fetal ductal constriction caused by maternal ingestion of green tea in late pregnancy: an experimental study

The aim of this study was to test the hypothesis that experimental maternal intake of green tea in late pregnancy causes fetal ductus arteriosus constriction, probably because of prostaglandin inhibition.

OC97: Ductal flow dynamics and right ventricular size are influenced by maternal ingestion of polyphenol‐rich common beverages in normal pregnancies

Objectives: We have already demonstrated that maternal consumption of beverages with high polyphenol compounds causes fetal ductal constriction, as a result of COX-2 and prostaglandin inhibition. This study tested the hypothesis that in normal pregnancies maternal ingestion of polyphenol-rich common beverages (MIPRB) interferes with fetal ductal flow velocities and with the size of the right ventricle. Methods: A prospective analysis of 140 third-trimester fetuses from normal mothers was carried out, determining systolic and diastolic ductal flow velocities (DFV) and right to left ventricular dimension ratio. Mean gestational age was 28.4 ± 3.1 weeks (range, 23–38 weeks). A questionnaire was applied about MIPRB during pregnancy (herbal teas, mate tea and grape derivatives). Results: The group of 100 fetuses whose mothers declared to have used herbal teas or grape juice derivatives showed higher mean systolic (0.96 ± 0.23 m/s) and diastolic (0.17 ± 0.05 m/s) DFV, as well as higher mean RV/LV ratio (1.23 ± 0.23) than the group of 40 fetuses whose mothers had not utilized these substances (mean systolic velocity: 0.61 ± 0.18 m/s, P 0.85 m/s (P 0.15 m/s (P 1.1 (P < 0.001, relative risk = 27.6; 95% CI, 3.96–192.01), independently of gestational age. Conclusions: Ductal flow velocities are higher and right ventricular to left ventricular dimension ratios are larger in fetuses exposed to maternal ingestion of polyphenol-rich substances than in those not exposed. It seems clear that the ductal flow response to consumption of polyphenols during pregnancy is not a categorical parameter, but rather a continuous dose-dependent variable.

OP18.03: Experimental study of the role of maternal consumption of green tea, mate tea and grape juice on fetal ductal constriction

treatment for placenta accreta or percreta) are at high risk for hemorrhage or systemic infection. The objective of this preliminary study was to evaluate radio-frequency (RF) efficiency and safety for trophoblast or placenta ablation. Methods: Several RF procedures (RITA medical systems, Starbust SDE) were tested on 50 pregnant ewe placental units in order to define two optimal procedures. Reproducibility of these two optimal procedures was then evaluated on 20 other pregnant ewe placental units. Each procedure was also tested twice on 10 human term placenta placed in an in-vitro model after normal delivery. Results: When tested on pregnant ewes, low-power (100 watts) and low target temperatures (80 and 60◦C) had to be applied in order to obtain homogeneous tissue destruction, without any myometrial lesion. Reproducibility of these two procedures was excellent for the 20 other pregnant ewes. No bleeding was observed in any of the 70 procedures. Lesions displayed the same pattern when RF was applied to human placentae. The ablation volume correlated with the time of deployment, and thus can be correctly targeted. Conclusions: RF seems to be an adequate method for ablation of retained trophoblast or placenta, with an optimal control of tissue destruction.

Maternal restriction of polyphenols and fetal ductal dynamics in normal pregnancy: an open clinical trial

Background We have recently demonstrated reversal of fetal ductal constriction after dietary maternal restriction of polyphenol-rich foods (PRF), due to its inhibitory action on prostaglandin synthesis. Objective To test the hyphotesis that normal third trimester fetuses also improve ductus arteriosus dynamics after maternal restriction of polyphenols. Methods Open clinical trial with 46 fetuses with gestational age (GA) ≥ 28 weeks submitted to 2 Doppler echocardiographic studies with an interval of at least 2 weeks, being the examiners blinded to maternal dietary habits. A validated food frequency questionnaire was applied and a diet based on polyphenol-poor foods (<30mg/100mg) was recommended. A control group of 26 third trimester fetuses was submitted to the same protocol. Statistics used t test for independent samples. Results Mean GA was 33±2 weeks. Mean daily maternal estimated polyphenol intake (DMPI) was 1277mg, decreasing to 126mg after dietary orientation (p=0.0001). Significant decreases in systolic (SDV) and diastolic (DDV) ductal velocities, and RV/LV diameters ratio, as well as increase in ductal PI were observed [DSV=1.2±0.4m/s (0.7-1.6) to 0.9±0.3m/s (0.6-1.3) (p=0.018); DDV=0.21±0.09m/s (0.15-0.32) to 0.18±0.06m/s (0.11-0.25) (p=0.016); RV/LV ratio =1.3±0.2 (0.9-1.4) to 1.1±0.2 (0.8-1.3) (p=0.004); ductal PI=2.2±0.03 (2.0-2.7) to 2.4±0.4(2.2-2.9) (p=0.04)]. In the control group, with GA of 32±4 weeks, there were no significant differences in DMPI, mean SDV, DDV, PI and RV/LV ratio. Conclusion The oriented restriction of third trimester maternal ingestion of polyphenol-rich foods for a period of 2 weeks or more improve fetal ductus arteriosus flow dynamics and right ventricular dimensions.