ABC | Volume 112, Nº5, May 2019

Guideline Brazilian Fetal Cardiology Guidelines – 2019 Arq Bras Cardiol. 2019; 112(5):600-648 The inhibitory effect of NSAID on PG biosynthesis has been broadly demonstrated. Meta-analysis conducted in a systematic review of 25 randomized clinical trials, which evaluated the risk of fetal ductal constriction in pregnant women exposed and not exposed to NSAID, concluded that the risk of ductal constriction is 15 times greater in acutely exposed fetuses. 66 Multiple randomized clinical trials, systematic reviews, and meta-analyses have established that polyphenols, in the various forms in which they are present in food, have a definite anti-inflammatory and antioxidant action, which culminates in the inhibition of circulating PG, with diversified clinical outcomes. In 2015, the International Federation of Gynecology and Obstetrics (FIGO) published its official recommendations for gestational nutrition. One point in the section, “Exposures to avoid” reads: “In late pregnancy, women should avoid high intakes of herbal teas and polyphenol-rich foods, which have been associated with effects on the fetal ductus arteriosus brought about by inhibition of prostaglandin synthesis.” (italics ours) 106 Specifically regarding the results of “abnormal ductal flow and ductal constriction” in fetuses exposed to a maternal diet rich in polyphenols, studies developed in Brazil, on all levels of the evidence pyramid, from experimental to case control studies, have unequivocally demonstrated the following: • Consumption of green tea, yerba mate, and grape juice, which are sources of high concentrations of polyphenols, causes ductal constriction in experimental models of sheep fetuses in the final trimester of gestation. 121 • There is a cause-effect relationship between maternal consumption of green tea and ductal constriction during the third trimester of gestation in experimental models of sheep fetuses. 74 • High maternal consumption of polyphenols induces fetal ductal constriction in sheep, with increased urinary excretion of total polyphenols and abnormalities in oxidative stress biomarkers, which characterize the anti- inflammatory and antioxidant actions of polyphenols. 122 • An expe r imen t a l s i ng l e - dos e o f cocoa administered to rats during the third trimester of gestation caused ductal constriction equivalent to that caused by indomethacin. 123 • Normal human fetuses during the third trimester, when exposed to maternal consumption of polyphenols above the 75 th percentile of the average population, exhibit worse ductus arteriosus flow dynamics and increased right-to-left ventricular diameter ratios (higher ductal flow velocities and larger right ventricular diameters), in comparison with those exposed to maternal consumption of polyphenols below the 25 th percentile. 76 • Normal human fetuses submitted to guided nutritional intervention (restriction of polyphenol-rich foods) in the third trimester showed, after 2 weeks, decreased ductal systolic and diastolic velocities, increased pulsatility index, and decreased right-to- left ventricular and pulmonary artery to aorta ratios, whereas these parameters did not change during the same period in control fetuses who were not submitted to the intervention. 77 • Human fetuses with ductal constriction during the third trimester showed, in more than 95% of cases, reversion of the echocardiographic signs of this condition, as well as its hemodynamic compromise, after 3 weeks of a restricted in polyphenols diet, whereas there were no changes in the parameters evaluated in fetuses controls of the same gestational age, who did not receive a nutritional intervention with restricted maternal intake of polyphenols. 78 • Polyphenol supplementation capsules inhibit physiological increase of PGE2 and other markers of inflammationandoxidative stress inwomenof childbearing age using combined hormonal contraceptives. 124 • Dietary intervention to restrict maternal consumption of polyphenol-rich foods in the third trimester in cases of fetuses with ductal constriction is accompanied by an increase in plasma levels of PGE2, with improvements in the condition. 125 • A 52-item food frequency questionnaire for quantifying consumption of polyphenol-rich foods in pregnant women, whose validity and reproducibility were evaluated in the South of Brazil, may be used in clinical practice. 71 6.5. Conclusions 6.5.1. Recommendations for Ductal Constriction Treatment When ductal constriction is diagnosed in the fetal echocardiogram, the complete use interruption of NSAID should be recommended, in addition to the restriction of polyphenol-rich foods, made up of products with a concentration ≥ 30 mg/100 g of food, in accordance with the recommendations in table 6.2, intending to maintain balanced diet that includes all necessary micronutrients during this gestational period, reducing, however, the concentration of total polyphenols below 125 mg per day, or to the 25 th consumption percentile 78 (Class of recommendation: I; level of evidence: A). If possible, consumption of other medications with 622