Objective: To test the hypothesis that maternal restriction of polyphenolrich foods (PRF), which, like non-steroidal anti-inflammatory drugs (NSAID), inhibit prostaglandin synthesis in the third trimester, reverse fetal ductal constriction (DC).
Study Design:An open clinical trial of 51 third trimester fetuses with DC with no history of NSAID intake was designed. All mothers were submitted to a food frequency questionnaire and were oriented to withdrawl PRF, being reassessed after 3 weeks. Doppler parameters were assessed before and after discontinuation of these substances. A control group of 26 third trimester normal fetuses, with no ductus arteriosus (DA) constriction, in which no dietary intervention was offered, was reviewed after 3 weeks. Student's t-test and Wilcoxon's test were used.Result: Mean gestational age was 32±3 weeks (28 to 37 weeks). After discontinuation of PRF (X3 weeks), 48/51 fetuses (96%) showed complete reversal of DC, with decrease in mean ductal systolic velocity (1.74 ± 0.20 m s À1 to 1.31 ± 0.34 m s À1 , P<0.001), mean diastolic velocity (0.33±0.09 m s À1 to 0.21±0.07 m s À1 , P<0.001) and mean right to left ventricular dimension ratio (1.37 ± 0.26 to 1.12 ± 0.17, P<0.001) and increase in mean ductal pulsatility index (PI) (1.98 ± 0.36 to 2.46±0.23, P<0.001). Median daily maternal consumption of PRF was 286 mg per day and decreased after orientation to 0 mg per day, P<0.001. In the control group, with GA of 32±4 w (29-37 w), there was no significant differences in median daily maternal consumption of PRF, mean ductal systolic velocitiy, diastolic velocity, PI and right ventricular to left ventricular diameter ratio (RV/LV) ratio. Keywords: fetal ductal constriction; prostaglandins; pulmonary hypertension; polyphenol-rich foods Introduction Ductal constriction (DC) has long been related to inhibition of the prostaglandin synthesis pathway, mainly as a result of maternal intake of non-steroidal anti-inflammatory drugs (NSAID) in the third trimester of pregnancy. 1-5 Constriction of fetal ductus arteriosus (DA) is a risk factor for pulmonary hypertension in the newborn period, with its known severe consequences. [6][7][8][9][10][11] For several years, many reports have been discussing the high prevalence of DC in the absence of a known trigger effect. 11 It has been discussed that other extrinsic factors, in addition to NSAID, could be involved in the genesis of this important clinical situation. 1,12,13 We and others have already suggested that maternal ingestion of polyphenol-rich foods (PRF) in late pregnancy, such as herbal teas, grape juice, dark chocolate and others, could be associated to fetal DC. [14][15][16][17][18] Experimental studies in fetal lambs have supported this hypothesis, showing a cause and effect relationship of maternal consumption of green tea and other polyphenol-rich substances with constriction of fetal DA in the animal model. 19 In the human setting, we have demonstrated that fetuses exposed to a maternal diet rich in polyphenols in the third trimester show h...