Objective:To test the hypothesis that maternal consumption of polyphenol-rich foods during third trimester interferes with fetal ductal dynamics by inhibition of prostaglandin synthesis.Study Design:In a prospective analysis, Doppler ductal velocities and right-to-left ventricular dimensions ratio of 102 fetuses exposed to polyphenol-rich foods (daily estimated maternal consumption >75th percentile, or 1089 mg) were compared with 41 unexposed fetuses (flavonoid ingestion <25th percentile, or 127 mg).Result:In the exposed fetuses, ductal velocities were higher (systolic: 0.96±0.23 m/s; diastolic: 0.17±0.05 m/s) and right-to-left ventricular ratio was higher (1.23±0.23) than in unexposed fetuses (systolic: 0.61±0.18 m/s, P<0.001; diastolic: 0.11±0.04 m/s, P=0.011; right-to-left ventricular ratio: 0.94±0.14, P<0.001).Conclusion:As maternal polyphenol-rich foods intake in late gestation may trigger alterations in fetal ductal dynamics, changes in perinatal dietary orientation are warranted.

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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...

Previous studies have shown that maternal consumption of polyphenol-rich foods after the third trimester of pregnancy may interfere with the anatomical and functional activity of the fetal heart as, to our knowledge, there are no validated instruments to quantify total polyphenols in pregnant women. The aim of this study was evaluate the reproducibility and validity of a food frequency questionnaire (FFQ), with 52 items, to assess the intake of polyphenol-rich foods in pregnant women in Brazil. This cross-sectional study included 120 pregnant women who participated in nutritional interviews in two moments. The intake of polyphenols estimated by the developed FFQ was compared with the average of two 24-h recalls (24HR), with the average intake measured by a 3-day food diary (D3days) and with the urinary excretion of total polyphenols. The triangular method was applied to calculate Pearson's correlation coefficients, intraclass correlation and Bland-Altman plots for the FFQ, using an independent biochemical marker, in addition to classification by quarters of consumption. The questionnaires were log transformed, adjusted for body mass index and gestational age. The adjustment for energy was applied only of 24HR and D3days. Analysis of the reproducibility between the FFQ showed a very high correlation (r = 0.72; P < 0.05). A low but significant association was observed between the FFQ and urinary excretion (0.23; P = 0.01). The association between the dietary survey methods was moderate to very high (r = 0.36 to r = 0.72; P < 0.001). In conclusion, this questionnaire showed reproducibility and validity for the quantification of consumption of total polyphenols in pregnant women.

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This study in fetal lambs shows a cause and effect relationship between experimental maternal exposure of green tea and fetal ductus arteriosus constriction in late pregnancy.

Dietary intervention for maternal restriction of polyphenol-rich foods in the third trimester of pregnancy is accompanied by increase in plasma levels of PGE2 and reversal of fetal ductal constriction. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Our results highlight the need to reduce maternal PRF intake in late pregnancy to prevent fetal duct constriction through NO-mediated vasoconstrictive action of polyphenols.