… could their antioxidant and antiinflammatory components interfere with prostaglandin metabolism and thus influence

fetal ductus arteriosus dynamics?

ORIENTATION TO WITHDRAWL FOODS WITH MORE OF 30mg/100g

COMPLETE REVERSION IN 96.3% (48/52 FETUSES WITH DUCTAL CONSTRICTION)

(3 WEEKS AFTER SUSPENSION OF THE SUBSTANCES)

FOOD FREQUENCY QUESTIONNAIRE FOR QUANTIFICATION OF DAILY INGESTION OF

POLIPHENOLS

PRE POST

1.70 ± 0.41

2.19 ± 0.43

P=0.001

Pulsatility Index

CONSTRICTION OF DUCTUS ARTERIOSUS

Polyphenols

FLAVONOLS

FLAVONS

FLAVONONS

FLAVAN - 3 - ONS

ANTOCYANIDINS

FLAVONOIDS

Catequinas

Epicatequinas

Teaflavinas

ANTIINFLAMMATORY AND ANTIOXIDANT EFFECTS OF COMMON FOODS

GREEN TEA

BLACK TEA

MATE TEA

ORANGE JUICE

DARK CHOCOLATE

RESVERATROL

• HERBAL TEAS AND OTHER FLAVONOID-RICH FOODS

[3-gallate-gallocatechin, quercitin, cacao,…]

• GRAPE DERIVATIVES

[resveratrol]

POLYPHENOLS WITH ANTIINFLAMMATORY ACTIONS DEPENDENT ON INHIBITION OF COX-2 AND PROSTAGLANDINS

FETAL DUCTAL CONSTRICTION ?

3rd TRIMESTER MATERNAL INGESTION

CONSTRICTION OF DUCTUS ARTERIOSUS

IN NORMAL FETUSES, DUCTAL FLOW DYNAMICS AND RIGHT

VENTRICULAR SIZE ARE INFLUENCED BY MATERNAL CONSUMPTION

OF POLYPHENOL-RICH FOODS (CASE-CONTROL STUDY)

Warn mothers about this...

zielinsky@cardiol.br

1509.05 mg/day (>perc 75)

Daily consumption of polyphenols

0

1000

2000

AT DIAGNOSIS

80.05 mg/day (<perc 25)

P= 0.0001

AFTER ORIENTATION

GA=32 ± 2 wks

(28 - 38 wks)

CONSTRICTION OF DUCTUS ARTERIOSUS

SYST VEL

DIAST VEL

PI

DOPPLER BEFORE AND AFTER

INGESTION OF GREEN TEA

(CASES)

p < 0.001

p =0.003

p < 0.001

VE

VD

Heart specimen of a fetal lamb

exposed to green tea

RV HYPERTROPHIC AND DILATED RV/LV RATIO

DUCTAL HISTOLOGY IN FETAL LAMB EXPOSED TO GREEN TEA

DECREASED DUCTAL LUMEN AND INCREASED

MEDIAL AVASCULAR ZONE THICKNESS

DUCTAL LUMEN

687.7 um

238.4

933.3

AVASCULAR ZONE

Control

AVASCULAR ZONE

Case

DUCTAL HISTOLOGY

746.6 ± 214.6

255.3 ± 97.9

p < 0.001

MEAN CONTROLS

THICKNESS:

MEAN CASES

THICKNESS:

OBJECTIVE

To investigate the interrelationships between fetal ductal flow dynamics, oxidative damage and polyphenol excretion after experimental exposure of PRF in sheep during late pregnancy

15

BASAL 14 DAYS

Control PRFControl PRF

N=5 N=10N= 2 N= 7

Statistics: Generalized Estimating Equations, post hoc Bonferroni.

SUFFOLK SHEEP (90-100kg) >120 DAYS GESTATION

STUDY SETUP

Habitual diet (basic

polyphenol ingestion)

PRF supplementation (basic ingestion +

3100 mg/day

OPEN CLINICAL TRIAL

2 weeks1st ECHO

SUSPENSION OF

POLYPHENOL_RICH FOODS

Nutritional Questionnaire

Nutritional Questionnaire

2nd ECHO 3rd ECHO2 weeks

n = 72 FETUSES GA > 28 WEEKS

1509.05 mg/day (>perc 75)

Daily consumption of polyphenols

0

1000

2000

AT DIAGNOSIS

80.05 mg/day (<perc 25)

P= 0.0001

AFTER ORIENTATION

GA=32 ± 2 wks

(28 - 38 wks)

CONSTRICTION OF DUCTUS ARTERIOSUS

CONCLUSION OF INTERVENTIONAL STUDY

The oriented restriction of maternal ingestion of

polyphenol-rich foods in the third trimester is

followed by regression of fetal ductal constriction.

CONSTRICTION OF DUCTUS ARTERIOSUS

IN NORMAL FETUSES, DUCTAL FLOW DYNAMICS AND RIGHT

VENTRICULAR SIZE ARE INFLUENCED BY MATERNAL CONSUMPTION

OF POLYPHENOL-RICH FOODS (CASE-CONTROL STUDY)

143 NORMAL FETUSES FROM NORMAL MOTHERS IN THE THIRD SEMESTER OF PREGNANCY

102 FETUSES WITH MATERNAL

INGESTION OF POLIPHENOLS

(> 75th PERCENTILE,

1089 MG)

41 FETUSES WITHOUT MATERNAL INGESTION OF POLIPHENOLS (< 25th PERCENTILE,

127 MG)

28.4 ± 3.1 wks (23-38 wks)

FETAL DOPPLER ECHOCARDIOGRAM

>PERC 75 <PERC 25PERC 75

SYST VEL DIAST VEL

RV/LV RATIO

P<0.001 P=0.011

P<0.001

FETAL DUCTAL FLOW VELOCITIES AND RV/LV RATIO ACCORDING TO MATERNAL POLYPHENOL CONSUMPTION

0.96

0.96

0.960.17

1.23

0.61 0.11

0.94

>PERC 75 <PERC 25

>PERC 75 <PERC 25

Fetal ductal constriction detection in fetal CHD

Consider the possibility of mild ductal constriction in any fetal left heart disease (HLHS) with a decreasing CV Profile score (TR, decreasing RV function)

Counsel mothers on polyphenol foods early after fetal diagnosis

Use of Maternal Indomethacin and Fetal Ductal Constriction

• Indomethacin doses of 25 mg PO BID or TID are effective for tocolysis

• Short course of 48 hours is well tolerated • Some types of ductal dependent CHD

can have short-course indomethacin tocolysis safely i.e. pulmonary atresia, Tetralogy of Fallot, etc.

Effects of Indomethacin ductal closure in R heart disease e.g. Ebstein and TV dysplasia

• Constriction/occlusion of the ductus arteriosus• Theoretical constriction of coronary arteries• Increase in pulmonary vascular resistance

Benefits• Prevent or reverse pulmonary valve regurgitation• Decrease tricuspid valve regurgitation • Promote systolic pulmonary arterial flow• Improve systemic flow

Approach to the fetus with CHDand preterm labor

• Early identification• Address the cause (i.e. infection, indocin for

poly) • Aggressive management of cervical

incompetence, Redefine “viability”• Screen for CHF• Consider tocolysis early

 

Advances in Perinatal Cardiology 10th Fun in the Sun Course

Focus: Fetal Cardiac Treatment

Arrhythmia ManagementSee www.allkids.org

“Conferences”

Oct.23-26, 2014St. Petersburg, FL