… could their antioxidant and
antiinflammatory components
interfere with prostaglandin
metabolism and thus influence fetal
ductus arteriosus dynamics?
FOOD FREQUENCY QUESTIONNAIRE FOR
QUANTIFICATION OF DAILY INGESTION OF
POLIPHENOLS
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)
CONSTRICTION OF DUCTUS ARTERIOSUS
Pulsatility Index
2.19 ± 0.43
1.70 ± 0.41
PRE
POST
P=0.001
Polyphenols
FLAVONOIDS
FLAVONOLS
FLAVONS
FLAVAN - 3 - ONS
FLAVONONS
ANTOCYANIDINS
Catequinas
Epicatequinas
Teaflavinas
ANTIINFLAMMATORY AND ANTIOXIDANT EFFECTS OF COMMON FOODS
GREEN
TEA
ORANGE
JUICE
BLACK
TEA
DARK
CHOCOLATE
MATE
TEA
RESVERATROL
3rd TRIMESTER MATERNAL INGESTION
• 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 ?
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
CONSTRICTION OF DUCTUS ARTERIOSUS
Daily consumption of polyphenols
1509.05 mg/day (>perc 75)
GA=32 ± 2 wks
2000
(28 - 38 wks)
1000
80.05 mg/day (<perc 25)
0
AT DIAGNOSIS
AFTER ORIENTATION
P= 0.0001
DOPPLER BEFORE AND AFTER
INGESTION OF GREEN TEA
(CASES)
p < 0.001
SYST VEL
p < 0.001
DIAST VEL
p =0.003
PI
Heart specimen of a fetal lamb
exposed to green tea
VD
VE
RV HYPERTROPHIC AND DILATED RV/LV RATIO
DUCTAL HISTOLOGY IN FETAL LAMB EXPOSED TO
GREEN TEA
687.7 um
DUCTAL LUMEN
DECREASED DUCTAL LUMEN AND INCREASED
MEDIAL AVASCULAR ZONE THICKNESS
DUCTAL HISTOLOGY
238.4
MEAN CONTROLS
THICKNESS:
AVASCULAR ZONE
Case
255.3 ± 97.9
AVASCULAR ZONE
Control
933.3
MEAN CASES
THICKNESS:
p < 0.001
746.6 ± 214.6
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
STUDY SETUP
SUFFOLK SHEEP (90-100kg)
>120 DAYS GESTATION
Control
PRF
N=5
N=10
BASAL
Control
PRF
N= 2
N= 7
14 DAYS
Habitual diet
(basic
polyphenol
ingestion)
Statistics:
Generalized Estimating Equations, post hoc Bonferroni.
PRF supplementation
(basic ingestion +
3100 mg/day
OPEN CLINICAL TRIAL
n = 72 FETUSES
1st ECHO
2 weeks
GA > 28 WEEKS
2nd ECHO
2 weeks
3rd ECHO
Nutritional
Questionnaire
Nutritional
Questionnaire
SUSPENSION
OF
POLYPHENOL_
RICH FOODS
CONSTRICTION OF DUCTUS ARTERIOSUS
Daily consumption of polyphenols
1509.05 mg/day (>perc 75)
GA=32 ± 2 wks
2000
(28 - 38 wks)
1000
80.05 mg/day (<perc 25)
0
AT DIAGNOSIS
AFTER ORIENTATION
P= 0.0001
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.
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
28.4 ± 3.1 wks
(23-38 wks)
102 FETUSES WITH
MATERNAL
INGESTION OF
POLIPHENOLS
(> 75th PERCENTILE,
1089 MG)
41 FETUSES WITHOUT
MATERNAL INGESTION
OF POLIPHENOLS
(< 25th PERCENTILE,
127 MG)
FETAL DOPPLER ECHOCARDIOGRAM
FETAL DUCTAL FLOW VELOCITIES AND RV/LV RATIO
ACCORDING TO MATERNAL POLYPHENOL CONSUMPTION
SYST VEL
DIAST VEL
P<0.001
P=0.011
0.17
0.96
0.96
>PERC 75
0.11
0.61
PERC 75
>PERC 75
<PERC 25
RV/LV RATIO
0.96
P<0.001
1.23
0.94
>PERC 75
<PERC 25
<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 CHD
and 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
Oct.23-26, 2014
St. Petersburg, FL
Focus: Fetal Cardiac
Treatment
Arrhythmia Management
See www.allkids.org
“Conferences”