Increase of Prostaglandin E2 in Reversal of Ductal Constriction After Dietary Restriction of Polyphenols
Primary Purpose
Pregnancy Complications
Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
restrict polyphenol-rich foods
Sponsored by
About this trial
This is an interventional treatment trial for Pregnancy Complications focused on measuring polyphenols, pregnant, fetal ductal constriction, prostaglandin E2
Eligibility Criteria
Inclusion Criteria
- Pregnancy with diagnosis of fetal ductal constriction
- Single fetus
- gestational age from 28 weeks
Exclusion Criteria
- cardiac malformations
- restricted intrauterine growth
- increased nuchal translucency
- present or suspected chromosomal disorders
- signs of any type of hydrops fetalis
- pregnancy
- hypertension
- diabetes mellitus
- structural or functional cardiac disorders
- current use of nonsteroidal anti-inflammatory drugs, steroids, antidepressants, illicit drugs, alcohol or smoking
- multiple pregnancy
- having received previous nutritional guidance in relation to restricted intake of polyphenol-rich foods
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
interventional group
control group
Arm Description
The interventional group was submitted to dietary orientation to restrict polyphenol-rich foods
healthy group as comparator
Outcomes
Primary Outcome Measures
Plasma levels of prostaglandin E2 (PGE2)
PGE2 was quantified by capture ELISA. The measurements were obtained through 4-parameter linear regression (Excel, Microsoft), and data were expressed in picograms of protein per milliliter (pg/mL).
Secondary Outcome Measures
Consumption of foods rich in Total Polyphenols (TP)
TP on the maternal diet were quantified using a Food Frequency Questionnaire (FFQ) validated for pregnant women. TP results after analysis of the dietary questionnaires were described in milligrams (mg)
Full Information
NCT ID
NCT03111602
First Posted
March 29, 2017
Last Updated
April 7, 2017
Sponsor
Instituto de Cardiologia do Rio Grande do Sul
1. Study Identification
Unique Protocol Identification Number
NCT03111602
Brief Title
Increase of Prostaglandin E2 in Reversal of Ductal Constriction After Dietary Restriction of Polyphenols
Official Title
Increase of Prostaglandin E2 in Reversal of Ductal Constriction After Dietary Restriction of Polyphenols
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
May 2011 (Actual)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
February 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Instituto de Cardiologia do Rio Grande do Sul
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
INCREASE OF PROSTAGLANDIN E2 IN REVERSAL OF DUCTAL CONSTRICTION AFTER DIETARY RESTRICTION OF POLYPHENOLS.
Clinical trial with a healthy group as comparator. The interventional group was made up of third-trimester mothers whose single fetuses had ductal constriction, excluding those exposed to NSAID, and the control group only by third-trimester normal fetuses. The interventional group was submitted to dietary orientation to restrict polyphenol-rich foods and both groups answered a food frequency questionnaire after fetal Doppler-echocardiographic examination and blood draw for PGE2 levels analysis. After two weeks, the women were again submitted to fetal echocardiogram, dietary assessment and blood draw.
Detailed Description
INCREASE OF PROSTAGLANDIN E2 IN REVERSAL OF DUCTAL CONSTRICTION AFTER DIETARY RESTRICTION OF POLYPHENOLS.
Fetal ductal constriction is a clinical situation with high morbidity and potential mortality. Patency the fetal ductus arteriosus (DA) depends on circulating prostaglandin (PG), which is produced by the cyclooxygenase (COX) pathway during inflammatory response(1) and from the third trimester of pregnancy on, is physiologically released. COX-inhibiting substances, such as nonsteroidal anti-inflammatory drugs (NSAIDs), can interfere with PG metabolism and induce constriction of the DA. To treat or prevent DA constriction, it is therefore important to reduce fetal exposure to drugs that may interfere with prostaglandin biosynthesis, such as natural anti-inflammatory drugs and polyphenol-rich foods.
Polyphenols, the most abundant antioxidants present in the diet, are widely distributed in vegetable foods. One of the possible mechanisms to explain their activity is inhibition of synthesis and release of inflammatory mediators. However, clinical studies investigating the effect of polyphenols on inflammatory responses are inconclusive and, in most cases, only evaluate clinical outcomes. The role of polyphenols on the inflammatory response, and associated modifications of the plasma concentration of PGE2 in pregnant women, has not yet been studied.
Despite the potential benefits of a diet rich in polyphenols, a high consumption of these substances in the third trimester of pregnancy may reduce plasma levels of PGE2 and result in DA constriction,so that a restriction in their ingestion during this period is already recommended.This functional problem has high prevalence and may result in severe fetal and neonatal complications. These considerations raised the hypothesis that reversal of fetal ductal constriction after maternal restriction of polyphenol-rich foods is accompanied by increased in prostaglandin E2 levels. Demonstration of this effect would represent an advancement in knowledge and might result in changes in dietary guidance during pregnancy and prevention of perinatal complications, with potential impact in terms of public health.
The aim of this study was to test the hypothesis that reversal of fetal ductal constriction in the third trimester of pregnancy, after maternal restriction of polyphenol-rich foods, is accompanied by increased plasma levels of prostaglandin E2.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pregnancy Complications
Keywords
polyphenols, pregnant, fetal ductal constriction, prostaglandin E2
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Clinical trial with a healthy group as comparator.
Masking
Care ProviderInvestigator
Masking Description
Researchers were blinded to the allocation data of pregnant women in the groups
Allocation
Non-Randomized
Enrollment
75 (Actual)
8. Arms, Groups, and Interventions
Arm Title
interventional group
Arm Type
Experimental
Arm Description
The interventional group was submitted to dietary orientation to restrict polyphenol-rich foods
Arm Title
control group
Arm Type
No Intervention
Arm Description
healthy group as comparator
Intervention Type
Other
Intervention Name(s)
restrict polyphenol-rich foods
Intervention Description
dietary orientation to restrict polyphenol-rich foods
Primary Outcome Measure Information:
Title
Plasma levels of prostaglandin E2 (PGE2)
Description
PGE2 was quantified by capture ELISA. The measurements were obtained through 4-parameter linear regression (Excel, Microsoft), and data were expressed in picograms of protein per milliliter (pg/mL).
Time Frame
baseline and two weeks
Secondary Outcome Measure Information:
Title
Consumption of foods rich in Total Polyphenols (TP)
Description
TP on the maternal diet were quantified using a Food Frequency Questionnaire (FFQ) validated for pregnant women. TP results after analysis of the dietary questionnaires were described in milligrams (mg)
Time Frame
baseline and two weeks
Other Pre-specified Outcome Measures:
Title
Diagnostic parameters of fetal ductus arteriosus constriction
Description
The peak systolic, peak diastolic and end diastolic velocities (m/s) were determined. The pulsatility index of the ductus arteriosus was calculated automatically by the echocardiography system after manual tracing of the spectral curve, using the formula: (peak systolic velocity - diastolic peak velocity)/mean velocity.
Time Frame
baseline and two weeks
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
pregnant: third-trimester mothers
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria
Pregnancy with diagnosis of fetal ductal constriction
Single fetus
gestational age from 28 weeks
Exclusion Criteria
cardiac malformations
restricted intrauterine growth
increased nuchal translucency
present or suspected chromosomal disorders
signs of any type of hydrops fetalis
pregnancy
hypertension
diabetes mellitus
structural or functional cardiac disorders
current use of nonsteroidal anti-inflammatory drugs, steroids, antidepressants, illicit drugs, alcohol or smoking
multiple pregnancy
having received previous nutritional guidance in relation to restricted intake of polyphenol-rich foods
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
23316751
Citation
Vian I, Zielinsky P, Zilio AM, Mello A, Lazzeri B, Oliveira A, Lampert KV, Piccoli A, Nicoloso LH, Bubols GB, Garcia SC. Development and validation of a food frequency questionnaire for consumption of polyphenol-rich foods in pregnant women. Matern Child Nutr. 2015 Oct;11(4):511-24. doi: 10.1111/mcn.12025. Epub 2013 Jan 15.
Results Reference
background
PubMed Identifier
16257930
Citation
Momma K, Toyoshima K, Takeuchi D, Imamura S, Nakanishi T. In vivo constriction of the fetal and neonatal ductus arteriosus by a prostanoid EP4-receptor antagonist in rats. Pediatr Res. 2005 Nov;58(5):971-5. doi: 10.1203/01.pdr.0000182182.49476.24.
Results Reference
background
PubMed Identifier
22052330
Citation
Zielinsky P, Piccoli AL Jr, Manica JL, Nicoloso LH, Vian I, Bender L, Pizzato P, Pizzato M, Swarowsky F, Barbisan C, Mello A, Garcia SC. Reversal of fetal ductal constriction after maternal restriction of polyphenol-rich foods: an open clinical trial. J Perinatol. 2012 Aug;32(8):574-9. doi: 10.1038/jp.2011.153. Epub 2011 Nov 3.
Results Reference
background
Learn more about this trial
Increase of Prostaglandin E2 in Reversal of Ductal Constriction After Dietary Restriction of Polyphenols
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