A Randomized Trial of Docosahexaenoic Acid Supplementation During Pregnancy to Prevent Deep Placentation Disorders

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

2400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-05-31

Study Completion Date

2018-04-30

Brief Summary

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This study evaluates the effectiveness of maternal supplementation with Docosahexaenoic acid (DHA) early in pregnancy to reduce the incidence of deep placentation disorders: preterm birth, preterm labor, preterm premature rupture of membranes, preeclampsia and fetal growth restriction. Half of the participants in early pregnancy will receive DHA 600 mg per day, while the other half will receive placebo. Investigators will study also the ability of DHA supplementation, early in pregnancy, to enhance invasion and transformation of spiral arteries by trophoblast, as deep placentation indicators.

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Detailed Description

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Introduction: uteroplacental ischemia may cause preterm birth, either due to preterm labor, preterm premature rupture of membranes, or medical indication (in the presence of preeclampsia or fetal growth restriction). Uteroplacental ischemia is the product of defective deep placentation, that is a failure of invasion and transformation of the spiral arteries by the trophoblast. It has been reported that the failure of normal placentation generates a series of clinical abnormalities nowadays called "deep placentation disorders"; they include preeclampsia (PE), fetal growth restriction (FGR), preterm labor (PL), preterm premature rupture of membranes (PPROM), in utero fetal death and placental abruption. Strategies to prevent deep placentation disorders have been just partially effective. Docosahexaenoic acid (DHA) is an essential fatty acid of the family of long chain polyunsaturated fatty acids (LC-PUFAs) or omega-3 fatty acids. Early reports, suggested that a LC-PUFAs rich diet reduces the incidence of deep placentation disorders. Recent randomized controlled trials are inconsistent to show the benefit of DHA supplementation during pregnancy to prevent deep placentation disorders; but most of them showed that DHA supplementation was associated to lower risk of early preterm birth.

Hypothesis: investigators propose that Docosahexaenoic acid (DHA) supplementation, early in pregnancy, reduces the incidence of deep placentation disorders (preterm birth, preterm labor, preterm premature rupture of membranes, preeclampsia and fetal growth restriction), by improving deep placentation physiology: invasion and transformation of spiral arteries by trophoblast.

General Goals: in this proposal investigators aimed to

1. Assess the effectiveness of maternal supplementation with Docosahexaenoic acid (DHA) early in pregnancy to reduce the incidence of deep placentation disorders: preterm birth, preterm labor, preterm premature rupture of membranes, preeclampsia and fetal growth restriction.
2. Study the ability of DHA supplementation, early in pregnancy, to enhance invasion and transformation of spiral arteries by trophoblast, as deep placentation indicators. Methodology: investigators will conduct a randomized, placebo controlled, double blind, clinical trial of maternal supplementation with DHA (Docosahexaenoic acid) to prevent deep placentation disorders. Women will be recruited before 16 weeks of pregnancy from 5 ambulatory centers, 2.400 pregnant women will be assigned to 600 mg DHA per day or placebo. A composite outcome will be the primary outcome of the study. The components of the composite outcome will be: preterm birth \< 34+0 weeks gestation; early preeclampsia (\<34+0 weeks) and severe fetal growth restriction (lower than the 2 percentile and \< 34+0 weeks). Each of the outcomes of the composite outcome and other clinically relevant maternal and fetal outcomes will be evaluated as the secondary outcomes of the study. Clinical samples will be obtained from pregnant women on both groups, including: plasma, trophoblast, placental bed and myometrium, to study changes of deep placentation or defective placentation markers. Trophoblast cell lines will be used to study the effect of DHA on trophoblast function in vitro.

Expected outcome: In the randomized clinical trial, a 50% reduction in the incidence of the composite outcome in the DHA group (4% placebo vs. 2% DHA) is expected. Investigators expect to decrease defective deep placentation (placental bed biopsies) and defective placentation markers in DHA supplemented women. Investigators expect also to demonstrate that DHA enhances trophoblast migration and invasion in vitro and decreases production of inflammatory cytokines and anti-vasculogenic mediators.

Relevance: if the findings are positive, DHA supplementation, early in pregnancy, will become a safe and effective strategy for primary prevention of highly relevant pregnancy diseases, such as preterm birth, preeclampsia and fetal growth restriction.

Conditions

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Premature Birth Preeclampsia Fetal Growth Retardation Stillbirth

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Docosahexaenoic acid (DHA)

Docosahexaenoic acid (DHA) 200 mg capsules, 3 capsules by mouth every day, from early gestation until the end of pregnancy

Group Type EXPERIMENTAL

Docosahexaenoic acid (DHA)

Intervention Type DIETARY_SUPPLEMENT

Docosahexaenoic acid (DHA), 600 mg per day. Each woman will take three DHA capsules per day (200 mg each), as early in gestation as possible and until the end of pregnancy.

Placebo

Placebo 200 mg capsules, 3 capsules by mouth every day, from early gestation until the end of pregnancy

Group Type PLACEBO_COMPARATOR

Placebo (for Docosahexaenoic acid (DHA))

Intervention Type DIETARY_SUPPLEMENT

Each women allocated to the placebo group, will receive three placebo capsules per day. The placebo capsules will have same size, aspect and flavor than the DHA capsules.

Interventions

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Docosahexaenoic acid (DHA)

Docosahexaenoic acid (DHA), 600 mg per day. Each woman will take three DHA capsules per day (200 mg each), as early in gestation as possible and until the end of pregnancy.

Intervention Type DIETARY_SUPPLEMENT

Placebo (for Docosahexaenoic acid (DHA))

Each women allocated to the placebo group, will receive three placebo capsules per day. The placebo capsules will have same size, aspect and flavor than the DHA capsules.

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

* Women 18 years old or older at time of consent
* Capability of the subject to comprehend and comply with study requirements
* Live embryo or fetus (documented with positive fetal heart rate prior randomisation)
* Gestational age before 16+0 weeks of pregnancy
* Planning to deliver at Hospital Dr. Sótero del Río, Hospital Padre Hurtado, or Hospital Clínico Universidad Católica de Chile.

Exclusion Criteria

* Preexisting diabetes mellitus.
* Uterine anatomic malformation (bicornuate, septate uterus).
* Already taking a prenatal supplement with DHA.
* Bleeding disorder in which DHA was contraindicated.
* Anticoagulant therapy.
* Documented history of drug or alcohol abuse.
* Embryo or Fetus with a known mayor abnormality.
* Unable to give written informed consent.
* In the judgment of the investigator, will be unwilling or unable to comply with study protocol.
* Currently participating in another fatty acid trial

Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Responsible Party

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Responsibility Role SPONSOR