Omega-3 Fatty Acid Supplementation to Prevent Preterm Birth in High Risk Pregnancies

Preterm Birth Clinical Trial

Official title:

A Randomized Trial of Omega-3 Fatty Acid Supplementation to Prevent Preterm Birth in Pregnancies at High Risk

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00135902
• Other study ID #: HD36801-Omega-3
• Secondary ID: U10HD021410U10HD
• Status: Completed
• Phase: Phase 3
• Start date: February 2005
• Est. completion date: March 2008

Study information

• Verified date: July 2019
• Source: The George Washington University Biostatistics Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A recently completed trial of weekly injections of 17 alpha hydroxyprogesterone caproate (17P) found significant effectiveness for 17P in preventing recurrent preterm birth. However, the group who received 17P in this trial still had a high rate of preterm birth. Several reports have shown that dietary supplementation of fish oil, which is rich in Omega-3 fatty acids, reduces the risk of preterm birth. This trial tests whether adding the Omega-3 supplement to 17P therapy has the potential for further reducing the risk of preterm birth in women who have previously had a spontaneous preterm delivery. The trial will compare Omega-3 fatty acid with placebo in women receiving 17P therapy. The hypothesis being tested is: "Among women at high risk for preterm birth receiving weekly injections of 17P, the addition of Omega-3 nutritional supplement will further reduce the rate of preterm birth."

Description:

Preterm birth is the leading cause of perinatal mortality and morbidity. In a recently completed trial of weekly injections of 17 alpha hydroxyprogesterone caproate (17P), the National Institute of Child Health and Human Development (NICHD) Maternal Fetal Medicine Units (MFMU) Network found the treatments significantly beneficial in the prevention of recurrent preterm birth. Other studies have shown that fish oil supplementation can reduce the risk for preterm birth. The purpose of this study is to determine whether Omega-3, a polyunsaturated fatty acid nutritional supplement, in addition to injections of 17P, further decreases the rate of preterm birth in women at risk.

This study is a randomized, double-masked clinical trial with two study arms: a daily supplement of Omega-3 capsules containing 800 mg of DHA and 1200 mg of EPA or a daily supplement of a matching placebo. All patients will also receive weekly injections of 17P. Eight hundred pregnant women with a history of previous preterm delivery will be recruited for this study. After successfully completing a compliance run-in, which can begin as early as 15 weeks gestation, patients will be randomized and begin treatment between 16 and 22 weeks gestation. They will remain on study drug until 36 week and 6 days or delivery, whichever occurs first. Blood will be drawn at randomization and at a monthly visit falling between 25-29 weeks of gestation to test for compliance, to analyze genetic polymorphisms and to determine whether Omega-3 affects the production of inflammatory cytokines.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 800
• Est. completion date: March 2008
• Est. primary completion date: March 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Documented history of previous singleton spontaneous birth

• Singleton pregnancy

• Gestational age at randomization between 16 and 22 weeks

Exclusion Criteria:

• Major fetal anomaly or demise

• Regular intake of fish oil supplements

• Daily use of nonsteroidal anti-inflammatory agents

• Allergy to fish or fish products

• Gluten intolerant

• Heparin use or known thrombophilia

• Hemophilia

• Planned termination

• Current hypertension or current use of antihypertensive medications

• Type D, F or R diabetes

• Maternal medical complications

• Current or planned cerclage

• Illicit drug or alcohol abuse during current pregnancy

• Delivery at a non-Network hospital

• Participation in another pregnancy intervention study

• Participation in this trial in a previous pregnancy

Related Conditions & MeSH terms

• Premature Birth
• Preterm Birth

Intervention

Drug:
• 17 alpha-Hydroxyprogesterone Caproate and Omega-3 supplement
Participants receive a weekly progesterone injection (17 alpha hydroxyprogesterone caproate) up to 37 weeks gestation and take daily Omega-3 supplements.
• 17 alpha-hydroxy progesterone caproate and Placebo supplement
Participants receive a weekly progesterone injection (17P) up to 37 weeks gestation and take daily placebo supplements

Locations

Country	Name	City	State
United States	University of Alabama - Birmingham	Birmingham	Alabama
United States	University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Case Western University	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Wayne State University	Detroit	Michigan
United States	Columbia University	New York	New York
United States	Drexel University	Philadelphia	Pennsylvania
United States	University of Pittsburgh Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	Brown University	Providence	Rhode Island
United States	University of Utah Medical Center	Salt Lake City	Utah
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
The George Washington University Biostatistics Center	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (11)

Cadroy Y, Dupouy D, Boneu B. Arachidonic acid enhances the tissue factor expression of mononuclear cells by the cyclo-oxygenase-1 pathway: beneficial effect of n-3 fatty acids. J Immunol. 1998 Jun 15;160(12):6145-50. — View Citation

Calder PC. Dietary fatty acids and the immune system. Nutr Rev. 1998 Jan;56(1 Pt 2):S70-83. Review. — View Citation

Duley L. Prophylactic fish oil in pregnancy. The Cochrane Pregnancy & Childbirth Database (Issue 2, 1995).

Dunstan JA, Mori TA, Barden A, Beilin LJ, Taylor AL, Holt PG, Prescott SL. Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: a randomized, controlled trial. J Allergy Clin Immunol. 2003 Dec;112(6):1178-84. — View Citation

Harper M, Thom E, Klebanoff MA, Thorp J Jr, Sorokin Y, Varner MW, Wapner RJ, Caritis SN, Iams JD, Carpenter MW, Peaceman AM, Mercer BM, Sciscione A, Rouse DJ, Ramin SM, Anderson GD; Eunice Kennedy Shriver National Institute of Child Health and Human Devel — View Citation

Lee JY, Plakidas A, Lee WH, Heikkinen A, Chanmugam P, Bray G, Hwang DH. Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids. J Lipid Res. 2003 Mar;44(3):479-86. Epub 2002 Dec 1. — View Citation

Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, Caritis SN, Iams JD, Wapner RJ, Conway D, O'Sullivan MJ, Carpenter M, Mercer B, Ramin SM, Thorp JM, Peaceman AM, Gabbe S; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med. 2003 Jun 12;348(24):2379-85. Erratum in: N Engl J Med. 2003 Sep 25;349(13):1299. — View Citation

Olsen SF, Secher NJ, Björnsson S, Weber T, Atke A. The potential benefits of using fish oil in relation to preterm labor: the case for a randomized controlled trial? Acta Obstet Gynecol Scand. 2003 Nov;82(11):978-82. Review. — View Citation

Olsen SF, Secher NJ, Tabor A, Weber T, Walker JJ, Gluud C. Randomised clinical trials of fish oil supplementation in high risk pregnancies. Fish Oil Trials In Pregnancy (FOTIP) Team. BJOG. 2000 Mar;107(3):382-95. — View Citation

Olsen SF, Secher NJ. Low consumption of seafood in early pregnancy as a risk factor for preterm delivery: prospective cohort study. BMJ. 2002 Feb 23;324(7335):447. — View Citation

Reece MS, McGregor JA, Allen KG, Harris MA. Maternal and perinatal long-chain fatty acids: possible roles in preterm birth. Am J Obstet Gynecol. 1997 Apr;176(4):907-14. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Delivery before than 37 weeks gestation	Delivery before 37 weeks including any miscarriages occurring after randomization	Up to 37 weeks gestation
Secondary	Delivery before 35 weeks gestation		Up to 35 weeks gestation
Secondary	Delivery before 32 weeks gestation		Up to 32 weeks gestation
Secondary	Delivery after 40 weeks gestation		40 weeks gestation or greater
Secondary	Pregnancy loss or neonatal death		Randomization to hospital discharge (up to 25 weeks)
Secondary	Gestational age at delivery		Delivery
Secondary	Birth weight less than 2,500 grams		Birth
Secondary	Birth weight less than 1,500 grams		Birth
Secondary	Birth size small for gestational age at less than 10th percentile		Birth
Secondary	Birth size large for gestational age at more than 90th percentile		Birth
Secondary	Admission to neonatal intensive care or intermediate care nursery		Delivery through neonatal discharge (up to 2 weeks)
Secondary	Neonatal retinopathy of prematurity		Delivery through neonatal discharge (up to 2 weeks)
Secondary	Intraventricular Hemorrhage at any grade		Delivery through neonatal discharge (up to 2 weeks)
Secondary	Intraventricular Hemorrhage Grade 3 or 4		Delivery through neonatal discharge (up to 2 weeks)
Secondary	Neonatal patent ductus arteriosus		Delivery through neonatal discharge (up to 2 weeks)
Secondary	Neonatal necrotizing enterocolitis		Delivery through neonatal discharge (up to 2 weeks)
Secondary	Neonatal sepsis		Delivery through neonatal discharge (up to 2 weeks)
Secondary	Neonatal respiratory distress syndrome		Delivery through neonatal discharge (up to 2 weeks)
Secondary	Neonatal surfactant use		Delivery through neonatal discharge (up to 2 weeks)
Secondary	Neonatal bronchopulmonary dysplasia		Delivery through neonatal discharge (up to 2 weeks)
Secondary	Neonatal transient tacypnea		Delivery through neonatal discharge (up to 2 weeks)
Secondary	Neonatal supplemental oxygen support		Delivery through neonatal discharge (up to 2 weeks)
Secondary	Neonatal ventilator support		Delivery through neonatal discharge (up to 2 weeks)

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