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

Condition(s) targeted: Preterm Birth

Intervention: 17 P Hydroxyprogesterone Caproate and Omega-3 fish oils (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: National Institute of Child Health and Human Development (NICHD)

Official(s) and/or principal investigator(s):
Catherine Y Spong, MD, Principal Investigator, Affiliation: National Institute of Child Health and Human Development (NICHD)
Elizabeth A Thom, PhD, Principal Investigator, Affiliation: George Washington University Biostatistics Center
Margaret Harper, MD, Principal Investigator, Affiliation: Wake Forest University

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."

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

Study design: Prevention, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Delivery less than 37 completed weeks gestation including any miscarriages occurring after randomization

Secondary outcome:

MATERNAL: Delivery less than 35 weeks

Delivery less than 32 weeks

Spontaneous preterm delivery

Indicated preterm delivery

Tocolytic therapy

Time from randomization to delivery

Delivery on or after 41 weeks of gestation

Occurrence of gestational hypertension or preeclampsia

Maternal hospital days

Fatty acid constituents in maternal plasma samples, before and after supplementation

Postpartum hemorrhage

FETAL AND NEONATAL: Fetal and neonatal death

Gestational age at delivery

Small for gestational age

Birth weight

Apgar score at 1 and 5 minutes

Number of days of neonatal respiratory therapy

Admission to NICU and total number of days in hospital

Intraventricular hemorrhage

Retinopathy of prematurity

Necrotizing enterocolitis

Deep infection

Periventricular leukomalacia

Bronchopulmonary dysplasia

Respiratory distress syndrome

Composite neonatal outcome

Detailed 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.

Minimum age: N/A. Maximum age: N/A. Gender(s): Female.

Criteria:

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

University of Alabama - Birmingham, Birmingham, Alabama, United States

Northwestern University, Chicago, Illinois, United States

Wayne State University, Detroit, Michigan, United States

Columbia University, New York, New York, United States

Wake Forest University School of Medicine, Winston Salem, North Carolina, United States

University of North Carolina - Chapel Hill, Chapel Hill, North Carolina, United States

Ohio State University, Columbus, Ohio, United States

Case Western University, Cleveland, Ohio, United States

University of Pittsburgh Magee Womens Hospital, Pittsburgh, Pennsylvania, United States

Drexel University, Philadelphia, Pennsylvania, United States

Brown University, Providence, Rhode Island, United States

University of Texas - Southwest, Dallas, Texas, United States

University of Utah Medical Center, Salt Lake City, Utah, United States

Related publications:

Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, Spong CY, Hauth JC, Miodovnik M, Varner MW, Leveno KJ, 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. New England Journal of Medicine 348(24):2379-85,

Olsen SF, Secher NJ, Bjornsson 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. No abstract available.

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

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.

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.

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.

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.

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.

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.

Calder PC. Dietary fatty acids and the immune system. Nutr Rev. 1998 Jan;56(1 Pt 2):S70-83. Review. No abstract available.

Starting date: February 2005
Ending date: June 2007
Last updated: February 14, 2007