Omega-3 fatty acid supplementation to prevent recurrent preterm birth: a randomized controlled trial.
OBJECTIVE
To assess whether the addition of an omega-3 long-chain polyunsaturated fatty acid supplement would reduce preterm birth in women with at least one prior spontaneous preterm birth receiving 17alpha-hydroxyprogesterone caproate.


METHODS
We conducted a randomized, double-masked, placebo-controlled trial in 13 centers. Women with a history of prior spontaneous singleton preterm birth and a current singleton gestation were assigned to either a daily omega-3 supplement (1,200 mg eicosapentaenoic acid and 800 mg docosahexaenoic acid) or matching placebo from 16-22 through 36 weeks of gestation. All participants received weekly intramuscular 17alpha-hydroxyprogesterone caproate (250 mg). The primary study outcome was delivery before 37 weeks of gestation. A sample size of 800 was necessary to have 80% power to detect a 30% reduction in the primary outcome from 30%, assuming a type I error two-sided of 5%.


RESULTS
A total of 852 women were included, and none was lost to follow up. Delivery before 37 weeks of gestation occurred in 37.8% (164/434) of women in the omega-3 group and 41.6% (174/418) in the placebo group (relative risk 0.91, 95% confidence interval 0.77-1.07).


CONCLUSIONS
Omega-3 long-chain polyunsaturated fatty acid supplementation offered no benefit in reducing preterm birth among women receiving 17alpha-hydroxyprogesterone caproate who have a history of preterm delivery.


BACKGROUND
ClinicalTrials.gov, www.clinicaltrials.gov, NCT00135902.


METHODS
I.
Harper
Margaret
M
From the Departments of Obstetrics and Gynecology, Wake Forest University Health Sciences, Winston-Salem, North Carolina; the University of North Carolina, Chapel Hill, North Carolina; Wayne State University, Detroit, Michigan; the University of Utah Health Sciences Center, Salt Lake City, Utah; Columbia University, New York, New York; the University of Pittsburgh, Pittsburgh, Pennsylvania; The Ohio State University, Columbus, Ohio; Women and Infants Hospital, Brown University, Providence, Rhode Island; Northwestern University, Chicago, Illinois; Case Western Reserve University-MetroHealth Medical Center, Cleveland, Ohio; Drexel University College of Medicine, Philadelphia, Pennsylvania; the University of Alabama at Birmingham, Birmingham, Alabama; the University of Texas at Houston, Houston, Texas; the University of Texas Medical Branch, Galveston, Texas; and the George Washington University Biostatistics Center, Washington DC; and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
Thom
Elizabeth
E
Klebanoff
Mark A
MA
Thorp
John
J
Sorokin
Yoram
Y
Varner
Michael W
MW
Wapner
Ronald J
RJ
Caritis
Steve N
SN
Iams
Jay D
JD
Carpenter
Marshall W
MW
Peaceman
Alan M
AM
Mercer
Brian M
BM
Sciscione
Anthony
A
Rouse
Dwight J
DJ
Ramin
Susan M
SM
Anderson
Garland D
GD
D000077713:17 alpha-Hydroxyprogesterone Caproate; D019587:Dietary Supplements; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006908:Hydroxyprogesterones / Q000008:administration & dosage; D007231:Infant, Newborn; D007273:Injections, Intramuscular; D011247:Pregnancy; D047928:Premature Birth / Q000517:prevention & control*; D045167:Progesterone Congeners / Q000008:administration & dosage; D012008:Recurrence
D015525:Fatty Acids, Omega-3; D006908:Hydroxyprogesterones; D045167:Progesterone Congeners; D000077713:17 alpha-Hydroxyprogesterone Caproate