Assessment of DHA On Reducing Early Preterm Birth (ADORE)

The purpose of this study is to determine if giving a larger amount of DHA than currently included in some prenatal supplements can reduce early preterm birth (birth before 34 weeks of pregnancy).

Docosahexaenoic acid (DHA) is a nutrient found in some fish and eggs and its intake in US diets is typically low. Because DHA is important for early brain development, it has recently been added to many prenatal supplements. The usual amount is around 200 mg/day. Participants in this study are guaranteed to receive at least 200 mg/day of DHA. Almost 5 in 100 births in the US occur before 34 weeks of pregnancy. There is no way to predict which births will occur before 34 weeks. In an earlier study conducted at the University of Kansas Medical Center, women who received 600 mg DHA/day compared to no DHA had fewer births before 34 weeks of pregnancy with fewer complications of preterm birth. This study is designed to compare standard care (200 mg/day of DHA) to a higher amount of DHA (1000 mg/day) to determine if the higher amount will reduce early preterm birth (birth before 34 weeks of pregnancy). Individual participation in this study is expected last about 5 months.

Preterm birth, Early preterm birth, Very low birth weight, Low birth weight, Pregnancy outcome, Docosahexaenoic acid (DHA), Randomized cliinical trial, Superiority trial, Adaptive design

Participants will receive 2 placebo pills/day that do not contain DHA. Like the experimental group, they will be given a supplement of Docosahexaenoic acid - 200mg/day , a common amount in prenatal vitamins.

The intervention includes Docosahexaenoic acid - 800mg/day per day provided in two 400 mg capsules. The intervention group as well as the active comparator group will be given 1-200 mg/capsule per day of DHA that is a common amount in prenatal vitamins.

All participants will take 1000 mg/DHA per day (1 capsule will be labeled with 200 mg; 2 capsules will be masked with 400 mg each)

Participants will receive 2 capsules (masked) containing half soybean oil and half corn oil equaling 800 mg.The soybean and corn oil combination does not contain DHA.

Bayesian posterior mean and 95% credible interval of pregnancies which result in an early preterm birth (birth before 34 weeks of pregnancy) by DHA dose

Bayesian posterior mean and 95% credible interval of pregnancies which result in an early preterm birth (birth before 34 weeks of pregnancy) by DHA dose and DHA status at enrollment (low/high) (modified statistical analysis plan while study was underway)

Bayesian posterior mean and 95% credible interval red blood cell phospholipid DHA (weight percent of total fatty acids) at enrollment and birth by dose

Inclusion Criteria: Pregnant females 18 years and older 12 to 20 weeks gestation at study entry Agree to consume study capsules and a typical prenatal supplement of 200 mg DHA Available by telephone Able to speak and read in either English or Spanish language Exclusion Criteria: Expecting multiple infants Gestational age at baseline <12 weeks or >20 weeks Unable or unwilling to agree to consume capsules until delivery Unwilling to discontinue use of another prenatal supplement that contains greater than or equal to 200 mg DHA per day Women with allergy to any component of DHA product (including algae), soybean oil or corn oil

Mudaranthakam DP, Brown A, Kerling E, Carlson SE, Valentine CJ, Gajewski B. The Successful Synchronized Orchestration of an Investigator-Initiated Multicenter Trial Using a Clinical Trial Management System and Team Approach: Design and Utility Study. JMIR Form Res. 2021 Dec 22;5(12):e30368. doi: 10.2196/30368.

Carlson SE, Gajewski BJ, Valentine CJ, Kerling EH, Weiner CP, Cackovic M, Buhimschi CS, Rogers LK, Sands SA, Brown AR, Mudaranthakam DP, Crawford SA, DeFranco EA. Higher dose docosahexaenoic acid supplementation during pregnancy and early preterm birth: A randomised, double-blind, adaptive-design superiority trial. EClinicalMedicine. 2021 May 17;36:100905. doi: 10.1016/j.eclinm.2021.100905. eCollection 2021 Jun.

Carlson SE, Gajewski BJ, Valentine CJ, Rogers LK, Weiner CP, DeFranco EA, Buhimschi CS. Assessment of DHA on reducing early preterm birth: the ADORE randomized controlled trial protocol. BMC Pregnancy Childbirth. 2017 Feb 13;17(1):62. doi: 10.1186/s12884-017-1244-5.