Omega-3 Fatty Acid Supplements for Preterm Labor Prevention in Smokers

(INFANTS Trial)

Overseen By Harvey J Murff, MD, MPH

Age: < 65

Sex: Female

Trial Phase: Phase 2

Sponsor: Vanderbilt University Medical Center

Must not be taking: Fish oil supplements

Disqualifiers: Substance abuse, Hypertension, Seizure, Diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16-28 weeks

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether omega-3 fatty acid supplements can lower the risk of preterm labor and reduce cigarette cravings in pregnant smokers. Participants will receive either fish oil capsules (containing omega-3 acids) or placebo capsules made of olive oil. Researchers will track changes in smoking behavior and pregnancy outcomes. Pregnant individuals between 12 and 24 weeks who smoke daily might find this trial relevant. The goal is to find a safe way to improve health outcomes for both mother and baby by addressing smoking-related risks. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are currently using fish oil supplements, you cannot participate in the trial.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are using fish oil supplements, you would need to stop, as they are part of the exclusion criteria.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that omega-3 fatty acids are generally safe for pregnant women. Studies have found that taking omega-3 supplements during pregnancy can help lengthen the pregnancy and lower the risk of early birth. Specifically, omega-3s like EPA and DHA, often found in fish oil, are linked to positive pregnancy outcomes.

Most people who have taken these supplements have tolerated them well, with few reports of serious side effects. Usually, any side effects are mild, such as a fishy aftertaste or an upset stomach. These supplements are already recommended for pregnant women to support overall health.

In this trial, participants will take fish oil capsules that provide a high dose of omega-3s each day. Previous studies suggest this method can be safe and beneficial for both the mother and the baby. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for preterm labor prevention in smokers?

Unlike the standard treatments for preterm labor, which often involve medications like tocolytics to delay labor, fish oil supplements offer a natural alternative. Researchers are excited about this treatment because it uses omega-3 fatty acids, specifically EPA and DHA, which are believed to have anti-inflammatory properties that could reduce the risk of early labor. This approach is particularly intriguing for smokers, who are at an increased risk of preterm birth, as omega-3s could help counteract some negative effects of smoking on pregnancy. Plus, taking fish oil in capsule form is a convenient and non-invasive option.

What evidence suggests that Omega-3 fatty acid supplements might be an effective treatment for preterm labor prevention in smokers?

Research has shown that omega-3 fatty acids, found in fish oil, might lower the risk of early labor in pregnant smokers. In this trial, participants will receive either fish oil supplements, which provide omega-3 fatty acids, or a placebo of olive oil capsules. One study found that smokers who took omega-3 supplements had a lower chance of early labor than those who did not. These fatty acids might also reduce nicotine cravings, potentially aiding in quitting smoking. By addressing omega-3 deficiencies caused by smoking, the supplements could support healthier pregnancies. This makes omega-3s a promising option for pregnant smokers aiming to improve both birth outcomes and smoking habits. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for pregnant smokers aged 16-40, who are between 12 and 24 weeks gestation, smoke at least one cigarette per day (previously ten before pregnancy), and have a carbon monoxide reading of at least 8 ppm. They must not be using fish oil supplements or have allergies to fish, substance abuse issues, certain medical conditions like chronic hypertension or clotting disorders, nor plans to move from Middle-Tennessee within nine months.

Inclusion Criteria

I have a working phone.

I am between 16 and 40 years old.

An exhaled carbon monoxide reading of at least 8 ppm

Exclusion Criteria

I have a blood clotting disorder.

I am scheduled for a procedure to prevent premature birth.

My diabetes is classified as severe.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive n-3 LCPUFA or placebo supplementation from 12 to 24 weeks gestation until delivery

16-28 weeks

Regular visits for supplementation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Fish Oil (Containing Omega-3 Acids)

Trial Overview The study tests if Omega-3 acids in fish oil can help prevent premature labor in pregnant women who smoke by potentially reducing nicotine cravings and cigarette use. It's a double-blinded study with two groups: one taking fish oil and the other olive oil as a placebo. The effects on both preterm labor risk and smoking behavior will be monitored.

How Is the Trial Designed?

Group I: Fish Oil Experimental Treatment 1 Intervention

Participants allocated to n-3 LCPUFA supplementation will be instructed to take four 1000 mg n-3 LCPUFA capsules (Metagenics™) daily. This will provide a total daily dose of 4000 mg n-3 LCPUFAs (2840 EPA and 1160 DHA).

Group II: Olive Oil Placebo Group 1 Intervention

Oleic acid (olive oil) capsules have a similar texture, size, color, and consistency to EPA capsules. Participant will be instructed to take four 100mg olive oil capsules

Fish Oil (Containing Omega-3 Acids) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Fish Oil for:

• Dietary supplement
• Hypertriglyceridemia

Approved in European Union as Omega-3 fatty acids for:

• Hypertriglyceridemia
• Prevention of cardiovascular disease

Approved in Canada as Fish Oil for:

• Dietary supplement
• Hypertriglyceridemia

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

Preterm birth is a major cause of perinatal complications, with over 85% of cases leading to serious health issues for infants, and about 50% of these births have unclear causes.

Epidemiological studies suggest that omega-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy may help delay preterm birth, indicating potential for this dietary intervention as a preventive strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docosahexaenoic Acid and Preterm Birth. Makrides, M., Best, K.[2018]

A study involving 1310 pregnant women found that those consuming less than 150 mg/day of DHA had a significantly lower risk of early preterm birth when assigned to high dose DHA supplementation (1.4% vs 3.9%).

The validated DHA food frequency questionnaire (DHA-FFQ) effectively identifies pregnant women who would benefit from high dose DHA supplementation, making it a practical tool for clinicians to reduce the risk of preterm births.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docosahexaenoic acid (DHA) intake estimated from a 7-question survey identifies pregnancies most likely to benefit from high-dose DHA supplementation. Christifano, DN., Crawford, SA., Lee, G., et al.[2023]

A systematic review of nine trials involving 5980 women found that omega-3 fatty acids significantly reduced the risk of early preterm delivery by 58% and any preterm delivery by 17%.

The use of omega-3 fatty acids also led to an increase in mean gestational age by nearly 2 weeks and an increase in mean birth weight by 122 grams, suggesting a positive impact on pregnancy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of omega-3 fatty acids in prevention of early preterm delivery: a systematic review and meta-analysis of randomized studies. Kar, S., Wong, M., Rogozinska, E., et al.[2022]

Prenatal supplementation of omega-3 polyunsaturated fatty acids (n-3 PUFA) has been investigated for its potential to reduce the incidence of preterm delivery, which is a significant cause of perinatal complications.

Epidemiological studies suggest that populations with high marine oil consumption experience longer pregnancies, prompting clinical trials to explore the preventive benefits of n-3 PUFA against preterm labor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impacto de la suplementación con ácidos grasos omega-3 en el embarazo y la reducción del riesgo de parto pretérmino. Sosa, SEY., Reyes-Muñoz, E., García-Jiménez, G., et al.[2021]

Supplementation with n-3 long-chain polyunsaturated fatty acids (LCPUFA) during pregnancy is associated with a modest increase in birthweight (average increase of 42.2 grams) and a 26% lower risk of early preterm delivery.

The review of 15 randomized controlled trials and 14 observational studies found no significant impact of n-3 LCPUFA on other outcomes like pre-eclampsia or infant mortality, indicating its specific benefits for birthweight and preterm delivery without affecting other serious pregnancy complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of n-3 long-chain polyunsaturated fatty acid intake during pregnancy on maternal, infant, and child health outcomes: a systematic review. Imhoff-Kunsch, B., Briggs, V., Goldenberg, T., et al.[2018]

Maternal supplementation with omega-3 long chain polyunsaturated fatty acids (LCPUFA), particularly DHA, has shown a promising 50% reduction in early preterm births (EPTBs) based on previous trial outcomes, highlighting its potential as a preventive strategy.

The ongoing trial aims to further evaluate the effectiveness of DHA supplementation in a large cohort of 5540 women, with the goal of confirming its ability to reduce EPTB incidence and improve overall pregnancy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for a randomised controlled trial evaluating the effect of prenatal omega-3 LCPUFA supplementation to reduce the incidence of preterm birth: the ORIP trial. Zhou, SJ., Best, K., Gibson, R., et al.[2022]

Dietary intake of Omega-3 fatty acids can significantly prolong gestation by 4-7 days in cases of preterm delivery, likely by inhibiting certain prostaglandins that trigger labor.

Given the low dietary intake of Omega-3 in Western populations, increasing consumption through supplementation or dietary changes could be an effective strategy for preventing preterm delivery, alongside existing pharmacological treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polyunsaturated fatty acids and risk of preterm delivery. Facchinetti, F., Fazzio, M., Venturini, P.[2005]

Infusing omega-3 fatty acids in pregnant ewes delayed the onset of labor and delivery, suggesting a potential protective effect against preterm labor.

The study found that omega-3 fatty acids may alter hormonal responses related to labor, indicating their potential use as a treatment to prevent preterm delivery in humans, which is crucial for reducing neonatal complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delay of preterm delivery in sheep by omega-3 long-chain polyunsaturates. Baguma-Nibasheka, M., Brenna, JT., Nathanielsz, PW.[2019]

Preterm infants often have lower levels of omega-3 fatty acids due to missing the last trimester of in utero transfer, leading to the supplementation of preterm infant formula with docosahexaenoic acid (DHA) and arachidonic acid (AA) since 2000 to improve visual acuity.

While DHA supplementation has not consistently shown improvements in clinical or developmental outcomes beyond certain levels, maternal omega-3 supplementation during pregnancy may help reduce preterm birth rates, although it could also lead to longer gestation and increased fetal size in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of long chain polyunsaturated fatty acids in perinatal nutrition. Collins, CT., Gibson, RA., McPhee, AJ., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8669400/

Investigating N-3 Fatty Acids to prevent Neonatal Tobacco ... This study tests the hypothesis that smoking-induced n-3 LCPUFA deficiencies contribute to tobacco-related adverse pregnancy outcomes.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04417595

Omega-3 Fatty Acids for Smoking Cessation in Pregnancy ... Acids Supplementation to Prevent Preterm Birth trial that found that only smokers taking n-3 LCPUFAs had a reduction in preterm labor risk as compared to non- ...

3. withpower.com withpower.com/trial/phase-3-obstetric-labor-premature-10-2020-ec03e

Omega-3 Fatty Acid Supplements for Preterm Labor ... What data supports the effectiveness of the treatment Fish Oil (Containing Omega-3 Acids) for preventing preterm labor in smokers? Research shows that omega-3 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2589933323003932

Omega-3 fatty acid supply in pregnancy for risk reduction of ... Women with a history of PTB were provided fish oil capsules containing 2.7 g of omega-3 LCPUFA including 900-mg/d DHA and 1200-mg/d EPA from 20 weeks of ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04417595/smoking-cessation-in-pregnancy

Omega-3 Fatty Acids for Smoking Cessation in Pregnancy ... Acids Supplementation to Prevent Preterm Birth trial that found that only smokers taking n-3 LCPUFAs had a reduction in preterm labor risk as compared to non- ...

6. ajogmfm.org ajogmfm.org/article/S2589-9333(23)00393-2/fulltext

Omega-3 fatty acid supply in pregnancy for risk reduction ... Women of childbearing age should obtain a supply of at least 250 mg/d of docosahexaenoic+eicosapentaenoic acid from diet or supplements, and in ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0952327822001077

Omega-3 fatty acids during pregnancy to reduce preterm birth Data from both the 1995 and 2000 Olsen trials indicate that omega-3 LCPUFA supplementation extended the duration of gestation and reduced the risk of ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8157397/

Supplementation of Omega 3 during Pregnancy and the Risk ... Increased tissue levels of omega-3 polyunsaturated fatty acids prevents pathological preterm birth. Sci. Rep. 2013;3:1–7. doi: 10.1038 ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa1816832

A Randomized Trial of Prenatal n−3 Fatty Acid ... Epidemiologic studies have shown significant associations between lower fish consumption in pregnancy and increased rates of preterm delivery.

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11095130/

Differential DHA and EPA Levels in Women with Preterm ... This study aimed to compare DHA and EPA levels in 44 women with preterm births and 44 women with term births at a tertiary hospital in West Java Province, ...