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

Trial Summary

What is the purpose of this trial?

Smoking is the most important modifiable risk factor for adverse pregnancy outcomes including preterm birth, neonatal death, and maternal complications. Rates of smoking cessation during pregnancy are low, particularly in underserved populations, and currently approved pharmacotherapies for smoking cessation either are considered unsafe in pregnancy or have uncertain effectiveness. Identifying safe and effective interventions, which might mitigate the adverse effects of smoking on maternal-fetal outcomes, is a major public health priority. We hypothesize that smoking-induced n-3 LCPUFA relative deficiencies may be an important mechanism contributing to tobacco-related adverse pregnancy outcomes and that n-3 LCPUFA supplementation specifically targeted to pregnant smokers may reduce these complications. Support for this hypothesis comes from a recent secondary analysis of the Omega-3 Fatty 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-smokers. While compelling, this study was a post hoc analysis that included only a small sample of smokers and did not collect data on smoking behaviors during follow up. Yet the ascertainment of longitudinal smoking behavior is critical, as some clinical studies have found that supplemental n-3 LCPUFAs might also reduce nicotine cravings, and lower daily cigarette use. Thus, smokers may doubly benefit from replenishing n-3 LCPUFAs via lower risk of preterm labor and/or increased smoking cessation. To address these knowledge gaps, we are proposing a multi-center, randomized, placebo-controlled, double-blinded study of n-3 LCPUFA supplementation in 400 pregnant smokers. We will collect detailed information on smoking behavior, validated biological markers of cigarette exposure (urinary cotinine, end-expiratory carbon monoxide) and biomarkers of n-3 LCPUFA status (red blood cell phospholipid membrane fatty acids). Our specific aims of this proposal are to 1) determine the effect of supplemental n-3 LCPUFAs on gestational age at delivery and preterm labor in pregnant smokers and 2) determine the effect of n-3 LCPUFA supplementation on tobacco use in pregnant smokers. We will recruit potential participants from eight obstetrics clinics across the Middle-Tennessee area. Our study could have a major translational impact on both adverse tobacco-related birth outcomes and smoking cessation efforts.

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.

What data supports the idea that Omega-3 Fatty Acid Supplements for Preterm Labor Prevention in Smokers is an effective treatment?

The available research shows that omega-3 fatty acid supplements, like fish oil, may help delay preterm labor. Studies have found that populations with high fish consumption tend to have longer pregnancies. In experiments with sheep, omega-3 supplements delayed labor and even stopped contractions in some cases. This suggests that omega-3s could be useful in preventing early births in humans. However, while some studies show potential benefits, there is no widespread recommendation for their use in preventing preterm labor. ^{1 2 3 4 5}

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 fatty acids, found in fish oil, may help delay preterm birth. Studies have observed longer pregnancies in populations with high fish consumption, and trials suggest omega-3 supplements can delay birth timing, potentially reducing preterm delivery risk. ^{1 2 3 4 5}

What safety data exists for omega-3 supplements in preventing preterm labor?

The safety of omega-3 fatty acid supplements, including EPA and DHA, has been evaluated in various studies. These supplements are generally considered safe and are available over the counter. Randomized controlled trials and systematic reviews have shown that omega-3 supplementation during pregnancy may delay the timing of birth and reduce the risk of early preterm delivery. No significant adverse effects on maternal or child health outcomes have been reported, making them a potentially safe option for preventing preterm labor. ^{1 2 4 6 7}

Is it safe to take omega-3 supplements during pregnancy?

Omega-3 supplements, like fish oil, are generally considered safe for pregnant women and have been studied for their potential benefits in reducing preterm birth. They are available over the counter and are often taken to improve pregnancy outcomes without significant safety concerns. ^{1 2 4 6 7}

Is Fish Oil a promising treatment for preventing preterm labor in smokers?

Yes, Fish Oil, which contains Omega-3 fatty acids, is a promising treatment for preventing preterm labor. Studies show that Omega-3s can help extend pregnancy duration, especially in populations with high fish consumption. This suggests that taking Omega-3 supplements like Fish Oil may help delay preterm birth. ^{1 2 4 8 9}

How does the treatment of omega-3 fatty acids differ from other treatments for preventing preterm labor in smokers?

Omega-3 fatty acids, found in fish oil supplements, are unique because they are a natural dietary supplement that may help prolong pregnancy by balancing fatty acids in the body and reducing inflammation, unlike other treatments that might involve medications or hormones. This approach is based on observations that populations with high fish consumption tend to have longer pregnancies, and it offers a potentially safe and accessible option for preventing preterm labor. ^{1 2 4 8 10}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

References

1. Mexico 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. [2021]

2. Ireland 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Delay of preterm delivery in sheep by omega-3 long-chain polyunsaturates. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Docosahexaenoic Acid and Preterm Birth. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

The role of long chain polyunsaturated fatty acids in perinatal nutrition. [2020]

6. England 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. [2018]

7. England 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. [2022]

8. Italy pubmed.ncbi.nlm.nih.gov

Polyunsaturated fatty acids and risk of preterm delivery. [2005]

9. England 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. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Higher dose docosahexaenoic acid supplementation during pregnancy and early preterm birth: A randomised, double-blind, adaptive-design superiority trial. [2023]