Routine screening and treating low omega-3 levels in pregnancy reduces preterm birth.

Today we published the economic evaluation of introducing routine omega-3 testing and targeted supplementation during pregnancy to reduce early preterm births in Australia. This culminates 20 years of research including our two large Australian randomised trials that contributed to a Cochrane review showing that treating low omega 3 levels in pregnancy will significantly reduce early preterm birth. The current research paper highlights that introducing routine screening and treating in pregnancy will save 640 early preterm births every year and save direct healthcare costs of $44.7million. This excludes the stress and impact on families affected by early preterm birth, that is birth of the baby before 34 weeks of pregnancy. 
Cost-Effectiveness of Omega-3 Testing in Pregnancy
Our economic modelling conclusively shows that routine omega-3 testing and targeted supplementation in early pregnancy could reduce early preterm births and save healthcare costs in Australia.

• The analysis compares current practice with a new strategy involving blood testing and high-dose omega-3 supplements.
• In 2022, approximately 17.5% of pregnant women (about 50,609 of 289,195) would be eligible for supplementation due to low omega-3 levels.
• The model predicts 640 early preterm births (before 34 weeks) could be prevented annually.
• Implementing this approach could save $26.1 million in direct healthcare costs and $44.7 million overall.
• The intervention is considered dominant, being more effective and less costly than current practice.
• Cost savings are robust across most scenarios, with the strongest influence from the estimated treatment effect.

Clinical and Epidemiological Data
Preterm birth is a leading cause of neonatal death and long-term disability, with significant health and economic impacts in Australia.

• In 2022, around 25,000 babies were born preterm in Australia.
• The total cost to the government for preterm births in one year is estimated at AUD 1.41 billion.
• Early preterm infants (<34 weeks) face higher risks of adverse outcomes, including neurodevelopmental issues and chronic diseases.
• The risk of early preterm birth can be significantly reduced by omega-3 supplementation, especially in women with low omega-3 levels.
• The ORIP trial showed a 77% reduction in early preterm birth with omega-3 supplementation among women with low omega-3 status.
• Australian guidelines recommend omega-3 supplements (800 mg DHA and 100 mg EPA daily) for women with low omega-3 levels.

Model Design and Key Inputs
A decision analytic model was developed using Australian data to evaluate costs and benefits of omega-3 testing and supplementation.

• The model includes a cohort of 289,195 singleton pregnancies, focusing on live births before 34 weeks.
• It considers screening uptake (80%), eligibility (17.5%), adherence (65%), and treatment effectiveness (RR=0.23).
• Costs include testing ($50 per woman), supplementation ($100 per woman), birth, neonatal, hospital, education, family out-of-pocket, and maternal income loss.
• The model predicts the number of early preterm births prevented and associated cost savings over 18 years.
• Sensitivity analyses tested the robustness of results against key variables like relative risk, coverage, adherence, and costs.

Main Results and Economic Impact
The analysis indicates that omega-3 testing and targeted supplementation could prevent 640 early preterm births and generate substantial savings.

• Current practice predicts 1,599 early preterm births with costs of $151.9 million.
• The new strategy could reduce early preterm births to 959, preventing 640 cases.
• Total direct costs could decrease by $26.1 million, and overall costs by $44.7 million.
• The intervention's total cost is estimated at $15.6 million.
• The approach is cost-saving and more effective, with a benefit of $1.67 in direct costs and $3 in total costs per dollar invested.
• Sensitivity analyses show the results are robust, except when the treatment effect is less than expected, which could make the strategy more costly.

Sensitivity and Threshold Analyses
The model's outcomes are most sensitive to the estimated treatment effect (relative risk).

• When the upper confidence limit of RR (0.79) is used, the intervention may not be cost-saving, with an ICER of $24,132 per early preterm birth prevented.
• The intervention remains cost-effective if it prevents at least 28% of early preterm births.
• Higher adherence (90%) and conservative treatment effects can increase costs, reducing cost savings.
• Threshold analysis shows the intervention is cost-neutral if the relative risk exceeds approximately 0.712, meaning less than 28.8% reduction in early preterm births.

Broader Implications and Utility
Implementing omega-3 testing and supplementation could improve maternal and infant health outcomes while reducing long-term societal costs.

• The approach is scalable and aligns with Australian guidelines.
• It offers a cost-effective, evidence-based strategy to address preterm birth.
• Preventing preterm birth could generate approximately 600 QALYs over 18 years, indicating significant health benefits.
• The findings support adopting this strategy on a national level to reduce preterm birth rates and associated costs.

Cost-Effectiveness of Omega-3 Testing and Supplementation
The analysis indicates that implementing omega-3 testing and supplementation during pregnancy is a cost-effective strategy to reduce early preterm births in Australia. - Generates 164 additional QALYs, with a cost per QALY of $25,751 AUD. - The ICER is below the willingness-to-pay threshold of $50,000 per QALY. - The ICER is also lower than the Australian reference estimate of $28,000 per QALY. - The approach is likely to be more beneficial in real-world settings due to higher testing uptake and adherence. - Embedding testing into routine antenatal care is feasible, utilizing existing blood testing infrastructure. - The model's conservative assumptions suggest actual benefits could be greater. - The cost savings are projected to be over AUD 44.7 million annually, preventing approximately 640 early preterm births. - The economic benefits are sensitive to the estimated treatment effect, with a large effect size (77% reduction) observed in the subgroup analysis. - The proportion of omega-3 depletion among pregnant women is about 17%, supporting targeted testing. - The intervention is likely to be both cost-saving and more effective than current practices.
Strengths, Limitations, and Future Research Directions
The model's conservative assumptions and potential for greater real-world benefits are key strengths, while uncertainties in treatment effect estimates and subgroup analysis introduce limitations. - Conservative assumptions avoid overestimating benefits. - Real-world implementation may lead to higher testing and adherence rates. - The model defines early preterm birth as before 34 weeks, with cost estimates based on births between 32-36 weeks. - Incorporates mortality rates and ongoing costs up to 18 years of age, likely underestimating total savings. - Sensitivity analysis shows treatment effect variation is the most influential factor. - The treatment effect estimate is derived from a subgroup, adding uncertainty. - The large and significant effect (77% reduction) exceeds the 42% reduction reported in the Cochrane review. - Additional real-world data could refine estimates and reduce uncertainty. - Embedding evaluation during implementation can optimize delivery and outcomes. - The open-source model can be adapted for other health systems and populations.
Policy and Health System Implications
Integrating omega-3 testing and supplementation into routine antenatal care offers a low-cost, scalable, and potentially high-value intervention to reduce preterm birth-related costs and disparities. - Requires modest upfront investment; potential for substantial net healthcare savings. - Testing can be integrated into existing diagnostic infrastructure and blood panels. - Suitable for primary, secondary, tertiary, rural, and remote health settings. - Benefits extend beyond immediate cost savings, reducing societal and long-term system burdens. - Each new birth cohort adds to cumulative societal costs, which preventive strategies can mitigate. - Implementation could help address disparities, especially among Aboriginal and Torres Strait Islander women. - Broader adoption supports national health priorities and Closing the Gap initiatives. - Embedding evaluation will support ongoing optimization and evidence collection.
Conclusion and Future Outlook
Omega-3 testing and supplementation during pregnancy is a promising, cost-effective strategy to prevent early preterm births, with potential for large-scale health and economic benefits. - Estimated to prevent about 640 early preterm births annually. - Projected to save over AUD 26 million in direct healthcare costs and reduce total costs by AUD 44.7 million. - The economic value is sensitive to the treatment effect estimate but remains favorable. - Further real-world evaluation is necessary to confirm effectiveness and economic outcomes. - The approach has demonstrated feasibility and acceptability in South Australia. - Potential for scalable implementation to benefit mothers, infants, and health systems nationally.

Professor Julie Quinlivan