Cost-effectiveness of antenatal screening for pre-eclampsia using PlGF and sFlt-1/PlGF ratio in Tanzania: A pre-trial health economic modelling study

This pre-trial health economic modelling study suggests that introducing antenatal biomarker screening for pre-eclampsia using PlGF and sFlt-1/PlGF ratios is potentially cost-effective in Tanzania, particularly when targeted at nulliparous women, with incremental cost-effectiveness ratios ranging from $184.15 to $1,011.78 per disability-adjusted life year averted.

The Gist

Imagine pregnancy as a long, important journey. For most, it's smooth sailing, but for some, a dangerous storm called pre-eclampsia can suddenly appear. This storm causes high blood pressure and can hurt both the mother and the baby. In places like Tanzania, this storm is a major cause of tragedy, often going unnoticed until it's too late because the current way of checking for it is like trying to predict a storm by just looking at the clouds and asking, "Have you had a storm before?"

This paper is a financial and health forecast (a "pre-trial" study) asking a simple question: Would it be worth it for Tanzania to start using special "storm detectors" (blood tests) to find these dangerous pregnancies early?

Here is the breakdown of the study using everyday analogies:

The Three Routes

The researchers compared three different ways to manage this journey:

1. The Old Map (Current Practice): Doctors look at the mother's history and check her blood pressure. If she looks risky, they keep an eye on her. If she doesn't look risky, they might miss the storm entirely.
2. Route 1: The Early Warning System (Strategy 1): This adds a special blood test called PlGF early in the pregnancy (before 16 weeks). If the test says "Storm coming," the mother gets a daily low-dose aspirin (like a shield) and extra check-ups.
3. Route 2: The Mid-Journey Check (Strategy 2): This waits until the middle of the pregnancy (24 weeks) to check a different blood test (the sFlt-1/PlGF ratio). If the test says "Storm coming," the mother gets extra check-ups but no aspirin, because it's too late for the shield to work.

The Cost vs. The Benefit

The researchers built a computer model to see what happens to 3,000 women under each route. They measured two things:

• The Cost: How much money the healthcare system and patients spend.
• The Benefit: How many "bad days" (disabilities or early deaths) were prevented. They call these "DALYs" (Disability-Adjusted Life Years). Think of a DALY as a "health debt" that the country owes. The goal is to pay off this debt.

The Results:

• Route 1 (Early Warning) is the winner. For every "health debt" (DALY) it prevents, it costs the system about $410. In Tanzania, this is considered a "very good deal" (like buying a high-quality umbrella for a cheap price).
• Route 2 (Mid-Journey Check) is more expensive. It costs about $1,011 to prevent the same amount of bad outcomes. It's still a "good deal" by some standards, but not as good as Route 1.
• The "Nulliparous" Twist: The researchers also asked, "What if we only use these expensive tests on women having their first baby?" (First-time moms are harder to predict with the old map). In this scenario, Route 1 became even cheaper and more effective (about $184 per benefit), making it an even better deal.

Why Route 1 Wins

The study found that timing is everything.

• Route 1 catches the storm early. This allows doctors to give the "shield" (aspirin) before the storm starts, which is very good at stopping the most dangerous type of storm (preterm pre-eclampsia).
• Route 2 waits too long. By the time the test is done, the "shield" (aspirin) doesn't work anymore. You can only monitor the storm, which is less effective at preventing the worst damage.

The "What If" Scenarios

The researchers were careful to test their assumptions, like checking if their map was accurate:

• Adherence: They assumed 80% of women would actually take the aspirin and show up for extra check-ups. If fewer women do this, the plan becomes less cost-effective.
• Prevalence: If pre-eclampsia is less common than they thought, the tests aren't as valuable.
• Sensitivity: They used test accuracy numbers from rich countries, assuming the tests work just as well in Tanzania.

The Bottom Line

The paper concludes that introducing the early blood test (Route 1) is a smart financial and health move for Tanzania. It saves lives and reduces suffering for a price the system can likely afford.

However, the authors are clear: This is just a forecast. It's a "pre-trial" study. They haven't actually run the full experiment yet. They are saying, "Based on our math and the data we have, this looks like a great idea. We should go ahead and run the real trial to prove it works in the real world, especially focusing on first-time moms."

In short: It's better to buy a cheap, early warning system and a shield than to wait until the storm hits and try to fix the damage.

Technical Summary

Technical Summary: Cost-effectiveness of Antenatal Screening for Pre-eclampsia in Tanzania

Problem Statement
Pre-eclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality, particularly in low- and middle-income countries (LMICs). In Tanzania, PE and eclampsia account for approximately 22% of maternal deaths and 41% of stillbirths. Current antenatal care (ANC) in Tanzania relies on opportunistic, risk-factor-based screening, which has limited predictive value and fails to identify a substantial portion of high-risk women. While biomarker-based screening (using placental growth factor [PlGF] and the soluble fms-like tyrosine kinase-1 [sFlt-1]/PlGF ratio) has proven effective in high-income countries (HICs), its suitability, performance, and economic impact in low-resource settings remain unexplored. This study addresses the evidence gap by conducting a pre-trial health economic evaluation to inform the design of the PRESHA (PREventing Severe Hypertensive Adverse events in pregnancy and childbirth) study in Tanzania.

Methodology
The authors developed a decision tree model using Microsoft Excel to compare three strategies within a hypothetical cohort of 3,000 Tanzanian women (gestational age <20 weeks) over a one-year time horizon (pregnancy plus three months postpartum). The analysis adopted a healthcare sector perspective, with costs expressed in 2023 US dollars and health outcomes measured in disability-adjusted life years (DALYs).

The three compared strategies were:

1. Current Practice: Identification of maternal risk factors only, without specific risk stratification or preventive measures for high-risk women.
2. Strategy 1: Addition of mean arterial pressure (MAP) and PlGF measurement before 16 weeks gestation. High-risk women receive early low-dose aspirin prophylaxis and close monitoring (four additional ANC visits and two ultrasounds).
3. Strategy 2: Addition of MAP and sFlt-1/PlGF ratio measurement from 24 weeks gestation. High-risk women receive close monitoring only (no aspirin, as it is ineffective when started late).

Key data inputs included local prevalence rates (4.2% PE/E), screening sensitivity/specificity derived from HIC studies (assuming local thresholds would yield comparable performance), and cost estimates for screening, aspirin, monitoring, and adverse outcomes. The study utilized two cost-effectiveness thresholds (CETs): the WHO-CHOICE standard (1x and 3x GDP per capita) and a threshold based on opportunity cost (45% of GDP per capita). Sensitivity analyses included probabilistic sensitivity analysis (PSA) with 2,000 Monte Carlo iterations and one-way sensitivity analyses. A scenario analysis was also conducted to evaluate screening limited to nulliparous women.

Key Results

• Base Case Analysis: Compared to current practice, Strategy 1 yielded an incremental cost-effectiveness ratio (ICER) of $410.45 per DALY averted, while Strategy 2 yielded an ICER of $1,011.78 per DALY averted.
• Cost-Effectiveness Determination: Under the WHO-CHOICE threshold (3x GDP per capita, ~$3,673), both strategies were deemed cost-effective. However, under the more stringent opportunity-cost-based threshold (45% of GDP per capita, ~$551), only Strategy 1 remained cost-effective. Strategy 2 was found to be dominated by Strategy 1 in most iterations.
• Clinical Outcomes: Strategy 1 was most effective in preventing stillbirths, while Strategy 2 resulted in the lowest number of maternal near misses (MNMs). Neither strategy significantly improved maternal mortality rates in the model.
• Scenario Analysis (Nulliparous Women): When screening was restricted to nulliparous women (approx. 23% of the population) while strengthening care for the rest, the ICERs improved significantly: $184.15 for Strategy 1 and $413.33 for Strategy 2. Both remained cost-effective under all tested thresholds in this scenario.
• Sensitivity: The ICER for Strategy 1 was most sensitive to the proportion of term PE cases, PE prevalence, and the effectiveness of close monitoring.

Key Contributions

• First Pre-Trial Evaluation in Sub-Saharan Africa: This is the first planned cost-effectiveness analysis of biomarker-based PE screening in sub-Saharan Africa, providing a framework for the ongoing PRESHA trial.
• Identification of Key Parameters: The study identifies critical data gaps, specifically regarding local screening sensitivity/specificity, adherence rates to preventive treatment, and the relative risk reduction of adverse outcomes in LMIC settings. These parameters are prioritized for data collection in the upcoming trial.
• Strategic Targeting: The analysis suggests that targeting nulliparous women with biomarker screening while maintaining risk-factor-based care for parous women offers a highly cost-effective implementation pathway for resource-constrained settings.
• Validation of Early Intervention: The results reinforce the economic value of early screening (Strategy 1) that enables aspirin prophylaxis, which is effective primarily for preventing preterm PE.

Significance and Claims
The paper claims that biomarker-based screening for pre-eclampsia has the potential to be cost-effective in Tanzania, particularly when introduced early in pregnancy and targeted at nulliparous women. The authors emphasize that their findings are based on a pre-trial model and should not be used to guide immediate clinical practice without further validation.

The significance of the study lies in its role as a preparatory step for a full trial-based economic evaluation. It demonstrates that introducing PlGF screening (Strategy 1) is likely to be "very cost-effective" even under conservative thresholds, whereas later screening (Strategy 2) is less favorable. The authors conclude that while final policy recommendations must await the PRESHA trial results, their analysis supports the phased integration of early biomarker screening into ANC, starting with nulliparous women, to improve maternal and neonatal outcomes in low-resource settings. They also highlight the necessity of developing locally appropriate biomarker thresholds and point-of-care testing to ensure feasibility.