Objective
We sought to estimate the cost-effectiveness of magnesium neuroprophylaxis for all women at risk for preterm birth <32 weeks.
Study Design
A decision analytic and cost-effectiveness model was designed to compare use of magnesium for neuroprophylaxis vs no treatment for women at risk for preterm birth <32 weeks due to preterm premature rupture of membranes or preterm labor from 24-32 weeks. Outcomes included neonatal death and moderate-severe cerebral palsy. Effectiveness was reported in quality-adjusted life years.
Results
Magnesium for neuroprophylaxis led to lower costs ($1739 vs $1917) and better outcomes (56.684 vs 56.678 quality-adjusted life years). However, sensitivity analysis revealed the model to be sensitive to estimates of effect of magnesium on risk of moderate or severe cerebral palsy as well as neonatal death.
Conclusion
Based on currently published evidence for efficacy, magnesium for neuroprophylaxis in women at risk to deliver preterm is cost-effective.
After years of published observational data suggesting a relationship between maternal exposure to magnesium sulfate and a decrease in adverse neonatal neurologic outcomes in infants born preterm, 4 trials were published over the past 8 years with conflicting results regarding the impact of magnesium in the setting of pregnancies delivering preterm. The most recent of these trials by Rouse et al was a multicenter trial conducted in the United States, and the results offered the most promising evidence that magnesium decreased the risk of moderate or severe cerebral palsy (CP) in infants born preterm who survived. However, CP was not the primary outcome of this trial, but was part of a composite with death due to the design challenge of competing risks and there was a trend toward an increase in death in the infants exposed to magnesium compared to those exposed to placebo. In light of these recent and complex findings as well as the rare nature of these outcomes, it seems reasonable to include a formal estimate of cost-effectiveness of this therapy when considering a sweeping change in practice.
We undertook this study to test the hypothesis that magnesium was cost-effective in women at risk for preterm birth for the prevention of CP, and further, to explore whether the cost-effectiveness was limited to particular subgroups of women.
Materials and Methods
A decision-analytic and cost-effectiveness model was designed to compare 2 strategic approaches for the prevention of CP in preterm infants from a societal prospective. The use of magnesium for neonatal neuroprophylaxis was compared to nonuse, with the latter representative of the accepted standard of care prior to recent publications. The model was constructed for women carrying singleton pregnancies between 24 weeks 0/7 days’ and 31 weeks 6/7 days’ gestation at high risk for spontaneous preterm birth <32 weeks’ gestation due to either preterm labor (PTL) or preterm premature rupture of membranes (PPROM) ( Figure 1 ). Two additional models were constructed to estimate the cost-effectiveness of magnesium for neuroprophylaxis in at-risk subpopulations: PPROM only between 24 weeks 0/7 days’ and 31 weeks 6/7 days’ gestation, and patients at risk for preterm birth <28 weeks (due to either PPROM or PTL). Cost was estimated in US dollars, effectiveness was reported as quality-adjusted life-years (QALYs), and strategies were compared in terms of number of cases of CP prevented, number of neonatal or infant deaths, and cost-effectiveness.
Since only one of the placebo-controlled trials demonstrated statistically significant magnesium efficacy for the reduction in risk of CP, magnesium exposure was modeled with the dosing protocol used in that trial. Magnesium treatment was initiated at presentation, and given as a 6-g bolus followed by 2 g/h infusion for 12 hours or until delivery. If delivery did not occur, a patient was eligible for retreatment when preterm delivery threatened again. It was assumed that all women eligible for retreatment received magnesium again for purposes of cost estimates in the model.
Clinical outcomes considered in the models were the occurrence of mild or severe adverse maternal reaction to magnesium, birth of a neonate with moderate or severe CP diagnosed by age 2 years, neonatal or infant death by 1 year, and unaffected neonate. The model was constructed with some notable definitions and assumptions. CP was diagnosed, and its severity determined, by accepted pediatric standards. PPROM was defined by clinical criteria described by the American College of Obstetricians and Gynecologists (ACOG), and all patients with PPROM delivered preterm (<32 weeks). PTL, defined clinically by contractions that change the cervical examination presenting between 24-32 weeks, was assumed to result in preterm delivery by 32 weeks 0 days in only a proportion of cases. The proportion of patients admitted with PTL going on to deliver preterm was based on available published evidence ( Table 1 ).
| Variable | Point estimate | Range | Source |
|---|---|---|---|
| Probabilities | |||
| PTB <32 wk | 0.025 | 0.015–0.038 | |
| Proportion of PTB <28 wk | 0.250 | 0.200–0.300 | |
| PPROM <32 wk | 0.011 | 0.006–0.018 | |
| Preterm labor <32 wk | 0.020 | 0.010–0.080 | |
| Proportion of PTB after preterm labor <32 wk | 0.250 | 0.100–0.400 | |
| CP after PTB <32 wk | 0.035 | 0.020–0.061 | |
| CP after birth ≥32 wk | 0.001 | 0.0004–0.003 | |
| Death after PTB <32 wk | 0.119 | 0.033–0.171 | |
| Death after birth ≥32 wk | 0.0003 | 0.0002–0.0006 | |
| Relative risk of CP with magnesium | 0.71 | 0.50–0.82 | |
| Relative risk of death with magnesium | 1.06 | 1.00–1.15 | |
| Severe adverse magnesium reaction | 0.047 | 0.001–0.081 | |
| Mild adverse magnesium reaction | 0.696 | 0.540–0.920 | |
| Maternal life expectancy, y | 55.4 | 50.1–58.2 | |
| Neonatal life expectancy, y | 77.2 | 70.3–82.0 | |
| Neonatal life expectancy, with CP, y | 28.7 | 20.6–36.8 | |
| Utilities | |||
| Neonatal death | 0.01 | 0.001–0.02 | |
| Moderate-severe CP | 0.55 | 0.50–0.60 | |
| Normal child | 1.0 | — | |
| Costs, $US | |||
| Magnesium treatment | 124.24 | 75.00–250.00 | |
| Severe magnesium reaction | 145.40 | 80.95–287.88 | |
| Mild magnesium reaction | 2.52 | 0.16–5.04 | |
| Moderate-severe CP | 955,940 | 700,000–1,300,000 | |
| Neonatal death after PTB <32 wk | 71,001 | 452–351,237 | |
| Neonatal survival after PTB <32 wk | 45,710 | 13,560–123,207 | |
| Neonatal death after birth ≥32 wk | 67,758 | 466–283,910 |
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