One-way sensitivity analyses were performed for all variables. These analyses revealed that the base-case conclusion of the top two ranking strategies were affected only when one of three variables (the incidence of premature rupture of membranes, perinatal mortality in the setting of premature rupture of membranes, and the positive predictive value of ultrasonography for vasa previa) was altered. When the probability of preterm premature rupture of membranes was at the low end of the analyzed ranges, the preferred strategy switches from delivery at 34 weeks of gestation to delivery at 35 weeks of gestation. Figure 1 assesses the effect of varying the probability of perinatal mortality in the setting of premature rupture of membranes. There are two thresholds at which the most effective strategy is no longer delivery at 34 weeks of gestation. If the incidence of perinatal mortality in the setting of premature rupture of membranes falls to between 8.6% and 17.6%, the preferred strategy is to deliver at 35 weeks of gestation. Only when the incidence of perinatal mortality with premature rupture of membranes is less than 8.6% does expectant management until 37 weeks of gestation without amniocentesis become the most preferred strategy. When performing one-way sensitivity analysis on the positive predictive value of ultrasonography for vasa previa, the preferred strategy becomes delivery at 35 weeks of gestation at values of 55.8% or lower.
The results were also determined after incorporation of a more liberal betamethasone administration policy, in which mothers delivering in a nonemergent fashion between 36 and 38 weeks of gestation received betamethasone 2 days to 1 week before delivery. The only mothers who did not receive betamethasone were those for whom an amniocentesis was performed with mature results, those delivering emergently, or those delivered at 39 weeks of gestation. Thus, steroids were administered at 35, 36, and 37 weeks of gestation with patients delivered at 36, 37, and 38 weeks of gestation, respectively, for strategies 5, 7, and 9. For strategies 6 and 8, steroids were administered at 36 and 37 weeks of gestation, respectively, only if amniocentesis demonstrated lung immaturity, with all patients delivered 1 week later. Even when administered beyond 34 weeks, steroids were presumed to decrease the risks of respiratory distress syndrome by 50%. Incorporation of this more liberal antenatal corticosteroid policy did not result in any notable change in the quality-adjusted life-years associated with each strategy or ranking of the delivery strategies.
Two-way sensitivity analyses were performed for all combinations of variables. Analyses that led to a change in the preferred strategy were those that included one of the three variables identified in one-way sensitivity analysis as well as two other specific combinations in which varying the incidence of labor onset and bleeding, the incidence of fetal death in the setting of labor onset and bleeding, and the incidence of infant mortality affected ranking. These two specific combinations that contained variables distinct from those identified in the one-way analysis resulted in the preferred strategy switching to delivery at 35 weeks of gestation only under very select circumstances. Figure 2 illustrates a two-way sensitivity analysis examining the relationship between the probability of perinatal mortality in the setting of premature rupture of membranes and the positive predictive value of ultrasonography for vasa previa. The graph depicts that when the positive predictive value of ultrasonography for vasa previa is as low as 50%, the preferred strategy shifts to delivery at 35 weeks of gestation if the perinatal mortality risk with premature rupture of membranes is between approximately 23% and 38%. In the setting of less reliable ultrasonographic diagnoses for vasa previa and a perinatal mortality risk of less than 23%, the preferred strategy is to deliver at 37 weeks of gestation without amniocentesis. As the ultrasonographic reliability for vasa previa improves to estimates at the upper end of the range of published values, delivery at 34 weeks of gestation remains the preferred strategy except for when the incidence of perinatal mortality with premature rupture of membranes is lower than 17%.
This decision analysis indicates that, in women with ultrasonographic diagnoses of vasa previa, the preferred strategy for timing of delivery under most but not all circumstances is scheduled delivery at either 34 or 35 weeks of gestation. Additionally, the model suggests that when delivery beyond 35 weeks is the preferred option, the advantages of amniocentesis for confirmation of fetal lung maturity fail to outweigh the disadvantages. It should be noted that this analysis is concerned with assessing the optimal approach when vasa previa has been diagnosed by ultrasonography and does not address what screening approach (ie, incidental compared with risk-based compared with universal) should be used in the quest to detect vasa previa.
The infrequency of patients with vasa previa likely precludes the undertaking of a prospective trial to address the proper timing of delivery. Decision analysis may be the only tool by which this question can be systematically explored. The values in the model were ascertained through a thorough search of the literature and include utilities dealing with the explicit pediatric health states of concern.23 Moreover, the elucidation of an optimal strategy for these patients is of particular relevance in the present day, given that in vitro fertilization, which is a major risk factor for vasa previa, is becoming increasingly common.5,25–26
This decision analysis demonstrates two particularly striking findings. The first is that in this population under no clinical circumstances is there demonstrable benefit to be gained by expectant management beyond 37 weeks of gestation, and in most cases, delivery at 34 or 35 weeks of gestation is preferred. The second point is that using amniocentesis to determine fetal lung maturity is never a more effective strategy than proceeding with delivery without the amniocentesis. This finding is likely the result of a combination of reasons: the relatively high frequency of falsely immature results at these gestational ages, the hazard of the rare but catastrophic event of perinatal mortality with expectant management outweighing the short-term consequences of respiratory distress syndrome, and the inability of fetal lung maturity testing to predict long-term consequences of preterm birth. Although the literature detailing the probability of events related to emergent delivery of women with vasa previa is not definitive enough to allow the unequivocal establishment of a single ideal gestational age at which to deliver these high-risk patients, the preferred gestational age is almost certainly at or beyond 34 weeks of gestation but no later than 37 weeks.
With respect to the differences in quality-adjusted life-years among the different strategies, the top two rankings were stable under most conditions (Table 5). Although controversy exists regarding the number of quality-adjusted life-years representing a clinically significant gain, Richardson et al has argued that a gain in quality-adjusted life-years of 2 or more months should be considered an important gain.27 Applying the 2-month standard (2 months of a 12-month year, or 0.166) to the differences in the ranking strategies suggests that the marginal benefit, in the base-case, of delivering at 34 weeks of gestation compared with 35 weeks of gestation achieves a gain in quality-adjusted life-years of borderline clinical significance (just over 1 month), whereas delivering at 34 weeks of gestation compared with 36 weeks of gestation or any strategy resulting in a delivery beyond 36 weeks of gestation achieves a gain of more than 3 months.
This analysis has several limitations. First, this is not a clinical trial or study. As a result of the relatively infrequent occurrence of vasa previa, it is unlikely that a randomized clinical trial or even properly powered observational study will ever be performed to address the decision of delivery timing in this population. Moreover, it is unlikely such a study would include long-term outcomes such as cerebral palsy included in the present analysis. In this setting, use of a decision analysis is a practical alternative to help inform our decision-making. Another limitation, inherent to all decision analyses, is the choice and precision of the estimates included in the model. Due to the relative paucity of data in the literature detailing the precise sequence of events and outcomes in women with prenatally diagnosed vasa previa, the frequency of preterm labor and premature rupture of membranes were derived from national statistics, with the data extrapolated to women with prenatal diagnoses of vasa previa. Nevertheless, because of the uncertainty of the base-case estimates, extensive sensitivity analyses were performed, and although some may disagree with the baseline values chosen, most would agree that the range of values over which the sensitivity analyses were conducted were likely to contain all reasonable estimates.
As demonstrated by the decision tree model, the preferred strategy for delivery timing in patients with ultrasonographically diagnosed vasa previa in the base-case as well as under a variety of circumstances is delivery at 34 weeks of gestation. This takes into account both long- and short-term outcomes for the child. This does not imply that all women with this prenatal diagnosis should be delivered at this gestational age. As is clear from the model, there are circumstances (eg, when the probability of premature rupture of membranes or the risk of perinatal mortality in the setting of premature rupture of membranes is low or when the positive predictive value of ultrasonography for vasa previa is low) that would lead one to advocate for awaiting planned delivery up to as late as 37 weeks of gestation. Unfortunately, no validated predictive models exist that allow physicians to confidently know which patients with vasa previa are most likely to experience premature rupture of membranes or have adverse outcomes related to premature rupture of membranes. Ultimately, clinical judgement and shared decision making are crucial. This decision analysis suggests that delivery at 34 to 35 weeks gestation may balance the risk of perinatal death with the risks of infant mortality, RDS, mental retardation, and cerebral palsy related to prematurity, and supports the concept that for any given gestational age at which delivery is planned for women with vasa previa, amniocentesis for FLM does not improve outcome.
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