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Obstetrics & Gynecology:
doi: 10.1097/AOG.0b013e3181f3588d
Original Research

Effectiveness of Timing Strategies for Delivery of Individuals With Placenta Previa and Accreta

Robinson, Barrett K. MD, MPH; Grobman, William A. MD, MBA

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Author Information

From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Prentice Women's Hospital, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.

Corresponding author: Barrett Robinson, MD, MPH, Northwestern University, Feinberg School, of Medicine, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, 250 E. Superior Street, Suite 05-2175, Chicago, IL 60611; e-mail: b-robinson@md.northwestern.edu.

Financial Disclosure The authors did not report any potential conflicts of interest.

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Abstract

OBJECTIVE: To compare strategies for the timing of delivery in individuals with placenta previa and ultrasonographic evidence of placenta accreta, and to determine the optimal gestational age at which to deliver individuals.

METHODS: A decision tree was designed comparing nine strategies for delivery timing in an individual with placenta previa and ultrasonographic evidence of placenta accreta. The strategies ranged from a scheduled delivery at 34, 35, 36, 37, 38, or 39 weeks of gestation to a scheduled delivery at 36, 37, or 38 weeks of gestation only after amniocentesis confirmation of fetal lung maturity. Outcomes factored into the model included maternal intensive care unit admission, perinatal mortality, infant mortality, respiratory distress syndrome, mental retardation, and cerebral palsy.

RESULTS: A scheduled delivery at 34 weeks of gestation was the preferred strategy and resulted in the highest quality-adjusted life years under the base case assumptions. Strategies awaiting confirmation of fetal lung maturity failed to result in better outcome than strategies that delivered at the corresponding gestational age without amniocentesis. After sensitivity analyses, delivery at 37 weeks of gestation without amniocentesis was the preferred strategy in limited situations, and delivery at 39 weeks of gestation was the preferred strategy only in unlikely situations.

CONCLUSION: This decision analysis suggests the preferred strategy for timing of delivery in individuals with ultrasonographic evidence of placenta previa and placenta accreta under a variety of circumstances is delivery at 34 weeks of gestation. At any given gestational age, incorporating amniocentesis for verification of fetal lung maturity does not assist in the management of such individuals.

LEVEL OF EVIDENCE: III

Placenta accreta is an obstetrical condition in which the placental villi are abnormally adhered to the uterine myometrium. Because of the life-threatening hemorrhage that often occurs with this condition in the context of delivery, the typical management includes peripartum hysterectomy. Moreover, placenta accreta is increasing in frequency,1 likely because of the increased frequency of cesarean delivery. It is well-established that cesarean delivery increases the risk of placenta previa, and these two factors are both associated with an increased risk of placenta accreta.2 Recent data have revealed an incidence of placenta accreta of 1 in 533 pregnancies.1

Antepartum recognition of placenta previa and accreta may be accomplished with ultrasonography.3 This recognition may assist in limiting maternal morbidity without increasing neonatal morbidity.4 The difficulty of performing a hysterectomy at the time of delivery, particularly in the presence of invasive placentation, may be significant and potentially lessened by advanced planning and interdisciplinary collaboration. Several studies have suggested the benefit of planned as opposed to emergent peripartum hysterectomy.4–11 In mothers with a previa and a suspected accreta who may require peripartum hysterectomy, a scheduled delivery has been associated with shorter operative times and lower frequency of transfusions, complications, and intensive care unit (ICU) admissions.

As gestational age increases, individuals with placenta previa have an increased risk of emergent bleeding. Studies have documented that approximately 90% of individuals with placenta previa had symptomatic bleeding before 37 weeks and that a majority of individuals with placenta previa required preterm delivery.12–14 Thus, the benefits of a scheduled delivery would require that delivery be planned at a preterm gestation. However, too early a delivery may expose a neonate to prematurity complications. Consequently, optimal care would strike a balance between the complications of prematurity and those related to emergent delivery. There is little evidence, however, to guide physicians in their choice of this optimal gestation, and there remains great variability with regard to delivery timing for these individuals.4,15 This decision analysis seeks to determine the optimal gestational age at which to deliver individuals with ultrasonographic evidence of both placenta previa and accreta in individuals who reach 34 weeks of gestation.

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MATERIALS AND METHODS

This study was considered exempt by the Institutional Review Board at Northwestern University (Chicago, IL). A decision analytical model was designed using DATA 3.5 software that compared nine different strategies for the timing of delivery of individuals with ultrasonographic evidence of placenta previa with accreta. The nine strategies are displayed in Table 1. Strategies 1 and 2 include delivery at 34 and 35 weeks, respectively, 1 week after previous administration of antenatal corticosteroids for neonatal benefit. The remaining strategies do not involve routine administration of antenatal corticosteroids. Strategies 3, 5, 7, and 9 are expectant management until the target gestational age of 36, 37, 38, or 39 weeks, respectively. Strategies 4, 6, and 8 involve expectant management until an amniocentesis test for fetal lung maturity at the indicated gestational age has been performed. In these strategies, in the event that testing shows lung immaturity, amniocentesis is repeated weekly and cesarean delivery is performed either when lung maturity is confirmed or at 39 weeks of gestation, whichever comes first. In all strategies, if life-threatening antepartum hemorrhage occurs, then expectant management is abandoned and an emergent cesarean delivery occurs.

Table 1
Table 1
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The base case estimates were chosen based on data in the published literature. A specific estimate for risk of ICU admission after cesarean delivery of individuals with placenta previa and accreta could not be found, but this estimate was approximated from data documenting the frequency of ICU admission associated with peripartum hysterectomy. Estimates of the weekly risk of hemorrhage necessitating delivery were derived from data documenting gestational age of delivery in three studies with more than 400 expectantly managed individuals with placenta previa.13,14,16 The risk of such bleeding increases with gestational age and this relationship was reflected in the model. A positive predictive value of 65% was used for ultrasonographic prediction of placenta accreta.3

Respiratory distress syndrome (RDS) estimates were derived from a multicenter observational study detailing neonatal morbidity among more than 20,000 neonates who were not routinely administered steroids.17 The frequency of RDS in the model was decreased by approximately half for those neonates who had received antenatal corticosteroids before delivery.18 The probability that the amniocentesis resulted in a mature value was based on the distribution of fetal lung maturity values at each gestational age19 according to the fluorescence polarization-fetal lung maturity (TDx-FLM) test, with 60 units20 used as a threshold to define maturity. When the test result was an immature value, expectant management was anticipated to result in an increase of 14 units per week.21 The risk of perinatal mortality in the setting of acute hemorrhage was derived from data documenting intrapartum and neonatal deaths in four studies containing 600 expectantly managed individuals with placenta previa. Only those perinatal deaths occurring in newborns beyond 33 weeks of gestation and heavier than 2,500 grams were included. For the purpose of this analysis, the risk of perinatal mortality in the setting of acute intrapartum hemorrhage was assumed to be at the lower end (1%) of the published range.12,14,16 The assumption was made that amniocentesis would not alter the risk of emergent bleeding or onset of labor.

The model assessed the effectiveness of each strategy with the perspective of the analysis as that of the pregnant woman and her child. The base case results were derived for a 30-year-old multiparous woman with a previous cesarean delivery who has reached 34 weeks of gestation with ultrasonographic evidence of placenta previa and accreta. The base case individual is managed as an outpatient. The individual life expectancies for both the mother and newborn were assumed to be 75 years. Quality-adjusted life years for each terminal branch were based on this anticipated life expectancy. When a range of values for a given variable was found in the literature, the ranges were evaluated using sensitivity analysis.

Both maternal and fetal outcomes were incorporated into the model. Adverse maternal outcomes included ICU admission because of major maternal morbidity. Cesarean deliveries were performed for all individuals, and those individuals without spontaneous placental separation underwent peripartum hysterectomy. Women with spontaneous placental separation were correspondingly considered to have been those with placenta previa whose ultrasound examinations had been falsely positive for accreta; these women were at markedly lower risk for ICU admission and morbidity than were those with actual accreta. Adverse perinatal outcomes considered in the model were maternal ICU admission, perinatal mortality, RDS, cerebral palsy, mental retardation, and infant mortality.

Maternal and newborn utilities for the various outcomes were determined on the basis of the literature. The maternal utility of ICU admission was based on a study that demonstrated individuals' estimations of their quality of life 3 years after their ICU stay.22 This utility therefore was assumed to represent a chronic outcome measurement that persisted for the duration of a woman's life, although this assumption was varied in the sensitivity analysis. Base case estimates for newborn utilities were based on a study detailing parental preferences for different morbidities affecting their children.23 Applied utilities for both mental retardation and cerebral palsy were those for moderate cerebral palsy and moderate mental retardation. The utilities associated with RDS were applied for shorter durations than the utilities for chronic conditions such as cerebral palsy and mental retardation. For the purpose of this analysis, cerebral palsy and mental retardation utilities were applied from 1 year of life onward. Infants who died within the first year of life were presumed to have died at 3.5 months of life.24. The estimate for the infant mortality rate was derived from literature regarding infants without congenital anomalies. Baseline risks of stillbirth were not assumed to differ outside of the setting of a serious hemorrhagic event necessitating delivery.

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RESULTS

When the baseline assumptions listed in Tables 2 through 4 are used, the strategy that provides the highest total quality-adjusted life years for the maternal-fetal dyad is delivery at 34 weeks of gestation after administration of antenatal corticosteroids (strategy 1). As illustrated in Table 5, another notable characteristic about the ranking of strategies is that delivering individuals without amniocentesis is always favored over delivery only after confirmation of fetal lung maturity at a given gestational age.

Table 2
Table 2
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Table 3
Table 3
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Table 4
Table 4
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Table 5
Table 5
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One-way sensitivity analyses were performed for all variables. These sensitivity analyses revealed that changes in three variables—the probability of antepartum hemorrhage with expectant management, the probability of perinatal mortality associated with antepartum hemorrhage requiring delivery, and the probability of ICU admission after scheduled cesarean delivery—affected the order of the strategy rankings. Figure 1 demonstrates that there are two thresholds at which the most effective strategy is no longer delivery at 34 weeks of gestation. If the risk of antepartum hemorrhage necessitating delivery is between 1% and 7% at 34 weeks of gestation, then the preferred strategy is to deliver at 37 weeks of gestation without performing amniocentesis. Only when the risk of serious hemorrhage necessitating delivery is less than 1%, a probability outside the range of published values, does expectant management until 39 weeks of gestation become the most preferred strategy. With respect to perinatal mortality associated with antepartum hemorrhage, only when the risk of perinatal mortality related to hemorrhage is 0.1% or lower is the preferred strategy delivery at 37 weeks of gestation without performing amniocentesis. Varying the probability of ICU admission after scheduled cesarean delivery resulted in the preferred strategy being either delivery at 34 weeks of gestation or delivery at 37 weeks of gestation without amniocentesis. When the risk of ICU admission after emergent cesarean delivery is 36% or higher, the preferred strategy is a scheduled delivery at 34 weeks of gestation after administration of steroids. In cases in which risk of ICU admission after scheduled cesarean delivery is higher than 36%, only in situations in which the scheduled delivery is associated with a higher maternal risk of ICU admission than emergent delivery does the preferred strategy switch in certain instances to delivery at 37 weeks of gestation with no testing for fetal lung maturity. Such a situation seems implausible.

Fig. 1
Fig. 1
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The results were also determined after incorporation of a more liberal betamethasone administration policy. Under this policy, mothers delivering in a nonemergent fashion between 34 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 amniocentesis demonstrated lung maturity, those delivering emergently, or those delivered at 39 weeks of gestation. Individuals for whom amniocentesis demonstrated fetal lung immaturity were administered betamethasone and delivered 1 week later. When administered beyond 34 weeks, steroids were still presumed to decrease the risks of RDS by 50%. Even under this alternate policy, no material differences were noted in the quality-adjusted life years or ranking of the delivery strategies from those displayed in Table 5.

Although two-way sensitivity analyses were performed for all combinations of variables, none of these analyses led to a change in the preferred strategy except those analyses that included at least one of the three variables of interest identified by the one-way sensitivity analyses. Figure 2 is a two-way sensitivity analysis examining the relationship between the probability of ICU admission after emergent delivery and the risk of hemorrhage requiring emergent delivery. The graph depicts that if an individual's risk of hemorrhage necessitating emergent delivery is approximately 11% or higher, delivery at 34 weeks of gestation after steroids is always the preferred strategy. When the risk of hemorrhage is between 2% and 8%, the preferred strategy is delivery at 37 weeks of gestation without testing for fetal lung maturity. However, when the risk of hemorrhage is less than 2%, the preferred strategy shifts to planned delivery at 39 weeks of gestation only if the risk of ICU admission after emergent cesarean delivery is higher than 1.5%.

Fig. 2
Fig. 2
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A two-way sensitivity analysis examining the relationship between probability of ICU admission after emergent delivery and probability of perinatal mortality during an acute hemorrhagic episode revealed that when the probability of perinatal mortality is 0.6% or higher, the preferred strategy is always delivery at 34 weeks of gestation after administration of steroids, irrespective of the maternal risk of ICU admission after an emergent delivery. When the risk of perinatal mortality reaches 0.1% or less, the preferred strategy switches to delivery at 37 weeks of gestation, except when the risk of maternal ICU admission after emergent cesarean delivery is between 1.5% and 8.4%.

An additional two-way sensitivity analysis examining the relationship between probability of perinatal mortality during an acute hemorrhagic event and the maternal utility assigned to ICU admission revealed that for situations in which the probability of perinatal mortality during acute hemorrhage is 0.5% or higher, the preferred strategy remains delivery at 34 weeks of gestation after administration of steroids, regardless of the maternal utility assigned to ICU admission. At lower probabilities of perinatal mortality, the preferred strategy becomes dependent on the maternal utility for ICU admission.

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DISCUSSION

This decision analysis indicates that in women with placenta previa and ultrasonographic evidence of placenta accreta, the preferred strategy for timing of delivery under a variety of (but not all) circumstances is a scheduled delivery at 34 weeks of gestation. Additionally, the model suggests that in circumstances when delivery at a given gestational age later than 34 weeks is the preferred option, the advantages of amniocentesis for confirmation of fetal lung maturity never outweigh the disadvantages.

The infrequency of individuals with placenta previa and accreta likely precludes the undertaking of a prospective trial to address the proper timing of delivery, making decision analysis potentially the only means by which to investigate the question. The values placed into the model were ascertained through a thorough search of the literature and included utilities that were contained in a recently published dataset dealing with the explicit pediatric disease states in question.23 Moreover, the elucidation of an optimal strategy for these individuals is of particular relevance today. The increasing incidence of cesarean delivery likely portends a future increase in this population of individuals, meaning that this clinical scenario may become more frequent in the coming years. Although obstetrics as a field has made significant advances with respect to individual safety, one complication that still not infrequently jeopardizes both maternal and perinatal health is peripartum hemorrhage.

This decision analysis demonstrates two particularly salient findings with respect to the timing of delivery in women with placenta previa and suspected accreta. The first point is that under most reasonable clinical circumstances, there is no benefit to be gained by expectantly managing these individuals beyond 37 weeks of gestation and, in many cases, delivery at 34 weeks of gestation is preferred. The second point is that in those individuals not delivered by 36 weeks of gestation, the practice of using amniocentesis for determination of fetal lung maturity does not improve outcome. Although the current literature detailing the probability of the events related to emergent delivery of women with placenta previa and suspected accreta is not definitive enough to allow the unequivocal establishment of a single ideal gestational age at which to deliver these individuals at high risk, the preferred gestational age is almost certainly at or beyond 34 weeks but not later than 37 weeks.

Examination of the two-way sensitivity analyses is notable for the stepwise appearance of the depiction in Figure 2. The preferred strategy progresses from a scheduled 34-week delivery under most circumstances to scheduled 37-week delivery under limited circumstances, to a 39-week delivery under unlikely circumstances. As the probabilities of adverse outcomes related to expectant management are decreased, the marginal benefits gained by delivery only 1 or 2 weeks later are outweighed by the additional benefit associated with delivery of a term neonate.

The differences in quality-adjusted life years among the various strategies certainly bear mentioning. Although a fair amount of controversy exists regarding the number of quality-adjusted life years that represent a clinically significant gain, Richardson et al36 have argued that a gain in quality-adjusted life years of 2 or more months should be considered an important gain. This is in contrast to gaining just a few days, which would more often be deemed as representing a “toss up.” Applying the standard of 2 months (2 months out of a 12-month year, or 0.166) to the differences in the ranking strategies would suggest that the marginal benefit 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 less than 2 months), 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 in quality-adjusted life years.

This analysis has several limitations. First, this is not a clinical trial. Because of the relatively infrequent occurrence of placenta accreta, it is unlikely that a prospective, randomized clinical trial will ever be performed to address the decision of delivery timing in this population of individuals. Utilization of a decision analysis is a sound alternative to help inform our decision-making, particularly when competing risks of preterm birth and the consequences of emergent delivery are weighed against one another. Another limitation, inherent to all decision analyses, is the choice and precision of the estimates included in the model. Although some probabilities were derived from large studies containing thousands of participants, other probability estimates relied on studies containing substantially smaller population sizes. Also, because of the relative paucity of data in the literature detailing all possible outcomes in women with placenta previa and ultrasonographic evidence of accreta, as well as the dearth of studies addressing emergent compared with scheduled delivery in such individuals, this analysis utilized numerous publications that reported on outcomes for women with similar morbidities, such as those having a peripartum hysterectomy. Similarly, the incidence and neonatal consequences of emergent delivery were derived from the abundance of data detailing clinical outcomes in women with placenta previa, although not always with accreta. Because of the uncertainty of the base case estimates, extensive sensitivity analyses that included varying the variable inputs over wide ranges were performed. Thus, although some may disagree with the baseline values chosen, few would disagree 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 timing of delivery in individuals with placenta previa and placenta accreta discovered by ultrasonography under a variety of circumstances is delivery at 34 weeks of gestation. This result takes into account both long-term and short-term outcomes of the mother and child. This result does not imply that all women with this condition should be delivered at this gestational age. As is also clear from the model, there are some circumstances (ie, when the probability of antepartum hemorrhage or the adverse consequences from such bleeding are lower) that would lead one to advocate for awaiting planned delivery until approximately 37 weeks of gestation. Unfortunately, there are no validated predictive models at this point in time that would allow physicians to know with confidence which individuals are most likely to bleed or have adverse outcomes related to such hemorrhagic episodes. Thus, clinical judgment to the best of one's ability will be crucial in discussions and decision-making with the individual. The results of the present decision analysis should support the concept that planned delivery at 34 weeks of gestation may be warranted under many circumstances and that there is little reason to believe that awaiting labor beyond 37 weeks of gestation is a beneficial strategy. Furthermore, this analysis should support the concept that for any given gestational age at which delivery is planned for women with a previa and suspected accreta, there seems little reason to use amniocentesis for confirmation of fetal lung maturity.

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© 2010 by The American College of Obstetricians and Gynecologists.

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