Rebecca F. Hamm, MD

Sudhof LS, Shainker SA, Einerson BD. Tranexamic acid in the routine treatment of postpartum hemorrhage in the United States: a cost-effectiveness analysis. Am J Obstet Gynecol. Published online June 18, 2019. doi.org/10.1016/j.ajog.2019.06.030.

EXPERT COMMENTARY

Postpartum hemorrhage is a leading cause of morbidity and mortality in the United States. The World Maternal Antifibrinolytic (WOMAN) trial showed that the use of TXA, an antifibrinolytic agent, for PPH decreases hemorrhage-related mortality and laparotomy. Routine use of TXA for PPH has demonstrated cost-effectiveness in low-resource countries, where hemorrhage-related mortality rates are higher than in the United States. This study aimed to determine if routine use of TXA for PPH in the United States also is cost-effective.

Details of the study

Sudhof and colleagues conducted a decision-tree analysis to compare the cost-effectiveness of 3 strategies regarding routine use of TXA for PPH in the United States: no TXA, TXA given at any time, and TXA given within 3 hours of delivery.

Health care system perspective. In the primary analysis, the 3 strategies were evaluated from the perspective of the health care system. Outcomes included cost, number of laparotomies, and maternal deaths from delivery until 6 weeks postpartum. Rates of hemorrhage and related complications, as well as cost assumptions, were derived from multiple US-based studies. The relative risk reduction in death and laparotomy with TXA in the United States was assumed to be similar to that found in the WOMAN trial (19% and 36%, respectively).

Societal perspective. In the secondary analysis, the 3 TXA strategies were evaluated from the societal perspective, comparing quality-adjusted life-years (QALYs) and cost per QALY. For both the primary and secondary analyses, sensitivity analyses were performed across a range of values for each input.

Main findings. Tranexamic acid use would be cost saving if the relative risk reduction for maternal death with TXA was greater than approximately 5%, which is significantly lower than that seen in the WOMAN trial (19%). The primary analysis demonstrated that—assuming a 3% rate of PPH—giving TXA to women with PPH would save $11.3 million, prevent 334 laparotomies, and avert 9 maternal deaths annually in the United States. This cost saving nearly tripled if TXA was administered within 3 hours of delivery, with 5 additional maternal deaths prevented.

Secondary analysis incorporating QALYs also showed TXA use to be cost-effective. These findings held through various sensitivity analyses.

Continue to: Study strengths and limitations...

Study strengths and limitations

This study is novel in its critical objective to determine the cost-effectiveness of routine use of TXA for PPH in the United States. Robust modeling using Monte Carlo estimation and a variety of sensitivity analyses add reliability to the authors’ findings.

This work is limited, however, by the assumptions put into the authors’ models. For example, outcome data regarding effectiveness of TXA was taken from the WOMAN trial, which was not performed within the United States. In addition, it is difficult to quantify in dollars an event as profound as a maternal death. The authors recognize that they likely underestimate the “cost” of a maternal death, but that this underestimation would only increase the cost-effectiveness of TXA.

Finally, it is important to take into account that such economic analyses are helpful to inform institutional guidelines and hemorrhage protocols, but that patient-specific decision-making should be individualized based on the clinical scenario at hand.

Sudhof LS, Shainker SA, Einerson BD. Tranexamic acid in the routine treatment of postpartum hemorrhage in the United States: a cost-effectiveness analysis. Am J Obstet Gynecol. Published online June 18, 2019. doi.org/10.1016/j.ajog.2019.06.030.

EXPERT COMMENTARY

Postpartum hemorrhage is a leading cause of morbidity and mortality in the United States. The World Maternal Antifibrinolytic (WOMAN) trial showed that the use of TXA, an antifibrinolytic agent, for PPH decreases hemorrhage-related mortality and laparotomy. Routine use of TXA for PPH has demonstrated cost-effectiveness in low-resource countries, where hemorrhage-related mortality rates are higher than in the United States. This study aimed to determine if routine use of TXA for PPH in the United States also is cost-effective.

Details of the study

Sudhof and colleagues conducted a decision-tree analysis to compare the cost-effectiveness of 3 strategies regarding routine use of TXA for PPH in the United States: no TXA, TXA given at any time, and TXA given within 3 hours of delivery.

Health care system perspective. In the primary analysis, the 3 strategies were evaluated from the perspective of the health care system. Outcomes included cost, number of laparotomies, and maternal deaths from delivery until 6 weeks postpartum. Rates of hemorrhage and related complications, as well as cost assumptions, were derived from multiple US-based studies. The relative risk reduction in death and laparotomy with TXA in the United States was assumed to be similar to that found in the WOMAN trial (19% and 36%, respectively).

Societal perspective. In the secondary analysis, the 3 TXA strategies were evaluated from the societal perspective, comparing quality-adjusted life-years (QALYs) and cost per QALY. For both the primary and secondary analyses, sensitivity analyses were performed across a range of values for each input.

Main findings. Tranexamic acid use would be cost saving if the relative risk reduction for maternal death with TXA was greater than approximately 5%, which is significantly lower than that seen in the WOMAN trial (19%). The primary analysis demonstrated that—assuming a 3% rate of PPH—giving TXA to women with PPH would save $11.3 million, prevent 334 laparotomies, and avert 9 maternal deaths annually in the United States. This cost saving nearly tripled if TXA was administered within 3 hours of delivery, with 5 additional maternal deaths prevented.

Secondary analysis incorporating QALYs also showed TXA use to be cost-effective. These findings held through various sensitivity analyses.

Continue to: Study strengths and limitations...

Study strengths and limitations

This study is novel in its critical objective to determine the cost-effectiveness of routine use of TXA for PPH in the United States. Robust modeling using Monte Carlo estimation and a variety of sensitivity analyses add reliability to the authors’ findings.

This work is limited, however, by the assumptions put into the authors’ models. For example, outcome data regarding effectiveness of TXA was taken from the WOMAN trial, which was not performed within the United States. In addition, it is difficult to quantify in dollars an event as profound as a maternal death. The authors recognize that they likely underestimate the “cost” of a maternal death, but that this underestimation would only increase the cost-effectiveness of TXA.

Finally, it is important to take into account that such economic analyses are helpful to inform institutional guidelines and hemorrhage protocols, but that patient-specific decision-making should be individualized based on the clinical scenario at hand.

Sudhof LS, Shainker SA, Einerson BD. Tranexamic acid in the routine treatment of postpartum hemorrhage in the United States: a cost-effectiveness analysis. Am J Obstet Gynecol. Published online June 18, 2019. doi.org/10.1016/j.ajog.2019.06.030.

EXPERT COMMENTARY

Postpartum hemorrhage is a leading cause of morbidity and mortality in the United States. The World Maternal Antifibrinolytic (WOMAN) trial showed that the use of TXA, an antifibrinolytic agent, for PPH decreases hemorrhage-related mortality and laparotomy. Routine use of TXA for PPH has demonstrated cost-effectiveness in low-resource countries, where hemorrhage-related mortality rates are higher than in the United States. This study aimed to determine if routine use of TXA for PPH in the United States also is cost-effective.

Details of the study

Sudhof and colleagues conducted a decision-tree analysis to compare the cost-effectiveness of 3 strategies regarding routine use of TXA for PPH in the United States: no TXA, TXA given at any time, and TXA given within 3 hours of delivery.

Health care system perspective. In the primary analysis, the 3 strategies were evaluated from the perspective of the health care system. Outcomes included cost, number of laparotomies, and maternal deaths from delivery until 6 weeks postpartum. Rates of hemorrhage and related complications, as well as cost assumptions, were derived from multiple US-based studies. The relative risk reduction in death and laparotomy with TXA in the United States was assumed to be similar to that found in the WOMAN trial (19% and 36%, respectively).

Societal perspective. In the secondary analysis, the 3 TXA strategies were evaluated from the societal perspective, comparing quality-adjusted life-years (QALYs) and cost per QALY. For both the primary and secondary analyses, sensitivity analyses were performed across a range of values for each input.

Main findings. Tranexamic acid use would be cost saving if the relative risk reduction for maternal death with TXA was greater than approximately 5%, which is significantly lower than that seen in the WOMAN trial (19%). The primary analysis demonstrated that—assuming a 3% rate of PPH—giving TXA to women with PPH would save $11.3 million, prevent 334 laparotomies, and avert 9 maternal deaths annually in the United States. This cost saving nearly tripled if TXA was administered within 3 hours of delivery, with 5 additional maternal deaths prevented.

Secondary analysis incorporating QALYs also showed TXA use to be cost-effective. These findings held through various sensitivity analyses.

Continue to: Study strengths and limitations...

Study strengths and limitations

This study is novel in its critical objective to determine the cost-effectiveness of routine use of TXA for PPH in the United States. Robust modeling using Monte Carlo estimation and a variety of sensitivity analyses add reliability to the authors’ findings.

This work is limited, however, by the assumptions put into the authors’ models. For example, outcome data regarding effectiveness of TXA was taken from the WOMAN trial, which was not performed within the United States. In addition, it is difficult to quantify in dollars an event as profound as a maternal death. The authors recognize that they likely underestimate the “cost” of a maternal death, but that this underestimation would only increase the cost-effectiveness of TXA.

Finally, it is important to take into account that such economic analyses are helpful to inform institutional guidelines and hemorrhage protocols, but that patient-specific decision-making should be individualized based on the clinical scenario at hand.

Zwertbroek EF, Franssen MT, Broekhuijsen K, et al; HYPITAT-II Study Group. Neonatal developmental and behavioral outcomes of immediate delivery versus expectant monitoring of mild hypertensive disorders of pregnancy: 2-year outcomes of the HYPITAT-II trial. Am J Obstet Gynecol. doi:10.1016/j.ajog.2019.03.024.

EXPERT COMMENTARY

In women with mild hypertensive disorders in the preterm period, the maternal benefits of delivery should be weighed against the consequences of preterm birth for the neonate. In a recent study, Zwertbroek and colleagues sought to evaluate the long-term neurodevelopmental effects of this decision on the offspring.

Details of the study

The authors conducted a follow-up study of the randomized, controlled Hypertension and Preeclampsia Intervention Trial At Term II (HYPITAT-II), in which 704 women diagnosed with late preterm (34–37 weeks) hypertensive disorders in pregnancy (gestational hypertension, chronic hypertension, or mild preeclampsia) were randomly assigned to immediate delivery or expectant management.

Expectant management consisted of close monitoring until 37 weeks or until an indication for delivery occurred, whichever came first. Children born to those mothers were eligible for this study (women enrolled during 2011–2015) when they reached 2 years of age; 342 children were included in this analysis. Of note, children from the expectant management group had been delivered at a more advanced gestational age (median, 37.0 vs 36.1 weeks; P<.001) than those in the immediate-delivery group.

Survey tools. Parents completed 2 response surveys, the Ages and Stages Questionnaire (ASQ) and the Child Behavior Checklist (CBCL), between 23 and 26 months’ corrected age. The ASQ is designed to detect developmental delay, while the CBCL assesses behavioral and emotional problems. The primary outcome was an abnormal result on either screen.

Results. Based on 330 returned questionnaires, the authors found more abnormal ASQ scores (45 of 162 [28%] vs 27 of 148 [18%] children; P = .045) in the immediate-delivery group versus the expectant management group, most pronounced in the fine motor domain. They found no difference in the CBCL scores. The authors concluded that immediate delivery for women with late preterm mild hypertensive disorders in pregnancy increases the risk of developmental delay in the children.

Study strengths and limitations

This study is unique as a planned follow-up to a randomized, controlled trial, allowing for 2-year outcomes to be assessed on children of enrolled women with mild hypertensive disorders in the late preterm period. The authors used validated surveys that are known to predict long-term neurodevelopmental outcomes.

Continue to: This work has several limitations...

This work has several limitations, however. Randomization was not truly maintained given the less than 50% response rate of original participants. Additionally, parents completed the surveys and provider confirmation of developmental concerns or diagnoses was not obtained. Further, assessments at 2 years of age may be too early to detect subtle differences, with evaluations at 5 years more predictive of long-term outcomes; the authors stated that these data already are being collected.

Finally, while these data importantly reinforce the conclusions of the parent HYPITAT-II trial, which support expectant management for mild hypertensive disorders in the late preterm period,¹ clinicians must always take care to individualize decisions in the face of worsening maternal disease.

Zwertbroek EF, Franssen MT, Broekhuijsen K, et al; HYPITAT-II Study Group. Neonatal developmental and behavioral outcomes of immediate delivery versus expectant monitoring of mild hypertensive disorders of pregnancy: 2-year outcomes of the HYPITAT-II trial. Am J Obstet Gynecol. doi:10.1016/j.ajog.2019.03.024.

EXPERT COMMENTARY

In women with mild hypertensive disorders in the preterm period, the maternal benefits of delivery should be weighed against the consequences of preterm birth for the neonate. In a recent study, Zwertbroek and colleagues sought to evaluate the long-term neurodevelopmental effects of this decision on the offspring.

Details of the study

The authors conducted a follow-up study of the randomized, controlled Hypertension and Preeclampsia Intervention Trial At Term II (HYPITAT-II), in which 704 women diagnosed with late preterm (34–37 weeks) hypertensive disorders in pregnancy (gestational hypertension, chronic hypertension, or mild preeclampsia) were randomly assigned to immediate delivery or expectant management.

Expectant management consisted of close monitoring until 37 weeks or until an indication for delivery occurred, whichever came first. Children born to those mothers were eligible for this study (women enrolled during 2011–2015) when they reached 2 years of age; 342 children were included in this analysis. Of note, children from the expectant management group had been delivered at a more advanced gestational age (median, 37.0 vs 36.1 weeks; P<.001) than those in the immediate-delivery group.

Survey tools. Parents completed 2 response surveys, the Ages and Stages Questionnaire (ASQ) and the Child Behavior Checklist (CBCL), between 23 and 26 months’ corrected age. The ASQ is designed to detect developmental delay, while the CBCL assesses behavioral and emotional problems. The primary outcome was an abnormal result on either screen.

Results. Based on 330 returned questionnaires, the authors found more abnormal ASQ scores (45 of 162 [28%] vs 27 of 148 [18%] children; P = .045) in the immediate-delivery group versus the expectant management group, most pronounced in the fine motor domain. They found no difference in the CBCL scores. The authors concluded that immediate delivery for women with late preterm mild hypertensive disorders in pregnancy increases the risk of developmental delay in the children.

Study strengths and limitations

This study is unique as a planned follow-up to a randomized, controlled trial, allowing for 2-year outcomes to be assessed on children of enrolled women with mild hypertensive disorders in the late preterm period. The authors used validated surveys that are known to predict long-term neurodevelopmental outcomes.

Continue to: This work has several limitations...

This work has several limitations, however. Randomization was not truly maintained given the less than 50% response rate of original participants. Additionally, parents completed the surveys and provider confirmation of developmental concerns or diagnoses was not obtained. Further, assessments at 2 years of age may be too early to detect subtle differences, with evaluations at 5 years more predictive of long-term outcomes; the authors stated that these data already are being collected.

Finally, while these data importantly reinforce the conclusions of the parent HYPITAT-II trial, which support expectant management for mild hypertensive disorders in the late preterm period,¹ clinicians must always take care to individualize decisions in the face of worsening maternal disease.

Zwertbroek EF, Franssen MT, Broekhuijsen K, et al; HYPITAT-II Study Group. Neonatal developmental and behavioral outcomes of immediate delivery versus expectant monitoring of mild hypertensive disorders of pregnancy: 2-year outcomes of the HYPITAT-II trial. Am J Obstet Gynecol. doi:10.1016/j.ajog.2019.03.024.

EXPERT COMMENTARY

In women with mild hypertensive disorders in the preterm period, the maternal benefits of delivery should be weighed against the consequences of preterm birth for the neonate. In a recent study, Zwertbroek and colleagues sought to evaluate the long-term neurodevelopmental effects of this decision on the offspring.

Details of the study

The authors conducted a follow-up study of the randomized, controlled Hypertension and Preeclampsia Intervention Trial At Term II (HYPITAT-II), in which 704 women diagnosed with late preterm (34–37 weeks) hypertensive disorders in pregnancy (gestational hypertension, chronic hypertension, or mild preeclampsia) were randomly assigned to immediate delivery or expectant management.

Expectant management consisted of close monitoring until 37 weeks or until an indication for delivery occurred, whichever came first. Children born to those mothers were eligible for this study (women enrolled during 2011–2015) when they reached 2 years of age; 342 children were included in this analysis. Of note, children from the expectant management group had been delivered at a more advanced gestational age (median, 37.0 vs 36.1 weeks; P<.001) than those in the immediate-delivery group.

Survey tools. Parents completed 2 response surveys, the Ages and Stages Questionnaire (ASQ) and the Child Behavior Checklist (CBCL), between 23 and 26 months’ corrected age. The ASQ is designed to detect developmental delay, while the CBCL assesses behavioral and emotional problems. The primary outcome was an abnormal result on either screen.

Results. Based on 330 returned questionnaires, the authors found more abnormal ASQ scores (45 of 162 [28%] vs 27 of 148 [18%] children; P = .045) in the immediate-delivery group versus the expectant management group, most pronounced in the fine motor domain. They found no difference in the CBCL scores. The authors concluded that immediate delivery for women with late preterm mild hypertensive disorders in pregnancy increases the risk of developmental delay in the children.

Study strengths and limitations

This study is unique as a planned follow-up to a randomized, controlled trial, allowing for 2-year outcomes to be assessed on children of enrolled women with mild hypertensive disorders in the late preterm period. The authors used validated surveys that are known to predict long-term neurodevelopmental outcomes.

Continue to: This work has several limitations...

This work has several limitations, however. Randomization was not truly maintained given the less than 50% response rate of original participants. Additionally, parents completed the surveys and provider confirmation of developmental concerns or diagnoses was not obtained. Further, assessments at 2 years of age may be too early to detect subtle differences, with evaluations at 5 years more predictive of long-term outcomes; the authors stated that these data already are being collected.

Finally, while these data importantly reinforce the conclusions of the parent HYPITAT-II trial, which support expectant management for mild hypertensive disorders in the late preterm period,¹ clinicians must always take care to individualize decisions in the face of worsening maternal disease.