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Objectives: Preeclampsia (PE) is a pregnancyrelated hypertensive disorder that can lead to severe complications and adverse maternal and fetal outcomes. This study aimed to estimate the economic impact of integrating the sFlt-1/PlGF ratio into Uruguay's healthcare system as part of routine clinical practice for diagnosing., Material and Methods: A decision tree model was used to estimate the annual economic impact on the Uruguayan healthcare system for a hypothetical cohort of women with suspected PE. This included relevant costs associated with diagnosis, monitoring, and treatment from the initial presentation of suspected PE until childbirth. The study analyzed the annual costs under two scenarios: the standard of care and a scenario incorporating the sFlt-1/PlGF ratio for PE, using 2022 as the reference year. Various deterministic and probabilistic sensitivity analyses were performed., Results: The economic model estimated that the implementation of the sFlt-1/PlGF ratio could save the Uruguayan healthcare system $95,432,678 Uruguayan pesos (2,320,269 United States Dollars [USD]) annually, representing a 5 % reduction in costs compared with the standard of care. These savings were primarily due to a reduction in hospitalizations of women with suspected PE. The estimated economic impact equated to an annual net saving of approximately $10,602 Uruguayan pesos (258 USD) per patient., Conclusions: The introduction of the sFlt-1/PlGF ratio into the Uruguayan healthcare system is likely to generate savings due to the optimization of the management of hospitalizations for women with suspected preeclampsia (PE). However, the potential for savings will primarily depend on the current hospitalization rate of these women (the efficiency of managing high-risk PE pregnancies) and the length of stay for hospitalized women.

Background: Most patients with signs or symptoms (s/s) of suspected preeclampsia are not diagnosed with preeclampsia. We sought to determine and compare the prevalence of s/s, pregnancy outcomes, and costs between patients with and without diagnosed preeclampsia., Methods: This retrospective cohort study analyzed a large insurance research database. Pregnancies with s/s of preeclampsia versus a confirmed preeclampsia diagnosis were identified using International Classification of Diseases codes. S/s include hypertension, proteinuria, headache, visual symptoms, edema, abdominal pain, and nausea/vomiting. Pregnancies were classed as 1) s/s of preeclampsia without a confirmed preeclampsia diagnosis (suspicion only), 2) s/s with a confirmed diagnosis (preeclampsia with suspicion), 3) diagnosed preeclampsia without s/s recorded (preeclampsia only), and 4) no s/s, nor preeclampsia diagnosis (control)., Results: Of 1,324,424 pregnancies, 29.2 % had ≥1 documented s/s of suspected preeclampsia, and 14.2 % received a preeclampsia diagnosis. Hypertension and headache were the most common s/s, leading 20.2 % and 9.2 % pregnancies developed to preeclampsia diagnosis, respectively. Preeclampsia, with or without suspicion, had the highest rates of hypertension-related severe maternal morbidity (HR [95 % CI]: 3.0 [2.7, 3.2] and 3.6 [3.3, 4.0], respectively) versus controls. A similar trend was seen in neonatal outcomes such as preterm delivery and low birth weight. Cases in which preeclampsia was suspected but not confirmed had the highest average total maternal care costs ($6096 [95 % CI: 602, 6170] over control)., Conclusion: There is a high prevalence but poor selectivity of traditional s/s of preeclampsia, highlighting a clinical need for improved screening method and cost-effectiveness disease management., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: YJ and MG are employees of Roche Diagnostics and hold stocks. LK, JH and YX were employees of Roche Diagnostics at the time the study was conducted. S-XN has received support for travel and meeting attendance, and consulting fees, both from Roche Diagnostics. JJS has received payments from Roche Diagnostics as a consultant for the current project and as an advisory board member. SR reports serving as a consultant to Roche Diagnostics and ThermoFisher Scientific, and has received funding from Roche Diagnostics and Siemens for studies related to the use of angiogenic factors in pregnancy. AM has received statistical consulting fees from Roche Diagnostics. KK, MK and JE report no conflicts of interest. WFP reports research grants from Brainbox, and Quidel; serving as a consultant for Abbott, Brainbox, Instrument Labs, Janssen, Osler, Roche, Siemens, Spinchip, and Vifor; as well as having stock/ownership interests in AseptiScope Inc, Brainbox Inc, Braincheck Inc, Coagulo Inc, Comprehensive Research Associates LLC, Comprehensive Research Management Inc, Emergencies in Medicine LLC, Fast Inc, Forrest Devices, Ischemia DX LLC, Lucia Inc, Prevencio Inc, RCE Technologies, ROMTech, ScPharma, Trivirum Inc, and Upstream Inc. DW has received honoraria for scientific presentations from Roche Diagnostics, Inc., and Progenity, Inc., and consulting fees for advisory board attendance from Progenity, Inc., and Quidel, Inc., (Copyright © 2024 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background: We investigated the impact of the soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio to predict short-term risk of preeclampsia on clinical utility and healthcare resource utilisation using real-world data (RWD), and compared findings with health economic modelling from previous studies., Methods and Findings: This retrospective analysis compared data from the German population of a multicentre clinical study (PROGNOSIS, n = 203; sFlt-1/PlGF ratio blinded and unavailable for decision-making) with RWD from University Hospital Leipzig, Germany (n = 281; sFlt-1/PlGF ratio used to guide clinical decision-making). A subgroup of the RWD cohort with the same inclusion criteria as the PROGNOSIS trial (RWD prediction only, n = 99) was also included. sFlt-1/PlGF ratio was measured using fully automated Elecsys® sFlt-1 and PlGF immunoassays (cobas e analyser; Roche Diagnostics). A similar proportion of women in the RWD and PROGNOSIS cohorts experienced preeclampsia (14.95% vs. 13.79%; p = 0.7938); a smaller proportion of women in the RWD prediction only cohort experienced preeclampsia versus PROGNOSIS (6.06%; p = 0.0526). In women with preeclampsia, median gestational age at delivery (weeks) was comparable in the RWD and PROGNOSIS cohorts (34.0 vs. 34.3, p = 0.5895), but significantly reduced in the RWD prediction only cohort versus PROGNOSIS (27.1, p = 0.0038). sFlt-1/PlGF ratio at baseline visit was not statistically significantly different for the RWD and PROGNOSIS cohorts, irrespective of preeclampsia outcome. Hospitalisations for confirmed preeclampsia were significantly shorter in the RWD cohort versus PROGNOSIS (median 1 vs. 4 days, p = 0.0093); there was no significant difference between RWD prediction only and PROGNOSIS (3 days, p = 0.9638). All-cause hospitalisations were significantly shorter in the RWD (median 1 day; p<0.0001) and RWD prediction only (1 day; p<0.0001) cohorts versus PROGNOSIS (3 days)., Conclusions: This study supports the findings of previous studies, showing that routine clinical use of the sFlt-1/PlGF ratio may result in shorter duration of hospitalisations, with potential economic benefits., Competing Interests: AD-S has nothing to disclose; AR is an employee of Roche Diagnostics GmbH; SV declares consulting fees, lecture fees and grant support from Roche Diagnostics and Thermo Fisher; CW is an employee of Roche Diagnostics International Ltd and is shareholder in F. Hoffmann-La Roche Ltd; HS declares speaker and consulting fees from Roche Diagnostics. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Preeclampsia is defined as hypertension arising after 20 weeks of gestational age with proteinuria or other signs of end-organ damage and is an important cause of maternal and perinatal morbidity and mortality, particularly when of early onset. Although a significant amount of research has been dedicated in identifying preventive measures for preeclampsia, the incidence of the condition has been relatively unchanged in the last decades. This could be attributed to the fact that the underlying pathophysiology of preeclampsia is not entirely understood. There is increasing evidence suggesting that suboptimal trophoblastic invasion leads to an imbalance of angiogenic and antiangiogenic proteins, ultimately causing widespread inflammation and endothelial damage, increased platelet aggregation, and thrombotic events with placental infarcts. Aspirin at doses below 300 mg selectively and irreversibly inactivates the cyclooxygenase-1 enzyme, suppressing the production of prostaglandins and thromboxane and inhibiting inflammation and platelet aggregation. Such an effect has led to the hypothesis that aspirin could be useful for preventing preeclampsia. The first possible link between the use of aspirin and the prevention of preeclampsia was suggested by a case report published in 1978, followed by the first randomized controlled trial published in 1985. Since then, numerous randomized trials have been published, reporting the safety of the use of aspirin in pregnancy and the inconsistent effects of aspirin on the rates of preeclampsia. These inconsistencies, however, can be largely explained by a high degree of heterogeneity regarding the selection of trial participants, baseline risk of the included women, dosage of aspirin, gestational age of prophylaxis initiation, and preeclampsia definition. An individual patient data meta-analysis has indicated a modest 10% reduction in preeclampsia rates with the use of aspirin, but later meta-analyses of aggregate data have revealed a dose-response effect of aspirin on preeclampsia rates, which is maximized when the medication is initiated before 16 weeks of gestational age. Recently, the Aspirin for Evidence-Based Preeclampsia Prevention trial has revealed that aspirin at a daily dosage of 150 mg, initiated before 16 weeks of gestational age, and given at night to a high-risk population, identified by a combined first trimester screening test, reduces the incidence of preterm preeclampsia by 62%. A secondary analysis of the Aspirin for Evidence-Based Preeclampsia Prevention trial data also indicated a reduction in the length of stay in the neonatal intensive care unit by 68% compared with placebo, mainly because of a reduction in births before 32 weeks of gestational age with preeclampsia. The beneficial effect of aspirin has been found to be similar in subgroups according to different maternal characteristics, except for the presence of chronic hypertension, where no beneficial effect is evident. In addition, the effect size of aspirin has been found to be more pronounced in women with good compliance to treatment. In general, randomized trials are underpowered to investigate the treatment effect of aspirin on the rates of other placental-associated adverse outcomes such as fetal growth restriction and stillbirth. This article summarizes the evidence around aspirin for the prevention of preeclampsia and its complications., (Copyright © 2020. Published by Elsevier Inc.)

Objective: To evaluate the economic impact of introducing the soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PlGF) ratio test into clinical practice in Belgium for the prediction of preeclampsia (PE)., Study Design: We developed a one-year time-horizon decision tree model to evaluate the short-term costs associated with the introduction of the sFlt-1/PlGF test for guiding the management of women with suspected PE from the Belgian public healthcare payers' perspective. The model estimated the costs associated with the diagnosis and management of PE in pregnant women managed in either a test scenario, in which the sFlt-1/PlGF test is used in addition to current clinical practice, or a no test scenario, in which clinical decisions are based on current practice alone. Test characteristics were derived from PROGNOSIS, a non-interventional study in women presenting with clinical suspicion of PE. Unit costs were obtained from Belgian-specific sources. The main model outcome was the total cost per patient., Results: Introduction of the sFlt-1/PlGF ratio test is expected to result in a cost saving of €712 per patient compared with the no test scenario. These savings are generated mainly due to a reduction in unnecessary hospitalizations., Conclusions: The sFlt-1/PlGF test is projected to result in substantial cost savings for the Belgian public healthcare payers through reduction of unnecessary hospitalization of women with clinical suspicion of PE that ultimately do not develop the condition. The test also has the potential to ensure that women at high risk of developing PE are identified and appropriately managed., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Preeclampsia is a major obstetric disorder that can lead to severe maternal, fetal and infant outcomes. In women with suspected preeclampsia, measurement of the soluble fms-like tyrosine kinase-1 (sFlt1) and placental growth factor (PlGF) ratio has been shown to have a high negative predictive value (>97%). Our aim was to estimate the value to the US healthcare system of adopting this test into clinical practice., Study Design: An economic model was developed for the evaluation of suspected preeclampsia from a US payer perspective using data from a US observational study of 459 women evaluated between 23 and 34.6 weeks. Test results were not available to clinicians. The model compares two strategies for managing suspected preeclampsia: standard care versus a biomarker-informed pathway utilizing the sFlt1/PlGF ratio., Results: Utilization of the sFlt1/PlGF ratio test reduced the number of women admitted for suspected preeclampsia by 34-49%. Despite fewer admissions, a higher proportion of women admitted to hospital subsequently developed preeclampsia, and the proportion of women not admitted who would subsequently develop preeclampsia remained low (3.2%-6.7%). Cost savings arising from a reduction in admissions are estimated to be $1050 in the base case; varying the hospitalization cost ±25% would lead to savings in the range $771 to $1330 per patient at 2020 prices., Conclusion: Adopting the sFlt1/PlGF ratio test as an adjunct to clinical criteria improves the assessment of risk in women presenting with suspicion of preeclampsia and has the potential to safely reduce unnecessary admissions and save costs., (Copyright © 2021 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objectives: Pre-eclampsia (PE) causes substantial maternal and neonatal mortality and morbidity. In addition to the personal impact on women, children and their families, PE has a significant economic impact on our society. Recent research suggests that a first-trimester multivariate model is highly predictive of preterm (< 37 weeks' gestation) PE and can be combined successfully with targeted prophylaxis (low-dose aspirin), resulting in an 80% reduction in prevalence of disease. The aim of this study was to examine the potential health outcomes and cost implications following introduction of first-trimester prediction and prevention of preterm PE within a public healthcare setting, compared with usual care, and to conduct a cost-effectiveness analysis to inform health-service decisions regarding implementation of such a program., Methods: A decision-analytic model was used to compare usual care with the proposed first-trimester screening intervention within the obstetric population (n = 6822) attending two public hospitals within a metropolitan district health service in New South Wales, Australia, between January 2015 and December 2016. The model, applied from early pregnancy, included exposure to a variety of healthcare professionals and addressed type of risk assessment (usual care or first-trimester screening) and use of (compliance with) low-dose aspirin prescribed prophylactically for prevention of PE. All pathways culminated in six possible health outcomes, ranging from no PE to maternal death. Results were presented as the number of cases of PE gained/avoided and the incremental increase/decrease in economic costs arising from the intervention compared with usual care. Significant assumptions were tested in sensitivity/uncertainty analyses., Results: The intervention produced, across all gestational ages, 31 fewer cases of PE and reduced aggregate economic health-service costs by 1 431 186 Australian dollars over the 2-year period. None of the tested iterations of uncertainty analyses reported additional cases of PE or higher economic costs. The new intervention based on first-trimester screening dominated usual care., Conclusion: This cost-effectiveness analysis demonstrated a reduction in prevalence of preterm PE and substantial cost savings associated with a population-based program of first-trimester prediction and prevention of PE, and supports implementation of such a policy. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: To assess the cost-effectiveness of the Fetal Medicine Foundation (FMF) combined first-trimester pre-eclampsia (PE) screening algorithm, coupled with low-dose aspirin treatment in high-risk patients, compared to the standard of care (SOC; screening based on maternal risk factors) for nulliparous pregnancies in Belgium., Study Design: A decision analytic model was used to estimate the costs and outcomes for patients screened using the SOC and for those using the FMF screening algorithm, from the Belgian payers' perspective. Where possible, the probabilities and associated costs at each decision point were calculated based on published literature and public databases., Main Outcome Measures: Cost-effectiveness was assessed using an incremental cost-effectiveness ratio. One-way sensitivity analyses were performed to assess the impact of independent variations in each model parameter. A probabilistic sensitivity analysis was used to estimate the impact of the overall uncertainty of the model on the estimated cost-effectiveness., Results: Considering an estimated 51,309 pregnancies in nulliparous women in Belgium per year, the FMF screening algorithm resulted in fewer cases of pre-term PE compared with the SOC (479 versus 816 cases) and a cost saving of €28.67 per patient. The outcome in quality-adjusted life-years was similar for both screening approaches (FMF screening algorithm 1.8521 versus SOC 1.8518). The FMF screening algorithm was cost-saving and more effective in 99.4% of simulations., Conclusions: The FMF screening algorithm coupled with early intervention using low-dose aspirin has the potential to prevent an additional 337 cases of pre-term PE per year compared with the current SOC in this population, along with a cost saving., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: American College of Cardiology and American Heart Association (ACC/AHA) published new guidelines which lower the cut-off for hypertension. We sought to evaluate the impact of these guidelines to cost and benefit of various low-dose aspirin prophylaxis approaches., Study Design: Decision tree analysis was created using R software to evaluate four approaches to aspirin prophylaxis in the United States: no aspirin, United States Preventive Service Task Force (USPSTF) with Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) hypertension guidelines, USPSTF with ACC/AHA hypertension guidelines, as well as universal aspirin prophylaxis. This model was executed to simulate a hypothetical cohort of 4 million pregnant women in the United States., Results: The new guidelines would expand the aspirin eligibility by 8% (76,953 women) in the USPSTF guidelines. Even with this increased eligibility, the USPSTF guidelines continue to be the approach with the most cost savings ($386.5 million) when compared with universal aspirin and no aspirin prophylaxis. The new hypertension guidelines are projected to increase the cost savings of the USPSTF approach by $9.4 million., Conclusion: Despite the small change in aspirin prophylaxis, using ACC/AHA definition of hypertension still results in an annual cost-saving of $9.4 million in the United States when compared with JNC7., Competing Interests: None declared., (Thieme. All rights reserved.)

Aim: Preeclampsia is a serious complication of pregnancy that occurs in approximately 2.3% of all pregnancies in Switzerland. The aim of this study was to determine inpatient costs based on actual services in suspected and confirmed cases of preeclampsia in two Swiss hospitals (University Hospital Basel, Lucerne Cantonal Hospital) for the year 2016. Methods: Costs for patients with suspected or diagnosed preeclampsia were determined based on the databases of the finance and controlling departments. The cases were identified according to ICD-10 codes and were divided into three main categories: (1) patients with suspected preeclampsia who were discharged without delivering; (2) patients with diagnosed preeclampsia followed by vaginal induction; (3) patients with diagnosed preeclampsia followed by cesarean delivery. Results: A total of 301 cases were included in the analysis, of which 36 (12%) were hospitalized with suspected preeclampsia and discharged after a few days without delivering. Costs for cases of suspected preeclampsia were the lowest, averaging CHF 7,159/EUR 6,658 (95% CI: CHF 5,361/EUR 4,986; CHF 8,958/EUR 8,331), followed by CHF 12,124/EUR 11,275 (95% CI: CHF 10,401/EUR 9,673; CHF 13,950/EUR 12,974) for cases of preeclampsia with vaginal delivery, and CHF 19,352/EUR 17,997 (95% CI: CHF 17,342/EUR 16,128; CHF 21,507/EUR 20,002) for preeclampsia with cesarean section. Overall medical costs were CHF 4.7 (EUR 4.4) million. In all patient groups, the actual patient costs exceeded the DRG revenue that inpatient care providers receive from payers for providing services. The budget deficit was seen in both hospitals, although the magnitude of the deficit was different. Limitation and conclusion: This is the first study to analyze costs for preeclampsia in Switzerland. It would be desirable if this cost analysis was to be performed in other hospitals in order to achieve greater representativity for Switzerland.

Objective: To provide U.S. case-based preeclampsia health care cost estimates for mothers and infants from a U.S. payer perspective, with comparisons with both uncomplicated and hypertensive pregnancies., Methods: Electronic health record and billing data from a large regional integrated health care system in Pennsylvania were used to identify mother-singleton infant pairs with deliveries between 2010 and 2015. Data on clinical care and costs using actual payment amounts were compiled from 20 weeks of gestation to 6 weeks postdelivery for mothers and birth to 12 months for infants. Three defined pregnancy study cohorts, uncomplicated, hypertension and preeclampsia, were matched using a 1:1:1 ratio on the basis of maternal age, parity, body mass index, and comorbidities. Costs per pregnancy were calculated in 2015 dollars and preeclampsia incremental costs estimated by subtracting the average cost of the matched cohorts., Results: The final study population included 712 matched mother-infant pairs in each cohort. The mean combined maternal and infant medical care costs in the preeclampsia cohort of $41,790 were significantly higher than those for the uncomplicated cohort of $13,187 (P<.001) and hypertension cohort of $24,182 (P<.001), and were largely driven by differences in the infant costs. The mean infant cost in the preeclampsia cohort were $28,898, in the uncomplicated cohort $3,669 and $12,648 in the hypertension cohort (P<.001). Mothers with preeclampsia delivered 3 weeks earlier (median 36.5 weeks of gestation) than women in the uncomplicated cohort and more than 2 weeks earlier than women in the hypertension cohort. A significantly larger percentage of women with preeclampsia and their infants experienced adverse events (13.9% for mothers and 14.6% for infants) compared with unaffected women (4.1% and 0.7%) and those with hypertension (9.4% and 4.8%), respectively (P<.001)., Conclusion: The economic burden of preeclampsia health care is significant with the main cost drivers being infant health care costs associated with lower gestational age at birth and greater adverse outcomes., Funding Source: This study is funded by Progenity, Inc.

Objective: To evaluate the cost effectiveness of various preeclampsia screening and aspirin prophylaxis strategies, including a strategy based on biomarker and ultrasound measures., Methods: We designed a decision analysis to compare preeclampsia-related costs and effects of four strategies for aspirin use in pregnancy initiated before 16 weeks of gestation to prevent preeclampsia. The four strategies were: 1) no aspirin use, 2) biomarker and ultrasound measure-predicated use, 3) use based on the U.S. Preventive Services Task Force guidelines, and 4) universal aspirin use. Our outcomes were preeclampsia-related costs and number of cases per 100,000 pregnant women. Using a threshold of $90,843 per case of preeclampsia, one-way, two-way, and Monte-Carlo sensitivity analyses incorporating varying probabilities of risk reduction due to aspirin use, aspirin-related side effects, and costs were performed to identify ranges at which costs and risks of aspirin-related complications shifted the preferred strategy., Results: Compared with universal aspirin administration, the use of U.S. Preventive Services Task Force guidelines is associated with $8,011,725 higher health care costs and 346 additional cases of preeclampsia per 100,000 pregnant women; biomarker and ultrasound screening is associated with an additional $19,216,551 and 308 additional cases. Similarly, no aspirin use is associated with an increased cost of $18,750,381 and 762 additional cases. Thus, universal aspirin use dominated all three other strategies. In a Monte Carlo simulation of 10,000 pregnant women, universal aspirin was the preferred strategy in 91% of simulations. The U.S. Preventive Task Force screen was preferred in 8.5% of simulations, and biomarker and ultrasound screening and no aspirin were preferred in 0% and 0.5% of simulations, respectively., Conclusion: Over a broad range of assumptions, universal aspirin administration is associated with fewer cases of preeclampsia and fewer costs relative to no aspirin administration and aspirin administration based on serum and ultrasound measures or clinical risk factors.

In Switzerland, 2.3% of pregnant women develop preeclampsia. Quantification of the soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio has shown a diagnostic value in the second and third trimesters of pregnancy, in particular in ruling out preeclampsia within one week. We estimated the economic impact of implementing sFlt-1/PlGF ratio evaluation, in addition to the standard of care (SOC), for women with suspected preeclampsia from a Swiss healthcare system's perspective. A decision tree model was developed to estimate direct medical costs of diagnosis and management of a simulated cohort of Swiss pregnant women with suspected preeclampsia (median week of gestation: 32) until delivery. The model compared SOC vs. SOC plus sFlt-1/PlGF ratio, using clinical inputs from a large multicenter study (PROGNOSIS). Resource use data and unit costs were obtained from hospital records and public sources. The assumed cost for sFlt-1/PlGF evaluation was €141. Input parameters were validated by clinical experts in Switzerland. The model utilized a simulated cohort of 6084 pregnant women with suspected preeclampsia (representing 7% of all births in Switzerland in 2015, n = 86,919). In a SOC scenario, 36% of women were hospitalized, of whom 27% developed preeclampsia and remained hospitalized until birth. In a sFlt-1/PlGF test scenario, 76% of women had a sFlt-1/PlGF ratio of ≤38 (2% hospitalized), 11% had a sFlt-1/PlGF ratio of >38-<85 (55% hospitalized), and 13% had a sFlt-1/PlGF ratio of ≥85 (65% hospitalized). Total average costs/pregnant woman (including birth) were €10,925 vs. €10,579 (sFlt-1/PlGF), and total costs were €66,469,362 vs. €64,363,060 (sFlt-1/PlGF). Implementation of sFlt-1/PlGF evaluation would potentially achieve annual savings of €2,105,064 (€346/patient), mainly due to reduction in unnecessary hospitalization. sFlt-1/PlGF evaluation appears economically promising in predicting short-term absence of preeclampsia in Swiss practice. Improved diagnostic accuracy and reduction in unnecessary hospitalization could lead to significant cost savings in the Swiss healthcare system., Competing Interests: P. R. Blank and P. Marty are employees of Roche Diagnostics (Switzerland) AG. O. Lapaire received honoraria from Roche for lectures. O. Lapaire and M. Hodel participated in an advisory board for Roche.

Hypertensive disorders in pregnancy are a leading cause of maternal and perinatal morbidity and mortality, especially in low-resource settings. Identifying mothers and babies at greatest risk of complications would enable intervention to be targeted to those most likely to benefit from them. However, current risk prediction models have a wide range of sensitivity (42-81%) and specificity (87-92%) indicating that improvements are needed. Furthermore, no predictive models have been developed or evaluated in Zimbabwe. This proposal describes a single centre retrospective cross-sectional study which will address the need to further develop and test statistical risk prediction models for adverse maternal and neonatal outcomes in low-resource settings; this will be the first such research to be carried out in Zimbabwe. Data will be collected on maternal demographics characteristics, outcome of prior pregnancies, past medical history, symptoms and signs on admission, results of biochemical and haematological investigations. Adverse outcome will be defined as a composite of maternal morbidity and mortality and perinatal morbidity and mortality. Association between variables and outcomes will be explored using multivariable logistic regression. Critically, new risk prediction models introduced for our clinical setting may reduce avoidable maternal and neonatal morbidity and mortality at local, national, regional and international level.

The temporal trend of hospitalizations, cost, and outcomes associated with preeclampsia with severe features have been inadequately studied. The publicly available Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) database was accessed to examine the temporal trend of total number of discharges, age, death, and mean charges per admission associated with preeclampsia with severe features. Eleven-year temporal trends (2004 to 2014) of these measures were compared using linear regression and run charts using the statistical process control rule. From 2004 to 2014, the total number of discharges related to preeclampsia with severe features increased both for Hawai'i and the U.S. (United States) (Hawai'i: 104 to 231; U.S.: 35,082 to 55,235; both P <.0001). The corresponding rates of discharges per 100,000 population also both increased (Hawai'i: 8.2 to 16.3; U.S.: 12.0 to 17.3; both P <.0001). Comparing the temporal trends between Hawai'i and the U.S., Hawai'i had a significantly higher average annual increase in the rate of incidence than the national level (an annual increase rate of 9.2% in Hawai'i vs 4.2% nationally; P =.0004). The cost of hospitalization for preeclampsia with severe features also showed an increased trend for both Hawai'i and the U.S. (Hawai'i: 33.1% increase, P =.0005; U.S.: 41.1% increase, P <.0001). In the U.S., in-hospital mortality rates associated with this condition decreased from 0.09% in 2004 to 0.02% in 2014 ( P =.03). In conclusion, the number of discharges related to preeclampsia with severe features increased over an 11-year period in Hawai'i and the U.S., and the rate of increase was higher in Hawai'i than the U.S. Maternal mortality rates from this condition also declined over the study period., Competing Interests: None of the authors identify any conflicts of interest.

The study objective was to evaluate the effect of the California Maternal Quality Care Collaborative (CMQCC) initiative, as implemented in a southwestern U.S. tertiary hospital, on associated patient costs and outcomes. Using a quasi-experimental study design, we collected existing data (cost and patient outcomes) comparing two six-month period at the baseline and one-year follow-up. Following descriptive statistics, Chi-square tests and t -tests were used to compare categorical and continuous variables, respectively. One hundred and eighty-nine women met the inclusion criteria for the study (93 and 96 women in the baseline and follow-up period, respectively). There was no significant difference in maternal health outcomes between both periods. However, there was a significant difference for newborns with almost 90% (95%CI = 0.06-0.92; p  = .027) reduction in stillbirths in the follow-up period. There was also a significant reduction in the days between discharge and follow-up appointments ( p  < .01). Importantly, the initiative bears no additional financial burden on patients, as hospitalisation cost was unchanged. Impact statement What is already known on this subject? In 2013, the California Maternal Quality Care Collaborative (CMQCC) set up a task force to develop guidelines for managing patients with preeclampsia based on global best practices. A previous study showed that despite system-level implementation challenges, the initiative led to significant increase in blood pressure treatments within one-hour and reduced severe maternal morbidity. What do the results of this study add? This study follows patients from admission, beyond the one-hour post-treatment and into the post-partum phase, to understand if outcomes of the initiative extend beyond the admission. While the study findings do not show any statistically significant difference in readmission before and after the initiative, nor any marked difference in maternal outcomes, it shows a significant difference in the prevalence of stillbirths at no additional cost to the patient. What are the implications of these findings for clinical practice and/or further research? Based on these findings, there is a case for scaling-up the initiative as in addition to its evidenced improvements in maternal outcomes; it is effective in improving newborn health outcomes at no additional cost. Further research, using larger sample size and exploring different care levels would be useful to verify these findings.

Background: Peripartum cardiomyopathy (PPCM) and preeclampsia are strongly associated, yet a description of risk factors for PPCM among women with preeclampsia is currently lacking. Additionally, the effect of preeclampsia on PPCM-related outcomes is not well known., Methods: We constructed a cohort of delivery admissions from 2011 to 2014 using a large US administrative database (Marketscan). We assessed risk factors for the development of PPCM among women with preeclampsia. We compared the risks of major adverse cardiovascular events (MACE) at 6 months between PPCM with co-incident preeclampsia (pePPCM) and PPCM without preeclampsia (npePPCM)., Results: We included 1,024,035 pregnancies, of which 64,503 (6.3%) had preeclampsia. A total of 874 had PPCM (283 with preeclampsia and 591 without preeclampsia). Among women with preeclampsia, clinical risk factors for PPCM consisted in chronic kidney disease (OR 3.18, 95% CI [1.51, 6.69]), multiple pregnancy (OR 2.11, 95% CI [1.49, 2.98]), chronic hypertension (OR 1.88, 95% CI [1.43, 2.47]), advanced maternal age (OR 1.82, 95% CI [1.42, 2.33]), and type 2 diabetes (OR 1.58, 95% CI [1.00, 2.48]). Women with pePPCM had a higher risk of MACE than women with npePPCM (adjusted RR 1.29, 95% CI [1.06, 1.57]) due to increased rates of clinical heart failure and pulmonary embolism in the pePPCM group. Mortality did not differ between groups., Conclusion: Preeclamptic women with risk factors for PPCM and women with pePPCM at increased risk of MACE should be followed closely. Further studies are required to determine whether preeclampsia affects the long-term prognosis of women with PPCM., (Copyright © 2019 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: Pre-eclampsia (PE) remains a leading cause of maternal and fetal morbidity and mortality. A first-trimester screening algorithm predicting the risk of early-onset PE has been developed and validated. Early prediction coupled with initiation of aspirin at 11-13 weeks in women identified as high risk is effective at reducing the prevalence of early-onset PE. The aim of this study was to evaluate the cost-effectiveness of this first-trimester screening program coupled with early use of low-dose aspirin in women at high risk of developing early-onset PE, in comparison to current practice in Canada., Methods: A decision analysis was performed based on a theoretical population of 387 516 live births in Canada in 1 year. The clinical and financial impact of early preventative screening using the Fetal Medicine Foundation algorithm for prediction of early-onset PE coupled with early (< 16 weeks) use of low-dose aspirin in those at high risk was simulated and compared with current practice using decision-tree analysis. The probabilities at each decision point and associated costs of utilized resources were calculated based on published literature and public databases., Results: Of the theoretical 387 516 births per year, the estimated prevalence of early PE based on first-trimester screening and aspirin use was 705 vs 1801 cases based on the current practice. This was associated with an estimated total cost of C$9.52 million with the first-trimester screening program compared with C$23.91 million with current practice for the diagnosis and management of women with early-onset PE. This equals an annual cost saving to the Canadian healthcare system of approximately C$14.39 million., Conclusions: The implementation of a first-trimester screening program for PE and early intervention with aspirin in women identified as high risk for early PE has the potential to prevent a significant number of early-onset PE cases with a substantial associated cost saving to the healthcare system in Canada. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Background: The PRediction of short-term Outcome in preGNant wOmen with Suspected preeclampsIa Study (PROGNOSIS) demonstrated that a soluble fms-like tyrosine kinase 1/placental growth factor (sFlt-1/PlGF) ratio ≤ 38 ruled out the occurrence of preeclampsia in the next week with a negative predictive value of 99.3%; a ratio > 38 indicates an increased risk of developing preeclampsia in the next 4 weeks. We performed an assessment of the economic impact of the sFlt-1/PlGF ratio test for short-term prediction of preeclampsia in Germany., Methods: We adapted a cost-effectiveness model, which had been developed to estimate the incremental value of adding the sFlt-1/PlGF ratio test with a cut-off ratio of 38 to standard diagnostic procedures for guiding the management of women with suspected preeclampsia in the UK. We used the adapted model to estimate the incremental value of the sFlt-1/PlGF ratio test (cut-off 38) for guiding the management of women with suspected preeclampsia from a German Diagnosis-Related Group (DRG) payer perspective. The economic model estimated costs associated with diagnosis and management of preeclampsia in women managed in either a 'no-test' scenario in which clinical decisions are based on standard diagnostic procedures alone, or a 'test' scenario in which the sFlt-1/PlGF test is used in addition to standard diagnostic procedures. Test characteristics and rates of hospitalization were derived from patient-level data from PROGNOSIS. The main outcome measure from the economic model was the total cost per patient., Results: In the model adapted to the German DRG payer system, introduction of the sFlt-1/PlGF ratio test with a cut-off value of 38 could reduce the proportion of women hospitalized in Germany from 44.6 to 24.0%, resulting in an expected cost saving of €361 per patient., Conclusions: The sFlt-1/PlGF ratio test is likely to reduce unnecessary hospitalization of women with a low risk of developing preeclampsia, and identify those at high risk to ensure appropriate management. Even within the restrictions of the DRG system in Germany, this results in substantial cost savings for women with suspected preeclampsia.

Introduction: The replacement of 24-h urine collection by protein-creatinine ratio (PCR) for the diagnosis of preeclampsia has been recently recommended. However, the literature is conflicting and there are concerns about the impact of demographic characteristics on the performance of PCR., Material and Methods: This was an implementation audit of the introduction of PCR in a London Tertiary obstetric unit. The performance of PCR in the prediction of proteinuria ≥300 mg/day was assessed in 476 women with suspected preeclampsia who completed a 24-h urine collection and an untimed urine sample for PCR calculation. Multivariate logistic regression was used to assess the independent predictors of significant proteinuria., Results: In a pregnant population, ethnicity and PCR are the main predictors of ≥300 mg proteinuria in a 24-h urine collection. A PCR cut-off of 30 mg/mmol would have incorrectly classified as non-proteinuric, 41.4% and 22.9% of black and non-black women, respectively. Sensitivity of 100% is achieved at cut-offs of 8.67 and 20.56 mg/mmol for black and non-black women, respectively. Applying these levels as a screening tool to inform the need to perform a 24-h urine collection in 1000 women, would lead to a financial saving of €2911 in non-black women and to an additional cost of €3269 in black women., Conclusions: Our data suggest that a move from screening for proteinuria with a 24-h urine collection to screening with urine PCR is not appropriate for black populations. However, the move may lead to cost-saving if used in the white population with a PCR cut-off of 20.5., (© 2018 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objectives: Hypertensive disorders of pregnancy (HDP) represent the most common cause of maternal-fetal morbidity and mortality. Yet, the prevalence and cost of postpartum (42-day) readmission (PPR) among HDP-complicated pregnancies in the United States remains unknown. This study provides national prevalence and cost estimates of HDP, and examine factors associated with potentially preventable PPR following HDP-complicated pregnancies., Method: The 2013 and 2014 Nationwide Readmissions Databases were used to investigate HDP and PPR among delivery hospitalizations to women aged 15-49 years. PPR rates, length of stay, and costs were stratified by four HDP subtypes based on timing and severity of their condition. Survey logistic regression was employed to generate adjusted odds ratios for the association between HDP and PPR., Result: In 2013 and 2014, there were 6.3 million delivery hospitalizations; 666 506 (10.6%) were complicated by HDP. Annually, HDP was responsible for higher rates of potentially preventable PPR. Among HDP-complicated pregnancies, the 42-day all-cause PPR rate ranged from 2.5% (gestational hypertension) to 4.6% (superimposed preeclampsia/eclampsia). Compared with normotensive pregnancies, HDP resulted in an excess 404 800 hospital days and inpatient care costs of $731 million. Even after controlling for patient-level and hospital-level confounders, all hypertensive subgroups continued to have at least two-fold, statistically significant, increased odds of potentially preventable PPR., Conclusion: HDP is associated with increased risk of PPR and substantial medical costs. Preventive efforts should be made to identify women at increased risk of PPR during hospitalization so that transition care intervention can be initiated.

Adequate calcium intake during pregnancy is important in the prevention of pre-eclampsia. A substantial proportion of pregnant women do not meet the recommended daily calcium intake, even in developed countries. Nonetheless, calcium supplementation is not routinely advised to pregnant women in most countries. We aimed to predict the impact of advising pregnant women to use calcium supplements (1,000 mg/day) on the number of cases of pre-eclampsia prevented and related health care costs. By use of a decision-analytic model, we assessed the expected impact of advising calcium supplementation to either (1) all pregnant women, (2) women at high risk of developing pre-eclampsia, or (3) women with a low dietary calcium intake compared with current care. Calculations were performed for a hypothetical cohort of 100,000 pregnant women living in a high-income country, although input parameters of the model can be adjusted so as to fit other settings. The incidence of pre-eclampsia could be reduced by 25%, 8%, or 13% when advising calcium supplementation to all pregnant women, women at high risk of pre-eclampsia, or women with a low dietary calcium intake, respectively. Expected net financial benefits of the three scenarios were of €4,621,465, €2,059,165, or €2,822,115 per 100,000 pregnant women, respectively. Advising pregnant women to use calcium supplements can be expected to cause substantial reductions in the incidence of pre-eclampsia as well as related health care costs. It appears most efficient to advise calcium supplementation to all pregnant women, not subgroups only., (© 2017 John Wiley & Sons Ltd.)

To estimate the cost of preeclampsia from the national health payer's perspective using secondary data from the SCOPE study (Screening for Pregnancy End Points). SCOPE is an international observational prospective study of healthy nulliparous women with singleton pregnancies. Using data from the Irish cohort recruited between November 2008 and February 2011, all women with preeclampsia and a 10% random sample of women without preeclampsia were selected. Additional health service use data were extracted from the consenting participants' medical records for maternity services which were not included in SCOPE. Unit costs were based on estimates from 3 existing Irish studies. Costs were extrapolated to a national level using a prevalence rate of 5% to 7% among nulliparous pregnancies. Within the cohort of 1774 women, 68 developed preeclampsia (3.8%) and 171 women were randomly selected as controls. Women with preeclampsia used higher levels of maternity services. The average cost of a pregnancy complicated by preeclampsia was €5243 per case compared with €2452 per case for an uncomplicated pregnancy. The national cost of preeclampsia is between €6.5 and €9.1 million per annum based on the 5% to 7% prevalence rate. Postpartum care was the largest contributor to these costs (€4.9-€6.9 million), followed by antepartum care (€0.9-€1.3 million) and peripartum care (€0.6-€0.7 million). Women with preeclampsia generate significantly higher maternity costs than women without preeclampsia. These cost estimates will allow policy-makers to efficiently allocate resources for this pregnancy-specific condition. Moreover, these estimates are useful for future research assessing the cost-effectiveness of preeclampsia screening and treatment., (© 2017 American Heart Association, Inc.)

Background: Preeclampsia is a leading cause of maternal morbidity and mortality and adverse neonatal outcomes. Little is known about the extent of the health and cost burden of preeclampsia in the United States., Objective: This study sought to quantify the annual epidemiological and health care cost burden of preeclampsia to both mothers and infants in the United States in 2012., Study Design: We used epidemiological and econometric methods to assess the annual cost of preeclampsia in the United States using a combination of population-based and administrative data sets: the National Center for Health Statistics Vital Statistics on Births, the California Perinatal Quality Care Collaborative Databases, the US Health Care Cost and Utilization Project database, and a commercial claims data set., Results: Preeclampsia increased the probability of an adverse event from 4.6% to 10.1% for mothers and from 7.8% to 15.4% for infants while lowering gestational age by 1.7 weeks (P < .001). Overall, the total cost burden of preeclampsia during the first 12 months after birth was $1.03 billion for mothers and $1.15 billion for infants. The cost burden per infant is dependent on gestational age, ranging from $150,000 at 26 weeks gestational age to $1311 at 36 weeks gestational age., Conclusion: In 2012, the cost of preeclampsia within the first 12 months of delivery was $2.18 billion in the United States ($1.03 billion for mothers and $1.15 billion for infants), and was disproportionately borne by births of low gestational age., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Between 62 000 and 77 000 women die annually from pre-eclampsia and eclampsia. Prompt delivery, preferably by the vaginal route, is vital for good maternal and neonatal outcomes. Two low-cost interventions-low-dose oral misoprostol tablets and transcervical Foley catheterisation-are already used in low-resource settings. We aimed to compare the relative risks and benefits of these interventions., Methods: We undertook this multicentre, open-label, randomised controlled trial in two public hospitals in Nagpur, India. Women (aged ≥18 years) who were at 20 weeks' gestation or later with a live fetus and required delivery as a result of pre-eclampsia or hypertension were randomly assigned (1:1), via computer-generated block randomisation (block sizes of four, six, and eight) with concealment by use of opaque, sequentially numbered, sealed envelopes, to receive labour induction with either oral misoprostol 25 μg every 2 h (maximum of 12 doses) or a transcervical Foley catheter (silicone, size 18 F with 30 mL balloon). Randomisation was stratified by study centre. The catheter remained in place until active labour started, the catheter fell out, or 12 h had elapsed. If the catheter did not fall out within 12 h, induction continued with artificial membrane rupture and oxytocin, administered through a micro-drip gravity infusion set. Fetal monitoring was by intermittent auscultation. The primary outcome was vaginal birth within 24 h. Due to the nature of the interventions, masking of participants, study investigators, and care providers to group allocation was not possible. We analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01801410., Findings: Between Dec 20, 2013, and June 29, 2015, we randomly assigned 602 women to induction with misoprostol (n=302) or the Foley catheter (n=300; intention-to-treat population). Vaginal birth within 24 h was more common in women in the misoprostol group than in the Foley catheter group (172 [57·0%] vs 141 [47·0%] women; absolute risk difference 10·0%, 95% CI 2·0-17·9; p=0·0136). Rates of uterine hyperstimulation were low in both the misoprostol and Foley catheter groups (two [0·7%] vs one [0·3%] cases; absolute risk difference 0·3%, 95% CI -0·8 to 1·5; p=0·566) and neonatal deaths did not differ significantly between groups (six [2·0%] vs three [1·0%] neonatal deaths; 1·0, -1·04 to 2·97; p=0·322). 17 serious adverse events (3%) were reported during the study: one case of intrapartum convulsion and one case of disseminated intravascular coagulation (both in the Foley group); ten perinatal deaths, including two stillbirths (both in the Foley catheter group) and eight neonatal deaths (n=5 in the misoprostol group and n=3 in the Foley catheter group); and five of neonatal morbidity, comprising birth asphyxia (n=3), septicaemia (n=1), and neonatal convulsion (n=1)., Interpretation: Oral misoprostol was more effective than transcervical Foley catheterisation for induction of labour in women with pre-eclampsia or hypertension. Future studies are required to assess whether oxytocin augmentation following misoprostol can be replaced by regular doses of oral misoprostol tablets., Funding: Medical Research Council, Department for International Development, and Wellcome Trust Joint Global Health Trials Scheme., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: To assess the economic impact of introducing into clinical practice in the UK the soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PlGF) ratio test for guiding the management of pre-eclampsia., Methods: We used an economic model estimating the incremental value of information, from a UK National Health Service payer's perspective, generated by the sFlt-1/PlGF ratio test, compared with current diagnostic procedures, in guiding the management of women with suspected pre-eclampsia. The economic model estimated costs associated with the diagnosis and management of pre-eclampsia in pregnant women between 24 + 0 and 36 + 6 weeks' gestation, managed in either a 'test' scenario in which the sFlt-1/PlGF test is used in addition to current diagnostic procedures, or a 'no-test' scenario in which clinical decisions are based on current diagnostic procedures alone. Test characteristics and resource use were derived from PROGNOSIS, a non-interventional study in women presenting with clinical suspicion of pre-eclampsia. The main outcome measure from the economic model was the cost per patient per episode of care, from first suspicion of pre-eclampsia to birth., Results: Introduction of the sFlt-1/PlGF ratio test into clinical practice is expected to result in cost savings of £344 per patient compared with a no-test scenario. Savings are generated primarily through an improvement in diagnostic accuracy and subsequent reduction in unnecessary hospitalization., Conclusions: Introducing the sFlt-1/PlGF ratio test into clinical practice in the UK was shown to be cost-saving by reducing unnecessary hospitalization of women at low risk of developing pre-eclampsia. In addition, the test ensures that those women at higher risk are identified and managed appropriately. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2016 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To model the resource implications of placental growth factor (PlGF) testing in women with suspected pre-eclampsia prior to 35 weeks' gestation as part of a management algorithm, compared with current practice., Methods: Data on resource use from 132 women with suspected pre-eclampsia prior to 35 weeks' gestation, enrolled in a prospective observational cohort study evaluating PlGF measurement within antenatal assessment units within two UK consultant-led maternity units was extracted by case note review. A decision analytic model was developed using these data to establish the budget impact of managing women with suspected pre-eclampsia for two weeks from the date of PlGF testing, using a clinical management algorithm and reference cost tariffs. The main outcome measures of resource use (numbers of outpatient appointments, ultrasound investigations and hospital admissions) were correlated to final diagnosis and used to calculate comparative management regimes., Results: The mean cost saving associated with the PlGF test (in the PlGF plus management arm) was £35,087 (95% CI -£33,181 to -£36,992) per 1,000 women. This equated to a saving of £582 (95% CI -552 to -£613) per woman tested. In 94% of iterations, PlGF testing was associated with cost saving compared to current practice., Conclusions: This analysis suggests PlGF used as part of a clinical management algorithm in women presenting with suspected pre-eclampsia prior to 35 weeks' gestation could provide cost savings by reducing unnecessary resource use. Introduction of PlGF testing could be used to direct appropriate resource allocation and overall would be cost saving., Competing Interests: Professor Shennan received honoraria for speaking at an Alere-sponsored symposium at an international conference in 2013 and was a paid consultant for Alere, Roche, and Perkin Elmer up to 2013. All other authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Preeclampsia is a hypertensive disorder of pregnancy associated with important maternal and perinatal mortality and morbidity. Although symptomatic management has improved, there is currently no curative treatment, and only childbirth and delivery of the placenta, usually prematurely, alleviate the mother's symptoms. Placental insufficiency plays a central role in the pathophysiology of preeclampsia. Abnormal placentation during the first trimester leads to defective remodeling of the uterine vascularization. This results progressively in placental hypoperfusion, which induces trophoblast dysfunction and the release in maternal circulation of trophoblastic factors leading to an excessive inflammatory response, endothelial dysfunction and glomerular damage. Among these factors, the most important is sFlt-1, which is a soluble form of the VEGF and PlGF receptor. sFlt-1 binds to free VEGF and PlGF in the maternal circulation, thus reducing their bioavailability for their membrane receptor. The result is inhibition of the effects of VEGF and PlGF on maternal endothelial cells and podocytes. The sFlt-1/PlGF ratio reflects the circulating angiogenic balance and is correlated with severity of the disease., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: To develop a decision model to evaluate the risks, benefits, and costs of different approaches to aspirin prophylaxis for the approximately 4 million pregnant women in the United States annually., Methods: We created a decision model to evaluate four approaches to aspirin prophylaxis in the United States: no prophylaxis, prophylaxis per American College of Obstetricians and Gynecologists (the College) recommendations, prophylaxis per U.S. Preventive Services Task Force recommendations, and universal prophylaxis. We included the costs associated with aspirin, preeclampsia, preterm birth, and potential aspirin-associated adverse effects. TreeAge Pro 2011 was used to perform the analysis., Results: The estimated rate of preeclampsia would be 4.18% without prophylaxis compared with 4.17% with the College approach in which 0.35% (n=14,000) of women receive aspirin, 3.83% with the U.S. Preventive Services Task Force approach in which 23.5% (n=940,800) receive aspirin, and 3.81% with universal prophylaxis. Compared with no prophylaxis, the U.S. Preventive Services Task Force approach would save $377.4 million in direct medical care costs annually, and universal prophylaxis would save $365 million assuming 4 million births each year. The U.S. Preventive Services Task Force approach is the most cost-beneficial in 79% of probabilistic simulations. Assuming a willingness to pay of $100,000 per neonatal quality-adjusted life-year gained, the universal approach is the most cost-effective in more than 99% of simulations., Conclusion: Both the U.S. Preventive Services Task Force approach and universal prophylaxis would reduce morbidity, save lives, and lower health care costs in the United States to a much greater degree than the approach currently recommended by the College.

Background: Pre-eclampsia is a pregnancy complication affecting both mother and fetus. Although there is no proven effective method to prevent pre-eclampsia, early identification of women at risk of pre-eclampsia could enhance appropriate application of antenatal care, management and treatment. Very little is known about the cost effectiveness of these and other tests for pre-eclampsia, mainly because there is no clear treatment path. The aim of this study was to provide a comprehensive overview of the existing evidence on the health economics of screening, diagnosis and treatment options in pre-eclampsia., Methods: We searched three electronic databases (PubMed, EMBASE and the Cochrane Library) for studies on screening, diagnosis, treatment or prevention of pre-eclampsia, published between 1994 and 2014. Only full papers written in English containing complete economic assessments in pre-eclampsia were included., Results: From an initial total of 138 references, six papers fulfilled the inclusion criteria. Three studies were on the cost effectiveness of treatment of pre-eclampsia, two of which evaluated magnesium sulphate for prevention of seizures and the third evaluated the cost effectiveness of induction of labour versus expectant monitoring. The other three studies were aimed at screening and diagnosis, in combination with subsequent preventive measures. The two studies on magnesium sulphate were equivocal on the cost effectiveness in non-severe cases, and the other study suggested that induction of labour in term pre-eclampsia was more cost effective than expectant monitoring. The screening studies were quite diverse in their objectives as well as in their conclusions. One study concluded that screening is probably not worthwhile, while two other studies stated that in certain scenarios it may be cost effective to screen all pregnant women and prophylactically treat those who are found to be at high risk of developing pre-eclampsia., Discussion: This study is the first to provide a comprehensive overview on the economic aspects of pre-eclampsia in its broadest sense, ranging from screening to treatment options. The main limitation of the present study lies in the variety of topics in combination with the limited number of papers that could be included; this restricted the comparisons that could be made. In conclusion, novel biomarkers in screening for and diagnosing pre-eclampsia show promise, but their accuracy is a major driver of cost effectiveness, as is prevalence. Universal screening for pre-eclampsia, using a biomarker, will be feasible only when accuracy is significantly increased.

Background: Data on the potential influence of macroeconomic recessions on maternal diseases during pregnancy are scarce. We aimed to assess potential change in prevalence of pregnancy-induced hypertensive disorders (preeclampsia and gestational hypertension) during the first years of the major national economic recession in Iceland, which started abruptly in October 2008., Methods and Findings: Women whose pregnancies resulted in live singleton births in Iceland in 2005-2012 constituted the study population (N = 35,211). Data on pregnancy-induced hypertensive disorders were obtained from the Icelandic Medical Birth Register and use of antihypertensive drugs during pregnancy, including β-blockers and calcium channel blockers, from the Icelandic Medicines Register. With the pre-collapse period as reference, we used logistic regression analysis to assess change in pregnancy-induced hypertensive disorders and use of antihypertensives during the first four years after the economic collapse, adjusting for demographic and pregnancy characteristics, taking aggregate economic indicators into account. Compared with the pre-collapse period, we observed an increased prevalence of gestational hypertension in the first year following the economic collapse (2.4% vs. 3.9%; adjusted odds ratio [aOR] 1.47; 95 percent confidence interval [95%CI] 1.13-1.91) but not in the subsequent years. The association disappeared completely when we adjusted for aggregate unemployment rate (aOR 1.04; 95% CI 0.74-1.47). Similarly, there was an increase in prescription fills of β-blockers in the first year following the collapse (1.9% vs.3.1%; aOR 1.43; 95% CI 1.07-1.90), which disappeared after adjusting for aggregate unemployment rate (aOR 1.05; 95% CI 0.72-1.54). No changes were observed for preeclampsia or use of calcium channel blockers between the pre- and post-collapse periods., Conclusions: Our data suggest a transient increased risk of gestational hypertension and use of β-blockers among pregnant women in Iceland in the first and most severe year of the national economic recession.

Objective: To explore hospital costs by pregnant women with a history of early-onset preeclampsia or HELLP syndrome, managed according to customary, but non-standardized prenatal care, by relating maternal and child outcome to maternal health care expenditure., Study Design: This was a cohort study, in women of 18 years or older who suffered from early-onset preeclampsia or HELLP syndrome in their previous pregnancy (n=104). We retrieved data retrospectively from hospital information systems and medical records of patients who had received customary, non-standardized prenatal care between 1996 and 2012. Our analyses focused on the costs generated between the first antenatal visit at the outpatient clinic and postpartum hospital discharge. Outcome measures were hospital resource use, costs, maternal and child outcome (recurrence of preeclampsia or HELLP syndrome, incidence of eclampsia, gestational age at delivery, intrauterine fetal demise, small-for-gestational-age birth and low 5min Apgar score). We used linear regression analyses to evaluate whether maternal and child outcome and baseline characteristics correlated with hospital costs., Results: Maternal hospital costs per patient averaged € 8047. The main cost drivers were maternal admissions and outpatient visits, together accounting for 80% of total costs. Primary cost drivers were preterm birth and recurrent preeclampsia or HELLP syndrome., Conclusion: Hospital costs in the next pregnancy of formerly preeclamptic women varied widely with over 70% being medically unexplainable. The results of this study support the view that care standardization in these women can be expected to improve costs and efficacy of care without compromising outcome., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To analyse the economic and resource implications of using plasma soluble fms-like tyrosine kinase-1 s(Flt1) and placenta growth factor (PlGF) measurements in pre-eclampsia evaluation and management., Design: Retrospective cost analysis of our prospective cohort study., Setting: Boston, Massachusetts (USA)., Population: Women (n = 176) presenting to the hospital at <34 weeks of gestation for evaluation of possible pre-eclampsia during 2009-10. Cases without complete cost or outcome data (n = 9) and re-enrolments (n = 18) were excluded., Methods: Modelled comparisons between the standard approach (combination of blood pressure, urinary protein excretion, alanine aminotransferase and platelet counts) and a novel approach (ratio of plasma sFlt1 and PlGF) using actual hospital data converted to 2012 US dollars in accordance with the Centers for Medicare and Medicaid Services., Main Outcome Measures: Direct 2-week costs and resource use by groups having true or false positive and negative test results for adverse outcomes according to approach., Results: The improved specificity of the novel approach decreased the proportion of women falsely labelled as test-positive from 42.3% (34.4-50.2%) to 4.0% (0.85-7.15%) and increased the proportion correctly labelled as test-negative from 23.5% (16.7-30.3%) to 61.7% (53.9-69.5%). This could potentially reduce average per-patient costs by $1215. Substantial quantities of resources [47.2% (35.7-58.7%) of antenatal admissions and 72.5% (68.0-77.0%) of tests for fetal wellbeing] were unnecessarily used for women who were truly negative. A proportion of iatrogenic preterm deliveries among women with negative results was potentially avoidable representing further cost and resource savings., Conclusions: Clinical use of the plasma sFlt1 and PlGF ratio improves risk stratification among women presenting for pre-eclampsia evaluation and has the potential to reduce costs and resource use., (© 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.)

Severe pre-eclampsia and eclampsia are rare but serious complications of pregnancy that threaten the lives of mothers during childbirth. Evidence supports the use of magnesium sulfate (MgSO4) as the first line treatment option for severe pre-eclampsia and eclampsia. Eclampsia is the third major cause of maternal mortality in Pakistan. As in many other Low- and Middle-Income Countries (LMIC), it is suspected that MgSO4 is critically under-utilized in the country. There is however a lack of information on context-specific health system barriers that prevent optimal use of this life-saving medicine in Pakistan. Combining quantitative and qualitative methods, namely policy document review, key informant interviews, focus group discussions and direct observation at health facility, we explored context-specific health system barriers and enablers that affect access and use of MgSO4 for severe pre-eclampsia and eclampsia in Pakistan. Our study finds that while international recommendations on MgSO4 have been adequately translated in national policies in Pakistan, the gap remains in implementation of national policies into practice. Barriers to access to and effective use of MgSO4 occur at health facility level where the medicine was not available and health staff was reluctant to use it. Low price of the medicine and the small market related to its narrow indications acted as disincentives for effective marketing. Results of our survey were further discussed in a multi-stakeholder round-table meeting and an action plan for increasing access to this life-saving medicine was identified.

Background: Pre-eclampsia is a major contributor to maternal and neonatal morbidity and mortality. Our objectives in this study are to economically assess, from the payer perspective, routine screening for pre-eclampsia using placental markers -placental protein 13 and placental growth factor - and uterine artery Doppler compared with standard care., Methods: A decision model was developed, which progresses through three sequential endpoints, and compares screening with no screening: (1) Pre-eclampsia yes/no: calculation of the incremental cost of pre-eclampsia-case averted; (2) Hospital discharge: calculation of the mean accumulated costs until discharge after delivery; and (3) Offspring death: calculation of the incremental cost per quality of life-adjusted life-year gained by screening. Data used includes: (1) Obstetrical data of 14 500 births; (2) cost data from the Israeli Ministry of Health and the literature; and (3) screening performance and outcome from the literature., Results: (1) The incremental cost of pre-eclampsia-case averted is $66,949 and $24,723 when the prevalence is 1.7 and 5% respectively. (2) With test cost of $112, the total cost until discharge with/without screening is equal. With pre-eclampsia prevalence of 3%, screening is cheaper. (3) The cost per quality of life-adjusted life-year with screening is $18,919 and < $10,000 with pre-eclampsia prevalence of 1.7 and 3%, respectively., Conclusions: Screening for pre-eclampsia is cost-effective under various scenarios., (© 2012 John Wiley & Sons, Ltd.)

Objective: To assess the maternal disease burden due to pre-eclampsia/eclampsia in Ethiopia and the national health system's readiness to respond to the needs of women with pre-eclampsia/eclampsia., Methods: The national emergency obstetric and newborn care (EmONC) assessment entailed collecting information from 112 hospitals and 685 health centers in Ethiopia, focusing on their infrastructure, the services they provided, human resources, equipment and supplies, case load, and mortality due to pre-eclampsia/eclampsia., Results: Pre-eclampsia/eclampsia complicated 1.2% of all institutional deliveries. Given the low institutional delivery rate and an expected incidence of 2%-8% of all deliveries, this implies that only a small fraction (3.8%) of all women with pre-eclampsia/eclampsia received care at health facilities. 11% of all maternal deaths and 16% of direct maternal deaths were due to this obstetric complication. The cause-specific case fatality rate was high (3.6%). Availability of urine test strips, anticonvulsants, antihypertensives, and actual service provision to treat these diseases was limited, especially at health centers., Conclusion: The salutary effects of the national EmONC assessment were immediate, as evidenced by how quickly the release of the Ethiopian report led to important national efforts to improve maternal and newborn health. Expansion of health services should be augmented with periodic assessments of logistics and quality-related issues to assure functioning facilities for women accessing obstetric services., (Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

The Pregenesys Consensus Meeting held in Cambridge on 13 July 2009 was organized by the Pregenesys Consortium to review and critically discuss current knowledge regarding early markers of preeclampsia, to identify priorities and opportunities for future research, to consider issues that may need to be addressed in future recommendations and to highlight key issues in cost effectiveness and national policies concerning prediction and early screening for the risk of developing preeclampsia. This report summarizes the outcome of the Consensus Meeting and draws attention to issues for further investigation with specific regard to single versus multiple markers, early versus late risk identification, and the long-term effects on both maternal and perinatal health and the need to include these in any future cost-benefit assessment., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objective: To assess the economic consequences of labour induction compared with expectant monitoring in women with gestational hypertension or pre-eclampsia at term., Design: An economic analysis alongside the Hypertension and Pre-eclampsia Intervention Trial At Term (HYPITAT)., Setting: Obstetric departments of six university and 32 teaching and district hospitals in the Netherlands., Population: Women diagnosed with gestational hypertension or pre-eclampsia between 36(+0) and 41(+0) weeks of gestation, randomly allocated to either induction of labour or expectant monitoring., Methods: A trial-based cost-effectiveness analysis was performed from a societal perspective during a 1-year time horizon., Main Outcome Measures: One-year costs were estimated and health outcomes were expressed as the prevalence of poor maternal outcome defined as either maternal complications or progression to severe disease., Results: The average costs of induction of labour (n = 377) were €7077 versus €7908 for expectant monitoring (n = 379), with an average difference of -€831 (95% CI -€1561 to -€144). This 11% difference predominantly originated from the antepartum period: per woman costs were €1259 for induction versus €2700 for expectant monitoring. During delivery, more costs were generated following induction (€2190) compared with expectant monitoring (€1210). No substantial differences were found in the postpartum, follow-up and for non-medical costs., Conclusion: In women with gestational hypertension or mild pre-eclampsia at term, induction of labour is less costly than expectant monitoring because of differences in resource use in the antepartum period. As the trial already demonstrated that induction of labour results in less progression to severe disease without resulting in a higher caesarean section rate, both clinical and economic consequences are in favour of induction of labour in these women., Trial Registration: The trial has been registered in the clinical trial register as ISRCTN08132825., (© 2010 The Authors Journal compilation © RCOG 2010 BJOG An International Journal of Obstetrics and Gynaecology.)

Background: Preeclampsia and HELLP syndrome may have serious consequences for both mother and fetus. Women who have suffered from preeclampsia or the HELLP syndrome, have an increased risk of developing preeclampsia in a subsequent pregnancy. However, most women will develop no or only minor complications. In this study, we intend to determine cost-effectiveness of recurrence risk guided care versus care as usual in pregnant women with a history of early-onset preeclampsia., Methods/design: We developed a prediction model to estimate the individual risk of recurrence of early-onset preeclampsia and the HELLP syndrome. In a before-after study, pregnant women with preeclampsia or HELLP syndrome in their previous pregnancy receiving care as usual (before introduction of the prediction model) will be compared with women receiving recurrence risk guided care (after introduction of the prediction model). Eligible and pregnant women will be recruited at six university hospitals and seven large non-university tertiary referral hospitals in the Netherlands. The primary outcome measure is the recurrence of early-onset preeclampsia or HELLP syndrome in women allocated to the regular monitoring group. For the economic evaluation, a modelling approach will be used. Costs and effects of recurrence risk guided care with those of care as usual will be compared by means of a decision model. Two incremental cost-effectiveness ratios will be calculated: 1) cost per Quality Adjusted Life Year (mother unit of analysis) and 2) cost per live born child (child unit of analysis)., Discussion: This is, to our knowledge, the first study that evaluates prospectively the efficacy of a multivariable prediction rule for recurrent hypertensive disease in pregnancy. Results of this study could either be integrated into the current guideline on Hypertensive Disorders in Pregnancy, or be used to develop a new guideline.

Objective: To assess the utilization of health care services by pregnant women affected by preeclampsia (PE)., Design: Population-based study., Setting: Perinatal partnership hospitals in Ontario., Population: Obstetric deliveries in 2005 Canadian province of Ontario (about 95% of births)., Methods: For each PE case, four subjects without PE matched by age, parity, plurality, and hospital at childbirth were chosen as the controls. We compared the utilization of intra-partum care services and infant outcomes between the two groups. We also estimated the extra costs to the health care system in Ontario for caesarean delivery and caring of extremely low birth weight infants attributable to PE during the neonatal period and in the first 2 years of life., Main Outcome Measures: Cesarean delivery, hospital stay, extremely low birth weight infants, cost., Results: Of the 120,611 obstetric deliveries included in this analysis, 1240 (1.3%) were diagnosed with PE. Patients with PE and matched controls were similar in maternal age, parity, and other demographic characteristics. Compared with study subjects without PE, those with PE had increased uses of spinal anesthesia, maternal transfer, Cesarean delivery, labour induction, neonatal transfer, newborn resuscitation, longer hospital stay for childbirth, and higher rates of preterm births and low birth weight. The extra costs to the health care system for cesarean delivery and caring of extremely low-birth-weight infants attributable to PE during the neonatal period and in the first 2 years of life in Ontario were $0.5 millions, 3.1 millions, and $5.1 million per year, respectively, if we use the reported PE rate in this database., Conclusion: PE is associated with substantially increased costs to the health care system.

Objectives: To investigate the accuracy of predictive tests for pre-eclampsia and the effectiveness of preventative interventions for pre-eclampsia. Also to assess the cost-effectiveness of strategies (test-intervention combinations) to predict and prevent pre-eclampsia., Data Sources: Major electronic databases were searched to January 2005 at least., Review Methods: Systematic reviews were carried out for test accuracy and effectiveness. Quality assessment was carried out using standard tools. For test accuracy, meta-analyses used a bivariate approach. Effectiveness reviews were conducted under the auspices of the Cochrane Pregnancy and Childbirth Group and used standard Cochrane review methods. The economic evaluation was from an NHS perspective and used a decision tree model., Results: For the 27 tests reviewed, the quality of included studies was generally poor. Some tests appeared to have high specificity, but at the expense of compromised sensitivity. Tests that reached specificities above 90% were body mass index greater than 34, alpha-foetoprotein and uterine artery Doppler (bilateral notching). The only Doppler test with a sensitivity of over 60% was resistance index and combinations of indices. A few tests not commonly found in routine practice, such as kallikreinuria and SDS-PAGE proteinuria, seemed to offer the promise of high sensitivity, without compromising specificity, but these would require further investigation. For the 16 effectiveness reviews, the quality of included studies was variable. The largest review was of antiplatelet agents, primarily low-dose aspirin, and included 51 trials (36,500 women). This was the only review where the intervention was shown to prevent both pre-eclampsia and its consequences for the baby. Calcium supplementation also reduced the risk of pre-eclampsia, but with some uncertainty about the impact on outcomes for the baby. The only other intervention associated with a reduction in RR of pre-eclampsia was rest at home, with or without a nutritional supplement, for women with normal blood pressure. However, this review included just two small trials and its results should be interpreted with caution. The cost of most of the tests was modest, ranging from 5 pounds for blood tests such as serum uric acid to approximately 20 pounds for Doppler tests. Similarly, the cost of most interventions was also modest. In contrast, the best estimate of additional average cost associated with an average case of pre-eclampsia was high at approximately 9000 pounds. The results of the modelling revealed that prior testing with the test accuracy sensitivities and specificities identified appeared to offer little as a way of improving cost-effectiveness. Based on the evidence reviewed, none of the tests appeared sufficiently accurate to be clinically useful and the results of the model favoured no-test/treat-all strategies. Rest at home without any initial testing appeared to be the most cost-effective 'test-treatment' combination. Calcium supplementation to all women, without any initial testing, appeared to be the second most cost-effective. The economic model provided little support that any form of Doppler test has sufficiently high sensitivity and specificity to be cost-effective for the early identification of pre-eclampsia. It also suggested that the pattern of cost-effectiveness was no different in high-risk mothers than the low-risk mothers considered in the base case., Conclusions: The tests evaluated are not sufficiently accurate, in our opinion, to suggest their routine use in clinical practice. Calcium and antiplatelet agents, primarily low-dose aspirin, were the interventions shown to prevent pre-eclampsia. The most cost-effective approach to reducing pre-eclampsia is likely to be the provision of an effective, affordable and safe intervention applied to all mothers without prior testing to assess levels of risk. It is probably premature to suggest the implementation of a treat-all intervention strategy at present, however the feasibility and acceptability of this to women could be explored. Rigorous evaluation is needed of tests with modest cost whose initial assessments suggest that they may have high levels of both sensitivity and specificity. Similarly, there is a need for high-quality, adequately powered randomised controlled trials to investigate whether interventions such as advice to rest are indeed effective in reducing pre-eclampsia. In future, an economic model should be developed that considers not just pre-eclampsia, but other related outcomes, particularly those relevant to the infant such as perinatal death, preterm birth and small for gestational age. Such a modelling project should make provision for primary data collection on the safety of interventions and their associated costs.

Objective: To assess the cost-effectiveness of using magnesium sulphate for pre-eclampsia to prevent eclampsia., Design: Multinational trial-based economic evaluation., Setting: Thirty-three countries participating in the Magnesium Sulphate for Prevention of Eclampsia (Magpie) Trial., Population: Women (9996) with pre-eclampsia from the Magpie Trial., Methods: Outcome and hospital resource use data were available for the trial period from the Magpie Trial. Country-specific unit costs (U.S. dollar, year 2001) were obtained subsequently from participating hospitals by questionnaire. Cost-effectiveness was estimated for three categories of countries grouped by gross national income (GNI) into high, middle and low GNI countries using a regression model. Uncertainty was explored in sensitivity analyses., Main Outcome Measures: Eclampsia, hospital care costs and the incremental cost per case of eclampsia prevented., Results: The number of women with pre-eclampsia who needed to receive magnesium sulphate to prevent one case of eclampsia was 324 [95% confidence interval (CI) 122, infinity] in high, 184 (95% CI 91, 6798) in middle and 43 (95% CI 30, 68) in low GNI countries. The additional hospital care cost per woman receiving magnesium sulphate was $65, $13 and $11, respectively. The incremental cost of preventing one case of eclampsia was $21,202 in high, $2473 in middle and $456 in low GNI countries. Reserving treatment for severe pre-eclampsia would lower these estimates to $12,942, $1179 and $263., Conclusions: Magnesium sulphate for pre-eclampsia costs less and prevents more eclampsia in low GNI than in high GNI countries. Cost-effectiveness substantially improves if it is used only for severe pre-eclampsia, or the purchase price is reduced in low GNI countries.

Objective: The purpose of this study was to evaluate factors affecting birth charges in twin pregnancies., Study Design: Clinical and financial data were obtained on 1486 twin pregnancies delivered between 1995 to 2002 at medical centers in Maryland, Florida, Michigan, and South Carolina. Maternal and neonatal length of stay (LOS) and charges were modeled by gestational age and other risk factors using a general linear model., Results: Maternal and infant birth admission LOS and charges increased significantly with a decline in gestational age. Maternal LOS and charges were also significantly increased by cesarean delivery and preeclampsia. Newborn LOS and charges increased significantly by monochorionicity and slowed growth between 20 to 28 weeks. For mother and infants, the shortest LOS and lowest birth charges were at 37 to 38 weeks., Conclusion: These findings reflect the substantial maternal and neonatal morbidity associated with twin pregnancies, and demonstrate that 37 to 38 weeks is their optimal gestation.

Background: Day care is increasingly being used for complications of pregnancy, but there is little published evidence on its efficacy. We assessed the clinical, psychosocial, and economic effects of day care for three pregnancy complications in a randomised trial of day care versus standard care on an antenatal ward., Methods: 395 women were randomly assigned day (263) or ward (132) care in a ratio of two to one, stratified for major diagnostic categories (non-proteinuric hypertension, proteinuric hypertension, and preterm premature rupture of membranes). The research hypothesis was that for these disorders, as an alternative to admission, antenatal day care will reduce specified interventions and investigations, result in no differences in clinical outcome, lead to greater satisfaction and psychological wellbeing, and be more cost-effective. Data were collected through case-note review, self-report questionnaires (response rates 81.0% or higher) and via the hospital's financial system. Analysis was by intention to treat., Findings: All participants were included in the analyses. There were no differences between the groups in antenatal tests or investigations or intrapartum interventions. The total duration of antenatal care episodes was shorter in the day-care group than in the ward group (median 17 [IQR 5-9] vs 57 [35-123] h; p=0.001). Overall stay was also significantly shorter in the day-care group (mean 7.22 [SE 0.31] vs 8.53 [0.44]; p=0.014). The median number of care episodes was three (range one to 14) in the day-care group and two (one to nine) in the ward group (p=0.01). There were no statistically or clinically significant differences in maternal or perinatal outcomes. The day-care group reported greater satisfaction, with no evidence of unintended psychosocial sequelae. There was no significant difference in either average cost per patient or average cost per day of care., Interpretation: Since clinical outcomes and costs are similar, adoption by maternity services of a policy providing specified women with the choice between admission and day-unit care seems appropriate.

Context: Despite known adverse health effects, many women continue to smoke during pregnancy. Public attention has now focused on the economic as well as health effects of this behavior., Objective: To estimate health care costs associated with smoking-attributable cases of placenta previa, abruptio placenta, ectopic pregnancy, preterm premature rupture of the membrane (PPROM), pre-eclampsia, and spontaneous abortion., Design: Pooled odds ratios were used with data on total cases to estimate smoking-attributable cases. Estimated average costs for cases of ectopic pregnancy and spontaneous abortion were used to estimate smoking-attributable health care costs for these conditions. Incremental costs, or costs above those for a "normal" delivery, were used to estimate smoking-attributable costs of placenta previa, abruptio placenta, PPROM, and pre-eclampsia associated with delivery., Setting: National estimates for 1993., Participants: Data from the National Hospital Discharge Survey (NHDS) and claims data from a sample of large, self-insured employers across the country., Results: Smoking-attributable costs ranged from $1.3 million for PPROM to $86 million for ectopic pregnancy. Smoking during pregnancy apparently protects against pre-eclampsia and saves between $36 and $49 million, depending on smoking prevalence. Over all conditions smoking-attributable costs ranged from $135 to $167 million., Conclusions: Smoking during pregnancy is a preventable cause of higher health care costs for the conditions studied. While smoking during pregnancy was found to be protective against pre-eclampsia and, hence, saves costs, the net costs were still positive and significant. Effective smoking-cessation programs can reduce health care costs but clinicians will perhaps need to manage increased cases of pre-eclampsia in a cost-effective manner.

Objective: The purpose of this study was to investigate the safety of treating pre-eclampsia with magnesium sulfate, with clinical determinants used for drug discontinuation., Study Design: One hundred sixty-eight patients were enrolled. After delivery, women with mild pre-eclampsia received a minimum of 6 hours of intravenous magnesium sulfate, whereas women with severe pre-eclampsia received a minimum of 12 hours. Magnesium sulfate was discontinued in the absence of clinical symptoms associated with spontaneous diuresis, minimal protein by urinary dipstick, and satisfaction of predetermined blood pressure criteria., Results: Patients with mild pre-eclampsia required significantly less magnesium sulfate (mean 9.5 +/- 4.2 hours) than did those with severe pre-eclampsia alone (mean 16 +/- 5.9 hours); pre-eclampsia superimposed on chronic hypertension (mean 16 +/- 5.8 hours); or hemolysis, elevated liver enzyme, and low platelet count syndrome (mean 20 +/- 6.7 hours). With this protocol there was no eclampsia, and recovery room time was reduced by 50%., Conclusion: Individual determination of postpartum magnesium sulfate therapy for pre-eclampsia appears to be a safe approach that carries minimal risk of eclampsia.