Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss.

Miscarriage is generally defined as the loss of a pregnancy before viability. An estimated 23 million miscarriages occur every year worldwide, translating to 44 pregnancy losses each minute. The pooled risk of miscarriage is 15·3% (95% CI 12·5-18·7%) of all recognised pregnancies. The population prevalence of women who have had one miscarriage is 10·8% (10·3-11·4%), two miscarriages is 1·9% (1·8-2·1%), and three or more miscarriages is 0·7% (0·5-0·8%). Risk factors for miscarriage include very young or older female age (younger than 20 years and older than 35 years), older male age (older than 40 years), very low or very high body-mass index, Black ethnicity, previous miscarriages, smoking, alcohol, stress, working night shifts, air pollution, and exposure to pesticides. The consequences of miscarriage are both physical, such as bleeding or infection, and psychological. Psychological consequences include increases in the risk of anxiety, depression, post-traumatic stress disorder, and suicide. Miscarriage, and especially recurrent miscarriage, is also a sentinel risk marker for obstetric complications, including preterm birth, fetal growth restriction, placental abruption, and stillbirth in future pregnancies, and a predictor of longer-term health problems, such as cardiovascular disease and venous thromboembolism. The costs of miscarriage affect individuals, health-care systems, and society. The short-term national economic cost of miscarriage is estimated to be £471 million per year in the UK. As recurrent miscarriage is a sentinel marker for various obstetric risks in future pregnancies, women should receive care in preconception and obstetric clinics specialising in patients at high risk. As psychological morbidity is common after pregnancy loss, effective screening instruments and treatment options for mental health consequences of miscarriage need to be available. We recommend that miscarriage data are gathered and reported to facilitate comparison of rates among countries, to accelerate research, and to improve patient care and policy development.

The cost-effectiveness of progesterone in preventing miscarriages in women with early pregnancy bleeding: an economic evaluation based on the PRISM trial.

OBJECTIVES: To assess the cost-effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding. DESIGN: Economic evaluation alongside a large multi-centre randomised placebo-controlled trial. SETTING: Forty-eight UK NHS early pregnancy units. POPULATION: Four thousand one hundred and fifty-three women aged 16-39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac. METHODS: An incremental cost-effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages. MAIN OUTCOME MEASURES: Cost per additional live birth at ≥34 weeks of gestation. RESULTS: Progesterone intervention led to an effect difference of 0.022 (95% CI -0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI -£559 to £711) more than the mean cost in the placebo group. The incremental cost-effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014-0.096) and this was associated with a cost saving of £322 (95% CI -£1318 to £673). CONCLUSIONS: The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost-effective intervention, particularly for women with previous miscarriage(s). TWEETABLE ABSTRACT: Progesterone treatment is likely to be cost-effective in women with early pregnancy bleeding and a history of miscarriage.

Cell-free DNA for Down syndrome screening in obese women: Is it a cost-effective strategy?

OBJECTIVE: Determine cost differences between cell-free DNA (cfDNA) and serum integrated screening (INT) in obese women given the limitations of aneuploidy screening in this population. METHODS: Using a decision-analytic model, we estimated the cost-effectiveness of trisomy 21 screening in class III obese women using cfDNA compared with INT. Primary outcomes of the model were cost, number of unnecessary invasive tests, procedure-related fetal losses, and missed cases of trisomy 21. RESULTS: In base case, the mean cost of cfDNA was $498 greater than INT ($1399 vs $901). cfDNA resulted in lower probabilities of unnecessary invasive testing (2.9% vs 3.5%), procedure-related loss (0.015% vs 0.019%), and missed cases of T21 (0.00013% vs 0.02%). cfDNA cost $87 485 per unnecessary invasive test avoided, $11 million per procedure-related fetal loss avoided, and $2.2 million per missed case of T21 avoided. In sensitivity analysis, when the probability of insufficient fetal fraction is assumed to be >25%, cfDNA is both costlier than INT and results in more unnecessary invasive testing (a dominated strategy). CONCLUSION: When the probability of insufficient fetal fraction more than 25% (a maternal weight of ≥300 lbs), cfDNA is costlier and results in more unnecessary invasive testing than INT.

Septate uterus according to ESHRE/ESGE, ASRM and CUME definitions: association with infertility and miscarriage, cost and warnings for women and healthcare systems.

OBJECTIVES: To estimate the differences in frequency of diagnosis of septate uterus using three different definitions and determine whether these differences are significant in clinical practice, and to examine the association between diagnosis of septate uterus, using each of the three definitions, and infertility and/or previous miscarriage as well as the cost of allocation to surgery. METHODS: This was a secondary analysis of data from a prospective study of 261 consecutive women of reproductive age attending a private clinic focused on the diagnosis and treatment of congenital uterine malformations. Reanalysis of the datasets was performed according to three different means of defining septate uterus: following the recommendations of the American Society for Reproductive Medicine (ASRM), a 2016 update of those of the American Fertility Society from 1988 (ASRM-2016: internal fundal indentation depth ≥ 1.5 cm, angle of internal indentation < 90° and external indentation depth < 1 cm); following the recommendations of the European Society of Human Reproduction and Embryology/European Society for Gynaecological Endoscopy (ESHRE/ESGE), published in 2013 and reaffirmed in 2016 (ESHRE/ESGE-2016: internal fundal/uterine indentation depth > 50% of uterine-wall thickness and external indentation depth < 50% of uterine-wall thickness, with uterine-wall thickness measured above interostial/intercornual line); and using a definition published last year which was based on the decision made most often by a group of experts (Congenital Uterine Malformation by Experts; CUME) (CUME-2018: internal fundal indentation depth ≥ 1 cm and external fundal indentation depth < 1 cm). We compared the rate of diagnosis of septate uterus using each of these three definitions and, for each, we estimated the association between the diagnosis and infertility and/or previous miscarriage, and anticipated the costs associated with their implementation using a guesstimation method. RESULTS: Although 32.6% (85/261) of the subjects met the criteria for one of the three definitions of septate uterus, only 2.7% (7/261) of them were defined as having septate uterus according to all three definitions. We diagnosed significantly more cases of septate uterus using ESHRE/ESGE-2016 than using ASRM-2016 (31% vs 5%, relative risk (RR) = 6.7, P < 0.0001) or CUME-2018 (31% vs 12%, RR = 2.6, P < 0.0001) criteria. We also observed frequent cases that could not be classified definitively by ASRM-2016 (gray zone: neither normal/arcuate nor septate; 6.5%). There were no significant differences (P > 0.05) in the prevalence of septate uterus in women with vs those without infertility according to ASRM-2016 (5% vs 4%), ESHRE/ESGE-2016 (35% vs 28%) or CUME-2018 (11% vs 12%). Septate uterus was diagnosed significantly more frequently in women with vs those without previous miscarriage according to ASRM-2016 (11% vs 3%; P = 0.04) and CUME-2018 (22 vs 10%; P = 0.04), but not according to ESHRE/ESGE-2016 (42% vs 28%; P = 0.8) criteria. Our calculations showed that global costs to the healthcare system would be highly dependent on the criteria used in the clinical setting to define septate uterus, with the costs associated with the ESHRE/ESGE-2016 definition potentially being an extra US$ 100-200 billion over 5 years in comparison to ASRM-2016 and CUME-2018 definitions. CONCLUSIONS: The prevalence of septate uterus according to ESHRE/ESGE-2016, ASRM-2016 and CUME-2018 definitions differs considerably. An important limitation of the ASRM classification, which needs to be addressed, is the high proportion of unclassifiable cases originally named, by us, the 'gray zone'. The high rate of overdiagnosis of septate uterus according to ESHRE/ESGE-2016 may lead to unnecessary surgery and therefore unnecessary risk in these women and may impose a considerable financial burden on healthcare systems. Efforts to define clinically meaningful and universally applicable criteria for the diagnosis of septate uterus should be encouraged. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Útero septo según las definiciones de ESHRE/ESGE, ASRM y CUME: la relación con la infertilidad y el aborto espontáneo, el costo y advertencias para las mujeres y los sistemas de salud OBJETIVO: Evaluar el rendimiento de la velocidad sistólica máxima de la arteria cerebral media fetal (MCA-PSV, por sus siglas en inglés) ≥1,5 múltiplos de la mediana (MdM) para la predicción de la anemia moderada-severa en fetos sometidos a transfusión y no sometidos. MÉTODOS: Se realizó una búsqueda sistemática para identificar estudios observacionales relevantes reportados en el período 2008-2018 que evaluaron el rendimiento de la MCA-PSV, utilizando un umbral de 1,5MdM para la predicción de la anemia fetal. El diagnóstico de la anemia fetal mediante la toma de muestras de sangre fue el estándar de referencia. Se utilizaron modelos de efectos aleatorios para la elaboración de una curva jerárquica resumen de las características operativas del receptor (hSROC, por sus siglas en inglés). Se realizaron análisis de subgrupos y metarregresión, según el número de transfusiones intrauterinas previas. RESULTADOS: En el metaanálisis se incluyeron doce estudios y 696 fetos. El área bajo la curva (ABC) hSROC para la anemia moderada-severa fue del 83%. La sensibilidad y especificidad agrupadas (IC 95%) fueron del 79% (70-86%) y 73% (62-82%), respectivamente, y los cocientes de verosimilitud positivos y negativos fueron 2,94 (IC 95%: 2,13-4,00) y 0,272 (IC 95%: 0,188-0,371). Cuando solo se consideraron los fetos no sometidos a transfusión, la predicción mejoró, pues se logró un ABC del 87%, una sensibilidad del 86% (IC 95%: 75-93%) y una especificidad del 71% (IC 95%: 49-87%). Se observó una disminución en la sensibilidad de la predicción de la anemia moderada-severa mediante la MCA-PSV ≥1.5MdM (estimación, -5,5% (IC 95%: -10,7 a -0,3%), P=0,039) en función del aumento del número de transfusiones previas. CONCLUSIONES: El uso de la MCA-PSV ≥1.5MdM para la predicción de la anemia moderada-severa en fetos no sometidos a transfusión muestra una precisión moderada (86% de sensibilidad y 71% de especificidad), que disminuye con el aumento del número de transfusiones intrauterinas.

Medical versus surgical treatment of first trimester spontaneous abortion: A cost-minimization analysis.

BACKGROUND: Traditionally the gold-standard technique for the treatment of spontaneous abortion has been uterine evacuation by aspiration curettage. However, many studies have proposed medical treatment with misoprostol as an alternative to the conventional surgical treatment. The aim of this study was to apply cost minimization methods to compare the cost and effectiveness of the use of vaginal misoprostol as a medical treatment for first trimester spontaneous abortion with those of evacuation curettage as a surgical treatment. METHODOLOGY/PRINCIPAL FINDINGS: We present a longitudinal, prospective and quasi-experimental research study including a total of 547 patients diagnosed with first-trimester spontaneous abortion, in the period from January 2013 to December 2015. Patients were offered medical treatment with 800 mg vaginal misoprostol or evacuation curettage. Patients treated with misoprostol were followed-up at 7 days and a transvaginal ultrasound was performed to confirm the success of the treatment. If it failed, a second dose of 800 mg of vaginal misoprostol was prescribed and a new control ultrasound was performed. In case of failure of medical treatment after the second dose of misoprostol, evacuation curettage was indicated. The effectiveness of each of the treatment options was calculated using a decision tree. The cost minimization study was carried out by weighting each cost according to the effectiveness of each branch of the treatment. Of the 547 patients who participated in the study, 348 (64%) chose medical treatment and 199 (36%) chose surgical treatment. The overall effectiveness of medical treatment was 81% (283/348) and surgical treatment of 100%. The estimated final cost for medical treatment was € 461.92 compared to € 2038.72 for surgical treatment, which represents an estimated average saving per patient of € 1576.8. CONCLUSIONS/SIGNIFICANCE: Medical treatment with misoprostol is a cheaper alternative to surgery: in the Spanish Public Healthcare System, it is five times more inexpensive than curettage. Given its success rates higher than 80%, mild side effects, controllable with additional medication and the high degree of overall satisfaction, it should be prioritized over the evacuation curettage in patients who meet the treatment criteria.

Implementation of the findings of a national enquiry into the misdiagnosis of miscarriage in the Republic of Ireland: impact on quality of clinical care.

OBJECTIVE: To describe the findings of a national inquiry into cases of misdiagnosis of miscarriage in the Republic of Ireland and to report the results of implementation of the findings of the inquiry, including investment in new equipment and training, new national guidelines, and rigorous annual audit of early pregnancy units. DESIGN: Narrative description of the inquiry and its findings and results of a subsequent audit. SETTING: Not applicable. PATIENT(S): Women with problems of bleeding and/or pain in early pregnancy who were erroneously diagnosed as having a nonviable intrauterine pregnancy. INTERVENTION(S): After two cases of misdiagnosis of miscarriage that were widely reported in the Republic of Ireland in June 2010, a Miscarriage Misdiagnosis Review Team was commissioned by the Irish Health Service Executive (HSE) to undertake a national review of other possible cases of misdiagnosis of miscarriage. The Review Team made a series of recommendations that were subsequently implemented in full. The results of the implementation of the findings of the Review Team have been the subject of three annual audits across the country. MAIN OUTCOME MEASURE(S): The main outcome measure was the occurrence of misdiagnosis of miscarriage in the Republic of Ireland before and after implementation of the findings of the Review Team. RESULT(S): Twenty-four confirmed cases of misdiagnosis of miscarriage were identified, mostly occurring between 2005 and 2010. Analysis led to a series of recommendations by the Review Team, which were implemented in full by the HSE. Over € 3 million was provided to fund implementation; 26 high-quality gynecological ultrasound machines were purchased to reequip 19 units involved in provision of care to women with suspected miscarriage. There was further allocation of resources for new equipment and improvement in the management and staffing of early pregnancy units across Ireland, with each center now having a dedicated and properly staffed Early Pregnancy Assessment Unit. A national training program in the management of early pregnancy problems has been implemented, along with regular national meetings to discuss early pregnancy problems. National clinical guidelines on the diagnosis and management of miscarriage for implementation have been distributed to all hospitals. CONCLUSION(S): No cases of miscarriage misdiagnosis were identified in any of the three annual audits, suggesting that implementation of the findings of the review has been successful. We believe that this is the first report of national change in practice leading to improvement in clinical outcomes in the management of suspected miscarriage.

Beyond usual care: the economic consequences of expanding treatment options in early pregnancy loss.

OBJECTIVE: The objective of this study was to estimate the economic consequences of expanding options for early pregnancy loss (EPL) treatment beyond expectant management and operating room surgical evacuation (usual care). STUDY DESIGN: We constructed a decision model using a hypothetical cohort of women undergoing EPL management within a 30 day horizon. Treatment options under the usual care arm include expectant management and surgical uterine evacuation in an operating room (OR). Treatment options under the expanded care arm included all evidence-based safe and effective treatment options for EPL: expectant management, misoprostol treatment, surgical uterine evacuation in an office setting, and surgical uterine evacuation in an OR. Probabilities of entering various treatment pathways were based on previously published observational studies. RESULTS: The cost per case was US $241.29 lower for women undergoing treatment in the expanded care model as compared with the usual care model (US $1033.29 per case vs US $1274.58 per case, expanded care and usual care, respectively). The model was the most sensitive to the failure rate of the expectant management arm, the cost of the OR surgical procedure, the proportion of women undergoing an OR surgical procedure under usual care, and the additional cost per patient associated with implementing and using the expanded care model. CONCLUSION: This study demonstrates that expanding women's treatment options for EPL beyond what is typically available can result in lower direct medical expenditures.

Return on investment: a fuller assessment of the benefits and cost savings of the US publicly funded family planning program.

UNLABELLED: Policy Points: The US publicly supported family planning effort serves millions of women and men each year, and this analysis provides new estimates of its positive impact on a wide range of health outcomes and its net savings to the government. The public investment in family planning programs and providers not only helps women and couples avoid unintended pregnancy and abortion, but also helps many thousands avoid cervical cancer, HIV and other sexually transmitted infections, infertility, and preterm and low birth weight births. This investment resulted in net government savings of $13.6 billion in 2010, or $7.09 for every public dollar spent. CONTEXT: Each year the United States' publicly supported family planning program serves millions of low-income women. Although the health impact and public-sector savings associated with this program's services extend well beyond preventing unintended pregnancy, they never have been fully quantified. METHODS: Drawing on an array of survey data and published parameters, we estimated the direct national-level and state-level health benefits that accrued from providing contraceptives, tests for the human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs), Pap tests and tests for human papillomavirus (HPV), and HPV vaccinations at publicly supported family planning settings in 2010. We estimated the public cost savings attributable to these services and compared those with the cost of publicly funded family planning services in 2010 to find the net public-sector savings. We adjusted our estimates of the cost savings for unplanned births to exclude some mistimed births that would remain publicly funded if they had occurred later and to include the medical costs for births through age 5 of the child. FINDINGS: In 2010, care provided during publicly supported family planning visits averted an estimated 2.2 million unintended pregnancies, including 287,500 closely spaced and 164,190 preterm or low birth weight (LBW) births, 99,100 cases of chlamydia, 16,240 cases of gonorrhea, 410 cases of HIV, and 13,170 cases of pelvic inflammatory disease that would have led to 1,130 ectopic pregnancies and 2,210 cases of infertility. Pap and HPV tests and HPV vaccinations prevented an estimated 3,680 cases of cervical cancer and 2,110 cervical cancer deaths; HPV vaccination also prevented 9,000 cases of abnormal sequelae and precancerous lesions. Services provided at health centers supported by the Title X national family planning program accounted for more than half of these benefits. The gross public savings attributed to these services totaled approximately $15.8 billion-$15.7 billion from preventing unplanned births, $123 million from STI/HIV testing, and $23 million from Pap and HPV testing and vaccines. Subtracting $2.2 billion in program costs from gross savings resulted in net public-sector savings of $13.6 billion. CONCLUSIONS: Public expenditures for the US family planning program not only prevented unintended pregnancies but also reduced the incidence and impact of preterm and LBW births, STIs, infertility, and cervical cancer. This investment saved the government billions of public dollars, equivalent to an estimated taxpayer savings of $7.09 for every public dollar spent.

A cost-effectiveness analysis of surgical versus medical management of early pregnancy loss.

OBJECTIVE: To determine the cost-effectiveness of medical and surgical management of early pregnancy loss. DESIGN: Analyses of cost, effectiveness, and incremental cost-effectiveness ratios and utilities of a multicenter trial with 652 women with first-trimester pregnancy failure randomized to medical or surgical management. SETTING: Analysis of data from a multicenter trial. PATIENT(S): Secondary analysis of a multicenter trial. INTERVENTION(S): Cost-effectiveness analysis. MAIN OUTCOME MEASURE(S): Cost and effectiveness of competing treatment strategies. RESULT(S): Cost analysis of treatment demonstrates an increased cost of US$336 for 13% increased efficacy of surgical management. This analysis was sensitive to the probability of an extra office visit, the cost of the visit, and the probability of success. When the surgical arm is divided into outpatient manual vacuum aspiration (MVA) versus inpatient electric vacuum aspiration (EVA), there is an increased cost of $745 for EVA but a decreased cost of $202 for MVA compared with medical management. In general, MVA was found to be more cost-effective than medical management. For treatment of incomplete or inevitable abortion, medical management was found to be less costly and more efficacious. Utilities studies demonstrated that a patient would need to prefer surgery 14% less than medication for its treatment efficacy to be outweighed by the desire to avoid surgery. CONCLUSION(S): Surgical or medical management of early pregnancy failure can be cost effective, depending on the circumstances. Surgery is cost effective and more efficacious when performed in an outpatient setting. For incomplete or inevitable abortion, medical management is cost effective and more efficacious.

Manual vacuum aspiration: a safe and cost-effective substitute of electric vacuum aspiration for the surgical management of early pregnancy loss.

OBJECTIVE: To compare the efficacy, safety and cost-effectiveness of Manual vacuum aspiration (MVA) with Electrical vacuum aspiration (EVA) in the management of first trimester pregnancy loss. METHODS: A single-centre randomized controlled trial (RCT) was conducted at Maternal and Child Health Centre (MCHC), Unit-I, Pakistan Institute of Medical Sciences (PIMS), Islamabad from April 2007-Dec 2008. A total of 176 cases with early pregnancy loss at < 12 weeks gestation, with a diagnosis of anembryonic pregnancy, incomplete, missed or septic induced abortion and molar pregnancy were randomly allocated to either MVA or EVA in the operation theatre. RESULTS: A total of 176 women were included out of which 70 underwent EVA and 106 had MVA. Baseline characteristics were similar in the two groups except significantly higher gestational age and gestational sac diameter in MVA group. Majority of EVA were performed under general anaesthesia (95.7%) while majority of MVA were performed under paracervical block (60.3%). Complete evacuation was achieved in 89.6% with MVA vs 91.4% with EVA (p=0.691). MVA was superior in terms of significantly less blood loss (62.08 +/- 32.19 vs 75.71 +/- 35.53; p=0.008), shorter hospital stay (12.26 hours +/- 6.97 vs 19.54 hours +/- 7.95; p=0.000) and less hospital cost (Rs 1419.5 +/- 1337.620 vs Rs. 3222.5 +/- 1816.02; p=0.000). Post-operative pain assessment by visual analogue score (VAS) at 0 and 6 hours showed no significant difference (p=0.845 and p=0.157 respectively). The only complication was uterine perforation in 2 (2.4%) cases both belonging to EVA. CONCLUSION: MVA is a safe and effective alternative of conventional EVA. It is superior to EVA in terms of reduced cost and need for general anaesthesia and is thus useful at low resource setting with scarcity of electricity and general anaesthesia.

A cost-benefit analysis of preimplantation genetic diagnosis for carrier couples of cystic fibrosis.

OBJECTIVE: To perform a cost-benefit analysis of preimplantation genetic diagnosis (PGD) for carrier couples of cystic fibrosis (CF) compared with the alternative of natural conception (NC) followed by prenatal testing and termination of affected pregnancies. DESIGN: Cost-benefit analysis using a decision analytic model. SETTING: Outpatient reproductive health practices. PATIENT(S): A simulated cohort of 1,000 female patients. INTERVENTION(S): We calculated the net benefit of giving birth to a child as the present value of lifetime earnings minus lifetime medical costs. MAIN OUTCOME MEASURE(S): Net benefits in dollars. RESULT(S): When used for women younger than 35 years of age, the net benefit of PGD over NC was $182,000 ($715,000 vs. $532,000, respectively). For women aged 35-40 years, the net benefit of PGD over NC was $114,000 ($634,000 vs. $520,000, respectively). For women older than 40 years, however, the net benefit of PGD over NC was -$148,000 ($302,000 vs. $450,000, respectively). CONCLUSION(S): Preimplantation genetic diagnosis provides net economic benefits when used by carrier couples of CF. Although there is an upper limit of maternal age at which economic benefit can be demonstrated, carrier couples of CF should be offered PGD for prevention of an affected child.

Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling.

OBJECTIVES: To identify combinations of tests and treatments to predict and prevent spontaneous preterm birth. DATA SOURCES: Searches were run on the following databases up to September 2005 inclusive: MEDLINE, EMBASE, DARE, the Cochrane Library (CENTRAL and Cochrane Pregnancy and Childbirth Group trials register) and MEDION. We also contacted experts including the Cochrane Pregnancy and Childbirth Group and checked reference lists of review articles and papers that were eligible for inclusion. REVIEW METHODS: Two series of systematic reviews were performed: (1) accuracy of tests for the prediction of spontaneous preterm birth in asymptomatic women in early pregnancy and in women symptomatic with threatened preterm labour in later pregnancy; (2) effectiveness of interventions with potential to reduce cases of spontaneous preterm birth in asymptomatic women in early pregnancy and to reduce spontaneous preterm birth or improve neonatal outcome in women with a viable pregnancy symptomatic of threatened preterm labour. For the health economic evaluation, a model-based analysis incorporated the combined effect of tests and treatments and their cost-effectiveness. RESULTS: Of the 22 tests reviewed for accuracy, the quality of studies and accuracy of tests was generally poor. Only a few tests had LR+ > 5. In asymptomatic women these were ultrasonographic cervical length measurement and cervicovaginal prolactin and fetal fibronectin screening for predicting spontaneous preterm birth before 34 weeks. In this group, tests with LR- < 0.2 were detection of uterine contraction by home uterine monitoring and amniotic fluid C-reactive protein (CRP) measurement. In symptomatic women with threatened preterm labour, tests with LR+ > 5 were absence of fetal breathing movements, cervical length and funnelling, amniotic fluid interleukin-6 (IL-6), serum CRP for predicting birth within 2-7 days of testing, and matrix metalloprotease-9, amniotic fluid IL-6, cervicovaginal fetal fibronectin and cervicovaginal human chorionic gonadotrophin (hCG) for predicting birth before 34 or 37 weeks. In this group, tests with LR- < 0.2 included measurement of cervicovaginal IL-8, cervicovaginal hCG, cervical length measurement, absence of fetal breathing movement, amniotic fluid IL-6 and serum CRP, for predicting birth within 2-7 days of testing, and cervicovaginal fetal fibronectin and amniotic fluid IL-6 for predicting birth before 34 or 37 weeks. The overall quality of the trials included in the 40 interventional topics reviewed for effectiveness was also poor. Antibiotic treatment was generally not beneficial but when used to treat bacterial vaginosis in women with intermediate flora it significantly reduced the incidence of spontaneous preterm birth. Smoking cessation programmes, progesterone, periodontal therapy and fish oil appeared promising as preventative interventions in asymptomatic women. Non-steroidal anti-inflammatory agents were the most effective tocolytic agent for reducing spontaneous preterm birth and prolonging pregnancy in symptomatic women. Antenatal corticosteroids had a beneficial effect on the incidence of respiratory distress syndrome and the risk of intraventricular haemorrhage (28-34 weeks), but the effects of repeat courses were unclear. For asymptomatic women, costs ranged from 1.08 pounds for vitamin C to 1219 pounds for cervical cerclage, whereas costs for symptomatic women were more significant and varied little, ranging from 1645 pounds for nitric oxide donors to 2555 pounds for terbutaline; this was because the cost of hospitalisation was included. The best estimate of additional average cost associated with a case of spontaneous preterm birth was approximately 15,688 pounds for up to 34 weeks and 12,104 pounds for up to 37 weeks. Among symptomatic women there was insufficient evidence to draw firm conclusions for preventing birth at 34 weeks. Hydration given to women testing positive for amniotic fluid IL-6 was the most cost-effective test-treatment combination. Indomethacin given to all women without any initial testing was the most cost-effective option for preventing birth before 37 weeks among symptomatic women. For a symptomatic woman, the most cost-effective test-treatment combination for postponing delivery by at least 48 h was the cervical length (15 mm) measurement test with treatment with indomethacin for all those testing positive. This combination was also the most cost-effective option for postponing delivery by at least 7 days. Antibiotic treatment for asymptomatic bacteriuria of all women without any initial testing was the most cost-effective option for preventing birth before 37 weeks among asymptomatic women but this does not take into account the potential side effects of antibiotics or issues such as increased resistance. CONCLUSIONS: For primary prevention, an effective, affordable and safe intervention applied to all mothers without preceding testing is likely to be the most cost-effective approach in asymptomatic women in early pregnancy. For secondary prevention among women at risk of preterm labour in later pregnancy, a management strategy based on the results of testing is likely to be more cost-effective. Implementation of a treat-all strategy with simple interventions, such as fish oils, would be premature for asymptomatic women. Universal provision of high-quality ultrasound machines in labour wards is more strongly indicated for predicting spontaneous preterm birth among symptomatic women than direct management, although staffing issues and the feasibility and acceptability to mothers and health providers of such strategies need to be explored. Further research should include investigations of low-cost and effective tests and treatments to reduce and delay spontaneous preterm birth and reduce the risk of perinatal mortality arising from preterm birth.

Cost utility of prenatal diagnosis and the risk-based threshold.

BACKGROUND: Prenatal testing guidelines recommend offering amniocentesis or chorionic villus sampling to women aged 35 years or older, or who have been found by screening to be at a similarly high risk of giving birth to an infant with Down's syndrome or another chromosomal abnormality. This threshold was chosen, in part, because 35 was the approximate age at which amniocentesis was cost beneficial when testing guidelines were developed in the USA in the 1970s. We aimed to assess the economic validity of thresholds based on age or risk for offering invasive prenatal diagnosis. METHODS: We did a cost-utility analysis of chorionic villus sampling and amniocentesis versus no invasive testing using data from randomised trials, case registries, and a utility assessment of 534 diverse pregnant women aged 16-47 years. FINDINGS: In the USA, compared with no diagnostic testing, amniocentesis costs less than US15000 dollars per quality-adjusted life year gained for women of all ages and risk levels. The results do not depend on maternal age or risk of Down's syndrome-affected birth. The cost-utility ratio for any individual woman depends on her preferences for reassurance about the chromosomal status of her fetus, and, to a lesser extent, for miscarriage. INTERPRETATION: Prenatal diagnostic testing can be cost effective at any age or risk level. Current guidelines should be changed to offer testing to all pregnant women, not just those whose risk of carrying an affected fetus exceeds a specified threshold.

Frequency of etiological factors and cost effectiveness of the work up for patients with history of recurrent pregnancy loss.

OBJECTIVE: To assess the frequency of the etiological factors during the evaluation of patients with recurrent abortions. The cost effectiveness of the most frequent positive findings will be assessed. STUDY DESIGN: This is a retrospective study in which 97 patient charts were evaluated and only 90 charts were included in this study. The diagnostic studies for every patient including hysterosalpingogram, endometrial biopsy, cervical cultures for Chlamydia and ureaplasma, and chromosomal karyotyping for the couple were assessed. The cost analysis was based on the CPT coding for each test. RESULTS: The frequency of the tests with highest positive findings were hysterosalpingogram, endometrial biopsy, cervical cultures, and immunologic studies. Chromosomal karyotyping has a low positive yield in evaluation of these patients. CONCLUSION: In evaluating patients with recurrent miscarriages, treating physicians should take into consideration the tests which have a high positive yield as a first step. Chromosomal karyotyping should be evaluated in specific situations.

Costs of maternal conditions attributable to smoking during pregnancy.

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.

Uso da aspiraçäo manual a vácuo na reduçäo do custo e duraçäo de internamentos por aborto incompleto em Fortaleza, CE, Brasil / Adoption of manual vacuum aspiration for treatment of incomplete abortion reduces costs and duration of patient's hospital stay in an urban area of Northeastern Brazil

O uso de aspiraçäo a vácuo (AV) no tratamento do aborto incompleto é prática bastante difundida em países desenvolvidos. Vários estudos nesses países indicam que o uso da técnica de aspiraçäo manual a vácuo (AMV) pode conservar recursos do sistema de saúde e melhorar a qualidade do tratamento do aborto. No Brasil, o uso da AMV é procedimento de rotina nos hospitais e clínicas privados. Entretanto, na maioria dos hospitais da rede pública é utilizada somente a técnica de dilataçäo e curetagem (D&C). Foram utilizados métodos de avaliaçäo rápida para estimar a variaçäo do custo médio do tratamento e duraçäo da estadia hospitalar, em um grupo de 30 pacientes admitidas com aborto incompleto em hospital público de Fortaleza, CE (Brasil). Participantes foram alocadas, randomicamente, em um dos dois grupos de tratamento investigados (AMV ou D&C). Os resultados sugerem que o uso da AMV, em substituiçäo a D&C, no tratamento do aborto incompleto, pode reduzir em até 41 por cento o custo médio do tratamento e em 77 por cento o tempo médio de hospitalizaçäo. Recomenda-se a realizaçäo de estudos confirmatórios, como também que se aprofunde os conhecimentos sobre a percepçäo do aborto e seu tratamento por parte do pessoal de saúde e da populaçäo feminina