High-throughput, non-invasive prenatal testing for fetal Rhesus D genotype to guide antenatal prophylaxis with anti-D immunoglobulin: a cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of high-throughput, non-invasive prenatal testing (HT-NIPT) for fetal Rhesus D (RhD) genotype to guide antenatal prophylaxis with anti-D immunoglobulin compared with routine antenatal anti-D immunoglobulin prophylaxis (RAADP). DESIGN: Cost-effectiveness decision-analytic modelling. SETTING: Primary care. PARTICIPANTS: A simulated population of 100 000 RhD-negative women not known to be sensitised to the RhD antigen. METHODS: A decision tree model was used to characterise the antenatal care pathway in England and the long-term consequences of sensitisation events. The diagnostic accuracy of HT-NIPT was derived from a systematic review and bivariate meta-analysis; estimates of other inputs were derived from relevant literature sources and databases. Women in whom the HT-NIPT was positive or inconclusive continued to receive RAADP, whereas women with a negative result received none. Five alternative strategies in which the use of HT-NIPT may affect the existing postpartum care pathway were considered. MAIN OUTCOME MEASURES: Costs expressed in 2015GBP and impact on health outcomes expressed in terms of quality-adjusted life-years over a lifetime. RESULTS: The results suggested that HT-NIPT appears cost saving but also less effective than current practice, irrespective of the postpartum strategy evaluated. A postpartum strategy in which inconclusive test results are distinguished from positive results performed best. HT-NIPT is only cost-effective when the overall test cost is £26.60 or less. CONCLUSIONS: HT-NIPT would reduce unnecessary treatment with routine anti-D immunoglobulin and is cost saving when compared with current practice. The extent of any savings and cost-effectiveness is sensitive to the overall test cost. TWEETABLE ABSTRACT: HT-NIPT is cost saving compared with providing anti-D to all RhD-negative pregnant women.

Trends in the incidence of diabetes, its clinical sequelae, and associated costs in pregnancy.

BACKGROUND: Increasing diabetes prevalence affects a substantial number of pregnant women in the United States. Our aims were to evaluate health outcomes, medical costs, risks and types of complications associated with diabetes in pregnancy for mothers and newborns. METHODS: In this retrospective claims analysis, patients were identified from the Truven Health MarketScan(®) database (2004-2011 inclusive). Participants were aged 18-45 years, with ascertainable diabetes status [Yes/No], date of birth event >2005 and continuous health plan enrolment ≥21 months before and 3 months after the birth. RESULTS: In total, 839 792 pregnancies were identified, and 66 041 (7.86%) were associated with diabetes mellitus [type 1 (T1DM), 0.13%; type 2 (T2DM), 1.21%; gestational (GDM), 6.29%; and GDM progressing to T2DM (patients without prior diabetes who had a T2DM diagnosis after the birth event), 0.23%]. Relative risk (RR) of stillbirth (2.51), miscarriage (1.28) and Caesarean section (C-section) (1.77) was significantly greater with T2DM versus non-diabetes. Risk of C-section was also significantly greater for other diabetes types [RR 1.92 (T1DM); 1.37 (GDM); 1.63 (GDM progressing to T2DM)]. Risk of overall major congenital (RR ≥ 1.17), major congenital circulatory (RR ≥ 1.19) or major congenital heart (RR ≥ 1.18) complications was greater in newborns of mothers with diabetes versus without. Mothers with T2DM had significantly higher risk (RR ≥ 1.36) of anaemia, depression, hypertension, infection, migraine, or cardiac, obstetrical or respiratory complications than non-diabetes patients. Mean medical costs were higher with all diabetes types, particularly T1DM ($27 531), than non-diabetes ($14 355). CONCLUSIONS: Complications and costs of healthcare were greater with diabetes, highlighting the need to optimize diabetes management in pregnancy.

Costs and benefits of non-invasive fetal RhD determination.

OBJECTIVE: Non-invasive fetal Rhesus (Rh) D genotyping, using cell-free fetal DNA (cffDNA) in the maternal blood, allows targeted antenatal anti-RhD prophylaxis in unsensitized RhD-negative pregnant women. The purpose of this study was to determine the cost and benefit of this approach as compared to routine antenatal anti-RhD prophylaxis for all unsensitized RhD-negative pregnant women, as is the current policy in the province of Alberta, Canada. METHODS: This study was a decision analysis based on a theoretical population representing the total number of pregnancies in Alberta over a 1-year period (n = 69 286). A decision tree was created that outlined targeted prophylaxis for unsensitized RhD-negative pregnant women screened for cffDNA (targeted group) vs routine prophylaxis for all unsensitized RhD-negative pregnant women (routine group). Probabilities at each decision point and costs associated with each resource were calculated from local clinical and administrative data. Outcomes measured were cost, number of women sensitized and doses of Rh immunoglobulin (RhIG) administered. RESULTS: The estimated cost per pregnancy for the routine group was 71.43 compared with 67.20 Canadian dollars in the targeted group. The sensitization rates per RhD-negative pregnancy were equal, at 0.0012, for the current and targeted programs. Implementing targeted antenatal anti-RhD prophylaxis would save 4072 doses (20.1%) of RhIG over a 1-year period in Alberta when compared to the current program. CONCLUSIONS: These data support the feasibility of a targeted antenatal anti-RhD prophylaxis program, at a lower cost than that of the existing routine prophylaxis program, with no increased risk of sensitization.

How do we treat fetal and neonatal alloimmune thrombocytopenia?

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially devastating disease, seen in one in 800 to 1000 neonates. FNAIT is the most common cause of early-onset isolated severe neonatal thrombocytopenia in maternity wards. The complication of this disorder most to be feared is intracranial hemorrhage, leading to death or to neurologic sequels. As there is no systematic screening of at-risk pregnancies, FNAIT is often discovered when signs of bleeding are observed during pregnancy or at delivery. Platelet transfusion is required in case of bleeding or severe thrombocytopenia (<30 × 10(9) /L) during the 48-hour-postdelivery period. Diagnosis of alloimmunization is important for management of the index case and for subsequent pregnancies, due to the increasing severity of this syndrome as it recurs. Noninvasive antenatal therapy is based on maternal perfusion of intravenous immunoglobulins and risk stratification. In our experience, the addition of corticoids during the last trimester significantly improves the efficiency of treatment. Follow-up of antibody concentration during pregnancy may constitute a useful variable for therapy effectiveness.

Screening for sickle cell and thalassaemia in primary care: a cost-effectiveness study.

BACKGROUND: Haemoglobinopathies, including sickle cell disease and thalassaemia (SCT), are inherited disorders of haemoglobin. Antenatal screening for SCT rarely occurs before 10 weeks of pregnancy. AIM: To explore the cost-effectiveness of offering SCT screening in a primary care setting, during the pregnancy confirmation visit. DESIGN AND SETTING: A model-based cost-effectiveness analysis of inner-city areas with a high proportion of residents from ethnic minority groups. METHOD: Comparison was made of three SCT screening approaches: 'primary care parallel' (primary care screening with test offered to mother and father together); 'primary care sequential (primary care screening with test offered to the mother and then the father only if the mother is a carrier); and 'midwife care' (sequential screening at the first midwife consultation). The model was populated with data from the SHIFT (Screening for Haemoglobinopathies In First Trimester) trial and other sources. RESULTS: Compared to midwife care, primary care sequential had a higher NHS cost of £34,000 per 10,000 pregnancies (95% confidence interval [CI] = £15,000 to £51,000) and an increase of 2623 women screened (95% CI: 1359 to 4495), giving a cost per additional woman screened by 10 weeks of £13. Primary care parallel was dominated by primary care sequential, with both higher costs and fewer women screened. CONCLUSION: The policy judgement is whether an earlier opportunity for informed reproductive choice has a value of at least £13. Further work is required to understand the value attached to earlier informed reproductive choices.

Routine antenatal anti-D prophylaxis for RhD-negative women: a systematic review and economic evaluation.

OBJECTIVES: To identify any evidence for advances in the use of routine antenatal anti-D prophylaxis (RAADP) since the 2002 National Institute for Health and Clinical Excellence (NICE) appraisal, and to assess the current clinical effectiveness and cost-effectiveness of RAADP for Rhesus D (RhD)-negative women. DATA SOURCES: Main bibliographic databases were searched from inception to July 2007. REVIEW METHODS: Selected studies were assessed and data extracted using a standard template and quality assessment based on published criteria. Meta-analysis was used where appropriate, otherwise outcomes were tabulated and discussed within a descriptive synthesis. The health economic model developed for the 2002 NICE appraisal of RAADP was modified to assess the cost-effectiveness of different regimens of RAADP. RESULTS: The clinical effectiveness searches identified 670 potentially relevant articles. Of these, 12 papers were included in the review, relating to eight studies of clinical effectiveness. With one exception, no additional studies were identified in comparison with the previous assessment report, and some of the studies of clinical effectiveness included in the 2002 review had to be excluded because they did not use currently licensed doses. Therefore, eight studies comparing RAADP with no prophylaxis were identified in the clinical effectiveness review and nine (including the 2001 assessment report itself) in the cost-effectiveness review. The clinical efficacy studies were generally of poor quality and did not provide a basis for differentiating between regimens of RAADP. The best indication of the likely efficacy of a programme of RAADP comes from two non-randomised community-based studies. The pooled results of these suggest that such a programme may reduce the sensitisation rate from 0.95% (95% CI 0.18-1.71) to 0.35% (95% CI 0.29-0.40). This gives an odds ratio for the risk of sensitisation of 0.37 (95% CI 0.21-0.65) and an absolute reduction in risk of sensitisation in RhD-negative mothers at risk (i.e. carrying a RhD-positive child) of 0.6%. The identified studies suggest that RAADP has minimal adverse effects. Of the nine studies in the cost-effectiveness review, only two described a model that could be applicable to the NHS. The economic model modified from the 2002 appraisal suggests that the cost per quality-adjusted life-year (QALY) gained of RAADP given to RhD-negative primigravidae versus no treatment is between 9000 pounds and 15,000 pounds, and for RAADP given to all RhD-negative women rather than to RhD-negative primigravidae only is between 20,000 pounds and 35,000 pounds depending upon the regimen. The sensitivity analysis suggests that the results are reasonably robust to changes in the assumptions within the model. CONCLUSIONS: RAADP reduces the incidence of sensitisation and hence of haemolytic disease of the newborn. The economic model suggests that RAADP given to all RhD-negative pregnant women is likely to be cost-effective at a threshold of around 30,000 pounds per QALY gained. The total cost of providing RAADP to RhD-negative primigravidae in England and Wales is estimated to be around 1.8-3.1 million pounds per year, depending upon regimen, and to all RhD-negative pregnant women in England and Wales around 2-3.5 million pounds.

Management of post-partum hemorrhage in low-income countries.

The provision of safe and effective delivery care for all women in poor countries remains elusive, resulting in a continuing burden of mortality in general and mortality from post-partum haemorrhage in particular. Deployment of a functional health system and effective linkage of the health system to communities are the necessary prerequisites for the provision of the life-saving technical interventions that will make a difference in individual cases. Sadly, two factors militate against progress: the mantra that 'we know what works' (resulting in some serious gaps in evidence for best practice in resource-poor settings) and a lack of large-scale investment in maternity services to counteract the degradation of infrastructure and depletion of human resources evident in many countries.

Misoprostol for the prevention and treatment of postpartum haemorrhage.

Postpartum haemorrhage (PPH) causes preventable maternal deaths, mainly in low-income countries. Misoprostol has powerful uterotonic effects and, because it is well absorbed orally and sublingually, has the potential to be used more widely than would be possible with injectable uterotonics alone. Misoprostol is clearly less effective than oxytocin. Placebo-controlled studies have had variable results, although two recent trials in low-income communities have shown promising results. The main recognized side effects have been dose-related pyrexia and shivering, including occasional hyperpyrexia. In the randomized trials reported to date, there has been a trend to more deaths with misoprostol than with the control groups. The dose that has been most commonly used in clinical trials for preventing PPH is 600 microg orally. Meta-analysis of direct and adjusted indirect comparisons between 600 and 400 microg showed very similar effectiveness. To date, there is very limited evidence for the effectiveness of misoprostol, the lowest effective dose and the magnitude of adverse effects, both direct and indirect. The need for further research is a matter of great urgency.

Comparison of efficacy, tolerability, and cost of iron polymaltose complex with ferrous sulphate in the treatment of iron deficiency anemia in pregnant women.

BACKGROUND: The efficacy of iron polymaltose complex (IPC) in the treatment of iron deficiency anemia (IDA) during pregnancy has not been well established, and the evidence is inconclusive. AIMS: The aim of the study was to compare efficacy, safety, compliance, and cost-effectiveness of IPC with ferrous sulphate (FS) in pregnant patients. SETTINGS AND DESIGNS: The randomized, double-blind, parallel-group study was conducted in the Department of Pharmacology in collaboration with the Department of Obstetrics and Gynaecology Postgraduate Institute of Medical Education and Research, Chandigarh, India. METHODS: One hundred pregnant women aged 20-40 years at 14 to 27 weeks' gestation, with hemoglobin (Hb) < 9 g/dL, and serum ferritin < 12 mcg/L, were classified into 2 groups. One group received IPC (100 mg elemental iron), and the other group received FS (120 mg elemental iron) daily for 8 weeks. At Week 0 and Week 8, Hb, packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), serum iron, and serum ferritin were measured. Compliance with study medication was determined by pill counting at each visit. Cost minimization analysis was done to compare the costs of the 2 treatments. STATISTICAL ANALYSIS: Data are expressed as mean -/+ SD. Paired and unpaired 't' test were used to analyze differences within groups and between groups. Chi-square (x2) test was used to analyze primary efficacy parameters and adverse drug reactions (ADR). RESULTS: Statistically significant increases in Hb, PCV, MCV, MCH, MCHC, serum iron, and serum ferritin levels were seen at the end of 8 weeks of treatment in both groups. The overall adverse effects were more common in the FS group compared with the IPC group [41 (78%) vs 15 (31%), P < .001]. The compliance rate was significantly (P < .05) higher for the IPC (91%) group than for the FS (87%) group. The average total cost (direct + indirect) of treatment of anemia was comparable between the 2 groups. CONCLUSION: The results of the present study suggest that IPC can be considered as a useful alternative formulation for the treatment of IDA during pregnancy for those patients who cannot tolerate other iron preparations (ferrous form); this is an important finding, as compliance is a significant concern during pregnancy.

Cost-effectiveness of antenatal screening for neonatal alloimmune thrombocytopenia.

OBJECTIVES: To estimate the costs and health consequences of three different screening strategies for neonatal alloimmune thrombocytopenia (NAIT). DESIGN: Cost-utility analysis on the basis of a decision tree that incorporates the relevant strategies and outcomes. SETTING: Three health regions in Norway encompassing a 2.78 million population. POPULATION: Pregnant women (n = 100,448) screened for human platelet antigen (HPA) 1a and anti-HPA 1a antibodies, and their babies. METHOD: Decision tree analysis. In three branches of the decision tree, pregnant women entered a programme while in one no screening was performed. The three different screening strategies included all HPA 1a negative women, only HPA 1a negative, HLA DRB3*0101 positive women or only HPA 1a negative women with high level of anti-HPA 1a antibodies. Included women underwent ultrasound examination and elective caesarean section 2-4 weeks before term. Severely thrombocytopenic newborn were transfused immediately with compatible platelets. MAIN OUTCOME MEASUREMENTS: Quality-adjusted life years (QALYs) and costs. RESULTS: Compared with no screening, a programme of screening and subsequent treatment would generate between 210 and 230 additional QALYs among 100,000 pregnant women, and at the same time, reduce health care costs by approximately 1.7 million euros. The sensitivity analyses indicate that screening is cost effective or even cost saving within a wide range of probabilities and costs. CONCLUSION: Our calculations indicate that it is possible to establish an antenatal screening programme for NAIT that is cost effective.

A cost utility analysis of the right method for screening hemoglobin E among Thai pregnant women.

BACKGROUND: Inherited hemoglobin disorders are an important problem in many developing countries including Thailand. Of the several inherited hemoglobin disorders, hemoglobin E (HbE) (beta 26, GAG-AAG, Glu-Lys) is the most common hemoglobinopathy in Thailand. Presently, screening to identify carriers of hemoglobin disorders among pregnant subjects is an interesting topic in antenatal care in Thailand. Of late, many trials have been conducted to identify the right screening methods for the detection of hemoglobin disorders among Thai pregnant women. The common screening methods include red blood cell (RBC) index determination, application of mathematical model and hemoglobin electrophoresis. METHODS: Here, the author presents an evaluation of the cost utility of those tests in medical practice in Thailand. The cost/utility of hemoglobin electrophoresis is the highest followed by RBC index determination, application of mathematical model and DCIP test. RESULTS: Here, it can be shown that the cost per accurate diagnosis for DCIP is the least expensive. CONCLUSION: It is interesting to note that DCIP also posed high sensitivity in the screening for HbE disorder. Therefore, this test is the best method for screening the population, particularly pregnant women, to identify carriers of hemoglobin disorders. It should be recommended as part of antenatal care in Thailand as well as its neighbouring countries which have a similar high rate of HbE disorder.

Perinatal stroke in baby, prothrombotic gene in mom: does this affect maternal health insurance?

BACKGROUND: Maternal prothrombotic disorders may contribute to stroke in the fetus before and during birth. Many of the mothers of children with perinatal stroke have no previous history of pathologic thrombosis. OBJECTIVE: To determine if finding the Factor V Leiden mutation, prothrombin 20210 G-A gene defect, or methylene tetrahydrofolate reductase C677T mutation in an asymptomatic mother of a child with perinatal stroke would affect that mother's ability to obtain health insurance. METHODS: 1) The authors reviewed the literature on genetic prothrombotic risk factors and health insurance. 2) The authors surveyed the 17 largest insurance carriers in Indiana to find if diagnosing genetic prothrombotic risk factors in asymptomatic mothers of children with perinatal stroke would affect the mothers' health insurance status. RESULTS: Three articles on genetic prothrombotic risk factors and insurance were identified. Twelve of 17 insurance companies responded to our survey; three had policies on genetic testing. Most companies refused to provide clear, useful information on their policies regarding these risk factors. CONCLUSIONS: The authors are currently unable to counsel their patients' families on the long-term insurance implications of screening for genetic prothrombotic risk factors. The insurance implications of diagnosing healthy women with genetic prothrombotic risk factors need further study.

The economics of routine antenatal anti-D prophylaxis for pregnant women who are rhesus negative.

OBJECTIVE: To investigate the economics of routine antenatal anti-D prophylaxis in the prevention of haemolytic disease of the newborn, in support of the NICE appraisals process. DESIGN: Cost effectiveness analysis. SETTING: UK NHS. POPULATION/SAMPLE: Pregnant women who are RhD-negative. METHODS: A model was constructed to estimate the incremental cost effectiveness and cost utility of: (1) offering routine antenatal anti-D prophylaxis to all pregnant women who are RhD-negative; (2) offering routine antenatal anti-D prophylaxis to RhD-negative primigravidae, compared with conventional management alone. Effectiveness estimates were derived from a meta-analysis of two UK community-based studies. Costs were derived from published sources and NHS product lists. Threshold analysis was conducted to reflect the social value of routine antenatal anti-D prophylaxis through incorporating valuations of parental grief and fetal/neonatal loss. MAIN OUTCOME MEASURES: Cost per life year gained and cost per quality adjusted life year (QALY) gained. RESULTS: The cost per life year gained is in the range pound 5,000- pound 15,000. The inclusion of long term neurodevelopmental problems results in a cost utility ranging between pound 11,000 and pound 52,000 per QALY gained. Threshold analysis suggests that if fetal loss, parental grief and subsequent high intervention pregnancy are valued at greater than 9 QALYs, the comprehensive policy would be more attractive than the primigravidae policy, assuming a maximum acceptable threshold of pound 30,000 per QALY. CONCLUSION: Routine antenatal anti-D prophylaxis provides a cost effective intervention for preventing haemolytic disease of the newborn in the pregnancies of women who are RhD-negative.

Automated computer result reporting for haemoglobinopathy screening.

The anticipated introduction of universal antenatal screening can be expected to increase the workload of haemoglobinopathy laboratories throughout the country. We have devised a rule-based system to process those results that does not require skilled interpretation, thereby freeing staff time for more specialized work. The system relies on a calculated test to create a total haemoglobin peak value, which incorporates the values for HbA, HbA2 and HbF, the MCV and MCH from the full blood count. Each parameter has a series of defined ranges which, when subjected to an interpretation process within the laboratory computer system, generates an automated result text for the sample. During a 6-month verification period, the automated result interpretation system in conjunction with laboratory information systems (LIS) validation reduced the number of samples requiring manual review by 60%. The system was found to be 100% sensitive and 61.8% specific. We feel that the current specificity is acceptable in order to maintain a safe system. The ability to concentrate on potentially abnormal results will allow laboratories and health care workers more time to develop appropriate and timely frameworks to deal with abnormal results.

"Preeclamptic labs" for evaluating hypertension in pregnancy.

OBJECTIVE: To determine the utility of evaluating coagulation function in patients with chronic hypertension, transient hypertension, preeclampsia, eclampsia and the HELLP syndrome. STUDY DESIGN: We retrospectively reviewed the charts of 244 patients who delivered between March 1992 and March 1994 at the University of New Mexico with a discharge diagnosis of either hypertension, preeclampsia or eclampsia. RESULTS: Nine patients were thrombocytopenic on admission, as defined by a platelet count of < 100,000/mm3. Three of the 244 patients had mild prolongation of the partial thromboplastin time, and none had prolongation of the prothrombin time. Two of the patients with prolongation of the partial thromboplastin time were thrombocytopenic on admission, and the last had elevation of liver enzymes. No patient had clinical evidence of coagulopathy. CONCLUSION: Measurement of the partial thromboplastin time and prothrombin time in the evaluation of preeclampsia/eclampsia can be avoided if the platelet count and liver enzymes are normal. This results in a decrease in hospital charges and no compromise in patient safety.

[To screen or systematically treat a population at risk? A method based on the analysis of costs applicable at the level of district health]. / Dépister ou traiter systématiquement une population à risque? Une méthode basée sur l'analyse des coûts utilisable au niveau du district sanitaire.

With severely limited resources, it is necessary for the health services to select the most efficient strategy for managing health problems in a population at risk. A simple method for cost analysis, which can be used at the district health care level, is proposed so that one can choose between selective treatment on the basis of case identification, or indiscriminate treatment of the entire population at risk. The treatment of anaemia at the antenatal clinic in health centres in southwestern Chad was studied and is presented as an example. The conditions for use and the limitations of the method are discussed.