Eline van den Akker

Intravenous Immunoglobulins without Initial and Follow-Up Cordocentesis in Alloimmune Fetal and Neonatal Thrombocytopenia at High Risk for Intracranial Hemorrhage

Objective: To report on a less invasive treatment strategy in alloimmune fetal and neonatal thrombocytopenia (FNAIT) at high risk for either in utero or neonatal intracranial hemorrhage (ICH). Methods: In 7 pregnancies, with a history of ICH in the older sibling, weekly intravenous immunoglobulin (IVIG) therapy to the mother (1 g/kg) without initial cordocentesis was started at a median gestational age of 16 weeks. Results: In 4 pregnancies cordocentesis was avoided. One predelivery cordocentesis with platelet transfusion was performed in 3 further cases. Although none of the cases had a platelet count of >50 × 109/l at cordocentesis, predelivery or birth, no ICHs were observed. The neonatal periods of the infants were uncomplicated. Conclusion: IVIG treatment alone might be considered in patients with both severe platelet alloimmunization and an increased risk for morbidity and mortality at cordocentesis.

Cost-effectiveness of cardiotocography plus ST analysis of the fetal electrocardiogram compared with cardiotocography only

Objective. To assess the cost‐effectiveness of addition of ST analysis of the fetal electrocardiogram (ECG; STAN®) to cardiotocography (CTG) for fetal surveillance during labor compared with CTG only. Design. Cost‐effectiveness analysis based on a randomized clinical trial on ST analysis of the fetal ECG. Setting. Obstetric departments of three academic and six general hospitals in The Netherlands. Population. Laboring women with a singleton high‐risk pregnancy, a fetus in cephalic presentation, a gestational age >36weeks and an indication for internal electronic fetal monitoring. Methods. A trial‐based cost‐effectiveness analysis was performed from a health‐care provider perspective. Main Outcome Measures. Primary health outcome was the incidence of metabolic acidosis measured in the umbilical artery. Direct medical costs were estimated from start of labor to childbirth. Cost‐effectiveness was expressed as costs to prevent one case of metabolic acidosis. Results. The incidence of metabolic acidosis was 0.7% in the ST‐analysis group and 1.0% in the CTG‐only group (relative risk 0.70; 95% confidence interval 0.38–1.28). Per delivery, the mean costs per patient of CTG plus ST analysis (n= 2 827) were €1 345 vs. €1 316 for CTG only (n= 2 840), with a mean difference of €29 (95% confidence interval −€9 to €77) until childbirth. The incremental costs of ST analysis to prevent one case of metabolic acidosis were €9 667. Conclusions. The additional costs of monitoring by ST analysis of the fetal ECG are very limited when compared with monitoring by CTG only and very low compared with the total costs of delivery.

Remifentanil patient controlled analgesia versus epidural analgesia in labour. A multicentre randomized controlled trial.

BackgroundPain relief during labour is a topic of major interest in the Netherlands. Epidural analgesia is considered to be the most effective method of pain relief and recommended as first choice. However its uptake by pregnant women is limited compared to other western countries, partly as a result of non-availability due to logistic problems. Remifentanil, a synthetic opioid, is very suitable for patient controlled analgesia. Recent studies show that epidural analgesia is superior to remifentanil patient controlled analgesia in terms of pain intensity score; however there was no difference in satisfaction with pain relief between both treatments.Methods/designThe proposed study is a multicentre randomized controlled study that assesses the cost-effectiveness of remifentanil patient controlled analgesia compared to epidural analgesia. We hypothesize that remifentanil patient controlled analgesia is as effective in improving pain appreciation scores as epidural analgesia, with lower costs and easier achievement of 24 hours availability of pain relief for women in labour and efficient pain relief for those with a contraindication for epidural analgesia.Eligible women will be informed about the study and randomized before active labour has started. Women will be randomly allocated to a strategy based on epidural analgesia or on remifentanil patient controlled analgesia when they request pain relief during labour. Primary outcome is the pain appreciation score, i.e. satisfaction with pain relief.Secondary outcome parameters are costs, patient satisfaction, pain scores (pain-intensity), mode of delivery and maternal and neonatal side effects.The economic analysis will be performed from a short-term healthcare perspective. For both strategies the cost of perinatal care for mother and child, starting at the onset of labour and ending ten days after delivery, will be registered and compared.DiscussionThis study, considering cost effectiveness of remifentanil as first choice analgesia versus epidural analgesia, could strongly improve the care for 180.000 women, giving birth in the Netherlands yearly by giving them access to pain relief during labour, 24 hours a day.Trial registration numberDutch Trial Register NTR2551, http://www.trialregister.nl

Non-invasive prenatal screening for trisomy 21: What women want and are willing to pay

OBJECTIVE To investigate the attitude among pregnant women regarding non-invasive prenatal testing (NIPT) for detecting trisomy 21 (T21) and to quantify their willingness to pay for NIPT. METHODS A questionnaire was administered to pregnant women who received counselling for first-trimester screening (FTS) in two hospitals and nine midwife practices in the Netherlands. RESULTS A total of 147 women completed the questionnaire, yielding a response rate of 43%. If NIPT for detecting T21 were available, 81% stated they would choose to have this test, and 57% of women who elected not to undergo FTS in their current pregnancy would perform NIPT if available. Willingness to pay for NIPT was correlated with age and income, but not education level. The price that participants were willing to pay for NIPT was similar to the current price for FTS. CONCLUSION The pregnant women in our study had a positive attitude regarding NIPT for T21, and more than half of the women who rejected prenatal screening would receive NIPT if available. PRACTICE IMPLICATIONS Due to the elimination of iatrogenic miscarriage, caregivers should be aware that informed decision-making can change with respect to prenatal screening with the introduction of NIPT.

Severe fetal thrombocytopenia in Rhesus D alloimmunized pregnancies

OBJECTIVE The objective of the study was to evaluate the incidence of fetal thrombocytopenia and association with hydrops in Rhesus D alloimmunization. STUDY DESIGN The study was a retrospective chart review of 914 intrauterine transfusions in 314 pregnancies performed between 1988 and 2005 in a single institution. The incidence of thrombocytopenia and severity of hydrops at cordocentesis were assessed and correlated with perinatal mortality. RESULTS Thrombocytopenia (less than 150 x 10(9)/L) was found in 241 of 914 (26%) and severe thrombocytopenia (less than 50 x 10(9)/L) in 25 of 914 (3%) cordocentesis. Twenty-three percent of severely hydropic fetuses had severe thrombocytopenia, compared with 3% and 1% of mildly hydropic and nonhydropic fetuses, respectively. Thrombocytopenia was an independent risk factor for perinatal mortality. Mortality in fetuses that were severely thrombocytopenic and severely hydropic was 67%. CONCLUSION Thrombocytopenia is common in hydropic anemic fetuses. Severe thrombocytopenia is associated with a poor prognosis, irrespective of the presence of hydrops. The option of platelet transfusion in severely hydropic anemic fetuses needs further study.

Low-Dose versus Standard-Dose Intravenous Immunoglobulin to Prevent Fetal Intracranial Hemorrhage in Fetal and Neonatal Alloimmune Thrombocytopenia: A Randomized Trial

Objective: Pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT) are commonly treated using weekly intravenous immunoglobulin (IVIG) at 1 g/kg maternal weight. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to evaluate the effectiveness of IVIG at a lower dose, i.e. 0.5 g/kg. Methods: This was a randomized controlled multicenter trial conducted in Sweden, the Netherlands and Australia. Pregnant women with human platelet antigen alloantibodies and an affected previous child without intracranial hemorrhage (ICH) were enrolled. The participants were randomized to IVIG at 0.5 or 1 g/kg per week. The analyses were per intention to treat. The primary outcome was fetal or neonatal ICH. Secondary outcomes were platelet count at birth, maternal and neonatal IgG levels, neonatal treatment and bleeding other than ICH. Results: A total of 23 women were randomized into two groups (low dose: n = 12; standard dose: n = 11). The trial was stopped early due to poor recruitment. No ICH occurred. The median newborn platelet count was 81 × 109/l (range 8-269) in the 0.5 g/kg group versus 110 × 109/l (range 11-279) in the 1 g/kg group (p = 0.644). Conclusion: The risk of adverse outcomes in FNAIT pregnancies treated with IVIG at 0.5 g/kg is very low, similar to that using 1 g/kg, although our uncompleted trial lacked the power to conclusively prove the noninferiority of using the low dose.

Predictive value of the baseline T-QRS ratio of the fetal electrocardiogram in intrapartum fetal monitoring: a prospective cohort study

Objective. To evaluate the added value of the baseline T/QRS ratio to other known risk factors in predicting adverse outcome and interventions for suspected fetal distress. Design. Prospective cohort study. Setting. Three academic and six non‐academic teaching hospitals in the Netherlands. Population. Laboring women with a high‐risk cephalic singleton pregnancy beyond 36 weeks of gestation. Methods. We obtained STAN® recordings (ST‐analysis, Neoventa, Sweden) from two previous studies. Three patient groups were defined: cases with adverse outcome, cases with emergency delivery because of suspected fetal distress without adverse outcome, and a reference group of uncomplicated cases. Baseline T/QRS ratios among the adverse outcome and intervention for suspected fetal distress cases were compared to those of the uncomplicated cases. The ability of baseline T/QRS to predict adverse outcome and suspected fetal distress was determined using a multivariable logistic model. Main outcome measures. The added value of the baseline T/QRS to other known risk factors in the prediction of adverse outcome and interventions for suspected fetal distress. Results. From 3462 recordings, 2459 were available for analysis. Median baseline T/QRS for uncomplicated cases, adverse outcome and interventions for suspected fetal distress were 0.12 (range 0.00–0.52), 0.12 (0.00–0.42) and 0.13 (0.00–0.39), respectively. There was no statistical difference between these groups. Multivariable analysis showed no added value of baseline T/QRS in the prediction of either adverse outcome or interventions for suspected fetal distress. Conclusion. Baseline T/QRS has no added value in the prediction of adverse neonatal outcome or interventions for suspected fetal distress.

An economic analysis of patient controlled remifentanil and epidural analgesia as pain relief in labour (RAVEL trial); a randomised controlled trial

Objective To compare the costs of a strategy of patient controlled remifentanil versus epidural analgesia for pain relief in labour. Design We performed a multicentre randomised controlled trial in 15 hospitals in the Netherlands, the RAVEL trial. Costs were analysed from a health care perspective alongside the RAVEL trial. Population Pregnant women of intermediate to high risk beyond 32 weeks gestation who planned vaginal delivery. Methods Women were randomised before the onset of labour, to receive either patient controlled remifentanil or epidural analgesia when pain relief was requested during labour. Main outcome measures Primary outcome for effectiveness was satisfaction with pain relief, expressed as the area under the curve (AUC). A higher AUC represents higher satisfaction with pain relief. Here, we present an economic analysis from a health care perspective including costs from the start of labour to ten days postpartum. Health-care utilization was documented in the Case Report Forms and by administering an additional questionnaire. Results The costs in the patient controlled remifentanil group (n = 687) and in the epidural group (n = 671) were €2900 versus €3185 respectively (mean difference of -€282 (95% CI -€611 to €47)). The (non-significant) higher costs in the epidural analgesia group could be mainly attributed to higher costs of neonatal admission. Conclusion From an economic perspective, there is no preferential pain treatment in labouring intermediate to high risk women. Since patient controlled remifentanil is not equivalent to epidural analgesia with respect to AUC for satisfaction with pain relief we recommend epidural analgesia as the method of choice. However, if appropriately counselled on effect and side effects there is, from an economic perspective, no reason to deny women patient controlled remifentanil.