Considerations on implementation of the newest treatment for symptomatic uterine fibroids: Oral GnRH antagonists.

Novel gonadotrophin releasing hormone (GnRH) antagonist treatments have recently been developed in combination with hormonal add-back therapy, as an oral treatment option for women suffering from uterine fibroids. Registration trials assessing the GnRH antagonist combination preparations with relugolix, elagolix and linzagolix have assessed treatment efficacy for fibroid-related heavy menstrual blood loss in comparison to placebo. Marketing authorization has been granted by several agencies including those in Europe, the United Kingdom and the United States. While the registration trials report a robust effect on the reduction of heavy menstrual blood loss and improvement in quality of life scores, reticence is advised before widespread prescription. In this review, we demonstrate limitations in the trial data, namely a lack of generalizability due to the restricted study population, the lack of transparency in the distribution of disease-level characteristics limiting the predictability of treatment success in the real-world diverse population, and the absence of any comparison to current alternative treatment methods. Importantly, no clinically meaningful volume reductions were found with GnRH antagonist combination preparations, and long-term safety data, particularly concerning modest but stable bone mineral density decline, need further addressing. Symptoms related to uterine fibroids adversely affect many women's quality of life and effective medical treatments are lacking. However, despite the urgent need for conservative treatments, it is vitally important that novel drugs, like combination oral GnRH antagonists, undergo sufficiently rigorous evaluation of safety, effectiveness and cost-effectiveness in a representative population and are compared with alternative treatment methods before introduction into mainstream clinical practice.

Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy : A Randomized, Controlled, 2 × 2 Factorial Trial.

BACKGROUND: An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. OBJECTIVE: To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384). SETTING: 13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022. PARTICIPANTS: 352 women in early pregnancy with moderate to severe NVP. INTERVENTION: Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days. MEASUREMENTS: The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications. RESULTS: No significant interaction was detected between the interventions (P = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]). LIMITATION: The placebo effects of the interventions and natural regression of the disease were not evaluated. CONCLUSION: Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.

The long-term costs and effects of tubal flushing with oil-based versus water-based contrast during hysterosalpingography.

RESEARCH QUESTION: What are the long-term costs and effects of oil- versus water-based contrast in infertile women undergoing hysterosalpingography (HSG)? DESIGN: This economic evaluation of a long-term follow-up of a multicentre randomized controlled trial involved 1119 infertile women randomized to HSG with oil- (n = 557) or water-based contrast (n = 562) in the Netherlands. RESULTS: In the oil-based contrast group, 39.8% of women needed no other treatment, 34.6% underwent intrauterine insemination (IUI) and 25.6% had IVF/intracytoplasmic sperm injection (ICSI) in the 5 years following HSG. In the water-based contrast group, 35.0% of women had no other treatment, 34.2% had IUI and 30.8% had IVF/ICSI in the 5 years following HSG (P = 0.113). After 5 years of follow-up, HSG using oil-based contrast resulted in equivalent costs (mean cost difference -€144; 95% confidence interval [CI] -€579 to +€290; P = 0.515) for a 5% increase in the cumulative ongoing pregnancy rate compared with HSG using water-based contrast (80% compared with 75%, Relative Risk (RR) 1.07; 95% CI 1.00-1.14). Similarly, HSG with oil-based contrast resulted in equivalent costs (mean cost difference -€50; 95% CI -€576 to +€475; P = 0.850) for a 7.5% increase in the cumulative live birth rate compared with HSG with water-based contrast (74.8% compared with 67.3%, RR 1.11; 95% CI 1.03-1.20), making it the dominant strategy. Scenario analyses suggest that the oil-based contrast medium is the dominant strategy up to a price difference of €300. CONCLUSION: Over a 5-year follow-up, HSG with an oil-based contrast was associated with a 5% increase in ongoing pregnancy rate, a 7.5% increase in live birth rate and similar costs to HSG with water-based contrast.

Tubal flushing for subfertility.

BACKGROUND: Establishing the subgroup analysis of the fallopian tubes (tubes) is a commonly undertaken diagnostic investigation for women with subfertility. This is usually achieved by flushing contrast medium through the tubes and visualising patency on radiographs, ultrasonography or laparoscopy. Many women were noted to conceive in the first three to six months after tubal flushing, raising the possibility that tubal flushing could also be a treatment for infertility. There has been debate about which contrast medium should be used (water-soluble or oil-soluble media) as this may influence pregnancy rates. An important adverse event during tubal flushing is intravasation (backflow of contrast medium into the blood or lymphatic vessels),which could lead to embolism although it is asymptomatic in most cases. OBJECTIVES: To evaluate the effectiveness and safety of tubal flushing with oil-soluble contrast media (OSCM) and water-soluble contrast media (WSCM) on subsequent fertility outcomes in women with subfertility. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group Specialised Register of controlled trials, MEDLINE, Embase, CENTRAL, PsycINFO, reference lists of identified articles and trial registries. The most recent search was conducted in April 2020. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing tubal flushing with OSCM, WSCM with each other or with no treatment, in women with subfertility. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the trials, assessed risk of bias and extracted data. We contacted study authors for additional information. The overall quality of the evidence was assessed using GRADE methods. MAIN RESULTS: Fifteen trials involving 3864 women were included in this systematic review. Overall, the quality of evidence varied from very low to moderate: the main limitations were risk of bias, heterogeneity and imprecision. OSCM versus no treatment Four studies (506 women) were included in this comparison. Tubal flushing with OSCM may increase the odds of live birth (odds ratio (OR) 3.27, 95% confidence interval (CI) 1.57 to 6.85, 3 RCTs, 204 women, I2 = 0, low-quality evidence). This suggests that if the chance of live birth following no treatment is assumed to be 11%, the chance following tubal flushing with OSCM would be between 16% and 46%. Tubal flushing with OSCM may increase in the odds of clinical pregnancy (OR 3.54, 95% CI 2.08 to 6.02, 4 RCTs, 506 women, I2 = 18%, low-quality evidence). This suggests that if the chance of clinical pregnancy following no treatment is assumed to be 9%, the chance following tubal flushing with OSCM would be between 17% and 37%. No study measured intravasation or other adverse events such as infection, haemorrhage and congenital abnormalities. WSCM versus no treatment Only one study (334 women) was included in this comparison. We are uncertain whether tubal flushing with WSCM increase live birth compared to no treatment (OR 1.13, 95% CI 0.67 to 1.91, 1 RCT, 334 women, low-quality evidence). This suggests that if the chance of live birth following no treatment is assumed to be 21%, the chance following tubal flushing with WSCM would be between 15% and 33%. We are uncertain whether tubal flushing with WSCM increases clinical pregnancy compared to no treatment (OR 1.14, 95% CI 0.71 to 1.84, 1 RCT, 334 women, low-quality evidence). This suggests that if the chance of clinical pregnancy following no treatment is assumed to be 27%, the chance following tubal flushing with WSCM would be between 29% and 40%. One case with pelvic infection was reported in the WSCM group and no case with infection in the no treatment group in a one study (334 women). Meta-analysis was not performed due to the rare events. No study measured intravasation or other adverse events such as infection, haemorrhage and congenital abnormalities. OSCM versus WSCM Six studies (2598 women) were included in this comparison. Three studies reported live birth, including two with higher live birth in the OSCM group (OR 1.64, 95% CI 1.27 to 2.11, 1119 women; OR 3.45, 95% CI 1.97 to 6.03, 398 women); and one with insufficient evidence of a difference between groups (OR 0.92, 95% CI 0.60 to 1.40, 533 women). Given the substantial heterogeneity observed (I2 = 86%), meta-analysis was not performed. Tubal flushing with OSCM probably increased in the odds of intravasation (asymptomatic) compared to tubal flushing with WSCM (OR 5.00, 95% CI 2.25 to 11.12, 4 RCTs, 1912 women, I2 = 0, moderate-quality evidence). This suggests that if the chance of intravasation following tubal flushing with WSCM is assumed to be 1%, the chance following tubal flushing with OSCM would be between 2% and 9%. Tubal flushing with OSCM may increase the odds of clinical pregnancy (OR 1.42, 95% CI 1.10 to 1.85, 6 RCTs, 2598 women, I2 = 41%, low-quality evidence). This suggests that if the chance of clinical pregnancy following tubal flushing with WSCM is assumed to be 26%, the chance following tubal flushing with OSCM would be between 28% and 39%. We are uncertain whether tubal flushing with OSCM decreases the odds of infection (OR 0.22, 95% CI 0.04 to 1.22, 2 RCTs, 662 women, I2 = 0, very low-quality evidence) or haemorrhage (OR 0.65, 95% CI 0.40 to 1.06, 2 RCTs, 662 women, I2 = 0, very low-quality evidence). Three neonates with congenital abnormalities were reported in the OSCM group while no congenital abnormality was reported in the WSCM group in one study (1119 women). No meta-analysis was performed due to the rare events. AUTHORS' CONCLUSIONS: The evidence suggests that compared to no treatment, tubal flushing with OSCM may increase the chance of live birth and clinical pregnancy, while it is uncertain whether tubal flushing with WSCM improves those outcomes. Compared to tubal flushing with WSCM, OSCM may improve clinical pregnancy while meta-analysis was impossible for live birth due to heterogeneity. Evidence also suggests that OSCM is associated with an increased risk of asymptomatic intravasation. Overall, adverse events, especially long-term adverse events, are poorly reported across studies.

Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial.

OBJECTIVE: To determine the efficacy of high dose folic acid supplementation for prevention of pre-eclampsia in women with at least one risk factor: pre-existing hypertension, prepregnancy diabetes (type 1 or 2), twin pregnancy, pre-eclampsia in a previous pregnancy, or body mass index ≥35. DESIGN: Randomised, phase III, double blinded international, multicentre clinical trial. SETTING: 70 obstetrical centres in five countries (Argentina, Australia, Canada, Jamaica, and UK). PARTICIPANTS: 2464 pregnant women with at least one high risk factor for pre-eclampsia were randomised between 2011 and 2015 (1144 to the folic acid group and 1157 to the placebo group); 2301 were included in the intention to treat analyses. INTERVENTION: Eligible women were randomised to receive either daily high dose folic acid (four 1.0 mg oral tablets) or placebo from eight weeks of gestation to the end of week 16 of gestation until delivery. Clinicians, participants, adjudicators, and study staff were masked to study treatment allocation. MAIN OUTCOME MEASURE: The primary outcome was pre-eclampsia, defined as hypertension presenting after 20 weeks' gestation with major proteinuria or HELLP syndrome (haemolysis, elevated liver enzymes, low platelets). RESULTS: Pre-eclampsia occurred in 169/1144 (14.8%) women in the folic acid group and 156/1157 (13.5%) in the placebo group (relative risk 1.10, 95% confidence interval 0.90 to 1.34; P=0.37). There was no evidence of differences between the groups for any other adverse maternal or neonatal outcomes. CONCLUSION: Supplementation with 4.0 mg/day folic acid beyond the first trimester does not prevent pre-eclampsia in women at high risk for this condition. TRIAL REGISTRATION: Current Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.

Nifedipine versus placebo in the treatment of preterm prelabor rupture of membranes: a randomized controlled trial: Assessment of perinatal outcome by use of tocolysis in early labor-APOSTEL IV trial.

OBJECTIVE: Preterm birth is the most common cause of neonatal morbidity and mortality. Around one third of preterm deliveries starts with preterm prelabor rupture of membranes (PPROM). The aim of this trial was to study the effect of prolonged tocolysis with nifedipine versus placebo in women with PPROM on perinatal outcome and prolongation of pregnancy. STUDY DESIGN: The Apostel IV was a nationwide multicenter randomized placebo controlled trial. We included women with PPROM without contractions between 24(+0) and 33(+6) weeks of gestation. Participants were randomly allocated to daily 80mg nifedipine or placebo, until the start of labor, with a maximum of 18 days. The primary outcome measure was a composite of poor neonatal outcome, including perinatal death, bronchopulmonary dysplasia, periventricular leukomalacia>grade 1, intraventricular hemorrhage>grade 2, necrotizing enterocolitis>stage 1 and culture proven sepsis. Secondary outcomes were gestational age at delivery and prolongation of pregnancy. Analysis was by intention to treat. To detect a reduction of poor neonatal outcome from 30% to 10%, 120 women needed to be randomized. TRIAL REGISTRY: NTR 3363. RESULTS: Between October 2012 and December 2014 we randomized 25 women to nifedipine and 25 women to placebo. Due to slow recruitment the study was stopped prematurely. The median gestational age at randomization was 29.9 weeks (IQR 27.7-31.3) in the nifedipine group and 27.0 weeks (IQR 24.7-29.9) in the placebo group. Other baseline characteristics were comparable. The adverse perinatal outcome occurred in 9 neonates (33.3%) in the nifedipine group and 9 neonates (32.1%) in the placebo group (RR 1.04, 95% CI 0.49-2.2). Two perinatal deaths occurred, both in the nifedipine group. Bronchopulmonary dysplasia was seen less frequently in the nifedipine group (0% versus 17.9%; p=0.03). Prolongation of pregnancy did not differ between the nifedipine and placebo group (median 11 versus 8 days, HR 1.02; 95% CI 0.58-1.79). CONCLUSION: This randomized trial did not show a beneficial effect of prolonged tocolysis on neonatal outcomes or prolongation of pregnancy in women with PPROM without contractions. However, since results are based on a small sample size, a difference in effectiveness cannot be excluded.

Tubal flushing for subfertility.

BACKGROUND: Establishing the patency of the fallopian tubes is a commonly undertaken diagnostic investigation for women with subfertility. This is usually achieved by flushing contrast medium through the tubes and taking radiographs. However, it has been noted that many women conceive in the first three to six months after the tubal flushing, which has raised the possibility that tubal flushing could also be a treatment for infertility. There has been debate about which contrast medium should be used (water-soluble or oil-soluble media) as this may influence pregnancy rates. OBJECTIVES: To evaluate the effect of flushing fallopian tubes with oil- or water-soluble contrast media on live birth and pregnancy rates in women with subfertility. SEARCH METHODS: We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of trials, MEDLINE, EMBASE, Biological Abstracts, trial registers and reference lists of identified articles. The most recent search was conducted in June 2014. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing tubal flushing with oil-soluble or water-soluble contrast media, or with no treatment, in women with subfertility. DATA COLLECTION AND ANALYSIS: Two authors independently selected the trials, assessed risk of bias and extracted data. We contacted study authors for additional information. The overall quality of the evidence was assessed using GRADE methods. MAIN RESULTS: Thirteen trials involving 2914 women were included, of whom 2494 were included in the analysis. Oil-soluble contrast media (OSCM) versus no interventionThe OSCM group had a higher rate of live birth (odds ratio (OR) 3.09, 95% CI 1.39 to 6.91, 1 RCT, 158 women, low quality evidence) and ongoing pregnancy (OR 3.59, 95% CI 2.06 to 6.26, 3 RCTs, 382 women, I(2) = 0%, low quality evidence) than women who had no intervention. Our findings suggest that among subfertile women with a 17% chance of an ongoing pregnancy if they have no intervention, the rate will increase to between 29% and 55% if they have tubal flushing with OSCM. Water-soluble contrast media (WSCM) versus no interventionThere was no evidence of a difference between the groups in rates of live birth (OR 1.13, 95% CI 0.67 to 1.91, 1 RCT, 334 women, very low quality evidence) or ongoing pregnancy (OR 1.14, 95% CI 0.71 to 1.84, 1 RCT, 334 women, very low quality evidence). OSCM versus WSCMTwo RCTs reported live birth: one found a higher live birth rate in the oil-soluble group and the other found no evidence of a difference between the groups. These studies were not pooled due to very high heterogeneity (I(2) = 93%). There was no evidence of a difference between the groups in rates of ongoing pregnancy, however there was high heterogeneity (OR 1.44, 95% CI 0.84 to 2.47, 5 RCTs, 1454 women, I(2) = 76%, random-effects model, very low quality evidence). OSCM plus WSCM versus WSCM aloneThere was no evidence of a difference between the groups in rates of live birth (OR 1.06, 95% CI 0.64 to 1.77, 1 RCT, 393 women, very low quality evidence) or ongoing pregnancy (OR 1.23, 95% CI 0.87 to 1.72, 4 RCTs, 633 women, I(2) = 0%, low quality evidence).There was no evidence of a difference between any of the interventions in rates of adverse events, but such events were poorly reported in most studies. AUTHORS' CONCLUSIONS: The evidence suggests that tubal flushing with oil-soluble contrast media may increase the chance of pregnancy and live birth compared to no intervention. Findings for other comparisons were inconclusive due to inconsistency and lack of statistical power. There was insufficient evidence on adverse events to reach firm conclusions. Further robust randomised controlled trials are needed.

Impact of a randomized trial on maintenance tocolysis on length of hospital admission of women with threatened preterm labor in The Netherlands.

INTRODUCTION: The APOSTEL-II trial was a multicenter randomized placebo-controlled trial, assessing the effectiveness of maintenance tocolysis with nifedipine. The trial showed maintenance tocolysis not to have an effect on perinatal outcome. Objective of the current study is to evaluate the effect of a negative trial on the length of hospital admission of women with threatened preterm labor. MATERIALS AND METHODS: We evaluated length of hospital admission of all patients admitted with threatened preterm labor with a gestational age <32 weeks in 8 perinatal centers that participated in the APOSTEL-II trial. We studied only the first admission with threatened preterm labor, readmissions were excluded. We distinguished between the period before, the period during and the period after the trial. In a subgroup analysis, we differentiated for the group of women who delivered and for the group of women who did not deliver during the initial admission. RESULTS: The mean length of hospital admission was 9.3 days before the start of the trial, 8.4 days during the recruitment period and 8.1 days after the trial was completed. The difference in mean length of hospital admission before and during the recruitment period was significantly different (p<001). COMMENTS: The length of hospital admission of women with threatened preterm labor is found to be reduced during the recruitment period of the APOSTEL-II trial. This shows that the conduct of a randomized controlled trial itself has the potential to change daily practice.

What is the risk of preterm delivery after arrested preterm labor?

OBJECTIVE: The aim of this study is to assess if women with arrested preterm labor (PTL) have an increased risk of preterm delivery (PTD) compared with healthy pregnant women, and if digital examination, fetal fibronectin (fFn) and cervical length (CL) are prognostic markers for PTD after arrested PTL. STUDY DESIGN: Prospective-matched cohort study among women with arrested PTL (cases) and healthy pregnant women (controls). RESULTS: We included 74 index cases and 74 controls. PTD occurred in 20 (27%) index cases and in 5 (7%) controls (hazard ratio [HR], 4.5; 95% confidence interval [CI], 1.7-12). A dilatation of the cervix ≥ 1 cm (HR, 9.1 [95% CI, 3.3-25], an fFn positive status (HR, 13 [95% CI, 4.3-40]), and a CL < 15 mm (HR, 11 [95% CI, 3.1-38]) increased this risk in cases compared with controls. Knowledge of the fFn result had additional value over the cervical dilatation or CL in the prediction of persistent PTD, with an increased risk in case of a positive fFn test. CONCLUSION: Women stay at increased risk for PTD after arrested PTL. This risk further increased in case of ≥ 1 cm cervical dilatation, CL < 15 mm and/or a positive fFn status.

Nifedipine versus atosiban in the treatment of threatened preterm labour (Assessment of Perinatal Outcome after Specific Tocolysis in Early Labour: APOSTEL III-Trial).

BACKGROUND: Preterm birth is the most common cause of neonatal morbidity and mortality. Postponing delivery for 48 hours with tocolytics to allow for maternal steroid administration and antenatal transportation to a centre with neonatal intensive care unit facilities is the standard treatment for women with threatening preterm delivery in most centres. However, there is controversy as to which tocolytic agent is the drug of first choice. Previous trials have focused on tocolytic efficacy and side effects, and are probably underpowered to detect clinically meaningfull differences in neonatal outcome. Thus, the current evidence is inconclusive to support a balanced recommendation for clinical practice. This multicenter randomised clinical trial aims to compare nifedipine and atosiban in terms of neonatal outcome, duration of pregnancy and maternal side effects. METHODS/DESIGN: The Apostel III trial is a nationwide multicenter randomised controlled study. Women with threatened preterm labour (gestational age 25 - 34 weeks) defined as at least 3 contractions per 30 minutes, and 1) a cervical length of ≤ 10 mm or 2) a cervical length of 11-30 mm and a positive Fibronectin test or 3) ruptured membranes will be randomly allocated to treatment with nifedipine or atosiban. Primary outcome is a composite measure of severe neonatal morbidity and mortality. Secondary outcomes will be time to delivery, gestational age at delivery, days on ventilation support, neonatal intensive care (NICU) admittance, length admission in neonatal intensive care, total days in hospital until 3 months corrected age, convulsions, apnoea, asphyxia, proven meningitis, pneumothorax, maternal side effects and costs. Furthermore, an economic evaluation of the treatment will be performed. Analysis will be by intention to treat principle. The power calculation is based on an expected 10% difference in the prevalence of adverse neonatal outcome. This implies that 500 women have to be randomised (two sided test, ß 0.2 at alpha 0.05). DISCUSSION: This trial will provide evidence on the optimal drug of choice in acute tocolysis in threatening preterm labour. CLINICAL TRIAL REGISTRATION: NTR2947, date of registration: June 20th 2011.

Facilitators and barriers to external cephalic version for breech presentation at term among health care providers in the Netherlands: a quantitative analysis.

OBJECTIVE: guidelines recommend that external cephalic version (ECV) should be offered to all women with a fetus in breech presentation at term. However, only 50-60% of the women receive an ECV attempt. We explored the determinants (barriers and facilitators) affecting the uptake of the guidelines among gynaecologists and midwives in the Netherlands. DESIGN: national online survey. SETTING: the Netherlands. PARTICIPANTS: gynaecologists and midwives. MEASUREMENTS: in the online survey, we identified the determinants that positively or negatively influenced the professionals׳ adherence to three key recommendations in the guidelines: (a) counselling, (b) advising for ECV, (c) arranging an ECV. Determinants were identified in a previously performed qualitative study and were categorised into five underlying constructs; attitude towards ECV, professional obligation, outcome expectations, self-efficacy and preconditions for successful ECV. We performed a multivariate analysis to assess the importance of the different constructs for adherence to the guideline. FINDINGS: 364 professionals responded to the survey. Adherence varied: 84% counselled, 73% advised, and 82% arranged an ECV for (almost) all their clients. Although 90% of respondents considered ECV to be an effective treatment for preventing caesarean childbirths, only 30% agreed that 'every client should undergo ECV'. Self-efficacy (perceived skills) was the most important determinant influencing adherence. KEY CONCLUSIONS: self-efficacy appears to be the most significant determinant for counselling, advising and arranging an ECV. IMPLICATIONS FOR PRACTICE: to improve adherence to the guidelines on ECV we must improve self-efficacy.

Lecithin/sphingomyelin ratio and lamellar body count for fetal lung maturity: a meta-analysis.

OBJECTIVE: To determine and compare the diagnostic accuracy of the lecithin/sphingomyelin (L/S) ratio and lamellar body count (LBC) in the prediction of neonatal respiratory distress syndrome (RDS). STUDY DESIGN: A systematic review was performed to identify studies comparing either the L/S ratio or the LBC with the occurrence of RDS published between January 1999 and February 2009. Two independent reviewers performed study selection and data extraction. For each study sensitivity and specificity were calculated. Summary receiver-operating characteristics (ROC) curves, assessing the diagnostic performance of both tests, were constructed. A subgroup analysis was performed to estimate the sensitivity and specificity of the various cut-off values. RESULTS: 13 studies were included. The ROC curves of the collected data illustrate that the LBC and L/S ratio perform equally well in the prediction of RDS. Comparison of the two summary ROC curves of each test indicates that the diagnostic performance of LBC might even have a slight advantage over L/S ratio. Due to the wide cut-off range it was not possible to define specific cut-off values with the best accuracy. CONCLUSION: We recommend replacing the L/S ratio as gold standard with the lamellar body count since the LBC is easy to perform, rapid, inexpensive, and available to all hospitals 24h per day.

[Insufficient evidence supporting iron supplementation in anaemia during pregnancy]. / Onvoldoende bewijs voor ijzersuppletie bij anemische zwangeren.

The Royal Dutch Organization of Midwives (KNOV) recently presented their practice guideline 'Anaemia in midwifery practice'. The guideline identified available evidence on diagnosis, prognosis and treatment of anaemia in pregnancy. Anaemia based on iron deficiency and subsequent treatment with iron supplementation are probably the most frequent aspects of care for pregnant women. However, there is surprisingly enough no evidence of the efficacy of iron supplementation treatment on relevant clinical outcomes in pregnant women with anaemia. We plead to make the next guideline a multidisciplinary one. Such a guideline may lead to a large pragmatic trial evaluating the efficacy of iron supplementation treatment for patients with anaemia.