Induction of labour at or near term for suspected fetal macrosomia

Background: Women with a suspected large-for-dates fetus or a fetus with suspected macrosomia (birthweight greater than 4000 g) are at risk of operative birth or caesarean section. The baby is also at increased risk of shoulder dystocia and trauma, in particular fractures and brachial plexus injury. Induction of labour may reduce these risks by decreasing the birthweight, but may also lead to longer labours and an increased risk of caesarean section. Objectives: To assess the effects of a policy of labour induction at or shortly before term (37 to 40 weeks) for suspected fetal macrosomia on theway of giving birth and maternal or perinatal morbidity. Search methods: We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (31 January 2016), contacted trial authors and searched reference lists of retrieved studies. Selection criteria: Randomised trials of induction of labour for suspected fetal macrosomia. Data collection and analysis: Review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We contacted study authors for additional information. For key outcomes the quality of the evidence was assessed using the GRADE approach. Main results: We included four trials, involving 1190 women. It was not possible to blind women and staff to the intervention, but for other ’Risk of bias’ domains these studies were assessed as being at low or unclear risk of bias.Compared to expectant management, there was no clear effect of induction of labour for suspected macrosomia on the risk of caesarean section (risk ratio (RR) 0.91, 95% confidence interval (CI) 0.76 to 1.09; 1190 women; four trials, moderate-quality evidence) or instrumental delivery (RR 0.86, 95% CI 0.65 to 1.13; 1190 women; four trials, low-quality evidence). Shoulder dystocia (RR 0.60, 95% CI 0.37 to 0.98; 1190 women; four trials, moderate-quality evidence), and fracture (any) (RR 0.20, 95% CI 0.05 to 0.79; 1190 women; four studies, high-quality evidence) were reduced in the induction of labour group. There were no clear differences between groups for brachial plexus injury (two events were reported in the control group in one trial, low-quality evidence). There was no strong evidence of any difference between groups for measures of neonatal asphyxia; low five-minute infant Apgar scores (less than seven) or low arterial cord blood pH (RR 1.51, 95% CI 0.25 to 9.02; 858 infants; two trials, low-quality evidence ; and, RR 1.01, 95% CI 0.46 to 2.22; 818 infants; one trial, moderate-quality evidence, respectively). Mean birthweight was lower in the induction group, but there was considerable heterogeneity between studies for this outcome (mean difference (MD) -178.03 g, 95% CI -315.26 to -40.81; 1190 infants; four studies; I= 89%). In one study with data for 818 women, third- and fourth-degree perineal tears were increased in the induction group (RR 3.70, 95% CI 1.04 to 13.17). For outcomes assessed using GRADE, we based our downgrading decisions on high risk of bias from lack of blinding and imprecision of effect estimates. Authors’ conclusions: Induction of labour for suspected fetal macrosomia has not been shown to alter the risk of brachial plexus injury, but the power of the included studies to show a difference for such a rare event is limited. Also antenatal estimates of fetal weight are often inaccurate so many women may be worried unnecessarily, and many inductions may not be needed. Nevertheless, induction of labour for suspected fetal macrosomia results in a lower mean birthweight, and fewer birth fractures and shoulder dystocia. The unexpected observation in the induction group of increased perineal damage, and the plausible, but of uncertain significance, observation of increased use of phototherapy, both in the largest trial, should also be kept in mind. Findings from trials included in the review suggest that to prevent one fracture it would be necessary to induce labour in 60 women. Since induction of labour does not appear to alter the rate of caesarean delivery or instrumental delivery, it is likely to be popular with many women. In settings where obstetricians can be reasonably confident about their scan assessment of fetal weight, the advantages and disadvantages of induction at or near term for fetuses suspected of being macrosomic should be discussed with parents. Although some parents and doctors may feel the evidence already justifies induction, others may justifiably disagree. Further trials of induction shortly before term for suspected fetal macrosomia are needed. Such trials should concentrate on refining the optimum gestation of induction, and improving the accuracy of the diagnosis of macrosomia

Antenatal corticosteroids for fetal lung maturation in threatened preterm delivery: indications and administration

Introduction: Antenatal maternal administration of corticosteroids has been shown to reduce morbidity and mortality rates in preterm delivery. Threatened spontaneous or medically indicated preterm delivery for maternal or fetal indications between 24 and 34weeks of gestation with unknown fetal lung maturity status are indications for antenatal corticosteroid administration. Recent studies have challenged current practice of antenatal glucocorticoid use. The goal of this expert letter is to provide recommendations based for the clinical use of antenatal glucocorticoids based on the current evidence from published studies. Methods: The published literature (PubMed search), as well as the recommendations of other national societies, has been searched and taken into consideration for these recommendations. Results/conclusions: The standard regimen of antenatal corticosteroids involves a single course of 2×12mg betamethasone administered intramuscularly within 24h. The administration of corticosteroids usually is performed between 24 and 34weeks gestation. However, under particular circumstances it may be beneficial even at 23weeks and at 35-36weeks of gestation. The evidence to date is clearly against the routine administration of multiple antenatal steroid courses. In special clinical situations, a second course of betamethasone ("rescue course”) may be justifiable. Tocolysis during administration of steroids is not routinely indicated in the absence of contractions, cervical shortening or rupture of membrane

Procalcitonin levels during pregnancy, delivery and postpartum

Aims: To determine the normal value ranges of procalcitonin (PCT) in women with uncomplicated pregnancies. Methods: This prospective cohort study was conducted between May 2009 and February 2010 among 60 women without signs of clinical infection (31 vaginal deliveries, 29 cesarean sections) attending the maternity unit of the University of Geneva Hospitals. Sequential follow-up of PCT levels was performed at 24-28 weeks (n=7), 36-40 weeks (n=60), at delivery (n=59), and at days 2-3 (n=58) and 10 (n=53) postpartum using a sensitive PCT assay with a functional sensitivity of 0.06 μg/L. Results: Median levels of PCT were: 24-28 weeks: 0.043 μg/L (range 0.010-0.080); 36-40 weeks: 0.061 μg/L (range 0.010-0.110); at delivery: 0.068 μg/L (range 0.010-0.170); days 2-3: 0.200 μg/L (range 0.030-5.00); and day 10: 0.060 μg/L (range 0.020-0.120). At days 2-3 postpartum, three women had a PCT level between 0.25 μg/L and 0.5 μg/L and two women had a level higher than 0.5 μg/L. Conclusions: This study provides reference values for PCT during the third trimester, at delivery and at the immediate postpartum period. A cut-off PCT level of 0.25 μg/L can be used during the third trimester, at delivery, and at the immediate postpartum period to rule out infectio

Increased peri- and post-elective cesarean section morbidity in women infected with human immunodeficiency virus-1: a case-controlled multicenter study

Objective: Although elective cesarean section (ECS) is the currently recommended modality for delivering women infected with the human immunodeficiency virus (HIV), historical evidence suggests that they are at higher risk of postoperative complications than noninfected women. Those risks have to be carefully balanced against the presumed minimal benefit of ECS, especially in the case of low viral load and high CD4 counts. We therefore compared the incidence and type of post-ECS complications in HIV-infected women, most with low viral loads and high CD4 cell counts, with those in matched noninfected women treated by the same surgical teams. Study design: A Swiss 8-center, prospective, matched case-control study compared minor and major post-ECS complication prevalence, hospital stay and confounding factors (surgeon experience) between HIV-infected and noninfected women. Results: Minor complications in the 53 matched pairs were eightfold more frequent overall in infected women. More frequent specific minor complications were anemia, blood loss and urinary tract infection. Yet the surgeons performing ECS in infected women were more experienced. Complications prolonged hospital stay in infected women. Major complication rates did not significantly differ between the groups. Conclusion: HIV-positive women have a higher risk of post-ECS morbidity, even with high CD4 counts and low viral load. Therefore, the blanket recommendation of ECS in HIV-infected women requires a revie

Intravenous iron treatment in pregnancy: comparison of high-dose ferric carboxymaltose vs. iron sucrose

Objective: Oral iron substitution has shown to be insufficient for treatment of severe iron deficiency anemia in pregnancy. Ferric carboxymaltose is a new intravenous (i.v.) iron formulation promising to be more effective and as safe as iron sucrose. We aimed to assess side effects and tolerance of ferric carboxymaltose compared to i.v. iron sucrose in pregnant women. Methods: We performed a retrospective analysis of 206 pregnant women who were treated either with ferric carboxymaltose or iron sucrose for iron-deficiency anemia with intolerability to oral iron substitution, or insufficient hemoglobin increase after oral iron treatment, or need for rapid hemoglobin reconstitution. Primary endpoint was to evaluate the maternal safety and tolerability. Secondary endpoint was to assess efficacy of the treatment and exclude safety concerns for the fetus. Results: The incidence of drug-related adverse events was low and mostly mild in both groups. Mild adverse events occurred in 7.8% for ferric carboxymaltose and in 10.7% for iron sucrose. The mean rise of hemoglobin value was 15.4 g/L for ferric carboxymaltose and 11.7 g/L for iron sucrose. Conclusion: Ferric carboxymaltose administration in pregnant women is well tolerated and is not associated with any relevant clinical safety concerns. Ferric carboxymaltose has a comparable safety profile to iron sucrose but offers the advantage of a much higher iron dosage at a time reducing the need for repeated applications and increasing patients' comfort. Ferric carboxymaltose is the drug of choice, if i.v. iron treatment becomes necessary in the second or third trimester of pregnanc

Effect of crew resource management training in a multidisciplinary obstetrical setting

Objective To assess the effect of a Crew Resource Management (CRM) intervention specifically designed to improve teamwork and communication skills in a multidisciplinary obstetrical setting. Method Design-A before-and-after cross-sectional study designed to assess participants' satisfaction, learning and change in behaviour, according to Kirkpatrick's evaluation framework for training programmes. Setting-Labour and delivery units of a large university-affiliated hospital. Participants-Two hundred and thirty nine midwives, nurses, physicians and technicians from the department of anaesthesia, obstetrics and paediatrics. Intervention-All participants took part in a CRM-based training programme specifically designed to improve teamwork and communication skills. Principal measures of outcome-We assessed participants' satisfaction by means of a 10-item standardized questionnaire. A 36-item survey was administered before and after the course to assess participants' learning. Behavioural change was assessed by a 57-item safety attitude questionnaire measuring staff's change in attitude to safety over 1 year of programme implementation. Results Most participants valued the experience highly and 63-90% rated their level of satisfaction as being very high. Except for seven items, the 36-item survey testing participants' learning demonstrated a significant change (P < 0.05) towards better knowledge of teamwork and shared decision making after the training programme. Over the year of observation, there was a positive change in the team and safety climate in the hospital [odds ratio (OR) 2.9, 95% confidence interval (CI) (1.3-6.3) to OR 4.7, 95% CI (1.2-17.2)]. **There was also improved stress recognition [OR 2.4, 95% CI (1.2-4.8) to OR 3.0, 95% CI (1.0-8.8)]. Conclusion The implementation of a training programme based on CRM in a multidisciplinary obstetrical setting is well accepted and contributes to a significant improvement in interprofessional teamwor

A teratocarcinoma-like human embryonic stem cell (hESC) line and four hESC lines reveal potentially oncogenic genomic changes

The first Swiss human embryonic stem cell (hESC) line, CH-ES1, has shown features of a malignant cell line. It originated from the only single blastomere that survived cryopreservation of an embryo, and it more closely resembles teratocarcinoma lines than other hESC lines with respect to its abnormal karyotype and its formation of invasive tumors when injected into SCID mice. The aim of this study was to characterize the molecular basis of the oncogenicity of CH-ES1 cells, we looked for abnormal chromosomal copy number (by array Comparative Genomic Hybridization, aCGH) and single nucleotide polymorphisms (SNPs). To see how unique these changes were, we compared these results to data collected from the 2102Ep teratocarcinoma line and four hESC lines (H1, HS293, HS401 and SIVF-02) which displayed normal G-banding result. We identified genomic gains and losses in CH-ES1, including gains in areas containing several oncogenes. These features are similar to those observed in teratocarcinomas, and this explains the high malignancy. The CH-ES1 line was trisomic for chromosomes 1, 9, 12, 17, 19, 20 and X. Also the karyotypically (based on G-banding) normal hESC lines were also found to have several genomic changes that involved genes with known roles in cancer. The largest changes were found in the H1 line at passage number 56, when large 5 Mb duplications in chromosomes 1q32.2 and 22q12.2 were detected, but the losses and gains were seen already at passage 22. These changes found in the other lines highlight the importance of assessing the acquisition of genetic changes by hESCs before their use in regenerative medicine applications. They also point to the possibility that the acquisition of genetic changes by ESCs in culture may be used to explore certain aspects of the mechanisms regulating oncogenesis

A teratocarcinoma-like human embryonic stem cell (hESC) line and four hESC lines reveal potentially oncogenic genomic changes

The first Swiss human embryonic stem cell (hESC) line, CH-ES1, has shown features of a malignant cell line. It originated from the only single blastomere that survived cryopreservation of an embryo, and it more closely resembles teratocarcinoma lines than other hESC lines with respect to its abnormal karyotype and its formation of invasive tumors when injected into SCID mice. The aim of this study was to characterize the molecular basis of the oncogenicity of CH-ES1 cells, we looked for abnormal chromosomal copy number (by array Comparative Genomic Hybridization, aCGH) and single nucleotide polymorphisms (SNPs). To see how unique these changes were, we compared these results to data collected from the 2102Ep teratocarcinoma line and four hESC lines (H1, HS293, HS401 and SIVF-02) which displayed normal G-banding result. We identified genomic gains and losses in CH-ES1, including gains in areas containing several oncogenes. These features are similar to those observed in teratocarcinomas, and this explains the high malignancy. The CH-ES1 line was trisomic for chromosomes 1, 9, 12, 17, 19, 20 and X. Also the karyotypically (based on G-banding) normal hESC lines were also found to have several genomic changes that involved genes with known roles in cancer. The largest changes were found in the H1 line at passage number 56, when large 5 Mb duplications in chromosomes 1q32.2 and 22q12.2 were detected, but the losses and gains were seen already at passage 22. These changes found in the other lines highlight the importance of assessing the acquisition of genetic changes by hESCs before their use in regenerative medicine applications. They also point to the possibility that the acquisition of genetic changes by ESCs in culture may be used to explore certain aspects of the mechanisms regulating oncogenesis

Tocolysis for preterm labor: Expert opinion

Tocolysis is an important treatment in the improvement of outcome in preterm labor and preterm birth, provided that its use follows clear evidence-based recommendations. In this expert opinion, the most recent evidence about efficacy and side effects of different tocolytics is being reviewed and evidence-based recommendation about diagnosis and treatment of preterm labor is given. Further aspects such as progesterone administration or antibiotic treatment for the prevention of preterm birth are included. Our review demonstrates that an individualized choice of different tocolytics and additional treatments is necessary to improve short- and long-term neonatal outcome in preterm labor and preterm birth

Immortalized human skin fibroblast feeder cells support growth and maintenance of both human embryonic and induced pluripotent stem cells

BACKGROUND Feeder cells are frequently used for the early-stage of derivation and culture of human embryonic stem cell (hESC) lines. METHODS We established a conditionally immortalized human foreskin fibroblast line that secreted basic fibroblast growth factor (bFGF). These cells were used as feeder cells for hESC culture and induced pluripotent stem (iPS) cell derivation and expansion. This conditional immortalization was performed using lentiviral vector (LV) mediated transduction of Bmi-1 and human telomerase reverse transcriptase genes and the resulting cell line was further modified by LV-mediated transduction of a secreted form of bFGF gene product. Three different laboratories have tested whether this feeder cell line could support the maintenance of four different hESC lines. RESULTS Immortalized fibroblasts secreting stable amounts of bFGF supported the growth of all hESC lines, which remained pluripotent and had a normal karyotype for at least 10 passages. Even at high passage (p56), these modified cells, when used as feeders, could support iPS derivation and propagation. Derived iPS cells expressed pluripotency markers, had hESC morphology and produced tissue components of the three germ layers when differentiated in vitro. CONCLUSION These modified fibroblasts are useful as a genetically-defined feeder cell line for reproducible and cost-effective culture of both hESC and iPS cell