Inter-institutional variations in oxytocin augmentation during labour in German university hospitals: a national survey.

BACKGROUND: There are several international guidelines on oxytocin regimens for induction and augmentation of labour, but no agreement on a standardised regimen in Germany. This study collated and reviewed the oxytocin regimens used for labour augmentation in university hospitals, with the long-term aim of contributing to the development of a national clinical guideline. METHODS: Germany has 34 university hospital compounds, representing 39 maternity units. In this observational study we asked units to provide standard operational procedures on oxytocin augmentation during labour or provide the details in a structured survey. Data were collected on the dosage of oxytocin, type and volume of solutions used, indications and contraindications for use and discontinuation, case-specific administration, and on who developed the procedures. Findings were analysed descriptively. RESULTS: A total of 35 (90%) units participated in this study. Standard operating procedures were available in 24 units (69%), seven units (20%) did not have procedures and information was missing from four units (11%). Midwives participated in the development of standard operating procedures in 15 units (43%). Infusions were most commonly prepared using six units of oxytocin in 500 ml 0.9% normal saline solution (12 mU/ml). The infusions were started at 120 mU/hour and increased by 120 mU/hour at 20-min intervals up to a maximum dosage of 1200 mU/hour. The most common indication for use was delayed progress in labour. Infusions were stopped when uterine contractions became hypertonic and/or the fetal heart rate showed signs of distress. Most of the practices described aligned with international guidance. All units used reduced oxytocin dosages for women with a history of previous caesareans section, as recommended in the international guidelines, and restrictive use was advised in multiparous women. The main difference between units related to combined use of amniotomy and oxytocin, recommended by three guidelines but used in only four maternity units (11%). CONCLUSIONS: While there was considerable variation in the oxytocin augmentation procedures, most but not all practices used in these 35 German maternity units were comparable. Establishing a national guideline on the criteria for and administration of oxytocin for augmentation of labour would eliminate the observed differences and minimise risk of administration and medication error.

Intrapartum Care Working Patterns of Midwives: The Long Road to Models of Care in Germany.

INTRODUCTION: Midwifery models of care help to enhance perinatal health outcomes, women's satisfaction, and continuity of care. Despite the ubiquitous presence of certified midwives at births in Germany, no research has investigated the diversity of midwives' practice patterns. Describing the variety of working patterns through which midwives provide intrapartum care may contribute to improving the organisation of midwifery services. METHODS: This cross-sectional survey took place in the region of Hannover and Hildesheim, Germany. Midwives attending births and practicing in hospitals and/or out-of-hospital were able to participate. Midwives who did not attend births were excluded. We assessed midwives' scope of services, practice locations, employment patterns, continuity of care, midwife-led births, and midwives' level of agreement with core values of midwifery care. The response rate of the survey was 32.7 % (69/211). RESULTS: We found that midwifery care services can be described according to midwives' employment patterns. The majority of midwives were employed in a hospital to provide intrapartum care (74.2 %, n = 49), and most also independently offered one or more antenatal and/or postpartum service/s. Only 25.8 % (n = 17) of midwives offered their services independently (laborist model of care). Independent midwives attended births in all three possible settings: hospital, free-standing birth centres and home. Significantly more independent midwives than employed midwives offered antenatal care and lactation consulting. Compared to employed midwives, significantly more independent midwives provided antenatal, intrapartum, and postpartum care to the same women, were more likely to know women before labour, and to offer one-to-one care during labour. DISCUSSION: The most common practice pattern among surveyed midwives was 'employment in a hospital' for provision of intrapartum care with additional postpartum and few antenatal services provided on an independent basis. Midwives who worked solely independently reported more continuity and one-to-one intrapartum care with women. Most midwives did not work in patterns that offered continuity of care or consistently provide one-to-one care. Future research should assess whether women in Germany desire more services similar to caseload midwifery.

Functional dissection of breast cancer risk-associated TERT promoter variants.

The multi-cancer susceptibility locus at 5p15.33 includes TERT, encoding the telomerase catalytic subunit. Genome-wide association studies (GWAS) have identified six single nucleotide polymorphisms (SNPs) in the TERT promoter associated with decreased breast cancer risk, although the precise causal variants and their mechanisms of action have remained elusive. Luciferase reporter assays indicated that the protective haplotype reduced TERT promoter activity in human mammary epithelial and cancer cells in an estrogen-independent manner. Using single variant constructs, we identified rs3215401 and rs2853669 as likely functional variants. Silencing of MYC decreased TERT promoter activity but neither MYC nor ETS2 silencing conferred allele-specificity. In chromatin immunoprecipitation experiments, the ETS protein GABPA, but not ETS2 or ELF1, bound rs2853669 in an allele-specific manner in mammary epithelial cells. Investigation of open chromatin in mammoplasty samples suggested involvement of three additional variants, though not rs3215401 or rs2853669. Chromosome conformation capture revealed no interaction of the TERT promoter with regulatory elements in the locus, indicating limited local impact of candidate variants on the TERT promoter. Collectively, our functional studies of the TERT-CLPTM1L breast cancer susceptibility locus describe rs2853669 as a functional variant of this association signal among three other potentially causal variants and demonstrate the versatile mechanisms by which TERT promoter variants may affect breast cancer risk.

Hereditary breast cancer: ever more pieces to the polygenic puzzle.

Several susceptibility genes differentially impact on the lifetime risk for breast cancer. Technological advances over the past years have enabled the detection of genetic risk factors through high-throughput screening of large breast cancer case-control series. High- to intermediate penetrance alleles have now been identified in more than 20 genes involved in DNA damage signalling and repair, and more than 70 low-penetrance loci have been discovered through recent genome-wide association studies. In addition to classical germ-line mutation and single-nucleotide polymorphism, copy number variation and somatic mosaicism have been proposed as potential predisposing mechanisms. Many of the identified loci also appear to influence breast tumour characteristics such as estrogen receptor status. In this review, we briefly summarize present knowledge about breast cancer susceptibility genes and discuss their implications for risk prediction and clinical practice.