Associations between maternal characteristics and pregnancy-related stress among low-risk mothers: An observational cross-sectional study

Background: Pregnancy is viewed as a major life event and, while the majority of healthy, low-risk women adapt well to pregnancy, there are those whose levels of stress are heightened by the experience.

Objectives: To determine the level of pregnancy-related stress experienced by a group of healthy, low-risk pregnant women and to relate the level of stress with a number of maternal characteristics.

Design: An observational cross-sectional study.

Setting: A large, urban maternity centre in Northern Ireland.

Participants: Of the 306 pregnant women who were invited to participate, 278 provided informed consent and were administered one self-complete questionnaire. Due to the withdrawal criteria, 15 questionnaires were removed from the analysis, resulting in a final sample of 263 healthy, low-risk pregnant women.

Methods: Levels of stress were measured using a self-report measure designed to assess specific worries and concerns relating to pregnancy. Maternal characteristics collected included age, marital status, social status, parity, obstetric history, perceived health status and 'wantedness' for the pregnancy. Regression analysis was undertaken using an ordinary linear regression model.

Results: The mean prenatal distress score in the sample was 15.1 (SD = 7.4; range 0-46). The regression model showed that women who had had previous pregnancies, with or without complications, had significantly lower mean prenatal distress scores than primiparous women (p < 0.01). Women reporting poorer physical health had higher mean prenatal distress scores than those who reported at least average health, while women aged 16-20 experienced a mean increase in the reported prenatal distress score (p < 0.05) in comparison to the reference group of 36 years and over.

Conclusions: This study brings to light the prevalence of pregnancy-related stress within a sample representative of healthy, low-risk women. Current antenatal care is ill-equipped to identify women suffering from high levels of stress; yet a growing body of research evidence links stress with adverse pregnancy outcomes. This study emphasises that healthy, low-risk women experience a range of pregnancy-related stress and identification of stress levels, either through the use of a simple stress measurement tool or through the associated factors identified within this research study, provides valuable data on maternal well-being. (C) 2010 Elsevier Ltd. All rights reserved.

Public health interventions in midwifery: a systematic review of systematic reviews

Background: Maternity care providers, particularly midwives, have a window of opportunity to influence pregnant women about positive health choices. This aim of this paper is to identify evidence of effective public health interventions from good quality systematic reviews that could be conducted by midwives.

Methods: Relevant databases including MEDLINE, Pubmed, EBSCO, CRD, MIDIRS, Web of Science, The Cochrane Library and Econlit were searched to identify systematic reviews in October 2010. Quality assessment of all reviews was conducted.

Results: Thirty-six good quality systematic reviews were identified which reported on effective interventions. The reviews were conducted on a diverse range of interventions across the reproductive continuum and were categorised under: screening; supplementation; support; education; mental health; birthing environment; clinical care in labour and breast feeding. The scope and strength of the review findings are discussed in relation to current practice. A logic model was developed to provide an overarching framework of midwifery public health roles to inform research policy and practice.

Conclusions: This review provides a broad scope of high quality systematic review evidence and definitively highlights the challenge of knowledge transfer from research into practice. The review also identified gaps in knowledge around the impact of core midwifery practice on public health outcomes and the value of this contribution. This review provides evidence for researchers and funders as to the gaps in current knowledge and should be used to inform the strategic direction of the role of midwifery in public health in policy and practice.

Public health education for midwives and midwifery students: a mixed methods study

Background: Current national and international maternity policy supports the importance of addressing public health goals and investing in early years. Health care providers for women during the reproductive and early postnatal period have the opportunity to encourage women to make choices that will impact positively on maternal and fetal health. Midwives are in a unique position, given the emphasis of the philosophy of midwifery care on building relationships and incorporating a holistic approach, to support women to make healthy choices with the aim of promoting health and preventing ill health. However, exploration of the educational preparation of midwives to facilitate public health interventions has been relatively limited. The aim of the study was to identify the scope of current midwifery pre registration educational provision in relation to public health and to explore the perspectives of midwives and midwifery students about the public health role of the midwife.

Methods: This was a mixed methods study incorporating a survey of Higher Educational Institutions providing pre registration midwifery education across the UK and focus groups with midwifery students and registered midwives.

Results: Twenty nine institutions (53% response) participated in the survey and nine focus groups were conducted (59 participants). Public health education was generally integrated into pre registration midwifery curricula as opposed to taught as a discrete subject. There was considerable variation in the provision of public health topics within midwifery curricula and the hours of teaching allocated to them. Focus group data indicated that it was consistently difficult for both midwifery students and midwives to articulate clearly their understanding and definition of public health in relation to midwifery.

Conclusions: There is a unique opportunity to impact on maternal and infant health throughout the reproductive period; however the current approach to public health within midwifery education should be reviewed to capitalise on the role of the midwife in delivering public health interventions. It is clear that better understanding of midwifery public health roles and the visibility of public health within midwifery is required in order to maximise the potential contribution of midwives to achieving short and long term public health population goals.

Regional Follow up of Late Preterm Neonatal Intensive Care Graduates: Methodological Considerations.

The aim is to guide researchers who are contemplating embarking on research by discussing the methodological challenges encountered in a retrospective follow-up study of three-year-old, late preterm infants (LPIs) who received neonatal intensive care (NIC) in Northern Ireland in 2006. The importance of effective research examining the longer term outcomes of infants admitted to NIC has received increasing recognition. Follow-up cohort and longitudinal studies have grown in number globally, yet the research methodology relating to follow up of NIC graduates is unclear. This paper highlights the methodological challenges of conducting retrospective follow-up research, from the initial planning stages through to the collection of data from the children, including identification of infants from a retrospective database, ethical issues, child-safety concerns and recruitment challenges. This paper creates an awareness of potential issues that may arise in follow-up research with NIC graduates. The paper also offers practical and effective examples of dealing with these issues, helping to ensure the smooth running of an ethical, professionally conducted, methodologically sound and clinically relevant follow-up study.

Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer

Epithelial ovarian cancer (EOC) has an innate susceptibility to become chemoresistant. Up to 30% of patients do not respond to conventional chemotherapy [paclitaxel (Taxol®) in combination with carboplatin] and, of those who have an initial response, many patients relapse. Therefore, an understanding of the molecular mechanisms that regulate cellular chemotherapeutic responses in EOC cells has the potential to impact significantly on patient outcome. The mitotic arrest deficiency protein 2 (MAD2), is a centrally important mediator of the cellular response to paclitaxel. MAD2 immunohistochemical analysis was performed on 82 high-grade serous EOC samples. A multivariate Cox regression analysis of nuclear MAD2 IHC intensity adjusting for stage, tumour grade and optimum surgical debulking revealed that low MAD2 IHC staining intensity was significantly associated with reduced progression-free survival (PFS) (p = 0.0003), with a hazard ratio of 4.689. The in vitro analyses of five ovarian cancer cell lines demonstrated that cells with low MAD2 expression were less sensitive to paclitaxel. Furthermore, paclitaxel-induced activation of the spindle assembly checkpoint (SAC) and apoptotic cell death was abrogated in cells transfected with MAD2 siRNA. In silico analysis identified a miR-433 binding domain in the MAD2 3' UTR, which was verified in a series of experiments. Firstly, MAD2 protein expression levels were down-regulated in pre-miR-433 transfected A2780 cells. Secondly, pre-miR-433 suppressed the activity of a reporter construct containing the 3'-UTR of MAD2. Thirdly, blocking miR-433 binding to the MAD2 3' UTR protected MAD2 from miR-433 induced protein down-regulation. Importantly, reduced MAD2 protein expression in pre-miR-433-transfected A2780 cells rendered these cells less sensitive to paclitaxel. In conclusion, loss of MAD2 protein expression results in increased resistance to paclitaxel in EOC cells. Measuring MAD2 IHC staining intensity may predict paclitaxel responses in women presenting with high-grade serous EOC.

MAD2 downregulation in hypoxia is independent of promoter hypermethylation

Aberrant expression of the MAD2 protein has been linked to chromosomal instability, malignant transformation and chemoresistance. Although reduced MAD2 expression is well recognised in human cancer cell lines, the mechanism(s) underlying its downregulation remain elusive. The objective of this study was to establish the impact of hypoxia on MAD2 expression and to investigate the potential role of aberrant promoter methylation as a possible mechanism of MAD2 downregulation. For this purpose, three ovarian cancer cell lines, displaying differing levels of MAD2, were treated with chromatin modifying drugs, pre and post-hypoxia exposure and a DHPLC analysis of DNA promoter methylation carried out. We show that hypoxia induces downregulation of MAD2 expression, independently of MAD2 promoter methylation. We also show no evidence of MAD2 promoter methylation in breast and prostate cancer cells or in breast cancer clinical material. While our findings provide no evidence for MAD2 promoter methylation, we show a concomitant upregulation of p21 with downregulation of MAD2 in hypoxia. Our in vitro results were also confirmed in an ovarian cancer tissue microarray (TMA), where a reciprocal staining of MAD2 and CAIX was found in 21/60 (35%) of tumours. In summary, MAD2 downregulation may be a crucial mechanism by which hypoxic cells become chemorefractory. This stems from our previous work where we demonstrated that MAD2 downregulation induces cellular senescence, a viable cellular fate, with resultant cellular resistance to paclitaxel. Moreover, MAD2 downregulation could play a central role in the induction of chemoresistance in hypoxia, a key tumour microenvironment associated with chemoresistance.

Recurrence of Urothelial Carcinoma of the Bladder: A Role for Insulin-Like Growth Factor-II Loss of Imprinting and Cytoplasmic E-Cadherin Immunolocalization

Purpose:This study documents the frequency of insulin-like growth factor-II (IGF-II) loss of imprinting (LOI) in a series of 87 bladder tissues. E-cadherin (CDH1) immunolocalization was also investigated due to the known redistribution of this adherence protein to the cytoplasm following exogenous exposure to IGF-II.
Experimental Design: Informative IGF-II cases were identified following DNA-PCR amplification and subsequent sequencing of the transcribable ApaI RFLP in exon 9 of IGF-II. Similar approaches using primer-specific cDNA templates identified the imprinting status of IGF-II in these informative cases. CDH1cellular localization was assessed on a tissue microarray platform of 114 urothelial carcinoma of the bladder (UCB) cases (70 pTanoninvasive and 44 pT1laminapropria invasive) using the commercially available Novocastra antibody.
Results: IGF-IILOI was evident in 7 of17 (41%) UCB tumors and 4 of11 (36%) tumor-associated normal urothelial samples.Two of four pT1grade 3 tumors, the subject of much debate concerning their suitability for radical cystectomy, showed LOI at the IGF-II locus. In those tumors showing IGF-II LOI, 4 of 7 (57%) displayed concomitant CDH1cytoplasmic staining. In contrast, only 3 of 10 (30%) IGF-IImaintenance ofimprinting tumorshad concomitant CDH1cytoplasmiclocalization. UCB cell lines displaying cytoplasmic CDH1immunolocalization expressed significantly higher levels of IGF-II (CAL29, HT1376, and RT112) compared with RT4, a cell line displaying crisp membranous CDH1staining. Finally, cytoplasmic CDH1staining was an independent predictor of a shorter time to recurrence independent of tumor grade and stage.
Conclusions: We suggest that CDH1 cytoplasmic immunolocalization as a result of increased IGF-II levels identifies those nonmuscle invasive presentations most likely to recur and therefore might benefit from more radical nonconserving bladder surgery