The application of epiphenotyping approaches to DNA methylation array studies of the human placenta.

BACKGROUND: Genome-wide DNA methylation (DNAme) profiling of the placenta with Illumina Infinium Methylation bead arrays is often used to explore the connections between in utero exposures, placental pathology, and fetal development. However, many technical and biological factors can lead to signals of DNAme variation between samples and between cohorts, and understanding and accounting for these factors is essential to ensure meaningful and replicable data analysis. Recently, "epiphenotyping" approaches have been developed whereby DNAme data can be used to impute information about phenotypic variables such as gestational age, sex, cell composition, and ancestry. These epiphenotypes offer avenues to compare phenotypic data across cohorts, and to understand how phenotypic variables relate to DNAme variability. However, the relationships between placental epiphenotyping variables and other technical and biological variables, and their application to downstream epigenome analyses, have not been well studied. RESULTS: Using DNAme data from 204 placentas across three cohorts, we applied the PlaNET R package to estimate epiphenotypes gestational age, ancestry, and cell composition in these samples. PlaNET ancestry estimates were highly correlated with independent polymorphic ancestry-informative markers, and epigenetic gestational age, on average, was estimated within 4 days of reported gestational age, underscoring the accuracy of these tools. Cell composition estimates varied both within and between cohorts, as well as over very long placental processing times. Interestingly, the ratio of cytotrophoblast to syncytiotrophoblast proportion decreased with increasing gestational age, and differed slightly by both maternal ethnicity (lower in white vs. non-white) and genetic ancestry (lower in higher probability European ancestry). The cohort of origin and cytotrophoblast proportion were the largest drivers of DNAme variation in this dataset, based on their associations with the first principal component. CONCLUSIONS: This work confirms that cohort, array (technical) batch, cell type proportion, self-reported ethnicity, genetic ancestry, and biological sex are important variables to consider in any analyses of Illumina DNAme data. We further demonstrate the specific utility of epiphenotyping tools developed for use with placental DNAme data, and show that these variables (i) provide an independent check of clinically obtained data and (ii) provide a robust approach to compare variables across different datasets. Finally, we present a general framework for the processing and analysis of placental DNAme data, integrating the epiphenotype variables discussed here.

Coping During Pregnancy Following Exposure to a Natural Disaster: The QF2011 Queensland Flood Study.

INTRODUCTION: This study investigated how coping strategies moderated the impact of disaster-related objective hardship on subjective distress in pregnant women. METHODS: The objective hardship (exposure severity), subjective distress (Peritraumatic Distress Inventory, Peritraumatic Dissociative Experiences Questionnaire and Impact of Event Scale-Revised) and coping styles (Brief COPE) of pregnant women (N = 226) exposed to the 2011 Queensland, Australia flood were assessed. Moderation analyses were used to assess how coping strategies moderated the relationship between objective hardship and subjective distress levels. RESULTS: We found that the more severe the objective flood exposure, the greater the women's subjective distress. The moderation analyses were significant for the Brief COPE's three coping styles (i.e., problem-focused coping, emotion-focused coping, and dysfunctional coping). For women experiencing high levels of objective hardship, problem-focused (∆R2 = 1.7%) and dysfunctional coping (∆R2 = 1.5%) elevated subjective distress levels. For women experiencing low or moderate levels of objective hardship, emotion-focused coping reduced levels of subjective distress (∆R2 = 1.3%). A three-way interaction between objective hardship, emotion-focused coping, and dysfunctional coping approached significance (∆R2 = 1.0%), indicating a protective role of emotion-focused coping under high levels of objective hardship, for women who frequently use maladaptive coping strategies. LIMITATIONS: Sample was generally high SES and no measure of social support was available. CONCLUSION: Results suggest that both problem-focused and dysfunctional coping strategies were maladaptive for women with relatively high exposure levels. Overall, emotion-focused coping strategies were more likely than problem-focused or dysfunctional strategies to reduce pregnant women's subjective distress following the flood.

Prenatal maternal stress shapes children's theory of mind: the QF2011 Queensland Flood Study.

Research shows that stress in pregnancy has powerful and enduring effects on many facets of child development, including increases in behavior problems and neurodevelopmental disorders. Theory of mind is an important aspect of child development that is predictive of successful social functioning and is impaired in children with autism. A number of factors related to individual differences in theory of mind have been identified, but whether theory of mind development is shaped by prenatal events has not yet been examined. In this study we utilized a sudden onset flood that occurred in Queensland, Australia in 2011 to examine whether disaster-related prenatal maternal stress predicts child theory of mind and whether sex of the child or timing of the stressor in pregnancy moderates these effects. Higher levels of flood-related maternal subjective stress, but not objective hardship, predicted worse theory of mind at 30 months (n=130). Further, maternal cognitive appraisal of the flood moderated the effects of stress in pregnancy on girls' theory of mind performance but not boys'. These results illuminate how stress in pregnancy can shape child development and the findings are discussed in relation to biological mechanisms in pregnancy and stress theory.

How optimal caseload midwifery can modify predictors for preterm birth in young women: Integrated findings from a mixed methods study.

OBJECTIVE: to identify possible mechanisms by which caseload midwifery reduces preterm birth for young childbearing women. DESIGN: a mixed methods triangulation, convergence design was used to answer the research question 'How does the way maternity care is provided affect the health and well-being of young women and their babies?' The project generated quantitative and qualitative findings which were collected and analysed concurrently then separately analysed and published. The research design enabled integration of the quantitative and qualitative findings for further interpretation through a critical pragmatic lens. SETTING: a tertiary maternity hospital in Australia providing care to approximately 500 pregnant young women (aged 21 years or less) each year. Three distinct models of care were offered: caseload midwifery, young women's clinic, and standard 'fragmented' care. PARTICIPANTS: a cohort study included data from 1971 young women and babies during 2008-2012. An ethnographic study included analysis of focus group interviews with four caseload midwives in the young women's midwifery group practice; as well as ten pregnant and postnatal young women receiving caseload midwifery care. FINDINGS: integrated analysis of the quantitative and qualitative findings suggested particular features in the model of care which facilitated young women turning up for antenatal care (at an earlier gestation and more frequently) and buying in to the process (disclosing risks, engaging in self-care activities and accepting referrals for assistance). We conceptualised that Optimal Caseload Midwifery promotes Synergistic Health Engagement between midwife and the young woman. KEY CONCLUSIONS: optimal Caseload Midwifery (which includes midwives with specific personal attributes and philosophical commitments, along with appropriate institutional infrastructure and support) facilitates midwives and young clients to develop trusting relationships and engage in maternity care. Health engagement can modify predictors for preterm birth that are common amongst pregnant adolescents by promoting earlier maternity booking, sufficient antenatal care, greater emotional resilience, ideal gestational weight gain, less smoking/drug use, and fewer untreated genito-urinary infections. IMPLICATIONS FOR PRACTICE: the institutional infrastructure and managerial support for caseload midwifery should value and prioritise the philosophical commitments and personal attributes required to optimise the model. Furthermore the location of visits, between appointment access to primary midwife, and back-up system should be organised to optimise the midwife-woman relationship in order to promote the young woman's engagement with maternity care.

Control of Zymoseptoria tritici cause of septoria tritici blotch of wheat using antifungal Lactobacillus strains.

AIMS: This study explored an effective biological control agent based on lactic acid bacteria culture or culture supernatant, which was effective against fungicide-resistant Zymoseptoria tritici, which causes septoria tritici blotch (STB). METHODS AND RESULTS: Three lactic acid bacteria strains which exhibited broad antifungal activity were investigated for their potential to control Z. tritici. Plate assays, liquid culture growth inhibition assays and STB biocontrol seedling tests were employed. Lactobacillus brevis JJ2P and Lactobacillus reuteri R2 caused significant fungal inhibition as observed by large mycelium clearing on modified MRS agar. Cell-free culture supernatants of Lact. brevis JJ2P and Lact. reuteri R2 showed antifungal activity against Z. tritici, as observed by mycelial radial growth inhibition and liquid culture growth inhibition. Cell-free supernatants of these anti-Z. tritici LAB strains were assessed in vivo for their abilities to inhibit STB development in seedling tests. Lact. brevis JJ2P was capable of inhibiting disease development and significantly reduced the diseased leaf area covered with pycnidia. CONCLUSIONS: Biological control accomplished by beneficial micro-organisms such as Lact. brevis JJ2P may represent an alternative control strategy for reducing STB. SIGNIFICANCE AND IMPACT OF THE STUDY: Globally, STB is regarded as one of the most important diseases of wheat. Control of Z. tritici is heavily reliant on fungicide application. The recent emergence of resistance or reduced sensitivity to fungicides among Z. tritici populations has urgently called for the development of new control strategies.

How does group antenatal care function within a caseload midwifery model? A critical ethnographic analysis.

BACKGROUND: caseload midwifery and CenteringPregnancy™ (a form of group antenatal care) are two models of maternity care that are separately associated with better clinical outcomes, maternal satisfaction scores and positive experiences compared to standard care. One study reported exclusively on younger women׳s experiences of caseload midwifery; none described younger women׳s experiences of group antenatal care. We retrieved no studies on the experiences of women who received a combination of caseload midwifery and group antenatal care. OBJECTIVE: examine younger women׳s experiences of caseload midwifery in a setting that incorporates group antenatal care. DESIGN: a critical, focused ethnographic approach. SETTING: the study was conducted in an Australian hospital and its associated community venue from 2011 to 2013. PARTICIPANTS: purposive sampling of younger (19-22 years) pregnant and postnatal women (n=10) and the caseload midwives (n=4) who provided group antenatal care within one midwifery group practice. METHODS: separate focus group interviews with women and caseload midwives, observations of the setting and delivery of group antenatal care, and examination of selected documents. Thematic analyses of the women׳s accounts have been given primary significance. Coded segments of the midwives interview data, field notes and documents were used to compare and contrast within these themes. FINDINGS: we report on women׳s first encounters with the group, and their interactions with peers and midwives. The group setting minimised the opportunity for the women and midwives to get to know each other. CONCLUSIONS: this study challenges the practice of combining group antenatal care with caseload midwifery and recommends further research.

Can the fetal fibronectin test be used by remote dwelling pregnant women to predict the onset of labour at term and delay transfer for birth in regional settings?

INTRODUCTION: The closure of rural maternity units in Australia means an increasing number of women are transferred into major centres to await birth. Accurately excluding the onset of labour could delay relocation. The fetal fibronectin (fFN) test is used to predict preterm birth; however, the accuracy of this test for determining impending term birth is unclear. METHODS: 75 women were recruited to this study from two remote maternity units. Eligibility criteria were: aged ≥18 years, singleton pregnancy, 37+0-40+3 weeks (37 weeks to 40 weeks and 3 days gestation) and no indication for induction of labour or caesarean section in next 7 days. The Quikcheck fFN® test was performed at 37 weeks and then repeated at 7 day intervals. Time-to-birth from test date was modelled using linear regression. Logistic regression models estimated odds of birth within 7 days. Separate models considered first and last test results and those at 38 weeks; adjusted for use of lubricant and gestational age. RESULTS: A shorter time-to-birth was found in women with positive compared with negative fFN tests; significant at first fFN test (adjusted mean difference [AMD] 5.4 days, 95% CI 2.0-8.8) and 38 weeks (AMD 5.7 days, 95% CI 2.2-9.2 days). A positive test was also associated with a significant increase in the odds of birthing within 7 days: first fFN test adjusted odds ratio (AOR) 11.0 (95% CI 2.5-48.7), 38 weeks test AOR 14.4 (95% CI 3.4-60.2), last fFN test AOR 8.1 (95% CI 1.6-39.8). However, of women who gave birth within 7 days of testing a significant proportion had a negative fFN result; first fFN test 8/17(47.1%), 38 weeks test 4/14(28.6%) and last fFN test 29/58(50.0%). CONCLUSION: The presence of fFN in cervical secretions was associated with impending term birth but its absence did not reliably exclude the onset of birth. Delaying transfer based on these findings would result in some women birthing in their home communities.

'Closing the Gap': how maternity services can contribute to reducing poor maternal infant health outcomes for Aboriginal and Torres Strait Islander women.

CONTEXT: The reproductive health outcomes for Aboriginal and Torres Strait Islander mothers and infants are significantly poorer than they are for other Australians; they worsen with increasing remoteness where the provision of services becomes more challenging. Australia has committed to 'Overcoming Indigenous Disadvantage' and 'Closing the Gap' in health outcomes. ISSUES: Fifty-five per cent of Aboriginal and Torres Strait Islander birthing women live in outer regional and remote areas and suffer some of the worst health outcomes in the country. Not all of these women are receiving care from a skilled provider, antenatally, in birth or postnatally while the role of midwives in reducing maternal and newborn mortality and morbidity is under-utilised. The practice of relocating women for birth does not address their cultural needs or self-identified risks and is contributing to these outcomes. An evidence based approach for the provision of maternity services in these areas is required. Australian maternal mortality data collection, analysis and reporting is currently insufficient to measure progress yet it should be used as an indicator for 'Closing the Gap' in Australia. LESSONS LEARNED: A more intensive, coordinated strategy to improve maternal infant health in rural and remote Australia must be adopted. Care needs to address social, emotional and cultural health needs, and be as close to home as possible. The role of midwives can be enabled to provide comprehensive, quality care within a collaborative team that includes women, community and medical colleagues. Service provision should be reorganised to match activity to need through the provision of caseload midwives and midwifery group practices across the country. Funding to embed student midwives and support Aboriginal and Torres Strait Islander women in this role must be realised. An evidence base must be developed to inform the provision of services in these areas; this could be through the testing of the Rural Birth Index in Australia. The provision of primary birthing services in remote areas, as has occurred in some Inuit and New Zealand settings, should be established. 'Birthing on Country' that incorporates local knowledge, on-site midwifery training and a research and evaluation framework, must be supported.

Reproductive health, infertility and sexually transmitted infections in indigenous women in a remote community in the Northern Territory.

OBJECTIVE: To investigate markers of reproductive health in a remote Indigenous community in Northern Australia. METHODS: A retrospective, cross-sectional analysis of case notes of 342 women between the ages of 20 and 45 years, living in one community in a remote region of the Northern Territory. RESULTS: The total rate of current infertility in the community was 26.3%; 8.2% for primary infertility and 18.1% for secondary infertility. An additional 3.3% of women had resolved infertility. Only 43% of the women had sought medical help for the problem. A history of ectopic pregnancy was recorded in 2.6%, stillbirth in 1.8%, miscarriage in 14.3% and neonatal death in 12.3%. Depot steroidal contraception or tubal ligation were used by 50% of the women but 45.9% used no contraception. A history of pelvic inflammatory disease (PID), T. vaginalis N. gonorrhoeae, genital C. trachomatis infection, syphilis or bacterial vaginosis was noted in 32%, 46%, 27%, 30%, 41% and 9% respectively. Current alcohol consumption was reported in 23% and cigarette smoking in 76%. In multivariate analysis, infertility was strongly associated with PID (adjusted OR 8.5), alcohol consumption (AOR 3.1), T. vaginalis (AOR 2.5), N. gonorrhoeae (AOR 2.2) and bacterial vaginosis (AOR 2.9). CONCLUSION: Reproductive health is poor in this community of Indigenous women, with endemic levels of STDs, PID and tobacco consumption. The absence of barrier contraception (e.g. condoms, diaphragms) has implications for HIV and STD control. Clinical and public health interventions are urgently required but the implementation of these is hindered by a number of structural, social and economic barriers.

Trial of scar--team midwifery makes a difference.

'Once, and certainly twice, a caesar always a caesar.' Where is the evidence to support this often expressed belief? As discussed by Roberts (1991) this is simply an opinion and not based on any form of scientific inquiry. This article describes two women requesting a vaginal delivery, one having had two, and the other, three previous Caesarean Sections. The doctors they had approached were unwilling to support them in their request and they had been told they would be unable to have a vaginal delivery. Both women decided to utilise the hospital's Team Midwifery service for their antenatal and intrapartum care and found the team, together with one of the hospital Registrars, sympathetic to their wishes. Carefully coordinated communication between these groups, and a supportive working relationship, enabled both women to have their vaginal delivery, one of which involved a twin birth. These are the type of services and support that should be available to all women.