Supporting carers to improve patient safety and maintain their well-being in transitions from mental health hospitals to the community: A prioritisation nominal group technique.

INTRODUCTION: Carers of people with mental illness may face distinct challenges, including navigating fragmented health and social services during discharge from mental health hospitals. Currently, limited examples of interventions that support carers of people with mental illness in improving patient safety during transitions of care exist. We aimed to identify problems and solutions to inform future carer-led discharge interventions, which is imperative for ensuring patient safety and the well-being of carers. METHODS: The nominal group technique was used which combines both qualitative and quantitative data collection methods in four distinct phases: (1) problem identification, (2) solution generation, (3) decision making and (4) prioritisation. The aim was to combine expertise from different stakeholder groups (patients, carers and academics with expertise in primary/secondary care, social care or public health) to identify problems and generate solutions. RESULTS: Twenty-eight participants generated potential solutions that were grouped into four themes. The most acceptable solution for each was as follows: (1) 'Carer Involvement and Improving Carer Experience' a dedicated family liaison worker, (2) 'Patient Wellness and Education' adapting and implementing existing approaches to help implement the patient care plan, (3) 'Carer Wellness and Education' peer/social support interventions for carers and (4) 'Policy and System Improvements' understanding the co-ordination of care. CONCLUSION: The stakeholder group concurred that the transition from mental health hospitals to the community is a distressing period, where patients and carers are particularly vulnerable to safety and well-being risks. We identified numerous feasible/acceptable solutions to enable carers to improve patient safety and maintain their own mental wellbeing. PATIENT AND PUBLIC CONTRIBUTION: Patient and public contributors were represented in the workshop and the focus of the workshop was to identify the problems they faced and co-design potential solutions. Patient and public contributors were involved in the funding application and study design.

Health-care practitioners' assessment and observations of birth trauma in mothers and partners.

BACKGROUND: Evidence shows that traumatic childbirth can cause ongoing distress, often referred to as birth trauma. This can have an impact on parents and the couple relationship, and consequently identifying and supporting parents with birth trauma is important to practice. AIM: To investigate the experiences of health-care practitioners from the United Kingdom (UK) in assessment for birth trauma, perceived occurrence of birth trauma and observed impact on parents and the couple relationship. METHODS: An online survey of UK health-care practitioners working with parents in the first postnatal year. RESULTS: A sample of 202 practitioners reported identifying birth trauma in 34.4% of mothers and 25.0% of partners. Assessment for birth trauma was only conducted for 50.3% of mothers and 25.9% of partners. The most observed symptoms were re-experiencing among mothers (87.1%) and avoidance among partners (50.9%). Birth trauma was perceived as impacting on the couple relationship for 29.8% of mothers and 26.9% of partners. Written responses provided more detailed observations of the impact of birth trauma. CONCLUSION: Understanding how birth trauma may present differently in mothers and partners could support effective assessment. Once birth trauma is identified, parents require personalised support to help them cope with the impact.

Organ Donation at the End of Life: Experiences From the 3 Wishes Project.

PURPOSE: The 3 Wishes Project (3WP) promotes holistic end-of-life care in the intensive care unit (ICU) to honor dying patients, support families, and encourage clinician compassion. Organ donation is a wish that is sometimes made by, or on behalf of, critically ill patients. Our objective was to describe the interface between the 3WP and organ donation as experienced by families, clinicians, and organ donation coordinators. METHODS: In a multicenter evaluation of the 3WP in 4 Canadian ICUs, we conducted a thematic analysis of transcripts from interviews and focus groups with clinicians, organ donation coordinators, and families of dying or died patients for whom donation was considered. RESULTS: We analyzed transcripts from 26 interviews and 2 focus groups with 18 family members, 17 clinicians, and 6 organ donation coordinators. The central theme describes the mutual goals of the 3WP and organ donation-emphasizing personhood and agency across the temporal continuum of care. During family decision-making, conversations encouraged by the 3WP can facilitate preliminary discussions about donation. During preparation for donation, memory-making activities supported by the 3WP redirect focus toward personhood. During postmortem family care, the 3WP supports families, including when donation is unsuccessful, and highlights aspirational pursuits of donation while encouraging reflections on other fulfilled wishes. CONCLUSIONS: Organ donation and the 3WP provide complementary opportunities to engage in value-based conversations during the dying process. The shared values of these programs may help to incorporate organ donation and death into a person's life narrative and incorporate new life into a person's death narrative.

Primary-level worker interventions for the care of people living with mental disorders and distress in low- and middle-income countries.

BACKGROUND: Community-based primary-level workers (PWs) are an important strategy for addressing gaps in mental health service delivery in low- and middle-income countries.  OBJECTIVES: To evaluate the effectiveness of PW-led treatments for persons with mental health symptoms in LMICs, compared to usual care.  SEARCH METHODS: MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, ICTRP, reference lists (to 20 June 2019).   SELECTION CRITERIA: Randomised trials of PW-led or collaborative-care interventions treating people with mental health symptoms or their carers in LMICs.  PWs included: primary health professionals (PHPs), lay health workers (LHWs), community non-health professionals (CPs).  DATA COLLECTION AND ANALYSIS: Seven conditions were identified apriori and analysed by disorder and PW examining recovery, prevalence, symptom change, quality-of-life (QOL), functioning, service use (SU), and adverse events (AEs).  Risk ratios (RRs) were used for dichotomous outcomes; mean difference (MDs), standardised mean differences (SMDs), or mean change differences (MCDs) for continuous outcomes.  For SMDs, 0.20 to 0.49 represented small, 0.50 to 0.79 moderate, and ≥0.80 large clinical effects.  Analysis timepoints: T1 (<1 month), T2 (1-6 months), T3 ( >6 months) post-intervention.  MAIN RESULTS: Description of studies 95 trials (72 new since 2013) from 30 LMICs (25 trials from 13 LICs).  Risk of bias Most common: detection bias, attrition bias (efficacy), insufficient protection against contamination.  Intervention effects *Unless indicated, comparisons were usual care at T2.  "Probably", "may", or "uncertain" indicates "moderate", "low," or "very low" certainty evidence.   Adults with common mental disorders (CMDs) LHW-led interventions a. may increase recovery (2 trials, 308 participants; RR 1.29, 95%CI 1.06 to 1.56); b. may reduce prevalence (2 trials, 479 participants; RR 0.42, 95%CI 0.18 to 0.96); c. may reduce symptoms (4 trials, 798 participants; SMD -0.59, 95%CI -1.01 to -0.16); d. may improve QOL (1 trial, 521 participants; SMD 0.51, 95%CI 0.34 to 0.69); e. may slightly reduce functional impairment (3 trials, 1399 participants; SMD -0.47, 95%CI -0.8 to -0.15); f. may reduce AEs (risk of suicide ideation/attempts); g. may have uncertain effects on SU. Collaborative-care a. may increase recovery (5 trials, 804 participants; RR 2.26, 95%CI 1.50 to 3.43); b. may reduce prevalence although the actual effect range indicates it may have little-or-no effect (2 trials, 2820 participants; RR 0.57, 95%CI 0.32 to 1.01); c. may slightly reduce symptoms (6 trials, 4419 participants; SMD -0.35, 95%CI -0.63 to -0.08); d. may slightly improve QOL (6 trials, 2199 participants; SMD 0.34, 95%CI 0.16 to 0.53); e. probably has little-to-no effect on functional impairment (5 trials, 4216 participants; SMD -0.13, 95%CI -0.28 to 0.03); f. may reduce SU (referral to MH specialists);  g. may have uncertain effects on AEs (death). Women with perinatal depression (PND) LHW-led interventions a. may increase recovery (4 trials, 1243 participants; RR 1.29, 95%CI 1.08 to 1.54); b. probably slightly reduce symptoms (5 trials, 1989 participants; SMD -0.26, 95%CI -0.37 to -0.14); c. may slightly reduce functional impairment (4 trials, 1856 participants; SMD -0.23, 95%CI -0.41 to -0.04); d. may have little-to-no effect on AEs (death);  e. may have uncertain effects on SU. Collaborative-care a. has uncertain effects on symptoms/QOL/SU/AEs. Adults with post-traumatic stress (PTS) or CMDs in humanitarian settings LHW-led interventions a. may slightly reduce depression symptoms (5 trials, 1986 participants; SMD -0.36, 95%CI -0.56 to -0.15); b. probably slightly improve QOL (4 trials, 1918 participants; SMD -0.27, 95%CI -0.39 to -0.15); c. may have uncertain effects on symptoms (PTS)/functioning/SU/AEs. PHP-led interventions a. may reduce PTS symptom prevalence (1 trial, 313 participants; RR 5.50, 95%CI 2.50 to 12.10) and depression prevalence (1 trial, 313 participants; RR 4.60, 95%CI 2.10 to 10.08);  b. may have uncertain effects on symptoms/functioning/SU/AEs.   Adults with harmful/hazardous alcohol or substance use LHW-led interventions a. may increase recovery from harmful/hazardous alcohol use although the actual effect range indicates it may have little-or-no effect (4 trials, 872 participants; RR 1.28, 95%CI 0.94 to 1.74); b. may have little-to-no effect on the prevalence of methamphetamine use (1 trial, 882 participants; RR 1.01, 95%CI 0.91 to 1.13) and  functional impairment (2 trials, 498 participants; SMD -0.14, 95%CI -0.32 to 0.03); c. probably slightly reduce risk of harmful/hazardous alcohol use (3 trials, 667 participants; SMD -0.22, 95%CI -0.32 to -0.11);  d. may have uncertain effects on SU/AEs. PHP/CP-led interventions a. probably have little-to-no effect on recovery from harmful/hazardous alcohol use (3 trials, 1075 participants; RR 0.93, 95%CI 0.77 to 1.12) or QOL (1 trial, 560 participants; MD 0.00, 95%CI -0.10 to 0.10); b. probably slightly reduce risk of harmful/hazardous alcohol and substance use (2 trials, 705 participants; SMD -0.20, 95%CI -0.35 to -0.05; moderate-certainty evidence); c. may have uncertain effects on prevalence (cannabis use)/SU/AEs. PW-led interventions for alcohol/substance dependence a. may have uncertain effects.  Adults with severe mental disorders *Comparisons were specialist-led care at T1. LHW-led interventions a. may have little-to-no effect on caregiver burden (1 trial, 253 participants; MD -0.04, 95%CI -0.18 to 0.11);  b. may have uncertain effects on symptoms/functioning/SU/AEs.  PHP-led or collaborative-care a. may reduce functional impairment (7 trials, 874 participants; SMD -1.13, 95%CI -1.78 to -0.47); b. may have uncertain effects on recovery/relapse/symptoms/QOL/SU.  Adults with dementia and carers PHP/LHW-led carer interventions a. may have little-to-no effect on the severity of behavioural symptoms in dementia patients (2 trials, 134 participants; SMD -0.26, 95%CI -0.60 to 0.08); b. may reduce carers' mental distress (2 trials, 134 participants; SMD -0.47, 95%CI -0.82 to -0.13);  c. may have uncertain effects on QOL/functioning/SU/AEs. Children with PTS or CMDs LHW-led interventions a. may have little-to-no effect on PTS symptoms (3 trials, 1090 participants; MCD -1.34, 95%CI -2.83 to 0.14); b. probably have little-to-no effect on depression symptoms (3 trials, 1092 participants; MCD -0.61, 95%CI -1.23 to 0.02) or on functional impairment (3 trials, 1092 participants; MCD -0.81, 95%CI -1.48 to -0.13);  c. may have little-or-no effect on AEs. CP-led interventions a. may have little-to-no effect on depression symptoms (2 trials, 602 participants; SMD -0.19, 95%CI -0.57 to 0.19) or on AEs;  b. may have uncertain effects on recovery/symptoms(PTS)/functioning. AUTHORS' CONCLUSIONS: PW-led interventions show promising benefits in improving outcomes for CMDs, PND, PTS, harmful alcohol/substance use, and dementia carers in LMICs.

Expanding the 3 Wishes Project for compassionate end-of-life care: a qualitative evaluation of local adaptations.

BACKGROUND: The 3 Wishes Project (3WP) is an end-of-life program that honors the dignity of dying patients by fostering meaningful connections among patients, families, and clinicians. Since 2013, it has become embedded in the culture of end-of-life care in over 20 ICUs across North America. The purpose of the current study is to describe the variation in implementation of 3WP across sites, in order to ascertain which factors facilitated multicenter implementation, which factors remain consistent across sites, and which may be adapted to suit local needs. METHODS: Using the methodology of qualitative description, we collected interview and focus group data from 85 clinicians who participated in the successful initiation and sustainment of 3WP in 9 ICUs. We describe the transition between different models of 3WP implementation, from core clinical program to the incorporation of various research activities. We describe various sources of financial and in-kind resources accessed to support the program. RESULTS: Beyond sharing a common goal of improving end-of-life care, sites varied considerably in organizational context, staff complement, and resources. Despite these differences, the program was successfully implemented at each site and eventually evolved from a clinical or research intervention to a general approach to end-of-life care. Key to this success was flexibility and the empowerment of frontline staff to tailor the program to address identified needs with available resources. This adaptability was fueled by cross-pollination of ideas within and outside of each site, resulting in the establishment of a network of like-minded individuals with a shared purpose. CONCLUSIONS: The successful initiation and sustainment of 3WP relied on local adaptations to suit organizational needs and resources. The semi-structured nature of the program facilitated these adaptations, encouraged creative and important ways of relating within local clinical cultures, and reinforced the main tenet of the program: meaningful human connection at the end of life. Local adaptations also encouraged a team approach to care, supplementing the typical patient-clinician dyad by explicitly empowering the healthcare team to collectively recognize and respond to the needs of dying patients, families, and each other. TRIAL REGISTRATION: NCT04147169 , retrospectively registered with clinicaltrials.gov on October 31, 2019.

Modelling maternal obesity: the effects of a chronic high-fat, high-cholesterol diet on uterine expression of contractile-associated proteins and ex vivo contractile activity during labour in the rat.

Maternal obesity is associated with prolonged and dysfunctional labour and emergency caesarean section, but the mechanisms are unknown. The present study investigated the effects of an adiposity-inducing high-fat, high-cholesterol (HFHC) diet on uterine contractile-associated protein (CAP) expression and ex vivo uterine contractility in term non-labouring (TNL) and term labouring (TL) rats. Female rats were fed either control chow (CON n=20) or HFHC (n=20) diet 6 weeks before conception and during pregnancy. On gestational day 21 (TNL) or day 22 (TL) CON and HFHC (n=10) rats were killed to determine plasma cholesterol, triacylglycerol and progesterone concentrations and collection of myometrium for contractility studies and expression of CAPs caveolin-1 (Cav-1), connexin-43 (CX-43) and it's phosphorylated form (pCX-43), oxytocin receptor (OXTR) and cyclooxygenase-2 (COX-2). HFHC feeding increased visceral fat (P≤0.001), plasma cholesterol (P≤0.001) and triacylglycerol (P=0.039) concentrations. Stage of labour effected uterine expression of CAV-1 (P<0.02), pCX43 and COX-2 (both P<0.03). CAV-1 and pCX43 decreased but COX-2 increased with parturition. Significant diet- and labour-stage interactions were evident for CX-43 and pCX43 (P<0.03 and P<0.004 respectively). CX-43 decreased with TL in HFHC animals but was unaltered in CON. pCX-43 fell with labour in CON but remained high in HFHC. OXTR expression was significantly higher in HFHC compared with CON animals (P<0.03). Progesterone was higher in HFHC rats at term (P<0.014) but fell significantly with labour to similar concentrations as CON. Contractility studies identified synchronous contractions of stable amplitude in lean animals, but unstable asynchronous contractions with obesity. Uterine dose response to oxytocin was blunted during labour in HFHC rats with a log EC50 of -8.84 compared with -10.25 M in CON for integral activity (P<0.05). In conclusion, our adiposity model exhibits adverse effects on contractile activity during labour that can be investigated further to unravel the mechanisms causing uterine dystocia in obese women.

UK women's experiences of breastfeeding and additional breastfeeding support: a qualitative study of Baby Café services.

BACKGROUND: Whilst 81 % of UK women initiate breastfeeding, there is a steep decline in breastfeeding rates during the early postnatal period, with just 55 % of women breastfeeding at six weeks. 80 % of these women stopped breastfeeding sooner than they intended, with women citing feeding difficulties and lack of adequate support. As part of efforts to increase breastfeeding continuation rates, many public and voluntary organisations offer additional breastfeeding support services, which provide practical support in the early postnatal period and beyond. This paper focuses on the qualitative experiences of UK users of Baby Café services to examine their experiences of breastfeeding and breastfeeding support. METHODS: The study was based upon in-depth interviews and focus groups with users of eight Baby Café breastfeeding support groups across the UK. Thirty-six interviews and five focus groups were conducted with a total of fifty-one mothers using the service. Interviews and group discussions were analysed using N Vivo software to draw out key themes and discussions. RESULTS: Whilst each mother's infant feeding journey is unique, reflecting her own personal circumstances and experiences, several themes emerged strongly from the data. Many women felt that they had been given unrealistic expectations of breastfeeding by professionals keen to promote the benefits. This left them feeling unprepared when they encountered pain, problems and relentlessness of early infant feeding, leading to feelings of guilt and inadequacy over their feeding decisions. Mothers valued the combination of expert professional and peer support provided by Baby Café services and emphasised the importance of social support from other mothers in enabling them to continue feeding for as long as they wished. CONCLUSIONS: The research emphasises the need for realistic rather than idealistic antenatal preparation and the importance of timely and parent-centred breastfeeding support, particularly in the immediate postnatal weeks. The findings suggest that effective social support, combined with reassurance and guidance from skilled practitioners, can help women to overcome difficulties and find confidence in their own abilities to achieve their feeding goals. However, further work is needed to make sure such services are readily accessible to women from all sectors of the community.

Pediatric pulmonary thromboembolism: a 3-year Canadian Pediatric Surveillance Program study.

BACKGROUND: Pediatric pulmonary embolism (PE) is a rare event associated with significant morbidity and mortality. Awareness of clinical presentation and practices unique to children may aid clinicians in prompt identification and treatment. OBJECTIVES: To describe the incidence, risk factors, clinical presentation, diagnostic and therapeutic practices, and short-term outcomes of pediatric PE. METHODS: We conducted a 3-year national surveillance study through the Canadian Pediatric Surveillance Program. Over 2800 pediatric specialists and subspecialists were contacted monthly from 2020 to 2022 and requested to report all new cases of PE in patients up to 18 years of age. Case-specific data were obtained through voluntary completion of a detailed questionnaire. RESULTS: Fifty-eight cases (78% female, n = 45) were reported (2.4 cases per million children), with rates highest in adolescents 15 to 18 years (6.6 cases per million). Detailed information, available for 31 (53%) cases, documented at least 1 risk factor in 28 (90%) cases; 24 (77%) patients presented with 2 or more symptoms. Computed tomography pulmonary angiography was used for diagnostic confirmation in 25 (81%) cases. Anticoagulation was initiated in 24 (77%) of 31 cases; fewer than 5 patients underwent thrombolysis or surgical interventions. Of 28 patients who received therapeutic interventions, 8 (29%) experienced treatment-related complications. Fewer than 5 mortalities were reported. CONCLUSION: Pediatric PE is a rare event, with female adolescents at the highest risk. Although the presentation is often nonspecific, clinicians should maintain a high index of suspicion, particularly in patients with risk factors and when other diagnoses that may explain symptoms have been excluded.

Conceptual framework on barriers and facilitators to implementing perinatal mental health care and treatment for women: the MATRIx evidence synthesis.

Background: Perinatal mental health difficulties can occur during pregnancy or after birth and mental illness is a leading cause of maternal death. It is therefore important to identify the barriers and facilitators to implementing and accessing perinatal mental health care. Objectives: Our research objective was to develop a conceptual framework of barriers and facilitators to perinatal mental health care (defined as identification, assessment, care and treatment) to inform perinatal mental health services. Methods: Two systematic reviews were conducted to synthesise the evidence on: Review 1 barriers and facilitators to implementing perinatal mental health care; and Review 2 barriers to women accessing perinatal mental health care. Results were used to develop a conceptual framework which was then refined through consultations with stakeholders. Data sources: Pre-planned searches were conducted on MEDLINE, EMBASE, PsychInfo and CINAHL. Review 2 also included Scopus and the Cochrane Database of Systematic Reviews. Review methods: In Review 1, studies were included if they examined barriers or facilitators to implementing perinatal mental health care. In Review 2, systematic reviews were included if they examined barriers and facilitators to women seeking help, accessing help and engaging in perinatal mental health care; and they used systematic search strategies. Only qualitative papers were identified from the searches. Results were analysed using thematic synthesis and themes were mapped on to a theoretically informed multi-level model then grouped to reflect different stages of the care pathway. Results: Review 1 included 46 studies. Most were carried out in higher income countries and evaluated as good quality with low risk of bias. Review 2 included 32 systematic reviews. Most were carried out in higher income countries and evaluated as having low confidence in the results. Barriers and facilitators to perinatal mental health care were identified at seven levels: Individual (e.g. beliefs about mental illness); Health professional (e.g. confidence addressing perinatal mental illness); Interpersonal (e.g. relationship between women and health professionals); Organisational (e.g. continuity of carer); Commissioner (e.g. referral pathways); Political (e.g. women's economic status); and Societal (e.g. stigma). These factors impacted on perinatal mental health care at different stages of the care pathway. Results from reviews were synthesised to develop two MATRIx conceptual frameworks of the (1) barriers and (2) facilitators to perinatal mental health care. These provide pictorial representations of 66 barriers and 39 facilitators that intersect across the care pathway and at different levels. Limitations: In Review 1 only 10% of abstracts were double screened and 10% of included papers methodologically appraised by two reviewers. The majority of reviews included in Review 2 were evaluated as having low (n = 14) or critically low (n = 5) confidence in their results. Both reviews only included papers published in academic journals and written in English. Conclusions: The MATRIx frameworks highlight the complex interplay of individual and system level factors across different stages of the care pathway that influence women accessing perinatal mental health care and effective implementation of perinatal mental health services. Recommendations for health policy and practice: These include using the conceptual frameworks to inform comprehensive, strategic and evidence-based approaches to perinatal mental health care; ensuring care is easy to access and flexible; providing culturally sensitive care; adequate funding of services; and quality training for health professionals with protected time to do it. Future work: Further research is needed to examine access to perinatal mental health care for specific groups, such as fathers, immigrants or those in lower income countries. Trial registration: This trial is registered as PROSPERO: (R1) CRD42019142854; (R2) CRD42020193107. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR 128068) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 2. See the NIHR Funding and Awards website for further award information.

Mental health problems affect one in five women during pregnancy and the first year after birth (the perinatal period). These include anxiety, depression and stress-related conditions. Mental health problems can have a negative effect on women, their partners and their children. They are also a leading cause of maternal death. It is therefore important that women who experience mental health problems get the care and treatment they need. However, only about half of women with perinatal mental health problems are identified by health services and even fewer receive treatment. This research aimed to understand what factors help or prevent women getting care or treatment for perinatal mental health problems. We did this by pulling together the findings from existing research in three phases. In phase 1 we reviewed the evidence from research studies to understand why it has been difficult for health services to assess, care for and treat women with perinatal mental health problems. In phase 2 we reviewed evidence from women's perspectives on all of the factors that prevent women from being able to get the care and treatment they need. In phase 3 we worked with a panel of women, health professionals (such as general practitioners and midwives) and health service managers to look at the findings from phases 1 and 2. We then developed frameworks that give a clear overview of factors that help or prevent women getting care and treatment. These frameworks show 39 factors that help women access services, and 66 factors that prevent access. Based on these results we have developed guidance for government, NHS service managers and health professionals, such as general practitioners, midwives, health visitors, nurses and wider teams such as receptionists. This will be shared widely with health services and professionals who support women during pregnancy and after birth to improve perinatal mental health services so that care meets women's needs.

Common phenotypes and the developmental origins of disease.

PURPOSE OF REVIEW: The association between nutrition during pregnancy and the development of metabolic disease in the offspring has been well evidenced in humans and animals. Whilst evidence has accumulated to support various theories linking maternal diet to long-term health, the precise mechanisms of action remain poorly understood. This review summarizes recent advances within the field, focusing on the use of animal models to investigate common phenotypic outcomes. RECENT FINDINGS: Continued characterization of postnatal phenotypes has highlighted the importance of postnatal diet in unmasking programming effects of prenatal diet. Whilst common phenotypes are observed across models, differences in associated regulatory processes exist dependent upon the dietary exposure used and sex of the offspring. The use of unbiased techniques at developmental stages has identified gene pathways sensitive to maternal diet, potentially explaining the induction of a common phenotype by different nutritional interventions. Evidence has also grown to support the role of epigenetic modification, with an increasing range of targets identified as being sensitive. SUMMARY: A challenge remains in identifying the direct functional and long-term consequences of changes in gene expression or epigenetic status during development, and to translate these back to human populations.

The effect of feeding a low iron diet prior to and during gestation on fetal and maternal iron homeostasis in two strains of rat.

BACKGROUND: Iron deficiency anaemia during pregnancy is a global problem, with short and long term consequences for maternal and child health. Animal models have demonstrated that the developing fetus is vulnerable to maternal iron restriction, impacting on postnatal metabolic and blood pressure regulation. Whilst long-term outcomes are similar across different models, the commonality in mechanistic events across models is unknown. This study examined the impact of iron deficiency on maternal and fetal iron homeostasis in two strains of rat. METHODS: Wistar (n=20) and Rowett Hooded Lister (RHL, n=19) rats were fed a control or low iron diet for 4 weeks prior to and during pregnancy. Tissues were collected at day 21 of gestation for analysis of iron content and mRNA/protein expression of regulatory proteins and transporters. RESULTS: A reduction in maternal liver iron content in response to the low iron diet was associated with upregulation of transferrin receptor expression and a reduction in hepcidin expression in the liver of both strains, which would be expected to promote increased iron absorption across the gut and increased turnover of iron in the liver. Placental expression of transferrin and DMT1+IRE were also upregulated, indicating adaptive responses to ensure availability of iron to the fetus. There were considerable differences in hepatic maternal and fetal iron content between strains. The higher quantity of iron present in livers from Wistar rats was not explained by differences in expression of intestinal iron transporters, and may instead reflect greater materno-fetal transfer in RHL rats as indicated by increased expression of placental iron transporters in this strain. CONCLUSIONS: Our findings demonstrate substantial differences in iron homeostasis between two strains of rat during pregnancy, with variable impact of iron deficiency on the fetus. Whilst common developmental processes and pathways have been observed across different models of nutrient restriction during pregnancy, this study demonstrates differences in maternal adaptation which may impact on the trajectory of the programmed response.

Glucose intolerance associated with early-life exposure to maternal cafeteria feeding is dependent upon post-weaning diet.

In addition to being a risk factor for adverse outcomes of pregnancy, maternal obesity may play a role in determining the long-term disease patterns observed in the resulting offspring, with metabolic and dietary factors directly programming fetal development. The present study evaluated the potential for feeding rats an obesogenic cafeteria diet (O) pre-pregnancy, during pregnancy, during lactation and for the offspring post-weaning, to programme glucose tolerance. Early-life exposure to an O diet had no significant effect on offspring food intake. Early-life programming associated with O feeding to induce maternal obesity was associated with reduced adiposity in offspring weaned onto low-fat chow. Adult offspring exposed to an O diet in early life and weaned on a chow diet had low fasting glucose and insulin concentrations and appeared to be more sensitive to insulin during an intraperitoneal glucose tolerance test. When weaned on an O diet, male offspring were more prone to glucose intolerance than females. On the basis of the area under the glucose curve, maternal O feeding at any point from pre-mating to lactation was associated with impaired glucose tolerance. The mechanism for this was not identified, although increased hepatic expression of Akt2 may have indicated disturbance of insulin signalling pathways. The observations in the present study confirm that maternal overnutrition and obesity during pregnancy are risk factors for metabolic disturbance in the resulting offspring. Although the effects on glucose homeostasis were independent of offspring adiposity, the programming of a glucose-intolerant phenotype was only observed when offspring were weaned on a diet that induced greater fat deposition.

Prenatal protein restriction leads to a disparity between aortic and peripheral blood pressure in Wistar male offspring.

A host of animal studies have been used to model the effects of exposure to a low protein diet in utero on adult blood pressure. Collection of systolic blood pressure data by the indirect tail-cuff plethysmography method consistently shows increased pressures in low protein exposed rodent offspring compared to controls, but this technique has been criticised as the associated stress artefacts may confound the observed effects. Conversely, radiotelemetry systems allow unrestrained and continuous monitoring of blood pressure through the awake and sleep phases of the diurnal cycle. In this novel study, we directly compared blood pressure parameters in male offspring from low protein and control-fed dams measured simultaneously using tail-cuff and radiotelemetry systems. Control rats showed a good correlation between tail-cuff and radiotelemetry derived blood pressure data. Conversely, low protein males were relatively hypertensive at 8 weeks of age when measured by tail-cuff, but had significantly lower blood pressure than controls at 12 weeks of age when measured by telemetry. Heart rate and length of systole did not differ between the two groups. Individual stress protocols mimicking those imposed by tail-cuff plethysmography (novel environment, heat, restraint, inflation), caused similar increases in blood pressure and heart rate in control and low protein animals, ruling out an effect of enhanced pressor response to stress following prenatal protein restriction. Instead, an increase in peripheral vascular resistance in these animals is considered possible. Such a disparity between central and peripheral blood pressure measurements could have important clinical implications regarding cardiovascular risk assessment and treatment.

The impact of maternal protein restriction during rat pregnancy upon renal expression of angiotensin receptors and vasopressin-related aquaporins.

BACKGROUND: Maternal protein restriction during rat pregnancy is known to impact upon fetal development, growth and risk of disease in later life. It is of interest to understand how protein undernutrition influences the normal maternal adaptation to pregnancy. Here we investigated the mechanisms regulating renal haemodynamics and plasma volume during pregnancy, in the context of both normal and reduced plasma volume expansion. The study focused on expression of renal angiotensin receptors (ATR) and vasopressin-related aquaporins (AQP), hypothesising that an alteration in the balance of these proteins would be associated with pregnancy per se and with compromised plasma volume expansion in rats fed a low-protein diet. METHODS: Female Wistar rats were mated and fed a control (18% casein) or low-protein (9% casein) diet during pregnancy. Animals were anaesthetised on days 5, 10, 15 and 20 of gestation (n = 8/group/time-point) for determination of plasma volume using Evans Blue dye, prior to euthanasia and collection of tissues. Expression of the ATR subtypes and AQP2, 3 and 4 were assessed in maternal kidneys by PCR and western blotting. 24 non-pregnant Wistar rats underwent the same procedure at defined points of the oestrous cycle. RESULTS: As expected, pregnancy was associated with an increase in blood volume and haemodilution impacted upon red blood cell counts and haemoglobin concentrations. Expression of angiotensin II receptors and aquaporins 2, 3 and 4 was stable across all stages of the oestrus cycle. Interesting patterns of intra-renal protein expression were observed in response to pregnancy, including a significant down-regulation of AQP2. In contrast to previous literature and despite an apparent delay in blood volume expansion in low-protein fed rats, blood volume did not differ significantly between groups of pregnant animals. However, a significant down-regulation of AT2R protein expression was observed in low-protein fed animals alongside a decrease in creatinine clearance. CONCLUSION: Regulatory systems involved in the pregnancy-induced plasma volume expansion are susceptible to the effects of maternal protein restriction.

Developmental origins of adult disease.

Variation in the quality or quantity of nutrients consumed during pregnancy can exert permanent and powerful effects upon the developing fetus. This programming of fetal development is emerging as a new risk factor for non-communicable diseases of adulthood, including coronary heart disease and the metabolic syndrome. Epidemiological studies show that indicators of nutritional deficit in pregnancy are associated with greater risk of diabetes and cardiovascular mortality. The study of programming in relation to disease processes has been advanced by the development of animal models, which have utilized both under- and overfeeding of specific nutrients in pregnancy. Studies of this nature support the nutritional programming hypothesis and provide tools with which to examine the mechanisms through which programming may occur. Studies of animals subject to undernutrition in utero generally exhibit changes in the structure of key organs, such as the kidney and pancreas. These effects are consistent with the concept that programming influences remodel the development of organs. The causal pathways which extend from tissue remodelling to disease processes are relatively well characterised. In contrast, the processes which drive disordered organ development are poorly understood. It is noteworthy that minor perturbation of maternal nutritional status can programme fetal development. It is suggested therefore that programming is a product of altered expression of key genes. This drives the tissue remodelling response and future disease risk.

Health care practitioners' views of the support women, partners, and the couple relationship require for birth trauma: current practice and potential improvements.

AIM: To examine health care practitioners' views of the support women, partners, and the couple relationship require when affected by birth trauma, barriers to gaining such support, and potential improvements. BACKGROUND: Ongoing distress following psychologically traumatic childbirth, also known as birth trauma, can affect women, partners, and the couple relationship. Birth trauma can lead to post traumatic stress symptoms (PTSS) or disorder (PTSD). Whilst there is a clear system of care for a PTSD diagnosis, support for the more prevalent experience of birth trauma is not well-defined. METHOD: An online survey of health care practitioners' views of the support parents require for birth trauma, barriers to accessing support, and potential improvements. Practitioners were recruited in 2018 and the sample for the results presented in the article ranged from 95 to 110. RESULTS: Practitioners reported differing needs of support for women, partners, and the couple as a unit. There was correlation between practitioners reporting having the skills and knowledge to support couples and feeling confident in giving support. The support most commonly offered by practitioners to reduce the impact on the couple relationship was listening to the couple. However practitioners perceived the most effective support was referral to a debriefing service. Practitioners observed several barriers to both providing support and parents accessing support, and improvements to birth trauma support were suggested. CONCLUSIONS: Practitioners indicate that some women, partners, and the couple as a unit require support with birth trauma and that barriers exist to accessing effective support. The support that is currently provided often conflicts with practitioners' perception of what is most effective. Practitioners indicate a need to improve the identification of parents who need support with birth trauma, and more suitable services to support them.

Obesity induced by cafeteria feeding and pregnancy outcome in the rat.

Obesity during pregnancy has major consequences for maternal and neonatal health, but the long-term effects on the offspring are less clear. It is not known whether the effects observed in animal models are a result of maternal obesity per se or of the high-fat diets used to induce obesity. This investigation aimed to develop a model for the evaluation of the independent effects of cafeteria feeding and maternal obesity, considering their impact on plasma volume expansion, circulating metabolites, and fetal and placental growth. Wistar rats were fed a control or cafeteria diet from weaning. After 8 weeks, all animals were mated and half of the animals within each group were crossed-over to the alternative diet. This generated four treatment groups, differing in their pre-gestational and gestational diets. Half of the animals were culled at day 5 of gestation and the remainder at day 20. Maternal body composition, blood volume and circulating glucose, TAG and cholesterol were determined. Cafeteria feeding was effective in inducing obesity, as demonstrated by increased fat depot weights and total body fat, without impacting upon reproductive success or circulating lipid concentrations. The study successfully demonstrated that there were differential effects of maternal body fatness and diet upon fetal and placental growth, with pre-gestational obesity leading to lower fetal weight at day 20 of gestation (P < 0.001). The model will provide a useful vehicle for the investigation of the complex interactions between dietary- and obesity-related factors during pregnancy in their effects on fetal development and postnatal metabolic function.

Rapid method for the determination and confirmation of fluoroquinolone residues in catfish using liquid chromatography/fluorescence detection and liquid chromatography-tandem mass spectrometry.

A simplified method for the extraction and determination of four fluoroquinolone (FQ) residues (ciprofloxacin, enrofloxacin, sarafloxacin, and difloxacin) in catfish is presented. In this method, the FQ residues were extracted with acidified acetonitrile, and the extract was defatted with dispersive C18 solid-phase extraction (SPE) sorbent or hexane. A portion of the extract was evaporated and reconstituted in the mobile phase. The quantitative determination was accomplished with LC-fluorescence detection (FLD), and the confirmation was by LC-MS/MS. Fortifications of catfish tissue were carried out at 0.5x, x, 2x, and 4x, where x = 5 ppb (U.S. Food and Drug Administration current regulatory target level). Recoveries for the LC/FLD determination of five replicates (for both cleanup routes) at each level ranged from 64 to 98%, with RSD values <8%. The method quantitation limits for all residues were <1 ng/g. The LC-MS/MS analysis of the same extracts confirmed all FQ residues at all levels. This method is an improvement over existing methodologies since additional cleanup steps, such as cation exchange SPE column cleanup, are not utilized. The C18 dispersive SPE method represents a novel cleanup approach for FQs in fish tissue.

Protocol for a two-arm feasibility RCT to support postnatal maternal weight management and positive lifestyle behaviour in women from an ethnically diverse inner city population: the SWAN feasibility trial.

INTRODUCTION: A high BMI during and after pregnancy is linked to poor pregnancy outcomes and contributes to long-term maternal obesity, hypertension, and diabetes. Evidence of feasible, effective postnatal interventions is lacking. This randomised controlled trial will assess the feasibility of conducting a future definitive trial to determine effectiveness and cost-effectiveness of lifestyle information and access to Slimming World® (Alfreton, UK) groups for 12 weeks commencing from 8 to 16 weeks postnatally, in relation to supporting longer-term postnatal weight management in women in an ethnically diverse inner city population. METHODS/ANALYSIS: Women will be recruited from one maternity unit in London. To be eligible, women will be overweight (BMI 25-29.9 kg/m2) or obese (BMI ≥ 30 kg/m2) as identified at their first antenatal contact, or have a normal BMI (18.5-24.9 kg/m2) at booking but gain excessive gestational weight as assessed at 36 weeks gestation. Women will be aged 18 and over, can speak and read English, expecting a single baby, and will not have accessed weight management groups in this pregnancy. Women will be randomly allocated to standard care plus lifestyle information and access to Slimming World® (Alfreton, UK) groups or standard care only. A sample of 130 women is required.Feasibility trial objectives reflect those considered most important inform a decision about undertaking a definitive future trial. These include estimation of impact of lifestyle information and postnatal access to Slimming World® (Alfreton, UK) on maternal weight change between antenatal booking weight and weight at 12 months postbirth, recruitment rate and time to recruitment, retention rate, influence of lifestyle information and Slimming World® (Alfreton, UK) groups on weight management, diet, physical activity, breastfeeding, smoking cessation, alcohol intake, physical and mental health, infant health, and health-related quality of life 6 and 12 months postnatally. An embedded process evaluation will assess acceptability of study processes and procedures to women. ETHICS/DISSEMINATION: London-Camberwell St Giles Research Ethics Committee, reference: 16/LO/1422. Outcomes will be disseminated in peer-reviewed journals and presentations at national and international conferences. TRIAL REGISTRATION: Trial registration number: ISRCTN 39186148. Protocol version number: v7, 13 August 17. Trial sponsor: King's College London.

Prenatal diet determines susceptibility to cardiac ischaemia-reperfusion injury following treatment with diethylmaleic acid and N-acetylcysteine.

Fetal undernutrition programmes increased risk of developing cardiovascular disease in adult life. We hypothesized that prenatal protein restriction would impair recovery in post-ischaemic cardiac function in adult offspring through antioxidant-mediated processes. Pregnant Wistar rats were fed control or maternal low protein diets (MLP) throughout gestation. The offspring of these rats were treated with either saline, N-acetylcysteine (NAC), diethylmaleate (DEM), or both NAC and DEM to manipulate glutathione status at 6 months of age. Hearts were rapidly excised and retro-perfused (Langendorff) to assess isolated cardiac function before (baseline), and during 30 min global ischaemia and 60 min reperfusion. Hearts from adult rats exposed to a MLP diet in utero suffered greater cardiac dysfunction than those from controls following 30 min ischaemia. Left ventricular developed pressure (LVDP) was significantly reduced upon early reperfusion (p<0.042) in MLP rats compared to controls. NAC pre-treatment had no effect on LVDP of hearts from control animal hearts but improved the revival of MLP hearts to the same level as controls. DEM treatment did not affect control hearts but significantly reduced recovery of LVDP of MLP hearts during early (p<0.008) and late reperfusion (0.035). Combined NAC and DEM treatment had no effect on LVDP between control and MLP fed offspring. Prenatal protein restriction throughout pregnancy increases the susceptibility of the adult rat heart to suffer a functional deficit following ischaemia-reperfusion injury. Pharmacologically improving antioxidant status prevented this injury. A nutritionally-imbalanced developmental environment may increase susceptibility to coronary heart disease through the programming of myocardial glutathione metabolism.