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BACKGROUND: Antenatal steroid therapy for fetal lung maturation is routinely administered to women at risk of preterm delivery. There is strong evidence to demonstrate benefit from antenatal steroids in terms of survival and respiratory disease, notably in infants delivered at or below 32 weeks' gestation. However, dosing remains unoptimized and lung benefits are highly variable. Current treatment regimens generate high-concentration, pulsatile fetal steroid exposures now associated with increased risk of childhood neurodevelopmental diseases. We hypothesized that damage-associated changes in the fetal hippocampal transcriptome would be independent of preterm lung function. METHODS: Date-mated ewes carrying a single fetus at 122 ± 2dGA (term = 150dGA) were randomized into 4 groups: (i) Saline Control Group, 4×2ml maternal saline intramuscular(IM) injections at 12hr intervals (n = 11); or (ii) Dex High Group, 2×12mg maternal IM dexamethasone phosphate injections at 12hr intervals followed by 2×2ml IM saline injections at 12hr intervals (n = 12; representing a clinical regimen used in Singapore); or (iii) Dex Low Group, 4×1.5mg maternal IM dexamethasone phosphate injections 12hr intervals (n = 12); or (iv) Beta-Acetate Group, 1×0.125mg/kg maternal IM betamethasone acetate injection followed by 3×2ml IM sterile normal saline injections 12hr intervals (n = 8). Lambs were surgically delivered 48hr after first maternal injection at 122-125dGA, ventilated for 30min to establish lung function, and euthanised for necropsy and tissue collection. RESULTS: Preterm lambs from the Dex Low and Beta-Acetate Groups had statistically and biologically significant lung function improvements (measured by gas exchange, lung compliance). Compared to the Saline Control Group, hippocampal transcriptomic data identified 879 differentially significant expressed genes (at least 1.5-fold change and FDR < 5%) in the steroid-treated groups. Pulsatile dexamethasone-only exposed groups (Dex High and Dex Low) had three common positively enriched differentially expressed pathways related in part to neurodegeneration ("Prion Disease", "Alzheimer's Disease", "Arachidonic Acid metabolism"). Adverse changes were independent of respiratory function during ventilation. CONCLUSIONS: Our data suggests that exposure to antenatal steroid therapy is an independent cause of damage- associated transcriptomic changes in the brain of preterm, fetal sheep. These data highlight an urgent need for careful reconsideration and balancing of how antenatal steroids are used, both for patient selection and dosing regimens.
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Hipocampo , Pulmão , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ovinos , Feminino , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Gravidez , Dexametasona/farmacologia , Betametasona/administração & dosagem , Feto/efeitos dos fármacosRESUMO
Despite proven efficacy, fatherhood interventions face challenges in attracting and retaining participants. This qualitative systematic review aims to inform the future design of fatherhood interventions by consolidating and synthesizing the evidence around fathers' experiences with interventions aimed at enhancing their involvement and relationships with their children. Following PRISMA guidelines, we analyzed 10 studies from a search of six electronic databases. Our analysis coalesced into three pivotal themes: (a) creating a sense of belonging: facilitating participation; (b) transformative takeaways; and (c) challenges of negotiating expectations of masculinity. Our findings indicate that group-based, culturally sensitive programs are advantageous but also reveal that fathers grapple with reconciling evolving fatherhood roles with societally entrenched expectations of masculinity. This review offers actionable insights for the future development, evaluation, and implementation of fatherhood interventions, particularly those utilizing qualitative research methodologies.
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BACKGROUND: Parents experience many challenges during the perinatal period. Mobile app-based interventions and chatbots show promise in delivering health care support for parents during the perinatal period. OBJECTIVE: This descriptive qualitative process evaluation study aims to explore the perinatal experiences of parents in Singapore, as well as examine the user experiences of the mobile app-based intervention with an in-built chatbot titled Parentbot-a Digital Healthcare Assistant (PDA). METHODS: A total of 20 heterosexual English-speaking parents were recruited via purposive sampling from a single tertiary hospital in Singapore. The parents (control group: 10/20, 50%; intervention group: 10/20, 50%) were also part of an ongoing randomized trial between November 2022 and August 2023 that aimed to evaluate the effectiveness of the PDA in improving parenting outcomes. Semistructured one-to-one interviews were conducted via Zoom from February to June 2023. All interviews were conducted in English, audio recorded, and transcribed verbatim. Data analysis was guided by the thematic analysis framework. The COREQ (Consolidated Criteria for Reporting Qualitative Research) checklist was used to guide the reporting of data. RESULTS: Three themes with 10 subthemes describing parents' perceptions of their parenting journeys and their experiences with the PDA were identified. The main themes were (1) new babies, new troubles, and new wonders; (2) support system for the parents; and (3) reshaping perinatal support for future parents. CONCLUSIONS: Overall, the PDA provided parents with informational, socioemotional, and psychological support and could be used to supplement the perinatal care provided for future parents. To optimize users' experience with the PDA, the intervention could be equipped with a more sophisticated chatbot, equipped with more gamification features, and programmed to deliver personalized care to parents. Researchers and health care providers could also strive to promote more peer-to-peer interactions among users. The provision of continuous, holistic, and family-centered care by health care professionals could also be emphasized. Moreover, policy changes regarding maternity and paternity leaves, availability of infant care centers, and flexible work arrangements could be further explored to promote healthy work-family balance for parents.
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Aplicativos Móveis , Poder Familiar , Pais , Pesquisa Qualitativa , Humanos , Pais/psicologia , Poder Familiar/psicologia , Feminino , Singapura , Masculino , Adulto , GravidezRESUMO
Introduction: Female fecundity decreases significantly after the age of 32, and rapidly so after age 37. There is no treatment to prevent this decline. Furthermore, globally, women are getting married later and the age at which they have their first child is increasing. As of July 2023, elective egg freezing (EEF) or oocyte cryopreservation (OC) for age-related fertility decline, commenced in Singapore. With medical advancements in OC, EEF is no longer considered experimental. The aim of this review is to examine the existing literature around EEF with regard to reproductive outcomes and its safety, to better guide clinicians in counselling young single women. Method: Published studies were examined to increase understanding on optimal age for EEF, ideal number of oocytes for a live birth, recommended OC protocols, cryopreservation techniques affecting thaw survival or fertilisation, oocyte storage and pregnancy risks. Results: Models predict that EEF should be performed at age <37 years and to achieve a 70% chance of live birth, women would need 14, 15 and 26 mature oocytes at ages 30-34, 35-37 and >38 years, respec-tively. An antagonist stimulation protocol with an agonist trigger would minimise ovarian hyper-stimulation syndrome and duration of stimulation without affecting outcomes. Oocyte vitrification in comparison to slow freezing increases thaw survival, fertilisation and clinical pregnancy rates. No increased risks exist for the woman, future pregnancy or child when compared with conventional IVF. Conclusion: EEF is a viable option for single women desiring fertility preservation. Financial costs are significant, but returns are worthwhile if oocytes are utilised.
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Criopreservação , Preservação da Fertilidade , Oócitos , Humanos , Criopreservação/métodos , Feminino , Gravidez , Preservação da Fertilidade/métodos , Adulto , Taxa de Gravidez , Singapura , Vitrificação , Nascido Vivo , Indução da Ovulação/métodos , Fatores EtáriosRESUMO
OBJECTIVES: To investigate multi-dose and timings of COVID-19 vaccines in preventing antenatal infection. DESIGN: Prospective observational study investigating primary vaccinations, boosters, antenatal COVID-19 infections, neutralizing antibody (Nab) durability, and cross-reactivity to Delta and Omicron variants of concern (VOCs). RESULTS: Ninety-eight patients completed primary vaccination prepregnancy (29.6%) and antenatally (63.3%), 24.2% of whom had antenatal COVID-19, while 7.1% were unvaccinated (28.6% had antenatal COVID-19). None had severe COVID-19. Prepregnancy vaccination resulted in vaccination-to-infection delay of 23.3 weeks, which extended to 45.2 weeks with a booster, compared to 16.9 weeks following antenatal vaccination (P < 0.001). Infections occurred at 26.2 weeks gestation in women vaccinated prepregnancy compared to 36.2 weeks gestation in those vaccinated during pregnancy (P < 0.007). The risk of COVID-19 infection was higher without antenatal vaccination (hazard ratio [HR] 14.6, P = 0.05) and after prepregnancy vaccination without a booster (HR 10.4, P = 0.002). Antenatal vaccinations initially led to high Nab levels, with mild waning but subsequent rebound. Significant Nab enhancement occurred with a third-trimester booster. Maternal-neonatal Nab transfer was efficient (transfer ratio >1), and cross-reactivity to VOCs was observed. CONCLUSION: Completing vaccination during any trimester delays COVID-19 infection and maintains effective neutralizing activity throughout pregnancy, with robust cross-reactivity to VOCs and efficient maternal-neonatal transfer.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , Complicações Infecciosas na Gravidez , SARS-CoV-2 , Vacinação , Humanos , Gravidez , Feminino , COVID-19/prevenção & controle , COVID-19/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , SARS-CoV-2/imunologia , Adulto , Estudos Prospectivos , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/virologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Reações Cruzadas/imunologia , Adulto JovemRESUMO
Human Wharton's jelly stem cells (hWJSCs) are multipotent stem cells that are extensively employed in biotechnology applications. However, the impact of simulated lunar microgravity (sµG) on the growth, differentiation, and viability of this cell population is incompletely characterized. We aimed to determine whether acute (72 h) exposure to sµG elicited changes in growth and lineage differentiation in hWJSCs and if putative changes were maintained once exposure to terrestrial gravity (1.0 G) was restored. hWJSCs were cultured under standard 1.0 G conditions prior to being passaged and cultured under sµG (0.16 G) using a random positioning machine. Relative to control, hWJSCs cultured under sµG exhibited marked reductions in growth but not viability. Cell population expression of characteristic stemness markers (CD 73, 90, 105) was significantly reduced under sµG conditions. hWJSCs had 308 significantly upregulated and 328 significantly downregulated genes when compared to 1.0 G culture conditions. Key markers of cell replication, including MKI67, were inhibited. Significant upregulation of osteocyte-chondrocyte lineage markers, including SERPINI1, MSX2, TFPI2, BMP6, COMP, TMEM119, LUM, HGF, CHI3L1 and SPP1, and downregulation of cell fate regulators, including DNMT1 and EZH2, were detected in sµG-exposed hWJSCs. When returned to 1.0 G for 3 days, sµG-exposed hWJSCs had accelerated growth, and expression of stemness markers increased, approaching normal (i.e. 95%) levels. Our data support earlier findings that acute sµG significantly reduces the cell division potential of hWJSCs and suggest that acute sµG-exposure induces reversible changes in cell growth accompanied by osteocyte-chondrocyte changes in lineage differentiation.
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OBJECTIVES: To evaluate the performance of an artificial intelligence (AI) and machine learning (ML) model for first-trimester screening for pre-eclampsia in a large Asian population. METHODS: This was a secondary analysis of a multicenter prospective cohort study in 10 935 participants with singleton pregnancies attending for routine pregnancy care at 11-13+6 weeks of gestation in seven regions in Asia between December 2016 and June 2018. We applied the AI+ML model for the first-trimester prediction of preterm pre-eclampsia (<37 weeks), term pre-eclampsia (≥37 weeks), and any pre-eclampsia, which was derived and tested in a cohort of pregnant participants in the UK (Model 1). This model comprises maternal factors with measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor (PlGF). The model was further retrained with adjustments for analyzers used for biochemical testing (Model 2). Discrimination was assessed by area under the receiver operating characteristic curve (AUC). The Delong test was used to compare the AUC of Model 1, Model 2, and the Fetal Medicine Foundation (FMF) competing risk model. RESULTS: The predictive performance of Model 1 was significantly lower than that of the FMF competing risk model in the prediction of preterm pre-eclampsia (0.82, 95% confidence interval [CI] 0.77-0.87 vs. 0.86, 95% CI 0.811-0.91, P = 0.019), term pre-eclampsia (0.75, 95% CI 0.71-0.80 vs. 0.79, 95% CI 0.75-0.83, P = 0.006), and any pre-eclampsia (0.78, 95% CI 0.74-0.81 vs. 0.82, 95% CI 0.79-0.84, P < 0.001). Following the retraining of the data with adjustments for the PlGF analyzers, the performance of Model 2 for predicting preterm pre-eclampsia, term pre-eclampsia, and any pre-eclampsia was improved with the AUC values increased to 0.84 (95% CI 0.80-0.89), 0.77 (95% CI 0.73-0.81), and 0.80 (95% CI 0.76-0.83), respectively. There were no differences in AUCs between Model 2 and the FMF competing risk model in the prediction of preterm pre-eclampsia (P = 0.135) and term pre-eclampsia (P = 0.084). However, Model 2 was inferior to the FMF competing risk model in predicting any pre-eclampsia (P = 0.024). CONCLUSION: This study has demonstrated that following adjustment for the biochemical marker analyzers, the predictive performance of the AI+ML prediction model for pre-eclampsia in the first trimester was comparable to that of the FMF competing risk model in an Asian population.
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ABSTRACT: Climate change is an existential threat to humanity. While the healthcare sector must manage the health-related consequences of climate change, it is a significant contributor to greenhouse gas emissions, responsible for up to 4.6% of global emission, aggravating global warming. Within the hospital environment, the three largest contributors to greenhouse gas emissions are the operating theatre, intensive care unit and gastrointestinal endoscopy. Knowledge of the health-related burden of climate change and the potential transformative health benefits of climate action is important to all health professionals, as they play crucial roles in effecting change. This article summarises the available literature on the impact of healthcare on climate change and efforts in mitigation, focusing on the intrinsic differences and similarities across the operating theatre complex, intensive care unit and gastrointestinal endoscopy unit. It also discusses strategies to reduce carbon footprint.
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Pegada de Carbono , Mudança Climática , Humanos , Gases de Efeito Estufa , Unidades de Terapia Intensiva , Atenção à Saúde , Salas Cirúrgicas , Endoscopia Gastrointestinal , Aquecimento Global , Conservação dos Recursos Naturais , Efeito EstufaRESUMO
OBJECTIVES: To examine and consolidate literature regarding the advantages and disadvantages of utilizing ChatGPT in healthcare education and research. DESIGN/METHODS: We searched seven electronic databases (PubMed/Medline, CINAHL, Embase, PsycINFO, Scopus, ProQuest Dissertations and Theses Global, and Web of Science) from November 2022 until September 2023. This scoping review adhered to Arksey and O'Malley's framework and followed reporting guidelines outlined in the PRISMA-ScR checklist. For analysis, we employed Thomas and Harden's thematic synthesis framework. RESULTS: A total of 100 studies were included. An overarching theme, "Forging the Future: Bridging Theory and Integration of ChatGPT" emerged, accompanied by two main themes (1) Enhancing Healthcare Education, Research, and Writing with ChatGPT, (2) Controversies and Concerns about ChatGPT in Healthcare Education Research and Writing, and seven subthemes. CONCLUSIONS: Our review underscores the importance of acknowledging legitimate concerns related to the potential misuse of ChatGPT such as 'ChatGPT hallucinations', its limited understanding of specialized healthcare knowledge, its impact on teaching methods and assessments, confidentiality and security risks, and the controversial practice of crediting it as a co-author on scientific papers, among other considerations. Furthermore, our review also recognizes the urgency of establishing timely guidelines and regulations, along with the active engagement of relevant stakeholders, to ensure the responsible and safe implementation of ChatGPT's capabilities. We advocate for the use of cross-verification techniques to enhance the precision and reliability of generated content, the adaptation of higher education curricula to incorporate ChatGPT's potential, educators' need to familiarize themselves with the technology to improve their literacy and teaching approaches, and the development of innovative methods to detect ChatGPT usage. Furthermore, data protection measures should be prioritized when employing ChatGPT, and transparent reporting becomes crucial when integrating ChatGPT into academic writing.
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Inteligência Artificial , Currículo , Pesquisa sobre Serviços de SaúdeRESUMO
The genitourinary symptom of menopause (GSM) affects up to 65% of women, resulting in symptoms such as vulvovaginal dryness, discomfort, and dysuria, which significantly impacts quality of life. The current assessment methods rely on subjective questionnaires that can be influenced by individual differences, as well as invasive measurements that are time-consuming and not easily accessible. In this study, we explore the potential of a non-invasive and objective assessment tool called diffuse reflectance spectroscopy and imaging (DRSI) to evaluate tissue chromophores, including water, lipid, oxyhemoglobin, and deoxyhemoglobin. These measurements provide information about moisture content, lipid levels, oxygen saturation, and blood fraction, which can serve as surrogate markers for genital estrogen levels. Our findings reveal distinct differences in these chromophores among pre, peri, and postmenopausal subjects. By using lipid and blood fraction tissue chromophores in a K-Nearest Neighbour classifier model, we achieved a prediction accuracy of 65% compared to vaginal maturation index (VMI) that is clinically used to assess estrogen-related hormonal changes. When age was included as the third feature, the accuracy increased to 78%. We believe that by refining the study protocol and configuring the fiber probe to examine tissue chromophores both in the superficial vulva skin for epidermal water content and the deeper layers, DRSI has the potential to provide objective diagnosis and aid in monitoring the treatment outcome of GSM.
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Menopausa , Qualidade de Vida , Feminino , Humanos , Projetos Piloto , Vagina/patologia , Análise Espectral , Estrogênios , Água , Lipídeos , Atrofia/patologiaRESUMO
OBJECTIVE: Extremely preterm infants have low Nuclear Receptor (NR) expression in their developing hepatobiliary systems, as they rely on the placenta and maternal liver for compensation. NRs play a crucial role in detoxification and the elimination of both endogenous and xenobiotic substances by regulating key genes encoding specific proteins. In this study, we utilized an Artificial Placenta Therapy (APT) platform to examine the liver tissue expression of NRs of extremely preterm ovine fetuses. This fetal model, resembling a "knockout placenta," lacks placental and maternal support, while maintaining a healthy extrauterine survival. METHODS: Six ovine fetuses at 95 ± 1 d gestational age (GA; term = â¼150 d)/â¼600 g delivery weight were maintained on an APT platform for a period of 120 h (APT Group). Six age-matched, in utero control fetuses were delivered at 99-100 d GA (Control Group). Fetal liver tissue samples and blood samples were collected at delivery from both groups and assessed mRNA expression of NRs and target transporters involved in the hepatobiliary transport system using quantitative PCR. Data were tested for group differences with ANOVA (p < .05 deemed significant). RESULTS: mRNA expression of NRs was identified in both the placenta and the extremely preterm ovine fetal liver. The expression of HNF4α, LRH1, LXR, ESR1, PXR, CAR, and PPARα/γ were significantly elevated in the liver of the APT Group compared to the Control Group. Moreover, target transporters NTCP, OATP1B3, BSEP, and MRP4 were upregulated, whereas MRP2 and MRP3 were unchanged. Although there was no evidence of liver necrosis or apoptotic changes histologically, there was an impact in the fetal liver of the ATP group at the tissue level with a significant increase in TNFα mRNA, a cytokine involved in liver inflammation, and blood elevation of transaminases. CONCLUSION: A number of NRs in the fetal liver were significantly upregulated after loss of placental-maternal support. However, the expression of target transporter genes appeared to be insufficient to compensate role of the placenta and maternal liver and avoid fetal liver damage, potentially due to insufficient excretion of organic anions.
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Lactente Extremamente Prematuro , Placenta , Recém-Nascido , Gravidez , Lactente , Ovinos , Animais , Feminino , Humanos , Regulação para Cima , Fígado , Feto , Receptores Citoplasmáticos e Nucleares , RNA MensageiroRESUMO
Advanced molecular and cellular technologies provide promising tools for wildlife and biodiversity conservation. Induced pluripotent stem cell (iPSC) technology offers an easily accessible and infinite source of pluripotent stem cells, and have been derived from many threatened wildlife species. This paper describes the first successful integration-free reprogramming of adult somatic cells to iPSCs, and their differentiation, from three endangered Southeast Asian primates: the Celebes Crested Macaque (Macaca nigra), the Lar Gibbon (Hylobates lar), and the Siamang (Symphalangus syndactylus). iPSCs were also generated from the Proboscis Monkey (Nasalis larvatus). Differences in mechanisms could elicit new discoveries regarding primate evolution and development. iPSCs from endangered species provides a safety net in conservation efforts and allows for sustainable sampling for research and conservation, all while providing a platform for the development of further in vitro models of disease.
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Células-Tronco Pluripotentes Induzidas , Primatas , Animais , Animais Selvagens , Diferenciação Celular , Reprogramação Celular , Espécies em Perigo de Extinção , Hylobates , MacacaRESUMO
BACKGROUND: Labour induction and augmentation procedures are commonly used in maternity units with or without medical indications. Research shows that healthcare professionals play a significant role in women's childbirth decisions. AIM: To consolidate healthcare professionals' perceptions about labour induction and augmentation. METHODS: Seven electronic databases were searched from their inception dates till January 2023: PubMed, Embase, CINAHL, PsycINFO, Web of Science, Scopus, ProQuest Dissertations, and Theses Global. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Sandelowski and Barroso's guidelines guided this review. Included studies' quality was appraised by the Critical Appraisal Skills Program tool. Data were thematically synthesised. Review findings were assessed using the Grading of Recommendations Assessment, Development, and Evaluation-Confidence in the Evidence from Reviews of Qualitative research approach. FINDINGS: Three main themes were identified from the 17 included studies: 1) Making sense of the phenomenon, 2) Two sides of the coin, and 3) The enlightened path ahead. DISCUSSION: Healthcare professionals' labour induction and augmentation decisions were affected by personal (knowledge and moral philosophies), and external factors (women, community members, colleagues, and healthcare institutions). Some clinicians were unfamiliar with the proper labour induction/augmentation procedures, while others were worried about their decisions and outcomes. CONCLUSION: Suggestions for improvement include conducting labour induction/augmentation training for clinicians, having sufficient resources in facilities, and developing appropriate labour induction/augmentation clinical guidelines. Women and their partners, community members, and traditional healers could benefit from receiving labour induction/augmentation education. To improve health outcomes, healthcare professionals could deliver woman-centred care and collaborate.
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Trabalho de Parto Induzido , Parto , Gravidez , Humanos , Feminino , Pessoal de Saúde , Atenção à Saúde , Pesquisa QualitativaRESUMO
Chorioamnionitis remains a major cause of preterm birth and maternal and neonatal morbidity. We reviewed the current evidence for the diagnostic tests of chorioamnionitis and how this relates to clinical practice today. A comprehensive literature search and review was conducted on chorioamnionitis and intra-uterine inflammation. Data from randomized control trials and systematic reviews were prioritized. This review highlights that sterile inflammation plays an important role in chorioamnionitis and that the current tests for chorioamnionitis including clinical criteria, maternal plasma and vaginal biomarkers lack diagnostic accuracy. Concerningly, these tests often rely on detecting an inflammatory response after damage has occurred to the fetus. Care should be taken when interpreting current investigations for the diagnosis of chorioamnionitis and how they guide obstetric/neonatal management. There is an urgent need for further validation of current diagnostic tests and the development of novel, accurate, minimally invasive tests that detect subclinical intra-uterine inflammation.
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AIM: To consolidate healthcare professionals' insights about waterbirths and water immersion during labour. DESIGN: Mixed studies review. DATA SOURCES: Seven electronic databases were searched from their inception dates till June 2023: PubMed, Embase, CINAHL, PsycINFO, Web of Science, Scopus, ProQuest Dissertations and Theses Global. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and Pluye and Hong's mixed studies review framework guided this review. The quality of included studies was evaluated using the Mixed Methods Appraisal Tool. Findings were synthesized using the convergent qualitative synthesis method, and results were thematically analysed using Braun and Clarke's framework. RESULTS: Three main themes were identified from the 22 included studies: (1) believing in waterbirths, (2) opposing forces and (3) plotting the course ahead. CONCLUSION: Healthcare professionals reported different views about waterbirths and water immersion practices; midwives were most likely to support these practices, followed by nurses and lastly, few physicians supported them. Reasons for opposing waterbirths include insufficient training and support from colleagues as well as concerns about work efficiency, waterbirth safety and litigation issues. IMPACT: The available evidence suggests the need to provide waterbirth training for healthcare professionals, equip healthcare facilities with necessary waterbirth-related infrastructure and develop appropriate waterbirth policies/guidelines. Healthcare professionals could also consider providing antenatal waterbirth education to women and obtain women's feedback to improve current policies/guidelines. Future research should explore the views of different types of healthcare professionals from more diverse cultures. REPORTING METHOD: The PRISMA guidelines. NO PATIENT OR PUBLIC CONTRIBUTION: Systematic review.
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Introduction: Artificial placenta therapy (APT) is an experimental life support system to improve outcomes for extremely preterm infants (EPI) less than 1,000 g by obviating the need for pulmonary gas exchange. There are presently no long-term survival data for EPI supported with APT. To address this, we aimed to maintain 95d-GA (GA; term-150d) sheep fetuses for up to 2 weeks using our APT system. Methods: Pregnant ewes (n = 6) carrying singleton fetuses underwent surgical delivery at 95d GA. Fetuses were adapted to APT and maintained for up to 2 weeks with constant monitoring of key physiological parameters and extensive time-course blood and urine sampling, and ultrasound assessments. Six age-matched in-utero fetuses served as controls. Data were tested for group differences with ANOVA. Results: Six APT Group fetuses (100%) were adapted to APT successfully. The mean BW at the initiation of APT was 656 ± 42 g. Mean survival was 250 ± 72 h (Max 336 h) with systemic circulation and key physiological parameters maintained mostly within normal ranges. APT fetuses had active movements and urine output constantly exceeded infusion volume over the experiment. At delivery, there were no differences in BW (with edema in three APT group animals), brain weight, or femur length between APT and in-utero Control animals. Organ weights and humerus lengths were significantly reduced in the APT group (p < 0.05). Albumin, IGF-1, and phosphorus were significantly decreased in the APT group (p < 0.05). No cases of positive blood culture were detected. Conclusion: We report the longest use of APT to maintain extremely preterm fetuses to date. Fetal systemic circulation was maintained without infection, but growth was abnormal. This achievement suggests a need to focus not only on cardiovascular stability and health but also on the optimization of fetal growth and organ development. This new challenge will need to be overcome prior to the clinical translation of this technology.
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BACKGROUND: Current strategies for preimplantation genetic testing for aneuploidy or structural rearrangements (PGT-A/SR) rely mainly on next-generation sequencing (NGS) and microarray platforms, which are robust but require expensive instrumentation. We explored the suitability of third-generation single-molecule sequencing as a PGT-A/SR screening platform for both aneuploidy and segmental imbalance. METHODS: Single-cell and multicell replicates from aneuploid or segmentally unbalanced cell lines (n = 208) were SurePlex-amplified, randomized, and subjected to (a) Nanopore-based single-molecule sequencing (Oxford Nanopore Technologies) and (b) NGS using a leading commercial PGT-A solution (Illumina VeriSeq PGS). Archival SurePlex-amplified trophectoderm biopsy samples (n = 96) previously analyzed using the commercial kit were blinded and reanalyzed using Nanopore. RESULTS: Nanopore-based PGT-A identified the specific aberration in 95.45% (84/88) and 97.78% (88/90) of single-/multicells with an aneuploidy or segmental imbalance (10-30.5 Mb), respectively. Comparison against the commercial kit's results revealed concordances of 98.86% (87/88) and 98.89% (89/90) for the aneuploid and segmentally unbalanced (10-30.5 Mb aberration) samples, respectively. Detection sensitivity for smaller segmental imbalances (5-5.8 Mb aberration, n = 30) decreased markedly on both platforms. Nanopore-based PGT-A reanalysis of trophectoderm biopsy samples was 97.92% (94/96) concordant with the commercial kit results. CONCLUSION: Up to 24 SurePlex-amplified single-cell, multicell, or trophectoderm samples could be sequenced in a single MinION flow-cell for subsequent preimplantation genetic testing for aneuploidy or structural rearrangements (PGT-A/SR) analysis, with results obtainable in ≤3 days and at per-sample costs that are competitive with commercial offerings. Nanopore's third-generation single-molecule sequencing represents a viable alternative to current commercial NGS-based PGT-A solutions for aneuploidy and segmental imbalance (≥10 Mb) screening of single-/multicell or trophectoderm biopsy samples.