Obstetrics and Gynaecology - Research Publications

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    Imprinted gene alterations in the kidneys of growth restricted offspring may be mediated by a long non-coding RNA
    Doan, TNA ; Cowley, JM ; Phillips, AL ; Briffa, JF ; Leemaqz, SY ; Burton, RA ; Romano, T ; Wlodek, ME ; Bianco-Miotto, T (TAYLOR & FRANCIS INC, 2024-12-31)
    Altered epigenetic mechanisms have been previously reported in growth restricted offspring whose mothers experienced environmental insults during pregnancy in both human and rodent studies. We previously reported changes in the expression of the DNA methyltransferase Dnmt3a and the imprinted genes Cdkn1c (Cyclin-dependent kinase inhibitor 1C) and Kcnq1 (Potassium voltage-gated channel subfamily Q member 1) in the kidney tissue of growth restricted rats whose mothers had uteroplacental insufficiency induced on day 18 of gestation, at both embryonic day 20 (E20) and postnatal day 1 (PN1). To determine the mechanisms responsible for changes in the expression of these imprinted genes, we investigated DNA methylation of KvDMR1, an imprinting control region (ICR) that includes the promoter of the antisense long non-coding RNA Kcnq1ot1 (Kcnq1 opposite strand/antisense transcript 1). Kcnq1ot1 expression decreased by 51% in growth restricted offspring compared to sham at PN1. Interestingly, there was a negative correlation between Kcnq1ot1 and Kcnq1 in the E20 growth restricted group (Spearman's ρ = 0.014). No correlation was observed between Kcnq1ot1 and Cdkn1c expression in either group at any time point. Additionally, there was a 11.25% decrease in the methylation level at one CpG site within KvDMR1 ICR. This study, together with others in the literature, supports that long non-coding RNAs may mediate changes seen in tissues of growth restricted offspring.
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    Near-to-patient-testing to inform targeted antibiotic use for sexually transmitted infections in a public sexual health clinic: the NEPTUNE cohort study
    Vodstrcil, LA ; Htaik, K ; Plummer, EL ; De Petra, V ; Sen, MG ; Williamson, DA ; Ong, JJ ; Wu, J ; Owlad, M ; Murray, G ; Chow, EPF ; Fairley, CK ; Bradshawa, CS (ELSEVIER, 2024-03)
    BACKGROUND: Empiric treatment of sexually transmitted infections can cause unnecessary antibiotic use. We determined if near-to-patient-testing (NPT) for Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium (MG) improved antibiotic-use for a range of clinical presentations. METHODS: Clients attending with non-gonococcal urethritis (NGU), proctitis, as STI-contacts, or for an MG-test-of-cure (MG-TOC) between March and December 2021 were recruited. Participants received near-to-patient-testing (NPT-group) for the three STIs using the GeneXpert® System (Cepheid), and concurrent routine-testing by transcription-mediated-amplification (TMA; Aptima, Hologic). Antibiotic-use among NGU or proctitis cases in the NPT-group was compared to clinic-controls undergoing routine-testing only. The proportion in the NPT-group who notified partners <24 hrs of their STI-specific result was calculated. FINDINGS: Among 904 consults by 808 NPT-participants, ≥1 STI was detected in 63/252 (25.0%) with NGU, 22/51 (43.1%) with proctitis, and 167/527 (31.7%) STI-contacts. MG was detected among 35/157 (22.3%) MG-TOC consults. Among NGU and proctitis cases, fewer in the NPT-group received empiric treatment compared to clinic-controls (29.4% [95% CI: 24.3-34.9%] vs 83.8% [95% CI: 79.2-87.8%], p < 0.001), resulting in more NPT-group cases appropriately treated (STI-specific drug/no drug appropriately; 80.9% [95% CI: 76.0-85.1%] vs 33.0% [95% CI: 27.7-38.6%], p < 0.001) and fewer mistreated (incorrect drug/treated but pathogen-negative; 17.8% [13.7-22.6%] vs 61.4% [55.6-66.9%], p < 0.001). Of 167/264 in the NPT-group with an STI who responded regarding partner-notification, 95.2% notified all/some partners; 85.9% notified them <24 hrs of the STI-specific result. INTERPRETATION: Near-to-patient-testing significantly improved antibiotic use and a high proportion of individuals rapidly notified partners of STI-specific results, highlighting the broad benefits of timely diagnostic strategies for STIs in clinical decision making and partner notification. FUNDING: ARC ITRP Hub-grant; NHMRC.
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    Concurrent parC and gyrA fluoroquinolone resistance mutations and associated strains in Mycoplasma genitalium in Queensland, Australia
    Ertl, NG ; Anderson, TK ; Pardo, CJ ; Maidment, T ; Murray, GL ; Bradshaw, CS ; Whiley, DM ; Sweeney, EL (OXFORD UNIV PRESS, 2024-02-01)
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    What do women undergoing in vitro fertilization (IVF) understand about their chance of IVF success?
    McMahon, C ; Hammarberg, K ; Lensen, S ; Wang, R ; Mol, BW ; Vollenhoven, BJN (OXFORD UNIV PRESS, 2024-01-05)
    STUDY QUESTION: How well informed are Australian women who undergo IVF about their chances of having a baby? SUMMARY ANSWER: Only one in four women estimated their individual chance of success with IVF accurately, with most women overestimating their chance. WHAT IS KNOWN ALREADY: Limited knowledge about infertility and infertility treatment in the general population is well-documented. The few studies that have investigated patients' knowledge about the chance of IVF success suggest that while IVF patients are aware of average success rates, they tend to be unrealistic about their own chance of success. STUDY DESIGN, SIZE, DURATION: We conducted an anonymous online survey of 217 women who had started IVF since 2018 in Australia. The survey was advertised on social media, enabling women from across Australia to participate. Responses were collected in June 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: The survey included questions on demographic characteristics and IVF history. It asked what participants thought their chance of having a baby from one IVF treatment cycle was, how they rated their knowledge about chance of success, and about their experience of receiving IVF-related information. Participants' estimations of their chance of success were compared with their chance as calculated by the Society for Assisted Reproductive Technology's (SART) online calculator. Responses to a free-text question about what information women wished they had been given when they started treatment were analysed thematically. MAIN RESULTS AND THE ROLE OF CHANCE: Only about a quarter (58/217, 27%) of participants accurately estimated their chance of having a baby within 20% relative to their SART calculated chance, with more than half (118/217, 54%) overestimating their chance. Ninety percent of women indicated that their preferred source of treatment information was a consultation with their doctor, despite less than half (44%) reporting that doctors explained the probability of having a baby with IVF well (mean 5.9/10). In free-text responses, many women also reported that they wished they had been given more realistic information about IVF and their chance of success. LIMITATIONS, REASONS FOR CAUTION: The dissemination method precludes calculation of response rate, and it is not possible to know if participants are representative of all women undergoing IVF. Additionally, we only surveyed women undergoing IVF, while those who decided not to have IVF were not included. Therefore, women who overestimated their chance may have been overrepresented. There is also inherent imprecision in the way understanding of chance of success was estimated. The potential impact of recall bias could neither be quantified nor excluded. It is difficult to determine to what extent women's lack of understanding of what is possible with IVF is due to poor information-provision by clinicians and the clinic, and how much can be explained by optimism bias. WIDER IMPLICATIONS OF THE FINDINGS: The finding of poor understanding of personal chance of success amongst women undergoing IVF in Australia requires further investigation to determine potential reasons for this. The findings can be used by clinics to develop strategies for improvement in the information-provision process to ensure that women can make informed decisions about their fertility treatment. STUDY FUNDING/COMPETING INTEREST(S): This study received no external funding. S.L. is supported by a NHMRC Investigator Grant (APP1195189). R.W. is supported by a NHMRC Investigator Grant (APP2009767). B.W.M. is supported by a NHMRC Investigator Grant (GNT1176437). B.W.M. reports consultancy for Merck and ObsEva and has received research funding and travel funding from Merck. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.
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    Development of a touchdown droplet digital PCR assay for the detection and quantitation of human papillomavirus 16 and 18 from self-collected anal samples
    Haqshenas, G ; Garland, SM ; Balgovind, P ; Cornall, A ; Danielewski, J ; Molano, M ; Machalek, DA ; Murray, G ; Starolis, M (AMER SOC MICROBIOLOGY, 2023-12-12)
    The quantity of the human papillomavirus (HPV) is associated with disease outcome. We designed an accurate and precise digital PCR assay for quantitating HPV in anal samples, a sample type that is typically problematic due to the presence of PCR inhibitors.
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    The Effect of Fetal Heart Rate Segment Selection on Deep Learning Models for Fetal Compromise Detection
    Mendis, L ; Palaniswami, M ; Brownfoot, F ; Keenan, E (IEEE, 2023)
    Monitoring the fetal heart rate (FHR) is common practice in obstetric care to assess the risk of fetal compromise. Unfortunately, human interpretation of FHR recordings is subject to inter-observer variability with high false positive rates. To improve the performance of fetal compromise detection, deep learning methods have been proposed to automatically interpret FHR recordings. However, existing deep learning methods typically analyse a fixed-length segment of the FHR recording after removing signal gaps, where the influence of this segment selection process has not been comprehensively assessed. In this work, we develop a novel input length invariant deep learning model to determine the effect of FHR segment selection for detecting fetal compromise. Using this model, we perform five times repeated five-fold cross-validation on an open-access database of 552 FHR recordings and assess model performance for FHR segment lengths between 15 and 60 minutes. We show that the performance after removing signal gaps improves with increasing segment length from 15 minutes (AUC = 0.50) to 60 minutes (AUC = 0.74). Additionally, we demonstrate that using FHR segments without removing signal gaps achieves superior performance across signal lengths from 15 minutes (AUC = 0.68) to 60 minutes (AUC = 0.76). These results show that future works should carefully consider FHR segment selection and that removing signal gaps might contribute to the loss of valuable information.
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    Parental Mental Health and Parenting Behaviors Following Very Preterm Birth: Associations in Mothers and Fathers and Implications for Child Cognitive Outcome.
    McMahon, GE ; Treyvaud, K ; Spittle, AJ ; Giallo, R ; Lee, KJ ; Cheong, JL ; Doyle, LW ; Spencer-Smith, MM ; Anderson, PJ (Oxford University Press (OUP), 2023-03-20)
    OBJECTIVES: To investigate the longitudinal associations between parental mental health symptoms within 4 weeks of birth, parenting behaviors at 1 year, and child general cognitive ability at 4.5-5 years in a sample of children born very preterm (VP). This study also examined whether these associations differed based on level of family social risk. METHODS: Participants were 143 children born <30 weeks' gestation and their parents. Within 4 weeks of birth, mothers' and fathers' depressive and anxiety symptoms were assessed using the Center for Epidemiologic Studies Depression Scale and Hospital Anxiety Depression Scale-Anxiety Subscale. Parents' sensitive and structuring parenting behaviors were assessed at 1 year using the Emotional Availability Scales. Child general cognitive ability was assessed at 4.5-5 years using the Wechsler Preschool & Primary Scale of Intelligence-Fourth Edition. RESULTS: Higher maternal depressive symptoms were associated with lower levels of sensitive and structuring parenting behavior, while higher maternal anxiety symptoms were associated with higher levels of structuring parenting behavior. There was weak evidence for positive associations between mothers' sensitive parenting behavior and fathers' structuring parenting behavior and child general cognitive ability. There was also weak evidence for stronger associations between mothers' mental health symptoms, parenting behaviors, and child general cognitive ability, in families of higher compared with lower social risk. CONCLUSIONS: Depressive and anxiety symptoms experienced by mothers in the initial weeks following VP birth can have long-term effects on their parenting behaviors. Enquiring about parents' mental health during their child's hospitalization in the neonatal intensive care unit is crucial.
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    "We are a unique breed": strategies to enhance physical activity participation for preschool-aged children born extremely preterm, a mixed-methods study
    Coulston, F ; Spittle, A ; McDonald, C ; Remedios, L ; Toovey, R ; Cheong, J ; Sellick, K (Taylor and Francis Group, 2023-11)
    PURPOSE: Preschool-aged children (three to five years old) born preterm participate in less physical activity (PA) than term-born children. Circus activities (a type of recreational PA) are a potential avenue to increase PA rates, but further insight into how to tailor these to address the participation gap is needed. This study investigated barriers and facilitators informing participation in recreational PA for preschool-aged children born extremely preterm and explored strategies to enhance participation in circus activities. MATERIALS AND METHODS: Sequential mixed-methods study utilizing surveys (n = 217), interviews (n = 43), and a focus group (n = 6) with key stakeholder groups (parents, coaches, and clinicians). Qualitative data (Framework Method) and quantitative data (descriptive statistics) were mixed during preliminary and final analyses. RESULTS: Five themes were developed from the mixed data: the crucial role of the coach and the need for specific training, the therapeutic role of PA and promoting outcomes beyond the physical, the impact of communication and class planning, consideration of convenience and cost, and finally, the role of clinicians. CONCLUSIONS: Barriers, facilitators, and strategies were identified which may be used to modify or co-design circus-based PA interventions to enhance participation and improve rates of PA for preschool-aged children born extremely preterm.IMPLICATIONS FOR REHABILITATIONFamilies consider recreational physical activities to be part of the therapeutic agenda for their preschool-aged children born extremely preterm.Key stakeholders feel that recreational physical activity should target outcomes beyond the physical.Coach attributes and capability impact participation of children born preterm and their families, and may be enhanced with specific training.Clinicians should be engaged in design of recreational physical activities for children born preterm.
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    Apnoeic oxygenation during neonatal intubation
    Baker, EK ; Davis, PG ; Hodgson, KA (ELSEVIER SCI LTD, 2023-10)
    'Apnoeic oxygenation' describes the diffusion of oxygen across the alveolar-capillary interface in the absence of tidal respiration. Apnoeic oxygenation requires a patent airway, the diffusion of oxygen to the alveoli, and cardiopulmonary circulation. Apnoeic oxygenation has varied applications in adult medicine including facilitating tubeless anaesthesia or improving oxygenation when a difficult airway is known or anticipated. In the paediatric population, apnoeic oxygenation prolongs the time to oxygen desaturation, facilitating intubation. This application has gained attention in neonatal intensive care where intubation remains a challenging procedure. Difficulties are related to the infant's size and decreased respiratory reserve. In addition, policy changes have led to limited opportunities for operators to gain proficiency. Until recently, evidence of benefit of apnoeic oxygenation in the neonatal population came from a small number of infants recruited to paediatric studies. Evidence specific to neonates is emerging and suggests apnoeic oxygenation may increase intubation success and limit physiological instability during the procedure. The best way to deliver oxygen to facilitate apnoeic oxygenation remains an important question.
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    Introduction to neonatal intubation and extubation
    Hodgson, KA ; Davis, PG (ELSEVIER SCI LTD, 2023-10)