Obstetrics and Gynaecology - Research Publications

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    Chlamydia retesting remains low among young women in Australia: an observational study using sentinel surveillance data, 2018-2022
    Munari, SC ; Wilkinson, AL ; Asselin, J ; Owen, L ; Read, P ; Finlayson, R ; Martin, S ; Bell, C ; O'Connor, CC ; Carter, A ; Guy, R ; McNulty, A ; Varma, R ; Chow, EPF ; Fairley, CK ; Donovan, B ; Stoove, M ; Goller, JL ; Hocking, J ; Hellard, ME ; Simms, I (CSIRO PUBLISHING, 2024)
    BACKGROUND: Chlamydia remains the most notified bacterial sexually transmissible infection in Australia with guidelines recommending testing for re-infection at 3months post treatment. This paper aimed to determine chlamydia retesting and repeat positivity rates within 2-4months among young women in Australia, and to evaluate what factors increase or decrease the likelihood of retesting. METHODS: Chlamydia retesting rates among 16-29-year-old women were analysed from Australian Collaboration for Coordinated Enhanced Sentinel Surveillance of sexually transmissible infection and bloodborne virus (ACCESS) sentinel surveillance data (n =62 sites). Among women with at least one positive test between 1 January 2018 and 31 August 2022, retesting counts and proportions within 2-4months were calculated. Logistic regression was performed to assess factors associated with retesting within 2-4months. RESULTS: Among 8758 women who were positive before 31 August 2022 to allow time for follow up, 1423 (16.2%) were retested within 2-4months, of whom 179 (12.6%) tested positive. The odds of retesting within 2-4months were 25% lower if tested in a coronavirus disease 2019 (COVID-9) pandemic year (2020-2022) (aOR=0.75; 95% CI 0.59-0.95). Among 9140 women with a positive test before 30 November 2022, 397 (4.3%) were retested too early (within 7days to 1month) and 81 (20.4%) of those were positive. CONCLUSIONS: Chlamydia retesting rates remain low with around a sixth of women retested within 2-4months in line with guidelines. Re-infection is common with around one in eight retesting positive. An increase in retesting is required to reduce the risk of reproductive complications and onward transmission.
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    Early Hyperoxemia and 2-year Outcomes in Infants with Hypoxic-ischemic Encephalopathy: A Secondary Analysis of the Infant Cooling Evaluation Trial
    Badurdeen, S ; Cheong, JLY ; Donath, S ; Graham, H ; Hooper, SB ; Polglase, GR ; Jacobs, S ; Davis, PG (MOSBY-ELSEVIER, 2024-04)
    OBJECTIVE: To determine the causal relationship between exposure to early hyperoxemia and death or major disability in infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: We analyzed data from the Infant Cooling Evaluation (ICE) trial that enrolled newborns ≥35 weeks' gestation with moderate-severe HIE, randomly allocated to hypothermia or normothermia. The primary outcome was death or major sensorineural disability at 2 years. We included infants with arterial pO2 measured within 2 hours of birth. Using a directed acyclic graph, we established that markers of severity of perinatal hypoxia-ischemia and pCO2 were a minimally sufficient set of variables for adjustment in a regression model to estimate the causal relationship between arterial pO2 and death/disability. RESULTS: Among 221 infants, 116 (56%) had arterial pO2 and primary outcome data. The unadjusted analysis revealed a U-shaped relationship between arterial pO2 and death or major disability. Among hyperoxemic infants (pO2 100-500 mmHg) the proportion with death or major disability was 40/58 (0.69), while the proportion in normoxemic infants (pO2 40-99 mmHg) was 20/48 (0.42). In the adjusted model, hyperoxemia increased the risk of death or major disability (adjusted risk ratio 1.61, 95% CI 1.07-2.00, P = .03) in relation to normoxemia. CONCLUSION: Early hyperoxemia increased the risk of death or major disability among infants who had an early arterial pO2 in the ICE trial. Limitations include the possibility of residual confounding and other causal biases. Further work is warranted to confirm this relationship in the era of routine therapeutic hypothermia.
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    The Knowledge Translation of Early Cerebral Palsy (KiTE CP) study: Implementing Screening among a High-risk Prospective Cohort of Australian Infants
    Kwong, AKL ; Eeles, AL ; Anderson, PJ ; Badawi, N ; Boyd, RN ; Cameron, KL ; Cheong, JLY ; Colditz, P ; Koorts, P ; Crowle, C ; Dale, RC ; Doyle, LW ; Fahey, M ; George, J ; Hunt, RW ; Mcnamara, L ; Morgan, C ; Novak, I ; Olsen, JE ; Reid, N ; Rieger, I ; Whittingham, K ; Spittle, AJ (MOSBY-ELSEVIER, 2024-05)
    OBJECTIVE: To describe the implementation of the international guidelines for the early diagnosis of cerebral palsy (CP) and engagement in the screening process in an Australian cohort of infants with neonatal risk factors for CP. STUDY DESIGN: Prospective cohort study of infants with neonatal risk factors recruited at <6 months corrected age from 11 sites in the states of Victoria, New South Wales, and Queensland, Australia. First, we implemented a multimodal knowledge translation strategy including barrier identification, technology integration, and special interest groups. Screening was implemented as follows: infants with clinical indications for neuroimaging underwent magnetic resonance imaging and/or cranial ultrasound. The Prechtl General Movements Assessment (GMA) was recorded clinically or using an app (Baby Moves). Infants with absent or abnormal fidgety movements on GMA videos were offered further assessment using the Hammersmith Infant Neurological Examination (HINE). Infants with atypical findings on 2/3 assessments met criteria for high risk of CP. RESULTS: Of the 597 infants (56% male) recruited, 95% (n = 565) received neuroimaging, 90% (n = 537) had scorable GMA videos (2% unscorable/8% no video), and 25% (n = 149) HINE. Overall, 19% of the cohort (n = 114/597) met criteria for high risk of CP, 57% (340/597) had at least 2 normal assessments (of neuroimaging, GMA or HINE), and 24% (n = 143/597) had insufficient assessments. CONCLUSIONS: Early CP screening was implemented across participating sites using a multimodal knowledge translation strategy. Although the COVID-19 pandemic affected recruitment rates, there was high engagement in the screening process. Reasons for engagement in early screening from parents and clinicians warrant further contextualization and investigation.
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    Joint developmental trajectories of internalizing and externalizing problems from mid-childhood to late adolescence and childhood risk factors: Findings from a prospective pre-birth cohort
    Bista, S ; Tait, RJ ; Straker, LM ; Lin, A ; Steinbeck, K ; Graham, PL ; Kang, M ; Lymer, S ; Robinson, M ; Marino, JL ; Skinner, SR (CAMBRIDGE UNIV PRESS, 2024-01-04)
    There is limited evidence on heterogenous co-developmental trajectories of internalizing (INT) and externalizing (EXT) problems from childhood to adolescence and predictors of these joint trajectories. We utilized longitudinal data from Raine Study participants (n = 2393) to identify these joint trajectories from 5 to 17 years using parallel-process latent class growth analysis and analyze childhood individual and family risk factors predicting these joint trajectories using multinomial logistic regression. Five trajectory classes were identified: Low-problems (Low-INT/Low-EXT, 29%), Moderate Externalizing (Moderate-EXT/Low-INT, 26.5%), Primary Internalizing (Moderate High-INT/Low-EXT, 17.5%), Co-occurring (High-INT/High-EXT, 17%), High Co-occurring (Very High-EXT/High-INT, 10%). Children classified in Co-occurring and High Co-occurring trajectories (27% of the sample) exhibited clinically meaningful co-occurring problem behaviors and experienced more adverse childhood risk-factors than other three trajectories. Compared with Low-problems: parental marital problems, low family income, and absent father predicted Co-occurring and High Co-occurring trajectories; maternal mental health problems commonly predicted Primary Internalizing, Co-occurring, and High Co-occurring trajectories; male sex and parental tobacco-smoking uniquely predicted High Co-occurring membership; other substance smoking uniquely predicted Co-occurring membership; speech difficulty uniquely predicted Primary Internalizing membership; child's temper-tantrums predicted all four trajectories, with increased odds ratios for High Co-occurring (OR = 8.95) and Co-occurring (OR = 6.07). Finding two co-occurring trajectories emphasizes the importance of early childhood interventions addressing comorbidity.
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    An audit of the maternal medicine clinic: Cancer and pregnancy.
    Harrison, M ; Umstad, MP ; Cui, W ; Thevathasan, I ; Price, SAL (Wiley, 2024-01-24)
    AIMS: To explore the incidence and complexity of women presenting for maternity care who require concurrent cancer care, and to report the birth outcomes of these women. MATERIALS AND METHODS: A retrospective audit of women attending a 'high risk' maternal medicine clinic at an Australian tertiary maternity hospital between 1 October 2021 and 30 April 2023 was conducted. The inclusion criteria were a diagnosis of cancer and a concurrent pregnancy, or a diagnosis of cancer prior to the current pregnancy. Clinic lists and coding data were screened via the electronic medical record to identify potential subjects. Data were collected from the individual maternity and neonatal records. RESULTS: Forty of 705 (5.7%) women attending the maternal medicine clinic met the inclusion criteria, of which ten had a new diagnosis of cancer in pregnancy and 30 presented for maternity care after a previous diagnosis of cancer. Cancer therapy during pregnancy included surgery and chemotherapy. Most pregnancies (92.5%) resulted in term deliveries (≥37 weeks gestation). Four neonates were preterm, and one was small-for-gestational-age. Caesarean section delivery and post-partum haemorrhage were more common than expected, but the rate of other adverse pregnancy outcomes was consistent with the background population. Over half of neonates required neonatal intensive care unit / special care nursery admission but the indications for admission were common, self-limiting conditions, and the length of stay was short (mean <5.0 days). CONCLUSIONS: Approximately 6% of women attending the maternal medicine clinic had a current or previous diagnosis of cancer. Most pregnancies resulted in term deliveries and neonatal outcomes were excellent.
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    Association of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival
    Morra, A ; Schreurs, MAC ; Andrulis, IL ; Anton-Culver, H ; Augustinsson, A ; Beckmann, MW ; Behrens, S ; Bojesen, SE ; Bolla, MK ; Brauch, H ; Broeks, A ; Buys, SS ; Camp, NJ ; Castelao, JE ; Cessna, MH ; Chang-Claude, J ; Chung, WK ; Colonna, S ; Couch, FJ ; Cox, A ; Cross, SS ; Czene, K ; Daly, MB ; Dennis, J ; Devilee, P ; Doerk, T ; Dunning, AM ; Dwek, M ; Easton, DF ; Eccles, DM ; Eriksson, M ; Evans, DG ; Fasching, PA ; Fehm, TN ; Figueroa, JD ; Flyger, H ; Gabrielson, M ; Gago-Dominguez, M ; Garcia-Closas, M ; Garcia-Saenz, JA ; Genkinger, JA ; Grassmann, F ; Guendert, M ; Hahnen, E ; Haiman, C ; Hamann, U ; Harrington, PA ; Hartikainen, JM ; Hoppe, R ; Hopper, JL ; Houlston, RS ; Howell, A ; Jakubowska, A ; Janni, W ; Jernstroem, H ; John, EM ; Johnson, N ; Jones, ME ; Kristensen, VN ; Kurian, AW ; Lambrechts, D ; Le Marchand, L ; Lindblom, A ; Lubinski, J ; Lux, MP ; Mannermaa, A ; Mavroudis, D ; Mulligan, AM ; Muranen, TA ; Nevanlinna, H ; Nevelsteen, I ; Neven, P ; Newman, WG ; Obi, N ; Offit, K ; Olshan, AF ; Park-Simon, T-W ; Patel, A ; Peterlongo, P ; Phillips, K-A ; Plaseska-Karanfilska, D ; Polley, EC ; Presneau, N ; Pylkas, K ; Rack, B ; Radice, P ; Rashid, MU ; Rhenius, V ; Robson, M ; Romero, A ; Saloustros, E ; Sawyer, EJ ; Schmutzler, RK ; Schuetze, S ; Scott, C ; Shah, MT ; Smichkoska, S ; Southey, MC ; Tapper, WJ ; Teras, LR ; Tollenaar, RAEM ; Tomczyk, K ; Tomlinson, I ; Troester, M ; Vachon, C ; van Veen, E ; Wang, Q ; Wendt, C ; Wildiers, H ; Winqvist, RA ; Ziogas, A ; Hall, P ; Pharoah, PDP ; Adank, M ; Hollestelle, A ; Schmidt, MK ; Hooning, MJ (WILEY, 2023-08)
    BACKGROUND: Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. AIM: To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. METHODS: Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. RESULTS: There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09-1.56)]. CONCLUSION: Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.
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    Statistical analyses of ordinal outcomes in randomised controlled trials: a scoping review
    Selman, CJ ; Lee, KJ ; Ferguson, KN ; Whitehead, CL ; Manley, BJ ; Mahar, RK (BMC, 2024-04-06)
    BACKGROUND: Randomised controlled trials (RCTs) aim to estimate the causal effect of one or more interventions relative to a control. One type of outcome that can be of interest in an RCT is an ordinal outcome, which is useful to answer clinical questions regarding complex and evolving patient states. The target parameter of interest for an ordinal outcome depends on the research question and the assumptions the analyst is willing to make. This review aimed to provide an overview of how ordinal outcomes have been used and analysed in RCTs. METHODS: The review included RCTs with an ordinal primary or secondary outcome published between 2017 and 2022 in four highly ranked medical journals (the British Medical Journal, New England Journal of Medicine, The Lancet, and the Journal of the American Medical Association) identified through PubMed. Details regarding the study setting, design, the target parameter, and statistical methods used to analyse the ordinal outcome were extracted. RESULTS: The search identified 309 studies, of which 144 were eligible for inclusion. The most used target parameter was an odds ratio, reported in 78 (54%) studies. The ordinal outcome was dichotomised for analysis in 47 ( 33 % ) studies, and the most common statistical model used to analyse the ordinal outcome on the full ordinal scale was the proportional odds model (64 [ 44 % ] studies). Notably, 86 (60%) studies did not explicitly check or describe the robustness of the assumptions for the statistical method(s) used. CONCLUSIONS: The results of this review indicate that in RCTs that use an ordinal outcome, there is variation in the target parameter and the analytical approaches used, with many dichotomising the ordinal outcome. Few studies provided assurance regarding the appropriateness of the assumptions and methods used to analyse the ordinal outcome. More guidance is needed to improve the transparent reporting of the analysis of ordinal outcomes in future trials.
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    Metformin in pregnancy and childhood neurodevelopmental outcomes: a systematic review and meta-analysis.
    Gordon, HG ; Atkinson, JA ; Tong, S ; Mehdipour, P ; Cluver, C ; Walker, SP ; Lindquist, AC ; Hastie, RM (Elsevier BV, 2024-03-07)
    OBJECTIVE: This study aimed to examine the impact of maternal metformin use during pregnancy on offspring neurodevelopmental outcomes. DATA SOURCES: MEDLINE, Embase, and Web of Science (Core Collection) were searched from inception until July 1, 2023. STUDY ELIGIBILITY CRITERIA: Studies of women who received treatment with metformin at any stage of pregnancy for any indication with neurodevelopmental data available for their offspring were included. Studies without a control group were excluded. Randomized controlled trials, case-control, cohort, and cross-sectional studies were included in the review. METHODS: Studies were screened for inclusion and data were extracted independently by 2 reviewers. Risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale for nonrandomized studies, and the Risk of Bias 2 tool for randomized trials. RESULTS: A total of 7 studies met the inclusion criteria, including a combined cohort of 14,042 children with 7641 children who were exposed and followed for up to 14 years of age. Metformin use during pregnancy was not associated with neurodevelopmental delay in infancy (relative risk, 1.09; 95% confidence interval, 0.54-2.17; 3 studies; 9668 children) or at ages 3 to 5 years (relative risk, 0.90; 95% confidence interval, 0.56-1.45; 2 studies; 6118 children). When compared with unexposed peers, metformin use during pregnancy was not associated with altered motor scores (mean difference, 0.30; 95% confidence interval, -1.15 to 1.74; 3 studies; 714 children) or cognitive scores (mean difference, -0.45; 95% confidence interval, -1.45 to 0.55; 4 studies; 734 children). Studies that were included were of high quality and deemed to be at low risk of bias. CONCLUSION: In utero exposure to metformin does not seem to be associated with adverse neurodevelopmental outcomes in children up to the age of 14 years. These findings provide reassurance to clinicians and pregnant women considering metformin use during pregnancy.
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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.