Obstetrics and Gynaecology - Research Publications

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    Telehealth in antenatal care: recent insights and advances
    Atkinson, J ; Hastie, R ; Walker, S ; Lindquist, A ; Tong, S (BMC, 2023-08-30)
    BACKGROUND: For decades, antenatal care in high-resource settings has involved 12-14 face-to-face visits across pregnancy. The COVID-19 pandemic forced many care providers to rapidly embrace telehealth to reduce face-to-face visits. Here we review recent advances in telehealth used to provide antenatal care. MAIN BODY: We conducted a narrative review examining the impact of telehealth on obstetric care. Two broad types of telehealth are used in antenatal care. The first is real-time telehealth, where consultations are done virtually instead of face-to-face. The second is remote monitoring, where in-clinic physical examinations are replaced with at-home alternatives. These can include blood pressure monitoring, fetal heart rate monitoring, and emerging technologies such as tele-ultrasound. Large cohort studies conducted during the pandemic era have shown that telehealth appears not to have increased adverse clinical outcomes for mothers or babies. However, further studies may be required to confidently conclude rare outcomes are unchanged, such as maternal mortality, serious morbidity, or stillbirth. Health economic studies suggest telehealth has the potential to reduce the financial cost of care provision. Telehealth in antenatal care seems to be acceptable to both pregnant women and healthcare providers. CONCLUSION: Adoption of telehealth technologies may improve the antenatal care experience for women and reduce healthcare expenditure without adversely impacting health outcomes for the mother or baby. More studies are warranted to confirm telehealth does not alter the risk of rare outcomes such as maternal or neonatal mortality.
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    The long-term risk of cardiovascular disease among women with a history of hypertensive disorders of pregnancy: a systematic review of clinical practice guidelines
    Atkinson, J ; Simpson, G ; Walker, SP ; Tong, S ; Hastie, R ; Lindquist, A (BMC, 2023-09-09)
    BACKGROUND: The lifelong risks of cardiovascular disease following preeclampsia and gestational hypertension are well-established. However, it is unclear whether this evidence has been translated into clinical practice guidelines. Thus, this review aimed to assess the quality and content of Australian clinical practice guidelines regarding the risk of cardiovascular disease following gestational hypertension and preeclampsia. METHODS: We conducted a systematic search of MEDLINE (Ovid), EMBASE (Ovid), and CINAHL databases, as well as hospital, obstetric society, and medical college websites. Publications were included if: they were a clinical practice guideline; were published in the previous ten years; and included recommendations for the management of future cardiovascular disease risk following hypertensive disorders of pregnancy. Quality assessment was performed using Appraisal of Guidelines for Research and Evaluation Instrument Version Two (AGREE-II) and AGREE Recommendations Excellence Instrument (AGREE-REX). RESULTS: Eighteen guidelines were identified, and of these, less than half (nā€‰=ā€‰8) included recommendations for managing future cardiovascular risk following hypertensive disorders of pregnancy. Across these eight, four main counselling recommendations were found regarding (1) risk of future cardiovascular disease; (2) risk factor screening; (3) lifestyle interventions; and (4) prenatal counselling for future pregnancies. The quality and content of these recommendations varied significantly, and the majority of guidelines (87.5%) were assessed as low to moderate quality. CONCLUSIONS: There are limited Australian clinical practice guidelines providing appropriate advice regarding future risk of cardiovascular disease following hypertensive disorders of pregnancy. The quality and content of these guidelines varied significantly. These findings highlight the need for improved translation from evidence-based research to enhance clinical care and guidance.
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    Oral vinorelbine to treat women with ectopic pregnancy: a phase 1 clinical safety and tolerability study
    Chowdary, P ; Hastie, R ; Lino, T ; Middleton, A ; Capes, G ; Humphries, A ; Abed-Ali, A ; Anderson, M ; Mol, BWJ ; Horne, A ; Lim, E ; Andrew, P ; Brownfoot, F ; Tong, S (ELSEVIER SCIENCE INC, 2023-09)
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    Low-Dose Aspirin Use in Pregnancy and the Risk of Preterm Birth: A Swedish Register-Based Cohort Study
    Kupka, E ; Hesselman, S ; Hastie, R ; Lomartire, R ; Wikstrƶm, AK ; Bergman, L (Ovid Technologies (Wolters Kluwer Health), 2023-09-01)
    ABSTRACT Evidence has shown that low-dose aspirin can reduce the risk of preeclampsia in women with risk factors; more recent evidence has shown that aspirin may also be useful for the prevention of spontaneous preterm birth, even among women without risk factors for preeclampsia. However, there are fewer studies examining the effectiveness of low-dose aspirin in this population, and the studies that have been done have generally been statistically underpowered. This study was meant to address this limitation in a large population of women who had previously experienced preterm birth, assessing whether low-dose aspirin treatment was associated with a lower risk for preterm birth. This study was a register-based cohort study performed using several different Swedish registries. The sample included all women with a first and second singleton birth between 2006 and 2019 and with a preterm birth in the first pregnancy. The primary outcome assessed was preterm birth during the second pregnancy, and secondary outcomes included assessment of preterm birth by severity (moderate preterm was between 32 and 36 weeks' gestation, and severe preterm was less than 32 weeks' gestation) and onset (spontaneous or medically indicated). The variable of interest was low-dose aspirin exposure or at least 1 dispensed prescription of 75 to 160 mg aspirin. The analysis included 22,127 women with a preterm birth in their first pregnancy followed by a second recorded pregnancy. Of this sample, 3057 (14%) were prescribed low-dose aspirin during their second pregnancy. Recurrent preterm birth occurred in 3703 individuals, of whom 547 (15%) had used low-dose aspirin. After adjusting for confounding variables, the incidence of preterm birth was lower in those using low-dose aspirin, with a marginal relative risk (mRR) of 0.87 (95% confidence interval [CI], 0.77ā€“0.99). However, there was no difference in risk for moderate or severe preterm birth (moderate group: mRR, 0.90 [95% CI, 0.78ā€“1.03]; severe group: mRR, 0.75 [95% CI, 0.54ā€“1.04]). In adjusted analyses, there were no statistically significant differences for either medically indicated or spontaneous preterm birth between individuals who used low-dose aspirin and those who did not. The study was limited by its retrospective nature. In addition, the authors acknowledge that a dispensed prescription for aspirin does not necessarily equate to consistent intake of low-dose aspirin throughout a pregnancy. In addition, the population for this study was limited to those who had already experienced a preterm birth, which could affect the generalizability of the results. Although limited differences were found, a small protective effect could not be ruled out, and randomized controlled trials to understand more fully the effect low-dose aspirin might have on preterm birth would be helpful. Further research should also focus on whether the benefits of aspirin use during pregnancy outweigh the potential risks, as well as what the lowest effective dose might be.
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    The effect of selenium supplementation in pregnant women on maternal, fetal, and newborn outcomes: a systematic review and meta-analysis
    McDougall, AR ; Dore, G ; Aboud, L ; Makama, M ; Nguyen, PY ; Mills, K ; Sanderson, B ; Hastie, R ; Ammerdorffer, A ; Vogel, JP (ELSEVIER, 2023-11)
    OBJECTIVE: Low maternal selenium status has been associated with poor pregnancy outcomes, including preterm birth. This study aimed to evaluate available evidence of the effects of selenium supplementation during pregnancy on preterm birth and related maternal, fetal, and newborn outcomes. DATA SOURCES: MEDLINE, Embase, CINAHL, Global Index Medicus, and the Cochrane Library were systematically searched on June 23, 2022, without language or time restrictions. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials and nonrandomized interventional studies were included if they compared the effects of selenium supplementation with placebo or no treatment among pregnant women. The review protocol was registered in the International Prospective Register of Systematic Reviews (identification number: CRD42022383669). METHODS: For outcomes reported by ā‰„1 study, a meta-analysis was conducted. Because of the small number of studies and high clinical heterogeneity between populations, random-effects models were used. The Risk of Bias 2 and Risk Of Bias In Non-randomized Studies - of Interventions tools were used to assess study quality, and Grading of Recommendations Assessment, Development, and Evaluation analysis was used to determine the certainty of evidence for each outcome. RESULTS: Literature searches identified 5105 unique records, and 32 studies met the eligibility criteria. Of note, 11 reports were not included for analysis following research integrity assessments. Moreover, 10 trials and 3 observational studies met the inclusion criteria; however, only 8 trials (1851 women) and 1 prospective cohort study (71,728 women) reported on at least 1 review outcome. Our results could not determine the effect of selenium supplementation on preterm birth at <37 weeks of gestation (relative risk, 0.65; 95% confidence interval, 0.26-1.63; very low certainty evidence) and <34 weeks of gestation (relative risk, 1.05; 95% confidence interval, 0.59-1.44; very low certainty evidence). CONCLUSION: There is limited evidence on the effects of selenium supplementation during pregnancy. Further trials, with larger sample sizes, more representative populations, and reliable assessment of maternal selenium status at trial entry, are required.
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    Risk of obstetric anal sphincter injury among women who birth vaginally after a prior caesarean section: A state-wide cohort study
    Uebergang, J ; Hiscock, R ; Hastie, R ; Middleton, A ; Pritchard, N ; Walker, S ; Tong, S ; Lindquist, A (WILEY, 2022-07)
    OBJECTIVE: Vaginal birth after caesarean (VBAC) has been suggested to be associated with an increased risk of obstetric anal sphincter injury (compared with primiparous women who birth vaginally). However, prior studies have been small or have used outdated methodology. We set out to validate whether the risk of obstetric anal sphincter injury among women having their first VBAC is greater than that among primiparous women having a vaginal birth. DESIGN: State-wide retrospective cohort study. SETTING: Victoria, Australia. POPULATION: All births (455 000) between 2009 and 2014. METHODS: The risk of severe perineal injury between the first vaginal birth and the first VBAC was compared, after adjustment for potential confounding variables. Covariates were examined using logistic regression for categorical data and the Wilcoxon rank-sum test for continuous data. Missing data were handled using multiple imputation; the analysis was performed using regression adjustment and stata 16 multiple imputation and suite of effects commands. RESULTS: Women having a VBAC (n = 5429) were significantly more likely than primiparous women (n = 123 353) to sustain a third- or fourth-degree tear during vaginal birth (7.1 versus 5.7%, p < 0.001). After adjustment for mode of birth, body mass index, maternal age, infant birthweight, episiotomy and epidural, there was a 21% increased risk of severe perineal injury (RR 1.21, 95% CI 1.07-1.38). CONCLUSIONS: Women having their first VBAC have a significantly increased risk of sustaining a third- or fourth-degree tear, compared with primiparous women having a vaginal birth. Patient counselling and professional guidelines should reflect this increased risk.
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    Systematic evaluation of the pre-eclampsia drugs, dietary supplements and biologicals pipeline using target product profiles
    McDougall, ARA ; Hastie, R ; Goldstein, M ; Tuttle, A ; Tong, S ; Ammerdorffer, A ; Guelmezoglu, AM ; Vogel, JP (BMC, 2022-11-04)
    BACKGROUND: The Accelerating Innovation for Mothers (AIM) project established a database of candidate medicines in research and development (R&D) between 2000 and 2021 for five pregnancy-related conditions, including pre-eclampsia. In parallel, we published target product profiles (TPPs) that describe optimal characteristics of medicines for use in preventing/treating pre-eclampsia. The study objective was to use systematic double screening and extraction to identify all candidate medicines being investigated for pre-eclampsia prevention/treatment and rank their potential based on the TPPs. METHODS: Adis Insight, Pharmaprojects, WHO international clinical trials registry platform (ICTRP), PubMed and grant databases were searched (Jan-May 2021). The AIM database was screened for all candidates being investigated for pre-eclampsia. Candidates in clinical development were evaluated against nine prespecified criteria from TPPs identified as key for wide-scale implementation, and classified as high, medium or low potential based on matching to the TPPs. Preclinical candidates were categorised by product type, archetype and medicine subclass. RESULTS: The AIM database identified 153 candidates for pre-eclampsia. Of the 87 candidates in clinical development, seven were classified as high potential (prevention: esomeprazole, L-arginine, chloroquine, vitamin D and metformin; treatment: sulfasalazine and metformin) and eight as medium potential (prevention: probiotic lactobacilli, dalteparin, selenium and omega-3 fatty acid; treatment: sulforaphane, pravastatin, rosuvastatin and vitamin B3). Sixty-six candidates were in preclinical development, the most common being amino acid/peptides, siRNA-based medicines and polyphenols. CONCLUSIONS: This is a novel, evidence-informed approach to identifying promising candidates for pre-eclampsia prevention and treatment - a vital step in stimulating R&D of new medicines for pre-eclampsia suitable for real-world implementation.
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    Circulating Chemerin Is Elevated in Women With Preeclampsia
    Bartho, LA ; Kandel, M ; Walker, SP ; Cluver, CA ; Hastie, R ; Bergman, L ; Pritchard, N ; Cannon, P ; Nguyen, T-V ; Wong, GP ; MacDonald, TM ; Keenan, E ; Hannan, NJ ; Tong, S ; Kaitu'u-Lino, TJ (ENDOCRINE SOC, 2023-03-13)
    BACKGROUND: Preeclampsia is a severe complication of pregnancy. Chemerin is an adipokine secreted from adipose tissue and highly expressed in placenta. This study evaluated the biomarker potential of circulating chemerin to predict preeclampsia. METHODS: Maternal plasma and placenta were collected from women with early-onset preeclampsia (<34 weeks), with preeclampsia and eclampsia, or before preeclampsia diagnosis (36 weeks). Human trophoblast stem cells were differentiated into syncytiotrophoblast or extravillous trophoblasts across 96ā€…hours. Cells were cultured in 1% O2 (hypoxia) or 5% O2 (normoxia). Chemerin was measured by enzyme-linked immunosorbent assay (ELISA) and RARRES2 (gene coding chemerin) by reverse transcription-quantitative polymerase chain reaction. RESULTS: Circulating chemerin was increased in 46 women with early-onset preeclampsia (<34 weeks) compared to 17 controls (P < .0006). Chemerin was increased in placenta from 43 women with early-onset preeclampsia compared to 24 controls (P < .0001). RARRES2 was reduced in placenta from 43 women with early-onset preeclampsia vs 24 controls (P < .0001). Chemerin was increased in plasma from 26 women with established preeclampsia (P = .006), vs 15 controls. Circulating chemerin was increased in 23 women who later developed preeclampsia vs 182 who did not (P = 3.23 Ɨ 10-6). RARRES2 was reduced in syncytiotrophoblast (P = .005) or extravillous trophoblasts (P < .0001). Hypoxia increased RARRES2 expression in syncytiotrophoblast (P = .01) but not cytotrophoblast cells. CONCLUSIONS: Circulating chemerin was elevated in women with early-onset preeclampsia, established preeclampsia, and preceding preeclampsia diagnosis of preeclampsia. RARRES2 was dysregulated in placenta complicated by preeclampsia and may be regulated through hypoxia. Chemerin may have potential as a biomarker for preeclampsia but would need to be combined with other biomarkers.
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    Management of late preterm preeclampsia: a comparison of maternal and fetal indications for delivery
    Galibert, S ; Keenan, E ; Hastie, R ; Brownfoot, FC (TAYLOR & FRANCIS LTD, 2022-01-01)
    OBJECTIVE: To investigate delivery indications for women with late preterm preeclampsia and evaluate whether disease characteristics at presentation are predictive of delivery indication. METHODS: We conducted a retrospective case-control study at the Mercy Hospital for Women (a tertiary hospital in Melbourne, Australia). Indication for delivery was assessed among women presenting with preeclampsia between 30+0 and 36+0 weeks' gestation. Baseline maternal and disease characteristics, preeclampsia features at delivery and postnatal outcomes were compared between patients delivering for maternal, fetal, or for both maternal and fetal indications. RESULTS: 173 women were diagnosed with preeclampsia between 30+0 and 36+0 weeks' gestation. Maternal baseline characteristics were similar between the groups. We found that 55.5% of women were delivered on maternal grounds compared to 27.2% requiring delivery for fetal indications; and 17.3% for both maternal and fetal indications (pā€‰<ā€‰.0001). At diagnosis, intrauterine growth restriction and abnormal Dopplers increased the risk of requiring delivery for fetal indications by 3.5 times and 2.4 times respectively. CONCLUSION: Women presenting with late preterm preeclampsia primarily required delivery for maternal disease progression rather than fetal compromise.