Obstetrics and Gynaecology - Research Publications
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ItemNo Preview AvailableTelehealth in antenatal care: recent insights and advances(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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ItemNo Preview AvailableThe long-term risk of cardiovascular disease among women with a history of hypertensive disorders of pregnancy: a systematic review of clinical practice guidelines(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 (n = 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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ItemRisk of obstetric anal sphincter injury among women who birth vaginally after a prior caesarean section: A state-wide cohort study(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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ItemNo Preview AvailableCirculating Chemerin Is Elevated in Women With Preeclampsia(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 96 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 × 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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ItemNo Preview AvailableDevelopmental Outcomes for Children After Elective Birth at 39 Weeks' Gestation(AMER MEDICAL ASSOC, 2022-07)IMPORTANCE: Elective births at 39 weeks' gestation are increasing. While this option may improve maternal and perinatal outcomes compared with expectant management, longer-term childhood developmental outcomes are uncertain. OBJECTIVE: To investigate the association between elective birth at 39 weeks' gestation and the risk of childhood developmental vulnerability. DESIGN, SETTING, AND PARTICIPANTS: For this cohort study, 2 causal inference analyses were conducted using Australian statewide, population-based data. Perinatal data from births between January 1, 2005, and December 31, 2013, were linked to childhood developmental outcomes at age 4 to 6 years (assessed using multiple imputation via inverse probability-weighted regression adjustment). Data analyses were conducted between September 7 and November 9, 2021. EXPOSURES: Two exposure groups were considered: (1) elective birth between 39 weeks and 0 days' and 39 weeks and 6 days' gestation vs expectant management and (2) birth via induction of labor vs planned cesarean delivery among those born electively at 39 weeks' gestation. MAIN OUTCOMES AND MEASURES: Childhood developmental vulnerability at school entry, defined as scoring below the 10th percentile in at least 2 of 5 developmental domains (physical health and well-being, social competence, emotional maturity, school-based language and cognitive skills, and communication skills and general knowledge). RESULTS: Of 176 236 births with linked outcome data, 88 165 met the inclusion criteria. Among these, 15 927 (18.1%) were elective births at 39 weeks' gestation (induction of labor or planned cesarean delivery), and 72 238 (81.9%) were expectantly managed with subsequent birth between 40 and 43 weeks' gestation. Compared with expectant management, elective birth at 39 weeks' gestation was not associated with an altered risk of childhood global developmental vulnerability (adjusted relative risk [aRR], 1.03; 95% CI, 0.96-1.12) or with developmental vulnerability in any of the individual domains. In an analysis restricted to elective births at 39 weeks' gestation, induction of labor (n = 7928) compared with planned cesarean delivery (n = 7999) was not associated with childhood developmental vulnerability (aRR, 0.96; 95% CI, 0.82-1.12) or with vulnerability in any individual domains. CONCLUSIONS AND RELEVANCE: In this cohort study, elective birth at 39 weeks' gestation was not associated with childhood developmental vulnerability. For those born electively at 39 weeks' gestation, birth after induction of labor or by elective cesarean delivery had similar developmental outcomes.
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ItemIncidence and causes of stillbirth in the only tertiary referral hospital in the Solomon Islands: a hospital-based retrospective cohort study(BMJ PUBLISHING GROUP, 2022-12)OBJECTIVES: Stillbirth is a major global health issue, which disproportionately affects families living in low-income and middle-income countries. The Solomon Islands is a Pacific nation with poor perinatal outcomes, however research investigating stillbirth is lacking. Thus, we aimed to investigate the incidence and cause of stillbirth occurring at the National Referral Hospital, Solomon Islands. DESIGN: We conducted a retrospective cohort study from January 2017 to December 2018. SETTING: At the only tertiary referral hospital in the Solomon Islands, on the main island of Guadalcanal. PARTICIPANTS: All births occurring in the hospital during the study period. OUTCOME MEASURES: Number of, causes and risk factors for stillbirths (fetal deaths before birth at ≥20 estimated gestational weeks, or ≥500 g in birth weight). RESULTS: Over 2 years 341 stillbirths and 11 056 total births were recorded, giving an institutional incidence of 31 stillbirths per 1000 births. Of the cases with a recorded cause of death, 72% were deemed preventable. Most stillbirths occurred antenatally and 62% at preterm gestations (<37 weeks). 59% had a birth weight below 2500 g and preventable maternal conditions were present in 42% of the cases. 46% of the cases were caused by an acute intrapartum event, and among these 92% did not receive intrapartum monitoring. CONCLUSIONS: Stillbirth affects 31 in every 1000 births at the National Referral Hospital in the Solomon Islands and many cases are preventable. Our findings highlight the urgent need for increased focus on perinatal deaths in the Solomon Islands with universal classification and targeted training, improved quality of obstetrical care and community awareness.
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ItemNo Preview AvailablePatients' understanding of long-term cardiovascular risks and associated health-seeking behaviours after pre-eclampsia(BMJ PUBLISHING GROUP, 2023-03)OBJECTIVE: The lifelong risks of cardiovascular disease following hypertensive disorders of pregnancy are well described. Awareness of these risks and associated health-seeking behaviours among affected individuals remains unclear. We aimed to assess participants' knowledge of their cardiovascular disease risk and relevant health-seeking behaviours following a pregnancy affected by preeclampsia or gestational hypertension. METHODS: We undertook a single-site, cross-sectional cohort study. The target population included individuals who birthed at a large tertiary referral centre in Melbourne, Australia, between 2016 and 2020, and were diagnosed with gestational hypertension or pre-eclampsia. Participants completed a survey assessing pregnancy details, medical comorbidities, knowledge of future risks and health-seeking behaviours post-pregnancy. RESULTS: 1526 individuals met inclusion criteria and 438 (28.6%) completed the survey. Of these, 62.6% (n=237) were unaware of their increased risk of cardiovascular disease following a hypertensive disorder of pregnancy. Participants who reported awareness of their increased risk were more likely to have annual blood pressure monitoring (54.6% vs 38.1%, p<0.01), and at least one assessment of blood cholesterol (p<0.01), blood glucose (p=0.03) and renal function (p=0.01). Participants who were aware were more likely to be taking antihypertensive medication (24.5% vs 6.6%, p<0.01) since pregnancy, compared with those who were unaware. There were no differences between groups in diet, exercise or smoking habits. CONCLUSION: Among our study cohort, risk awareness was associated with increased health-seeking behaviours. Participants who were aware of their increased risk of cardiovascular disease were more likely to have regular cardiovascular risk factor assessments. They were also more likely to be taking antihypertensive medication.
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ItemAssociations Between Soluble fms-Like Tyrosine Kinase-1 and Placental Growth Factor and Disease Severity Among Women With Preterm Eclampsia and Preeclampsia(WILEY, 2022-08-16)Background The angiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are postulated to be pathogenic disease drivers of preeclampsia. If true, then circulating levels should become more deranged with increasing disease severity. Methods and Results We investigated the association between circulating sFlt-1 and PlGF levels and severe adverse maternal outcomes among 348 women with preeclampsia. Compared with 125 women with preeclampsia without severe features, 25 women with preeclampsia and any of hemolysis, elevated liver enzymes, low platelet count syndrome, disseminated intravascular coagulation, or severe renal involvement had sFlt-1 levels that were 2.63-fold higher (95% CI, 1.81-3.82), sFlt-1/PlGF levels that were 10.07-fold higher (95% CI, 5.36-18.91) and PlGF levels that were 74% lower (adjusted fold change, 0.26 [95% CI, 0.18-0.39]). Compared with 125 women with preeclampsia without severe features, 37 with eclampsia had sFlt-1 levels that were 2-fold higher (2.02 [95% CI, 1.32-3.09]), sFlt-1/PIGF levels that were 4.71-fold higher (95% CI, 2.30-9.66) and PIGF levels that were 63% lower (0.43-fold change [95% CI, 0.27-0.68]). Compared with those without severe features, preeclampsia with severe hypertension (n=146) was also associated with altered angiogenic levels (sFlt-1, 1.71-fold change [95% CI, 1.39-2.11]; sFlt/PlGF, 2.91 [95% CI, 2.04-4.15]; PlGF, 0.59 [95%CI 0.47-0.74]). We also found that sFlt-1 and PlGF levels were altered by the number of maternal complications experienced. Conclusions Further angiogenic imbalance among women with preeclampsia is likely a pathogenic disease driver responsible for the life-threatening maternal complications.
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ItemCerebral biomarkers in neurologic complications of preeclampsia(MOSBY-ELSEVIER, 2022-08)BACKGROUND: There is no tool to accurately predict who is at risk of developing neurologic complications of preeclampsia, and there is no objective method to determine disease severity. OBJECTIVE: We assessed whether plasma concentrations of the cerebral biomarkers neurofilament light, tau, and glial fibrillary acidic protein could reflect disease severity in several phenotypes of preeclampsia. Furthermore, we compared the cerebral biomarkers with the angiogenic biomarkers soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin. STUDY DESIGN: In this observational study, we included women from the South African Preeclampsia Obstetric Adverse Events biobank. Plasma samples taken at diagnosis (preeclampsia cases) or admission for delivery (normotensive controls) were analyzed for concentrations of neurofilament light, tau, glial fibrillary acidic protein, placental growth factor, soluble fms-like tyrosine kinase 1, and soluble endoglin. The cerebrospinal fluid concentrations of inflammatory markers and albumin were analyzed in a subgroup of 15 women. Analyses were adjusted for gestational age, time from seizures and delivery to sampling, maternal age, and parity. RESULTS: Compared with 28 women with normotensive pregnancies, 146 women with preeclampsia demonstrated 2.18-fold higher plasma concentrations of neurofilament light (95% confidence interval, 1.64-2.88), 2.17-fold higher tau (95% confidence interval, 1.49-3.16), and 2.77-fold higher glial fibrillary acidic protein (95% confidence interval, 2.06-3.72). Overall, 72 women with neurologic complications (eclampsia, cortical blindness, and stroke) demonstrated increased plasma concentrations of tau (2.99-fold higher; 95% confidence interval, 1.92-4.65) and glial fibrillary acidic protein (3.22-fold higher; 95% confidence interval, 2.06-5.02) compared with women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications (n=31). Moreover, angiogenic markers were higher, but to a lesser extent. Women with hemolysis, elevated liver enzymes, and low platelet count (n=20) demonstrated increased plasma concentrations of neurofilament light (1.64-fold higher; 95% confidence interval, 1.06-2.55), tau (4.44-fold higher; 95% confidence interval, 1.85-10.66), and glial fibrillary acidic protein (1.82-fold higher; 95% confidence interval, 1.32-2.50) compared with women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications. There was no difference shown in the angiogenic biomarkers. There was no difference between 23 women with preeclampsia complicated by pulmonary edema and women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications for any of the biomarkers. Plasma concentrations of tau and glial fibrillary acidic protein were increased in women with several neurologic complications compared with women with eclampsia only. CONCLUSION: Plasma neurofilament light, glial fibrillary acidic, and tau were candidate biomarkers for the diagnosis and possibly prediction of cerebral complications of preeclampsia.
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ItemPSG7 and 9 (Pregnancy-Specific β-1 Glycoproteins 7 and 9): Novel Biomarkers for Preeclampsia(WILEY, 2022-04-05)Background Preeclampsia is pregnancy specific, involving significant maternal endothelial dysfunction. Predictive biomarkers are lacking. We evaluated the biomarker potential, expression, and function of PSG7 (pregnancy-specific β-1 glycoprotein 7) and PSG9 (pregnancy-specific β-1 glycoprotein 9) in preeclampsia. Methods and Results At 36 weeks gestation preceding term preeclampsia diagnosis, PSG7 and PSG9 (in Australian cohorts of n=918 and n=979, respectively) were significantly increased before the onset of term preeclampsia (PSG7, P=0.013; PSG9, P=0.0011). In samples collected at 28 to 32 weeks from those with preexisting cardiovascular disease and at high risk of preeclampsia (Manchester Antenatal Vascular Service, UK cohort, n=235), both PSG7 and PSG9 were also significantly increased preceding preeclampsia onset (PSG7, P<0.0001; PSG9, P=0.0003) relative to controls. These changes were validated in the plasma and placentas of patients with established preeclampsia who delivered at <34 weeks gestation (PSG7, P=0.0008; PSG9, P<0.0001). To examine whether PSG7 and PSG9 are associated with increasing disease severity, we measured them in a cohort from South Africa stratified for this outcome, the PROVE (Preeclampsia Obstetric Adverse Events) cohort (n=72). PSG7 (P=0.0027) and PSG9 (P=0.0028) were elevated among patients who were preeclamptic with severe features (PROVE cohort), but not significantly changed in those without severe features or with eclampsia. In syncytialized first trimester cytotrophoblast stem cells, exposure to TNFα (tumor necrosis factor α) or IL-6 (interleukin 6) significantly increased the expression and secretion of PSG7 and PSG9. In contrast, when we treated primary endothelial cells with recombinant PSG7 and PSG9, we only observed modest changes in Flt-1 (FMS-like tyrosine kinase-1) expression and Plgf (placental growth factor) expression, and no other effects on proangiogenic/antiangiogenic or endothelial dysfunction markers were observed. Conclusions Circulating PSG7 and PSG9 are increased before preeclampsia onset and among those with established disease with their production and release potentially driven by placental inflammation.