Obstetrics and Gynaecology - Research Publications
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ItemMesenchymal Stem/Stromal Cells and Their Role in Oxidative Stress Associated with Preeclampsia(YALE J BIOLOGY MEDICINE, INC, 2022-03)Preeclampsia (PE) is a serious medically important disorder of human pregnancy, which features de novo pregnancy-induced hypertension and proteinuria. The severe form of PE can progress to eclampsia, a convulsive, life-threatening condition. When placental growth and perfusion are abnormal, the placenta experiences oxidative stress and subsequently secretes abnormal amounts of certain pro-angiogenic factors (eg, PlGF) as well as anti-angiogenic factors (eg, sFlt-1) that enter the maternal circulation. The net effect is damage to the maternal vascular endothelium, which subsequently manifests as the clinical features of PE. Other than delivery of the fetus and placenta, curative treatments for PE have not yet been forthcoming, which reflects the complexity of the clinical syndrome. A major source of reactive oxygen species that contributes to the widespread maternal vascular endothelium damage is the PE-affected decidua. The role of decidua-derived mesenchymal stem/stromal cells (MSC) in normotensive and pathological placenta development is poorly understood. The ability to respond to an environment of oxidative damage is a "universal property" of MSC but the biological mechanisms that MSC employ in response to oxidative stress are compromised in PE. In this review, we discuss how MSC respond to oxidative stress in normotensive and pathological conditions. We also consider the possibility of manipulating the oxidative stress response of abnormal MSC as a therapeutic strategy to treat preeclampsia.
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ItemSuccessful pregnancy outcomes following intravenous immunoglobulin treatment in a woman with a previous fetal death in utero due to gestational alloimmune liver disease: A case report.(Elsevier BV, 2022-07)Gestational alloimmune liver disease resulting in neonatal haemochromatosis is a rare but often lethal neonatal and fetal condition and is the leading cause of fetal and neonatal liver injury. Chelation-antioxidant treatment, intravenous immunoglobulin therapy and exchange transfusions, as well as liver transplantation have been used as treatments for the affected newborn at birth. In the reported case, a woman with previous neonatal death at 34 weeks of gestation due to gestational alloimmune liver disease commenced weekly doses of intravenous immunoglobulin (1 mg/kg) from 15 weeks in a subsequent pregnancy. A healthy baby boy was delivered following induction of labour at 36 weeks and 5 days of gestation. Following the same protocol, another healthy baby boy was delivered at 37 weeks of gestation. This case report emphasises the clinical utility of antenatal prophylaxis with intravenous immunoglobulin in women at high risk of recurrent gestational alloimmune liver disease.
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ItemNo Preview AvailableClinical interpretation and implementation of the sFlt-1/PlGF ratio in the prediction, diagnosis and management of preeclampsia(ELSEVIER SCI LTD, 2022-03)Preeclampsia is associated with significant morbidity and mortality for mother and baby. Although around 30% of all pregnancies are evaluated for preeclampsia, diagnosis is difficult, especially in patients who have overlying symptoms from other diseases. Discovery of circulating angiogenic factors in the pathogenesis of preeclampsia has been a major advance for both diagnosis and prognosis. The anti-angiogenic factor, soluble fms-like tyrosine kinase 1 (sFlt-1) and the pro-angiogenic factor, placental growth factor (PlGF), can be measured in plasma and serum and are usually reported as a ratio, which specifically relates to the onset and severity of preeclampsia. The sFlt-1/PlGF ratio has a very high negative predictive value in ruling out the development of preeclampsia within 7 days among women with suspected preeclampsia. Currently, there is no clear consensus on the practical use of angiogenic biomarkers in the detection and management of preeclampsia in routine clinical practice. While major international clinical guidelines exist, they do not define which specific parameters signal patient admission, or outpatient evaluation of suspected preeclampsia, and most clinicians follow local practices. Better guidance is needed on risk stratification among women with suspected preeclampsia, as well as among women at high risk for preeclampsia. Prediction of adverse outcomes in women, after the clinical diagnosis of preeclampsia, is also important. This report has been developed following a meeting of international experts and aims to guide clinicians in the management of pregnant women at risk of preeclampsia using the sFlt-1/PlGF ratio test.
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ItemPrior term delivery increases risk of subsequent recurrent preterm birth: An unexpected finding(WILEY, 2022-08)BACKGROUND: Women with a prior pregnancy at term are generally considered to be at reduced risk for subsequent spontaneous preterm birth (sPTB), whereas a previous sPTB is a major predictor for a future sPTB. AIMS: The objective of this study was to investigate the risk of recurrent sPTB in women with a prior term birth and a subsequent sPTB. MATERIALS AND METHODS: This is a retrospective cohort study conducted at St Thomas' Hospital in London, UK. There were 430 women included: 230 with a term birth (caesarean section or vaginal delivery) preceding a sPTB (term + sPTB group) and 200 with a prior sPTB only (sPTB only group). The primary outcome was sPTB, <37 weeks gestation. RESULTS: Of the term + sPTB group, 38.7% (89/230) had a recurrent sPTB compared to 20% (40/200) in the sPTB only group (P < 0.0001), with a relative risk (RR) of 1.9. Of women who had a term caesarean section and a subsequent PTB, 50% (30/60) had a further sPTB (RR 2.5 compared to the sPTB only group), while 34.7% (59/170) of women who had a term vaginal birth and subsequent sPTB, had a further sPTB (RR 1.7 compared to the sPTB only group). CONCLUSION: In women who have had a previous sPTB, the risk of a recurrence is much higher than in women with a prior term birth. The aetiology of PTB may be different in this subgroup of women and needs to be further elucidated to determine how best to identify and treat them.
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ItemEvaluation of epigenetic age calculators between preeclampsia and normotensive pregnancies in an Australian cohort(NATURE PORTFOLIO, 2022-01-31)Advanced biological aging, as assessed through DNA methylation markers, is associated with several complex diseases. The associations between maternal DNA methylation age and preeclampsia (PE) have not been fully assessed. The aim of this study was to examine if increased maternal DNA methylation age (DNAmAge) was shown to be accelerated in women with PE when compared to women who had normotensive pregnancies. The case/control cohort available for study consisted of 166 women (89 with normotensive pregnancy, 77 with PE) recruited previously at the Royal Women's Hospital in Melbourne, Australia. DNA methylation profiles were obtained using the Illumina EPIC Infinium array for analysis of genomic DNA isolated from whole blood. These profiles were used to calculate seven estimates of DNAmAge and included (1) Horvath, (2) Hannum, (3) Horvath Skin and Blood, (4) Wu, (5) PhenoAge, (6) telomere length and (7) GrimAge and its surrogate measures. Three measures of DNA methylation age acceleration were calculated for all seven measures using linear regression. Pearson's correlation was performed to investigate associations between chronological age and DNAmAge. Differences between chronological age and DNAmAge and epigenetic age acceleration were investigated using t-tests. No significant difference was observed for chronological age between women with PE (age = 30.53 ± 5.68) and women who had normotensive pregnancies (age = 31.76 ± 4.76). All seven DNAmAge measures were significantly correlated (p < 0.001) with chronological age. After accounting for multiple testing and investigating differences in DNAmAge between normotensive women and women with PE, only Wu DNAmAge was significant (p = 0.001). When examining differences for epigenetic age acceleration between PE and normotensive women Hannum, Wu, and PhenoAge DNAmAge estimates (p < 0.001) were significant for both epigenetic age acceleration and intrinsic acceleration models. We found that accelerated maternal DNAmAge is increased in women with PE in some models of epigenetic aging. This research underlines the importance for further investigation into the potential changes of differential DNA methylation in PE.
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ItemAccuracy of second trimester prediction of preterm preeclampsia by three different screening algorithms(WILEY, 2018-04)AIM: To compare the performance of three different screening methods (National Institute for Health and Clinical Excellence (NICE) guidelines, American College of Obstetricians and Gynecologists (ACOG) recommendations and Fetal Medicine Foundation (FMF) algorithm) for second trimester prediction of preeclampsia. METHODS: This was a prospective non-intervention study in singleton pregnancies, including women attending for second trimester morphologic ultrasound at 19-22 weeks. Maternal characteristics, medical history, mean arterial pressure and mean uterine artery Doppler pulsatility index were recorded and used for risk assessment. Outcomes measured were preeclampsia with delivery before 34, before 37 and after 37 weeks gestation. Detection rates, false positive rates and positive likelihood ratios were calculated, and receiver operating characteristic curves were produced. RESULTS: We screened 543 women during the study. The incidence of preeclampsia before 34, before 37 and after 37 weeks was 0.5, 1.4 and 3.4%, respectively. Detection rates for prediction of preterm preeclampsia were 75% (95% CI 34.9-96.8), 87% (95% CI 47.3-99.6), 100% (95% CI 63.0-100) and 100% (95% CI 63.0-100) for NICE guidelines, ACOG recommendations, FMF algorithm with a 1:100 cut-off and FMF algorithm at 1:60 cut-off, respectively. False positive rates were, 22, 67, 19 and 12% for NICE guidelines, ACOG recommendations, FMF algorithm with a 1:100 cut-off and FMF algorithm at 1:60 cut-off, respectively. CONCLUSION: Second trimester combined screening for preterm preeclampsia by maternal history, mean arterial pressure and mean uterine artery Doppler pulsatility index (FMF algorithm) was superior to screening by maternal factors alone (NICE guidelines and ACOG recommendations).
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ItemMother Nature versus Father Time(WILEY, 2017-03-15)
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ItemOptic nerve sonography and ophthalmic artery Doppler velocimetry in healthy pregnant women: an Australian cohort study(WILEY, 2019-11)PURPOSE: Maternal ocular sonography offers a window into cerebrovascular and intracranial pressure changes in pregnancy. This study aimed to determine the Doppler velocimetric variables of the ophthalmic artery, and the mean diameter of the optic nerve sheath (ONSD), in an Australian cohort of healthy pregnant women. METHODS: A prospective observational cohort study of healthy women with uncomplicated singleton pregnancies in the third trimester was undertaken in a tertiary maternity service. A single prenatal ultrasonographic examination was performed on all participants, with a postnatal examination performed on a subgroup with uncomplicated deliveries. RESULTS: Fifty women were examined at a mean gestation of 35 weeks. The mean ± SD Doppler variables in the ophthalmic artery were peak systolic velocity (PSV) 41.89 ± 13.13 cm/s, second peak velocity 20.63 ± 8.97 cm/s, end diastolic velocity 9.29 ± 5.13 cm/s, pulsatility index 1.97 ± 0.53, resistive index 0.78 ± 0.07, peak ratio (second peak velocity/PSV) 0.49 ± 0.12, while the mean ONSD was 4.34 ± 0.4 mm. None of these variables had a demonstrable relationship with gestation or mean arterial pressure (MAP), nor did the sheath diameter have a relationship with any of the Doppler variables. CONCLUSIONS: The ocular sonographic variables observed in this population are similar to those reported in other cohorts. No clear relationship could be identified in this cohort between ophthalmic artery Doppler variables and the ONSD, and between each of these variables and gestation or MAP.
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ItemSetting the pace for labour(WILEY, 2018-07-15)