<p>CFTR expression in hAECs cultured in DMEM:F12 (white bars) and hAECs cultured in Small A... more <p>CFTR expression in hAECs cultured in DMEM:F12 (white bars) and hAECs cultured in Small Airway Epithelial Growth Medium (SAGM) (black bars) for 7, 14, 21 and 28 days (A) (n = 3). hAECs cultured in SAGM for 28 days had a 389.4±70.0 fold increase in CFTR gene expression (<i>p≤</i>0.001), (error bars represent SD). hAECs cultured in DMEM:F12 did not show a significant increase in CFTR gene expression. Human lung total RNA was utilized as a positive control for this study (grey bar). Western blot analysis of CFTR protein expression of freshly isolated hAECs or hAECs cultured in SAGM for 7, 14, 21 and 28 days (B). Both the immature (band A/B) and glycosylated (band C) forms of CFTR were detected in hAEC samples after culture in SAGM for 21 and 28 days (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046533#pone-0046533-g001" target="_blank">Figure 1B</a>). Only the glycosylated band C was detected in our human lung positive control sample. Flow cytometry analysis of CFTR expression in SAGM cultured hAECs demonstrated that approximately 65% of hAECs expressed the CFTR protein (C) (n = 3).</p
American Journal of Obstetrics and Gynecology, 2021
specified outcomes between randomization groups using an intentto-treat approach. RESULTS: 800 wo... more specified outcomes between randomization groups using an intentto-treat approach. RESULTS: 800 women were randomized between Feb 2018 and Jan 2020. Baseline characteristics were similar between treatment groups. Adherence to study drug was high in both groups (98%) and delivery outcomes were ascertained for all 800 participants. The primary outcome occurred in 36 (9.02%) participants assigned to 17P and 36 (8.98%) assigned to placebo (risk difference ¼ 0.05; 95% CI:-3.92, 4.01). In a pre-specified analysis excluding providerinitiated PTB phenotypes, 25 (6.36%) women randomized to 17P delivered spontaneously before 37 weeks compared to 26 (6.63%) of those receiving placebo (risk difference ¼-0.27; 95% CI:-3.72, 3.18). The timing of antiretroviral therapy initiation relative to conception did not affect the risk of the primary outcome nor did it modify the effect of the intervention. Related adverse events were low and occurred at similar rates between the study groups. CONCLUSION: In this trial with complete ascertainment of outcomes and very high adherence to study drug, weekly antenatal 17P injections did not reduce the composite risk of preterm delivery or stillbirth among women with HIV in Zambia.
A number of diseases over the life course such as cardiovascular disease, diabetes, asthma, cance... more A number of diseases over the life course such as cardiovascular disease, diabetes, asthma, cancer, allergies, and neurocognitive impairment occur at differing rates among people of different ethnicities. There is growing evidence to suggest that this is a consequence of fetal programming. Gestational diabetes mellitus (GDM) and hypertensive conditions in pregnancy such as gestational hypertension and preeclampsia both occur at elevated rates in women of certain ethnicities. Women of different ethnicities also experience higher rates of adverse pregnancy outcomes and interventions including preterm birth, low birth weight/small for gestational age, and cesarean birth. All of the outcomes listed above have been linked to fetal programming and may explain the increased rates of chronic diseases among people of different ethnicities. Compounding the issue further are the increasing rates of maternal obesity experienced among women in high-income nations. Emerging evidence has suggested...
Preeclampsia is a disease specific to pregnancy characterised by new-onset hypertension with mate... more Preeclampsia is a disease specific to pregnancy characterised by new-onset hypertension with maternal organ dysfunction and/or fetal growth restriction. It remains a major cause of maternal and perinatal morbidity and mortality. For sixty years, antihypertensives have been the mainstay of treating preeclampsia and only recently have insights into the pathogenesis of the disease opened new avenues for novel therapies. Melatonin is one such option, an endogenous and safe antioxidant, that may improve the maternal condition in preeclampsia while protecting the fetus from a hostile intrauterine environment. Here we review the evidence for melatonin as a possible adjuvant therapy for preeclampsia, including in vitro evidence supporting a role for melatonin in protecting the human placenta, preclinical models, vascular studies, and clinical studies in hypertension and pregnancy.
Reducing stillbirth safely in Australia Caution is needed so that population-level reductions in ... more Reducing stillbirth safely in Australia Caution is needed so that population-level reductions in the stillbirth rate are not offset by iatrogenic harm to healthy babies
Australian and New Zealand Journal of Obstetrics and Gynaecology, 2020
MB and SC are employees of RANZCOG, the provider of FSEP. EMW is the chairperson of the FSEP stee... more MB and SC are employees of RANZCOG, the provider of FSEP. EMW is the chairperson of the FSEP steering committee. ST has no competing interests.
BJOG: An International Journal of Obstetrics & Gynaecology, 2020
Objective: An estimated two billion people worldwide live with hepatitis B virus (HBV) infection.... more Objective: An estimated two billion people worldwide live with hepatitis B virus (HBV) infection. Many of these are women of reproductive age. Studies that have examined pregnancy outcomes in women living with HBV have reported conflicting results in relation to the incidence of gestational diabetes (GDM). The aim of this study is to examine if gestational diabetes is more common in women with chronic HBV residing in a non-Asian country Design: Cross sectional study Setting: Victoria, Australia Population: All singleton births between 2009 and 2017 Methods: Poisson regression was performed to determine if gestational diabetes is more common in women with HBV compared to women without HBV taking into account other risk factors such as maternal age, body mass index, parity, and country of birth. Main outcome measure: Gestational diabetes diagnosis in women with chronic HBV infection Results: For women with HBV, the unadjusted incidence risk ratio for GDM was 1.75 (95% CI 1.6, 1.9). After adjusting for region of birth, BMI, parity, age and smoking, the adjusted incidence risk ratio was 1.2 (95% CI 1.1, 1.3) The highest incidence (37.1%) of GDM was in women with HBV and a BMI of >40. Conclusions: The findings from this study confirm an association between HBV and GDM.
IntroductionCerebral palsy (CP) is the most common physical disability of childhood but has no cu... more IntroductionCerebral palsy (CP) is the most common physical disability of childhood but has no cure. Stem cells have the potential to improve brain injury and are proposed as a therapy for CP. However, many questions remain unanswered about the most appropriate cell type, timing of infusions, dose required and associated risks. Therefore, human safety and efficacy trials are necessary to progress knowledge in the field.Methods and analysisThis is a single group study with sample size n=12 to investigate safety of single-dose intravenous 12/12 human leucocyte antigen-matched sibling cord blood cell infusion to children with CP aged 1–16 years without immune suppression. The study is similar to a 3+3 design, where the first two groups of participants have severe CP, and the final six participants include children with all motor severities. Children will be monitored for adverse events and the duration that donor cells are detected. Assessments at baseline, 3 and 12 months will investi...
(1) Background: There is increasing understanding of the potential health benefits of cruciferous... more (1) Background: There is increasing understanding of the potential health benefits of cruciferous vegetables. In particular sulforaphane (SFN), found in broccoli, and its metabolites sulforaphane-glutathione (SFN-GSH), sulforaphane-cysteine (SFN-Cys), sulforaphane cysteine-glycine (SFN-CG) and sulforaphane-N-acetyl-cysteine (SFN-NAC) have potent antioxidant effects that may offer therapeutic value. Clinical investigation of sulforaphane as a therapeutic antioxidant requires a sensitive and high throughput process for quantification of sulforaphane and metabolites; (2) Methods: We collected plasma samples from healthy human volunteers before and for eight hours after consumption of a commercial broccoli extract supplement rich in sulforaphane. A rapid and sensitive method for quantification of sulforaphane and its metabolites in human plasma using Liquid Chromatography-Mass Spectrometry (LC-MS) has been developed; (3) Results: The LC-MS analytical method was validated at concentrations ranging between 3.9 nM and 1000 nM for SFN-GSH, SFN-CG, SFN-Cys and SFN-NAC and between 7.8 nM and 1000 nM in human plasma for SFN. The method displayed good accuracy (1.85%-14.8% bias) and reproducibility (below 9.53 %RSD) including low concentrations 3.9 nM and 7.8 nM. Four SFN metabolites quantitation was achieved using external standard calibration and in SFN quantitation, SFN-d 8 internal standardization was used. The reported method can accurately quantify sulforaphane and its metabolites at low concentrations in plasma; (4) Conclusions: We have established a time-and cost-efficient method of measuring sulforaphane and its metabolites in human plasma suitable for high throughput application to clinical trials.
BJOG: An International Journal of Obstetrics & Gynaecology, 2019
Article type : Main research article Title: Does public reporting of the detection of fetal growt... more Article type : Main research article Title: Does public reporting of the detection of fetal growth restriction improve clinical outcomes: a retrospective cohort study Short running title: Benefit versus harm of detecting fetal growth restriction
Australian and New Zealand Journal of Obstetrics and Gynaecology, 2019
This is the author manuscript accepted for publication and has undergone full peer review but has... more This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as
Introduction: Preeclampsia is a disease specific to pregnancy characterised by new onset hyperten... more Introduction: Preeclampsia is a disease specific to pregnancy characterised by new onset hypertension with maternal organ dysfunction and/or fetal growth restriction. It remains a major cause of maternal and perinatal morbidity and mortality. For fifty years, antihypertensives have been the mainstay of treating preeclampsia, reducing maternal morbidity and mortality. With increased knowledge of the mechanisms underlying the disease has come opportunities for novel therapies that complement antihypertensives by protecting the maternal vasculature. Areas covered: In this review, the authors consider, in detail, the antihypertensives commonly used today in the emergency care of women with severe preeclampsia. They also review less common antihypertensive agents and discuss the role of magnesium sulphate in the management of preeclampsia and the prevention of eclampsia. Finally, they explore novel therapeutics for the acute management of preeclampsia. Expert opinion: The rapid control of maternal hypertension will, and must, remain the mainstay of emergency treatment for women with severe preeclampsia. The role of magnesium sulphate as a primary prevention for eclampsia is context dependant and should not displace a focus on correcting blood pressure safely. The exploration of novel adjuvant therapies will likely allow us to prolong pregnancy longer and improve perinatal outcomes safely for the mother.
Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality. There hav... more Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality. There have been no material advances in the treatment of preeclampsia for nearly 50 years. Combining in vitro studies and a clinical trial, we aimed to determine if melatonin could be a useful adjuvant therapy. In a xanthine/xanthine oxidase (X/XO) placental explant model, melatonin reduced oxidative stress (8-isoprostane) and enhanced antioxidant markers (Nrf2 translocation, HO-1), but did not affect explant production of anti-angiogenic factors (sFlt, sEng, activin A). In cultured HUVECs, melatonin mitigated TNFα-induced vascular cell adhesion molecule expression and rescued the subsequent disruption to endothelial monolayer integrity but did not affect other markers for endothelial activation and dysfunction. In a phase I trial of melatonin in 20 women with preeclampsia we assessed the safety and efficacy of melatonin on (i) preeclampsia progression, (ii) clinical outcomes and (iii) oxidative stress, matching outcomes with recent historical controls receiving similar care. Melatonin therapy was safe for mothers and their fetuses. Compared to controls, melatonin administration extended the mean ±SEM diagnosis to delivery interval by 6 ± 2.3 days reduced the need for increasing antihypertensive medication on days 3-4 (13% vs 71%), days 6-7 (8% vs 51%) and at delivery (26% vs 75%). All other clinical and biochemical measures of disease severity were unaffected by melatonin. We have shown that melatonin has the potential to mitigate maternal endothelial pro-oxidant injury and could therefore provide effective adjuvant therapy to extend pregnancy duration to deliver improved clinical outcomes for women with severe preeclampsia.
Non-invasive fetal electrocardiogram (NIFECG) is an evolving technology in fetal surveillance whi... more Non-invasive fetal electrocardiogram (NIFECG) is an evolving technology in fetal surveillance which is attracting increasing research interest. There is however, only limited data outlining the reference ranges for normal cardiac time intervals (CTIs). The objective of our group was to carry out a systematic review to outline normal fetal CTIs using NIFECG. A systematic review of peer reviewed literature was performed, searching PUBMED,Ovid MEDLINE and EMBASE. The outcomes of interest included fetal CTIs (P wave duration, PR interval, QRS duration and QT interval) and a descriptive summary of relevant studies as well. The outcomes were grouped as early pre-term (≤ 32 weeks), moderate to late pre-term (32-37 weeks) and term (37-41 weeks). 8 studies were identified as suitable for inclusion. Reference ranges of CTIs were generated. Both PR interval and QRS duration demonstrated a linear correlation with advancing gestation. Several studies also demonstrated a reduction in signal acqui...
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that mainly affects premature babies w... more Bronchopulmonary dysplasia (BPD) is a chronic lung disease that mainly affects premature babies who require ventilator support. The pathogenesis of BPD is complex but includes vascular maldevelopment, alveolarization arrest, and lung inflammation. There is no cure for BPD. Clinical care is limited to supportive respiratory measures. A population of stem-like cells derived from placental membranes, human amnion epithelial cells (hAECs), has shown therapeutic promise in preclinical models of BPD. With a view to future efficacy trials, we undertook a first-in-human clinical trial of hAECs in babies with BPD to assess the safety of these cells. In a single-center, open-label phase I trial, we administered allogeneic hAECs (1 × 106 per kilogram bodyweight) by intravenous infusion to six premature babies with BPD. The primary outcomes of the study were focused on safety, including local site reaction, anaphylaxis, infection, features of rejection, or tumor formation. Outcomes to discharge...
<p>CFTR expression in hAECs cultured in DMEM:F12 (white bars) and hAECs cultured in Small A... more <p>CFTR expression in hAECs cultured in DMEM:F12 (white bars) and hAECs cultured in Small Airway Epithelial Growth Medium (SAGM) (black bars) for 7, 14, 21 and 28 days (A) (n = 3). hAECs cultured in SAGM for 28 days had a 389.4±70.0 fold increase in CFTR gene expression (<i>p≤</i>0.001), (error bars represent SD). hAECs cultured in DMEM:F12 did not show a significant increase in CFTR gene expression. Human lung total RNA was utilized as a positive control for this study (grey bar). Western blot analysis of CFTR protein expression of freshly isolated hAECs or hAECs cultured in SAGM for 7, 14, 21 and 28 days (B). Both the immature (band A/B) and glycosylated (band C) forms of CFTR were detected in hAEC samples after culture in SAGM for 21 and 28 days (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0046533#pone-0046533-g001" target="_blank">Figure 1B</a>). Only the glycosylated band C was detected in our human lung positive control sample. Flow cytometry analysis of CFTR expression in SAGM cultured hAECs demonstrated that approximately 65% of hAECs expressed the CFTR protein (C) (n = 3).</p
American Journal of Obstetrics and Gynecology, 2021
specified outcomes between randomization groups using an intentto-treat approach. RESULTS: 800 wo... more specified outcomes between randomization groups using an intentto-treat approach. RESULTS: 800 women were randomized between Feb 2018 and Jan 2020. Baseline characteristics were similar between treatment groups. Adherence to study drug was high in both groups (98%) and delivery outcomes were ascertained for all 800 participants. The primary outcome occurred in 36 (9.02%) participants assigned to 17P and 36 (8.98%) assigned to placebo (risk difference ¼ 0.05; 95% CI:-3.92, 4.01). In a pre-specified analysis excluding providerinitiated PTB phenotypes, 25 (6.36%) women randomized to 17P delivered spontaneously before 37 weeks compared to 26 (6.63%) of those receiving placebo (risk difference ¼-0.27; 95% CI:-3.72, 3.18). The timing of antiretroviral therapy initiation relative to conception did not affect the risk of the primary outcome nor did it modify the effect of the intervention. Related adverse events were low and occurred at similar rates between the study groups. CONCLUSION: In this trial with complete ascertainment of outcomes and very high adherence to study drug, weekly antenatal 17P injections did not reduce the composite risk of preterm delivery or stillbirth among women with HIV in Zambia.
A number of diseases over the life course such as cardiovascular disease, diabetes, asthma, cance... more A number of diseases over the life course such as cardiovascular disease, diabetes, asthma, cancer, allergies, and neurocognitive impairment occur at differing rates among people of different ethnicities. There is growing evidence to suggest that this is a consequence of fetal programming. Gestational diabetes mellitus (GDM) and hypertensive conditions in pregnancy such as gestational hypertension and preeclampsia both occur at elevated rates in women of certain ethnicities. Women of different ethnicities also experience higher rates of adverse pregnancy outcomes and interventions including preterm birth, low birth weight/small for gestational age, and cesarean birth. All of the outcomes listed above have been linked to fetal programming and may explain the increased rates of chronic diseases among people of different ethnicities. Compounding the issue further are the increasing rates of maternal obesity experienced among women in high-income nations. Emerging evidence has suggested...
Preeclampsia is a disease specific to pregnancy characterised by new-onset hypertension with mate... more Preeclampsia is a disease specific to pregnancy characterised by new-onset hypertension with maternal organ dysfunction and/or fetal growth restriction. It remains a major cause of maternal and perinatal morbidity and mortality. For sixty years, antihypertensives have been the mainstay of treating preeclampsia and only recently have insights into the pathogenesis of the disease opened new avenues for novel therapies. Melatonin is one such option, an endogenous and safe antioxidant, that may improve the maternal condition in preeclampsia while protecting the fetus from a hostile intrauterine environment. Here we review the evidence for melatonin as a possible adjuvant therapy for preeclampsia, including in vitro evidence supporting a role for melatonin in protecting the human placenta, preclinical models, vascular studies, and clinical studies in hypertension and pregnancy.
Reducing stillbirth safely in Australia Caution is needed so that population-level reductions in ... more Reducing stillbirth safely in Australia Caution is needed so that population-level reductions in the stillbirth rate are not offset by iatrogenic harm to healthy babies
Australian and New Zealand Journal of Obstetrics and Gynaecology, 2020
MB and SC are employees of RANZCOG, the provider of FSEP. EMW is the chairperson of the FSEP stee... more MB and SC are employees of RANZCOG, the provider of FSEP. EMW is the chairperson of the FSEP steering committee. ST has no competing interests.
BJOG: An International Journal of Obstetrics & Gynaecology, 2020
Objective: An estimated two billion people worldwide live with hepatitis B virus (HBV) infection.... more Objective: An estimated two billion people worldwide live with hepatitis B virus (HBV) infection. Many of these are women of reproductive age. Studies that have examined pregnancy outcomes in women living with HBV have reported conflicting results in relation to the incidence of gestational diabetes (GDM). The aim of this study is to examine if gestational diabetes is more common in women with chronic HBV residing in a non-Asian country Design: Cross sectional study Setting: Victoria, Australia Population: All singleton births between 2009 and 2017 Methods: Poisson regression was performed to determine if gestational diabetes is more common in women with HBV compared to women without HBV taking into account other risk factors such as maternal age, body mass index, parity, and country of birth. Main outcome measure: Gestational diabetes diagnosis in women with chronic HBV infection Results: For women with HBV, the unadjusted incidence risk ratio for GDM was 1.75 (95% CI 1.6, 1.9). After adjusting for region of birth, BMI, parity, age and smoking, the adjusted incidence risk ratio was 1.2 (95% CI 1.1, 1.3) The highest incidence (37.1%) of GDM was in women with HBV and a BMI of >40. Conclusions: The findings from this study confirm an association between HBV and GDM.
IntroductionCerebral palsy (CP) is the most common physical disability of childhood but has no cu... more IntroductionCerebral palsy (CP) is the most common physical disability of childhood but has no cure. Stem cells have the potential to improve brain injury and are proposed as a therapy for CP. However, many questions remain unanswered about the most appropriate cell type, timing of infusions, dose required and associated risks. Therefore, human safety and efficacy trials are necessary to progress knowledge in the field.Methods and analysisThis is a single group study with sample size n=12 to investigate safety of single-dose intravenous 12/12 human leucocyte antigen-matched sibling cord blood cell infusion to children with CP aged 1–16 years without immune suppression. The study is similar to a 3+3 design, where the first two groups of participants have severe CP, and the final six participants include children with all motor severities. Children will be monitored for adverse events and the duration that donor cells are detected. Assessments at baseline, 3 and 12 months will investi...
(1) Background: There is increasing understanding of the potential health benefits of cruciferous... more (1) Background: There is increasing understanding of the potential health benefits of cruciferous vegetables. In particular sulforaphane (SFN), found in broccoli, and its metabolites sulforaphane-glutathione (SFN-GSH), sulforaphane-cysteine (SFN-Cys), sulforaphane cysteine-glycine (SFN-CG) and sulforaphane-N-acetyl-cysteine (SFN-NAC) have potent antioxidant effects that may offer therapeutic value. Clinical investigation of sulforaphane as a therapeutic antioxidant requires a sensitive and high throughput process for quantification of sulforaphane and metabolites; (2) Methods: We collected plasma samples from healthy human volunteers before and for eight hours after consumption of a commercial broccoli extract supplement rich in sulforaphane. A rapid and sensitive method for quantification of sulforaphane and its metabolites in human plasma using Liquid Chromatography-Mass Spectrometry (LC-MS) has been developed; (3) Results: The LC-MS analytical method was validated at concentrations ranging between 3.9 nM and 1000 nM for SFN-GSH, SFN-CG, SFN-Cys and SFN-NAC and between 7.8 nM and 1000 nM in human plasma for SFN. The method displayed good accuracy (1.85%-14.8% bias) and reproducibility (below 9.53 %RSD) including low concentrations 3.9 nM and 7.8 nM. Four SFN metabolites quantitation was achieved using external standard calibration and in SFN quantitation, SFN-d 8 internal standardization was used. The reported method can accurately quantify sulforaphane and its metabolites at low concentrations in plasma; (4) Conclusions: We have established a time-and cost-efficient method of measuring sulforaphane and its metabolites in human plasma suitable for high throughput application to clinical trials.
BJOG: An International Journal of Obstetrics & Gynaecology, 2019
Article type : Main research article Title: Does public reporting of the detection of fetal growt... more Article type : Main research article Title: Does public reporting of the detection of fetal growth restriction improve clinical outcomes: a retrospective cohort study Short running title: Benefit versus harm of detecting fetal growth restriction
Australian and New Zealand Journal of Obstetrics and Gynaecology, 2019
This is the author manuscript accepted for publication and has undergone full peer review but has... more This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as
Introduction: Preeclampsia is a disease specific to pregnancy characterised by new onset hyperten... more Introduction: Preeclampsia is a disease specific to pregnancy characterised by new onset hypertension with maternal organ dysfunction and/or fetal growth restriction. It remains a major cause of maternal and perinatal morbidity and mortality. For fifty years, antihypertensives have been the mainstay of treating preeclampsia, reducing maternal morbidity and mortality. With increased knowledge of the mechanisms underlying the disease has come opportunities for novel therapies that complement antihypertensives by protecting the maternal vasculature. Areas covered: In this review, the authors consider, in detail, the antihypertensives commonly used today in the emergency care of women with severe preeclampsia. They also review less common antihypertensive agents and discuss the role of magnesium sulphate in the management of preeclampsia and the prevention of eclampsia. Finally, they explore novel therapeutics for the acute management of preeclampsia. Expert opinion: The rapid control of maternal hypertension will, and must, remain the mainstay of emergency treatment for women with severe preeclampsia. The role of magnesium sulphate as a primary prevention for eclampsia is context dependant and should not displace a focus on correcting blood pressure safely. The exploration of novel adjuvant therapies will likely allow us to prolong pregnancy longer and improve perinatal outcomes safely for the mother.
Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality. There hav... more Preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality. There have been no material advances in the treatment of preeclampsia for nearly 50 years. Combining in vitro studies and a clinical trial, we aimed to determine if melatonin could be a useful adjuvant therapy. In a xanthine/xanthine oxidase (X/XO) placental explant model, melatonin reduced oxidative stress (8-isoprostane) and enhanced antioxidant markers (Nrf2 translocation, HO-1), but did not affect explant production of anti-angiogenic factors (sFlt, sEng, activin A). In cultured HUVECs, melatonin mitigated TNFα-induced vascular cell adhesion molecule expression and rescued the subsequent disruption to endothelial monolayer integrity but did not affect other markers for endothelial activation and dysfunction. In a phase I trial of melatonin in 20 women with preeclampsia we assessed the safety and efficacy of melatonin on (i) preeclampsia progression, (ii) clinical outcomes and (iii) oxidative stress, matching outcomes with recent historical controls receiving similar care. Melatonin therapy was safe for mothers and their fetuses. Compared to controls, melatonin administration extended the mean ±SEM diagnosis to delivery interval by 6 ± 2.3 days reduced the need for increasing antihypertensive medication on days 3-4 (13% vs 71%), days 6-7 (8% vs 51%) and at delivery (26% vs 75%). All other clinical and biochemical measures of disease severity were unaffected by melatonin. We have shown that melatonin has the potential to mitigate maternal endothelial pro-oxidant injury and could therefore provide effective adjuvant therapy to extend pregnancy duration to deliver improved clinical outcomes for women with severe preeclampsia.
Non-invasive fetal electrocardiogram (NIFECG) is an evolving technology in fetal surveillance whi... more Non-invasive fetal electrocardiogram (NIFECG) is an evolving technology in fetal surveillance which is attracting increasing research interest. There is however, only limited data outlining the reference ranges for normal cardiac time intervals (CTIs). The objective of our group was to carry out a systematic review to outline normal fetal CTIs using NIFECG. A systematic review of peer reviewed literature was performed, searching PUBMED,Ovid MEDLINE and EMBASE. The outcomes of interest included fetal CTIs (P wave duration, PR interval, QRS duration and QT interval) and a descriptive summary of relevant studies as well. The outcomes were grouped as early pre-term (≤ 32 weeks), moderate to late pre-term (32-37 weeks) and term (37-41 weeks). 8 studies were identified as suitable for inclusion. Reference ranges of CTIs were generated. Both PR interval and QRS duration demonstrated a linear correlation with advancing gestation. Several studies also demonstrated a reduction in signal acqui...
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that mainly affects premature babies w... more Bronchopulmonary dysplasia (BPD) is a chronic lung disease that mainly affects premature babies who require ventilator support. The pathogenesis of BPD is complex but includes vascular maldevelopment, alveolarization arrest, and lung inflammation. There is no cure for BPD. Clinical care is limited to supportive respiratory measures. A population of stem-like cells derived from placental membranes, human amnion epithelial cells (hAECs), has shown therapeutic promise in preclinical models of BPD. With a view to future efficacy trials, we undertook a first-in-human clinical trial of hAECs in babies with BPD to assess the safety of these cells. In a single-center, open-label phase I trial, we administered allogeneic hAECs (1 × 106 per kilogram bodyweight) by intravenous infusion to six premature babies with BPD. The primary outcomes of the study were focused on safety, including local site reaction, anaphylaxis, infection, features of rejection, or tumor formation. Outcomes to discharge...
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