Hydroxychloroquine Mitigates the Production of 8-Isoprostane and Improves Vascular Dysfunction: Implications for Treating Preeclampsia.

In preeclampsia, widespread maternal endothelial dysfunction is often secondary to excessive generation of placental-derived anti-angiogenic factors, including soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), along with proinflammatory cytokines such as tumour necrosis factor-α (TNF-α) and activin A, understanding of which offers potential opportunities for the development of novel therapies. The antimalarial hydroxychloroquine is an anti-inflammatory drug improving endothelial homeostasis in lupus. It has not been explored as to whether it can improve placental and endothelial function in preeclampsia.

Two-year outcomes of infants enrolled in the first-in-human study of amnion cells for bronchopulmonary dysplasia.

We previously reported on the immediate safety and neonatal outcomes of six premature infants with severe bronchopulmonary dysplasia (BPD) who were administered human amnion epithelial cells (hAECs). One infant died in the neonatal period due to unrelated causes. In this study, we aimed to assess the long-term safety and follow-up outcomes of the five surviving infants until 2 years corrected age (CA).

Protect-me: a parallel-group, triple blinded, placebo-controlled randomised clinical trial protocol assessing antenatal maternal melatonin supplementation for fetal neuroprotection in early-onset fetal growth restriction.

Introduction: Fetal growth restriction (FGR) is a serious pregnancy complication, associated with increased rates of perinatal death and morbidity among survivors. Most commonly FGR results from placental insufficiency, where the placenta fails to deliver the oxygen and nutrients required for normal fetal growth. This leads to fetal oxidative stress, resulting in organ damage through lipid peroxidation.

Sulforaphane improves endothelial function and reduces placental oxidative stress in vitro.

Introduction: The maternal endothelial dysfunction characteristic of preeclampsia arises, in part, from excessive placental production of anti-angiogenic factors, including soluble Flt-1, soluble endoglin and activin A, inducing oxidative stress. We assessed whether the antioxidant and NRF2-activator sulforaphane could mitigate endothelial and trophoblast dysfunction in vitro.

Methods: We induced dysfunction in human umbilical vein endothelial cells (HUVECs) with TNF-α, assessing endothelial activation and dysfunction (endothelin-1, vascular cell adhesion molecule; VCAM1, intracellular adhesion molecule; ICAM1, e-selectin and endothelial permeability) in the presence or absence of sulforaphane.

First-In-Human Administration of Allogeneic Amnion Cells in Premature Infants With Bronchopulmonary Dysplasia: A Safety Study.

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.

Resveratrol mitigates trophoblast and endothelial dysfunction partly via activation of nuclear factor erythroid 2-related factor-2.

Introduction: Maternal endothelial dysfunction underlying preeclampsia arises from excessive placental release of anti-angiogenic factors, such as soluble fms-like tyrosine kinase-1 (sFlt1), soluble endoglin (sEng) and activin A. Resveratrol, an activator of the nuclear factor erythroid 2-related factor-2 (Nrf2) transcription factor, mediates the gene expression of antioxidant and vasoprotective factors that may counter the endothelial damage imposed by these anti-angiogenic factors. The objective of this study was to assess whether resveratrol could reduce placental oxidative stress and production of anti-angiogenic factors in vitro and/or improve in vitro markers of endothelial dysfunction via Nrf2 activation.

Role of Activin A in the Pathogenesis of Endothelial Cell Dysfunction in Preeclampsia.

This chapter describes the methodologies which may be used in evaluating in vitro endothelial cell dysfunction in preeclampsia.

Effects of foetal growth restriction and preterm birth on cardiac morphology and function during infancy.

Aim: To investigate the effects of foetal growth restriction (FGR) and prematurity on cardiac morphology and function in infancy. We hypothesised that FGR and prematurity would both alter cardiac development.

Methods: Cardiac morphology and function were evaluated in 24 preterm FGR infants (p-FGR) and 23 preterm and 19 term appropriately grown for gestational age infants (p-AGA and t-AGA, respectively) by conventional echocardiography and Tissue Doppler Imaging.

EEG power spectrum maturation in preterm fetal growth restricted infants.

Power spectral analysis of the electroencephalogram (EEG) is a non-invasive method to examine infant brain maturation. Preterm fetal growth restricted (p-FGR) neonates display an altered EEG power spectrum compared to appropriate-for-gestational-age (AGA) peers, suggesting delayed brain maturation. Longitudinal studies investigating EEG power spectrum maturation in p-FGR infants are lacking, however.

Creatine biosynthesis and transport by the term human placenta.

Introduction: Creatine is an amino acid derivative that is involved in preserving ATP homeostasis. Previous studies suggest an important role for the creatine kinase circuit for placental ATP turnover. Creatine is obtained from both the diet and endogenous synthesis, usually along the renal-hepatic axis.

Fetal-growth-restricted preterm infants display compromised autonomic cardiovascular control on the first postnatal day but not during infancy.

BackgroundFetal growth restriction (FGR) is associated with increased perinatal mortality and long-term cardiovascular and neurodevelopmental sequelae. We hypothesized that FGR impacts on the development of autonomic heart rate and blood pressure control, contributing to unfavorable short- and long-term outcomes following FGR.MethodsWe studied 25 preterm FGR and 22 preterm and 19 term appropriate for gestational age (AGA) infants.

Amnion Epithelial Cells Promote Lung Repair via Lipoxin A.

Human amnion epithelial cells (hAECs) have been shown to possess potent immunomodulatory properties across a number of disease models. Recently, we reported that hAECs influence macrophage polarization and activity, and that this step was dependent on regulatory T cells. In this study, we aimed to assess the effects of hAEC-derived proresolution lipoxin-A (LXA4) on T-cell, macrophage, and neutrophil phenotype and function during the acute phase of bleomycin-induced lung injury.

Human amnion epithelial cells rescue cell death via immunomodulation of microglia in a mouse model of perinatal brain injury.

Background: Human amnion epithelial cells (hAECs) are clonogenic and have been proposed to reduce inflammatory-induced tissue injury. Perturbation of the immune response is implicated in the pathogenesis of perinatal brain injury; modulating this response could thus be a novel therapy for treating or preventing such injury. The immunomodulatory properties of hAECs have been shown in other animal models, but a detailed investigation of the effects on brain immune cells following injury has not been undertaken.

Maternal Asian ethnicity and obstetric intrapartum intervention: a retrospective cohort study.

Background: Maternal ethnicity is a recognized risk factor for stillbirth, such that South Asian women have higher rates than their Caucasian counterparts. However, whether maternal ethnicity is a risk factor for intrapartum outcomes is less clear. The aim of this study is to explore associations between maternal country of birth, operative vaginal delivery and emergency cesarean section, and to identify possible mechanisms underlying any such associations.

The effects of hydroxychloroquine on endothelial dysfunction.

Hydroxychloroquine is an anti-malarial drug which, due to its anti-inflammatory and immunomodulatory effects, is widely used for the treatment of autoimmune diseases. In a model of systemic lupus erythematosus hydroxychloroquine has been shown to exert protective endothelial effects. In this study, we aimed to investigate whether hydroxychloroquine was endothelial protective in an in vitro model of TNF-α and preeclamptic serum induced dysfunction.

Obesity and pregnancy outcomes: Do the relationships differ by maternal region of birth? A retrospective cohort study.

Background: We aimed to determine whether the association between obesity and a range of adverse maternal and perinatal outcomes differed in South Asian and Australian and New Zealand born women.

Methods: A retrospective cohort study of singleton births in South Asian (SA) and Australian/New Zealand (AUS/NZ) born women at an Australian hospital between 2009 and 2013. The interaction between maternal region of birth and obesity on a range of maternal and perinatal outcomes was assessed using multivariate logistic regression.

Customised management of the third stage of labour.

Background: Postpartum haemorrhage (PPH) rates are increasing worldwide. The rate is particularly high in women undergoing an induced or augmented labour. In response to this, we altered our hospital's protocol for the management of the third stage of labour to recommend Syntometrine, in preference to oxytocin alone, for women being induced or augmented.

Evaluating the Impact of Human Amnion Epithelial Cells on Angiogenesis.

The effects of human amnion epithelial cells (hAECs) on angiogenesis remain controversial. It is yet unknown if the presence of inflammation and/or gestational age of hAEC donors have an impact on angiogenesis. In this study, we examined the differences between term and preterm hAECs on angiogenesis in vitro and in vivo.

An Australian and New Zealand survey of practice of the use of oxytocin at elective caesarean section.

Background: The use of oxytocin to prevent postpartum haemorrhage at elective caesarean section is largely based on evidence derived from vaginal births. Overseas studies indicate wide variation in practice with regard to specific doses of oxytocin administered at caesarean section. No such surveys have been undertaken in Australia or New Zealand.