Ryan Hodges

Amnion Epithelial Cells as a Candidate Therapy for Acute and Chronic Lung Injury

Acute and chronic lung injury represents a major and growing global burden of disease. For many of these lung diseases, the damage is irreparable, exhausting the hosts ability to regenerate new lung, and current therapies are simply supportive rather than restorative. Cell-based therapies offer the promise of tissue regeneration for many organs. In this paper, we examine the potential application of amnion epithelial cells, derived from the term placenta, to lung regeneration. We discuss their unique properties of plasticity and immunomodulation, reviewing the experimental evidence that amnion epithelial cells can prevent and repair lung injury, offering the potential to be applied to both neonatal, childhood, and adult lung disease. It is amazing to suggest that the placenta may offer renewed life after birth as well as securing new life before.

Testing for Down syndrome in the older woman: a risky business?

For over 30 years, antenatal diagnosis of Down syndrome has been offered on the basis of advanced maternal age. While this was appropriate in the 1970s, developments in antenatal screening have rendered this a most inefficient strategy that is associated with excessive costs and procedure‐related pregnancy losses. In this article we argue for a review of how we test for Down syndrome in the older woman.

Functional echocardiography in the fetus with non-cardiac disease

We describe the hemodynamic changes observed in fetuses with extra cardiac conditions such as intrauterine growth restriction, tumors, twin–twin transfusion syndrome, congenital infections, and in fetuses of mothers with diabetes. In most fetuses with mild extra cardiac disease, the alterations in fetal cardiac function remain subclinical. Cardiac function assessment has however helped us to achieve a better understanding of the pathophysiology of these diseases. In fetuses at the more severe end of the disease spectrum, functional echocardiography may help in guiding clinical decision‐making regarding the need for either delivery or fetal therapy.

Learning from Experience: Development of a Cognitive Task-List to Assess the Second Stage of Labour for Operative Delivery

OBJECTIVE Ensuring the availability of operative vaginal delivery is one strategy for reducing the rising Caesarean section rate. However, current training programs appear inadequate. We sought to systematically identify the core steps in assessing women in the second stage of labour for safe operative delivery, and to produce an expert task-list to assist residents and obstetricians in deciding on the safest mode of delivery for their patients. METHODS Labour and delivery nursing staff of three large university-associated hospitals identified clinicians they considered to be skilled in operative vaginal deliveries. Obstetricians who were identified consistently were invited to participate in the study. Participants were filmed performing their normal assessment of the second stage of labour on a model. Two clinicians reviewed all videos and documented all verbal and non-verbal components of the assessment; these components were grouped into overarching themes and combined into an integrated expert task-list. The task-list was then circulated to all participants for additional comments, checked against SOGC guidelines, and redrafted, allowing production of a final expert task-list. RESULTS Thirty clinicians were identified by this process and 20 agreed to participate. Themes identified were assessment of suitability, focused history, physical examination including importance of an abdominal examination, strategies to accurately assess fetal position, station, and the likelihood of success, cautionary signs to prompt reassessment in the operating room, and warning signs to abandon operative delivery for Caesarean section. Communication strategies were emphasized. CONCLUSION Having expert clinicians teach assessment in the second stage of labour is an important step in the education of residents and junior obstetricians to improve confidence in managing the second stage of labour.

Mending a growth-restricted fetal heart: should we use glucocorticoids?

Clinical and experimental studies suggest that the growth-restricted fetus at increased risk of impaired cardiovascular function that likely contributes to both increased mortality rate and in survivors, to cardiovascular dysfunction apparent in childhood and later life. Fetal growth restriction is also associated with a high risk of preterm birth. Accordingly, the growth-restricted fetus is more likely than average to receive antenatal glucocorticoids to accelerate lung maturation in preparation for birth. However, glucocorticoids are powerful regulators of vascular tone and antenatal glucocorticoid administration to the intrauterine growth restriction (IUGR) fetus results in systemic cardiovascular changes that are not observed in the healthy normal grown fetus. These responses to glucocorticoids may disturb the IUGR fetus’ ability to appropriately compensate to placental insufficiency. Indeed is it possible that in the setting of severe IUGR exogenous glucocorticoids are detrimental rather than beneficial to the fetus?

Vitamin D testing in pregnancy: Does one size fit all?

Vitamin D deficiency is common. What the optimum level of vitamin D in pregnancy and whether vitamin D supplementation in pregnancy confers improved health benefits remain controversial.

Fetal Echocardiography and Pulsed-wave Doppler Ultrasound in a Rabbit Model of Intrauterine Growth Restriction

Fetal intrauterine growth restriction (IUGR) results in abnormal cardiac function that is apparent antenatally due to advances in fetoplacental Doppler ultrasound and fetal echocardiography. Increasingly, these imaging modalities are being employed clinically to examine cardiac function and assess wellbeing in utero, thereby guiding timing of birth decisions. Here, we used a rabbit model of IUGR that allows analysis of cardiac function in a clinically relevant way. Using isoflurane induced anesthesia, IUGR is surgically created at gestational age day 25 by performing a laparotomy, exposing the bicornuate uterus and then ligating 40-50% of uteroplacental vessels supplying each gestational sac in a single uterine horn. The other horn in the rabbit bicornuate uterus serves as internal control fetuses. Then, after recovery at gestational age day 30 (full term), the same rabbit undergoes examination of fetal cardiac function. Anesthesia is induced with ketamine and xylazine intramuscularly, then maintained by a continuous intravenous infusion of ketamine and xylazine to minimize iatrogenic effects on fetal cardiac function. A repeat laparotomy is performed to expose each gestational sac and a microultrasound examination (VisualSonics VEVO 2100) of fetal cardiac function is performed. Placental insufficiency is evident by a raised pulsatility index or an absent or reversed end diastolic flow of the umbilical artery Doppler waveform. The ductus venosus and middle cerebral artery Doppler is then examined. Fetal echocardiography is performed by recording B mode, M mode and flow velocity waveforms in lateral and apical views. Offline calculations determine standard M-mode cardiac variables, tricuspid and mitral annular plane systolic excursion, speckle tracking and strain analysis, modified myocardial performance index and vascular flow velocity waveforms of interest. This small animal model of IUGR therefore affords examination of in utero cardiac function that is consistent with current clinical practice and is therefore useful in a translational research setting.

Detection and assessment of brain injury in the growth-restricted fetus and neonate

Fetal growth restriction (FGR) is a common complication of pregnancy and, in severe cases, is associated with elevated rates of perinatal mortality, neonatal morbidity, and poor neurodevelopmental outcomes. The leading cause of FGR is placental insufficiency, with the placenta failing to adequately meet the increasing oxygen and nutritional needs of the growing fetus with advancing gestation. The resultant chronic fetal hypoxia induces a decrease in fetal growth, and a redistribution of blood flow preferentially to the brain. However, this adaptation does not ensure normal brain development. Early detection of brain injury in FGR, allowing for the prediction of short- and long-term neurodevelopmental consequences, remains a significant challenge. Furthermore, in FGR infants the detection and diagnosis of neuropathology is complicated by preterm birth, the etiological heterogeneity of FGR, timing of onset of growth restriction, its severity, and coexisting complications. In this review, we examine existing and emerging diagnostic tools from human and preclinical studies for the detection and assessment of brain injury in FGR fetuses and neonates. Increased detection rates, and early detection of brain injury associated with FGR, will offer opportunities for developing and assessing interventions to improve long-term outcomes.

Acceptability of Stem Cell Therapy by Pregnant Women

BACKGROUND Cell-based therapies may soon be used to treat disorders in the perinatal period. Our aim was to assess pregnant womens knowledge, attitudes, and acceptance of different types of stem cell therapies. METHODS Pregnant women attending an Australian tertiary center were asked to complete a questionnaire to seek their views on the potential therapeutic use of stem cells in the future. Outcome measures were womens acceptability of different types of stem cell therapies for themselves and their baby, ethical concerns, knowledge, and willingness to use stem cells for different indications. RESULTS A total of 150 women completed the questionnaire. More women were happy to use any stem cell type (82%) than placental stem cells only (12.5%), adult stem cells only (2%), embryonic stem cells only (0), and 3.5 percent would not use. With respect to use for their baby, more women were happy to use any stem cell type (83%) than placental stem cells only (13%), embryonic stem cells only (2%), adult stem cells only (0), and 2 percent would not use. Ethical concerns were highest with embryonic stem cells (25%), than adult stem cells (11%), and placental stem cells (10%). Twelve percent of women were very confident and 66 percent reasonably confident with their knowledge, whereas 17 percent understood little and 5 percent reported no understanding. Acceptance of using any stem cell therapy was 75 percent for severe medical disorders, 57 percent for moderate disorders, and 25 percent for mild medical disorders. CONCLUSIONS Pregnant women are confident with their knowledge of stem cells and overwhelmingly support their use to treat both themselves and their baby. The level of this support, however, is proportionate to the severity of the medical disorder. (BIRTH 39:2 June 2012).

Perinatal and Maternal Outcomes after Training Residents in Forceps before Vacuum Instrumental Birth

OBJECTIVE To compare the rates of attempted and successful instrumental births, intrapartum cesarean delivery, and subsequent perinatal and maternal morbidity before and after implementing a training intervention to arrest the decline in forceps competency among resident obstetricians. METHODS This retrospective cohort study examined all attempted instrumental births at Monash Health from 2005 to 2014. We performed an interrupted time-series analysis to compare outcomes of attempted instrumental births in 2005-2009 with those in 2010-2014. RESULTS There were 72,490 births from 2005 to 2014 at Monash Health, of which 8,789 (12%) were attempted instrumental vaginal births. After the intervention, rates of forceps births increased [autoregressive integrated moving average coefficient (β) 1.5, 95% confidence interval (CI) 1.03-1.96; P<.001], and vacuum births decreased (β -1.43, 95% CI -2.5 to -0.37; P<.01). Rates of postpartum hemorrhage decreased (β -1.3, 95% CI -2.07 to -0.49; P=.002) and epidural use increased (β 0.03, 95% CI 0.02-0.05; P<.001). There was no change in rates of unsuccessful instrumental births (β -0.39, 95% CI -3.03 to 2.43; P=.83), intrapartum cesarean delivery (β -0.29, 95% CI -0.55 to 0.14; P=.24), third- and fourth-degree tears (β -1.04, 95% CI -3.1 to 1.00; P=.32), or composite neonatal morbidity (β -0.18, 95% CI -0.38 to 0.02, P=.08). Unsuccessful instrumental births were more likely to be in nulliparous women (P<.001), less likely to have a senior obstetrician present (P<.001), be at later gestation (P<.001), and involved larger birth weight neonates (P<.001). CONCLUSION A policy of ensuring obstetric forceps competency before beginning vacuum training results in more forceps births, fewer postpartum hemorrhages, and no increase in third- and fourth-degree perineal injuries or episiotomies.