Philip DeKoninck

The Fetal Heart in Twin-to-Twin Transfusion Syndrome

Twin-to-twin transfusion syndrome is a severe complication occurring in 10% of monochorionic twin pregnancies. The disease is usually explained as due to an intrauterine imbalance in intertwin blood exchange, which leads to a volume depleted-donor twin and an overfilled recipient twin. The recipient has signs of cardiac dysfunction, which can be measured using echocardiography or blood and amniotic fluid derived biomarkers. Whereas cardiac dysfunction typically progresses in pregnancies treated with amniodrainage, it usually disappears within a few weeks after fetoscopic laser coagulation of the connecting intertwin anastomoses. Nevertheless, recipients remain at a increased risk of pulmonary stenosis. In this paper, we summarize the cardiac alterations in twin-to-twin transfusion syndrome, describe the changes seen after fetal therapy, list the newly proposed staging systems based on fetal cardiac function, and make recommendations about the use of fetal echocardiography in the evaluation and followup of pregnancies complicated by twin-to-twin transfusion syndrome.

Unique Tracheal Fluid MicroRNA Signature Predicts Response to FETO in Patients With Congenital Diaphragmatic Hernia

Objective and Background: Our objective was to determine the fetal in vivo microRNA signature in hypoplastic lungs of human fetuses with severe isolated congenital diaphragmatic hernia (CDH) and changes in tracheal and amniotic fluid of fetuses undergoing fetoscopic endoluminal tracheal occlusion (FETO) to reverse severe lung hypoplasia due to CDH. Methods: We profiled microRNA expression in prenatal human lungs by microarray analysis. We then validated this signature with real-time quantitative polymerase chain reaction in tracheal and amniotic fluid of CDH patients undergoing FETO. We further explored the role of miR-200b using semiquantitative in situ hybridization and immunohistochemistry for TGF-&bgr;2 in postnatal lung sections. We investigated miR-200b effects on TGF-&bgr; signaling using a SMAD-luciferase reporter assay and Western blotting for phospho-SMAD2/3 and ZEB-2 in cultures of human bronchial epithelial cells. Results: CDH lungs display an increased expression of 2 microRNAs: miR-200b and miR-10a as compared to control lungs. Fetuses undergoing FETO display increased miR-200 expression in their tracheal fluid at the time of balloon removal. Future survivors of FETO display significantly higher miR-200 expression than those with a limited response. miR-200b was expressed in bronchial epithelial cells and vascular endothelial cells. TGF-&bgr;2 expression was lower in CDH lungs. miR-200b inhibited TGF-&bgr;-induced SMAD signaling in cultures of human bronchial epithelial cells. Conclusions: Human fetal hypoplastic CDH lungs have a specific miR-200/miR-10a signature. Survival after FETO is associated with increased miR-200 family expression. miR-200b overexpression in CDH lungs results in decreased TGF-&bgr;/SMAD signaling.

Optimal Interval between Ultrasound Scans for the Detection of Complications in Monochorionic Twins

Introduction: Monochorionic-diamniotic (MCDA) twin pregnancies are high risk, due to twin-to-twin transfusion syndrome (TTTS), twin anaemia polycythaemia sequence (TAPS) and intrauterine growth restriction (IUGR). There is limited evidence to guide ultrasound surveillance protocols. Using a retrospective cohort, we aimed to provide insight into the optimal interval of ultrasound surveillance. Methods: Retrospective cohort of women with MCDA pregnancies who received antenatal care at Monash Medical Centre (January 2011-October 2014). We reviewed all ultrasounds from ≥15 weeks gestation and collected perinatal outcomes. Results: A total of 162 women with MCDA pregnancies attended our care. Six women were excluded due to late referral. Of the remaining 156, 55% were uncomplicated. TTTS, TAPS, IUGR and fetal demise in utero occurred in 9%, 1%, 31% and 2%, respectively. Median interval between the last ultrasound and TTTS diagnosis was 3.1 weeks (IQR 0.8-5.8). There was a trend towards a longer interval for cases with advanced TTTS compared to early TTTS. Interval between ultrasound scans was longer in cases with unexplained fetal demise in utero and advanced TTTS than early TTTS [3.4 weeks (IQR 2.0-6.9) vs. 0.9 weeks (IQR 0.4-3.7); p < 0.05]. Discussion: Our observations support current recommendations for fortnightly ultrasound surveillance in MCDA pregnancies from 16 weeks gestation and suggest that longer intervals may be associated with poorer outcomes.

Treatment of preeclampsia with hydroxychloroquine: a review

Abstract In this review, we discuss the potential use of antimalarial drugs as an adjuvant therapy for preeclampsia, focusing on the mechanisms of action of this class of drugs in the context of preeclampsia. In particular, hydroxychloroquine has been shown to have various beneficial effects on patients with systemic lupus erythematosus. There are several pathways targeted by the antimalarial drugs that are similar to the pathophysiology of preeclampsia and hence offering opportunities to develop novel therapies to treat the disease. Given the safety profile of hydroxychloroquine in pregnancy, there is merit in exploring the efficacy of this drug as an adjuvant therapy in women with early onset preeclampsia.

Embedding assessment in a simulation skills training program for medical and midwifery students: A pre- and post-intervention evaluation

Simulation‐based programs are increasingly being used to teach obstetrics and gynaecology examinations, but it is difficult to establish student learning acquired through them. Assessment may test student learning but its role in learning itself is rarely recognised. We undertook this study to assess medical and midwifery student learning through a simulation program using a pre‐test and post‐test design and also to evaluate use of assessment as a method of learning.

Lung hypoplasia in newborn rabbits with a diaphragmatic hernia affects pulmonary ventilation but not perfusion

BackgroundA congenital diaphragmatic hernia (DH) can result in severe lung hypoplasia that increases the risk of morbidity and mortality after birth; however, little is known about the cardiorespiratory transition at birth.MethodsUsing phase-contrast X-ray imaging and angiography, we examined the cardiorespiratory transition at birth in rabbit kittens with DHs. Surgery was performed on pregnant New Zealand white rabbits (n=18) at 25 days’ gestation to induce a left-sided DH. Kittens were delivered at 30 days’ gestation, intubated, and ventilated to achieve a tidal volume (Vt) of 8u2009ml/kg in control and 4u2009ml/kg in DH kittens while they were imaged.ResultsFunctional residual capacity (FRC) recruitment and Vt in the hypoplastic left lung were markedly reduced, resulting in a disproportionate distribution of FRC into the right lung. Following lung aeration, relative pulmonary blood flow (PBF) increased equally in both lungs, and the increase in pulmonary venous return was similar in both control and DH kittens.ConclusionThese findings indicate that nonuniform lung hypoplasia caused by DH alters the distribution of ventilation away from hypoplastic and into normally grown lung regions. During transition, the increase in PBF and pulmonary venous return, which is vital for maintaining cardiac output, is not affected by lung hypoplasia.

Elevated airway liquid volumes at birth: a potential cause of transient tachypnea of the newborn

Excessive liquid in airways and/or distal lung tissue may underpin the respiratory morbidity associated with transient tachypnea of the newborn (TTN). However, its effects on lung aeration and respiratory function following birth are unknown. We investigated the effect of elevated airway liquid volumes on newborn respiratory function. Near-term rabbit kittens (30 days gestation; term ~32 days) were delivered, had their lung liquid-drained, and either had no liquid replaced (control; n = 7) or 30 ml/kg of liquid re-added to the airways [liquid added (LA); n = 7]. Kittens were mechanically ventilated in a plethysmograph. Measures of chest and lung parameters, uniformity of lung aeration, and airway size were analyzed using phase contrast X-ray imaging. The maximum peak inflation pressure required to recruit a tidal volume of 8 ml/kg was significantly greater in LA compared with control kittens (35.0u2009±u20090.7 vs. 26.8u2009±u20090.4 cmH2O, P < 0.001). LA kittens required greater time to achieve lung aeration (106u2009±u200914 vs. 60u2009±u20096 inflations, P = 0.03) and had expanded chest walls, as evidenced by an increased total chest area (32u2009±u20099%, P < 0.0001), lung height (17u2009±u20096%, P = 0.02), and curvature of the diaphragm (19u2009±u20098%, P = 0.04). LA kittens had lower functional residual capacity during stepwise changes in positive end-expiratory pressures (5, 3, 0, and 5 cmH20). Elevated lung liquid volumes had marked adverse effects on lung structure and function in the immediate neonatal period and reduced the ability of the lung to aerate efficiently. We speculate that elevated airway liquid volumes may underlie the initial morbidity in near-term babies with TTN after birth.NEW & NOTEWORTHY Transient tachypnea of the newborn reduces respiratory function in newborns and is thought to result due to elevated airway liquid volumes following birth. However, the effect of elevated airway liquid volumes on neonatal respiratory function is unknown. Using phase contrast X-ray imaging, we show that elevated airway liquid volumes have adverse effects on lung structure and function in the immediate newborn period, which may underlie the pathology of TTN in near-term babies after birth.

The effects of partial amniotic carbon dioxide insufflation in an ovine model

We aim to assess the effect of partial amniotic carbon dioxide insufflation (PACI) at increasing pressures on fetal acid‐base, fetal‐placental perfusion, and fetal membrane morphology in an ovine model.

Evaluation of learning from Practical Obstetric Multi-Professional Training and its impact on patient outcomes in Australia using Kirkpatrick’s framework: a mixed methods study

Objectives The aim of this study was to evaluate the implementation of the Practical Obstetric Multi-Professional Training (PROMPT) simulation using the Kirkpatrick’s framework. We explored participants’ acquisition of knowledge and skills, its impact on clinical outcomes and organisational change to integrate the PROMPT programme as a credentialing tool. We also aimed to assess participants’ perception of usefulness of PROMPT in their clinical practice. Study design Mixed methods approach with a pre-test/post-test design. Setting Healthcare network providing obstetric care in Victoria, Australia. Participants Medical and midwifery staff attending PROMPT between 2013 and 2015 (n=508); clinical outcomes were evaluated in two cohorts: 2011–2012 (n=15 361 births) and 2014–2015 (n=12 388 births). Intervention Attendance of the PROMPT programme, a simulation programme taught in multidisciplinary teams to facilitate teaching emergency obstetric skills. Main outcome measure Clinical outcomes compared before and after embedding PROMPT in educational practice. Secondary outcome measure Assessment of knowledge gained by participants through a qualitative analysis and description of process of embedding PROMPT in educational practice. Results There was a change in the management of postpartum haemorrhage by early recognition and intervention. The key learning themes described by participants were being prepared with a prior understanding of procedures and equipment, communication, leadership and learning in a safe, supportive environment. Participants reported a positive learning experience and increase in confidence in managing emergency obstetric situations through the PROMPT programme, which was perceived as a realistic demonstration of the emergencies. Conclusion Participants reported an improvement of both clinical and non-technical skills highlighting principles of teamwork, communication, leadership and prioritisation in an emergency situation. An improvement was observed in management of postpartum haemorrhage, but no significant change was noted in clinical outcomes over a 2-year period after PROMPT. However, the skills acquired by medical and midwifery staff justify embedding PROMPT in educational programmes.

Physiological-based cord clamping in preterm infants using a new purpose-built resuscitation table: a feasibility study

Objective Physiological-based cord clamping (PBCC) led to a more stable cardiovascular adaptation and better oxygenation in preterm lambs, but in preterm infants, this approach has been challenging. Our aim was to assess the feasibility of PBCC, including patterns of oxygen saturation (SpO2) and heart rate (HR) during stabilisation in preterm infants using a new purpose-built resuscitation table. Design Observational study. Setting Tertiary referral centre, Leiden University Medical Centre, The Netherlands. Patients Infants born below 35 weeks’ gestational age. Interventions Infants were stabilised on a new purpose-built resuscitation table (Concord), provided with standard equipment needed for stabilisation. Cord clamping was performed when the infant was stable (HR >100u2009bpm, spontaneous breathing on continuous positive airway pressure with tidal volumes >4u2009mL/kg, SpO2 ≥25th percentile and fraction of inspired oxygen (FiO2) <0.4). Results Thirty-seven preterm infants were included; mean (SD) gestational age of 30.9 (2.4) weeks, birth weight 1580 (519) g. PBCC was successful in 33 infants (89.2%) and resulted in median (IQR) cord clamping time of 4:23 (3:00–5:11) min after birth. There were no maternal or neonatal adverse events. In 26/37 infants, measurements were adequate for analysis. HR was 113 (81–143) and 144 (129–155) bpm at 1 min and 5u2009min after birth. SpO2 levels were 58%(49%–60%) and 91%(80%–96%)%), while median FiO2 given was 0.30 (0.30–0.31) and 0.31 (0.25–0.97), respectively. Conclusion PBCC in preterm infants using the Concord is feasible. HR remained stable, and SpO2 quickly increased with low levels of oxygen supply. Trial registration number NTR6095, results.