Blood pressure postpartum (BP2) RCT protocol: Follow-up and lifestyle behaviour change strategies in the first 12 months after hypertensive pregnancy.

OBJECTIVES: Women who had hypertensive disorders of pregnancy (HDP) are twice as likely to experience maternal cardiovascular disease later in life. The primary aim of this study (BP2) is to compare outcomes of 3 different management strategies, including lifestyle behaviour change (LBC), in the first 12 months postpartum in women who had HDP in their preceding pregnancy. Secondary aims include assessing the effects on other cardiometabolic parameters. STUDY DESIGN: Three-arm multicentre randomised trial in metropolitan Australian hospitals, (registration: ACTRN12618002004246) target sample size 480. Participants are randomised to one of three groups: 1) Optimised usual care: information package and family doctor follow-up 6 months postpartum 2) Brief intervention: information package as per group 1, plus assessment and brief LBC counselling at a specialised clinic with an obstetric physician and dietitian 6 months postpartum 3) Extended intervention: as per group 2 plus enrolment into a 6 month telephone-based LBC program from 6 to 12 months postpartum. All women have an outcome assessment at 12 months. MAIN OUTCOME MEASURES: Primary outcomes: (a) BP change or (b) weight change and/or waist circumference change. SECONDARY OUTCOMES: maternal health-related quality of life, engagement and retention in LBC program, biochemical markers, vascular function testing, infant weight trajectory, incremental cost-effectiveness ratios. The study is powered to detect a 4 mmHg difference in systolic BP between groups, or a 4 kg weight loss difference/2cm waist circumference change. CONCLUSIONS: BP2 will provide evidence regarding the feasibility and effectiveness of postpartum LBC interventions and structured clinical follow-up in improving cardiovascular health markers after HDP.

Women's experiences of antenatal transfer for threatened premature labour in NSW: A qualitative study.

BACKGROUND: Each year thousands of pregnant women experiencing threatened premature labour are transferred considerable distances across Australia to access higher level facilities but only a small proportion of these women go on to actually give birth to a premature baby. Women from regional areas are required to move away from their home, children and support networks because of a perceived risk of birthing in a centre without neonatal intensive care facilities. AIM: This study examines the experience of women undergoing antenatal transfer for threatened premature labour in New South Wales and the Australian Capital Territory who do not give birth during their transfer admission. METHODS: Thirteen semi-structured in-depth interviews were held with women across five tertiary referral sites across New South Wales and the Australian Capital Territory, and analysed until saturation for themes. FINDINGS: Seven urban and six rural women were interviewed. Women and their families were all negatively affected by antenatal transfer. Factors that helped enable a positive experience were; enhanced sense of safety in the tertiary unit, and individual qualities of staff. Factors that contributed to negative experiences were; inadequate and conflicting information, and no involvement or choice in the clinical decision-making process to move to another facility. CONCLUSIONS: Antenatal transfer is an extremely stressful experience for women and their families. The provision of high quality written and verbal information, and the inclusion of women's perception of risk in the clinical decision making process will improve the experience for women and their families in NSW and the ACT.

Active care of infants born between 22 and 26 weeks of gestation does not follow consensus expert recommendations.

AIM: To determine the relationship between clinical practice and publication of an Australian consensus statement for management of extremely preterm infants in 2006. METHODS: A population-based study using linked data from New South Wales, Australia for births between 22 + 0 and 26 + 6 weeks of gestation between 2000 and 2011. RESULTS: There were 4746 births of whom 2870 were liveborn and 1876 were stillborn. Of the live births, 2041 (71%) were resuscitated, 1914 (67%) were admitted into a neonatal intensive care unit (NICU) and 1310 (46%) survived to hospital discharge. Thirty-nine (2%) stillbirths were resuscitated but none survived. No 22-week infant survived to hospital discharge. Fewer 23-week gestation infants were resuscitated between 2004 (52%) and 2005 (20%) but resuscitation rates increased by 2008 (44%). There was no difference at other gestations. Adjusted odds ratio (OR) for resuscitation was increased by birthweight (OR: 1.01), tertiary hospital birth (OR: 3.4) and Caesarean delivery (OR: 11.3) and decreased by rural residence (OR: 0.4) and male gender (OR: 0.7). CONCLUSION: Expert recommendations may be shaped by clinical practice rather than the converse, especially for 23-week gestation infants. Recommendations should be revised regularly to include clinical practice changes.

Population-based study shows that resuscitating apparently stillborn extremely preterm babies is associated with poor outcomes.

AIM: This population-based study determined the delivery room management and outcomes of extremely preterm infants born with Apgar scores of 0. METHODS: We linked birth, neonatal intensive care unit (NICU) and death records for babies who were born between 22 + 0 and 27 + 6 weeks of gestation with a one-minute Apgar score of 0, in New South Wales, Australia, between 1998 and 2011. RESULTS: We classified 2173/2262 (96%) of infants with a one-minute Apgar score of 0 as stillborn. Resuscitation was provided for 48/89 (54%) live births and 40/2173 (2%) stillbirths. Cardiac massage was given to 44 infants, including three 22-week stillborn babies. Of the 13 live births admitted to an NICU, 11 survived to hospital discharge. Most (98%) of the 2212 deaths occurred on the first day of life. One baby who was classified as stillborn lived for 51 days. Resuscitation increased the mean (95% confidence interval) duration of survival from 1 (0-2) to 45 (0-104) hours (p < 0.001). No infant with a five-minute Apgar score of 0 survived. CONCLUSION: Clinicians resuscitated extremely preterm infants without a detectable heartbeat, even at 22 weeks of gestation. No infant survived without resuscitation or if their heartbeat was not regained by five minutes.

Audit of immediate outcomes for MCDA twins following laser therapy for twin-twin transfusion syndrome at the NSW Fetal Therapy Centre.

OBJECTIVE: To audit immediate pregnancy and neonatal outcomes of selective laser photocoagulation of communicating vessels (SLPCV) for twin-twin transfusion syndrome (TTTS) at the New South Wales Fetal Therapy Centre. METHODS: Retrospective cohort study of 151 TTTS cases undergoing SLPCV between July 2003 and May 2013, evaluating procedural details, delivery and perinatal outcomes. RESULTS: The majority of cases were Stage III at SLPCV (56.9%), although proportion of Stage II SLPCV increased over time (P = 0.03). Survival to hospital discharge of at least one baby was 85.6% and dual survival was 52.5%. Median gestational age at delivery was 32.6 weeks (IQR 29.0-35.0 weeks) with a median of 11.4 weeks (IQR 8.3-14.7) from laser to delivery. Median birthweight was 1792 g (IQR 1288-2233 g), with 75% of babies admitted to the nursery, predominantly secondary to prematurity. Immediate SLPCV complications were in utero fetal demise <1 week postprocedure in 27 fetuses (19.6%) and/or ruptured membranes <1 week postprocedure in 9 fetuses (6.6%). CONCLUSIONS: This Australian series shows that local outcomes after SLPCV for stages II-IV TTTS remain equal to the international published literature and have remained stable after an initial learning curve. Women were more likely to be Stage II rather than III in the more recent years. However, this does not appear to be attributable to altered referral patterns.

Caring for pregnant women for whom transfusion is not an option. A national review to assist in patient care.

Postpartum haemorrhage (PPH) is the leading cause of maternal mortality and morbidity globally. Obstetric bleeding can be catastrophic and management is challenging, involving a coordinated multidisciplinary approach, which may include blood products. In settings where blood transfusion is not an option, either because of patient refusal (most commonly in Jehovah Witnesses) or because of unavailability of blood, management becomes even more challenging. Observational studies have demonstrated an association between refusal of blood products in major obstetric haemorrhage and increased morbidity and mortality. This review draws upon evidence in the literature, physiological principles and expert opinion for strategies and guidance to optimise the outcomes of pregnant women in whom blood transfusion is either refused or impossible. The importance of a multidisciplinary antenatal and perinatal management plan, including optimisation of haemoglobin and iron stores pre-delivery, blood loss minimisation, early haemorrhage control and postpartum anaemia treatment, is discussed.

Low-Dose versus Standard-Dose Intravenous Immunoglobulin to Prevent Fetal Intracranial Hemorrhage in Fetal and Neonatal Alloimmune Thrombocytopenia: A Randomized Trial.

OBJECTIVE: Pregnancies at risk of fetal and neonatal alloimmune thrombocytopenia (FNAIT) are commonly treated using weekly intravenous immunoglobulin (IVIG) at 1 g/kg maternal weight. IVIG is an expensive multidonor human blood product with dose-related side effects. Our aim was to evaluate the effectiveness of IVIG at a lower dose, i.e., 0.5 g/kg. METHODS: This was a randomized controlled multicenter trial conducted in Sweden, the Netherlands and Australia. Pregnant women with human platelet antigen alloantibodies and an affected previous child without intracranial hemorrhage (ICH) were enrolled. The participants were randomized to IVIG at 0.5 or 1 g/kg per week. The analyses were per intention to treat. The primary outcome was fetal or neonatal ICH. Secondary outcomes were platelet count at birth, maternal and neonatal IgG levels, neonatal treatment and bleeding other than ICH. RESULTS: A total of 23 women were randomized into two groups (low dose: n = 12; standard dose: n = 11). The trial was stopped early due to poor recruitment. No ICH occurred. The median newborn platelet count was 81 × 10(9)/l (range 8-269) in the 0.5 g/kg group versus 110 × 10(9)/l (range 11-279) in the 1 g/kg group (p = 0.644). CONCLUSION: The risk of adverse outcomes in FNAIT pregnancies treated with IVIG at 0.5 g/kg is very low, similar to that using 1 g/kg, although our uncompleted trial lacked the power to conclusively prove the noninferiority of using the low dose.

Congenital anterior urethral diverticulum: antenatal diagnosis with subsequent neonatal endoscopic management.

Congenital anterior urethral diverticulum is a rare cause of urethral obstruction in boys. We report on the antenatal diagnosis of this rare phenomenon, making this the sixth prenatally diagnosed case in the English literature (to the best of our knowledge). Our initial prenatal assessment, postnatal endoscopic management, along with the eventual clinical course is outlined. The embryologic theories, differential diagnosis, literature review, imaging, and treatment modalities of this entity are discussed.

Accessory diaphragm associated with non-immune hydrops fetalis.

An accessory diaphragm, also known as diaphragmatic duplication, is a congenital anomaly in which there is a fibromuscular membrane on top of the normally formed diaphragm dividing the hemithorax into two compartments trapping part of the pulmonary parenchyma. It is a very rare anomaly with less than 40 cases reported in the literature, of which only five were diagnosed in the newborn period, with no reports on any clinical clues for the antenatal diagnosis of this condition. We describe a case of congenital accessory diaphragm presenting in the antenatal period as hydrops fetalis. We also describe the radiological features of this rare anomaly on the antenatal fetal ultrasound.

Congenital Epulis: a clinical case presentation.

Congenital Epulis (CE) is a rare, benign tumour of the mucosa of the mouth in a neonate. It presents as an intraoral tumour and is rarely diagnosed prenatally. Complications include neonatal airway compromise, difficulty feeding and aesthetic considerations. Ultrasound is useful in aiding decisions regarding site, age, method of delivery and preparing parents and staff for the appearances of the tumour at birth. We present a case where CE was identified at 35 weeks gestational age during a routine third trimester prenatal ultrasound. The patient was scanned at a rural centre, referred to a tertiary institution for follow up and delivered at a specialist perinatal surgical centre, in preparation for neonatal surgery. The outcome was excellent and this case is a good example of multi-centre cooperation.

Integrative annotation of variants from 1092 humans: application to cancer genomics.

Interpreting variants, especially noncoding ones, in the increasing number of personal genomes is challenging. We used patterns of polymorphisms in functionally annotated regions in 1092 humans to identify deleterious variants; then we experimentally validated candidates. We analyzed both coding and noncoding regions, with the former corroborating the latter. We found regions particularly sensitive to mutations ("ultrasensitive") and variants that are disruptive because of mechanistic effects on transcription-factor binding (that is, "motif-breakers"). We also found variants in regions with higher network centrality tend to be deleterious. Insertions and deletions followed a similar pattern to single-nucleotide variants, with some notable exceptions (e.g., certain deletions and enhancers). On the basis of these patterns, we developed a computational tool (FunSeq), whose application to ~90 cancer genomes reveals nearly a hundred candidate noncoding drivers.

Outpatient Foley catheter versus inpatient prostaglandin E2 gel for induction of labour: a randomised trial.

BACKGROUND: Induction of labour (IOL) is one of the commonest obstetric interventions, with significant impact on both the individual woman and health service delivery. Outpatient IOL is an attractive option to reduce these impacts. To date there is little data comparing outpatient and inpatient IOL methods, and potential safety concerns (hyperstimulation) if prostaglandins, the standard inpatient IOL medications, are used in the outpatient setting. The purpose of this study was to assess feasibility, clinical effectiveness and patient acceptability of outpatient Foley catheter (OPC) vs. inpatient vaginal PGE2 (IP) for induction of labour (IOL) at term. METHODS: Women with an unfavourable cervix requiring IOL at term (N=101) were randomised to outpatient care using Foley catheter (OPC, n=50) or inpatient care using vaginal PGE2 (IP, n=51). OPC group had Foley catheter inserted and were discharged overnight following a reassuring cardiotocograph. IP group received 2 mg/1 mg vaginal PGE2 if nulliparous or 1 mg/1 mg if multiparous. Main outcome measures were inpatient stay (prior to birth, in Birthing Unit, total), mode of birth, induction to delivery interval, adverse reactions and patient satisfaction. RESULTS: OPC group had shorter hospital stay prior to birth (21.3 vs. 32.4 hrs, p< .001), IP were more likely to achieve vaginal birth within 12 hours of presenting to Birthing Unit (53% vs. 28%, p= .01). Vaginal birth rates (66% OPC Vs. 71% IP), total induction to delivery time (33.5 hrs vs. 31.3 hrs) and total inpatient times (96 hrs OPC Vs. 105 hrs IP) were similar. OPC group felt less pain (significant discomfort 26% Vs 58%, p=.003), and had more sleep (5.8 Vs 3.4 hours, p< .001), during cervical preparation, but were more likely to require oxytocin IOL (88 Vs 59%, p=.001). CONCLUSIONS: OPC was feasible and acceptable for IOL of women with an unfavourable cervix at term compared to IP, however did not show a statistically significant reduction in total inpatient stay and was associated with increased oxytocin IOL. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN:12609000420246.

Advances in maternal fetal medicine practice.

Maternal fetal medicine (MFM) is a subspecialty of obstetrics that focuses on identified risk pregnancies. The role includes obstetric ultrasound for fetal assessment and diagnosis of anomalies, invasive prenatal diagnosis and management of pregnancies complicated by maternal medical disorders, multiple fetuses and the antenatal management of extreme prematurity. Skill specialisation within MFM includes fetal interventions such as fetal shunting procedures, intrauterine transfusion, fetoscopic laser photocoagulation of anastomotic vessels for twin to twin transfusion syndrome and ex utero intrapartum treatment. MFM specialists are actively involved in clinical and basic science research to improve maternal and neonatal outcomes. Most Australian MFM specialists are associated with metropolitan teaching hospitals. MFM sub-specialisation has reduced the impact of disability associated with aneuploidy, structural anomalies, multiple pregnancy and extreme prematurity. Management aims are to give families timely counselling, appropriate intervention, and optimisation of the time and location of delivery. The aim of this paper is to update the reader regarding current advances in MFM practices.

Australian maternity reform through clinical redesign.

The current Australian national maternity reform agenda focuses on improving access to maternity care for women and their families while preserving safety and quality. The caseload midwifery model of care offers the level of access to continuity of care proposed in the reforms however the introduction of these models in Australia continues to meet with strong resistance. In many places access to caseload midwifery care is offered as a token, usually restricted to well women, within limited metropolitan and regional facilities and where available, places for women are very small as a proportion of the total service provided. This case study outlines a major clinical redesign of midwifery care at a metropolitan tertiary referral maternity hospital in Sydney. Caseload midwifery care was introduced under randomised trial conditions to provide midwifery care to 1500 women of all risk resulting in half of the publicly insured women receiving midwifery group practice care. The paper describes the organisational quality and safety tools that were utilised to facilitate the process while discussing the factors that facilitated the process and the barriers that were encountered within the workforce, operational and political context.

Intra-amniotic surfactant for women at risk of preterm birth for preventing respiratory distress in newborns.

BACKGROUND: Early surfactant reduces mortality and pulmonary complications in preterm infants with respiratory distress syndrome. However, current surfactant administration strategies require endotracheal intubation with or without continued mechanical ventilation. Bronchopulmonary dysplasia and chronic lung disease (CLD) are associated with mechanical ventilation and potentially life-long effects. Non-invasive methods of surfactant administration including intra-amniotic surfactant may avoid endotracheal intubation and mechanical ventilation, potentially preventing development of CLD. OBJECTIVES: To determine if intra-amniotic instillation of surfactant for women at risk of preterm birth, compared to placebo or no treatment or post-delivery tracheal surfactant instillation, reduces morbidity or mortality, or both, in preterm infants. If intra-amniotic instillation is effective, in subgroup analysis to determine the effect of 1) gestational age; 2) type of surfactant; 3) dose; 4) timing; 5) indication; and 6) multiple pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (August 2009), MEDLINE (1950-August 2009), handsearched the Proceedings of Pediatric Academic Societies (American Pediatric Society, Society for Pediatric Research and European Society for Pediatric Research) from 1990-2009 in Pediatric Research Journal and Abstracts online and the Proceedings of Perinatal Society of Australia and New Zealand (PSANZ) (1996-2009). We also searched the Science Citation Index (Web of Science) (August 2009) and checked reference lists of identified studies. We contacted Abbott Laboratories, Inc for unpublished studies. SELECTION CRITERIA: Published, unpublished and ongoing randomised controlled, cluster-randomised or quasi-randomised trials of intra-amniotic instillation of surfactant for women at risk of preterm birth, compared to placebo or no treatment or post-delivery tracheal surfactant instillation. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed study eligibility and quality. MAIN RESULTS: We found no trials were found met the inclusion criteria for this review. AUTHORS' CONCLUSIONS: We identified no randomised trials that evaluated the effect of intra-amniotic instillation of surfactant for women at risk of preterm birth. Evidence from animal and observational human studies suggest that intra-amniotic surfactant administration is potentially safe, feasible and effective. Well designed trials of intra-amniotic instillation of surfactant for women at risk of preterm birth are needed.

Mutations in contactin-1, a neural adhesion and neuromuscular junction protein, cause a familial form of lethal congenital myopathy.

We have previously reported a group of patients with congenital onset weakness associated with a deficiency of members of the syntrophin-alpha-dystrobrevin subcomplex and have demonstrated that loss of syntrophin and dystrobrevin from the sarcolemma of skeletal muscle can also be associated with denervation. Here, we have further studied four individuals from a consanguineous Egyptian family with a lethal congenital myopathy inherited in an autosomal-recessive fashion and characterized by a secondary loss of beta2-syntrophin and alpha-dystrobrevin from the muscle sarcolemma, central nervous system involvement, and fetal akinesia. We performed homozygosity mapping and candidate gene analysis and identified a mutation that segregates with disease within CNTN1, the gene encoding for the neural immunoglobulin family adhesion molecule, contactin-1. Contactin-1 transcripts were markedly decreased on gene-expression arrays of muscle from affected family members compared to controls. We demonstrate that contactin-1 is expressed at the neuromuscular junction (NMJ) in mice and man in addition to the previously documented expression in the central and peripheral nervous system. In patients with secondary dystroglycanopathies, we show that contactin-1 is abnormally localized to the sarcolemma instead of exclusively at the NMJ. The cntn1 null mouse presents with ataxia, progressive muscle weakness, and postnatal lethality, similar to the affected members in this family. We propose that loss of contactin-1 from the NMJ impairs communication or adhesion between nerve and muscle resulting in the severe myopathic phenotype. This disorder is part of the continuum in the clinical spectrum of congenital myopathies and congenital myasthenic syndromes.

Diagnosis and management of fetal growth restriction: the role of fetal therapy.

Fetal growth restriction remains a major cause of perinatal morbidity and mortality in modern obstetric practice. Placental insufficiency is the most common association, but is often a diagnosis of exclusion. Currently, no treatment can ameliorate or reverse established growth restriction: maximising gestational age and judicious timing of steroid administration and delivery are the primary tasks for the obstetrician. Although comprehensive surveillance of the preterm fetus now includes ductus venosus Doppler studies, its effectiveness in timing delivery has yet to be confirmed in randomised controlled trials. More basic research on the regulation of fetal growth is needed before specific therapies for established growth restriction can be developed.