Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine.

BACKGROUND: Although Zika virus (ZIKV) infection is typically self-limiting, other associated complications such as congenital birth defects and the Guillain-Barré syndrome are well described. There are no approved vaccines against ZIKV infection. METHODS: In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each. The participants received either 1 mg or 2 mg of vaccine intradermally, with each injection followed by electroporation (the use of a pulsed electric field to introduce the DNA sequence into cells) at baseline, 4 weeks, and 12 weeks. RESULTS: The median age of the participants was 38 years, and 60% were women; 78% were White and 22% Black; in addition, 30% were Hispanic. At the interim analysis at 14 weeks (i.e., after the third dose of vaccine), no serious adverse events were reported. Local reactions at the vaccination site (e.g., injection-site pain, redness, swelling, and itching) occurred in approximately 50% of the participants. After the third dose of vaccine, binding antibodies (as measured on enzyme-linked immunosorbent assay) were detected in all the participants, with geometric mean titers of 1642 and 2871 in recipients of 1 mg and 2 mg of vaccine, respectively. Neutralizing antibodies developed in 62% of the samples on Vero-cell assay. On neuronal-cell assay, there was 90% inhibition of ZIKV infection in 70% of the serum samples and 50% inhibition in 95% of the samples. The intraperitoneal injection of postvaccination serum protected 103 of 112 IFNAR knockout mice (bred with deletion of genes encoding interferon-α and interferon-ß receptors) (92%) that were challenged with a lethal dose of ZIKV-PR209 strain; none of the mice receiving baseline serum survived the challenge. Survival was independent of the neutralization titer. CONCLUSIONS: In this phase 1, open-label clinical trial, a DNA vaccine elicited anti-ZIKV immune responses. Further studies are needed to better evaluate the safety and efficacy of the vaccine. (Funded by GeneOne Life Science and others; ZIKA-001 ClinicalTrials.gov number, NCT02809443.).

Preclinical safety assessment of the suction-assisted intradermal injection of the SARS-CoV-2 DNA vaccine candidate pGO-1002 in white rabbit.

pGO-1002, a non-viral DNA vaccine that expresses both spike and ORF3a antigens of SARS-CoV-2, is undergoing phase 1 and phase 2a clinical trials in Korea and the US. A preclinical repeated-dose toxicity study in New Zealand white rabbits in compliance with Good Laboratory Practice (GLP) was conducted to assess the potential toxicity, local tolerance, and immunogenicity of the vaccine and GeneDerm suction device. The dose rate was 1.2 mg/head pGO-1002, and this was administered intradermally to a group of animals (eight animals/sex/group) three times at 2-week intervals, followed by a 4-week recovery period. After each administration, suction was applied to the injection site using the GeneDerm device. Mortality, clinical signs, body weight, food consumption, skin irritation, ophthalmology, body temperature, urinalysis, and clinical pathology were also monitored. Gross observations and histopathological evaluation were performed. Overall, pGO-1002 administration-related changes were confined to minor damage or changes at the injection site, increased spleen weight and minimal increased cellularity in white pulp. All changes of injection site were considered local inflammatory changes or pharmacological actions due to the vaccine with the changes in spleen considered consistent with vaccine-induced immune activation. All findings showed reversibility during the 4-week recovery period. Animals vaccinated with pGO-1002, administered by intradermal injection and followed by application of suction with GeneDerm, developed humoral and cellular responses against the SARS-CoV-2 antigens consistent with prior studies in rats. Collectively, it was concluded that the pGO-1002 vaccine was safe and effective under these experimental conditions and these data supported future human study of the vaccine, now known as GLS-5310, for clinical trial use.

Welder's Anthrax: A Tale of 2 Cases.

Bacillus anthracis has traditionally been considered the etiologic agent of anthrax. However, anthrax-like illness has been documented in welders and other metal workers infected with Bacillus cereus group spp. harboring pXO1 virulence genes that produce anthrax toxins. We present 2 recent cases of severe pneumonia in welders with B. cereus group infections and discuss potential risk factors for infection and treatment options, including antitoxin.

Learning beyond a single field of nursing through a virtual case-based approach to pre-registration nurse education.

Ensuring that pre-registration student nurses gain the richness of clinical practice to allow them to feel confident and knowledgeable to care for patients of the 21st century is often a challenge. Clinical practice challenges often mean that students will be strategic learners. This article discusses the development of a virtual case-based learning site to provide a rich experience for students to learn.

Amyloid beta acts synergistically as a pro-inflammatory cytokine.

The amyloid beta (Aß) peptide is believed to play a central role in Alzheimer's disease (AD), the most common age-related neurodegenerative disorder. However, the natural, evolutionarily selected functions of Aß are incompletely understood. Here, we report that nanomolar concentrations of Aß act synergistically with known cytokines to promote pro-inflammatory activation in primary human astrocytes (a cell type increasingly implicated in brain aging and AD). Using transcriptomics (RNA-seq), we show that Aß can directly substitute for the complement component C1q in a cytokine cocktail previously shown to induce astrocyte immune activation. Furthermore, we show that astrocytes synergistically activated by Aß have a transcriptional signature similar to neurotoxic "A1" astrocytes known to accumulate with age and in AD. Interestingly, we find that this biological action of Aß at low concentrations is distinct from the transcriptome changes induced by the high/supraphysiological doses of Aß often used in in vitro studies. Collectively, our results suggest an important, cytokine-like function for Aß and a novel mechanism by which it may directly contribute to the neuroinflammation associated with brain aging and AD.

COVID-19-Associated Deaths After SARS-CoV-2 Infection During Pregnancy - Mississippi, March 1, 2020-October 6, 2021.

Pregnant and recently pregnant women are at increased risk for severe illness and death from COVID-19 compared with women who are not pregnant or were not recently pregnant (1,2). CDC recommends COVID-19 vaccination for women who are pregnant, recently pregnant, trying to become pregnant, or might become pregnant in the future.*,† This report describes 15 COVID-19-associated deaths after infection with SARS-CoV-2 (the virus that causes COVID-19) during pregnancy in Mississippi during March 1, 2020-October 6, 2021.

Intradermal SynCon® Ebola GP DNA Vaccine Is Temperature Stable and Safely Demonstrates Cellular and Humoral Immunogenicity Advantages in Healthy Volunteers.

BACKGROUND: Nonlive vaccine approaches that are simple to deliver and stable at room temperature or 2-8°C could be advantageous in controlling future Ebola virus (EBOV) outbreaks. Using an immunopotent DNA vaccine that generates protection from lethal EBOV challenge in small animals and nonhuman primates, we performed a clinical study to evaluate both intramuscular (IM) and novel intradermal (ID) DNA delivery. METHODS: Two DNA vaccine candidates (INO-4201 and INO-4202) targeting the EBOV glycoprotein (GP) were evaluated for safety, tolerability, and immunogenicity in a phase 1 clinical trial. The candidates were evaluated alone, together, or in combination with plasmid-encoded human cytokine interleukin-12 followed by in vivo electroporation using either the CELLECTRA® IM or ID delivery devices. RESULTS: The safety profile of all 5 regimens was shown to be benign, with the ID route being better tolerated. Antibodies to EBOV GP were generated by all 5 regimens with the fastest and steepest rise observed in the ID group. Cellular immune responses were generated with every regimen. CONCLUSIONS: ID delivery of INO-4201 was well tolerated and resulted in 100% seroreactivity after 2 doses and elicited interferon-γ T-cell responses in over 70% of subjects, providing a new approach for EBOV prevention in diverse populations. Clinical Trials Registration. NCT02464670.

Zika-Induced Male Infertility in Mice Is Potentially Reversible and Preventable by Deoxyribonucleic Acid Immunization.

Background: Zika virus (ZIKV) infection has been associated with prolonged viral excretion in human semen and causes testicular atrophy and infertility in 10-week-old immunodeficient mice. Methods: Male IFNAR-/- mice, knockout for type I interferon receptor, were immunized with GLS-5700, a deoxyribonucleic acid-based vaccine, before a subcutaneous ZIKV challenge with 6 × 105 plaque-forming units at 13 weeks of age. On day 28 postinfection, testes and epididymides were collected in some mice for histological and functional analyses, whereas others were mated with naive female wild-type C57BL/6J. Results: Although all mice challenged with ZIKV developed viremia, most of them were asymptomatic, showed no weight loss, and survived infection. On day 28 postinfection, none of the unvaccinated, infected mice (9 of 9) exhibited abnormal spermatozoa counts or motility. However, 33% (3 of 9) and 36% (4 of 11) of mated males from this group were infertile, from 2 independent studies. Contrarily, males from the noninfected and the vaccinated, infected groups were all fertile. On days 75 and 207 postinfection, partial recovery of fertility was observed in 66% (2 of 3) of the previously infertile males. Conclusions: This study reports the effects of ZIKV infection on male fertility in a sublethal, immunodeficient mouse model and the efficacy of GLS-5700 vaccination in preventing male infertility.

TDP-1, the Caenorhabditis elegans ortholog of TDP-43, limits the accumulation of double-stranded RNA.

Caenorhabditis elegans mutants deleted for TDP-1, an ortholog of the neurodegeneration-associated RNA-binding protein TDP-43, display only mild phenotypes. Nevertheless, transcriptome sequencing revealed that many RNAs were altered in accumulation and/or processing in the mutant. Analysis of these transcriptional abnormalities demonstrates that a primary function of TDP-1 is to limit formation or stability of double-stranded RNA. Specifically, we found that deletion of tdp-1: (1) preferentially alters the accumulation of RNAs with inherent double-stranded structure (dsRNA); (2) increases the accumulation of nuclear dsRNA foci; (3) enhances the frequency of adenosine-to-inosine RNA editing; and (4) dramatically increases the amount of transcripts immunoprecipitable with a dsRNA-specific antibody, including intronic sequences, RNAs with antisense overlap to another transcript, and transposons. We also show that TDP-43 knockdown in human cells results in accumulation of dsRNA, indicating that suppression of dsRNA is a conserved function of TDP-43 in mammals. Altered accumulation of structured RNA may account for some of the previously described molecular phenotypes (e.g., altered splicing) resulting from reduction of TDP-43 function.

Final efficacy, immunogenicity, and safety analyses of a nine-valent human papillomavirus vaccine in women aged 16-26 years: a randomised, double-blind trial.

BACKGROUND: Primary analyses of a study in young women aged 16-26 years showed efficacy of the nine-valent human papillomavirus (9vHPV; HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) vaccine against infections and disease related to HPV 31, 33, 45, 52, and 58, and non-inferior HPV 6, 11, 16, and 18 antibody responses when compared with quadrivalent HPV (qHPV; HPV 6, 11, 16, and 18) vaccine. We aimed to report efficacy of the 9vHPV vaccine for up to 6 years following first administration and antibody responses over 5 years. METHODS: We undertook this randomised, double-blind, efficacy, immunogenicity, and safety study of the 9vHPV vaccine study at 105 study sites in 18 countries. Women aged 16-26 years old who were healthy, with no history of abnormal cervical cytology, no previous abnormal cervical biopsy results, and no more than four lifetime sexual partners were randomly assigned (1:1) by central randomisation and block sizes of 2 and 2 to receive three intramuscular injections over 6 months of 9vHPV or qHPV (control) vaccine. All participants, study investigators, and study site personnel, laboratory staff, members of the sponsor's study team, and members of the adjudication pathology panel were masked to vaccination groups. The primary outcomes were incidence of high-grade cervical disease (cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, invasive cervical carcinoma), vulvar disease (vulvar intraepithelial neoplasia grade 2/3, vulvar cancer), and vaginal disease (vaginal intraepithelial neoplasia grade 2/3, vaginal cancer) related to HPV 31, 33, 45, 52, and 58 and non-inferiority (excluding a decrease of 1·5 times) of anti-HPV 6, 11, 16, and 18 geometric mean titres (GMT). Tissue samples were adjudicated for histopathology diagnosis and tested for HPV DNA. Serum antibody responses were assessed by competitive Luminex immunoassay. The primary evaluation of efficacy was a superiority analysis in the per-protocol efficacy population, supportive efficacy was analysed in the modified intention-to-treat population, and the primary evaluation of immunogenicity was a non-inferiority analysis. The trial is registered with ClinicalTrials.gov, number NCT00543543. FINDINGS: Between Sept 26, 2007, and Dec 18, 2009, we recruited and randomly assigned 14 215 participants to receive 9vHPV (n=7106) or qHPV (n=7109) vaccine. In the per-protocol population, the incidence of high-grade cervical, vulvar and vaginal disease related to HPV 31, 33, 45, 52, and 58 was 0·5 cases per 10 000 person-years in the 9vHPV and 19·0 cases per 10 000 person-years in the qHPV groups, representing 97·4% efficacy (95% CI 85·0-99·9). HPV 6, 11, 16, and 18 GMTs were non-inferior in the 9vHPV versus qHPV group from month 1 to 3 years after vaccination. No clinically meaningful differences in serious adverse events were noted between the study groups. 11 participants died during the study follow-up period (six in the 9vHPV vaccine group and five in the qHPV vaccine group); none of the deaths were considered vaccine-related. INTERPRETATION: The 9vHPV vaccine prevents infection, cytological abnormalities, high-grade lesions, and cervical procedures related to HPV 31, 33, 45, 52, and 58. Both the 9vHPV vaccine and qHPV vaccine had a similar immunogenicity profile with respect to HPV 6, 11, 16, and 18. Vaccine efficacy was sustained for up to 6 years. The 9vHPV vaccine could potentially provide broader coverage and prevent 90% of cervical cancer cases worldwide. FUNDING: Merck & Co, Inc.

Educational outcomes for children with cerebral palsy: a linked data cohort study.

AIM: To identify a cohort of children with cerebral palsy (CP) from hospital data; determine the proportion that participated in standardized educational testing and attained a score within the normal range; and describe the relationship between test results and motor symptoms. METHOD: This population-based retrospective cohort study used data from New South Wales, Australia. We linked hospital data for children younger than 16 years of age admitted between 1st July 2000 and 31st March 2014 to education data from 2009 to 2014. Hospital diagnosis codes were used to identify a cohort of children with CP (n=3944) and describe their motor symptoms. Educational outcomes in the CP cohort were compared with those among children without CP. RESULTS: Of those with educational data (n=1770), 46% were exempt from reading assessment because of intellectual or functional disability, 7% were absent or withdrawn from testing and 47% participated in testing. About 30% of all children with educational data had test scores in the normal range. The proportion was greatest among those with hemiplegia (>40%) and lowest among those with tetraplegia (<10%). INTERPRETATION: One-third of children with CP participated in standardized testing and achieved a result in the normal range. The proportions were lower in children with more severe motor symptoms. WHAT THIS PAPER ADDS: From 2009 to 2014, most Australian children with cerebral palsy (CP) attended a mainstream school. The rate of disability-related exemption from standardized educational testing was almost 50%. Thirty per cent of children with CP achieved educational scores in the normal range.

Knowledge, experience and attitudes towards skin-to-skin contact following Caesarean sections among health professionals in Vietnam.

AIM: This study explored knowledge, experience and attitudes of health professionals towards early essential newborn care and skin-to-skin contact following Caesarean sections in a tertiary hospital in Central Vietnam. METHOD: We conducted a cross-sectional descriptive study using an anonymous questionnaire in March 2016. Health professionals from obstetrics, anaesthesiology and neonatology departments were surveyed. RESULTS: All of the 204 surveys were returned, accounting for 82% of total staff involved in the care for women and newborns with Caesarean sections. Correct knowledge of early essential newborn care was lowest among anaesthesiology staff. Health professionals reported that ≥90% of Caesarean section births they attended in the preceding week had skin-to-skin contact. Approximately 16% obstetricians, 71% midwives, 49% anaesthesiology and 76% neonatology staff considered the current frequency of skin-to-skin contact to be about right. The remainder considered the current rate too high. All professional groups identified the main difficulties of conducting skin-to-skin contact as the temperature in the operating theatre and the need for additional staff. Other concerns included increasing the risk of the baby of falling off, prolonging the operation and difficulty to monitor mothers. CONCLUSION: The study identifies issues where improvements can be made in the implementation of skin-to-skin contact following Caesarean sections.

Pediatric admissions that include intensive care: a population-based study.

BACKGROUND: Pediatric admissions to intensive care outside children's hospitals are generally excluded from registry-based studies. This study compares pediatric admission to specialist pediatric intensive care units (PICU) with pediatric admissions to intensive care units (ICU) in general hospitals in an Australian population. METHODS: We undertook a population-based record linkage cohort study utilizing longitudinally-linked hospital and death data for pediatric hospitalization from New South Wales, Australia, 2010-2013. The study population included all new pediatric, post-neonatal hospital admissions that included time in ICU (excluding neonatal ICU). RESULTS: Of 498,466 pediatric hospitalizations, 7525 (1.5%) included time in an intensive care unit - 93.7% to PICU and 6.3% to ICU in a general (non-PICU) hospital. Non-PICU admissions were of older children, in rural areas, with shorter stays in ICU, more likely admitted for acute conditions such as asthma, injury or diabetes, and less likely to have chronic conditions, receive continuous ventilatory support, blood transfusion, parenteral nutrition or die. CONCLUSIONS: A substantial proportion of children are admitted to ICUs in general hospitals. A comprehensive overview of pediatric ICU admissions includes these admissions and the context of the total hospitalization.

Contribution of maternal age, medical and obstetric history to maternal and perinatal morbidity/mortality for women aged 35 or older.

BACKGROUND: As age is not modifiable, pregnancy risk information based on age alone is unhelpful for older women. AIM: To determine severe morbidity/mortality rates for women aged ≥35 years according to maternal profile based on parity, pre-existing medical conditions and prior pregnancy complications, and to assess the independent contribution of age. MATERIALS AND METHODS: Population-based record-linkage study using NSW hospitalisation and birth records 2006-2012. Maternal and perinatal mortality/morbidity were assessed for non-anomalous singleton births to women aged ≥35 years. RESULTS: For 117 357 pregnancies among 99 375 women aged ≥35 years, the median age at delivery was 37 years (range 35-56 years), including: 35 652 (30.4%) multiparae without pre-existing medical or obstetric complications, 33,058 (28.2%) nulliparae without pre-existing medical conditions and 30 325 (25.8%) multiparae with prior pregnancy complications. Maternal and perinatal mortality/morbidity varied by maternal profile with ranges of 0.9-3.5% and 2.4-11.9%, respectively. For nulliparae, each five-year increase in age did not contribute significantly to maternal risk after controlling for medical conditions (adjustedodds ratio 1.08, 95% CI 0.93-1.25), but did confer perinatal risk (1.14; 1.05-1.25). For multiparae, each five-year increase in age beyond 35 years was independently associated with adverse maternal (1.23; 1.09-1.39) and perinatal outcomes (1.23; 1.09-1.39). CONCLUSIONS: For women aged ≥35 years, presence of medical conditions conferred a greater risk for morbidity/mortality than age itself. For multiparous women, the effects of medical and obstetric history were additive. The contribution of maternal age to adverse outcomes in pregnancies without significant medical and obstetric history is modest.

Sedimentation Velocity Analysis with Fluorescence Detection of Mutant Huntingtin Exon 1 Aggregation in Drosophila melanogaster and Caenorhabditis elegans.

At least nine neurodegenerative diseases that are caused by the aggregation induced by long tracts of glutamine sequences have been identified. One such polyglutamine-containing protein is huntingtin, which is the primary factor responsible for Huntington's disease. Sedimentation velocity with fluorescence detection is applied to perform a comparative study of the aggregation of the huntingtin exon 1 protein fragment upon transgenic expression in Drosophila melanogaster and Caenorhabditis elegans. This approach allows the detection of aggregation in complex mixtures under physiologically relevant conditions. Complementary methods used to support this biophysical approach included fluorescence microscopy and semidenaturing detergent agarose gel electrophoresis, as a point of comparison with earlier studies. New analysis tools developed for the analytical ultracentrifuge have made it possible to readily identify a wide range of aggregating species, including the monomer, a set of intermediate aggregates, and insoluble inclusion bodies. Differences in aggregation in the two animal model systems are noted, possibly because of differences in levels of expression of glutamine-rich sequences. An increased level of aggregation is shown to correlate with increased toxicity for both animal models. Co-expression of the human Hsp70 in D. melanogaster showed some mitigation of aggregation and toxicity, correlating best with inclusion body formation. The comparative study emphasizes the value of the analytical ultracentrifuge equipped with fluorescence detection as a useful and rigorous tool for in situ aggregation analysis to assess commonalities in aggregation across animal model systems.

Immediate delivery compared with expectant management after preterm pre-labour rupture of the membranes close to term (PPROMT trial): a randomised controlled trial.

BACKGROUND: Preterm pre-labour ruptured membranes close to term is associated with increased risk of neonatal infection, but immediate delivery is associated with risks of prematurity. The balance of risks is unclear. We aimed to establish whether immediate birth in singleton pregnancies with ruptured membranes close to term reduces neonatal infection without increasing other morbidity. METHODS: The PPROMT trial was a multicentre randomised controlled trial done at 65 centres across 11 countries. Women aged over 16 years with singleton pregnancies and ruptured membranes before the onset of labour between 34 weeks and 36 weeks and 6 days weeks who had no signs of infection were included. Women were randomly assigned (1:1) by a computer-generated randomisation schedule with variable block sizes, stratified by centre, to immediate delivery or expectant management. The primary outcome was the incidence of neonatal sepsis. Secondary infant outcomes included a composite neonatal morbidity and mortality indicator (ie, sepsis, mechanical ventilation ≥24 h, stillbirth, or neonatal death); respiratory distress syndrome; any mechanical ventilation; and duration of stay in a neonatal intensive or special care unit. Secondary maternal outcomes included antepartum or intrapartum haemorrhage, intrapartum fever, postpartum treatment with antibiotics, and mode of delivery. Women and caregivers could not be masked, but those adjudicating on the primary outcome were masked to group allocation. Analyses were by intention to treat. This trial is registered with the International Clinical Trials Registry, number ISRCTN44485060. FINDINGS: Between May 28, 2004, and June 30, 2013, 1839 women were recruited and randomly assigned: 924 to the immediate birth group and 915 to the expectant management group. One woman in the immediate birth group and three in the expectant group were excluded from the primary analyses. Neonatal sepsis occurred in 23 (2%) of 923 neonates whose mothers were assigned to immediate birth and 29 (3%) of 912 neonates of mothers assigned to expectant management (relative risk [RR] 0·8, 95% CI 0·5-1·3; p=0·37). The composite secondary outcome of neonatal morbidity and mortality occurred in 73 (8%) of 923 neonates of mothers assigned to immediate delivery and 61 (7%) of 911 neonates of mothers assigned to expectant management (RR 1·2, 95% CI 0·9-1·6; p=0·32). However, neonates born to mothers in the immediate delivery group had increased rates of respiratory distress (76 [8%] of 919 vs 47 [5%] of 910, RR 1·6, 95% CI 1·1-2·30; p=0·008) and any mechanical ventilation (114 [12%] of 923 vs 83 [9%] of 912, RR 1·4, 95% CI 1·0-1·8; p=0·02) and spent more time in intensive care (median 4·0 days [IQR 0·0-10·0] vs 2·0 days [0·0-7·0]; p<0·0001) compared with neonates born to mothers in the expectant management group. Compared with women assigned to the immediate delivery group, those assigned to the expectant management group had higher risks of antepartum or intrapartum haemorrhage (RR 0·6, 95% CI 0·4-0·9), intrapartum fever (0·4, 0·2-0·9), and use of postpartum antibiotics (0·8, 0·7-1·0), and longer hospital stay (p<0·0001), but a lower risk of caesarean delivery (RR 1·4, 95% CI 1·2-1·7). INTERPRETATION: In the absence of overt signs of infection or fetal compromise, a policy of expectant management with appropriate surveillance of maternal and fetal wellbeing should be followed in pregnant women who present with ruptured membranes close to term. FUNDING: Australian National Health and Medical Research Council, the Women's and Children's Hospital Foundation, and The University of Sydney.

Uptake of external cephalic version for term breech presentation: an Australian population study, 2002-2012.

BACKGROUND: The safety, efficacy, and cost-effectiveness of external cephalic version (ECV) for term breech presentation has been demonstrated. Clinical guidelines recommend ECV for all eligible women, but the uptake of this procedure in the Australian healthcare setting is unknown. This study aimed to describe ECV uptake in New South Wales, the most populous state of Australia, during 2002 to 2012. METHODS: Data from routine hospital and birth records were used to identify ECVs conducted at ≥36 weeks' gestation. Women with ECV were compared to women who were potentially eligible for but did not have ECV. Eligibility for ECV was based on clinical guidelines. For those with ECV, birth outcomes following successful and unsuccessful procedures were examined. RESULTS: In N = 32,321 singleton breech pregnancies, 10.5% had ECV, 22.3% were ineligible, and 67.2% were potentially eligible but did not undergo ECV. Compared to women who were eligible but who did not attempt ECV, those who had ECV were more likely to be older, multiparous, overseas-born, public patients at delivery, and to deliver in tertiary hospitals in urban areas (p < 0.01). Fewer women who underwent ECV smoked during pregnancy, fewer were morbidly obese, and fewer had a hypertensive disorder of pregnancy, compared to those who were eligible. Caesarean section occurred in 25.9% of successful compared to 95.6% of unsuccessful ECVs. Infant outcomes did not differ by ECV success. CONCLUSIONS: The majority of women with a breech presentation did not receive ECV. It is unclear whether this is attributable to issues with service provision or low acceptability among women. Policies to improve access to and information about ECV appear necessary to improve uptake among women with term breech presentation. Improved data collection around the diagnosis of breech presentation, ECV attempts, and outcomes may help to identify specific barriers to ECV uptake.

Variation in clinical decision-making for induction of labour: a qualitative study.

BACKGROUND: Unexplained variation in induction of labour (IOL) rates exist between hospitals, even after accounting for casemix and hospital differences. We aimed to explore factors that influence clinical decision-making for IOL that may be contributing to the variation in IOL rates between hospitals. METHODS: We undertook a qualitative study involving semi-structured, audio-recorded interviews with obstetricians and midwives. Using purposive sampling, participants known to have diverse opinions on IOL were selected from ten Australian maternity hospitals (based on differences in hospital IOL rate, size, location and case-mix complexities). Transcripts were indexed, coded, and analysed using the Framework Approach to identify main themes and subthemes. RESULTS: Forty-five participants were interviewed (21 midwives, 24 obstetric medical staff). Variations in decision-making for IOL were based on the obstetrician's perception of medical risk in the pregnancy (influenced by the obstetrician's personality and knowledge), their care relationship with the woman, how they involved the woman in decision-making, and resource availability. The role of a 'gatekeeper' in the procedural aspects of arranging an IOL also influenced decision-making. There was wide variation in the clinical decision-making practices of obstetricians and less accountability for decision-making in hospitals with a high IOL rate, with the converse occurring in hospitals with low IOL rates. CONCLUSION: Improved communication, standardised risk assessment and accountability for IOL offer potential for reducing variation in hospital IOL rates.

Long-term childhood outcomes of breech presentation by intended mode of delivery: a population record linkage study.

INTRODUCTION: There is a lack of information on long-term outcomes by mode of delivery for term breech presentation. We aimed to compare childhood mortality, cerebral palsy, hospitalizations, developmental, and educational outcomes associated with intended vaginal breech birth (VBB) with planned cesarean section. MATERIAL AND METHODS: Population birth and hospital records from New South Wales, Australia, were used to identify women with non-anomalous pregnancies eligible for VBB during 2001-2012. Intended mode of delivery was inferred from labor onset and management. Death, hospital, and education records were used for follow up until 2014. Cox proportional hazards regression and modified Poisson regression were used for analysis. RESULTS: Of 15 281 women considered eligible for VBB, 7.7% intended VBB, 74.2% planned cesarean section, and intention was uncertain for 18.1%. Intended VBB did not differ from planned cesarean section on infant mortality (Fisher's exact p = 0.55), childhood mortality (Fisher's exact p = 0.50), cerebral palsy (Fisher's exact p = 1.00), hospitalization in the first year of life [adjusted hazard ratio (HR) 1.04; 95% CI 0.90-1.20], hospitalization between the first and sixth birthdays (HR 0.92; 95% CI 0.82-1.04), being developmentally vulnerable [adjusted relative risk (RR) 1.22; 95% CI 0.48-1.69] or having special needs status (RR 0.95; 95% CI 0.48-1.88) when aged 4-6, or scoring more than 1 standard deviation below the mean on tests of reading (RR 1.10; 95% CI 0.87-1.40) and numeracy (RR 1.04; 95% CI 0.81-1.34) when aged 7-9. CONCLUSIONS: Planned VBB confers no additional risks for child health, development or educational achievement compared with planned cesarean section.

"Very Good" Ratings in a Survey of Maternity Care: Kindness and Understanding Matter to Australian Women.

BACKGROUND: Surveys have shown that women are highly satisfied with their maternity care. Their satisfaction has been associated with various demographic, personal, and care factors. Isolating the factors that most matter to women about their care can guide quality improvement efforts. This study aimed to identify the most significant factors associated with high ratings of care by women in the three maternity periods (antenatal, birth, and postnatal). METHODS: A survey was sent to 2,048 women who gave birth at seven public hospitals in New South Wales, Australia, exploring their expectations of, and experiences with maternity care. Women's overall ratings of care for the antenatal, birth, and postnatal periods were analyzed, and a number of maternal characteristics and care factors examined as potential predictors of "Very good" ratings of care. RESULTS: Among 886 women with a completed survey, 65 percent assigned a "Very good" rating for antenatal care, 74 percent for birth care, 58 percent for postnatal care, and 44 percent for all three periods. One factor was strongly associated with care ratings in all three maternity periods: women who were "always or almost always" treated with kindness and understanding were 1.8-2.8 times more likely to rate their antenatal, birth, and postnatal care as "Very good." A limited number of other factors were significantly associated with high care ratings for one or two of the maternity periods. CONCLUSIONS: Women's perceptions about the quality of their interpersonal interactions with health caregivers have a significant bearing on women's views about their maternity care journey.