A natively flexible 32-bit Arm microprocessor.

Nearly 50 years ago, Intel created the world's first commercially produced microprocessor-the 4004 (ref. 1), a modest 4-bit CPU (central processing unit) with 2,300 transistors fabricated using 10 µm process technology in silicon and capable only of simple arithmetic calculations. Since this ground-breaking achievement, there has been continuous technological development with increasing sophistication to the stage where state-of-the-art silicon 64-bit microprocessors now have 30 billion transistors (for example, the AWS Graviton2 (ref. 2) microprocessor, fabricated using 7 nm process technology). The microprocessor is now so embedded within our culture that it has become a meta-invention-that is, it is a tool that allows other inventions to be realized, most recently enabling the big data analysis needed for a COVID-19 vaccine to be developed in record time. Here we report a 32-bit Arm (a reduced instruction set computing (RISC) architecture) microprocessor developed with metal-oxide thin-film transistor technology on a flexible substrate (which we call the PlasticARM). Separate from the mainstream semiconductor industry, flexible electronics operate within a domain that seamlessly integrates with everyday objects through a combination of ultrathin form factor, conformability, extreme low cost and potential for mass-scale production. PlasticARM pioneers the embedding of billions of low-cost, ultrathin microprocessors into everyday objects.

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.).

Rapid energy-efficient manufacturing of polymers and composites via frontal polymerization.

Thermoset polymers and composite materials are integral to today's aerospace, automotive, marine and energy industries and will be vital to the next generation of lightweight, energy-efficient structures in these enterprises, owing to their excellent specific stiffness and strength, thermal stability and chemical resistance1-5. The manufacture of high-performance thermoset components requires the monomer to be cured at high temperatures (around 180 °C) for several hours, under a combined external pressure and internal vacuum 6 . Curing is generally accomplished using large autoclaves or ovens that scale in size with the component. Hence this traditional curing approach is slow, requires a large amount of energy and involves substantial capital investment6,7. Frontal polymerization is a promising alternative curing strategy, in which a self-propagating exothermic reaction wave transforms liquid monomers to fully cured polymers. We report here the frontal polymerization of a high-performance thermoset polymer that allows the rapid fabrication of parts with microscale features, three-dimensional printed structures and carbon-fibre-reinforced polymer composites. Precise control of the polymerization kinetics at both ambient and elevated temperatures allows stable monomer solutions to transform into fully cured polymers within seconds, reducing energy requirements and cure times by several orders of magnitude compared with conventional oven or autoclave curing approaches. The resulting polymer and composite parts possess similar mechanical properties to those cured conventionally. This curing strategy greatly improves the efficiency of manufacturing of high-performance polymers and composites, and is widely applicable to many industries.

Shoulder dystocia in babies born to Aboriginal mothers with diabetes: a population-based cohort study, 1998-2015.

BACKGROUND: Australian Aboriginal and Torres Strait Islander women with diabetes in pregnancy (DIP) are more likely to have glycaemic levels above the target range, and their babies are thus at higher risk of excessive fetal growth. Shoulder dystocia, defined by failure of spontaneous birth of fetal shoulder after birth of the head requiring obstetric maneuvers, is an obstetric emergency that is strongly associated with DIP and fetal size. The aim of this study was to investigate the epidemiology of shoulder dystocia in Aboriginal babies born to mothers with DIP. METHODS: Stratifying by Aboriginal status, characteristics of births complicated by shoulder dystocia in women with and without DIP were compared and incidence and time-trends of shoulder dystocia were described. Compliance with guidelines aiming at preventing shoulder dystocia in women with DIP were compared. Post-logistic regression estimation was used to calculate the population attributable fractions (PAFs) for shoulder dystocia associated with DIP and to estimate probabilities of shoulder dystocia in babies born to mothers with DIP at birthweights > 3 kg. RESULTS: Rates of shoulder dystocia from vaginal births in Aboriginal babies born to mothers with DIP were double that of their non-Aboriginal counterparts (6.3% vs 3.2%, p < 0.001), with no improvement over time. Aboriginal mothers with diabetes whose pregnancies were complicated by shoulder dystocia were more likely to have a history of shoulder dystocia (13.1% vs 6.3%, p = 0.032). Rates of guideline-recommended elective caesarean section in pregnancies with diabetes and birthweight > 4.5 kg were lower in the Aboriginal women (28.6% vs 43.1%, p = 0.004). PAFs indicated that 13.4% (95% CI: 9.7%-16.9%) of shoulder dystocia cases in Aboriginal (2.7% (95% CI: 2.1%-3.4%) in non-Aboriginal) women were attributable to DIP. Probability of shoulder dystocia among babies born to Aboriginal mothers with DIP was higher at birthweights > 3 kg. CONCLUSIONS: Aboriginal mothers with DIP had a higher risk of shoulder dystocia and a stronger association between birthweight and shoulder dystocia. Many cases were recurrent. These factors should be considered in clinical practice and when counselling women.

The Relationship Between Early Term Birth and the Risk of Later Childhood Mental Disorders Within a Pregnancy Cohort.

This study examines whether gestational age, birth weight, and early term birth is associated with childhood mental disorders in 342 pregnant women recruited at less than 20 weeks gestation and were then followed up until 4 years postpartum, including 93 children born at early term. Women were assessed at recruitment using the Structured Clinical Interview for DSM. At 4 years of age their children were assessed using the Preschool Age Psychiatric Assessment (PAPA) and the Child Behavior Checklist (CBCL). This study found earlier birth predicted an increased risk for anxiety disorders and demonstrated a significant interaction between gestational age and lower birthweight. The risk for ADHD increased with lower gestational age independent of birthweight. In contrast, gestational age was not associated with Oppositional Defiant Disorder, Conduct Disorder, internalizing or externalizing symptoms. These findings highlight the important differences in the association of early term birth and vulnerability for specific mental disorders.

Oxygen-insensitive nitroreductase E. coli NfsA, but not NfsB, is inhibited by fumarate.

Escherichia coli NfsA and NfsB are founding members of two flavoprotein families that catalyze the oxygen-insensitive reduction of nitroaromatics and quinones by NAD(P)H. This reduction is required for the activity of nitrofuran antibiotics and the enzymes have also been proposed for use with nitroaromatic prodrugs in cancer gene therapy and biocatalysis, but the roles of the proteins in vivo in bacteria are not known. NfsA is NADPH-specific whereas NfsB can also use NADH. The crystal structures of E. coli NfsA and NfsB and several analogs have been determined previously. In our crystal trials, we unexpectedly observed NfsA bound to fumarate. We here present the X-ray structure of the E. coli NfsA-fumarate complex and show that fumarate acts as a weak inhibitor of NfsA but not of NfsB. The structural basis of this differential inhibition is conserved in the two protein families and occurs at fumarate concentrations found in vivo, so impacting the efficacy of these proteins.

Early mortality among aboriginal and non-aboriginal women who had a preterm birth in Western Australia: A population-based cohort study.

BACKGROUND: Having a preterm (<37 weeks' gestation) birth may increase a woman's risk of early mortality. Aboriginal and Torres Strait Islander (hereafter Aboriginal) women have higher preterm birth and mortality rates compared with other Australian women. OBJECTIVES: We investigated whether a history of having a preterm birth was associated with early mortality in women and whether these associations differed by Aboriginal status. METHODS: This retrospective cohort study used population-based perinatal records of women who had a singleton birth between 1980 and 2015 in Western Australia linked to Death Registry data until June 2018. The primary and secondary outcomes were all-cause and cause-specific mortality respectively. After stratification by Aboriginal status, rate differences were calculated, and Cox proportional hazard regression was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and cause-specific mortality. RESULTS: There were 20,244 Aboriginal mothers (1349 deaths) and 457,357 non-Aboriginal mothers (7646 deaths) with 8.6 million person-years of follow-up. The all-cause mortality rates for Aboriginal mothers who had preterm births and term births were 529.5 and 344.0 (rate difference 185.5, 95% CI 135.5, 238.5) per 100,000 person-years respectively. Among non-Aboriginal mothers, the corresponding figures were 125.5 and 88.6 (rate difference 37.0, 95% CI 29.4, 44.9) per 100,000 person-years. The HR for all-cause mortality for Aboriginal and non-Aboriginal mothers associated with preterm birth were 1.48 (95% CI 1.32, 1.66) and 1.35 (95% CI 1.26, 1.44), respectively, compared with term birth. Compared with mothers who had term births, mothers of preterm births had higher relative risks of mortality from diabetes, cardiovascular, digestive and external causes. CONCLUSIONS: Both Aboriginal and non-Aboriginal women who had a preterm birth had a moderately increased risk of mortality up to 38 years after the birth, reinforcing the importance of primary prevention and ongoing screening.

The Western Australian preterm birth prevention initiative: a whole of state singleton pregnancy cohort study showing the need to embrace alternative models of care for Aboriginal women.

BACKGROUND: Preterm birth (PTB) is the greatest cause of mortality and morbidity in children up to five years of age globally. The Western Australian (WA) PTB Prevention Initiative, the world's first whole-of-population whole-of-state program aimed at PTB prevention, was implemented across WA in 2014. METHODS: We conducted a prospective population-based cohort study using pregnancy data for singleton births in WA from 2009 to 2019. Logistic regression using the last full year before the Initiative (2013) as the reference, and run charts were used to examine changes in PTB rates compared to pre-Initiative levels, by gestational age group, hospital type, low and high risk of PTB in mid-pregnancy, and onset of labour (spontaneous/medically initiated). Analyses were stratified by Aboriginal and non-Aboriginal maternal ethnicity. RESULTS: Amongst non-Aboriginal women, there was initially a reduction in the PTB rate across the state, and in recent years it returned to pre-Initiative levels. Amongst Aboriginal women there was a small, non- significant reduction in the state-wide PTB rate in the first three years of the Initiative, followed by a rise in recent years. For non-Aboriginal women, the reduction in the rate of PTB at the tertiary centre was sustained and improved further for women of all risk levels and onsets of labour. This reduction was not observed for Aboriginal women giving birth at the tertiary centre, amongst whom there was an increase in the PTB rate overall and in all subgroups, with the exception of medically initiated PTB. Amongst Aboriginal women the PTB rate has also increased across the state. At non-tertiary hospitals there was a large increase in PTB amongst both Aboriginal and non-Aboriginal women, largely driven by medically initiated late PTB. Maternal risk factors cannot account for this increase. CONCLUSIONS: The reduction in PTB rates amongst non-Aboriginal women at the state's tertiary hospital demonstrates that with the right strategies, PTB can be reduced. A sustained collaborative model is required to realise this success in non-tertiary hospitals. The series of interventions was of limited use in Aboriginal women, and future efforts will need to be directed at strategies more likely to be successful, such as midwifery continuity of care models, with Aboriginal representation in the healthcare workforce.

Severe maternal morbidity following stillbirth in Western Australia 2000-2015: a population-based study.

PURPOSE: There is scant literature about the management of stillbirth and the subsequent risk of severe maternal morbidity (SMM). We aimed to assess the risk of SMM associated with stillbirths compared with live births and whether this differed by the presence of maternal comorbidities. METHODS: In this retrospective cohort study, we used a population-based dataset of all stillbirths and live births ≥ 20 weeks' gestation in Western Australia between 2000 and 2015. SMM was identified using a published Australian composite for use with routinely collected hospital morbidity data. Maternal comorbidities were identified in the Hospital Morbidity Data Collection or the Midwives Notification System using a modified Australian chronic disease composite. Multivariable Poisson regression was used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for factors associated with SMM in analyses stratified by the presence of maternal comorbidities. Singleton and multiple pregnancies were examined separately. RESULTS: This study included 458,639 singleton births (2319 stillbirths and 456,320 live births). The adjusted RRs for SMM among stillbirths were 2.30 (95% CI 1.77, 3.00) for those without comorbidities and 4.80 (95% CI 4.11, 5.59) (Interaction P value < 0.0001) for those with comorbidities compared to live births without and with comorbidities, respectively. CONCLUSION: In Western Australia between 2000 and 2015, mothers of stillbirths both with and without any maternal comorbidities had an increased risk of SMM compared with live births. Further investigation into why women who have had a stillbirth without any existing conditions or pregnancy complications develop SMM is warranted.

The prevalence and significance of gestational cannabis use at an Australian tertiary hospital.

BACKGROUND: Cannabis is one of the most common non-prescribed psychoactive substances used in pregnancy. The prevalence of gestational cannabis use is increasing. AIM: The aim was to examine the prevalence of gestational cannabis use and associated pregnancy and neonate outcomes. MATERIALS AND METHODS: A retrospective observational study involving pregnant women delivering in 2019 was conducted at a tertiary hospital in Perth, Western Australia. Gestational cannabis and other substance use records were based on maternal self-report. Pregnancy outcomes included neonatal gestational age, birthweight, birth length, head circumference, resuscitation measures, special care nursery admission, 5-min Apgar score and initial neonatal feeding method. RESULTS: Among 3104 pregnant women (mean age: 31 years), gestational cannabis use was reported by 1.6% (n = 50). Cannabis users were younger, more likely to use other substances and experience mental illness or domestic violence compared with non-users. Neonates born to cannabis users had a lower mean gestational age, birthweight and birth length compared to those born to non-cannabis users. Gestational cannabis use (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.6-6.7) and tobacco smoking (OR 2.2, 95% CI 1.5-3.6) were associated with increased odds of a low-birthweight neonate. Combined cannabis and tobacco use during pregnancy further increased the likelihood of low birthweight (LBW, adjusted OR 3.9, 95% CI 1.6-9.3). Multivariate logistic regression analysis adjusted for maternal sociodemographical characteristics, mental illness, alcohol, tobacco and other substance use demonstrated gestational cannabis use to be independently associated with LBW (OR 2.3, 95% CI 1.1-5.2). CONCLUSION: Gestational cannabis use was independently associated with low birthweight, synergistically affected by tobacco smoking.

Structure and Dynamics of Three Escherichia coli NfsB Nitro-Reductase Mutants Selected for Enhanced Activity with the Cancer Prodrug CB1954.

Escherichia coli NfsB has been studied extensively for its potential for cancer gene therapy by reducing the prodrug CB1954 to a cytotoxic derivative. We have previously made several mutants with enhanced activity for the prodrug and characterised their activity in vitro and in vivo. Here, we determine the X-ray structure of our most active triple and double mutants to date, T41Q/N71S/F124T and T41L/N71S. The two mutant proteins have lower redox potentials than wild-type NfsB, and the mutations have lowered activity with NADH so that, in contrast to the wild-type enzyme, the reduction of the enzyme by NADH, rather than the reaction with CB1954, has a slower maximum rate. The structure of the triple mutant shows the interaction between Q41 and T124, explaining the synergy between these two mutations. Based on these structures, we selected mutants with even higher activity. The most active one contains T41Q/N71S/F124T/M127V, in which the additional M127V mutation enlarges a small channel to the active site. Molecular dynamics simulations show that the mutations or reduction of the FMN cofactors of the protein has little effect on its dynamics and that the largest backbone fluctuations occur at residues that flank the active site, contributing towards its broad substrate range.

Developing a text message intervention for fathers with partners experiencing perinatal depression or anxiety.

BACKGROUND: Support from fathers to their partners is important to reduce distress in mothers during the perinatal period when conditions such as depression and anxiety can be common. The SMS4dads digital platform delivers text messages to fathers but has not previously addressed specific messages to fathers with partners who are experiencing perinatal depression and/or anxiety (PNDA). AIM: To develop messages, in collaboration with experienced parents and clinicians, that are suitable for fathers whose partner is experiencing PNDA. METHODS: Messages designed to enhance the quality of partner support for mothers experiencing PNDA were drafted by the SMS4dads team based on suggestions from mothers with lived experience of PNDA. Mothers and fathers with lived experience and expert clinicians rated the messages for importance and understanding. Clinicians additionally rated clinical relevance. Open response comments from parents and clinicians were collated for each message. Re-drafted messages were screened again and checked for literacy level. RESULTS: Forty-one draft messages received a total of 170 ratings from 24 parents and 164 ratings from 32 clinicians. Over three quarters of parents and clinicians agreed or strongly agreed that messages were understandable (parents 85.6%; clinicians 77.4%), important (parents 86.3%; clinicians 86.6%), and 85.5% of clinicians rated the messages as clinically relevant. Comments from clinicians (n = 99) and parents (n = 46) were reviewed and guided message development. Thirty re-drafted messages were screened and 16 edited based on a second round of ratings and comments from parents and clinicians. CONCLUSION: Messages for fathers whose partners are experiencing depression and anxiety can be developed and evaluated in collaboration with lived experience of parents and clinicians.

Equipping fathers to support distressed mothers: What do mothers want fathers to know and do?

ISSUE ADDRESSED: Up to one in five new mothers experience depression or anxiety, and their partners are often the first line of social and practical support. However, many fathers are unprepared for their role as support person. The SMS4dads program (www.sms4dads.com) provides text-based support to new fathers but lacks specific messages addressing maternal mental distress. METHODS: A mixed methods process engaged mothers with lived experience of perinatal mental distress to identify message content for co-designing texts in SMS4dads. Participants completed surveys derived from research literature and parenting websites using the theoretical framework of support domains: emotional or affectionate support, informational support, tangible support and positive social interaction. Mothers also indicated the most appropriate timing of support: at the point of identifying the distress (emerging), with ongoing symptoms (persistent) or during recovery (easing). Free text comments from mothers were linked to survey topics to provide examples of wording suitable for text messages to fathers. RESULTS: Fifty-five mothers with lived experience completed the surveys. All support items were more often endorsed as helpful rather than not helpful by mothers. Emotional support was thought helpful in the early stages, tangible support was valued with ongoing symptoms and social interaction appreciated as symptoms eased. CONCLUSIONS: Mothers experiencing perinatal depression and anxiety require a range of supportive actions by their partners, including household tasks and baby-care, encouragement, listening and managing relationships with family and friends. SO WHAT?: Information provided by distressed mothers can provide guidance to professionals when designing information for fathers/partners. Digital delivery of this co-designed information to fathers across urban and rural areas may enhance the competence of fathers working to support mothers experiencing mental distress in the perinatal period.

Relationships between intrauterine fetal growth trajectories and markers of adiposity and inflammation in young adults.

BACKGROUND: There is now good evidence that events during gestation significantly influence the developmental well-being of an individual in later life. This study aimed to investigate the relationships between intrauterine growth trajectories determined by serial ultrasound and subsequent markers of adiposity and inflammation in the 27-year-old adult offspring from the Raine Study, an Australian longitudinal pregnancy cohort. METHODS: Ultrasound fetal biometric measurements including abdominal circumference (AC), femur length (FL), and head circumference (HC) from 1333 mother-fetal pairs (Gen1-Gen2) in the Raine Study were used to develop fetal growth trajectories using group-based trajectory modeling. Linear mixed modeling investigated the relationship between adult body mass index (BMI), waist circumference (WC), and high-sensitivity C-reactive protein (hs-CRP) of Gen2 at 20 (n = 485), 22 (n = 421) and 27 (n = 437) years and the fetal growth trajectory groups, adjusting for age, sex, adult lifestyle factors, and maternal factors during pregnancy. RESULTS: Seven AC, five FL and five HC growth trajectory groups were identified. Compared to the average-stable (reference) group, a lower adult BMI was observed in two falling AC trajectories: (ß = -1.45 kg/m2, 95% CI: -2.43 to -0.46, P = 0.004) and (ß = -1.01 kg/m2, 95% CI: -1.96 to -0.05, P = 0.038). Conversely, higher adult BMI (2.58 kg/m2, 95% CI: 0.98 to 4.18, P = 0.002) and hs-CRP (37%, 95% CI: 9-73%, P = 0.008) were observed in a rising FL trajectory compared to the reference group. A high-stable HC trajectory associated with 20% lower adult hs-CRP (95% CI: 5-33%, P = 0.011). CONCLUSION: This study highlights the importance of understanding causes of the unique patterns of intrauterine growth. Different fetal growth trajectories from early pregnancy associate with subsequent adult adiposity and inflammation, which predispose to the risk of diabetes and cardiometabolic disease.

Polymers with autonomous life-cycle control.

The lifetime of man-made materials is controlled largely by the wear and tear of everyday use, environmental stress and unexpected damage, which ultimately lead to failure and disposal. Smart materials that mimic the ability of living systems to autonomously protect, report, heal and even regenerate in response to damage could increase the lifetime, safety and sustainability of many manufactured items. There are several approaches to achieving these functions using polymer-based materials, but making them work in highly variable, real-world situations is proving challenging.

The structures of E. coli NfsA bound to the antibiotic nitrofurantoin; to 1,4-benzoquinone and to FMN.

NfsA is a dimeric flavoprotein that catalyses the reduction in nitroaromatics and quinones by NADPH. This reduction is required for the activity of nitrofuran antibiotics. The crystal structure of free Escherichia coli NfsA and several homologues have been determined previously, but there is no structure of the enzyme with ligands. We present here crystal structures of oxidised E. coli NfsA in the presence of several ligands, including the antibiotic nitrofurantoin. Nitrofurantoin binds with the furan ring, rather than the nitro group that is reduced, near the N5 of the FMN. Molecular dynamics simulations show that this orientation is only favourable in the oxidised enzyme, while potentiometry suggests that little semiquinone is formed in the free protein. This suggests that the reduction occurs by direct hydride transfer from FMNH- to nitrofurantoin bound in the reverse orientation to that in the crystal structure. We present a model of nitrofurantoin bound to reduced NfsA in a viable hydride transfer orientation. The substrate 1,4-benzoquinone and the product hydroquinone are positioned close to the FMN N5 in the respective crystal structures with NfsA, suitable for reaction, but are mobile within the active site. The structure with a second FMN, bound as a ligand, shows that a mobile loop in the free protein forms a phosphate-binding pocket. NfsA is specific for NADPH and a similar conformational change, forming a phosphate-binding pocket, is likely to also occur with the natural cofactor.

Trends and burden of diabetes in pregnancy among Aboriginal and non-Aboriginal mothers in Western Australia, 1998-2015.

BACKGROUND: Diabetes in pregnancy (DIP), which includes pre-gestational and gestational diabetes, is more prevalent among Aboriginal women. DIP and its adverse neonatal outcomes are associated with diabetes and cardiovascular disease in the offspring. This study investigated the impact of DIP on trends of large for gestational age (LGA) in Aboriginal and non-Aboriginal populations, and added to the limited evidence on temporal trends of DIP burden in these populations. METHODS: We conducted a retrospective cohort study that included all births in Western Australia between 1998 and 2015 using linked population health datasets. Time trends of age-standardised and crude rates of pre-gestational and gestational diabetes were estimated in Aboriginal and non-Aboriginal mothers. Mixed-effects multivariable logistic regression was used to estimate the association between DIP and population LGA trends over time. RESULTS: Over the study period, there were 526,319 births in Western Australia, of which 6.4% were to Aboriginal mothers. The age-standardised annual rates of pre-gestational diabetes among Aboriginal mothers rose from 4.3% in 1998 to 5.4% in 2015 and remained below 1% in non-Aboriginal women. The comparable rates for gestational diabetes increased from 6.7 to 11.5% over the study period in Aboriginal women, and from 3.5 to 10.2% among non-Aboriginal mothers. LGA rates in Aboriginal babies remained high with inconsistent and no improvement in pregnancies complicated by gestational diabetes and pre-gestational diabetes, respectively. Regression analyses showed that DIP explained a large part of the increasing LGA rates over time in Aboriginal babies. CONCLUSIONS: There has been a substantial increase in the burden of pre-gestational diabetes (Aboriginal women) and gestational diabetes (Aboriginal and non-Aboriginal) in recent decades. DIP appears to substantially contribute to increasing trends in LGA among Aboriginal babies.

COVID-19 vaccination rates in an antenatal population: A survey of women's perceptions, factors influencing vaccine uptake and potential contributors to vaccine hesitancy.

BACKGROUND: Pregnant women are at increased risk for severe COVID-19 and are a priority group for vaccination. The discrepancy in vaccination rates between pregnant and non-pregnant cohorts is concerning. AIMS: This study aimed to assess the perceptions and intentions of pregnant women toward COVID-19 vaccination and explored vaccine uptake and reasons for vaccine hesitancy. MATERIALS AND METHOD: A cross-sectional exploratory design was performed evaluating pregnant women receiving care in two metropolitan maternity units in Western Australia. The main measurable outcomes included vaccination status, intention to be vaccinated, and reasons for delaying or declining vaccination. RESULTS: In total, 218 women participated. Of these, 122 (56%) had not received either dose of the COVID-19 vaccine. Sixty (28%) claimed that vaccination was not discussed with them and 33 (15%) reported being dissuaded from vaccination by a healthcare practitioner. Compared to vaccinated women, those who had not accepted vaccination were less likely to have had vaccination discussed by maternity staff, less aware that pregnant women are a priority group, and less aware that pregnancy increased the risk of severe illness. Unvaccinated women were concerned about the side effects of the vaccine for their newborn and their own health, felt there was inadequate information on safety during pregnancy, and felt that a lack of community transmission in Western Australia reduced the necessity to be vaccinated. CONCLUSION: Vaccine delay and hesitancy is common among pregnant women in Western Australia. Education of healthcare professionals and pregnant women on the recommendation for COVID-19 vaccination in pregnancy is required.

Associations between aspirin prophylaxis and fetal growth and preeclampsia in women with pregestational diabetes.

BACKGROUND: Current guidelines recommend low-dose aspirin for preeclampsia prophylaxis in all women with pregestational (type one and type two) diabetes mellitus. Most trials showing the efficacy of low-dose aspirin in reducing preeclampsia risk have either excluded or included only small numbers of such women. AIM: To evaluate the association of low-dose aspirin prophylaxis in women with pregestational diabetes with the incidence of large for gestational age (LGA) infants and preeclampsia. MATERIALS AND METHODS: A retrospective observational study of pregnancies to women with pregestational diabetes. Outcomes included rates of LGA and preeclampsia. Women were prescribed low-dose aspirin prophylaxis from early pregnancy according to physician discretion after considering preeclampsia risk. Statistical analyses assessed the group overall and with stratification by diabetes type and other preeclampsia risk factors. RESULTS: Of 716 pregnancies, aspirin was prescribed in 296 (41%). Preeclampsia occurred more frequently in women who received aspirin (58 of 296, 20%) than those who did not (39 of 420, 9%, P < 0.001). This association was maintained after adjustment for diabetes type and other preeclampsia risk factors (adjusted odds ratio (aOR) 1.78; 95% CI 1.02-3.11). LGA infants were commoner in women with type one diabetes of short duration who took aspirin (aOR 2.21; 95% CI 1.05-4.66). CONCLUSION: Low-dose aspirin use in women with pregestational diabetes may be associated with an increased risk of preeclampsia. In women with type one diabetes of short duration aspirin use may be associated with an increased risk of LGA infants. The retrospective nature of this study is acknowledged and assessment of such prophylaxis by further studies is warranted.

The clinical utility of ongoing sonographic cervix length surveillance in pregnancies prescribed vaginal progesterone therapy.

BACKGROUND: Vaginal progesterone therapy significantly reduces preterm birth (PTB) rates in those high-risk pregnancies with a sonographic short cervix (≤25 mm) and/or a history of spontaneous PTB. Cervical length (CL) is routinely measured at the midtrimester morphology scan; however, CL surveillance thereafter is not currently recommended. Progesterone's precise mechanism of action remains unknown, though if it indeed influences CL, shortening after treatment initiation could indicate therapeutic failure and risk of PTB. AIMS: The aim was to explore the utility of serial transvaginal ultrasound (TVU) measurement of CL at 16, 19 and 22 weeks for predicting PTB in high-risk pregnancies prescribed progesterone therapy. METHODS: A retrospective cohort study was conducted involving women who attended the King Edward Memorial Hospital PTB Prevention Clinic from 2015 to 2019 and were prescribed progesterone therapy. CL was measured at 16, 19 and 22 weeks by TVU. CL change across three time points was assessed using linear mixed models; then relationships between CL change between 16-19 and 19-22 weeks and PTB were analysed using logistic regression models. RESULTS: Term birth was most likely when CL did not decrease across both time periods. The addition of 16-19 week decrease in CL to a model, including CL at 19 weeks alone, for predicting PTB increased sensitivity from 43.2 to 56.3%, specificity from 73.2 to 77.4%, and overall accuracy from 61.7 to 70.2%. CONCLUSION: For high-risk women prescribed vaginal progesterone therapy, serial measurement of the cervix at 16 and 19 weeks improves clinical ability to predict PTB from current recommendations of 19-week measurement alone.