Statistical analyses of ordinal outcomes in randomised controlled trials: a scoping review.

BACKGROUND: Randomised controlled trials (RCTs) aim to estimate the causal effect of one or more interventions relative to a control. One type of outcome that can be of interest in an RCT is an ordinal outcome, which is useful to answer clinical questions regarding complex and evolving patient states. The target parameter of interest for an ordinal outcome depends on the research question and the assumptions the analyst is willing to make. This review aimed to provide an overview of how ordinal outcomes have been used and analysed in RCTs. METHODS: The review included RCTs with an ordinal primary or secondary outcome published between 2017 and 2022 in four highly ranked medical journals (the British Medical Journal, New England Journal of Medicine, The Lancet, and the Journal of the American Medical Association) identified through PubMed. Details regarding the study setting, design, the target parameter, and statistical methods used to analyse the ordinal outcome were extracted. RESULTS: The search identified 309 studies, of which 144 were eligible for inclusion. The most used target parameter was an odds ratio, reported in 78 (54%) studies. The ordinal outcome was dichotomised for analysis in 47 ( 33 % ) studies, and the most common statistical model used to analyse the ordinal outcome on the full ordinal scale was the proportional odds model (64 [ 44 % ] studies). Notably, 86 (60%) studies did not explicitly check or describe the robustness of the assumptions for the statistical method(s) used. CONCLUSIONS: The results of this review indicate that in RCTs that use an ordinal outcome, there is variation in the target parameter and the analytical approaches used, with many dichotomising the ordinal outcome. Few studies provided assurance regarding the appropriateness of the assumptions and methods used to analyse the ordinal outcome. More guidance is needed to improve the transparent reporting of the analysis of ordinal outcomes in future trials.

Reduction in spontaneous and iatrogenic preterm births in twin pregnancies during COVID-19 lockdown in Melbourne, Australia: a multicenter cohort study.

BACKGROUND: Melbourne, Australia, recorded one of the longest and most stringent pandemic lockdowns in 2020, which was associated with an increase in preterm stillbirths among singleton pregnancies. Twin pregnancies may be particularly susceptible to the impacts of pandemic disruptions to maternity care due to their higher background risk of adverse perinatal outcomes. METHODS: Multicenter retrospective cohort study of all twin pregnancies birthing in public maternity hospitals in Melbourne. Multivariable log-binomial regression models were used to compare perinatal outcomes between a pre-pandemic group to women in whom weeks 20+0 to 40+0 of gestation occurred entirely during one of two lockdown-exposure periods: exposure 1 from 22 March 2020 to 21 March 2021 and exposure 2 from 22 March 2021 to 27 March 2022. RESULTS: Total preterm births < 37 weeks were significantly lower in exposure 1 compared with the pre-pandemic period (63.1% vs 68.3%; adjusted risk ratio 0.92 95% CI 0.87-0.98, p = 0.01). This was mainly driven by fewer spontaneous preterm births (18.9% vs 20.3%; adjusted risk ratio 0.95 95% CI 0.90-0.99, p = 0.04). There were also lower rates of preterm birth < 34 weeks (19.9% vs 23.0%, adjusted risk ratio 0.93 95% CI 0.89-0.98 p = 0.01) and total iatrogenic births for fetal compromise (13.4% vs 20.4%; adjusted risk ratio 0.94 95% CI 0.89-0.98, p = 0.01). There were fewer special care nursery admissions (38.5% vs 43.4%; adjusted risk ratio 0.91 95% CI 0.87-0.95, p < 0.001) but no significant changes in stillbirth (1.5% vs 1.6%; adjusted risk ratio 1.00 95% CI 0.99-1.01, p = 0.82). Compared with the pre-pandemic period, there were more preterm births < 28 weeks and neonatal intensive care unit admissions in exposure 2. CONCLUSIONS: Melbourne's first lockdown-exposure period was associated with lower preterm births in twins without significant differences in adverse newborn outcomes. Our findings provide insights into the influences on preterm birth and the optimal timing of delivery for twins.

Immune profiling of SARS-CoV-2 infection during pregnancy reveals NK cell and γδ T cell perturbations.

Pregnancy poses a greater risk for severe COVID-19; however, underlying immunological changes associated with SARS-CoV-2 during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in unvaccinated pregnant and nonpregnant women with acute and convalescent COVID-19, quantifying 217 immunological parameters. Humoral responses to SARS-CoV-2 were similar in pregnant and nonpregnant women, although our systems serology approach revealed distinct antibody and FcγR profiles between pregnant and nonpregnant women. Cellular analyses demonstrated marked differences in NK cell and unconventional T cell activation dynamics in pregnant women. Healthy pregnant women displayed preactivated NK cells and γδ T cells when compared with healthy nonpregnant women, which remained unchanged during acute and convalescent COVID-19. Conversely, nonpregnant women had prototypical activation of NK and γδ T cells. Activation of CD4+ and CD8+ T cells and T follicular helper cells was similar in SARS-CoV-2-infected pregnant and nonpregnant women, while antibody-secreting B cells were increased in pregnant women during acute COVID-19. Elevated levels of IL-8, IL-10, and IL-18 were found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, we demonstrate perturbations in NK cell and γδ T cell activation in unvaccinated pregnant women with COVID-19, which may impact disease progression and severity during pregnancy.

Statistical analyses of ordinal outcomes in randomised controlled trials: protocol for a scoping review.

INTRODUCTION: Randomised controlled trials (RCTs) aim to assess the effect of one (or more) unproven health interventions relative to other reference interventions. RCTs sometimes use an ordinal outcome, which is an endpoint that comprises of multiple, monotonically ordered categories that are not necessarily separated by a quantifiable distance. Ordinal outcomes are appealing in clinical settings as specific disease states can represent meaningful categories that may be of clinical importance to researchers. Ordinal outcomes can also retain information and increase statistical power compared to dichotomised outcomes and can allow multiple clinical outcomes to be comprised in a single endpoint. Target parameters for ordinal outcomes in RCTs may vary depending on the nature of the research question, the modelling assumptions and the expertise of the data analyst. The aim of this scoping review is to systematically describe the use of ordinal outcomes in contemporary RCTs. Specifically, we aim to: [Formula: see text] Identify which target parameters are of interest in trials that use an ordinal outcome, and whether these parameters are explicitly defined. [Formula: see text] Describe how ordinal outcomes are analysed in RCTs to estimate a treatment effect. [Formula: see text] Describe whether RCTs that use an ordinal outcome adequately report key methodological aspects specific to the analysis of the ordinal outcome. Results from this review will outline the current state of practice of the use of ordinal outcomes in RCTs. Ways to improve the analysis and reporting of ordinal outcomes in RCTs will be discussed. METHODS AND ANALYSIS: We will review RCTs that are published in the top four medical journals (British Medical Journal, New England Journal of Medicine, The Lancet and the Journal of the American Medical Association) between 1 January 2012 and 31 July 2022 that use an ordinal outcome as either a primary or a secondary outcome. The review will identify articles through a PubMed-specific search strategy. Our review will adhere to guidelines for scoping reviews as described in the PRISMA-ScR checklist. The study characteristics and details of the study design and analysis, including the target parameter(s) and statistical methods used to analyse the ordinal outcome, will be extracted from eligible studies. The screening, review and data extraction will be conducted using Covidence, a web-based tool for managing systematic reviews. The data will be summarised using descriptive statistics.

Pre-eclampsia.

Pre-eclampsia is a life-threatening disease of pregnancy unique to humans and a leading cause of maternal and neonatal morbidity and mortality. Women who survive pre-eclampsia have reduced life expectancy, with increased risks of stroke, cardiovascular disease and diabetes, while babies from a pre-eclamptic pregnancy have increased risks of preterm birth, perinatal death and neurodevelopmental disability and cardiovascular and metabolic disease later in life. Pre-eclampsia is a complex multisystem disease, diagnosed by sudden-onset hypertension (>20 weeks of gestation) and at least one other associated complication, including proteinuria, maternal organ dysfunction or uteroplacental dysfunction. Pre-eclampsia is found only when a placenta is or was recently present and is classified as preterm (delivery <37 weeks of gestation), term (delivery ≥37 weeks of gestation) and postpartum pre-eclampsia. The maternal syndrome of pre-eclampsia is driven by a dysfunctional placenta, which releases factors into maternal blood causing systemic inflammation and widespread maternal endothelial dysfunction. Available treatments target maternal hypertension and seizures, but the only 'cure' for pre-eclampsia is delivery of the dysfunctional placenta and baby, often prematurely. Despite decades of research, the aetiology of pre-eclampsia, particularly of term and postpartum pre-eclampsia, remains poorly defined. Significant advances have been made in the prediction and prevention of preterm pre-eclampsia, which is predicted in early pregnancy through combined screening and is prevented with daily low-dose aspirin, starting before 16 weeks of gestation. By contrast, the prediction of term and postpartum pre-eclampsia is limited and there are no preventive treatments. Future research must investigate the pathogenesis of pre-eclampsia, in particular of term and postpartum pre-eclampsia, and evaluate new prognostic tests and treatments in adequately powered clinical trials.

A prospective, longitudinal, case-control study to evaluate the neurodevelopment of children from birth to adolescence exposed to COVID-19 in utero.

BACKGROUND: The Coronavirus disease (COVID-19) pandemic has created unprecedented acute global health challenges. However, it also presents a set of unquantified and poorly understood risks in the medium to long term, specifically, risks to children whose mothers were infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy. Infections during pregnancy can increase the risk of atypical neurodevelopment in the offspring, but the long-term neurodevelopmental impact of in utero COVID-19 exposure is unknown. Prospective, longitudinal studies are needed to evaluate children exposed in utero to SARS-CoV2 to define this risk. METHODS: We have designed a prospective, case-controlled study to investigate the long-term impacts of SARS-CoV2 exposure on children exposed in utero. Women infected with SARS-CoV-2 during pregnancy will be recruited from Monash Health, the Royal Women's Hospital and Western Health (Melbourne, Australia) and Londrina Municipal Maternity Hospital Lucilla Ballalai and PUCPR Medical Clinical (Londrina, Brazil). A control group in a 2:1 ratio (2 non-exposed: 1 exposed mother infant dyad) comprising women who gave birth in the same month of delivery, are of similar age but did not contract SARS-CoV-2 during their pregnancy will also be recruited. We aim to recruit 170 exposed and 340 non-exposed mother-infant dyads. Clinical and socio-demographic data will be collected directly from the mother and medical records. Biospecimens and clinical and epidemiological data will be collected from the mothers and offspring at multiple time points from birth through to 15 years of age using standardised sample collection, and neurological and behavioural measures. DISCUSSION: The mapped neurodevelopmental trajectories and comparisons between SARS-CoV-2 exposed and control children will indicate the potential for an increase in atypical neurodevelopment. This has significant implications for strategic planning in the mental health and paediatrics sectors and long-term monitoring of children globally.

Reductions in stillbirths and preterm birth in COVID-19-vaccinated women: a multicenter cohort study of vaccination uptake and perinatal outcomes.

BACKGROUND: COVID-19 infection in pregnancy is associated with a higher risk of progression to severe disease, but vaccine uptake by pregnant women is hindered by persistent safety concerns. COVID-19 vaccination in pregnancy has been shown to reduce stillbirth, but its relationship with preterm birth is uncertain. OBJECTIVE: This study aimed to measure the rate of COVID-19 vaccine uptake among women giving birth in Melbourne, Australia, and to compare perinatal outcomes by vaccination status. STUDY DESIGN: This was a retrospective multicenter cohort study conducted after the June 2021 government recommendations for messenger RNA COVID-19 vaccination during pregnancy. Routinely collected data from all 12 public maternity hospitals in Melbourne were extracted on births at ≥20 weeks' gestation from July 1, 2021 to March 31, 2022. Maternal sociodemographic characteristics were analyzed from the total birth cohort. Perinatal outcomes were compared between vaccinated and unvaccinated women for whom weeks 20 to 43 of gestation fell entirely within the 9-month data collection period. The primary outcomes were the rates of stillbirth and preterm birth (spontaneous and iatrogenic) in singleton pregnancies of at least 24 weeks' gestation, after exclusion of congenital anomalies. Secondary perinatal outcomes included the rate of congenital anomalies among infants born at ≥20 weeks' gestation and birthweight ≤third centile and newborn intensive care unit admissions among infants born without congenital anomalies at ≥24 weeks' gestation. We calculated the adjusted odds ratio of perinatal outcomes among vaccinated vs unvaccinated women using inverse propensity score-weighting regression adjustment with multiple covariates; P<.05 was considered statistically significant. RESULTS: Births from 32,536 women were analyzed: 17,365 (53.4%) were vaccinated and 15,171 (47.6%) were unvaccinated. Vaccinated women were more likely to be older, nulliparous, nonsmoking, not requiring an interpreter, of higher socioeconomic status, and vaccinated against pertussis and influenza. Vaccination status also varied by region of birth. Vaccinated women had a significantly lower rate of stillbirth compared with unvaccinated women (0.2% vs 0.8%; adjusted odds ratio, 0.18; 95% confidence interval, 0.09-0.37; P<.001). Vaccination was associated with a significant reduction in total preterm births at <37 weeks (5.1% vs 9.2%; adjusted odds ratio, 0.60; 95% confidence interval, 0.51-0.71; P<.001), spontaneous preterm birth (2.4% vs 4.0%; adjusted odds ratio, 0.73; 95% confidence interval, 0.56-0.96; P=.02), and iatrogenic preterm birth (2.7% vs 5.2%; adjusted odds ratio, 0.52; 95% confidence interval, 0.41-0.65; P<.001). Infants born to vaccinated mothers also had lower rates of admission to the neonatal intensive care unit. There was no significant increase in the rate of congenital anomalies or birthweight ≤3rd centile in vaccinated women. Vaccinated women were significantly less likely to have an infant with a major congenital anomaly compared with the unvaccinated group (2.4% vs 3.0%; adjusted odds ratio, 0.72; 95% confidence interval, 0.56-0.94; P=.02). This finding remained significant even when the analysis was restricted to women vaccinated before 20 weeks' gestation. CONCLUSION: COVID-19 vaccination during pregnancy was associated with a reduction in stillbirth and preterm birth, and not associated with any adverse impact on fetal growth or development. Vaccine coverage was substantially influenced by known social determinants of health.

The National COVID-19 Clinical Evidence Taskforce: pregnancy and perinatal guidelines.

INTRODUCTION: Pregnant women are at higher risk of severe illness from coronavirus disease 2019 (COVID-19) than non-pregnant women of a similar age. Early in the COVID-19 pandemic, it was clear that evidenced-based guidance was needed, and that it would need to be updated rapidly. The National COVID-19 Clinical Evidence Taskforce provided a resource to guide care for people with COVID-19, including during pregnancy. Care for pregnant and breastfeeding women and their babies was included as a priority when the Taskforce was set up, with a Pregnancy and Perinatal Care Panel convened to guide clinical practice. MAIN RECOMMENDATIONS: As of May 2022, the Taskforce has made seven specific recommendations on care for pregnant women and those who have recently given birth. This includes supporting usual practices for the mode of birth, umbilical cord clamping, skin-to-skin contact, breastfeeding, rooming-in, and using antenatal corticosteroids and magnesium sulfate as clinically indicated. There are 11 recommendations for COVID-19-specific treatments, including conditional recommendations for using remdesivir, tocilizumab and sotrovimab. Finally, there are recommendations not to use several disease-modifying treatments for the treatment of COVID-19, including hydroxychloroquine and ivermectin. The recommendations are continually updated to reflect new evidence, and the most up-to-date guidance is available online (https://covid19evidence.net.au). CHANGES IN MANAGEMENT RESULTING FROM THE GUIDELINES: The National COVID-19 Clinical Evidence Taskforce has been a critical component of the infrastructure to support Australian maternity care providers during the COVID-19 pandemic. The Taskforce has shown that a rapid living guidelines approach is feasible and acceptable.

Increase in preterm stillbirths in association with reduction in iatrogenic preterm births during COVID-19 lockdown in Australia: a multicenter cohort study.

BACKGROUND: The COVID-19 pandemic has been associated with a worsening of perinatal outcomes in many regions around the world. Melbourne, Australia, had one of the longest and most stringent lockdowns worldwide in 2020 while recording only rare instances of COVID-19 infection in pregnant women. OBJECTIVE: This study aimed to compare the stillbirth and preterm birth rates in women who were exposed or unexposed to lockdown restrictions during pregnancy. STUDY DESIGN: This was a retrospective, multicenter cohort study of perinatal outcomes in Melbourne before and during the COVID-19 lockdown. The lockdown period was defined as the period from March 23, 2020 to March 14, 2021. Routinely-collected maternity data on singleton pregnancies ≥24 weeks gestation without congenital anomalies were obtained from all the 12 public hospitals in Melbourne. We defined the lockdown-exposed cohort as those women for whom weeks 20 to 40 of gestation occurred during the lockdown and the unexposed control group as women from the corresponding calendar periods 12 and 24 months before. The main outcome measures were stillbirth, preterm birth, fetal growth restriction (birthweight < third centile), and iatrogenic preterm birth for fetal compromise. We performed multivariable logistic regression analysis to compare the odds of stillbirth, preterm birth, fetal growth restriction, and iatrogenic preterm birth for fetal compromise, adjusting for multiple covariates. RESULTS: There were 24,817 births in the exposed group and 50,017 births in the control group. There was a significantly higher risk of preterm stillbirth in the exposed group than the control group (0.26% vs 0.18%; adjusted odds ratio, 1.49; 95% confidence interval, 1.08-2.05; P=.015). There was also a significant reduction in the preterm birth of live infants <37 weeks (5.68% vs 6.07%; adjusted odds ratio, 0.93; 95% confidence interval, 0.87-0.99; P=.02), which was largely mediated by a significant reduction in iatrogenic preterm birth (3.01% vs 3.27%; adjusted odds ratio, 0.91; 95% confidence interval, 0.83-0.99; P=.03), including iatrogenic preterm birth for fetal compromise (1.25% vs 1.51%; adjusted odds ratio, 0.82; 95% confidence interval, 0.71-0.93; P=.003). There were also significant reductions in special care nursery admissions during lockdown (11.53% vs 12.51%; adjusted odds ratio, 0.90; 95% confidence interval, 0.86-0.95; P<.0001). There was a trend to fewer spontaneous preterm births <37 weeks in the exposed group of a similar magnitude to that reported in other countries (2.69% vs 2.82%; adjusted odds ratio, 0.95; 95% confidence interval, 0.87-1.05; P=.32). CONCLUSION: Lockdown restrictions in Melbourne, Australia were associated with a significant reduction in iatrogenic preterm birth for fetal compromise and a significant increase in preterm stillbirths. This raises concerns that pandemic conditions in 2020 may have led to a failure to identify and appropriately care for pregnant women at an increased risk of antepartum stillbirth. Further research is required to understand the relationship between these 2 findings and to inform our ongoing responses to the pandemic.

Identifying preeclampsia-associated genes using a control theory method.

Preeclampsia is a pregnancy-specific disease that can have serious effects on the health of both mothers and their offspring. Predicting which women will develop preeclampsia in early pregnancy with high accuracy will allow for improved management. The clinical symptoms of preeclampsia are well recognized, however, the precise molecular mechanisms leading to the disorder are poorly understood. This is compounded by the heterogeneous nature of preeclampsia onset, timing and severity. Indeed a multitude of poorly defined causes including genetic components implicates etiologic factors, such as immune maladaptation, placental ischemia and increased oxidative stress. Large datasets generated by microarray and next-generation sequencing have enabled the comprehensive study of preeclampsia at the molecular level. However, computational approaches to simultaneously analyze the preeclampsia transcriptomic and network data and identify clinically relevant information are currently limited. In this paper, we proposed a control theory method to identify potential preeclampsia-associated genes based on both transcriptomic and network data. First, we built a preeclampsia gene regulatory network and analyzed its controllability. We then defined two types of critical preeclampsia-associated genes that play important roles in the constructed preeclampsia-specific network. Benchmarking against differential expression, betweenness centrality and hub analysis we demonstrated that the proposed method may offer novel insights compared with other standard approaches. Next, we investigated subtype specific genes for early and late onset preeclampsia. This control theory approach could contribute to a further understanding of the molecular mechanisms contributing to preeclampsia.

Transcriptomic analysis of patient plasma reveals circulating miR200c as a potential biomarker for high-grade serous ovarian cancer.

BACKGROUND: High-grade serous tubo-ovarian cancer (HGSC) is the most common histological subtype of epithelial ovarian cancer, and highly lethal. Currently there is no effective screening test and prognosis is poor as the majority of cases are diagnosed at the advanced stage. Cell free RNAs including microRNAs (miRNAs) are dysregulated in ovarian cancer tissue and are detectable in the circulation. This study aimed to determine whether circulating cell free miRNAs may be potential biomarkers for the detection of HGSC. METHODS: Plasma was collected from women with HGSC (Grade 3, n = 24), and benign ovarian masses (n = 24). RNA was extracted from patient plasma and subjected to miRNA targeted next generation sequencing (NGS). A subsequent validation cohort was assessed using plasma collected from women with HGSC (n = 14) and controls (with a benign ovarian mass; n = 15). RNA was extracted and assessed using quantitative RT-PCR. RESULTS: Differential gene expression (DGE) of the NGS data revealed a significant increase in the miRNA, miR200c, in the circulation of women with HGSC (p less than 0.05) compared to controls. In the validation cohort miR200c expression by qPCR was found to also be increased in the circulation of women with HGSC compared to controls (p = 0.0023). CONCLUSIONS: Circulating miR200c may be a promising candidate biomarker for the detection of HGSC. Further larger cohort studies exploring earlier stages are needed to determine whether circulating miR200c may be a sensitive and specific biomarker of tubo-ovarian cancer.

Doppler Ultrasound of the Fetal Descending Aorta: An Objective Tool to Assess Placental Blood Flow Resistance in Pregnancies With Discordant Umbilical Arteries.

OBJECTIVES: To determine the relationship between blood flow in the fetal descending aorta and discordant umbilical arteries (UAs). METHODS: Pulsed wave Doppler of both UAs and the descending aorta was performed at 4-weekly intervals between 14 and 40 weeks of gestation in 209 pregnant women. In datasets with discordant UAs, a linear mixed effects model was used to determine the categorical relationship between the UA pulsatility index (PI) (high, low and average) and the descending aorta PI. RESULTS: Of the 209 cases, 81 had a discordance of greater than 25% in UA PI during one of their visits. There were no differences in birth outcomes between the groups with concordant and discordant UA PIs. In the cases with discordant UA PIs, the descending aorta PI was most strongly associated with both the average UA PI (P = .008), and with the UA with the lower PI (P = .008). CONCLUSIONS: The relationship between blood flow in the descending aorta and UAs is consistent with the law for combining resistances in parallel. Measurements of the descending aorta PI, particularly in a scenario with discordant UAs, may inform the stability of the feto-placental circulation where discordant UA PIs are found.

Collaborative maternity and newborn dashboard (CoMaND) for the COVID-19 pandemic: a protocol for timely, adaptive monitoring of perinatal outcomes in Melbourne, Australia.

BACKGROUND: The COVID-19 pandemic has resulted in a range of unprecedented disruptions to maternity care with documented impacts on perinatal outcomes such as stillbirth and preterm birth. Metropolitan Melbourne has endured one of the longest and most stringent lockdowns in globally. This paper presents the protocol for a multicentre study to monitor perinatal outcomes in Melbourne, Australia, during the COVID-19 pandemic. METHODS: Multicentre observational study analysing monthly deidentified maternal and newborn outcomes from births >20 weeks at all 12 public maternity services in Melbourne. Data will be merged centrally to analyse outcomes and create run charts according to established methods for detecting non-random 'signals' in healthcare. Perinatal outcomes will include weekly rates of total births, stillbirths, preterm births, neonatal intensive care admissions, low Apgar scores and fetal growth restriction. Maternal outcomes will include weekly rates of: induced labour, caesarean section, births before arrival to hospital, postpartum haemorrhage, length of stay, general anaesthesia for caesarean birth, influenza and COVID-19 vaccination status, and gestation at first antenatal visit. A prepandemic median for all outcomes will be calculated for the period of January 2018 to March 2020. A significant shift is defined as ≥6 consecutive weeks, all above or below the prepandemic median. Additional statistical analyses such as regression, time series and survival analyses will be performed for an in-depth examination of maternal and perinatal outcomes of interests. ETHICS AND DISSEMINATION: Ethics approval for the collaborative maternity and newborn dashboard project has been obtained from the Austin Health (HREC/64722/Austin-2020) and Mercy Health (ref. 2020-031). TRIAL REGISTRATION NUMBER: ACTRN12620000878976; Pre-results.

The international Perinatal Outcomes in the Pandemic (iPOP) study: protocol.

Preterm birth is the leading cause of infant death worldwide, but the causes of preterm birth are largely unknown. During the early COVID-19 lockdowns, dramatic reductions in preterm birth were reported; however, these trends may be offset by increases in stillbirth rates. It is important to study these trends globally as the pandemic continues, and to understand the underlying cause(s). Lockdowns have dramatically impacted maternal workload, access to healthcare, hygiene practices, and air pollution - all of which could impact perinatal outcomes and might affect pregnant women differently in different regions of the world. In the international Perinatal Outcomes in the Pandemic (iPOP) Study, we will seize the unique opportunity offered by the COVID-19 pandemic to answer urgent questions about perinatal health. In the first two study phases, we will use population-based aggregate data and standardized outcome definitions to: 1) Determine rates of preterm birth, low birth weight, and stillbirth and describe changes during lockdowns; and assess if these changes are consistent globally, or differ by region and income setting, 2) Determine if the magnitude of changes in adverse perinatal outcomes during lockdown are modified by regional differences in COVID-19 infection rates, lockdown stringency, adherence to lockdown measures, air quality, or other social and economic markers, obtained from publicly available datasets. We will undertake an interrupted time series analysis covering births from January 2015 through July 2020. The iPOP Study will involve at least 121 researchers in 37 countries, including obstetricians, neonatologists, epidemiologists, public health researchers, environmental scientists, and policymakers. We will leverage the most disruptive and widespread "natural experiment" of our lifetime to make rapid discoveries about preterm birth. Whether the COVID-19 pandemic is worsening or unexpectedly improving perinatal outcomes, our research will provide critical new information to shape prenatal care strategies throughout (and well beyond) the pandemic.

Business as usual during the COVID-19 pandemic? Reflections on state-wide trends in maternity telehealth consultations during lockdown in Victoria and New South Wales.

COVID-19 has resulted in unprecedented changes to maternity care across Australia. This study aims to analyse trends in maternity consultations and the uptake of telehealth in Victoria and New South Wales (NSW) since the first restrictions to reduce COVID-19 transmission were implemented. From March 2020 to April 2021, a higher proportion of antenatal care consultations was delivered via telehealth in Victoria compared to NSW (13.8% vs 7.4%, P < 0.0001). Uptake of telehealth and a shift from in-person care has been a major contributor to maintaining pregnancy care during pandemic restrictions. However, further research is required to understand women's perspectives and health outcomes.

A simplified point-of-care testing approach for preeclampsia blood biomarkers based on nanoscale field effect transistors.

Rapid diagnosis of preeclampsia is necessary to ensure timely administration of appropriate care and prevent the potentially catastrophic complications of the condition affecting both mothers and babies. While the diagnostic superiority of angiogenic blood biomarkers such as placental growth factor has recently been demonstrated, there is an urgent need to develop point-of-care (PoC) technologies that allow rapid, quantitative, and accurate testing for these markers within local communities. Towards addressing this need, here we report on a fully integrated biodiagnostic platform based on nanoscale indium oxide field effect transistor (FET) sensors. The high-performance FET sensors are integrated with blood sample processing cartridges that minimize the need for operator intervention during the assay and eliminate the need for analytical equipment. Within 40 minutes and from 30 µL of blood, the FET platform could reliably measure PlGF with a limit of detection of 0.06 pg mL-1 and a five order of magnitudes dynamic range. Pilot clinical validation in four preeclamptic pregnancies confirmed that the accuracy and reliability of the FET platform, paving the way for further development to a much-needed point-of-care preeclampsia testing.

Clinical manifestations and health outcomes associated with Zika virus infections in adults: A systematic review.

BACKGROUND: Zika virus (ZIKV) has generated global interest in the last five years mostly due to its resurgence in the Americas between 2015 and 2016. It was previously thought to be a self-limiting infection causing febrile illness in less than one quarter of those infected. However, a rise in birth defects amongst children born to infected pregnant women, as well as increases in neurological manifestations in adults has been demonstrated. We systemically reviewed the literature to understand clinical manifestations and health outcomes in adults globally. METHODS: This review was registered prospectively with PROPSERO (CRD 42018096558). We systematically searched for studies in six databases from inception to the end of September 2020. There were no language restrictions. Critical appraisal was completed using the Joanna Briggs Institute Critical Appraisal Tools. FINDINGS: We identified 73 studies globally that reported clinical outcomes in ZIKV-infected adults, of which 55 studies were from the Americas. For further analysis, we considered studies that met 70% of critical appraisal criteria and described subjects with confirmed ZIKV. The most common symptoms included: exanthema (5,456/6,129; 89%), arthralgia (3,809/6,093; 63%), fever (3,787/6,124; 62%), conjunctivitis (2,738/3,283; 45%), myalgia (2,498/5,192; 48%), headache (2,165/4,722; 46%), and diarrhea (337/2,622; 13%). 36/14,335 (0.3%) of infected cases developed neurologic sequelae, of which 75% were Guillain-Barré Syndrome (GBS). Several subjects reported recovery from peak of neurological complications, though some endured chronic disability. Mortality was rare (0.1%) and hospitalization (11%) was often associated with co-morbidities or GBS. CONCLUSIONS: The ZIKV literature in adults was predominantly from the Americas. The most common systemic symptoms were exanthema, fever, arthralgia, and conjunctivitis; GBS was the most prevalent neurological complication. Future ZIKV studies are warranted with standardization of testing and case definitions, consistent co-infection testing, reporting of laboratory abnormalities, separation of adult and pediatric outcomes, and assessing for causation between ZIKV and neurological sequelae.