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Objective: To compare the performance at 35 + 0 to 36 + 6 weeks' gestation of screening for delivery with pre‐eclampsia (PE) at various timepoints, using one of three approaches: placental growth factor (PlGF) concentration, soluble fms‐like tyrosine kinase‐1 (sFlt‐1) to PlGF concentration ratio, or the competing‐risks model, which combines maternal risk factors with biomarkers to estimate patient‐specific risk. Methods: This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation at one of two maternity hospitals in England between 2016 and 2022. During the visit, maternal demographic characteristics and medical history were recorded and serum PlGF, serum sFlt‐1 and mean arterial pressure (MAP) were measured. Detection rates (DRs) were evaluated for delivery with PE (defined as per American College of Obstetricians and Gynecologists 2019 criteria) within 1 week, within 2 weeks or at any time after screening, using the following strategies: (i) low PlGF (< 10th percentile); (ii) high sFlt‐1/PlGF ratio (> 90th percentile); or (iii) the competing‐risks model, in which maternal factors were combined with multiples of the median values of PlGF ('single test'), PlGF and sFlt‐1 ('double test') or PlGF, sFlt‐1 and MAP ('triple test'). Risk cut‐offs corresponded to a screen‐positive rate of 10%. DRs were compared between tests. Results: Of 34 782 pregnancies, 831 (2.4%) developed PE. In screening for delivery with PE at any time from assessment, the DR at 10% screen‐positive rate was 47% by low PlGF alone, 54% by the single test, 55% by high sFlt‐1/PlGF ratio, 61% by the double test and 68% by the triple test. In screening for delivery with PE within 2 weeks from assessment, the respective values were 67%, 74%, 74%, 80% and 87%. In screening for delivery with PE within 1 week from assessment, the respective values were 77%, 81%, 85%, 88% and 91%. For prediction of PE at any time, the DR was significantly higher with the triple test compared to PlGF alone or the sFlt‐1/PlGF ratio, with a DR difference (95% CI) of 20.1% (16.7–23.0%) and 12.4% (9.7–15.3%), respectively. Similar results were seen for prediction of PE within 2 weeks (20.6% (14.9–26.8%) and 12.9% (7.7–17.5%), respectively) and prediction of PE within 1 week (13.5% (5.4–21.6%) and 5.4% (0.0–10.8%), respectively). The double test was superior to the sFlt‐1/PlGF ratio and the single test was superior to PlGF alone in the prediction of PE within 2 weeks and at any time from assessment, but not within 1 week of assessment. Conclusion: At 35 + 0 to 36 + 6 weeks' gestation, the performance of screening for PE by the competing‐risks model triple test is superior to that of PlGF alone or the sFlt‐1/PlGF ratio for the development of disease within 1 week, within 2 weeks and at any time from screening. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: The competing-risks model for assessment of risk for pre-eclampsia (PE) at 35-37 weeks' gestation identifies the majority of women who are at high risk of subsequent delivery with PE. We aimed to examine the incidence and relative risk of adverse pregnancy outcomes in patient groups stratified according to the estimated risk of delivery with PE.Methods: This was a prospective non-interventional, observational study in women with a singleton pregnancy attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. The risk of delivery with PE for each patient in the study population was estimated using the competing-risks model, combining the prior distribution of gestational age at delivery with PE and the likelihood from multiples of the median values of mean arterial pressure, placental growth factor and soluble fms-like tyrosine kinase-1. The patients were assigned to one of the following five risk categories: Group A, ≥ 1 in 2; Group B, 1 in 5 to 1 in 3; Group C, 1 in 20 to 1 in 6; Group D, 1 in 50 to 1 in 21; and Group E, < 1 in 50. The outcome measures were delivery with PE, gestational hypertension (GH), small-for-gestational age (SGA) at birth, delivery by Cesarean section, stillbirth, neonatal death, perinatal death and admission to the neonatal unit (NNU) for at least 48 h. In each risk category, the proportion of women with each adverse outcome was determined and relative risks (RR) were calculated as compared with the lowest-risk Group E.Results: In the study population of 29 035 women, 1.6%, 2.7%, 8.2%, 9.8% and 77.8% were categorized into Groups A, B, C, D and E, respectively. Compared with women in Group E, women in the higher-risk groups were more likely to have an adverse outcome. The RR of delivery with PE in Group A compared with Group E was 65.5 (95% CI, 54.1-79.1) and the respective values were 11.9 (95% CI, 9.1-15.5) for GH, 1.8 (95% CI, 1.5-2.1) for delivery by emergency Cesarean section, 1.5 (95% CI, 1.2-1.8) for delivery by elective Cesarean section, 8.9 (95% CI, 7.4-10.8) for SGA with birth weight < 3rd percentile, 4.8 (95% CI, 4.3-5.4) for SGA with birth weight < 10th percentile, 5.3 (95% CI, 1.4-20.5) for stillbirth and 3.4 (95% CI, 2.8-4.2) for NNU admission for ≥ 48 h. The RR for these pregnancy complications in higher-risk groups (vs Group E) was particularly high for cases with delivery within 2 weeks after assessment. In terms of SGA, both for birth weight < 10th and < 3rd percentiles, the trend in all cases was stronger than that observed when the analysis was confined to normotensive pregnancies. The rates of neonatal death were too small to allow meaningful comparisons between risk groups.Conclusion: Pregnant women identified by the competing-risks model to be at high risk of PE are also at increased risk of GH, Cesarean section, stillbirth, SGA and NNU admission for ≥ 48 h. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Linked article: This is a mini commentary on Hauspurg et al., pp. 715–726 in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.17381. [ABSTRACT FROM AUTHOR]

Treat hypertension (BP >= 140/90 mmHg) with antihypertensive therapy Oral antihypertensive therapy halves the risk of severe hypertension (systematic review, 31 trials, 3485 women)[11], which is an outcome that warrants face-to-face assessment in all jurisdictions, even during the COVID-19 pandemic. BP control was achieved by a simple algorithm of up or down titration of antihypertensive medication (Figure 1), using single or multiple medications; in Figure 2, we provide practical advice and a protocol for dosing escalation from starting to maximum dosage and medication combinations. *If systolic BP is >= 160 mmHg, increase dose of existing medication or start new antihypertensive medication to get systolic BP < 160 mmHg, regardless of diastolic BP (dBP). In a systematic review of maternal risk stratification in pregnancy hypertension (32 studies), miniPIERS (Pre-eclampsia Integrated Estimate of Risk Score) was the only model for all pregnancy hypertension types[18]. [Extracted from the article]

The authors reflect on the study of the significant role of out-of-office or ambulary blood pressure (BP) measurement in evaluating pregnancy hypertension. Authors explain that the said methodology assure accurate results for BP measurement in hypertension pregnant women. They discover that when out-of-office BP is <135/85, pregnant women are in less complications. They confirm that the out-of-office hypertension are detached and less complicated medication in pregnancy.

Background: Satisfaction with maternity care is strongly related to the patient-caregiver relationship and involvement in the decision-making process. We sought to compare women's views about their care in a randomized trial of 'less tight' vs. 'tight' control of non-proteinuric pre-existing or gestational hypertension in pregnancy. Methods: In the CHIPS Pilot Trial, women completed a postpartum questionnaire to assess their likes and dislikes about their blood pressure (BP) management and trial participation. Comparisons were descriptive. Results: Baseline information was similar for the 'less tight' and 'tight' control groups. Of 132 women, 126 (95.5%) from 17 centers completed a postpartum questionnaire, usually within days of delivery. At least 90% of women in both groups were satisfied with their care, and would be willing to participate again or recommend participation to a friend. Women in both the 'less tight' and 'tight' groups were satisfied with BP management (98.4% vs. 95.1%), and the frequency of tests of maternal and fetal well being. Half of women in both groups perceived that their BP was too high and that caregivers thought that their BP was too high. More women in the 'less tight' (vs. the 'tight') control group took less medication than expected (71.7% vs. 38.2%). More women in the 'tight' (vs. the 'less tight') group took more medication than they expected (60.0% vs. 22.2%). At least 60% of all women used home BP monitoring. Conclusion: In the CHIPS Pilot Trial, while women stated that they were satisfied with their BP management and care, a surprising 50% in both groups thought that their BP was too high. The majority of women used home BP monitoring, the role of which must be further defined in hypertensive pregnancies. [ABSTRACT FROM AUTHOR]

Objective: To determine the association between adverse maternal/perinatal outcomes and Canadian and U.S. preeclampsia severity criteria. Methods: Using PIERS data (Preeclampsia Integrated Estimate of RiSk), an international continuous quality improvement project for women hospitalized with preeclampsia, we examined the association between preeclampsia severity criteria and adverse maternal and perinatal outcomes (univariable analysis, Fisher's exact test). Not evaluated were variables performed in <80% of pregnancies (e.g., 24-hour proteinuria). Results: Few of the evaluated variables were associated with adverse maternal (chest pain/dyspnea, thrombocytopenia, 'elevated liver enzymes', HELLP syndrome, and creatinine >110 μM) or perinatal outcomes (dBP >110 mm Hg and suspected abruption) (at p < 0.01). Conclusions: In the PIERS cohort, most factors used in the Canadian or American classifications of severe preeclampsia do not predict adverse maternal and/or perinatal outcomes. Future classification systems should take this into account. [ABSTRACT FROM AUTHOR]

Objective: To examine fetal (FHR) and neonatal heart rate patterns following use of common oral antihypertensives in pregnancy. Methods: A systematic review of randomized controlled trials (RCTs), observational studies (N ≥ 6 women), and animal studies. Data were abstracted (two reviewers) to determine relative risk (RR) (or risk difference (RD) for low event rates) and 95% CI. Results: Eighteen RCTs (1858 women), one controlled observational study (N = 22), and seven case series (N = 117) were reviewed. Most hypertension was pregnancy-induced (N = 14 studies). The FHR was assessed by cardiotocogram (CTG) (N = 17 studies (visual interpretation); 1 study (computerized CTG), or umbilical artery velocimetry (N = 4). Four studies examined neonatal heart rate. In placebo-controlled RCTs (N = 192 women), adverse FHR effects did not differ between groups [9/101 (drugs) vs. 7/91 (placebo); RD 0.02, 95% CI (- 0.06, 0.11); χ² = 1.02]. In six drug vs. drug RCTs (295 women), adverse FHR effects did not differ between groups [29/144 (methyldopa) vs. 42/151 (other drugs); RR 0.72, 95% CI (0.49, 1.07); χ² = 0.69]. In one labetalol vs. placebo trial, neonatal bradycardia did not differ between groups [4/70 (labetalol) vs. 4/74 (placebo); OR 1.06, 95% CI (0.26, 4.39)], while in three drug vs. drug RCTs, neonatal bradycardia was not observed (0/24 vs. 0/26). Conclusions: Available data are inadequate to conclude whether oral methyldopa, labetalol, nifedipine, or hydralazine adversely affect fetal or neonatal heart rate and pattern. Until definitive data are available, FHR changes cannot be reliably attributed to drug effect, but may be due to progression of the underlying maternal or placental disease. [ABSTRACT FROM AUTHOR]

: ObjectiveA relationship between autism and gastrointestinal (GI) immune dysregulation has been postulated based on incidence of GI complaints as well as macroscopically observed lymphonodular hyperplasia and microscopically determined enterocolitis in pediatric patients with autism. To evaluate GI immunity, we quantitatively assessed levels of proinflammatory cytokines, interleukin (IL)-6, IL-8, and IL-1β, produced by intestinal biopsies of children with pervasive developmental disorders.: MethodsFifteen patients, six with pervasive developmental disorders and nine age-matched controls, presenting for diagnostic colonoscopy were enrolled. Endoscopic biopsies were organ cultured, supernatants were harvested, and IL-6, IL-8, and IL-1β levels were quantified by ELISA. Tissue histology was evaluated by blinded pathologists.: ResultsConcentrations of IL-6 from intestinal organ culture supernatants of patients with pervasive developmental disorders (median 318.5 pg/ml, interquartile range 282.0–393.0 pg/ml) when compared with controls (median 436.9 pg/ml, interquartile range 312.6–602.5 pg/ml) were not significantly different (p = 0.0987). Concentrations of IL-8 (median 84,000 pg/ml, interquartile range 16,000–143,000 pg/ml) when compared with controls (median 177,000 pg/ml, interquartile range 114,000–244,000 pg/ml) were not significantly different (p = 0.0707). Concentrations of IL-1β (median 0.0 pg/ml, interquartile range 0.0–94.7 pg/ml) when compared with controls (median 0.0 pg/ml, interquartile range 0.0–60.2 pg/ml) were not significantly different (p = 0.8826). Tissue histology was nonpathological for all patients.: ConclusionsWe have demonstrated no significant difference in production of IL-6, IL-8, and IL-1β between patients with pervasive developmental disorders and age-matched controls. In general, intestinal levels of IL-6 and IL-8 were lower in patients with pervasive developmental disorders than in age-matched controls. These data fail to support an association between autism and GI inflammation. [Copyright &y& Elsevier]

Compares the economic policy on the education premiums in the U.S. and Canada. Median weekly earnings by education; Earnings ratios for university and nonuniversity males and females; Use of survey of labor income dynamics and labor force survey.

Discusses the clinical management of hypertension during pregnancy in Great Britain. Details on the clinical trials conducted; Incidence of hypertension in later pregnancy; Description of chronic and severe hypertension.

The author reflects on the issue of preeclampsia and increased cardiovascular risk. She suggests that guidelines for primary prevention of cardiovascular disease are appropriate for all women since cardiovascular disease is the leading cause of death in women. She argues that women with a history of preeclampsia should have their risk of cardiovascular disease assessed three to six months after giving birth and begin a healthy diet and lifestyle because preeclampsia increases the long term risk of cardiovascular disease.

Objectives: To examine the relationship between the English index of multiple deprivation (IMD) and the incidence of pre‐eclampsia (PE), evaluate the distribution of IMD in a cohort of ethnically diverse pregnant women in South East England and assess whether IMD improves the prediction of PE compared with that provided by the 'history‐only' competing‐risks model (based on maternal characteristics and medical history). Methods: This was a prospective, observational study of 159 125 women with a singleton pregnancy who attended their first routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation in two maternity hospitals in the UK. The inclusion criteria were delivery at ≥ 24 weeks' gestation of babies without major abnormality. Participants completed a questionnaire on demographic characteristics and obstetric and medical history, which was then reviewed by a doctor together with the woman. Patients were asked to self‐identify as white, black, South Asian, East Asian or mixed race. IMD was used as a measure of socioeconomic status, which takes into account income, employment, education, skills and training, health and disability, crime, barriers to housing and services, and living environment. Each neighborhood is ranked according to their level of deprivation relative to that of other areas into one of five equal groups, with Quintile 1 containing the 20% most deprived areas and Quintile 5 containing the 20% least deprived areas. IMD was assigned based on a woman's postcode. Risk factors for PE and its incidence were assessed across IMD using chi‐square test or t‐test, as appropriate. The relationship between IMD and gestational age at delivery with PE was evaluated by fitting parametric survival models for IMD alone, IMD combined with race and IMD combined with the Fetal Medicine Foundation history‐only competing‐risks model. Results: The incidence of PE (n = 4088, 2.6%) increased progressively across IMD quintiles, from 2.0% in Quintile 5 (least deprived) to 3.0% in Quintile 1 (most deprived). Compared with white women and those in other racial groups, black women had a higher incidence of PE (4.8%), were less often in IMD Quintiles 4 and 5, and were more often in IMD Quintiles 1 and 2. None of the IMD quintiles improved the prediction of PE compared with that provided by the history‐only competing‐risks model (which includes race). The history‐only competing‐risks model with vs without IMD had a similar detection rate for delivery with PE at < 37 weeks' gestation (44.1% (95% CI, 41.1–47.2%) vs 43.9% (95% CI, 40.1–47.0%)) and at any gestational age (35.2% (95% CI, 33.8–36.7%) vs 35.1% (95% CI, 33.7–36.6%)), at a 10% screen‐positive rate. Conclusions: The incidence of PE is higher in women living in the most deprived areas in South East England and in black women (vs those of other racial groups), who also live in areas of higher deprivation. However, in screening for PE, inclusion of IMD does not improve the prediction of PE provided by race and other maternal characteristics and elements of medical history. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective To determine whether ‘less tight’ (versus ‘tight’) control of nonsevere hypertension results in a difference in diastolic blood pressure (dBP) between groups. Design Randomised controlled trial (ISRCTN#57277508). Setting Seventeen obstetric centres in Canada, Australia, New Zealand, and UK. Population Inclusion: pregnant women, dBP 90–109 mmHg, pre-existing/gestational hypertension; live fetus(es); and 20–33+6 weeks. Exclusion: systolic blood pressure ≥ 170 mmHg and proteinuria, contraindication, or major fetal anomaly. Methods Randomisation to less tight (target dBP, 100 mmHg) or tight (target dBP, 85 mmHg) blood pressure control. Main outcome measures Primary: mean dBP at 28, 32 and 36 weeks. Secondary: clinician compliance and women’s satisfaction. Other: serious perinatal and maternal complications. Results A total of 132 women were randomised to less tight ( n= 66; seven had no study visit) or tight control ( n= 66; one was lost to follow up; seven had no study visit). Mean dBP was significantly lower with tight control: −3.5 mmHg, 95% credible interval (−6.4, −0.6). Clinician compliance was 79% in both groups. Women were satisfied with their care. With less tight (versus tight) control, the rates of other treatments and outcomes were the following: post-randomisation antenatal antihypertensive medication use: 46 (69.7%) versus 58 (89.2%), severe hypertension: 38 (57.6%) versus 26 (40.0%), proteinuria: 16 (24.2%) versus 20 (30.8%), serious maternal complications: 3 (4.6%) versus 2 (3.1%), preterm birth: 24 (36.4%) versus 26 (40.0%), birthweight: 2675 ± 858 versus 2501 ± 855 g, neonatal intensive care unit (NICU) admission: 15 (22.7%) versus 22 (34.4%), and serious perinatal complications: 9 (13.6%) versus 14 (21.5%). Conclusion The CHIPS pilot trial confirms the feasibility and importance of a large definitive trial to determine the effects of less tight control on serious perinatal and maternal complications. [ABSTRACT FROM AUTHOR]

Recurrent infections and low IgG treated with immunoglobulin replacement therapy have been reported in one patient [[3]]. Early recognition, evaluation, and appropriate treatment for immune abnormalities in patients with MOPD I/III may improve survival and quality of life for these patients. Based on the report of these 2 patients, as well as the I RNU4ATAC i spectrum disorder for which it is a part, immune deficiency is a likely feature of MOPD I/III, similar to other I RNU4ATAC i -opathies. Immunoglobulin replacement therapy may have decreased frequency and severity of infections and extended life expectancy for these patients. [Extracted from the article]

Objective: There is little evidence related to the effects of the Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant on pregnancy outcomes, particularly in unvaccinated women. This study aimed to compare pregnancy outcomes of unvaccinated women infected with SARS-CoV-2 during the pre-Delta, Delta and Omicron waves.Methods: This was a retrospective cohort study conducted at two tertiary care facilities: Sancaktepe Training and Research Hospital, Istanbul, Turkey, and St George's University Hospitals NHS Foundation Trust, London, UK. Included were women who tested positive for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction (RT-PCR) during pregnancy, between 1 April 2020 and 14 February 2022. The cohort was divided into three periods according to the date of their positive RT-PCR test: (i) pre-Delta (1 April 2020 to 8 June 2021 in Turkey, and 1 April 2020 to 31 July 2021 in the UK), (ii) Delta (9 June 2021 to 27 December 2021 in Turkey, and 1 August 2021 to 27 December 2021 in the UK) and (iii) Omicron (after 27 December 2021 in both Turkey and the UK). Baseline data collected included maternal age, parity, body mass index, gestational age at diagnosis and comorbidities. The primary outcome was the need for oxygen supplementation, classified as oxygen support via nasal cannula or breather mask, non-invasive mechanical ventilation with continuous positive airway pressure (CPAP) or high-flow oxygen, mechanical ventilation with intubation, or extracorporeal membrane oxygenation (ECMO). Inferences were made after balancing of confounders, using an evolutionary search algorithm. Selected confounders were maternal age, body mass index and gestational age at diagnosis of infection.Results: During the study period, 1286 unvaccinated pregnant women with RT-PCR-proven SARS-CoV-2 infection were identified, comprising 870 cases during the pre-Delta period, 339 during the Delta wave and 77 during the Omicron wave. In the confounder-balanced cohort, infection during the Delta wave vs during the pre-Delta period was associated with increased need for nasal oxygen support (risk ratio (RR), 2.53 (95% CI, 1.75-3.65); P < 0.001), CPAP or high-flow oxygen (RR, 2.50 (95% CI, 1.37-4.56); P = 0.002), mechanical ventilation (RR, 4.20 (95% CI, 1.60-11.0); P = 0.003) and ECMO (RR, 11.0 (95% CI, 1.43-84.7); P = 0.021). The maternal mortality rate was 3.6-fold higher during the Delta wave compared to the pre-Delta period (5.3% vs 1.5%, P = 0.010). Infection during the Omicron wave was associated with a similar need for nasal oxygen support (RR, 0.62 (95% CI, 0.25-1.55); P = 0.251), CPAP or high-flow oxygen (RR, 1.07 (95% CI, 0.36-3.12); P = 0.906) and mechanical ventilation (RR, 0.44 (95% CI, 0.06-3.45); P = 0.438) with that in the pre-Delta period. The maternal mortality rate was similar during the Omicron wave and the pre-Delta period (1.3% vs 1.3%, P = 0.999). The need for nasal oxygen support during the Omicron wave was significantly lower compared to the Delta wave (RR, 0.26 (95% CI, 0.11-0.64); P = 0.003). Perinatal outcomes were available for a subset of the confounder-balanced cohort. Preterm birth before 34 weeks' gestation was significantly increased during the Delta wave compared with the pre-Delta period (15.4% vs 4.9%, P < 0.001).Conclusions: Among unvaccinated pregnant women, SARS-CoV-2 infection during the Delta wave, in comparison to the pre-Delta period, was associated with increased requirement for oxygen support (including ECMO) and higher maternal mortality. Disease severity and pregnancy complications were similar between the Omicron wave and pre-Delta period. SARS-CoV-2 infection of unvaccinated pregnant women carries considerable risks of morbidity and mortality regardless of variant, and vaccination remains key. Miscommunication of the risks of Omicron infection may impact adversely vaccination uptake among pregnant women, who are at increased risk of complications related to SARS-CoV-2. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

I Sir, i We wish to thank Yoong et al. for their interest in our report on modifications to standard maternity care in the UK surveyed during the COVID-19 pandemic,1 and for their subsequent letter.2 We had reported the extent to which maternity services had been modified in the UK, in response to a need to protect staff and service users from the risk of infection with SARS-CoV-2, but also in response to staff shortages caused by redeployment and periods of staff self-isolation. Joint RCOG & RCM Statement - planning for Winter 2020/21: reducing the impact of COVID-19 on maternity services in the UK. 2020 [ www.rcog.org.uk/globalassets/documents/guidelines/2020-10-08-rcog%5frcm%5fwinter%5fsecondwave%5fstatement.pdf ]. [Extracted from the article]

Objective: Stillbirth is a potentially preventable complication of pregnancy. Identifying women at high risk of stillbirth can guide decisions on the need for closer surveillance and timing of delivery in order to prevent fetal death. Prognostic models have been developed to predict the risk of stillbirth, but none has yet been validated externally. In this study, we externally validated published prediction models for stillbirth using individual participant data (IPD) meta-analysis to assess their predictive performance.Methods: MEDLINE, EMBASE, DH-DATA and AMED databases were searched from inception to December 2020 to identify studies reporting stillbirth prediction models. Studies that developed or updated prediction models for stillbirth for use at any time during pregnancy were included. IPD from cohorts within the International Prediction of Pregnancy Complications (IPPIC) Network were used to validate externally the identified prediction models whose individual variables were available in the IPD. The risk of bias of the models and cohorts was assessed using the Prediction study Risk Of Bias ASsessment Tool (PROBAST). The discriminative performance of the models was evaluated using the C-statistic, and calibration was assessed using calibration plots, calibration slope and calibration-in-the-large. Performance measures were estimated separately in each cohort, as well as summarized across cohorts using random-effects meta-analysis. Clinical utility was assessed using net benefit.Results: Seventeen studies reporting the development of 40 prognostic models for stillbirth were identified. None of the models had been previously validated externally, and the full model equation was reported for only one-fifth (20%, 8/40) of the models. External validation was possible for three of these models, using IPD from 19 cohorts (491 201 pregnant women) within the IPPIC Network database. Based on evaluation of the model development studies, all three models had an overall high risk of bias, according to PROBAST. In the IPD meta-analysis, the models had summary C-statistics ranging from 0.53 to 0.65 and summary calibration slopes ranging from 0.40 to 0.88, with risk predictions that were generally too extreme compared with the observed risks. The models had little to no clinical utility, as assessed by net benefit. However, there remained uncertainty in the performance of some models due to small available sample sizes.Conclusions: The three validated stillbirth prediction models showed generally poor and uncertain predictive performance in new data, with limited evidence to support their clinical application. The findings suggest methodological shortcomings in their development, including overfitting. Further research is needed to further validate these and other models, identify stronger prognostic factors and develop more robust prediction models. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

The neutrophil–lymphocyte ratio (NLR) and the absolute lymphocyte count (ALC) have been proposed as prognostic markers in non-small cell lung cancer (NSCLC). The objective of this study was to examine the association of NLR/ALC before and after curative-intent radiotherapy for NSCLC on disease recurrence and overall survival. A retrospective study of consecutive patients who underwent curative-intent radiotherapy for NSCLC across nine sites in the UK from 1 October 2014 to 1 October 2016. A multivariate analysis was carried out to assess the ability of pre-treatment NLR/ALC, post-treatment NLR/ALC and change in NLR/ALC, adjusted for confounding factors using the Cox proportional hazards model, to predict disease recurrence and overall survival within 2 years of treatment. In total, 425 patients were identified with complete blood parameter values. None of the NLR/ALC parameters were independent predictors of disease recurrence. Higher pre-NLR, post-NLR and change in NLR plus lower post-ALC were all independent predictors of worse survival. Receiver operator curve analysis found a pre-NLR > 2.5 (odds ratio 1.71, 95% confidence interval 1.06–2.79, P < 0.05), a post-NLR > 5.5 (odds ratio 2.36, 95% confidence interval 1.49–3.76, P < 0.001), a change in NLR >3.6 (odds ratio 2.41, 95% confidence interval 1.5–3.91, P < 0.001) and a post-ALC < 0.8 (odds ratio 2.86, 95% confidence interval 1.76–4.69, P < 0.001) optimally predicted poor overall survival on both univariate and multivariate analysis when adjusted for confounding factors. Median overall survival for the high-versus low-risk groups were: pre-NLR 770 versus 1009 days (P = 0.34), post-NLR 596 versus 1287 days (P ≤ 0.001), change in NLR 553 versus 1214 days (P ≤ 0.001) and post-ALC 594 versus 1287 days (P ≤ 0.001). NLR and ALC, surrogate markers for systemic inflammation, have prognostic value in NSCLC patients treated with curative-intent radiotherapy. These simple and readily available parameters may have a future role in risk stratification post-treatment to inform the intensity of surveillance protocols. • Multi-centre UK study of 425 patients undergoing curative intent radiotherapy for NSCLC. • Higher pre-NLR, post-NLR and change in NLR plus lower post-ALC were all independent predictors of worse survival. • Pre-NLR > 2.5, post-NLR > 5.5, change in NLR > 3.6 and post-ALC < 0.8 optimally predicted poor survival. • Median OS high vs low-risk group: pre-NLR 770 vs 1009, post-NLR 596 vs 1287, change in NLR 553 vs 1214 and post-ALC 594 vs 1287 days. [ABSTRACT FROM AUTHOR]

Recent research has shown an association between monthly law enforcement drug seizure events and accidental drug overdose deaths using cross-sectional data in a single state, whereby increased seizures correlated with more deaths. In this study, we conduct statistical analysis of street-level data on law enforcement drug seizures, along with street-level data on fatal and non-fatal overdose events, to determine possible micro-level causal associations between opioid-related drug seizures and overdoses. For this purpose, we introduce a novel, modified two-process Knox test that controls for self-excitation to measure clustering of overdoses nearby in space and time following law enforcement seizures. We observe a small, but statistically significant (p < 0.001), effect of 17.7 excess non-fatal overdoses per 1000 law enforcement seizures within three weeks and 250 m of a seizure. We discuss the potential causal mechanism for this association along with policy implications. [ABSTRACT FROM AUTHOR]

Historically, pregnant women have been excluded from the majority of drug and vaccine trials, a practice that has been criticized widely by the scientific community1-3. The principles of this vaccination technology should also apply to COVID-19 vaccines and provides generic reassurance around the use of mRNA vaccines in pregnancy. Available SARS-CoV-2 vaccines and their safety profiles Four different types of COVID-19 vaccine are currently available (Table 3): mRNA, viral vector, inactivated virus and recombinant antigen. As with the mRNA vaccines, there are limited data on the safety of adenovirus vector-based vaccines in pregnancy, though adenovirus vector-based Zika virus vaccines have been tested in pregnant mice without safety concerns35. [Extracted from the article]

There is a paucity of evidence on which to produce recommendations on neither the clinical nor the imaging follow-up of lung cancer patients after curative-intent radiotherapy. In the 2019 National Institute for Health and Care Excellence lung cancer guidelines, further research into risk-stratification models to inform follow-up protocols was recommended. A retrospective study of consecutive patients undergoing curative-intent radiotherapy for non-small cell lung cancer from 1 October 2014 to 1 October 2016 across nine UK trusts was carried out. Twenty-two demographic, clinical and treatment-related variables were collected and multivariable logistic regression was used to develop and validate two risk-stratification models to determine the risk of disease recurrence and death. In total, 898 patients were included in the study. The mean age was 72 years, 63% (562/898) had a good performance status (0–1) and 43% (388/898), 15% (134/898) and 42% (376/898) were clinical stage I, II and III, respectively. Thirty-six per cent (322/898) suffered disease recurrence and 41% (369/898) died in the first 2 years after radiotherapy. The ASSENT score (age, performance status, smoking status, staging endobronchial ultrasound, N-stage, T-stage) was developed, which stratifies the risk for disease recurrence within 2 years, with an area under the receiver operating characteristic curve (AUROC) for the total score of 0.712 (0.671–0.753) and 0.72 (0.65–0.789) in the derivation and validation sets, respectively. The STEPS score (sex, performance status, staging endobronchial ultrasound, T-stage, N-stage) was developed, which stratifies the risk of death within 2 years, with an AUROC for the total score of 0.625 (0.581–0.669) and 0.607 (0.53–0.684) in the derivation and validation sets, respectively. These validated risk-stratification models could be used to inform follow-up protocols after curative-intent radiotherapy for lung cancer. The modest performance highlights the need for more advanced risk prediction tools. • Two validated risk prediction models for disease recurrence and death are presented. • The performance of the scores are modest. • Rates of further curative intent treatment for disease recurrence were low (4%). • The majority with disease recurrence were managed with best supportive care (57%). • More advanced risk prediction tools and research into optimal follow-up is needed. [ABSTRACT FROM AUTHOR]

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and has significant alterations to its spike protein structure, providing it with significant ability to evade immune response elicited by coronavirus disease 2019 (COVID-19) vaccines1. However, these reports are based on data derived mostly from countries with a high vaccination rate, and there are no data on the outcome of Omicron variant infection in vaccinated and unvaccinated pregnant women. Our findings emphasize the importance of full SARS-CoV-2 vaccination to protect pregnant women during the Omicron wave despite its apparently lower effectiveness against PCR-confirmed infection with the Omicron variant11. [Extracted from the article]

Background: Stillbirth accounts for over 2 million deaths a year worldwide and rates remains stubbornly high. Multivariable prediction models may be key to individualised monitoring, intervention or early birth in pregnancy to prevent stillbirth. Objectives: To collate and evaluate systematic reviews of factors associated with stillbirth in order to identify variables relevant to prediction model development. Search strategy: MEDLINE, Embase, DARE and Cochrane Library databases and reference lists were searched up to November 2019. Selection criteria: We included systematic reviews of association of individual variables with stillbirth without language restriction. Data collection and analysis: Abstract screening and data extraction were conducted in duplicate. Methodological quality was assessed using AMSTAR and QUIPS criteria. The evidence supporting association with each variable was graded. Results: The search identified 1198 citations. Sixty‐nine systematic reviews reporting 64 variables were included. The most frequently reported were maternal age (n = 5), body mass index (n = 6) and maternal diabetes (n = 5). Uterine artery Doppler appeared to have the best performance of any single test for stillbirth. The strongest evidence of association was for nulliparity and pre‐existing hypertension. Conclusion: We have identified variables relevant to the development of prediction models for stillbirth. Age, parity and prior adverse pregnancy outcomes had a more convincing association than the best performing tests, which were PAPP‐A, PlGF and UtAD. The evidence was limited by high heterogeneity and lack of data on intervention bias. Review shows key predictors for use in developing models predicting stillbirth include age, prior pregnancy outcome and PAPP‐A, PLGF and Uterine artery Doppler. Review shows key predictors for use in developing models predicting stillbirth include age, prior pregnancy outcome and PAPP‐A, PLGF and Uterine artery Doppler. [ABSTRACT FROM AUTHOR]

Background and purpose: There is a lack of comparative safety data on the risk of pseudotumor cerebri syndrome (PTCS) associated with different hormonal contraceptives. We sought to quantify the risk of PTCS associated with eight different types of hormonal contraceptives compared with oral levonorgestrel. Methods: We conducted a retrospective cohort study, with a case–control analysis of 4 871 504 women aged 15–45 years in the period 2008–2015, using IQVIA Ambulatory Electronic Medical Records data in the USA. Patients who used nine different contraceptive agents including intrauterine levonorgestrel, medroxyprogesterone injection, etonogestrel/ethinyl estradiol vaginal ring and combination oral contraceptives (COCs) that contained ethinyl estradiol and the progestins levonorgestrel, norgestimate, desogestrel, norethindrone and drospirenone, were included. Diagnosis of PTCS was defined using the first International Classification of Diseases, 9th or 10th revision, code for intracranial hypertension in patients who had also received an imaging code in the 30 days prior to the index date. Results: A total of 3323 PTCS cases and 13 292 matched controls were identified. No increase in risk was found when analysing intrauterine levonorgestrel or COCs containing desogestrel, norethindrone, drospirenone, norgestimate or norgestrel versus COC levonorgestrel. The adjusted incidence rate ratio for etonogestrel/etonogestrel/ethinyl estradiol vaginal ring and medroxyprogesterone suspension compared with levonorgestrel COC was 4.45 [95% confidence interval (CI) 1.98–9.96] and 2.20 (95% CI 1.33–3.64), respectively. Conclusions: This study found an elevated risk for PTCS among users of etonogestrel vaginal ring and medroxyprogesterone suspension when compared with oral levonorgestrel. Future studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Developing a shared agenda is an important step in ensuring future research has the necessary relevance.Objective: To characterise research priority setting partnerships (PSPs) relevant to women's health.Search Strategy: Included studies were identified by searching MEDLINE and the James Lind Alliance (JLA) database.Selection Criteria: Priority setting partnerships using formal consensus methods.Data Collection and Analysis: Descriptive narrative to describe the study characteristics, methods, and results.Main Results: Ten national and two international PSPs were identified. All PSPs used the JLA method to identify research priorities. Nine PSPs had published a protocol. Potential research uncertainties were gathered from guidelines (two studies), Cochrane reviews (five studies), and surveys (12 studies). The number of healthcare professionals (31-287), patients (44-932), and others (33-139) who responded to the survey, and the number of uncertainties submitted (52-4767) varied. All PSPs entered confirmed research uncertainties (39-104) into interim priority setting surveys and healthcare professionals (31-287), patients (44-932), and others (33-139) responded. All PSPs entered a short list of research uncertainties into a consensus development meeting, which enabled healthcare professionals (six to 21), patients (eight to 14), and others (two to 13) to identify research priorities (ten to 15). Four PSPs have published their results.Conclusion: Future research priority setting studies should publish a protocol, use formal consensus development methods, and ensure their methods and results are comprehensively reported.Tweetable Abstract: Research published in @BJOGtweets highlights future research priorities across women's health, including @FertilityTop10, @jamesmnduffy. [ABSTRACT FROM AUTHOR]

Objectives: Fetal growth restriction (FGR) is associated with maternal cardiovascular changes. Sildenafil, a phosphodiesterase type-5 inhibitor, potentiates the actions of nitric oxide, and it has been suggested that it alters maternal hemodynamics, potentially improving placental perfusion. Recently, the Dutch STRIDER trial was stopped prematurely owing to excess neonatal mortality secondary to pulmonary hypertension. The main aim of this study was to investigate the effect of sildenafil on maternal hemodynamics in pregnancies with severe early-onset FGR.Methods: This was a cardiovascular substudy within a UK multicenter, placebo-controlled trial, in which 135 women with a singleton pregnancy and severe early-onset FGR (defined as a combination of estimated fetal weight or abdominal circumference below the 10th centile and absent/reversed end-diastolic flow in the umbilical artery on Doppler velocimetry, diagnosed between 22 + 0 and 29 + 6 weeks' gestation) were assigned randomly to receive either 25 mg sildenafil three times daily or placebo until 32 + 0 weeks' gestation or delivery. Maternal blood pressure (BP), heart rate (HR), augmentation index, pulse wave velocity (PWV), cardiac output, stroke volume (SV) and total peripheral resistance were recorded before randomization, 1-2 h and 48-72 h post-randomization, and 24-48 h postnatally. For continuous data, analysis was performed using repeated measures ANOVA methods including terms for timepoint, treatment allocation and their interaction.Results: Included were 134 women assigned randomly to sildenafil (n = 69) or placebo (n = 65) who had maternal BP and HR recorded at baseline. At 1-2 h post-randomization, compared with baseline values, sildenafil increased maternal HR by 4 bpm more than did placebo (mean difference, 5.00 bpm (95% CI, 1.00-12.00 bpm) vs 1.25 bpm (95% CI, -5.38 to 7.88 bpm); P = 0.004) and reduced systolic BP by 1 mmHg more (mean difference, -4.13 mmHg (95% CI, -9.94 to 1.44 mmHg) vs -2.75 mmHg (95% CI, -7.50 to 5.25 mmHg); P = 0.048). Even after adjusting for maternal mean arterial pressure, sildenafil reduced aortic PWV by 0.60 m/s more than did placebo (mean difference, -0.90 m/s (95% CI, -1.31 to -0.51 m/s) vs -0.26 m/s (95% CI, -0.75 to 0.59 m/s); P = 0.001). Sildenafil was associated with a non-significantly greater decrease in SV index after 1-2 h post-randomization than was placebo (mean difference, -5.50 mL/m2 (95% CI, -11.00 to -0.50 mL/m2 ) vs 0.00 mL/m2 (95% CI, -5.00 to 4.00 mL/m2 ); P = 0.056).Conclusions: Sildenafil in a dose of 25 mg three times daily increases HR, reduces BP and reduces arterial stiffness in pregnancies complicated by severe early-onset FGR. These changes are short term, modest and consistent with the anticipated vasodilatory effect. They have no short- or long-term clinical impact on the mother. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of maternal ethnicity on the risk of adverse perinatal outcome in pregnant women with chronic hypertension.Methods: Demographic and delivery data were collated of women with chronic hypertension and singleton pregnancy who delivered at one of three UK obstetric units between 2000 and 2014. Multivariable logistic regression models were used to calculate risk ratios (RR), according to ethnic group, for adverse perinatal outcome, adjusted for other maternal characteristics including age, parity, body mass index, smoking status, deprivation index and year of delivery. The impact of maternal ethnicity on birth-weight centile calculation was investigated by comparing the birth-weight centile chart customized for ethnicity (Gestation Related Optimal Weight; GROW) with a birth-weight centile calculator that does not adjust for that factor (INTERGROWTH-21st ).Results: The study cohort included 4481 pregnancies (4045 women) with chronic hypertension. Women of white ethnicity accounted for 47% (n = 2122) of the cohort and 36% (n = 1601) were of black, 8.5% (n = 379) of Asian and 8.5% (n = 379) of other ethnicity. The overall incidence of stillbirth was 1.6%, that of preterm birth < 37 weeks was 16% and that of fetal growth restriction (birth weight < 3rd centile) was 11%. Black women, compared with white women, had the highest risk for all adverse perinatal outcomes, with stillbirth occurring in 3.1% vs 0.6% of pregnancies (adjusted RR (aRR), 5.56 (95% CI, 2.79-11.09)), preterm birth < 37 weeks in 21% vs 11% (aRR, 1.70 (95% CI, 1.43-2.01)) and birth weight < 3rd centile in 15% vs 7.4% (aRR, 2.07 (95% CI, 1.71-2.51)). Asian women, compared with white women, were also at increased risk of adverse perinatal outcome, with stillbirth occurring in 1.6% vs 0.6% (aRR, 3.03 (95% CI, 1.11-8.28)), preterm birth < 37 weeks in 20% vs 11% (aRR, 1.82 (95% CI, 1.41-2.35)) and birth weight < 3rd centile in 12% vs 7.4% (aRR, 1.69 (95% CI, 1.24-2.30)). The sensitivity and specificity for prediction of infants requiring neonatal unit admission were 40% and 93%, respectively, for those with birth weight < 3rd centile according to GROW charts, compared with 16% and 96%, respectively, for those with birth weight < 3rd centile according to INTERGROWTH-21st charts.Conclusions: Black ethnicity, compared with white, is associated with the greatest risk of adverse perinatal outcome in women with chronic hypertension, even after adjusting for other maternal characteristics. Women of Asian ethnicity are also at increased risk, but to a lesser extent. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Newborn screening (NBS) for severe combined immunodeficiency (SCID) can identify infants with non-SCID T cell lymphopenia (TCL). The purpose of this study was to characterize the natural history and genetic findings of infants with non-SCID TCL identified on NBS. We analyzed data from 80 infants with non-SCID TCL in the mid-Atlantic region between 2012 and 2019. 66 patients underwent genetic testing and 41 (51%) had identified genetic variant(s). The most common genetic variants were thymic defects (33%), defects with unknown mechanisms (12%) and bone marrow production defects (5%). The genetic cohort had significantly lower median initial CD3+, CD4+, CD8+ and CD4/CD45RA+ T cell counts compared to the non-genetic cohort. Thirty-six (45%) had either viral, bacterial, or fungal infection; only one patient had an opportunistic infection (vaccine strain VZV infection). Twenty-six (31%) of patients had resolution of TCL during the study period. • Newborn screening for severe combined immunodeficiency can detect T cell lymphopenia. • There is limited data on the cause or natural history of idiopathic T lymphopenia. • 51% of infants had genetic findings; these infants had lower initial T cell counts. • 45% had infection but only one patient had opportunistic infection. • 31% had resolution of lymphopenia during the study. [ABSTRACT FROM AUTHOR]

Conclusions COVID-19 mRNA vaccination in pregnancy appears to be effective in preventing proven SARS-CoV-2 infection in pregnancy. To synthesise evidence on vaccine effectiveness and perinatal outcomes after COVID-19 vaccination in pregnancy. Studies reporting perinatal outcomes or vaccine effectiveness after COVID-19 vaccination in pregnancy were included. [Extracted from the article]

Objective Pre-eclampsia involves a maternal inflammatory response that differs from both normal pregnancy and normotensive intrauterine growth restriction (IUGR). Our objective was to examine neutrophil Toll-like receptor (TLR), cryopyrin, nuclear factor-κB (NF-κB) subunit and interleukin-1β (IL-1β), and inflammatory cytokine profiles in women with pre-eclampsia or normotensive IUGR, as well as in normal pregnancy and non-pregnancy controls. Design and method A case–control study was performed. We examined the messenger RNA (mRNA) and protein expressions of TLR4 and TLR2, mRNA levels of cryopyrin, IL-1β, NF-κB subunits p50 and p65, as well as maternal serum inflammatory cytokine profiles (IL-2, IL-6, tumour necrosis factor-α [TNF-α], interferon-γ [IFN-γ] and IL-10) in women with and without pre-eclampsia using real-time reverse transcription polymerase chain reactions, flow cytometry and multiplex immunoassays. Setting A single tertiary maternity hospital in Vancouver, Canada. Population Women with early-onset pre-eclampsia (<34 weeks of gestation, n = 25), women with late-onset pre-eclampsia (≥34+0 weeks of gestation, n = 25), women with normotensive IUGR ( n = 25), women with normal pregnancy ( n = 75) and non-pregnancy ( n = 25) controls. Results Women with pre-eclampsia (as a single combined group of early- and late-onset, and particularly in women with early-onset pre-eclampsia) had increased TLR2 and TLR4 mRNA and protein expressions elevated cryopyrin, NF-κB subunit, and IL-1β mRNA expression, and TNF-α:IL-10 and IL-6:IL-10 ratios compared with other groups. Conclusions These data suggest that TLRs and cryopyrin may modulate the innate immune response of the maternal syndrome of pre-eclampsia, and might also trigger the differential inflammatory response existing between early onset pre-eclampsia and normotensive IUGR. [ABSTRACT FROM AUTHOR]

Background: We investigated the relation between fetoplacental growth and the use of oral antihypertensive medication to treat mild-to-moderate pregnancy hypertension.Methods: The study design was a metaregression analysis of published data from randomised controlled trials. Data from a paper that was regarded as an extreme statistical outliner were excluded from primary analyses. The change in (group) mean arterial pressure (MAP) from enrolment to delivery was compared with indicators of fetoplacental growth.Findings: Greater mean difference in MAP with antihypertensive therapy was associated with the birth of a higher proportion of small-for-gestational-age (SGA) infants (slope: 0.09 [SD 0.03], r2=0.48, p=0.006, 14 trials) and lower mean birthweight significant after exclusion of data from another paper regarded as an extreme statistical outliner (slope: -14.49 [6.98] r=0.16, p=0.049, 27). No relation with mean placental weight was seen (slope -2.01 [1.62], r2=0.15, p=0.25, 11 trials).Interpretation: Treatment-induced falls in maternal blood pressure may adversely affect fetal growth. Given the small maternal benefits that are likely to be derived from therapy, new data are urgently needed to elucidate the relative maternal and fetal benefits and risks of oral antihypertensive drug treatment of mild-to-moderate pregnancy hypertension. [ABSTRACT FROM AUTHOR]

SummaryBackgroundWe investigated the relation between fetoplacental growth and the use of oral antihypertensive medication to treat mild-to-moderate pregnancy hypertension.MethodsThe study design was a metaregression analysis of published data from randomised controlled trials. Data from a paper that was regarded as an extreme statistical outliner were excluded from primary analyses. The change in (group) mean arterial pressure (MAP) from enrolment to delivery was compared with indicators of fetoplacental growth.FindingsGreater mean difference in MAP with antihypertensive therapy was associated with the birth of a higher proportion of small-for-gestational-age (SGA) infants (slope: 0.09 [SD 0.03], r [sup2]=0.48, p=0.006, 14 trials) and lower mean birthweight significant after exclusion of data from another paper regarded as an extreme statistical outliner (slope: -14.49 [6.98] r [sup2]=0.16, p=0.049, 27). No relation with mean placental weight was seen (slope -2.01 [1.62], r [sup2]=0.15, p=0.25, 11 trials).InterpretationTreatment-induced falls in maternal blood pressure may adversely affect fetal growth. Given the small maternal benefits that are likely to be derived from therapy, new data are urgently needed to elucidate the relative maternal and fetal benefits and risks of oral antihypertensive drug treatment of mild-to-moderate pregnancy hypertension. [ABSTRACT FROM AUTHOR]

Assesses an interactive system (PAPNET) for primary screening of cervical or pap smears. How technology for computer-assisted screening of cervical smears uses neural networks which could potentially decrease the number of screening errors and improve productivity; Background; Methods; Findings; Interpretation.

Users immersed in virtual environments (VEs) are prone to disorientation and have difficulty transferring spatial knowledge to the real world. A single experiment investigated the contribution of inadequate proprioception to this problem by providing participants with interfaces to a virtual environment that either did (a walking interface) or did not (a joystick) afford proprioceptive feedback similar to that obtained during real walking. The 2 groups explored a large, complex building using a low-resolution head-mounted display. Later, their navigational abilities within the actual building were compared with those of control groups who either studied a map of the building, walked through the real building, or received no prior training. The walking interface conveyed no benefit on an orientation task performed during training in the VE, but it did benefit participants when they tried to find objects in the real world. Actual or potential applications include simulations of environments that are normally explored on foot but cannot be readily visited, such as infantry battlefields and facilities contaminated with chemical, biological, or radiological materials. [ABSTRACT FROM AUTHOR]

Ling et al. ( I BJOG i 2020;127:1018-25) have contributed important information on cardiovascular (CV) assessment over the course of pregnancy, with and without aspirin treatment, associated with risk of preterm pre-eclampsia, as assessed by the multivariable competing risks model at 11-13 weeks. First, women at low (versus high) risk of preterm pre-eclampsia appear to have lower cardiac output (CO), stroke volume (SV) and blood pressure (BP) in early pregnancy, consistent with the hypothesis that maternal CV predisposition plays a major role in pre-eclampsia risk (Ridder et al. I Int J Mol Sci i 2019;20:3263). Although the authors were concerned that aspirin might disrupt the vasoconstrictor/vasodilator balance in high-risk women, there was no evidence of this, despite aspirin significantly decreasing the incidence of preterm pre-eclampsia (Rolnik et al. I N Engl J Med i 2017;377:613-22). [Extracted from the article]

The main aim of this study was to investigate the effect of sildenafil on maternal hemodynamics in pregnancies complicated by severe early-onset fetal growth restriction (FGR). The maternal blood pressure (BP), heart rate (HR), augmentation index (AIx), pulse wave velocity (PWV), cardiac output (CO), stroke volume (SV) and total peripheral resistance (TPR) were recorded before, one hour after, and 48-72 hours post-randomisation, and postnatally. [Extracted from the article]