Cytokines in Bladder Pain Syndrome: A Review of the Literature.

INTRODUCTION AND HYPOTHESIS: Bladder pain syndrome (BPS) is poorly understood with both the aetiology and pathophysiology being unknown. Symptoms overlap with other disorders, such as overactive bladder (OAB) and chronic pelvic pain disorders such as endometriosis, making a consensus on how to diagnosis and manage patients challenging. The development of biomarkers for BPS may be the key to understanding more about its pathophysiology, as well as aiding diagnosis, subclassification, and discovering new drug targets for its management. As inflammation is widely understood to hold a central role in BPS, the evaluation of cytokines has gained interest. This article summarises the current literature and understanding of urinary, serum, and bladder tissue cytokines found elevated in patients with bladder pain syndrome. METHODS: literature search using Pub Med with the keywords "bladder pain syndrome", "painful bladder syndrome", "bladder pain", "Interstitial cystitis" AND "cytokines" or "inflammation". This study was except from institutional approval. RESULTS: Thirty-six cytokines have been identified as being statistically significantly elevated in either the serum, urine, or bladder tissue of patients with bladder pain syndrome in the 22 studies identified in this review of the literature. These cytokines include those from the interleukin group (n = 14), the CXC chemokine group (n = 5), and the C-C chemokine group (n = 7). CONCLUSIONS: CXCL-1, CXCL-8, CXCL-9, CXCL-10, CXCL-11 from the CXC chemokine group, and CCL2, CCL4, CCL5, CCL7, and CCL11 from the C-C chemokine group have been found to be significantly elevated in patients with bladder pain in the literature. Many of these analytes also have supporting evidence for their roles in bladder pain from animal models and studies in other chronic inflammatory conditions. It is likely that a single cytokine will not serve as an adequate biomarker of disease in bladder pain syndrome for either diagnosis or disease severity. Instead, panels of inflammatory mediators may reveal more about the different pathways of inflammation leading to similar presentations of bladder pain in patients.

Retrospective cohort study of the association between socioeconomic deprivation and incidence of gestational diabetes and perinatal outcomes.

INTRODUCTION: Socioeconomic disparities have been shown to correlate with perinatal mortality and the incidence of type 2 diabetes. Few studies have explored the relationship between deprivation and the incidence of gestational diabetes (GDM). We aimed to identify the relationship between deprivation and incidence of GDM, after adjusting for age, BMI, and ethnicity. We also examined for relationships between deprivation and perinatal outcomes. METHODS: A retrospective cohort analysis of 23,490 pregnancies from a major National Health Service Trust in Northwest London was conducted. The 2019 English Indices of Multiple Deprivation was used to identify the deprivation rank and decile for each postcode. Birthweight centile was calculated from absolute birthweight after adjusting for ethnicity, maternal height, maternal weight, parity, sex and outcome (live birth/stillbirth). Logistic regression and Kendall's Tau were used to identify relationships between variables. RESULTS: After controlling for age, BMI & ethnicity, Index of Multiple Deprivation postcode decile was not associated with an increased risk of developing gestational diabetes. Each increase in decile of deprivation was associated with an increase in birthweight centile by 0.471 (p < 0.001). After adjusting for confounders, age was associated with a 7.1% increased GDM risk (OR: 1.076, p < 0.001); BMI increased risk by 5.81% (OR: 1.059, p < 0.001). There was no significant correlation between Index of Multiple Deprivation rank and perinatal outcomes. DISCUSSION: Our analysis demonstrates that socioeconomic deprivation was not associated with incidence of GDM or adverse perinatal outcomes. Factors such as genetic predisposition and lifestyle habits may likely play a larger role in the development of GDM compared to socioeconomic deprivation alone.

Inequalities in smoking among pregnant women in North West London.

BACKGROUND: London has the lowest smoking prevalence among pregnant women in England. However, it was unclear whether the low overall prevalence masked inequalities. This study investigated the prevalence of smoking among pregnant women in North West London stratified by ethnicity and deprivation. METHODS: Data regarding smoking status, ethnicity and deprivation were extracted from electronic health records collected by maternity services at Imperial Healthcare NHS Trust between January 2020 and August 2022. RESULTS: A total of 25 231 women were included in this study. At the time of booking of antenatal care (mean of 12 weeks), 4% of women were current smokers, 17% were ex-smokers and 78% never smokers. There were marked differences in the smoking prevalence between ethnic groups. Women of Mixed-White and Black Caribbean ethnicity and White Irish women had the highest prevalence of smoking (12 and 9%, respectively). There was an over 4-fold increase in the prevalence of smoking between the most and the least deprived groups (5.6 versus 1.3%). CONCLUSIONS: Even in a population with an overall low prevalence of smoking in pregnancy, women experiencing deprivation and from certain ethnic backgrounds have a high smoking prevalence and hence are the most likely to benefit from smoking cessation interventions.

Current practice in the diagnosis and management of fetal growth restriction: An international survey.

INTRODUCTION: The aim of this survey was to evaluate the current practice in respect of diagnosis and management of fetal growth restriction among obstetricians in different countries. MATERIAL AND METHODS: An e-questionnaire was sent via REDCap with "click thru" links in emails and newsletters to obstetric practitioners in different countries and settings with different levels of expertise. Clinical scenarios in early and late fetal growth restriction were given, followed by structured questions/response pairings. RESULTS: A total of 275 participants replied to the survey with 87% of responses complete. Participants were obstetrician/gynecologists (54%; 148/275) and fetal medicine specialists (43%; 117/275), and the majority practiced in a tertiary teaching hospital (56%; 153/275). Delphi consensus criteria for fetal growth restriction diagnosis were used by 81% of participants (223/275) and 82% (225/274) included a drop in fetal growth velocity in their diagnostic criteria for late fetal growth restriction. For early fetal growth restriction, TRUFFLE criteria were used for fetal monitoring and delivery timing by 81% (223/275). For late fetal growth restriction, indices of cerebral blood flow redistribution were used by 99% (250/252), most commonly cerebroplacental ratio (54%, 134/250). Delivery timing was informed by cerebral blood flow redistribution in 72% (176/244), used from ≥32 weeks of gestation. Maternal biomarkers and hemodynamics, as additional tools in the context of early-onset fetal growth restriction (≤32 weeks of gestation), were used by 22% (51/232) and 46% (106/230), respectively. CONCLUSIONS: The diagnosis and management of fetal growth restriction are fairly homogeneous among different countries and levels of practice, particularly for early fetal growth restriction. Indices of cerebral flow distribution are widely used in the diagnosis and management of late fetal growth restriction, whereas maternal biomarkers and hemodynamics are less frequently assessed but more so in early rather than late fetal growth restriction. Further standardization is needed for the definition of cerebral blood flow redistribution.

SARS-CoV-2 (COVID-19): What Do We Know About Children? A Systematic Review.

BACKGROUND: Few pediatric cases of coronavirus disease 2019 (COVID-19) have been reported and we know little about the epidemiology in children, although more is known about other coronaviruses. We aimed to understand the infection rate, clinical presentation, clinical outcomes, and transmission dynamics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in order to inform clinical and public health measures. METHODS: We undertook a rapid systematic review and narrative synthesis of all literature relating to SARS-CoV-2 in pediatric populations. The search terms also included SARS-CoV and MERS-CoV. We searched 3 databases and the COVID-19 resource centers of 11 major journals and publishers. English abstracts of Chinese-language papers were included. Data were extracted and narrative syntheses conducted. RESULTS: Twenty-four studies relating to COVID-19 were included in the review. Children appear to be less affected by COVID-19 than adults by observed rate of cases in large epidemiological studies. Limited data on attack rate indicate that children are just as susceptible to infection. Data on clinical outcomes are scarce but include several reports of asymptomatic infection and a milder course of disease in young children, although radiological abnormalities are noted. Severe cases are not reported in detail and there are few data relating to transmission. CONCLUSIONS: Children appear to have a low observed case rate of COVID-19 but may have rates similar to adults of infection with SARS-CoV-2. This discrepancy may be because children are asymptomatic or too mildly infected to draw medical attention and be tested and counted in observed cases of COVID-19.

Umbilical venous flow rate in term fetuses: can variations in flow predict intrapartum compromise?

OBJECTIVE: The objective of the study was to investigate the distribution of umbilical venous flow rates, measured in early labor, in a cohort of normal term pregnancies and to establish the relationship between umbilical venous flow and subsequent intrapartum outcome. STUDY DESIGN: Five hundred eighty-nine women with uncomplicated, term, singleton pregnancies were recruited to this prospective observational study prior to active labor (dilation of 4 cm or less) at Queen Charlotte's and Chelsea Hospital (London, UK). All participants underwent an ultrasound examination, during which fetal biometry, umbilical venous flow velocity, and umbilical vein diameter were recorded. Umbilical venous flow rate was then calculated. Following delivery, intrapartum and neonatal outcomes were correlated with the ultrasound findings. Cases were subdivided according to mode of delivery, and mean umbilical venous flow rates were compared between the groups. Cases were also subdivided according to umbilical venous flow rate (less than the 20th centile, 20th-80th centile, and greater than the 80th centile), and the incidence of diagnoses of fetal compromise was compared. RESULTS: Fetuses delivered by emergency cesarean for presumed fetal compromise had the lowest umbilical venous flow rates (both corrected for and uncorrected for birthweight) (P = .02 and P = .001, respectively). Fetuses with the lowest umbilical venous flow rates were significantly more likely to require emergency cesarean for presumed fetal compromise than those with the highest flow rates (15.7% vs 5.6%, relative risk, 2.83; 95% confidence interval, 1.16-6.91). CONCLUSION: Fetuses with the lowest umbilical venous flow rates are at increased risk of a subsequent diagnosis of intrapartum fetal compromise. Measurement of umbilical venous flow could contribute to the risk stratification of pregnancies prior to labor.

Are 1st-trimester ß-human chorionic gonadotrophin and pregnancy-associated plasma protein A levels predictive of intrapartum fetal compromise in a selected normal population?

BACKGROUND: The incidence of cerebral palsy in term infants has not changed over the last 30 years. Current intrapartum monitoring techniques are limited by their inherent poor specificity. Changes in fetal haemodynamics in the term fetus, similar to those seen in fetal growth restriction, have been associated with an increased risk of subsequent intrapartum fetal compromise. Alterations in first-trimester ß-hCG and PAPP-A levels are predictive of fetal growth restriction. AIMS: In this study, we aimed to establish whether first-trimester ß-hCG and PAPP-A levels were predictive of fetal compromise in labour and whether these first-trimester markers could be correlated with fetal haemodynamics at term in a low-risk population. MATERIALS AND METHODS: Over a two-year period, 427 women with low risk, uncomplicated pregnancies were recruited to this study. All participants underwent a prelabour ultrasound examination during which fetal biometry and haemodynamics were assessed. First-trimester ß-hCG and PAPP-A levels were recorded from the case notes. All cases were followed up within 48 hours of delivery, and first-trimester ß-hCG and PAPP-A levels correlated with intrapartum outcomes and fetal haemodynamics. RESULTS: No significant relationship between first-trimester ß-hCG and PAPP-A levels and subsequent intrapartum fetal compromise was observed. Weak but significant correlations were observed between ß-hCG levels and umbilical venous flow rate, as well as PAPP-A levels and uterine artery pulsatility index. CONCLUSIONS: ß-hCG and PAPP-A levels measured during the first trimester are not predictive of subsequent intrapartum fetal compromise within a low-risk population.

Beetroot juice, exercise, and cardiovascular function in women planning to conceive.

OBJECTIVE: Prepregnancy optimization of cardiovascular function may reduce the risk of pre-eclampsia. We aimed to assess the feasibility and effect of preconception cardiovascular monitoring, exercise, and beetroot juice on cardiovascular parameters in women planning to conceive. DESIGN AND METHOD: Prospective single-site, open-label, randomized controlled trial. Thirty-two women, aged 18-45 years, were allocated into one of four arms (1 : 1 : 1 : 1): exercise, beetroot juice, exercise plus beetroot juice and no intervention for 12 weeks. Blood pressure (BP) was measured at home daily. Cardiac output ( CO ) and total peripheral resistance (TPR) were assessed via bio-impedance. RESULTS: Twenty-nine out of 32 (91%) participants completed the study. Adherence to daily BP and weight measurements were 81% and 78%, respectively ( n  = 29). Eight out of 15 (53%) of participants did not drink all the provided beetroot juice because of forgetfulness and taste. After 12 weeks, exercise was associated with a reduction in standing TPR (-278 ±â€Š0.272 dynes s cm -5 , P  < 0.05), and an increase in standing CO (+0.88 ±â€Š0.71 l/min, P  < 0.05). Exercise and beetroot juice together was associated with a reduction in standing DBP ( 7 ±â€Š6 mmHg, P  < 0.05), and an increase in standing CO (+0.49 ±â€Š0.66 l/min, P  < 0.05). The control group showed a reduction in standing TPR ( 313 ±â€Š387 dynes s cm -5 ) and standing DBP ( 8 ±â€Š5mmHg). All groups gained weight. CONCLUSION: Exercise and beetroot juice in combination showed a signal towards improving cardiovascular parameters. The control group showed improvements, indicating that home measurement devices and regular recording of parameters are interventions in themselves. Nevertheless, interventions before pregnancy to improve cardiovascular parameters may alter the occurrence of hypertensive conditions during pregnancy and require further investigation in adequately powered studies.

Prediction of intrapartum fetal compromise using the cerebroumbilical ratio: a prospective observational study.

OBJECTIVE: To investigate the use of the fetal cerebroumbilical ratio to predict intrapartum compromise in appropriately grown fetuses. STUDY DESIGN: A prospective observational study set at Queen Charlotte's and Chelsea hospital, London, UK. Fetal biometry and Doppler resistance indices were measured in 400 women immediately before established labor. Labor was then managed according to local protocols and guidelines, and intrapartum and neonatal outcome details recorded. RESULTS: Infants delivered by cesarean section for fetal compromise had significantly lower cerebroumbilical ratios than those born by spontaneous vaginal delivery (1.52 vs 1.82, P ≤ .001). Infants with a cerebroumbilical ratio <10th percentile were 6 times more likely to be delivered by cesarean section for fetal compromise than those with a cerebroumbilical ratio ≥10th percentile (odds ratio, 6.1; 95% confidence interval, 3.03-12.75). A cerebroumbilical ratio >90th percentile appears protective of cesarean section for fetal compromise (negative predictive value 100%). CONCLUSION: The fetal cerebroumbilical ratio can identify fetuses at high and low risk of a subsequent diagnosis of intrapartum compromise, and may be used to risk stratify pregnancies before labor.

£25 and a biscuit: Women's Health Research and Public Engagement in the UK.

It is over a  year since the Department of Health launched the Women's Health Strategy for England and included the rally cry of "women's voices". However, methods and modes of the inclusion of women in their own health and health research still fall short. Patient and public engagement and involvement (PPIE) in women's health research is considered a hallmark of a moral, ethical, and democratic society. Despite the call for the inclusion of "women's voices" and "women's stories", approaches to PPIE often remain tokenistic and don't address issues of representation, equality, and diversity or respond to wider racial inequalities in health. This past August marked the 103rd birthday of the late Henrietta Lacks who died of cervical cancer. Clones of her cells (HeLa cells) obtained without consent, continue to be used in laboratories around the world and serves as an ongoing reminder of dynamics and power in health research relationships with the public today. Historically, women have been mistreated and excluded from research and the reality that Black women in the UK remain 3.7 times more likely to die in childbirth makes the effectiveness of our research pathways critical (MBRRACE-UK, https://www.npeu.ox.ac.uk/mbrrace-uk ). PPIE holds much potential to contribute to the improvement of shortcomings in maternity and women's health, but not without deeper understanding of the ways in which engagement intrinsically, works. This article raises criticism of the current quality of engagement in women's health research and calls for a redesign of our frameworks and the need to explore new configurations of the relationship between women's health, research, and people.

It is one year since the Department of Health launched the Women's Health Strategy for England and included the rally cry of "women's voices". However, methods and modes of the inclusion of women in their own health and health research still fall short. Patient and public engagement and involvement (PPIE) in women's health research is considered a hallmark of a moral, ethical, and democratic society. Despite the call for the inclusion of "women's voices" and "women's stories", approaches to PPIE often remain tokenistic and don't address issues of representation, equality, and diversity, or respond wider racial inequalities in health. This past August marked the 103rd birthday of the late Henrietta Lacks who died of cervical cancer. Clones of her cells (HeLa cells) obtained without consent, continue to be used in laboratories around the world and serves as an ongoing reminder of dynamics and power in health research relationships with the public today. Historically, women have been mistreated and excluded from research and the reality that Black women in the UK remain 3.7 times more likely to die in childbirth makes the effectiveness of our research pathways critical [9]. PPIE holds much potential to contribute to the improvement of shortcomings in maternity and women's health, but not without deeper understanding of the ways in which engagement intrinsically, works. This article raises criticism of the current quality of engagement in women's health research and calls for a redesign of our frameworks and the need to explore new configurations of the relationship between women's health, research, and people.

A community-based intervention to improve screening, referral and follow-up of non-communicable diseases and anaemia amongst pregnant and postpartum women in rural India: study protocol for a cluster randomised trial.

BACKGROUND: Medical complications during pregnancy, including anaemia, gestational diabetes mellitus and hypertensive disorders of pregnancy place women are at higher risk of long-term complications. Scalable and low-cost strategies to integrate non-communicable disease screening into pregnancy care are needed. We aim to determine the effectiveness and implementation components of a community-based, digitally enabled approach, "SMARThealth Pregnancy," to improve health during pregnancy and the first year after birth. METHODS: A pragmatic, parallel-group, cluster randomised, type 2 hybrid effectiveness-implementation trial of a community-based, complex intervention in rural India to decrease anaemia (primary outcome, defined as haemoglobin < 12g/dL) and increase testing for haemoglobin, glucose and blood pressure (secondary outcomes) in the first year after birth. Primary Health Centres (PHCs) are the unit of randomisation. PHCs are eligible with (1) > 1 medical officer and > 2 community health workers; and (2) capability to administer intravenous iron sucrose. Thirty PHCs in Telangana and Haryana will be randomised 1:1 using a matched-pair design accounting for cluster size and distance from the regional centre. The intervention comprises (i) an education programme for community health workers and PHC doctors; (ii) the SMARThealth Pregnancy app for health workers to support community-based screening, referral and follow-up of high-risk cases; (iii) a dashboard for PHC doctors to monitor high-risk women in the community; (iv) supply chain monitoring for consumables and medications and (v) stakeholder engagement to co-develop implementation and sustainability pathways. The comparator is usual care with additional health worker education. Secondary outcomes include implementation outcomes assessed by the RE-AIM framework (reach, effectiveness, adoption, implementation, maintenance), clinical endpoints (anaemia, diabetes, hypertension), clinical service delivery indicators (quality of care score), mental health and lactation practice (PHQ9, GAD7, EuroQoL-5D, WHO IYCF questionnaire). DISCUSSION: Engaging women with screening after a high-risk pregnancy is a challenge and has been highlighted as a missed opportunity for the prevention of non-communicable diseases. The SMARThealth Pregnancy trial is powered for the primary outcome and will address gaps in the evidence around how pregnancy can be used as an opportunity to improve women's lifelong health. If successful, this approach could improve the health of women living in resource-limited settings around the world. TRIAL REGISTRATION: ClinicalTrials.gov NCT05752955. Date of registration 3 March 2023.

Perinatal outcomes of fetal echogenic bowel.

OBJECTIVE: To investigate perinatal outcomes of fetal echogenic bowel (FEB). METHOD: This is a retrospective observational study of FEB cases from Jan 2005-Dec 2010. Data from ultrasound and fetal medicine investigations, uterine artery Doppler (UAD), intra-partum care and neonatal outcome were obtained from Fetal Medicine, Obstetric and Neonatal Databases. RESULTS: There were 139 cases presenting at 21(+5) (15(+1) -35(+5) ) weeks gestation. Overall, 106/139 (76.2%) were live born (LB), 8/139 (5.8%) were complicated by intra-uterine deaths (IUD), 11/139 (7.9%) had termination of pregnancy (TOP) and 14/139 (10.1%) were lost to follow-up after 28 weeks gestation. Six had chromosomal/genetic abnormalities, two had congenital cytomegalovirus, none had cystic fibrosis.Uterine artery Doppler was normal in 106/130 (81.5%) cases. In this group, there were no cases of fetal growth restriction (FGR), 95/106 (89.6%) were LB, 1/106 (0.94%) had an IUD. In the abnormal UAD group, 17/24 (70.1%) developed FGR, 11/24 (45.8%) were LB, 4/24 (16.7%) had TOP, 7/24 (29.2%) had IUD.In total, 20/106 (18.9%) live births were admitted for specialist neonatal care, 12/20 (60%) for prematurity. Only one had primary bowel pathology. CONCLUSION: Pregnancies with FEB and screen positive UAD are at risk of adverse perinatal outcome. Primary bowel pathology is rare following the finding of FEB.

Older mothers do not confer greater perinatal risk to dichorionic diamniotic twins.

Advanced maternal age may be associated with adverse maternal and perinatal outcomes in singleton pregnancies. It is unclear whether a similar association exists for dichorionic twins. This objective of this study was to ascertain whether advanced maternal age was associated with increased perinatal morbidity and mortality in a 15 year retrospective review of dichorionic diamniotic (DCDA) twins delivered at Queen Charlotte's and Chelsea Hospital, a tertiary referral center in London, UK, between 1994 and 2008. In all, 1 174 DCDA deliveries occurred in the study period. Maternal age was not associated with neonatal unit admission or composite fetal and neonatal mortality. Advanced maternal age appeared to have no deleterious effect on the perinatal outcomes of DCDA twin pregnancies.

The feasibility of multimodality remote monitoring of maternal physiology during pregnancy.

CONDENSED ABSTRACT: To ascertain whether remote multimodality cardiovascular monitoring of health in pregnancy is feasible, 24 participants were asked to daily monitor body weight, heart rate, blood pressure, activity levels, and sleep patterns. Study participants took on average 4.3 (standard deviation = 2.20) home recordings of each modality per week across the 3 trimesters and 2.0 postpartum (standard deviation = 2.41), out of a recommended maximum of 7. Thus, remote monitoring indicative of cardiovascular health throughout and after pregnancy might be feasible for routine clinical care or within the context of a research study.

Remote multimodality monitoring of maternal physiology from the first trimester to postpartum period: study results.

OBJECTIVES: Current antenatal care largely relies on widely spaced appointments, hence only a fraction of the pregnancy period is subject to monitoring. Continuous monitoring of physiological parameters could represent a paradigm shift in obstetric care. Here, we analyse the data from daily home monitoring in pregnancy and consider the implications of this approach for tracking pregnancy health. METHODS: Prospective feasibility study of continuous home monitoring of blood pressure, weight, heart rate, sleep and activity patterns from the first trimester to 6 weeks postpartum. RESULTS: Fourteen out of 24 women completed the study (58%). Compared to early pregnancy [week 13, median heart rate (HR) 72/min, interquartile range (IQR) 12.8], heart rate increased by week 35 (HR 78/min, IQR 16.6; P  = 0.041) and fell postpartum (HR 66/min, IQR 11.5, P  = 0.021). Both systolic and diastolic blood pressure were lower at mid-gestation (week 20: SBP 103 mmHg, IQR 6.6; DPB 63 mmHg, IQR 5.3 P  = 0.005 and P  = 0.045, respectively) compared to early pregnancy (week 13, SBP 107 mmHg, IQR 12.4; DPB 67 mmHg, IQR 7.1). Weight increased during pregnancy between each time period analyzed, starting from week 15. Smartwatch recordings indicated that activity increased in the prepartum period, while deep sleep declined as pregnancy progressed. CONCLUSION: Home monitoring tracks individual physiological responses to pregnancy in high resolution that routine clinic visits cannot. Changes in the study protocol suggested by the study participants may improve compliance for future studies, which was particularly low in the postpartum period. Future work will investigate whether distinct adaptative patterns predate obstetric complications, or can predict long-term maternal cardiovascular health.

Tracking the incidence and risk factors for SARS-CoV-2 infection using historical maternal booking serum samples.

The early transmission dynamics of SARS-CoV-2 in the UK are unknown but their investigation is critical to aid future pandemic planning. We tested over 11,000 anonymised, stored historic antenatal serum samples, given at two north-west London NHS trusts in 2019 and 2020, for total antibody to SARS-CoV-2 receptor binding domain (anti-RBD). Estimated prevalence of seroreactivity increased from 1% prior to mid-February 2020 to 17% in September 2020. Our results show higher prevalence of seroreactivity to SARS-CoV-2 in younger, non-white ethnicity, and more deprived groups. We found no significant interaction between the effects of ethnicity and deprivation. Derived from prevalence, the estimated incidence of seroreactivity reflects the trends observed in daily hospitalisations and deaths in London that followed 10 and 13 days later, respectively. We quantified community transmission of SARS-CoV-2 in London, which peaked in late March / early April 2020 with no evidence of community transmission until after January 2020. Our study was not able to determine the date of introduction of the SARS-CoV-2 virus but demonstrates the value of stored antenatal serum samples as a resource for serosurveillance during future outbreaks.

Protocol for a sequential, prospective meta-analysis to describe coronavirus disease 2019 (COVID-19) in the pregnancy and postpartum periods.

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.

Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise: the TRUFFLE 2 randomised trial protocol.

INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.

COVID-19 and pregnancy: Lessons from 2020.

The outbreak and spread of the coronavirus disease 2019 pandemic has led to an unprecedented wealth of literature on the impact of human coronaviruses on pregnancy. The number of case studies and publications alone are several orders of magnitude larger than those published in all previous human coronavirus outbreaks combined, enabling robust conclusions to be drawn from observations for the first time. However, the importance of learning from previous human coronavirus outbreaks cannot be understated. In this narrative review, we describe what we consider to the major learning points arising from the SARS-CoV-2 pandemic in relation to pregnancy, and where these confound what might have been expected from previous coronavirus outbreaks.