Lessons learned from co-production in public health research: the MAMAH case study involving underserved migrant mothers in the UK.

BACKGROUND: Research suggests some migrant women are at increased risk of mortality and morbidity in the perinatal period; however, there is a gap in co-produced research to improve care. The UK National Institute for Health and Care Research (NIHR) defines co-production as "an approach in which researchers, practitioners, and members of the public work together, sharing power and responsibility". We summarise learnings from our study, which aimed to co-produce solutions to improve maternity care for migrant women in the UK, by working with women to identify the most important research priorities. METHODS: We recruited 18 underserved migrant women living in the UK who had given birth in the UK within the past 15 years to create a patient advisory panel. They were recruited via national and local non-governmental organisations and snowball sampling using purposive methods to ensure representation from a range of backgrounds, including those who were refugees, asylum seekers, and undocumented. Underserved was defined as asylum seeking, refugee, undocumented, or low-income mothers (those who were experiencing homelessness or in receipt of welfare support). The women are involved in conceptualisation, analysis, and dissemination of the project. The project is a UK National Institute of Health and Care Research (NIHR) Doctoral Fellowship project lasting 3 years with a variety of research workstreams. FINDINGS: The research funding application process began in January, 2021, and the project was funded and began in November, 2022. The research team struggled to access comprehensive training on co-production, particularly in how to counter power dynamics. We appointed a Lead Patient Advisor who manages the relationship between the academics and the patient advisors. Additionally, we reimburse women's time, childcare, and travel. We have found that online meetings are preferable, as women do not need to travel or arrange childcare. We meet our patient advisory panel four times per year. Some women have been directly involved in research such as systematic review screening and qualitative interviewing and have been given research training. Our initial research priorities did not align with those of the women, and this helped us to reshape our work. Women said that having a Lead Patient Advisor made it easier to participate, particularly as some issues are traumatic. To mitigate this, we have offered support resources and debriefing. Using online interpreters has been challenging, and we have recently split into different language groups to maximise engagement. INTERPRETATION: Overall, as researchers, we have learned that taking a truly co-produced approach is time-consuming but has ensured our research prioritises the views of migrant women giving birth in the UK. FUNDING: National Institute for Health and Care Research (NIHR).

Methods of identifying surgical Necrotizing Enterocolitis-a systematic review and meta-analysis.

BACKGROUND: Current data suggests potential benefit of earlier surgery for necrotizing enterocolitis (NEC) however this requires accurate prognostication early in the disease course. This study aims to identify and determine the effectiveness of previously reported methods or tests for the identification of surgical NEC. METHODS: Systematic review and meta-analysis with registration on PROSPERO including articles describing a method of identifying surgical NEC. Outcomes of interest were effectiveness and repeatability of index test. RESULTS: Of the 190 full-text articles screened, 90 studies were included which contained 114 methods of identifying surgical NEC in 9546 infants. Of these methods, 44 were a scoring system, 37 a single biomarker, 24 an imaging method, and 9 an invasive method. Sensitivity and specificity ranged from 12.8-100% to 13-100%, respectively. Some methods (9.6%) provided insufficient methods for repeatability within clinical practice or research. Meta-analyses were possible for only 2 methods, the metabolic derangement 7 score and abdominal ultrasound. CONCLUSIONS: A range of methods for identifying surgical NEC have been identified with varying overall performance and uncertainties about reproducibility and superiority of any method. External validation in large multicentre datasets should allow direct comparison of accuracy and prospective study should evaluate impact on clinical outcomes. IMPACT: Earlier identification of need for surgery in necrotizing enterocolitis (NEC) has the potential to improve the unfavourable outcomes in this condition. As such, many methods have been developed and reported to allow earlier identification of surgical NEC. This study is the first synthesis of the literature which identifies previously reported methods and the effectiveness of these. Many methods, including scoring systems and biomarkers, appear effective for prognostication in NEC and external validation is now required in multicentre datasets prior to clinical utility.

Aetiology and use of antibiotics in pregnancy-related infections: results of the WHO Global Maternal Sepsis Study (GLOSS), 1-week inception cohort.

BACKGROUND: Pregnancy-related infections are important contributors to maternal sepsis and mortality. We aimed to describe clinical, microbiological characteristics and use of antibiotics by source of infection and country income, among hospitalized women with suspected or confirmed pregnancy-related infections. METHODS: We used data from WHO Global Maternal Sepsis Study (GLOSS) on maternal infections in hospitalized women, in 52 low-middle- and high-income countries conducted between November 28th and December 4th, 2017, to describe the frequencies and medians of maternal demographic, obstetric, and clinical characteristics and outcomes, methods of infection diagnosis and causative pathogens, of single source pregnancy-related infection, other than breast, and initial use of therapeutic antibiotics. We included 1456 women. RESULTS: We found infections of the genital (n = 745/1456, 51.2%) and the urinary tracts (UTI) (n = 531/1456, 36.5%) to be the most frequent. UTI (n = 339/531, 63.8%) and post-caesarean skin and soft tissue infections (SSTI) (n = 99/180, 55.0%) were the sources with more culture samples taken and microbiological confirmations. Escherichia coli was the major uropathogen (n = 103/118, 87.3%) and Staphylococcus aureus (n = 21/44, 47.7%) was the commonest pathogen in SSTI. For 13.1% (n = 191) of women, antibiotics were not prescribed on the same day of infection suspicion. Cephalosporins (n = 283/531, 53.3%) were the commonest antibiotic class prescribed for UTI, while metronidazole (n = 303/925, 32.8%) was the most prescribed for all other sources. Ceftriaxone with metronidazole was the commonest combination for the genital tract (n = 98/745, 13.2%) and SSTI (n = 22/180, 12.2%). Metronidazole (n = 137/235, 58.3%) was the most prescribed antibiotic in low-income countries while cephalosporins and co-amoxiclav (n = 129/186, 69.4%) were more commonly prescribed in high-income countries. CONCLUSIONS: Differences in antibiotics used across countries could be due to availability, local guidelines, prescribing culture, cost, and access to microbiology laboratory, despite having found similar sources and pathogens as previous studies. Better dissemination of recommendations in line with antimicrobial stewardship programmes might improve antibiotic prescription.

Management and outcomes of women with low fibrinogen concentration during pregnancy or immediately postpartum: A UK national population-based cohort study.

INTRODUCTION: Pregnant women with a fibrinogen level <2 g/L represent a high-risk group that is associated with severe postpartum hemorrhage and other complications. Women who would qualify for fibrinogen therapy are not yet identified. MATERIAL AND METHODS: A population-based cross-sectional study was conducted using the UK Obstetric Surveillance System between November 2017 and October 2018 in any UK hospital with a consultant-led maternity unit. Any woman pregnant or immediately postpartum with a fibrinogen <2 g/L was included. Our aims were to determine the incidence of fibrinogen <2 g/L in pregnancy, and to describe its causes, management and outcomes. RESULTS: Over the study period 124 women with fibrinogen <2 g/L were identified (1.7 per 10 000 maternities; 95% confidence interval 1.4-2.0 per 10 000 maternities). Less than 5% of cases of low fibrinogen were due to preexisting inherited dysfibrinogenemia or hypofibrinogenemia. Sixty percent of cases were due to postpartum hemorrhage caused by placental abruption, atony, or trauma. Amniotic fluid embolism and placental causes other than abruption (previa, accreta, retention) were associated with the highest estimated blood loss (median 4400 mL) and lowest levels of fibrinogen. Mortality was high with two maternal deaths due to massive postpartum hemorrhage, 27 stillbirths, and two neonatal deaths. CONCLUSIONS: Fibrinogen <2 g/L often, but not exclusively, affected women with postpartum hemorrhage due to placental abruption, atony, or trauma. Other more rare and catastrophic obstetrical events such as amniotic fluid embolism and placenta accreta also led to low levels of fibrinogen. Maternal and perinatal mortality was extremely high in our cohort.

Long-gap esophageal atresia: gastric transposition or esophageal lengthening with delayed primary anastomosis? A systematic review.

PURPOSE: This study aims to evaluate different surgical approaches to long-gap esophageal atresia (LGEA) with or without tracheoesophageal fistula (TEF) is unclear. METHODS: A systematic literature review was done comparing gastric transposition versus esophageal lengthening with delayed primary anastomosis in infants with LGEA+/-TEF. The primary outcome was time to full oral feeds. Secondary outcomes were time to full enteric feeds, need for further surgery, growth, mortality, and postoperative adverse events. RESULTS: No comparative studies were found. However, the literature was re-interrogated for non-comparative studies. Four hundred thirty-eight articles were identified and screened, and 18 met the inclusion criteria. All were case series. Forty-three infants underwent gastric transposition, and 106 had esophageal lengthening with delayed primary anastomosis. One study on gastric transposition reported time to full oral feeds, and one study in each group reported growth. Time to full enteric feeds was reported in one study in each group. 30% of infants had further surgery following gastric transposition, including hiatus hernia repair (5/43, 12%) and esophageal dilation (7/43, 16%). Following esophageal lengthening, 62/106 (58%) had anti-reflux surgery, 58/106 (55%) esophageal dilatation and 11/106 (10%) esophageal stricture resection. Anastomotic complications occurred in 13/43 (30%), gastrointestinal in 16/43 (37%), respiratory in 17/43 (40%), and nerve injury in 2/43 (5%) of the gastric transposition group. In the esophageal lengthening group, anastomotic complications occurred in 68/106 (64%), gastrointestinal in 62/106 (58%), respiratory in 6/106 (6%), and none sustained nerve injury. Each group had one death due to a cause not directly related to the surgical procedure. CONCLUSIONS: This systematic review highlights the morbidity associated with both surgical procedures and the variety in reporting outcomes.

Maternal and perinatal death surveillance and response: a systematic review of qualitative studies.

Objective: To understand the experiences and perceptions of people implementing maternal and/or perinatal death surveillance and response in low- and middle-income countries, and the mechanisms by which this process can achieve its intended outcomes. Methods: In June 2022, we systematically searched seven databases for qualitative studies of stakeholders implementing maternal and/or perinatal death surveillance and response in low- and middle-income countries. Two reviewers independently screened articles and assessed their quality. We used thematic synthesis to derive descriptive themes and a realist approach to understand the context-mechanism-outcome configurations. Findings: Fifty-nine studies met the inclusion criteria. Good outcomes (improved quality of care or reduced mortality) were underpinned by a functional action cycle. Mechanisms for effective death surveillance and response included learning, vigilance and implementation of recommendations which motivated further engagement. The key context to enable effective death surveillance and response was a blame-free learning environment with good leadership. Inadequate outcomes (lack of improvement in care and mortality and discontinuation of death surveillance and response) resulted from a vicious cycle of under-reporting, inaccurate data, and inadequate review and recommendations, which led to demotivation and disengagement. Some harmful outcomes were reported, such as inappropriate referrals and worsened staff shortages, which resulted from a fear of negative consequences, including blame, disciplinary action or litigation. Conclusion: Conditions needed for effective maternal and/or perinatal death surveillance and response include: separation of the process from litigation and disciplinary procedures; comprehensive guidelines and training; adequate resources to implement recommendations; and supportive supervision to enable safe learning.

Factors associated with infection after operative vaginal birth-a secondary analysis of a randomized controlled trial of prophylactic antibiotics for the prevention of infection following operative vaginal birth.

BACKGROUND: A recent randomized controlled trial of prophylactic antibiotics for the prevention of infection following operative vaginal birth showed that women allocated prophylactic intravenous amoxicillin and clavulanic acid had a significantly lower risk of developing confirmed or suspected infection within 6 weeks after operative vaginal birth (risk ratio [RR], 0.58; 95% confidence interval [CI], 0.49-0.69; P < .001). Some international and national guidelines have subsequently been updated to include prophylactic antibiotics after operative vaginal birth. However, the generalizability of the trial results may be limited in settings where the episiotomy rate is lower (89% of women in the trial had an episiotomy). In addition, there was a high burden of infection in the prophylactic antibiotics group despite the administration of prophylactic antibiotics. It is essential to identify modifiable risk factors for infection after operative vaginal birth, including the timing of antibiotic administration. OBJECTIVE: This study aimed to evaluate if the effectiveness of the prophylactic antibiotic in reducing confirmed or suspected infection was independent of perineal trauma, identify risk factors for infection after operative vaginal birth, and investigate variation in efficacy with the timing of antibiotic administration. STUDY DESIGN: This study was a secondary analysis of 3225 women with primary outcome data from the prophylactic antibiotics for the prevention of infection following operative vaginal birth randomized controlled trial. Women were divided into subgroups according to the perineal trauma experienced (episiotomy and/or perineal tear). The consistency of the prophylactic antibiotics in preventing infection across the subgroups was assessed using log-binomial regression and the likelihood ratio test. Multivariable log-binomial regression was used to investigate factors associated with infection. The multivariable risk factor model was subsequently fitted to the group of women who received amoxicillin and clavulanic acid to investigate the timing of antibiotic administration. RESULTS: Of the 3225 women included in the secondary analysis, 2144 (66.5%) had an episiotomy alone, 726 (22.5%) had an episiotomy and a tear, 277 (8.6%) had a tear alone, and 78 (2.4%) had neither episiotomy nor tear. Among women who experienced perineal trauma, amoxicillin and clavulanic acid administration was protective against infection in all subgroups compared with placebo with no significant interaction between subgroup and trial allocation (P=.17). Moreover, 2925 women were included in the multivariable risk factor analysis. The following were associated with adjusted risk ratios of infection: episiotomy, 2.94 (95% confidence interval, 1.62-5.31); forceps, 1.37 (95% confidence interval, 1.12-1.69) compared to vacuum extraction; primiparity, 1.34 (95% confidence interval, 1.05-1.70); amoxicillin and clavulanic acid administration, 0.60 (95% confidence interval, 0.51-0.72); body mass index of 25.0 to 29.9 kg/m2, 1.21 (95% confidence interval, 1.00-1.47), and body mass index of ≥30 kg/m2, 1.22 (95% confidence interval, 0.98-1.52) compared to body mass index of <25 kg/m2. Each 15-minute increment between birth and antibiotic administration was associated with a 3% higher risk of infection (adjusted risk ratio, 1.03; 95% confidence interval, 1.01-1.06). CONCLUSION: Timely prophylactic antibiotics should be administered to all women after operative vaginal birth, irrespective of the type of perineal trauma. The use of episiotomy, forceps birth, primiparity, and overweight were associated with an increased risk of confirmed or suspected infection after operative vaginal birth.

Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: a sequential, prospective meta-analysis.

OBJECTIVE: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes. DATA SOURCES: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020. STUDY ELIGIBILITY CRITERIA: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. METHODS: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis. RESULTS: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81). CONCLUSION: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.

Antenatal and neonatal exposure to SARS-CoV-2 and children's development: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review of the impact of antenatal and neonatal exposure to SARS-CoV-2 on developmental outcomes in preterm and term-born infants. METHODS: We searched Embase, Emcare, MEDLINE, PsycINFO, Web of Science and grey literature on May 27, 2022 and updated on May 8, 2023. Studies defining exposure with a positive SARS-CoV-2 protein or genetic material, used a contemporaneous non-exposed cohort, and reported developmental outcomes up to 2 years of age were included. RESULTS: Four out of 828 screened studies were included. Meta-analysis included 815 infants screened for developmental delay (n = 306 exposed; n = 509 non-exposed) between 3- and 11-months of age. Among term-born infants, we did not find an increased risk of delay in communication (odd's ratio: 0.73 (95% CI: 0.24-2.24)), gross motor (1.50 (0.62, 3.62)), fine motor (2.90 (0.58, 14.43)), problem-solving (1.19 (0.54, 2.66)) or personal-social development (1.93 (0.78, 4.75)) in exposed infants. The number of preterm-born infants in the exposed (n = 37) and comparison cohorts (n = 41) were too few to report meaningful comparisons. CONCLUSION: Evidence regarding the potential impact of antenatal or neonatal exposure to SARS-CoV-2 infection on developmental outcomes in early infancy is limited and inconsistent. Larger cohorts with outcomes beyond the first year of life are needed. IMPACT: The current evidence examining associations between SARS-CoV-2 exposure during the neonatal period and developmental outcomes in infancy is limited by there being few studies with extremely small sample sizes. Based on sparse data there was no consistent association between antenatal or neonatal exposure to SARS-CoV-2 infection and an adverse impact on developmental outcomes below 12 months of age for babies born preterm or at term. This study highlights that larger cohorts with outcomes assessed beyond the first year are needed to determine the potential longer-term impact of SARS-CoV-2 infection exposure on child development.

Neonatal outcomes of maternal SARS-CoV-2 infection in the UK: a prospective cohort study using active surveillance.

BACKGROUND: Newborns may be affected by maternal SARS-CoV-2 infection during pregnancy. We aimed to describe the epidemiology, clinical course and short-term outcomes of babies admitted to a neonatal unit (NNU) following birth to a mother with confirmed SARS-CoV-2 infection within 7 days of birth. METHODS: This is a UK prospective cohort study; all NHS NNUs, 1 March 2020 to 31 August 2020. Cases were identified via British Paediatric Surveillance Unit with linkage to national obstetric surveillance data. Reporting clinicians completed data forms. Population data were extracted from the National Neonatal Research Database. RESULTS: A total of 111 NNU admissions (1.98 per 1000 of all NNU admissions) involved 2456 days of neonatal care (median 13 [IQR 5, 34] care days per admission). A total of 74 (67%) babies were preterm. In all, 76 (68%) received respiratory support; 30 were mechanically ventilated. Four term babies received therapeutic hypothermia for hypoxic ischaemic encephalopathy. Twenty-eight mothers received intensive care, with four dying of COVID-19. Eleven (10%) babies were SARS-CoV-2 positive. A total of 105 (95%) babies were discharged home; none of the three deaths before discharge was attributed to SARS-CoV-2. CONCLUSION: Babies born to mothers with SARS-CoV-2 infection around the time of birth accounted for a low proportion of total NNU admissions over the first 6 months of the UK pandemic. Neonatal SARS-CoV-2 was uncommon. STUDY REGISTRATION: ISRCTN60033461; protocol available at http://www.npeu.ox.ac.uk/pru-mnhc/research-themes/theme-4/covid-19 . IMPACT: Neonatal unit admissions of babies born to mothers with SARS-CoV-2 infection comprised only a small proportion of total neonatal admissions in the first 6 months of the pandemic. A high proportion of babies requiring neonatal admission who were born to mothers with confirmed SARS-CoV-2 infection were preterm and had neonatal SARS-CoV-2 infection and/or other conditions associated with long-term sequelae. Adverse neonatal conditions were more common in babies whose SARS-CoV-2-positive mothers required intensive care compared to those whose SARS-CoV-2-positive mothers who did not.

Postpartum haemorrhage in high-resource settings: Variations in clinical management and future research directions based on a comparative study of national guidelines.

OBJECTIVE: To compare guidelines from eight high-income countries on prevention and management of postpartum haemorrhage (PPH), with a particular focus on severe PPH. DESIGN: Comparative study. SETTING: High-resource countries. POPULATION: Women with PPH. METHODS: Systematic comparison of guidance on PPH from eight high-income countries. MAIN OUTCOME MEASURES: Definition of PPH, prophylactic management, measurement of blood loss, initial PPH-management, second-line uterotonics, non-pharmacological management, resuscitation/transfusion management, organisation of care, quality/methodological rigour. CONCLUSIONS: Our study highlights areas where strong evidence is lacking. There is need for a universal definition of (severe) PPH. Consensus is required on how and when to quantify blood loss to identify PPH promptly. Future research may focus on timing and sequence of second-line uterotonics and non-pharmacological interventions and how these impact maternal outcome. Until more data are available, different transfusion strategies will be applied. The use of clear transfusion-protocols are nonetheless recommended to reduce delays in initiation. There is a need for a collaborative effort to develop standardised, evidence-based PPH guidelines. RESULTS: Definitions of (severe) PPH varied as to the applied cut-off of blood loss and incorporation of clinical parameters. Dose and mode of administration of prophylactic uterotonics and methods of blood loss measurement were heterogeneous. Recommendations on second-line uterotonics differed as to type and dose. Obstetric management diverged particularly regarding procedures for uterine atony. Recommendations on transfusion approaches varied with different thresholds for blood transfusion and supplementation of haemostatic agents. Quality of guidelines varied considerably.

Variations across Europe in hospitalization and management of pregnant women with SARS-CoV-2 during the initial phase of the pandemic: Multi-national population-based cohort study using the International Network of Obstetric Survey Systems (INOSS).

INTRODUCTION: The majority of data on COVID-19 in pregnancy are not from sound population-based active surveillance systems. MATERIAL AND METHODS: We conducted a multi-national study of population-based national or regional prospective cohorts using standardized definitions within the International Network of Obstetric Survey systems (INOSS). From a source population of women giving birth between March 1 and August 31, 2020, we included pregnant women admitted to hospital with a positive SARS-CoV-2 PCR test ≤7 days prior to or during admission and up to 2 days after birth. The admissions were further categorized as COVID-19-related or non-COVID-19-related. The primary outcome of interest was incidence of COVID-19-related hospital admission. Secondary outcomes included severe maternal disease (ICU admission and mechanical ventilation) and COVID-19-directed medical treatment. RESULTS: In a source population of 816 628 maternities, a total of 2338 pregnant women were admitted with SARS-CoV-2; among them 940 (40%) were COVID-19-related admissions. The pooled incidence estimate for COVID-19-related admission was 0.59 (95% confidence interval 0.27-1.02) per 1000 maternities, with notable heterogeneity across countries (I2 = 97.3%, P = 0.00). In the COVID-19 admission group, between 8% and 17% of the women were admitted to intensive care, and 5%-13% needed mechanical ventilation. Thromboprophylaxis was the most frequent treatment given during COVID-19-related admission (range 14%-55%). Among 908 infants born to women in the COVID-19-related admission group, 5 (0.6%) stillbirths were reported. CONCLUSIONS: During the initial months of the pandemic, we found substantial variations in incidence of COVID-19-related admissions in nine European countries. Few pregnant women received COVID-19-directed medical treatment. Several barriers to rapid surveillance were identified. Investment in robust surveillance should be prioritized to prepare for future pandemics.

A study of diabetic ketoacidosis in the pregnant population in the United Kingdom: Investigating the incidence, aetiology, management and outcomes.

AIM: To estimate the incidence of diabetic ketoacidosis (DKA) among pregnant women, describe its clinical features, management and outcomes and identify the risk factors for the condition. METHODS: A national population-based case-control study was conducted in the UK using the UK Obstetric Surveillance System between April 2019 and September 2020 including all pregnant women with DKA irrespective of the level of blood glucose. The incidence rate of DKA in pregnancy was estimated. A case-control analysis limited to women with type 1 diabetes was performed comparing characteristics of women with DKA (cases) to those of women whose pregnancies were not complicated by DKA (controls). RESULTS: In all, 82 women were identified with DKA in pregnancy; 6.3 per 100,000 maternities (95% CI: 5.0-7.9). No maternal deaths occurred, but perinatal mortality was 12/73 (16%) with 11 stillbirths and one neonatal death. DKA episodes mostly occurred in women with type 1 diabetes (85%) and in the 3rd trimester of pregnancy (71%). Episodes were mainly precipitated by infection (21%), vomiting (21%), steroid therapy (13%) and medication errors (10%). Fifteen percent of women had more than one episode of DKA during their pregnancy. Risk factors associated with DKA among women with type 1 diabetes identified through the case-control analysis were the woman and/or partner not being in a paid employment and having at least one microvascular complication of diabetes before pregnancy. CONCLUSION: DKA in pregnancy was associated with high perinatal mortality and was linked with factors related to socio-economic deprivation, mental health problems and long-term difficulties with glycaemic control.

Placenta accreta spectrum - variations in clinical practice and maternal morbidity between the UK and France: a population-based comparative study.

OBJECTIVE: To compare the management and outcomes of women with placenta accreta spectrum (PAS) in France and the UK. DESIGN: Two population-based cohorts. SETTING: All obstetrician-led hospitals in the UK and maternity hospitals in eight French regions. POPULATION: A cohort of 219 women with PAS in France and a cohort of 154 women with PAS in the UK. METHODS: The management and outcomes of women with PAS were compared between the UK and France. MAIN OUTCOME MEASURES: Median blood loss, severe postpartum haemorrhage (≥3 l), postpartum infection and damage to surrounding organs. RESULTS: The management of PAS differed between the two countries: a larger proportion of women with PAS in the UK had a caesarean hysterectomy compared with France (43% vs 26%, p < 0.001), whereas in France a larger proportion of women with PAS received a uterus-preserving approach compared with the UK (36% vs 19%, p < 0.001). The total median blood loss in the UK was 3 l (IQR 1.7-6.5 l), compared with 1 l (IQR 0.5-2.5 l) in France; more women with PAS had a severe postpartum haemorrhage (PPH) in the UK compared with women with PAS in France (58% vs 21%, p < 0.001) [Correction added on 06 May 2022, after first online publication: '24 hour' has been changed to 'total' in the preceding sentence]. There was no difference between the UK and French populations for postpartum infection or organ damage. CONCLUSIONS: The UK and France have very different approaches to managing PAS, with more women in France receiving a uterine-conserving approach and more women in the UK undergoing caesarean hysterectomy. A life-threatening haemorrhage was more common in the UK than in France, which may be the result of differential management and/or the organisation of the healthcare systems. In women with placenta accreta spectrum, severe haemorrhage was more common in the UK than in France. TWEETABLE ABSTRACT: In women with placenta accreta spectrum, severe haemorrhage was more common in the UK than in France.

Management and implications of severe COVID-19 in pregnancy in the UK: data from the UK Obstetric Surveillance System national cohort.

INTRODUCTION: There is a lack of population level data on risk factors and impact of severe COVID-19 in pregnancy. The aims of this study were to determine the characteristics, and maternal and perinatal outcomes associated with severe COVID-19 in pregnancy compared with those with mild and moderate COVID-19 and to explore the impact of timing of birth. MATERIAL AND METHODS: This was a secondary analysis of a national, prospective cohort study. All pregnant women admitted to hospital in the UK with symptomatic SARS-CoV-2 from March 1, 2020 to October 31, 2021 were included. The severity of maternal infection (need for high flow or invasive ventilation, intensive care admission or died), pregnancy and perinatal outcomes, and the impact of timing of birth were analyzed using multivariable logistic regression. RESULTS: Of 4436 pregnant women, 13.9% (n = 616) had severe infection. Women with severe infection were more likely to be aged ≥30 years (adjusted odds ratio [aOR] aged 30-39 1.48, 95% confidence interval [CI] 1.20-1.83), be overweight or obese (aOR 1.73, 95% CI 1.34-2.25 and aOR 2.52 95% CI 1.97-3.23, respectively), be of mixed ethnicity (aOR 1.93, 95% CI 1.17-3.21) or have gestational diabetes (aOR 1.43, 95% CI 1.09-1.87) compared with those with mild or moderate infection. Women with severe infection were more likely to have a pre-labor cesarean birth (aOR 8.84, 95% CI 6.61-11.83), a very or extreme preterm birth (28-31+ weeks' gestation, aOR 18.97, 95% CI 7.78-14.85; <28 weeks' gestation, aOR 12.35, 95% CI 6.34-24.05) and their babies were more likely to be stillborn (aOR 2.51, 95% CI 1.35-4.66) or admitted to a neonatal unit (aOR 11.61, 95% CI 9.28-14.52). Of 112 women with severe infection who were discharged and gave birth at a later admission, the majority gave birth ≥36 weeks (85.7%), noting that three women in this group (2.7%) had a stillbirth. CONCLUSIONS: Severe COVID-19 in pregnancy increases the risk of adverse outcomes. Information to promote uptake of vaccination should specifically target those at greatest risk of severe outcomes. Decisions about timing of birth should be informed by multidisciplinary team discussion; however, our data suggest that women with severe infection who do not require early delivery have mostly good outcomes but that those with severe infection at term may warrant rapid delivery.

Management of Gastroschisis: Results From the NETS2G Study, a Joint British, Irish, and Canadian Prospective Cohort Study of 1268 Infants.

OBJECTIVE: In infants with gastroschisis, outcomes were compared between those where operative reduction and fascial closure were attempted ≤24 hours of age (PC), and those who underwent planned closure of their defect >24 hours of age following reduction with a pre-formed silo (SR). SUMMARY OF BACKGROUND DATA: Inadequate evidence exists to determine how best to treat infants with gastroschisis. METHODS: A secondary analysis was conducted of data collected 2006-2008 using the British Association of Pediatric Surgeons Congenital Anomalies Surveillance System, and 2005-2016 using the Canadian Pediatric Surgery Network.28-day outcomes were compared between infants undergoing PC and SR. Primary outcome was number of gastrointestinal complications. Interactions were investigated between infant characteristics and treatment to determine whether intervention effect varied in sub-groups of infants. RESULTS: Data from 341 British and Irish infants (27%) and 927 Canadian infants (73%) were used. 671 infants (42%) underwent PC and 597 (37%) underwent SR. The effect of SR on outcome varied according to the presence/absence of intestinal perforation, intestinal matting and intestinal necrosis. In infants without these features, SR was associated with fewer gastrointestinal complications [aIRR 0.25 (95% CI 0.09-0.67, P = 0.006)], more operations [aIRR 1.40 (95% CI 1.22-1.60, P < 0.001)], more days PN [aIRR 1.08 (95% CI 1.03-1.13, P < 0.001)], and a higher infection risk [aOR 2.06 (95% CI 1.10-3.87, P = 0.025)]. In infants with these features, SR was associated with a greater number of operations [aIRR 1.30 (95% CI 1.17-1.45, P < 0.001)], and more days PN [aIRR 1.06 (95% CI 1.02-1.10, P = 0.003)]. CONCLUSIONS: In infants without intestinal perforation, matting, or necrosis, the benefits of SR outweigh its drawbacks. In infants with these features, the opposite is true. Treatment choice should be based upon these features.

The top 10 research priorities in diabetes and pregnancy according to women, support networks and healthcare professionals.

AIMS: To undertake a Priority Setting Partnership (PSP) to establish priorities for future research in diabetes and pregnancy, according to women with experience of pregnancy, and planning pregnancy, with any type of diabetes, their support networks and healthcare professionals. METHODS: The PSP used established James Lind Alliance (JLA) methodology working with women and their support networks and healthcare professionals UK-wide. Unanswered questions about the time before, during or after pregnancy with any type of diabetes were identified using an online survey and broad-level literature search. A second survey identified a shortlist of questions for final prioritisation at an online consensus development workshop. RESULTS: There were 466 responses (32% healthcare professionals) to the initial survey, with 1161 questions, which were aggregated into 60 unanswered questions. There were 614 responses (20% healthcare professionals) to the second survey and 18 questions shortlisted for ranking at the workshop. The top 10 questions were: diabetes technology, the best test for diabetes during pregnancy, diet and lifestyle interventions for diabetes management during pregnancy, emotional and well-being needs of women with diabetes pre- to post-pregnancy, safe full-term birth, post-natal care and support needs of women, diagnosis and management late in pregnancy, prevention of other types of diabetes in women with gestational diabetes, women's labour and birth experiences and choices and improving planning pregnancy. CONCLUSIONS: These research priorities provide guidance for research funders and researchers to target research in diabetes and pregnancy that will achieve greatest value and impact.

One-year Outcomes of Congenital Duodenal Obstruction: A Population-based Study.

OBJECTIVES: Congenital duodenal obstruction (CDO) occurs in 1.2 per 10,000 live births and is frequently associated with other anomalies, most commonly cardiac. The aim of this study was to report important outcomes to 1 year following surgical repair. METHODS: This was a prospective population-based study using the British Association of Paediatric Surgeons Congenital Anomaly Surveillance System. Cases were identified at specialist pediatric surgical centres in the United Kingdom during a 12-month period starting in March 2016. Outcomes were recorded at 1 year following surgical repair. RESULTS: There were 100 infants with possible follow-up at 1 year and follow-up was achieved in 80 of these (80%) of whom 76 were alive at 1 year. The remainder had been discharged home, although one remained on parenteral nutrition. Five (6.1%) infants underwent repeat surgery for reasons related to CDO and overall 23 (23%) experienced at least 1 central venous catheter-related complication within 1 year. Overall mortality either before repair or within 1 year following surgical repair was 8.4% (95% CI 2.5%-14.4%), no deaths were related to CDO. CONCLUSIONS: One year outcomes for CDO are generally very good with poor outcomes typically related to comorbidities. These data are useful for national benchmarking and parental counselling.

Management of major obstetric hemorrhage prior to peripartum hysterectomy and outcomes across nine European countries.

INTRODUCTION: Peripartum hysterectomy is applied as a surgical intervention of last resort for major obstetric hemorrhage. It is performed in an emergency setting except for women with a strong suspicion of placenta accreta spectrum (PAS), where it may be anticipated before cesarean section. The aim of this study was to compare management strategies in the case of obstetric hemorrhage leading to hysterectomy, between nine European countries participating in the International Network of Obstetric Survey Systems (INOSS), and to describe pooled maternal and neonatal outcomes following peripartum hysterectomy. MATERIAL AND METHODS: We merged data from nine nationwide or multi-regional obstetric surveillance studies performed in Belgium, Denmark, Finland, France, Italy, the Netherlands, Slovakia, Sweden and the UK collected between 2004 and 2016. Hysterectomies performed from 22 gestational weeks up to 48 h postpartum due to obstetric hemorrhage were included. Stratifying women with and without PAS, procedures performed in the management of obstetric hemorrhage prior to hysterectomy between countries were counted and compared. Prevalence of maternal mortality, complications after hysterectomy and neonatal adverse events (stillbirth or neonatal mortality) were calculated. RESULTS: A total of 1302 women with peripartum hysterectomy were included. In women without PAS who had major obstetric hemorrhage leading to hysterectomy, uterotonics administration was lowest in Slovakia (48/73, 66%) and highest in Denmark (25/27, 93%), intrauterine balloon use was lowest in Slovakia (1/72, 1%) and highest in Denmark (11/27, 41%), and interventional radiology varied between 0/27 in Denmark and Slovakia to 11/59 (79%) in Belgium. In women with PAS, uterotonics administration was lowest in Finland (5/16, 31%) and highest in the UK (84/103, 82%), intrauterine balloon use varied between 0/14 in Belgium and Slovakia to 29/103 (28%) in the UK. Interventional radiology was lowest in Denmark (0/16) and highest in Finland (9/15, 60%). Maternal mortality occurred in 14/1226 (1%), the most common complications were hematologic (95/1202, 8%) and respiratory (81/1101, 7%). Adverse neonatal events were observed in 79/1259 (6%) births. CONCLUSIONS: Management of obstetric hemorrhage in women who eventually underwent peripartum hysterectomy varied greatly between these nine European countries. This potentially life-saving procedure is associated with substantial adverse maternal and neonatal outcome.

Mode of birth and risk of infection-related hospitalisation in childhood: A population cohort study of 7.17 million births from 4 high-income countries.

BACKGROUND: The proportion of births via cesarean section (CS) varies worldwide and in many countries exceeds WHO-recommended rates. Long-term health outcomes for children born by CS are poorly understood, but limited data suggest that CS is associated with increased infection-related hospitalisation. We investigated the relationship between mode of birth and childhood infection-related hospitalisation in high-income countries with varying CS rates. METHODS AND FINDINGS: We conducted a multicountry population-based cohort study of all recorded singleton live births from January 1, 1996 to December 31, 2015 using record-linked birth and hospitalisation data from Denmark, Scotland, England, and Australia (New South Wales and Western Australia). Birth years within the date range varied by site, but data were available from at least 2001 to 2010 for each site. Mode of birth was categorised as vaginal or CS (emergency/elective). Infection-related hospitalisations (overall and by clinical type) occurring after the birth-related discharge date were identified in children until 5 years of age by primary/secondary International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes. Analysis used Cox regression models, adjusting for maternal factors, birth parameters, and socioeconomic status, with results pooled using meta-analysis. In total, 7,174,787 live recorded births were included. Of these, 1,681,966 (23%, range by jurisdiction 17%-29%) were by CS, of which 727,755 (43%, range 38%-57%) were elective. A total of 1,502,537 offspring (21%) had at least 1 infection-related hospitalisation. Compared to vaginally born children, risk of infection was greater among CS-born children (hazard ratio (HR) from random effects model, HR 1.10, 95% confidence interval (CI) 1.09-1.12, p < 0.001). The risk was higher following both elective (HR 1.13, 95% CI 1.12-1.13, p < 0.001) and emergency CS (HR 1.09, 95% CI 1.06-1.12, p < 0.001). Increased risks persisted to 5 years and were highest for respiratory, gastrointestinal, and viral infections. Findings were comparable in prespecified subanalyses of children born to mothers at low obstetric risk and unchanged in sensitivity analyses. Limitations include site-specific and longitudinal variations in clinical practice and in the definition and availability of some data. Data on postnatal factors were not available. CONCLUSIONS: In this study, we observed a consistent association between birth by CS and infection-related hospitalisation in early childhood. Notwithstanding the limitations of observational data, the associations may reflect differences in early microbial exposure by mode of birth, which should be investigated by mechanistic studies. If our findings are confirmed, they could inform efforts to reduce elective CS rates that are not clinically indicated.