Association of antenatal or neonatal SARS-COV-2 exposure with developmental and respiratory outcomes, and healthcare usage in early childhood: a national prospective cohort study.

Background: Perinatal exposure to SARS-CoV-2 may affect neurodevelopment before 12 months of age, but longer-term outcomes remain unknown. We examined whether antenatal or neonatal SARS-CoV-2 exposure compared with non-exposure is associated with neurodevelopment, respiratory symptoms, and health care usage in early childhood. Methods: This prospective national population-based cohort study was conducted in England and Wales, United Kingdom. We enrolled term-born children (≥37 weeks' gestation) with and without antenatal or neonatal exposure to SARS-CoV-2 infection by approaching parents of eligible children who were cared for in 87 NHS hospitals. Potential participants were identified through the national active surveillance studies of pregnant women and newborn infants hospitalised with confirmed SARS-CoV-2 infection conducted through the UK Obstetric Surveillance System and the British Paediatric Surveillance Unit. We defined antenatal and neonatal SARS-CoV-2 exposure as infants born to mothers hospitalised with confirmed SARS-CoV-2 infection between 14 + 0 and 36 + 6 weeks gestation and infants admitted to hospital with confirmed SARS-CoV-2 infection within the first 28 days after birth. Children born preterm or with major congenital anomaly or who were not residing in the UK were excluded. We assessed children's development (Ages and Stages Questionnaire 3rd Edition (ASQ-3); Ages and Stages Questionnaire Social-Emotional 2nd Edition (ASQ:SE-2)), respiratory symptoms (Liverpool Respiratory Symptom Questionnaire (LRSQ)) and health care usage (parent-completed questionnaire) at 21-32 months of age. Primary outcome: total ASQ-3 score, converted to z-scores. Secondary outcomes: ASQ:SE-2 z-scores; risk of delay in ASQ-3 domains; total LRSQ scores, converted to z-scores. Analyses were adjusted for children's age, sex, maternal ethnicity, parental education, and index of multiple deprivation. Findings: Between October 20, 2021 and January 27, 2023, we approached 668 and 1877 families out of 712 and 1917 potentially eligible participants in the exposed and comparison cohort. Of the 125 and 306 participants who were enrolled to the exposed and comparison cohort 121 and 301 participants completed the questionnaires and 96 and 243 participants were included in the analysis. In the age adjusted analysis, the mean total ASQ-3 z-score was lower in the exposed than the comparison cohort (-0.3, 95% CI: -0.6 to -0.05), however, when adjusted for sex, parental education, ethnicity and IMD quintile, there was no significant difference (difference in mean z-score = -0.2 95% CI: -0.5 to 0.03). SARS-CoV-2 exposure was associated with increased risk of delayed personal-social skills (odds ratio = 3.81; 95% CI: 1.07-13.66), higher ASQ:SE-2 total z-scores (difference in mean z-score = 0.4; 95% CI: 0.2-0.6) and increased risk of delayed social-emotional development (OR = 3.58, 95% CI: 1.30-9.83), after adjusting for sex, age at assessment, parental education, ethnicity and IMD quintile. The exposed cohort had a higher mean total LRSQ z-score than the comparison cohort (0.3 95% CI: 0-0.6) and higher inpatient (38% vs. 21%, p = 0.0001), outpatient (38% vs. 30%, p = 0.0090), and General Practitioner appointments (60% vs. 50%, p = 0.021) than the comparison cohort, after adjusting for sex, age at assessment, parental education, ethnicity and IMD quintile. No differences in other secondary outcomes between the exposed and comparison cohorts were found. Interpretation: Although the exposed cohort did not differ from the comparison cohort on the primary outcome, total ASQ-3 score, the exposed cohort were at greater risk of delayed social-emotional development, had a greater prevalence of respiratory symptoms and increased health care usage relative to the comparison cohort. The study is limited by the smaller sample size due to the low response rate and lack of clinical developmental assessments. Given the association of poor social-emotional development with antenatal or neonatal SARS-CoV-2 exposure, developmental screening, and follow-up of children with confirmed antenatal or neonatal SARS-CoV-2 infection may be warranted to identify those in need of early intervention. Funding: Action Medical Research for Children.

Efficacy and Safety Analyses of Recombinant Factor VIIa in Severe Post-Partum Hemorrhage.

Background: Despite a range of available treatments, it is still sometimes challenging to treat patients with severe post-partum hemorrhage (sPPH). Objective: This study evaluated the efficacy and safety of recombinant activated factor VIIa (rFVIIa) in sPPH management. Methods: An open-label, multi-center, randomized controlled trial (RCT; NCT00370877) and four observational studies (OS; OS-1 (NCT04723979), OS-2, OS-3, and OS-4) were analyzed regarding efficacy (need for subsequent invasive procedures, including uterine compression sutures, uterine or iliac artery ligations, arterial embolization, or hysterectomy) and safety (incidence of thromboembolic events (TE) and maternal mortality) of rFVIIa for sPPH. The RCT, and OS-1 and OS-2, included a control group of women who did not receive rFVIIa (with propensity score-matching used in OS-1 and OS-2), whereas OS-3 and OS-4 provided descriptive data for rFVIIa-exposed women only. Results: A total of 446 women exposed to rFVIIa and 1717 non-exposed controls were included. In the RCT, fewer rFVIIa-exposed women (50% [21/42]) had an invasive procedure versus non-exposed women (91% [38/42]; odds ratio: 0.11; 95% confidence interval: 0.03-0.35). In OS-1, more rFVIIa-exposed women (58% [22/38]) had an invasive procedure versus non-exposed women (35% [13.3/38]; odds ratio: 2.46; 95% confidence interval: 1.06-5.99). In OS-2, 17% (3/18) of rFVIIa-exposed women and 32% (5.6/17.8) of non-exposed women had an invasive procedure (odds ratio: 0.33; 95% confidence interval: 0.03-1.75). Across all included women, TEs occurred in 1.5% (0.2% arterial and 1.2% venous) of rFVIIa-exposed women and 1.6% (0.2% arterial and 1.4% venous) of non-exposed women with available data. Conclusions: The positive treatment effect of rFVIIa on the RCT was not confirmed in the OS. However, the safety analysis did not show any increased incidence of TEs with rFVIIa treatment.

Perinatal outcomes after admission with COVID-19 in pregnancy: a UK national cohort study.

There are few population-based studies of sufficient size and follow-up duration to have reliably assessed perinatal outcomes for pregnant women hospitalised with SARS-CoV-2 infection. The United Kingdom Obstetric Surveillance System (UKOSS) covers all 194 consultant-led UK maternity units and included all pregnant women admitted to hospital with an ongoing SARS-CoV-2 infection. Here we show that in this large national cohort comprising two years' active surveillance over four SARS-CoV-2 variant periods and with near complete follow-up of pregnancy outcomes for 16,627 included women, severe perinatal outcomes were more common in women with moderate to severe COVID-19, during the delta dominant period and among unvaccinated women. We provide strong evidence to recommend continuous surveillance of pregnancy outcomes in future pandemics and to continue to recommend SARS-CoV-2 vaccination in pregnancy to protect both mothers and babies.

Preterm prelabour rupture of membranes before 23 weeks' gestation: prospective observational study.

Objective: To describe perinatal and maternal outcomes of preterm prelabour rupture of membranes (PPROM) before 23 weeks' gestation in a national cohort. Design: Prospective observational study. Setting: National population based cohort study with the UK Obstetric Surveillance System (UKOSS), a research infrastructure of all 194 obstetric units in the UK, 1 September 2019 to 28 February 2021. Participants: 326 women with singleton and 38 with multiple pregnancies with PPROM between 16+0 and 22+6 weeks+days' gestation. Main outcome measures: Perinatal outcomes of live birth, survival to discharge from hospital, and severe morbidity, defined as intraventricular haemorrhage grade 3 or 4, or requiring supplemental oxygen at 36 weeks' postmenstrual age, or both. Maternal outcomes were surgery for removal of the placenta, sepsis, admission to an intensive treatment unit, and death. Clinical data included rates of termination of pregnancy for medical reasons. Results: Perinatal outcomes were calculated with all terminations of pregnancy for medical reasons excluded, and a worst-best range was calculated assuming that all terminations for medical reasons and those with missing data would have died (minimum value) or all would be liveborn (maximum value). For singleton pregnancies, the live birth rate was 44% (98/223), range 30-62% (98/326-201/326), perinatal survival to discharge from hospital was 26% (54/207), range 17-53% (54/326-173/326), and 18% (38/207), range 12-48% (38/326-157/326) of babies survived without severe morbidity. The rate of maternal sepsis was 12% (39/326) in singleton and 29% (11/38) in multiple pregnancies (P=0.004). Surgery for removal of the placenta was needed in 20% (65/326) and 16% (6/38) of singleton and twin pregnancies, respectively. Five women became severely unwell with sepsis; two died and another three required care in the intensive treatment unit. Conclusions: In this study, 26% of women who had very early PPROM with expectant management had babies that survived to discharge from hospital. Morbidity and mortality rates were high for both mothers and neonates. Maternal sepsis is a considerable risk that needs more research. These data should be used in counselling families with PPROM before 23 weeks' gestation, and currently available guidelines should be updated accordingly.

A Population-Based Cohort Study on Diagnosis and Early Management of Anorectal Malformation in the UK and Ireland.

BACKGROUND: This study describes the presentation and initial management of anorectal malformation (ARM); evaluating the frequency, causes and consequences of late diagnosis. METHODS: A prospective, population cohort study was undertaken for newly diagnosed ARMs in the UK and Ireland from 01/10/2015 and 30/09/2016. Follow-up was completed at one year. Data are presented as n (%), appropriate statistical methods used. Factors associated with late diagnosis; defined as: detection of ARM either following discharge or more than 72 h after birth were assessed with univariable logistic regression. RESULTS: Twenty six centres reported on 174 cases, 158 of which were classified according to the type of malformation and 154 had completed surgical data. Overall, perineal fistula was the most commonly detected anomaly 43/158 (27%); of the 41 of these children undergoing surgery, 15 (37%) had a stoma formed. 21/154 (14%, CI95{9-20}) patients undergoing surgery experienced post-operative complications. Thirty-nine (22%) were diagnosed late and 12 (7%) were detected >30 days after birth. Factors associated with late diagnosis included female sex (OR 2.06; 1.0-4.26), having a visible perineal opening (OR 2.63; 1.21-5.67) and anomalies leading to visible meconium on the perineum (OR 18.74; 2.47-141.73). 56/174 (32%) had a diagnosis of VACTERL association (vertebral, anorectal, cardiac, tracheal, oesophageal, renal and limb); however, not all infants were investigated for commonly associated anomalies. 51/140 (36%) had a cardiac anomaly detected on echocardiogram. CONCLUSION: There is room for improvement within the care for infants born with ARM in the UK and Ireland. Upskilling those performing neonatal examination to allow timely diagnosis, instruction of universal screening for associated anomalies and further analysis of the factors leading to clinically unnecessary stoma formation are warranted. LEVEL OF EVIDENCE: II (Prospective Cohort Study <80% follow-up).

Infection-related severe maternal outcomes and case fatality rates in 43 low and middle-income countries across the WHO regions: Results from the Global Maternal Sepsis Study (GLOSS).

The highest toll of maternal mortality due to infections is reported in low and middle-income countries (LMICs). However, more evidence is needed to understand the differences in infection-related severe maternal outcomes (SMO) and fatality rates across the WHO regions. This study aimed to compare the burden of infection-related SMO and case fatality rates across the WHO regions using the Global Maternal Sepsis Study (GLOSS) data. GLOSS was a hospital-based one-week inception prospective cohort study of pregnant or recently pregnant women admitted with suspected or confirmed infection in 2017. Four hundred and eight (408) hospitals from 43 LMICs in the six WHO regions were considered in this analysis. We used a logistic regression model to compare the odds of infection-related SMOs by region. We then calculated the fatality rate as the proportion of deaths over the total number of SMOs, defined as maternal deaths and near-misses. The proportion of SMO was 19.6% (n = 141) in Africa, compared to 18%(n = 22), 15.9%(n = 50), 14.7%(n = 48), 12.1%(n = 95), and 10.8%(n = 21) in the Western Pacific, European, Eastern Meditteranean, Americas, and South-Eastern Asian regions, respectively. Women in Africa were more likely to experience SMO than those in the Americas (aOR = 2.41, 95%CI: [1.78 to 2.83]), in South-East Asia (aOR = 2.60, 95%CI: [1.57 to 4.32]), and the Eastern Mediterranean region (aOR = 1.58, 95%CI: [1.08 to 2.32]). The case fatality rate was 14.3%[3.05% to 36.34%] (n/N = 3/21) and 11.4%[6.63% to 17.77%] (n/N = 16/141) in the South-East Asia and Africa, respectively. Infection-related SMOs and case fatality rates were highest in Africa and Southeast Asia. Specific attention and actions are needed to prevent infection-related maternal deaths and severe morbidity in these two regions.

Impact of maternal risk factors on ethnic disparities in maternal mortality: a national population-based cohort study.

Background: Ethnic disparities in maternal mortality are consistently reported. This study aimed to investigate the contribution of known risk factors including age, socioeconomic status, and medical comorbidities to observed ethnic disparities in the United Kingdom (UK). Methods: A cohort of all women who died during or up to six weeks after pregnancy in the UK 2009-2019 were identified through national surveillance. No single denominator population included data on all risk factors, therefore we used logistic regression modelling to compare to 1) routine population birth and demographic data (2015-19) (routine data comparator) and 2) combined control groups of four UK Obstetric Surveillance System studies (UKOSS) control comparator)). Findings: There were 801 maternal deaths in the UK between 2009 and 2019 (White: 70%, Asian: 13%, Black: 12%, Chinese/Other: 3%, Mixed: 2%). Using the routine data comparator (n = 3,519,931 maternities) to adjust for demographics, including social deprivation, women of Black ethnicity remained at significantly increased risk of maternal death compared with women of white ethnicity (adjusted OR 2.43 (95% Confidence Interval 1.92-3.08)). The risk was greatest in women of Caribbean ethnicity (aOR 3.55 (2.30-5.48)). Among women of White ethnicity, risk of mortality increased as deprivation increased, but women of Black ethnicity had greater risk irrespective of deprivation. Using the UKOSS control comparator (n = 2210), after multiple adjustments including smoking, body mass index, and comorbidities, women of Black and Asian ethnicity remained at increased risk (aOR 3.13 (2.21-4.43) and 1.57 (1.16-2.12) respectively). Interpretation: Known risk factors do not fully explain ethnic disparities in maternal mortality. The impact of socioeconomic deprivation appears to differ between ethnic groups. Funding: This research is funded by the National Institute for Health and Care Research (NIHR) Policy Research Programme, conducted through the Policy Research Unit in Maternal and Neonatal Health and Care, PR-PRU-127-21202.

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 health research during emerging and ongoing epidemic threats: a landscape analysis and expert consultation.

INTRODUCTION: Pregnant women and their offspring are often at increased direct and indirect risks of adverse outcomes during epidemics and pandemics. A coordinated research response is paramount to ensure that this group is offered at least the same level of disease prevention, diagnosis, and care as the general population. We conducted a landscape analysis and held expert consultations to identify research efforts relevant to pregnant women affected by disease outbreaks, highlight gaps and challenges, and propose solutions to addressing them in a coordinated manner. METHODS: Literature searches were conducted from 1 January 2015 to 22 March 2022 using Web of Science, Google Scholar and PubMed augmented by key informant interviews. Findings were reviewed and Quid analysis was performed to identify clusters and connectors across research networks followed by two expert consultations. These formed the basis for the development of an operational framework for maternal and perinatal research during epidemics. RESULTS: Ninety-four relevant research efforts were identified. Although well suited to generating epidemiological data, the entire infrastructure to support a robust research response remains insufficient, particularly for use of medical products in pregnancy. Limitations in global governance, coordination, funding and data-gathering systems have slowed down research responses. CONCLUSION: Leveraging current research efforts while engaging multinational and regional networks may be the most effective way to scale up maternal and perinatal research preparedness and response. The findings of this landscape analysis and proposed operational framework will pave the way for developing a roadmap to guide coordination efforts, facilitate collaboration and ultimately promote rapid access to countermeasures and clinical care for pregnant women and their offspring in future epidemics.

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.

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.

Place of birth and postnatal transfers in infants with congenital diaphragmatic hernia in England and Wales: a descriptive observational cohort study.

OBJECTIVE: To describe clinical pathways for infants with congenital diaphragmatic hernia (CDH) and short-term outcomes. DESIGN: Retrospective observational cohort study using the UK National Neonatal Research Database (NNRD). PATIENTS: Babies with a diagnosis of CDH admitted to a neonatal unit in England and Wales between 2012 and 2020. MAIN OUTCOME MEASURES: Clinical pathways defined by place of birth (with or without colocated neonatal and surgical facilities), transfers, clinical interventions, length of hospital stay and discharge outcome. RESULTS: There were 1319 babies with a diagnosis of CDH cared for in four clinical pathways: born in maternity units with (1) colocated tertiary neonatal and surgical units ('neonatal surgical units'), 50% (660/1319); (2) designated tertiary neonatal unit and transfer to stand-alone surgical centre ('tertiary designated'), 25% (337/1319); (3) non-designated tertiary neonatal unit ('tertiary non-designated'), 7% (89/1319); or (4) non-tertiary unit ('non-tertiary'), 18% (233/1319)-the latter three needing postnatal transfers. Infant characteristics were similar for infants born in neonatal surgical and tertiary designated units. Excluding 149 infants with minimal data due to early transfer (median (IQR) 2.2 (0.4-4.5) days) to other settings, survival to neonatal discharge was 73% (851/1170), with a median (IQR) stay of 26 (16-44) days. CONCLUSIONS: We found that half of the babies with CDH were born in hospitals that did not have on-site surgical services and required postnatal transfer. Similar characteristics between infants born in neonatal surgical units and tertiary designated units suggest that organisation rather than infant factors influence place of birth. Future work linking the NNRD to other datasets will enable comparisons between care pathways.

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial.

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome.

Determinants of behaviors influencing implementation of maternal and perinatal death surveillance and response in low- and middle-income countries: A systematic review of qualitative studies.

BACKGROUND: Maternal and Perinatal Death Surveillance and Review (MPDSR) can reduce mortality but its implementation is often suboptimal, especially in low- and middle-income countries (LMICs). OBJECTIVES: To understand the determinants of behaviors influencing implementation of MPDSR in LMICs (through a systematic review of qualitative studies), in order to plan an intervention to improve its implementation. SEARCH STRATEGY: Terms for maternal or perinatal death reviews and qualitative studies. SELECTION CRITERIA: Qualitative studies regarding implementation of MPDSR in LMICs. DATA COLLECTION AND ANALYSIS: We coded the included studies using the Theoretical Domains Framework and COM-B model of behavior change (Capability, Opportunity, Motivation). We developed guiding principles for interventions to improve implementation of MPDSR. MAIN RESULTS: Fifty-nine studies met our inclusion criteria. Capabilities required to conduct MPDSR (knowledge and technical/leadership skills) increase cumulatively from community to health facility and leadership levels. Physical and social opportunities depend on adequate data, human and financial resources, and a blame-free environment. All stakeholders were motivated to avoid negative consequences (blame, litigation, disciplinary action). CONCLUSIONS: Implementation of MPDSR could be improved by (1) introducing structural changes to reduce negative consequences, (2) strengthening data collection tools and information systems, (3) mobilizing adequate resources, and (4) building capabilities of all stakeholders.

Characteristics and outcomes of pregnant women hospitalized with severe maternal outcomes in eastern Ethiopia: Results from the Ethiopian Obstetric Surveillance System study.

OBJECTIVE: The aim of the present study was to identify facility-based incidence of severe obstetric complications through a newly established obstetric surveillance system in eastern Ethiopia. METHODS: Monthly registration of obstetric hemorrhage, eclampsia, uterine rupture, severe anemia and sepsis was introduced in 13 maternity units in eastern Ethiopia. At each hospital, a designated clinician reported details of women admitted during pregnancy, childbirth or within 42 days of termination of pregnancy from April 01, 2021 to March 31, 2022 developing any of these conditions. Detailed data on sociodemographic characteristics, obstetric complications and status at discharge were collected by trained research assistants. RESULTS: Among 38 782 maternities during the study period, 2043 (5.3%) women had any of the five conditions. Seventy women died, representing a case fatality rate of 3.4%. The three leading reasons for admission were obstetric hemorrhage (972; 47.6%), severe anemia (727; 35.6%), and eclampsia (438; 21.4%). The majority of the maternal deaths were from obstetric hemorrhage (27/70; 38.6%) followed by eclampsia (17/70; 24.3%). CONCLUSION: Obstetric hemorrhage, severe anemia and eclampsia were the leading causes of severe obstetric complications in eastern Ethiopia. Almost one in 29 women admitted with obstetric complications died. Audit of quality of care is indicated to design tailored interventions to improve maternal survival and obstetric complications.

Characteristics and outcomes of neonates hospitalised with SARS-CoV-2 infection in the UK by variant: a prospective national cohort study.

OBJECTIVE: Neonatal infection with wildtype SARS-CoV-2 is rare and good outcomes predominate. We investigated neonatal outcomes using national population-level data to describe the impact of different SARS-CoV-2 variants. DESIGN: Prospective population-based cohort study. SETTING: Neonatal, paediatric and paediatric intensive care inpatient care settings in the UK. PATIENTS: Neonates (first 28 days after birth) with confirmed SARS-CoV-2 infection who received inpatient care, March 2020 to April 2022. Neonates were identified through active national surveillance with linkage to national SARS-CoV-2 testing data, routinely recorded neonatal data, paediatric intensive care data and obstetric and perinatal mortality surveillance data. OUTCOMES: Presenting signs, clinical course, severe disease requiring respiratory support are presented by the dominant SARS-CoV-2 variant in circulation at the time. RESULTS: 344 neonates with SARS-CoV-2 infection received inpatient care; breakdown by dominant variant: 146 wildtype, 123 alpha, 57 delta and 18 omicron. Overall, 44.7% (153/342) neonates required respiratory support; short-term outcomes were good with 93.6% (322/344) of neonates discharged home. Eleven neonates died: seven unrelated to SARS-CoV-2 infection, four were attributed to neonatal SARS-CoV-2 infection (case fatality 4/344, 1.2% 95% CI 0.3% to 3.0%) of which three were born preterm due to maternal COVID-19. More neonates were born very preterm (23/54) and required invasive ventilation (27/57) when delta variant was predominant, and all four SARS-CoV-2-related deaths occurred in this period. CONCLUSIONS: Inpatient care for neonates with SARS-CoV-2 was uncommon. Although rare, severe neonatal illness was more common during the delta variant period, potentially reflecting more severe maternal disease and associated preterm birth. TRIAL REGISTRATION NUMBER: ISRCTN60033461.

Defining treatment success in children with surgical conditions.

OBJECTIVES: Develop a score summarising how successfully a child with any surgical condition has been treated, and test the clinical validity of the score. DESIGN: Discrete choice experiment (DCE), and secondary analysis of data from six UK-wide prospective cohort studies. PARTICIPANTS: 253 people with lived experience of childhood surgical conditions, 114 health professionals caring for children with surgical conditions and 753 members of the general population completed the DCE. Data from 1383 children with surgical conditions were used in the secondary analysis. MAIN OUTCOME MEASURES: Normalised importance value of attribute (NIVA) for number/type of operations, hospital-treated infections, quality of life and duration of survival (reference attribute). RESULTS: Quality of life and duration of survival were the most important attributes in deciding whether a child had been successfully treated. Parents, carers and previously treated adults placed equal weight on both attributes (NIVA=0.996; 0.798 to 1.194). Healthcare professionals placed more weight on quality of life (NIVA=1.469; 0.950 to 1.987). The general population placed more weight on survival (NIVA=0.823; 95% CI 0.708 to 0.938). The resulting score (the Children's Surgery Outcome Reporting (CSOR) Treatment Success Score (TSS)) has the best possible value of 1, a value of 0 describes palliation and values less than 0 describe outcomes worse than palliation. CSOR TSSs varied clinically appropriately for infants whose data were included in the UK-wide cohort studies. CONCLUSIONS: The CSOR TSS summarises how successfully children with surgical conditions have been treated, and can therefore be used to compare hospitals' observed and expected outcomes.