RSS 1.0Family Health
Recent Submissions
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Role of early management of hyperornithinaemia-hyperammonaemia-homocitrullinuria syndrome in pregnancyHyperornithinaemia-hyperammonaemia-homocitrullinuria (HHH) syndrome is a rare inherited metabolic disorder of the urea cycle. Few reports exist to guide practices during pregnancy and fetal delivery. Yet, with affected patients often surviving into reproductive age, appropriate management of the peripartum phase is essential to ensure positive maternal and fetal outcomes.Reassuringly, the vast majority of offspring of parturients with HHH syndrome have normal developmental outcomes; yet as seen here, fetal growth restriction does appear more frequently. Furthermore, in addition to the absent fetal corpus callosum observed in this case, other fetal cerebral abnormalities, including speech delay and intellectual impairment, have been recognised.Unregulated dietary intake is one proposed factor for the observed disruption in fetal growth and early cerebral development. These stipulations not only reinforce the importance of extensive planning and teamwork, but also demonstrate the importance of timely intervention by a metabolic dietician and dietary compliance in the early organogenesis stage of pregnancy.
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Rapid intrapartum test for maternal group B streptococcal colonisation and its effect on antibiotic use in labouring women with risk factors for early-onset neonatal infection (GBS2): cluster randomised trial with nested test accuracy studyBackground: Mother-to-baby transmission of group B Streptococcus (GBS) is the main cause of early-onset infection. We evaluated whether, in women with clinical risk factors for early neonatal infection, the use of point-of-care rapid intrapartum test to detect maternal GBS colonisation reduces maternal antibiotic exposure compared with usual care, where antibiotics are administered due to those risk factors. We assessed the accuracy of the rapid test in diagnosing maternal GBS colonisation, against the reference standard of selective enrichment culture. Methods: We undertook a parallel-group cluster randomised trial, with nested test accuracy study and microbiological sub-study. UK maternity units were randomised to a strategy of rapid test (GeneXpert GBS system, Cepheid) or usual care. Within units assigned to rapid testing, vaginal-rectal swabs were taken from women with risk factors for vertical GBS transmission in established term labour. The trial primary outcome was the proportion of women receiving intrapartum antibiotics to prevent neonatal early-onset GBS infection. The accuracy of the rapid test was compared against the standard of selective enrichment culture in diagnosing maternal GBS colonisation. Antibiotic resistance profiles were determined in paired maternal and infant samples. Results: Twenty-two maternity units were randomised and 20 were recruited. A total of 722 mothers (749 babies) participated in rapid test units; 906 mothers (951 babies) were in usual care units. There was no evidence of a difference in the rates of intrapartum antibiotic prophylaxis (relative risk 1.16, 95% CI 0.83 to 1.64) between the rapid test (41%, 297/716) and usual care (36%, 328/906) units. No serious adverse events were reported. The sensitivity and specificity measures of the rapid test were 86% (95% CI 81 to 91%) and 89% (95% CI 85 to 92%), respectively. Babies born to mothers who carried antibiotic-resistant Escherichia coli were more likely to be colonised with antibiotic-resistant strains than those born to mothers with antibiotic-susceptible E. coli. Conclusion: The use of intrapartum rapid test to diagnose maternal GBS colonisation did not reduce the rates of antibiotics administered for preventing neonatal early-onset GBS infection than usual care, although with considerable uncertainty. The accuracy of the rapid test is within acceptable limits. Trial registration: ISRCTN74746075 . Prospectively registered on 16 April 2015
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Rapid exome sequencing: revolutionises the management of acutely unwell neonatesDiagnosing acutely unwell infants with a potential genetic diagnosis can be challenging for healthcare professionals. Evidence suggests that up to 13% of critically unwell infants on the neonatal intensive care unit (NICU) have an underlying molecular diagnosis and when identified directly affects treatment decisions in 83%. On 1st October 2019, the National Health Service England (NHSE) launched a nationally commissioned service so that rapid whole-exome sequencing can be offered to critically unwell babies and children with a likely monogenic disorder who are admitted to NICU and paediatric intensive care unit (PICU). We present 7 cases from two neonatal units in the West Midlands (UK), where rapid exome sequencing has revealed a genetic diagnosis. Early genetic diagnosis in this cohort has influenced management in all (100%) cases, and in 57% (4 in 7 cases), it has helped in the decision to reorientate care. In some cases, early diagnosis has reduced the need for invasive and unnecessary investigations and avoided the need for post-mortem investigations. The genetic diagnosis has helped in counselling the families regarding the recurrence risk for future pregnancies. In some cases, this has provided parents with the reassurance of a low recurrence. In others, it has resulted in the offer of prenatal diagnosis or assisted conception technologies. What is Known: • Rapid whole-exome sequencing was commissioned in the UK in October 2019. • It is available for critically unwell babies with a likely monogenic aetiology. What is New: • It helps management planning for rare genetic disorders and future pregnancies counselling. • It can reduce the need for invasive investigations and overall intensive care costs.
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Emerging integrase resistance in an international perinatal virtual clinicObjective: The aim of this study was to identify the prevalence of emergent integrase drug resistance mutations (INSTI-DRMs) in international referrals to a perinatal virtual clinic (PVC). Design: A retrospective cohort study. Setting: Monthly multidisciplinary PVC reviewing complex case management for children and adolescents with perinatally acquired HIV (CAWHIV). Participants: One hundred fourteen cases referred for virological failure between October 2018 and January 2024. Main outcome measures: Data collected included age, sex, weight, country of residence, antiretroviral therapy (ART) history, HIV viral load, CD4+ cell count, and comorbidities. Resistance mutations were interpreted using the Stanford HIV Drug Resistance database with emergent major INSTI-DRMs described. Results: Of 114 referrals, 103 (90%) had resistance sequences available. Prior INSTI exposure was documented in 61/103 (59%) with 19/61 (31%) having INSTI-DRMs. For these 19, median (IQR) age was 11 years (6-14), weight 25 kg (17-50), CD4+ cell count 485 cells/μl (153-805), and viral load 84 000 copies/ml (2380-137 000). Twelve of 19 (65%) were from low/middle-income countries (LMIC), 6/19 (32%) had current AIDS diagnoses with 14/19 (74%) referred from 2022 onwards. There were a median three prior regimens with 13/19 (68%) having at least 3 class resistance. Two developed INSTI-DRMs on first-line dolutegravir (DTG)-based ART, 17 on second+ line therapy. PVC recommendations were for tenofovir+ lamivudine/emtricitabine (six split adult tablets) with boosted darunavir [19; six twice daily (b.i.d.)], with b.i.d. DTG (6), plus fostemsavir (1) and ibalizumab (1). Conclusion: Although uncommon, INSTI resistance is emerging, mainly in highly treatment experienced CAWHIV from LMIC, highlighting the global need for access to boosted protease inhibitors and novel classes, including formulations for children less than 35 kg.
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Are trainees working in obstetrics and gynecology confident and competent in the care of frail gynecological oncology patients?Introduction: Older patients undergoing cancer surgery are at increased risk of post-operative complications, prolonged hospital stay, and mortality. Identification of frailty can help predict patients at high risk of peri-operative complications and allow a collaborative, multidisciplinary team approach to their care. A survey was conducted to assess the confidence and knowledge of trainees in obstetrics and gynecology regarding identification and management of peri-operative issues encountered in frail gynecological oncology patients. Methods: A web-based survey was distributed via the Audit and Research in Gynaecological Oncology (ARGO) collaborative and UK Audit and Research Collaborative in Obstetrics and Gynaecology (UKARCOG) . The survey on the management of frail peri-operative patients was disseminated to doctors-in-training (trainees) working in obstetrics and gynecology in the United Kingdom (UK) and Ireland. Specialty (ST1-7), subspecialty, and general practice trainees, non-training grade doctors, and foundation year doctors currently working in obstetrics and gynecology were eligible. Consultants were excluded. Study data were collected using REDCAP software hosted at the University of Manchester. Responses were collected over a 6-week period between January and February 2020. Results: Of the 666 trainees who participated, 67% (425/666) reported inadequate training in peri-operative management of frail patients. Validated frailty assessment tools were used by only 9% (59/638) of trainees and less than 1% (4/613) were able to correctly identify all the diagnostic features of frailty. Common misconceptions included the use of chronological age and gender in frailty assessments. The majority of trainees (76.5%, 448/586) correctly answered a series of questions relating to mental capacity; however, only 6% (36/606) were able to correctly identify all three diagnostic features of delirium. A total of 87% (495/571) of trainees supported closer collaboration with geriatricians and a multidisciplinary approach. Conclusions: Obstetrics and gynecology trainees reported inadequate training in the peri-operative care of frail gynecological oncology patients, and overwhelmingly favored input from geriatricians. Routine use of validated frailty assessment tools may aid diagnosis of frailty in the peri-operative setting. There is an unmet need for formal education in the management of frail surgical patients within the UK and Irish obstetrics and gynecology curriculum.
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The immune landscape of SARS-CoV-2-associated Multisystem Inflammatory Syndrome in Children (MIS-C) from acute disease to recoveryMultisystem inflammatory syndrome in children (MIS-C) is a life-threatening disease occurring several weeks after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Deep immune profiling showed acute MIS-C patients had highly activated neutrophils, classical monocytes and memory CD8+ T-cells, with increased frequencies of B-cell plasmablasts and double-negative B-cells. Post treatment samples from the same patients, taken during symptom resolution, identified recovery-associated immune features including increased monocyte CD163 levels, emergence of a new population of immature neutrophils and, in some patients, transiently increased plasma arginase. Plasma profiling identified multiple features shared by MIS-C, Kawasaki Disease and COVID-19 and that therapeutic inhibition of IL-6 may be preferable to IL-1 or TNF-α. We identified several potential mechanisms of action for IVIG, the most commonly used drug to treat MIS-C. Finally, we showed systemic complement activation with high plasma C5b-9 levels is common in MIS-C suggesting complement inhibitors could be used to treat the disease.
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The impact of COVID-19 on the wellbeing of the UK nursing and midwifery workforce during the first pandemic wave: a longitudinal survey studyBackground: The specific challenges experienced by the nursing and midwifery workforce in previous pandemics have exacerbated pre-existing professional and personal challenges, and triggered new issues. We aimed to determine the psychological impact of the COVID-19 pandemic on the UK nursing and midwifery workforce and identify potential factors associated with signs of post-traumatic stress disorder. Methods: A United Kingdom national online survey was conducted at three time-points during the first wave of the COVID-19 pandemic between April and August 2020 (T1 and T2 during initial wave; T3 at three-months following the first wave). All members of the UK registered and unregistered nursing and midwifery workforce were eligible to participate. The survey was promoted via social media and through organisational email and newsletters. The primary outcome was an Impact of Events Scale-Revised score indicative of a post-traumatic stress disorder diagnosis (defined using the cut-off score ≥33). Multivariable logistic regression modelling was used to assess the association between explanatory variables and post-traumatic stress disorder. Results: We received 7840 eligible responses (T1- 2040; T2- 3638; T3- 2162). Overall, 91.6% participants were female, 77.2% were adult registered nurses, and 28.7% were redeployed during the pandemic. An Impact of Events Scale-Revised score ≥33 (probable post-traumatic stress disorder) was observed in 44.6%, 37.1%, and 29.3% participants at T1, T2, and T3 respectively. At all three time-points, both personal and workplace factors were associated with probable post-traumatic stress disorder, although some specific associations changed over the course of the pandemic. Increased age was associated with reduced probable post-traumatic stress disorder at T1 and T2 (e.g. 41-50 years at T1 odds ratio (OR) 0.60, 95% confidence interval (CI) 0.42-0.86), but not at T3. Similarly, redeployment with inadequate/ no training was associated with increased probable post-traumatic stress disorder at T1 and T2, but not at T3 (T1 OR 1.37, 95% CI 1.06-1.77; T3 OR 1.17, 95% CI 0.89-1.55). A lack of confidence in infection prevention and control training was associated with increased probable post-traumatic stress disorder at all three time-points (e.g. T1 OR 1.48, 95% CI 1.11-1.97). Conclusion: A negative psychological impact was evident 3-months following the first wave of the pandemic. Both personal and workplace are associated with adverse psychological effects linked to the COVID-19 pandemic. These findings will inform how healthcare organisations should respond to staff wellbeing needs both during the current pandemic, and in planning for future pandemics.
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TRAPPC11-related muscular dystrophy with hypoglycosylation of alpha-dystroglycan in skeletal muscle and brainAims: TRAPPC11, a subunit of the transport protein particle (TRAPP) complex, is important for complex integrity and anterograde membrane transport from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment. Several individuals with TRAPPC11 mutations have been reported with muscle weakness and other features including brain, liver, skeletal and eye involvement. A detailed analysis of brain and muscle pathology will further our understanding of the presentation and aetiology of TRAPPC11 disease. Methods: We describe five cases of early-onset TRAPPC11-related muscular dystrophy with a systematic review of muscle pathology in all five individuals, post-mortem brain pathology findings in one and membrane trafficking assays in another. Results: All affected individuals presented in infancy with muscle weakness, motor delay and elevated serum creatine kinase (CK). Additional features included cataracts, liver disease, intellectual disability, cardiomyopathy, movement disorder and structural brain abnormalities. Muscle pathology in all five revealed dystrophic changes, universal hypoglycosylation of alpha-dystroglycan and variably reduced dystrophin-associated complex proteins. Membrane trafficking assays showed defective Golgi trafficking in one individual. Neuropathological examination of one individual revealed cerebellar atrophy, granule cell hypoplasia, Purkinje cell (PC) loss, degeneration and dendrite dystrophy, reduced alpha-dystroglycan (IIH6) expression in PC and dentate neurones and absence of neuronal migration defects. Conclusions: This report suggests that recessive mutations in TRAPPC11 are linked to muscular dystrophies with hypoglycosylation of alpha-dystroglycan. The structural cerebellar involvement that we document for the first time resembles the neuropathology reported in N-linked congenital disorders of glycosylation (CDG) such as PMM2-CDG, suggesting defects in multiple glycosylation pathways in this condition.
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HIV postnatal prophylaxis and infant feeding policies vary across Europe: results of a Penta surveyObjectives: This survey was conducted to describe current European postnatal prophylaxis (PNP) and infant feeding policies with the aim of informing future harmonized guidelines. Methods: A total of 32 senior clinicians with relevant expertise, working in 20 countries within the European Region, were invited to complete a REDCap questionnaire between July and September 2023. Results: Twenty-three of the 32 invited paediatricians responded, representing 16/20 countries. There were multiple respondents from the same country for Italy (n = 5), the UK (n = 2), Germany (n = 2) and France (n = 2). All countries use risk stratification to guide PNP regimen selection. Nine out of 16 countries reported three risk categories, six out of 16 reported two, and one country reported differences in categorization. Criteria used to stratify risk varied between and within countries. For the lowest risk category, the PNP regimen reported ranged from no PNP to up to four weeks of one drug; the drug of choice reported was zidovudine, apart from one country which reported nevirapine. For the highest risk category, the most common regimen was zidovudine/lamivudine/nevirapine (20/23 respondents); regimen duration varied from two to six weeks with variation in recommended dosing. Guidelines support breastfeeding for infants born to people living with HIV in eight out of 16 countries; in the other eight, guidelines do not support/specify. Conclusions: Guidelines and practice for PNP and infant feeding vary substantially across Europe and within some countries, reflecting the lack of robust evidence. Effort is needed to align policies and practice to reflect up-to-date knowledge to ensure the vertical transmission risk is minimized and unnecessary infant HIV testing and PNP avoided, while simultaneously supporting families to make informed decisions on infant feeding choice.
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Prioritisation of early pregnancy risk factors for stillbirth: An international multistakeholder modified e-Delphi consensus study.Objective: To identify and prioritise early pregnancy risk factors for stillbirth to inform prognostic factor and model research. Study design: We used a modified e-Delphi method and consultation meeting to achieve consensus. Risk factors for early, late and stillbirth at any gestation identified from an umbrella review of risk factors for stillbirth were entered into a two-stage online Delphi survey with an international group of stakeholders made up of healthcare professionals and researchers. The RAND/ University of California at Los Angeles appropriateness method was used to evaluate consensus. Responders voted on a scale of 1-9 for each risk factor in terms of importance for early, late, and stillbirth at any gestation. Consensus for inclusion was reached if the median score was in the top tertile and at least two thirds of panellists had scored the risk factor within the top tertile. Results: Twenty-six risk factors were identified from an umbrella review and presented to stakeholders in round 1 of our e-Delphi survey. Round 1 was completed by 68 stakeholders, 79% (54/68) of whom went on to complete the second round. Seventeen risk factors were discussed at the consensus meeting. From the twenty-six risk factors identified, fifteen of these were prioritised for stillbirth at any gestation, eleven for early stillbirth, and sixteen for late stillbirth, across three domains of maternal characteristics, ultrasound markers and biochemical markers. The prioritised maternal characteristics common to early, late, and stillbirth at any gestation were: maternal age, smoking, drug misuse, history of heritable thrombophilia, hypertension, renal disease, diabetes, previous stillbirth and multiple pregnancy. Maternal BMI, access to healthcare, and socioeconomic status were prioritised for late stillbirth and stillbirth at any gestation. Previous pre-eclampsia and previous small for gestational age baby were prioritised for late stillbirth. Of the ultrasound markers, uterine artery Doppler pulsatility index and congenital fetal anomaly were prioritised for all. One biochemical marker, placental growth factor, was prioritised for stillbirth at any gestation. Conclusions: Our prioritised risk factors for stillbirth can inform formal factor-outcome evaluation of early pregnancy risk factors to influence public health strategies on prevention of such risk factors to prevent stillbirth.
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Preventing tuberculosis in paediatric kidney transplant recipients: is there a role for BCG immunisation pre-transplantation in low tuberculosis incidence countries?The risk of tuberculosis (TB) disease is increased in children with chronic kidney disease (CKD), even higher in stage 5 CKD/kidney failure and especially high after kidney transplantation due to immunosuppression. TB disease may follow recent primary infection, or result from reactivation of latent infection. Reactivation is more common in adults, while progression following primary infection makes up a greater proportion of disease in children. Recommendations for preventing TB disease in some low TB incidence countries have previously included offering Bacillus Calmette-Guérin (BCG) vaccine to all children listed for kidney transplant if they had not received this as part of previous national immunisation programmes. Based on the available evidence, we recommend modifying this practice, focusing instead on awareness of risk factors for TB exposure, infection and disease and the use of appropriate testing strategies to identify and treat TB infection and disease.
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Prediagnosis pathway benchmarking audit in patients with Duchenne muscular dystrophyObjective: To describe age and time at key stages in the Duchenne muscular dystrophy (DMD) prediagnosis pathway at selected centres to identify opportunities for service improvement. Design: A multicentre retrospective national audit. Setting: Nine tertiary neuromuscular centres across the UK and Ireland. A prior single-centre UK audit of 20 patients with no DMD family history provided benchmark criteria. Patients: Patients with a definitive diagnosis of DMD documented within 3 years prior to December 2018 (n=122). Main outcome measures: Mean age (months) at four key stages in the DMD diagnostic pathway and mean time (months) of presentational and diagnostic delay, and time from first reported symptoms to definitive diagnosis. Type of symptoms was also recorded. Results: Overall, mean age at definitive diagnosis, age at first engagement with healthcare professional (HCP) and age at first reported symptoms were 53.9±29.7, 49.9±28.9 and 36.4±26.8 months, respectively. The presentational delay and time to diagnosis were 21.1 (±21.1) and 4.6 (±7.9) months, respectively. The mean time from first reported symptoms to definitive diagnosis was 24.2±20.9. The percentages of patients with motor and/or non-motor symptoms recorded were 88% (n=106/121) and 47% (n=57/121), respectively. Conclusions: Majority of data mirrored the benchmark audit. However, while the time to diagnosis was shorter, a presentational delay was observed. Failure to recognise early symptoms of DMD could be a contributing factor and represents an unmet need in the diagnosis pathway. Methods determining how to improve this need to be explored.
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Diagnosis and management of selective fetal growth restriction in monochorionic twin pregnancies: A cross-sectional international survey.Objective: To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies. Design: Cross-sectional survey. Setting: International. Population: Clinicians involved in the management of MCDA twin pregnancies with sFGR. Methods: A structured, self-administered survey. Main outcome measures: Clinical practices and attitudes to diagnostic criteria and management strategies. Results: Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of <10th centile for the smaller twin and an inter-twin EFW discordance of >25% for the diagnosis of sFGR. For early-onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early-onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early-onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early-onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide. Conclusions: There is significant variation in clinician practices and attitudes towards the management of early-onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high-level evidence to guide management.
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X-linked Ohdo syndrome due to a novel MED12 variant detected by Rapid Exome Sequencing.No abstract available
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The burden of critical illness in hospitalized children in low- and middle-income countries: protocol for a systematic review and meta-analysis.Background: The majority of childhood deaths occur in low- and middle-income countries (LMICs). Many of these deaths are avoidable with basic critical care interventions. Quantifying the burden of pediatric critical illness in LMICs is essential for targeting interventions to reduce childhood mortality. Objective: To determine the burden of hospitalization and mortality associated with acute pediatric critical illness in LMICs through a systematic review and meta-analysis of the literature. Data sources and search strategy: We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, and LILACS using MeSH terms and keywords. Results will be limited to infants or children (ages >28 days to 12 years) hospitalized in LMICs and publications in English, Spanish, or French. Publications with non-original data (e.g., comments, editorials, letters, notes, conference materials) will be excluded. Study selection: We will include observational studies published since January 1, 2005, that meet all eligibility criteria and for which a full text can be located. Data extraction: Data extraction will include information related to study characteristics, hospital characteristics, underlying population characteristics, patient population characteristics, and outcomes. Data synthesis: We will extract and report data on study, hospital, and patient characteristics; outcomes; and risk of bias. We will report the causes of admission and mortality by region, country income level, and age. We will report or calculate the case fatality rate (CFR) for each diagnosis when data allow. Conclusions: By understanding the burden of pediatric critical illness in LMICs, we can advocate for resources and inform resource allocation and investment decisions to improve the management and outcomes of children with acute pediatric critical illness in LMICs.
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Neurodevelopmental outcomes following paracetamol use for treatment of patent ductus arteriosus: a review.Aim: Concerns exist regarding potential adverse neurodevelopmental outcomes associated with paracetamol exposure during pregnancy and early infancy. This review evaluates the evidence for the impact of paracetamol use for patent ductus arteriosus (PDA) treatment on neurodevelopmental outcomes in preterm infants. Methods: A literature search was performed via Medline, Ovid Embase and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. The search details are below: ('Infant, Newborn' [MeSH] OR 'neonate*' [Title/Abstract]) AND ('Paracetamol' [MeSH] OR 'Acetaminophen' [Title/Abstract]) AND ('Ductus Arteriosus, Patent/drug therapy' [MeSH] OR 'patent ductus arteriosus' [Title/Abstract]) AND ('Neurodevelopmental Disorders' [MeSH] OR 'neurodevelopment*' [Title/Abstract] OR 'Child Development' [MeSH] OR 'Developmental Disabilities' [MeSH]). All studies were critically appraised and synthesised. Results: Seven studies reported neurodevelopmental outcomes after paracetamol use for PDA treatment in preterm infants <32 weeks gestation. The studies varied in dosage, route, and duration of paracetamol administration and in the methods used to assess neurodevelopmental outcomes. None of the studies revealed different outcomes between paracetamol-exposed preterm infants and controls. Conclusion: Current low-to-moderate quality evidence suggests no association between paracetamol used for PDA treatment and adverse neurodevelopmental outcomes in preterm infants. Future well-powered studies with standardised neurodevelopmental assessments are warranted to strengthen the current evidence base.
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Vitamin D status of children with paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (PIMS-TS).Coronavirus disease 2019 (COVID-19) has caused mild illness in children, until the emergence of the novel hyperinflammatory condition paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS). PIMS-TS is thought to be a post-SARS-CoV-2 immune dysregulation with excessive inflammatory cytokine release. We studied 25 hydroxyvitamin D (25OHD) concentrations in children with PIMS-TS, admitted to a tertiary paediatric hospital in the UK, due to its postulated role in cytokine regulation and immune response. Eighteen children (median (range) age 8·9 (0·3-14·6) years, male = 10) met the case definition. The majority were of Black, Asian and Minority Ethnic (BAME) origin (89 %, 16/18). Positive SARS-CoV-2 IgG antibodies were present in 94 % (17/18) and RNA by PCR in 6 % (1/18). Seventy-eight percentage of the cohort were vitamin D deficient (< 30 nmol/l). The mean 25OHD concentration was significantly lower when compared with the population mean from the 2015/16 National Diet and Nutrition Survey (children aged 4-10 years) (24 v. 54 nmol/l (95 % CI -38·6, -19·7); P < 0·001). The paediatric intensive care unit (PICU) group had lower mean 25OHD concentrations compared with the non-PICU group, but this was not statistically significant (19·5 v. 31·9 nmol/l; P = 0·11). The higher susceptibility of BAME children to PIMS-TS and also vitamin D deficiency merits contemplation. Whilst any link between vitamin D deficiency and the severity of COVID-19 and related conditions including PIMS-TS requires further evidence, public health measures to improve vitamin D status of the UK BAME population have been long overdue.
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FERN: is it possible to conduct a randomised controlled trial of intervention or expectant management for early-onset selective fetal growth restriction in monochorionic twin pregnancy - protocol for a prospective multicentre mixed-methods feasibility studyIntroduction: Selective fetal growth restriction (sFGR) in monochorionic twin pregnancy, defined as an estimated fetal weight (EFW) of one twin <10th centile and EFW discordance ≥25%, is associated with stillbirth and neurodisability for both twins. The condition poses unique management difficulties: on the one hand, continuation of the pregnancy carries a risk of death of the smaller twin, with a high risk of co-twin demise (40%) or co-twin neurological sequelae (30%). On the other, early delivery to prevent the death of the smaller twin may expose the larger twin to prematurity, with the associated risks of long-term physical, emotional and financial costs from neurodisability, such as cerebral palsy.When there is severe and early sFGR, before viability, delivery is not an option. In this scenario, there are currently three main management options: (1) expectant management, (2) selective termination of the smaller twin and (3) placental laser photocoagulation of interconnecting vessels. These management options have never been investigated in a randomised controlled trial (RCT). The best management option is unknown, and there are many challenges for a potential RCT. These include the rarity of the condition resulting in a small number of eligible pregnancies, uncertainty about whether pregnant women will agree to participate in such a trial and whether they will agree to be randomised to expectant management or active fetal intervention, and the challenges of robust and long-term outcome measures. Therefore, the main objective of the FERN study is to assess the feasibility of conducting an RCT of active intervention vs expectant management in monochorionic twin pregnancies with early-onset (prior to 24 weeks) sFGR. Methods and analysis: The FERN study is a prospective mixed-methods feasibility study. The primary objective is to recommend whether an RCT of intervention vs expectant management of sFGR in monochorionic twin pregnancy is feasible by exploring women's preference, clinician's preference, current practice and equipoise and numbers of cases. To achieve this, we propose three distinct work packages (WPs). WP1: A Prospective UK Multicentre Study, WP2A: a Qualitative Study Exploring Parents' and Clinicians' Views and WP3: a Consensus Development to Determine Feasibility of a Trial. Eligible pregnancies will be recruited to WP1 and WP2, which will run concurrently. The results of these two WPs will be used in WP3 to develop consensus on a future definitive study. The duration of the study will be 53 months, composed of 10 months of setup, 39 months of recruitment, 42 months of data collection, and 5 months of data analysis, report writing and recommendations. The pragmatic sample size for WP1 is 100 monochorionic twin pregnancies with sFGR. For WP2, interviews will be conducted until data saturation and sample variance are achieved, that is, when no new major themes are being discovered. Based on previous similar pilot studies, this is anticipated to be approximately 15-25 interviews in both the parent and clinician groups. Engagement of at least 50 UK clinicians is planned for WP3. Ethics and dissemination: This study has received ethical approval from the Health Research Authority (HRA) South West-Cornwall and Plymouth Ethics Committee (REC reference 20/SW/0156, IRAS ID 286337). All participating sites will undergo site-specific approvals for assessment of capacity and capability by the HRA. The results of this study will be published in peer-reviewed journals and presented at national and international conferences. The results from the FERN project will be used to inform future studies. Trial registration number: This study is included in the ISRCTN Registry (ISRCTN16879394) and the NIHR Central Portfolio Management System (CPMS), CRN: Reproductive Health and Childbirth Specialty (UKCRN reference 47201).