Risk factors for infection and outcomes in infants with neonatal encephalopathy: a cohort study.

BACKGROUND: To determine the association between early infection risk factors and short-term outcomes in infants with neonatal encephalopathy following perinatal asphyxia (NE). METHODS: A retrospective population-based cohort study utilizing the National Neonatal Research Database that included infants with NE admitted to neonatal units in England and Wales, Jan 2008-Feb 2018. EXPOSURE: one or more of rupture of membranes >18 h, maternal group B streptococcus colonization, chorioamnionitis, maternal pyrexia or antepartum antibiotics. PRIMARY OUTCOME: death or nasogastric feeds/nil by mouth (NG/NBM) at discharge. SECONDARY OUTCOMES: organ dysfunction; length of stay; intraventricular hemorrhage; antiseizure medications use. RESULTS: 998 (13.7%) out of 7265 NE infants had exposure to early infection risk factors. Primary outcome (20.3% vs. 23.1%, OR 0.87 (95% CI 0.71-1.08), p = 0.22), death (12.8% vs. 14.0%, p = 0.32) and NG/NBM (17.4% vs. 19.9%. p = 0.07) did not differ between the exposed and unexposed group. Time to full sucking feeds (OR 0.81 (0.69-0.95)), duration (OR 0.82 (0.71-0.95)) and the number of antiseizure medications (OR 0.84 (0.72-0.98)) were lower in exposed than unexposed infants after adjusting for confounders. Therapeutic hypothermia did not alter the results. CONCLUSIONS: Infants with NE exposed to risk factors for early-onset infection did not have worse short-term adverse outcomes. IMPACT: Risk factors for early-onset neonatal infection, including rupture of membranes >18 h, maternal group B streptococcus colonization, chorioamnionitis, maternal pyrexia or antepartum antibiotics, were not associated with death or short-term morbidity after cooling for NE. Despite exposure to risk factors for early-onset neonatal infection, infants with NE reached oral feeds earlier and needed fewer anti-seizure medications for a shorter duration than infants with NE but without such risk factors. This study supports current provision of therapeutic hypothermia for infants with NE and any risk factors for early-onset neonatal infection.

Race and Ethnicity, Deprivation, and Infant Mortality in England, 2019-2022.

Importance: England has one of the highest infant mortality rates in Europe. Much of the variation in infant mortality rates between races and ethnicities may be due to socioeconomic factors, but how deprivation and race and ethnicity are associated with infant mortality is unclear. Objectives: To investigate the association of infant race and ethnicity with the infant mortality rate in England, adjusted for preterm birth and level of deprivation. Design, Setting, and Participants: This cohort study included children who died younger than 1 year of age, born at or after 22 weeks' gestation, occurring from April 1, 2019, to March 31, 2022, in England. Characteristics of the infant were derived from death notifications. Exposures: The racial and ethnic groups were derived from National Health Service data and were reported by the parents and characterized using the Office of National Statistics classification: Asian or Asian British (Bangladeshi, Chinese, Indian, Pakistani, or any other Asian background), Black or Black British (African, Caribbean, or any other Black background), multiracial (White and Asian, White and Black African, White and Black Caribbean, or any other multiracial background), White or White British (British, Irish, any other White background, or Gypsy or Irish Traveler), and other (Arab or any other racial or ethnic group). Main Outcomes and Measures: Risk of death for all racial and ethnic groups and relative risk of death compared with the reference group (White) were calcuated. Analyses were repeated, adjusting for deprivation, gestational age of infants, and region of England. Results: A total of 5621 infants who died younger than 1 year of age were reported to the National Child Mortality Database. A total of 2842 of 5130 infants (55.4%) were male; the median gestational age was 33 weeks (IQR, 25-38 weeks); of 5149 infants, 927 (18.0%) were Asian, 448 (8.7%) were Black, 3318 (64.4%) were White, 343 (6.7%) were multiracial, and 113 (2.2%) were from other racial and ethnic groups; and the median deprivation score was 4 (IQR, 3-5). In the unadjusted analysis, the relative risk of death compared with White infants was higher for Black (1.93 [95% CI, 1.75-2.13]) and Asian (1.67 [95% CI, 1.55-1.80]) infants. The population attributable risk fraction for all mortality rates among infants who were not White was 12.0% (95% CI, 10.3%-13.8%) (unadjusted), 9.8% (95% CI, 8.0%-11.7%) (adjusted for deprivation), 7.7% (95% CI, 5.9%-9.5%) (adjusted for gestational age at birth), and 12.8% (95% CI, 11.0%-14.5%) (adjusted for region of England). Conclusions and Relevance: This cohort study suggests that the proportion of infants who died before 1 year of age is associated with race and ethnicity, with a population attributable risk fraction of 12.0%. An overconservative adjustment for deprivation did not explain the overall patterns seen. Approximately half the population attributable risk fraction may be due to increased risk of preterm birth in Asian and Black communities. Work is needed to identify what can be done to reduce this incidence of infant mortality.

Newborn Health and Child Mortality Across England.

Importance: Although the immediate impact of neonatal illness is well recognized, its wider and longer term outcomes on childhood mortality and the role of specific illnesses across childhood are unclear. Objective: To investigate how many deaths in childhood are associated with neonatal illness and the underlying conditions of the children who died. Design, Setting, and Participants: This population-based cohort study of children who died before age 10 years in England between April 1, 2019, and March 31, 2021, used data from the National Child Mortality Database. Data analysis was performed from September 2022 to May 2023. Exposure: Children who received care in a neonatal unit after birth plus those who died in the first day of life, before admission to a neonatal unit, were considered to have likely neonatal illness. Main Outcomes and Measures: The primary outcome was the relative risk (RR) of dying, stratified by likely neonatal illness and specific neonatal conditions. Comparisons were made using the χ2 or likelihood ratio test, as appropriate. Results: A total of 4829 children were included (median [IQR] age at death, 28 [2-274] days; 2606 boys [54.8%]; 2690 White children [64.0%]). Overall, 3456 children who died (71.6%) had evidence of likely neonatal illness. Children with neonatal illness were more likely to die before their tenth birthday than those without evidence of neonatal illness (RR, 13.82; 95% CI, 13.00-14.71). The estimated population-attributable risk fraction for neonatal illness among all deaths before age 10 years was 66.4% (95% CI, 64.9%-67.9%). Children with preceding neonatal illness who died were more likely to have underlying behavioral or developmental disorders (odds ratio [OR], 3.31; 95% CI, 2.47-4.42), chronic neurological disease (OR, 3.00; 95% CI, 2.51-3.58), and chronic respiratory disease (OR, 3.01; 95% CI, 2.43-3.73) than children without neonatal illness. Conclusions and Relevance: In this cohort study, most children who died before age 10 years had some evidence of neonatal illness, and they died of a range of causes, including infections and sudden, unexpected, unexplained death. These findings suggest that improvements to perinatal morbidity, an area with an existing evidence base for improvement, may have important impacts on child health across the next decade.

Quality of Life at a 10-Year Follow-Up of Children Born Preterm with Post-Hemorrhagic Ventricular Dilatation: A Cohort Study.

BACKGROUND: Post-haemorrhagic ventricular dilatation (PHVD) is commonly seen in extremely preterm babies, carries significant morbidity, and may cause neonatal mortality. There is a lack of literature on the subsequent health-related quality of life (HRQoL) in childhood. The aim of this work was to assess the quality of life of preterm babies after PHVD at 10 years of age using two validated questionnaires. METHODS: Children with PHVD were assessed as part of the 10-year follow-up of the drainage, irrigation, and fibrinolytic therapy trial. The HRQoL outcome was measured using parent-reported EQ-5D-5L and HUI-3 questionnaires. Both questionnaires produce a summary score anchored at 1 (best health) and 0 (equivalent to death). RESULTS: Median scores at follow-up were 0.65 (IQR 0.36-0.84; n = 44) for the EQ-5D-5L and 0.52 (IQR 0.22-0.87; n = 51) for the HUI-3. Similar proportions had a score below 0.2 (HRQoL [20%], HUI-3 [21%]), while 20% had a HRQoL score above 0.80 compared to 34% using HUI-3. The most severe problems from the EQ-5D-5L were reported in the self-care, mobility, and activity domains, while the HUI-3 reported worse problems in ambulation, cognition, and dexterity domains. Infants with worse (grade 4) intraventricular haemorrhage had poorer HRQoL than those with grade 3 bleeds. CONCLUSION: Children who survive to 10 years of age after PHVD have on average lower HRQoL than their peers. However, the reported range is wide, with a quarter of the children having scores above 0.87 (similar to population norms), while a fifth have very low HRQol scores. Impact was not uniform across domains, with mobility/ambulation a concern across both measures.

Measuring the impact of deprivation on learning difficulties and behaviour among infants born preterm: A cohort study.

BACKGROUND: Preterm birth and social deprivation are known risk factors for learning difficulties. However there has been little work looking into the interaction between these two risks. We aimed to identify if children born preterm to families with higher levels of social deprivation are disproportionately more likely to have learning difficulties than those with lower levels of social deprivation. METHODS: Data from the RANOPS (Respiratory And Neurological Outcomes in children born Preterm Study) was used to assess prevalence of learning difficulties. The effects of preterm birth and deprivation were reviewed. Multi-level logistic regression models were used to examine if gestational age and deprivation impacts interacted after adjustment for possible confounders. Primary outcome measure was parent-reported learning difficulties. Secondary outcome measures were parent-reported behavioural problems and a statement of special educational need. RESULTS: We investigated the developmental outcomes of 6,691 infants with a median age of 5 years at time of survey (IQR 5). Deprivation decile (OR 1.08 (1.03,1.12)) and preterm birth (OR 2.67 (2.02,3.53)) were both associated with increased risk of learning difficulties. There was little evidence for any interaction between preterm birth and deprivation (p = 0.298) and the risk of learning difficulties. CONCLUSIONS: Deprivation and preterm birth have significant associations with learning difficulties. While deprivation does not appear to have potentiated the impact of preterm birth, preterm infants in the most deprived areas have the highest risk of learning difficulties with almost 1 in 3 extremely premature infants with a learning difficulty in the most deprived areas.

What matters to families about the healthcare of preterm or low birth weight infants: A qualitative evidence synthesis.

OBJECTIVE: We examined what matters to families about the healthcare provided to preterm or LBW infants in hospital and the community, to ensure that care meets the needs of infants and parents. METHODS: We searched databases to identify eligible studies examining the views and expectations of families. Study quality was assessed using the CASP checklist for qualitative studies. The GRADE-CERQual approach was used to assess confidence in review findings. Studies were sampled and data analysed using thematic synthesis. RESULTS: 222 studies (227 papers) were eligible for inclusion. 54 studies (57 papers) were sampled based on data richness, methodological quality, and representation across settings. Eight analytical themes were identified. Confidence in results was moderate to high. What mattered was a positive outcome for the child; active involvement in care; being supported to cope at home after discharge; emotional support; the healthcare environment; information needs met; logistical support available; and positive relationships with staff. CONCLUSION: Although parents and family members reported a variety of experiences in the care of their infant, we found high consistency in what matters to families. PRACTICE IMPLICATIONS: This review identifies approaches to improve experiences of parents which are consistent with the Family Centred Care model of healthcare.

Early childhood parent-reported speech problems in small and large for gestational age term-born and preterm-born infants: a cohort study.

OBJECTIVE: (1) To assess if preterm and term small for gestational age (SGA) or large for gestational age (LGA) infants have more parent-reported speech problems in early childhood compared with infants with birth weights appropriate for gestational age (AGA). (2) To assess if preterm and term SGA and LGA infants have more parent-reported learning, behavioural, hearing, movement and hand problems in early childhood compared with AGA infants. DESIGN: Cohort study. SETTING: Wales, UK. PARTICIPANTS: 7004 children with neurodevelopmental outcomes from the Respiratory and Neurological Outcomes of Children Born Preterm Study which enrolled 7129 children, born from 23 weeks of gestation onwards, to mothers aged 18-50 years of age were included in the analysis. OUTCOME MEASURES: Parent-reported single-answer questionnaires were completed in 2013 to assess early childhood neurodevelopmental outcomes. The primary outcome was parent-reported speech problems in early childhood adjusted for clinical and demographic confounders in SGA and LGA infants compared with AGA infants. Secondary outcomes measured were parent-reported early childhood learning, behavioural, hearing, movement and hand problems. RESULTS: Median age at the time of study was 5 years, range 2-10 years. Although the adjusted OR was 1.19 (0.92 to 1.55) for SGA infants and OR 1.11 (0.88 to 1.41) for LGA infants, this failed to reach statistical significance that these subgroups were more likely to have parent-reported speech problems in early childhood compared with AGA infants. This study also found parent-reported evidence suggestive of potential learning difficulties in early childhood (OR 1.51 (1.13 to 2.02)) and behavioural problems (OR 1.35 (1.01 to 1.79)) in SGA infants. CONCLUSION: This study of 7004 infants in Wales suggests that infants born SGA or LGA likely do not have higher risks of parent-reported speech problems in early childhood compared with infants born AGA. To further ascertain this finding, studies with wider population coverage and longer-term follow-up would be needed.

Postnatal phenobarbital for the prevention of intraventricular haemorrhage in preterm infants.

BACKGROUND: Intraventricular haemorrhage (IVH) is a major complication of preterm birth. Large haemorrhages are associated with a high risk of disability and hydrocephalus. Instability of blood pressure and cerebral blood in the newborn flow are postulated as causative factors. Another mechanism may involve reperfusion damage from oxygen free radicals. It has been suggested that phenobarbital stabilises blood pressure and may protect against free radicals. This is an update of a review first published in 2001 and updated in 2007 and 2013. OBJECTIVES: To assess the benefits and harms of the postnatal administration of phenobarbital in preterm infants at risk of developing IVH compared to control (i.e. no intervention or placebo). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CINAHL and clinical trial registries in January 2022. A new, more sensitive search strategy was developed, and searches were conducted without date limits.  SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs in which phenobarbital was given within the first 24 hours of life to preterm infants identified as being at risk of IVH because of gestational age below 34 weeks, birth weight below 1500 g or respiratory failure. Phenobarbital was compared to no intervention or placebo. We excluded infants with serious congenital malformations. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were all grades of IVH and severe IVH (i.e. grade III and IV); secondary outcomes were ventricular dilation or hydrocephalus, hypotension, pneumothorax, hypercapnia, acidosis, mechanical ventilation, neurodevelopmental impairment and death. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included 10 RCTs (792 infants). The evidence suggests that phenobarbital results in little to no difference in the incidence of IVH of any grade compared with control (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.84 to 1.19; risk difference (RD) 0.00, 95% CI -0.06 to 0.07; I² for RD = 65%; 10 RCTs, 792 participants; low certainty evidence) and in severe IVH (RR 0.88, 95% CI 0.64 to 1.21; 10 RCTs, 792 participants; low certainty evidence). The evidence is very uncertain about the effect of phenobarbital on posthaemorrhagic ventricular dilation or hydrocephalus (RR 0.62, 95% CI 0.31 to 1.26; 4 RCTs, 271 participants; very low certainty evidence), mild neurodevelopmental impairment (RR 0.57, 95% CI 0.15 to 2.17; 1RCT, 101 participants; very low certainty evidence), and severe neurodevelopmental impairment (RR 1.12, 95% CI 0.44 to 2.82; 2 RCTs, 153 participants; very low certainty evidence). Phenobarbital may result in little to no difference in death before discharge (RR 0.88, 95% CI 0.64 to 1.21; 9 RCTs, 740 participants; low certainty evidence) and mortality during study period (RR 0.98, 95% CI 0.72 to 1.33; 10 RCTs, 792 participants; low certainty evidence) compared with control. We identified no ongoing trials. AUTHORS' CONCLUSIONS: The evidence suggests that phenobarbital results in little to no difference in the incidence of IVH (any grade or severe) compared with control (i.e. no intervention or placebo). The evidence is very uncertain about the effects of phenobarbital on ventricular dilation or hydrocephalus and on neurodevelopmental impairment. The evidence suggests that phenobarbital results in little to no difference in death before discharge and all deaths during the study period compared with control. Since 1993, no randomised studies have been published on phenobarbital for the prevention of IVH in preterm infants, and no trials are ongoing. The effects of postnatal phenobarbital might be assessed in infants with both neonatal seizures and IVH, in both randomised and observational studies. The assessment of benefits and harms should include long-term outcomes.

Child Mortality in England During the First 2 Years of the COVID-19 Pandemic.

Importance: During the first year of the COVID-19 pandemic, child mortality in England was the lowest on record, but if this trend will continue, or if unrecognized morbidity during the first year of the pandemic will manifest as increased deaths over the next few years is unclear. Objective: To examine the risks and patterns of childhood deaths before and during the COVID-19 pandemic. Design, Setting, and Participants: This population-based cohort study includes all child deaths in England from April 1, 2019, to March 31, 2022. Exposures: The year of death. Main Outcomes and Measures: The primary outcome measure is risk of death. Results: Of the 9983 child deaths reported during the study period, 9872 (98.8%) were linked to demographic and population data with 3409 deaths (34.5%) between April 2019 and March 2020, 3035 (30.7%) between April 2020 and March 2021, and 3428 (34.7%) between April 2021 and March 2022. Most deaths occurred in children who were younger than 1 year (6257 of 9872 [62.7%]), the majority were male (5534 of 9760 [56.7%]), and lived in an urban area (8766 of 9872 [88.8%]). The risk of death was lower between April 2020 and March 2021 (relative risk [RR], 0.89 [95% CI, 0.84-0.93]), but not between April 2021 and March 2022 (RR, 1.00 [95% CI, 0.95-1.05]) when compared with April 2019 to March 2020. A population attributable risk (PAF) of 4.0% (95% CI, 0.1%-6.8%) suggested fewer deaths occurred during the whole 3-year period than expected. Reductions were seen in risk of dying by infection (PAF, 22.8% [95% CI, 8.2%-37.0%]) and underlying disease (PAF, 13.3% [95% CI, 8.1%-18.8%]), but there was evidence of an increasing risk of death by trauma (PAF, 14.7% [95% CI, 2.9%-25.2%]). Any reduction in the risk of death was greater in rural areas than in urban areas (RR, 0.73 [95% CI, 0.63-0.85] vs RR, 0.91 [95% CI, 0.86-0.95]) and was not seen in children older than 9 years. Conclusions and Relevance: In this cohort study, there was a significant reduction in all-cause child mortality during the first year of the COVID-19 pandemic (2020-2021), which returned to close to prepandemic levels the following year (2021-2022). However, there was a net reduction in deaths despite this, with 4% fewer deaths during the 3-year period than would have been expected from the 2019 to 2020 risks. The reductions were largest in rural areas and in children younger than 10 years.

The effectiveness of interventions to prevent intraventricular haemorrhage in premature infants: A systematic review and network meta-analysis.

BACKGROUND: Intraventricular haemorrhage (IVH) is a common problem in preterm infants, being a major cause of morbidity and mortality. Despite many randomised controlled trials comparing interventions to prevent IVH, the best prevention remains unclear. This study aims to review all the interventions which intended to reduce the incidence of IVH and compare them in a network meta-analysis. METHODS: A search on MEDLINE, EMBASE, Emcare, and CENTRAL was performed. Randomised controlled trials which evaluated neonatal interventions with a primary aim to reduce incidence of IVH in preterm infants were eligible. A surface under a cumulative ranking curve (SUCRA) was produced to indicate the intervention's likelihood of being the most effective for preventing IVH. RESULTS: 40 studies were eligible, enrolling over 6760 infants. Twelve intervention groups were found, including delayed cord clamping, erythropoietin, ethamsylate, fresh frozen plasma, heparin, ibuprofen, indomethacin, magnesium, nursing interventions, sedation, tranexamic acid, and vitamin E. Vitamin E and indomethacin had the highest probability of being the best interventions to prevent IVH in premature infants, but interpretation of these results is difficult due to study limitations. CONCLUSION: Despite the impact of IVH, we were unable to identify a clearly beneficial treatment to reduce its incidence. Interpretation of the network meta-analysis was limited due to differences within studied populations, wide range of therapies trialled, and underlying advances in neonatal care between units, and over time. Although vitamin E and indomethacin appear to be promising candidates, contemporaneous trials of these, or novel agents, enrolling the most at-risk infants is needed urgently.

Population birth outcomes in 2020 and experiences of expectant mothers during the COVID-19 pandemic: A 'born in Wales' mixed methods study using routine data.

BACKGROUND: Pregnancy can be a stressful time and the COVID-19 pandemic has affected all aspects of life. This study aims to investigate the pandemic impact on pregnancy experience, rates of primary childhood immunisations and the differences in birth outcomes in during 2020 to those of previous years. METHODS: Self-reported pregnancy experience: 215 expectant mothers (aged 16+) in Wales completed an online survey about their experiences of pregnancy during the pandemic. The qualitative survey data was analysed using codebook thematic analysis. Population-level birth outcomes in Wales: Stillbirths, prematurity, birth weight and Caesarean section births before (2016-2019) and during (2020) the pandemic were compared using anonymised individual-level, population-scale routine data held in the Secure Anonymised Information Linkage (SAIL) Databank. Uptake of the first three scheduled primary childhood immunisations were compared between 2019 and 2020. FINDINGS: The pandemic had a negative impact on the mental health of 71% of survey respondents, who reported anxiety, stress and loneliness; this was associated with attending scans without their partner, giving birth alone, and minimal contact with midwives. There was no significant difference in annual outcomes including gestation and birth weight, stillbirths, and Caesarean sections for infants born in 2020 compared to 2016-2019. There was an increase in late term births (≥42 weeks gestation) during the first lockdown (OR: 1.28, p = 0.019) and a decrease in moderate to late preterm births (32-36 weeks gestation) during the second lockdown (OR: 0.74, p = 0.001). Fewer babies were born in 2020 (N = 29,031) compared to 2016-2019 (average N = 32,582). All babies received their immunisations in 2020, but there were minor delays in the timings of immunisations. Those due at 8-weeks were 8% less likely to be on time (within 28-days) and at 16-weeks, they were 19% less likely to be on time. INTERPRETATION: Whilst the pandemic had a negative impact on mothers' experiences of pregnancy. Population-level data suggests that this did not translate to adverse birth outcomes for babies born during the pandemic.

'Opportunity to bond and a sense of normality': Parent and staff views of cuddling babies undergoing therapeutic hypothermia in neonatal intensive care: 'CoolCuddle'.

BACKGROUND: Currently, parents whose sick babies are undergoing three days of cooling therapy for hypoxic-ischaemic encephalopathy in neonatal intensive care units (NICUs) are not permitted to cuddle their cooled babies, due to concerns of warming the baby or dislodging breathing tubes or vascular catheters. Parents want to stay and care for their cooled babies and have reported that bonding is adversely affected when they are not permitted to hold them. DESIGN AND PARTICIPANTS: Qualitative interviews with 21 parents of cooled babies in NICU (11 mothers and 10 fathers) and 10 neonatal staff (4 consultants and 6 nurses) explored their views and experiences of an intervention to enable parents to cuddle their cooled babies (CoolCuddle). Thematic analysis methods were used to develop the themes and compare them between parents and staff. RESULTS: Five themes were produced. Three themes were comparable between parents and staff: Closeness, a sense of normality and reassurance and support. An additional parent theme reflected their mixed feelings about initial participation as they were apprehensive, but felt that it was an amazing opportunity. Parents and staff described the closeness between parents and babies as important for bonding and breastfeeding. Fathers particularly appreciated the opportunity to hold and bond with their infants. Parents valued the reassurance and support received from staff, and the cuddles helped them feel more normal and more like a family at a very stressful time. In a final staff theme, they discussed the skills, number of staff and training needed to undertake CoolCuddle in NICU. CONCLUSIONS: Parents cuddling their babies during cooling therapy enhanced parent-infant bonding and family-centred care in NICU and was positively received. Adverse perinatal mental health, impaired mother-infant bonding and their effects on the establishment of breastfeeding may be ameliorated by introducing CoolCuddle. PATIENT CONTRIBUTION: Our parent advisors contributed to the interview topic guides and endorsed the themes from the analysis.

Child mortality in England during the first year of the COVID-19 pandemic.

OBJECTIVES: To quantify the relative risk (RR) of childhood deaths across the whole of England during the first year of the COVID-19 pandemic, compared with a similar period of 2019. DESIGN: This work is based on data collected by the National Child Mortality Database (NCMD). Deaths from 1 April 2020 until 31 March 2021 (2020-2021) were compared with those from the same period of 2019-2020. RR and excess mortality were derived for deaths in 2020-2021 vs 2019-2020. SETTING: All deaths reported to NCMD in England of children under 18 years of age, between April 2019 and March 2021. PARTICIPANTS: 6490 deaths of children, under the age of 18 years, reported to the NCMD over the study period. RESULTS: Children had similar demographics in the 2 years. There were 356 (198-514) fewer deaths in 2020-2021 than in 2019-2020 (RR 0.90 (0.85 to 0.94), p<0.001). Deaths from infection (RR 0.49 (0.38 to 0.64)) and from other underlying medical conditions (RR 0.75 (0.68 to 0.82)) were lower in 2020-2021 than 2019-2020, and weak evidence (RR 0.50 (0.23 to 1.07), p=0.074) that this was also true of deaths from substance abuse. CONCLUSIONS: Childhood mortality in England during the first year of the SARS-CoV-2 pandemic was lower than expected, with over 300 fewer deaths than the preceding 12 months. The greatest reduction was in children less than 10 years old. It is important that we learn from this effect that potentially offers alternative ways to improve the outcome for the most vulnerable children in our society.

Barriers and facilitators to shared decision-making in neonatal medicine: A systematic review and thematic synthesis of parental perceptions.

OBJECTIVES: Systematically review parental perceptions of shared decision-making (SDM) in neonatology, identifying barriers and facilitators to implementation. METHODS: Electronic database (Medline, PsycINFO, CINAHL and Scopus) and follow-up searches were conducted to identify qualitative studies. Data were extracted, thematically analysed and synthesised. RESULTS: Searches yielded 2445 papers, of which 25 were included. Thematic analysis identified six key themes. Key barriers included emotional crises experienced in the NICU setting, lack of medical information provided to parents to inform decision-making, inadequate communication of information, poor relationships with caregivers, lack of continuity in care, and perceived power imbalances between HCPs and parents. Key facilitators included clear, honest and compassionate communication of medical information, caring and empathetic caregivers, continuity in care, and tailored approaches that reflected parent's desired level of involvement. CONCLUSION: The highly specialised environment, and the emotional crises experienced by parents impact significantly on their perceived capacity to engage in surrogate decision-making. PRACTICE IMPLICATIONS: Complex and multi-factorial interventions that address the training needs of HCPs, and the emotional, informational and decision support needs of parents are needed. SDM skills training, improved information delivery, and integrated emotional and decisional support could help parents to become more involved in SDM for their infant.

Deaths in children and young people in England after SARS-CoV-2 infection during the first pandemic year.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is rarely fatal in children and young people (CYP, <18 years old), but quantifying the risk of death is challenging because CYP are often infected with SARS-CoV-2 exhibiting no or minimal symptoms. To distinguish between CYP who died as a result of SARS-CoV-2 infection and those who died of another cause but were coincidentally infected with the virus, we undertook a clinical review of all CYP deaths with a positive SARS-CoV-2 test from March 2020 to February 2021. The predominant SARS-CoV-2 variants were wild-type and Alpha. Here we show that, of 12,023,568 CYP living in England, 3,105 died, including 61 who were positive for SARS-CoV-2. Of these deaths, 25 were due to SARS-CoV-2 infection (mortality rate, two per million), including 22 due to coronavirus disease 2019-the clinical disease associated with SARS-CoV-2 infection-and 3 were due to pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. In total, 99.995% of CYP with a positive SARS-CoV-2 test survived. CYP older than 10 years, Asian and Black ethnic backgrounds and comorbidities were over-represented in SARS-CoV-2-related deaths compared with other CYP deaths. These results are important for guiding decisions on shielding and vaccinating children. New variants might have different mortality risks and should be evaluated in a similar way.

Child mortality in England during the COVID-19 pandemic.

OBJECTIVES: Using the National Child Mortality Database (NCMD), this work aims to investigate and quantify the characteristics of children dying of COVID-19, and to identify any changes in rate of childhood mortality during the pandemic. DESIGN: We compared the characteristics of the children who died in 2020, split by SARS-CoV-2 status. A negative binomial regression model was used to compare mortality rates in lockdown (23 March-28 June), with those children who died in the preceding period (6 January-22 March), as well as a comparable period in 2019. SETTING: England. PARTICIPANTS: Children (0-17 years). MAIN OUTCOME MEASURES: Characteristics and number of the children who died in 2020, split by SARS-CoV-2 status. RESULTS: 1550 deaths of children between 6th of January and 28 June 2020 were notified to the NCMD; 437 of the deaths were linked to SARS-CoV-2 virology records, 25 (5.7%) had a positive PCR result. PCR-positive children were less likely to be white (37.5% vs 69.4%, p=0.003) and were older (12.2 vs 0.7 years, p<0.0006) compared with child deaths without evidence of the virus. All-cause mortality rates were similar during lockdown compared with both the period before lockdown in 2020 (rate ratio (RR) 0.93 (0.84 to 1.02)) and a similar period in 2019 (RR 1.02 (0.92 to 1.13)). CONCLUSIONS: There is little to suggest that there has been excess mortality during the period of lockdown. The apparent higher frequency of SARS-CoV-2-positive tests among children from black, Asian and minority ethnic groups is consistent with findings in adults. Ongoing surveillance is essential as the pandemic continues.

What is the relationship between deprivation, modifiable factors and childhood deaths: a cohort study using the English National Child MortalityDatabase.

OBJECTIVES: The aim of this analysis is to identify the patterns of social deprivation and childhood mortality; and identify potential points where public health, social and education interventions, or health policy may be best targeted. DESIGN: Decile of deprivation and underlying population distribution was derived using Office for National Statistics data. The risk of death was then derived using a Poisson regression model, calculating the increasing risk of death for each increasing deprivation decile. SETTING: England. PARTICIPANTS: 2688 deaths before 18 years of age reviewed between April 2019 and March 2020. MAIN OUTCOME MEASURES: The relationship between deprivation and risk of death; for deaths with, and without modifiable factors. RESULTS: There was evidence of increasing mortality risk with increase in deprivation decile, with children in the least deprived areas having a mortality of 13.25 (11.78-14.86) per 100 000 person-years, compared with 31.14 (29.13-33.25) in the most deprived decile (RR 1.08 (95% CI 1.07 to 1.10)); with the gradient of risk stronger in children who died with modifiable factors than those without (RR 1.12 (95% CI 1.09 to 1.15)) vs (RR 1.07 (95% CI 1.05 to 1.08)). Deprivation subdomains of employment, adult education, barriers to housing and services, and indoor living environments appeared to be the most important predictors of child mortality CONCLUSIONS: There is a clear gradient of increasing child mortality across England as measures of deprivation increase; with a striking finding that this varied little by area, age or other demographic factor. Over one-fifth of all child deaths may be avoided if the most deprived half of the population had the same mortality as the least deprived. Children dying in more deprived areas may have a greater proportion of avoidable deaths. Adult employment, and improvements to housing, may be the most efficient place to target resources to reduce these inequalities.

Feasibility and design of a trial regarding the optimal mode of delivery for preterm birth: the CASSAVA multiple methods study.

BACKGROUND: Around 60,000 babies are born preterm (prior to 37 weeks' gestation) each year in the UK. There is little evidence on the optimal birth mode (vaginal or caesarean section). OBJECTIVE: The overall aim of the CASSAVA project was to determine if a trial to define the optimal mode of preterm birth could be carried out and, if so, determine what sort of trial could be conducted and how it could best be performed. We aimed to determine the specific groups of preterm women and babies for whom there are uncertainties about the best planned mode of birth, and if there would be willingness to recruit to, and participate in, a randomised trial to address some, but not all, of these uncertainties. This project was conducted in response to a Heath Technology Assessment programme commissioning call (17/22 'Mode of delivery for preterm infants'). METHODS: We conducted clinician and patient surveys (n = 224 and n = 379, respectively) to identify current practice and opinion, and a consensus survey and Delphi workshop (n = 76 and n = 22 participants, respectively) to inform the design of a hypothetical clinical trial. The protocol for this clinical trial/vignette was used in telephone interviews with clinicians (n = 24) and in focus groups with potential participants (n = 13). RESULTS: Planned sample size and data saturation was achieved for all groups except for focus groups with participants, as this had to be curtailed because of the COVID-19 pandemic and data saturation was not achieved. There was broad agreement from parents and health-care professionals that a trial is needed. The clinician survey demonstrated a variety of practice and opinion. The parent survey suggested that women and their families generally preferred vaginal birth at later gestations and caesarean section for preterm infants. The interactive workshop and Delphi consensus process confirmed the need for more evidence (hence the case for a trial) and provided rich information on what a future trial should entail. It was agreed that any trial should address the areas with most uncertainty, including the management of women at 26-32 weeks' gestation, with either spontaneous preterm labour (cephalic presentation) or where preterm birth was medically indicated. Clear themes around the challenges inherent in conducting any trial emerged, including the concept of equipoise itself. Specific issues were as follows: different clinicians and participants would be in equipoise for each clinical scenario, effective conduct of the trial would require appropriate resources and expertise within the hospital conducting the trial, potential participants would welcome information on the trial well before the onset of labour and minority ethnic groups would require tailored approaches. CONCLUSION: Given the lack of evidence and the variation of practice and opinion in this area, and having listened to clinicians and potential participants, we conclude that a trial should be conducted and the outlined challenges resolved. FUTURE WORK: The CASSAVA project could be used to inform the design of a randomised trial and indicates how such a trial could be carried out. Any future trial would benefit from a pilot with qualitative input and a study within a trial to inform optimal recruitment. LIMITATIONS: Certainty that a trial could be conducted can be determined only when it is attempted. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12295730. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 61. See the NIHR Journals Library website for further project information.

Around 60,000 babies are born preterm each year in the UK. We do not know what the safest mode of birth is for these babies. Birth options include a vaginal birth or a caesarean section (which involves an operation for the mother). Normally, the ideal way to find out what clinical options are best is to carry out a 'randomised trial' in which participants are allocated to a particular treatment group (in this case, vaginal birth or caesarean section) by chance. It is not clear if women who have their babies preterm would want to take part in such a trial or that the clinicians looking after the women would be happy to ask them to, as previous trials have failed to recruit sufficient participants. The purpose of the CASSAVA research project was to find out what people think is the best and safest method of delivering preterm babies, their views on doing a research trial and what sort of research trial could be carried out. We conducted a survey asking clinicians and women their views. We gathered clinicians and women together to discuss and agree the key questions for a trial to answer. We then developed a protocol (plan) for a possible trial. Using this trial protocol, we conducted telephone interviews with clinicians, asking them if they would be willing to be involved and if they would be willing to ask pregnant women to participate. We also conducted focus groups with women, using a vignette (storyboard) about a possible trial. We found that there is a lot of uncertainty about the best way for preterm babies to be born. Clinicians and women broadly agreed that it would be good to resolve this uncertainty through a trial. We were able to identify some areas of the greatest uncertainty where clinicians and women would consider participating in a study. We gained a lot of useful information about how we could best set up a trial and support clinicians and women to get involved.

Child suicide rates during the COVID-19 pandemic in England.

BACKGROUND: There is concern about the impact of COVID-19, and the control measures to prevent the spread, on children's mental health. The aim of this work was to identify if there had been a rise of childhood suicide during the COVID pandemic. METHOD: Using data from England's National Child Mortality Database (NCMD) the characteristics and rates of children dying of suicide between April and December 2020 were compared with those in 2019. In a subset (1st January to 17th May 2020) further characteristics and possible contributing factors were obtained. RESULTS: A total of 193 likely childhood deaths by suicide were reported. There was no evidence overall suicide deaths were higher in 2020 than 2019 (RR 1.09 (0.80-1.48), p = 0.584) but weak evidence that the rate in the first lockdown period (April to May 2020) was higher than the corresponding period in 2019 (RR 1.56 (0.86-2.81), p = 0.144). Characteristics of individuals were similar between periods. Social restrictions (e.g. to education), disruption to care and support services, tensions at home and isolation appeared to be contributing factors. LIMITATIONS: As child suicides are fortunately rare, the analysis is based on small numbers of deaths with limited statistical power to detect anything but major increases in incidence. CONCLUSION: We found no consistent evidence that child suicide deaths increased during the COVID-19 pandemic although there was a possibility that they may have increased during the first UK lockdown. A similar peak was not seen during the following months, or the second lockdown.

Volatile organic compounds as disease predictors in newborn infants: a systematic review.

Volatile organic compounds (VOCs) detected in human breath, urine, stool, sweat, saliva, and blood result from metabolic processes in the body during health or disease. Using sophisticated measurement systems, small amounts of these compounds can be detected in the above bodily fluids. Multiple studies in adults and children have shown the potential of these compounds to differentiate between healthy individuals and patients by detecting profiles of compounds in non-invasively collected samples. However, the detection of biomarkers in VOCs from neonates is particularly attractive due to the non-invasive nature of its approach, and its ability to track disease progress by longitudinal sampling. In this work we have reviewed the literature on the use of VOCs in neonates and identified areas for future work. Overview of VOCs and their usefulness as metabolic signatures. Detailed review of studies on VOCs in neonates Learn about potential uses of VOCs as derived from adult and paediatric studies. Examine current limitations and identify future work. Detailed studies on VOCs involving neonatal patients including sick preterm infants and term infants with specific morbidities are needed. These studies should collect longitudinal samples using non-invasive methods for the detection of potential biomarkers. Underlying metabolic processes need to be identified so that any therapeutic options can be clarified.