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.

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.

'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.

Elevated International Normalized Ratio (INR) is Associated With an Increased Risk of Intraventricular Hemorrhage in Extremely Preterm Infants.

INTRODUCTION: The international normalized ratio (INR), a standardized method of reporting the prothrombin time, can be a surrogate marker of the vitamin K-dependent coagulation pathways. OBJECTIVE: To evaluate the relationship between INR measurements in the first 48 hours of life and subsequent development of intraventricular hemorrhage (IVH) in extremely preterm infants. MATERIALS AND METHODS: A single-center retrospective, observational cohort study of infants born at <28 weeks gestation. The main outcome measure was defined as the degree of IVH seen on cranial ultrasound examinations at day 7 postnatal age. RESULTS: Of 200 infants, 109 (mean gestational age, 25.2 wk [SD, 1.27]) had coagulation results available. Of 109, 26 developed IVH. Elevated INR was associated with increased risk of a severe IVH (odds ratio [OR] 6.50; 95% confidence interval [CI], 1.65-25.62; P=0.008) adjusted for gestation, birth weight, and sex. INR was significantly associated with severe IVH in infants who did not receive blood products (OR, 64.60; 95% CI, 1.35-3081.25; P=0.035), but not in those who did (OR, 2.93; 95% CI, 0.67-12.71; P=0.151) (Pinteraction=0.086). CONCLUSION: An elevated INR in the first 48 hours of life may be useful to identify preterm infants at risk of severe IVH and may guide strategies to prevent the development, or limit the extension, of IVH.

The cost of local, multi-professional obstetric emergencies training.

INTRODUCTION: We aim to outline the annual cost of setting up and running a standard, local, multi-professional obstetric emergencies training course, PROMPT (PRactical Obstetric Multi-Professional Training), at Southmead Hospital, Bristol, UK - a unit caring for approximately 6500 births per year. MATERIAL AND METHODS: A retrospective, micro-costing analysis was performed. Start-up costs included purchasing training mannequins and teaching props, printing of training materials and assembly of emergency boxes (real and training). The variable costs included administration time, room hire, additional printing and the cost of releasing all maternity staff in the unit, either as attendees or trainers. Potential, extra start-up costs for maternity units without established training were also included. RESULTS: The start-up costs were €5574 and the variable costs for 1 year were €143 232. The total cost of establishing and running training at Southmead for 1 year was €148 806. Releasing staff as attendees or trainers accounted for 89% of the total first year costs, and 92% of the variable costs. The cost of running training in a maternity unit with around 6500 births per year was approximately €23 000 per 1000 births for the first year and around €22 000 per 1000 births in subsequent years. CONCLUSIONS: The cost of local, multi-professional obstetric emergencies training is not cheap, with staff costs potentially representing over 90% of the total expenditure. It is therefore vital that organizations consider the clinical effectiveness of local training packages before implementing them, to ensure the optimal allocation of finite healthcare budgets.

Association between neonatal resuscitation and a single nucleotide polymorphism rs1835740.

AIM: The aim of this work was to test whether three single nucleotide polymorphisms (SNPs) implicated in glutamate homoeostasis or signalling and cellular survival are associated with birth condition. METHODS: This study is drawn from the Avon Longitudinal Study of Parents and Children. A total of 7611 term infants were genotyped and patient outcome data retrieved from routine medical records. Exposure measures were the presence of one or more minor alleles in one of 3 SNPs (rs2284411, rs2498804, rs1835740). The primary outcome was the need for resuscitation at birth. RESULTS: For SNP rs1835740, infants homozygous for the minor allele compared to wild type were more likely to need resuscitation (9.2% vs. 7.0%, p = 0.041), while the odds ratio for resuscitation was associated with each increasing minor allele [OR 1.17 (1.01-1.35)]. Population attributable risk fraction was 6.5%. There was no evidence that the other two SNPs investigated were associated with birth condition. CONCLUSION: We have tested three candidate SNPs to measure any association with birth condition. The study revealed that the rs1835740 was associated with the need for resuscitation and Apgar scores, with a substantial population impact.

Paediatric ED reattendance rates: comparing nurse practitioners and other clinicians.

OBJECTIVE: The aim of this project is to establish the unplanned reattendance rate for paediatric emergency nurse practitioners (PENPs) working in a designated paediatric emergency department (PED) while identifying the case mix of patients seen by PENPs compared with their medical counterparts. DESIGN: Quantitative data regarding patient characteristics and reattendance were collected during retrospective review of case notes across two representative 2-week periods. SETTING: The study site is a tertiary urban PED with an annual attendance of 32 000 patients aged from birth to 15 years. MAIN OUTCOME MEASURES: Reattendance rates, patient characteristics, triage scores, presenting complaint and numbers of patients discussed with a paediatric emergency medicine consultant were evaluated. RESULTS: The results showed that PENPs have a lower reattendance rate (1.75%) when compared with senior and junior doctors in training (4.29%, 5.76%); however, PENPs treat a different population of children. When the odds of PENP reattendance are adjusted for this, the significance of the difference becomes less certain. CONCLUSIONS: PENPs work autonomously when seeing children presenting with minor trauma and make a positive contribution in achieving the reattendance Clinical Quality Indicator.

Detection of three closely located single nucleotide polymorphisms in the EAAT2 promoter: comparison of single-strand conformational polymorphism (SSCP), pyrosequencing and Sanger sequencing.

BACKGROUND: Single-strand conformational polymorphism (SSCP) is still a frequently used genotyping method across different fields for the detection of single nucleotide polymorphisms (SNPs) due to its simplicity, requirement for basic equipment accessible in most laboratories and low cost. This technique was previously used to detect rs4354668:A > C (g.-181A > C) SNP in the promoter of astroglial glutamate transporter (EAAT2) and the same approach was initially used here to investigate this promoter region in a cohort of newborns. RESULTS: Unexpectedly, four distinct DNA migration patterns were identified by SSCP. Sanger sequencing revealed two additional SNPs: g.-200C > A and g.-168C > T giving a rise to a total of ten EAAT2 promoter variants. SSCP failed to distinguish these variants reliably and thus pyrosequencing assays were developed. g.-168C > T was found in heterozygous form in one infant only with minor allele frequency (MAF) of 0.0023. In contrast, g.-200C > A and -181A > C were more common (with MAF of 0.46 and 0.49, respectively) and showed string evidence of linkage disequilibrium (LD). In a systematic comparison, 16% of samples were miss-classified by SSCP with 25-31% errors in the identification of the wild-type and homozygote mutant genotypes compared to pyrosequencing or Sanger sequencing. In contrast, SSCP and pyrosequencing of an unrelated single SNP (rs1835740:C > T), showed 94% concordance. CONCLUSION: Our data suggest that SSCP cannot always detect reliably several closely located SNPs. Furthermore, caution is needed in the interpretation of the association studies linking only one of the co-inherited SNPs in the EAAT2 promoter to human diseases.

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.

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 flow are postulated as causative factors. Another mechanism may involve reperfusion damage from oxygen free radicals. Phenobarbital has been suggested as a safe treatment that stabilises blood pressure and may protect against free radicals. OBJECTIVES: To determine the effect of postnatal administration of phenobarbital on the risk of IVH, neurodevelopmental impairment or death in preterm infants. SEARCH METHODS: We used the search strategy of the Neonatal Collaborative Review Group. The original review author (A Whitelaw) was an active trialist in this area and had personal contact with many groups in this field. He handsearched journals from 1976 (when cranial computed tomography (CT) scanning started) to October 2000; these included: Pediatrics, Journal of Pediatrics, Archives of Disease in Childhood, Pediatric Research, Developmental Medicine and Child Neurology, Acta Paediatrica, European Journal of Pediatrics, Neuropediatrics, New England Journal of Medicine, Lancet and British Medical Journal. We searched the National Library of Medicine (USA) database (via PubMed) and the Cochrane Central Register of Controlled Trials (CENTRAL, 2012, Issue 10) through to 31 October 2012. We did not limit the searches to the English language, as long as the article included an English abstract. We read identified articles in the original language or translated. SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials in which phenobarbital was given to preterm infants identified as being at risk of IVH because of gestational age below 34 weeks, birthweight below 1500 g or respiratory failure. Adequate determination of IVH by ultrasound or CT was also required. DATA COLLECTION AND ANALYSIS: In addition to details of patient selection and control of bias, we extracted the details of the administration of phenobarbital. We searched for the following endpoints: IVH (with grading), posthaemorrhagic ventricular dilation or hydrocephalus, neurodevelopmental impairment and death. In addition, we searched for possible adverse effects of phenobarbitone, for example hypotension, mechanical ventilation, pneumothorax, hypercapnia and acidosis. MAIN RESULTS: We included 12 controlled trials that recruited 982 infants. There was heterogeneity between trials for the outcome IVH, with three trials finding a significant decrease in IVH and one trial finding an increase in IVH in the group receiving phenobarbital. Meta-analysis showed no difference between the phenobarbital-treated group and the control group in either all IVH (typical risk ratio (RR) 0.91; 95% CI 0.77 to 1.08), severe IVH (typical RR 0.77; 95% CI 0.58 to 1.04), posthaemorrhagic ventricular dilation (typical RR 0.89; 95% CI 0.38 to 2.08), severe neurodevelopmental impairment (typical RR 1.44; 95% CI 0.41 to 5.04) or death before hospital discharge (typical RR 0.88; 95% CI 0.64 to 1.21). There was a consistent trend in the trials towards increased use of mechanical ventilation in the phenobarbital-treated group, which was supported by the meta-analysis (typical RR 1.18; 95% CI 1.06 to 1.32; typical risk difference 0.129; 95% CI 0.04 to 0.21), but there was no significant difference in pneumothorax, acidosis or hypercapnia. AUTHORS' CONCLUSIONS: Postnatal administration of phenobarbital cannot be recommended as prophylaxis to prevent IVH in preterm infants and is associated with an increased need for mechanical ventilation.

Movement outcomes of infants born moderate and late preterm.

AIM: To investigate whether children born between 32 and 36 weeks of gestation have an increased risk of motor coordination difficulties or cerebral palsy (CP) at age 7 years. METHODS: A cohort study based on the Avon Longitudinal Study of Parents and Children (ALSPAC). The primary outcomes were poor motor coordination, defined as an ALSPAC coordination test score <5th centile or the presence of CP. Exposure groups were defined as moderate or late preterm (32-36 weeks of gestation) or term (37-42 weeks). Regression models were used to investigate the association between gestational age and outcomes. Multiple imputation was used to account for missing covariate data. RESULTS: In the fully adjusted model, there was strong evidence that children born at moderate or late preterm had worse coordination (OR 1.41 (1.14-1.74)) and higher risk of CP (OR 6.38 (2.28-17.76)) than term peers. However, restricting the analysis to well-grown infants born vaginally, in good condition, the associations attenuated substantially. CONCLUSIONS: Moderate or late preterm infants were at increased risk of developing coordination problems and cerebral palsy. After restricting the analysis to 'well' infants the associations of gestation with the coordination measures and CP reduced substantially, suggesting that antenatal, intrapartum and neonatal causal pathways are likely to be involved.

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.

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.

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.

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.

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.

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.

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.

Long-term cognitive outcomes of infants born moderately and late preterm.

AIM: To investigate whether infants born late preterm have poorer cognitive outcomes than term-born infants. METHOD: A cohort study based on the Avon Longitudinal Study of Parents and Children. Cognitive measures were assessed between the ages of 8 and 11 years. Exposure groups were defined as moderate/late preterm (32-36 weeks' gestation) or term (37-42 wk). Regression models were used to investigate the association between gestational age and IQ. RESULTS: Seven hundred and forty-one infants (5.4% of total eligible population; 422 males, 319 females; mean (SD) birthweight 2495 g [489]) were born between 32 and 36 weeks' gestation. The analysis was based on 6957 infants with IQ data at age 11 (50% of eligible infants). In the adjusted model, children born moderately and late preterm had similar IQ scores to peers born at term (mean difference [95% confidence interval] -0.18 [-1.88 to 1.52]). However, the preterm infants had a higher risk of having special educational needs at school (odds ratio 1.56 [1.18-2.07]). INTERPRETATION: Despite an increased risk of special educational needs, there is little evidence of a reduction in IQ, memory, or attention measures at school age in children born between 32 and 36 weeks' gestation. Although interpretation is limited by the amount of missing data, further work is needed to identify why these infants have increased educational needs.