Archives of Disease in Childhood - Fetal and Neonatal Edition最新文献

Objectives: To assess the comparative effectiveness of different umbilical cord management strategies for preventing intraventricular haemorrhage (IVH) in preterm neonates.

Design: A systematic review and meta-analysis.

Study sources: PubMed, Scopus and Web of Science were searched from inception to March 2025 for relevant randomised controlled trials.

Participants: All preterm neonates born <37+0 weeks of gestation.

Interventions: All umbilical cord management strategies, including immediate cord clamping (ICC), delayed cord clamping (DCC), intact umbilical cord milking (I-UCM), cut umbilical cord milking (C-UCM), intact cord stabilisation (ICS), physiology-based cord clamping and extrauterine placental perfusion.

Main outcome measures: Any grade IVH (grades I-IV) and severe IVH (grades III-IV).

Data synthesis: Random-effects meta-analyses were conducted to calculate risk ratios (RRs) with 95% CIs. Analyses were stratified for very preterm (<32 weeks) and extremely preterm neonates (<28 weeks).

Results: Forty-nine studies with 8706 neonates were included. Thirty-five direct comparisons between strategies were made, but no clear evidence of benefit or harm emerged. Certainty of evidence ranged from moderate to very low, often downgraded due to imprecision, risk of bias and inconsistency. The most frequent comparison was DCC versus ICC, with 14 studies (RR 0.90, CI 0.65 to 1.26) for any grade IVH and 11 studies (RR 1.14, CI 0.69 to 1.87) for severe IVH. The second most common comparison, DCC versus I-UCM, showed no benefit: RR 1.03 (CI 0.80 to 1.32; eight studies, 2200 participants) and RR 0.77 (CI 0.35 to 1.66; seven studies, 2032 participants). ICS versus DCC was the only comparison which was rated as moderate certainty of evidence for both, any grade IVH (RR 0.96, CI 0.82 to 1.13) and severe IVH (RR 0.91, CI 0.62 to 1.35).

Conclusions: No umbilical cord management strategy was clearly associated with increased or decreased IVH risk. Evidence certainty was generally low to very low, primarily due to bias and imprecision.

Objective: Central apnoea due to immaturity of the respiratory drive constitutes the main cause of frequent and prolonged desaturations in extremely preterm (EPT) infants <28 weeks. We investigated the impact of varying the duration of apnoea before backup ventilation (BUV) on the measures of oxygenation in EPT infants during nasal continuous positive airway pressure (nCPAP) therapy.

Design: Single-centre randomised cross-over trial.

Setting: Level 3 neonatal intensive care unit.

Patients: 24 EPT infants on nCPAP with BUV.

Main outcome measures: The primary outcome was the time spent within a predefined oxygen saturation (SpO₂) target (88%-95% or ≥88% with fraction of inspired oxygen (FiO₂) =0.21) during start of BUV after 4 s of apnoea duration (AD 4) or 16 s of apnoea duration (AD 16) RESULTS: The study was successfully completed in 22 children (median gestational age 24+5 weeks, birth weight 628 g, postnatal age 48 days). Mean time spent within the SpO₂ target didn't differ between AD 4 and AD 16 (66.9% vs 67.2%, p=0.88). There were no differences in the time below or above the SpO₂ target, prolonged (>30 s, >60 s, >120 s) and severe (<80%, <70%) episodes of hypoxaemias and cerebral tissue oxygenation. Mean FiO₂, mean airway pressure, transcutaneous carbon dioxide pressure, heart rate and respiratory frequency did not differ while the rate of BUV was significantly higher during AD 4.

Conclusion: Reducing the time of apnoea until start of BUV didn't improve the time spent within the SpO₂ target in respiratory unstable EPT infants. Our data demand intensified efforts to specify these settings of non-invasive respiratory support that better achieve this important clinical goal.

Trial registration number: DRKS00031911.

Objective: Bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (BPD-PH) is the most severe endotype of BPD; there is insufficient evidence to support the optimal screening strategy in at-risk infants. We hypothesised that serial echocardiography throughout hospitalisation would improve PH detection with increased negative predictive value (NPV) beyond 36 week's postmenstrual age (PMA).

Study design: This was a single centre cohort study conducted between 2017 and 2023. In infants with BPD-PH, all echocardiograms preceding a diagnostic echocardiogram were included and considered false negatives for prediction of later PH. In infants with BPD alone, all echocardiograms were included and were considered true negatives. These indices were then used to estimate the sensitivity and NPV of echocardiographic screening for PH. In addition, we compared the performance of four different potential echocardiographic screening approaches on the ability to identify infants with BPD-PH.

Results: Data from 394 infants were available for this analysis of whom 258 had BPD alone and 136 had BPD-PH. 2542 echocardiograms were used in estimates of diagnostic accuracy. The highest NPVs occurred with echocardiographic screening starting at 36 weeks' and continuing monthly until discharge. Detection of BPD-PH among infants with BPD differed by screening strategy: 34.5% for comprehensive screening, 20.0% for early screening, 15.0% for singular screening and 30.7% for late screening (p<0.05).

Conclusions: While the diagnostic accuracy of echocardiographic screening increases at and beyond 36 weeks' PMA, obtaining a singular echocardiogram may be an insufficient screening strategy for the detection of BPD-PH in at-risk infants.

Context: Children born very preterm (<32 weeks' gestation) have increased risk of neurodevelopmental difficulties compared with those born at term. While various neonatal exposures have been linked with later developmental challenges, identifying those at risk of difficulties later in childhood remains a challenge but is essential for targeting early intervention and counselling families.

Objective: To systematically review and synthesise the evidence regarding early medical and environmental factors for neurodevelopmental impairment, cognitive, motor and behavioural outcomes for children born very preterm.

Design: Ovid MEDLINE, Embase and PubMed were searched for articles between 1 January 1990 and 29 April 2024 reporting on a representative, prospective geographical, network-based or multisite cohorts of children born <32 weeks' gestation.

Main outcome measures: Neurodevelopmental impairment, cognitive, motor and emotional-behavioural functioning in children aged 36 months to 18 years. Data were extracted and reported descriptively due to heterogeneity in study measures.

Results: From 18 012 records, 29 studies from 16 cohorts were included. Brain injury, bronchopulmonary dysplasia, male sex and lower socioeconomic status were the most consistent predictors of neurodevelopmental impairment, IQ, working memory, cerebral palsy, fine motor skills and some behavioural measures. Emotional problems were generally not associated with neonatal variables investigated to date.

Conclusion: Numerous factors are independently associated with childhood outcomes after being born very preterm, with specific predictors varying across domains of functioning and limited available evidence for some predictor-outcome combinations. Knowledge of these factors may assist in targeting those at highest risk for closer surveillance and early intervention.PROSPERO registration numberCRD42022368957.

Background: In neonatal trials, verbal opt-out consent has been used to reduce burden on families and make recruitment more efficient and representative. It involves information provision through posters and leaflets before randomisation, and parents can verbally 'opt out' of their baby being randomised to the trial. There is limited understanding of how opt-out consent is operationalised in a multicentre neonatal trial, and its acceptability to staff and parents.

Objective: To explore views and experiences of verbal opt-out consent in neoGASTRIC, a neonatal randomised trial comparing routine and no routine measurements of gastric contents in preterm babies.

Methods: A mixed methods (questionnaires, interviews and focus groups) process evaluation within a trial.

Setting: Four UK neonatal units.

Participants: 253 participants: 167 staff (149 questionnaires; 18 across two focus groups), 86 parents (85 questionnaires; 15 interviews; 14 took part in both).

Results: Parents and staff supported opt-out consent in neoGASTRIC as interventions were viewed as low risk and non-invasive. Parents appreciated an appropriately timed research conversation; only 21% noticed study information banners/posters. Operationalisation of opt-out consent varied in terms of when information was provided and randomisation timing. Women approached during labour or within hours of birth reported feeling overwhelmed and lacking capacity to consider research. Some staff operationalised a modified opt-in approach.

Conclusions: An appropriately timed verbal opt-out approach to consent was seen acceptable as proportionate in the neonatal context in a low-risk trial comparing different accepted clinical, non-pharmaceutical, practices. Findings informed neoGASTRIC and will guide approaches to consent in this setting.

Objective: To determine whether full body in-utero MRI (iuMRI) rather than targeted imaging adds useful clinical information when a fetal anomaly is suspected in the brain or the body.

Design: Single-centre retrospective cohort study, from October 2011 to May 2022.

Setting: Regional fetal MRI service in Sheffield, UK.

Patients: All pregnant people undergoing iuMRI.

Interventions: iuMRI of the brain and body was reviewed by a fetal radiologist, and the results discussed by a multidisciplinary team.

Main outcome measures: Additional abnormalities detected on iuMRI outside of the initial area of interest on ultrasound.

Results: 1876 participants: 916 participants had a fetus with brain anomalies only on ultrasound, of which 12 (1.3%) had additional body abnormalities on iuMRI. 960 participants had body anomalies only on ultrasound, of whom 8 (0.8%) had an additional brain abnormality. The additional findings from 12 cases (0.6% of whole cohort) added useful clinical information to guide care or counselling.

Conclusion: If brain or body anomalies are found on ultrasound in the fetus, whole-body iuMRI reveals additional abnormalities in a small number of cases. However, these may provide important information that changes counselling or care. Further research is required to determine how significant this impact is for clinicians and families, whether normal findings reassure families, how long whole-body iuMRI adds to the MRI acquisition time and the health economics implications.

Objective: Babies born between 27⁺⁰ and 31⁺⁶ weeks of gestation contribute substantially towards infant mortality and morbidity. In England, their care is delivered in maternity services colocated with highly specialised neonatal intensive care units (NICU) or less specialised local neonatal units (LNU). We investigated whether birth setting offered survival and/or morbidity advantages to inform National Health Service delivery.

Design: Retrospective national cohort study.

Setting: LNU, NICU, England.

Patients: UK National Neonatal Research Database whole population data for births between 27⁺⁰ and 31⁺⁶ weeks of gestation, discharged from/died within neonatal units between 1 January 2014 and 31 December 2018. We linked baby-level data to mortality information from the Office for National Statistics.

Outcome measures: Death during neonatal care, up to 1 year (infant mortality), surgically treated necrotising enterocolitis, retinopathy of prematurity, severe brain injury (SBI), bronchopulmonary dysplasia.

Intervention: Birth in NICU versus LNU setting. We used an instrumental variable (maternal excess travel time between the nearest NICU and LNU) estimation approach to determine treatment effect.

Results: Of 18 847 babies (NICU: 10 379; LNU: 8468), 574 died in NICU/LNU care, and 121 postdischarge (infant mortality 3.7%). We found no effect of birth setting on neonatal or infant mortality. Significantly more babies born into LNU settings experienced SBI (mean difference -1.1% (99% CI -2.2% to -0.1%)). This was attenuated after excluding births at 27 weeks, and early postnatal transfers.

Conclusions: In England, LNU teams should use clinical judgement, risk assessing benefits of transfer versus risk of SBI for preterm births at 27 weeks of gestation. 28 weeks of gestation is a safe threshold for preterm birth in either NICU/LNU settings.

Trial registration number: NCT02994849/ISRCTN74230187.

Objective: Fetomaternal transfusion (FMT) is associated with increased perinatal mortality and morbidity, but data on postnatal outcomes are scarce. Our aim was to determine the incidence of adverse short-termand long-term sequelae of severe FMT.

Design: Retrospective cohort study.

Setting: Dutch tertiary neonatal intensive care unit.

Patients: Liveborn neonates with FMT admitted in 2017-2022.

Main outcome measures: Severe FMT was defined as ≥30 mL of fetal red blood cells in the maternal circulation diagnosed with positive Kleihauer-Betke/flow cytometry test. Adverse outcomes were compared between severe and mild FMT (10-30 mL blood loss) to highlight the impact of FMT severity. Primary outcome was an adverse composite outcome consisting of neonatal mortality or severe neurological morbidity (ie, severe cerebral injury and/or neurodevelopmental impairment (NDI) at 2 years). Secondary outcome was perinatal asphyxia.

Results: 109 neonates with FMT were included, 16 with severe FMT and 93 with mild FMT. Neonatal mortality occurred in 19% (3/16) of neonates with severe FMT and in 4% (4/93) with mild FMT (p=0.063). Perinatal asphyxia was diagnosed in 25% (4/16) of neonates with severe FMT compared with 6% (6/93) with mild FMT (p=0.038). Long-term outcome was assessed in 60 neonates. NDI occurred in 22% (2/9) of children with severe FMT compared with 16% (8/51) with mild FMT (p=0.637). Adverse outcome occurred in 43% (95% CI 38 to 50%) of neonates with severe FMT compared with 18% (95% CI 17% to 24%) with mild FMT (p=0.074).

Conclusion: Neonatal mortality or long-term neurological morbidity occurred in 38%-50% of children with fetal blood loss and anaemia due to severe FMT.