Showing papers in "Archives of Disease in Childhood-fetal and Neonatal Edition in 2020"

Perinatal management of extreme preterm birth before 27 weeks of gestation: a framework for practice.

Abstract: 1. This Framework has been developed by a multidisciplinary working group in the light of evidence of improving outcomes for babies born before 27 completed weeks of gestation, and evolving national and international changes in the approach to their care. 2. Management of labour, birth and the immediate neonatal period should reflect the wishes and values of the mother and her partner, informed and supported by consultation and in partnership with obstetric and neonatal professionals. 3. Whenever possible, extreme preterm birth should be managed in a maternity facility co-located with a designated neonatal intensive care unit. 4. Neonatal stabilisation may be considered for babies born from 22+0 weeks of gestation following assessment of risk and multiprofessional discussion with parents. It is not appropriate to attempt to resuscitate babies born before 22+0 weeks of gestation. 5. Decision-making for babies born before 27 weeks of gestation should not be based on gestational age alone, but on assessment of the baby’s prognosis taking into account multiple factors. Decisions should be made with input from obstetric and neonatal teams in the relevant referral centre if transfer is being contemplated. 6. Risk assessment should be performed with the aim of stratifying the risk of a poor outcome into three groups: extremely high risk, high risk and moderate risk. 7. For fetuses/babies at extremely high risk, palliative (comfort focused) care would be the usual management. 8. For fetuses/babies at high risk of poor outcome, the decision to provide either active (survival focused) management or palliative care should be based primarily on the wishes of the parents. 9. For fetuses/babies at moderate risk, active management should be planned. 10. If life-sustaining treatment for the baby is anticipated, pregnancy and delivery should be managed with the aim of optimising the baby’s condition at birth and subsequently. 11. Conversations with parents should be clearly documented and care taken to ensure that the agreed management plan is communicated between professionals and staff shifts. 12. Decisions and management should be regularly reviewed before and after birth in conjunction with the parents; plans may be reconsidered if the risk for the fetus/baby changes or if parental wishes change.

Core outcomes in neonatology: Development of a core outcome set for neonatal research

Abstract: Background Neonatal research evaluates many different outcomes using multiple measures. This can prevent synthesis of trial results in meta-analyses, and selected outcomes may not be relevant to former patients, parents and health professionals. Objective To define a core outcome set (COS) for research involving infants receiving neonatal care in a high-income setting. Design Outcomes reported in neonatal trials and qualitative studies were systematically reviewed. Stakeholders were recruited for a three-round international Delphi survey. A consensus meeting was held to confirm the final COS, based on the survey results. Participants Four hundred and fourteen former patients, parents, healthcare professionals and researchers took part in the eDelphi survey; 173 completed all three rounds. Sixteen stakeholders participated in the consensus meeting. Results The literature reviews identified 104 outcomes; these were included in round 1. Participants proposed 10 additional outcomes; 114 outcomes were scored in rounds 2 and 3. Round 1 scores showed different stakeholder groups prioritised contrasting outcomes. Twelve outcomes were included in the final COS: survival, sepsis, necrotising enterocolitis, brain injury on imaging, general gross motor ability, general cognitive ability, quality of life, adverse events, visual impairment/blindness, hearing impairment/deafness, retinopathy of prematurity and chronic lung disease/bronchopulmonary dysplasia. Conclusions and relevance A COS for clinical trials and other research studies involving infants receiving neonatal care in a high-income setting has been identified. This COS for neonatology will help standardise outcome selection in clinical trials and ensure these are relevant to those most affected by neonatal care.

Incidence of necrotising enterocolitis before and after introducing routine prophylactic Lactobacillus and Bifidobacterium probiotics.

Abstract: Objective: To compare rates of necrotising enterocolitis (NEC), late-onset sepsis, and mortality in 5-year epochs before and after implementation of routine daily multistrain probiotics administration in high-risk neonates. Design: Single-centre retrospective observational study over the 10-year period from 1 January 2008 to 31 December 2017. Setting: Level 3 neonatal intensive care unit (NICU) of the Norfolk and Norwich University Hospital, UK. Patients: Preterm neonates at high risk of NEC: Admitted to NICU within 3 days of birth at <32 weeks' gestation or at 32-36 weeks' gestation and of birth weight <1500 g. Intervention: Prior to 1 January 2013 probiotics were not used. Thereafter, dual-species Lactobacillus acidophilus and Bifidobacterium bifidum combination probiotics were routinely administered daily to high-risk neonates; from April 2016 triple-species probiotics (L.acidophilus,B.bifidum, and B.longum subspecies infantis) were used. Main outcome measures: Incidence of NEC (modified Bell's stage 2a or greater), late-onset sepsis, and mortality. Results: Rates of NEC fell from 7.5% (35/469 neonates) in the pre-implementation epoch to 3.1% (16/513 neonates) in the routine probiotics epoch (adjusted sub-hazard ratio=0.44, 95% CI 0.23 to 0.85, p=0.014). The more than halving of NEC rates after probiotics introduction was independent of any measured covariates, including breast milk feeding rates. Cases of late-onset sepsis fell from 106/469 (22.6%) to 59/513 (11.5%) (p<0.0001), and there was no episode of sepsis due to Lactobacillus or Bifidobacterium. All-cause mortality also fell in the routine probiotics epoch, from 67/469 (14.3%) to 47/513 (9.2%), although this was not statistically significant after multivariable adjustment (adjusted sub-hazard ratio=0.74, 95% CI 0.49 to 1.12, p=0.155). Conclusions: Administration of multispecies Lactobacillus and Bifidobacterium probiotics has been associated with a significantly decreased risk of NEC and late-onset sepsis in our neonatal unit, and no safety issues. Our data are consistent with routine use of Lactobacillus and Bifidobacterium combination probiotics having a beneficial effect on NEC prevention in very preterm neonates.

Serious games, a game changer in teaching neonatal resuscitation? A review.

Abstract: Background Neonatal healthcare professionals require frequent simulation-based education (SBE) to improve their cognitive, psychomotor and communication skills during neonatal resuscitation. However, current SBE approaches are resource-intensive and not routinely offered in all healthcare facilities. Serious games (board and computer based) may be effective and more accessible alternatives. Objective To review the current literature about serious games, and how these games might improve knowledge retention and skills in neonatal healthcare professionals. Method Literature searches of PubMed, Google Scholar, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science and EMBASE databases were performed to identify studies examining serious games in neonatology. All games, such as board games, tabletop games, video games, screen-based simulators, tabletop simulators and virtual reality games were included. Results Twelve serious games were included in this review (four board games, five video games and three virtual reality games). Overall, knowledge improvement was reported for the RETAIN (REsuscitationTrAINing for healthcare professionals) board game (10% increase in knowledge retention) and The Neonatology Game (4.15 points higher test score compared with control). Serious games are increasingly incorporated into Nursing and Medical School Curriculums to reinforce theoretical and practical learning. Conclusions Serious games have the potential to improve healthcare professionals’ knowledge, skills and adherence to the resuscitation algorithm and could enhance access to SBE in resource-intensive and resource-limited areas. Future research should examine important clinical outcomes in newborn infants.

Effect of intrapartum antibiotics on the intestinal microbiota of infants: a systematic review

Abstract: Introduction The use of intrapartum antibiotic prophylaxis (IAP) has become common practice in obstetric medicine and is used in up to 40% of deliveries. Despite its benefits, the risks associated with exposing large numbers of infants to antibiotics, especially long-term effects on health through changes in the microbiota, remain unclear. This systematic review summarises studies that have investigated the effect of IAP on the intestinal microbiota of infants. Methods A systematic search in Ovid MEDLINE was used to identify original studies that investigated the effect of IAP on the intestinal microbiota in infants. Studies were excluded if: they included preterm infants, the antibiotic regimen was not specified, antibiotics were used for indications other than prophylaxis, probiotics were given to mothers or infants, or antibiotics were given to infants. Results We identified six studies, which investigated a total of 272 infants and included 502 stool samples collected up to 3 months of age. In all the studies, IAP was given for group B streptococcus (GBS) colonisation. Infants who were exposed to GBS IAP had a lower bacterial diversity, a lower relative abundance of Actinobacteria, especially Bifidobacteriaceae, and a larger relative abundance of Proteobacteria in their intestinal microbiota compared with non-exposed infants. Conflicting results were reported for the phyla Bacteroidetes and Firmicutes. Conclusions GBS IAP has profound effects on the intestinal microbiota of infants by diminishing beneficial commensals. Such changes during the early-life ‘critical window’ during which the intestinal microbiota and the immune response develop concurrently may have an important influence on immune development. The potential long-term adverse consequences of this on the health of children warrant further investigation.

School-age outcomes of children without cerebral palsy cooled for neonatal hypoxic-ischaemic encephalopathy in 2008-2010

Abstract: Objective Since therapeutic hypothermia became standard care for neonatal hypoxic–ischaemic encephalopathy (HIE), even fewer infants die or have disability at 18-month assessment than in the clinical trials. However, longer term follow-up of apparently unimpaired children is lacking. We investigated the cognitive, motor and behavioural performances of survivors without cerebral palsy (CP) cooled for HIE, in comparison with matched non-HIE control children at 6–8 years. Design Case–control study. Participants 29 case children without CP, cooled in 2008–2010 and 20 age-matched, sex-matched and social class-matched term-born controls. Measures Wechsler Intelligence Scales for Children, Fourth UK Edition, Movement Assessment Battery for Children, Second Edition (MABC-2) and Strengths and Difficulties Questionnaire. Results Cases compared with controls had significantly lower mean (SD) full-scale IQ (91 [10.37]vs105[13.41]; mean difference (MD): −13.62, 95% CI −20.53 to –6.71) and total MABC-2 scores (7.9 [3.26]vs10.2[2.86]; MD: −2.12, 95% CI −3.93 to –0.3). Mean differences were significant between cases and controls for verbal comprehension (−8.8, 95% CI –14.25 to –3.34), perceptual reasoning (−13.9, 95% CI–20.78 to –7.09), working memory (−8.2, 95% CI–16.29 to –0.17), processing speed (−11.6, 95% CI–20.69 to –2.47), aiming and catching (−1.6, 95% CI–3.26 to –0.10) and manual dexterity (−2.8, 95% CI–4.64 to –0.85). The case group reported significantly higher median (IQR) total (12 [6.5–13.5] vs 6 [2.25–10], p=0.005) and emotional behavioural difficulties (2 [1–4.5] vs 0.5 [0–2.75], p=0.03) and more case children needed extra support in school (34%vs5%, p=0.02) than the control group. Conclusions School-age children without CP cooled for HIE still have reduced cognitive and motor performance and more emotional difficulties than their peers, strongly supporting the need for school-age assessments.

Neonatal lung ultrasonography to evaluate need for surfactant or mechanical ventilation: a systematic review and meta-analysis

Abstract: Context Lung ultrasonography (LUS) is increasingly used to identify various neonatal respiratory disorders. There is emerging evidence that it can identify infants with significant lung disease who need surfactant treatment or mechanical ventilation. Objective To systematically review the accuracy of LUS in determining the need for surfactant treatment or mechanical ventilation in infants with respiratory distress treated with nasal continuous positive airway pressure (NCPAP). Methods Database search include EMBASE, Medline, CINAHL and Cochrane central from inception until 17 October 2018. Included is diagnostic accuracy studies reporting LUS evaluating surfactant therapy/mechanical ventilation. Two authors extracted data independently and assessed quality. Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to determine the methodological quality. Results Six studies involving 485 infants included in the review. Three studies used LUS score, two used type 1 lung profile, and one used high-risk LUS to evaluate the outcome. The pooled sensitivity and specificity at LUS score cut-off >5–6 was 88% (95% CI 80% to 93%) and 82% (95% CI 74% to 89%), respectively. Infants with LUS score >5–6 were at significantly increased risk of surfactant treatment compared with infants with LUS score Conclusions LUS, particularly LUS score, can be used accurately to determine the need for surfactant replacement treatment or mechanical ventilation in infants with respiratory distress treated with NCPAP support. The accuracy is better in younger preterm infants compared with late preterm and term infants. PROSPERO registration number CRD42018115135.

Improving incidence trends of severe intraventricular haemorrhages in preterm infants <32 weeks gestation: a cohort study

Abstract: Objective To describe the trend and risk factors for severe intraventricular haemorrhage (IVH) among infants Design Population-based cohort study. Setting Australia and New Zealand. Patients All preterm infants Interventions Comparison of IVH incidence between 6-year epochs. Main outcome measures Overall IVH and severe IVH incidence. Results A total of 60 068 infants were included, and overall survival to discharge increased from 89% to 93% over the three epochs. As the percentage of infants with IVH decreased from 23.6% to 21.3% and 21.4% (p Conclusions Along with increased survival among infants born

Neonatal care bundles are associated with a reduction in the incidence of intraventricular haemorrhage in preterm infants: a multicentre cohort study

Abstract: Objective To investigate the effect of a nursing intervention bundle, applied during the first 72 hours of life, on the incidence of germinal matrix-intraventricular haemorrhage (GMH-IVH) in very preterm infants. Design Multicentre cohort study. Setting Two Dutch tertiary neonatal intensive care units. Patients The intervention group consisted of 281 neonates, whereas 280 infants served as historical controls (gestational age for both groups Interventions After a training period, the nursing intervention bundle was implemented and applied during the first 72 hours after birth. The bundle consisted of maintaining the head in the midline, tilting the head of the incubator and avoidance of flushing/rapid withdrawal of blood and sudden elevation of the legs. Main outcome measures The incidence of GMH-IVH occurring and/or increasing after the first ultrasound (but within 72 hours), cystic periventricular leukomalacia and/or in-hospital death was the primary composite outcome measure. Logistic regression analysis was used to explore differences between groups. Results The nursing intervention bundle was associated with a lower risk of developing a GMH-IVH (any degree), cystic periventricular leukomalacia and/or mortality (adjusted OR 0.42, 95% CI 0.27 to 0.65). In the group receiving the bundle, also severe GMH-IVH, cystic periventricular leukomalacia and/or death were less often observed (adjusted OR 0.54, 95% CI 0.33 to 0.91). Conclusions The application of a bundle of nursing interventions is associated with reduced risk of developing a new/progressive (severe) GMH-IVH, cystic periventricular leukomalacia and/or mortality in very preterm infants when applied during the first 72 hours postnatally.

Screening for early onset neonatal sepsis: NICE guidance-based practice versus projected application of the Kaiser Permanente sepsis risk calculator in the UK population.

Abstract: Objective To compare management recommendations of the National Institute for Health and Care Excellence (NICE) guidelines with the Kaiser Permanente sepsis risk calculator (SRC) for risk of early onset neonatal sepsis (EONS). Design Multicentre prospective observational projection study. Setting Eight maternity hospitals in Wales, UK. Patients All live births ≥34 weeks gestation over a 3-month period (February–April 2018). Methods Demographics, maternal and infant risk factors, infant’s clinical status, antibiotic usage and blood culture results from first 72 hours of birth were collected. Infants were managed using NICE recommendations and decisions compared with that projected by SRC. Main outcome measure Proportion of infants recommended for antibiotics on either tool. Results Of 4992 eligible infants, complete data were available for 3593 (71.9%). Of these, 576 (16%) were started on antibiotics as per NICE recommendations compared with 156 (4.3%) projected by the SRC, a relative reduction of 74%. Of the 426 infants avoiding antibiotics, SRC assigned 314 (54.6%) to normal care only. There were seven positive blood cultures—three infants were recommended antibiotics by both, three were not identified in the asymptomatic stage by either; one was a contaminant. No EONS-related readmission was reported. Conclusion The judicious adoption of SRC in UK clinical practice for screening and management of EONS could potentially reduce interventions and antibiotic usage in three out of four term or near-term infants and promote earlier discharge from hospital in >50%. We did not identify any EONS case missed by SRC when compared with NICE. These results have significant implications for healthcare resources.

Therapeutic hypothermia for mild neonatal encephalopathy: a systematic review and meta-analysis

Abstract: Objectives To examine if therapeutic hypothermia reduces the composite outcome of death, moderate or severe disability at 18 months or more after mild neonatal encephalopathy (NE). Data source MEDLINE, Cochrane database, Scopus and ISI Web of Knowledge databases, using ‘hypoxic ischaemic encephalopathy’, ‘newborn’ and ‘hypothermia’, and ‘clinical trials’ as medical subject headings and terms. Manual search of the reference lists of all eligible articles and major review articles and additional data from the corresponding authors of selected articles. Study selection Randomised and quasirandomised controlled trials comparing therapeutic hypothermia with usual care. Data extraction Safety and efficacy data extracted independently by two reviewers and analysed. Results We included the data on 117 babies with mild NE inadvertently recruited to five cooling trials (two whole-body cooling and three selective head cooling) of moderate and severe NE, in the meta-analysis. Adverse outcomes occurred in 11/56 (19.6%) of the cooled babies and 12/61 (19.7%) of the usual care babies (risk ratio 1.11 (95% CIs 0.55 to 2.25)). Conclusions Current evidence is insufficient to recommend routine therapeutic hypothermia for babies with mild encephalopathy and significant benefits or harm cannot be excluded.

Umbilical cord milking in preterm infants: a systematic review and meta-analysis.

Abstract: Objective To conduct a systematic review and meta-analysis of the efficacy and safety of umbilical cord milking in preterm infants. Design Randomised controlled trials comparing umbilical cord milking with delayed cord clamping/immediate cord clamping in preterm infants were identified by searching databases, clinical trial registries and reference list of relevant studies in November 2019. Fixed effects model was used to pool the data on various clinically relevant outcomes. Main outcome measures Mortality and morbidities in preterm neonates. Results Nineteen studies (2014 preterm infants) were included. Five studies (n=922) compared cord milking with delayed cord clamping, whereas 14 studies (n=1092) compared milking with immediate cord clamping. Cord milking, as opposed to delayed cord clamping, significantly increased the risk of intraventricular haemorrhage (grade III or more) (risk ratio (RR): 1.95 (95% CI 1.01 to 3.76), p=0.05). When compared with immediate cord clamping, cord milking reduced the need for packed RBC transfusions (RR:0.56 (95% CI 0.43 to 0.73), p Conclusion Umbilical cord milking, when compared with delayed cord clamping, significantly increased the risk of severe intraventricular haemorrhage in preterm infants, especially at lower gestational ages. Cord milking, when compared with immediate cord clamping, reduced the need for packed RBC transfusions but did not improve clinical outcomes. Hence, cord milking cannot be considered as placental transfusion strategy in preterm infants based on the currently available evidence.

Congenital duodenal obstruction in the UK: a population-based study

Abstract: Objective Congenital duodenal obstruction (CDO) comprising duodenal atresia or stenosis is a rare congenital anomaly requiring surgical correction in early life. Identification of variation in surgical and postoperative practice in previous studies has been limited by small sample sizes. This study aimed to prospectively estimate the incidence of CDO in the UK, and report current management strategies and short-term outcomes. Design Prospective population-based, observational study for 12 months from March 2016. Setting Specialist neonatal surgical units in the UK. Main outcome measures Incidence of CDO, associated anomalies and short-term outcomes. Results In total, 110 cases were identified and data forms were returned for 103 infants giving an estimated incidence of 1.22 cases per 10 000 (95% CI 1.01 to 1.49) live births. Overall, 59% of cases were suspected antenatally and associated anomalies were seen in 69%. Operative repair was carried out mostly by duodenoduodenostomy (76%) followed by duodenojejunostomy (15%). Postoperative feeding practice varied with 42% having a trans-anastomotic tube placed and 88% receiving parenteral nutrition. Re-operation rate related to the initial procedure was 3% within 28 days. Two infants died within 28 days of operation from unrelated causes. Conclusion This population-based study of CDO has shown that the majority of infants have associated anomalies. There is variation in postoperative feeding strategies which represent opportunities to explore the effects of these on outcome and potentially standardise approach. Short-term outcomes are generally good.

Randomised trial of azithromycin to eradicate Ureaplasma in preterm infants

Abstract: Objective To test whether azithromycin eradicates Ureaplasma from the respiratory tract in preterm infants. Design Prospective, phase IIb randomised, double-blind, placebo-controlled trial. Setting Seven level III–IV US, academic, neonatal intensive care units (NICUs). Patients Infants 240–286 weeks’ gestation (stratified 240–266; 270–286 weeks) randomly assigned within 4 days following birth from July 2013 to August 2016. Interventions Intravenous azithromycin 20 mg/kg or an equal volume of D5W (placebo) every 24 hours for 3 days. Main outcome measures The primary efficacy outcome was Ureaplasma-free survival. Secondary outcomes were all-cause mortality, Ureaplasma clearance, physiological bronchopulmonary dysplasia (BPD) at 36 weeks’ postmenstrual age, comorbidities of prematurity and duration of respiratory support. Results One hundred and twenty-one randomised participants (azithromycin: n=60; placebo: n=61) were included in the intent-to-treat analysis (mean gestational age 26.2±1.4 weeks). Forty-four of 121 participants (36%) were Ureaplasma positive (azithromycin: n=19; placebo: n=25). Ureaplasma-free survival was 55/60 (92% (95% CI 82% to 97%)) for azithromycin compared with 37/61 (61% (95% CI 48% to 73%)) for placebo. Mortality was similar comparing the two treatment groups (5/60 (8%) vs 6/61 (10%)). Azithromycin effectively eradicated Ureaplasma in all azithromycin-assigned colonised infants, but 21/25 (84%) Ureaplasma-colonised participants receiving placebo were culture positive at one or more follow-up timepoints. Most of the neonatal mortality and morbidity was concentrated in 21 infants with lower respiratory tract Ureaplasma colonisation. In a subgroup analysis, physiological BPD-free survival was 5/10 (50%) (95% CI 19% to 81%) among azithromycin-assigned infants with lower respiratory tract Ureaplasma colonisation versus 2/11 (18%) (95% CI 2% to 52%) in placebo-treated infants. Conclusion A 3-day azithromycin regimen effectively eradicated respiratory tract Ureaplasma colonisation in this study. Trial registration number NCT01778634.

Neurodevelopmental impairment in necrotising enterocolitis survivors: systematic review and meta-analysis

Abstract: Aim To determine (1) the incidence of neurodevelopmental impairment (NDI) in necrotising enterocolitis (NEC), (2) the impact of NEC severity on NDI in these babies and (3) the cerebral lesions found in babies with NEC. Methods Systematic review: three independent investigators searched for studies reporting infants with NDI and a history of NEC (PubMed, Medline, Cochrane Collaboration, Scopus). Meta-analysis: using RevMan V.5.3, we compared NDI incidence and type of cerebral lesions between NEC infants versus preterm infants and infants with medical vs surgical NEC. Results Of 10 674 abstracts screened, 203 full-text articles were examined. In 31 studies (n=2403 infants with NEC), NDI incidence was 40% (IQR 28%–64%) and was higher in infants with surgically treated NEC (43%) compared with medically managed NEC (27%, p Conclusions This study shows that a large proportion of NEC survivors has NDI. NEC babies are at higher risk of developing IVH and/or PVL than babies with prematurity alone. The degree of NDI seems to correlate to the severity of gut damage, with a worse status in infants with surgical NEC compared with those with medical NEC. Trial registration number CRD42019120522.

Proposal for prevention and control of the 2019 novel coronavirus disease in newborn infants.

Abstract: Since the end of 2019, an outbreak of the 2019 novel coronavirus disease (COVID-19)1 has fast spread widely. By 19 February 2020, over 70 000 laboratory-confirmed COVID-19 have been reported, with over 1800 patients died. At least 12 neonates have been diagnosed with COVID-19.2 Newborn infants deserve more concern due to their immature immune system and the possibility of mother to infant transmission. Neonatologists belonging to the Chinese Neonatologist Association of Chinese Doctor Association have proposed measurements for the prevention and control of COVID-19 in neonates. The delivery room or operating room serving suspected or confirmed infected mothers should be specially prepared, preferably with negative pressure.3 Medical staff involved must be equipped with required protective equipment. Neonatal resuscitation is performed according to the Neonatal …

Trends in sex-specific differences in outcomes in extreme preterms: progress or natural barriers?

Abstract: Objective To examine the differences and trends of outcomes of preterm boys and girls born at Design A retrospective cohort study. Setting Data collected by the Canadian Neonatal Network. Patients Neonates born at Main outcome measures We examined rate differences in mortality, major morbidities (bronchopulmonary dysplasia, severe brain injury, retinopathy of prematurity, necrotising enterocolitis and late-onset sepsis) and care practices (antenatal steroids, magnesium sulfate, maternal antibiotics, ventilation and surfactant administration) between boys and girls and evaluated trends in these rate differences over the study period. Our primary outcome was a composite of mortality and any one of the five morbidities. Results Our study included 8219 boys and 6934 girls with median gestational age of 26 (IQR 25–28) weeks. The composite of death or major morbidity was more common in boys (adjusted risk ratio 1.07, 95% CI 1.05 to 1.10) and remained higher in boys over the study period. The gap between boys and girls for mortality, however, decreased over time: the slope for boys was −0.043 (95% CI −0.071 to −0.015) and for girls was −0.012 (95% CI −0.045 to 0.020) (p=0.04). All other morbidities remained higher in boys. Care practices changed at similar rates between the sexes. Conclusion The difference between the mortality rates for boys and girls decreased over the study period but the difference between rates of the major morbidities was unchanged. More research is needed to understand biological differences and outcome disparities.

Physiological effects of high-flow nasal cannula therapy in preterm infants

Abstract: Objective High-flow nasal cannula (HFNC) therapy is increasingly used in preterm infants despite a paucity of physiological studies. We aimed to investigate the effects of HFNC on respiratory physiology. Study design A prospective randomised crossover study was performed enrolling clinically stable preterm infants receiving either HFNC or nasal continuous positive airway pressure (nCPAP). Infants in three current weight groups were studied: 1500 g. Infants were randomised to either first receive HFNC flows 8–2 L/min and then nCPAP 6 cm H2O or nCPAP first and then HFNC flows 8–2 L/min. Nasopharyngeal end-expiratory airway pressure (pEEP), tidal volume, dead space washout by nasopharyngeal end-expiratory CO2 (pEECO2), oxygen saturation and vital signs were measured. Results A total of 44 preterm infants, birth weights 500–1900 g, were studied. Increasing flows from 2 to 8 L/min significantly increased pEEP (mean 2.3–6.1 cm H2O) and reduced pEECO2 (mean 2.3%–0.9%). Tidal volume and transcutaneous CO2 were unchanged. Significant differences were seen between pEEP generated in open and closed mouth states across all HFNC flows (difference 0.6–2.3 cm H2O). Infants weighing 1000 g. Variability of pEEP generated at HFNC flows of 6–8 L/min was greater than nCPAP (2.4–13.5 vs 3.5–9.9 cm H2O). Conclusions HFNC therapy produces clinically significant pEEP with large variability at higher flow rates. Highest pressures were observed in infants weighing

Early cortical maturation predicts neurodevelopment in very preterm infants

Abstract: Objective To evaluate the ability of four objectively defined, cortical maturation features—surface area, gyrification index, sulcal depth and curvature—from structural MRI at term-equivalent age (TEA) to independently predict cognitive and language development at 2 years corrected age in very preterm (VPT) infants. Design Population-based, prospective cohort study. Structural brain MRI was performed at term, between 40 and 44 weeks postmenstrual age and processed using the developing Human Connectome Project pipeline. Setting Multicentre study comprising four regional level III neonatal intensive care units in the Columbus, Ohio region. Patients 110 VPT infants (gestational age (GA) ≤ 31 weeks). Main outcome measures Cognitive and language scores at 2 years corrected age on the Bayley Scales of Infant and Toddler Development, Third Edition. Results Of the 94 VPT infants with high-quality T2-weighted MRI scans, 75 infants (80%) returned for Bayley-III testing. Cortical surface area was positively correlated with cognitive and language scores in nearly every brain region. Curvature of the inner cortex was negatively correlated with Bayley scores in the frontal, parietal and temporal lobes. In multivariable regression models, adjusting for GA, sex, socioeconomic status, and injury score on MRI, regional measures of surface area and curvature independently explained more than one-third of the variance in cognitive and language scores at 2 years corrected age in our cohort. Conclusions We identified increased cortical curvature at TEA as a new prognostic biomarker of adverse neurodevelopment in very premature infants. When combined with cortical surface area, it enhanced prediction of cognitive and language development. Larger studies are needed to externally validate our findings.

Drainage, irrigation and fibrinolytic therapy (DRIFT) for posthaemorrhagic ventricular dilatation: 10-year follow-up of a randomised controlled trial

Abstract: Background Progressive ventricular dilatation after intraventricular haemorrhage (IVH) in preterm infants has a very high risk of severe disability and death. Drainage, irrigation and fibrinolytic therapy (DRIFT), in a randomised controlled trial (RCT), reduced severe cognitive impairment at 2 years. Objective To assess if the cognitive advantage of DRIFT seen at 2 years persisted until school age. Participants The RCT conducted in four centres recruited 77 preterm infants with IVH and progressive ventricular enlargement over specified measurements. Follow-up was at 10 years of age. Intervention Intraventricular injection of a fibrinolytic followed by continuous lavage, until the drainage was clear, and standard care consisting of control of expansion by lumbar punctures and if expansion persisted via a ventricular access device. Primary outcome Cognitive quotient (CQ), derived from the British Ability Scales and Bayley III Scales, and survival without severe cognitive disability. Results Of the 77 children randomised, 12 died, 2 could not be traced, 10 did not respond and 1 declined at 10-year follow-up. 28 in the DRIFT group and 24 in the standard treatment group were assessed by examiners blinded to the intervention. The mean CQ score was 69.3 (SD=30.1) in the DRIFT group and 53.7 (SD=35.7) in the standard treatment group (unadjusted p=0.1; adjusted p=0.01, after adjustment for the prespecified variables sex, birth weight and IVH grade). Survival without severe cognitive disability was 66% in the DRIFT group and 35% in the standard treatment group (unadjusted p=0.019; adjusted p=0.003). Conclusion DRIFT is the first intervention for posthaemorrhagic ventricular dilatation to objectively demonstrate sustained cognitive improvement. Trial registration number ISRCTN80286058.

Consensus outcome rating for international neonatal resuscitation guidelines

Abstract: The International Liaison Committee on Resuscitation uses the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) working group method to evaluate the quality of evidence and the strength of treatment recommendations. This method requires guideline developers to use a numerical rating of the importance of each specified outcome. There are currently no uniform reporting guidelines or outcome measures for neonatal resuscitation science. We describe consensus outcome ratings from a survey of 64 neonatal resuscitation guideline developers representing seven international resuscitation councils. Among 25 specified outcomes, 10 were considered critical for decision-making. The five most critically rated outcomes were death, moderate-severe neurodevelopmental impairment, blindness, cerebral palsy and deafness. These data inform outcome rankings for systematic reviews of neonatal resuscitation science and international guideline development using the GRADE methodology.

Breast feeding at the time of COVID-19: do not forget expressed mother's milk, please.

Abstract: In the context of the coronavirus disease (COVID-19) prevention and cure, a remarkable issue, particularly in maternity hospitals, is represented by the risk of mother to child transmission by a breastfeeding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive woman.1 In a recent letter, Li states ‘all infants with suspected COVID-19 should be isolated and monitored regardless of whether or not they present with symptoms’,2 without giving further details on the management of newborn infant feeding. Moreover, Chinese colleagues who have recently coped with COVID-19 just do not consider the breast feeding option, nor the use of expressed breast milk for newborn infants.3 We can assume …

Active perinatal care of preterm infants in the German Neonatal Network.

Abstract: Objective To determine if survival rates of preterm infants receiving active perinatal care improve over time. Design The German Neonatal Network is a cohort study of preterm infants with birth weight Setting 43 German level III neonatal intensive care units (NICUs). Patients 8222 preterm infants with a gestational age between 22/0 and 28/6 weeks who received active perinatal care. Interventions Participating NICUs were grouped according to their specific survival rate from 2011 to 2013 to high (percentile >P75), intermediate (P25–P75) and low ( Main outcome measures Death by any cause before discharge. Results Total survival increased from 85.8% in 2011–2013 to 87.4% in 2014–2016. This increase was due to reduced mortality of NICUs with low survival rates in 2011–2013. Survival increased in these centres from 53% to 64% in the 22–24 weeks strata and from 73% to 84% in the 25–26 weeks strata. Conclusions Our data support previous reports that active perinatal care of very immature infants improves outcomes at the border of viability and survival rates at higher gestational ages. The high total number of surviving infants below 24 weeks of gestation challenges national recommendations exclusively referring to gestational age as the single criterion for providing active care. However, more data are needed before recommendations for parental counselling should be reconsidered. Trial registration Approval by the local institutional review board for research in human subjects of the University of Lubeck (file number 08–022) and by the local ethic committees of all participating centres has been given.

Initiating resuscitation before umbilical cord clamping in infants with congenital diaphragmatic hernia: a pilot feasibility trial.

Abstract: Background Infants with congenital diaphragmatic hernia (CDH) often experience hypoxaemia with acidosis immediately after birth. The traditional approach in the delivery room is immediate cord clamping followed by intubation. Initiating resuscitation prior to umbilical cord clamping (UCC) may support this transition. Objectives To establish the safety and feasibility of intubation and ventilation prior to UCC for infants with CDH. To compare short-term outcomes between trial participants and matched controls treated with immediate cord clamping before intubation and ventilation. Design Single-arm, single-site trial of infants with CDH and gestational age ≥36 weeks. Infants were placed on a trolley immediately after birth and underwent intubation and ventilation, with UCC performed after qualitative CO2 detection. The primary feasibility endpoint was successful intubation prior to UCC. Prespecified safety and physiological outcomes were compared with historical controls matched for prognostic variables using standard bivariate tests. Results Of 20 enrolled infants, all were placed on the trolley, and 17 (85%) infants were intubated before UCC. The first haemoglobin and mean blood pressure at 1 hour of life were significantly higher in trial participants than controls. There were no significant differences between groups for subsequent blood pressure values, vasoactive medications, inhaled nitric oxide or extracorporeal membrane oxygenation. Blood gas and oxygenation index values did not differ between groups at any point. Conclusions Intubation and ventilation prior to UCC is safe and feasible among infants with CDH. The impact of this approach on clinically relevant outcomes deserves investigation in a randomised trial.

Postnatally acquired cytomegalovirus infection in extremely premature infants: how best to manage?

Abstract: Postnatal cytomegalovirus (pCMV) infection is a common viral infection typically occurring within the first months of life. pCMV refers to postnatal acquisition of CMV rather than postnatal manifestations of antenatal or perinatal acquired CMV. pCMV is usually asymptomatic in term infants, but can cause symptomatic disease in preterm (gestational age

Improving infant outcomes through implementation of a family integrated care bundle including a parent supporting mobile application.

Abstract: Objective The aim of the Integrated Family Delivered Care (IFDC) programme was to improve infant health outcomes and parent experience through education and competency-based training. Design In collaboration with veteran parents’ focus groups, we created an experienced co-designed care bundle including IFDC mobile application, which together with staff training programme comprised the IFDC programme. Infant outcomes were compared with retrospective controls in a prepost intervention analysis. Main outcome measures The primary outcome measure was the length of stay (LOS). Results Between April 2017 and May 2018, 89 families were recruited; 37 infants completed their entire care episode in our units with a minimum LOS >14 days. From a gestational age (GA) and birth weight-matched retrospective cohort, 57 control infants were selected. Data were also analysed for subgroup under 30 weeks GA (n=20). Infants in the IFDC group were discharged earlier: median corrected GA (36+0 (IQR 35+0–38+0) vs 37+1 (IQR 36+3–38+4) weeks; p=0.003), with shorter median LOS (41 (32–63) vs 55 (41–73) days; p=0.022). This was also evident in the subgroup Conclusion This is the first reported study from a UK tertiary neonatal unit demonstrating significant benefits of family integrated care programme. The IFDC programme has significantly reduced LOS, resulted in the earlier achievement of full enteral and suck feeds.

Physiologically based cord clamping improves cardiopulmonary haemodynamics in lambs with a diaphragmatic hernia

Abstract: Objective Lung hypoplasia associated with congenital diaphragmatic hernia (CDH) results in respiratory insufficiency and pulmonary hypertension after birth. We have investigated whether aerating the lung before removing placental support (physiologically based cord clamping (PBCC)), improves the cardiopulmonary transition in lambs with a CDH. Methods At ≈138 days of gestational age, 17 lambs with surgically induced left-sided diaphragmatic hernia (≈d80) were delivered via caesarean section. The umbilical cord was clamped either immediately prior to ventilation onset (immediate cord clamping (ICC); n=6) or after achieving a target tidal volume of 4 mL/kg, with a maximum delay of 10 min (PBCC; n=11). Lambs were ventilated for 120 min and physiological changes recorded. Results Pulmonary blood flow (PBF) increased following ventilation onset in both groups, but was 19-fold greater in PBCC compared with ICC lambs at cord clamping (19±6.3 vs 1.0±0.5 mL/min/kg, p Conclusions Compared with ICC, PBCC prevented the severe asphyxia immediately after birth and resulted in a higher PBF due to a lower PVR, which persisted for at least 120 min after birth in CDH lambs.

Feasibility of automated insulin delivery guided by continuous glucose monitoring in preterm infants

Abstract: Objective Closed-loop systems have been used to optimise insulin delivery in children with diabetes, but they have not been tested in neonatal intensive care. Extremely preterm infants are prone to hyperglycaemia and hypoglycaemia; both of which have been associated with adverse outcomes. Insulin sensitivity is notoriously variable in these babies and glucose control is time-consuming, with management requiring frequent changes of dextrose-containing fluids and careful monitoring of insulin treatment. We aimed to evaluate the feasibility of closed-loop management of glucose control in these infants. Design and setting Single-centre feasibility study with a randomised parallel design in a neonatal intensive care unit. Eligibility criteria included birth weight Results The mean (SD) gestational age and birth weight of intervention and control study arms were 27.0 (2.4) weeks, 962 (164) g and 27.5 (2.8) weeks, 823 (282) g, respectively, and were not significantly different. The time in target was dramatically increased from median (IQR) 26% (6-64) with paper guidance to 91% (78-99) during closed loop (p Conclusions Closed-loop glucose control based on subcutaneous glucose measurements appears feasible as a potential method of optimising glucose control in extremely preterm infants.

Therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy in India (THIN study): a randomised controlled trial.

Abstract: Objective To evaluate the neuroprotective effect of therapeutic hypothermia (TH) induced by phase changing material (PCM) on MRI biomarkers in infants with hypoxic-ischaemic encephalopathy (HIE) in a low-resource setting. Design Open-label randomised controlled trial. Setting One neonatal intensive care unit in a tertiary care centre in India. Patients 50 term/near-term infants admitted within 5 hours after birth with predefined physiological criteria and signs of moderate/severe HIE. Interventions Standard care (n=25) or standard care plus 72 hours of hypothermia (33.5°C±0.5°C, n=25) induced by PCM. Main outcome measures Primary outcome was fractional anisotropy (FA) in the posterior limb of the internal capsule (PLIC) on neonatal diffusion tensor imaging analysed according to intention to treat. Results Primary outcome was available for 22 infants (44%, 11 in each group). Diffusion tensor imaging showed significantly higher FA in the cooled than the non-cooled infants in left PLIC and several white matter tracts. After adjusting for sex, birth weight and gestational age, the mean difference in PLIC FA between groups was 0.026 (95% CI 0.004 to 0.048, p=0.023). Conventional MRI was available for 46 infants and demonstrated significantly less moderate/severe abnormalities in the cooled (n=2, 9%) than in the non-cooled (n=10, 43%) infants. There was no difference in adverse events between groups. Conclusions This study confirmed that TH induced by PCM reduced brain injury detected on MRI in infants with moderate HIE in a neonatal intensive care unit in India. Future research should focus on optimal supportive treatment during hypothermia rather than looking at efficacy of TH in low-resource settings. Trial registration number CTRI/2013/05/003693.

EPICE cohort: two-year neurodevelopmental outcomes after very preterm birth

Abstract: Objective To determine whether the variation in neurodevelopmental disability rates between populations persists after adjustment for demographic, maternal and infant characteristics for an international very preterm (VPT) birth cohort using a standardised approach to neurodevelopmental assessment at 2 years of age. Design Prospective standardised cohort study. Setting 15 regions in 10 European countries. Patients VPT births: 22+0–31+6 weeks of gestation. Data collection Standardised data collection tools relating to pregnancy, birth and neonatal care and developmental outcomes at 2 years corrected age using a validated parent completed questionnaire. Main outcome measures Crude and standardised prevalence ratios calculated to compare rates of moderate to severe neurodevelopmental impairment between regions grouped by country using fixed effects models. Results Parent reported rates of moderate or severe neurodevelopmental impairment for the cohort were: 17.3% (ranging 10.2%–26.1% between regions grouped by country) with crude standardised prevalence ratios ranging from 0.60 to 1.53. Adjustment for population, maternal and infant factors resulted in a small reduction in the overall variation (ranging from 0.65 to 1.30). Conclusion There is wide variation in the rates of moderate to severe neurodevelopmental impairment for VPT cohorts across Europe, much of which persists following adjustment for known population, maternal and infant factors. Further work is needed to investigate whether other factors including quality of care and evidence-based practice have an effect on neurodevelopmental outcomes for these children.