Eligible babies were healthy, term, appropriately grown singletons born in a birthing centre, hospital or home within the greater Hamilton area and then discharged home. Babies had subcutaneous continuous glucose monitoring placed soon after birth, up to 14 heel-prick blood samples, twice-daily home visits and parents were asked to record all feeds. At study completion, both parents were asked to independently complete a questionnaire about their experience.

All eligible babies completed the study and every parent completed the questionnaire (65 fathers, 66 mothers). Parents reported they liked contributing to improving healthcare (126/131, 96%) and support from the GLOW team (119/131, 91%). Nearly all (127/131, 97%) would participate in GLOW again if they had another eligible baby, and all would recommend GLOW to family and friends. Two-thirds of parents (87/131, 66%) reported that participation had made them more likely to contribute to clinical research in the future.

Non-therapeutic studies involving invasive procedures in healthy term babies are feasible, and parents were positive about their experience.

Case–control study.

29 case children without CP, cooled in 2008–2010 and 20 age-matched, sex-matched and social class-matched term-born controls.

Wechsler Intelligence Scales for Children, Fourth UK Edition, Movement Assessment Battery for Children, Second Edition (MABC-2) and Strengths and Difficulties Questionnaire.

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.

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.

Randomised controlled trial.

Mothers of term infants born vigorous by vaginal delivery with informed consent provided in early labour were randomly assigned to oxytocin (10 IU) given intravenously within 15 s of birth (group 1) or after clamping the umbilical cord 3 min after delivery (group 2). Soon after birth, all infants were weighed using a 1 g precision scale and subsequently placed on the mother’s abdomen or chest. At 3 min, in both groups, the cord was clamped and cut, and the weight was again obtained. The primary outcome (volume of placental transfusion) was estimated by the difference in weights.

144 patients were included. There were no differences in the primary outcome: infants in group 1 (n=70) gained a mean weight of 85.9 g (SD 48.3), and in group 2 (n=74) 86.7 g (SD 49.6) (p=0.92). No differences were found in secondary outcomes, including newborns’ haematocrit and bilirubin concentrations and severe maternal postpartum haemorrhage. On the advice of the Data and Safety Monitoring Committee, the trial was stopped due to futility at 25% of the planned sample size.

When umbilical cord clamping is delayed for 3 min, term newborn infants born vigorous receive a clinically significant placental transfusion which is not modified by the administration of intravenous oxytocin immediately after birth.

NCT02618499.

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.

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<0.001). Cerebral tissue oxygenation was higher in PBCC than ICC lambs during the first 10 min after cord clamping (59%±4% vs 30%±5%, p<0.001). PBF was threefold higher (23±4 vs 8±2 mL/min/kg, p=0.01) and pulmonary vascular resistance (PVR) was threefold lower (0.6±0.1 vs 2.2±0.6 mm Hg/(mL/min), p<0.001) in PBCC lambs compared with ICC lambs at 120 min after ventilation onset.

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.

Investigate the effect of spontaneous breathing on umbilical venous flow and body weight in preterm lambs.

Pregnant sheep were instrumented at 132–133 days gestational age to measure fetal common umbilical venous, pulmonary and cerebral blood flows as well as arterial and intrapleural (IP) pressures. At delivery, doxapram and caffeine were administered to promote breathing. Lamb body weights were measured continuously and breathing was assessed by IP pressure changes.

In 6 lambs, 491 out of 1117 breaths were analysed for change in body weight. Weight increased in 46.6% and decreased in 47.5% of breaths. An overall mean increase of 0.02±2.5 g per breath was calculated, and no net placental transfusion was observed prior to cord clamping (median difference in body weight 52.3 [–54.9–166.1] g, p=0.418). Umbilical venous (UV) flow transiently decreased with each inspiration, and in some cases ceased, before UV flow normalised during expiration. The reduction in UV flow was positively correlated with the standardised reduction in (IP) pressure, increasing by 109 mL/min for every SD reduction in IP pressure. Thus, the reduction in UV flow was closely related to inspiratory depth.

Spontaneous breathing had no net effect on body weight in preterm lambs at birth. UV blood flow decreased as inspiratory effort increased, possibly due to constriction of the inferior vena cava caused by diaphragmatic contraction, as previously observed in human fetuses.

Multiple neonatal intensive care units (NICU) across the USA.

Singleton neonates born at 22–29 weeks’ gestation with no major anomalies who were admitted to a NICU and discharged between 2000 and 2014. Outborn neonates were restricted to those who transferred into a NICU on the day of birth.

The association between inborn-outborn status and the time-to-event outcomes of in-hospital mortality and necrotising enterocolitis (NEC) were assessed using Cox proportional hazards regression. Logistic regression was used to assess the remaining secondary outcomes: retinopathy of prematurity requiring treatment (tROP), chronic lung disease (CLD), periventricular leucomalacia (PVL) and severe intraventricular haemorrhage (IVH). Since outborn status was not random, we used 1:1 propensity score matching to reduce the imbalance in illness severity.

There were 59 942 neonates (7991 outborn) included in the study. Outborn neonates had poorer survival than inborns and higher rates of NEC, severe IVH, tROP and PVL. Inborn-outborn disparities in mortality were reduced over the study period. When analysing the matched cohort (6524 matched pairs), outborns were less likely to die in-hospital compared with inborns (HR 0.84, 95% CI 0.77 to 0.91). However, outborns experienced higher rates of NEC (HR 1.14, 95% CI 1.04 to 1.25), severe IVH (OR 1.52, 95% CI 1.38 to 1.68), tROP (OR 1.45, 95% CI 1.25 to 1.69) and CLD (OR 1.12, 95% CI 1.01 to 1.24).

Additional research is needed to understand the contributors to increased morbidity for outborn extremely preterm neonates and identify interventions that mitigate this risk.

This was a randomised controlled cross-over (AB/BA) study evaluating HR assessment using auscultation plus NeoTapAS compared with auscultation plus mental computation in a high-fidelity simulated newborn resuscitation scenario. Twenty teams each including three paediatric residents were randomly assigned to AB or BA arms. The primary outcome was the timing of the first HR communication. Secondary outcomes included the timing of the following four HR communications and the timing of resuscitation interventions (positive pressure ventilation, chest compressions, intubation and administration of first dose of epinephrine).

NeoTapAS reduced the time to the first HR communication (mean difference –13 s, 95% CI –23 to –4; p=0.009), and the time of initiation of chest compressions (mean difference –68 s, 95% CI –116 to –18; p=0.01) and administration of epinephrine (mean difference –76 s, 95% CI –115 to –37; p=0.0004) compared with mental computation.

In a neonatal resuscitation simulated scenario, NeoTapAS reduced the time to the first HR communication and the time of initiation of chest compressions and administration of epinephrine compared with mental computation. This app can be especially useful in settings with limited availability of monitoring equipment, but further studies in clinical scenarios are warranted.

NCT03730025.

We conducted a retrospective analysis of 2688 infants >35 weeks’ gestation who were screened for NH before and after implementation of a clinical guideline for NH evaluation and treatment. We analysed the proportion of infants who required intravenous dextrose for NH before and after guideline implementation, the change in blood glucose concentrations with gel by feeding type and the odds of successful NH treatment with gel and feeding by feeding type.

Following implementation of the guideline, a lower proportion of infants required intravenous dextrose for NH treatment (8.6% (60 infants) before guideline vs. 5.6% (112 infants) after guideline (p=0.007)). The median rise in blood glucose concentration with gel administration in the entire cohort was 0.61 mmol/L (11 mg/dL) (IQR 0.28–1.06 mmol/L (5–19 mg/dL)). Blood glucose concentration of formula-fed infants rose more in response to feeding and gel than breastfed infants (p≤0.0001). Formula feeding was associated with a lower odds of recurrent hypoglycaemia, as defined by requiring a second gel, in a fully adjusted model. Specifically, in infants with a pregel blood glucose of 2.00–2.17 mmol/L (36–39 mg/dL), formula feeding with gel was associated with a lower odds of recurrent hypoglycaemia.

Dextrose gel is an effective tool in the treatment of NH. An infant’s pregel blood glucose concentration may be helpful in guiding decisions around type of feeding provided.

This retrospective cohort study was conducted at Monash Health.

Data were collected from neonatal and birth records of moderate-late preterm (32–36 weeks) infants born between 2012 and 2015 to SA-born and Aus/NZ-born women.

Rates of nursery admissions and neonatal respiratory outcomes were compared.

Babies born to Aus/NZ-born women were more likely to be admitted to a nursery (80%) compared with SA-born babies (72%, p=0.004). Babies born to SA-born mothers experienced significantly less hyaline membrane disease (7.8%), required less resuscitation at birth (28.6%) and were less likely to require ventilation (20%) than babies born to Aus/NZ-born mothers (18%, 42.2%, 34.6%; p<0.001). There was no difference in the duration of ventilation or length of stay in hospital.

Moderate-late preterm babies born to SA-born women appear to have earlier functional maturity, as indicated by respiratory outcomes, than Aus/NZ-born babies. Our findings support the hypothesis of earlier fetal maturation in SA-born women.

National birth cohort study.

England and Wales 2006–2012.

Singleton live births at 24–36 completed weeks’ gestation (n=256 142).

Adjusted rate ratios for death in infancy by cause (three groups), within categories of gestational age at birth (24–27, 28–31, 32–36 weeks), by baby’s ethnicity (nine groups) or area deprivation score (Index of Multiple Deprivation quintiles).

Among 24–27 week births (5% of subjects; 47% of those who died in infancy), all minority ethnic groups had lower risk of immaturity-related death than White British, the lowest rate ratios being 0.63 (95% CI 0.49 to 0.80) for Black Caribbean, 0.74 (0.64 to 0.85) for Black African and 0.75 (0.60 to 0.94) for Indian. Among 32–36 week births, all minority groups had higher risk of death from congenital anomalies than White British, the highest rate ratios being 4.50 (3.78 to 5.37) for Pakistani, 2.89 (2.10 to 3.97) for Bangladeshi and 2.06 (1.59 to 2.68) for Black African; risks of death from congenital anomalies and combined rarer causes (infection, intrapartum conditions, SIDS and unclassified) increased with deprivation, the rate ratios comparing the most with the least deprived quintile being, respectively, 1.54 (1.22 to 1.93) and 2.05 (1.55 to 2.72). There was no evidence of socioeconomic variation in deaths from immaturity-related conditions.

Gestation-specific preterm infant mortality shows contrasting ethnic patterns of death from immaturity-related conditions in extremely-preterm babies, and congenital anomalies in moderate/late-preterm babies. Socioeconomic variation derives from congenital anomalies and rarer causes in moderate/late-preterm babies. Future research should examine biological origins of extremely preterm birth.

Observational study.

Twenty-eight of 768 infants registered in the Baby Cooling Registry of Japan between 2012 and 2016, at >34 weeks’ gestation, with Apgar scores of zero at 10 min who were treated with therapeutic hypothermia.

We investigated the time of first heartbeat detection in infants with favourable outcomes and who had neurodevelopmental impairments or died.

Clinical characteristics, mortality rate and neurodevelopmental outcomes at 18–22 months of age were evaluated.

Nine (32%) of the 28 infants died before 18 months of age; 16 (57%) survived, but with severe disabilities and 3 (11%) survived without moderate-to-severe disabilities. At 20 min after birth, 14 of 27 infants (52%) did not have a first heartbeat, 13 of them died or had severe disabilities and one infant, who had the first heartbeat at 20 min, survived without disability.

Our study adds to the recent evidence that neurodevelopmental outcomes among infants with Apgar scores of zero at 10 min may not be uniformly poor. However, in our study, all infants with their first heartbeat after 20 min of age died or had severe disabilities.

A literature search of CENTRAL, CINAHL, EMBASE and MEDLINE was conducted; randomised trials published between 1 July 2012 and 1 July 2017 and involving at least 100 infants in each arm were included. Outcomes and outcome measures were extracted and categorised by physiological system; reported former patient and parent involvement in outcome selection was extracted.

Seventy-six trials involving 43 126 infants were identified; 216 different outcomes with 889 different outcome measures were reported. Outcome reporting covered all physiological systems but was variable between individual trials: only 67/76 (88%) of trials reported survival and 639 outcome measures were only reported in a single trial. Thirty-three composite outcomes were used in 41 trials. No trials reported former patient or parent involvement in outcome selection.

Inconsistent outcome reporting and a lack of parent and former patient involvement in outcome selection in neonatal clinical trials limits the ability of such trials to answer clinically meaningful questions. Developing and implementing a core outcome set for future neonatal trials, with input from all stakeholders, should address these issues.

To systematically review literature to determine whether NIRS is a reliable tool to monitor gut oxygenation on neonatal units.

PubMed and Embase databases were searched using the terms ‘neonate’, ‘preterm infants’, ‘NIRS’ and ‘gut oxygenation’ (2001–2018).

Studies were included if they met inclusion criteria (clinical trial, observational studies, neonatal population, articles in English and reviewing regional gut oxygen saturations) and exclusion criteria (not evaluating abdominal NIRS or regional oxygen saturations).

Two authors independently searched PubMed and Embase using the predefined terms, appraised study quality and extracted from 30 studies the study design and outcome data.

Potential for publication bias, majority of studies were prospective cohort studies and small sample sizes.

Thirty studies were reviewed assessing the validity of abdominal NIRS and potential application in neonates. Studies reviewed assessed abdominal NIRS in different settings including normal neonates, bolus and continuous feeding, during feed intolerance, necrotising enterocolitis and transfusion with packed red cells. Several observational studies demonstrated how NIRS could be used in clinical practice.

NIRS may prove to be a useful bedside tool on the neonatal unit, working alongside current clinical tools in the monitoring of newborn infants (preterm and term) and inform clinical management. We recommend further studies including randomised controlled trials looking at specific measurements and cut-offs for abdominal NIRS for use in further clinical practice.

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: <1000 g, 1000–1500 g and >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.

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 received higher pEEP at the same HFNC flow than 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).

HFNC therapy produces clinically significant pEEP with large variability at higher flow rates. Highest pressures were observed in infants weighing <1000 g. Flow, weight and mouth position are all important determinants of pressures generated. Reductions in pEECO₂ support HFNC’s role in dead space washout.