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Objectives: To report the current incidence of bronchopulmonary dysplasia (BPD) and to compare changes in weight and head circumference between infants who developed BPD and infants who did not.Design: Retrospective, whole-population study.Setting: All neonatal units in England between 2014 and 2018.Patients: All liveborn infants born <28 completed weeks of gestation.Interventions: The change in weight z-score (ΔWz) was calculated by subtracting the birthweight z-score from the weight z-score at 36 weeks postmenstrual age (PMA) and at discharge. The change in head circumference z-score (ΔHz) was calculated by subtracting the birth head circumference z-score from the head circumference z-score at discharge.Main Outcome Measure: BPD was defined as the need for any respiratory support at 36 weeks PMA.Results: 11 806 infants were included in the analysis. The incidence of BPD was 57.5%, and 18.9% of the infants died before 36 weeks PMA. The median (IQR) ΔWz from birth to 36 weeks PMA was significantly smaller in infants who developed BPD (-0.69 (-1.28 to -0.14), n=6105) than in those who did not develop BPD (-0.89 (-1.40 to -0.33), n=2390; adjusted p<0.001). The median (IQR) ΔHz from birth to discharge was significantly smaller in infants who developed BPD (-0.33 (-1.69 to 0.71)) than in those who did not develop BPD (-0.61 (-1.85 to 0.35); adjusted p<0.001).Conclusions: Postnatal growth was better in infants diagnosed with BPD compared with infants without BPD possibly due to more aggressive nutrition strategies. [ABSTRACT FROM AUTHOR]

Aim: To determine whether closed loop automated oxygen control resulted in a reduction in the duration and severity of desaturation episodes and the number of blood gases and chest radiographs in preterm, ventilated infants. Methods: Infants were studied on two consecutive days for 12 hours on each day. They were randomised to receive standard care (standard period) or standard care with a closed loop automated oxygen control system (automated oxygen control period) first. Results: Twenty‐four infants with a median gestational age of 25.7 (range 23.1‐32.6) weeks were studied at a median postconceptional age of 27.4 (range 24.3‐34.9) weeks. During the automated oxygen control period, there were fewer desaturations that lasted >30 seconds (P =.032) or >60 seconds (P =.002), infants spent a higher proportion of the time within their target SpO2 range during the automated oxygen control period (P <.001), and fewer manual adjustments were made to the inspired oxygen concentration (mean 0.58 vs mean 11.29) (P <.001). There were no significant differences in the number of blood gases (P =.872) or chest radiographs (P =.366) between the two periods. Conclusion: Closed loop automated oxygen delivery resulted in fewer prolonged desaturations with more time spent in the targeted oxygen range. [ABSTRACT FROM AUTHOR]

Aim: Neonates frequently require supplementary oxygen but may develop complications if the oxygen saturation is outside the target range. This review aimed to determine whether the algorithms used in closed loop automated oxygen control systems influenced their efficacy and whether use of the systems reduced relevant, long-term neonatal complications.Methods: A literature search was conducted using PubMed and Google Scholar. The search terms were 'closed loop' or 'automat*', 'oxygen' and 'neonat*'.Results: Eighteen studies were identified: sixteen comparison clinical studies, an observational study and an animal study. Overall, closed loop automated oxygen control was associated with an increased percentage of time spent within the target oxygen saturation range and there were fewer manual adjustments to the inspired oxygen concentration when compared with manual oxygen control. The systems were effective in infants on non-invasive respiratory support or mechanically ventilated, but no study included term-born infants. No long-term data were available to determine if complications of oxygen toxicity were reduced.Conclusion: Closed loop automated oxygen control has been shown in short term trials including preterm and low birth weight infants to improve target saturation achievement. Whether long-term outcomes will be improved with their use requires investigation. [ABSTRACT FROM AUTHOR]

Objectives  To compare the adjusted and unadjusted-for-weight tidal volume (V T) in ventilated prematurely born infants who were successfully extubated compared with the ones who failed extubation and explore the ability of V T to predict successful extubation. Study Design  This is a two-center, prospective, observational, cohort study of ventilated infants born <32 weeks of gestational age (GA) at King's College Hospital and St George's University Hospital, London, United Kingdom between February and September 2018. Expiratory V T was recorded before extubation, and extubation was considered successful if the infants were not reintubated within 72 hours. Results  Fifty-six (29 male) infants with a median (interquartile range) GA of 26 (25–29) weeks were studied. The infants who successfully extubated (N  = 36) had a higher GA (27 [25–30] weeks) and V T (7.2 [4.8–9.5] mL) compared with the GA (25 [24–26] weeks) and V T (4.3 [4.0–5.5] mL) of the infants who failed extubation (p  = 0.002 and p  = 0.001, respectively). V T /kg was not different in infants who successfully extubated compared with the ones who failed extubation (p  = 0.643). Following multivariate regression, V T was associated with extubation success (adjusted p  = 0.022) and GA was not (adjusted p  = 0.167). A V T  > 4.5 mL predicted successful extubation with 82% sensitivity and 58% specificity (area under the curve = 0.786). Conclusion  Successful extubation was associated with higher unadjusted-for-weight V T s compared with failed extubation, and unadjusted V T predicted extubation outcome with moderate sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Background: Extremely premature infants often need invasive respiratory support from birth, but have low nutritional reserves and high metabolic demands. Our aim was to determine if there was a relationship between prolonged ventilation and reduced postnatal growth in such infants. Methods: A retrospective, observational study was undertaken. Data from infants born at less than 28 weeks of gestational age and ventilated for 7 days or more were collected and analysed including gestational age, gender, birth and discharge weight, birth and discharge head circumference, days of invasive mechanical ventilation and use of postnatal corticosteroids. The duration of invasive mechanical ventilation and the differences in weight (ΔWz) and head circumference (ΔHz) z-score from birth to discharge were calculated. Results: Fifty-five infants were studied with a median [interquartile range (IQR)] gestational age at birth of 25.3 (24.3–26.7) weeks and birth weight of 0.73 (0.65–0.87) kg. The median duration of mechanical ventilation was 45 (33–68) days. Both ΔWz and ΔHz were significantly negatively correlated to the number of invasive mechanical ventilation days (P = 0.01 and P = 0.03, respectively), but not to the use of postnatal corticosteroids. Conclusion: Poor postnatal growth is significantly negatively associated with a longer duration of mechanical ventilation in extremely prematurely born infants. [ABSTRACT FROM AUTHOR]

Objective: To describe the effect of systemic corticosteroids administered to treat evolving bronchopulmonary dysplasia on oxygen diffusion and ventilation efficiency.Study Design: This was a retrospective cohort study of ventilated infants who received a 9-day course of dexamethasone in a tertiary neonatal unit. We calculated the transcutaneous oxygen saturation-to-fraction of inspired oxygen (FiO2) ratio (SFR), the ventilation perfusion ratio (VA/Q), and the ventilation efficiency index (VEI) before, during, and after the course of corticosteroids. The response to corticosteroids was calculated as the difference between the FiO2 percentage before starting steroids and the lowest FiO2 value during the course of steroid treatment.Results: Seventy infants (38 males) with a median gestational age (GA) of 25.0 weeks (IQR, 24.3-26.0 weeks) and a median birth weight of 0.70 kg (IQR, 0.63-0.82 kg) were studied at a median postnatal age of 39 days (IQR, 29-48 days). The median SFR before treatment was 1.42 (IQR, 1.19-1.72), and the highest SFR was 2.35 (IQR, 1.87-2.83) after 9 days of treatment. The median VA/Q before treatment was 0.14 (IQR, 0.11-0.18) and was significantly higher at 72 hours after the start of treatment (0.22; IQR, 0.15-0.29; P < .001). The median VEI was 0.06 (IQR, 0.04-0.08) before treatment and was highest, 0.10 (IQR, 0.07-0.13) at 48 hours after starting treatment. The median rate of response to corticosteroids was 28% (IQR, 20%-37%). GA was significantly related to the response to corticosteroids (ρ = 0.283; P = .019).Conclusions: Oxygen diffusion continues to improve throughout the entire duration of a 9-day course of systemically administered corticosteroids in ventilated extremely preterm infants. More immature infants are less responsive to corticosteroids. [ABSTRACT FROM AUTHOR]

Heated, humidified, high-flow nasal cannula (HHHFNC) is increasingly being used, but there is a paucity of evidence as to the optimum flow rates in prematurely born infants. We have determined the impact of three flow rates on the work of breathing (WOB) assessed by transcutaneous diaphragm electromyography (EMG) amplitude in infants with respiratory distress or bronchopulmonary dysplasia (BPD). Flow rates of 4, 6 and 8 L/min were delivered in random order. The mean amplitude of the EMG trace and mean area under the EMG curve (AEMGC) were calculated and the occurrence of bradycardias and desaturations recorded. Eighteen infants were studied with a median gestational age of 27.8 (range 23.9-33.5) weeks and postnatal age of 54 (range 3-122) days. The median flow rate prior to the study was 5 (range 3-8) L/min and the fraction of inspired oxygen (FiO2) was 0.29 (range 0.21-0.50). There were no significant differences between the mean amplitude of the diaphragm EMG and the AEGMC and the number of bradycardias or desaturations between the three flow rates.Conclusions: In infants with respiratory distress or BPD, there was no advantage of using high (8 L/min) compared with lower flow rates (4 or 6 L/min) during support by HHHFNC. What is known: • Humidified high flow nasal cannulae (HHHFNC) is increasingly being used as a non-invasive form of respiratory support for prematurely born infants. • There is a paucity of evidence regarding the optimum flow rate with 1 to 8 L/min being used. What is new: • We have assessed the work of breathing using the amplitude of the electromyogram of the diaphragm at three HHHFNC flow rates in infants with respiratory distress or BPD. • No significant differences were found in the EMG amplitude results or the numbers of bradycardias or desaturations at 4, 6 and 8 L/min. [ABSTRACT FROM AUTHOR]

Purpose: To compare the outcomes of infants with a right (RCDH) versus a left-sided (LCDH) congenital diaphragmatic hernia (CDH) and whether these differed according to whether the infants had undergone fetoscopic tracheal occlusion (FETO).Methods: Demographics, the type of surgical repair, preoperative and postoperative courses and respiratory, gastrointestinal, surgical and skeletal morbidities at follow-up were compared between infants with a RCDH or LCDH. A sub-analysis was undertaken in those who had undergone FETO.Results: During the study period, there were 167 infants with a LCDH and 24 with a RCDH; 106 underwent FETO (15 RCDH). Overall, the need for inhaled nitric oxide (p = 0.036) was higher in the RCDH group and, at follow-up, infants with RCDH were more likely to have a hernia recurrence (p = 0.043), pectus deformity (p = 0.019), scoliosis (p = 0.029) and suffer chronic respiratory morbidity (p = 0.001). There were, however, no significant differences in short term or long term outcomes (hernia recurrence (p = 0.237), pectus deformity (p = 0.322), scoliosis (p = 0.0174) or chronic respiratory morbidity (p = 0.326)) between infants with a right or left sided CDH who had undergone FETO.Conclusion: Overall, infants with a RCDH compared to those with a LCDH had greater long-term morbidity, but not if they had undergone FETO. [ABSTRACT FROM AUTHOR]

Volutrauma is an important factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Our aims were to identify risk factors in the first 24 h for prolonged ventilator dependence and assess volume delivery and carbon dioxide levels in infants with evolving BPD. A retrospective study was undertaken of 41 infants born at less than 32 weeks of gestational age (GA). A higher tidal volume, minute volume and resistance and a lower GA, birth weight and compliance were associated with a significantly higher risk of ventilator dependence at 28 days. The strongest relationships were with birth weight (area under the receiver operating characteristic curve, AUROC = 0.771) and GA (AUROC = 0.813). Tidal volume remained significantly higher after adjusting for GA in those who remained ventilator dependent at 28 days. The 18 who remained ventilator dependent at 28 days had increased mean carbon dioxide (PCO2) levels with increasing age from a mean of 41 mmHg in the first 24 h to 65 mmHg at 28 days PMA (p < 0.001). The increase in PCO2 occurred despite increases in peak inflation pressures (p < 0.001), tidal volumes (p = 0.002) and minute volumes (p < 0.001).Conclusion: These results suggest that initial volutrauma may contribute to the development of chronic ventilator dependence. What is Known: • In prematurely born infants, excessive tidal volumes are important in the pathogenesis of bronchopulmonary dysplasia (BPD), but a tidal volume that is too low will increase the risk of atelectasis, work of breathing and energy expenditure. What is New: • A high tidal volume in the first 24 h was associated with an increased risk of ventilator dependence at 28 days, which remained significant after adjusting for gestational age. Carbon dioxide levels significantly increased over the first month despite increased pressures and volumes in those who remained ventilator dependent. [ABSTRACT FROM AUTHOR]

BACKGROUND: CPAP improves respiratory function in prematurely born infants by establishing and maintaining functional residual capacity, but the level of CPAP that optimizes respiratory function has not been adequately described. We compared ventilation efficiency and respiratory muscle function at different levels of CPAP. METHODS: We studied spontaneously breathing, intubated convalescent premature infants at King's College Hospital NHS Foundation Trust and calculated the ventilation efficiency index and the respiratory muscle time constant of relaxation (τ) at the end of 3 consecutive 5-min periods at 4, 6, and 8 cm H2O of CPAP delivered in random order. RESULTS: Between February 2016 and August 2016, 38 infants with a median gestational age of 27 (interquartile range [IQR], 25-30) weeks and a median birthweight of 0.88 (IQR, 0.73-1.02) kg were studied. At a CPAP level of 6 cm H2O, the median ventilation efficiency index was higher (1.52 [IQR, 1.02-2.27]) and median τ was lower (15.6 [IQR, 10.1-21.3]) s/cm H2O] compared with the median ventilation efficiency index (0.75 [IQR, 0.56 -1.03]) and median τ (23.3 [IQR, 15.4-35.2] sec/cm H2O) at CPAP of 4 cm H2O (P < .001 for both). At a CPAP level of 8 cm H2O, median ventilation efficiency index was significantly lower (1.27 [IQR, 1.04 -1.91]) and median τ was not significantly different (11.2 [IQR, 8.3-18.9] s/cm H2O) compared with ventilation efficiency index and τ at CPAP of 6 cm H2O (P < .001 and P = .12, respectively). After multiple logistic regression, the level of CPAP was independently associated with the ventilation efficiency index (adjusted P < .001) and τ (adjusted P = .003). CONCLUSIONS: Increasing the level of CPAP from 4 to 6 cm H2O was associated with enhanced ventilation efficiency and respiratory muscle function in convalescent premature infants on ventilation, but there was no further benefit from increasing the pressure >6 cm H2O. [ABSTRACT FROM AUTHOR]

Background: Hypoglycaemia accounts for approximately one-tenth of term admissions to neonatal units can cause long-term neurodevelopmental impairment and is associated with the significant burden to the affected infants, families and the health system.Objective: To define the prevalence, length and cost of admissions for hypoglycaemia in infants born at greater than 35 weeks gestation and to identify antenatal and perinatal predictors of those outcomes.Materials and Methods: This was a retrospective audit of infants admitted for hypoglycaemia between 1 January 2012 and 31 December 2015, in a level three neonatal intensive care unit at King's College Hospital NHS Foundation Trust, London. The main outcome measures were the prevalence, length and cost of admissions for hypoglycaemia and antenatal and postnatal predictors of the length and cost of the stay.Results: There were 474 admissions for hypoglycaemia (17.8% of total admissions). Their median (IQR) blood glucose on admission was 2.1 (1.7-2.4) mmol/l, gestation at delivery 38.1 (36.7-39.3) weeks, birthweight percentile 31.4 (5.4-68.9), their length of stay was 3.0 (2.0-5.0). Admissions equated to a total of 2107 hospital days. The total cost of the stay was 1,316,591 Great Britain pound. The antenatal factors associated with admission for hypoglycaemia were maternal hypertension (19.8%), maternal diabetes (24.5%), foetal growth restriction (FGR) (25.9%) and pathological intrapartum cardiotocograph (23.4%). In 13.7% of cases, there was no associated pregnancy complication. Multivariate logistic regression analysis demonstrated lower gestational age, z-score birthweight squared, exclusive breastfeeding and maternal prescribed nifedipine were independently associated with the length and cost of the stay.Conclusion: Hypoglycaemia accounted for approximately one-fifth of admissions after 35-week gestation. Lower gestational age and admission blood glucose, low and high z-score birthweight, maternal nifedipine and exclusive breastfeeding are associated with longer duration of stay. [ABSTRACT FROM AUTHOR]

Aim: To determine how oxygenation, ventilation efficiency and tidal volume requirements changed with the development of pulmonary interstitial emphysema (PIE) and whether in affected patients a composite gas exchange index predicted death or bronchopulmonary dysplasia (BPD).Methods: Infants who developed PIE from 2010 to 2016 were identified. The oxygenation index (OI), ventilation efficiency index (VEI), ventilation to perfusion ratio and inspiratory tidal volume were calculated before radiological evidence of PIE (pre-PIE) and at the worst PIE radiographic appearance (PIE-worst).Results: Thirty infants, median (IQR) gestational age of 24.6 (24.3-26.7) weeks were assessed. Their age at pre-PIE was 11 (6-19) days and 23 (13-42) days at PIE-worst. Compared to pre-PIE, at PIE-worst, the OI was higher [14.5 (10.7-19.2) vs 4.8 (3.1-6.1), respectively, p < 0.001], VEI was lower [0.01 (0.01-0.11) vs 0.16 (0.13-0.19), respectively, p < 0.001], ventilation to perfusion ratio was lower [0.15 (0.11-0.40) vs 0.26 (0.20-0.37), p = 0.033] and tidal volume was higher [9.9 (7.2-13.1) vs 6.4 (5.5-6.8) mL/kg, p = 0.007]. An OI >11.4 at PIE-worst predicted death or BPD with 80% sensitivity and 100% specificity.Conclusion: Development of PIE was associated with poorer oxygenation and ventilation efficiency despite increased tidal volumes. The OI at PIE-worst predicted death or BPD. [ABSTRACT FROM AUTHOR]

Objective: To explore whether the average price of houses per postcode sector [sector house average prices (SHAP)] is related to perinatal outcomes and whether gestational age would be lower and mortality higher in the least expensive areas compared to the most expensive. Methods: All neonatal unit admissions at King's College Hospital from 1/1/2012 to 31/12/2016 were reviewed. The SHAP was retrieved from the Land Registry and the population was divided in equal quintiles with quintiles 1 and 5 representing the most and least expensive areas, respectively. Gestational age and birth weight z-score were collected. Mortality was defined as death before discharge from neonatal care. Results: Three thousand three hundred and sixty infants were included and divided in quintiles consisting of 672 infants. Gestational age was lower in quintile 5 compared to all other quintiles (adjusted P<0.001). Birthweight z-score was not significantly different between the quintiles. The SHAP was lower in the infants who died before discharge (n=92) compared to the SHAP of the infants who were alive at discharge (n=3268) (P<0.001). Infants of quintile 5 had 6 times higher risk of death before discharge from neonatal care compared to infants of quintile 1. Conclusion: Low SHAPs were associated with poorer perinatal outcomes suggesting SHAP could potentially be used in perinatal populations to determine socio-economic status and associated outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To assess the work of breathing at different levels of volume targeting in prematurely born infants with evolving or established bronchopulmonary dysplasia (BPD).Design: Randomised crossover study.Setting: Tertiary neonatal intensive care unit.Patients: Eighteen infants born at <32 weeks gestation who remained ventilated at or beyond 1 week after birth, that is, they had evolving or established BPD.Interventions: Infants received ventilation at volume targeting levels of 4, 5, 6 and 7 mL/kg each for 20 minutes, the levels were delivered in random order. Baseline ventilation (without volume targeting) was delivered for 20 minutes between each epoch of volume-targeting.Main Outcome Measures: Pressure-time product of the diaphragm (PTPdi), a measure of the work of breathing, at different levels of volume targeting.Results: The 18 infants had a median gestational age of 26 (range 24-30) weeks and were studied at a median of 18 (range 7-60) days. The mean PTPdi was higher at 4 mL/kg than at baseline, 5 mL/kg, 6 mL/kg and 7 mL/kg (all P≤0.001). The mean PTPdi was higher at 5 mL/kg than at 6 mL/kg (P=0.008) and 7 mL/kg (P<0.001) and higher at 6 mL/kg than 7 mL/kg (P=0.003). Only at 7 mL/kg was the PTPdi significantly lower than at baseline (P=0.001).Conclusions: Only a tidal volume target of 7 mL/kg reduced the work of breathing below the baseline and may be more appropriate for infants with evolving or established BPD who remained ventilator dependent at or beyond 7 days of age. [ABSTRACT FROM AUTHOR]

Admission to neonatal care causes separation of infants from their parents, can adversely affect breast-feeding and is associated with painful procedures. Our aim was to identify perinatal factors and cost of care associated with transient neonatal hyperinsulinaemic hypoglycaemia (HH). Infants born after 35 weeks of gestation admitted because of hypoglycaemia were studied. The neonates were divided into two groups (HH and non-HH), and their length and cost of care were compared and perinatal factors predicting those outcomes explored. Forty of the 474 infants admitted with hypoglycaemia were diagnosed with HH. The HH group had a lower median (IQR) glucose level on admission compared to the non-HH group (p < 0.001). The median (IQR) cost of stay was higher in the HH group (p < 0.001). In the HH group, the GIRmax was significantly correlated with cost of stay (p < 0.001). GIRmax predicted a cost of stay > £9140 with an area under the ROC curve of 0.956. GIRmax > 13.9 mg/kg/min predicted admission cost > £9140 with 86% sensitivity and 93% specificity.Conclusion: Transient neonatal HH was associated with a higher length and cost of stay in infants admitted for hypoglycaemia. The GIRmax can predict the length and cost of stay. What is Known: • Neonatal hypoglycaemia is the leading cause of term and late preterm neonatal admissions. • Hyperinsulinism (HH) is the commonest cause of persistent hypoglycaemia, and delay in the diagnosis and management can have a detrimental impact on long-term development. What is New: • We have demonstrated prior to NICU admission that blood glucose concentrations were lower in infants with HH compared to those without. • The maximum GIR had a stronger correlation with total length and cost of hospital stay compared to insulin levels in HH infants. [ABSTRACT FROM AUTHOR]

Conventionally, the alveolar surface area (S A ) has been measured by using post-mortem morphometry. Such studies have highlighted that S A in prematurely-born infants is markedly smaller when compared to term-born infants as a result of postnatal impairment or arrest of alveolar development. We herein explore how, non-invasive measurements of the ventilation/perfusion ratio (V A /Q) can be used to estimate S A in prematurely-born surviving, convalescent infants. We also compare S A in prematurely-born infants measured at term-corrected age, to term-born infants using previously published datasets of V A /Q. Fick’s first law of diffusion is employed for the conversion of V A /Q measurements to S A values after correcting for differences in pulmonary perfusion, thickness of the respiratory membrane and alveolar-arterial gradient. We report that S A is fivefold smaller in prematurely-born compared to term-born infants. We conclude that non-invasive measurements of V A /Q can be used for the functional estimation of S A which could, in turn, be used as a future outcome measure in respiratory studies of prematurely-born infants. [ABSTRACT FROM AUTHOR]

Aim: To assess the respiratory muscle time constant of relaxation (τ), an index of respiratory muscle function in ventilated newborns.Methods: Sixty-two infants (42 born prematurely) with a median gestational age of 29 [interquartile range (IQR) 26-37] weeks were prospectively studied. Measurement of τ was taken during spontaneous breathing on endotracheal continuous positive airway pressure prior to extubation, and τ was calculated from the reciprocal of the slope of the airway pressure decline versus time. Infants were classified as having had systemic or respiratory infection (positive microbiology) if they had any positive bacterial blood or respiratory culture prior to measurement.Results: Measurement of τ was taken at a median post-natal age of 6 (IQR 3-29) days. The median τ was higher in premature infants [17.4 (IQR 7.7-28.3) sec/cmH2 O] compared to term infants [6.8 (IQR 4.4-8.7) sec/cmH2 O, p < 0.001]. The median τ was higher in infants who had had positive microbiology [17.6 (IQR 9.9-29.1) sec/cmH2 O] compared to infants with negative microbiology [8.0 (IQR 6.3-17.9) sec/cmH2 O, p = 0.034]. τ was related to gestational age (r = -0.265, p = 0.003) and weight at measurement (r = -0.269, p = 0.002).Conclusion: Respiratory muscle function in ventilated newborns is negatively affected by prematurity and previous systemic or respiratory infection. [ABSTRACT FROM AUTHOR]