Temporal effects of caffeine on intrapulmonary shunt in preterm ventilated infants.

OBJECTIVES: We hypothesized that caffeine would be associated with a transient reduction in the right-to-left shunt and VA/Q. We aimed to explore the temporal effects of caffeine on right-to-left shunt, ventilation perfusion ratio (VA/Q) and shift of the oxyhaemoglobin dissociation curve (ODC) in premature ventilated infants. METHODS: Retrospective cohort study at a tertiary neonatal unit of infants born at less than 31 weeks of gestation that were mechanically ventilated on day three of life. The non-invasive method of the ODC was used to determine the right-to-left shunt, VA/Q and shift before and at 1, 4 and 20 h after a maintenance dose of caffeine citrate. RESULTS: A total of 21 infants were included with a median (range) gestational age of 27 (23.7-30.7) weeks. The median shunt percentage was significantly reduced, compared to baseline at 1 h (8 (range: 7-9) % vs. 4 (range: 0-6) %, p=0.042) and 4 h post caffeine administration (8 (range: 7-9) % vs. 0 (range: 0-3) %, p=0.042), but the VA/Q and the right shift of the ODC did not differ significantly between these time points. At 20 h, there were no significant differences between these indices compared to baseline values. CONCLUSIONS: Caffeine led to a transient decrease in intrapulmonary shunt from one to 4 h after administration and this may be due to its diuretic action.

Ventilatory response to added dead space in infants exposed to second-hand smoke in pregnancy.

Maternal cigarette smoking in pregnancy can adversely affect infant respiratory control. In utero nicotine exposure has been shown to blunt the infant ventilatory response to hypercapnia, which could increase the risk of sudden infant death syndrome. The potential impact of maternal second-hand smoke exposure, however, has not yet been determined. The aim of this study was to assess ventilatory response to added dead-space (inducing hypercapnia) in infants with second-hand smoke exposure during pregnancy, in infants whose mothers smoked and in controls (non-smoke exposed). Infants breathed through a face mask and specialised "tube-breathing" circuit, incorporating a dead space of 4.4 ml/kg body weight. The maximum minute ventilation (MMV) during added dead space breathing was determined and the time taken to achieve 63% of the MMV calculated (the time constant (TC) of the response). Infants were studied on the postnatal ward prior to discharge home. Thirty infants (ten in each group) were studied with a median gestational age of 39 [range 37-41] weeks, birthweight of 3.1 [2.2-4.0] kg, and postnatal age of 33 (21-62) h. The infants whose mothers had second-hand smoke exposure (median TC 42 s, p = 0.001), and the infants of cigarette smoking mothers (median TC 37 s, p = 0.002) had longer time constants than the controls (median TC 29 s). There was no significant difference between the TC of the infants whose mothers had second-hand smoke exposure and those whose mothers smoked (p = 0.112).    Conclusion: Second-hand smoke exposure during pregnancy was associated with a delayed newborn ventilatory response. What is Known: • Maternal cigarette smoking in pregnancy can adversely affect infant respiratory control. • The potential impact of maternal second-hand smoke exposure, however, has not yet been determined. What is New: • We have assessed the ventilatory response to added dead-space (inducing hypercapnia) in newborns with second-hand smoke exposure during pregnancy, in infants whose mothers smoked, and in controls (non-smoke exposed). • Maternal second-hand smoke exposure, as well as maternal smoking, during pregnancy was associated with a delayed newborn ventilatory response.

Closed-loop automated oxygen control in ventilated infants born at or near term: A crossover trial.

AIM: To determine if the use of closed-loop automated oxygen control (CLAC) reduced the incidence and duration of hypoxemic episodes (SpO2  < 92%) in ventilated infants born at or above 34 weeks of gestation. METHODS: Infants were studied on two consecutive days for 6 h each day. They were randomised to receive standard care (manual oxygen control) or standard care with a CLAC system (automated oxygen control) first. RESULTS: Sixteen infants with a median (IQR) gestational age of 37.4 (36.6-38.8) weeks were studied at a median (IQR) postmenstrual age of 38.8 (37.4-39.8) weeks. During the automated oxygen control period, infants spent less time in hypoxemia (SpO2  < 92%) (p = 0.033), episodes of desaturation were shorter (p = 0.001), the time spent within target SpO2 range (92%-96%) was increased (p = 0.001), and the FiO2 delivery was lower (p = 0.018). The time spent in hyperoxemia (SpO2  > 96%) was reduced during automated oxygen control (p = 0.011), the episodes of hyperoxemia were of shorter duration (p = 0.008) and fewer manual adjustments were made to the FiO2 (p = 0.005). CONCLUSIONS: Closed-loop automated oxygen control in ventilated infants born at or near term was associated with a reduction in the incidence and duration of hypoxemic episodes with more time spent in the target oxygen range.

Postnatal corticosteroid usage in United Kingdom and Ireland neonatal units.

AIM: To perform a survey on postnatal corticosteroids usage in neonatal units in the United Kingdom and Ireland. METHODS: An 18-item structured questionnaire was created asking for the level of neonatal care and corticosteroid prescribing practices. A consultant neonatologist or senor specialty training registrar/advanced neonatal nurse practitioner was contacted in every neonatal unit in the UK and Ireland between September and December 2022. RESULTS: The response rate to the survey was 96% (203 of 211 units). Postnatal corticosteroids were prescribed in 48% of units: 5% of special care units, 43% of local neonatal units and 100% of neonatal intensive care units. Most units (90%) prescribed dexamethasone, which was prescribed to infants born at gestational ages less than 30 weeks in all those units prescribing postnatal corticosteroids, however, eight units also reported use in infants greater than 30 weeks of gestation. Dexamethasone regimens varied with starting doses from 50 to 500 µg/kg/day. Most tertiary units (97%) prescribed repeated courses of dexamethasone. In all levels of neonatal care, postnatal corticosteroids were prescribed to ventilated infants as well as those receiving non-invasive respiratory support. CONCLUSION: There is use of postnatal corticosteroids in all levels of neonatal care and much of the practice is not evidence based.

Closed-loop oxygen system in late preterm/term, ventilated infants with different severities of respiratory disease.

AIM: To evaluate closed-loop automated oxygen control (CLAC) in ventilated infants >33 weeks of gestation with different respiratory disease severities. METHODS: Infants were studied on two consecutive days for 6 h each day. They were randomised to receive standard care or standard care with CLAC (Oxygenie) first. Analyses were performed of the results of infants with or without an FiO2 ≥ 0.3 and infants with congenital diaphragmatic hernia (CDH). RESULTS: Thirty-one infants with a median (IQR) gestational age of 37.9 (37.1-38.9) weeks were studied at a median postmenstrual age (IQR) of 38.9 (37.4-39.8) weeks. In infants with an FiO2 ≥ 0.3 (n = 8), CLAC increased the time spent in target oxygen range (92-96%) by 61.6% (p = 0.018), whereas in infants with an FiO2 < 0.3, the time in target was increased by 3.8% (p = 0.019). During CLAC, only infants with an FiO2 ≥ 0.3 spent less time in hyperoxemia (SpO2 > 96%) (p = 0.012) and hyperoxemic episodes were shorter (p = 0.012). In both groups, CLAC reduced the duration of desaturations (SpO2 < 92%, p < 0.001). In CDH infants, CLAC increased the time spent in target oxygen range by 34% (p = 0.036) and the median duration of desaturations was reduced (p = 0.028). CONCLUSION: CLAC may be more useful in infants with more severe respiratory distress.

Systematic review of the long-term effects of postnatal corticosteroids.

BACKGROUND: Dexamethasone administration can reduce bronchopulmonary dysplasia, our objective was to identify long term adverse effects. CONTENT: A systematic review was performed to determine the childhood and adolescent cardiopulmonary and cognitive effects of dexamethasone systemically administered to preterm infants during neonatal intensive care. Relevant studies were identified by searching two electronic health databases and the grey literature. Spirometry assessments were used as respiratory outcomes, blood pressure and echocardiography assessments as cardiovascular outcomes and cognitive and motor function as cognitive outcomes. From 1,479 articles initially identified, 18 studies (overall 1,609 patients) were included (respiratory n=8, cardiovascular n=2, cognitive n=10); all were observational cohort studies. Dexamethasone exposure was associated with worse pulmonary outcomes in children and adolescents (more abnormal FVC and FEV1:FVC z scores). Dexamethasone exposure was associated in one study with lower IQ scores compared to preterm controls (mean 78.2 [SD 15.0] vs. 84.4 [12.6], [p=0.008]) and in two others was associated with lower total and performance IQ when compared to term controls (p<0.001). SUMMARY AND OUTLOOK: Postnatal dexamethasone exposure has a negative influence on pulmonary and cognitive outcomes in childhood and adolescence. Medications with a better benefit to risk profile need to be identified.

Chronology and Determinants of Respiratory Function Changes Following Administration of Systemic Postnatal Corticosteroids in Extremely Preterm Infants.

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.

Deltoid muscle morphometry as an index of impaired skeletal muscularity in neonatal intensive care.

We hypothesised that extremely premature infants would have decreased muscle mass at term-corrected age compared to term-born infants and that the degree of reduced muscle mass acquisition would correlate with the duration of invasive mechanical ventilation. The MRI brain scans of infants admitted in the neonatal unit at King's College Hospital between 1 January 2010 and 1 June 2016 were retrospectively reviewed. The coronal cross-sectional area of the left deltoid muscle (DCSA) was measured in 17 infants born < 28 weeks of gestation and in 20 infants born at term. The prematurely born infants had a median (IQR) gestation age of 25 weeks (24-27) and the term infants 40 weeks (38-41). The duration of invasive mechanical ventilation for the prematurely born infants was 39 days (14-62) and that for the term infants 4 days (2-5), p < 0.001. DCSA was smaller in prematurely born infants (median 189, IQR 176-223 mm2) compared to term-born infants (median 302, IQR 236-389 mm2), p < 0.001. DCSA was related to gestation age (r = 0.545, p = 0.001), weight z-score at MRI (r = 0.658, p < 0.001) and days of invasive mechanical ventilation (r = - 0.583, p < 0.001). In conclusion, extremely premature infants studied at term had a lower muscle mass compared to term-born infants. CONCLUSION: Our results suggest that prolonged mechanical ventilation in infants admitted in neonatal intensive care is associated with reduced skeletal muscle mass acquisition. What is Known: • Prolonged mechanical ventilation in adult intensive care patients has been associated with skeletal muscle dysfunction and atrophy. • The cross-sectional area of the deltoid muscle has been used to evaluate muscle atrophy in infants with a previous branchial plexus birth injury. What is New: • Premature infants studied at term exhibit lower cross-sectional area of the deltoid muscle than their term counterparts. • Prolonged mechanical ventilation could be associated with skeletal muscle impairment.

Effect of maturity and infection on the rate of relaxation of the respiratory muscles in ventilated, newborn infants.

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.

Neonatal respiratory support strategies-short and long-term respiratory outcomes.

Mechanical ventilation (MV), although life-saving, is associated with chronic respiratory morbidity in both preterm and term born infants. New ventilation modes have been developed with the aim of minimising lung injury. These include invasive and non-invasive respiratory support strategies, techniques for less invasive surfactant administration (LISA) and closed-loop automated oxygen control (CLAC) systems. Increasingly, newborn infants with signs of respiratory distress are stabilised on continuous positive airway pressure (CPAP) and receive LISA. Early CPAP when compared to mechanical ventilation reduced the incidence of BPD and respiratory morbidity at 18 to 22 months corrected age. Nasal intermittent positive pressure ventilation reduced treatment failure rates compared to CPAP, but not bronchopulmonary dysplasia (BPD). LISA compared with intubation and surfactant delivery reduced BPD, but there is no evidence from randomised trials regarding long-term respiratory and neurodevelopmental outcomes. Synchronisation of positive pressure inflations with the infant's respiratory efforts used with volume targeting should be applied for infants requiring intubation as this strategy reduces BPD. A large RCT with long term follow up data demonstrated that prophylactic high frequency oscillatory ventilation (HFOV) improved respiratory and functional outcomes at school age, but those effects were not maintained after puberty. CLAC systems appear promising, but their effect on long term clinical outcomes has not yet been explored in randomised trials. Further studies are required to determine the role of newer ventilation modes such as neurally adjusted ventilator assist (NAVA). All such respiratory support strategies should be tested in randomised controlled trials powered to assess long-term outcomes.

Does closed-loop automated oxygen control reduce the duration of supplementary oxygen treatment and the amount of time spent in hyperoxia? A randomised controlled trial in ventilated infants born at or near term.

BACKGROUND: Ventilated infants frequently require supplemental oxygen, but its use should be monitored carefully due to associated complications. The achievement of oxygen saturation (SpO2) targets can be challenging as neonates experience frequent fluctuations of their oxygen levels that further increase the risk of complications. Closed-loop automated oxygen control systems (CLAC) improve achievement of oxygen saturation targets, reduce hyperoxaemic episodes and facilitate weaning of the inspired oxygen concentration in ventilated infants born at or near term. This study investigates whether CLAC compared with manual oxygen control reduces the time spent in hyperoxia and the overall duration of supplemental oxygen treatment in ventilated infants born at or above 34 weeks gestation. METHODS: This randomised controlled trial performed at a single tertiary neonatal unit is recruiting 40 infants born at or above 34 weeks of gestation and within 24 h of initiation of mechanical ventilation. Infants are randomised to CLAC or manual oxygen control from recruitment till successful extubation. The primary outcome is the percentage of time spent in hyperoxia (SpO2 > 96%). The secondary outcomes are the overall duration of supplementary oxygen treatment, the percentage of time spent with an oxygen requirement above thirty per cent, the number of days on mechanical ventilation and the length of neonatal unit stay. The study is performed following informed parental consent and was approved by the West Midlands-Edgbaston Research Ethics Committee (Protocol version 1.2, 10/11/2022). DISCUSSION: This trial will investigate the effect of CLAC on the overall duration of oxygen therapy and the time spent in hyperoxia. These are important clinical outcomes as hyperoxic injury is related to oxidative stress that can adversely affect multiple organ systems. TRIAL REGISTRATION: ClinicalTrials.Gov NCT05657795. Registered on 12/12/2022.

A neonatal in-vitro study on the effect of the inflation pressure on end-tidal carbon dioxide levels.

BACKGROUND: Describing the association of the peak inflation pressure (PIP) with end-tidal carbon dioxide (ETCO2) is a prerequisite for the development of closed loop ventilation in neonatal intensive care. We aimed to develop an in-vitro system to study this relationship. METHODS: A ventilator was connected to a test lung, supplied with a stable CO2 concentration from a cylinder. The PIP was altered and the change in ETCO2 per unit of PIP was calculated in three models mimicking respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD) and viral bronchiolitis. RESULTS: The median (IQR) change in ETCO2 per unit of PIP was 0.23(0.13-0.38) kPa/cmH2O, using 138 paired measurements of PIP and ETCO2. The median (IQR) change in ETCO2 per unit of PIP, was higher when starting at an ETCO2 > 6 kPa [0.43(0.33-0.58) kPa/cmH2O] compared to starting at an ETCO2 < 6 kPa [0.14(0.08-0.20) kPa/cmH2O, p < 0.001]. The median (IQR) change in ETCO2 per unit of PIP, was larger in the model of RDS [0.33(0.13-0.51) kPa/cmH2O] compared to the BPD [0.23(0.13-0.33) kPa/cmH2O, p = 0.043] and the bronchiolitis models [0.15(0.10-0.31) kPa/cmH2O, p = 0.017]. CONCLUSIONS: The change in ETCO2 in response to increasing PIP was larger for higher ETCO2 values and in a model simulating neonatal RDS, compared to BPD and bronchiolitis.

Permissive hypercapnia and oxygenation impairment in premature ventilated infants.

AIM: In permissive hypercapnia high levels of carbon dioxide (CO2) are tolerated in ventilated preterm infants to minimise lung injury, but hypercapnia could directly impair oxygenation. We aimed to quantify the association of elevated CO2 with oxygenation impairment in preterm infants by measuring the right-to-left shunt and the ventilation/perfusion (VA/Q) ratio. METHODS: Pre-existing datasets from preterm infants during the acute phase of respiratory distress syndrome or with evolving or established bronchopulmonary dysplasia were analysed. Non-invasive paired measurements of the fraction of inspired oxygen (FIO2) and transcutaneous oxygen saturation (SpO2) were used to calculate the degree of right-to-left shunt, right shift of the FIO2 versus SpO2 curve and the VA/Q. RESULTS: A total of 75 infants (43 male) with a median (IQR) gestational age of 26.4 (24.7-27.7) weeks were studied at 7 (2-31) days. Thirty-six infants (48 %) had an arterial partial pressure of CO2 (PaCO2) above 6 kPa. The PaCO2 was independently associated with the right shift of the curve [adjusted p < 0.001, unstandardised coefficient; 2.26, 95 % CI: 1.51-2.95] and the right-to-left shunt [adjusted p = 0.016, unstandardised coefficient; 1.86, 95 % CI: 0.36-3.36] after adjusting for confounders. An increase of the PaCO2 from 5 to 8 kPa, corresponded to a right shift of the curve of 20.2 kPa or a decrease in the VA/Q from 0.66 to 0.24. CONCLUSIONS: Increased carbon dioxide levels were significantly associated with impaired oxygenation in preterm infants with respiratory distress syndrome or bronchopulmonary dysplasia.

Race, hypoxaemia and oxidative stress in prematurely-born infants.

BACKGROUND: Disparities in neonatal respiratory outcomes in prematurely-born infants might be partially explained by racial differences and the relationship of hypoxia and oxidative stress. AIMS: To determine if Black, preterm infants were exposed more frequently to hypoxaemia compared to White infants and had a higher level of oxidative damage. STUDY DESIGN: Single-centre retrospective cohort study at King's College Hospital, London, UK between 2018 and 2021. SUBJECTS: Infants born before 32 completed weeks of gestational age. OUTCOME MEASURES: The median arterial oxygen saturation (SaO2) over the first seven days was measured. The maximum carboxyhaemoglobin (COHb) level for the first three days was also recorded as an index of oxidative stress. RESULTS: Two thousand and sixty blood gases from 87 infants (38 Black) with a median (IQR) gestational age of 26.4 (24.6-28.3) weeks were analysed. The median (IQR) SaO2 was not significantly different in Black [96.1 (95.2-96.8) %] compared to White infants [96.7 (95.6-97.7) %, p = 0.24]. The median (IQR) COHb was not significantly different in Black infants [1.9 (1.7-2.4) %] compared to White infants [1.9 (1.7-2.3) %, p = 0.77]. The highest COHb was significantly related to the median SaO2 in all infants (r = -0.51, p < 0.001) and separately in Black (r = -0.50, p = 0.002) and White (r = -0.56, p < 0.001) infants. CONCLUSIONS: Preterm, Black infants were not exposed more frequently to hypoxaemia compared to White infants. Lower saturation levels were associated with higher maximum carboxyhaemoglobin levels indicating a higher risk of oxidative stress, irrespective of racial background.

Second course of systemic dexamethasone: efficacy and respiratory function changes.

BACKGROUND: There is a paucity of data concerning the efficacy of a second course of systemic postnatal corticosteroids resulting in a successful extubation of prematurely-born, ventilated infants and its effect on their respiratory function. OBJECTIVES: To determine the efficacy of a second course of systemic dexamethasone in successful extubation of prematurely-born infants and to describe the respiratory function changes that occur following the administration of the second course. METHODS: Retrospective cohort study of ventilated infants less than 30 weeks of gestation who received a nine-day second course of intravenous dexamethasone in a tertiary neonatal unit. Extubation was deemed successful if the infants were not re-intubated within 72 h of the extubation attempt. We calculated the ventilation perfusion ratio (VA/Q) and the fraction of required oxygen (FIO2) requirement expressed as a percentage before and after the course. RESULTS: Fifteen (10 male) infants with a median (IQR) gestational age (GA) of 25.7 (24.7-26.6) weeks and a birth weight of 0.79 (0.67-0.93) kg were studied at a postnatal age of 60 (48-73) days. Fourteen of fifteen infants (93%) were successfully extubated. The VA/Q before the course was 0.13 (0.11-0.16) and significantly higher at 72 h after starting the course [0.26 (0.19-0.36), p = 0.001]. The FIO2 requirement decreased from 0.70 (0.59-0.79) to 0.34 (0.28-0.52) nine days after starting the course (p < .001). CONCLUSIONS: A second course of systemic dexamethasone appears efficient in weaning premature infants off invasive ventilation and is associated with a significant improvement in oxygenation.

Does closed-loop automated oxygen control reduce the duration of mechanical ventilation? A randomised controlled trial in ventilated preterm infants.

BACKGROUND: Many preterm infants require supplemental oxygen in the newborn period but experience frequent fluctuations of their oxygen saturation levels. Intermittent episodes of hypoxia or hyperoxia increase the risk of complications. Compliance with achievement of oxygen saturation targets is variable, and the need for frequent adjustments of the inspired oxygen concentration increases workload. Closed-loop automated oxygen control systems (CLAC) improve achievement of oxygen saturation targets and reduce both episodes of hypoxia and hyperoxia and the number of manual adjustments. This study investigates whether CLAC compared with manual oxygen control reduces the duration of mechanical ventilation in preterm infants born at less than 31 weeks of gestation. METHODS: This randomised controlled trial performed at a single tertiary neonatal unit is recruiting 70 infants born at less than 31 weeks of gestational age and within 48 h of initiation of mechanical ventilation. Infants are randomised to CLAC or manual oxygen control from recruitment until successful extubation. The primary outcome is the duration of mechanical ventilation, and secondary outcomes are the percentage of time spent within target oxygen saturation ranges, the time spent in hypoxia or hyperoxia, the number of manual adjustments required, the number of days on oxygen, the incidence of bronchopulmonary dysplasia and the length and cost of neonatal unit stay. The study is performed following informed parental consent and was approved by the Yorkshire and the Humber-Sheffield Research Ethics Committee (protocol version 1.1, 13 July 2021). DISCUSSION: This trial will investigate the effect of CLAC on the duration of mechanical ventilation, which is an important clinical outcome as prolonged mechanical ventilation is associated with important adverse outcomes, such as bronchopulmonary dysplasia. TRIAL REGISTRATION: ClinicalTrials.Gov NCT05030337 . Registered on 17 August 2021.

Cumulative hypoxia, socioeconomic deprivation and neurodevelopmental outcomes in preterm infants.

BACKGROUND: Hypoxia can adversely affect cognition, while socioeconomic deprivation has also been associated with impaired neurodevelopment in the newborn. We aimed to assess the impact of hypoxia and socioeconomic deprivation on the neurodevelopmental outcomes of preterm infants. METHODS: Retrospective cohort study at a tertiary neonatal unit between 2015 and 2018. The motor, cognitive and language domain scores of the Bayley-III assessment were recorded at 24 months of corrected gestational age. The percentage of time with pulse oximetry (SpO2) < 75% was measured from the nursing records, from admission to 36 weeks postmenstrual age in infants born < 30 weeks gestational age. The multiple deprivation index (MDI) and the main care giver's education domain of the MDI were also recorded. RESULTS: A total of 93,767 data points from 80 infants (34 male) with a median (IQR) gestational age of 27.9(25.9-29.0) weeks and a birth weight of 0.94(0.74-1.23) kg were analysed. The median (IQR) motor score [103(91-110)] was significantly related to the median (IQR) time with SpO2 < 75% [1.5(0.9-3.4)%, adjusted p = 0.020]. The median (IQR) cognitive score [100(90-105)] was negatively significantly related to the time with SpO2 < 75% (adjusted p = 0.012) and the median (IQR) education decile of the MDI [7(6-9), adjusted p = 0.011]. The median (IQR) language score [91(77-100)] was significantly positively related to the education domain of the MDI (adjusted p = 0.025). CONCLUSIONS: Hypoxia in preterm infants exerted a negative impact on motor function and cognition and conversely, higher educational attainment had a positive impact on cognition and language.