Sex differences in preterm respiratory morbidity: A recent whole-population study.

AIM: To determine whether there were differences between male and female infants in respiratory morbidity in a whole population of extremely preterm infants, including infants born below 24 weeks of gestation. METHODS: Retrospective whole-population study of all infants <28 weeks of gestation admitted to a neonatal unit in England from 2014 to 2019. Bronchopulmonary dysplasia (BPD) development was defined as any respiratory support at 36 weeks postmenstrual age. RESULTS: The 11 844 infants had a median (IQR) gestational age of 26.0 (24.9-27.1) weeks and a birth weight of 0.81 (0.67-0.96) kg. The duration of invasive ventilation was longer in male compared to female infants who were born at 24-27 completed weeks of gestation (p < 0.001), but not significantly different between male and female infants born at 22 and 23 weeks of gestation (p = 0.446). The incidence of BPD was higher in male compared to female infants born at 24-27 weeks of gestation (p < 0.001) but not different between male and female infants born at 22 and 23 weeks of gestation (p = 0.148). CONCLUSION: Respiratory morbidity was more pronounced in male compared to female extremely preterms, only in gestations 24-27 completed weeks. Male predominance was absent in infants born below 24 weeks of gestation.

Artificial intelligence in the NICU to predict extubation success in prematurely born infants.

OBJECTIVES: Mechanical ventilation in prematurely born infants, particularly if prolonged, can cause long term complications including bronchopulmonary dysplasia. Timely extubation then is essential, yet predicting its success remains challenging. Artificial intelligence (AI) may provide a potential solution. CONTENT: A narrative review was undertaken to explore AI's role in predicting extubation success in prematurely born infants. Across the 11 studies analysed, the range of reported area under the receiver operator characteristic curve (AUC) for the selected prediction models was between 0.7 and 0.87. Only two studies implemented an external validation procedure. Comparison to the results of clinical predictors was made in two studies. One group reported a logistic regression model that outperformed clinical predictors on decision tree analysis, while another group reported clinical predictors outperformed their artificial neural network model (AUCs: ANN 0.68 vs. clinical predictors 0.86). Amongst the studies there was an heterogenous selection of variables for inclusion in prediction models, as well as variations in definitions of extubation failure. SUMMARY: Although there is potential for AI to enhance extubation success, no model's performance has yet surpassed that of clinical predictors. OUTLOOK: Future studies should incorporate external validation to increase the applicability of the models to clinical settings.

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.

Chest radiographic thoracic areas and respiratory outcomes in infants with anterior abdominal wall defects.

OBJECTIVES: Infants with anterior abdominal wall defects (AWD) can suffer from pulmonary complications. Our aims were to determine if the chest radiographic thoracic areas (CRTAs) on day one differed between infants with exomphalos or gastroschisis, whether this related to differing severity of outcomes and if they were lower than those of controls indicating abnormal antenatal lung growth. METHODS: A review of infants with exomphalos or gastroschisis born between January 2004 and January 2023 was conducted. The control group was term, newborn infants ventilated for poor respiratory drive at birth. Chest radiographs on day one were analysed and the highest CRTA in the first 24 h after birth for each infant included in the analysis. RESULTS: The 127 infants with gastroschisis had a lower gestational age and birthweight than the 62 exomphalos infants and 130 controls (all p<0.001) The CRTAs of the controls were greater than the CRTAs of the exomphalos and the gastroschisis infants (p = 0.001). The median CRTA corrected for birthweight was lower in the exomphalos infants [688, IQR 568-875 mm2/kg] than the gastroschisis infants [813, IQE 695-915 mm2/kg] No gastroschisis infant developed bronchopulmonary dysplasia (BPD). A CRTA of 1759 mm2 had a sensitivity of 81 % and specificity of 71 % in predicting BPD in infants with exomphalos. CONCLUSIONS: Infants with gastroschisis or exomphalos had lower CRTAs than controls suggesting both groups had abnormal antenatal lung development. The CRTA was lower in the exomphalos infants who also had worse respiratory outcomes, hence CRTA assessment may a useful prognostic aid.

Prediction of bronchopulmonary dysplasia by the chest radiographic thoracic area on day one in infants with exomphalos.

OBJECTIVES: To determine if infants with exomphalos had abnormal antenatal lung growth as indicated by lower chest radiographic thoracic areas (CRTA) on day one compared to controls and whether the CRTA could predict the development of bronchopulmonary dysplasia (BPD). METHODS: Infants with exomphalos cared for between January 2004 and January 2023 were included. The controls were term, newborn infants ventilated for absent respiratory drive at birth, without lung disease and had no supplemental oxygen requirement by 6 h of age. The radiographs were imported as digital image files by Sectra PACS software (Sectra AB, Linköping, Sweden). Free-hand tracing of the perimeter of the thoracic area was undertaken and the CRTA calculated by the software. RESULTS: Sixty-four infants with exomphalos and 130 controls were included. Infants with exomphalos had a lower median (IQR) CRTA (1,983 [1,657-2,471] mm2) compared to controls (2,547 [2,153-2,932] mm2, p<0.001). Following multivariable regression analysis, infants with exomphalos had lower CRTAs compared to controls (p=0.001) after adjusting for differences in gestational age and male sex. In the exomphalos group, the CRTAs were lower in those who developed BPD (n=14, 1,530 [1,307-1,941] mm2) compared to those who did not (2,168 [1,865-2,672], p<0.001). Following multivariable regression analysis, the CRTA was associated with BPD development (p=0.021) after adjusting for male sex and gestational age. CONCLUSIONS: Lower CRTAs on day one in the exomphalos infants compared to the controls predicted BPD development.

Monitoring persistent pulmonary hypertension of the newborn using the arterial to end tidal carbon dioxide gradient.

Persistent pulmonary hypertension of the newborn (PPHN) can be monitored theoretically by the difference of the partial pressure of arterial (PaCO2) to end-tidal CO2 (EtCO2). We aimed to test the hypothesis that the PaCO2-EtCO2 gradient in infants with PPHN would be higher compared to infants without PPHN. Prospective, observational study of term-born ventilated infants with echocardiographically-confirmed PPHN with right-to-left shunting and term-born control infants without respiratory disease. The PaCO2-EtCO2 gradient was calculated as the difference between the PaCO2 measured from indwelling arterial sample lines and EtCO2 measured by continuous Microstream sidestream capnography. Twenty infants (9 with PPHN and 11 controls) were studied with a median (IQR) gestational age of 39.5 (38.7-40.4) weeks, a birthweight of 3.56 (3.15-3.93) kg and a birthweight z-score of 0.03 (- 0.91 to 1.08). The PaCO2-EtCO2 gradient was larger in the infants with PPHN compared to those without PPHN after adjusting for differences in the mean airway pressure and fraction of inspired oxygen (adjusted p = 0.037). In the infants with PPHN the median PaCO2-EtCO2 gradient decreased from 10.7 mmHg during the acute illness to 3.3 mmHg pre-extubation. The median difference in the gradient was significantly higher in infants with PPHN (6.2 mmHg) compared to infants without PPHN (-3.2 mmHg, p = 0.022). The PaCO2-EtCO2 gradient was higher in infants with PPHN compared to term born infants without PPHN and decreased over the first week of life in infants with PPHN. The gradient might be utilised to monitor the evolution and resolution of PPHN.

Functional morphometry: non-invasive estimation of the alveolar surface area in extremely preterm infants.

BACKGROUND: The main pathophysiologic characteristic of chronic respiratory disease following extremely premature birth is arrested alveolar growth, which translates to a smaller alveolar surface area (SA). We aimed to use non-invasive measurements to estimate the SA in extremely preterm infants. METHODS: Paired measurements of the fraction of inspired oxygen and transcutaneous oxygen saturation were used to calculate the ventilation/perfusion ratio, which was translated to SA using Fick's law of diffusion. The SA was then adjusted using volumetric capnography. RESULTS: Thirty infants with a median (range) gestational age of 26.3 (22.9-27.9) weeks were studied. The median (range) adjusted SA was 647.9 (316.4-902.7) cm2. The adjusted SA was lower in the infants who required home oxygen [637.7 (323.5-837.5) cm2] compared to those who did not [799.1 (444.2-902.7) cm2, p = 0.016]. In predicting the need for supplemental home oxygen, the adjusted SA had an area under the receiver operator characteristic curve of 0.815 (p = 0.017). An adjusted SA ≥688.6 cm2 had 86% sensitivity and 77% specificity in predicting the need for supplemental home oxygen. CONCLUSIONS: The alveolar surface area can be estimated non-invasively in extremely preterm infants. The adjusted alveolar surface area has the potential to predict the subsequent need for discharge home on supplemental oxygen. IMPACT: We describe a novel biomarker of respiratory disease following extremely preterm birth. The adjusted alveolar surface area index was derived by non-invasive measurements of the ventilation/perfusion ratio and adjusted by concurrent measurements of volumetric capnography. The adjusted alveolar surface area was markedly reduced in extremely preterm infants studied at 7 days of life and could predict the need for discharge home on supplemental oxygen. This method could be used at the bedside to estimate the alveolar surface area and provide an index of the severity of lung disease, and assist in monitoring, clinical management and prognosis.

Use of impulse oscillometry to assess lung function in prematurely born children and young people: Comparisons with spirometry.

Premature birth is a risk factor for bronchopulmonary dysplasia (BPD); both of which are associated with obstructive airway disease throughout childhood. Impulse oscillometry (IOS) is an effort-independent, passive measure of tidal breathing, which could have benefits in assessing lung function amongst younger patients unable to perform valid spirometry. A literature search was conducted to investigate the use of IOS in prematurely born children and young people. IOS results correlate with those of spirometry. Reversibility of airway obstruction in children with BPD is variable. IOS could have benefits in assessing individual patient response and suitability for bronchodilator therapy. More work, however, is required to establish multi-ethnic reference ranges and standardise commercially available devices prior to its routine incorporation into clinical practice.

Airwave oscillometry and spirometry in children with asthma or wheeze.

OBJECTIVE: Lung function testing is used in diagnosing asthma and assessing asthma control. Spirometry is most commonly used, but younger children can find performing this test challenging. Non-volitional tests such as airwave oscillometry (AOS) may be helpful in that population. We compared the success of spirometry and AOS in assessing bronchodilator responsiveness in children. METHODS: AOS was conducted alongside routine lung function testing. Resistance at 5 Hz (R5), the difference between the resistance at 5 and 20 Hz (R5-20) and the area under the reactance curve (AX) were assessed. Patients between 5 and 16 years old attending clinic with wheeze or asthma were assessed. Patients performed AOS, followed by spirometry and were then given 400 µg salbutamol; the tests were repeated 15 minutes later. RESULTS: Lung function testing was performed in 47 children of whom 46 (98%) and 32 (68%) performed acceptable baseline oscillometry and spirometry, respectively (p < 0.001). Children unable to perform acceptable spirometry were younger (7.35, range: 5.4-10.3 years) than those who could (10.4, range: 5.5-16.9 years), p < 0.001. The baseline z-scores of AOS R5 correlated with FEV1 (r = 0.499, p = 0.004), FEF75 (r = 0.617, p < 0.001), and FEV1/FVC (r = 0.618, p < 0.001). There was a positive bronchodilator response assessed by spirometry (change in FEV1 ≥ 12%) in eight children which corresponded to a change in R5 of 36% (range: 30%-50%) and a change in X5 of 39% (range: 15%-54%). CONCLUSIONS: Oscillometry is a useful adjunct to spirometry in assessing young asthmatic children's lung function. The degree of airway obstruction, however, might affect the comparability of the results of the two techniques.

Influence of sex on the requirement for and outcomes following late postnatal corticosteroid treatment.

There remains a disparity between the outcomes of male and female prematurely born infants. Our aim was to assess the influence of sex on the requirement for late (> 7 days) postnatal corticosteroid (PNS) treatment and the outcomes following treatment. A retrospective whole population study of infants born at less than 28 weeks of gestation in all neonatal units in England between 2014 and 2018. The impact of exposure to at least five consecutive days of dexamethasone or hydrocortisone on bronchopulmonary dysplasia (BPD) at 36 weeks corrected gestation and survival to discharge from neonatal care was determined. Ten thousand, six hundred and fifty-five infants survived to seven days. Male sex was associated with an increased incidence of BPD (OR 1.41, 95%CI 1.287-1.552, p < 0.001) and death (OR 1.227, 95%CI 1.123-1.452, p < 0.001). Two thousand, three hundred and forty-four infants (22%) received at least one course of PNS at a median of 23 (IQR 15-40) days after birth. Males (23.6%) were more likely to receive PNS than females (20.1%), p < 0.001 and receive repeated courses (mean 1.67 compared to a mean of 1.59 in the females), p = 0.027. Multivariate regression analysis identified no significant differences in the incidence of BPD or death between male and females who received PNS.  Conclusions: Males and females had similar outcomes after receiving PNS, but a significantly greater proportion of males met the clinical threshold to receive PNS and were more likely to receive repeated courses which may expose them to a greater risk of adverse long-term outcomes. What is Known: • There remains a difference in outcomes of male and female infants born prematurely. • Prematurely born male infants were more likely to receive postnatal corticosteroids and a greater number of courses but had similar outcomes compared to female infants. What is New: • Postnatal corticosteroids have long-term adverse effects. Such outcomes should be considered when weighing up the risk-benefit ratio of prescribing postnatal corticosteroids, particularly in very prematurely born male infants.

Physical activity and liver disease affect the fat-free mass in adolescents with cystic fibrosis.

Cystic fibrosis (CF) is predominantly a lung disease but is also characterised by impaired skeletal muscularity and a reduction in fat-free mass. We aimed to test the hypothesis that clinical and anthropometric parameters would determine fat-free mass impairment in adolescents with CF. We measured the fat-free mass index (FFMI) using bioelectrical impedance, the lung function using spirometry, the number of shuttles as a measure of exercise tolerance and the reported physical activity in children and young people with CF in a tertiary centre at King's College Hospital, London, UK. CF-related liver disease was diagnosed by abnormal liver enzymes and/or ultrasonography. We studied 28 children and young people (11 male) with a median (interquartile range (IQR)) age of 15 (13-17) years. They had a median (IQR) FFMI of 13.5 (11.6-15.1) kg/m2. The FFMI significantly correlated with age (rho = 0.568, p = 0.002), number of shuttles (rho = 0.691, p < 0.001) and reported hours of activity per day (rho = 0.426, p = 0.024). The median (IQR) FFMI was significantly higher in male [15.1 (13.1-18.6) kg/m2] compared to female participants [12.7 (11.6-14.1) kg/m2, p = 0.008]. The median (IQR) FFMI was significantly lower in the 10 (36%) participants with liver disease [11.9 (11.5-13.4) kg/m2] compared to the FFMI in the remaining 18 participants without liver disease [14.4 (12.5-15.9) kg/m2, p = 0.027]. CONCLUSION: Fat-free mass increases with increasing age and growth in adolescents with CF. Physical activity exerts a beneficial effect on fat-free mass, and CF-related liver disease negatively affects fat-free mass in adolescents with CF. WHAT IS KNOWN: • Health behaviours in adolescence influence lifelong health in cystic fibrosis (CF). • A normal body mass index in CF might fail to reveal a low fat-free mass (FFM), and quality of life in CF is strongly associated with a reduced FFM. WHAT IS NEW: • FFM increases with increasing age and growth in adolescents with CF. • Physical activity exerts a beneficial effect, and liver disease negatively affects FFM in adolescents with CF.

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.

Hypothermia and adverse outcomes during the transfer of extremely low birth weight infants.

AIM: We aimed to explore whether hypothermia during the transfer of extremely low birth weight (ELBW) infants was associated with increased morbidity and mortality. METHODS: Retrospective cohort study of transfers of ELBW infants by the London Neonatal Transfer Service between April 2015 and January 2017. Hypothermia was defined as an axillary temperature below 36.5°C. RESULTS: Hypothermia was recorded in 36-47% of the 146 transfers depending on the time point of measurement from admission at the referring unit to admission at the receiving unit. Infants with hypothermia had a lower gestational age [25.1 (24.1-26.6) versus 26.0 (25.3-27.0) weeks, p < 0.001], birth weight [750 (600-830) versus 800 (730-885) gr, p = 0.004) and age at referral [1 (0.8-3) versus 1.5 (1-4) hours, p = 0.049] compared to infants without hypothermia. Infants with hypothermia had a longer median (IQR) duration of invasive ventilation [22(6-44) days] compared to infants without hypothermia [10 (4-21) days, p = 0.002]. Infants with hypothermia had a higher incidence of a patent ductus arteriosus and mortality before discharge from neonatal care compared to infants without hypothermia (79% vs. 27%, p = 0.043 and 29% vs. 13%, p = 0.025, respectively). CONCLUSION: Among ELBW infants, hypothermia during transfer was common, particularly in infants of lower gestational age. Hypothermia was associated with a longer duration of ventilation and increased mortality before discharge from neonatal care.

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.

Early origins of respiratory disease.

Chronic respiratory morbidity is unfortunately common in childhood, particularly in those born very prematurely or with congenital anomalies affecting pulmonary development and those with sickle cell disease. Our research group, therefore, has focused on the early origins of chronic respiratory disease. This has included assessing antenatal diagnostic techniques and potentially therapeutic interventions in infants with congenital diaphragmatic hernia. Undertaking physiological studies, we have increased the understanding of the premature baby's response to resuscitation and evaluated interventions in the delivery suite. Mechanical ventilation modes have been optimised and randomised controlled trials (RCTs) with short- and long-term outcomes undertaken. Our studies highlighted respiratory syncytial virus lower respiratory tract infections (LRTIs) and other respiratory viral LRTIs had an adverse impact on respiratory outcomes of prematurely born infants, who we demonstrated have a functional and genetic predisposition to respiratory viral LRTIs. We have described the long-term respiratory outcomes for children with sickle cell disease and importantly identified influencing factors. In conclusion, it is essential to undertake long term follow up of infants at high risk of chronic respiratory morbidity if effective preventative strategies are to be developed.

Carboxyhaemoglobin levels in infants with hypoxic ischaemic encephalopathy.

OBJECTIVES: Hypoxic ischaemic encephalopathy (HIE) is associated with oxidative stress. A potential marker of oxidative damage is carboxyhaemoglobin (COHb) which is the product of the reaction between carbon monoxide and haemoglobin and is routinely assessed on blood gas analysis. Our objective was to test the hypothesis that higher COHb levels would be associated with worse outcomes in infants treated for HIE. METHODS: A retrospective, observational study was performed of all infants who received whole body hypothermia for HIE at a tertiary neonatal intensive care unit between January 2018 and August 2021. For each participating infant, the highest COHb level per day was recorded for days one, three and five after birth. RESULTS: During the study period, 67 infants with a median (IQR) gestational age of 40 (38-41) weeks underwent therapeutic hypothermia for HIE. The median (IQR) COHb level on day three was higher in infants without electroencephalographic seizures (1.4 [1.1-1.4] %) compared with infants with seizures (1.1 [0.9-1.3] %, p=0.024). The median (IQR) COHb on day five was higher in infants without MRI brain abnormalities (1.4 [1.2-1.7] %) compared with infants with MRI abnormalities (1.2 [1.0-1.4] %, p=0.032). The COHb level was not significantly different between the nine infants who died compared to the infants who survived. CONCLUSIONS: COHb levels were higher in infants with HIE without seizures and in those with normal MRI brain examinations. We suggest that carbon monoxide has a potential protective role in HIE.

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.

Respiratory function monitoring during early resuscitation and prediction of outcomes in prematurely born infants.

OBJECTIVES: Over the last decade, there has been increased use of end-tidal carbon dioxide (ETCO2) and oxygen saturation (SpO2) monitoring during resuscitation of prematurely born infants in the delivery suite. Our objectives were to test the hypotheses that low end-tidal carbon dioxide (ETCO2) levels, low oxygen saturations (SpO2) and high expiratory tidal volumes (VTE) during the early stages of resuscitation would be associated with adverse outcomes in preterm infants. METHODS: Respiratory recordings made in the first 10 min of resuscitation in the delivery suite of 60 infants, median GA 27 (interquartile range 25-29) weeks were analysed. The results were compared of infants who did or did not die or did or did not develop intracerebral haemorrhage (ICH) or bronchopulmonary dysplasia (BPD). RESULTS: Twenty-five infants (42%) developed an ICH and 23 (47%) BPD; 11 (18%) died. ETCO2 at approximately 5 min after birth was lower in infants who developed an ICH, this remained significant after adjusting for gestational age, coagulopathy and chorioamnionitis (p=0.03). ETCO2 levels were lower in infants who developed ICH or died compared to those that survived without ICH, which remained significant after adjustment for gestational age, Apgar score at 10 min, chorioamnionitis and coagulopathy (p=0.004). SpO2 at approximately 5 min was lower in the infants who died compared to those who survived which remained significant after adjusting for the 5-min Apgar score and chorioamnionitis (p=0.021). CONCLUSIONS: ETCO2 and SpO2 levels during early resuscitation in the delivery suite were associated with adverse outcomes.