Maternal and infant outcomes in women with sickle cell disease: a matched cohort study.

OBJECTIVE: Women with sickle cell disease (SCD) have adverse maternal and infant outcomes. Our aim was to determine whether the outcomes of SCD mothers and their infants differed from African or Caribbean women not affected by SCD and whether there were differences between SCD individuals with the haemoglobin SS (HbSS) or haemoglobin SC (HbSC) genotypes. Furthermore, we wished to determine if any differences related to deprivation. DESIGN: A matched cohort study. SETTING: Tertiary perinatal centre in London PATIENTS: 4964 African or Caribbean women without SCD and 148 with SCD. MAIN OUTCOME MEASURES: Mode of delivery, maternal exchange transfusion, birthweight, neonatal unit admission, neonatal death and deprivation indices RESULTS: SCD women were more likely to be delivered by caesarean section (p<0.001) and had babies of lower birthweight (p<0.001). Their infants were no more likely to be admitted to neonatal intensive care unit or suffer a neonatal death. There were no significant differences between the SCD women and those without SCD in their deprivation index or deprivation decile. The women with the HbSS genotype compared to those with the HbSC genotype were more anaemic (p<0.02), required more exchange transfusions (p<0.001) and were more likely to be delivered by caesarean section (p=0.008). The infant outcomes did not differ significantly between the genotypes. CONCLUSIONS: Although, the SCD women, particularly those with the HbSS genotype, had greater morbidity, infant morbidity, and mortality was similar in mothers with the HbSS or HbSC genotypes and those without SCD.

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.

Tackling obesity while preventing obesity stigma.

Obesity is a significant public health problem. Prevalence is rising in children and young people, with lifelong health impacts and implications for paediatric clinical practice. Obesity stigma is increasingly acknowledged as a problem within health services. Health professionals can inadvertently contribute to this stigma, which is harmful and in itself can promote weight gain. A complex web of factors contributes to obesity, and a simplistic approach exclusively focused on personal responsibility, diet and exercise is unhelpful. A more nuanced, sensitive and informed approach is needed, with careful use of language and non-judgemental partnership working.

The genomic evolutionary dynamics and global circulation patterns of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in young children and the second leading cause of infant death worldwide. While global circulation has been extensively studied for respiratory viruses such as seasonal influenza, and more recently also in great detail for SARS-CoV-2, a lack of global multi-annual sampling of complete RSV genomes limits our understanding of RSV molecular epidemiology. Here, we capitalise on the genomic surveillance by the INFORM-RSV study and apply phylodynamic approaches to uncover how selection and neutral epidemiological processes shape RSV diversity. Using complete viral genome sequences, we show similar patterns of site-specific diversifying selection among RSVA and RSVB and recover the imprint of non-neutral epidemic processes on their genealogies. Using a phylogeographic approach, we provide evidence for air travel governing the global patterns of RSVA and RSVB spread, which results in a considerable degree of phylogenetic mixing across countries. Our findings highlight the potential of systematic global RSV genomic surveillance for transforming our understanding of global RSV spread.

Capnography waveforms: basic interpretation in neonatal intensive care.

End-tidal capnography can provide useful clinical information displayed on the ventilator screen or bedside monitor. It is important that clinicians can assess and utilise this information to assist in identifying underlying complications and pulmonary pathology. Sudden change or loss of the CO2 waveform can act as a safety measure in alerting clinicians of a dislodged or blocked endotracheal tube, considering the concurrent flow and volume waveforms. Visual pattern recognition by the clinicians of commonly seen waveform traces may act as an adjunct to other modes of ventilatory monitoring techniques. Waveforms traces can aid clinical management, help identify cases of ventilation asynchrony between the infant and the ventilator. We present some common clinical scenarios where tidal capnography can be useful in the timely identification of pulmonary complication and for practical troubleshooting at the cot-side.

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: 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.

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.

Study protocol for a randomised cross-over trial of Neurally adjusted ventilatory Assist for Neonates with Congenital diaphragmatic hernias: the NAN-C study.

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a mode of mechanical ventilation that delivers oxygen pressures in proportion to electrical signals of the diaphragm. The proportional assistance can be adjusted by the clinician to reduce the patient's work of breathing. Several case series of infants with congenital diaphragmatic hernias (CDH) have shown that NAVA may reduce oxygenation index and mean airway pressures. To date, no clinical trial has compared NAVA to standard methods of mechanical ventilation for babies with CDH. METHODS: The aim of this dual-centre randomised cross-over trial is to compare post-operative NAVA with assist control ventilation (ACV) for infants with CDH. If eligible, infants will be enrolled for a ventilatory support tolerance trial (VSTT) to assess their suitability for randomisation. If clinically stable during the VSTT, infants will be randomised to receive either NAVA or ACV first in a 1:1 ratio for a 4-h period. The oxygenation index, respiratory severity score and cumulative sedative medication use will be measured. DISCUSSION: Retrospective studies comparing NAVA to ACV in neonates with congenital diaphragmatic hernia have shown the ventilatory mode may improve respiratory parameters and benefit neonates. To our knowledge, this is the first prospective cross-over trial comparing NAVA to ACV. TRIAL REGISTRATION: NAN-C was prospectively registered on ClinicalTrials.gov NCT05839340  Registered on May 2023.

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.

Functional MRI assessment of the lungs in fetuses that deliver very Preterm: An MRI pilot study.

OBJECTIVES: To compare mean pulmonary T2* values and pulmonary volumes in fetuses that subsequently spontaneously delivered before 32 weeks with a control cohort with comparable gestational ages and to assess the value of mean pulmonary T2* as a predictor of preterm birth < 32 weeks' gestation. METHODS: MRI datasets scanned at similar gestational ages were selected from fetuses who spontaneously delivered < 32 weeks of gestation and a control group who subsequently delivered at term with no complications. All women underwent a fetal MRI on a 3 T MRI imaging system. Sequences included T2-weighted single shot fast spin echo and T2* sequences, using gradient echo single shot echo planar sequencing of the fetal thorax. Motion correction was performed using slice-to-volume reconstruction and T2* maps generated using in-house pipelines. Lungs were manually segmented and volumes and mean T2* values calculated for both lungs combined and left and right lung separately. Linear regression was used to compare values between the preterm and control cohorts accounting for the effects of gestation. Receiver operating curves were generated for mean T2* values and pulmonary volume as predictors of preterm birth < 32 weeks' gestation. RESULTS: Datasets from twenty-eight preterm and 74 control fetuses were suitable for analysis. MRI images were taken at similar fetal gestational ages (preterm cohort (mean ± SD) 24.9 ± 3.3 and control cohort (mean ± SD) 26.5 ± 3.0). Mean gestational age at delivery was 26.4 ± 3.3 for the preterm group and 39.9 ± 1.3 for the control group. Mean pulmonary T2* values remained constant with increasing gestational age while pulmonary volumes increased. Both T2* and pulmonary volumes were lower in the preterm group than in the control group for all parameters (both combined, left, and right lung (p < 0.001 in all cases). Adjusted for gestational age, pulmonary volumes and mean T2* values were good predictors of premature delivery in fetuses < 32 weeks (area under the curve of 0.828 and 0.754 respectively). CONCLUSION: These findings indicate that mean pulmonary T2* values and volumes were lower in fetuses that subsequently delivered very preterm. This may suggest potentially altered oxygenation and indicate that pulmonary morbidity associated with prematurity has an antenatal antecedent. Future work should explore these results correlating antenatal findings with long term pulmonary outcomes.

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.

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.

PPAR Gamma Receptor: A Novel Target to Improve Morbidity in Preterm Babies.

Worldwide, three-quarters of a million babies are born extremely preterm (<28 weeks gestation) with devastating outcomes: 20% die in the newborn period, a further 35% develop bronchopulmonary dysplasia (BPD), and 10% suffer from cerebral palsy. Pioglitazone, a Peroxisome Proliferator Activated Receptor Gamma (PPARγ) agonist, may reduce the incidence of BPD and improve neurodevelopment in extreme preterm babies. Pioglitazone exerts an anti-inflammatory action mediated through Nuclear Factor-kappa B repression. PPARγ signalling is underactive in preterm babies as adiponectin remains low during the neonatal period. In newborn animal models, pioglitazone has been shown to be protective against BPD, necrotising enterocolitis, and lipopolysaccharide-induced brain injury. Single Nucleotide Polymorphisms of PPARγ are associated with inhibited preterm brain development and impaired neurodevelopment. Pioglitazone was well tolerated by the foetus in reproductive toxicology experiments. Bladder cancer, bone fractures, and macular oedema, seen rarely in adults, may be avoided with a short treatment course. The other effects of pioglitazone, including improved glycaemic control and lipid metabolism, may provide added benefit in the context of prematurity. Currently, there is no formulation of pioglitazone suitable for administration to preterm babies. A liquid formulation of pioglitazone needs to be developed before clinical trials. The potential benefits are likely to outweigh any anticipated safety concerns.

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.

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.

Risk assessment of survival and morbidity of infants born at <24 completed weeks of gestation.

BACKGROUND: Infants born at the threshold of viability have a high risk of mortality and morbidity. The British Association of Perinatal Medicine (BAPM) provided updated guidance in 2019 advising a risk-based approach to balancing decisions about active versus redirected care at birth. AIMS: To determine survival and morbidity of infants born between 22 and 24 completed weeks of gestation. To develop a scoring system to categorise infants at birth according to risk for mortality or severe adverse outcome. METHODS: A retrospective, single centre observational study of infants who received neonatal care from 2011 to 2021. Data were collected on mortality, morbidity and two-year neurodevelopmental outcomes. Each infant was risk categorised utilising the proposed tools in the BAPM (2019) framework. A composite adverse score for either dying or surviving with severe impairment was created. RESULTS: Four infants born at 22 weeks, 49 at 23 weeks and 105 at 24 weeks of gestation were included. The mortality rate was 23.4 %. Following risk categorisation there were 8 (5.1 %) extremely high risk, 44 (27.8 %) high risk and 106 (67.1 %) moderate risk infants. The rate of dying or surviving with severe impairment for extremely high risk, high risk and moderate risk were 100 %, 88.9 % and 53 % respectively. The proportions with the composite adverse outcome differed significantly according to the risk category (p < 0.001). CONCLUSIONS: When applying a scoring system to risk categorise infants at birth, high rates of dying or surviving with severe impairment were found in infants born at 22 or 23 weeks of gestation.

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.

Exercise Capacity in Very Low Birth Weight Adults: A Systematic Review and Meta-Analysis.

There is an association between very low birth weight (VLBW) and cardiovascular morbidity and mortality in adulthood. Aerobic fitness, measured as the maximal oxygen consumption (VO2 max), is a good indicator of cardiopulmonary health and predictor of cardiovascular mortality. Our aim was to determine the effect of birth weight on aerobic exercise capacity and physical activity. We systematically identified studies reporting exercise capacity (VO2 max and VO2 peak) and physical activity levels in participants born at VLBW aged eighteen years or older compared to term-born controls from six databases (MEDLINE, OVID, EMBASE, CI NAHL, CENTRAL, and Google Scholar). Meta-analysis of eligible studies was conducted using a random effect model. We screened 6202 articles and identified 15 relevant studies, 10 of which were eligible for meta-analysis. VLBW participants had a lower VO2 max compared to their term counterparts (-3.35, 95% CI: -5.23 to -1.47, p = 0.0005), as did VLBW adults who had developed bronchopulmonary dysplasia (-6.08, 95% CI -11.26 to -0.90, p = 0.02). Five of nine studies reported significantly reduced self-reported physical activity levels. Our systematic review and meta-analysis demonstrated reduced maximal aerobic exercise capacity in adults born at VLBW compared to term-born controls.