Missed or delayed diagnosis of anorectal malformations: a review of the literature, current training and practice in the UK in relation to detection via the NIPE programme.

Anorectal malformations (ARMs) are a spectrum of congenital anomalies where there is abnormal development of the anus and rectum. With an incidence of 1:5000 live births and affecting both males and females, these anomalies vary in their appearance and presentation, lack features enabling antenatal detection and should be detected at birth by the examining midwife or within 72 hours through the newborn and infant physical examination (NIPE) screening programme. However, it is recognised that the diagnosis of ARMs can be missed or delayed leading to morbidity and mortality. In the UK, despite the existence of the NIPE screening programme and NICE guidelines, published literature shows that nearly a quarter of ARMs are not diagnosed at birth. This review takes a critical look at the frequency of missed/delayed diagnosis of ARMs at birth, the implications of delayed diagnosis, and the possible reasons for this related to education and training of healthcare professionals involved in newborn examination, focusing on the UK national screening programme for NIPE. We propose a strategy for enhancing detection of ARMs in a timely manner through the existing framework of the NIPE screening programme.

Less-Invasive Surfactant Administration for Neonatal Respiratory Distress Syndrome: A Consensus Guideline.

INTRODUCTION: Less-invasive surfactant administration (LISA) is a method of surfactant delivery to preterm infants for treating respiratory distress syndrome (RDS), which can reduce the composite risk of death or bronchopulmonary dysplasia and the time on mechanical ventilation. METHODS: A systematic literature search of studies published up to April 2021 on minimally invasive catheter surfactant delivery in preterm infants with RDS was conducted. Based on these studies, with parental feedback sought via an online questionnaire, 9 UK-based specialists in neonatal respiratory disease developed their consensus for implementing LISA. Recommendations were developed following a modified, iterative Delphi process using a questionnaire employing a 9-point Likert scale and an a priori level of agreement/disagreement. RESULTS: Successful implementation of LISA can be achieved by training the multidisciplinary team and following locally agreed guidance. From the time of the decision to administer surfactant, LISA should take <30 min. The comfort of the baby and requirements to maintain non-invasive respiratory support are important. While many infants can be managed without requiring additional sedation/analgesia, fentanyl along with atropine may be considered. Parents should be provided with sufficient information about medication side effects and involved in treatment discussions. CONCLUSION: LISA has the potential to improve outcomes for preterm infants with RDS and can be introduced as a safe and effective part of UK-based neonatal care with appropriate training.

Point-of-care glucose monitoring on the neonatal unit.

AIM: This study aims to compare the accuracy and precision of the Nova StatStrip glucometer against the Radiometer ABL gas analyser. Based on the results, to establish if the Nova StatStrip glucometer could be adopted as a reliable alternative for near-patient glucose monitoring on the neonatal unit. METHODS: Seven hundred twenty-eight paired samples were collected prospectively from babies on a neonatal intensive care unit. Analytical performance of the Nova StatStrip glucometer was assessed based on the ISO 15197 criteria and the American Diabetic Association standards. Its performance compared with the Radiometer ABL gas analyser was assessed statistically using Bland-Altman analysis and clinically by use of an error grid. RESULTS: A percentage of 98.8 of StatStrip values less than 4.2 mmol/L and 97.9% of values greater than 4.2 mmol/L met the ISO criteria. Bland-Altman analysis showed good correlation between the readings. An error grid showed that most infants would be appropriately managed for hypoglycaemic episodes as per local guidelines. CONCLUSIONS: The Nova StatStrip performed well on statistical analysis compared with the Radiometer. Very few hypoglycaemic patients would be missed using the Nova StatStrip glucometer. We would recommend its use on our unit.

Congenital hypopituitarism and renal failure.

Congenital hypopituitarism is potentially fatal in the newborn period but treatable if the diagnosis is made early. We report a neonate who presented with hypothermia and severe hypoglycemia. He also had undescended testis and micropenis. Initial screening revealed panhypopituitarism, which was corrected promptly. He developed renal failure due to initial cardiovascular compromise related to hypotension but recovered quickly with standard management. Magnetic resonance imaging revealed absent stalk of anterior pituitary.

Differential response of the epithelium and interstitium in developing human fetal lung explants to hyperoxia.

Hyperoxia is closely linked with the development of chronic lung disease of prematurity (CLD), but the exact mechanisms whereby hyperoxia alters the lung architecture in the developing lung remain largely unknown. We developed a fetal human lung organ culture model to investigate (a) the morphologic changes induced by hyperoxia and (b) whether hyperoxia resulted in differential cellular responses in the epithelium and interstitium. The effects of hyperoxia on lung morphometry were analyzed using computer-assisted image analysis. The lung architecture remained largely unchanged in normoxia lasting as long as 4 d. In contrast, hyperoxic culture of pseudoglandular fetal lungs resulted in significant dilatation of airways, thinning of the epithelium, and regression of the interstitium including the pulmonary vasculature. Although there were no significant differences in Ki67 between normoxic and hyperoxic lungs, activated caspase-3 was significantly increased in interstitial cells, but not epithelial cells, under hyperoxic conditions. These changes show that exposure of pseudoglandular lungs to hyperoxia modulates the lung architecture to resemble saccular lungs.

Spontaneous contraction of pseudoglandular-stage human airspaces is associated with the presence of smooth muscle-alpha-actin and smooth muscle-specific myosin heavy chain in recently differentiated fetal human airway smooth muscle.

BACKGROUND: Recent investigations demonstrating that pseudoglandular-stage airspaces contract spontaneously suggest that the production of contractile proteins by airway wall smooth muscle (ASM) is an important factor in the functional and structural differentiation of ASM. AIMS: Ouraim was to determine if smooth muscle (SM)-myosin heavy chain (MHC) myofilaments, the 'motor' underlying SM contraction, and SM-alpha-actin myofilaments were distributed simultaneously in pseudoglandular-stage human lungs and to further define the nature of fetal airway contractions. METHODS: Immunohistochemically stained sections of fetal lung (14 fetuses, 10.1-17 weeks gestation) were analysed by computer-assisted morphometry to determine airspace dimensions and detect SM-MHC- and SM-alpha-actin-ASM. Lung tissue from the same fetuses was also placed in explant culture to observe airway contractions using videomicroscopy. We found that the smallest airspaces were just as likely to be invested by a layer of SM-MHC-positive ASM as by a layer of SM-alpha-actin-positive ASM. In addition, larger airways or airways from more mature fetal lungs were more likely to be invested by either SM-MHC- or SM-alpha-actin-positive ASM. Spontaneous airspace contractions were peristalsis-like and variable in amplitude. The time interval between contractions was temperature dependent (mean+/-SEM, 44+/-7.5 s at 37 degrees C), shortened by carbachol and increased by nitric oxide (NO)-donating drugs. CONCLUSIONS: These observations suggest that ASM differentiation is characterised by the simultaneous production of SM-alpha-actin and SM-MHC myofilaments and that the presence of these proteins is likely to be responsible for cholinergic- and NO-sensitive spontaneous contractions of fetal human airspaces.

Role of cytokines in hyperoxia mediated inflammation in the developing lung.

The development of Chronic Lung Disease of Prematurity (CLD) has been associated with the use of hyperoxic conditions during ventilation. Inflammation has been demonstrated to contribute to the development of this disease, both on histological examination of diseased lungs, and by the use of bronchoalveolar lavage. Hyperoxia is believed to contribute to this inflammatory process by causing direct injury to epithelial and endothelial cells. The formation of reactive oxygen species is thought to result in production of cytokines. These act within a complex network, orchestrating an inflammatory response. Evidence for a role of cytokines in CLD has been inferred by studies in human infants showing increased concentrations of cytokines, growth factors and inflammatory cells at early stages in infants destined to develop CLD. These findings have been supported by the use of animal models of hyperoxic lung injury. The treatment of CLD is currently centered on the suppression of cytokine production. As understanding of this disease increases, more specific targets are being developed which aim to reduce the oxidative load on the lung, and prevent recruitment of inflammatory cells that are responsible for the tissue damage underlying this disease.