Immature Infants Research Articles

58: An Evaluation of a Vancomycin Dosing Protocol in the Neonatal Intensive Care Unit (NICU)

Vancomycin is often prescribed in the NICU for suspected or proven gram-positive infections. Achieving therapeutic serum concentrations can be challenging in neonates, particularly if aiming for high trough concentrations (15–20 mg/L) when MRSA is a concern. To evaluate our vancomycin dosing protocol to determine the proportion of infants with adequate dosing at first check and assess safety. Retrospective chart review of neonates admitted to two university-affiliated NICUs who received IV vancomycin between January 1st and December 31, 2012 (Period 1, 15–20 mg/kg/dose) and January 1, 2013 and February 28th, 2014 (Period 2, 20–22 mg/kg/dose). The outcomes were the proportion of neonates with target trough levels (5–15 mg/L), the proportion with higher trough levels (15–20 mg/L) and the proportion with toxic trough levels (>20 mg/L). 116 neonates received vancomycin, including 74 (mean gestational age 29.8+/− 4.8 weeks, mean birth weight 1.5 +/− 0.9 kg) with trough levels pre-3rd dose. There was no difference between the dose/kg of vancomycin between the two periods (Period 1 mean 20.4 mg/kg; Period 2 mean 20.9 mg/kg). 56 of 74 neonates (75.7%) achieved the target trough (Table 1). Only seven (9.5%) achieved a higher trough. Four (5.4%) infants had a trough level >20 mg/L. Less than 2/3 of infants ≤28 weeks and ≤14 days achieved an adequate trough. Our vancomycin dosing protocol is effective when targeting trough levels of 5–15 mg/L, except in the most immature infants. It is suboptimal if targeting higher trough levels. Further research is needed to develop a protocol that effectively achieves therapeutic trough levels in extremely preterm infants in their first weeks of life.

Effect of surfactant on regional lung function in an experimental model of respiratory distress syndrome in rabbit.

We assessed the changes in regional lung function following instillation of surfactant in a model of respiratory distress syndrome (RDS) induced by whole lung lavage and mechanical ventilation in eight anaesthetized, paralyzed, and mechanically ventilated New Zealand White rabbits. Regional specific ventilation (sV̇) was measured by K-edge subtraction synchrotron computed tomography during xenon washin. Lung regions were classified as poorly aerated (PA), normally aerated (NA), or hyperinflated (HI) based on regional density. A functional category was defined within each class based on sV̇ distribution (High, Normal, and Low). Airway resistance (Raw), respiratory tissue damping (G), and elastance (H) were measured by forced oscillation technique at low frequencies before and after whole lung saline lavage-induced (100 ml/kg) RDS, and 5 and 45 min after intratracheal instillation of beractant (75 mg/kg). Surfactant instillation improved Raw, G, and H (P < 0.05 each), and gas exchange and decreased atelectasis (P < 0.001). It also significantly improved lung aeration and ventilation in atelectatic lung regions. However, in regions that had remained normally aerated after lavage, it decreased regional aeration and increased sV̇ (P < 0.001) and sV̇ heterogeneity. Although surfactant treatment improved both central airway and tissue mechanics and improved regional lung function of initially poorly aerated and atelectatic lung, it deteriorated regional lung function when local aeration was normal prior to administration. Local mechanical and functional heterogeneity can potentially contribute to the worsening of RDS and gas exchange. These data underscore the need for reassessing the benefits of routine prophylactic vs. continuous positive airway pressure and early "rescue" surfactant therapy in very immature infants.

Proactive care at the edge of viability: making the gray zone less gray?

One of the great success stories in neonatology is the gains made in survival of the smallest and most immature infants over the past 25 years.1,2 However, concerns persist that increased survival may be complicated by increased neurodevelopmental impairment (NDI) for infants born at the edge of viability.3,4 This balance between potential for survival and that of severe NDI weighs heavily on counseling for parents threatened with the birth of an extremely preterm infant. In this issue of Pediatrics , Serenius and colleagues from the Extremely Preterm Infant Study in Sweden (EXPRESS) team address this concern directly.5 Acknowledging that for some patients the burdens of intensive care (deaths in the NICU but especially long-term morbidity among survivors) may outweigh benefits, they present data to support a proactive approach beginning in utero, aiming to optimize a “trial of life” for infants born at the edge of viability. The EXPRESS investigators recently reported rates of death and NDI at 2.5 years in a cohort of live fetuses at 22 to 26 weeks’ gestation.6 … Address correspondence to Eric C. Eichenwald, MD, Department of Pediatrics, University of Texas Medical School, Houston, 6431 Fannin St, MSB 3.020, Houston, TX 77030. E-mail: Eric.c.eichenwald{at}uth.tmc.edu

Prevention of Central Line–Associated Bloodstream Infections Among Infants in the Neonatal Intensive Care Unit

Hospital-acquired infection complicates the care of 30% to 50% of infants born at less than 28 weeks’ gestation and cared for in neonatal intensive care units (NICUs). Such infections have negative effects on survival, short-term morbidities, and long-term neurodevelopment. Central line–associated bloodstream infections (CLABSIs) are the most common type of hospital-acquired infection among infants in the NICU. Poor neonatal immune defenses, invasive technical care, multiple exposures to antibiotics, prolonged periods without enteral feeding, and pathogenic, hospital-derived microbial species combine to place infants in the NICU at high risk of infection. Multiple studies support the use of bundled care strategies that focus on minimizing pathogenic colonization of the infant, preventing contamination of the central line, decreasing duration of central line use, and using real-time infection surveillance and communication to prevent CLABSIs. Consistent use of best practices can decrease the incidence of CLABSIs among even the most immature infants in the NICU.

Sonographic and Doppler Sonographic Diagnosis of Posthemorrhagic Hydrocephalus.

Severe intracranial hemorrhages occur especially in very immature premature infants born with a gestational age under 28 weeks of gestation and a birth weight below 1000 g. Severe hemorrhages are often complicated by a post-hemorrhagic hydrocephalus (PHH). PHH can be caused by a blockage of the cerebro-spinal fluid pathways or by obliterative arachnoiditis of the posterior cranial fossa. Cerebral sonography can differentiate between both entities. In cases of obstruction of the cerebro-spinal fluid circulation the parts of the ventricular system infront of the obstruction are dilated. Color coded Doppler sonography can display the patency or obstruction of the physiologic constrictions of the ventricular system. Increased intracranial pressure can noninvasively be detected by spectral Doppler: The increase of the peak systolic flow velocity in the intracranial section of the internal carotid artery in comparison with the extra-cranial part is an early indication of a raised intracranial pressure. The decrease of the end-diastolic flow velocity during fontanel compression is indicative of abolished cranial compliance and increased intracranial pressure. In the case of raised intracranial pressure diastolic amplitudes and end-diastolic flow velocities are decreased and the resistive-indices are increased.

Effect of premedication regimen on infant pain and stress response to endotracheal intubation.

(1) Evaluate the effect of different medications on pain and stress in neonates during nonemergent endotracheal intubation; (2) determine whether gestational age affects medication use; (3) determine whether better sedation results in a decrease in the number of attempts and/or total time for the procedure. Prospective observational study. Infant responses were measured using a clinical pain scale and blood glucose, a biochemical marker of acute stress. A total of 166 infants were included, with adjusted gestational ages 24 to 44 weeks at the time of procedure. Premedication regimens included no medication ('none,' 27%), morphine (19%), morphine+midazolam (11%), fentanyl (14%), fentanyl+midazolam (19%) and midazolam alone (10%). Fentanyl+midazolam resulted in lower pain scores and less increase in blood glucose (both P<0.0001). No other regimen was different from 'none'. The most immature infants were less likely to receive premedication (P=0.023), although their pain scores and blood glucose responses were similar to more mature infants. None of the medication regimens reduced the total procedure time (P=0.55) or the number of attempts (P=0.145). Only fentanyl+midazolam significantly attenuated both the clinical pain score and the increase in blood glucose. Less mature infants had responses similar to those of more mature infants, but were less likely to receive premedication. None of the regimens decreased the time or number of attempts required for successful intubation.

Use of Medical Resources by Preterm Infants Born at Less than 33 Weeks' Gestation Following Discharge from the Neonatal Intensive Care Unit in Korea.

This study was aimed to provide data on the use of medical resources by preterm infants following discharge from the neonatal intensive care unit (NICU). The cohort included preterm infants (n=2,351) born at 22-32 weeks' gestation who were discharged from the NICUs of 44 Korean hospitals between April 2009 to March 2010. Mean duration of post-discharge follow-up was 425±237 days. After discharge from the NICU, 94.5% of total infants visited a pediatric outpatient clinic (11.5±9.8 mean visits), 42.9% visited a pediatric clinic for respiratory problems irregularly (4.9±6.6 mean visits), and 31.1% utilized emergency center at least once. Among all visits to the emergency center, 24.7% resulted in readmission and 50.8% of those visits were due to respiratory problems. At least one episode of readmission was required by 33.6% (788/2,346) of total infants, and 18.4% (431/2,346) of total infants were readmitted with respiratory problems at least once. Among all infants readmitted for respiratory problems, 16.2% (70/341) were diagnosed with respiratory syncytial virus infection which accounted for 30.3% of viral etiologies confirmed by laboratory testing. Infants born at <30 weeks' gestation had more frequent total readmission and respiratory readmission than those ≥30 weeks' gestation (2±1.7 vs. 1.7±1.2, P=0.009, 1.8±1.2 vs. 1.5±1.1, 0.027, respectively). Overall, use of medical resources is common, and respiratory problems are the leading cause of use of medical resources. Total readmissions and respiratory readmissions are more frequent in more immature infants.

Animal models of bronchopulmonary dysplasia. The preterm baboon models

Much of the progress in improved neonatal care, particularly management of underdeveloped preterm lungs, has been aided by investigations of multiple animal models, including the neonatal baboon ( Papio species). In this article we highlight how the preterm baboon model at both 140 and 125 days gestation (term equivalent 185 days) has advanced our understanding and management of the immature human infant with neonatal lung disease. Not only is the 125-day baboon model extremely relevant to the condition of bronchopulmonary dysplasia but there are also critical neurodevelopmental and other end-organ pathological features associated with this model not fully discussed in this limited forum. We also describe efforts to incorporate perinatal infection into these preterm models, both fetal and neonatal, and particularly associated with Ureaplasma/ Mycoplasma organisms. Efforts to rekindle the preterm primate model for future evaluations of therapies such as stem cell replacement, early lung recruitment interventions coupled with noninvasive surfactant and high-frequency nasal ventilation, and surfactant therapy coupled with antioxidant or anti-inflammatory medications, to name a few, should be undertaken.

Control of breathing

Late preterm infants have been called “great imposters” [1] because they often appear to be and are therefore treated as term infants, however their brainstem development and neural control of respiration are less mature than in full-term infants. During late gestation there are dramatic developmental changes in the brainstem and forebrain: at 34 gestational weeks the total brain weight is 65% of that at term [2]. The control of lung volume, laryngeal reflexes, upper airways, chemoreceptor activity, coordination of sucking, swallowing, breathing, the incidence of apnea and periodic breathing and the control of heart rate are still developing during late gestation and the degree of maturity of these mechanisms appears to lie on a continuum that extends from more immature infants to after term. Also, these reflexes are influenced by sleep-wake states whose neurobiological development is still evolving. The brainstem is not completely mature even at term, as confirmed by the fact that its myelination, the marker of completed neuronal/axonal maturation, is still incomplete at that time. This protracted maturation is not surprising, considering that the neurodevelopment of the respiratory control and sleep-wake cycle continues into infancy. The few data on control of breathing in late preterm infants indicate that ventilatory responses to CO2 and hypoxia as well as autonomic control of heart rate are not yet mature at 36 weeks PMA. Clinically, late preterm infants have more apnea and periodic breathing than term infants and immature coordination of sucking, swallowing and breathing often delay their ability to feed without episodes of bradycardia, desaturation and even apnea [3]. The incidence of apparent life-threatening events is more common in preterm infants (8-10%) than full-term infants (1% or less). In the Collaborative Home Infant Monitoring Evaluation studies the frequency of conventional and extreme (clinically relevant) events in near term infants is intermediate between preterm infants <34 weeks at birth and full-term infants [4]. Clinical data indicate that late preterm are also predisposed to wheezing in infancy and early childhood although not exposed to excessive supplemental oxygen or ventilator support [5]. Exposure to 21% oxygen could represent premature exposure to hyperoxic environment compared to that in utero, with long-term effects on the still immature conducting airways. Recent data demonstrate that immature human airway smooth muscle are highly sensitive to even short durations of hyperoxia, with increased proliferation at moderate levels of oxygen (< 60%) but apoptosis at higher levels [6].

PS-280 Surface Film Fromationin VitroBy Infant And Therapeutic Surfactants: Role Of Surfactant Protein B

Background Essential surfactant properties include transfer to gas-liquid interface, reduction of surface tension and film replenishment during respiratory cycles. Objective To compare component-specific film formation properties of infant and therapeutic surfactants. Design/methods Using a multiwell fluorescence assay, we compared maximal fluorescence (Max), time to reach Max (tMax) and phospholipid concentration for ½ maximal signal (½Max) for calfactant (CAL), poractant (POR), beractant (BER), colfosceryl palmitate (COL), with surfactant from immature infants with RDS. Dose-response studies were performed for addition of SP-B, albumin and budesonide. Results Max and ½Max values for CAL were higher/similar to those of rat surfactant. There were significant differences between CAL and other therapeutic surfactants for Max (CAL >COL >POR >BER) whereas ½Max were similar except for COL. In surfactant from 39 infant tracheal aspirates, ½Max was inversely correlated with SP-B content (p = 0.001). Addition of SP-B to samples with low endogenous content ( Conclusions This assay reveals differences in film formation efficiency for therapeutic surfactants reflecting differences in SP-B content and lipid composition. Film formation by infant surfactant is strongly influenced by SP-B content. The findings support the key physiological role of SP-B and the safety of surfactant as anti-inflammatory drug vehicle.

Preterm infants’ orally directed behaviors and behavioral state responses to the integrated H-HOPE intervention

Preterm infants are challenged by immature infant behavioral organization which may negatively influence their ability to oral feed. The purpose of this study was to determine whether the integrated H-HOPE (Hospital to Home: Optimizing the Infant's Environment) intervention would improve infant behavioral organization by increasing the frequency of orally directed behaviors and the proportion of time spent in an alert behavioral state when offered prior to oral feeding. Mother–infant dyads (n=198) were randomly assigned to the H-HOPE intervention or the Attention Control groups. Infants were born at 29–34 weeks gestation and were clinically stable. Mothers had at least two social environmental risk factors such as minority status or less than high school education. H-HOPE is an integrated intervention that included (1) twice-daily infant directed stimulation using the ATVV intervention (auditory, tactile, visual, and vestibular stimuli) and (2) maternal participatory guidance sessions by a nurse-community advocate team. Orally directed behaviors and behavioral states were assessed weekly prior to feeding during hospitalization when infants were able to feed orally. There were no differences between the groups at baseline (Day 0, prior to the initiation of the integrated H-HOPE intervention). We observed a pattern of increased frequency of orally directed behaviors in the H-HOPE intervention group when compared to the Attention Control group, however, the proportion of time spent in an alert behavioral state remained stable in both groups over the course of the study. On Day 7, the H-HOPE intervention group exhibited a significantly higher mean frequency of orally directed behaviors than the Attention Control group (12.6 vs. 7.1 pre-intervention, 51.8 vs. 33.2 during intervention, 4.3 vs. 3.2 immediately after intervention, and 8.9 vs. 5.3 immediately prior to feeding). On Day 7, the H-HOPE intervention group exhibited a significantly higher proportion of time spent in an alert behavioral state only during intervention (0.26 vs. 0.11) and immediately after intervention (0.28 vs. 0.06). These findings are suggestive that the integrated H-HOPE intervention facilitated infant behavioral organization for clinically stable infants born between 29 and 34 weeks gestation. The orally directed behaviors appear to be an important indicator of the infant's preparation for feeding, and when used in conjunction with assessment of behavioral states, are especially valuable to the clinician. Use of this combined assessment approach in practice would strengthen clinician assessment for initiation of (beginning the first oral feeding) and daily preparation for oral feeding in preterm infants.

Current management of apnea in premature infants: Is caffeine the magic bullet?

Apnea of prematurity is one of the most common problems observed in premature infants and it is associated with other morbidities including worse neurodevelopmental outcome. The incidence is higher in the more immature infants and it occurs in up to 90% of infants born under 28 weeks of gestation. The pathogenesis of apnea is due to immaturity of the respiratory control systems characterized by an abnormal ventilatory response to carbon dioxide and hypoxia combined with immature reflex responses. Upper airway obstruction due to airway instability is also a frequent component in apnea of prematurity. These abnormalities frequently persist until the infants reach 32–36 weeks corrected age or longer in the more immature infants. Severe apneic episodes are frequently associated with hypoxia and bradycardia and because of this they can lead to increased risk of CNS damage and neurological sequelae [1]. Infants who are mechanically ventilated also present frequently with episodes of hypoxemia but the mechanisms for these episodes differ from those of apnea of prematurity. The management of the infant with apnea episodes should start by identifying and correcting known conditions that can increase their incidence. These include metabolic abnormalities such as hypoglycemia, hypocalcemia and metabolic alkalosis, anemia and arterial hypotension, and any condition that increases the work of breathing. Medications that depress CNS activity also favor apnea and should be avoided. The level of arterial oxygenation plays a critical role in control of breathing in premature infants and low arterial oxygen tension increases the incidence of periodic breathing and apnea episodes [2].

Building simulation model of infant-incubator system with decoupling predictive controller

This paper introduces theoretical modelling working on the thermal behavior of the premature infant. This study aims at developing a model useful for the prediction and design of the appropriate controller in objective to reduce evaporative heat loss. A calculation code has been developed to simulate the thermal response of a premature baby to climatic solicitation inside the incubator system. The model allows us to take into consideration radiative, conductive, convective, and evaporative heat transfers inside the incubator system. The air temperature and the humidity rate, which play a salient part in the convective and evaporative exchanges, are calculated by a coupled transfer function. At present, the environmental conditions (temperature and humidity) inside incubator are controlled with a classical Proportional Integral Differential (PID). In this work, we proposed a decoupling Generalized Predictive Controller (DGPC) based on the model described below to achieve an optimal thermal conditions (36.5–37.5) for immature newborn infants (birthweight <1000grams). Real and simulations results prove the feasibility and effectiveness of the proposed model and controller.

Marked methylation changes in intestinal genes during the perinatal period of preterm neonates.

BackgroundThe serious feeding- and microbiota-associated intestinal disease, necrotizing enterocolitis (NEC), occurs mainly in infants born prematurely (5-10% of all newborns) and most frequently after formula-feeding. We hypothesized that changes in gene methylation is involved in the prenatal maturation of the intestine and its response to the first days of formula feeding, potentially leading to NEC in preterm pigs used as models for preterm infants.ResultsReduced Representation Bisulfite Sequencing (RRBS) was used to assess if changes in intestinal DNA methylation are associated with formula-induced NEC outbreak and advancing age from 10 days before birth to 4 days after birth. Selected key genes with differentially methylated gene regions (DMRs) between groups were further validated by HiSeq-based bisulfite sequencing PCR and RT-qPCR to assess methylation and expression levels. Consistent with the maturation of many intestinal functions in the perinatal period, methylation level of most genes decreased with advancing pre- and postnatal age. The highest number of DMRs was identified between the newborn and 4 d-old preterm pigs. There were few intestinal DMR differences between unaffected pigs and pigs with initial evidence of NEC. In the 4 d-old formula-fed preterm pigs, four genes associated with intestinal metabolism (CYP2W1, GPR146, TOP1MT, CEND1) showed significant hyper-methylation in their promoter CGIs, and thus, down-regulated transcription. Methylation-driven down-regulation of such genes may predispose the immature intestine to later metabolic dysfunctions and severe NEC lesions.ConclusionsPre- and postnatal changes in intestinal DNA methylation may contribute to high NEC sensitivity in preterm neonates. Optimizing gene methylation changes via environmental stimuli (e.g. diet, nutrition, gut microbiota), may help to make immature newborn infants more resistant to gut dysfunctions, both short and long term.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-716) contains supplementary material, which is available to authorized users.

PC.42 Compliance with Oxygen Saturation Targets during Neonatal Transport

BackgroundThere is a new emphasis in neonatal care in ensuring target levels of oxygen saturation are achieved to maximise the benefits and minimise the complications of oxygen therapy.MethodsAll infants <36...

Effect of thyroxine on brain microstructure in extremely premature babies: magnetic resonance imaging findings in the TIPIT study

In order to assess relationships between thyroid hormone status and findings on brain MRI, a subset of babies was recruited to a multi-centre randomised, placebo-controlled trial of levothyroxine (LT4) supplementation for babies born before 28 weeks' gestation (known as the TIPIT study, for Thyroxine supplementation In Preterm InfanTs). These infants were imaged at term-equivalence. Forty-five TIPIT participants had brain MRI using diffusion tensor imaging (DTI) to estimate white matter development by apparent diffusion coefficient (ADC), fractional anisotropy (FA) and tractography metrics of number and length of streamlines. We made comparisons between babies with the lowest and highest plasma FT4 concentrations during the initial 4 weeks after birth. There were no differences in DTI metrics between babies who had received LT4 supplementation and those who had received a placebo. Among recipients of a placebo, babies in the lowest quartile of plasma-free thyroxine (FT4) concentrations had significantly higher apparent diffusion coefficient measurements in the posterior corpus callosum and streamlines that were shorter and less numerous in the right internal capsule. Among LT4-supplemented babies, those who had plasma FT4 concentrations in the highest quartile had significantly lower apparent diffusion coefficient values in the left occipital lobe, higher fractional anisotropy in the anterior corpus callosum and longer and more numerous streamlines in the anterior corpus callosum. DTI variables were not associated with allocation of placebo or thyroid supplementation. Markers of poorly organised brain microstructure were associated with low plasma FT4 concentrations after birth. The findings suggest that plasma FT4 concentrations affect brain development in very immature infants and that the effect of LT4 supplementation for immature babies with low FT4 plasma concentrations warrants further study.

Challenges of Minimizing Heat Loss at Birth: A Narrative Overview of Evidence-Based Thermal Care Interventions

Evidence-based thermal care recommendations designed to minimize heat loss immediately at birth are readily available however, hypothermia still persists as a global challenge especially when caring for the most immature and smallest preterm infants. In this narrative overview we aim to provide the reader with a succinct summary of the causes and consequences of hypothermia, the extent of the problem (rates of hypothermia), principles of good thermal care, delivery room preventative measures, the research evidence underpinning existing interventions, current issues in practice, and the way forward. Due to the plethora of research literature available in this subject area, our article will focus primarily on evidence derived from systematic reviews and randomized or quasi-randomized controlled trials assessing the effectiveness of interventions to prevent hypothermia in the most vulnerable (preterm/low birth weight) infants where the intervention or combination of interventions is applied immediately at birth.

Lactobacillus paracasei CBA L74 Metabolic Products and Fermented Milk for Infant Formula Have Anti-Inflammatory Activity on Dendritic Cells In Vitro and Protective Effects against Colitis and an Enteric Pathogen In Vivo

The rapid expansion of commercially available fermented food products raises important safety issues particularly when infant food is concerned. In many cases, the activity of the microorganisms used for fermentation as well as what will be the immunological outcome of fermented food intake is not known. In this manuscript we used complex in vitro, ex-vivo and in vivo systems to study the immunomodulatory properties of probiotic-fermented products (culture supernatant and fermented milk without live bacteria to be used in infant formula).We found in vitro and ex-vivo that fermented products of Lactobacillus paracasei CBA L74 act via the inhibition of proinflammatory cytokine release leaving anti-inflammatory cytokines either unaffected or even increased in response to Salmonella typhimurium. These activities are not dependent on the inactivated bacteria but to metabolic products released during the fermentation process. We also show that our in vitro systems are predictive of an in vivo efficacy by the fermented products. Indeed CBA L74 fermented products (both culture medium and fermented milk) could protect against colitis and against an enteric pathogen infection (Salmonella typhimurium). Hence we found that fermented products can act via the inhibition of immune cell inflammation and can protect the host from pathobionts and enteric pathogens. These results open new perspectives in infant nutrition and suggest that L. paracasei CBA L74 fermented formula can provide immune benefits to formula-fed infants, without carrying live bacteria that may be potentially dangerous to an immature infant immune system.

Effectiveness and safety of seasonal influenza vaccination in children with underlying respiratory diseases and allergy.

Influenza causes acute respiratory infections and various complications. Children in the high-risk group have higher complication and hospitalization rates than high-risk elderly individuals. Influenza prevention in children is important, as they can be a source infection spread in their communities. Influenza vaccination is strongly recommended for high-risk children with chronic underlying circulatory and respiratory disease, immature infants, and children receiving long-term immunosuppressant treatment or aspirin. However, vaccination rates in these children are low because of concerns regarding the exacerbation of underlying diseases and vaccine efficacy. To address these concerns, many clinical studies on children with underlying respiratory diseases have been conducted since the 1970s. Most of these reported no differences in immunogenicity or adverse reactions between healthy children and those with underlying respiratory diseases and no adverse effects of the influenza vaccine on the disease course. Further to these studies, the inactivated split-virus influenza vaccine is recommended for children with underlying respiratory disease, in many countries. However, the live-attenuated influenza vaccine (LAIV) is not recommended for children younger than 5 years with asthma or recurrent wheezing. Influenza vaccination is contraindicated in patients with severe allergies to egg, chicken, or feathers, because egg-cultivated influenza vaccines may contain ovalbumin. There has been no recent report of serious adverse events after influenza vaccination in children with egg allergy. However, many experts recommend the trivalent influenza vaccine for patients with severe egg allergy, with close observation for 30 minutes after vaccination. LAIV is still not recommended for patients with asthma or egg allergy.

Persisting hypoxaemia is an insufficient measure of adverse lung function in very immature infants

BackgroundBronchopulmonary dysplasia (BPD), defined as protracted neonatal hypoxaemia, is considered a risk factor for respiratory disease in adulthood. The relationship between this diagnosis and the actual lung injury appearing in...