Genetic predisposition of RSV infection-related respiratory morbidity in preterm infants

The aim of this study was to assess whether prematurely born infants have a genetic predisposition to respiratory syncytial virus (RSV) infection-related respiratory morbidity. One hundred and forty-six infants born at less than 36 weeks of gestation were prospectively followed. Nasopharygeal aspirates were obtained on every occasion the infants had a lower respiratory tract infection (LRTI) regardless of need for admission. DNA was tested for 11 single-nucleotide polymorphisms (SNPs). Chronic respiratory morbidity was assessed using respiratory health-related questionnaires, parent-completed diary cards at a corrected age of 1 year and review of hospital notes. Lung function was measured at a post menstrual age (PMA) of 36 weeks and corrected age of 1 year. A SNP in ADAM33 was associated with an increased risk of developing RSV LRTIs, but not with significant differences in 36-week PMA lung function results. SNPs in several genes were associated with increased chronic respiratory morbidity (interleukin 10 (IL10), nitric oxide synthase 2A (NOS2A), surfactant protein C (SFTPC), matrix metalloproteinase 16 (MMP16) and vitamin D receptor (VDR)) and reduced lung function at 1 year (MMP16, NOS2A, SFTPC and VDR) in infants who had had RSV LRTIs. Conclusions: Our results suggest that prematurely born infants may have a genetic predisposition to RSV LRTIs and subsequent respiratory morbidity which is independent of premorbid lung function.     

Respiratory outcome of prematurely born infants following human rhinovirus A and C infections

Human rhinoviruses (HRVs) are a common cause of lower respiratory tract infections (LRTIs) and are associated with chronic respiratory morbidity. Our aim was to determine whether HRV species A or C were associated with chronic respiratory morbidity and increased health care utilisation in prematurely born infants. A number of 153 infants with a median gestational age of 34 (range 23–35) weeks were prospectively followed. Nasopharyngeal aspirates were collected whenever the infants had LRTIs regardless of hospitalisation status. Parents completed a respiratory diary card and health questionnaire about their infant when they were 11 and 12 months corrected age, respectively. The health-related cost of care during infancy was calculated from the medical records using the National Health Service (NHS) reference costing scheme and the British National Formulary for children. There were 32 infants that developed 40 HRV LRTIs; samples were available from 23 of the 32 infants for subtyping. Nine infants had HRV-A LRTIs, 13 HRV-C LRTIs, and one infant had a HRV-B LRTI. Exclusion of infants who also had RSV LRTIs revealed that the infants who had a HRV-C LRTI were more likely to wheeze (p?<?0.0005) and use respiratory medications (p?<?0.0005) and had more days of wheeze (p?=?0.01) and used an inhaler (p?=?0.02) than the no LRTI group. In addition, the respiratory cost of care was greater for the HRV-C LRTI than the no LRTI group (p?<?0.0005). Conclusion: Our results suggest HRV-C is associated with chronic respiratory morbidity during infancy in prematurely born infants.     

Diminished lung function, RSV infection, and respiratory morbidity in prematurely born infants

Background

Diminished lung function appears to be a risk factor for respiratory syncytial virus (RSV) infection/bronchiolitis in term born infants.

Aims

To determine if diminished lung function prior to neonatal unit discharge was associated with subsequent symptomatic RSV lower respiratory tract infection (LRTI) and respiratory morbidity in prematurely born infants.

Methods

Of 39 infants in a tertiary neonatal intensive care unit (median gestational age 28 weeks, range 23–31), 20 had bronchopulmonary dysplasia. Lung function (compliance and resistance of the respiratory system (C_rs and R_rs) and functional residual capacity (FRC)) was measured on the neonatal unit at 36 weeks postmenstrual age (PMA). Following neonatal unit discharge, nasopharyngeal aspirates were obtained on every occasion, at home or in hospital, an infant had an LRTI. RSV was identified by immunofluorescence and/or culture.

Results

The 15 infants who suffered a symptomatic RSV LRTI had a higher mean R_rs and suffered more wheeze at follow up than the rest of the cohort. Regression analysis showed that a high R_rs was significantly associated with a symptomatic RSV LRTI; significant factors for cough were a high R_rs and a symptomatic RSV LRTI, and for wheeze were a high R_rs.

Conclusion

Prematurely born infants, who had a symptomatic RSV LRTI and/or respiratory morbidity at follow up, had worse lung function prior to neonatal unit discharge.     

Diminished lung function, RSV infection, and respiratory morbidity in prematurely born infants.

BACKGROUND: Diminished lung function appears to be a risk factor for respiratory syncytial virus (RSV) infection/bronchiolitis in term born infants. AIMS: To determine if diminished lung function prior to neonatal unit discharge was associated with subsequent symptomatic RSV lower respiratory tract infection (LRTI) and respiratory morbidity in prematurely born infants. METHODS: Of 39 infants in a tertiary neonatal intensive care unit (median gestational age 28 weeks, range 23-31), 20 had bronchopulmonary dysplasia. Lung function (compliance and resistance of the respiratory system (C(rs) and R(rs)) and functional residual capacity (FRC)) was measured on the neonatal unit at 36 weeks postmenstrual age (PMA). Following neonatal unit discharge, nasopharyngeal aspirates were obtained on every occasion, at home or in hospital, an infant had an LRTI. RSV was identified by immunofluorescence and/or culture. RESULTS: The 15 infants who suffered a symptomatic RSV LRTI had a higher mean R(rs) and suffered more wheeze at follow up than the rest of the cohort. Regression analysis showed that a high R(rs) was significantly associated with a symptomatic RSV LRTI; significant factors for cough were a high R(rs) and a symptomatic RSV LRTI, and for wheeze were a high R(rs). CONCLUSION: Prematurely born infants, who had a symptomatic RSV LRTI and/or respiratory morbidity at follow up, had worse lung function prior to neonatal unit discharge.     

Incidence and risk factors of lower respiratory tract illnesses during infancy in a Mediterranean birth cohort

Abstract Aim: To investigate the incidence rate, viral respiratory agents and determinants of lower respiratory tract illnesses (LRTIs) in infants younger than 1 year. Methods: A total of 487 infants were recruited at birth for the Asthma Multicenter Infant Cohort Study in Barcelona (Spain). Cases of LRTIs were ascertained through an active register including a home visit and viral test in nasal lavage specimens during the first year of life. Cotinine in cord blood, household aeroallergens, indoor NO(2) and maternal and neonatal IgE were measured. Other maternal and infants' characteristics were obtained from structured questionnaires. Results: The incidence rate of at least one LRTI was 38.7 infants per 100 persons-years. The most frequently isolated viral agent was respiratory syncytial virus (44.7%). The risk of LRTIs was higher in infants with a maternal history of asthma and in those with siblings (OR = 2.4; 95% CI: 0.98-6.08 and OR = 1.8; 95% CI: 1.04-3.21, respectively). The risk of LRTIs was lower in infants who were breast fed for more than 12 weeks (OR = 0.26; 95% CI: 0.26-0.86) and in those from a low socioeconomic class (OR = 0.16; 95% CI: 0.06-0.42). Conclusion: Viral LRTIs are frequent in infants younger than 1 year of age and there is an inter-relationship between maternal asthma, siblings, breast feeding and socioeconomic status.     

Effect of position on oxygen saturation and requirement in convalescent preterm infants

Aims: To document the effect of position on oxygen saturation and changes in oxygen requirement in convalescent preterm infants. Methods: Twelve infants born ≥24 and ≤32 weeks gestation, extubated and without congenital anomaly were studied using nap polysomnography in prone and supine, twice weekly until discharge. Mean oxygen saturation (SpO₂), minimum SpO₂, mean minimum SpO₂ and time with SpO₂ < 90% were measured in active sleep. Results: Eight male and four female infants [median gestation 28 (24–31) weeks and median birthweight 1059 (715–1840) g] had 39 studies. For 21 of 39 studies, the infant was on respiratory support. Four infants had chronic lung disease (CLD). SpO₂ varied with postmenstrual age (PMA) (p = 0.003) but not with position (p = 0.36), and PMA did not influence the effect of position on SpO₂ (p = 0.19). SpO₂ was lower for those with CLD (p < 0.0001) and those on respiratory support (p < 0.001), but there was no effect of position (p = 0.97 and p = 0.67, respectively). From 36 weeks PMA, a change to supine did not increase oxygen requirement. Conclusion: In preterm infants, PMA and residual respiratory disease have greater effects on oxygenation than position. A supine sleep position is not disadvantageous for preterm infants at discharge.     

Lower respiratory tract illness and RSV prophylaxis in very premature infants.

AIMS: To determine the frequency of and the risk factors for readmissions for any lower respiratory tract illness (LRTI) and for respiratory syncytial virus (RSV) documented LRTI in children born very prematurely who had or had not received RSV prophylaxis. METHODS: Multicentre prospective longitudinal cohort study of 2813 infants, born between April 2000 and December 2000 at less than 33 weeks of gestational age, and followed until the end of the epidemic season. RESULTS: Among the 2256 children who had no bronchopulmonary dysplasia at 36 weeks of postmenstrual age and were not submitted to RSV prophylaxis, 27.4% were readmitted at least once for any reason during the epidemic season; 15.1% and 7.2% were readmitted at least once for any LRTI and RSV related LRTI, respectively. Children born at less than 31 weeks' gestation, having an intrauterine growth restriction, or living in a single mother family were at a significantly higher risk of readmission for LRTI in general as well as for RSV related LRTI. Of the 376 children submitted to prophylaxis, 28.2% were readmitted at least once for any LRTI and 6.1% for RSV related LRTI. CONCLUSION: One out of four children who had received no prophylaxis, was born very prematurely, and was without bronchopulmonary dysplasia at 36 weeks of postmenstrual age, was readmitted at least once for any reason. Roughly 50% and 20% of these readmissions were related to a LRTI and an RSV infection, respectively. Further epidemiological studies are warranted to assess the aetiology and impact of other respiratory pathogens on post-discharge readmission and respiratory morbidity in this population.     

Adenovirus respiratory infection in hospitalized children in Hong Kong: serotype–clinical syndrome association and risk factors for lower respiratory tract infection

Lower respiratory tract infections (LRTI) caused by adenovirus can be severe with resultant chronic pulmonary sequelae. More than 50 serotypes have been recognized; however, the exact association of serotype with clinical phenotype is still unclear. There have been no reports on the adenovirus serotype pattern in Hong Kong, and their relationships with disease manifestations and complications are not known. Clinical and epidemiological data on 287 children (<6 years old) admitted with adenovirus respiratory infections from 2001 to 2004 were reviewed. Common presenting symptoms included fever (97.9 %) and cough and rhinitis (74 %). Extra-pulmonary manifestations were present in 37.3 %. The clinical picture mimicked bacterial infection for its prolonged high fever and neutrophilic blood picture. Forty-two patients (14.6 %) had LRTI, either pneumonia or acute bronchiolitis, but none had severe acute respiratory compromise. Children aged 1 to 2 years old were most at risk for adenovirus LRTI (adjusted p?=?0.0165). Serotypes 1 to 7 could be identified in 93.7 % of the nasopharyngeal specimens, with serotypes 2 and 3 being the most prevalent. Different serotypes showed predilection for different age groups and with different respiratory illness association. The majority of acute bronchiolitis (71.4 %) were associated with serotype 2 infection, and this association was statistically significant (p?<?0.0001). Serotype 3 infection accounted for over half of the pneumonia cases (57–75 %) in those aged 3–5 years old. Only one patient developed mild bronchiectasis after serotype 7 pneumonia. Children aged 1 to 2 years old were the at-risk group for adenovirus LRTI, but respiratory morbidity was relatively mild in our locality. There was an apparent serotype–respiratory illness association.     

Bronchopulmonary dysplasia and neurodevelopmental outcome in extremely preterm neonates

We tested the hypothesis that the use of supplemental oxygen (sO₂) at discharge from the NICU in extremely preterm neonates is associated with a greater risk of neurodevelopmental impairment (NDI) at 18 months corrected gestational age (CGA) than the risk of NDI of those neonates discharged in room air. Four hundred twenty-four charts were retrospectively reviewed from infants born at <27 weeks and transferred to Nationwide Children’s Hospital from December 1, 2004 to June 14, 2010. Use of sO₂ was evaluated on day of life (dol) 28, at 36 weeks post-menstrual age (PMA), and at discharge. Logistic regression was used to identify postnatal risk factors associated with sO₂ at discharge and NDI. At dol 28, 96 % of surviving patients received sO₂, and therefore had bronchopulmonary dysplasia (BPD) by definition from a National Institutes of Child Health and Human Development workshop. At 36 weeks PMA, 89 % continued on sO₂ (moderate/severe BPD), and at discharge, 74 % continued on sO₂. When factors associated with NDI were examined, the need for mechanical ventilation ≥28 days (adjOR?=?3.21, p?=?0.01), grade III–IV intraventricular hemorrhage (IVH) (adjOR?=?4.61, p?<?0.01), and discharge at >43 weeks PMA (adjOR?=?2.12, p?=?0.04) were the strongest predictors of NDI at 18 months CGA. There was no difference in Bayley Scales of Infant Development, third edition composite scores between patients with no/mild BPD and patients with moderate/severe BPD (cognitive p?=?0.60, communication p?=?0.53, motor p?=?0.19) or those scores between patients on and off oxygen at discharge (cognitive p?=?0.58, communication p?=?0.70, motor p?=?0.62). Conclusions: The need for sO₂ at discharge is not associated with an increased risk of NDI in these patients. The strongest predictors of poor neurodevelopmental outcome in this population were prolonged positive pressure support, grade III–IV IVH, and discharge at >43 weeks PMA.     

Enteral vitamin A for reducing severity of bronchopulmonary dysplasia in extremely preterm infants: a randomised controlled trial

Background

Intramuscular vitamin A supplementation decreases the risk of bronchopulmonary dysplasia (BPD) in very-low-birth-weight preterm infants without significant adverse effects. However, intramuscular vitamin A supplementation is not widely accepted because of the discomfort and risk of trauma associated with repeated injections. Enteral vitamin A supplementation has not been studied adequately in the clinical trials. Enterally administered water-soluble vitamin A is absorbed better than the fat-soluble form. We hypothesised that enteral administration of a water-soluble vitamin A preparation will decrease severity of BPD compared with a control group receiving placebo.

Methods

We plan a double-blind randomised placebo-controlled trial at a tertiary neonatal-perinatal intensive care unit. Eligibility criteria include infants born at less than 28 weeks’ gestational age and less than 72 h of life. Infants with major congenital gastrointestinal or respiratory tract abnormalities will be excluded. After parental consent, infants will be randomized to receive either enteral water-soluble vitamin A (5000 IU once a day) or placebo. The intervention will be started within 24 h of introduction of feeds and continued until 34 weeks’ post-menstrual age (PMA).The primary outcome is severity of BPD at 36 weeks’ PMA. Severity of BPD will be assessed objectively from the right-shift of the peripheral oxyhaemoglobin saturation versus partial pressure of inspired oxygen (SpO₂-PiO₂) curve. We require 188 infants for 80% power and 5% significance level based on an expected 20% decrease in the right shift of the SpO₂-PiO₂ curve in the vitamin A group (primary outcome) compared with control group at 36 weeks’ PMA, and a 20% attrition rate.Secondary outcomes will be plasma and salivary concentrations of vitamin A on day 28 of the trial (first 30 infants), lung and diaphragm function, clinical outcomes at 36 week’ PMA or before discharge/death, and safety of vitamin A.

Discussion

BPD poses a significant economic burden on the health-care system. If our study shows that enteral supplementation of water-soluble vitamin A is safe and effective for decreasing the severity of BPD, it will provide the opportunity to further evaluate a simple, globally acceptable preventive therapy for BPD.

Trial registration

ANZCTR; ACTRN12616000408482 (30th March 2016).

     

Respiratory syncytial virus infection and chronic respiratory morbidity – is there a functional or genetic predisposition?

A systematic literature review has been undertaken. Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) in infancy is associated with chronic respiratory morbidity. Premorbid abnormal lung function may predispose to RVS LRTI in prematurely born infants. Conclusion: Single‐nucleotide polymorphisms in genes coding for IL‐8, IL‐19, IL‐20, IL‐13 mannose‐binding lectin, IFNG and a RANTES polymorphism have been associated with subsequent wheeze following RSV LRTI in term‐born infants.     

Sleeping position, oxygen saturation and lung volume in convalescent, prematurely born infants

OBJECTIVE: To determine whether the effects of sleeping position on lung volume and oxygenation are influenced by postmenstrual age (PMA) and oxygen dependency in convalescent prematurely born infants. DESIGN: Prospective study. SETTING: Tertiary neonatal unit. PATIENTS: 41 infants (21 oxygen dependent), median gestational age 28 weeks (range 24-31 weeks) and birth weight 1120 g (range 556-1780 g). INTERVENTION: Infants were studied both supine and prone at two-weekly intervals from 32 weeks' PMA until discharge. Each posture was maintained for 1 h. MAIN OUTCOME MEASURES: Pulse oximeter oxygen saturation (Spo(2)) was monitored continuously, and at the end of each hourly period functional residual capacity (FRC) was measured. RESULTS: Overall, lung volumes were higher in the prone position throughout the study period; there was no significant effect of PMA on lung volumes. Overall, Spo(2) was higher in the prone position (p = 0.02), and the effect was significant in the oxygen-dependent infants (p = 0.03) (mean difference in Spo(2) between prone and supine was 1.02%, 95% CI 0.11% to 1.92%), but not in the non-oxygen-dependent infants. There was no significant influence of PMA on Spo(2). CONCLUSION: In the present study, prone sleeping did not improve oxygenation in prematurely born infants, 32 weeks' PMA or older and with no ongoing respiratory problems. However, the infants were monitored in each position for an hour, thus it is recommended that oxygen saturation should continue to be monitored after 32 weeks' PMA to be certain that longer periods of supine sleeping are not associated with loss of lung volume and hypoxaemia.     

Lung Function and Respiratory Health at School Age in Ventilated Very Low Birth Weight Infants

Objective

To investigate respiratory health and lung function in school-aged children without broncho-pulmonary dysplasia (BPD), who were very low birth weight (VLBWi) and randomized at birth to high frequency oscillatory ventilation (HFOV) or volume guarantee (VG) ventilation for severe respiratory distress syndrome (RDS).

Methods

In this observational study, 7-y-old ex-preterm infants with severe RDS, randomly assigned at birth to receive assisted/control ventilation?+?VG (Vt?=?5 mL/kg, PEEP?=?5 cmH₂O)(VG group; mean GA 27?±?2 wk; mean BW 1086?±?158 g) or HFOV (HFOV group; mean GA: 27?±?2; mean BW: 1090?±?139 g) (both groups were ventilated with Drager Babylog 8000 plus) were recalled. Neonatal clinical data and outcome were known. Actual outcomes were investigated with an interview; lung function was measured by whole-body plethysmography.

Results

Twenty five children were studied (VG group, n?=?13 vs. HFOV group, n?=?12). There were no differences in anthropometric data, drugs (steroids/bronchodilators and antibiotics) or hospital readmission for respiratory disorders. Compliance to the test was adequate. The authors found a similar obstructive deficit (elevated values: airway resistance (RAW), residual volume (RV), total lung capacity (TLC) with near-normal spirometry) in both groups suggesting a persistent airflow limitation even in absence of BPD.

Conclusions

VLBW infants even in absence of BPD, need long term respiratory follow-up, because they frequently show an impairment of lung function, independent from initial respiratory support, even if at birth the choice is a lung protective approach (e.g., HFOV or VG ventilation).     

Are late preterm infants as susceptible to RSV infection as full term infants?

Preterm infants are at increased risk of being rehospitalised during the first few months of life with severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) that usually manifests as apnea and hypoxemia. This occurs more commonly in preterm infants < 33 weeks gestational age (GA), but recent studies demonstrate that late preterm infants (those born between 34 weeks and 0 days to 36 weeks and 6 days GA) are equally susceptible to RSV LRTI as those with lower GA. Factors associated with severe LRTI include immaturity of both the humoral and cell-mediated immune system and interrupted lung development prior to 36 weeks GA which results in lower functional residual capacity, reduced compliance, diminished forced expiratory air flow and impaired gas exchange. Morbidity and mortality are significantly increased in late preterms compared to their term counterparts. Prophylaxis with palivizumab against RSV infection seems to be crucial. Due to the large number of infants in this age group, additional risk factors have been identified in order to tailor palivizumab prophylaxis effectively to those at highest risk for severe RSV LRTI.     

Swimming pool attendance, respiratory symptoms and infections in the first year of life

We evaluated the relationship between indoor and outdoor swimming pool attendance and respiratory symptoms and infections during the first year of life. A population-based mother–child cohort study was conducted in four Spanish areas (INMA project). Study subjects were recruited at pregnancy, followed to delivery and 14 months after birth. Information on swimming pool attendance and health manifestations during the first year of life was collected at 14 months: low respiratory tract infection (LRTI), persistent cough, wheezing, atopic eczema and otitis. Odds ratios and 95 % confidence interval (OR 95 %CI) were calculated by logistic regression adjusting for confounders. Among the 2,205 babies included, 37 % reported having LRTI, 37 % wheezing, 16 % persistent cough, 22 % atopic eczema, 33 % otitis and 50 % attended swimming pools during the first year of life. Around 40 % went to outdoor pools in summer with a median cumulative duration of 7.5 h/year, and 20 % attended indoor pools with a median cumulative duration of 18 h/year. Pool attendance differed by area, season of birth and sociodemographic characteristics, and was not associated with LRTI, wheezing, persistent cough, atopic eczema or otitis. Adjusted OR of wheezing and LRTI were, respectively, 1.06 (95 %CI, 0.88–1.28) and 1.09 (0.90–1.31) for babies attending vs. babies not attending pools. Stratification by type of swimming pool, cumulative duration or parental atopy did not modify the results. Conclusion: No association was detected between pool attendance and LRTI, wheezing, persistent cough, atopic eczema or otitis during the first year of life in Spain.     

Pulmonary Functions Before and After Pediatric Cardiac Surgery

This study aimed to assess pulmonary functions before and after cardiac surgery in infants with congenital heart diseases and pulmonary overflow and to clarify which echocardiographic parameter correlates best with lung mechanics. Between 2008 and 2009, 30 infants with left-to-right shunt congenital acyanotic heart diseases who had indications for reparative surgery of these lesions were assessed by echocardiography and infant pulmonary function tests before the operation and 6 months afterward. Tests using baby body plethysmography were performed to assess the following infant pulmonary functions: tidal volume, respiratory rate, respiratory system compliance (C _rs) and respiratory system resistance, functional residual capacity (FRC), and airway resistance. The mean age of the patients was 10.47 ± 3.38 months, and their mean weight was 6.81 ± 1.67 kg. Ventricular septal defect and combined lesions were the predominant cardiac diseases (26.7 %). Comparison of the infant pulmonary function tests showed a highly significant improvement in all the parameters between the preoperative and 6-month postoperative visits (p < 0.0001). Systolic pulmonary artery pressure had a statistically significant negative correlation with C _rs (r = ?0.493, p = 0.006) and a positive correlation with FRC (r = 0.450, p = 0.013). The findings showed that C _rs had a statistically significant negative correlation with the pulmonary artery size (r = ?0.398, p = 0.029) and the left atrium size (r = ?0.395, p = 0.031), whereas the pulmonary artery size had a statistically positive correlation with effective resistance (r = 0.416, p = 0.022) and specific effective resistance (r = 0.604, p = 0.0001). Surgical correction of left-to-right shunt congenital heart diseases had a positive impact on lung compliance, airway resistance, and FRC. Noninvasive echocardiographic parameters assessing pulmonary vascular engorgement and pulmonary artery pressure were closely related to these infant pulmonary function test indexes.     

Severe bronchiolitis in infants born very preterm and neurodevelopmental outcome at 2 years

Preterm infants are at greater risk of bronchopulmonary dysplasia, which is associated with neurodevelopmental impairment. These infants are also more likely to develop severe bronchiolitis, which can contribute to neurodevelopmental impairment. The aim of this study was to determine whether severe bronchiolitis in very preterm infants (born before 33 weeks of gestation) was associated with an increased risk of neurodevelopmental impairment at 2 years of age. We analyzed a population-based cohort of infants (the Loire Infant Follow-up Team cohort) born between 1 January 2003 and 31 December 2009. Severe bronchiolitis was defined as hospitalization due to bronchiolitis during the first year of life. Neurodevelopmental outcome was assessed at 2 years of corrected age. A total of 2,405 infants were included in this analysis and categorized based on neonatal respiratory status: 1,308 (54.4 %) received no respiratory assistance, 864(35.9 %) received oxygen for <28 days, and 167 (6.9 %) had mild and 66 (2.7) moderate or severe bronchopulmonary dysplasia. At 2 years, 502 children displayed non-optimal neurodevelopmental outcome (20.9 %). Moderate or severe bronchopulmonary dysplasia was significantly associated with non-optimal neurodevelopmental outcome at 2 years (adjusted odds ratios (OR)?=?2.3 [95 % confidence interval (CI): 1.3–3.9], p?=?0.003). In the first year, 318 infants acquired severe bronchiolitis (13.2 %), which was not associated with non-optimal neurodevelopmental outcome (adjusted OR?=?1.0 [95 % CI: 0.8–1.4]; p?=?0.88). In conclusion, respiratory status in the neonatal period was significantly associated with non-optimal neurodevelopmental outcome at 2 years, while severe bronchiolitis was not.     

Effect of non-human neutral and acidic oligosaccharides on allergic and infectious diseases in preterm infants

Short-term supplementation of non-human neutral and acidic oligosaccharides during the first postnatal weeks may enhance the maturation of the immune response in preterm infants and may lead to less allergic and infectious diseases during the first year of life. In a randomized controlled trial, 113 preterm infants (gestational age <32 weeks and/or birth weight <1500 g) were allocated to receive enteral neutral and acidic oligosaccharide supplementation or placebo between days 3 and 30 of life. The median age at follow-up was not different in both groups: 12 months corrected age (interquartile range [IQR], 11–15) in the prebiotic mixture group and 12 months corrected age in the placebo group (IQR, 10–19), respectively. In addition, baseline patient, maternal, and environmental characteristics were not different between the prebiotic mixture (n?=?48) and placebo (n?=?46) group. Incidence of allergic and infectious diseases was assessed by validated questionnaires. In total, 94/98 (96 %) of the eligible, surviving infants participated in this follow-up study. The incidence of atopic dermatitis (odds ratio [OR], 0.80; 95 % confidence interval [CI], 0.24–2.67), bronchial hyper-reactivity (OR, 1.04; 95 % CI, 0.38–2.87) and infections of the upper respiratory (OR, 0.95; 95 % CI, 0.37–2.44), lower respiratory (OR, 1.03; 95 % CI, 0.37–2.88), and gastrointestinal (OR, 1.77; 95 % CI, 0.55–5.73) tract was not different between the groups. Adjustment for potential confounding factors did not change the results of the primary analysis. Conclusion: Short-term enteral supplementation of non-human neutral and acidic oligosaccharides during the neonatal period in preterm infants does not decrease the incidence of allergic and infectious diseases during the first year of life.     

Radiological outcome of very prematurely born infants randomised to high frequency oscillatory or conventional ventilation

The appearance of the chest radiograph (CXR) at 28 days after birth or 36 weeks post-menstrual age (PMA) has been shown to be predictive of respiratory symptoms at follow-up. The aim of this study was to determine whether the CXR appearance at 28 days or 36 weeks PMA differed according to the ventilatory mode used in the perinatal period. CXRs were routinely obtained at 28 days and 36 weeks PMA from infants entered into a multicentre randomised trial (UKOS) comparing high frequency oscillatory ventilation (HFOV) and conventional mechanical ventilation (CMV); the ventilation allocation mode had been instituted within 60 min of birth. The CXRs were assessed using a scoring system (maximum score 8) for the presence of fibrosis/interstitial shadows, cystic elements and hyperinflation. A total of 487 infants, median gestational age 26+5 weeks (range 23–28+6 weeks) and birth weight 865 g (range 428–1459 g) who had had a CXR taken at 28 days and/or 36 weeks PMA. No significant differences were found between the total CXR scores of the two groups either at 28 days or 36 weeks PMA (mean scores 3.2 HFOV versus 3.5 CMV, 95%CI for difference –0.66 to 0.06, P=0.11 at 28 days and mean scores 3.5 HFOV versus 3.6 CMV, 95% for difference –0.49 to 0.29, P=0.61 at 36 weeks PMA). Conclusion:These results are consistent with high frequency oscillatory ventilation and conventional mechanical ventilation having similar effects on pulmonary function in very prematurely born infants.