Prone or supine for infants with chronic lung disease at neonatal discharge?

OBJECTIVE: To determine whether infants with chronic lung disease (CLD), ready for neonatal unit discharge, maintain cardiorespiratory stability while sleeping supine. METHODS: Subjects were 15 infants born < 32 weeks gestational age (GA) and ready for discharge from the regional tertiary neonatal intensive care unit. Polysomnography recordings of sleep state, heart rate, arterial oxygen saturation, respiratory effort and nasal/oral airflow were taken prone and supine for up to 3 h post feed with the first position randomly allocated. The main outcome measures were oxygen saturation and apnoea hypopnoea index (AHI). RESULTS: Seven infants (median GA 27 weeks, birthweight 945 g) had CLD and eight infants (median GA 29 weeks, birthweight 1160 g) did not. CLD infants were more mature at study than non-CLD infants (median 39 vs 36 weeks, P = 0.019). Neither oxygen saturation nor AHI were position dependent and no group differences were noted with respect to CLD status. There was a significant interaction of GA and sleep position with less-mature infants spending less time in quiet sleep (QS) in supine position (P = 0.006). These less-mature infants also had a higher AHI (P = 0.033). As expected, the AHI and arousal index (AI) were higher in active sleep (P < or = 0.001, P = 0.013, respectively) and mean oxygen saturation was lower (P = 0.001). CONCLUSIONS: The supine position appears appropriate for very preterm infants with CLD going home from the neonatal unit. Respiratory instability on neonatal discharge is more likely to be associated with immaturity than CLD.     

Awake and asleep oxygen saturations in infants with chronic neonatal lung disease

Aim: There is uncertainty about the best method of withdrawing supplemental oxygen in babies with chronic neonatal lung disease (CNLD). Some authors advocate withdrawal of oxygen in the day, but continuing supplementation during sleep, based on early work suggesting that oxygen saturations are lower during sleep, which did not accord with our clinical impression. We re‐examined the hypothesis that babies have lower saturations while asleep. Methods: We studied infants with CNLD during the day, while awake and asleep. We recorded video with simultaneous real‐time capture of oxygen saturation (SpO₂), heart rate and plethysmographic waveform from pulse oximetry. Behavioural state was scored using observation and video and classified as awake (feeding, active or quiet) or sleep. Results: Thirteen infants had analysable data, although one had strikingly lower SpO₂ values while awake and was excluded from analysis. The infants had a median gestation of 26 weeks and were studied at a median (range) postmenstrual age of 66 (37–130) weeks, for 229 (89–330) min. Mean SpO₂ was 97.6% during sleep and 97.0% awake (p = 0.011). Conclusion: Babies with CNLD have lower oxygen saturation while awake. There is no physiological justification for increasing oxygen during sleep, or withdrawing selectively during the daytime, although larger studies are needed to confirm this finding.     

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.     

Targeted oxygen therapy in special care nurseries: Is uniformity a good thing?

Aim: There is wide variation in the commencement of inspired oxygen (FiO2) and the oxygen saturation (SpO₂) targets set in special care nurseries (SCNs). Evidence supports minimising unnecessary oxygen exposure. Does the introduction of a protocol advocating the uniform approach of commencing FiO2 at 30% and targeting SpO2 of 94–96% for infants ≥33 weeks gestation with respiratory distress reduce oxygen exposure? Methods: A ‘Before After’ study was undertaken in three SCNs. Data were recorded for all infants admitted to the SCNs who required oxygen over a 3‐year period. Infants were analysed in gestational age groups: 33–36 weeks (late preterm) and +37 weeks (term/post‐term). Results: Of the 19 830 infants born, 868 (4%) were treated with oxygen. The introduction of an oxygen‐targeting protocol resulted in a statistically and clinically significant reduction in the proportion of infants who were treated with any oxygen for 1 h or more, 4 h or more and in the proportion who received >30% FiO2 for 1 h or more (all P≤ 0.01). This reduction was significant for infants of both gestational age groups. The median duration of oxygen for term/post‐term infants was reduced from 12 h pre‐protocol to 10 h post‐protocol (P= 0.01); however, no significant difference was found for the preterm group (reduced from 11 to 8 h, P= 0.07). Conclusion: Introduction of a uniform oxygen protocol in SCNs for infants ≥33 weeks gestation with respiratory distress reduces the number of infants receiving oxygen and, in term infants, the duration of oxygen exposure.     

‘Propped and prone’ positioning reduces respiratory events in spontaneously breathing preterm infants: A randomised triple crossover study

Aim

We compared effects of infant positioning and feed-rate interventions on respiratory events and oximetry parameters in spontaneously breathing preterm infants born <32 weeks gestation managed in a neonatal unit.

Methods

A randomised triple crossover design was employed. n = 68 infants underwent three test conditions A: control (supine/flat, gravity bolus feeds), B: position intervention (propped/prone) and C: feed-rate intervention (continuous pump feeds) in randomised sequence over three consecutive days. Primary outcomes were number of events (apnoea, bradycardia and desaturation) and percentage time SpO₂ < 80% over 24 h. The secondary outcome was percentage time SpO₂ ≥ 88%. Treatment effects were estimated using linear mixed-effects models.

Results

Propped/prone positioning significantly reduced events and improved percentage time SpO₂ < 80% and ≥88% compared to both other conditions (all P < 0.001). Outcomes for the feed-rate intervention were not significantly different to control.

Conclusions

Alternative infant positioning should be considered in preterm infants managed in the neonatal unit.     

Sidestream end-tidal capnometry as related to infant's position and maturation

The objective of this study was to investigate the effect of body position on sidestream, end-tidal carbon dioxide (EtCO2) wave measurements in maturing infants. Sidestream EtCO2 wave patterns were analysed longitudinally in 20 preterm infants (born at > or = 32 wk) at 32-37 wk gestation, and in 39 full-term controls. Capnography measurements included maximal EtCO2, inspired CO2 and frequency of apnoea events (>3 s) in the supine, supine with inclination, side and prone positions. Apnoea frequency decreased during maturation, and was less prevalent in the prone than in the supine and side positions in preterm as well as in term infants (p < 0.05). No clinically significant apnoea episodes were found in our cohort. EtCO2 in term infants was lower than that in preterm infants (p < 0.05) and was not affected by sleep position in the most premature (<33 wk) and in term infants (>36 wk). EtCO2 was higher in the prone position than in supine or side positions in infants between 33 and 35 wk gestation (p < 0.01). Conclusion: Short apnoeic episodes decrease during maturation, and are less prevalent in the prone position in maturing infants (32-37 wk). Only modest changes in EtCO2 were recorded in the different positions during maturation.     

The use of pulse oximetry in the prevention of hyperoxaemia in preterm infants

When deciding an appropriate upper limit for pulse oxygen saturation (SpO₂) in preterm infants the usefuleness of current data is limited by the fact that previous studies have examined a population of more mature infants and children or have applied various exclusion criteria which produce results unrepresentative of clinical practice. We tested the hypothesis of previous workers that maintaining the SpO₂ below 98% would ensure an arterial oxygen tension (PaO₂) less than 12 kPa. A total of 477 simultaneous measurements ofPaO₂ and SpO₂ were made using Ohmeda Biox oximeters on 43 infants who were less than 33 weeks gestation and receiving supplementary oxygen. Of 435 measurements performed when the SpO₂ was 97% or less, 26 (6%) had aPaO₂ greater than 12 kPa. Further examination of the data showed that of 108 estimations performed when the SpO₂ was less than 94%, none had aPaO₂ greater than 12kPa.Conclusion When using Ohmeda Biox pulse oximeters an upper limit of 97% for SaO₂ is not effective in preventing hyperoxaemia; however, a linit of 93% is likely to maintain thePaO₂ below 12 kPa.     

血氧饱和度对超早早产儿预后影响的Meta分析

目的本研究收集了NeOProM团队发表的比较超早早产儿不同血氧饱和度预后的临床文献,并对其进行系统评价,试图寻找适合超早早产儿的血氧饱和度。方法采用STATA 12.0软件,对NeOProM团队发表的文献进行Meta分析,分别比较在胎龄小于28周的超早早产儿中,高血氧饱和度组(91%~95%)和低血氧饱和度组(85%~89%)在出院前或18月龄前病死率、早产儿视网膜病(ROP)、新生儿坏死性小肠结肠炎(NEC)、支气管肺发育不良(BPD)、脑室内出血(IVH)、动脉导管未闭(PDA)发生率等方面内容。结果纳入3篇文献,包括4 919名超早早产儿,其中低血氧饱和度组患儿2 460例,高血氧饱和度组患儿2 459例。系统评价显示,与高血氧饱和度组患儿比较,低血氧饱和度组患儿出院前或18月龄前病死率的风险增加(RR:1.19,95%CI:1.05~1.35);ROP发生率降低(RR:0.73,95%CI:0.53~1.00);NEC发生率增高(RR:1.26,95%CI:1.06~1.49);BPD、IVH及PDA发生率两组比较差异无统计学意义。结论维持低血氧饱和度能降低超早早产儿ROP的发生率,但增加了超早早产儿病死率及NEC的发生率。     

Longitudinal study of sleep behavior and motor development in low-birth-weight preterm children from infancy to preschool years

ObjectiveTo verify the relationship between sleep characteristics and motor development in low-birth-weight preterm infants during infancy and preschool years.MethodForty-one healthy preterm infants (<37 weeks’ gestation) with low birth weight (≤1500 g) were assessed longitudinally at three different time points: at 6 months of corrected age, at 12 months of corrected age, and at 4–5 years of chronological age. At 6 and 12 months, motor development was assessed using the Denver Developmental Screening Test II and Alberta Infant Motor Scale, while sleep-related habits and disturbances were assessed using the Brief Infant Sleep Questionnaire. At 4–5 years, motor development was reassessed using the Pediatric Evaluation of Disability Inventory and sleep was reassessed using the Sleep Disturbance Scale for Children. Correlations were performed using sleep quality as the predictor variable and motor development as the outcome variable.ResultsMost infants had suspected delay/atypical development at 6 and 12 months, with no difference between the scales (p = 1.000). Suspected delay/atypical development were associated with lateral sleep position (p = 0.004), greater number of nighttime awakenings (p = 0.008), and longer awake periods (p = 0.014) only at 6 months. At 4–5 years, the suspected delay/atypical development observed at 6 and 12 months disappeared.ConclusionsSleep quality correlated with delayed/atypical motor development in healthy preterm infants with low birth weight only at 6 months of corrected age, which did not appear to affect later development of motor skills.     

Rehospitalization for respiratory syncytial virus infection in infants with extremely low gestational age or birthweight in Denmark

AIM: To determine the risk of rehospitalization for respiratory syncytial virus (RSV) infection during the first 2 y of life in extremely preterm infants. METHODS: Records on all rehospitalizations during the first 2 living years of all infants born with gestational age <28 wk or birthweight <1,000g during 1994 and 1995 in Denmark were retrospectively reviewed. RESULTS: Among 240 eligible infants, 43 (18%) had been rehospitalized 48 times owing to RSV. In infants (n = 210) without CLD the risk of rehospitalization for RSV was 16%, whereas in infants with CLD (n = 30) it was 30% (p = 0.065). Eighteen infants (38%) required respiratory support (supplemental oxygen only 3, continuous positive airway pressure 14, mechanical ventilation 1). Apart from CLD the only factor that could be associated with increased risk of hospitalization for RSV was discharge during autumn (p = 0.05). No infant died from RSV infection. CONCLUSION: The high rate of rehospitalization for RSV in extremely preterm infants in Denmark, especially in infants with CLD, should lead to considerations concerning more widespread use of prophylaxis against RSV in these infants.     

Association of development of chronic lung disease of newborns with neonatal colonization of Ureaplasma and cord blood interleukin‐8 level

Background: The aim of the present study was to investigate the association of chronic lung disease (CLD), neonatal Ureaplasma colonization, and interleukin‐8 (IL‐8) level of cord blood in preterm infants. Methods: In 77 infants of <32 weeks gestation, the relationship between IL‐8 level of cord blood, neonatal colonization of Ureaplasma, histological chorioamnionitis (CAM), and development of CLD was studied. Results: Five infants died and 29 infants developed CLD. The CLD group had significantly lower gestation (mean ± SD: 26.6 ± 1.8 weeks) compared with the infants without CLD (28.9 ± 1.9 weeks, P < 0.0001). Logistic analysis showed that the development of CLD was associated with gestational age (odds ratio [OR], 0.5; 95% confidence interval (CI): 0.4–0.8) and Ureaplasma colonization (OR, 4.1; 95%CI: 1.2–14.4). Ureaplasma colonization was also associated with CAM (OR, 6.5; 95%CI: 1.8–23.5), absence of respiratory distress syndrome (OR, 6.2; 95%CI: 1.3–30.5), and development of CLD (OR, 4.0; 95%CI: 1.1–15.3). Elevated cord blood IL‐8 ≥100 pg/mL was associated with female sex and the isolation of microorganisms (OR, 49.4; 95%CI: 4.6–525). Conclusion: The development of CLD defined by oxygen requirement at 36 weeks was associated with neonatal Ureaplasma colonization but not with IL‐8 level of cord blood. Elevated cord blood IL‐8 was associated with neonatal microorganisms isolation.     

Chronic lung disease of prematurity and respiratory outcome at eight years of age

AIM: The study aimed to determine the respiratory outcome of children who had chronic lung disease of prematurity (CLD) compared with a preterm control group of children at school age. METHODS: Fifty-two preterm infants with CLD born between 26 and 33 weeks gestation were assessed regarding respiratory illness with 47 having lung function testing. Information regarding respiratory illness was obtained from 52 children in the birthweight-matched control group of whom 45 had lung function testing. The results were compared between the CLD and control groups. RESULTS: There was no difference in respiratory symptomatology between CLD groups and control preterm infants. On lung function testing, a significantly lower mean forced expiratory flow at 25-75% of vital capacity was identified compared with the preterm controls (P=0.024). This significant difference did not persist after bronchodilator therapy. There was no evidence of increased air trapping or bronchial hyper-reactivity in the CLD children compared with the controls. CONCLUSION: Lung function in CLD children is largely normal in comparison with preterm controls, apart from some evidence of reversible small airway obstruction. Respiratory symptomatology is not increased in chronic disease children in comparison with control preterm children.     

Arousal from sleep pathways are affected by the prone sleeping position and preterm birth: Preterm birth,prone sleeping and arousal from sleep

Objectives

Preterm infants exhibit depressed arousability from sleep when compared with term infants. As the final cortical element of the arousal process may be the most critical for survival, we hypothesized that the increased vulnerability of preterm infants to the Sudden Infant Death Syndrome (SIDS) could be explained by depressed cortical arousal (CA) responses. We evaluated the effects of preterm birth on stimulus-induced arousal processes in both the prone and supine sleeping positions.

Study design

10 healthy preterm infants were studied with daytime polysomnography, in both supine and prone sleeping positions, at 36 weeks gestational age, 2–4 weeks, 2–3 months and 5–6 months post-term corrected age. Sub-cortical activations and cortical arousals (CA) were expressed as proportions of total arousal responses. Preterm data were compared with data from 13 healthy term infants studied at the same corrected ages.

Results

In preterm infants increased CAs were observed in the prone position at all ages studied. Compared to term infants, preterm infants had significantly fewer CAs in QS when prone at 2–3 months of age and more CAs when prone at 2–4 weeks in AS. There were no differences in either sleep state when infants slept supine.

Conclusions

Prone sleeping promoted CA responses in healthy preterm infants throughout the first six months of post-term age. We have previously suggested that in term infants enhanced CA represents a critical protection against a potentially harmful situation; we speculate that for preterm-born infants the need for this protection is greater than in term infants.     

Hospital admissions in the first year of life in very preterm infants

OBJECTIVE: To analyse hospital readmissions to 1 year in infants < 33 weeks' gestation. STUDY DESIGN: Cohort of very preterm infants born in Western Australia. METHODS: Parental social class, history of asthma, race, gestational age, birthweight, sex, severity of respiratory disease and oxygen requirement at 28 days chronic lung disease (CLD), 36 weeks and term, maternal smoking, cohabitation with siblings, breast-feeding duration and hospital readmissions were recorded prospectively. RESULTS: Data were available for 538 of 560 (96%) infants discharged. Eight died in the first year. Two hundred and twenty-five infants (42%) had 443 readmissions, of which 370 were medical and 73 surgical. Risk factors for medical readmission were Aboriginal race, male sex and CLD. Breast-feeding was protective. Risk factors for surgical admission were male sex, lower gestation, severe hyaline membrane disease, severe CLD and birthweight < 10th centile. CONCLUSIONS: Readmission is common after very preterm birth. Risk factors for medical and surgical admission differ with CLD being the only perinatal factor associated with both medical and surgical admission.     

极早产儿俯卧位机械通气对呼吸功能的影响

目的 探讨极早产儿俯卧位机械通气对呼吸功能的影响。方法 83例经口气管插管机械通气极早产儿随机分为仰卧位组和俯卧位组,4例退出研究,79例完成治疗和观察（仰卧位组37例,俯卧位组42例）,以容量辅助/控制模式机械通气。俯卧位组患儿每仰卧位通气4 h行俯卧位通气2 h。分组干预之前以及分组干预后仰卧位组每6 h、俯卧位组每于转换为俯卧位后的1 h,分别记录呼吸机参数、动脉血气分析和生命体征。结果 俯卧位组FiO₂、气道峰压,平均气道压、机械通气时间低于仰卧位组,差异有统计学意义（P < 0.05）;两组潮气量、呼气末正压的差异无统计学意义（P > 0.05）;俯卧位组的PO₂/FiO₂比值高于仰卧位组,而氧合指数、呼吸频率较低,差异均有统计学意义（P < 0.05）。两组PaO₂、pH、BE、心率和有创动脉血压平均压的差异无统计学意义（P > 0.05）。结论 俯卧位与仰卧位交替通气能改善机械通气极早产儿的氧合功能,降低吸入氧体积分数,缩短机械通气时间。     

Development of chronic lung disease in preterm infants treated with surfactant

BACKGROUND: Chronic lung disease (CLD) is generally known to develop among preterm infants who have severe respiratory distress syndrome (RDS) at birth. Many clinical trials have established the efficacy of surfactant replacement therapy to treat RDS at birth with differing doses. In this study, the preterm infants diagnosed to have RDS at birth and treated with one or two doses of surfactant, depending on the severity of the RDS, were studied to evaluate the effect of surfactant on the later development of CLD. METHODS: A retrospective examination of case records of preterm infants who were born at < or = 28 weeks gestation period were studied. The subjects received a natural surfactant product (survanta) between September 1994 and April 1996 at the Monash Medical Center, Australia. RESULTS: Despite less severe initial lung disease, the subsequent respiratory outcome of infants who received one dose of surfactant, showed a trend towards being poorer compared to those who were diagnosed as having severe RDS at birth and received two doses of surfactant. At the corrected gestational age of 36 weeks, 54% of those infants began with mild RDS required oxygen, while only 44% of those who started with a severe RDS required supplemental O2. CONCLUSION: This study reports the infants with severe RDS at birth had responded slightly better or equally, compared to those with mild RDS, in terms of later development of CLD under surfactant treatment proportional to the severity.     

Clinical characteristics of chronic lung disease without preceding respiratory distress syndrome in preterm infants

BACKGROUND: Recently, the incidence of atypical presentation of chronic lung disease (CLD) that develops in infants without a history of preceding respiratory distress syndrome (RDS) is increasing. Therefore, the clinical characteristics of CLD without RDS in comparison with CLD with RDS were assessed. METHODS: Prospective cohort analysis was done from 117 very low-birthweight infants who were born in Seoul National University Hospital and survived more than 36 weeks postmenstrual age (PMA). RESULTS: Of the 117 infants analyzed, CLD developed in 44 infants (38%). Among these 44 infants, CLD with RDS developed in 27 infants (23%) and CLD without RDS developed in 17 infants (15%). Each type of CLD was subgrouped according to the presence of chorioamnionitis (CA): RDS(+)CA(+) CLD (n = 8) and RDS(+)CA(-) CLD (n = 19); and RDS(-)CA(+) CLD (n = 12) and RDS(-)CA(-) CLD (n = 5). There were no significant differences in the demographic characteristics between CLD with RDS and CLD without RDS. Chorioamnionitis was significantly more common in CLD without RDS, while patent ductus arteriosus was more common in CLD with RDS. Although the severity of initial respiratory failure was not greater than that of CLD with RDS, CLD without RDS showed a gradually increasing chronic oxygen requirement pattern. Chronic oxygen requirement pattern showed that infants with RDS(+)CA(+)CLD required the highest concentrations of oxygen not only initially but also thereafter until the 28th day of life and 36 weeks PMA. CONCLUSIONS: Although CLD without RDS was still less common than CLD with RDS, it comprised over a third of all cases of CLD in our study. Clinical characteristics and chronic oxygen requirement pattern of CLD without RDS seems to be less severe than those of CLD with RDS. Our data suggest that CLD without RDS may be developed by causes other than initial acute lung injury. Chorioamnionitis may be one of antecedents of CLD without RDS.     

The prone sleeping position impairs arousability in term infants

OBJECTIVE: To investigate whether the prone sleeping position impaired arousal from sleep in healthy infants and whether this impairment was related to cardiorespiratory variables, temperature, or age.Study design: Healthy term infants (n = 24) were studied with daytime polysomnography on 3 occasions: 2 to 3 weeks after birth, 2 to 3 months after birth, and 5 to 6 months after birth. Multiple measurements of arousal threshold (cm H(2)O) in response to air-jet stimulation applied alternately to the nares were made in both active sleep and quiet sleep when infants slept both prone and supine. RESULTS: Arousal thresholds were significantly higher in both active sleep and quiet sleep when infants slept prone at 2 to 3 weeks and 2 to 3 months, but not at 5 to 6 months. These increases were independent of any sleep position-related change in either rectal or abdominal skin temperature, respiratory rate, oxygen saturation, or heart rate. CONCLUSIONS: The prone position significantly impairs arousal from both active sleep and quiet sleep in healthy term infants. This impairment in arousability occurred with no clinically significant changes in cardiorespiratory variables or body temperature. Decreased arousability from sleep in the prone position provides an important insight into its role as a risk factor for sudden infant death syndrome.     

Role of ureaplasma urealyticum in lung disease of prematurity.

AIM: To examine the role of Ureaplasma urealyticum colonisation or infection in neonatal lung disease. METHODS: Endotracheal aspirates from ventilated infants less than 28 weeks of gestation were cultured for U urealyticum and outcomes compared in infants with positive and negative cultures. RESULTS: U urealyticum was isolated from aspirates of 39 of 143 (27%) infants. Respiratory distress syndrome (RDS) occurred significantly less often in colonised, than in non-colonised infants (p=0.002). Multivariate logistic regression analysis showed that in singleton infants, ureaplasma colonisation was the only independent (negative) predictor of RDS (OR 0.36; p=0. 02). Both gestational age (OR 0.46; p=0.006) and isolation of U urealyticum (OR 3.0; p=0.05) were independent predictors of chronic lung disease (CLD), as defined by requirement for supplemental oxygen at 36 weeks of gestational age. Multiple gestation was also a major independent predictor of RDS and CLD. CONCLUSIONS: Colonisation or infection with ureaplasma apparently protects premature infants against the development of RDS (suggesting intrauterine infection). However, in singleton infants, it predisposes to development of CLD, independently of gestational age. Treatment of affected infants after birth is unlikely to significantly improve the outcome and methods are required to identify and treat the women with intrauterine ureaplasmal infection, before preterm delivery occurs.     

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).