Lung Function and Respiratory Symptoms at 11 Years in Children Born Extremely Preterm The EPICure Study

Portex Unit: Respiratory Physiology and Medicine, UCL, Institute of Child Health, WC1N 1EH London, UK.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 04/2010; 182(2):237-45. DOI: 10.1164/rccm.200912-1806OC
Source: PubMed


The long-term respiratory sequelae of infants born extremely preterm (EP) and now graduating from neonatal intensive care remains uncertain.
To assess the degree of respiratory morbidity and functional impairment at 11 years in children born EP (i.e., at or less than 25 completed weeks of gestation) in relation to neonatal determinants and current clinical status.
Pre- and postbronchodilator spirometry were undertaken at school in children born EP and classroom control subjects. Physical examination and respiratory health questionnaires were completed. Multivariable regression was used to estimate the predictive power of potential determinants of lung function.
Spirometry was obtained in 182 of 219 children born EP (129 with prior bronchopulmonary dysplasia [BPD]) and 161 of 169 classmates, matched for age, sex, and ethnic group. Children born EP had significantly more chest deformities and respiratory symptoms than classmates, with twice as many (25 vs. 13%; P < 0.01) having a current diagnosis of asthma. Baseline spirometry was significantly reduced (P < 0.001) and bronchodilator responsiveness was increased in those born EP, the changes being most marked in those with prior BPD. EP birth, BPD, current symptoms, and treatment with beta-agonists are each associated independently with lung function z-scores (adjusted for age, sex, and height) at 11 years. Fifty-six percent of children born EP had abnormal baseline spirometry and 27% had a positive bronchodilator response, but less than half of those with impaired lung function were receiving any medication.
After extremely preterm birth, impaired lung function and increased respiratory morbidity persist into middle childhood, especially among those with BPD. Many of these children may not be receiving appropriate treatment.

Download full-text


Available from: Neil Marlow,
18 Reads
  • Source
    • "The study limitations include its retrospective design and the lack of a control group of healthy infants [43]. Because this study was retrospective, important maternal (e.g., smoking, atopy, asthma, education), neonatal (e.g., birth characteristics, resuscitation management, postnatal steroids, infections) and environmental parameters (e.g., smoking exposure, air pollution) which may affect the postnatal lung development [44,45] were unavailable. Further clinical data (e.g., the duration of non-invasive respiratory support or oxygen treatment) may help to understand the pathophysiology underlying this condition. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Exhaled nitric oxide (eNO) is a marker of established airway inflammation in adults and children, but conflicting results have been reported in preterm infants when postnatal eNO is measured during tidal breathing. This study investigated the extent to which intubation and mechanical ventilation (MV) affect eNO and NO production (V’NO) in preterm infants with and without bronchopulmonary dysplasia (BPD). Patients and methods A total of 176 very low birth weight (VLBW) infants (birth weight <1500 g), including 74 (42%) with and 102 (58%) without BPD, were examined at a median postmenstrual age of 49 weeks. Of the 176 infants, 84 (48%) did not require MV, 47 (27%) required MV for <7 days and 45 (26%) required MV for ≥7 days. Exhaled NO and tidal breathing parameters were measured in sleeping infants during tidal breathing, respiratory mechanics were assessed by occlusion tests, and arterialized capillary blood gas was analyzed. Results eNO was significantly correlated with tidal breathing parameters, while V’NO was correlated with growth parameters, including age and body length (p < 0.001 each). Infants who were intubated and received MV for <7 days had significantly lower eNO (p < 0.01) and V’NO (p < 0.01) than non-ventilated infants. In contrast, eNO and V’NO did not differ significantly in non-ventilated infants and those receiving MV for ≥7 days. Multivariate analysis showed that independent on the duration of MV eNO (p = 0.003) and V’NO (p = 0.018) were significantly increased in BPD infants comparable with the effects of intubation and MV on eNO (p = 0.002) and V’NO (p = 0.017). Conclusions Preterm infants with BPD show only weak postnatal increases in eNO and V’NO, but these changes may be obscured by the distinct influences of breathing pattern and invasive respiratory support. This limits the diagnostic value of postnatal eNO measurements in the follow-up of BPD infants.
    BMC Research Notes 06/2014; 7(1):389. DOI:10.1186/1756-0500-7-389
  • Source
    • "The widely reported importance of chronic respiratory morbidity in prematurely born infants is due to their smaller and hyper-responsive airways [36-38], and there is also evidence that they may also have a genetic predisposition to viral infections [39], a combination that can facilitate catarrhal obstruction of the airways and lung inflammation. Up to 73% of pre-term infants with pulmonary bronchodysplasia require readmission to hospital because of lower respiratory tract diseases in the first years of life, and chronic respiratory morbidity requiring the use of healthcare facilities remains even at school age [40]. It should be investigated whether, in addition to adequate vaccinations, all pre-term babies and those with respiratory distress at birth would benefit from regular chest physiotherapy during respiratory illnesses in order to enhance secretion mobilisation and prevent recurrent infections. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this case--control study was to analyse the clinical characteristics of children with recurrent community-acquired pneumonia (rCAP) affecting different lung areas (DLAs) and compare them with those of children who have never experienced CAP in order to contribute to identifying the best approach to such patients. The study involved 146 children with >=2 episodes of radiographically confirmed CAP in DLA in a single year (or >=3 episodes in any time frame) with radiographic clearing of densities between occurrences, and 145 age- and gender-matched controls enrolled in Milan, Italy, between January 2009 and December 2012. The demographic and clinical characteristics of the cases and controls were compared, and a comparison was also made between the cases with rCAP (i.e. <=3 episodes) and those with highly recurrent CAP (hrCAP: i.e. >3 episodes). Gestational age at birth (p = 0.003), birth weight (p = 0.006), respiratory distress at birth (p < 0.001), and age when starting day care attendance (p < 0.001) were significantly different between the cases and controls, and recurrent infectious wheezing (p < 0.001), chronic rhinosinusitis with post-nasal drip (p < 0.001), recurrent upper respiratory tract infections (p < 0.001), atopy/allergy (p < 0.001) and asthma (p < 0.001) were significantly more frequent. Significant risk factors for hrCAP were gastroesophageal reflux disease (GERD; p = 0.04), a history of atopy and/or allergy (p = 0.005), and a diagnosis of asthma (p = 0.0001) or middle lobe syndrome (p = 0.001). Multivariate logistic regression analysis, adjusted for age and gender, showed that all of the risk factors other than GERD and wheezing were associated with hrCAP. The diagnostic approach to children with rCAP in DLAs is relatively easy in the developed world, where the severe chronic underlying diseases favouring rCAP are usually identified early, and patients with chronic underlying disease are diagnosed before the occurrence of rCAP in DLAs. When rCAP in DLAs does occur, an evaluation of the patients' history and clinical findings make it possible to limit diagnostic investigations.
    BMC Pulmonary Medicine 10/2013; 13(1):60. DOI:10.1186/1471-2466-13-60 · 2.40 Impact Factor
  • Source
    • "Preterm birth is the leading cause of newborn mortality–more than half of all infant deaths in the United States occur to infants born prior to 32 weeks gestation [3]. Preterm infants that survive the newborn period are at increased risk for long-term health complications including neurodevelopmental disability, decreased growth, chronic lung disease and cardiovascular morbidity [4]–[7]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Ascending infection from the colonized vagina to the normally sterile intrauterine cavity is a well-documented cause of preterm birth. The primary physical barrier to microbial ascension is the cervical canal, which is filled with a dense and protective mucus plug. Despite its central role in separating the vaginal from the intrauterine tract, the barrier properties of cervical mucus have not been studied in preterm birth. To study the protective function of the cervical mucus in preterm birth we performed a pilot case-control study to measure the viscoelasticity and permeability properties of mucus obtained from pregnant women at high-risk and low-risk for preterm birth. Using extensional and shear rheology we found that cervical mucus from women at high-risk for preterm birth was more extensible and forms significantly weaker gels compared to cervical mucus from women at low-risk of preterm birth. Moreover, permeability measurements using fluorescent microbeads show that high-risk mucus was more permeable compared with low-risk mucus. Our findings suggest that critical biophysical barrier properties of cervical mucus in women at high-risk for preterm birth are compromised compared to women with healthy pregnancy. We hypothesize that impaired barrier properties of cervical mucus could contribute to increased rates of intrauterine infection seen in women with preterm birth. We furthermore suggest that a robust association of spinnbarkeit and preterm birth could be an effectively exploited biomarker for preterm birth prediction.
    PLoS ONE 08/2013; 8(8):e69528. DOI:10.1371/journal.pone.0069528 · 3.23 Impact Factor
Show more