Fractional exhaled nitric oxide in preterm-born subjects: A systematic review and meta-analysis

Background Decreased lung function is common in preterm‐born survivors. Increased fractional exhaled nitric oxide (FeNO) appears to be a reliable test for eosinophillic airway inflammation especially in asthma. We, systematically, reviewed the literature to compare FeNO levels in preterm‐born children and adults who did or did not have chronic lung disease of prematurity (CLD) in infancy with term‐born controls. Methods We searched eight databases up to February 2018. Studies comparing FeNO levels in preterm‐born subjects (<37 weeks’ gestation) in childhood and adulthood with and without (CLD) with term‐born subjects were identified and extracted by two reviewers. Data were analysed using Review Manager v5.3. Results From 6042 article titles, 183 full articles were screened for inclusion. Nineteen studies met the inclusion criteria. Seventeen studies compared FeNO levels in preterm‐ and term‐born children and adults; 11 studies (preterm n = 640 and term n = 4005) were included in a meta‐analysis. The mean FeNO concentration difference between the preterm‐born and term‐born group was −0.74 (95% CI −1.88 to 0.41) ppb. For the six studies reporting data on CLD (preterm n = 204 and term n = 211) the mean difference for FeNO levels was −2.82 (95% CI −5.87 to 0.22) ppb between the preterm‐born CLD and term‐born groups. Conclusions Our data suggest that preterm born children with and without CLD have similar FeNO levels to term‐born children suggesting an alternative mechanism to eosinophilic inflammation for symptoms of wheezing and airway obstruction observed in preterm‐born subjects

Expiratory airflow in late adolescence and early adulthood in individuals born very preterm or with very low birthweight compared with controls born at term or with normal birthweight : a meta-analysis of individual participant data

Background Maximal expiratory airflow peaks early in the third decade of life, then gradually declines with age. The pattern of airflow through adulthood for individuals born very preterm (at 2499 g) or at term. Methods We did a meta-analysis of individual participant data from cohort studies, mostly from the pre-surfactant era. Studies were identified through the Adults born Preterm International Collaboration and by searching PubMed and Embase (search date May 25, 2016). Studies were eligible if they reported on expiratory flow rates beyond 16 years of age in individuals born very preterm or with very low birthweight, as well as controls born at term or with normal birthweight. Studies with highly selected cohorts (eg, only participants with bronchopulmonary dysplasia) or in which few participants were born very preterm or with very low birthweight were excluded. De-identified individual participant data from each cohort were provided by the holders of the original data to a central site, where all the data were pooled into one data file. Any data inconsistencies were resolved by discussion with the individual sites concerned. Individual participant data on expiratory flow variables (FEV1, forced vital capacity [FVC], FEV1/FVC ratio, and forced expiratory flow at 25-75% of FVC [FEF25-75%]) were converted to Z scores and analysed with use of generalised linear mixed models in a one-step approach. Findings Of the 381 studies identified, 11 studies, comprising a total of 935 participants born very preterm or with very low birthweight and 722 controls, were eligible and included in the analysis. Mean age at testing was 21 years (SD 3.4; range 16-33). Mean Z scores were close to zero (as expected) in the control group, but were reduced in the very preterm or very low birthweight group for FEV1 (-0.06 [SD 1.03] vs -0.81 [1.33], mean difference -0.78 [95% CI -0.96 to -0.61], p Interpretation Individuals born very preterm or with very low birthweight are at risk of not reaching their full airway growth potential in adolescence and early adulthood, suggesting an increased risk of chronic obstructive pulmonary disease in later adulthood. Copyright (C) 2019 Elsevier Ltd. All rights reserved.Peer reviewe

Maternal education and cognitive development in 15 European very-preterm birth cohorts from the RECAP Preterm platform

Background: Studies are sparse and inconclusive about the association between maternal education and cognitive development among children born very preterm (VPT). Although this association is well established in the general population, questions remain about its magnitude among children born VPT whose risks of medical and developmental complications are high. We investigated the association of maternal education with cognitive outcomes in European VPT birth cohorts. Methods: We used harmonized aggregated data from 15 population-based cohorts of children born at = 37 weeks of GA) were available in eight cohorts. Maternal education was classified as: low (primary/lower secondary); medium (upper secondary/short tertiary); high (bachelor's/higher). Pooled standardized mean differences (SMDs) in cognitive scores were estimated (reference: high educational level) for children assessed at ages 2-3, 4-7 and 8-15 years. Results: The study included 10 145 VPT children from 12 cohorts at 2-3 years, 8829 from 12 cohorts at 4-7 years and 1865 children from 6 cohorts at 8-15 years. Children whose mothers had low, compared with high, educational attainment scored lower on cognitive measures [pooled unadjusted SMDs: 2-3 years = -0.32 (95% confidence intervals: -0.43 to -0.21); 4-7 years = -0.57 (-0.67; -0.47); 8-15 years = -0.54 (-0.72; -0.37)]. Analyses by GA subgroups (= 27 weeks) in children without severe neonatal morbidity and term controls yielded similar results. Conclusions: Across diverse settings and regardless of the degree of prematurity, low maternal education was associated with lower cognition.Peer reviewe

Preterm birth: inflammation, fetal injury and treatment strategies

Preterm birth (PTB) is the leading cause of childhood mortality in children under 5 and accounts for approximately 11% of births worldwide. Premature babies are at risk of a number of health complications, notably cerebral palsy, but also respiratory and gastrointestinal disorders. Preterm deliveries can be medically indicated/elective procedures or they can occur spontaneously. Spontaneous PTB is commonly associated with intrauterine infection/inflammation. The presence of inflammatory mediators in utero has been associated with fetal injury, particularly affecting the fetal lungs and brain. This review will outline (i) the role of inflammation in term and PTB, (ii) the effect infection/inflammation has on fetal development and (iii) recent strategies to target PTB. Further research is urgently required to develop effective methods for the prevention and treatment of PTB and above all, to reduce fetal injury

Bronchial hyper-responsiveness in preterm-born subjects: A systematic review and meta-analysis

Background Preterm‐born survivors have increased respiratory symptoms and decreased lung function, but the nature of bronchial hyper‐responsiveness (BHR) is unclear. We conducted a systematic review and meta‐analysis for BHR in preterm‐born survivors including those with and without chronic lung disease in infancy (CLD) comparing results to term‐born subjects. Methods We searched eight databases up to December 2016. Included articles compared BHR in preterm‐born and term‐born subjects. Studies reporting BHR as decreases in forced expiratory volume in 1 second (FEV1) after provocation stimuli were included. The analysis used Review Manager V5.3. Results From 10 638 titles, 265 full articles were screened, and 28 included in a descriptive analysis. Eighteen articles were included in a meta‐analysis as they reported the proportion of subjects who had BHR. Pooled odds ratio (OR) estimates (95% confidence interval) for BHR comparing the preterm and term‐born groups was 1.88 (1.32, 2.66). The majority of the studies reported BHR after a methacholine challenge or an exercise test. Odds ratio was 1.89 (1.12, 3.19) after methacholine challenge and 2.59 (1.50, 4.50) after an exercise test. Nine of fifteen articles reporting BHR in CLD subjects were included in a meta‐analysis. Differences for BHR including for methacholine (OR 4.35; 2.36, 8.03) and exercise (OR 5.13; 1.82, 14.47) were greater in the CLD group compared to the term group. Conclusions Preterm‐born subjects especially those who had CLD had increased rates of BHR to direct (methacholine) and indirect (exercise) stimuli compared to term‐born subjects suggesting subgroups might benefit from anti‐inflammatory or bronchodilator therapies

Myocardial function including estimates of myocardial work in young adults born very preterm or with extremely low birthweight - a cohort study

Abstract Background Preterm birth and low birthweight have been associated with increased risk of heart failure and cardiovascular disease in young adulthood. However, results from clinical studies of myocardial function are not consistent. Echocardiographic strain analyses allow detection of early stages of cardiac dysfunction, and non-invasive estimates of myocardial work can provide additional information on cardiac function. We aimed to evaluate left ventricular (LV) myocardial function including measures of myocardial work in young adults born very preterm (gestational age -16%, but 22% had borderline impaired GLS between − 16% and − 18%. Mean GLS in PB/ELBW (-19.4% (95% confidence interval (CI) -20.0, -18.9)) was impaired compared to controls (-20.6% (95% CI -21.1, -20.1)), p = 0.003. Lower birthweight was associated to more impaired GLS (Pearson correlation coefficient − 0.2). Means of EF, measures of diastolic function including left atrial reservoir strain, global constructive and wasted work, global work index and global work efficiency was similar in PB/ELBW and controls. Conclusion The young adults born very preterm or with extremely low birthweight had impaired LV-GLS compared to controls, although systolic function mainly within normal range. Lower birthweight was associated with more impaired LV-GLS. These findings could indicate an elevated lifetime risk of developing heart failure in preterm born individuals. Measures of diastolic function and myocardial work were similar compared to controls