Effect of Early-Term Birth on Respiratory Symptoms and Lung Function in Childhood and Adolescence

Background Early-term-born subjects, (37–38 weeks’ gestation), form a large part of the population and have an increased risk of neonatal respiratory morbidity and childhood respiratory symptoms; there is a paucity of data on their later lung function. We sought to (1) compare lung function at 8–9 and 14–17 years in early-term-born children with full-term-born children (39–43 weeks’ gestation); (2) assess the role of caesarean section delivery; and (3) compare respiratory symptoms and diagnosis of asthma. Methods Caucasian, singleton, term births from the Avon Longitudinal Study of Parents and Children (n = 14,062) who had lung spirometry at 8–9 (n = 5,465) and/or 14–17 (n = 3,666) years were classified as early or full term. Results At 8–9 years, standardized spirometry measures, although within the normal range, were lower in the early-term-born group, (n = 911), compared to full-term controls (n = 4,554). Delivery by caesarean section did not influence later spirometry, and the effect of early-term birth was not modified by delivery by caesarean section. At 14–17 years, the spirometry measures in the early-term group, (n = 602), were similar to the full-term group (3,064), and the rates of asthma and respiratory symptoms were also similar between the two gestation groups. Conclusions Early-term-born children had lower lung function values at 8–9 years compared to the full-term group, but were similar by 14–17 years of age. Delivery at early term should be avoided due to early and late morbidity

Effect of foetal and infant growth and body composition on respiratory outcomes in preterm-born children

Body composition and growth outcomes of preterm-born subjects have been studied by many researchers. In general, preterm-born children have lower height and weight especially in infancy. Despite showing potential for catch-up growth, they continue to lag behind their term counterparts in adolescence and adulthood. The various methods of studying body composition and the differing gestations and ages at which it is assessed may go some way to explaining the inconsistent results observed in different studies. In addition, there is a paucity of data on the effects of foetal and infant growth and of body composition on later respiratory outcomes. In largely term-born subjects, foetal growth and growth trajectories appear to have differential effects on later respiratory outcomes. Early weight gain in infancy appears to be associated with increased respiratory symptoms in childhood but catch-up growth in infancy appears to be associated with possible improved lung function status

Early childhood parent-reported speech problems in small and large for gestational age term-born and preterm-born infants: a cohort study

Objective (1) To assess if preterm and term small for gestational age (SGA) or large for gestational age (LGA) infants have more parent-reported speech problems in early childhood compared with infants with birth weights appropriate for gestational age (AGA). (2) To assess if preterm and term SGA and LGA infants have more parent-reported learning, behavioural, hearing, movement and hand problems in early childhood compared with AGA infants. Design Cohort study. Setting Wales, UK. Participants 7004 children with neurodevelopmental outcomes from the Respiratory and Neurological Outcomes of Children Born Preterm Study which enrolled 7129 children, born from 23 weeks of gestation onwards, to mothers aged 18–50 years of age were included in the analysis. Outcome measures Parent-reported single-answer questionnaires were completed in 2013 to assess early childhood neurodevelopmental outcomes. The primary outcome was parent-reported speech problems in early childhood adjusted for clinical and demographic confounders in SGA and LGA infants compared with AGA infants. Secondary outcomes measured were parent-reported early childhood learning, behavioural, hearing, movement and hand problems. Results Median age at the time of study was 5 years, range 2–10 years. Although the adjusted OR was 1.19 (0.92 to 1.55) for SGA infants and OR 1.11 (0.88 to 1.41) for LGA infants, this failed to reach statistical significance that these subgroups were more likely to have parent-reported speech problems in early childhood compared with AGA infants. This study also found parent-reported evidence suggestive of potential learning difficulties in early childhood (OR 1.51 (1.13 to 2.02)) and behavioural problems (OR 1.35 (1.01 to 1.79)) in SGA infants. Conclusion This study of 7004 infants in Wales suggests that infants born SGA or LGA likely do not have higher risks of parent-reported speech problems in early childhood compared with infants born AGA. To further ascertain this finding, studies with wider population coverage and longer-term follow-up would be needed

Association of early and current life factors with telomere length in preterm-born children

Background: Telomeres shorten after each cell division. Since preterm-born babies are delivered early and often suffer from inflammatory conditions such as bronchopulmonary dysplasia (BPD), their telomere length may be altered. Objectives: We assessed associations of early and current life factors with telomere length in saliva samples obtained from 7–12-year-old children born at ≤34 weeks’ gestation and term-born controls. Study design: Relative telomere length was measured by qPCR on extracted DNA. Groups were compared using independent t-tests or ANOVA with post-hoc correction. Linear regression analysis was also used. Results: 534 children had satisfactory telomere data including 383 who were preterm-born (mean (SD) birthweight 1732g (558g), gestation 31.1 (2.6) weeks) and 151 term-born (3464g (510g); 39.8 (1.3) weeks). Telomere length was longer in children who had intrauterine growth restriction (IUGR) at birth: mean (SD): 464.6 (166.3) vs. 418.6 (110.7) in the no-IUGR group; in females: 440.2 (130.1) vs. 405.7 (101.5) in males; and in the least deprived group (397.8 (95.0) vs. 437.6 (121.9) most vs least deprivation quintile). Differences were most notable in females with IUGR. However, telomere length was not different between the preterm and term groups; the BPD and no BPD groups nor was it related to lung function or cardiovascular measurements. In multivariable regression analyses, telomere length was associated with sex, IUGR and deprivation with the greatest difference observed in females with IUGR. Conclusions: Telomere length was associated with sex, IUGR and deprivation, especially in females with IUGR, but not with prematurity, BPD, lung function or cardiovascular measurements

Association of early life factors with wheezing phenotypes in preterm-born children compared to term-born children

Introduction: Respiratory symptoms including wheezing are common in preterm-born children but the natural history of wheezing and the influence of early life factors on wheezing phenotypes are unclear. Aims: We identified wheezing phenotypes in preterm-born children and investigated associations with early life factors compared with term-born children. Methods: Machine-learning using reports of wheezing from the Millennium Cohort Study (n=13,356) at 3, 5, 7 and 11 years was used to derive wheezing phenotypes. Logistic regression was used to test associations with early life factors comparing preterm with term-born children. Results: Four wheezing phenotypes were identified: no/infrequent, early, persistent and late, from 1,049 preterm-born children and 12,307 term-born who had recent-wheeze data for three- or four-time points. Recent-wheeze was greater at all time-points in preterm-born than term-born group although not significantly so at 11 years. Preterm-born children were more likely to have early and persistent wheeze. Although similar early life factors were associated with wheeze phenotypes in both preterm and term groups, including antenatal maternal smoking, atopy, male gender, and breast feeding (which was protective), the effects were generally stronger for preterms. Conclusions: Preterm-born children have similar wheeze phenotypes to term-born children but are more likely than term-born children to have early and persistent wheeze. Wheezing was associated with similar early life factors in both term and preterm children but with greater effect sizes in the latter

Impact of ambient air pollution on lung function in preterm-born school-aged children

Rationale Increased outdoor air pollution worsens lung function in children. However, these associations are less well studied in preterm-born individuals. Objectives We assessed associations between ambient air pollutants and spirometry measures in preterm-born children. Methods The Respiratory Health Outcomes in Neonates study recruited preterm-born children aged 7–12 years who were born at ≤34 week's gestation. We associated four ambient air pollutants (particulate matter with aerodynamic diameter ≤2.5 µm (PM2.5), PM10, nitrogen dioxide (NO2) and sulfur dioxide) at time of birth and spirometry assessment and averaged exposure between these two time points with spirometry measures, using linear regression analyses. Gestational age was banded into 23–28, 29–31 and 32–34 week's. Regression models estimated spirometry values against pollutant levels at birth and at the time of spirometry. Measurements and main results From 565 preterm-born children, 542 (96%) had satisfactory data. After adjustments for early and current life factors, significant detrimental associations were noted between PM10 at birth and per cent predicted forced vital capacity (%FVC) for the 23–28 and 29–31 week's gestation groups and between current PM2.5 and NO2 exposure and %FVC for the 23–28 week's gestation group. No associations with spirometry were noted for the averaged pollution exposure between birth and spirometry. Predictive models showed 5.9% and 7.4% differences in %FVC between the highest and lowest current pollution exposures for PM2.5 and NO2, respectively, in the 23–28 week group. Conclusions Birth and current exposures to road-traffic-associated pollutants detrimentally affected %FVC in preterm-born school-aged children, who already have compromised lung function

Measuring the impact of deprivation on learning difficulties and behaviour among infants born preterm: A cohort study

BACKGROUND:Preterm birth and social deprivation are known risk factors for learning difficulties. However there has been little work looking into the interaction between these two risks. We aimed to identify if children born preterm to families with higher levels of social deprivation are disproportionately more likely to have learning difficulties than those with lower levels of social deprivation. METHODS:Data from the RANOPS (Respiratory And Neurological Outcomes in children born Preterm Study) was used to assess prevalence of learning difficulties. The effects of preterm birth and deprivation were reviewed. Multi-level logistic regression models were used to examine if gestational age and deprivation impacts interacted after adjustment for possible confounders. Primary outcome measure was parent-reported learning difficulties. Secondary outcome measures were parent-reported behavioural problems and a statement of special educational need. RESULTS:We investigated the developmental outcomes of 6,691 infants with a median age of 5 years at time of survey (IQR 5). Deprivation decile (OR 1.08 (1.03,1.12)) and preterm birth (OR 2.67 (2.02,3.53)) were both associated with increased risk of learning difficulties. There was little evidence for any interaction between preterm birth and deprivation (p = 0.298) and the risk of learning difficulties. CONCLUSIONS:Deprivation and preterm birth have significant associations with learning difficulties. While deprivation does not appear to have potentiated the impact of preterm birth, preterm infants in the most deprived areas have the highest risk of learning difficulties with almost 1 in 3 extremely premature infants with a learning difficulty in the most deprived areas

Association of early life factors with prematurity-associated lung disease: prospective cohort study

Introduction Although bronchopulmonary dysplasia (BPD) is associated with lung function deficits in childhood, many who develop BPD have normal lung function in childhood, and many without BPD including those born at 33–34 weeks’ gestation, have lung dysfunction in childhood. Since the predictability of BPD for future lung deficits is increasingly doubted, we prospectively recruited preterm-born children to identify early life factors which are associated with lung function deficits after preterm-birth. Methods From 767 children aged 7–12 years, who had their respiratory symptoms assessed, and had spirometry before and after a bronchodilator in our Respiratory Health Outcomes in Neonates (RHiNO) study, 739 (544 preterm-born at ≤34 weeks’ gestation and 195 term-born) had satisfactory lung function. Data were analysed using multivariable logistic regression and mediation. Results When preterm-born children were classified according to their lung function, low lung function (prematurity-associated lung disease, PLD) was associated with BPD, gestation and intrauterine growth restriction on univariable logistic regression analyses. However, on multivariable logistic regression analyses, gestation (Beta=−0.153, se: 0.051, p=0.003) and intrauterine growth restriction (odds ratio 1.783, 95% confidence interval: 1.06, 3.00, p=0.029) remained significantly associated with later deficits of lung function but BPD (0.99; 0.52, 1.89, p=0.974) did not. Mediation analyses confirmed these results. Conclusions Although traditionally BPD has been associated with low lung function in later life, these data show that gestation and IUGR are significantly associated with PLD in childhood but BPD is not. By identifying children with PLD, we can better understand the underlying mechanisms and develop optimal therapies