Salivary Telomere Length and Lung Function in Adolescents Born Very Preterm: A Prospective Multicenter Study

<div><p>Preterm birth is associated with abnormal respiratory functions throughout life. The mechanisms underlying these long-term consequences are still unclear. Shortening of telomeres was associated with many conditions, such as chronic obstructive pulmonary disease. We aimed to search for an association between telomere length and lung function in adolescents born preterm. Lung function and telomere length were measured in 236 adolescents born preterm and 38 born full-term from the longitudinal EPIPAGE cohort. Associations between telomere length and spirometric indices were tested in univariate and multivariate models accounting for confounding factors in the study population. Airflows were significantly lower in adolescents born preterm than controls; forced expiratory volume in one second was 12% lower in the extremely preterm born group than controls (p<0.001). Lower birth weight, bronchopulmonary dysplasia and postnatal sepsis were significantly associated with lower airflow values. Gender was the only factor that was significantly associated with telomere length. Telomere length correlated with forced expiratory flow 25–75 in the extremely preterm adolescent group in univariate and multivariate analyses (p = 0.01 and p = 0.02, respectively). We evidenced an association between telomere length and abnormal airflow in a population of adolescents born extremely preterm. There was no evident association with perinatal events. This suggests other involved factors, such as a continuing airway oxidative stress leading to persistent inflammation and altered lung function, ultimately increasing susceptibility to chronic obstructive pulmonary disease.</p></div

Flowchart of the study population.

<p>For each group, age at the time of the study is expressed as medians [IQR]. *probable move without leaving a forwarding address. LFT: lung function tests; QC: quality control; qPCR: quantitative polymerase chain reaction; wPMA: weeks of post-menstrual age.</p

Telomere length and lung function parameters before and after adjustment for potential confounders.

<p>*Coefficient for an increase of 0.1 in telomere length</p><p>Adjustment for birth weight, BPD, sex, postnatal sepsis and maternal cigarette smoking during pregnancy</p><p>Telomere length and lung function parameters before and after adjustment for potential confounders.</p

Telomere length and lung function parameters in ex-preterm adolescents.

<p>Telomere length and lung function parameters in ex-preterm adolescents.</p

Epidemiological and clinical characteristics of the study population.

<p>Continuous variables are expressed as medians [IQR] and categorical variables as numbers (%).</p><p>NA: not available data</p><p>Epidemiological and clinical characteristics of the study population.</p

LFT and telomere length according to group of gestational age.

<p>Continuous variables are shown as medians [IQR] and categorical variables are shown as numbers (%).</p><p>*Comparison between the 24–28 wPMA, 29–32 wPMA and 39–40 wPMA groups with chi-square test or Kruskal-Wallis test, as appropriate.</p><p>†Compared to the normal control group (Z-score ≥ -1.64)</p><p>LFT and telomere length according to group of gestational age.</p

Association between maximal non conjugated bilirubin level and non-optimal neurological outcome in 631 infants at 2-year corrected age (subpopulations studies).

<p>Adjustment was performed for pregnancy, infant and neonatal hospitalization characteristics. Pregnancy characteristics included prenatal corticosteroid treatment, multiple pregnancies, hypertension during pregnancy, premature rupture of membranes >24 h, and cesarean section. Mother characteristics included health insurance for low financial income and upper socio-demographic level. Infant characteristics included GA, birthweight, small for GA, gender. Neonatal hospitalization characteristics included surfactant therapy, maternofetal sepsis, nosocomial sepsis, bronchopulmonary dysplasia, hemodynamic failure and patent ductus arteriosus requiring treatment.</p

Changes in mean serum unconjugated bilirubin levels (SBL) during the first week of life in relation to birthweight.

<p>This figure shows three graphs: (1) the upper graph concerns infants with birthweight under 1500 g; (2) the intermediary graph concerns infants with birthweight between 1001 and 1500 g, and (3) the lower graph concerns the smallest infants (under 1001 g). Each graph is composed by four curves: three curves representing changes in mean SBL in infants of the first tertile (line a), second tertile (line b) and third tertile (line c). The fourth curve (dotted line or line d) represents the 95^th percentile of SBL in infants with an optimal neurological outcome at 2-year corrected age.</p

Association between maximal serum non-conjugated bilirubin level and non-optimal neurological outcome at 2-year corrected age (n = 631).

<p>Pregnancy characteristics included prenatal corticosteroid treatment, multiple pregnancies, hypertension during pregnancy, premature rupture of membranes >24 h and cesarean section. Mother characteristics included health insurance for low financial income and upper socio-demographic level. Infant characteristics included GA, birthweight, small for GA and gender. Neonatal hospitalization characteristics included surfactant therapy, maternofetal sepsis, nosocomial sepsis, bronchopulmonary dysplasia, hemodynamic failure and patent ductus arteriosus requiring treatment.</p

Characteristics of the study population.

<p>Characteristics of the study population.</p