[Show abstract][Hide abstract] ABSTRACT: 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.
PLoS ONE 09/2015; 10(9):e0136123. DOI:10.1371/journal.pone.0136123 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: There is currently no consensus for the screening and treatment of patent ductus arteriosus (PDA) in extremely preterm infants. Less pharmacological closure and more supportive management have been observed without evidence to support these changes.
To evaluate the association between early screening echocardiography for PDA and in-hospital mortality.
Comparison of screened and not screened preterm infants enrolled in the EPIPAGE 2 national prospective population-based cohort study that included all preterm infants born at less than 29 weeks of gestation and hospitalized in 68 neonatal intensive care units in France from April through December 2011. Two main analyses were performed to adjust for potential selection bias, one using propensity score matching and one using neonatal unit preference for early screening echocardiography as an instrumental variable.
Early screening echocardiography before day 3 of life.
The primary outcome was death between day 3 and discharge. The secondary outcomes were major neonatal morbidities (pulmonary hemorrhage, severe bronchopulmonary dysplasia, severe cerebral lesions, and necrotizing enterocolitis).
Among the 1513 preterm infants with data available to determine exposure, 847 were screened for PDA and 666 were not; 605 infants from each group could be paired. Exposed infants were treated for PDA more frequently during their hospitalization than nonexposed infants (55.1% vs 43.1%; odds ratio [OR], 1.62 [95% CI, 1.31 to 2.00]; absolute risk reduction [ARR] in events per 100 infants, -12.0 [95% CI, -17.3 to -6.7). Exposed infants had a lower hospital death rate (14.2% vs 18.5% ; OR, 0.73 [95% CI, 0.54 to 0.98]; ARR, 4.3 [95% CI, 0.3 to 8.3]) and a lower rate of pulmonary hemorrhage (5.6% vs 8.9%; OR, 0.60 [95% CI, 0.38 to 0.95]; ARR, 3.3 [95% CI, 0.4 to 6.3]). No differences in rates of necrotizing enterocolitis, severe bronchopulmonary dysplasia, or severe cerebral lesions were observed. In the overall cohort, instrumental variable analysis yielded an adjusted OR for in-hospital mortality of 0.62 [95% CI, 0.37 to 1.04].
In this national population-based cohort of extremely preterm infants, screening echocardiography before day 3 of life was associated with lower in-hospital mortality and likelihood of pulmonary hemorrhage but not with differences in necrotizing enterocolitis, severe bronchopulmonary dysplasia, or severe cerebral lesions. However, results of the instrumental variable analysis leave some ambiguity in the interpretation, and longer-term evaluation is needed to provide clarity.
JAMA The Journal of the American Medical Association 06/2015; 313(24):2441-2448. DOI:10.1001/jama.2015.6734 · 35.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Up-to-date estimates of the health outcomes of preterm children are needed for assessing perinatal care, informing parents, making decisions about care, and providing evidence for clinical guidelines.
To determine survival and neonatal morbidity of infants born from 22 through 34 completed weeks' gestation in France in 2011 and compare these outcomes with a comparable cohort in 1997.
The EPIPAGE-2 study is a national, prospective, population-based cohort study conducted in all maternity and neonatal units in France in 2011. A total of 2205 births (stillbirths and live births) and terminations of pregnancy at 22 through 26 weeks' gestation, 3257 at 27 through 31 weeks, and 1234 at 32 through 34 weeks were studied. Cohort data were collected from January 1 through December 31, 1997, and from March 28 through December 31, 2011. Analyses for 1997 were run for the entire year and then separately for April to December; the rates for survival and morbidities did not differ. Data are therefore presented for the whole year in 1997 and the 8-month and 6-month periods in 2011.
Survival to discharge and survival without any of the following adverse outcomes: grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, severe bronchopulmonary dysplasia, retinopathy of prematurity (stage 3 or higher), or necrotizing enterocolitis (stages 2-3).
A total of 0.7% of infants born before 24 weeks' gestation survived to discharge: 31.2% of those born at 24 weeks, 59.1% at 25 weeks, and 75.3% at 26 weeks. Survival rates were 93.6% at 27 through 31 weeks and 98.9% at 32 through 34 weeks. Infants discharged home without severe neonatal morbidity represented 0% at 23 weeks, 11.6% at 24 weeks, 30.0% at 25 weeks, 47.5% at 26 weeks, 81.3% at 27 through 31 weeks, and 96.8% at 32 through 34 weeks. Compared with 1997, the proportion of infants surviving without severe morbidity in 2011 increased by 14.4% (P < .001) at 25 through 29 weeks and 6% (P < .001) at 30 through 31 weeks but did not change appreciably for those born at less than 25 weeks. The rates of antenatal corticosteroid use, induced preterm deliveries, cesarean deliveries, and surfactant use increased significantly in all gestational-age groups, except at 22 through 23 weeks.
The substantial improvement in survival in France for newborns born at 25 through 31 weeks' gestation was accompanied by an important reduction in severe morbidity, but survival remained rare before 25 weeks. Although improvement in survival at extremely low gestational age may be possible, its effect on long-term outcomes requires further studies. The long-term results of the EPIPAGE-2 study will be informative in this regard.
[Show abstract][Hide abstract] ABSTRACT: Objective Twins have inconsistently shown poorer outcomes than singletons. Although a high proportion of twins are born very preterm, data are sparse on the long-term outcomes in very preterm twins. The objective of this study was to compare mortality and neurodevelopmental outcomes of very preterm singletons and twins and to study outcomes in relation to factors specific to twins.
Design Birth cohort study Etude Epidemiologique sur les Petits Ages Gestationnels (EPIPAGE).
Setting Nine regions in France.
Patients All very preterm live births occurring from 22 to 32 weeks of gestation in all maternity wards of nine French regions in 1997 (n=2773).
Main outcomes measures Neurodevelopmental status, including cerebral palsy, and a cognitive assessment with the Kaufman Assessment Battery for Children, with scores on the Mental Processing Composite (MPC) scale, was available for 1732 and 1473 children at 5 years of age, respectively.
Results Among live births, twins had higher hospital mortality than singletons (adjusted (a)OR: 1.4 (95% CI 1.1 to 1.9)). Among survivors, there was no crude difference at 5 years between twins and singletons in the prevalence of cerebral palsy (8.0% vs 9.1%, respectively), MPC <70 (9.5% vs 11.1%) and mean MPC (94.6 vs 94.4). However, after adjustment for sex, gestational age, intrauterine growth restriction and social factors, twins were more likely to have lower MPC scores (mean difference: −2.4 (95% CI–4.8 to 0.01)). Live born twins had a higher risk of mortality when birth weight discordance was present (aOR:2.9 (95% CI 1.7 to 4.8)), but there were no differences in long-term outcomes.
Conclusions Compared with very preterm singletons, twins had higher mortality, no difference with respect to severe deficiencies, but slightly lower MPC scores at 5 years.
Archives of Disease in Childhood - Fetal and Neonatal Edition 10/2013; 98(6):F480-F487. DOI:10.1136/archdischild-2013-303737 · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate the association of motor and cognitive/learning deficiencies and overall disabilities in very preterm (VPT) children and their relations to gestational age (GA) and brain lesions.
EPIPAGE is a longitudinal population-based cohort study of children born before 33 weeks' gestation (WG) in 9 French regions in 1997-1998. Cumulating data from all follow up stages, neurodevelopmental outcomes were available for 90% of the 2480 VPT survivors at 8 years. Main outcomes were association of motor and cognitive deficiencies and existence of at least one deficiency (motor, cognitive, behavioral/psychiatric, epileptic, visual, and/or hearing deficiencies) in three GA groups (24-26, 27-28, and 29-32WG) and four groups of brain lesions (none, minor, moderate, or severe).
VPT had high rates of motor (14%) and cognitive (31%) deficiencies. Only 6% had an isolated motor deficiency, 23% an isolated cognitive one and 8% both types. This rate reached 20% among extremely preterm. Psychiatric disorders and epilepsy were observed in 6% and 2% of children, respectively. The risks of at least one severe or moderate deficiency were 11 and 29%. These risks increased as GA decreased; only 36% of children born extremely preterm had no reported deficiency. Among children with major white matter injury (WMI), deficiency rates reached 71% at 24-26WG, 88% at 27-28WG, and 80% at 29-32WG; more than 40% had associated motor and cognitive deficiencies. By contrast, isolated cognitive deficiency was the most frequent problem among children without major lesions.
In VPT, the lower the GA, the higher the neurodisability rate. Cerebral palsy is common. Impaired cognitive development is more frequent. Its occurrence in case without WMI or early motor disorders makes long-term follow up necessary. The strong association between motor impairments, when they exist, and later cognitive dysfunction supports the hypothesis of a common origin of these difficulties.
PLoS ONE 05/2013; 8(5):e62683. DOI:10.1371/journal.pone.0062683 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective:
To compare 3 methods of identifying small-for-gestational-age (SGA) status in very preterm children as related to cognitive function and academic outcome.
There were 1038 singletons in the Epipage Study, born before 33 weeks in 1997 without severe neurosensory impairment, who were classified as SGA when birth weight was below the 10th percentile according to: (1) birth weight (bw) reference: SGA(bw)/appropriate for gestational age (AGA)(bw); (2) intrauterine (intraut) reference: SGA(intraut)/AGA(intraut); and (3) intrauterine reference customized (cust) according to individual characteristics: SGA(cust)/AGA(cust). Cognitive function was assessed by the mental processing composite (MPC) score of the Kaufman Assessment Battery for Children at age 5 and academic achievement by a parental questionnaire at age 8.
Of the children, 15% were SGA(bw), 38% were SGA(intraut), and 39% were SGA(cust). All children SGA(bw) were also SGA(intraut) and SGA(cust). MPC was <85 in 32% of children and 27% had low academic achievement. AGA(bw)/SGA(intraut) children had a significantly increased risk of MPC <85 (adjusted OR 1.74, 95% CI 1.22-2.28) or low academic achievement (adjusted OR 1.64, 95% CI 1.05-2.55) compared with AGA(bw)/AGA(intraut) children. The SGA(cust) group was only slightly different from the SGA(intraut) group.
An intrauterine reference identified very preterm infants at risk of poor cognitive or academic outcomes better than a birth weight reference. Customization resulted in only slight modifications of the SGA group.
The Journal of pediatrics 07/2012; 161(6). DOI:10.1016/j.jpeds.2012.05.037 · 3.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objectives of the study were (1) to assess prevalence of social withdrawal behaviour in infants aged 12 months included in the French Perinatal Risk Factor Study Eden; (2) To study the correlation between relational withdrawal and several perinatal and parental factors assessed in the EDEN study. A longitudinal study using the ADBB scale was conducted within the Eden Cohort in the year 2008. 1,586 infants were included in the study. Fourteen percent of the children who had an ADBB assessment had a score at 5 and over on the ADBB, a scale designed to assess social withdrawal behaviour at age 0-24 months. Social withdrawal at 12 months was associated with low birth weight, low gestational age and with intra uterine growth retardation. Social withdrawal was independently associated with several maternal and paternal risk factors. The level of social withdrawal behaviour increased with a score of maternal difficulties. This study on a large longitudinally followed volunteer sample demonstrate a clear association of social withdrawal behaviour at age one with low birth weight and preterm birth, possibly mediated by parental vulnerabilities. Social withdrawal behaviour seems to be an important alarm signal to detect early on particularly in premature and small for date babies.
[Show abstract][Hide abstract] ABSTRACT: Background: Being born small for gestational age (SGA) is associated with developmental disabilities but associations may vary depending on the definition of SGA.Aim: To analyse the impact of this definition on the relation between SGA and cognitive or school outcome.Methods: 980 singletons born before 33 weeks in 1997 in France, part of the Epipage study, free of cerebral palsy, were classified SGA when birth weight was < 10th percentile, according to 3 French standards: 1. neonatal standard: nSGA or nAGA; 2. intrauterine standard using Hadlock's formula: fSGA or fAGA; 3. customised standard taking into account maternal characteristics: cSGA or cAGA.Outcomes were cognitive dysfunction at age 5 defined as a score < -1 SD for the term control group (K-ABC battery), and school difficulties at age 8.Results: 149 children were nSGA (15.2 %), 368 fSGA (37.6 %) and 378 (38.6 %) cSGA. All nSGA children were fSGA and cSGA. Cognitive dysfunction was present in 300 children (35.0 %) and school difficulties in 173 (25.1 %). Children nAGA/fSGA did not have a significant increase of cognitive dysfunction compared to children nAGA/fAGA. Compared to children nAGA/fAGA, children nSGA/fSGA had an adjusted OR of school difficulties of 2.48 [1.52;4.05] while it was 1.63 [1.05;2.55] for children nAGA/fSGA. Children fAGA/cSGA (N=18) had a higher rate of school difficulties compared to children fAGA/cAGA (p=0.03).Conclusions: Intratuerine standard for birth weight is more appropriate than neonatal one to predict school outcome for very preterm singletons. The utility of customisation should be clarified.
Pediatric Research 11/2011; 70:310-310. DOI:10.1038/pr.2011.535 · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate growth for children born very preterm with particular focus on those born small-for-gestational age (SGA) or with ex utero growth restraint (GR), and to identify risk factors for short stature at 5 years of age.
Population-based study of children born at less than 33 completed weeks of gestation (Étude Epidémiologique sur les Petits Ages Gestationnels (EPIPAGE)). Short stature was defined as height <-2SD on WHO growth curves. Ex utero GR was considered to have occurred in children with appropriate size for gestational age at birth and with a height and/or weight below -2SD at 2 years of corrected age. Logistic regression models were used to test associations between risk factors and short stature.
The authors measured height at 5 years of age for 1,597 of 2,193 children (73%), 5.6% (95% CI 4.6 to 6.9) of whom were diagnosed as having a short stature. Height was measured at 2 and 5 years of age in 1417 children. Among these, 24% of those born SGA and 36% of those with ex utero GR (p=0.002) had a short stature at 5 years. Predictors of short stature were SGA or birth length <-2SD, maternal height ≤ 160 cm, gestational age <29 weeks and systemic corticosteroids. Breastfeeding at discharge decreased the risk of short stature.
Short stature at 5 years of age is common in children born preterm. The highest incidence was observed in the group with ex utero GR. Systemic steroids have a long-term impact on growth and should be used with caution. Breastfeeding at discharge appeared to be protective.
Archives of Disease in Childhood - Fetal and Neonatal Edition 08/2011; 96(5):F348-54. DOI:10.1136/adc.2010.185470 · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate school difficulties, special care and behavioral problems in 8 year-old very preterm (VPT) children.
Longitudinal population-based cohort in nine regions of France of VPT children and a reference group born at 39-40 weeks of gestation (WG). The main outcome measures were information about school, special care and behavioral problems using Strengths and Difficulties Questionnaire from a questionnaire to parents.
Among the 1439 VPT children, 5% (75/1439) were in a specialised school or class, 18% (259/1439) had repeated a grade in a mainstream class and 77% (1105/1439) were in the appropriate grade-level in mainstream class; these figures were 1% (3/327) , 5% (16/327) and 94% (308/327) , respectively, for the reference group. Also, 15% (221/1435) of VPT children in a mainstream class received support at school versus 5% (16/326) of reference group. More VPT children between the ages of five and eight years received special care (55% (794/1436)) than children born at term (38% (124/325)); more VPT children (21% (292/1387)) had behavioral difficulties than the reference group (11% (35/319)). School difficulties, support at school, special care and behavioral difficulties in VPT children without neuromotor or sensory deficits varied with gestational age, socioeconomic status, and cognitive score at the age of five.
Most 8-year-old VPT children are in mainstream schools. However, they have a high risk of difficulty in school, with more than half requiring additional support at school and/or special care. Referral to special services has increased between the ages of 5 and 8 years, but remained insufficient for those with borderline cognitive scores.
PLoS ONE 07/2011; 6(7):e21361. DOI:10.1371/journal.pone.0021361 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study the predictive value of a developmental assessment at 2 years corrected age (CA) for schooling at age 8 in children born very preterm and free of disability or delay; to identify other factors associated with schooling in this population.
244 children born before 33 weeks in 1997, part of the population-based EPIPAGE cohort study, free of disability or delay, had their developmental quotient (DQ) evaluated with the Brunet-Lezine scale at 2 years CA. The mental processing composite (MPC) score was evaluated at age 5 with the K-ABC battery. Data on schooling were obtained at age 8 by postal questionnaire. Schooling was considered appropriate if the child was attending age-appropriate grade level in a regular classroom environment without support at school.
Schooling was appropriate for 172 (70%) children. The predictive value of a DQ≥100 for appropriate schooling was 0.80 [0.75;0.85]. In children with a DQ at age 2<100, schooling varied significantly according to their MPC score at age 5 whereas it didn't in children with a DQ≥100. In multivariate analysis, the rate of appropriate schooling was significantly related to global DQ at age 2 (p<0.01), gestational age≥29 weeks (p<0.05), head circumference at age 2 (p<0.05) and mother's educational level (p<0.05).
A DQ≥100 cannot be solely used for the prediction of appropriate schooling at age 8. Mother's educational level, gestational age and head circumference at age 2 could be taken account. These factors could be used to individualise follow-up.
Early human development 02/2011; 87(4):297-302. DOI:10.1016/j.earlhumdev.2011.01.033 · 1.79 Impact Factor