Educational and health outcomes associated with bronchopulmonary dysplasia in 15-year-olds born preterm
Authors:
David Drummond aff001; Alice Hadchouel aff001; Heloise Torchin aff002; Jean-Christophe Rozé aff004; Catherine Arnaud aff006; Adèle Bellino aff009; Laure Couderc aff010; Stéphane Marret aff011; Marie Mittaine aff012; Didier Pinquier aff011; Marie Vestraete aff013; Jessica Rousseau aff014; Pierre-Yves Ancel aff002; Christophe Delacourt aff001;
Authors place of work:
Paediatric Pulmonology, University Hospital Necker-Enfants Malades, AP-HP, Paris, France
aff001; Paris Descartes University, Paris, France
aff002; Port Royal Hospital, AP-HP, Paris, France
aff003; Department of Neonatal Medicine, Nantes University Hospital, Nantes, France
aff004; CIC004, Nantes University Hospital, Nantes, France
aff005; UMR1027, INSERM, Toulouse, France
aff006; Paul Sabatier University, Toulouse, France
aff007; Clinical Epidemiology Unit, CHU Purpan, Toulouse, France
aff008; Clinical Research Unit Cochin-Necker, AP-HP, Paris, France
aff009; Rouen University Hospital, Pediatric Pulmonology and Allergology, Inserm CIC-CRB 1404 Rouen, France
aff010; INSERM U1245, Team 4, Perinatal Neurological Handicap and Brain Protection, IRIB, School of Medicine, Normandy University, Rouen, France and Department of Neonatal Medicine and Neuropediatrics, Rouen University Hospital, Rouen, France
aff011; Paediatric Pulmonology and Allergology Department, CHU Purpan, Toulouse, France
aff012; CRCM Enfants, University Hospital, Nantes, France
aff013; Obstetrical, Perinatal, and Paediatric Epidemiology Team, Epidemiology and Biostatistics Sorbonne Paris Cité Research Centre (U1153), INSERM, Paris, France
aff014; Clinical Research Unit, Centre for Clinical Investigation, P1419 Cochin Broca Hôtel-Dieu, APHP, Paris, France
aff015
Published in the journal:
PLoS ONE 14(9)
Category:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0222286
Summary
Introduction
To evaluate the consequences of bronchopulmonary dysplasia (BPD) on academic outcomes and healthcare use in adolescents born very preterm.
Methods
This cohort study included 15-year-old adolescents born very preterm (< 32 weeks) between 2011 and 2013, with and without BPD, and controls born full term. Data regarding academic performance, current medical follow-up, and family characteristics were collected. Multivariate logistic regression was used to quantify relationships between academic outcomes and BPD.
Results
From the 1341 children included in the initial cohort, 985 adolescents were eligible and 351 included (55 preterms with a history of BPD, 249 without, and 47 controls). Among adolescents born very preterm, a history of BPD was associated with a higher risk to attend a school for children with special needs (p < 0.05) and to have repeated a grade (p = 0.01). It was also associated with an increased number of medical and paramedical consultations. A history of BPD was not associated with the parents’ employment status, family structure, or the presence of younger siblings.
Conclusion
This study highlights that a history of BPD is associated with poorer academic outcomes and high healthcare use in adolescence.
Keywords:
Biology and life sciences – Physical sciences – Chemistry – Social sciences – Sociology – People and places – Population groupings – Developmental biology – Medicine and health sciences – Chemical compounds – Pathology and laboratory medicine – Organic compounds – Organic chemistry – Neonates – Diagnostic medicine – Signs and symptoms – Education – Schools – Age groups – children – Families – Vascular medicine – Steroids – Ethnicities – European people – Hemorrhage – Adolescents – French people – Dysplasia
Introduction
Extreme and very preterm births are associated with cognitive impairment and lower academic outcomes in school-age children [1–3]. Bronchopulmonary dysplasia (BPD) appears in many studies to be a worsening factor, with poorer educational outcomes, regardless of the neurological prognosis [2,4–9]. A recent meta-analysis confirmed BPD as an important and independent risk factor for poor academic outcomes in school-age children born preterm [10]. It is unknown whether a history of BPD is still associated with lower academic outcomes and increased healthcare use in adolescence. Previous studies which evaluated these outcomes included adolescents born before the surfactant and antenatal steroid treatment era [11–15] and/or did not differentiate between adolescents with or without a history of BPD [11–19]. In this report, we compare the academic outcomes and healthcare use at age 15 in adolescents born very preterm who developed BPD to those of adolescents who did not develop BPD or were born full term.
Methods
Study design
EPIPAGE (Etude EPIdémiologique sur les Petits Ages Gestationnels) was a prospective observational population-based cohort that included all births (live births and stillbirths) and late pregnancy terminations that occurred between 22 and 32 completed weeks of gestation in all maternity wards of nine French regions in 1997[20]. A control group of individuals born at term (one in every four births at 39 or 40 weeks of gestation during 1 week in 1997) was also included. Because the study focused on the causes and consequences of prematurity, and because the control group was expected to be more homogenous than the preterm group, less children were included in the control group than in the preterm group.
At recruitment in the maternity or neonatal unit, parents were informed of the study and given written information. Oral consent was given to the medical team in charge of the study in accordance with French rules in force in 1997. The study was approved by the French Commission Nationale de l’Informatique et des Libertés (the French data protection agency).
Data for mothers, pregnancies, births, and neonatal outcomes were recorded on standardized questionnaires at each maternity and neonatal intensive care unit. Maternal data included ethnic origin, tobacco consumption during pregnancy, and causes of preterm birth. Neonatal data included gender, gestational age (determined from the last menstrual period and findings from early prenatal ultrasound scans, calculated in complete weeks), birth weight, postnatal sepsis (defined as a postnatally acquired infection treated with antibiotics for at least 7 days), necrotising enterocolitis, and bronchopulmonary dysplasia (BDP). BPD was defined as the need for supplemental oxygen and/or ventilatory support at 36 weeks of post-menstrual age. Information about the health and the development of the children was subsequently collected by questionnaires sent to the families two months after discharge, and when the child was nine months, and one, two, three, and four years old. At two years of age, a questionnaire was also sent to the child’s physician. At five years of age, the children were invited for a check-up with a physician and a psychologist at local centres in every region. At eight years of age, a questionnaire was sent to the families.
EPIPAGEADO was part of the EPIPAGE study but was restricted to the very preterm born children in four French regions: Paris, Normandie, Pays-de-la-Loire, and Midi-Pyrénées. The EPIPAGEADO (“Etude EPIdémiologique sur les Petits Ages Gestationnels- Adolescents”) study was registered at clinicaltrials.gov (NCT01424553) and approved by the ethical committee CPP Ile de France VI. The inclusion criteria were complete participation in EPIPAGE from birth, available assessment at five and/or eight years of age, coverage by national health insurance, and written parental informed consent. Inclusion took place between November 2011 and June 2013, when adolescents reached the age of 15 years.
Data collection
Data for mothers, pregnancies, births, and neonatal outcomes were recorded on standardised questionnaires at each maternity and neonatal intensive care unit.
The assessment at 15 years of age included a questionnaire completed by the investigator with the participants and their parents (S1 and S2 Figs). Data regarding academic performance, current medical follow-up, and family characteristics were collected. The assessment also included anthropometric measures and lung function tests that were published in a previous study[21].
Statistics
Continuous variables were compared using the Kruskal-Wallis test and categorical variables using the Chi-2 and Fisher’s exact tests. Multivariate logistic regression was used to quantify relationships between academic outcomes and BPD before and after adjustment for potential confounders identified as relevant factors from the literature (S1 Table). Retinopathy of prematurity (ROP) was not included in the main analyses as a parameter for adjustment because 26% of values were missing. However, analyses on a smaller dataset including ROP as a potential confounder were conducted (S2 Table).
Results are reported as crude and adjusted ORs with 95% confidence intervals (CIs). Significance was set at p ≤ 0.05. Analyses were performed with SAS version 9.3 software (SAS Institute, Inc, Cary, NC).
Results
Population
From the 1341 children included in the four French regions participating to EPIPAGEADO, 985 adolescents were eligible and 351 included (Fig 1).
Flow-chart of the study population.
The study included 304 adolescents born very preterm, 55 with and 249 without a history of BPD, and 47 controls born full term. Their characteristics are presented in Table 1.
Characteristics of adolescents born very preterm with and without BPD, and controls.
Compared to adolescents born very preterm, those born full-term lived in families with a higher socio-economic status, from mothers with a higher level of education and a lower level of parity, and more frequently born in France (Table 1).
Among adolescents born very preterm, those with a history of BPD were born at a lower gestational age, with a lower birth weight, had a lower Apgar score at 1 min, were more frequently diagnosed with patent ductus arteriosus, intraventricular haemorrhage of all grades, and sepsis, and were more frequently treated with post-natal steroids (Table 1).
The included adolescents belonged to families characterised by a higher socio-economic status, a higher maternal level of education, and a higher proportion of mothers born in France than those lost to follow-up (S3 and S4 Tables).
Academic achievement
Academic achievement among adolescents born very preterm with or without a history of BPD, and controls born full term, is shown in Table 2.
Academic, health and family outcomes of adolescents born very preterm with BPD, born very preterm without BPD, and controls born full term.
Significantly more adolescents born very preterm had repeated a grade (i.e., were not considered ready to graduate by their teachers and had to repeat a year at the same grade) than controls born full preterm.
Among adolescents born very preterm, significantly more adolescents with a history of BPD attended a school adapted for children with special needs, had repeated a grade, and needed personalized assistance at school than adolescents without a history of BPD (Table 2). After adjustment for sex, gestational age, small for gestational age, intraventricular hemorrhage, periventricular leukomalacia, necrotising enterocolitis, late-onset sepsis, post-natal steroids, family structure, maternal level of education and socio-economic status, a history of BPD was still associated with attending a school adapted for children with special needs and repeating a grade (Table 3).
Comparison of academic, health and family outcomes of adolescents born very preterm with and without BPD.
Healthcare use
Significantly more adolescents born very preterm (with and without BPD) had been under the care of a psychologist of a psychiatrist in the previous 12 months than controls born full preterm (Table 2). By contrast, the proportion of adolescents who had been under the care of a medical specialist, a psychomotor therapist, a speech therapist in the previous 12 months, or who required a hospital admission in the past 5 years did not differ significantly between adolescents born very preterm and controls born full term.
Among adolescents born very preterm, those with a history of BPD were more likely to have been under the care of a psychomotor therapist, a speech therapist, and a psychologist or psychiatrist in the previous 12 months (Table 2). However, after adjustment for sex, gestational age, small for gestational age, intraventricular haemorrhage, periventricular leukomalacia, and necrotising enterocolitis, a history of BPD remained only associated with visiting a speech therapist in the previous 12 months (Table 3).
Although the overall use of a specialist or physiotherapist was identical between adolescents with or without a history of BPD, a detailed analysis by specialty showed that BPD infants used more respiratory care resources (S5 Table)
Family characteristics
Neither a history of prematurity nor a history of BPD were associated with the parents’ employment status, family structure, or the presence of younger siblings (Table 2 and S6 Table).
Discussion
This cohort study shows that the burden of BPD on health and educational services extends after childhood to 15-year-old adolescents, despite the progress made in the 1990’s in perinatal management of very preterm infants, with the generalization of surfactant use and antenatal steroid treatment.
Concerning academic achievement, one quarter of the adolescents with BPD included in our cohort attended a school adapted for children with special needs or a specialised institution and 40% had repeated a grade. These results are in accordance with previous studies which consistently found lower academic achievement among younger children who had BPD than among their peers. A meta-analysis identified BPD as the most important risk factor for poor academic outcomes in preterm children born in the antenatal steroid and surfactant era, accounting for 44% of the variance in academic performance [10]. Our study provides new insight showing that this finding extends to adolescence.
The negative impact of BPD on academic achievement does not appear to be attributable to the persistence of respiratory morbidity associated with this disease throughout childhood and adolescence. Indeed, no hospital admission for respiratory conditions in adolescents with BPD was recorded during the previous 12 months in our series. Instead, our data indicate an association between BPD and neurological morbidity, with more adolescents with BPD requiring consultations with psychomotor therapists, speech therapists, and psychologists or psychiatrists.
The family characteristics of adolescent born very preterm with BPD are more reassuring. In this study, being born very preterm with BPD was not associated with lower parental employment rates than in the French general population [22] and did not prevent families from having other children.
The main limitation of this cohort study, as in other longitudinal studies, was the high proportion of adolescents lost to follow-up (64%). Similar studies that further investigated children who were initially lost to follow-up report a worse outcome for such dropout groups [23,24]. It is likely that this is also true for our cohort. The rate of adolescents born full term who repeated a grade that we observed (4%) was much lower compared to the rates of 23.7% and 28% recorded in two surveys conducted among French 15-year-old adolescents during the same year [25]. This lower rate is explained by the higher socio-economic status and higher maternal level of education in the families of included adolescents, two factors associated with higher academic achievement. Because adolescents born very preterm also belonged to families with higher socio-economic status and higher level of education than those who were lost to follow-up, our results may underestimate the impact of prematurity and BPD on academic outcomes. A second limitation was that the evaluation of academic achievements was solely based on family interviews and not on objective assessments of different educational dimensions. Finally, BPD was defined by the need for supplemental oxygen at 36 weeks of post-menstrual age as it was common practice in 1997, before Walsh et al. published their oxygen reduction challenge in 2003 [26]. The limitation of the definition used in our study is that the need for oxygen was determined by individual physicians, while divergent practices regarding oxygen saturation exist among neonatologists.
In conclusion, this study highlights that a history of BPD is associated with poorer academic outcomes and important healthcare use in adolescence. The magnitude of these effects may be underestimated due to a non-response bias.
Supporting information
S1 Fig [pdf]
Questionnaire (in French) used to collect data from 15 years-old patients and their parents participating in the EPIPAGEADO study.
S2 Fig [pdf]
English translation of the questions used for the study.
S1 Table [pdf]
Characteristics used for adjustment for each outcome studied.
S2 Table [pdf]
Comparison of academic and health outcomes of adolescents born very preterm with and without BPD, adjusted on parameters presented in and retinopathy of prematurity.
S3 Table [pdf]
Characteristics of adolescents born very preterm included and lost to follow-up.
S4 Table [pdf]
Characteristics of adolescents control (full term) included and lost to follow-up.
S5 Table [pdf]
Healthcare use in adolescents born very preterm with and without BPD.
S6 Table [pdf]
Family characteristics of adolescents born very preterm with and without BPD.
Zdroje
1. Larroque B, Ancel P-Y, Marret S, Marchand L, André M, Arnaud C, et al. Neurodevelopmental disabilities and special care of 5-year-old children born before 33 weeks of gestation (the EPIPAGE study): a longitudinal cohort study. Lancet Lond Engl. 2008;371: 813–820. doi: 10.1016/S0140-6736(08)60380-3
2. Larroque B, Ancel P-Y, Marchand-Martin L, Cambonie G, Fresson J, Pierrat V, et al. Special care and school difficulties in 8-year-old very preterm children: the Epipage cohort study. PloS One. 2011;6: e21361. doi: 10.1371/journal.pone.0021361 21760892
3. Serenius F, Ewald U, Farooqi A, Fellman V, Hafström M, Hellgren K, et al. Neurodevelopmental Outcomes Among Extremely Preterm Infants 6.5 Years After Active Perinatal Care in Sweden. JAMA Pediatr. 2016;170: 954–963. doi: 10.1001/jamapediatrics.2016.1210 27479919
4. Sriram S, Schreiber MD, Msall ME, Kuban KCK, Joseph RM, O’ Shea TM, et al. Cognitive Development and Quality of Life Associated With BPD in 10-Year-Olds Born Preterm. Pediatrics. 2018;141. doi: 10.1542/peds.2017-2719 29773664
5. Short EJ, Klein NK, Lewis BA, Fulton S, Eisengart S, Kercsmar C, et al. Cognitive and academic consequences of bronchopulmonary dysplasia and very low birth weight: 8-year-old outcomes. Pediatrics. 2003;112: e359. 14595077
6. Trittmann JK, Nelin LD, Klebanoff MA. Bronchopulmonary dysplasia and neurodevelopmental outcome in extremely preterm neonates. Eur J Pediatr. 2013;172: 1173–1180. doi: 10.1007/s00431-013-2016-5 23644648
7. Gray PH, O’Callaghan MJ, Rogers YM. Psychoeducational outcome at school age of preterm infants with bronchopulmonary dysplasia. J Paediatr Child Health. 2004;40: 114–120. 15009575
8. Hughes CA, O’Gorman LA, Shyr Y, Schork MA, Bozynski ME, McCormick MC. Cognitive performance at school age of very low birth weight infants with bronchopulmonary dysplasia. J Dev Behav Pediatr JDBP. 1999;20: 1–8. 10071939
9. Robertson CM, Etches PC, Goldson E, Kyle JM. Eight-year school performance, neurodevelopmental, and growth outcome of neonates with bronchopulmonary dysplasia: a comparative study. Pediatrics. 1992;89: 365–372. 1741206
10. Twilhaar ES, de Kieviet JF, Aarnoudse-Moens CS, van Elburg RM, Oosterlaan J. Academic performance of children born preterm: a meta-analysis and meta-regression. Arch Dis Child Fetal Neonatal Ed. 2018;103: F322–F330. doi: 10.1136/archdischild-2017-312916 28847871
11. Moster D, Lie RT, Markestad T. Long-term medical and social consequences of preterm birth. N Engl J Med. 2008;359: 262–273. doi: 10.1056/NEJMoa0706475 18635431
12. Hille ETM, Weisglas-Kuperus N, van Goudoever JB, Jacobusse GW, Ens-Dokkum MH, de Groot L, et al. Functional outcomes and participation in young adulthood for very preterm and very low birth weight infants: the Dutch Project on Preterm and Small for Gestational Age Infants at 19 years of age. Pediatrics. 2007;120: e587–595. doi: 10.1542/peds.2006-2407 17766499
13. Saigal S, Stoskopf B, Streiner D, Boyle M, Pinelli J, Paneth N, et al. Transition of extremely low-birth-weight infants from adolescence to young adulthood: comparison with normal birth-weight controls. JAMA. 2006;295: 667–675. doi: 10.1001/jama.295.6.667 16467235
14. Cooke RWI. Health, lifestyle, and quality of life for young adults born very preterm. Arch Dis Child. 2004;89: 201–206. doi: 10.1136/adc.2003.030197 14977689
15. Hack M, Flannery DJ, Schluchter M, Cartar L, Borawski E, Klein N. Outcomes in young adulthood for very-low-birth-weight infants. N Engl J Med. 2002;346: 149–157. doi: 10.1056/NEJMoa010856 11796848
16. Cheong JLY, Anderson PJ, Roberts G, Burnett AC, Lee KJ, Thompson DK, et al. Contribution of brain size to IQ and educational underperformance in extremely preterm adolescents. PloS One. 2013;8: e77475. doi: 10.1371/journal.pone.0077475 24130887
17. Litt JS, Gerry Taylor H, Margevicius S, Schluchter M, Andreias L, Hack M. Academic achievement of adolescents born with extremely low birth weight. Acta Paediatr Oslo Nor 1992. 2012;101: 1240–1245. doi: 10.1111/j.1651-2227.2012.02790.x
18. McNicholas F, Healy E, White M, Sherdian-Pereira M, O’Connor N, Coakley S, et al. Medical, cognitive and academic outcomes of very low birth weight infants at age 10–14 years in Ireland. Ir J Med Sci. 2014;183: 525–532. doi: 10.1007/s11845-013-1040-9 24306730
19. Holsti A, Adamsson M, Hägglöf B, Farooqi A, Serenius F. Chronic Conditions and Health Care Needs of Adolescents Born at 23 to 25 Weeks’ Gestation. Pediatrics. 2017;139. doi: 10.1542/peds.2016-2215
20. Larroque B, Bréart G, Kaminski M, Dehan M, André M, Burguet A, et al. Survival of very preterm infants: Epipage, a population based cohort study. Arch Dis Child Fetal Neonatal Ed. 2004;89: F139–144. doi: 10.1136/adc.2002.020396 14977898
21. Hadchouel A, Rousseau J, Rozé J-C, Arnaud C, Bellino A, Couderc L, et al. Association between asthma and lung function in adolescents born very preterm: results of the EPIPAGE cohort study. Thorax. 2018; doi: 10.1136/thoraxjnl-2017-211115
22. Guedj H. Le taux d’emploi des hommes et des femmes. Des écarts plus marqués en équivalent temps plein. Insee Première. 2013 pp. 1–4. Report No.: 1462.
23. Callanan C, Doyle L, Rickards A, Kelly E, Ford G, Davis N. Children followed with difficulty: how do they differ? J Paediatr Child Health. 2001;37: 152–156. 11328470
24. Hille ETM, Elbertse L, Gravenhorst JB, Brand R, Verloove-Vanhorick SP, Dutch POPS-19 Collaborative Study Group. Nonresponse bias in a follow-up study of 19-year-old adolescents born as preterm infants. Pediatrics. 2005;116: e662–666. doi: 10.1542/peds.2005-0682 16263980
25. Mons N, Blanchard-Schneider A. Lutter contre les difficultés scolaires: le redoublement et ses alternatives? [Internet]. Paris: Cnesco; 2014. Available: http://www.cnesco.fr/wp-content/uploads/2014/08/280814CNESCO_redoublement1.pdf
26. Walsh MC, Wilson-Costello D, Zadell A, Newman N, Fanaroff A. Safety, reliability, and validity of a physiologic definition of bronchopulmonary dysplasia. J Perinatol Off J Calif Perinat Assoc. 2003;23: 451–456. doi: 10.1038/sj.jp.7210963
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