National PEP 99-00 follow-up 2017-2018
The purpose of PEP is to study short- and long-term health and well-being in children born extremely prematurely. Such knowledge is needed to improve treatment in pregnancy, in the neonatal period and later, and could be used to better facilitate optimal outcomes for the children and their families through life.
In PEP, we follow all children born in Norway in 1999-2000 with a gestational age lower than 28 weeks (extremely preterm) or a birth weight lower than 1000 gram (extremely low birth weight). All examinations are based on written informed consents from parents or guardians.
Leader of National PEP 99-00 follow-up:
MD, PhD Maria Vollsæter
What do we know so far?
We have included comprehensive information, clinical and questionnaire-based, on the children from their pregnancy, the neonatal period and from 2, 5 and 11 years of age.
Extended examinations of those born in Western Norway:
The children from Western Norway Health Authority (Helse Vest, born in the counties Sogn og Fjordane, Hordaland and Rogaland) were seen with individually matched term-born control children at 11 years of age. Extensive investigations were made, with clinical examinations, anthropometric measures (height, weight, skinfolds, blood pressure), lung function studies and measurements of bone mineral density and muscle-fat distribution.
Blood samples were collected to investigate whether extreme prematurity influences body growth and development and the risk for later chronic diseases.
Functional MRI (magnetic resonance imaging) investigations were performed in the children born in Sogn og Fjordane and Hordaland. In this study, the children perform certain intellectual tasks in order to investigate whether children born extremely preterm use their brain in a different way from those born at term.
What happens next?
The regional ethical committee for medical research has approved a new national questionnaire-based study to obtain information on the health and well-being of the extremely preterm 1999-2000 cohort at 18 years of age. This study is in collaboration with Uni Helse, Bergen. We have also gained approval for a new clinical study of those born in Helse Vest at 18 years of age, along with their term-born controls.
We depend on a high participation rate to gain valid statistical results, and sincerely hope that our participants will take time to answer both questionnaires and to perform clinical examinations!
Most studies reporting data from long-term follow-ups after preterm birth, have rather few participants, and hence impaired statistical power. To solve this, international projects have been formed in order to collect data internationally in larger databases. Currently, our group is involved in to such projects, both relevant to the PEP project and the respiratory group:
Individual patient data analysis of respiratory health and function in adulthood of very low birthweight or very preterm survivors. This projects is leaded by Prof Les Doyle, The Murdoch Children’s Research Institute, Melbourne, Australia, and in collaboration with a larger international group; Adults Born Preterm International Collaboration (APIC), for more information see http://www.apic-preterm.org/.
Specifically, our group will contribute data for lung function from several preterm groups.
The EU-project “RECAP” from Horizon 2020 “Networking and optimizing the use of population and patient cohorts at EU level”.
Specifically, our group will contribute data from the national PEP 1999-2000 study.
These two projects are reliable, with strong leadership as well as transparency. Data will be shared in anonymous and de-identified formats, according to Norwegian law and in collaboration with relevant national and local institutions and the person safety representative at Haukeland University Hospital.
Communication of research findings:
Results from the studies have been presented in national and international research congresses, and multiple studies have been published in peer-reviewed journals.
Several studies are on the way in international journals.
Four have dissertated with Ph.D degrees/doctorates, and others are on their way.
1: Bjorke-Monsen AL, Vollsaeter M, Ueland PM, Markestad T, Oymar K, Halvorsen T. Increased Bronchial Hyperresponsiveness and Higher ADMA Levels After Fetal Growth Restriction. American journal of respiratory cell and molecular biology. 2016.
2: Skromme K, Leversen KT, Eide GE, Markestad T, Halvorsen T. Respiratory illness contributed significantly to morbidity in children born extremely premature or with extremely low birth weights in 1999-2000. Acta Paediatr 2015 Aug 25. [Epub ahead of print]
3: Westby Eger SH, Kessler J, Kiserud T, Markestad T, Sommerfelt K. Foetal Doppler abnormality is associated with increased risk of sepsis and necrotising enterocolitis in preterm infants. Acta Paediatr. 2015;104:368-76.
4: Elgen SK, Sommerfelt K, Leversen KT, Markestad T. Minor neurodevelopmental impairments are associated with increased occurrence of ADHD symptoms in children born extremely pretermature. Eur Child Adolesc Psychiatry. 2015;24:463-70.
5: Griffiths ST, Aukland SM, Markestad T, Eide GE, Elgen I, Craven AR, Hugdahl K. Association between brain activation (fMRI), cognition and school performance in extremely preterm and term born children. Scand J Psychol. 2014;55:427-32.
6: Griffiths ST, Elgen IB, Chong WK, Odberg MD, Markestad T, Neto E, Aukland SM. Cerebral magnetic resonance imaging findings in children born extremely preterm, very preterm, and at term. Pediatr Neurol. 2013;49:113-8.
7: Griffiths ST, Gundersen H, Neto E, Elgen I, Markestad T, Aukland SM, Hugdahl K. fMRI: blood oxygen level-dependent activation during a working memory-selective attention task in children born extremely preterm. Pediatr Res. 2013;74196-205.
8: Vollsæter M, Røksund OD, Eide GE, Markestad T, Halvorsen T. Lung function after preterm birth: development from mid-childhood to adulthood. Thorax. 2013;68:767-76. PMID: 23749815.
9: Eger SH, Sommerfelt K, Kiserud T, Markestad T. Foetal umbilical artery Doppler in small preterms: (IQ) neurocognitive outcome at 5 years of age. Acta Paediatr. 2013;102:403-9.
10: Elgen SK, Leversen KT, Grundt JH, Hurum J, Sundby AB, Elgen IB, Markestad T. Mental health at 5 years among children born extremely preterm: a national population-based study. Eur Child Adolesc Psychiatry. 2012;21583-9.
11: Leversen KT, Sommerfelt K, Elgen IB, Eide GE, Irgens LM, Júlíusson PB, Markestad T. Prediction of outcome at 5 years from assessments at 2 years among extremely preterm children: a Norwegian national cohort study. Acta Paediatr. 2012;101264-70.
12: Leversen KT, Sommerfelt K, Rønnestad A, Kaaresen PI, Farstad T, Skranes J, Støen R, Bircow Elgen I, Rettedal S, Egil Eide G, Irgens LM, Markestad T. Prediction of neurodevelopmental and sensory outcome at 5 years in Norwegian children born extremely preterm. Pediatrics 2011;127:e630-8.
13: Leversen KT, Sommerfelt K, Rønnestad A, Kaaresen PI, Farstad T, Skranes J, Støen R, Elgen IB, Rettedal S, Eide GE, Irgens LM, Markestad T. Predicting neurosensory disabilities at two years of age in a national cohort of extremely premature infants. Early Hum Dev. 2010;86:581-6.
14: Farstad T, Bratlid D, Medbø S, Markestad T; Norwegian Extreme Pematurity Study Group. Bronchopulmonary dysplasia - prevalence, severity and predictive factors in a national cohort of extremely premature infants. Acta Paediatr. 2011;100:53-8.
15: Westby Wold SH, Sommerfelt K, Reigstad H, Rønnestad A, Medbø S, Farstad T, Kaaresen PI, Støen R, Leversen KT, Irgens LM, Markestad T. Neonatal mortality and morbidity in extremely preterm small for gestational age infants: a population based study. Arch Dis Child Fetal Neonatal Ed. 2009;94:F363-7.
16: Markestad T, Kaaresen PI, Rønnestad A, Reigstad H, Lossius K, Medbø S, Zanussi G, Engelund IE, Skjaerven R, Irgens LM; Norwegian Extreme Prematurity Study Group. Early death, morbidity, and need of treatment among extremely premature infants. Pediatrics. 2005;115:1289-98.
17: Rønnestad A, Abrahamsen TG, Medbø S, Reigstad H, Lossius K, Kaaresen PI, Engelund IE, Irgens LM, Markestad T. Septicemia in the first week of life in a Norwegian national cohort of extremely premature infants. Pediatrics. 2005;115:e262-8.
18: Rønnestad A, Abrahamsen TG, Medbø S, Reigstad H, Lossius K, Kaaresen PI, Egeland T, Engelund IE, Irgens LM, Markestad T. Late-onset septicemia in a Norwegian national cohort of extremely premature infants receiving very early full human milk feeding. Pediatrics. 2005;115:e269-76.
PhD dissertations based on the PEP-studies:
Silje Katrine Elgen Fevang. Mental health among children born extremely preterm or with extremely low birth weight at preschool- and school age. A national population based study. University of Bergen 2016.
Maria Vollsæter. Long-term respiratory Outcomes of Extreme preterm Birth. A population-based cohort study. University of Bergen 2016.
Silja Torvik Griffiths. Functional MRI, structural MRI and school performance in extremely preterm/extremely low birth weight children. University of Bergen 2013.
Katrine Tyborg Leversen. Neurodevelopmental outcome at two and five years of age, and prediction of outcome in children born extremely preterm. University of Bergen 2012.
Arild Rønnestad. Neonatal septicaemia: Epidemiology, diagnostics and therapeutic aspects. University of Oslo 2006.
Prof. Emeritus Trond Markestad,
The founder and previous leader of the national
PEP 1999-2000 follow-up