NeoLifeS

Evaluating health and neurodevelopmental problems in preterm children. Cohort

Evaluating health and neurodevelopmental problems in preterm children.

Preterm birth occurs in approximately 10% of live births globally, corresponding to ~450,000 cases annually in Europe.

Advances in neonatal care have improved survival rates; however, preterm infants remain at elevated risk for developing non-communicable diseases (NCDs) throughout life due to adverse early-life exposures. Common long-term sequelae include necrotizing enterocolitis (NEC), neurodevelopmental delay, autism spectrum disorders, psychiatric conditions, obesity, and premature adult mortality. Stress during pregnancy, preterm delivery, and neonatal intensive care unit (NICU) hospitalization may play a significant role in the pathogenesis of these conditions.

The economic impact is considerable: in Europe, the estimated healthcare cost for preterm infants during the first four years of life is approximately €30 billion. Current research is hindered by insufficient biological data, limiting the ability to identify mechanistic links between preterm birth and NCDs. This gap impedes the development of targeted interventions. There is an urgent need for large-scale, prospective, multi-omics studies to improve early risk stratification and design personalized preventive strategies within the critical first 1,000 days of life.

Towards prevention and long-term follow-up

Preventive interventions, such as probiotic supplementation for NEC prevention, have shown promise but remain controversial due to incomplete understanding of their mechanisms and long-term effects. Furthermore, standardized international guidelines for lifelong follow-up of preterm-born individuals are lacking. Prospective cohort efforts can facilitate early detection and prevention of both early-onset NCDs (e.g., NEC) and late-onset conditions associated with preterm birth.

NeoLifeS aims to:

Identify risk factors—maternal, fetal, and neonatal—associated with impaired health and neurodevelopment, including prematurity, hypoxia, immune dysregulation, congenital anomalies, and neonatal stress.
Apply non-invasive monitoring tools, such as Near-Infrared Spectroscopy (NIRS) and GMA, to optimize cerebral and multi-organ oxygenation and minimize stress in early life.
Conduct long-term follow-up into adolescence, assessing physical health, growth, and neurodevelopment (motor, cognitive, behavioural domains).

Please visit the UMCG Research Data Catalogue for more detailed information on our data and samples.
In 2024, Prof. Dr. E.M.W. Kooi assumed leadership, expanding the scope from neurocognitive outcomes to the broader concept of sustainable health development. While neonatal mortality among critically ill preterm infants has markedly decreased, a substantial proportion experience long-term complications, including developmental, cognitive, behavioural, and chronic health disorders.

Integration of clinical and translational research—microbiome profiling, DNA methylation analysis—aims to elucidate underlying disease mechanisms and inform early interventions.

The UMCG Beatrix Children’s Hospital serves as the Dutch Expertise Centre for Neonatal Gastrointestinal Disorders, participates in the European Reference Network ERNICA, and is active in the Netherlands Neonatal Network (N3) and the European Society for Paediatric Research. Database restructuring and biobank establishment are underway to support these goals.
- Adapt REDCap database to align with the updated research scope
- Secure funding for a dedicated research nurse (informed consent, database management, legal compliance, participant follow-up)
- Draft governance plan outlining ethical oversight and data-sharing principles
- Launch new sub-studies integrated within NeoLifeS 2.0
- Obtain ethical approval for renewed nWMO protocols (umbrella framework)
- Explore external access and research valorization strategies
- Optimize video-bank for GMA via EarlyMoves implementation
- Prepare and operationalize the biobank (collaborating with UMCG biobank hub) including proteomic, metabolomic, microbiomic data, and potential data-sharing agreements.
- Secure funding for a postdoctoral researcher to lead biobank activities
- Integrate data science/AI expertise for advanced analytics
- Enhance long-term follow-up, incorporating somatic health markers
- Strengthen collaborations with national and international preterm biobanks
NeoLifeS 2.0 is a unique cohort compared to other preterm cohorts—for the in-depth and rich combination of clinical and outcome variables. continuous NIRS monitoring, multi-omics data, epigenetics and extensive longitudinal follow-up including GMA data. This allows for insight in multifactorial origins of health outcomes.
- UMCG Department of Neonatology
- UMCG Department of Perinatology/Obstetrics
- UMCG Department of Pediatric Surgery
- UMCG Department of Pediatric Cardiology
- UMCG Department of Genetics
1. Lahr BE, Brunsch CL, Dikkers R, Bos AF, Kooi EMW. Cerebrovascular Autoregulation in Preterm Infants Using Heart Rate or Blood Pressure: A Pilot Study. Children (Basel). 2024 Jun 24;11(7):765. doi: 10.3390/children11070765. PMID: 39062215; PMCID: PMC11276379.

2. van der Heide M, Muller Kobold AC, Koerts-Steijn KKR, Hulzebos CV, Hulscher JBF, Eaton S, Orford M, Bos AF, Koerts J, Kooi EMW. Ischemia modified albumin as a marker of hypoxia in preterm infants in the first week after birth. Early Hum Dev. 2024 Feb;189:105927. doi: 10.1016/j.earlhumdev.2023.105927. Epub 2023 Dec 30. PMID: 38183863.

3. Arjaans S, Fries MWF, Schoots MH, Schilte CFM, Roofthooft MTR, Vrijlandt EJLE, Bos AF, Kooi EMW, Berger RMF. Clinical Significance of Early Pulmonary Hypertension in Preterm Infants. J Pediatr. 2022 Dec;251:74-81.e3. doi: 10.1016/j.jpeds.2022.07.039. Epub 2022 Aug 4. PMID: 35934129.

4. Palleri E, van der Heide M, Hulscher JBF, Bartocci M, Wester T, Kooi EMW. Clinical usefulness of splanchnic oxygenation in predicting necrotizing enterocolitis in extremely preterm infants: a cohort study. BMC Pediatr. 2023 Jul 1;23(1):336. doi: 10.1186/s12887-023-04145-4. PMID: 37393233.

5. van Dokkum NH, Bao M, Verkaik-Schakel RN, Reijneveld SA, Bos AF, de Kroon MLA, Plösch T. Neonatal stress exposure and DNA methylation of stress-related and neurodevelopmentally relevant genes: An exploratory study. Early Hum Dev. 2023 Nov;186:105868. doi: 10.1016/j.earlhumdev.2023.105868. Epub 2023 Sep 29. PMID: 37797474.

6. Bosch T, Salavati S, Ter Horst HJ, Bos AF, den Heijer AE. Favorable parental perception of behaviour at two years' corrected age in very preterm-born children. Early Hum Dev. 2021 Dec;163:105504. doi: 10.1016/j.earlhumdev.2021.105504. Epub 2021 Oct 29. PMID: 34749129.

7. van Dokkum NH, de Kroon MLA, Bos AF, Reijneveld SA, Kerstjens JM. Attainment of gross motor milestones by preterm children with normal development upon school entry. Early Hum Dev. 2018 Apr;119:62-67. doi: 10.1016/j.earlhumdev.2018.03.005. Epub 2018 Mar 23. PMID: 29579559.

8. Arjaans S, Zwart EAH, Roofthooft M, Kooi EMW, Bos AF, Berger RMF. Pulmonary hypertension in extremely preterm infants: a call to standardize echocardiographic screening and follow-up policy. Eur J Pediatr. 2021 Jun;180(6):1855-1865. doi: 10.1007/s00431-021-03931-5. Epub 2021 Feb 2. PMID: 33528615.

9. Kraft KE, Jaschke AC, Ravensbergen AG, Feenstra-Weelink A, van Goor MEL, de Kroon MLA, Reijneveld SA, Bos AF, van Dokkum NH. Maternal Anxiety, Infant Stress, and the Role of Live-Performed Music Therapy during NICU Stay in The Netherlands. Int J Environ Res Public Health. 2021 Jul 2;18(13):7077. doi: 10.3390/ijerph18137077. PMID: 34281014.

10. Arjaans S, Haarman MG, Roofthooft MTR, Fries MWF, Kooi EMW, Bos AF, Berger RMF. Fate of pulmonary hypertension associated with bronchopulmonary dysplasia beyond 36 weeks postmenstrual age. Arch Dis Child Fetal Neonatal Ed. 2021 Jan;106(1):45-50. doi: 10.1136/archdischild-2019-318531. Epub 2020 Jun 22. PMID: 32571832.

11. van Dokkum NH, de Kroon MLA, Dijk PH, Kraft KE, Reijneveld SA, Bos AF. Course of Stress during the Neonatal Intensive Care Unit Stay in Preterm Infants. Neonatology. 2022;119(1):84-92. doi: 10.1159/000520513. Epub 2021 Dec 9. PMID: 34883490.

12. Wolthuis-Stigter MI, Luinge MR, da Costa SP, Krijnen WP, van der Schans CP, Bos AF. The association between sucking behavior in preterm infants and neurodevelopmental outcomes at 2 years of age. J Pediatr. 2015 Jan;166(1):26-30. doi: 10.1016/j.jpeds.2014.09.007. Epub 2014 Oct 11. PMID: 25311711.

13. van der Heide M, Muller Kobold AC, Koerts-Steijn KKR, Hulzebos CV, Hulscher JBF, Eaton S, Orford M, Bos AF, Koerts J, Kooi EMW. Ischemia modified albumin as a marker of hypoxia in preterm infants in the first week after birth. Early Hum Dev. 2024 Feb;189:105927. doi: 10.1016/j.earlhumdev.2023.105927. Epub 2023 Dec 30. PMID: 38183863.

14. van Dokkum NH, Bos AF, Kraft KE, Bouma HA, Reijneveld SA, Krabbe PFM, de Kroon MLA. Early stress during NICU stay and parent-reported health-related quality of life after extremely preterm birth: an exploratory study with possible targets for early intervention. Front Pediatr. 2024 Apr 8;12:1381008. doi: 10.3389/fped.2024.1381008. eCollection 2024. PMID: 38650996.

15. Abrudan AS, Schoots MH, Kooi EMW, Gordijn SJ, Kraft KE, Prins JR, Roescher AM. Placental pathology is associated with lower quality fidgety movements in preterm infants. Pediatr Res. 2025 Feb 12. doi: 10.1038/s41390-025-03905-5. PMID: 39934646.

16. Verhoeven R, Kupers T, Brunsch CL, Hulscher JBF, Kooi EMW. Using Vital Signs for the Early Prediction of Necrotizing Enterocolitis in Preterm Neonates with Machine Learning. Children (Basel). 2024 Nov 28;11(12):1452. doi: 10.3390/children11121452. PMID: 39767881.

17. Klerk DH, Kooi EM, Bos AF, Hulscher JB, Verkaik-Schakel RN, Plösch T. Hypermethylation of CTDSPL2 prior to necrotizing enterocolitis onset. Epigenomics. 2023 Apr;15(8):479-486. doi: 10.2217/epi-2023-0119. Epub 2023 Jun 13. PMID: 37309586.

18. Martins RDS, Kooi EMW, Poelstra K, Hulscher JBF. The role of intestinal alkaline phosphatase in the development of necrotizing enterocolitis. Early Hum Dev. 2023 Aug;183:105797. doi: 10.1016/j.earlhumdev.2023.105797. Epub 2023 Jun 7. PMID: 37300991.

19. Kalteren WS, Bos AF, van Oeveren W, Hulscher JBF, Kooi EMW. Neonatal anemia relates to intestinal injury in preterm infants. Pediatr Res. 2022 May;91(6):1452-1458. doi: 10.1038/s41390-021-01903-x. Epub 2021 Dec 14. PMID: 34907357.

20. Kalteren WS, Bos AF, Bergman KA, van Oeveren W, Hulscher JBF, Kooi EMW. The short-term effects of RBC transfusions on intestinal injury in preterm infants. Pediatr Res. 2023 Apr;93(5):1307-1313. doi: 10.1038/s41390-022-01961-9. Epub 2022 Feb 4. PMID: 35115712.

21. Kalteren WS, Mebius MJ, Verhagen EA, Tanis JC, Kooi EMW, Bos AF. Neonatal Hemoglobin Levels in Preterm Infants Are Associated with Early Neurological Functioning. Neonatology. 2021;118(5):593-599. doi: 10.1159/000518655. Epub 2021 Sep 7. PMID: 34515185.

22. Martins RDS, Kooi EMW, Kalteren WS, Poelstra K, Bos AF, Hulscher JBF. Blood group AB is associated with poor outcomes in infants with necrotizing enterocolitis. J Pediatr Surg. 2021 Nov;56(11):1911-1915. doi: 10.1016/j.jpedsurg.2021.07.010. Epub 2021 Jul 18. PMID: 34392969.

23. Klerk DH, Plösch T, Verkaik-Schakel RN, Hulscher JBF, Kooi EMW, Bos AF. DNA Methylation of TLR4, VEGFA, and DEFA5 Is Associated With Necrotizing Enterocolitis in Preterm Infants. Front Pediatr. 2021 Mar 4;9:630817. doi: 10.3389/fped.2021.630817. eCollection 2021. PMID: 33748044.

24. van der Heide M, Dotinga BM, Stewart RE, Kalteren WS, Hulscher JBF, Reijneveld SA, Bos AF, Kooi EMW. Regional splanchnic oxygen saturation for preterm infants in the first week after birth: reference values. Pediatr Res. 2021 Oct;90(4):882-887. doi: 10.1038/s41390-020-01323-3. Epub 2021 Jan 27. PMID: 33504960.

25. Richter AE, Bos AF, Huiskamp EA, Kooi EMW. Postnatal Cerebral Hyperoxia Is Associated with an Increased Risk of Severe Retinopathy of Prematurity. Neonatology. 2019;116(4):356-362. doi: 10.1159/000501859. Epub 2019 Sep 5. PMID: 31487704.

26. Schat TE, van Zoonen AGJF, van der Laan ME, Mebius MJ, Bos AF, Hulzebos CV, Boezen HM, Hulscher JBF, Kooi EMW. Early cerebral and intestinal oxygenation in the risk assessment of necrotizing enterocolitis in preterm infants. Early Hum Dev. 2019 Apr;131:75-80. doi: 10.1016/j.earlhumdev.2019.03.001. Epub 2019 Mar 11. PMID: 30870625.

27. Kalteren WS, Kuik SJ, Van Braeckel KNJA, Hulscher JBF, Bos AF, Kooi EMW, van der Laan ME. Red Blood Cell Transfusions Affect Intestinal and Cerebral Oxygenation Differently in Preterm Infants with and without Subsequent Necrotizing Enterocolitis. Am J Perinatol. 2018 Sep;35(11):1031-1037. doi: 10.1055/s-0038-1636532. Epub 2018 Mar 6. PMID: 29510424.

28. Hulzebos CV, van Zoonen AG, Hulscher JB, Schat TE, Kooi EM, Koehorst M, Boverhof R, Krabbe PF, Groen AK, Verkade HJ. Fecal Bile Salts and the Development of Necrotizing Enterocolitis in Preterm Infants. PLoS One. 2017 Jan 3;12(1):e0168633. doi: 10.1371/journal.pone.0168633. eCollection 2017. PMID: 2804598