{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T01:55:50Z","timestamp":1788314150458,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01ER0805"],"award-info":[{"award-number":["01ER0805"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01GL1746D"],"award-info":[{"award-number":["01GL1746D"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>This study is aimed at detecting the rate of untimely immunization in a large cohort of extremely low gestational age neonates (ELGANs) of the German Neonatal Network (GNN) and at addressing risk factors for delayed vaccination and associated long-term consequences. We performed an observational study of the GNN between 1st January 2010 and 31st December 2019. The immunization status for the hexavalent and pneumococcal immunization was evaluated in n = 8401 preterm infants &lt;29 weeks of gestation. Univariate analysis and logistic\/linear regression models were used to identify risk factors for vaccination delay and outcomes at a 5-year follow-up. In our cohort n = 824 (9.8%) ELGANs did not receive a timely first immunization with the hexavalent and pneumococcal vaccine. Risk factors for delayed vaccination were SGA status (18.1% vs. 13.5%; OR 1.3; 95% CI: 1.1\u20131.7), impaired growth and surrogates for complicated clinical courses (i.e., need for inotropes, necrotizing enterocolitis). At 5 years of age, timely immunized children had a lower risk of bronchitis (episodes within last year: 27.3% vs. 37.7%; OR 0.60, 95% CI: 0.42\u20130.86) but spirometry measures were unaffected. In conclusion, a significant proportion of ELGANs are untimely immunized, specifically those with increased vulnerability, even though they might particularly benefit from the immune-promoting effects of a timely vaccination.<\/jats:p>","DOI":"10.3390\/vaccines9050493","type":"journal-article","created":{"date-parts":[[2021,5,13]],"date-time":"2021-05-13T03:08:12Z","timestamp":1620875292000},"page":"493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Five Year Follow Up of Extremely Low Gestational Age Infants after Timely or Delayed Administration of Routine Vaccinations"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1676-8340","authenticated-orcid":false,"given":"Ingmar","family":"Fortmann","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Hamburg-L\u00fcbeck-Borstel-Riems, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Theres","family":"Dammann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Humberg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastian","family":"Siller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Stichtenoth","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraldine","family":"Engels","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janina","family":"Mari\u00dfen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirstin","family":"Faust","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Hanke","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1005-4873","authenticated-orcid":false,"given":"Sybelle","family":"Goedicke-Fritz","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics and Neonatology, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Derouet","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics and Neonatology, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6016-4558","authenticated-orcid":false,"given":"Sascha","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics and Neonatology, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regine","family":"Stutz","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics and Neonatology, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1771-8479","authenticated-orcid":false,"given":"Elisabeth","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics and Neonatology, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egbert","family":"Herting","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"G\u00f6pel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of L\u00fcbeck, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"H\u00e4rtel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of W\u00fcrzburg, 97080 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9528-7419","authenticated-orcid":false,"given":"Michael","family":"Zemlin","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics and Neonatology, Saarland University, 66421 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the German Neonatal Network (GNN) and the PRIMAL Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S1084-2756(02)00221-X","article-title":"Health and hospitalisations after discharge in extremely low birth weight infants","volume":"8","author":"Doyle","year":"2003","journal-title":"Semin. Neonatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.siny.2012.01.009","article-title":"Long term respiratory outcomes of very premature birth (<32 weeks)","volume":"17","author":"Greenough","year":"2012","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1097\/01.inf.0000226912.88900.a3","article-title":"Role of respiratory viruses in acute upper and lower respiratory tract illness in the first year of life: A birth cohort study","volume":"25","author":"Kusel","year":"2006","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jpeds.2017.04.026","article-title":"Prematurity and Respiratory Outcomes Program. Bronchopulmonary Dysplasia and Perinatal Characteristics Predict 1-Year Respiratory Outcomes in Newborns Born at Extremely Low Gestational Age: A Prospective Cohort Study","volume":"187","author":"Keller","year":"2017","journal-title":"J. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Fortmann, I., Mari\u00dfen, J., Siller, B., Spiegler, J., Humberg, A., Hanke, K., Faust, K., Pagel, J., Eyvazzadeh, L., and Brenner, K. (2020). Lactobacillus Acidophilus\/Bifidobacterium Infantis Probiotics Are Beneficial to Extremely Low Gestational Age Infants Fed Human Milk. Nutrients, 12.","DOI":"10.3390\/nu12030850"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1055\/s-0034-1396865","article-title":"Increased risk for bronchitis after discharge in non-vaccinated very low birth weight infants","volume":"227","author":"Stichtenoth","year":"2015","journal-title":"Klin. Padiatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/infdis\/jir240","article-title":"Randomized trial of BCG vaccination at birth to low-birth-weight children: Beneficial nonspecific effects in the neonatal period?","volume":"204","author":"Aaby","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coi.2014.02.006","article-title":"Innate immune memory: Towards a better understanding of host defense mechanisms","volume":"29","author":"Quintin","year":"2014","journal-title":"Curr. Opin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1189\/jlb.5RI0315-096R","article-title":"Trained innate immunity as underlying mechanism for the long-term, nonspecific effects of vaccines","volume":"98","author":"Blok","year":"2015","journal-title":"J. Leukoc. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.smim.2018.06.002","article-title":"Non-specific effects of vaccines: Current evidence and potential implications","volume":"39","author":"Koeken","year":"2018","journal-title":"Semin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"586076","DOI":"10.1155\/2013\/586076","article-title":"Neonatal sepsis due to coagulase-negative staphylococci","volume":"2013","author":"Marchant","year":"2013","journal-title":"Clin. Dev. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s00281-020-00803-2","article-title":"Preterm birth and sustained inflammation: Consequences for the neonate","volume":"42","author":"Humberg","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Puri, K., Taft, D.H., Ambalavanan, N., Schibler, K.R., Morrow, A.L., and Kallapur, S.G. (2016). Association of chorioamnionitis with aberrant neonatal gut colonization and adverse clinical outcomes. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162734"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/cei.12810","article-title":"Regulatory T cell frequencies are increased in preterm infants with clinical early-onset sepsis","volume":"185","author":"Pagel","year":"2016","journal-title":"Clin. Exp. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.chom.2014.02.006","article-title":"Gut microbiota promote hematopoiesis to control bacterial infection","volume":"15","author":"Khosravi","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.mam.2011.09.001","article-title":"Autophagy, nutrition and immunology","volume":"33","author":"Cuervo","year":"2012","journal-title":"Mol. Asp. Med."},{"key":"ref_17","unstructured":"AG 6-fach-Impfung (DTaP-IPV-Hib-HepB) der St\u00e4ndigen Impfkommission (STIKO) (2020). Wissenschaftliche Begr\u00fcn-dung f\u00fcr die Empfehlung der 6-fach Impfung (DTaP-IPV-Hib-HepB) nach dem 2+1-Impfschema. Epid. Bull., 26, 3\u201321."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1055\/s-0030-1247586","article-title":"Impfstatus bei Fr\u00fchgeborenen mit einem Geburtsgewicht unter 1500 g im Alter von 2 Jahren--eine deutschlandweite Piloterhebung [Vaccination status in very and extremely preterm infants at the age of 2 years--a nationwide pilot analysis]","volume":"222","author":"Ziegler","year":"2010","journal-title":"Klin. Padiatr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1515\/jpm.2010.031","article-title":"Birth weight percentile charts based on daily measurements for very preterm male and female infants at the age of 154-223 days","volume":"38","author":"Voigt","year":"2010","journal-title":"J. Perinat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0022-3476(78)80282-0","article-title":"Incidence and evolution of sub-ependymal and intraventricular hemorrhage: A study of infants with birth weights less than 1500 gm","volume":"92","author":"Papile","year":"1978","journal-title":"J. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1080\/14760584.2019.1604230","article-title":"Update on vaccination of preterm infants: A systematic review about safety and efficacy\/effectiveness. Proposal for a position statement by Italian Society of Pediatric Allergology and Immunology jointly with the Italian Society of Neonatology","volume":"18","author":"Chiappini","year":"2019","journal-title":"Expert Rev. Vaccines"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6681","DOI":"10.1016\/j.vaccine.2016.11.015","article-title":"Vaccination of special populations: Protecting the vulnerable","volume":"34","author":"Doherty","year":"2016","journal-title":"Vaccine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4094","DOI":"10.1111\/jocn.13916","article-title":"Vaccination timeliness in preterm infants: An integrative review of the literature","volume":"26","author":"Sisson","year":"2017","journal-title":"J. Clin. Nurs."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1097\/INF.0000000000000106","article-title":"Delayed start of diphtheria, tetanus, acellular pertussis and inactivated polio vaccination in preterm and low birth weight infants in the Netherlands","volume":"33","author":"Woestenberg","year":"2014","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1542\/peds.2008-0231","article-title":"Vaccine Safety Datalink. Evaluation of vaccine coverage for low birth weight infants during the first year of life in a large managed care population","volume":"123","author":"Batra","year":"2009","journal-title":"Pediatrics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"D66","DOI":"10.1016\/j.vaccine.2015.09.035","article-title":"Vaccine hesitancy: Causes, consequences, and a call to action","volume":"33","author":"Salmon","year":"2015","journal-title":"Vaccine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1136\/archdischild-2018-316770","article-title":"Active perinatal care of preterm infants in the German Neonatal Network","volume":"105","author":"Humberg","year":"2020","journal-title":"Arch. Dis. Child. Fetal Neonatal Ed."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.vaccine.2006.09.065","article-title":"Safety of DTaP-IPV-HIb-HBV hexavalent vaccine in very premature infants","volume":"25","author":"Faldella","year":"2007","journal-title":"Vaccine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5012","DOI":"10.1016\/j.vaccine.2010.05.021","article-title":"Efficacy of 7-valent pneumococcal conjugate vaccination in Germany: An analysis using the indirect cohort method","volume":"28","author":"Reinert","year":"2010","journal-title":"Vaccine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1487214","DOI":"10.1080\/20018525.2018.1487214","article-title":"The impact of respiratory viruses on lung health after preterm birth","volume":"5","author":"Townsi","year":"2018","journal-title":"Eur. Clin. Respir. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10967","DOI":"10.1038\/ncomms10967","article-title":"Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans","volume":"7","author":"Houtepen","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41577-020-0285-6","article-title":"Defining trained immunity and its role in health and disease","volume":"20","author":"Netea","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.earlhumdev.2012.07.009","article-title":"Very low birth weight neonates who survive early-onset sepsis do not have an increased risk of developing late-onset sepsis","volume":"88","author":"Lin","year":"2012","journal-title":"Early Hum. Dev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3389\/fmed.2015.00055","article-title":"Effect of Early Life Oxygen Exposure on Proper Lung Development and Response to Respiratory Viral Infections","volume":"2","author":"Domm","year":"2015","journal-title":"Front. Med."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/5\/493\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:59:34Z","timestamp":1760162374000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/5\/493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,12]]},"references-count":34,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["vaccines9050493"],"URL":"https:\/\/doi.org\/10.3390\/vaccines9050493","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,12]]}}}