TY  - JOUR
A1  - Fortmann, Ingmar
A1  - Dammann, Marie-Theres
A1  - Humberg, Alexander
A1  - Siller, Bastian
A1  - Stichtenoth, Guido
A1  - Engels, Geraldine
A1  - Marißen, Janina
A1  - Faust, Kirstin
A1  - Hanke, Kathrin
A1  - Goedicke-Fritz, Sybelle
A1  - Derouet, Christoph
A1  - Meyer, Sascha
A1  - Stutz, Regine
A1  - Kaiser, Elisabeth
A1  - Herting, Egbert
A1  - Göpel, Wolfgang
A1  - Härtel, Christoph
A1  - Zemlin, Michael
T1  - Five year follow up of extremely low gestational age infants after timely or delayed administration of routine vaccinations
JF  - Vaccines
N2  - 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 <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: 1.1–1.7), 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: 0.42–0.86) 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.
KW  - immunization
KW  - prematurity
KW  - trained immunity
KW  - long-term outcome
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239592
SN  - 2076-393X
VL  - 9
IS  - 5
ER  - 
TY  - JOUR
A1  - Twisselmann, Nele
A1  - Pagel, Julia
A1  - Künstner, Axel
A1  - Weckmann, Markus
A1  - Hartz, Annika
A1  - Glaser, Kirsten
A1  - Hilgendorff, Anne
A1  - Göpel, Wolfgang
A1  - Busch, Hauke
A1  - Herting, Egbert
A1  - Weinberg, Jason B.
A1  - Härtel, Christoph
T1  - Hyperoxia/Hypoxia Exposure Primes a Sustained Pro-Inflammatory Profile of Preterm Infant Macrophages Upon LPS Stimulation
JF  - Frontiers in Immunology
N2  - Preterm infants are highly susceptible to sustained lung inflammation, which may be triggered by exposure to multiple environmental cues such as supplemental oxygen (O\(_2\)) and infections. We hypothesized that dysregulated macrophage (MФ) activation is a key feature leading to inflammation-mediated development of bronchopulmonary dysplasia (BPD) in preterm infants. Therefore, we aimed to determine age-dependent differences in immune responses of monocyte-derived MФ comparing cord blood samples derived from preterm (n=14) and term (n=19) infants as well as peripheral blood samples from healthy adults (n=17) after lipopolysaccharide (LPS) exposure. Compared to term and adult MФ, LPS-stimulated preterm MФ showed an enhanced and sustained pro-inflammatory immune response determined by transcriptome analysis, cytokine release inducing a RORC upregulation due to T cell polarization of neonatal T cells, and TLR4 surface expression. In addition, a double-hit model was developed to study pulmonary relevant exposure factors by priming MФ with hyperoxia (O\(_2\) = 65%) or hypoxia (O\(_2\) = 3%) followed by lipopolysaccharide (LPS, 100ng/ml). When primed by 65% O\(_2\), subsequent LPS stimulation in preterm MФ led to an exaggerated pro-inflammatory response (e.g. increased HLA-DR expression and cytokine release) compared to LPS stimulation alone. Both, exposure to 65% or 3% O\(_2\) together with subsequent LPS stimulation, resulted in an exaggerated pro-inflammatory response of preterm MФ determined by transcriptome analysis. Downregulation of two major transcriptional factors, early growth response gene (Egr)-2 and growth factor independence 1 (Gfi1), were identified to play a role in the exaggerated pro-inflammatory response of preterm MФ to LPS insult after priming with 65% or 3% O\(_2\). Preterm MФ responses to LPS and hyperoxia/hypoxia suggest their involvement in excessive inflammation due to age-dependent differences, potentially mediated by downregulation of Egr2 and Gfi1 in the developing lung.
KW  - preterm infants
KW  - sustained inflammation
KW  - macrophages
KW  - hyperoxia
KW  - hypoxia
KW  - infection
KW  - bronchopulmonary dysplasia
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250356
SN  - 1664-3224
VL  - 12
ER  -