TY - JOUR A1 - Härtel, Christoph A1 - Spiegler, Juliane A1 - Fortmann, Ingmar A1 - Astiz, Mariana A1 - Oster, Henrik A1 - Siller, Bastian A1 - Viemann, Dorothee A1 - Keil, Thomas A1 - Banaschewski, Tobias A1 - Romanos, Marcel A1 - Herting, Egbert A1 - Göpel, Wolfgang T1 - Breastfeeding for 3 months or longer but not probiotics is associated with reduced risk for inattention/hyperactivity and conduct problems in very-low-birth-weight children at early primary school age JF - Nutrients N2 - (1) Background: We aimed to evaluate the effect of proposed “microbiome-stabilising interventions”, i.e., breastfeeding for ≥3 months and prophylactic use of Lactobacillus acidophilus/ Bifidobacterium infantis probiotics on neurocognitive and behavioral outcomes of very-low-birthweight (VLBW) children aged 5–6 years. (2) Methods: We performed a 5-year-follow-up assessment including a strength and difficulties questionnaire (SDQ) and an intelligence quotient (IQ) assessment using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI)-III test in preterm children previously enrolled in the German Neonatal Network (GNN). The analysis was restricted to children exposed to antenatal corticosteroids and postnatal antibiotics. (3) Results: 2467 primary school-aged children fulfilled the inclusion criteria. In multivariable linear regression models breastfeeding ≥3 months was associated with lower conduct disorders (B (95% confidence intervals (CI)): −0.25 (−0.47 to −0.03)) and inattention/hyperactivity (−0.46 (−0.81 to −0.10)) as measured by SDQ. Probiotic treatment during the neonatal period had no effect on SDQ scores or intelligence. (4) Conclusions: Prolonged breastfeeding of highly vulnerable infants may promote their mental health later in childhood, particularly by reducing risk for inattention/hyperactivity and conduct disorders. Future studies need to disentangle the underlying mechanisms during a critical time frame of development. KW - breastfeeding KW - probiotic prophylaxis KW - preterm children KW - strength and difficulties KW - inattention/hyperactivity KW - intelligence Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216319 SN - 2072-6643 VL - 12 IS - 11 ER - 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 - Humberg, Alexander A1 - Fortmann, Ingmar A1 - Siller, Bastian A1 - Kopp, Matthias Volkmar A1 - Herting, Egbert A1 - Göpel, Wolfgang A1 - Härtel, Christoph T1 - Preterm birth and sustained inflammation: consequences for the neonate JF - Seminars in Immunopathology N2 - Almost half of all preterm births are caused or triggered by an inflammatory process at the feto-maternal interface resulting in preterm labor or rupture of membranes with or without chorioamnionitis (“first inflammatory hit”). Preterm babies have highly vulnerable body surfaces and immature organ systems. They are postnatally confronted with a drastically altered antigen exposure including hospital-specific microbes, artificial devices, drugs, nutritional antigens, and hypoxia or hyperoxia (“second inflammatory hit”). This is of particular importance to extremely preterm infants born before 28 weeks, as they have not experienced important “third-trimester” adaptation processes to tolerate maternal and self-antigens. Instead of a balanced adaptation to extrauterine life, the delicate co-regulation between immune defense mechanisms and immunosuppression (tolerance) to allow microbiome establishment is therefore often disturbed. Hence, preterm infants are predisposed to sepsis but also to several injurious conditions that can contribute to the onset or perpetuation of sustained inflammation (SI). This is a continuing challenge to clinicians involved in the care of preterm infants, as SI is regarded as a crucial mediator for mortality and the development of morbidities in preterm infants. This review will outline the (i) role of inflammation for short-term consequences of preterm birth and (ii) the effect of SI on organ development and long-term outcome. KW - preterm infants KW - sustained inflammation KW - sepsis KW - microbiome KW - neurocognitive outcome KW - chronic pulmonary insufficiency of prematurity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235019 SN - 1863-2297 VL - 42 ER - TY - JOUR A1 - Fortmann, Mats Ingmar A1 - Dirks, Johannes A1 - Goedicke-Fritz, Sybelle A1 - Liese, Johannes A1 - Zemlin, Michael A1 - Morbach, Henner A1 - Härtel, Christoph T1 - Immunization of preterm infants: current evidence and future strategies to individualized approaches JF - Seminars in Immunopathology N2 - Preterm infants are at particularly high risk for infectious diseases. As this vulnerability extends beyond the neonatal period into childhood and adolescence, preterm infants benefit greatly from infection-preventive measures such as immunizations. However, there is an ongoing discussion about vaccine safety and efficacy due to preterm infants’ distinct immunological features. A significant proportion of infants remains un- or under-immunized when discharged from primary hospital stay. Educating health care professionals and parents, promoting maternal immunization and evaluating the potential of new vaccination tools are important means to reduce the overall burden from infectious diseases in preterm infants. In this narrative review, we summarize the current knowledge about vaccinations in premature infants. We discuss the specificities of early life immunity and memory function, including the role of polyreactive B cells, restricted B cell receptor diversity and heterologous immunity mediated by a cross-reactive T cell repertoire. Recently, mechanistic studies indicated that tissue-resident memory (Trm) cell populations including T cells, B cells and macrophages are already established in the fetus. Their role in human early life immunity, however, is not yet understood. Tissue-resident memory T cells, for example, are diminished in airway tissues in neonates as compared to older children or adults. Hence, the ability to make specific recall responses after secondary infectious stimulus is hampered, a phenomenon that is transcriptionally regulated by enhanced expression of T-bet. Furthermore, the microbiome establishment is a dominant factor to shape resident immunity at mucosal surfaces, but it is often disturbed in the context of preterm birth. The proposed function of Trm T cells to remember benign interactions with the microbiome might therefore be reduced which would contribute to an increased risk for sustained inflammation. An improved understanding of Trm interactions may determine novel targets of vaccination, e.g., modulation of T-bet responses and facilitate more individualized approaches to protect preterm babies in the future. KW - preterm infants KW - immunization KW - vaccination KW - safety KW - mechanisms KW - resident memory T cells Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-324261 VL - 44 IS - 6 ER -