83 research outputs found
Preterm birth and sustained inflammation: consequences for the neonate.
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 28Â 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
Glucocorticoid Receptor Gene Variants and Neonatal Outcome in Very-Low-Birth-Weight Preterm Infants
Background: Induction of lung maturation by prenatal steroid treatment has become the standard of care for pregnant women at risk for preterm birth. In addition to the beneficial effects on lung maturation, prenatal steroids have been shown to reduce the incidence of neonatal death, necrotizing enterocolitis, sepsis, and intraventricular hemorrhage. However, little is known about the role of interindividual differences in corticoid sensitivity arising from polymorphisms in the glucocorticoid receptor (GR) gene. Objectives: To assess the impact of GR polymorphisms N363S (rs56149945), R23K (rs6190), and BclI (rs41423247) on neonatal outcome. Methods: The GR polymorphisms N363S, R23K, and BclI were examined in 10,490 very-low-birth-weight (VLBW) preterm infants from 49 German tertiary level neonatal units (German Neonatal Network, GNN) with respect to neonatal outcome. Results: Infants carrying the BclI genotype were at higher risk to develop bronchopulmonary dysplasia (BPD) (OR 1.12 per BclI allele, 95% CI: 1.02-1.23, p = 0.013) in a logistic regression model adjusted for gestational age, mechanical ventilation, and small for gestational age status. A similar relative risk was seen in the children (89.4%) who received antenatal betamethasone treatment (OR 1.16, 95% CI: 1.05-1.27, p = 0.003), whereas no such effect was detectable in infants without antenatal steroids. N363S and R23K did not show any stable association with neonatal outcome parameters. Conclusion: Except for a slightly higher risk of BPD in carriers of the GRBclI variant, the GR gene polymorphisms BclI, N363S, and R23K did not affect neonatal outcome parameters in this large multicenter cohort of VLBW preterm infants
Sepsis related mortality of extremely low gestational age newborns after the introduction of colonization screening for multi-drug resistant organisms
Background: In 2013 German infection surveillance guidelines recommended weekly colonization screening for
multidrug-resistant (MDRO) or highly epidemic organisms for neonatal intensive care units (NICUs) and extended
hygiene measures based on screening results. It remains a matter of debate whether screening is worth the effort.
We therefore aimed to evaluate sepsis related outcomes before and after the guideline update.
Methods: The German Neonatal Network (GNN) is a prospective cohort study including data from extremely
preterm infants between 22 + 0 and 28 + 6 gestational weeks born in 62 German level III NICUs.
Results: Infants treated after guideline update (n = 8.903) had a lower mortality (12.5% vs. 13.8%, p = 0.036), reduced
rates for clinical sepsis (31.4 vs. 42.8%, p < 0.001) and culture-proven sepsis (14.4% vs. 16.5%, p = 0.003) as compared
to infants treated before update (n = 3.920). In a multivariate logistic regression analysis, nine pathogens of cultureproven sepsis were associated with sepsis-related death, e.g. Pseudomonas aeruginosa [OR 59 (19–180), p < 0.001)].
However, the guideline update had no significant effect on pathogen-specific case fatality, total sepsis-related
mortality and culture-proven sepsis rates with MDRO. While the exposure of GNN infants to cefotaxime declined
over time (31.1 vs. 40.1%, p < 0.001), the treatment rate with meropenem was increased (31.6 vs. 26.3%, p < 0.001).
Conclusions: The introduction of weekly screening and extended hygiene measures is associated with reduced
sepsis rates, but has no effects on sepsis-related mortality and sepsis with screening-relevant pathogens. The high
exposure rate to meropenem should be a target of antibiotic stewardship programs
Efficacy of Bifidobacterium animalis subsp. lactis (BB-12), B. infantis and Lactobacillus acidophilus (La-5) probiotics to prevent gut dysbiosis in preterm infants of 28+0–32+6 weeks of gestation: a randomised, placebocontrolled, double-blind, multicentre trial: the PRIMAL Clinical Study Protocol
Introduction The healthy ‘eubiosis’ microbiome in infancy is regarded as the microbiome derived from term, vaginally delivered, antibiotic free, breastfed infants at 4–6 months. Dysbiosis is regarded as a deviation from a healthy state with reduced microbial diversity and deficient capacity to control drug-resistant organisms. Preterm infants are highly sensitive to early gut dysbiosis. Latter has been associated with sepsis and necrotising enterocolitis, but may also contribute to long-term health problems. Probiotics hold promise to reduce the risk for adverse short-term outcomes but the evidence from clinical trials remains inconclusive and none has directly assessed the effects of probiotics on the microbiome at high resolution.
Methods and analysis A randomised, double blind, placebo-controlled study has been designed to assess the safety and efficacy of the probiotic mix of Bifidobacterium animalis subsp. lactis, B. infantis and Lactobacillus acidophilus in the prevention of gut dysbiosis in preterm infants between 28+0 and 32+6 weeks of gestation. The study is conducted in 18 German neonatal intensive care units. Between April 2018 and March 2020, 654 preterm infants of 28+0–32+6 weeks of gestation will be randomised in the first 48 hours of life to 28 days of once daily treatment with either probiotics or placebo. The efficacy endpoint is the prevention of gut dysbiosis at day 30 of life. A compound definition of gut dysbosis is used: (1) colonisation with multidrug-resistant organisms or gram-negative bacteria with high epidemic potential or (2) a significant deviation of the gut microbiota composition as compared with healthy term infants. Dysbiosis is determined by (1) conventional microbiological culture and (2) phylogenetic microbiome analysis by high-throughput 16S rRNA and metagenome sequencing. Persistence of dysbiosis will be assessed at 12-month follow-up visits. Side effects and adverse events related to the intervention will be recorded. Key secondary endpoint(s) are putative consequences of dysbiosis. A subgroup of infants will be thoroughly phenotyped for immune parameters using chipcytometry.
Ethics and dissemination Ethics approval was obtained in all participating sites. Results of the trial will be published in peer-review journals, at scientific meetings, on the website (www.primal-study.de) and via social media of parent organisations. Trial registration number DRKS00013197; Pre-results
Lactobacillus Acidophilus/Bifidobacterium Infantis Probiotics Are Beneficial to Extremely Low Gestational Age Infants Fed Human Milk
To evaluate the nutrition-related effects of prophylactic Lactobacillus acidophilus/
Bifidobacterium infantis probiotics on the outcomes of preterm infants <29 weeks of gestation that
receive human milk and/or formula nutrition. We hypothesize that human-milk-fed infants benefit
from probiotics in terms of sepsis prevention and growth. Methods: We performed an observational
study of the German Neonatal Network (GNN) over a period of six years, between 1 January, 2013
and 31 December, 2018. Prophylactic probiotic use of L. acidophilus/B. infantis was evaluated in preterm
infants <29 weeks of gestation (n = 7516) in subgroups stratified to feeding type: (I) Exclusively
human milk (HM) of own mother and/or donors (HM group, n = 1568), (II) HM of own mother and/or
donor and formula (Mix group, n = 5221), and (III) exclusive exposure to formula (F group, n = 727).
The effect of probiotics on general outcomes and growth was tested in univariate models and adjusted
in linear/logistic regression models. Results: 5954 (76.5%) infants received L. acidophilus/B. infantisprophylactically for the prevention of necrotizing enterocolitis (NEC). Probiotic use was associated
with improved growth measures in the HM group (e.g., weight gain velocity in g/day: effect size
B = 0.224; 95% CI: 2.82–4.35; p < 0.001) but not in the F group (effect size B = −0.06; 95% CI: −3.05–0.28;
p = 0.103). The HM group had the lowest incidence of clinical sepsis (34.0%) as compared to the
Mix group (35.5%) and the F group (40.0%). Only in the Mix group, probiotic supplementation
proved to be protective against clinical sepsis (OR 0.69; 95% CI: 0.59–0.79; p < 0.001). Conclusion:
Our observational data indicate that the exposure to L. acidophilus/B. infantis probiotics may promote
growth in exclusively HM-fed infants as compared to formula-fed infants. To exert a sepsis-preventive
effect, probiotics seem to require human milk
Five Year Follow Up of Extremely Low Gestational Age Infants after Timely or Delayed Administration of Routine Vaccinations
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
Epidemic Microclusters of Blood-Culture Proven Sepsis in Very-Low-Birth Weight Infants: Experience of the German Neonatal Network
INTRODUCTION: We evaluated blood culture-proven sepsis episodes occurring in microclusters in very-low-birth-weight infants born in the German Neonatal Network (GNN) during 2009-2010. METHODS: Thirty-seven centers participated in GNN; 23 centers enrolled ≥50 VLBW infants in the study period. Data quality was approved by on-site monitoring. Microclusters of sepsis were defined as occurrence of at least two blood-culture proven sepsis events in different patients of one center within 3 months with the same bacterial species. For microcluster analysis, we selected sepsis episodes with typically cross-transmitted bacteria of high clinical significance including gram-negative rods and Enterococcus spp. RESULTS: In our cohort, 12/2110 (0.6%) infants were documented with an early-onset sepsis and 235 late-onset sepsis episodes (≥72 h of age) occurred in 203/2110 (9.6%) VLBW infants. In 182/235 (77.4%) late-onset sepsis episodes gram-positive bacteria were documented, while coagulase negative staphylococci were found to be the most predominant pathogens (48.5%, 95%CI: 42.01-55.01). Candida spp. and gram-negative bacilli caused 10/235 (4.3%, 95%CI: 1.68% -6.83%) and 43/235 (18.5%) late-onset sepsis episodes, respectively. Eleven microclusters of blood-culture proven sepsis were detected in 7 hospitals involving a total 26 infants. 16/26 cluster patients suffered from Klebsiella spp. sepsis. The median time interval between the first patient's Klebsiella spp. sepsis and cluster cases was 14.1 days (interquartile range: 1-27 days). First patients in the cluster, their linked cases and sporadic sepsis events did not show significant differences in short term outcome parameters. DISCUSSION: Microclusters of infection are an important phenomenon for late-onset sepsis. Most gram-negative cluster infections occur within 30 days after the first patient was diagnosed and Klebsiella spp. play a major role. It is essential to monitor epidemic microclusters of sepsis in surveillance networks to adapt clinical practice, inform policy and further improve quality of care
Covid-19 triage in the emergency department 2.0: how analytics and AI transform a human-made algorithm for the prediction of clinical pathways
The Covid-19 pandemic has pushed many hospitals to their capacity limits. Therefore, a triage of patients has been discussed controversially primarily through an ethical perspective. The term triage contains many aspects such as urgency of treatment, severity of the disease and pre-existing conditions, access to critical care, or the classification of patients regarding subsequent clinical pathways starting from the emergency department. The determination of the pathways is important not only for patient care, but also for capacity planning in hospitals. We examine the performance of a human-made triage algorithm for clinical pathways which is considered a guideline for emergency departments in Germany based on a large multicenter dataset with over 4,000 European Covid-19 patients from the LEOSS registry. We find an accuracy of 28 percent and approximately 15 percent sensitivity for the ward class. The results serve as a benchmark for our extensions including an additional category of palliative care as a new label, analytics, AI, XAI, and interactive techniques. We find significant potential of analytics and AI in Covid-19 triage regarding accuracy, sensitivity, and other performance metrics whilst our interactive human-AI algorithm shows superior performance with approximately 73 percent accuracy and up to 76 percent sensitivity. The results are independent of the data preparation process regarding the imputation of missing values or grouping of comorbidities. In addition, we find that the consideration of an additional label palliative care does not improve the results
Mitochondrial mutation m.1555A>G as a risk factor for failed newborn hearing screening in a large cohort of preterm infants
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