The association of γδ-T cells with bronchopulmonary dysplasia in premature infants.

BACKGROUND: As the survival rate of premature infants increases, the incidence of bronchopulmonary dysplasia (BPD), a chronic complication of premature infants, is also higher than before. The pathogenesis of BPD is complicated, and immune imbalance and inflammatory response may play important roles in it. OBJECTIVE: To investigate the correlation between lymphocyte subsets in peripheral blood, especially γδ-T cells, and BPD of preterm infants. MATERIALS AND METHOD: The study was carried out with the peripheral blood of premature infants (GA < 32 weeks, BW < 1500 g), which were collected at 24 h or 3-4 weeks after birth. The infants were divided into non-BPD groups and BPD groups that were classified as mild or moderate and severe in preterm infants based on the magnitude of respiratory support at 28 days age and 36 weeks postmenstrual age. The γδ-T, CD3+, CD4+, CD8+ and total lymphocyte subsets in peripheral blood were detected by flow cytometry. RESULTS: The percentages of T lymphocyte subsets in peripheral blood were not different between BPD and non-BPD within 24 h after birth. And no significant difference was found in T lymphocyte subsets among neonates with BPD of different severities. However, the infants who developed BPD had a significant increase in γδ-T cells compared to non-BPD ones within 3-4 weeks after birth. CONCLUSIONS: It seems that γδ-T cells in peripheral blood are correlated with BPD. However, the causality of BPD and various lymphocytes remains unclear, which need to be further studied.

An exclusive human milk diet for very low birth weight newborns-A cost-effectiveness and EVPI study for Germany.

OBJECTIVES: Human milk-based fortifiers have shown a protective effect on major complications for very low birth weight newborns. The current study aimed to estimate the cost-effectiveness of an exclusive human milk diet (EHMD) compared to the current approach using cow's milk-based fortifiers in very low birth weight newborns. METHODS: A decision tree model using the health states of necrotising enterocolitis (NEC), sepsis, NEC + sepsis and no complication was used to calculate the cost-effectiveness of an EHMD. For each health state, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (RoP) and neurodevelopmental problems were included as possible complications; additionally, short-bowel syndrome (SBS) was included as a complication for surgical treatment of NEC. The model was stratified into birth weight categories. Costs for inpatient treatment and long-term consequences were considered from a third party payer perspective for the reference year 2017. Deterministic and probabilistic sensitivity analyses were performed, including a societal perspective, discounting rate and all input parameter-values. RESULTS: In the base case, the EHMD was estimated to be cost-effective compared to the current nutrition for very low birth weight newborns with an incremental cost-effectiveness ratio (ICER) of €28,325 per Life-Year-Gained (LYG). From a societal perspective, the ICER is €27,494/LYG using a friction cost approach and €16,112/LYG using a human capital approach. Deterministic sensitivity analyses demonstrated that the estimate was robust against changes in the input parameters and probabilistic sensitivity analysis suggested that the probability EHMD was cost-effective at a threshold of €45,790/LYG was 94.8 percent. CONCLUSION: Adopting EHMD as the standard approach to nutrition is a cost-effective intervention for very low birth weight newborns in Germany.

Humoral immune response to measles and varicella vaccination in former very low birth weight preterm infants

ABSTRACT Introduction: Immune response to vaccination in infants born prematurely may be lower than in infants born at full-term. Some clinical factors might be associated with humoral immune response. Objectives: The objectives of this study were to compare the immune response to measles and varicella vaccination in infants born prematurely with those born at full-term and to analyze factors associated with measles and varicella antibody levels. Methods: Prospective study including two groups of infants aged 12 months. One group of infants born prematurely with birth-weight <1500 g and who were in follow-up at the outpatient clinic for preterm infants at the institution and other group of infants born at full-term. Infants with malformations, primary immunodeficiency diseases, born to HIV-positive mothers or who had received plasma or immunoglobulin transfusions five months before or three weeks after vaccination were excluded. Plasma antibodies were measured by ELISA and factors associated with antibody levels were assessed by linear regression. Results: Sixty-five premature and 56 full-term infants were included. The percentage of immune individuals after vaccination against measles (100% vs. 100%) and varicella (92.5% vs. 93.2%) were similar in both groups, as well as the antibody levels against measles (2.393 vs. 2.412 UI/mL; p = 0.970) and varicella (0.551 vs. 0.399 UI/mL; p = 0.114). Use of antenatal corticosteroids decreased measles antibody levels whereas breastfeeding for more than six months increased varicella antibody levels. Conclusions: Humoral responses to measles and varicella were similar between infants born prematurely and full-term infants. Measles antibody levels were negatively associated with antenatal corticosteroid use; varicella antibodies were positively associated with prolonged breastfeeding.

Inflammatory mediator patterns in tracheal aspirate and their association with bronchopulmonary dysplasia in very low birth weight neonates.

OBJECTIVE: Alterations in inflammatory mediators are an important finding in neonates who develop bronchopulmonary dysplasia (BPD); however, there is a lack of research examining the relationship between multiple inflammatory mediators in premature neonates and the development of BPD. This study investigated whether the distribution of 12 inflammatory mediators detected in the tracheal aspirate (TA) of neonates within 24 h of birth could differentiate between neonates who did and who did not develop BPD. STUDY DESIGN: TA samples were collected from 27 very low birth weight neonates (BPD+=11), and the concentrations of 12 biomarkers associated with BPD were determined. Linear discriminant analysis (LDA) was used to classify neonates into two outcome groups. RESULT: LDA based on the 12 measured biomarkers displayed a significant level of discriminant function (P=0.007). CONCLUSION: Using linear discriminant analysis, predictive models of BPD can be generated. Our results suggest that multiple inflammatory mediators collected within 24 h of birth may be used to classify neonates into who will and who will not develop BPD.

Low monocyte HLA-DR expression as an indicator of immunodepression in very low birth weight infants.

BACKGROUND: As a protective response to an inflammatory stimulus, the antigen-presenting molecules (human leukocyte antigen-DR (HLA-DR)) on monocytes are downregulated. If severe, the response may lead to immunodepression or immunoparalysis, associated with an increased rate of morbidity and mortality in adults. In very low birth weight (VLBW) infants, birth and intensive care present major immunological challenges. METHODS: We measured monocyte HLA-DR expression by flow cytometry and determined 13 plasma cytokines in 56 VLBW infants (gestational age (GA): 23.7-31.8 wk) and 25 controls (GA: 34.1-41.4 wk). RESULTS: HLA-DR expression decreased postnatally both in VLBW and in control infants. In VLBW infants, GA and respiratory distress syndrome (RDS) both showed associations with HLA-DR nadir on day 3, when 45% of them met the criteria of immunodepression. HLA-DR expression was lower in those infants subsequently developing infection (74 vs. 49% (day 3) and 85 vs. 68% (day 7); both P = 0.002). Interleukin (IL)-6 on day 1 was a predictor of the HLA-DR nadir. CONCLUSION: VLBW infants are in a state of immunodepression postnatally. This immunodepression correlated with GA and was a predisposing factor for late infections. The downregulation of HLA-DR during RDS probably indicates an RDS-induced antigen load on the immune system.

Cytokine responses in very low birth weight infants receiving glutamine-enriched enteral nutrition.

OBJECTIVE: Very low birth weight (VLBW) infants receiving glutamine-enriched enteral nutrition may present with a lower infection rate, which may result from enhanced antimicrobial innate or Th1 cytokine responses. We investigated whether glutamine-enriched enteral nutrition in VLBW infants increased these cytokine responses following in vitro stimulation of whole blood cells. METHODS: In a double-blind, placebo-controlled, randomized controlled trial, VLBW infants (gestational age <32 weeks and/or birth weight <1500 g) received enteral glutamine supplementation (0.3 g x kg(-1) x day(-1)) or isonitrogenous placebo supplementation (alanine) between days 3 and 30 of life. Cytokine responses following in vitro whole blood cell stimulation with anti-(alpha)CD3/alphaCD28 or lipopolysaccharide were analyzed by cytometric bead array at 3 time points: before the start of the study, at day 7 of life, and at day 14 of life. RESULTS: Baseline patient and nutritional characteristics were not different between groups. At least 2 blood samples were analyzed in 25 of 52 (48%) and 38 of 50 (76%) infants in the glutamine-supplemented and control groups, respectively. Glutamine-enriched enteral nutrition was not associated with significant alterations in cytokine responses (interferon-gamma, tumor necrosis factor-alpha, interleukin [IL]-2, IL-4, IL-5, and IL-10) of peripheral blood cells upon stimulation with either anti-alphaCD3/alphaCD28 or lipopolysaccharide. CONCLUSIONS: We hypothesize that glutamine-enriched enteral nutrition decreases the infection rate in VLBW infants by influencing the mucosal and not the systemic immune system.

Postsurgical meningitis caused by Acinetobacter baumannii associated with high mortality.

Twenty five (25) cases of nosocomial postsurgical meningitis due to Acinetobacter baumannii meningitis were compared to other 146 cases of meningitis after surgery caused by other pathogens. Prior neurosurgical ventriculo-peritoneal shunt insertion and CNS abnormality as well as very low birth weight were significant risk factors for acquisition of Acinetobacter baumannii meningitis. Mortality - 40% among children with nosocomial meningitis was unacceptably high and significantly higher than among meningitis caused by microorganisms other than Acinetobacter baumannii.

Particularidades imunológicas do pré-termo extremo: um desafio para a prevenção da sepse hospitalar / Immunological peculiarities of extremely preterm infants: a challenge for the prevention of nosocomial sepsis

OBJETIVO: Realizar revisão sobre os principais aspectos do desenvolvimento imunológico fetal, salientando a defesa de prematuros extremos contra patógenos bacterianos e descrevendo a situação atual de intervenções imunoterapêuticas para a prevenção de sepse hospitalar. FONTES DOS DADOS: Obtiveram-se, por meio de busca eletrônica, no banco de dados MEDLINE, artigos publicados nos últimos 15 anos referentes ao tema, e foram selecionados aqueles que trouxessem informações relevantes. SíNTESE DOS DADOS: A imunidade de prematuros extremos é deficiente devido à fragilidade da pele, à carência dos produtos de ativação do sistema complemento, ao menor pool de reserva de precursores de neutrófilos na medula óssea e à quimiotaxia, aderência, deformabilidade e atividade enzimática neutrofílicas reduzidas. Limitações adicionais são detectadas na citotoxicidade de células NK, na proliferação e produção de citocinas dos linfócitos T, na cooperação entre células T e B e na síntese de anticorpos pelos linfócitos B. Ainda não foram demonstrados benefícios definitivos de intervenções para incremento da função imunológica dessas crianças, tais como o uso de imunoglobulinas endovenosas e de fatores estimuladores de colônias mielóides. CONCLUSAO: Em conseqüência à imaturidade de diversos componentes da imunidade, prematuros extremos são altamente suscetíveis a infecções nosocomiais. As possibilidades ainda muito limitadas para a intervenção nesse sistema fazem com que o controle dos fatores extrínsecos sejam essenciais para a prevenção da sepse nosocomial nessas crianças.

Imunização ativa e passiva no prematuro extremo / Active and passive immunization in the extremely preterm infant

OBJETIVO: Revisão sobre a indicação, contra-indicação, época ideal, eficácia imunogênica e reatogenicidade (eventos adversos) das imunizações passiva e ativa nos RN pré-termo extremos. FONTE DOS DADOS: Pesquisa em livros-textos clássicos de infectologia pediátrica e nas bases de dados eletrônicas MEDLINE, Lilacs, PubMed e Akwanmed, utilizando os seguintes descritores de ciências da saúde: prematuro, recém-nascido de muito baixo peso, imunização, imunização ativa, imunização passiva, vacinas, imunoglobulina. SíNTESE DOS DADOS: A imunização do recém-nascido pré-termo extremo ou de muito baixo peso ao nascer é um grande desafio para o pediatra, por não haver conhecimento suficiente da eficácia da resposta imunitária e das reações indesejáveis. Talvez, por isto, seja comum encontrar estas crianças com o seu esquema de imunizações incompleto ou atrasado. No entanto, apesar da escassez de publicações sobre o tema, em princípio, a idade gestacional e o baixo peso ao nascer não devem ser considerados fatores limitantes para que um recém-nascido prematuro clinicamente estável seja imunizado na mesma idade cronológica indicada para as crianças nascidas a termo. CONCLUSAO: Não é possível, baseado em evidências, apresentar uma conduta inquestionável para a aplicação de vacinas e imunoglobulinas em recém-nascidos prematuros extremos ou de muito baixo peso. A tendência é - com raras exceções, como, por exemplo, a vacina BCG - manter o mesmo esquema de imunização ativa do recém-nascido a termo, independentemente do peso ao nascer ou da idade gestacional. A imunização passiva merece especial atenção, tendo indicações mais liberais neste grupo de recém-nascidos.

Increased interleukin-8 and monocyte chemoattractant protein-1 concentrations in mechanically ventilated preterm infants with pulmonary hemorrhage.

Pulmonary hemorrhage (PH) is a serious complication causing acute respiratory distress in the premature infant, and it is associated with significant mortality and morbidity. The role of inflammatory mediators in this condition is largely undefined. Serial tracheal aspirates (TA) were obtained at intervals from 65 mechanically ventilated infants with birth weights less than 1,250 g during the first 21 days of life. Clinically significant PH developed in 15 infants. TA concentrations of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) were determined by enzyme-linked immunosorbent assay (ELISA).PH was associated with an increased risk of death, bronchopulmonary dysplasia, intraventricular hemorrhage, and prolonged need for mechanical ventilation and supplemental oxygen. TA aspirate concentrations of IL-8 and MCP-1 (P = 0.001, ANOVA) were significantly increased in infants with PH compared to infants who did not develop this condition. TA cytokine concentrations were also significantly increased in infants who developed bronchopulmonary dysplasia (BPD). Peak TA concentrations of IL-8 and MCP-1 were significantly higher in infants with poor outcome (BPD or death). TA MCP-1 but not IL-8 concentrations were significantly higher in infants who were oxygen-dependent at 36 weeks postconceptional age. These data suggest a pathogenic role for IL-8 and MCP-1 in the development of adverse pulmonary outcome in preterm infants with clinically significant PH.

Neonatal leukemoid reaction and early development of bronchopulmonary dysplasia in a very low-birth-weight infant.

The factors controlling the recruitment of inflammatory cells and the activation of the cytokine cascade in low-birth-weight premature infants have been implicated in the sequence of multiorgan inflammatory diseases, including the chronic lung disease of prematurity, bronchopulmonary dysplasia. This article describes a 982-gram, 25 (+2 days) weeks' gestation male infant, who had a leukemoid reaction throughout the first week of life, followed by early development of bronchopulmonary dysplasia.

Postpartum smoking behaviors and immune response in mothers of term and preterm infants.

Infants exposed to secondhand smoke, especially preterm infants with a very low birth weight (VLBW), have an increased risk for developing health problems. Smoking has been associated with numerous health problems in mothers and may reduce immune functioning as well. The purposes of this study were to examine smoking in postpartum mothers of term and preterm infants and to examine the relationship between smoking and immune status. Peripheral blood was drawn on 142 women at four data-collection points and tested for cotinine, immune cell phenotypes, and immune functioning. Overall, 39% of the participants smoked in the postpartum period, but 49% of mothers who delivered preterm infants smoked compared to only 28% of mothers who delivered term infants. There was no difference in cotinine levels between the smokers in both groups of postpartum mothers, nor was smoking related to immune phenotypes or immune function. Given the documented health risks to the mother and infant and the significant number of women who continue to smoke in the postpartum period, it is imperative that health care providers continue to assess smoking status and provide smoking-cessation counseling at every encounter.