The developing human preterm neonatal immune system: A case for more research in this area

Sharma, Ashish; Jen, Roger; Butler, A.J.; Lavoie, Pascal M.

doi:10.1016/j.clim.2012.08.006

Cited by 165 publications

(151 citation statements)

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“…The immune system of a full-term infant is thought to be well-adapted to its developmental period [19,31]. Most recently, studies have demonstrated other unique functional features of the newborn immune system, potentially allowing age-specific interactions between innate and adaptive immune cells during the course of an infection.…”

Section: Box 2 Relative Importance Of the Innate And Adaptive Immune mentioning

confidence: 99%

An Immunological Perspective on Neonatal Sepsis

Kan

Razzaghian

Lavoie

2016

Trends in Molecular Medicine

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Despite concerted international efforts, mortality from neonatal infections remains unacceptably high in some areas of the world, particularly for premature infants. Recent developments in flow cytometry and next-generation sequencing technologies have led to major discoveries over the past few years, providing a more integrated understanding of the developing human immune system in the context of its microbial environment. We review these recent findings, focusing on how in human newborns incomplete maturation of the immune system before a full term of gestation impacts on their vulnerability to infection. We also discuss some of the clinical implications of this research in guiding the design of more-accurate age-adapted diagnostic and preventive strategies for neonatal sepsis.

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Section: Box 2 Relative Importance Of the Innate And Adaptive Immune mentioning

confidence: 99%

An Immunological Perspective on Neonatal Sepsis

Kan

Razzaghian

Lavoie

2016

Trends in Molecular Medicine

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“…[45][46][47][48][49] Preterm infants also have a limited ability to counteract inflammatory and oxidative stress during the neonatal period. 50 Sustained oxidative stress and inflammation are key factors contributing to the development of BPD as well as other neonatal complications. Dietary LCPUFA, particularly DHA and eicosapentaenoic acid are important modulators of inflammation.…”

Section: Figurementioning

confidence: 99%

Omega-3 Long-Chain Polyunsaturated Fatty Acids for Extremely Preterm Infants: A Systematic Review

et al. 2014

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BACKGROUND AND OBJECTIVE: Omega-3 long chain polyunsaturated fatty acid (LCPUFA) exposure can be associated with reduced neonatal morbidities. We systematically review the evidence for the benefits of omega-3 LCPUFAs for reducing neonatal morbidities in extremely preterm infants.METHODS: Data sources were PubMed, Embase, Center for Reviews and Dissemination, and the Cochrane Register of Controlled Trials. Original studies were selected that included infants born at ,29 weeks' gestation, those published until May 2013, and those that evaluated the relationship between omega-3 LCPUFA supplementation and major adverse neonatal outcomes. Data were extracted on study design and outcome. Effect estimates were pooled. RESULTS:Of the 1876 studies identified, 18 randomized controlled trials (RCTs) and 6 observational studies met the defined criteria. No RCT specifically targeted a population of extremely preterm infants. Based on RCTs, omega-3 LCPUFA was not associated with a decreased risk of bronchopulmonary dysplasia in infants overall (pooled risk ratio [RR] 0.97, 95% confidence interval [CI] 0.82-1.13], 12 studies, n = 2809 infants); however, when considering RCTs that include only infants born at #32 weeks' gestation, a trend toward a reduction in the risk of bronchopulmonary dysplasia (pooled RR 0.88, 95% CI 0.74-1.05, 7 studies, n = 1156 infants) and a reduction in the risk of necrotizing enterocolitis (pooled RR 0.50, 95% CI 0.23-1.10, 5 studies, n = 900 infants) was observed with LCPUFA.CONCLUSIONS: Large-scale interventional studies are required to determine the clinical benefits of omega-3 LCPUFA, specifically in extremely preterm infants, during the neonatal period. Dr Marc conceptualized and designed the protocol, screened the titles and abstracts, and retrieved articles for inclusion and quality, performed the analyses, drafted the initial manuscript, and approved the final manuscript as submitted; Ms Zhang critically reviewed the protocol, screened the titles and abstracts and retrieved articles for inclusion and quality, drafted the tables and figures, and reviewed the final manuscript as submitted; Dr Lavoie screened the articles for quality, revised the manuscript, participated in the redaction of the final manuscript, and reviewed the final manuscript as submitted; Dr Rhainds designed and conducted the systematic database search, reviewed the manuscript, and approved the final manuscript as submitted; and Dr Lacaze-Masmonteil reviewed the manuscript and approved the final manuscript as submitted.www.pediatrics.org/cgi

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“…Neonates and in particular preterm infants are extremely vulnerable to states of inflammation [1]. They have an increased susceptibility to microbial infections with an enhanced morbidity and Correspondence: Mr. Thomas Winterberg e-mail: Winterberg.thomas@mh-hannover.de mortality [2].…”

Section: Introductionmentioning

confidence: 99%

Distinct phenotypic features of neonatal murine macrophages

et al. 2014

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Neonates rely on their innate immune system. Resident tissue macrophages are considered to be initiators and regulators of the innate immune response and thus, appear to be especially important to neonates. We hypothesized that the phenotype and function of neonatal tissue macrophages differ from their adult counterparts. Peritoneal macrophages from neonatal (<24 h) and adult (6 weeks old) C57BL/6J mice were isolated and analyzed by high-content chipcytometry. After stimulation for 6 h with LPS (0, 1, 10, 100 ng/mL), macrophage transcriptome was analyzed by microarray and cytokine release was measured using multiparametric bead assays. Antigen presenting capacity was compared by T-cell stimulation assays. We observed that neonatal murine peritoneal macrophages are characterized by selective lack of expression of F4/80, MHC class II, and costimulatory molecules (CD80, CD86). Furthermore, we found differences in the transcriptome between neonatal and adult macrophages, unstimulated and after LPS stimulation. Although neonatal macrophages showed a significantly increased secretion of proinflammatory cytokines upon LPS stimulation, their potential to induce T-cell proliferation was significantly reduced. In conclusion, we observed a distinct phenotype of the neonatal macrophage population. The specific functions of this macrophage population could help to understand the excessive inflammatory reactions observed in the very young.Keywords: Immune responses r Macrophages r Neonate immunity r Toll-like receptors (TLRs) Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionNeonates and in particular preterm infants are extremely vulnerable to states of inflammation [1]. They have an increased susceptibility to microbial infections with an enhanced morbidity and Correspondence: Mr. Thomas Winterberg e-mail: Winterberg.thomas@mh-hannover.de mortality [2]. Sepsis, pneumonia, and gastrointestinal disorders such as necrotizing enterocolitis are a common threat to patients in neonatal intensive care. The first days of life represent a period of transition of the immune system: The protection of the fetus by the maternal immune system and the sterile environment are lost and the newborn has to cope with the outside world and its multiple foreign antigens. Although maternal antibodies help the neonate in the first weeks, it has to develop its own adaptive immune capacities during infancy [2]. In the neonatal period, monocytes and [6][7][8][9]. Until now, neonatal monocytes and macrophages have been described as immature or dormant myeloid cells. However, these studies are based on peripheral blood monocytes or CBMs, which further differentiate into macrophages ex vivo. Little is known about tissue macrophages in neonates, due to technical difficulties of their isolation and evaluation, but a recent study demonstrated their unique function during heart tissue regeneration [10].It has been shown that the heterogeneous murine macrophage populations are orig...

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The developing human preterm neonatal immune system: A case for more research in this area

Cited by 165 publications

References 86 publications

An Immunological Perspective on Neonatal Sepsis

An Immunological Perspective on Neonatal Sepsis

Omega-3 Long-Chain Polyunsaturated Fatty Acids for Extremely Preterm Infants: A Systematic Review

Distinct phenotypic features of neonatal murine macrophages

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