Impact of Early-Life Exposures to Infections, Antibiotics, and Vaccines on Perinatal and Long-term Health and Disease.
Impact of Early-Life Exposures to Infections, Antibiotics, and Vaccines on Perinatal and Long-term Health and Disease.
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DOI：
10.3389/fimmu.2017.00729
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发表时间：
2017
影响因子：
7.3
通讯作者：
Larson SD
中科院分区：
文献类型：
--
作者：
Raymond SL;Rincon JC;Wynn JL;Moldawer LL;Larson SD
从本质上讲，所有新生儿在生命早期都暴露于感染、抗生素或疫苗。对于出生体重不足或早产的新生儿尤其如此。与脓毒症成人和儿童的后续感染风险增加相反，新生儿期暴露于感染与后续感染风险增加无关，并且可能与大多数早产儿迟发性脓毒症（LOS）的减少相矛盾。围产期炎症也与以后生活中哮喘和特应性的发病率降低有关。相反，败血症新生儿的长期神经发育受损的风险增加。虽然抗生素在感染背景下的积极作用是无可辩驳的，但在无感染记录的新生儿中，长期使用广谱经验性抗生素与LOS、坏死性小肠结肠炎或死亡风险增加相关。疫苗为预防感染相关疾病提供了独特的机会;不幸的是，除了针对B型肝炎和结核病的疫苗之外，在出生后的第一个月接种疫苗大多不成功。未来的疫苗将需要使用新的佐剂来克服这一挑战。这篇综述描述了感染、抗生素和疫苗在生命最初几天的影响，以及对未来健康和疾病的影响。我们还将讨论潜在的免疫调节疗法，这可能有助于训练早产儿的免疫系统，并减少随后的感染负担，而不会使新生儿遭受伴随着致命病原体的风险。
Essentially, all neonates are exposed to infections, antibiotics, or vaccines early in their lives. This is especially true for those neonates born underweight or premature. In contrast to septic adults and children who are at an increased risk for subsequent infections, exposure to infection during the neonatal period is not associated with an increased risk of subsequent infection and may be paradoxically associated with reductions in late-onset sepsis (LOS) in the most premature infants. Perinatal inflammation is also associated with a decreased incidence of asthma and atopy later in life. Conversely, septic neonates are at increased risk of impaired long-term neurodevelopment. While the positive effects of antibiotics in the setting of infection are irrefutable, prolonged administration of broad-spectrum, empiric antibiotics in neonates without documented infection is associated with increased risk of LOS, necrotizing enterocolitis, or death. Vaccines provide a unique opportunity to prevent infection-associated disease; unfortunately, vaccinations have been largely unsuccessful when administered in the first month of life with the exception of vaccines against hepatitis B and tuberculosis. Future vaccines will require the use of novel adjuvants to overcome this challenge. This review describes the influence of infections, antibiotics, and vaccines during the first days of life, as well as the influence on future health and disease. We will also discuss potential immunomodulating therapies, which may serve to train the preterm immune system and reduce subsequent infectious burden without subjecting neonates to the risks accompanied by virulent pathogens.