Division of Neonatology, Department of Women's and Children's Health, University of Leipzig Medical Center, Leipzig, Germany.
Department of Pediatrics, Division of Neonatology, Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Neonatology. 2024;121(5):636-645. doi: 10.1159/000539303. Epub 2024 Jun 13.
The rates of major neonatal morbidities, such as bronchopulmonary dysplasia, necrotizing enterocolitis, preterm white matter disease, and retinopathy of prematurity, remain high among surviving preterm infants. Exposure to inflammatory stimuli and the subsequent host innate immune response contribute to the risk of developing these complications of prematurity. Notably, the burden of inflammation and associated neonatal morbidity is inversely related to gestational age - leaving primarily but not exclusively the tiniest babies at highest risk.
Avoidance, prevention, and treatment of inflammation to reduce this burden remain a major goal for neonatologists worldwide. In this review, we discuss the link between the host response to inflammatory stimuli and the disease state. We argue that inflammatory exposures play a key role in the pathobiology of preterm birth and that preterm neonates hereafter are highly susceptible to immune stimulation not only from their surrounding environment but also from therapeutic interventions employed in clinical care. Using bronchopulmonary dysplasia as an example, we report clinical studies demonstrating the potential utility of targeting inflammation to prevent this neonatal morbidity. On the contrary, we highlight limitations in our current understanding of how inflammation contributes to disease prevention and treatment.
To be successful in preventing and treating inflammation-driven morbidity in neonatal intensive care, it may be necessary to better identify at-risk patients and pair therapeutic interventions to key pathways and mediators of inflammation-associated neonatal morbidity identified in pre-clinical and translational studies.
在幸存的早产儿中，诸如支气管肺发育不良、坏死性小肠结肠炎、早产儿脑白质病和早产儿视网膜病变等主要新生儿疾病的发病率仍然很高。炎症刺激的暴露以及随后的宿主固有免疫反应导致了这些早产儿并发症的发生风险。值得注意的是，炎症负担和相关新生儿发病率与胎龄呈反比关系，这使得最小的婴儿面临着最大的风险。
避免、预防和治疗炎症以减轻这种负担仍然是全世界新生儿科医生的主要目标。在这篇综述中，我们讨论了宿主对炎症刺激的反应与疾病状态之间的联系。我们认为，炎症暴露在早产的发病机制中起着关键作用，此后早产儿不仅容易受到周围环境的免疫刺激，而且容易受到临床护理中采用的治疗干预的影响。我们以支气管肺发育不良为例，报告了一些临床研究，这些研究表明靶向炎症以预防这种新生儿发病率的潜在效用。相反，我们强调了我们目前对炎症如何促进疾病预防和治疗的理解的局限性。
要成功预防和治疗新生儿重症监护中的炎症驱动性发病率，可能有必要更好地识别高危患者，并将治疗干预与在临床前和转化研究中确定的与炎症相关的新生儿发病率的关键途径和介质相匹配。
