Section for Comparative Pediatrics and Nutrition, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.
Front Immunol. 2019 Oct 10;10:2402. doi: 10.3389/fimmu.2019.02402. eCollection 2019.
Many preterm infants are born with growth restriction (GR) following maternal or fetal complications before birth. Such infants may continue to grow slowly after birth, regardless of birth weight (BW), due to morbidities related to their immature organs. Severe GR increases the susceptibility to infections, but it is not clear if this is a consequence of impaired systemic immunity or other factors, such as prolonged hospital stay or poor mucosal barrier function. Using preterm pigs as models for preterm infants, we hypothesized that moderate GR, exerting limited clinical effects, does not influence systemic immune development. Preterm pigs were delivered by cesarean section and fed bovine milk diets until 19 d. Piglets with fetal growth restriction (F-GR, the lowest 25% of BW, = 27, excluding those with BW <350 g) and postnatal growth restriction (P-GR, the lowest 25% of postnatal growth rate, = 24) were compared with their corresponding controls (F-CON, = 92, and P-CON, = 85, respectively). Organ weights were determined and blood collected for assessment of clinical status (blood chemistry and hematology). For a subgroup ( = 58), in depth analyses of neutrophil function, T cell counts, plasma cytokine levels, and leucocyte gene expression were performed. For F-GR pigs, adrenal gland weight was increased and bone mineral content decreased at 19 d. Total leucocyte levels were lower at birth and interleukin-10 levels increased at d 8-10. In P-GR pigs, total leucocyte, neutrophil, monocyte, and eosinophil counts along with helper T cell fractions were elevated at 8-19 d of age, while the fraction of neutrophils with phagocytic capacity was reduced. Diarrhea and all remaining organ weights, blood chemistry, and immune variables were not affected by F-GR or P-GR. Moderate GR before and after preterm birth has limited effect on systemic immune development in preterm pigs, despite marginal effects on immune cell populations, adrenocortical function, and body composition. Similar responses may be observed for preterm infants with moderate fetal and postnatal growth restriction.
许多早产儿在出生前因母体或胎儿并发症而出现生长受限（GR）。即使出生体重（BW）正常，这些婴儿出生后也可能继续生长缓慢，这是由于其未成熟器官的疾病引起的。严重的 GR 会增加感染的易感性，但尚不清楚这是全身免疫受损的结果，还是其他因素的结果，如住院时间延长或黏膜屏障功能差。我们使用早产猪作为早产儿模型，假设适度的 GR（临床影响有限）不会影响全身免疫发育。通过剖宫产分娩并喂养牛初乳饮食直至 19 天，早产猪被喂养至 19 天。生长受限的胎儿（F-GR，BW 的最低 25%，n=27，排除 BW<350g 的个体）和出生后生长受限（P-GR，出生后生长率的最低 25%，n=24）与相应的对照组（F-CON，n=92 和 P-CON，n=85）进行比较。测定器官重量并采集血液以评估临床状况（血液化学和血液学）。对于亚组（n=58），还进行了中性粒细胞功能、T 细胞计数、血浆细胞因子水平和白细胞基因表达的深入分析。对于 F-GR 猪，19 天时肾上腺重量增加，骨矿物质含量降低。出生时总白细胞计数较低，第 8-10 天白细胞介素-10 水平升高。在 P-GR 猪中，8-19 日龄时总白细胞、中性粒细胞、单核细胞和嗜酸性粒细胞计数以及辅助性 T 细胞比例升高，而吞噬能力的中性粒细胞比例降低。F-GR 或 P-GR 并不影响腹泻和所有剩余器官重量、血液化学和免疫变量。尽管对免疫细胞群、肾上腺皮质功能和身体成分有轻微影响，但出生前和出生后早产儿的适度 GR 对全身免疫发育的影响有限。对于有适度胎儿和出生后生长受限的早产儿，可能会出现类似的反应。
