Ahnfeldt Agnethe May, Bæk Ole, Hui Yan, Nielsen Charlotte Holme, Obelitz-Ryom Karina, Busk-Anderson Tilla, Ruge Anne, Holst Jens Juul, Rudloff Silvia, Burrin Douglas, Nguyen Duc Ninh, Nielsen Dennis Sandris, Zachariassen Gitte, Bering Stine Brandt, Thymann Thomas, Sangild Per Torp
Department of Veterinary and Animal Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Food Science, Food Microbiology, University of Copenhagen, Copenhagen, Denmark.
J Nutr. 2020 May 1;150(5):1196-1207. doi: 10.1093/jn/nxaa030.
Extrauterine growth restriction (EUGR) in preterm infants is associated with higher morbidity and impaired neurodevelopment. Early nutrition support may prevent EUGR in preterm infants, but it is not known if this improves organ development and brain function in the short and long term.
Using pigs as models for infants, we hypothesized that diet-induced EUGR impairs gut, immunity, and brain development in preterm neonates during the first weeks after birth.
Forty-four preterm caesarean-delivered pigs (Danish Landrace × Large White × Duroc, birth weight 975 ± 235 g, male:female ratio 23:21) from 2 sows were fed increasing volumes [32-180 mL/(kg·d)] of dilute bovine milk (EUGR group) or the same diet fortified with powdered bovine colostrum for 19 d (CONT group, 50-100% higher protein and energy intake than the EUGR group).
The EUGR pigs showed reduced body growth (-39%, P < 0.01), lower plasma albumin, phosphate, and creatine kinase concentrations (-35 to 14%, P < 0.05), increased cortisol and free iron concentrations (+130 to 700%, P < 0.05), and reduced relative weights of the intestine, liver, and spleen (-38 to 19%, all P < 0.05). The effects of EUGR on gut structure, function, microbiota, and systemic immunity were marginal, although EUGR temporarily increased type 1 helper T cell (Th1) activity (e.g. more blood T cells and higher Th1-related cytokine concentrations on day 8) and reduced colon nutrient fermentation (lower SCFA concentration; -45%, P < 0.01). Further, EUGR pigs showed increased relative brain weights (+19%, P < 0.01), however, memory and learning, as tested in a spatial T-maze, were not affected.
Most of the measured organ growth, and digestive, immune, and brain functions showed limited effects of diet-induced EUGR in preterm pigs during the first weeks after birth. Likewise, preterm infants may show remarkable physiological adaptation to deficient nutrient supply during the first weeks of life although early life malnutrition may exert negative consequences later.
早产儿宫外生长受限（EUGR）与更高的发病率及神经发育受损相关。早期营养支持可能预防早产儿发生EUGR，但尚不清楚这在短期和长期内是否能改善器官发育及脑功能。
以猪作为婴儿模型，我们假设饮食诱导的EUGR会在出生后的头几周损害早产新生儿的肠道、免疫及脑发育。
从2头母猪获取44头早产剖宫产仔猪（丹麦长白猪×大白猪×杜洛克猪，出生体重975±235 g，雄雌比例23:21），给它们喂食逐渐增加量[32 - 180 mL/(kg·d)]的稀释牛乳（EUGR组），或喂食添加了牛初乳粉的相同饮食19天（CONT组，蛋白质和能量摄入量比EUGR组高50 - 100%）。
EUGR仔猪体重增长减少（-39%，P < 0.01），血浆白蛋白、磷酸盐和肌酸激酶浓度降低（-35%至14%，P < 0.05），皮质醇和游离铁浓度升高（+130%至700%，P < 0.05），肠道、肝脏和脾脏相对重量降低（-38%至19%，均P < 0.05）。EUGR对肠道结构、功能、微生物群和全身免疫的影响较小，尽管EUGR暂时增加了1型辅助性T细胞（Th1）活性（例如第8天血液中T细胞更多且Th1相关细胞因子浓度更高）并降低了结肠营养物质发酵（短链脂肪酸浓度降低；-45%，P < 0.01）。此外，EUGR仔猪脑相对重量增加（+19%，P < 0.01），然而，在空间T迷宫中测试的记忆和学习能力未受影响。
在出生后的头几周，大多数所测量的器官生长以及消化、免疫和脑功能显示饮食诱导的EUGR对早产仔猪影响有限。同样，早产儿在生命的头几周可能对营养供应不足表现出显著的生理适应能力，尽管早期营养不良可能在以后产生负面后果。
