Department of Development and Regeneration, Cluster Woman and Child, Group Biomedical Sciences, KU Leuven University of Leuven, Leuven, Belgium.
Division Woman and Child, Department of Obstetrics and Gynaecology, University Hospitals Leuven, Leuven, Belgium.
PLoS One. 2021 Jan 27;16(1):e0246008. doi: 10.1371/journal.pone.0246008. eCollection 2021.
Preterm birth (PTB) and particularly late preterm PTB has become a research focus for obstetricians, perinatologists, neonatologists, pediatricians and policy makers alike. Translational models are useful tools to expedite and guide clinical but presently no model exists that contextualizes the late PTB scenario. Herein we aimed to develop a rabbit model that echo's the clinical neurocognitive phenotypes of early and late PTB.
Time mated rabbit does underwent caesarean delivery at a postconceptional age (PCA) of either 28 (n = 6), 29 (n = 5), 30 (n = 4) or 31 (n = 4) days, term = 31 d. Newborn rabbits were mixed and randomly allocated to be raised by cross fostering and underwent short term neurobehavioral testing on corrected post-natal day 1. Open field (OFT), spontaneous alteration (TMT) and novel object recognition (NORT) tests were subsequently performed at 4 and 8 weeks of age.
PTB was associated with a significant gradient of short-term mortality and morbidity inversely related to the PCA. On postnatal day 1 PTB was associated with a significant sensory deficit in all groups but a clear motor insult was only noted in the PCA 29d and PCA 28d groups. Furthermore, PCA 29d and PCA 28d rabbits had a persistent neurobehavioral deficit with less exploration and hyperanxious state in the OFT, less alternation in TMT and lower discriminatory index in the NORT. While PCA 30d rabbits had some anxiety behavior and lower spontaneous alteration at 4 weeks, however at 8 weeks only mild anxiety driven behavior was observed in some of these rabbits.
In this rabbit model, delivery at PCA 29d and PCA 28d mimics the clinical phenotype of early PTB while delivery at PCA 30d resembles that of late PTB. This could serve as a model to investigate perinatal insults during the early and late preterm period.
早产（PTB），尤其是晚期早产，已成为产科医生、围产学家、新生儿科医生、儿科医生和政策制定者共同关注的研究焦点。转化模型是加速和指导临床研究的有用工具，但目前还没有一种模型能够使晚期 PTB 情况具体化。在此，我们旨在开发一种能够模拟早期和晚期 PTB 临床神经认知表型的兔模型。
时间匹配的兔受孕后行剖宫产，分别在妊娠后 28 天（n = 6）、29 天（n = 5）、30 天（n = 4）或 31 天（n = 4）进行。新生兔混合并随机分配接受交叉寄养，在矫正后的出生后第 1 天进行短期神经行为测试。随后在 4 周和 8 周龄时进行旷场（OFT）、自发交替（TMT）和新物体识别（NORT）测试。
PTB 与短期死亡率和发病率呈显著梯度相关，而死亡率和发病率与 PCA 呈反比。在出生后第 1 天，所有组均存在明显的感觉缺陷，但只有 PCA 29d 和 PCA 28d 组存在明显的运动损伤。此外，PCA 29d 和 PCA 28d 兔在 OFT 中表现出持续的神经行为缺陷，探索行为减少，焦虑状态增加，在 TMT 中交替减少，在 NORT 中的鉴别指数降低。而 PCA 30d 兔在 4 周时有一些焦虑行为和自发交替减少，但在 8 周时，只有部分兔子表现出轻微的焦虑驱动行为。
在这个兔模型中，PCA 29d 和 PCA 28d 的分娩模拟了早期 PTB 的临床表型，而 PCA 30d 的分娩则类似于晚期 PTB。这可以作为研究早期和晚期早产期间围产期损伤的模型。
