Boggini Tiziana, Pozzoli Sara, Schiavolin Paola, Erario Raffaele, Mosca Fabio, Brambilla Paolo, Fumagalli Monica
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, NICU, Milan, Italy.
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Neurosciences and Mental Health, Milan, Italy.
Neurosci Biobehav Rev. 2021 Apr;123:320-336. doi: 10.1016/j.neubiorev.2020.12.016. Epub 2020 Dec 20.
Very preterm infants may manifest neurodevelopmental impairments, even in the absence of brain lesions. Pathogenesis is complex and multifactorial. Evidence suggests a role of early adversities on neurodevelopmental outcomes, via epigenetic regulation and changes in brain architecture. In this context, we focused on cumulative pain exposure which preterm neonates experience in neonatal intensive care unit (NICU). We systematically searched for: i) evidence linking pain with brain development and exploring the potential pathogenetic role of epigenetics; ii) preclinical research supporting clinical observational studies. Nine clinical neuroimaging studies, during neonatal or school age, mostly from the same research group, revealed volume reduction of white and gray matter structures in association with postnatal pain exposure. Three controlled animal studies mimicking NICU settings found increased cell death or apoptosis; nevertheless, eligible groups were limited in size. Epigenetic modulation (SLC6A4 promoter methylation) was identified in only two clinical trials. We call for additional research and, although knowledge gaps, we also point out the urgent need of minimizing painful procedures in NICUs.
极早产儿即使没有脑损伤也可能出现神经发育障碍。其发病机制复杂且具有多因素性。有证据表明，早期逆境通过表观遗传调控和脑结构变化，对神经发育结局产生影响。在此背景下，我们关注早产儿在新生儿重症监护病房（NICU）所经历的累积疼痛暴露。我们系统地搜索了：i）将疼痛与脑发育联系起来并探索表观遗传学潜在致病作用的证据；ii）支持临床观察性研究的临床前研究。九项在新生儿期或学龄期进行的临床神经影像学研究，大多来自同一研究小组，揭示了与出生后疼痛暴露相关的白质和灰质结构体积减小。三项模拟NICU环境的对照动物研究发现细胞死亡或凋亡增加；然而，符合条件的组规模有限。仅在两项临床试验中发现了表观遗传调控（SLC6A4启动子甲基化）。我们呼吁开展更多研究，并且尽管存在知识空白，但我们也指出在NICU中尽量减少痛苦操作的迫切需求。
