Lorenger Laura E, Boly Timothy J, Hyland Rachael M, Bermick Jennifer R
Stead Family Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA; Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.
Stead Family Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA; Iowa Inflammation Program, University of Iowa, Iowa City, Iowa, USA.
Cytokine. 2025 Jun;190:156916. doi: 10.1016/j.cyto.2025.156916. Epub 2025 Mar 25.
Intrauterine growth restriction (IUGR) places premature infants at an increased risk of multiple neonatal morbidities. Previous studies have found increased concentrations of pro-inflammatory biomarkers in IUGR infants at the time of birth and through the first postnatal month. This study aims to assess the longitudinal inflammatory profile of IUGR infants from birth to discharge from the neonatal intensive care unit.
A case-control study was performed with 24 IUGR infants and 24 appropriate for gestational age (AGA) infants born prematurely at or before 32 6/7 weeks' gestational age included. Residual clinical serum samples were collected and serum concentrations of IL-1β, sIL2Rα, IL-6, IL-8, IL-10, IP-10, MCP-1, MIP-1α, and TNF-α were measured by multi-plex protein assay. Residual clinical whole blood samples were collected, peripheral mononuclear blood cells were isolated, and flow cytometry was performed to assess differences in populations of peripheral immune cells.
There were significant differences in the birth weight and birth weight percentile between the IUGR and AGA groups, but no further demographic differences. The was significant elevation of IL-8, IL-10, and MCP-1 in the IUGR population at various timepoints during admission. There were no differences in overall cell populations between the two groups, however there were significantly increased activated classical monocytes and cytotoxic T cells in the IUGR group one month post-delivery.
Intrauterine growth restriction contributes to a fetal and continued neonatal pro-inflammatory state, as evidenced by elevation in IL-8 and MCP-1. Though there are increased populations of activated classical monocytes and cytotoxic T cells in these infants, this pro-inflammatory state may also contribute to tissue-specific inflammation which contributes to worsened neonatal outcomes for premature IUGR infants.
宫内生长受限（IUGR）会使早产儿出现多种新生儿疾病的风险增加。先前的研究发现，IUGR婴儿在出生时及出生后的第一个月内促炎生物标志物浓度升高。本研究旨在评估IUGR婴儿从出生到新生儿重症监护病房出院期间的纵向炎症特征。
进行了一项病例对照研究，纳入24例IUGR婴儿和24例孕龄32 6/7周及以前早产的适于胎龄（AGA）婴儿。收集剩余的临床血清样本，通过多重蛋白质测定法测量血清中白细胞介素-1β（IL-1β）、可溶性白细胞介素-2受体α（sIL2Rα）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、白细胞介素-10（IL-10）、干扰素诱导蛋白10（IP-10）、单核细胞趋化蛋白-1（MCP-1）、巨噬细胞炎性蛋白-1α（MIP-1α）和肿瘤坏死因子-α（TNF-α）的浓度。收集剩余的临床全血样本，分离外周血单个核细胞，并进行流式细胞术以评估外周免疫细胞群体的差异。
IUGR组和AGA组在出生体重和出生体重百分位数上存在显著差异，但在其他人口统计学特征上无差异。IUGR组在入院期间的不同时间点，IL-8、IL-10和MCP-1显著升高。两组的总体细胞群体无差异，但在分娩后1个月，IUGR组活化的经典单核细胞和细胞毒性T细胞显著增加。
宫内生长受限会导致胎儿期及新生儿期持续的促炎状态，IL-8和MCP-1升高证明了这一点。尽管这些婴儿中活化的经典单核细胞和细胞毒性T细胞群体增加，但这种促炎状态也可能导致组织特异性炎症，从而使早产IUGR婴儿的新生儿结局恶化。
