Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Pediatrics, Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Am J Reprod Immunol. 2023 Apr;89(4):e13680. doi: 10.1111/aji.13680. Epub 2023 Jan 29.
Maternal markers of intestinal immune activation may be used to predict preterm birth (PTB) in pregnant women living with HIV.
This study used de-identified samples from the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) Protocol P1025 study. Singleton pregnancies with ≥3 ml plasma available and HIV viral load ≤400 copies/ml within 4 weeks of specimen collection were included. Frequency matching of PTB cases and term birth controls was performed on basis of maternal race, number of available plasma specimens, and timing of plasma sample collection in a 1:1 ratio. Plasma progesterone, 25-hydroxy vitamin D, soluble CD14, intestinal fatty acid binding protein (I-FABP), Lipopolysaccharide (LPS)-binding protein, and inflammatory cytokines (IL-1B, IFN-gamma, IL-6, TNF-alpha) were measured. Generalized mixed linear regression modeling was used to examine the association between PTB and biomarkers, adjusting for covariates and confounders. Data analyses were performed using SAS 9.4 (Cary, NC).
We included 104 PTB compared to 104 controls. Third trimester log2 IL-1B was lower among PTB versus term birth controls by univariate analysis (-1.50 ± 2.26 vs. -.24 ± 2.69, p = .01) though this association was no longer significant by regression modeling. In an uncontrolled, exploratory sub-analysis, subjects with prior PTB had increased odds of PTB with higher I-FABP [aOR 2.72, 95% CI 1.18-6.24] and lower IFN-gamma [aOR .23, 95% CI .12-.41] after adjustment for covariates and confounders.
Intestinal immune activation measured by soluble CD14 or intestinal fatty acid binding protein was not associated with preterm birth among pregnant women with low-level HIV viremia.
母体肠道免疫激活标志物可用于预测 HIV 感染孕妇的早产(PTB)。
本研究使用了国际母婴儿科艾滋病临床试验组(IMPAACT)协议 P1025 研究的匿名样本。纳入了满足以下条件的单胎妊娠:有≥3ml 血浆且在标本采集后 4 周内 HIV 病毒载量≤400 拷贝/ml。PTB 病例和足月分娩对照病例以母体种族、可用血浆标本数量和血浆标本采集时间为基础进行频数匹配,匹配比例为 1:1。检测血浆孕激素、25-羟维生素 D、可溶性 CD14、肠脂肪酸结合蛋白(I-FABP)、脂多糖(LPS)结合蛋白和炎症细胞因子(IL-1B、IFN-γ、IL-6、TNF-α)。采用广义混合线性回归模型,调整协变量和混杂因素后,考察 PTB 与生物标志物之间的关联。数据分析使用 SAS 9.4(北卡罗来纳州卡里)。
我们纳入了 104 例 PTB 病例和 104 例对照病例。单因素分析显示,PTB 组第三孕期 log2IL-1B 较足月分娩对照病例低(-1.50±2.26 比 -.24±2.69,p=0.01),但回归模型分析时这种关联不再显著。在未控制的探索性亚分析中,校正协变量和混杂因素后,既往有 PTB 史的患者 I-FABP 水平较高(aOR 2.72,95%CI 1.18-6.24)和 IFN-γ 水平较低(aOR.23,95%CI.12-.41),其发生 PTB 的可能性更高。
在 HIV 病毒载量低的孕妇中,可溶性 CD14 或肠脂肪酸结合蛋白测定的肠道免疫激活与早产无关。