维生素D与早期先兆流产孕妇免疫微环境的关系及对妊娠结局的预测价值

The relationship between vitamin D and immune microenvironment of pregnant women with early threatened abortion and its predictive value for pregnancy outcome

摘要

目的 探讨维生素D(VD)与早期先兆流产(TA)孕妇免疫微环境的相关性及对妊娠结局的预测价值。方法 选择2021年1月至2022年9月于在河北省廊坊市人民医院治疗的早期TA孕妇110例为研究对象,纳入训练集;按随机数字表法,将其分为研究组(口服黄体酮+VD,55例)与对照组(口服黄体酮,55例),根据早期TA孕妇的妊娠情况,将其分为妊娠失败组(38例)与继续妊娠组(72例)。另选择2020年1月至2021年1月在该院治疗的早期TA孕妇36例纳入验证集。收集孕妇的临床资料、免疫微环境及VD水平。采用Pearson进行相关性分析;采用多因素Logistic回归分析影响妊娠失败的危险因素,并构建列线图预测模型进行评价;采用受试者工作特征(ROC)曲线评估VD水平对妊娠结局的预测价值。结果 研究组孕妇的白细胞介素(IL)-4、IL-10、转化生长因子β(TGF-β)及VD水平均明显高于对照组(t值分别为2.186、6.809、2.648、5.780,P<0.05),研究组孕妇的IL-17、IL-23及干扰素γ(IFN-γ)水平均明显低于对照组(t值分别为3.521、3.777、4.330,P<0.05)。相关性分析显示,VD与IL-4、IL-10及TGF-β均呈正相关(r值分别为0.569、0.709、0.602,P<0.05),与IL-17、IL-23及IFN-γ均呈负相关(r值分别为-0.537、-0.584、-0.634,P<0.05)。妊娠失败组孕妇流产次数≥2次、生殖道支/衣原体感染及黄体功能不全的比例,以及IL-17、IL-23和IFN-γ水平均明显高于继续妊娠组(χ²值分别为5.609、8.399、16.082,t值分别为4.668、4.793、3.919),而妊娠失败组孕妇IL-4、IL-10、TGF-β及VD水平均明显低于继续妊娠组(t值分别为8.019、12.362、9.131、4.755),差异均有统计学意义(P<0.05)。多因素Logistic回归分析显示,流产次数≥2次(OR=1.720,95%CI:1.488~2.376)、生殖道支/衣原体感染(OR=1.301,95%CI:1.164~1.597)、IL-17≥35pg/mL(OR=2.088,95%CI:1.649~2.577)及VD<25ng/mL(OR=2.634,95%CI:1.548~3.870)均是早期TA孕妇妊娠失败的独立危险因素(P<0.05)。经ROC曲线分析显示,VD水平预测孕妇妊娠失败的曲线下面积(AUC)为0.815(95%CI:0.779~2.069),最佳截断值为25ng/mL,灵敏度为96.04%,特异度为60.31%。预测妊娠失败的列线图模型的评估结果显示,其具有较高的精准度,且有效性较好、安全可靠、实用性强。结论 VD与IL-4、IL-10及TGF-β均呈正相关,与IL-17、IL-23及IFN-γ均呈负相关。流产≥2次、生殖道支/衣原体感染、IL-17≥35pg/mL及VD<25ng/mL均是早期TA孕妇妊娠失败的独立危险因素。VD水平对孕妇妊娠失败具有一定的预测价值。

Abstract

Objective To investigate the correlation between vitamin D (VD) and the immune microenvironment of early threatened abortion (TA) in pregnant women, and to assess its predictive value on pregnancy outcomes. Methods A total of 110 early TA pregnant women treated at Langfang People's Hospital, Hebei Province, from January 2021 to September 2022 were selected as the research subjects and included in the training set. They were divided into a study group (oral progesterone + VD, 55 cases) and a control group (oral progesterone only, 55 cases) using a random number table method. Based on the pregnancy outcome of early TA pregnant women, they were categorized into pregnancy failure group (38 cases) and continued pregnancy group (72 cases). Additionally, 36 early TA pregnant women treated at the same hospital from January 2020 to January 2021 were selected as the validation set. Clinical data, immune microenvironment, and VD levels of pregnant women were collected. Pearson correlation analysis was used to assess correlations. Multivariable logistic regression analysis was employed to identify the risk factors affecting pregnancy failure, and a nomogram prediction model was constructed for evaluation. Receiver operating characteristic (ROC) curves were used to evaluate the predictive value of VD levels on pregnancy outcomes. Results In the research group, levels of interleukin (IL)-4, IL-10, transforming growth factor β (TGF-β), and VD in pregnant women were significantly higher compared to the control group (t = 2.186, 6.809, 2.648 and 5.780 respectively, P < 0.05). Conversely, levels of IL-17, IL-23, and interferon γ (IFN-γ) were significantly lower in the research group compared to the control (t = 3.521, 3.777 and 4.330 respectively, P < 0.05). Correlation analysis showed positive associations of VD with IL-4, IL-10, and TGF-β (r = 0.569, 0.709 and 0.602 respectively, P < 0.05), and negative associations with IL-17, IL-23, and IFN-γ (r = -0.537, -0.584 and -0.634 respectively, P < 0.05). In the group of pregnant women with pregnancy failure, a history of ≥2 abortions, genital tract mycoplasma/chlamydia infection, and luteal insufficiency, as well as the levels of IL-17, IL-23, and IFN-γ, were significantly higher compared to the group with continuing pregnancies (χ ² = 5.609, 8.399 and 16.082 respectively; t = 4.668, 4.793 and 3.919 respectively). Conversely, in the pregnancy failure group, the levels of IL-4, IL-10, TGF-β, and VD were significantly lower compared to the continuing pregnancy group (t = 8.019, 12.362, 9.131 and 4.755 respectively), with statistically significant differences (P < 0.05). Multivariable logistic regression analysis showed that a history of ≥2 abortions (OR = 1.720, 95% CI: 1.488-2.376), genital tract mycoplasma/chlamydia infection (OR = 1.301, 95% CI: 1.164-1.597), IL-17 levels ≥35 pg/mL (OR = 2.088, 95% CI: 1.649-2.577), and VD levels <25 ng/mL (OR = 2.634, 95% CI: 1.548-3.870) were independent risk factors for early pregnancy failure in women with TA (P < 0.05). ROC curve analysis indicated that VD level predicting pregnancy failure had an area under the curve (AUC) of 0.815 (95% CI: 0.779-2.069), with an optimal cutoff value of 25 ng/mL, sensitivity of 96.04%, and specificity of 60.31%. The predictive model evaluation of pregnancy failure demonstrated high accuracy, effectiveness, safety, and practicality. Conclusion VD is positively correlated with IL-4, IL-10, and TGF-β, and negatively correlated with IL-17, IL-23, and IFN-γ. History of ≥2 abortions, genital tract mycoplasma/chlamydia infection, IL-17 levels ≥35 pg/mL, and VD <25 ng/mL are independent risk factors for early pregnancy failure in women with TA. VD levels have a certain predictive value for pregnancy failure.

关键词

维生素D / 先兆流产 / 免疫微环境 / 妊娠结局

Key words

vitamin D / threatened abortion / immune microenvironment / pregnancy outcomes

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基金资助

廊坊市科技支撑计划项目(2022013036)