极/超低出生体重早产儿早期凝血功能异常的危险因素及预测模型

Risk factors and prediction model for early coagulation abnormalities in extremely/very low birth weight preterm infants

摘要

目的 探讨极/超低出生体重早产儿早期凝血功能异常的危险因素,并构建其早期凝血功能异常的风险预测模型。方法 采用回顾性研究方法,选取2022年3月至2025年3月本院新生儿科收治的573例极/超低出生体重早产儿为研究对象。收集其临床基线资料、母婴疾病史、凝血功能指标及临床特征,并进行凝血功能评估,根据其是否发生凝血功能障碍建立早期凝血功能异常组(n=352)和凝血功能正常组(n=221)。采用单因素分析两组临床资料数据差异,采用多因素Logistic回归分析极/超低出生体重早产儿生后早期凝血功能异常的危险因素,采用LASSO回归法筛选预测变量,构建并验证极/超低出生体重早产儿生后早期凝血功能异常的风险预测模型。结果 纳入的所有研究对象中并发早期凝血功能异常的患儿共352例,占比61.43%。早期凝血功能异常组胎龄(Z=6.180,P<0.001)、出生体质量(t=12.263,P<0.001)显著低于凝血功能正常组,早期凝血功能异常组宫内窘迫(χ²=6.380,P=0.012)、羊水污染(χ²=6.508,P=0.011)及母体妊娠期高血压疾病(χ²=4.830,P=0.028)发生率明显高于凝血功能正常组,住院时间较凝血功能正常组更长(t=6.610,P<0.001);两组研究对象出生后临床表现分布情况对比显示,早期凝血功能异常组动脉导管未闭(χ²=15.373,P<0.001)、肝功能异常(χ²=5.620,P=0.018)、血小板减少症(χ²=9.494,P=0.002)的发生率明显高于凝血功能正常组。Logistic回归分析显示,出生体重<1000g(OR=2.869,95%CI:1.052~5.320)、宫内窘迫(OR=3.640,95%CI:1.347~10.103)、动脉导管未闭(OR=2.542,95%CI:1.673~8.227)、血小板减少症(OR=4.986,95%CI:2.332~10.745)是极/超低出生体重早产儿生后早期凝血功能异常的独立危险因素(均P<0.05)。基于上述危险因素构建风险预测模型,经内部验证,该列线图模型的C-index为0.828(95%CI:0.747~0.872),校准曲线贴合良好(χ²=0.264,P=0.587);受试者工作特征(ROC)曲线分析显示,曲线下面积(AUC)为0.875(95%CI:0.717~0.963),灵敏度为85.50%,特异度为88.00%。结论 出生体重<1 000 g、宫内窘迫、动脉导管未闭、血小板减少症是极/超低出生体重早产儿生后早期凝血功能异常的危险因素。基于LASSO回归筛选变量的Logistic回归预测模型,具有良好的区分度与拟合优度,可有效预测极/超低出生体重早产儿生后早期凝血功能异常的发生风险,为临床早期干预与风险管控提供参考依据。

Abstract

Objective To explore the risk factors of early coagulation abnormalities in extremely/very low birth weight preterm infants,and to construct the risk prediction model of early coagulation abnormalities. Methods A retrospective study was conducted,enrolling 573 extremely/very low birth weight preterm infants admitted to the Department of Neonatology of our hospital from March 2022 to March 2025.Their clinical baseline data,maternal and infant disease histories,coagulation function indicators,and clinical characteristics were collected,and coagulation function was assessed.According to the presence or absence of coagulation abnormalities,the infants were divided into an early coagulation abnormalities group (n=352) and a normal coagulation group (n=221).Univariate analysis was used to compare differences in clinical data between the two groups.Multivariate logistic regression analysis was used to identify risk factors for early coagulation abnormalities after birth in extremely/very low birth weight preterm infants.LASSO regression was employed to screen predictive variables,and a risk prediction model for early coagulation abnormalities after birth in extremely/very low birth weight preterm infants was constructed and validated. Results A total of 352 children with early coagulation abnormalities were included,accounting for 61.43%.The gestational age (Z=6.180,P<0.001) and birth weight (t=12.263,P<0.001) in the early coagulation abnormalities group were significantly lower than those in the normal coagulation group.The incidences of fetal distress (χ ²=6.380,P=0.012),amniotic fluid contamination (χ ²=6.508,P=0.011),and maternal hypertensive disorders of pregnancy (χ ²=4.830,P=0.028) in the early coagulation abnormalities group were significantly higher than those in the normal coagulation group,and the length of hospital stay was longer than that in the normal coagulation group (t=6.610,P<0.001).Comparison of the distribution of clinical manifestations after birth between the two groups showed that the incidences of patent ductus arteriosus (χ ²=15.373,P<0.001),liver function abnormality (χ ²=5.620,P=0.018),and thrombocytopenia (χ ²=9.494,P=0.002) in the early coagulation abnormalities group were significantly higher than those in the normal coagulation group.Logistic regression analysis showed that birth weight<1 000 g (OR=2.869,95%CI:1.052-5.320),fetal distress (OR=3.640,95%CI:1.347-10.103),patent ductus arteriosus (OR=2.542,95%CI:1.673-8.227),and thrombocytopenia (OR=4.986,95%CI:2.332-10.745) were independent risk factors for early coagulation abnormalities after birth in extremely/very low birth weight preterm infants (P<0.05).A risk prediction model was constructed based on the above risk factors.After internal validation,the C-index of this nomogram model was 0.828 (95%CI:0.747-0.872),and the calibration curve showed good fit (χ ²=0.264,P=0.587).Receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) was 0.875 (95%CI:0.717-0.963),with a sensitivity of 85.50% and a specificity of 88.00%. Conclusion Birth weight<1000g,fetal distress,patent ductus arteriosus,and thrombocytopenia are risk factors for early coagulation abnormalities after birth in extremely/very low birth weight preterm infants.The logistic regression prediction model based on variables selected by LASSO regression demonstrates good discrimination and calibration,and can effectively predict the risk of early coagulation abnormalities after birth in extremely/very low birth weight preterm infants,thereby providing a reference for early clinical intervention and risk management.

关键词

极/超低出生体重早产儿 / 凝血功能异常 / 危险因素 / 风险预测

Key words

extremely/very low birth weight infant / coagulation abnormality / risk factor / risk prediction

参考文献

[1] 马徜徉, 张晨, 李文丽, 等. 河南省市县级危重新生儿救治中心建设及救治情况的多中心调查[J]. 中华新生儿科杂志(中英文), 2023,38(7): 419-423.

[2] 蒋思远, 杨传忠, 田秀英, 等. 中国新生儿协作网出生胎龄22~25周超早产儿出院预后及治疗现状[J]. 中华儿科杂志, 2024,62(1): 22-28.

[3] 肖娜娜, 闫学爽, 张彩宁, 等. 不同胎龄早产儿凝血功能比较及颅内出血影响因素分析[J]. 中南医学科学杂志, 2024,52(3): 446-448.

[4] 赵娟娟, 韩树萍, 余章斌, 等. 江苏省15家医院极低/超低出生体重儿抗生素使用现状调查[J]. 中国当代儿科杂志, 2022,24(9): 988-993.

[5] 杨小莉, 张索飞, 郎瑜, 等. 个案管理在极低出生体重儿中的研究进展[J]. 国际护理学杂志, 2020,39(15): 2876-2878.

[6] Yang Y N. Current concepts of very low birth weight infants with extra-uterine growth restriction[J]. Pediatr Neonatol, 2022,63(1): 3-4.

[7] 贾文婷, 汪灵芝, 刘敏敏, 等. 不同胎龄新生儿凝血功能及血小板计数的临床分析[J]. 中华全科医学, 2022,20(11): 1878-1880.

[8] Park J, Park S H, Kwon Y R, et al. Long-term outcomes of very low birth weight infants with intraventricular hemorrhage:a nationwide population study from 2011 to 2019[J]. World J Pediatr, 2024,20(7): 692-700.

[9] Battarbee A N, Sandoval G, Grobman W A, et al. Antenatal corticosteroids and preterm neonatal morbidity and mortality among women with and without diabetes in pregnancy[J]. Am J Perinatol, 2022,39(1): 67-74.

[10] Ignjatovic V, Kenet G, Monagle P, et al. Developmental hemostasis:recommendations for laboratories reporting pediatric samples[J]. J Thromb Haemost, 2012,10(2): 298-300.

[11] 全美盈, 冯淑菊, 张玉, 等. 降低新生儿重症监护室极低出生体重早产儿抗生素使用时间的质量改进研究[J]. 中国当代儿科杂志, 2024,26(7): 736-742.

[12] 陈嘉雯, 李敏许, 阮敏仪, 等. 胎龄小于32周超低出生体重儿早产儿视网膜病变的危险因素分析及预测指标研究[J]. 中国妇幼健康研究, 2025,36(7): 58-63.

[13] Zhou F, Huang M, Zhang G. Coagulation profile of neonates with hyperbilirubinaemia in full-term newborns[J]. J Int Med Res, 2023,51(11): 3000605231207531.

[14] 朱晶文, 张雪峰. 新生儿出生后24小时内凝血功能检测的临床意义分析[J]. 发育医学电子杂志, 2020,8(2): 157-162.

[15] 李丽娜. 不同胎龄早产儿凝血功能监测结果及与出血性疾病的相关性分析[J]. 哈尔滨医药, 2021,41(4): 26-27.

[16] 张娇, 吴棋, 胡仁宜, 等. 不同胎龄早产儿凝血功能指标及其与颅内出血发生风险的关系[J]. 河北医学, 2022,28(5): 813-818.

[17] Yildirim Ş, Çoban A, Ünüvar A, et al. The impact of intrauterine growth on coagulation and factor Ⅻ function in preterm infants[J]. Blood Coagul Fibrinolysis, 2025,36(5): 164-170.

[18] 王其茂, 杨小婷, 王波. 血清白蛋白水平与早产儿重度脑室内出血病死率相关性[J]. 湖南师范大学学报(医学版), 2021,18(4): 90-93.

[19] 严婷, 王琴, 黎渊明. 子痫前期孕妇血浆miR-16-5p水平与凝血功能和妊娠结局的关系研究[J]. 标记免疫分析与临床, 2022,29(1): 56-59, 66.

[20] Sallmon H, Timme N, Atasay B, et al. Current controversy on platelets and patent ductus arteriosus closure in preterm infants[J]. Front Pediatr, 2021,9: 612242.

[21] 高润光, 杨坤, 李北, 等. HPA基因多态性和交互作用与新生儿血小板减少症的关联研究[J]. 血栓与止血学, 2024,30(3): 106-112.

[22] 江倩男, 刘婷婷, 刘莹莹, 等. 动脉导管未闭严重程度在胎龄≤32周早产儿肺出血发生和死亡中的预测价值[J]. 实用医学杂志, 2025,41(10): 1575-1583.

[23] 蔡志勇, 刘进娣, 卞洪亮, 等. 孕母合并HCA应用产前糖皮质激素与早产儿预后相关性分析[J]. 中国妇幼健康研究, 2021,32(1): 13-20.

[24] 张彩宁, 吴萍, 闫学爽, 等. 不同胎龄早产儿凝血功能与颅内出血发生风险的关系[J]. 中国妇幼健康研究, 2024,35(10): 27-32.

基金资助

山西省医学重点科研项目(2020XM29)