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Article(id=1241067199004210041, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241067197318091153, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202410264, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1728921600000, receivedDateStr=2024-10-15, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773823078155, onlineDateStr=2026-03-18, pubDate=1741536000000, pubDateStr=2025-03-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773823078155, onlineIssueDateStr=2026-03-18, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773823078155, creator=13701087609, updateTime=1773823078155, updator=13701087609, issue=Issue{id=1241067197318091153, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', issue='5', pageStart='769', pageEnd='960', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773823077754, creator=13701087609, updateTime=1773823268053, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241067995544482681, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241067197318091153, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241067995544482682, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241067197318091153, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=955, endPage=960, ext={EN=ArticleExt(id=1241067202573562752, articleId=1241067199004210041, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Clinical value of maternal liver function combined with umbilical artery blood flow in diagnosing fetal growth restriction, columnId=1228016569138213037, journalTitle=Modern Preventive Medicine, columnName=Clinical Medicine and Prevention, runingTitle=null, highlight=null, articleAbstract=
Objective

To evaluate the clinical value of maternal liver function indicators combined with umbilical artery blood flow parameters in diagnosing fetal growth restriction (FGR).

Methods

This study employed a case-control design, including pregnant women who underwent prenatal examinations and delivered at Southern Hospital of Southern Medical University from December 2017 to July 2022. The case group consisted of 172 pregnant women clinically diagnosed with FGR, while the control group included 292 pregnant women with normal pregnancies who were examined at the same hospital during the same period. Maternal late-pregnancy liver function indicators and umbilical artery blood flow parameters were collected. Multivariate logistic regression analysis was conducted to assess the association of these indicators with the risk of FGR. The performance of each indicator and the combined model was evaluated using receiver operating characteristic curves, net reclassification improvement index, and integrated discrimination improvement index.

Results

In this study, pregnant women in the FGR group had significantly higher levels of ALT, ALB, and S/D ratio of umbilical artery blood flow compared to the control group. Multivariate logistic regression analysis indicated that ALT (OR=1.744, 95%CI: 1.332-2.283), ALB (OR=1.290, 95%CI: 1.002-1.661), and S/D ratio (OR=1.778,95%CI: 1.324-2.387) were significant risk factors for FGR, and the combined model of these three indicators exhibited high diagnostic value for fetal growth restriction.

Conclusion

Maternal liver function indicators (ALT, ALB) and umbilical artery blood flow parameters (S/D ratio) are associated with the risk of FGR, and the combined analysis of these factors can significantly enhance the diagnostic efficiency for FGR.

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目的

评估母体肝功能指标联合脐动脉血流参数诊断胎儿生长受限（fetal growth restriction, FGR）的临床价值。

方法

本研究采用病例对照设计，纳入2017年12月—2022年7月在南方医科大学南方医院接受产检并分娩的孕妇，其中临床诊断FGR的172例孕妇为病例组，同期292例在该院产检的正常妊娠孕妇为对照组。采集孕妇孕晚期肝功能指标及脐动脉血流参数，通过多因素logistic回归分析评估与FGR风险的关联，并使用受试者工作特征曲线、净重分类改善指数和综合判别改善指数评估各指标及联合模型的效能。

结果

本研究FGR组孕妇的丙氨酸氨基转移酶（ALT）、血清白蛋白（ALB）水平和脐动脉血流参数（S/D）值显著高于对照组。多因素logistic回归分析显示，ALT（OR=1.744，95%CI：1.332～2.283）、ALB（OR=1.290，95%CI：1.002～1.661）和S/D（OR=1.778，95%CI：1.324～2.387）是FGR的重要危险因素，且三者联合模型对胎儿生长受限诊断价值较高。

结论

母体肝功能指标（ALT、ALB）和脐动脉血流参数（S/D）与FGR的发生风险有关，且三者的联合分析可以显著提高FGR的诊断效率。

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胡贵方，E-mail:
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刘书洁（1999—），女，硕士在读，研究方向：产科流行病学

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刘书洁（1999—），女，硕士在读，研究方向：产科流行病学

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刘书洁（1999—），女，硕士在读，研究方向：产科流行病学

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Clinical value of color Doppler ultrasound combined with serological detection in the diagnosis of late-onset fetal growth restriction[J]. Journal of Clinical Ultrasound in Medicine, 2024, 26(7): 606-610.(In Chinese), articleTitle=Clinical value of color Doppler ultrasound combined with serological detection in the diagnosis of late-onset fetal growth restriction, refAbstract=null), Reference(id=1241067226791473970, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067199004210041, doi=null, pmid=null, pmcid=null, year=2024, volume=44, issue=8, pageStart=1126, pageEnd=1133, url=null, language=null, rfNumber=[26], rfOrder=35, authorNames=孙博, 周斌, 王冠嘉, journalName=南京医科大学学报:自然科学版, refType=null, unstructuredReference=孙博，周斌，王冠嘉，等.血栓弹力图联合超声定量参数对胎儿生长受限的诊断效能研究[J].南京医科大学学报:自然科学版，2024，44（8）：1126-1133., articleTitle=血栓弹力图联合超声定量参数对胎儿生长受限的诊断效能研究, refAbstract=null), Reference(id=1241067226887942966, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067199004210041, doi=null, pmid=null, pmcid=null, year=2024, volume=44, issue=8, pageStart=1126, pageEnd=1133, url=null, language=null, rfNumber=[26], rfOrder=36, authorNames=Sun B, Zhou B, Wang GJ, journalName=Journal of Nanjing Medicial University, refType=null, unstructuredReference=Sun B, Zhou B, Wang GJ, et al. Study on diagnostic efficacy of thromboelastography combined with ultrasonic quantitative parameters on fetal growth restriction[J]. Journal of Nanjing Medicial University, 2024, 44(8): 1126-1133.(In Chinese), articleTitle=Study on diagnostic efficacy of thromboelastography combined with ultrasonic quantitative parameters on fetal growth restriction, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1241067208521085072, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067199004210041, xref=1., ext=[AuthorCompanyExt(id=1241067208529473681, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067199004210041, companyId=1241067208521085072, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, China), AuthorCompanyExt(id=1241067208537862291, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067199004210041, companyId=1241067208521085072, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.南方医科大学公共卫生学院流行病学系，广东 广州 510515)]), AuthorCompany(id=1241067208718217374, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067199004210041, xref=2., ext=[AuthorCompanyExt(id=1241067208726605985, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067199004210041, companyId=1241067208718217374, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.南方医科大学南方医院临床研究中心)]), AuthorCompany(id=1241067208890183851, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067199004210041, xref=3., ext=[AuthorCompanyExt(id=1241067208906961069, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067199004210041, companyId=1241067208890183851, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=3.南方医科大学南方医院妇产科)])], figs=[ArticleFig(id=1241067217291375128, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067199004210041, language=EN, label=Figure 1, caption=Results of 1 000 resamplings using the bootstrap method, figureFileSmall=xkr63qNWHrPbLn6FMp00Ag==, figureFileBig=cYYRg9a1H+roQfZVq2srog==, tableContent=null), ArticleFig(id=1241067217421398561, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067199004210041, language=CN, label=图1, caption=Bootstrap法重抽样1 000次结果, figureFileSmall=xkr63qNWHrPbLn6FMp00Ag==, figureFileBig=cYYRg9a1H+roQfZVq2srog==, tableContent=null), ArticleFig(id=1241067217656279604, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067199004210041, language=EN, label=Table 1, caption=

Basic characteristics of the study subjects ［M（P25，P75），（），n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
项目总人数 (n=464)对照组 (n=292)病例组 (n=172)统计量P值
年龄(岁)29.00(26.00, 32.00)29.48(27.00, 32.00)28.00(25.00, 31.00)-2.5620.010
产前BMI(kg/m2)25.546(23.69, 27.54)25.75(24.05, 27.84)24.72(23.23, 27.04)-3.3330.001
孕次2.00(1.00, 3.00)2.00(1.00, 3.00)1.00(1.00, 2.00)-2.6150.009
既往产次0.00(0.00, 1.00)0.00(1.00, 1.00)0.00(0.00, 1.00)-4.667<0.001
孕周39.143(38.04, 40.00)39.57(38.71, 40.25)38.14(37.29, 39.25)-9.622<0.001
白细胞计数(×109/L)9.95(8.48, 11.58)9.82(8.48, 11.51)10.21(8.53, 11.73)-0.6950.487
中性粒总数(×109/L)7.32(6.17, 8.96)7.28(6.13, 8.89)1.74(1.44, 2.20)-0.4380.662
淋巴细胞总数(×109/L)1.73(1.42, 2.08)1.72(1.41, 2.04)1.74(1.44, 2.20)-1.0670.286
红细胞计数(×1012/L)4.06(3.85, 4.32)4.03(3.83, 4.29)4.15(3.91, 4.35)-1.9030.057
血红蛋白(g/L)122.00(113.00, 129.00)120.00(111.00, 129.00)123.50(117.00, 131.75)-2.7120.007
血小板计数(×109/L)216.50(180.25, 250.00)215.50(179.00, 250.00)219.50(187.00, 251.50)-0.9370.349
血小板比积测定 (mL/L)2.30(2.00, 2.69)2.30(2.00, 2.60)2.30(2.00, 2.70)-0.5810.561
平均血小板容积 (fl)10.60(10.00, 11.40)10.60(10.00, 11.48)10.65(9.90, 11.40)-0.390.693
血小板分布宽度 (fl)12.40(11.10, 14.30)12.50(11.20, 14.48)12.20(11.00, 14.30)-1.0000.317
ALT (U/L)9.00(7.00, 12.00)8.00(7.00, 11.00)11.00(8.00, 15.00)-7.122<0.001
AST (U/L)16.00(14.00, 18.00)15.00(13.00, 17.00)16.00(14.00, 20.00)-4.435<0.001
ALB (g/L)37.25±2.3836.999 ±2.4737.682 ±2.173.0100.003
RI0.56(0.50, 0.62)0.54(0.49, 0.58)0.61(0.55, 0.65)-7.974<0.001
PI0.82(0.69, 0.94)0.77(0.67, 0.88)0.93(0.79, 1.09)-8.329<0.001
S/D2.26(1.99, 2.60)2.15(1.94, 2.39)2.53(2.23, 2.90)-8.257<0.001
有无不良孕产史7.7370.005
无269(58.0)155(53.1)114(66.3)
有195(42.0)137(46.9)58(33.7)
), ArticleFig(id=1241067217756942903, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067199004210041, language=CN, label=表1, caption=

研究对象的基本特征［M（P25，P75），（），n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
项目总人数 (n=464)对照组 (n=292)病例组 (n=172)统计量P值
年龄(岁)29.00(26.00, 32.00)29.48(27.00, 32.00)28.00(25.00, 31.00)-2.5620.010
产前BMI(kg/m2)25.546(23.69, 27.54)25.75(24.05, 27.84)24.72(23.23, 27.04)-3.3330.001
孕次2.00(1.00, 3.00)2.00(1.00, 3.00)1.00(1.00, 2.00)-2.6150.009
既往产次0.00(0.00, 1.00)0.00(1.00, 1.00)0.00(0.00, 1.00)-4.667<0.001
孕周39.143(38.04, 40.00)39.57(38.71, 40.25)38.14(37.29, 39.25)-9.622<0.001
白细胞计数(×109/L)9.95(8.48, 11.58)9.82(8.48, 11.51)10.21(8.53, 11.73)-0.6950.487
中性粒总数(×109/L)7.32(6.17, 8.96)7.28(6.13, 8.89)1.74(1.44, 2.20)-0.4380.662
淋巴细胞总数(×109/L)1.73(1.42, 2.08)1.72(1.41, 2.04)1.74(1.44, 2.20)-1.0670.286
红细胞计数(×1012/L)4.06(3.85, 4.32)4.03(3.83, 4.29)4.15(3.91, 4.35)-1.9030.057
血红蛋白(g/L)122.00(113.00, 129.00)120.00(111.00, 129.00)123.50(117.00, 131.75)-2.7120.007
血小板计数(×109/L)216.50(180.25, 250.00)215.50(179.00, 250.00)219.50(187.00, 251.50)-0.9370.349
血小板比积测定 (mL/L)2.30(2.00, 2.69)2.30(2.00, 2.60)2.30(2.00, 2.70)-0.5810.561
平均血小板容积 (fl)10.60(10.00, 11.40)10.60(10.00, 11.48)10.65(9.90, 11.40)-0.390.693
血小板分布宽度 (fl)12.40(11.10, 14.30)12.50(11.20, 14.48)12.20(11.00, 14.30)-1.0000.317
ALT (U/L)9.00(7.00, 12.00)8.00(7.00, 11.00)11.00(8.00, 15.00)-7.122<0.001
AST (U/L)16.00(14.00, 18.00)15.00(13.00, 17.00)16.00(14.00, 20.00)-4.435<0.001
ALB (g/L)37.25±2.3836.999 ±2.4737.682 ±2.173.0100.003
RI0.56(0.50, 0.62)0.54(0.49, 0.58)0.61(0.55, 0.65)-7.974<0.001
PI0.82(0.69, 0.94)0.77(0.67, 0.88)0.93(0.79, 1.09)-8.329<0.001
S/D2.26(1.99, 2.60)2.15(1.94, 2.39)2.53(2.23, 2.90)-8.257<0.001
有无不良孕产史7.7370.005
无269(58.0)155(53.1)114(66.3)
有195(42.0)137(46.9)58(33.7)
), ArticleFig(id=1241067217874383426, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067199004210041, language=EN, label=Table 2, caption=

Multivariate logistic regression analysis of liver function and umbilical artery blood flow in relation to FGR

, figureFileSmall=null, figureFileBig=null, tableContent=
项目OR值(95%CI)P值
ALTa1.744(1.332～2.283)<0.001
Q11.00 (ref)
Q21.068(0.045～2.537)0.881
Q31.772(0.774～4.057)0.176
Q43.964(1.666～9.433)0.002
P趋势<0.001
ALBb1.290(1.002～1.661)0.048
Q11.00 (ref)
Q21.192(0.607～2.340)0.611
Q30.971(0.485～1.942)0.934
Q41.616(0.809～3.227)0.174
P趋势0.258
S/Da1.778(1.324～2.387)<0.001
Q11.00 (ref)
Q21.510(0.713～3.198)0.282
Q31.928(0.947～3.928)0.071
Q49.517(4.594～19.715)<0.001
P趋势<0.001
), ArticleFig(id=1241067217966658122, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067199004210041, language=CN, label=表2, caption=

肝功能和脐动脉血流与FGR的多因素logistic回归分析

, figureFileSmall=null, figureFileBig=null, tableContent=
项目OR值(95%CI)P值
ALTa1.744(1.332～2.283)<0.001
Q11.00 (ref)
Q21.068(0.045～2.537)0.881
Q31.772(0.774～4.057)0.176
Q43.964(1.666～9.433)0.002
P趋势<0.001
ALBb1.290(1.002～1.661)0.048
Q11.00 (ref)
Q21.192(0.607～2.340)0.611
Q30.971(0.485～1.942)0.934
Q41.616(0.809～3.227)0.174
P趋势0.258
S/Da1.778(1.324～2.387)<0.001
Q11.00 (ref)
Q21.510(0.713～3.198)0.282
Q31.928(0.947～3.928)0.071
Q49.517(4.594～19.715)<0.001
P趋势<0.001
), ArticleFig(id=1241067218042155600, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067199004210041, language=EN, label=Table 3, caption=

Parameters for the combined prediction of FGR by ALT, ALB and S/D

, figureFileSmall=null, figureFileBig=null, tableContent=
变量AUC值(95%CI)P值Continuous NRI值
(95%CI)		P值IDI值(95%CI)P值灵敏度特异度
基础模型*0.662(0.610～0.715)<0.001Ref.Ref.0.4940.767
基础模型联合ALT0.727(0.679～0.774)<0.0010.497(0.319～0.676)<0.0010.094(0.063～0.124)<0.0010.5120.829
基础模型联合ALB0.673(0.621～0.724)<0.0010.110(-0.078～0.298)0.2510.013(0.003～0.023)0.0120.6280.668
基础模型联合S/D0.767(0.720～0.813)<0.0010.707(0.530～0.884)<0.0010.116(0.085～0.145)<0.0010.6050.815
基础模型联合ALT及ALB0.736(0.689～0.783)<0.0010.528(0.348～0.708)<0.0010.102(0.071～0.133)<0.0010.6980.692
基础模型联合ALT及S/D0.811(0.770～0.853)<0.0010.832(0.659～1.004)<0.0010.191(0.154～0.228)<0.0010.7210.777
基础模型联合ALB及S/D0.769(0.723～0.816)<0.0010.721(0.545～0.897)<0.0010.120(0.091～0.150)<0.0010.6100.822
基础模型联合ALT、ALB及S/D0.814(0.772～0.855)<0.0010.876(0.705～1.046)<0.0010.193(0.156～0.231)<0.0010.7670.743
), ArticleFig(id=1241067221426958937, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241067199004210041, language=CN, label=表3, caption=

ALT、ALB和S/D联合对FGR的诊断价值

, figureFileSmall=null, figureFileBig=null, tableContent=
变量AUC值(95%CI)P值Continuous NRI值
(95%CI)		P值IDI值(95%CI)P值灵敏度特异度
基础模型*0.662(0.610～0.715)<0.001Ref.Ref.0.4940.767
基础模型联合ALT0.727(0.679～0.774)<0.0010.497(0.319～0.676)<0.0010.094(0.063～0.124)<0.0010.5120.829
基础模型联合ALB0.673(0.621～0.724)<0.0010.110(-0.078～0.298)0.2510.013(0.003～0.023)0.0120.6280.668
基础模型联合S/D0.767(0.720～0.813)<0.0010.707(0.530～0.884)<0.0010.116(0.085～0.145)<0.0010.6050.815
基础模型联合ALT及ALB0.736(0.689～0.783)<0.0010.528(0.348～0.708)<0.0010.102(0.071～0.133)<0.0010.6980.692
基础模型联合ALT及S/D0.811(0.770～0.853)<0.0010.832(0.659～1.004)<0.0010.191(0.154～0.228)<0.0010.7210.777
基础模型联合ALB及S/D0.769(0.723～0.816)<0.0010.721(0.545～0.897)<0.0010.120(0.091～0.150)<0.0010.6100.822
基础模型联合ALT、ALB及S/D0.814(0.772～0.855)<0.0010.876(0.705～1.046)<0.0010.193(0.156～0.231)<0.0010.7670.743
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母体肝功能联合脐动脉血流诊断胎儿生长受限的临床价值
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刘书洁 1 , 张敏怡 1 , 徐映华 1 , 霍佳欣 2 , 尹倩 3 , 胡贵方 1
现代预防医学 | 临床与预防 2025,52(5): 955-960
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现代预防医学 | 临床与预防 2025, 52(5): 955-960
母体肝功能联合脐动脉血流诊断胎儿生长受限的临床价值
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刘书洁1, 张敏怡1, 徐映华1, 霍佳欣2, 尹倩3, 胡贵方1
作者信息
  • 1.南方医科大学公共卫生学院流行病学系，广东 广州 510515
  • 2.南方医科大学南方医院临床研究中心
  • 3.南方医科大学南方医院妇产科

    • 刘书洁（1999—），女，硕士在读，研究方向：产科流行病学

通讯作者:

胡贵方，E-mail:
Clinical value of maternal liver function combined with umbilical artery blood flow in diagnosing fetal growth restriction
Shu-jie LIU1, Min-yi ZHANG1, Ying-hua XU1, Jia-xin HUO2, Qian YIN3, Gui-fang HU1
Affiliations
  • Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, Guangdong 510515, China
出版时间: 2025-03-10 doi: 10.20043/j.cnki.MPM.202410264
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摘要
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目的

评估母体肝功能指标联合脐动脉血流参数诊断胎儿生长受限（fetal growth restriction, FGR）的临床价值。

方法

本研究采用病例对照设计，纳入2017年12月—2022年7月在南方医科大学南方医院接受产检并分娩的孕妇，其中临床诊断FGR的172例孕妇为病例组，同期292例在该院产检的正常妊娠孕妇为对照组。采集孕妇孕晚期肝功能指标及脐动脉血流参数，通过多因素logistic回归分析评估与FGR风险的关联，并使用受试者工作特征曲线、净重分类改善指数和综合判别改善指数评估各指标及联合模型的效能。

结果

本研究FGR组孕妇的丙氨酸氨基转移酶（ALT）、血清白蛋白（ALB）水平和脐动脉血流参数（S/D）值显著高于对照组。多因素logistic回归分析显示，ALT（OR=1.744，95%CI：1.332～2.283）、ALB（OR=1.290，95%CI：1.002～1.661）和S/D（OR=1.778，95%CI：1.324～2.387）是FGR的重要危险因素，且三者联合模型对胎儿生长受限诊断价值较高。

结论

母体肝功能指标（ALT、ALB）和脐动脉血流参数（S/D）与FGR的发生风险有关，且三者的联合分析可以显著提高FGR的诊断效率。

胎儿生长受限  /  妊娠  /  丙氨酸转氨酶  /  白蛋白  /  脐动脉血流参数
Objective

To evaluate the clinical value of maternal liver function indicators combined with umbilical artery blood flow parameters in diagnosing fetal growth restriction (FGR).

Methods

This study employed a case-control design, including pregnant women who underwent prenatal examinations and delivered at Southern Hospital of Southern Medical University from December 2017 to July 2022. The case group consisted of 172 pregnant women clinically diagnosed with FGR, while the control group included 292 pregnant women with normal pregnancies who were examined at the same hospital during the same period. Maternal late-pregnancy liver function indicators and umbilical artery blood flow parameters were collected. Multivariate logistic regression analysis was conducted to assess the association of these indicators with the risk of FGR. The performance of each indicator and the combined model was evaluated using receiver operating characteristic curves, net reclassification improvement index, and integrated discrimination improvement index.

Results

In this study, pregnant women in the FGR group had significantly higher levels of ALT, ALB, and S/D ratio of umbilical artery blood flow compared to the control group. Multivariate logistic regression analysis indicated that ALT (OR=1.744, 95%CI: 1.332-2.283), ALB (OR=1.290, 95%CI: 1.002-1.661), and S/D ratio (OR=1.778,95%CI: 1.324-2.387) were significant risk factors for FGR, and the combined model of these three indicators exhibited high diagnostic value for fetal growth restriction.

Conclusion

Maternal liver function indicators (ALT, ALB) and umbilical artery blood flow parameters (S/D ratio) are associated with the risk of FGR, and the combined analysis of these factors can significantly enhance the diagnostic efficiency for FGR.

Fetal growth restriction  /  Pregnancy  /  Alanine aminotransferase  /  Albumin  /  Umbilical artery blood flow parameters
刘书洁, 张敏怡, 徐映华, 霍佳欣, 尹倩, 胡贵方. 母体肝功能联合脐动脉血流诊断胎儿生长受限的临床价值. 现代预防医学, 2025 , 52 (5) : 955 -960 . DOI: 10.20043/j.cnki.MPM.202410264
Shu-jie LIU, Min-yi ZHANG, Ying-hua XU, Jia-xin HUO, Qian YIN, Gui-fang HU. Clinical value of maternal liver function combined with umbilical artery blood flow in diagnosing fetal growth restriction[J]. Modern Preventive Medicine, 2025 , 52 (5) : 955 -960 . DOI: 10.20043/j.cnki.MPM.202410264
正文
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胎儿生长受限（fetal growth restriction, FGR），也称宫内生长受限，是指由于母体、胎儿或胎盘的病理因素导致胎儿生长未达到其遗传潜能，通常表现为胎儿超声估测体重或腹围低于相应胎龄的第10百分位。这种状况不仅影响胎儿健康，还显著增加了围产期死亡率、新生儿并发症及新生儿死亡率的风险[1]。FGR已成为发展中国家不良妊娠结局的主要原因之一，并且是围生儿死亡的第二大原因[2]。全球FGR的发病率为5%～10%，在中国约为6.39%[3-4]。此外，FGR还可能导致儿童期认知迟缓，并与成年后肥胖、2型糖尿病和心血管疾病的发生率增加相关[5]。因此，早期发现FGR成为降低围产期和新生儿并发症的重要手段之一。
目前，临床上FGR的诊断多通过宫高腹围测量及超声评估胎儿发育，该方法基于孕妇的身体变化和胎儿生长的一般规律，通过统计学方法构建预测模型估计胎儿体重从而判断其发育情况；但由于胎儿的发育情况和孕妇的身体状况存在个体差异，这些评估方法所得结果可能存在一定的误差[6]。近年来，研究发现彩超检测脐动脉的血流动力学指标可用于评估子宫-胎儿-胎盘循环的血流灌注阻力[7]，这些指标一定程度上反映胎儿及胎盘的灌注情况；而胎儿及胎盘灌注不足引发的氧气和营养物质缺乏是FGR常见诱因之一。因此，已有研究探讨脐动脉血流动力学指标与FGR之间的关联性；但单独使用脐动脉血流诊断敏感性仍然不高，晚期生长受限中可能出现脐血流正常但胎儿已经存在宫内缺氧的现象[8]，故目前诊断模型多数选择将脐动脉血流与其他指标联合使用。目前模型多采用子宫动脉血流[9]、三维能量多普勒超声[10]、大脑中动脉血流和羊水量[11]等联合脐血流共同诊断，但存在指标成本高、不易获得等缺陷；相比之下，母体肝功能指标具有经济、无创、易于获得等优点。同时，有学者提出母体肝功能异常与FGR的发生存在一定关联，可能与母体代谢状态异常或胎盘血流灌注异常有关[12-13]，因此肝功能亦可以作为反映胎儿宫内营养供应和氧供状态的指标之一。但是，在现有文献中，有关肝功能联合脐动脉对FGR诊断的研究尚未见报道。本研究旨在测定正常孕妇与FGR孕妇的肝功能指标以及胎儿脐动脉多普勒血流参数，探讨指标联合应用在FGR诊断中的价值，以期能够综合考虑个体的具体情况，提高FGR诊断水平，更加准确的识别胎盘功能异常的胎儿，提供更为精准和针对性的医疗建议。
1　资料与方法
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1.1　研究对象
选取2017年12月—2022年7月在南方医科大学南方医院接受产检并分娩的临床诊断FGR的孕妇为病例组，并选取同期接受产检，胎儿发育正常并分娩的孕妇作为对照组。本研究经南方医科大学附属南方医院伦理委员会批准（批件号:NFEC-2021-159），所有研究对象或其家属已签署知情同意书。
1.2　纳入及排除标准
1.2.1　病例组纳入及排除标准
纳入标准：（1）孕妇年龄≥18周岁，自然受孕，单胎妊娠,；（2）孕妇无精神病史，且无吸烟、饮酒嗜好及放射性物质或毒物接触史；（3）孕周准确，定期进行规范产检，孕妇及胎儿的临床数据完整；（4）符合《胎儿生长受限专家共识（2019版）》[14]相关诊断标准。排除标准：（1）孕妇患有临床诊断的肝病、自身免疫性疾病、肺结核、心脏病、子痫前期或妊娠期糖尿病；（2）孕早期存在不良用药或接触史；（3）胎儿已知宫内感染、结构异常或遗传异常；（4）医源性早产。
1.2.2　对照组纳入及排除标准
纳入标准：（1）孕妇年龄≥18周岁，自然受孕，单胎妊娠；（2）孕妇无精神病史，且无吸烟、饮酒嗜好及放射性物质或毒物接触史；（3）孕周准确，定期进行规范产检，孕妇及胎儿的临床数据完整；（4）与病例组同期接受产检，胎儿发育正常并分娩。排除标准：排除其他可能导致胎儿发育异常的妊娠期并发症，其余与病例组排除标准相同。
1.3　基本特征
根据医院信息系统收集孕妇的基本信息，包括（1）基本信息：年龄、末次月经、孕次、既往产次、产前身体质量指数（body mass index, BMI）、孕产史、孕周等；（2）血常规指标：孕晚期白细胞计数、中性粒细胞总数、淋巴细胞总数等；（3）肝功能指标：丙氨酸氨基转移酶（alanine aminotransferase, ALT）、天门冬氨酸氨基转移酶（aspartate aminotransferase,AST）、血清白蛋白（serum albumin, ALB）等；（4）超声指标：孕晚期脐动脉搏动指数（plusatility index, PI）、阻力指数（resistance index, RI）、血流收缩末期/舒张末期峰值（end-systolic/end-diastolic peak value, S/D）等。
1.4　统计学方法
采用IBM SPSS Statistics 26.0软件和R语言4.2.3进行统计分析；其中使用R语言计算净重新分类指数（net reclassification improvement,NRI）和综合判别改善指数（integrated discrimination improvement index, IDI）并进行bootstrap内部验证，其余统计学分析使用SPSS。服从正态分布的连续变量采用（均数±标准差）表示，否则采用中位数（四分位间距）表示；分类变量以频率和百分比表示。差异性检验采用独立样本t检验、非参数检验、χ2检验或Fisher确切概率法。校正不良孕产史、年龄、产前BMI、孕次、孕周、既往产次和血红蛋白等混杂因素，采用多因素logistic回归模型评估肝功能和脐动脉血流与FGR发生风险的关系。采用受试者操作特征曲线（receiver operating characteristic curve, ROC）评估诊断效能，曲线下面积（area under the curve, AUC）大于0.7表示诊断效果良好，并使用IDI和NRI值比较不同模型间性能的变化。使用bootstrap法对模型进行内部验证。检验水准α=0.05。
2　结果
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2.1　研究对象基本情况
本研究共纳入孕妇464名，其中病例组172名，对照组292名。不同年龄、BMI、孕次、既往产次、孕周、孕产史、血红蛋白水平、ALT、AST、ALB以及脐动脉多普勒PI、RI、S/D参数的孕妇发生FGR的差异具有统计学意义（P<0.05），见表1。
2.2　肝功能和脐动脉血流与FGR的多因素logistic回归分析
通过共线性诊断及临床意义对变量进行筛选，排除具有共线性的AST、PI及RI指标，保留变量ALT及S/D，以ALT、S/D和ALB为自变量，分别将其作为连续变量（每增加一个四分位间距或标准差）和逐层划分的分类变量（Q1～Q4）进行分析，以年龄、BMI、孕次、孕周、既往产次、孕产史以及血红蛋白为协变量，建立多因素logistic回归模型。结果显示，每增加一个四分位间距的ALT（OR=1.744，95%CI：1.332～2.283）和S/D（OR=1.778，95%CI：1.324～2.387）以及每增加一个标准差的ALB（OR=1.290，95%CI：1.002～1.661）与孕妇发生FGR的风险显著相关，见表2。将自变量视为分类变量时，暴露于较高水平ALT和S/D 的孕妇更有可能发生FGR，且随着四分位位数的增加,FGR风险呈显著上升趋势(P趋势<0.05)。
2.3　肝功能指标与脐动脉血流参数对FGR的诊断价值
纳入不良孕产史、产前BMI及既往产次构建基础模型，在此基础上分别及联合纳入ALT、ALB和S/D参数构建多个联合模型，绘制ROC曲线并获取曲线下面积，同时使用IDI和NRI评估模型效能。结果显示，三项指标（ALT、ALB和S/D）联合后，模型的IDI和NRI均达到最大值，且与AUC的结果一致，表明ALT、ALB及S/D联合对于FGR的诊断价值较高。见表3。
2.4　内部验证
采用bootstrap法对模型进行内部验证，将原始数据进行1 000次重复抽样后，计算平均AUC值（95%CI）为0.812（0.777～0.847），提示模型准确率良好，见图1。
3　讨论
收起
胎儿生长受限是一种复杂的病理状态，由包括母体健康状况、胎儿遗传特性及胎盘功能异常等多种因素引起，不仅影响围生儿死亡率和胎儿近期生长发育，还可能增加成年期慢性疾病的发生风险[15]。本研究发现，FGR组孕妇的ALT、ALB水平和脐动脉S/D值均显著高于对照组。通过多因素logistic回归分析，我们发现ALT、ALB和S/D是FGR的重要危险因素，且这三者的联合模型在诊断FGR方面具有一定的价值。
ALT作为肝功能损伤的敏感性指标，其在FGR孕妇中的异常升高可能与胎盘功能不全、母体代谢压力增加及氧化应激状态而导致的血管抵抗反应相关[16-17]。本研究表明，FGR组孕妇在ALT水平上显著高于非FGR组，且ALT升高与FGR发生风险呈现正向关联。这一结果与Dacaj[18]等人的研究一致，该研究指出，ALT升高与妊娠期肝功能异常及生长受限发生风险有关。此外，已有研究显示，ALT与妊娠期糖尿病、子痫前期及妊娠期高血压等不良妊娠结局相关[19-21]，而这些病理状态也常与FGR并存。因此，ALT的监测可作为评估母体肝脏健康和胎盘功能的重要指标，对FGR的早期识别具有潜在应用价值。
本研究发现FGR组孕妇的ALB水平显著高于非FGR组，且ALB水平与FGR的发生呈正向趋势。ALB水平的升高可能反映了母体血浆容量扩张不充分的状态，而这与FGR的发病机制密切相关。正常妊娠过程中，血浆容量的增加对胎儿的生长发育至关重要。然而，当母体血浆扩张不足时，胎盘的血液和营养供应可能受限，从而导致FGR的发生。现有研究表明，ALB水平的升高与FGR的风险增加显著相关[12，22]，与本研究结果一致，进一步支持了ALB作为FGR诊断指标的价值。
脐动脉血流参数S/D比值的异常也是本研究的主要发现之一。结果显示，FGR组的S/D比值显著高于非FGR组，且S/D比值与FGR的发生风险也呈现出正向的关联，这与既往研究结果相符[7]。脐动脉血流参数包含PI、RI和S/D，其中RI和PI被认为是反映子宫动脉血流阻力的敏感指标，它们能够有效地量化子宫螺旋动脉的血流动态和血管壁的阻抗；S/D是评估胎盘血管阻力的重要参数，能够反映胎盘绒毛间隙的血流特性和胎盘的血管灌注状况。S/D比值升高表明胎儿脐动脉的血流受阻，提示胎盘灌注不足，从而导致胎儿宫内缺氧和营养供给不足，引发FGR[23]。当前，大量临床证据已证实，多普勒超声测量是辅助临床诊断FGR的有效辅助手段。在本次研究中，单独使用S/D比值的模型ROC曲线下面积AUC为0.767，模型效能良好，和既往研究结果[24]相符。多普勒超声作为一种无创检测手段，能敏感地捕捉这些血流动力学改变，是临床辅助诊断FGR的重要工具。本研究进一步验证了脐动脉血流参数在FGR诊断中的重要性。
在此基础上，本研究进一步建立多个模型探讨母体肝功能指标联合脐动脉血流参数在FGR诊断中的价值。结果显示，包含ALT、ALB和S/D比值的联合模型诊断效能显著优于单一指标，三者联合ROC曲线下面积AUC达到最大值。本研究单独引入S/D比值模型AUC为0.767，罗丽萍等人[25]基于佛山市孕妇人群的结果显示单独使用S/D值AUC为0.783，孙博等人[26]基于郑州市孕妇人群的研究亦有相近结果；而联合后模型AUC可达0.814，高于各单一指标，且IDI和NRI均达到最大值，反映联合肝功能指标提高了S/D诊断FGR的能力。这表明，多指标联合分析能够更准确地评估FGR的发生风险。基于ALT和ALB的肝功能检测加上脐动脉血流参数的动态监测，能够为临床早期识别和管理FGR提供新的策略。因此，临床应对早期肝功能指标异常孕妇进行及时干预，尤其重视ALT和ALB水平较高者。
本研究具有一定的局限性。一是，研究对象主要来自单一中心，结果的外推性受到限制，并且由于样本含量较少，本研究缺乏外部验证，无法验证模型的泛化能力。二是，本研究无法评估监测指标的动态变化对FGR发生风险的影响。此外，尽管统计分析中控制了多种混杂因素，但仍然存在一些无法量化的潜在混杂因素，如饮食习惯和生活方式等可能影响研究结果。
综上所述，母体肝功能指标（ALT、ALB）和脐动脉血流参数（S/D）与FGR的发生风险有关，且三者的联合分析可以显著提高FGR的诊断效能。本研究为FGR的早期诊断和高危孕妇的临床管理提供了新的思路。未来需进一步扩大样本量进行多中心研究，探究肝功能及脐动脉血流指标的纵向动态变化和FGR发生风险的量化关系，为临床决策提供更有力的支持。
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doi: 10.20043/j.cnki.MPM.202410264
  • 接收时间：2024-10-15
  • 首发时间：2026-03-18
  • 出版时间：2025-03-10
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  • 收稿日期：2024-10-15
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    1.南方医科大学公共卫生学院流行病学系，广东 广州 510515
    2.南方医科大学南方医院临床研究中心
    3.南方医科大学南方医院妇产科

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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
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红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
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