Clinical predictive value of urine organic acid metabolites in intrahepatic cholestasis of pregnancy

doi:10.3969/j.issn.1004-583X.2025.06.007

Abstract

Abstract:

Objective To identify the role of organic acid metabolites in the prediction of intrahepatic cholestasis of pregnancy (ICP) by performing targeted metabolomic analysis of urine samples from pregnant women. Methods A total of 10 pregnant women with ICP from Wuxi Maternity and Child Health Care Hospital were selected as the observation group and 10 healthy pregnant women as the control group. Their general information was collected. Targeted metabolomics studies were carried out on the urine of both groups. Differences in metabolites between the two groups were examined using the Student's t-test, and preliminary screening was performed based on the fold change. The receiver operating characteristic curve was drawn to analyze the diagnostic performance of the initially screened organic acid metabolites and screen out metabolites with high diagnostic performance. Pearson correlation was performed to analyze the correlation of the urine levels of seven organic acid metabolites with liver function indexes and the newborn weight in ICP patients.Results A total of 18 metabolites, such as oleic acid, and linoleic acid in the urine of the observation group significantly differed from those in the control group (P<0.05). The area under the curve (AUC) of 12 metabolites in distinguishing ICP among pregnant women was larger than 0.8, showing good sensitivity and specificity. The AUC of 7 metabolites (nonanoic acid, sebacic acid, oleic acid, linoleic acid, palmitic acid, 3-hydroxypropionic acid, and L-phenylalanine) was larger than 0.9, showing more significant differences between the observation group and the control group and more desirable predictive abilities. The seven metabolites were correlated with some indexes of liver function (total bile acids, aspartate aminotransferase, alanine aminotransferase)(P<0.05). Nonanoic acid and 3-hydroxypropionic acid were correlated with the newborn weight (P<0.05). Conclusion The expression levels of nonanoic acid and sebacic acid in the urine are upregulated in pregnant women with ICP, while those of oleic acid, linoleic acid, palmitic acid, 3-hydroxypropionic acid, and L-phenylalanine are downregulated. These seven metabolites have important clinical predictive value for ICP patients.

Key words: cholestasis, intrahepatic, targeted metabolomics, urine organic acid metabolites, clinical predictive value

CLC Number:

R575

You Yilan, Chen Lingyan, Miao Keyan, Ni Luohang, Zhang Yan, Xiao Jianping. Clinical predictive value of urine organic acid metabolites in intrahepatic cholestasis of pregnancy[J]. Clinical Focus, 2025, 40(6): 519-526.

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URL: http://www.lchc.cn/EN/10.3969/j.issn.1004-583X.2025.06.007

http://www.lchc.cn/EN/Y2025/V40/I6/519

Figures/Tables 8

References 25

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组别	例数	年龄(岁)		体质指数(kg/m²)	TBA(μmol/L)		AST(IU/L)		ALT(IU/L)		ALP(IU/L)
对照组	10	33.3±5.6		26.9±3.3	3.6±2.2		18.8±5.6		11.7±7.1		167.7±84.2
观察组	10	31.4±4.2		26.6±3.0	61.8±40.7		57.6±38		91.8±67.9		227.4±47.4
t值		0.944		0.271	4.940		3.501		3.561		2.140
P值		0.356		0.789	0.000		0.002		0.002		0.047
组别	发病孕天(d)		分娩孕天(d)			孕次(次)		产次(次)		新生儿出生体重(g)
对照组	-		273.3±2.6			2.6±1.3		0.8±0.6		3430.0±455.4
观察组	215.6±55.9		256.8±8.2			3.1±1.6		0.9±0.8		2827.1±435.3
t值			6.668			0.849		0.573		3.068
P值			0.000			0.406		0.573		0.006

组别	例数	年龄(岁)		体质指数(kg/m²)	TBA(μmol/L)		AST(IU/L)		ALT(IU/L)		ALP(IU/L)
对照组	10	33.3±5.6		26.9±3.3	3.6±2.2		18.8±5.6		11.7±7.1		167.7±84.2
观察组	10	31.4±4.2		26.6±3.0	61.8±40.7		57.6±38		91.8±67.9		227.4±47.4
t值		0.944		0.271	4.940		3.501		3.561		2.140
P值		0.356		0.789	0.000		0.002		0.002		0.047
组别	发病孕天(d)		分娩孕天(d)			孕次(次)		产次(次)		新生儿出生体重(g)
对照组	-		273.3±2.6			2.6±1.3		0.8±0.6		3430.0±455.4
观察组	215.6±55.9		256.8±8.2			3.1±1.6		0.9±0.8		2827.1±435.3
t值			6.668			0.849		0.573		3.068
P值			0.000			0.406		0.573		0.006

组别	例数	油酸			亚油酸		棕榈酸	壬酸		癸二酸		草酸
对照组	10	488.35±155.97			195.68±114.64		1113.22±674.54	104.62±57.66		815.26±114.26		6542.63±3682.01
观察组	10	309.53±56.15			74.40±25.78		467.21±460.79	1260.79±405.67		159.98±67.91		10372.78±3894.39
变化倍数 (观察组/对照组)		0.634			0.380		0.420	1.546		0.380		1.585
P值		0.003			0.004		0.022	0.045		0.039		0.036
组别	L-苯丙氨酸		3-羟基丙酸			柠檬酸			乙醇酸		L-苹果酸		尿嘧啶
对照组	2467.92±985.14		47372.17±20851.61			141568.05±70636.63			61405.95±29008.71		2442.89±1682.24		3950.87±1648.88
观察组	1128.04±604.12		15732.55±10120.39			66582.48±32340.82			29776.15±22874.65		1034.51±967.84		1793.62±1123.919
变化倍数 (观察组/对照组)	0.457		0.332			0.470			0.485		0.423		0.454
P值	0.002		<0.001			0.007			0.014		0.034		0.003
组别	L-4-羟脯氨酸			顺式乌头酸			琥珀酸	DL-焦谷氨酸			3-(4-羟基苯基)乳酸			尿黑酸
对照组	2802.90±1870.56			98772.97±53695.87			1804.07±838.35	72246.58±38762.87			582.55±249.04			120.45±88.21
观察组	1360.91±747.21			49167.89±38805.84			913.76±747.21	37181.64±27278.68			298.92±206.05			46.54±35.95
变化倍数 (观察组/对照组)	0.486			0.498			0.506	0.515			0.513			0.386
P值	0.036			0.029			0.022	0.031			0.012			0.024

组别	例数	油酸			亚油酸		棕榈酸	壬酸		癸二酸		草酸
对照组	10	488.35±155.97			195.68±114.64		1113.22±674.54	104.62±57.66		815.26±114.26		6542.63±3682.01
观察组	10	309.53±56.15			74.40±25.78		467.21±460.79	1260.79±405.67		159.98±67.91		10372.78±3894.39
变化倍数 (观察组/对照组)		0.634			0.380		0.420	1.546		0.380		1.585
P值		0.003			0.004		0.022	0.045		0.039		0.036
组别	L-苯丙氨酸		3-羟基丙酸			柠檬酸			乙醇酸		L-苹果酸		尿嘧啶
对照组	2467.92±985.14		47372.17±20851.61			141568.05±70636.63			61405.95±29008.71		2442.89±1682.24		3950.87±1648.88
观察组	1128.04±604.12		15732.55±10120.39			66582.48±32340.82			29776.15±22874.65		1034.51±967.84		1793.62±1123.919
变化倍数 (观察组/对照组)	0.457		0.332			0.470			0.485		0.423		0.454
P值	0.002		<0.001			0.007			0.014		0.034		0.003
组别	L-4-羟脯氨酸			顺式乌头酸			琥珀酸	DL-焦谷氨酸			3-(4-羟基苯基)乳酸			尿黑酸
对照组	2802.90±1870.56			98772.97±53695.87			1804.07±838.35	72246.58±38762.87			582.55±249.04			120.45±88.21
观察组	1360.91±747.21			49167.89±38805.84			913.76±747.21	37181.64±27278.68			298.92±206.05			46.54±35.95
变化倍数 (观察组/对照组)	0.486			0.498			0.506	0.515			0.513			0.386
P值	0.036			0.029			0.022	0.031			0.012			0.024

影响因素	TBA		AST		ALT		ALP
影响因素	r值	P值	r值	P值	r值	P值	r值	P值
壬酸	0.827	0.000	0.728	0.000	0.713	0.000	0.371	0.107
癸二酸	0.369	0.110	0.532	0.016	0.357	0.122	0.289	0.217
油酸	-0.542	0.014	-0.571	0.009	-0.522	0.018	-0.216	0.361
亚油酸	-0.489	0.029	-0.443	0.050	-0.426	0.061	-0.117	0.622
棕榈酸	-0.527	0.017	-0.409	0.074	-0.443	0.050	-0.097	0.686
3-羟基丙酸	-0.605	0.005	-0.440	0.052	-0.427	0.061	-0.174	0.462
L-苯丙氨酸	-0.576	0.008	-0.472	0.036	-0.485	0.030	-0.074	0.755