Correlation between pruritus and the prognosis of intrahepatic cholestasis of pregnancy and prediction of its risks

doi:10.3969/j.issn.1004-583X.2023.05.003

Abstract

Abstract:

Objective To compare the clinical characteristics of intrahepatic cholestasis of pregnancy (ICP) with or without pruritus and to evaluate the significance of pruritus in ICP. Methods A total of 359 ICP patients were divided into different groups according to the presence or absence of pruritus, the onset of gestational age and the total bile acid (TBA) levels. Pregnant women with normal birth examination during the same period were randomly selected as the control group. The correlation of pruritus and TBA levels with perinatal morbidity was evaluated. Results The incidence of ICP was about 1.1%, and most of them were asymptomatic (71.03%). Liver function, gestational diabetes mellitus (GDM), low birth weight, preterm birth and cesarean section rate were significantly higher in ICP patients with or without pruritus than those in the control group (P <0.05). The cord blood flow before delivery was within the normal range in all three recruited pregnant women. In ICP group, especially in symptomatic ICP group, the cord blood flow values were within the upper limit of the normal range (P <0.05). Pregnant women with mild and asymptomatic ICP had the lowest rates of cesarean section and preterm birth (P<0.05). Pruritus and TBA level were positively correlated with perinatal morbidity, especially when TBA≥40 μmol/L. Conclusion Pruritus should not be a prerequisite for the diagnosis of ICP. Regardless of the presence or absence of pruritus, ICP increases perinatal morbidity, but pruritus and TBA≥40 μmol/L are risk factors for perinatal morbidity. Cases of asymptomatic ICP are mostly mild, but intrauterine fetal death can occur without warning. Therefore, TBA and liver function should be regularly monitored during pregnancy to prevent missed diagnosis in asymptomatic ICP patients.

Key words: cholestasis, intrahepatic, pregnant women, pruritus, bile acids, perinatal period

CLC Number:

R575

Zhang Yuan, Zhou Juan, Li Wenxiang, Liu Jinxiang, Tang Xiaomei, Luo Huijuan. Correlation between pruritus and the prognosis of intrahepatic cholestasis of pregnancy and prediction of its risks[J]. Clinical Focus, 2023, 38(5): 405-411.

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Figures/Tables 5

References 35

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项目	对照组 (n=200)	有症状ICP组 (n=104)	无症状ICP组 (n=255)	P值
年龄(岁)	30.0(27.0, 33.0)	29.0(27.0, 33.7)	30.0(27.0, 33.0)	0.887
孕次(次)	2.0(1.0, 2.0)	2.0(1.0, 3.0)	2.0(1.0, 3.0)^*	0.035
分娩次数(次)	1.0(1.0, 2.0)	1.0(1.0, 2.0)	2.0(1.0, 2.0)^*	0.013
BMI(kg/m²)	26.2(24.1, 28.1)	25.1(23.3, 27.6)^*	25.7(23.5, 27.2)	0.025
胆汁酸异常时胎龄(周)	-	34.3(30.0, 37.0)	33.0(24.4, 37.3)	0.254
TBA(μmol/L)	3.8(2.7, 4.5)	23.8(15.0, 43.2)^*	21.4(14.5, 31.3)^*	<0.01
ALT(IU/L)	12.5(9.0, 14.0)	46.5(15.3, 159.3)^*	14.0(10.0, 16.0)^*#	<0.01
AST(IU/L)	18.0(15.0, 20.0)	50.5(21.3, 104.3)^*	18.0(15.0, 20.0)^#	<0.01
TBIL(μmol/L)	8.2(6.5, 9.0)	12.3(7.7, 15.5)^*	8.5(7.0, 8.6)^*#	<0.01
GC(μmol/L)	2.8(2.2, 3.7)	18.2(7.9, 35.8)^*	13.2(7.7, 22.6)^*	<0.01
GDM[例(%)]	23(11.5)	26(25.0)^*	58(22.8)^*	0.002
脐血流量
S/D	2.1(1.9, 2.3)	2.4(2.1, 2.7)^*	2.2(2.0, 2.5)^*#	<0.01
PI	0.7(0.7, 0.9)	0.8(0.7, 1.0)^*	0.8(0.7, 0.9)^#	0.002
RI	0.5(0.5, 0.6)	0.6(0.5, 0.6)^*	0.6(0.5, 0.6)	0.012
早产[例(%)]	6(3.0)	30(28.8)^*	47(18.4)^*#	<0.01
医源性早产	0	15(14.4)^*	16 (6.3)^*#	<0.01
自发性早产	6(3.0)	15(14.4)^*	31(12.2)^*	0.001
分娩时胎龄(周)	39.4(38.6, 40.2)	37.6(36.4, 38.5)^*	38.3(37.2, 39.1)^*#	<0.01
分娩方式[例(%)]
剖宫产	40(20.0)	71(68.3)^*	123 (48.2)^*#	<0.01
阴道助产	8(4.0)	2(1.9)	6(2.4)	0.912
正常分娩	152(76.0)	31(29.8)^*	126 (49.4)^*#	<0.01
新生儿体重(g)	3250(2950, 3450)	3000(2650, 3200)^*	3000(2700, 3300)^*	<0.01
新生儿性别(女)[例(%)]	96(48.0)	45(43.3)	124(48.6)	0.639
胎儿宫内窘迫[例(%)]	31(15.5)	18(17.3)	44(17.2)	0.853
羊水异常[例(%)]	14(7.0)	21(20.2)^*	26(10.2)^#	0.002
MSAF	11(5.5)	17(16.4)^*	24(9.4)	0.008
羊水过少	3(1.5)	4(3.8)	2(0.8)	0.110
新生儿窒息[例(%)]	3(1.5)	4(3.8)	12(4.7)	0.164

项目	对照组 (n=200)	有症状ICP组 (n=104)	无症状ICP组 (n=255)	P值
年龄(岁)	30.0(27.0, 33.0)	29.0(27.0, 33.7)	30.0(27.0, 33.0)	0.887
孕次(次)	2.0(1.0, 2.0)	2.0(1.0, 3.0)	2.0(1.0, 3.0)^*	0.035
分娩次数(次)	1.0(1.0, 2.0)	1.0(1.0, 2.0)	2.0(1.0, 2.0)^*	0.013
BMI(kg/m²)	26.2(24.1, 28.1)	25.1(23.3, 27.6)^*	25.7(23.5, 27.2)	0.025
胆汁酸异常时胎龄(周)	-	34.3(30.0, 37.0)	33.0(24.4, 37.3)	0.254
TBA(μmol/L)	3.8(2.7, 4.5)	23.8(15.0, 43.2)^*	21.4(14.5, 31.3)^*	<0.01
ALT(IU/L)	12.5(9.0, 14.0)	46.5(15.3, 159.3)^*	14.0(10.0, 16.0)^*#	<0.01
AST(IU/L)	18.0(15.0, 20.0)	50.5(21.3, 104.3)^*	18.0(15.0, 20.0)^#	<0.01
TBIL(μmol/L)	8.2(6.5, 9.0)	12.3(7.7, 15.5)^*	8.5(7.0, 8.6)^*#	<0.01
GC(μmol/L)	2.8(2.2, 3.7)	18.2(7.9, 35.8)^*	13.2(7.7, 22.6)^*	<0.01
GDM[例(%)]	23(11.5)	26(25.0)^*	58(22.8)^*	0.002
脐血流量
S/D	2.1(1.9, 2.3)	2.4(2.1, 2.7)^*	2.2(2.0, 2.5)^*#	<0.01
PI	0.7(0.7, 0.9)	0.8(0.7, 1.0)^*	0.8(0.7, 0.9)^#	0.002
RI	0.5(0.5, 0.6)	0.6(0.5, 0.6)^*	0.6(0.5, 0.6)	0.012
早产[例(%)]	6(3.0)	30(28.8)^*	47(18.4)^*#	<0.01
医源性早产	0	15(14.4)^*	16 (6.3)^*#	<0.01
自发性早产	6(3.0)	15(14.4)^*	31(12.2)^*	0.001
分娩时胎龄(周)	39.4(38.6, 40.2)	37.6(36.4, 38.5)^*	38.3(37.2, 39.1)^*#	<0.01
分娩方式[例(%)]
剖宫产	40(20.0)	71(68.3)^*	123 (48.2)^*#	<0.01
阴道助产	8(4.0)	2(1.9)	6(2.4)	0.912
正常分娩	152(76.0)	31(29.8)^*	126 (49.4)^*#	<0.01
新生儿体重(g)	3250(2950, 3450)	3000(2650, 3200)^*	3000(2700, 3300)^*	<0.01
新生儿性别(女)[例(%)]	96(48.0)	45(43.3)	124(48.6)	0.639
胎儿宫内窘迫[例(%)]	31(15.5)	18(17.3)	44(17.2)	0.853
羊水异常[例(%)]	14(7.0)	21(20.2)^*	26(10.2)^#	0.002
MSAF	11(5.5)	17(16.4)^*	24(9.4)	0.008
羊水过少	3(1.5)	4(3.8)	2(0.8)	0.110
新生儿窒息[例(%)]	3(1.5)	4(3.8)	12(4.7)	0.164

项目	有症状ICP组		无症状ICP组		P值
项目	轻度(n=67)	重度(n =37)	轻度(n=196)	重度(n=59)	P值
早发型	12(17.9)	7(18.9)	45(23.0)	29(49.2)^*#△	<0.01
迟发型	55(82.1)	30(81.1)	151(76.3)	30(50.9)
分娩方式
剖宫产	46(68.7)	27(75.7)	89(45.4)^*#	39(66.1)^△	<0.01
阴道分娩	21(31.3)	10(27.0)	107(54.6)	20(33.9)
早产	15(22.4)	16(43.2)^*	25(12.8)^#	21(35.6)^△	<0.01
医源性早产	6(9.0)	10(27.0)^*	6(3.1)^#	10(17.0)^△	<0.01
自发性早产	9(13.4)	6(16.2)	19(9.7)	11(18.6)	0.266
胎儿宫内死亡	0	1(2.7)	1(0.5)	0	0.285
胎儿窘迫	13(5.2)	4(10.8)	35(17.9)	6(10.2)	0.350
羊水异常	12(17.9)	10(27.0)	20(10.2)^#	6(10.2)^#	0.025
MSAF	9(13.4)	8(21.6)	19(9.7)	5(8.5)	0.161
羊水过少	3(4.5)	2(5.4)	1(0.5)	1(1.7)	0.082
新生儿窒息	4(6.0)	0	8(4.1)	4(6.8)	0.400
胎儿宫内死亡	0	1(2.7)	1(0.5)	0	0.285

项目	有症状ICP组		无症状ICP组		P值
项目	轻度(n=67)	重度(n =37)	轻度(n=196)	重度(n=59)	P值
早发型	12(17.9)	7(18.9)	45(23.0)	29(49.2)^*#△	<0.01
迟发型	55(82.1)	30(81.1)	151(76.3)	30(50.9)
分娩方式
剖宫产	46(68.7)	27(75.7)	89(45.4)^*#	39(66.1)^△	<0.01
阴道分娩	21(31.3)	10(27.0)	107(54.6)	20(33.9)
早产	15(22.4)	16(43.2)^*	25(12.8)^#	21(35.6)^△	<0.01
医源性早产	6(9.0)	10(27.0)^*	6(3.1)^#	10(17.0)^△	<0.01
自发性早产	9(13.4)	6(16.2)	19(9.7)	11(18.6)	0.266
胎儿宫内死亡	0	1(2.7)	1(0.5)	0	0.285
胎儿窘迫	13(5.2)	4(10.8)	35(17.9)	6(10.2)	0.350
羊水异常	12(17.9)	10(27.0)	20(10.2)^#	6(10.2)^#	0.025
MSAF	9(13.4)	8(21.6)	19(9.7)	5(8.5)	0.161
羊水过少	3(4.5)	2(5.4)	1(0.5)	1(1.7)	0.082
新生儿窒息	4(6.0)	0	8(4.1)	4(6.8)	0.400
胎儿宫内死亡	0	1(2.7)	1(0.5)	0	0.285

TBA (μmol/L)	有症状ICP围产期发病率				无症状ICP围产期发病率
	OR值	P值	95%CI		OR值	P值	95%CI
	OR值	P值	下限	上限	OR值	P值	下限	上限
10~19.999	7.710	<0.01	3.370	17.638	2.934	<0.01	1.827	4.712
20~29.999	4.681	0.001	1.853	11.829	3.755	<0.01	2.135	6.606
30~39.999	7.710	0.11	1.594	37.303	1.589	0.249	0.723	3.495
≥40	12.047	<0.01	4.031	36.004	6.302	<0.01	2.824	14.067