Prevalence, risk factors and adverse perinatal outcomes for Chinese women with intrahepatic cholestasis of pregnancy: a large cross-sectional retrospective study

Figures & data

Table 1. Demographic and clinical characteristics of the study population according to intrahepatic cholestasis of pregnancy.

	ICP (1516)	Non-ICP (38,226)	p Value
Maternal age, mean (SD), years	31.20 ± 4.48	31.13 ± 4.41	0.52
Maternal age category [n (%)], years			<0.01
<25	114 (7.52)	1751 (4.58)
25–34	1008 (66.49)	27,892 (72.97)
≥35	394 (25.99)	8583 (22.45)
Pre-pregnancy BMI [n (%)] (kg/m^2)			0.01
Underweight (<18.5)	290 (19.13)	6563 (17.17)
Normal weight (18.5–24.9)	957 (63.13)	26,115 (68.33)
Overweight (25.0–29.9)	88 (5.80)	2458 (6.43)
Obesity (≥30)	19 (1.25)	233 (0.61)
Data missing	162 (10.69)	2857 (7.47)
Maternal education [n (%)]			<0.01
Low	150 (9.89)	2378 (6.22)
Medium	182 (12.01)	3927 (10.27)
High	1151 (75.92)	31,079 (81.30)
Data missing	33 (2.18)	842 (2.21)
Occupational physical activity [n (%)]			<0.01
Light	877 (57.85)	24,225 (63.37)
Moderate	352 (23.22)	7255 (18.98)
Active	254 (16.75)	5934 (15.52)
Data missing	33 (2.18)	852 (2.23)
Gestational weight gain [n (%)]			<0.01
Inadequate	456 (30.08)	9319 (24.38)
Adequate	523 (34.50)	15,322 (40.08)
Excessive	338 (22.30)	10,109 (26.44)
Data missing	199 (13.12)	3476 (9.10)
Parity [n (%)]			<0.01
Primiparous	528 (34.83)	15,579 (40.75)
Multiparous	988 (65.17)	22,687 (59.25)
Twin pregnancies [n (%)]			<0.01
No	1295 (85.42)	36,832 (96.35)
Yes	221 (14.58)	1394 (3.65)
IVF [n (%)]			<0.01
No	1323 (87.27)	35,224 (92.15)
Yes	193 (12.73)	3002 (7.85)
Caesarean history [n (%)]			<0.01
No	575 (37.93)	22,146 (57.93)
Yes	941 (62.07)	16,140 (42.22)
Abortion history [n (%)]			0.01
0	760 (50.13)	20,792 (54.39)
1	426 (28.10)	10,286 (26.91)
≥2	330 (21.77)	7148 (18.70)
HBsAg [n (%)]			<0.01
Negative	1304 (86.02)	36,261 (94.86)
Positive	212 (13.98)	1965 (5.14)
GDM [n (%)]			0.18
No	1210 (79.82)	31,053 (81.24)
Yes	306 (20.18)	7173 (18.76)
HDP [n (%)]
No	1451 (95.71)	37,253 (97.45)	<0.01
Yes	65 (4.29)	973 (2.55)
Laboratory measurements
TBA, median (range) (μmol/L)	24.00 (11.00–264.00)	2.00 (0.00–9.00)	<0.01
ALT, median (IQR) (U/L)	81 (56–215)	31 (24–46)	<0.01
AST, median (IQR) (U/L)	73 (46–183)	21 (15–28)	<0.01

Two independent sample t-tests were used for normally distributed variables; Pearson’s Chi-square test or Fisher’s exact test were used for categorical variables; The differences of non-normally distributed parameters were analyzed using Mann–Whitney U-test.

ICP, intrahepatic cholestasis pregnancy; SD, standard deviation; BMI, body mass index; IVF, in vitro fertilization; GDM, gestational diabetes mellitus; HDP, hypertensive disorders of pregnancy; IQR, interquartile range; TBA, total bile acid; ALT, Alanine transaminase; AST, Aspartate transaminase.

Figure 1. Flowchart of the study population.

Figure 2. Incidence of intrahepatic cholestasis of pregnancy (ICP) by age and hepatitis B surface antigen (HBsAg) status.

Figure 3. Incidence of intrahepatic cholestasis of pregnancy (ICP) by age and pre-pregnancy body mass index (ppBMI).

Table 2. Factors associated with the incidence of ICP by multivariate logistic regression models.

	Crude OR	p Value	Adjusted OR	p Value
Maternal age category [n (%)], years^a
<25	1.78 (1.46–2.17)	<0.01	1.81 (1.44–2.28)	<0.01
25–34	1.00		1.00
≥35	1.27 (1.13–1.43)	<0.01	1.23 (1.07–1.42)	0.04
Pre-pregnancy BMI [n (%)] (kg/m^2)^a
Underweight (<18.5)	1.20 (1.05–1.38)	0.01	1.27 (1.11–1.46)	0.01
Normal weight (18.5–24.9)	1.00		1.00
Overweight (25.0–29.9)	0.97 (0.78–1.22)	0.81	0.90 (0.71–1.14)	0.39
Obesity (≥30)	2.12 (1.32–3.39)	<0.01	1.96 (1.20–3.21)	0.01
Maternal education^a
Low	1.69 (1.42–2.02)	<0.01	1.46 (1.18–1.80)	<0.01
Medium	1.24 (1.06–1.46)	0.01	1.12 (0.93–1.33)	0.23
High	1.00		1.00
Occupational physical activity
Light	1.00		1.00
Moderate	1.34 (1.18–1.52)	<0.01	1.11 (0.92–1.43)	0.26
Active	1.18 (1.03–1.08)	0.02	1.01 (0.87–1.04)	0.37
Gestational weight gain^a
Inadequate	1.43 (1.26–1.63)	<0.01	1.45 (1.27–1.65)	<0.01
Adequate	1.00		1.00
Excessive	0.98 (0.85–1.13)	0.77	0.91 (0.78–1.04)	0.17
Parity^a
Primiparous	1.00		1.00
Multiparous	1.83 (1.54–1.99)	<0.01	1.53 (1.35–1.73)	<0.01
IVF^a
No	1.00		1.00
Yes	1.70 (1.45–1.98)	<0.01	1.22 (1.03–1.46)	0.02
Caesarean history^a
No	1.00		1.00
Yes	2.55 (2.12–2.87)		2.04 (1.81–2.31)	<0.01
Abortion history^a
0	1.00		1.00
1	1.13 (1.00–1.28)	0.04	1.15 (1.01–1.31)	0.04
≥2	1.26 (1.11–1.44)	<0.01	1.21 (1.03–1.41)	0.02
Twin pregnancies^a
No	1.00		1.00
Yes	4.17 (3.60–4.84)	<0.01	3.14 (2.63–3.73)	<0.01
HBsAg^a
Negative	1.00		1.00
Positive	2.96 (2.54–3.44)	<0.01	2.79 (2.36–3.30)	<0.01

^aFactors for which the multivariate analyses were adjusted.

ICP, intrahepatic cholestasis pregnancy; BMI, body mass index; IVF, in vitro fertilization; OR, odds ratio.

Table 3. Perinatal outcomes of single pregnancy with respect to ICP.

	ICP (1295)	Non-ICP (36,834)	p Value	Crude OR (95%CI)	Adjusted OR (95%CI)
Maternal outcome
Caesarean section	727 (56.14)	14,704 (39.92)	<0.01	1.93 (1.73–2.16)^a	1.72 (1.54–1.91)^a
PROM	78 (6.02)	148 (4.02)	0.01	0.48 (0.40–0.56)^a	0.77 (0.61–1.23)
Preterm birth	288 (22.24)	3411 (9.26)	<0.01	2.81 (2.45–3.22)^a	2.56 (2.21–3.02)^a
Abruptio placentae	21(1.62)	722 (1.35)	0.26	0.78 (0.50–1.21)	0.84 (0.52–1.42)
Meconium amniotic fluid	5 (0.39)	251 (0.68)	0.12	0.45 (0.17–2.22)	0.53 (0.25–2.36)
Postpartum haemorrhage	55 (4.25)	1736 (4.71)	0.44	0.90 (0.68–1.18)	1.18 (0.74–1.38)
Neonatal outcome
Stillbirth	10 (0.77)	262 (0.71)	0.58	1.01 (0.95–1.18)	1.00 (0.98–1.13)
Macrosomia	47 (3.63)	1817 (4.93)	0.03	0.73 (0.54–0.98)^b	0.87 (0.74–1.26)
LBW	60 (4.63)	405 (1.10)	<0.01	2.14 (1.47–3.11)^a	2.06 (1.38–3.04)^a
Foetal distress	175 (13.51)	5911 (16.05)	0.02	0.82 (0.70–0.96)^b	1.09 (0.86–1.22)
Neonatal asphyxia	15 (1.16)	343 (0.93)	0.40	1.25 (0.74–2.10)	1.48 (0.87–2.42)
Neonatal unit admission	355 (27.41)	5572 (15.13)	<0.01	2.67 (2.13–3.15)^a	2.42 (1.99–3.02)^a

Note. Multivariate analyses were adjusted for age, pre-pregnancy BMI, maternal education, gestational weight gain, parity, IVF, caesarean history, abortion history, HBsAg status, HDP. The results were presented with an adjusted odds ratio, aOR (95% CI).

HDP, hypertensive disorders of pregnancy; ICP, intrahepatic cholestasis pregnancy; PROM, premature rupture of the membranes; LBW, low birth weight; OR, odds ratio; p-value was calculated by Pearson’s Chi-square or Fisher’s exact test, which were used to compare the proportions of maternal and neonatal outcomes between the two groups.

^ap < 0.01; ^bp < 0.05.

Table 4. Perinatal outcomes of twin pregnancy with respect to ICP.

	ICP (221 women, 442 newborns)	Non-ICP (1394 women, 2788 newborns)	p Value	Crude OR (95%CI)	Adjusted OR (95%CI)
Maternal outcome
Caesarean section	207 (93.67)	1032 (74.03)	<0.01	2.55 (1.45–4.46)^a	2.31 (1.24–3.67)^a
PROM	25 (11.31)	198 (14.20)	0.05	0.65 (0.42–1.00)	0.74 (0.37–0.92)
Preterm birth	166 (75.11)	780 (55.95)	<0.01	1.81 (1.30–2.50)^a	1.58 (1.22–2.35)^a
Abruptio placentae	2 (0.90)	36 (2.58)	0.09	0.29 (0.07–1.21)	0.53 (0.11–1.53)
Meconium amniotic fluid	1 (0.45)	1 (0.07)	0.18	6.58 (0.41–12.64)	6.01 (0.78–10.65)
Postpartum haemorrhage	15 (6.79)	109 (7.82)	0.26	0.73 (0.42–1.27)	0.86 (0.56–1.51)
Neonatal outcome
Stillbirth	1 (0.23)	15 (1.08)	0.12	0.66 (0.39–3.19)	0.89 (0.61–2.14)
Macrosomia	0	0
LBW	301 (68.10)	1694 (60.76)	<0.01	1.38 (1.11–1.71)^a	1.22 (1.08–1.59)^a
Foetal distress	24 (10.86)	186 (6.67)	0.26	0.71 (0.39–1.29)	0.83 (0.54–1.48)
Neonatal asphyxia	12 (5.43)	106 (3.80)	0.33	0.81 (0.42–1.87)	0.92 (0.63–1.78)
Neonatal unit admission	22(49.77)	1157 (41.50)	<0.01	1.74 (1.33–2.08)^a	1.55 (1.20–1.92)^a

Note. Multivariate analyses were adjusted for pre-pregnancy BMI, gestational weight gain, parity, IVF, caesarean history, abortion history, HBsAg status, HDP. The results were presented with an adjusted odds ratio, aOR (95% CI).

HDP, hypertensive disorders of pregnancy; ICP, intrahepatic cholestasis pregnancy; PROM, premature rupture of the membranes; LBW, low birth weight; OR, odds ratio; p-value was calculated by Pearson’s Chi-square or Fisher’s exact test, which were used to compare the proportions of maternal and neonatal outcomes between the two groups.

^ap < 0.01; ^bp < 0.05.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to privacy or ethical restrictions.