Intrahepatic cholestasis of pregnancy

Table 1 The reported incidence of ICP in different countries and ethnic groups

Country	Prevalence (%)	Year of study	Diagnostic criteria	References
Australia	0.2	1964-1966	P, J, LFT, PR1	[5]
Australia	1.5	1968-1970	P, J, LFT, R	[8]
Australia	0.2	1975-1984	P, J, LFT, PR; SBA (from 1982)	[3]
Bolivia	9.2	1976	P, J, B, LD	[7]
Aimaras	13.8
Quechas	4.3
Caucasians	7.8
Mixed Indian	7.3
Canada	0.07	1963-1976	J, P, LFT, LD, R	[4]
Chile		1974-1975	P, J, B, LD	[6]
Aimaras	11.8
Araucanian	27.6
Caucasian	15.1
Chile	4.7	NA	P, SBA (10 &mgr;mol/L), B, LFT	[10]
Chile	6.5	1988-1990	P, LD2	[18]
China	0.32	1981-1983	J, LFT, B, SBA, LD, R3	[12]
Chongqing
China	0.05	2003-2005	LFT, SBA (11 &mgr;mol/L), B, LD	[14]
Hong Kong
Finland	1.1	1971-1972	P, LFT	[13]
Finland	0.54	1990-1996	P, LFT, SBA (8 &mgr;mol/L), LD	[11]
Finland	0.54	1994-1998	P, LFT, SBA (8 &mgr;mol/L), LD	[9]
France	0.2	1953-1961	P, J, LFT, PR, R	[16]
France	0.53	1988-1989	LFT, B, SBA (6 &mgr;mol/L)	[19]
India	0.08	2002-2004	P, LD, LFT	[17]
Italy	0.96	1996-1999	P, LFT, SBA4	[15]
Italy	1	1989-1997	P, PR, LFT ± SBA	[20]
Poland	1.5	NA	P, LFT, B, LD	[21]
Portugal	1	NA	P, SBA, LFT, B, LD5	[24]
Sweden	1.5	1971-1974	P, LFT, LD	[23]
	1	1980-1982
Sweden	1.5	1999-2002	P, SBA (10 &mgr;mol/L), LFT, LD	[25]
USA	0.32	1997-1999	P, SBA or LFT, PR6	[26]
USA	5.6	1997-1998	P, SBA (20 &mgr;mol/L)	[27]
Latina
UK	0.7	1995-1997	P, SBA (14 &mgr;mol/L), LFT, LD	[22]
Caucasian	0.62
Indian	1.24
Pakistani	1.46

P: Pruritus; J: Jaundice; LFT: Raised AST and/or ALT; SBA: Raised serum bile acids [upper limit of normal defined as in the study (&mgr;mol/L)]; B: Raised bilirubin; PR: Postnatal resolution; LD: Other liver diseases excluded; R: Recurrence in subsequent pregnancy; NA: Information not available.

¹Absence of parenchymal necrosis on liver biopsy;

²Absence of fever or malaise, LFT’s only performed if jaundiced, dark urine or doubt over diagnosis;

³Absence of hepatomegaly;

⁴Absence of gallstones;

⁵Increased cholic acid percentage;

⁶Absence of other hepatic disease associated with pregnancy.

Table 2 The incidences of adverse fetal outcomes reported in the literature

Study period	Number of cases (controls)	Preterm delivery (< 37 wk)	Abnormal CTG (timing)	Apgar score ≤7 (min)	Meconium staining of amniotic fluid	PPH (> 500 mL)	References
1951-1983	100 (156)	38%	-	-	-	7%	[12]
		38% U
1963-1976	42 (42)	39%	-	-	-	19%	[4]
		39% S
1965-1974	56	36%	14% (NS)	-	27%	9%	[38]
		36% S	8 B		NS
1971-1972	116 (116)	-	19% (labour)	7% (1)	28%	-	[13]
			3% LD	3% (5)	7% < 37 wk
			16% B or T		21% > 37 wk
1971-1974	100 (100)	-	-	10% (1)	12%	-	[23]
				8% (5)	NS
1975-1984	83	44%	-	-	45%	-	[46]
		44% S			10% < 37 wk
					35% > 37 wk
1979-1981	18	-	-	-	58.30%	22%	[39]
					NS
1980–1981	117	-	14% (antepartum)	10% (NS)	16.20%	-	[48]
			4% (labour)		NS
1988-1990	320 (320)	19%	12.8% (NS)	8% (1)	38%	-	[18]
		12% S		2% (5)	13% < 37 wk
		7% I			25% > 37 wk
1988-1995	79 (792)	14%	2% (NS)	None	44%	-	[57]
		14% S	2% B		NS
1989-1995	50	60%	-	-	-	2%	[56]
		60% U
1989-1997	206	27%	-	1% (5)	21%	-	[20]
		4% S			5% < 37 wk
		23% I			16% > 37 wk
1990-1996	91 (16, 818)	14%	20% (labour)	8% (1)	15%	-	[11]
		14% U		2% (5)	NS
1999-2001	70	17%	-	-	14%	17%	[30]
		6% S			4% < 37 wk
		11% I			10% > 37 wk
1999-2002	690 (44, 792)	12%	7%3	7%3	25%	-	[25]
		12% U
1999-20031	352	38%	-	-	-	-	[31]
		16% S
		22% I
2000-2007	122	4%	-	8% (1)	13%	7%	[49]
		4% S		2% (5)
2003-2005	8	50%	-	-	62%	-	[14]
		50% U			NS

S: Spontaneous preterm labour; I: Iatrogenic preterm labour; U: Unspecified preterm labour; NS: Not specified; B: Bradycardia; T: Tachycardia; LD: Late decelerations; PPH: Post-partum hemorrhage; -: Not reported.

¹Cases were recruited between 1999 and 2003, but the affected pregnancies had occurred from 1986;

²Controls in this study had a history of stillbirth in a previous pregnancy;

³Glantz et al[25] report findings of asphyxial events (defined as operative delivery due to abnormal CTG, post-partum umbilical artery pH < 7.05 or Apgar score < 7 at 5 min).

Table 3 Additional biochemical markers that have been investigated in relation to ICP

Number of cases (controls)	Gestation	Parameter investigated	Main findings	References
76	NR	Serum human placental lactogen and AFP	↑ hPL, no difference in AFP	[88]
68	37-38/40	Pregnancy specific β-1-glycoprotein	↓ Levels	[89]
76 (150)	T3	Prolactin	↑ Prolactin from 33 wk	[94]
10 (288)	T3	Placental protein 10	↓ Placental protein 10 in ICP-negatively correlated with AST and SBA	[98]
NR	T3 + PN	Serum copper and zinc	↑ Copper in ICP	[91]
			No difference in zinc
NR	T3	Serum 25(OH)D, 24, 25(OH)D, 1, 25(OH)D, total protein, calcium, phosphorus, magnesium and alkaline phosphatase	25(OH)D initially higher in patients than controls, but decreased by delivery	[92]
			No change in any other parameter
12 (12)	T3	Serum selenium and glutathione peroxidase	↓ Selenium in ICP	[90]
			↓ Glutathione peroxidase activity
33 (5680)	T2	Serum AFP and hCG	No differences	[87]
26 (13)	NR	Thyroid hormones	↓ T3	[93]
21 (98)	T3	Serum selenium, zinc and copper	↓ Selenium in ICP	[96]
			↑ (Double) copper in ICP
			No difference in zinc
72 (30)	T3	Renal function tests: uric acid, urea, potassium, sodium, creatinine	↑ Uric acid and creatinine	[97]
22 (21)	NR	Maternal-fetal mixed lymphocyte reaction	↓ Transformation rate of lymphocytes	[86]
24 (1148)	T3	Serum AFP and β-hCG	No differences	[95]
30 (30)	T3	Serum neopterin and soluble interleukin 2 receptor (sIL-2R)	↑ Neopterin and sIL-2R	[99]
58 (42)	T3	Alpha-hydroxybutyrate dehydrogenase (α-HBDH) activity	↑α-HBDH	[100]

NR: Not reported; T3: Third trimester; T2: Second trimester; PN: Postnatal.