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Table 1 Characteristics of the 14 Included Studies

From: Application of metabolomics in intrahepatic cholestasis of pregnancy: a systematic review

First Author (Year)

Country

Outcome

Case

Control

Bio

specimen

Sampling time

Analytic platform

Targeted/untargeted

Up-regulated

Down-regulated

Yifan He (2022) [12]

China

ICP

93

75

Serum

Not mentioned

UPLC-QTOF-MS/MS

Targeted

Glycocholic acid; Taurocholic acid; Glycochenodeoxycholic acid; Taurochenodeoxycholic acid; Glycoursodeoxycholic acid; Tauroursodeoxycholic acid; Glycodeoxycholic acid; Taurodeoxycholic acid; Hyocholic acid; Glycohyocholic acid; Taurohyocholic acid; Glycolithocholic acid; Taurolithocholic acid; Glycohyodeoxycholic acid; Taurohyodeoxychlic acid; ω-Muricholic acid; Tauro-ω- muricholic acid; Tauro-α- muricholic acid; Gdi-1; Tdi-1; Tri-1; Tri-3; Gtri-1; Gtri-3; Gtri-4; Gtri-5; Gtri-6; Gtri-7; Gtri-8; Ttri-1; Ttri-2; Ttri-3; Ttri-4; Ttri-5; Di-S-1; Di-S-2; Di-S-3; Di-S-4; Di-S-5; Gdi-S-1; Gdi-S-2

Chenodeoxycholic acid; Deoxycholic acid; Lithocholic acid; Di-1; Di-2; Tri-5

Ruirui Dong (2021) [13]

China

ICP

10

10

Placenta

After caesarian section

LC–MS/MS

Untargeted

Glyceraldehyde; l-Proline; Glycocholic acid; l-Palmitoylcarnitine

d-Glucuronic acid; Thyroxine; Xanthurenic acid; Levulinic acid; n-Oleoylethanolamine

40/24/20

40/40/33

Serum

During the third/first/second trimester

l-Palmitoylcarnitine

None

Jamie V.de Seymour (2018) [14]

China

ICP

38

46

Hair

17-41 W

GC–MS

Untargeted

None

None

Yuchao Li (2018) [15]

China

Mild ICP Severe ICP

29(11 + 18)

22

Urine

At the first visit for the definite diagnosis

HPLC–MS/MS

Targeted

Di-GBA-S-3; Glycocholic acid-3S; Di-TBA-S-3; Di-TBA-S-2; Taurocholic acid-3S; Cholic acid-3S; Taurolithocholic acid-3S

None

Li Ma (2017) [16]

China

ICP

30

30

Urine

At the third-trimester (≥ 28 W)

HPLC/Q–TOF–MS

Untargeted

LysoSM(d18:1); 17-Hydroxy-E4-neuroprostane; Dynorphin A (6–8); Varanic acid; MG(22:5(7Z,10Z,13Z,16Z,19Z)/0:0/0:0); LysoPE(22:5(7Z,10Z,13Z,16Z,19Z)/0:0); 5b-Cyprinol sulfate; 3-Oxooctadecanoic acid; Testosterone glucuronide; Phosphorylcholine; Xanthine; Dodecanedioic acid; 18-Oxocortisol; Tauromuricholic acid; Glycocholic acid; Pyridinoline; Chenodeoxyglycocholic acid; n-Ribosylhistidine; Chenodeoxycholic acid-3S; 1-Methylguanosine; Glycochenodeoxycholate-3S; Taurohyocholate; (Z)-Narceine imide; 11-Oxo-androsterone glucuronide; 2-Deoxypentonic acid; Oxidized glutathione; Estrone glucuronide; Estriol-3-glucuronide

l-Homocysteine sulfonic acid; Galactonic acid; Isocitric acid; Cortolone-3-glucuronide

Yue Cui (2018) [9]

China

ICP

42

55

Serum

At the first time visit to take the confirmation diagnosis

UPLC-Triple TOF–MS/MS

Targeted

Tauroursodeoxycholic acid; Taurohyodeoxychlic acid; Taurochenodeoxycholic acid; Taurodeoxycholic acid; Glycohyodeoxycholic acid; Glycochenodeoxycholic acid; Glycodeoxycholic acid; ω-Muricholic acid; α-Muricholic acid; β-Muricholic acid; Hyocholic acid; Tauro-ω- muricholic acid; Tauro-α-muricholic acid; Taurohyocholic acid; Taurocholic acid; Glycohyocholic acid; Glycocholic acid; Taurolithocholic acid; Glycolithocholic acid; Tdi-1; Gdi-1; Tri-1; Tri-2; Tri-3; Tri-4; Ttri-1; Ttri-2; Ttri-3; Ttri-4; Ttri-5; Gtri-1; Gtri-2; Gtri-3; Gtri-4; Gtri-5; Gtri-6; Gtri-7; Gtri-8; Di-S-1; Di-S-2; Di-S-3; Di-S-4; Di-S-5; Gdi-S-1; Gdi-S-2; Gdi-S-3; Gdi-S-4; Gdi-S-5; Gtri-S-1

Di-2

X Sun (2021) [17]

China

Mild ICP Severe ICP

60(30 + 30)

30

Plasma

On the second day after the initial diagnosis of ICP

LC–MS/MS

Untargeted

SM(d34:0); SM(d18:0/16:0); SM(d42:1); SM(d22:0/18:1); Cer(d18:0/24:1); SM(d20:0/16:0); SM(d18:1/24:1); SM(d24:0/18:2); PC(32:0); PC(40:5); PI(16:0/22:6)

TG(18:3/18:2/18:2); TG(18:2/18:2/18:2); SM(d22:1/19:1); SM(d41:2); Cer(d18:1/23:0); SM(d39:1); SM(d41:1); SM(d22:1/18:0); PS(36:1); PC(17:0/18:2); PC(35:2); PS(41:5); PE(36:2p); Cer(d18:2/24:0); Cer(d18:1/22:0); Cer(d18:1/24:0); SM(d22:0/18:2); TG(16:0/18:1/18:3); DG(34:3e)

Qihong Zheng (2021) [18]

China

Mild ICP Severe ICP

32(14 + 18)

28

Plasma

Not mentioned

HPLC–MS/MS

Targeted

Norcholic acid; Glycochenodeoxycholic acid; Glycocholic acid; Taurocholic acid; Hyocholic acid; Glycohyocholic acid; Taurochenodeoxycholic acid; Taurohyocholic acid; Taurolithocholic acid-3S; Glycoursodeoxycholic acid

3-β-Cholic acid

Jianbo Chen (2013) [19]

China

Mild ICP

28

35

Serum

In the last trimester of pregnancy

HPLC–MS/MS

Targeted

Glycocholic acid; Glycochenodeoxycholic acid; Glycoodeoxycholic acid; Taurocholic acid; Taurodeoxycholic acid; Tauroursodeoxycholic acid

None

Severe ICP

33

35

Cholic acid; Glycocholic acid; Glycochenodeoxycholic acid; Glycodeoxycholic acid; Taurocholic acid; Taurochenodeoxycholic acid; Taurodeoxycholic acid; Tauroursodeoxycholic acid

None

Lian Ye (2007) [20]

China

ICP

43

53

Serum

Not mentioned

HPLC–MS/MS

Targeted

Glycocholic acid; Glycochenodeoxycholic acid; Taurocholic acid; Tauroursodeoxycholic acid

Taurochenodeoxycholic acid

Antonín Pařízek (2016) [21]

Czech Republic

ICP

15

17

Serum

Not mentioned

GC–MS

Untargeted

16α-Hydroxyestrone; Conjugated epipregnanolone (3β,5β-THP); Conjugated 5α-pregnane-3α,20α-diol; Androsterone (3α,5α-THA) sulfate; Epiandrosterone (3β,5α-THA) sulfate; Epietiocholanolone (3β,5β-THA) sulfate; Conjugated 5α-androstane-3α,17β-diol; 3α,5α,20α-PD/3α,5α-THA, conjugates; 3β,5α,20α-PD/3β,5α-THA, conjugates; 3α,5β,20α-PD/3α,5β-THA, conjugates; 3β,5β,20α-PD/3β,5β-THA, conjugates

None

Guo-Hua Li (2020) [22]

China

ICP

15

15

Serum

38 W(case)

33.4 W(control)

LC–MS

Untargeted

Tauroursodeoxycholic acid; Glycolithocholic acid; Taurochenodeoxycholate; Cholic acid; Glycodeoxycholic acid; Glycochenodeoxycholate; Glycocholic acid; Chenodeoxycholate; Pregnenolone sulfate; Progesterone; l-Palmitoylcarnitine; Creatinine; 1-Aminocyclopropanecarboxylic acid; 1-Palmitoyl Lysophosphatidic Acid; 3-Methoxy-4-Hydroxyphenylglycol Sulfate; 2-Hydroxy-3-methylbutyric acid; DL-3-Phenyllactic acid; Alpha-N-Phenylacetyl-l-glutamine; N6-methyladenosine; 1-Methylnicotinamide; Succinate; 1-Oleoyl-L-alpha-lysophosphatidic acid; Ramipril; S-Methyl-5'-thioadenosine; Adenine; l-Threonine; l-Glutamine; l-Pyroglutamic acid; d-Proline; l-Tyrosine; Gly-Glu; Sphingosine; N6,N6,N6-Trimethyl-l-lysine; N6-Methyl-l-lysine; Urea; Adynerin

1-Myristoyl-sn-glycero-3-phosphocholine; n-(omega)-Hydroxyarginine; Inosine; Betaine; Phe-Trp; Phe-Phe; His-Ala; Pro-Arg; His-Glu; Ser-Arg; His-Ser; His-Gly; Pro-Val; Phe-Gly; Phe-Ile; His-Gln; Lys-Ser; Phe-Thr; Phe-Pro; His-Thr; Val-His; His-Ile

Xiao Chen (2019) [23]

China

ICP

33

35

Urine

 > 28 W

UPLC-QTOF-MS/MS

Targeted

Tauroursodeoxycholic acid; Taurochenodeoxycholic acid; Glycoursodeoxycholic acid; Glycohyodeoxycholic acid; Tauro-ω- muricholic acid; Tauro-α-muricholic acid; Taurohyocholic acid; Taurocholic acid; Glycocholic acid; Taurolithocholic acid-S; Tdi-1; Tdi-2; Tdi-3; Gdi-1; Ttri-1; Ttri-2; Ttri-3; Ttri-4; Ttri-5; Gtri-2; Di-S-3; Di-S-4; Di-S-5; Di-S-6; Di-S-7; Di-S-8; Tdi-S-1; Tdi-S-2; Tdi-S-3; Tdi-S-4; Tdi-S-5; Tdi-S-6; Gdi-S-1; Gdi-S-2; Gdi-S-3; Gdi-S-4; Ttri-S-1; Ttri-S-2; Gtri-S-1; Gtri-S-2; Mono-S; Gmono-S-1; Gmono-S-2; Gmono-S-3; Gmono-S-4

None

Rachel M. Tribe (2010) [24]

UK

ICP

63

26

Serum

16–40 W

HPLC–MS

Targeted

Cholic acid; Taurocholic acid; Taurochenodeoxycholic acid; Taurolithocholic acid; Tauroursodeoxycholic acid; Glycocholic acid; Glycochenodeoxycholic acid

None

  1. The prefix “G-” or “T-”mean the bile acids exist in glycine- or taurine-conjugated form, respectively. The prefix “mono-”, “di-”, or “tri-” mean the bile acids may have one, two, or three -OHs, respectively. The prefix “S-” means the BAs are sulfated
  2. GBA Glycine bile acid; TBA Taurine bile acid