Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

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Original Article

Volume 10, Number 1, February 2017, pages 21-27

Predictors of Fetal and Maternal Outcome in the Crucible of Hepatic Dysfunction During Pregnancy

Figure 1. ROC curves showing predictive performance of bilirubin and INR in (a) fetal adversities and (b) maternal adversities.

**Table 1.** Pregnancy-Specific Causes for Hepatic Dysfunction
	PEC/EC	HELLP	ICP	HG	AFLP
ALT: alanine aminotransferase; STB: serum total bilirubin; PEC/EC: preeclampsia/eclampsia; HELLP: hemolysis, elevated liver enzymes, low platelets; AFLP: acute fatty liver of pregnancy; ICP: intrahepatic cholestasis of pregnancy; HG: hyperemesis gravidarum.
Incidence	3%	0.2-0.8%	0.1-0.2%	0.3-2%	0.008%
Maternal mortality	15-20%	1.1-3.4%	Unknown	Rare	12.5-18%
Fetal mortality	13-30%	6-70%	8-35%	Rare	7-66%
LFT derangement	20-30%	40-50%	60-90%	40-50%	100%
Occurrence (trimester)	Second/third	Third	Second/third	First	Third
ALT	× 2 to × 5	× 2 to × 30	× 1.5 to × 8	× 2 to × 5	× 3 to × 15
STB (mg/dL)	< 5	1.5-10x	< 6	< 4	4-15x

Table 1. Pregnancy-Specific Causes for Hepatic Dysfunction

PEC/EC

HELLP

ICP

AFLP

ALT: alanine aminotransferase; STB: serum total bilirubin; PEC/EC: preeclampsia/eclampsia; HELLP: hemolysis, elevated liver enzymes, low platelets; AFLP: acute fatty liver of pregnancy; ICP: intrahepatic cholestasis of pregnancy; HG: hyperemesis gravidarum.

Incidence

0.2-0.8%

0.1-0.2%

0.3-2%

0.008%

Maternal mortality

15-20%

1.1-3.4%

Unknown

Rare

12.5-18%

Fetal mortality

13-30%

6-70%

8-35%

Rare

7-66%

LFT derangement

20-30%

40-50%

60-90%

40-50%

100%

Occurrence (trimester)

Second/third

Third

Second/third

First

Third

ALT

× 2 to × 5

× 2 to × 30

× 1.5 to × 8

× 2 to × 5

× 3 to × 15

STB (mg/dL)

< 5

1.5-10x

< 6

< 4

4-15x

**Table 2.** Age Wise Demographics and Etiology of Hepatic Dysfunction
	Age
BOH: bad obstetric history; CLD: chronic liver disease.
Demographics
Primigravida	28 (97%)	58 (65%)	32 (52%)	2 (18%)	2 (33%)	122 (62%)
Booked	23 (79%)	81 (91%)	58 (94%)	11 (100%)	6 (100%)	179 (91%)
BOH	1 (3%)	18 (20%)	25 (40%)	6 (54%)	3 (50%)	53 (27%)
Hypothyroidism	2 (7%)	9 (10%)	16 (26%)	2 (18%)	3 (50%)	32 (16%)
Anemia	11 (38%)	31 (35%)	25 (40%)	1 (9%)	4 (67%)	72 (37%)
Diabetes	1 (3%)	8 (9%)	2 (3%)	1 (9%)	2 (33%)	14 (7%)
Twin pregnancy	-	3 (3%)	1 (2%)	1 (9%)	1 (17%)	6 (3%)
Cesarean	18 (62%)	69 (78%)	49 (79%)	9 (81%)	5 (83%)	150 (76%)
Causality
Pre-eclampsia	11 (38%)	50 (56%)	39 (63%)	8 (73%)	5 (83%)	113 (57%)
Eclampsia	9 (31%)	18 (20%)	7 (11%)	2 (18%)	1 (17%)	37 (19%)
HELLP	2 (7%)	9 (10%)	4 (6%)	-	-	15 (8%)
Viral infection	2 (7%)	4 (4%)	5 (8%)	1 (9%)	-	12 (6%)
Hyperemesis	2 (7%)	4 (4%)	3 (5%)	-	-	9 (5%)
ICP	2 (7%)	3 (3%)	3 (5%)	-	-	8 (4%)
CLD	-	1 (1%)	1 (2%)	-	-	2 (1%)
Sepsis	1 (3%)	-	-	-	-	1 (0.5%)

Table 2. Age Wise Demographics and Etiology of Hepatic Dysfunction

Age

< 21 (N = 29)

21 - 25 (N = 89)

26 - 30 (N = 62)

31 - 35 (N = 11)

> 35 (N = 6)

Total (%) (N = 197)

BOH: bad obstetric history; CLD: chronic liver disease.

Demographics

Primigravida

28 (97%)

58 (65%)

32 (52%)

2 (18%)

2 (33%)

122 (62%)

Booked

23 (79%)

81 (91%)

58 (94%)

11 (100%)

6 (100%)

179 (91%)

BOH

1 (3%)

18 (20%)

25 (40%)

6 (54%)

3 (50%)

53 (27%)

Hypothyroidism

2 (7%)

9 (10%)

16 (26%)

2 (18%)

3 (50%)

32 (16%)

Anemia

11 (38%)

31 (35%)

25 (40%)

1 (9%)

4 (67%)

72 (37%)

Diabetes

1 (3%)

8 (9%)

2 (3%)

1 (9%)

2 (33%)

14 (7%)

Twin pregnancy

3 (3%)

1 (2%)

1 (9%)

1 (17%)

6 (3%)

Cesarean

18 (62%)

69 (78%)

49 (79%)

9 (81%)

5 (83%)

150 (76%)

Causality

Pre-eclampsia

11 (38%)

50 (56%)

39 (63%)

8 (73%)

5 (83%)

113 (57%)

Eclampsia

9 (31%)

18 (20%)

7 (11%)

2 (18%)

1 (17%)

37 (19%)

HELLP

2 (7%)

9 (10%)

4 (6%)

15 (8%)

Viral infection

2 (7%)

4 (4%)

5 (8%)

1 (9%)

12 (6%)

Hyperemesis

2 (7%)

4 (4%)

3 (5%)

9 (5%)

ICP

2 (7%)

3 (3%)

3 (5%)

8 (4%)

CLD

1 (1%)

1 (2%)

2 (1%)

Sepsis

1 (3%)

1 (0.5%)

**Table 3.** Population Demographics and Symptomatology
	PEC (N = 113)	EC (N = 37)	HELLP (N = 15)	V (N = 12)	HG (N = 9)	ICP (N = 8)	CLD (N = 2)	S (N = 1)	Total (N = 197)
Demographics
Age, median (IQR)	25 (23 - 28)	23 (21 - 26)	23 (22 - 29)	26 (22 - 29)	24 (21 - 29)	25 (20 - 28)	24	19	25 (22 - 28)
Primigravida	68 (60%)	25 (68%)	9 (60%)	7 (58%)	6 (67%)	5 (63%)	1 (50%)	1 (100%)	122 (62%)
BOH	32 (28%)	5 (14%)	5 (33%)	5 (42%)	2 (22%)	3 (38%)	1 (50%)	-	53 (27%)
Diabetes	10 (9%)	1 (3%)	0	-	-	3 (38%)	0	-	14 (7%)
Hypothyroidism	22 (19%)	3 (8%)	2 (13%)	-	1 (11%)	3 (38%)	1 (50%)	-	32 (16%)
Obesity	12 (11%)	-	1 (7%)	-	1 (11%)	1 (13%)	-	-	15 (8%)
Symptoms
Headache	21 (19%)	9 (24%)	5 (33%)	2 (17%)	1 (11%)	-	-	-	38 (19%)
Nausea/vomiting	15 (13%)	6 (16%)	7 (46%)	3 (25%)	9 (100%)	1 (13%)	1 (50%)	1 (100%)	43 (22%)
Pruritus	27 (24%)	5 (14%)	3 (20%)	7 (58%)	-	8 (100%)	1 (50%)	-	51 (26%)
Jaundice	2 (2%)	2 (5%)	3 (20%)	10 (83%)	-	2 (25%)	1 (50%)	1 (100%)	21 (11%)
Abruptio placentae	1 (1%)	-	2 (13%)	-	-	-	-	1 (100%)	4 (2%)
Renal dysfunction	2 (2%)	2 (5%)	1 (7%)	-	-	-	-	1 (100%)	6 (3%)

Table 3. Population Demographics and Symptomatology

PEC (N = 113)

EC (N = 37)

HELLP (N = 15)

V (N = 12)

HG (N = 9)

ICP (N = 8)

CLD (N = 2)

S (N = 1)

Total (N = 197)

Demographics

Age, median (IQR)

25 (23 - 28)

23 (21 - 26)

23 (22 - 29)

26 (22 - 29)

24 (21 - 29)

25 (20 - 28)

25 (22 - 28)

Primigravida

68 (60%)

25 (68%)

9 (60%)

7 (58%)

6 (67%)

5 (63%)

1 (50%)

1 (100%)

122 (62%)

BOH

32 (28%)

5 (14%)

5 (33%)

5 (42%)

2 (22%)

3 (38%)

1 (50%)

53 (27%)

Diabetes

10 (9%)

1 (3%)

3 (38%)

14 (7%)

Hypothyroidism

22 (19%)

3 (8%)

2 (13%)

1 (11%)

3 (38%)

1 (50%)

32 (16%)

Obesity

12 (11%)

1 (7%)

1 (11%)

1 (13%)

15 (8%)

Symptoms

Headache

21 (19%)

9 (24%)

5 (33%)

2 (17%)

1 (11%)

38 (19%)

Nausea/vomiting

15 (13%)

6 (16%)

7 (46%)

3 (25%)

9 (100%)

1 (13%)

1 (50%)

1 (100%)

43 (22%)

Pruritus

27 (24%)

5 (14%)

3 (20%)

7 (58%)

8 (100%)

1 (50%)

51 (26%)

Jaundice

2 (2%)

2 (5%)

3 (20%)

10 (83%)

2 (25%)

1 (50%)

1 (100%)

21 (11%)

Abruptio placentae

1 (1%)

2 (13%)

1 (100%)

4 (2%)

Renal dysfunction

2 (2%)

2 (5%)

1 (7%)

1 (100%)

6 (3%)

**Table 4.** Laboratory Investigations in Various Etiologies and Outcomes
	STB	AST	ALT	INR	Hb%	PLT
PLT: platelet count.
Pre-eclampsia	1.2 (0.9 - 1.4)	48 (45 - 52)	56 (52 - 60)	1 (0.9 - 1.1)	12.2 (10.3 - 12.7)	2.1 (1.75 - 2.5)
Eclampsia	1.4 (1.3 - 1.5)	53 (44 - 61)	60 (51 - 67)	1.1 (1 - 1.5)	12.4 (10.7 - 13)	1.9 (1.4 - 2.4)
HELLP	1.3 (1 - 1.5)	108 (88 - 136)	130 (97 - 152)	1 (0.9 - 1.1)	10.2 (9.7 - 12.7)	1 (0.9 - 1.2)
Viral infection	2.8 (2.6 - 3.1)	192 (87 - 317)	216 (93 - 348)	1.2 (1 - 1.6)	12.1 (10.7 - 12.9)	1.9 (1.2 - 2.1)
Hyperemesis	0.9 (0.9 - 1.1)	50 (47 - 57)	55 (51 - 67)	1 (0.9 - 1)	12.9 (12.4 - 13.2)	2.2 (1.9 - 2.5)
ICP	1.1 (1 - 2.2)	59 (53 - 66)	66 (60 - 70)	0.9 (0.9 - 1)	12.7 (11.2 - 13.4)	1.9 (1.3 - 2.3)
CLD	2.1	40	48	1.3	9	1
Sepsis	2.8	131	142	1.1	7.7	1.8
Adverse events
Fetal	1.5 (1.4 - 2.7)	61 (52 - 94)	70 (58 - 107)	1.1 (1 - 1.6)	11 (9 - 13)	1.3 (1 - 2)
Maternal	3.3 (2.9 - 4.5)	131 (100 - 217)	142 (110 - 253)	1.1 (1 - 2)	8.8 (8 - 11)	0.8 (0.4 - 1.3)

Table 4. Laboratory Investigations in Various Etiologies and Outcomes

STB

AST

ALT

INR

Hb%

PLT

PLT: platelet count.

Pre-eclampsia

1.2 (0.9 - 1.4)

48 (45 - 52)

56 (52 - 60)

1 (0.9 - 1.1)

12.2 (10.3 - 12.7)

2.1 (1.75 - 2.5)

Eclampsia

1.4 (1.3 - 1.5)

53 (44 - 61)

60 (51 - 67)

1.1 (1 - 1.5)

12.4 (10.7 - 13)

1.9 (1.4 - 2.4)

HELLP

1.3 (1 - 1.5)

108 (88 - 136)

130 (97 - 152)

1 (0.9 - 1.1)

10.2 (9.7 - 12.7)

1 (0.9 - 1.2)

Viral infection

2.8 (2.6 - 3.1)

192 (87 - 317)

216 (93 - 348)

1.2 (1 - 1.6)

12.1 (10.7 - 12.9)

1.9 (1.2 - 2.1)

Hyperemesis

0.9 (0.9 - 1.1)

50 (47 - 57)

55 (51 - 67)

1 (0.9 - 1)

12.9 (12.4 - 13.2)

2.2 (1.9 - 2.5)

ICP

1.1 (1 - 2.2)

59 (53 - 66)

66 (60 - 70)

0.9 (0.9 - 1)

12.7 (11.2 - 13.4)

1.9 (1.3 - 2.3)

CLD

2.1

1.3

Sepsis

2.8

131

142

1.1

7.7

1.8

Adverse events

Fetal

1.5 (1.4 - 2.7)

61 (52 - 94)

70 (58 - 107)

1.1 (1 - 1.6)

11 (9 - 13)

1.3 (1 - 2)

Maternal

3.3 (2.9 - 4.5)

131 (100 - 217)

142 (110 - 253)

1.1 (1 - 2)

8.8 (8 - 11)

0.8 (0.4 - 1.3)

**Table 5.** Feto-Maternal Outcomes in Patients With Hepatic Dysfunction
	PEC (N = 118)	EC (N = 37)	HELLP (N = 15)	V (N = 12)	HG (N = 9)	ICP (N = 9)	CLD (N = 2)	S (N = 1)	Total (N = 203)
ICU: intensive care unit; LBW: low birth weight; FDR: fetal death rate; NICU: neonatal intensive care unit.
Fetal outcome (N = 203)
Single fetus	108 (92%)	37 (100%)	15 (100%)	12 (100%)	9 (100%)	7 (78%)	2 (100%)	1 (100%)	191 (94%)
Male fetus	64 (54%)	19 (51%)	5 (33%)	7 (58%)	4 (44%)	3 (33%)	2 (100%)	1 (100%)	105 (52%)
Pre-term	52 (44%)	18 (49%)	10 (67%)	1 (8%)	2 (22%)	-	2 (100%)	1 (100%)	86 (42%)
LBW	75 (64%)	27 (73%)	14 (93%)	4 (33%)	2 (22%)	2 (22%)	2 (100%)	1 (100%)	127 (63%)
Infant death	8 (7%)	9 (24%)	3 (20%)	1 (8%)	-	-	-	-	21 (10%)
Miscarriage	3 (3%)	1 (3%)	2 (13%)	-	-	-	-	-	6 (3%)
Stillbirth	5 (4%)	4 (11%)	2 (13%)	1 (8%)	-	-	1 (50%)	1 (100%)	14 (7%)
FDR	16 (14%)	14 (38%)	7 (47%)	2 (17%)	-	-	1 (50%)	1 (100%)	41 (20%)
NICU	30 (25%)	16 (43%)	6 (40%)	1 (8%)	-	1	-	-	54 (27%)
Maternal outcome (N = 197)
Death	-	2 (5%)	2 (13%)	-	-	-	-	1 (100%)	5 (2.5%)
ICU	1	4	4	-	-	-	-	1	10 (5%)
Cesarean	89 (79%)	31 (84%)	10 (67%)	12 (100%)	2 (22%)	3 (38%)	2 (100%)	1 (100%)	150 (76%)

Table 5. Feto-Maternal Outcomes in Patients With Hepatic Dysfunction

PEC (N = 118)

EC (N = 37)

HELLP (N = 15)

V (N = 12)

HG (N = 9)

ICP (N = 9)

CLD (N = 2)

S (N = 1)

Total (N = 203)

ICU: intensive care unit; LBW: low birth weight; FDR: fetal death rate; NICU: neonatal intensive care unit.

Fetal outcome (N = 203)

Single fetus

108 (92%)

37 (100%)

15 (100%)

12 (100%)

9 (100%)

7 (78%)

2 (100%)

1 (100%)

191 (94%)

Male fetus

64 (54%)

19 (51%)

5 (33%)

7 (58%)

4 (44%)

3 (33%)

2 (100%)

1 (100%)

105 (52%)

Pre-term

52 (44%)

18 (49%)

10 (67%)

1 (8%)

2 (22%)

2 (100%)

1 (100%)

86 (42%)

LBW

75 (64%)

27 (73%)

14 (93%)

4 (33%)

2 (22%)

2 (100%)

1 (100%)

127 (63%)

Infant death

8 (7%)

9 (24%)

3 (20%)

1 (8%)

21 (10%)

Miscarriage

3 (3%)

1 (3%)

2 (13%)

6 (3%)

Stillbirth

5 (4%)

4 (11%)

2 (13%)

1 (8%)

1 (50%)

1 (100%)

14 (7%)

FDR

16 (14%)

14 (38%)

7 (47%)

2 (17%)

1 (50%)

1 (100%)

41 (20%)

NICU

30 (25%)

16 (43%)

6 (40%)

1 (8%)

54 (27%)

Maternal outcome (N = 197)

Death

2 (5%)

2 (13%)

1 (100%)

5 (2.5%)

ICU

10 (5%)

Cesarean

89 (79%)

31 (84%)

10 (67%)

12 (100%)

2 (22%)

3 (38%)

2 (100%)

1 (100%)

150 (76%)

**Table 6.** Risk Factors in Maternal and Fetal Outcomes
Maternal risk factor	Adverse fetal outcome	Adverse maternal outcome
Primigravida	0.95	1	0.4	0.37
Hypothyroidism	1.62	0.34	3.6	0.18
Diabetes	0.27	0.3	-	1
Anemia	2.16	0.03	7.29	0.06
Thrombocytopenia	3.47	0.0006	9.4	0.03
Coagulopathy	1.36	0.005	0.69	1
Hyperbilirubinemia	5.18	0.002	3.9	0.0001

Table 6. Risk Factors in Maternal and Fetal Outcomes

Maternal risk factor

Adverse fetal outcome

Adverse maternal outcome

Odds ratio

P value

Odds ratio

P value

Primigravida

0.95

0.4

0.37

Hypothyroidism

1.62

0.34

3.6

0.18

Diabetes

0.27

0.3

Anemia

2.16

0.03

7.29

0.06

Thrombocytopenia

3.47

0.0006

9.4

0.03

Coagulopathy

1.36

0.005

0.69

Hyperbilirubinemia

5.18

0.002

3.9

0.0001