Conjugated hyperbilirubinemia presenting in first fourteen days in term neonates

Table 1 Baseline clinical characteristics and biochemical indices at onset of conjugated hyperbilirubinemia

Baseline characteristics	ECHB (n = 65, %)	LCHB (n = 52, %)	P value
Ethnic origin
Chinese	34 (52.3)	27 (51.9)	0.547
Malay	15 (23.1)	18 (34.6)
Indian	8 (12.3)	4 (7.7)
Others	8 (12.3)	3 (5.8)
Male gender	38 (58.5)	40 (76.9)	0.035
Gestational age (wk)	38 (37-39)	38 (37-39)	0.303
Birth weight (g)	2918 (2570-3245)	3068 (2753-3416)	0.114
Apgar
At 1 min	9 (6-9)	9 (9-10)	0.217
At 5 min	9 (8-9)	9 (9-10)	0.134
Cesarean section	25 (38.5)	14 (26.9)	0.190
Clinically ill status on presentation	52 (80.0)	22 (42.3)	< 0.001
LFT (at diagnosis)
Total bilirubin (µmol/L)	147 (100-201)	120 (91-163)	0.033
Conjugated bilirubin (µmol/L)	46 (32-65)	38 (30-74)	0.310
Conjugated fraction (%)	35.7 (24.0-51.4)	37.4 (26.3-61.5)	0.159
ALP (IU/L)	160 (119-261)	322 (238-418)	< 0.001
ALT (IU/L)	20 (13-42)	23 (16-32)	0.377
AST (IU/L)	35 (26-75)	35 (25-52)	0.512
GGT (IU/L)	142 (74-334)	199 (131-273)	0.045

ECHB: Early-onset conjugated hyperbilirubinemia; LCHB: “Late-onset” conjugated hyperbilirubinemia; LFT: Liver function test; ALP: Alkaline phosphatase; ALT: Alanine transaminase; AST: Aspartate transaminase; GGT: Gamma-glutamyl transferase.

Table 2 Comparison of causes between early-onset conjugated hyperbilirubinemia and "late-onset" conjugated hyperbilirubinemia groups n (%)

Etiology	ECHB (n = 65)	LCHB (n = 52)	Total (n = 117)	P value
Non-surgical causes	56 (86.2)	45 (86.5)	101 (86.3)	0.962
Multifactorial liver injury	39 (60.0)	18 (34.6)	57 (48.7)	0.007
Sepsis	9 (13.8)	3 (5.8)	12 (10.3)	0.154
Inborn errors of metabolism	3 (4.6)	1 (1.9)	4 (3.4)	0.428
CMV infection	0 (0)	2 (3.8)	2 (1.7)	0.112
Idiopathic	5 (7.7)	21 (40.4)	26 (22.2)	< 0.001
Surgical causes	9 (13.8)	7 (13.5)	16 (13.7)	0.952
Biliary Atresia	8 (12.3)	5 (9.6)	13 (11.1)	0.647
Choledochal cyst	1 (1.5)	2 (3.8)	3 (2.6)	0.435
Non-hepatic causes	48 (73.8)	23 (44.2)	71 (61)	0.001

ECHB: Early-onset conjugated hyperbilirubinemia; LCHB: “Late-onset” conjugated hyperbilirubinemia; CMV: Cytomegalovirus.

Table 3 Factors associated with multifactorial liver injury n (%)

Factors associated with multifactorial liver injury	ECHB (n = 39)	LCHB (n = 18)	Total (n = 57)
Antibiotics	38 (97.4)	18 (100.0)	56 (98.2)
Parenteral nutrition	35 (89.7)	16 (88.9)	51 (89.5)
Sedatives/opioid	29 (74.4)	14 (77.8)	43 (75.4)
Mechanical ventilation	26 (66.7)	12 (66.7)	38 (66.7)
Inotropic support	23 (59.0)	9 (50.0)	32 (56.1)
Recent surgery	20 (51.3)	12 (66.7)	32 (56.1)
PPHN	19 (48.7)	4 (22.2)	23 (40.4)
Intestinal obstruction	13 (33.3)	7 (38.9)	20 (35.1)
Congenital heart disease	12 (30.8)	4 (22.2)	16 (28.1)
HFOV	11 (28.2)	3 (16.7)	14 (24.6)
Pneumothorax	8 (20.5)	1 (5.6)	9 (15.8)
CDH	5 (12.8)	4 (22.2)	9 (15.8)
MAS	6 (15.4)	2 (11.1)	8 (14.0)
Renal impairment	6 (15.4)	2 (11.1)	8 (14.0)
Seizures/anti-epileptic	4 (10.3)	2 (11.8)	6 (10.7)
Perinatal asphyxia	3 (7.7)	3 (16.7)	6 (10.5)
Intracranial haemorrhage	2 (5.1)	1 (5.6)	3 (5.3)
Trisomy 21	2 (5.1)	1 (5.6)	3 (5.3)
ECMO	2 (5.1)	1 (5.6)	3 (5.3)
Turner’s syndrome	1 (2.6)	0	1 (1.8)
Trisomy 18	1 (2.6)	0	1 (1.8)

ECHB: Early-onset conjugated hyperbilirubinemia; LCHB: “Late-onset” conjugated hyperbilirubinemia; PPHN: Persistent pulmonary hypertension of the newborn; HFOV: High frequency oscillatory ventilation; CDH: Congenital diaphragmatic hernia; MAS: Meconium aspiration syndrome; ECMO: Extra-corporeal membrane oxygenation.

Table 4 Comparison of causes of early-onset conjugated hyperbilirubinemia and “late-onset” conjugated hyperbilirubinemia between subgroups of clinically well and unwell infants n (%)

	ECHB (n = 65)		LCHB (n = 52)
	Unwell (n = 52)	Well (n = 13)	Unwell (n = 22)	Well (n = 30)
Non-surgical causes
Multifactorial liver injury	39 (75.0)	0 (0)	18 (81.8)	0 (0)
Sepsis	9 (17.3)	0 (0)	3 (13.6)	0 (0)
Inborn errors of metabolism	3 (5.8)	0 (0)	1 (4.5)	0 (0)
CMV infection	0 (0)	0 (0)	0 (0)	2 (6.7)
Idiopathic	0 (0)	5 (38.5)	0 (0)	21 (70.0)
Surgical causes
Biliary atresia	0 (0)	8 (61.5)	0 (0)	5 (16.7)
Choledochal cyst	1 (1.9)	0 (0)	0 (0)	2 (6.7)

ECHB: Early-onset conjugated hyperbilirubinemia; LCHB: “Late-onset” conjugated hyperbilirubinemia; CMV: Cytomegalovirus.