BACKGROUND AND OBJECTIVES: The cause of hyperbilirubinemia cannot be found in 
about 45% of cases of neonatal jaundice. Gilbert syndrome (GS) is the most 
common congenital disease associated with bilirubin metabolism in the liver. 
Since the screening value of genetic tests cannot be fully determined until 
accurate data on the prevalence and penetrance of the GS genotype are known, we 
sought to estimate whether the prevalence of GS is higher in the parents of 
neonates with severe unexplained indirect hyperbilirubinemia.
DESIGN AND SETTING: Case-control study of parents of neonates with severe 
unexplained indirect hyperbilirubinemia admitted to a neonatal ward.
METHODS: We used the rifampin test (checked bilirubin before and 4 hours after 
administration of 600 mg rifampin) for diagnosis of GS in parents of 115 
neonates with severe unexplained indirect hyperbilirubinemia. We compared the 
prevalence of GS in these parents with that of a control group of 115 couples 
referred for premarital counseling.
RESULTS: The 115 neonates were aged 5.2 (1.6) days (mean, standard deviation), 
all were breast-fed, and males constituted 56.5%. Mean total serum bilirubin 
(TSB) level was 20.96 (5.48) mg/dL. 14.8% were glucose 6 phosphate dehydrogenase 
(G6PD) deficiency was present in 14.8%, and 10.4% had A, B or O blood group 
(ABO) incompatibilities with their mothers. There was no difference in the 
prevalence of GS between parents of the group with hyperbilirubinemia (22.2%) 
and the control group (19.13%) (P=.42). Mean TSB in neonates with parents who 
had GS was more (about 3 mg/dL) than in neonates with normal parents (P=.004). 
Fathers had GS twice as often as the mothers among the parents of neonates with 
hyperbilirubinemia (P=.003), among the control group (P=.009) and among neonates 
(P=.014).
CONCLUSION: This study showed that GS cannot cause severe indirect 
hyperbilirubinemia by itself, but it may have a summative effect on rising 
bilirubin when combined with other factors, for example, G6PD. Our results 
showed that in GS, males are affected about twice as much as the females.