Estimated incidence of Crigler-Najjar syndrome(CNS) is 1 case per 1,000,000 births(1 million). The overall prevalence of CN syndrome is unknown, with only several hundred people reported to have this disease. It is interestingly very rare to encounter a pregnant adult women with congenital jaundice. Pregnancy in CN type II patients is a diagnostic and a therapeutic challenge because of the high risk of bilirubin encephalopathy with serious neurological damage as life-threatening complications for the fetus. To date 8 pregnancy outcome have been reported from 5 women and we report the6 woman with a successful 9 th pregnancy outcome. We have discussed detail history, presentation and management during pregnancy and care of the new born

Padmalatha, VV

Poornima, M

Rao, SR

Shakuntala, PN

English

Cognitive Sciences ePrint Archive

1 
 
  
 
 
Case Report: 
Successful Pregnancy Outcome in Maternal Crigler Najjar Syndrome Type II. 
Authors 
Shakuntala PN, Poornima M, Padmalatha VV, Shubha R Rao, 
Department of Obstetrics and Gynaecology, St. Martha’s Hospital, Bengaluru, India. 
Address for Correspondence 
Dr. Shakuntala PN, 
Department of Obstetrics and Gynaecology, 
St. Martha’s Hospital, 
Bengaluru, India.  
E-mail: shakuntala_pn@yahoo.com 
Citation 
Shakuntala PN, Poornima M, Padmalatha VV, Rao SR. Successful Pregnancy Outcome In Maternal Crigler Najjar Syndrome Type 
II. Online J Health Allied Scs. 2012;11(3):12. Available at URL: http://www.ojhas.org/issue43/2012-3-12.htm 
Open Access Archives 
http://cogprints.org/view/subjects/OJHAS.html 
http://openmed.nic.in/view/subjects/ojhas.html 
Submitted: Jul 29, 2012; Accepted: Oct 3, 2012; Published: Oct 25, 2012 
Abstract: Estimated incidence of Crigler-Najjar 
syndrome(CNS) is 1 case per 1,000,000 births(1 million). 
The overall prevalence of CN syndrome is unknown, with 
only several hundred people reported to have this disease. It 
is interestingly very rare to encounter a pregnant adult 
women with congenital jaundice. Pregnancy in CN type II 
patients is a diagnostic and a therapeutic challenge because of 
the high risk of bilirubin encephalopathy with serious 
neurological damage as life-threatening complications for the 
fetus. To date 8 pregnancy outcome have been reported from 
5 women and we report the6 woman with a successful 9 th 
pregnancy outcome. We have discussed detail history, 
presentation and management during pregnancy and care of 
the new born. 
Keywords: Crigler Najjer Syndrome type II; Unconjugated 
hyperbilurubinemia; Phenobarbitone; Phototherapy. 
 
Introduction 
Crigler Najjar Syndrome (CNS) is a rare autosomal recessive 
condition associated with two types in clinical practice. CNS 
Type I is characterised by complete deficiency and CNS type 
II by severely reduced activity of hepatic microsomal 
bilirubin- uridine 5-diphosphate-glucuronosyltransferase 
(UDPG-T)(1). First case of CNS type I was reported by 
Crigler and Najjar in 1952 which results in severe 
unconjugated hyperbilirubinemia and thus neurologic 
impairment (kernicterus) in the new born, Affected 
individuals do not respond to Phenobarbital therapy, need 
prolonged hours of intensive phototherapy, exchange 
transfusions and, without liver transplantation, usually die in 
infancy from kernicterus.(1,2) Arias first described CNS 
Type II, causes milder unconjugated hyperbilirubinemia and 
responds to phenobarbital treatment and present with 
episodes of jaundice responding to phenobarbitone.(3-5) The 
gene coding for UDPG-T, UGT1A1, has been mapped to 
2q37 and mutations associated with both type I and type II 
have been reported.(6-8) Maternal CNS type II is a rare 
clinical entity with only 8 pregnancies reported from 5 CNS 
type II pregnant women. We present the 9th pregnancy from 
6th woman with CNS type II. Due to paucity of information, 
we reviewed the literature and with the experience shared by 
authors,(9-17) were able to have a successful experience 
through out pregnancy, delivery and the puerperium and we 
are very grateful to all the authors. 
 
Case Report: 
A 27 year old Gravida 2, para 0, abortion 1, living 0, 
presented to us at 24 weeks of gestation, with complaints of 
malaise, low grade fever, yellow discolouration of sclera, 
high coloured urine. She revealed a past history of first 
episode of severe jaundice at 5 months of age requiring 
hospital admission, responded to phototherapy and daily dose 
of phenobarbitone. Multiple episodes of treatable jaundice 
were reported. As it is customery in hindu society(tamil 
origin), women being admitted repeatedly for problems are 
looked down upon and her mother took the help of ayurvedic 
practioner, which is indegenious to our country and had 
noticed alleviation of episodes of jaundice. Husband was also 
of tamil origin and was unaware of her situation. Following 
her first abortion 2 years back at 12 weeks of pregnancy 
associated with sever jaundice, she was investigated at a 
tertiary centre and produced a stamped referral slip as a case 
of Crigler Najjar syndrome type II. She responded to 
phenobarbitone 60 mg/day and 2 years later had a 
spontaneous conception, with no antenatal care at any 
medical centre. She looked deeply icteric and dehydrated 
with 24 weeks of pregnancy. After reviewing the earlier 
diagnosis and discussing with our gastroenterology collegues 
we decided to treat her with tablet phenobarbitone 60 mg 
once a day, maintain hydration and supportive care. Her 
complete haemogram was normal, anti HIV , anti HbsAg , 
anti HBC, anti HBE antibodies were negative. She had raised 
total bilurubin of 13.3 mg/dl, conjugate bilurubin of 0.1 
mg/dl, unconjugated bilurubin :13.2 mg/dl. Normal total 
proteins: 7.4 g/dl, albumin:4.1 mg/dl, normal liver 
enzymes.blood group was A negative and husband was A 
 
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positive Ultrasonography of upper abdomen was normal, 
without any organomegaly. Obstetric scan documented a 
single live intrauterine pregnancy with fetus in breech, 
corresponding to dates, normal placenta, liquor volume and 
no gross congential anomaly. A fetal echo performed was 
normal. She was kept on follow up every 2 weekly and we 
plotted her unconjugated bilurubin levels as shown in figure-
1 . at 29 completed weeks she had an episode of premature 
contractions and so we administered steroids to enhance fetal 
lung maturity. Her unconjugated bilurubin levels were 
between 8-9 mg/dl.we continued with phenobarbitone, oral 
haematenics, calcium, multi vitamin and protein 
supplements. She went into spontaneous labour at 35-36 
weeks of pregnancy and delivered a live male baby weighing 
2200 grams, length of baby was 43 centimeters with an 
APGAR score of 5,6,7,8 at1,5,10,and 15 minutes 
respectively, length of cord was 34 cms and shifted to 
neonatal intensive care unit. Neonate had the following 
Haemoglobin was - 16.9 gm% PCV: 57.3%. reticulocyte 
count-0.3%, total wbc count - 10,000 cells/mm3, Platelet 
count: 1.95 lakh/ mm3 PBS: normocytic and normochromic 
Blood group and type: A positive. Direct Coombs Test was 
negative. Total bilurubin- 12.1 mg/dl, direct- 0.6, indirect- 
11.5, C-Reactive Protien- 26 mg/litre. Neonatal 
hyperbilurubinemia table-2 and hypoglycaemia were treated 
with Intravenous Phenobarbitone. 5 mg/kg body weight 12 
hrly and dextrose bolus respectively. By 16 hours of birth 
baby needed phototherapy as his total bilurubin was stalling. 
Hence, intensive phototherapy has to be started, total serum 
bilurubin levels started to decline , by day 5 total Serum 
bilurubin reached values below 5 mg/dl and declined to reach 
3.3 mg/dl and 1.3 mg/dl by day 8 and 14 respectively. Baby 
was discharged on day 14 . 
 
Discussion 
Crigler-Najjar Syndrome (CNS) is a rare autosomal recessive 
disorder of bilurubin conjugation as substantiated by many 
authors.(6-8) Incidence of CNS is probably less than 1 case 
per 1,000,000 births. Only a few hundred cases have been 
described in literature and the exact prevalence is unknown 
(Table-1). 
Type I presents at birth and is more severe form associated 
with kernicterus and neurologic morbidity, whereas, type II 
CNS has late neonatal presentation, lower serum 
unconjugated bilurubin concentration, which responds to 
phototherapy and phenobarbital therapy. 
Due to the rarity of the condition, about 4 pregnancies have 
been reported in 4 cases of maternal CNS type I and 8 
pregnacies from 5 maternal CNS type II (Table-1). 
With the knowledge we gained by reviewing the literature we 
realised it would be prudent to start phenobarbital therapy 
from her past history, rather than debate her genetic basis and 
perform a liver biopsy which she anyway declined. Gilbert’s 
syndrome was the other possibility, usualty it presents with 
hyperbilurubinemai during puberty possibly because of the 
inhibition of bilirubin glucuronidation by endogenous steroid 
hormones. Anti HIV, anti HbsAg, anti HBC, anti HBE 
antibodies were negative ruling out hepatitis, she was not in 
sepsis as total count was 10,000 cells/mm3. Her blood group 
was A Rh typing was negative. We kept her on a close follow 
up for every two weekly serum total, conjugated and 
unconjugated bilurubin levels which is depicted in Figure-1. 
 
 
 
 
 
 
 
 
Table 1: Review of literature 
Author, 
year 
Disease 
type 
Mater
nal 
serum 
bilir-
ubin, 
mg/dl 
Maternal 
treatment 
Delivery 
Newborn 
treatment/ 
outcome 
Taylor et 
al (9), 
1991 
CNS type 
I 
17–
21.8 
None 
Caesarean 
section 
Phototherapy/ 
quadriplegic 
Smith et 
al(10)., 
1994 
CNS type 
II 
5.3–9.6 None 
Spontane
ous, 
vaginal, 
at term 
No treatment 
required/normal 
Ito et 
al(11).,200
1 
CNS type 
II(2 
pregnanci
es) 
NA 
Phototherap
y, 
Phenobarbit
al 
NA Normal 
Holstein et 
al.(12), 
2005 
CNS type 
II 
4.2–8.9 
Phototherap
y, 
Phenobarbit
al 
Primary 
caesarean 
section 
No treatment 
required/normal 
Pinkee et 
al.(13), 
2005 
CNS type 
II 
10.8 (at 
deliver
y) 
None 
Spontane
ous, 
vaginal, 
at term 
Blood 
transfusion, 
phototherapy, 
phenobarbital/n
ormal 
Gajdos et 
al.(14), 
2006 
CNS type 
I 
13.5–
23.5 
Phototherap
y, Albumin 
infusions 
Caesarean 
section 
Phototherapy/no
rmal 
Passuello.(
16) V et al 
2009 
CNS type 
II 
4–6 
mg/dl 
Phenobarbit
one and 
insulin for 
GDM 
Vaginal Normal 
Hannam.S 
et al,(17) 
2008 
CNS type 
I 
200-
300 
micro 
mol/L 
Phototherap
y 
Emergenc
y 
cesarean 
Phototherapy 
and 
phenobarbitone, 
double 
exchange 
transfusion 
Hannam.S
,et al(17) 
2008 
CNS type 
I 
399-
510mic
ro 
mol/L 
Phototherap
y, Albumin 
Vaginal 
Phototherapy 
and 
phenobarbitone, 
double 
exchange 
transfusion 
Holstein et 
al.(15), 
2010 
CNS type 
II, 2 
pregnanci
es 
4.2 
mg/dl 
and 5.5 
mg/dl 
until 
deliver
y. 
Phototherap
y, 
Phenobarbit
one 
Both 
pregnanci
es 
primary 
caesarean 
section 
No treatment 
required/normal 
Shakuntal
a et al 
2012, 
Present 
case 
CNS type 
II 
8-9 
mg/dl 
until 
deliver
y 
Phenobarbit
one 
Spontane
ous 
vaginal 
Phototherapy 
and 
phenobarbitone/ 
normal. 
NA: not available 
Values have  ranged from 4.2-10.8 mg/dl, present case it was 
maintained between 8-9 mg/dl on Phenobarbital therapy 60 
mg daily. Similar observations were shared by other 
authors.(10-13,15,16) Good maternal and fetal outcomes 
have been reported when, dual treatment consisting of 
phototherapy during embryogenesis and phenobarbital during 
the rest of the pregnancy.(15) Though we did not have an 
opportunity to use phototherapy during the embryogenesis as 
the patient registered with us at 24 weeks, our maternal and 
fetal outcomes concur with Ito et al and Holstein et al, 
Passuello V et al.(11,12,15,16) Rest of the pregnancy and 
antenatal care was carried out as usual procedure with the 
fetal anomaly scan, cardiac scan,growth parameter, liquor 
volume , placental maturity all were correlating with the 
period of gestation. She had an episode of preterm pain at 29 
3 
 
weeks of gestation and betamethasone 12 miiligrams was 
given intramuscularly 24 hours apart to enhance lung 
maturity, to prevent the further burden on immature liver. 
However, she continued pregnancy and delivered a male 
baby weighing 2200 grams, length of 43 centimeters at 35-36 
weeks of gestation. Baby had initial cyanosis and on bagging 
and masking the APGAR score improved. But, due to the 
high risk associated with preterm birth and maternal CNS 
type II ,baby was immediately transferred to the neonatal 
intensive care unit. Figure 2 reflects the serial serum total 
bilurubin levels measured in the baby. At 4 hours and 16 
hours of birth total bilurubin levels were 11.5 mg/dl and 11.2 
mg/dl even with commencement of f intravenous 
phenobarbitone 5 mg/kg body weight.hence intensive 
phototherapy was started at 16 hours of birth. Baby recovered 
by 8 days and was discharged on request by the parents. 
Baby had normal developmental miles stones until 1 year of 
follow up. Similar treatment modalities and nennatal 
outcomes have been report by some authors.(10-13,15,16) 
We continued the use of oral Phenobarbital therapy in the 
mother who later followed up with gastroenterologists. She 
did not report any puerperial problems. 
 
Figure:1 Maternal levels of unconjugated bilurubin in 
mg/dl plotted on the Vertical axis.Horizontal axis depicts 
pregnancy in weeks, PD-1 week post delivery. Inital 
values of 13.03 mg/dl has substantially decreased 
following the start of Phenobarbital therapy- 60 mg/day-
red line. 
 
Figure 2: Neonatal total serum bilurubin levels .Vertical 
axis –mg/dl and neonatal age in hours after birth on 
horizontal axis, d- days. 
We report this case due to its rarity, may be the 6th case of 
maternal Crigler-Najjar Syndrome Type II who successfully 
delivered the 9th such baby. When suddenly encountered by 
such pregnant women with congenital jaundice we were 
faced with a clinical dielemma, as to are we offering the 
correct standard of care to optimise the maternal and fetal 
outcome? This clinical scenario also highlights the 
importance of basic history taking and consider this condition 
also in the differential diagnosis of hyperbilurubinemia in 
pregnancy, which typically has elevated uncongugated 
bilurubin levels, normal liver enzymes and proteins, may be 
with an affected member in the family. 
Data suggest that pregnancy need not be contraindicated in 
Crigler-Najjar Syndrome Type II. But prompt recognition 
and interdisciplinary involvement of paediatrician, 
obstetrician, gastroenterologists, blood bank officer and 
laboratory technician in these high risk pregnancies we can 
achieve optimum maternal and fetal outcome( prevent 
neurologic morbidity and sequale). 
Acknowledgement: 
We would like to thank the patient and her family for their 
ever day to day co-operation. We also thank all the members 
of Department of Obstetrics, Paediatrics, Gastroenterology, 
Medicine, Bood bank officials, maternity nurses, Lab 
technicians and pharmacy members for their valuable inputs. 
We are grateful to sisters of Good Sheperd convent for all the 
moral, spiritual and financial support rendered to the patient 
and her family, without their help we clinicians would not be 
able to report this case. 
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Successful Pregnancy Outcome In Maternal Crigler Najjar Syndrome Type II.

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