it is estimated to be the most common cause of neonatal hospital readmission in north america ( 1 ) . it may lead to bilirubin accumulation in basal ganglia and brain stem nuclei and lead to kernicterus . if the infants survive the acute phase , which is marked by lethargy , hypotonia , poor feeding and opisthotonus , they may develop chronic encephalopathy . this condition is manifested by cerebral palsy , sensory neural hearing loss , dental dysplasia , upward gaze paralysis and mental retardation ( 2 ) . causes of severe neonatal hyperbilirubinemia are categorized either as hemolytic ( blood group mismatch , sepsis , g6pd deficiency ) or non - hemolytic ( breast feeding jaundice , internal hemorrhage , gestational diabetes , pyloric stenosis , hypothyroidism and some mutations in hepatic enzymes ) . prematurity , jaundice in the first 24 hours of life , jaundice noted before discharge from hospital , a history of jaundice treated with phototherapy in siblings and asian race are other predisposing factors for severe hyperbilirubinemia noted by various studies ( 3 - 5 ) . however , severe hyperbilirubinemia is mainly treated by exchange transfusion ( et).according to american academy of pediatrics ( aap ) , neonates with weight  2500 grams in healthy term , et is indicated when indirect bilirubin level reaches 25 mg / dl and 20 mg / dl and in cases with risk factors or gestational age of35 - 37 wk and well despite 6 hr of intensive phototherapy . in newborns of 35 - 37 wk and risk factors , et is indicated when the indirect bilirubin level reaches  18 mg / dl despite 6 hr of intensive phototherapy ( 2 ) . et is associated with many complications such as hypersensitivity reactions , sepsis , catheter - induced vascular damage , hypotension , necrotizing enterocolitis , etc ( 5 ) . the present study has been conducted to investigate the causes of severe hyperbilirubinemia leading to exchange transfusion from march 2009 to march 2011 in bahrami children hospital , tehran , iran . the aim was to identify neonatal predisposing factors that can be prevented by screening or other measures , thus reducing the incidence of kernicterus , which can be prevented and also to avoid et and its side effects . all infants below 30 days who underwent et for severe hyperbilirubinemia in bahrami children hospital during 2009 - 2011 were enrolled into this cross sectional study . a questionnaire prepared consisted of neonates gender , gestational age , age at the time of admission , birth weight , time of jaundice appearance , history of severe hyperbilirubinemia in siblings , blood group and rh of both mother and neonate , g6pd activity , complete blood count , reticulocyte count , peripheral blood smear , total and direct bilirubin before and after exchange transfusion , direct coombs in mother and indirect coombs in neonates , times of transfusion , any other diagnostic laboratory data based on attending neonatologist 's decision and the cause of hyperbilirubinemia stated by the attending neonatologist . criteria for diagnosis of abo incompatibility were type o maternal blood group and a , b or ab neonatal blood group associated with neonatal hb drop . positive coombs , peripheral blood spherocytosis and high corrected reticulocyte count were other diagnostic criteria . icteric breastfed newborns with the beginning of jaundice in the second or third day of life and 2% or more weight loss per day of life with or without uremia or hypernatremia were considered breastfeeding jaundice . during the study period , 94 neonates ( 56.4% boys and 43.6% girls ) underwent exchange transfusion due to severe hyperbilirubinemia . the infants had a mean birth weight of 195040 g and a mean gestational age of 35.21.4 weeks . fifty nine ( 63% ) of neonates were preterm , and history of neonatal jaundice in siblings was reported in 50% of cases . however , only 18(19% ) had a history of severe hyperbilirubinemia leading to et in their siblings . most cases ( 40.5% ) of severe hyperbilirubinmia started to become icteric on the second day after birth . first day jaundice was observed in 10 neonates , all of them due to hemolysis . table 1 shows a summary of underlying factors for severe hyperbilirubinemia according to the onset of jaundice . the majority of infants ( 91.5% ) had only one episode of et , and hemolysis was the sole underlying reason in the remaining who had 2 or 3 episodes of et . totally , after prematurity , the second most prevalent underlying factor for severe hyperbilirubinemia was breastfeeding jaundice that included 33(35% ) of neonates . we found that the next most prevalent causes were abo mismatch and g6pd deficiency ( table 2 ) . there was no kriglernajar cases in our study because no significant hyperbilirubinemia was found after discharging and fallow up . according to epidemiological studies , some risk factors are associated with severe hyperbilirubinemia in neonates . the risk factors are male gender , jaundice presenting in the first 24 hours after birth , jaundice noted at discharge from the hospital , previous sibling with jaundice , preterm labor , breast feeding , rh and abo incompatibility , g6pd deficiency and sepsis ( 4,6 ) . 
 
 according to the canadian pediatric society , gestational age of 35 - 36 weeks is an important risk factor for hyperbilirubinemia ( 7 ) . kuzniewicz et al also reported gestational age to be the main predictor of severe hyperbilirubinemia ( 8) . in our series , infants had a mean gestational age of 35.2 weeks and fifty nine ( 63% ) of neonates were preterm . most cases ( 40.5% ) of severe hyperbilirubinmia started on the second day after birth . this corresponds with views of american academy of pediatrics and canadian pediatric society , which recommend clinical assessment of infants for jaundice within the first 48 hours of birth ( 6 , 7 ) . however , clinical assessment of newborns is not an accurate means of assessing the severity of hyperbilirubinemia ( 1 ) . 
 
 in the present study , breastfeeding jaundice , as the most important factor associated with severe hyperbilirubinemia and according to salas and mazzi ( 9 ) , is encountered in 33(35% ) of cases . the data also corresponds with findings of huang et al ( 6 ) , who reported an odds ratio of 3.2 for severe hyperbilirubinemia in neonates who were breastfed ( 10 ) . guidelines advise mothers to nurse their infants at least 8 to 12 times per day for the first several days , rooming in with night feeding , discouraging 5% dextrose or water supplementation and ongoing lactation support for reducing the incidence of breast feeding jaundice ( 2 ) . 
 
 in this study , abo mismatch was the third most common cause of severe hyperbilirubinemia and accounted for 24.5% of cases . this is similar to the reports of badee and sanpavat who reported abo mismatch in 22% and 21.3% of cases , respectively ( 11 , 12 ) . however , according to canadian surveillance program , the most common causes of severe hyperbilirubinemia were incompatibility abo blood group and g6pd deficiency . the g6pd deficiency was the fourth most prevalent risk factor for severe hyperbilirubinemia leading to et and accounted for 12(12.8% ) of cases . badee also reported g6pd deficiency in 19.1% of neonates who underwent et ( 11 ) . according to johnson et al , g6pd deficiency was considered to be the main cause of hyperbilirubinemia in 19 of 61 ( 31.5% ) infants who developed kernicterus ( 14 ) . sepsis was the most common underlying cause for et in the study performed by koosha and rafizadeh ( 15 ) . prematurity was the most prevalent risk factor for severe hyperbilirubinemia . thus following protocols for prevention of premature labor is recommended . educating mothers for breast feeding in regard to the right times and method of feeding are important issue that should be considered . since blood group mismatch and g6pd deficiency were the third and fourth most prevalent underlying factors , screening infants for blood group and if proven to be cost effective , g6pd activity in the first day of life are also recommended . arranging earlier and continuous visits in neonates with these risk factors during the first four days of life are also mandatory .
background : severe neonatal hyperbilirubinemia is associated with significant morbidity and mortality . 
 this study was conducted to investigate the causes of severe hyperbilirubinemia leading to exchange transfusion ( et ) from march 2009 to march 2011 in bahrami children hospital , tehran , iran in order to establish guidelines to prevent profound jaundice & et . 
 methods : 94 neonates underwent et for severe hyperbilirubinemia data for demographic data , and onset of jaundice , history of severe hyperbilirubinemia in siblings , blood group of both mother and neonate , g6pd activity , hemoglobin , hematocrite , reticulocyte count , peripheral blood smear , total and direct bilirubin before and after et , direct and indirect coombs , times of transfusion and the cause of hyperbilirubinemia were all recorded for analysis . 

 results : ninety four neonates ( 56.4% boys and 43.6% girls ) underwent et with a mean birth weight of 195040 g and a mean gestational age of 35.21.4 weeks . 
 premature labor , breastfeeding jaundice , abo incompatibility and g6pdd with the frequency of 59(63% ) , 33(35% ) , 25(24/5% ) and 12(12.8% ) were of major causes of et . 
 conclusions : predisposing factors for severe hyperbilirubinemia in this study were premature labor , breastfeeding jaundice , abo incompatibility and g6pdd . the authors recommend prevention of premature labor , reevaluation of successful breastfeeding education for mothers and screening infants for blood group and g6pd in the first of life . arranging earlier and continuous visits in neonates with these risk factors during the first four 
 days of life is also recommended .