Neonatal jaundice in full-term infants. Role of breast-feeding and other causes

Serum bilirubin determinations were performed on 264 term infants who were consecutively delivered via the vaginal route. Forty-one infants (15.5%) had serum bilirubin concentrations greater than 12 mg/dL. No cause for this was found, initially, in 23 (56%) of these infants. On the third hospital day, the mean (+/- SD) serum bilirubin level was 6.9 +/- 3.6 mg/dL in breast-fed infants and 6.5 +/- 3.2 mg/dL in bottle-fed infants. Of the 23 infants without obvious cause for hyperbilirubinemia, eight (four bottle-fed and four breast-fed infants) had serum bilirubin concentrations greater than 12 mg/dL on the third hospital day, whereas in 15 (14 breast-fed infants and one bottle-fed infant), the elevated serum bilirubin level occurred on day 4 or 5. Breast-feeding does not seem to affect the total serum bilirubin level in the first three days of life but may be associated with an increased incidence of hyperbilirubinemia subsequently. In a normal full-term population, routine investigations do not disclose a cause for hyperbilirubinemia in about half of the patients.     

Jaundice in the healthy newborn infant: a new approach to an old problem

We measured the serum bilirubin concentrations in 2,416 consecutive infants admitted to our well baby nursery. The maximal serum bilirubin concentration exceeded 12.9 mg/dL (221 mumol/L) in 147 infants (6.1%), and these infants were compared with 147 randomly selected control infants with maximal serum bilirubin levels less than or equal to 12.9 mg/dL. A serum bilirubin concentration greater than 12.9 mg/dL was associated strongly with breast-feeding (P = .0000) and percentage of weight loss after birth (P = .0001), as well as with maternal diabetes, oriental race, decreased gestational age, male sex, bruising, and induction of labor with oxytocin. Risk ratios and the risk of jaundice were calculated for hypothetical infants in the presence and absence of these variables. These calculations show that, in certain infants, "nonphysiologic" jaundice is likely to develop and its presence in such infants might not require laboratory investigations. In others, a modest degree of hyperbilirubinemia could be cause for concern. An awareness of these factors and their potential contribution to serum bilirubin levels permits a more rational approach to the action levels used for the investigation of jaundice in the newborn. We need a new definition of physiologic jaundice.     

Serum bile acids and their conjugates in breast-fed infants with prolonged jaundice

Serum bile acids and their conjugates were analysed in 20 breast-fed infants with prolonged jaundice. The mean total bile acid levels in serum were increased in the breast-fed infants with jaundice, as compared with those in either breastor bottle-fed infants without jaundice. However, there were no significant differences between the groups. All the breast-fed infants examined, regardless of association with jaundice, had a bile acid pattern dominated by taurine conjugates (the ratio of glycine- to taurine-conjugated bile acid, G/T ratio, less than 1.00). In contrast, the bottle-fed infants without jaundice had a pattern dominated by glycine conjugates (G/T ratio, more than 1.00). Among the breast-fed infants with jaundice, the mean G/T ratio in those who had serum bilirubin levels over 10 mg/100 ml was significantly lower than that in those who had serum bilirubin levels of less than 10 mg/100 ml. The altered bile acid metabolism might be associated with the pathology of breast milk jaundice.Abbreviation LP-X lipoprotein-X     

Fecal bilirubin excretion and serum bilirubin concentrations in breast-fed and bottle-fed infants

To assess the rate of excretion of bilirubin in the stools and its effects on serum bilirubin concentrations, we studied 24 breast-fed and 13 bottle-fed infants during the first 3 days after birth. Bottle-fed infants passed significantly more stool (3-day totals, 82 vs 58 gm, P less than 0.001), excreted more bilirubin (3-day totals, 23.8 vs 15.7 mg, P less than 0.05), and had lower serum bilirubin values (day 3, 6.8 vs 9.5 mg/dl, P less than 0.02). Among the breast-fed infants, greater stool output was associated with greater fecal bilirubin excretion (r = 0.56, P less than 0.05) and lower serum bilirubin concentrations (r = 0.66, P less than 0.001). Our data suggest that hyperbilirubinemia in breast-fed infants may be related to a delay in bilirubin clearance resulting from low stool output.     

Extreme hyperbilirubinemia in newborn infants

This study was undertaken to determine the frequency and investigate the etiology of extreme hyperbilirubinemia (total serum bilirubin [TSB]>or=25 mg/dL [428 micromol/L]) in newborns admitted to a neonatal intensive care unit in southern Turkey. The charts of 93 term and near-term infants admitted with TSB levels of 25 mg/dL (428 micromol/L) or greater in the first 30 days after birth were retrospectively reviewed. During the 4.5-year study period, 774 infants were admitted to our unit with neonatal jaundice. Ninety-three (12%) of these infants had TSB levels of 25 mg/dL (428 micromol/L) or greater. The mean TSB level in the 93 cases was 30.1+/-5.7 mg/dL (514.7+/-97.5 micromol/L), and the peak levels ranged from 25.0 to 57.4 mg/dL (428-981.5 micromol/L). Thirty-three (35.5%) of the 93 babies had TSB levels of 30 mg/dL (513 micromol/L) or greater. Eighty-nine of 93 infants were being exclusively breast-fed. Nineteen babies were isoimmunized, 7 were bacteremic, 2 of the 39 babies tested for glucose-6-phosphate dehydrogenase had this enzyme deficiency, and 1 of the 71 infants tested for thyroid function had hypothyroidism. No cause for extreme hyperbilirubinemia was found in 61 (65.6%) cases.     

The natural history of neonatal jaundice

The relationship between infant feeding type and the occurrence and natural history of neonatal jaundice in term newborn infants has been studied. A retrospective chart review of 124 records confirmed earlier reports indicating that jaundice is recognized more often in breast-fed than in formula-fed infants. A prospective cohort study of 140 term newborn infants was conducted using the Minolta Air-Shields transcutaneous jaundice meter. For 3 weeks, 115 white infants and 25 black infants were followed at predetermined intervals. The peak jaundice meter readings were higher and the elevated levels lasted longer in breast-fed than in formula-fed infants. Formula-fed infants' readings returned to base-line levels in eight days whereas the readings were still elevated in breast-fed infants when the study ended on the 21st day. Black infants had higher transcutaneous readings than white infants due to their deeper skin pigmentation, but otherwise they followed a course identical with that of the white babies. The distribution of jaundice in the white infants was bimodal; in approximately one fourth of the breast-fed infants, the jaundice meter readings reached levels corresponding to bilirubin values greater than 13 mg/dL whereas the remaining three fourths followed a pattern similar to that of the formula-fed infants. It can be concluded that human milk feeding is associated with more prolonged hyperbilirubinemia than formula-feeding in normal term infants.     

Weight loss and hypernatremia in breast-fed babies: frequency in neonates with non-hemolytic jaundice

OBJECTIVE: The aim of this study was to determine what proportion of newborns admitted with idiopathic non-hemolytic hyperbilirubinemia exhibit severe weight loss and hypernatremia. METHODS: The prospective study involved 115 infants >48 h old who were admitted with jaundice between July 2002 and July 2003, and had unconjugated bilirubin levels >12 mg/dL. Premature babies (gestational age <37 weeks) and those with hemolytic jaundice and other pathologic causes of non-hemolytic jaundice were excluded. Postnatal age (days) at admission, bodyweight at admission, weight change since birth (percentage weight loss calculated at admission) and mode of feeding (breast-feeding, formula feeding, mixed feeding) were recorded. Severe weight loss was defined in babies who showed >10% weight loss or had not regained enough to reach birthweight by postnatal day 10. Serum Na levels and breast-milk Na levels were also measured. RESULTS: Twenty-eight (33%) of the 86 newborns with idiopathic hyperbilirubinemia in the study exhibited severe weight loss. Almost all the 86 babies were exclusively breast-fed, and 10 babies (12%) had severe weight loss combined with hypernatremia. The group with severe weight loss and hypernatremia had higher breast-milk Na levels than the other infants. CONCLUSION: The results indicate that a large proportion of babies with non-hemolytic jaundice have severe weight loss, and that breast-fed newborns with the combination of weight loss and hypernatremia may present with non-hemolytic jaundice.     

Vitamin K deficiency in newborns: a case report in alpha-1-antitrypsin deficiency and a review of factors predisposing to hemorrhage

A 4-week-old, breast-fed female infant appeared healthy until signs and symptoms of CNS deterioration suddenly occurred. At presentation the infant was found to have a left-sided parietal intracerebral hematoma, markedly prolonged prothrombin time, and partial thromboplastin time, normal platelet count, and jaundice with a total and direct serum bilirubin level of 5.4 mg/dL and 2.6 mg/dL, respectively. Vitamin K1 and fresh frozen plasma returned the prothrombin time and partial thromboplastin time to normal values within 18 hours, suggesting that the infant had severe vitamin K deficiency complicated by intracerebral hemorrhage. Evaluation of the infant's direct hyperbilirubinemia led to the diagnosis of homozygous (pi-type ZZ [PiZZ] ) alpha-1-antitrypsin deficiency. The clinical circumstances predisposing to vitamin K deficiency in newborns and infants are discussed. Based on our observations in this case, we suggest that cholestatic liver disease should be suspected when unexplained vitamin K deficiency occurs in early infancy. The role of vitamin K in hemostasis and the laboratory diagnosis of vitamin K deficiency are discussed as they apply to the evaluation of hemorrhage in newborns and infants.     

Neonatal hyperbilirubinemia in African American males: the importance of glucose-6-phosphate dehydrogenase deficiency

OBJECTIVE: To perform risk factor analysis for the prediction of hyperbilirubinemia in an African American male neonatal cohort. STUDY DESIGN: A database of 500 previously published term and near-term African American male neonates was further analyzed to determine the role of risk factors for hyperbilirubinemia. Factors studied included birth weight >/=4.0 kg, gestational age /=75(th) percentile. Hyperbilirubinemia was defined as any bilirubin value >/=95(th) percentile on the hour-of-life-specific bilirubin nomogram. RESULTS: Forty-three (8.6%) neonates developed hyperbilirubinemia. At 48 +/- 12 hours, median transcutaneous bilirubin was 8.3 mg/dL, 75(th) percentile 10.0 mg/dL, and 95(th) percentile 12.6 mg/dL. Of the risk factors, only exclusive breast-feeding, G-6-PD deficiency and predischarge bilirubin >/=75(th) percentile were significant (Adjusted Odds Ratios [95% Confidence Intervals; CI] 3.15 [1.39-7.14], P = .006; 4.96 [2.28-10.80], P = .001; and 7.47 [3.50-15.94], P < .0001, respectively). G-6-PD-deficient neonates who were also premature and breast-feeding had the highest incidence of hyperbilirubinemia (60%). CONCLUSIONS: African American male neonates may be at higher risk for hyperbilirubinemia than previously thought. Screening for G-6-PD deficiency and predischarge bilirubin determination may be useful adjuncts in hyperbilirubinemia prediction in these newborns.     

Incidence of hyperbilirubinemia in breast- vs. formula-fed infants

A retrospective study of 233 consecutively born full-term infants was performed to determine the effect of several variables on the development of hyperbilirubinemia. Thirty-five (15%) of the infants developed peak bilirubin levels greater than 12 mg/dl in the first week of life. Step-wise multiple regression analysis revealed that breast-feeding was the most predictive of a group of eight variables for the development of hyperbilirubinemia greater than 12 mg/dl. The correlation between type of feeding and hyperbilirubinemia was significant (p less than 0.02). None of the other factors evaluated was significantly associated with hyperbilirubinemia. Breast-fed infants also were found to have a significantly higher incidence of hyperbilirubinemia greater than 15 mg/dl; 12 of 101 (12%) infants compared with 2 of 117 (2%) formula-fed infants (p less than 0.002). This group of infants accounted for the increased incidence of hyperbilirubinemia greater than 12 mg/dl in breast-fed infants. There was no significant correlation between weight loss and development of hyperbilirubinemia in the breast-fed infants.     

Alterations of serum bile acid profile in breast-fed infants with prolonged jaundice

Serum bile acid conjugates in breast-fed infants with prolonged jaundice were analyzed by a newly developed procedure using high-performance liquid chromatography with fluorescence labeling. Major bile acids were cholate and chenodeoxycholate conjugates. Some of the breast-fed jaundiced infants had high levels of serum bile acid conjugates (greater than 25 mumol/L), but the mean levels of individual bile acid conjugates found in jaundiced breastfed infants were not significantly different from those in breast-fed infants without jaundice. The glycine- to taurine-conjugated bile acid ratio in breast-fed jaundiced infants was significantly lower than in breast-fed nonjaundiced infants or bottle-fed nonjaundiced infants. In breast-fed infants, the portion of taurine-conjugated bile acids increased in proportion to serum bilirubin levels. These findings suggest that alteration in conjugated bile acid patterns of breast milk jaundice is related to an increased enterohepatic circulation of bile acids as well as bilirubin in infants fed on breast milk that contains high amounts of taurine.     

The occurrence and significance of the bilirubin species, including delta bilirubin, in jaundiced infants

An improved technique for bilirubin analysis, using high-performance liquid chromatography, has enabled us to study the occurrence and significance of four species of bilirubin (unconjugated, monoconjugated, diconjugated, and delta bilirubin) in 40 infants with jaundice of various etiologies. We found that: (a) infants with indirect hyperbilirubinemia showed greater than 90% of their total serum bilirubin as unconjugated bilirubin. The small remaining fraction consisted of conjugated bilirubin; predominantly delta bilirubin (5%); (b) infants with elevated direct serum bilirubin (greater than or equal to 2 mg/dl) showed almost twice more monoconjugated than diconjugated bilirubin fractions; (c) the standard diazo test for bilirubin analysis underestimates the direct bilirubin by as much as 34%; and (d) delta bilirubin, a tightly protein bound bilirubin, was observed in significant amounts in infants with elevated direct bilirubin. Its concentration, which ranged from 10-73% of the total bilirubin, was related to the duration rather than to the cause of the jaundice. It was also observed at birth in an infant with giant-cell hepatitis. It is concluded that the identification of more specific bilirubin species in jaundiced infants, especially in those with elevated direct serum bilirubin, will further help in the understanding and management of their disease.     

Enterohepatic circulation of nonconjugated bilirubin in rats fed with human milk

To test the hypothesis that enhanced intestinal absorption of bilirubin may contribute to prolonged nonconjugated hyperbilirubinemia in human milk-fed infants, we studied a cross-section of 36 healthy infants and mothers. Milk from mothers and serum from infants were collected at 16.3 +/- 2.4 days. Milk was studied for its effect on the absorption of bilirubin labeled with carbon 14 in rats and compared with buffer and iron-fortified infant formula (Similac With Iron). The percentage of a 1 mg bilirubin dose absorbed by the rat was 25.29 +/- 4.0% when it was administered into the duodenum with buffer, 4.67 +/- 2.4% with Similac formula, and 7.7 +/- 2.9% with human milk. Linear regression analysis, using the infant's serum nonconjugated bilirubin level as the dependent variable and the percentage of (14C)bilirubin absorbed by the rat with the corresponding mother's milk as the independent variable, revealed a significant correlation (r = 0.40; p = 0.016). Inspection of the data suggested that absorptive permissiveness correlated closely with infant serum bilirubin values greater than 24 mumol/L (1.4 mg/dl) (r = 0.55; p = 0.007), whereas in those with bilirubin values less than or equal to 24 mumol/L, there was no apparent correlation. Milk was also analyzed for beta-glucuronidase, nonesterified fatty acids, and the ability to inhibit glucuronosyltransferase activity of rat liver microsomes in vitro, none of which correlated with the infant's serum bilirubin. These data support the theory that enhanced intestinal absorption of bilirubin contributes to the jaundice associated with breast-feeding.     

Breast-feeding-associated hypernatremia: retrospective analysis of 169 term newborns.

BACKGROUND: The aim of the present paper was to define the incidence, complications, morbidity and mortality of hypernatremic dehydration due to inadequate breast-feeding in a neonatal intensive care unit. METHODS: A retrospective study was carried out between 2002 and 2005, to identify the term breast-fed neonates with serum sodium level > or =150 mEq/L at the Ministry of Health Ankara Diskapi Children's and Research Hospital. RESULTS: The incidence of hypernatremic dehydration secondary to inadequate breast-feeding was 4.1%, occurring in 169 term infants among 4136 hospitalized term neonates with the following characteristics: mean gestational age, 39.1 weeks (37-42 weeks); birthweight, 3352 g (2200-4500 g); mother's age, 26.1 years (17-38 years); weight loss, 15.9% (5.4-32.7%); proportion of spontaneous vaginal deliveries, 75.7%; and proportion of first-time mothers, 74.6%. Major presenting symptoms were neonatal jaundice (47.3%) and poor infant suck (29.6%). The median sodium; blood urea nitrogen (BUN); and creatinine levels on admission were 155 mmol/L (150-194 mmol/L), 35 mg/dL (7-253 mg/dL), and 0.9 mg/dL (0.2-10 mg/dL), respectively. Major complications were as follows: acute renal failure, 82.8%; elevated liver enzymes, 20.7%; disseminated intravascular coagulation, 6.5%; brain edema, 5.2%; intracranial hemorrhage, 3.6%; cavernous sinus thrombosis, 1.2%; and bilateral iliac artery thrombosis, 0.6%. Ten patients (5.9%) developed seizure within the first 24 h of rehydration therapy with a mean sodium decrease of 11.9 mmol/L per day (4-19 mmol/L per day). Two patients (1.2%) died. There were positive correlation between weight loss and serum sodium, BUN, bilirubin levels (P < 0.01); there was no correlation between weight loss and mothers' age, education level, delivery route, or first-born status (P > 0.05). CONCLUSIONS: Hypernatremic dehydration in neonates due to inadequate breast-feeding is a serious, potentially devastating and life-threatening disorder, and can damage the central nervous system. Follow up of infants for adequate breast-feeding is important. Pediatricians must maintain a high level of suspicion, especially in cases of pathologic infant weight loss after delivery.     

An evidence-based review of important issues concerning neonatal hyperbilirubinemia

This article is adapted from a published evidence report concerning neonatal hyperbilirubinemia with an added section on the risk of blood exchange transfusion (BET). Based on a summary of multiple case reports that spanned more than 30 years, we conclude that kernicterus, although infrequent, has at least 10% mortality and at least 70% long-term morbidity. It is evident that the preponderance of kernicterus cases occurred in infants with a bilirubin level higher than 20 mg/dL. Given the diversity of conclusions on the relationship between peak bilirubin levels and behavioral and neurodevelopmental outcomes, it is apparent that the use of a single total serum bilirubin level to predict long-term outcomes is inadequate and will lead to conflicting results. Evidence for efficacy of treatments for neonatal hyperbilirubinemia was limited. Overall, the 4 qualifying studies showed that phototherapy had an absolute risk-reduction rate of 10% to 17% for prevention of serum bilirubin levels higher than 20 mg/dL in healthy infants with jaundice. There is no evidence to suggest that phototherapy for neonatal hyperbilirubinemia has any long-term adverse neurodevelopmental effects. Transcutaneous measurements of bilirubin have a linear correlation to total serum bilirubin and may be useful as screening devices to detect clinically significant jaundice and decrease the need for serum bilirubin determinations. Based on our review of the risks associated with BETs from 15 studies consisting mainly of infants born before 1970, we conclude that the mortality within 6 hours of BET ranged from 3 per 1000 to 4 per 1000 exchanged infants who were term and without serious hemolytic diseases. Regardless of the definitions and rates of BET-associated morbidity and the various pre-exchange clinical states of the exchanged infants, in many cases the morbidity was minor (eg, postexchange anemia). Based on the results from the most recent study to report BET morbidity, the overall risk of permanent sequelae in 25 sick infants who survived BET was from 5% to 10%.     

Risk of sepsis in newborns with severe hyperbilirubinemia.

Because bacterial infection is a potential cause of hyperbilirubinemia, some authors suggest that newborns with significant unexplained indirect hyperbilirubinemia should be evaluated for sepsis. We reviewed the charts of 306 newborns admitted to a pediatric ward within 21 days of birth with a diagnosis of indirect hyperbilirubinemia (peak serum bilirubin level 316 +/- 48, range 217 to 498 mumol/L) (18.5 +/- 2.8, 12.7 to 29.1 mg/dL). Ninety percent were fully or partially breast-fed. Sepsis was identified in 0 of 306 newborns (upper 95% confidence limit for the risk of sepsis = 1%). The overwhelming majority of newborns who require readmission to hospital for indirect hyperbilirubinemia are healthy, breast-fed newborns and do not need to be investigated for sepsis. If indirect hyperbilirubinemia is ever the only manifestation of bacteremia or incipient sepsis, it must be a rare event.     

Neonatal hyperbilirubinemia associated with glucose-6-phosphate dehydrogenase deficiency in Sephardic-Jewish neonates: incidence, severity, and the effect of phototherapy.

Glucose-6-phosphate dehydrogenase (G-6-PD) deficiency is frequently associated with neonatal hyperbilirubinemia, and sometimes kernicterus, often in the absence of any identifiable trigger or hematological evidence of hemolysis. The aim of this study was to compare the incidence and severity of, and the effect of phototherapy on, jaundice in G 6-PD-deficient vs G-6-PD-normal neonates in the Sephardic-Jewish community. Healthy term newborns, born to mothers of families stemming from geographic areas known to be "at risk" for G-6-PD deficiency, were screened for the condition and surveyed for hyperbilirubinemia. Seventy-five G-6-PD-deficient neonates formed the study group, while 266 neonates with normal levels of the enzyme formed the control group. Neonates with any other identifiable cause for jaundice were excluded. Phototherapy was commenced when the serum bilirubin levels reached 16 mg/dL (274 mumol/L) or more, and it was discontinued at 12 mg/dL (205 mumol/L) or less. Hyperbilirubinemia developed in 27 (36%) of the deficient neonates (serum total bilirubin greater than 13.9 mg/dL [238 mumol/L]), compared with 50 (18.8%) of control neonates (P = .002), while 20 (26.7%) of the study group required phototherapy, compared with 31 (11.7%) of control neonates (P = .002). Two neonates in the study group required exchange transfusion (serum bilirubin greater than 20 mg/dL [342 mumol/L]), vs 0 in the control group (not significant).(ABSTRACT TRUNCATED AT 250 WORDS)     

Gilbert's syndrome is a contributory factor in prolonged unconjugated hyperbilirubinemia of the newborn

OBJECTIVE: Prolonged neonatal jaundice, beyond day 14 of life, is very common and of concern to the clinician. The aim of this study was to investigate whether a genetic mutation in the bilirubin UGT1A1 gene, which has been associated with Gilbert's syndrome in adults, is a contributory factor in prolonged neonatal jaundice. STUDY DESIGN: Blood was collected from 85 term newborns with unexplained hyperbilirubinemia, and DNA was prepared. The neonates were divided into 6 groups depending on whether they were breast-fed or bottle-fed and whether they had acute, prolonged, or very prolonged jaundice. UGT1A1 TATA promoter genotyping (DNA test for Gilbert's syndrome) was performed on all samples, and analysis of the entire UGT1A1 coding sequence was performed in a representative sample (11 of 26) of very prolonged cases. RESULTS: In addition to the known common UGT1A1 TATA alleles (TA6 and TA7), a novel TATA allele (TA5) in a neonate with very prolonged jaundice was identified. Statistical analysis of the TATA genotype distributions within the group of breast-fed neonates revealed significant differences among the acute, prolonged, and very prolonged subgroups (.05 > P >.01): the incidence of familial hyperbilirubinemia genotypes (7/7 and 5/7) is 5 times greater in very prolonged cases (31%) relative to acute cases (6%). Neonates with prolonged jaundice from family pedigrees were observed to demonstrate the Gilbert's phenotype as children or young adults. CONCLUSIONS: A genetic predisposition to develop prolonged neonatal hyperbilirubinemia in breast-fed infants is associated with TATA box polymorphism of the UGT1A1 gene and will be recognized as Gilbert's syndrome in adulthood.     

Jaundice and breast-feeding among Alaskan Eskimo newborns.

The course, incidence, and severity of neonatal jaundice was studied in 95 Alaskan Eskimo infants. Breast-fed infants had higher bilirubin concentrations than bottle-fed babies. Both groups experienced high bilirubin levels, similar to those previously reported in Navajo and Oriental infants but greater than those observed in whites and blacks. A marked capacity to inhibit hepatic glucuronyl transferase was observed in breast-milk specimens but only partly accounted for the bilirubin differences between breast-fed and bottle-fed Eskimo infants. These data suggest that in some racial groups predisposed to neonatal jaundice, feeding practices significantly alter the course and severity of hyperbilirubinemia.     

Acute management of extreme neonatal jaundice–––the potential benefits of intensified phototherapy and interruption of enterohepatic bilirubin circulation

Abstract Increasing numbers of neonates are being admitted to hospital because of extreme jaundice. Phototherapy should be very effective in such infants, because the efficacy of phototherapy is proportional to the concentration of bilirubin in the skin. Here, I report on four infants who were admitted for indirect serum bilirubin levels of >500 µmol/1 (>>30mg/dl). In one of them, unrecognized Rhesus immunization was the main cause of hyperbilirubinemia, while in the other three increased enterohepatic circulation of bilirubin was thought to be an important contributory factor. In all four infants phototherapy (11–14 µW/cm²/nm) with whole body exposure plus ad lib feeding with milk were initiated immediately upon admission to the nursery. After 2h serum bilirubin values were reduced by 170–185 µmol/1 (10-11mg/dl) in the first three infants, while in the fourth infant a reduction of 195 µmol/1 (11.3mg/dl) was seen in the 5h interval between the first and second bilirubin measurement. This experience suggests that in some infants with extreme jaundice, intensified phototherapy plus feeding with milk may be very effective in reducing serum bilirubin levels. Even if an exchange transfusion is performed, using this strategy in the waiting period may be beneficial, as both the rapid reduction in serum bilirubin levels as well as the conversion of significant amounts of bilirubin into water-soluble isomers may reduce the risk of neurotoxicity.