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Is Breastfeeding Really Favoring Early

Neonatal Jaundice?
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Is Breastfeeding Really Favoring Early Neonatal Jaundice?

Giovanna Bertini, Carlo Dani, Michele Tronchin and Firmino F. Rubaltelli
Pediatrics 2001;107;e41
DOI: 10.1542/peds.107.3.e41

The online version of this article, along with updated information and services, is
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Is Breastfeeding Really Favoring Early Neonatal Jaundice?

Giovanna Bertini, MD; Carlo Dani, MD; Michele Tronchin, PhD; and Firmino F. Rubaltelli, MD
ABSTRACT. Objective. The purpose of this study
was to evaluate the development of significant hyperbilirubinemia in a large unselected newborn population
in a metropolitan area with particular attention to the
relationship between type of feeding and incidence of
neonatal jaundice in the first week of life.
Study Design. A population of 2174 infants with gestational age >37 weeks was prospectively investigated
during the first days of life. Total serum bilirubin determinations were performed on infants with jaundice. The
following variables were studied: type of feeding,
method of delivery, weight loss after birth in relationship to the type of feeding, and maternal and neonatal
risk factors for jaundice. Statistical analyses were performed using the z test for parametric variables and the t
test for nonparametric variables. In addition, the multiple logistic regression allows for the estimation of the
role of the individual characteristics in the development
of hyperbilirubinemia. Data concerning serum bilirubin
peak distribution in jaundiced newborns were analyzed
using a single and a double Gaussian best fit at least
squares. The t test was performed to compare 2 values
(high and low) of the serum bilirubin peak in breastfed
and supplementary-fed infants with those in bottle-fed
infants.
Results. The maximal serum bilirubin concentration
exceeded 12.9 mg/dL (221 mol/L) in 112 infants (5.1%).
The study demonstrated a statistically significant positive correlation between patients with a total serum bilirubin concentration >12.9 mg/dL (221 mol/L) and supplementary feeding; oppositely, breastfed neonates did
not present a higher frequency of significant hyperbilirubinemia in the first days of life. However, best Gaussian fitting of our data suggests that a small subpopulation of breastfed infants have a higher serum bilirubin
peak than do bottle-fed infants.
Newborns with significant hyperbilirubinemia underwent a greater weight loss after birth compared with the
overall studied population, and infants given mixed
feeding lost more weight than breastfed and formula-fed
newborns, indicating that formula has been administered in neonates who had a weight loss beyond a predetermined percentage of birth weight. Significant hyperbilirubinemia was also strongly associated with
delivery by vacuum extractor, some perinatal complications (cephalohematoma, positive Coombs test, and
blood group systems of A, AB, B, and O [ABO] incompatibility) and Asian origin. Multiple logistic regression
analysis shows that supplementary feeding, weight loss

From the Department of Critical Care Medicine and Surgery, Section of

Neonatology, University of Florence School of Medicine, Florence, Italy.
Received for publication Nov 1, 1999; accepted Nov 15, 2000.
Reprint requests to (F.F.R.) Section of Neonatology, Careggi University
Hospital, Viale Morgagni 85, 50134, Florence, Italy. E-mail: rubaltelli@
unifi.it
PEDIATRICS (ISSN 0031 4005). Copyright 2001 by the American Academy of Pediatrics.

percentage, ABO incompatibility, and vacuum extraction

significantly increase the risk of jaundice, while only
cesarean section decreases the risk.
Conclusion. The present study confirms the important role of fasting in the pathogenesis of neonatal hyperbilirubinemia, although breastfeeding per se does not
seem related to the increased frequency of neonatal jaundice but to the higher bilirubin level in a very small
subpopulation of infants with jaundice. In fact, in the
breastfed infants, there is a small subpopulation with
higher serum bilirubin levels. These infants, when
starved and/or dehydrated, could probably be at high
risk of bilirubin encephalopathy. Pediatrics 2001;107(3).
URL: http://www.pediatrics.org/cgi/content/full/107/3/
e41; newborn infant, hyperbilirubinemia, neonatal jaundice.
ABBREVIATIONS. ABO, blood group systems of A, AB, B, and O;
TBS, total serum bilirubin.

eonatal jaundice remains the most common

and, perhaps, the most vexing problem in
full-term infants during the immediate postnatal period. Despite the numerous articles published on this subject, many aspects of neonatal
hyperbilirubinemia remain unexplained.17 In particular, there is an important debate on the role of
breastfeeding versus formula feeding in determining
the number of infants with significant hyperbilirubinemia as well as influencing the peak serum bilirubin concentration17 in the first days of life.
The aim of this study was to investigate the occurrence of significant hyperbilirubinemia in a large
unselected population of full-term newborns in a
metropolitan area.
METHODS
A population of 2174 newborn infants with gestational age 37
weeks consecutively born in the Department of Obstetrics and
Gynecology of the University of Florence Hospital between November 15, 1997 and November 14, 1998 was prospectively studied. Gestational age was determined according to last menstrual
period. No participants presented severe asphyxia, infections, abnormal direct serum bilirubin values, malformations, or other
pathologic conditions. All infants admitted to the study were in a
continuous rooming-in setting, meaning that newborns were in
their cots near their mothers beds.
Mothers had their blood group typed and all newborns had
blood group determination and the Coombs test performed on
cord blood. Total bilirubinemia in infants with jaundice was measured by direct spectrophotometry of the serum in a microhematocrit tube (using the Elmed Ginevri bilirubinometer). A bilirubin
level 12.9 mg/dL (221 mol/L) was considered significant. Infants with bilirubin level 12.9 mg/dL (221 mol/L) at 24 hours
of life and with bilirubin level 17 mg/dL (291 mol/L) in the
days that followed were candidates for phototherapy according to
the guidelines of the Italian Society of Neonatology.8 Serum bili-

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1 of 5

rubin levels were monitored in infants with jaundice twice daily in

subsequent days until a steady decrease was observed. The variables evaluated in this study are the following: type of feeding
(breastfeeding, formula feeding, or supplementary feeding);
method of delivery (vaginal delivery, cesarean section, or vacuum
extractor); weight loss after birth in relationship to type of feeding;
and maternal and neonatal risk factors for jaundice development
(maternal diabetes and hypertension, neonatal gender, origin and
gestational age, positive Coombs test, blood group systems of A,
AB, B, and O [ABO] incompatibility, and the presence of cephalohematoma).
Breastfeeding refers to infants who were exclusively breastfed.
The mothers started nursing in the delivery room and breastfed on
their infants demand every 1 to 3 hours (generally 10 minutes on
each breast) with no supplementation of water or formula at any
time. Pacifiers were forbidden and the number of feedings was
between 6 and 12 per day.
Supplementary feeding refers to infants who were breastfed
and received additional formula supplements. In our nursery, the
attending neonatologist commonly prescribed supplementary formula if birth weight was 2500 g or if weight loss after birth was
significant (4% after 24 hours or 8% after 48 hours or 10%
after 72 hours). No water or glucose water was administered at
any time.
Formula feeding refers to infants who were exclusively bottlefed because their mothers presented some pathologic conditions
that represented contraindications to breastfeeding or declined to
breastfeed.
Most infants were discharged after 72 hours of life. Newborns
who were born by cesarean section, were jaundiced, or presented
significant weight loss remained in the hospital longer. The range
of length of stay was 83.43 0.53 hours.
Statistical analyses were performed using the z test for parametric variables and the t test for nonparametric variables. A P
value .05 was considered statistically significant. In addition, the
multiple logistic regression allows us to estimate the role of the
individual characteristics in the development of hyperbilirubinemia; a value of t 1.96 (P .05) was chosen as the significant
cutoff value. Data concerning serum bilirubin peak distribution in
jaundiced newborns were analyzed using a single and a double
Gaussian best fit at least squares. The t test was performed to
compare 2 values (high and low) of serum bilirubin peak in
breastfed and supplementary-fed infants with those in bottle-fed
infants.

RESULTS

The characteristics of the study group are shown in

Table 1. During their hospital stay, 528 infants (24.3%
of the 2174 studied) were recognized to be clinically
jaundiced and required bilirubin determination, of
whom there were 43% on the second day of life and
46% on the third day of life. Among these, only 112
(5.1%) had total serum bilirubin (TSB) 12.9 mg/dL
or 221 mol/L (significant hyperbilirubinemia). A
TABLE 1.
Characteristics of the Study Group (Mean Values
Standard Deviation or Percentage)
Number of Neonates Studied
Birth weight (g)
Males
Females
Gestational age (wk)
Vaginal delivery
Cesarean section
Vacuum extractor
Breastfed
Formula-fed
Supplementary feeding
European origin
Asian origin
African origin
Mediterranean origin
South American origin

2 of 5

2174
3290.12 162.65
1143 (52.6%)
1031 (47.4%)
39.2 1.7
1691 (77.8%)
426 (19.6%)
57 (2.6%)
1595 (73.4%)
101 (4.6%)
478 (22%)
1997 (91.8%)
102 (4.8%)
18 (0.8%)
39 (1.8%)
18 (0.8%)

serum bilirubin peak 12.9 mg/dL occurred more

frequently on the third and fourth days of life. A
statistically significant positive correlation was
found between TSB 12.9 mg/dL (221 mol/L) and
supplementary feeding (P .001), delivery by vacuum extractor (P .001), perinatal complications
(cephalohematoma, positive Coombs test, and ABO
incompatibility; P .001), and Asian origin (P
.001). Breastfeeding showed a negative correlation
with TSB 12.9 mg/dL (P .001) (Table 2). Newborns with TSB 12.9 mg/dL (221 mol/L) underwent a greater weight loss after 72 hours of life than
did the overall studied population (8.0% vs 6.4%; P
.001; Table 3). Infants given mixed feeding lost more
weight than did breastfed and formula-fed newborns. The additional multiple logistic regression
analysis shows a positive, statistically significant correlation between TSB 12.9 and supplementary
feeding, delivery by vacuum extractor, ABO incompatibility, and weight loss percentage after birth. A
negative, statistically significant correlation was observed between TSB 12.9 and cesarean section (Table 4). In this type of analysis, neonatal characteristics, just as the appearance of cephalohematoma, a
positive Coombs test, and Asian origin, have not
proved to be statistically significant: probably, the
number of infants with these disorders are too few to
have sufficient statistical power. Best Gaussian fitting of our data suggests that 2 subpopulations are
present among breastfed and supplementary-fed infants with jaundice of unknown origin: a subpopulation with a low serum bilirubin peak and a subpopulation with a high serum bilirubin peak. In
bottle-fed newborns, only 1 population seems
present. The subgroups of breastfed and supplementary-fed infants have a higher second serum bilirubin
peak compared with bottle-fed newborns (14.4 2.9
mg/dL, 14.1 3.1 mg/dL vs 11.0 4.5 mg/dL; P
.05; data are shown in Fig 1).
DISCUSSION

This epidemiologic study investigated the effects

of different variables on nonphysiologic hyperbilirubinemia in a large cohort of full-term newborn infants in the first week of life. Several authors have
reported an increase in the frequency of readily visible jaundice in the last 25 years, probably secondary
to breastfeeding encouragement in the same period.2,3 In our study, the incidence of clinically evident
jaundice resulted similar to the National Collaborative Perinatal Project conducted from 1959 to 1966
(24.3% vs 26.3%)8; at that time, only 22% to 23% of
mothers in the United States were breastfeeding their
infants. Because 73.4% of our infants were breastfed,
our findings seem to suggest that the frequency of
infants with clinically evident jaundice is not related
to the type of feeding in our study population.
During the first week of life, the incidence of nonphysiologic hyperbilirubinemia (TSB 10 12.9
mg/dL or 171221 mol/L) in full-term newborns
was reported in different studies to be between 4.8%
and 15.5%1,3,5: in our study population the incidence
of significant hyperbilirubinemia is low (5.15%).
Our findings confirm the strong association be-

IS BREASTFEEDING REALLY FAVORING EARLY NEONATAL JAUNDICE?

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TABLE 2.
Neonatal Hyperbilirubinemia in Relation to Selected Neonatal and Maternal Characteristics: A Comparison Between All
Neonates and Those With TSB 12.9
Infants With TSB 12.9
mg/dL (221 mol/L)

Infants
Number

Number

2174
1595
101
478
1691
426
57
136
37
24
73
293
1143
1031
1997
102
18
18
39

73.4
4.6
22.0
77.8
19.6
2.6
6.2
1.7
1.1
3.3
13.5
52.6
47.4
91.8
4.8
0.8
0.8
1.8

112
43
6
63
82
20
10
9
2
7
17
38
60
52
92
16
1
1
2

5.15
2.7
5.9
13.1
4.8
4.7
17.5
6.6
5.4
29.1
23.2
13.0
5.2
5.0
4.6
15.6
5.5
5.5
5.1

Neonates studied
Breastfed
Formula-fed
Supplementary feeding
Vaginal delivery
Cesarean section
Vacuum extractor
Maternal diabetes
Maternal hypertension
Cephalehematoma
Positive Coombs test
ABO incompatibility
Males
Females
European origin
Asian origin
African origin
South American origin
Mediterranean origin

TABLE 3.
binemia

Weight Loss After Birth and Neonatal Hyperbiliru-

All infants studied

Infants with TSB
12.9 mg/dL
Supplementary-fed
infants
Breastfed infants
Formula-fed infants

Weight Loss After 72

Hour of Life (Grams)

P Value

214.63 146
264.49 74

266 150

200.33 145
207.2 70

P .001 among infants with TSB 12.9 mg/dL and all infants
studied.
P .01 among supplementary and breastfed infants.
f P .01 among supplementary and formula-fed infants.

tween neonatal jaundice and known risk factors such

as a positive Coombs test and ABO incompatibility;
a policy of watchful anticipation justifies repetitive
serum bilirubin determinations if indicated. It is
not surprising that a known cause of hyperbilirubinemia was not found in 65/112 of our infants
(58%) in agreement with previous investigations
(55%56%).1,3 The controversy in literature regarding
hyperbilirubinemia of unknown origin is whether
breastfeeding increases the incidence of jaundice in
the first days of life. Numerous authors1 4,10,12 have
reported a striking association between breastfeeding and significant hyperbilirubinemia, but other reports5,11 have not substantiated this observation. Our
data show that a TSB 12.9 mg/dL (221 mol/L) is
significantly associated with supplementary feeding
and weight loss after birth, whereas breastfeeding is
not correlated with hyperbilirubinemia in the first
days of life: breastfed infants represent only 38.4% of
infants with a bilirubin level 12.9 mg/dL (221
mol/L). One possible explanation is that in our
hospital, full-term newborn infants start breastfeeding in the delivery room, they are in a rooming-in
setting, and are breastfed on demand. Infants receive
supplementary feeding only when adequate breast-

P Value

.001
.91
.001
.67
.79
.001
.59
.75
.001
.001
.001
.98
.92
.45
.001
.64
.64
.72

feeding has failed. In fact, breastfed infants, compared with newborns given supplementary feeding,
had lower weight loss after birth than did the overall
studied population. Moreover, jaundice was first evident in 42% of infants on the second day and in 55%
on the third day when the percentage of infants with
a maximum weight loss was 52% and 45%, respectively. Multiple regression logistic analysis shows a
statistically positive correlation between TSB 12.9
mg/dL (221 mol/L) and weight loss percentage
after birth. These data confirm that the development
of neonatal jaundice is not associated with breastfeeding per se but rather with increased weight loss
after birth subsequent to fasting, suggesting the important role of caloric intake in the regulation of
serum bilirubin. In fact, Osborn et al2 as well as
Maisels et al4 found that jaundiced infants did lose
more weight than control infants. A relationship between fasting and hyperbilirubinemia has been previously reported both in adults and animals.13,14 The
effect of caloric restriction on serum bilirubin was
first noted by Gilbert and Hershi15 in 1906. Later on,
Barrett16 and Felsher et al17 showed that fasting
causes a significant elevation of unconjugated bilirubin. Bloomer et al,13 by injecting bilirubin H3 into
normal adult volunteers and in patients with Gilberts syndrome, demonstrated that the decrease in
clearance was the result of reduced hepatic ability to
extract bilirubin from the blood. Moreover, in the
Cooperative National Institute of Child Health and
Human Development phototherapy, Wu et al18
found that infants receiving 90 calories/kg/24
hours had significantly higher peaks in bilirubin concentrations than did those fed 90 calories/kg/24
hours, and phototherapy was much less effective
when caloric and fluid intake was low. In contrast,
measurements of pulmonary excretion of carbon
monoxide (an index of bilirubin production) showed
no effect of caloric deprivation on bilirubin production.19 A recent article by Gartner et al20 investigated
the effect of fasting in rats using a technique that

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TABLE 4.
Multiple Logistic Regression Analysis for Characteristics Potentially Associated With
Neonatal Hyperbilirubinemia

Sex
Cesarean section
Vacuum extractor
Birth weight
Gestational age
Supplementary feeding
Formula feeding
ABO incompatibility
Maternal hypertension
Maternal diabetes
Weight loss percentage

Value

Standard Error

0.02069183018
0.15284435683
0.30723170710
0.00004338651
0.00109275960
0.30536674845
0.13541467312
0.14240080203
0.31065205899
0.21423038422
0.00044801641

0.049716455409
0.06037950031
0.11652928879
0.00006470326
0.00529995650
0.05504706766
0.10814557069
0.05850289887
0.19735173451
0.15274667994
0.00017684607

0.4161968
2.5313949*
2.6365192*
0.67705460
0.2061827
5.5473754*
1.2521518
2.4340811*
1.5741035
1.4025207
2.5333693*

* P .05.

Fig 1. Best Gaussian fitting of the distribution peak of serum

bilirubin in newborns with jaundice: effect of type of feeding. Two
subpopulations are present among breastfed and supplementaryfed newborns: a subpopulation with a low serum bilirubin peak
(-) and a subpopulation with a high serum bilirubin peak
(. . . . .). In bottle-fed newborns, only one population seems present
(- - - -). The subgroups of breastfed and supplementary-fed infants
have a higher second serum bilirubin peak compared with bottlefed newborns (P .05).

enables the assessment of the hepatic handling of

unconjugated bilirubin independent of nonhepatic
factors. This study clearly documents that enhanced
enterohepatic circulation of bilirubin, not altered intrinsic hepatic transport, is a major factor in the
pathogenesis of fasting-induced hyperbilirubinemia.
In our study, best Gaussian fitting of data concerning
4 of 5

serum bilirubin peak distribution in breastfed newborns shows that there is a subpopulation with a
high serum bilirubin peak, which is not present in
bottle-fed infants. However, this subpopulation
seems to be very large among infants with mixed
feeding who were the infants with the higher weight
loss (Fig 1). It is worthwhile to underline that the
occurrence of a decreased incidence of significant
jaundice in breastfed infants is related to the first
days of life (early jaundice). The incidence of late
jaundice, whose onset generally occurs on the fourth
day and lasts 9 weeks having a peak at 5 to 15 days,
was not studied in our population.
It is well known that genetic and environmental
factors influence neonatal jaundice. According to
previous data in literature, the method of delivery
also influences serum bilirubin concentration2,10,21
and this report found that cesarean sections preserve
newborn infants by the development of neonatal
hyperbilirubinemia. There are some possible explanations. The infants born by emergency cesarean
section are stressed before birth and, therefore, induce conjugating enzymes before delivery. Moreover, Osborn et al2 have suggested a probable association between delivery by cesarean section and
method of feeding. In their hospital, because women
who underwent cesarean section breastfed infrequently during the newborns first 48 hours of life,
these infants, unlike other breastfed infants, were
supplemented with formula until nursing was well
established. Nevertheless, our setting after cesarean
section provides for supplementation with formula
only at the mothers request or if weight loss after
birth is significant. Yamauchi and Yamanouchi21
demonstrated that from day 1 to day 7 of life, transcutaneous bilirubin measurement in infants born by
cesarean section was significantly lower than those
of infants born vaginally, likely because of less placental transfusion in infants born by cesarean section. In addition, a strong association was found
between significant hyperbilirubinemia in the first
week and delivery by means of vacuum extractor;
this is probably because of the development of hemorrhaging consequent to this method of delivery as
has been observed in the past,22 but currently it is not
widely recognized. Ethnic differences in the incidence of neonatal jaundice are significant9,23 and the
present investigation confirms that race plays an im-

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portant role in determining neonatal hyperbilirubinemia; 15.6% of Asian newborn infants compared
with 5.1% of the total population (91.8% European
newborns) showed a TSB 12.9 mg/dL (221
mol/L; P .001). Recently, Akaba et al24 suggested
that the high incidence of neonatal hyperbilirubinemia in Japanese, Korean, and Chinese populations is associated with high frequency of the
Gly71Arg mutation (missense mutation) of the bilirubin uridine diphosphate-glucuronosyltransferase
gene. Our data on the effect of gestational age do not
agree with those found by others authors,4,11,25,26 but
our population was composed of newborn infants
with 39 weeks of gestational age (73%). Even if
other variables also play a role in hyperbilirubinemia
of full-term infants, breastfeeding failure and the
lack of breastfeeding are major factors in the pathogenesis of neonatal jaundice.
CONCLUSION

The present study confirms the important role of

fasting in the pathogenesis of neonatal hyperbilirubinemia, although breastfeeding per se does not
seem related to the increased frequency of neonatal
jaundice in the first days of life, but rather to the
higher bilirubin level in a very small subpopulation
of infants with jaundice. These infants, when starved
and/or dehydrated, could probably be at high risk of
bilirubin encephalopathy, especially after discharge
from the hospital when careful follow-up is lacking.
Among other well-known conditions favoring neonatal jaundice, it must be emphasized that infants
born by vacuum extraction are at risk of exaggerated
neonatal jaundice.
ACKNOWLEDGMENTS
We thank Dr Alessandro Ambrosi of the University of Padova
for the multiple logistic regression analysis and Kathryn Rakich
for her editorial assistance. We also thank Dr M. Jeffrey Maisels of
William Beaumont Hospital (Royal Oak, MI) and Dr Vinod K.
Buthani of Pennsylvania Hospital (Philadelphia, PA) for reviewing the manuscript and for their suggestions.

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Is Breastfeeding Really Favoring Early Neonatal Jaundice?

Giovanna Bertini, Carlo Dani, Michele Tronchin and Firmino F. Rubaltelli
Pediatrics 2001;107;e41
DOI: 10.1542/peds.107.3.e41
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

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