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Neonatal Jaundice in Asian, White, and Mixed-Race Infants
Sabeena Setia, MPH;
Andrés Villaveces, MD, PhD;
Preet Dhillon, MPH;
Beth A. Mueller, DrPH
Arch Pediatr Adolesc Med. 2002;156:276-279.
ABSTRACT
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Background East Asians have inherently higher bilirubin levels at birth than whites.
The potential for unnecessary treatment makes jaundice a problem of public
health and clinical significance.
Objectives To report the occurrence of jaundice diagnoses in East Asian and mixed
East Asian/white infants in Washington State in recent years, and to compare
the risk of diagnosis with neonatal jaundice among these infants, relative
to white infants.
Design Population-based cohort study in Washington state. Participants were
infants of full East Asian parentage (n = 3000), maternal Asian parentage
(n = 2997), paternal Asian parentage (n = 2048), and white parentage (n =
3000). Diagnoses of jaundice and "severe jaundice" were identified using International Classification of Diseases, Ninth Revision (ICD-9) diagnosis and procedure codes from hospital discharge records.
Results Infants of full East Asian parentage were more likely to be diagnosed
with jaundice than were white infants (relative risk [RR], 1.37; 95% confidence
interval [CI], 1.16-1.62). For infants with Asian mothers and white fathers,
the RR was 1.09 (95% CI, 0.91-1.30). Infants with Asian fathers and white
mothers had an RR of 1.26 (95% CI, 1.05-1.52). The risk of severe jaundice
requiring phototherapy, blood transfusion, or rehospitalization, however,
was significantly elevated only for infants of full East Asian parentage (RR,
1.7; 95% CI, 1.12-2.58).
Conclusions Diagnoses of neonatal jaundice occurred more often among East Asian
and mixed Asian/white infants than among white infants. However, the risk
of jaundice requiring extended hospital stay, rehospitalization, phototherapy,
or blood transfusion was elevated only for infants of full East Asian parentage.
INTRODUCTION
APPROXIMATELY 60% to 70% of the 4 million infants born annually in the
United States become clinically jaundiced.1
East Asians have higher bilirubin levels at birth than whites.2-10
Previous reports from the United States indicate that 31% of East Asian infants
meet the standard criteria for nonphysiologic hyperbilirubinemia11
and have an approximately 3-fold increased risk of jaundice.12-13
We compared the rates of diagnosis with jaundice in infants born to
East Asian, mixed East Asian/white, and white parents in Washington State.
We also assessed differences in the proportion of severe jaundice among these
cohorts, using procedures performed and duration of hospital stay as indicators
of severity.
PARTICIPANTS AND METHODS
SUBJECT IDENTIFICATION
We conducted a population-based cohort study of infants born in Washington
state from 1987-1995. Data were obtained from the Washington State Birth Events
Records Database. This database, created by the Washington State Department
of Health Office of Hospital and Patient Data, links birth certificates to
hospital discharge information for the birth hospitalizations of mother and
child. Four cohorts of infants defined by parental race/ethnicity as indicated
on the birth certificate (based on prenatal record or self-reported) were
identified: those born to 2 white parents, those born to 2 East Asian (hereafter
called "Asian") parents, those born to an Asian mother and white father, and
those born to a white mother and Asian father. Asian infants included those
of Chinese, Japanese, or Filipino descent. We selected these infants because
much of the existing literature on jaundice focuses on these ethnicities and
because they were the largest Asian cohorts. We excluded other ethnicities
such as Korean and Vietnamese to create more homogeneity and to increase our
power to examine associations within groups. We also excluded groups such
as "Samoan" and "Pacific Islander" because of their small numbers and the
"other Asian" category because it was not well defined. Infants with parents
identified as Native American or other nonwhite classifications were not included.
A random sample of 3000 infants born from 1987-1995 to white parents
was the reference group. The 3 comparison groups included a random sample
of 3000 infants born to 2 Asian parents, a random sample of 3000 infants born
to an Asian mother and white father, and all 2048 infants born to a white
mother and Asian father.
OUTCOME MEASUREMENTS
Infants with neonatal jaundice were identified by screening all available International Classification of Diseases, Ninth Revision (ICD-9)14 diagnosis fields in the child's hospital
discharge record for codes indicating jaundice (774.1, 774.2, 774.39, 774.4,
and 774.6). Information concerning rehospitalization 28 or fewer days after
birth was obtained by linking subjects' records with Comprehensive Hospital
Abstract Reporting System (CHARS) records for 1987-1996. Created by the Washington
State Department of Health, CHARS contains discharge data for all hospitalizations
in nonmilitary hospitals.
STATISTICAL ANALYSES
Stratified analyses were conducted to calculate Mantel-Haenszel relative
risk estimates and to evaluate the presence of confounding and/or effect modification.
Variables considered for their potential effects included maternal age (<20,
20-24, 25-29, 30-34, or  35 years), sex, gravidity, parity (0, 1, 2, or 3
prior births), duration of gestation (20-36, 37-42, or >42 weeks), maternal
established or gestational diabetes, prenatal smoking or alcohol use (yes/no),
birth weight (<2500, 2500-4500, or >4500 g), and preeclampsia (ICD-9 code 642.4 or 642.5). Factors that altered risk estimates more
than 10% were considered confounders. Other factors possibly related to jaundice,
such as maternal hepatitis (ICD-9 code 070), congenital
anemia (ICD-9 code 776.5), and newborn sepsis (per
the birth certificate), were also considered.
Initially, we evaluated jaundice from any cause as a single outcome.
However, we were concerned that infants with jaundice might differ across
cohorts with respect to short gestational duration (20-36 weeks), preterm
delivery, hepatitis, hemolysis/bruising, maternal hepatitis, or congenital
anemia. To isolate relationships of interest, we excluded infants with these
potential causes to identify infants with presumed physiologic jaundice.
Infants with hospital stays of more than 5 days, procedure codes indicating
phototherapy or blood transfusion during birth hospitalization, or rehospitalization
for jaundice 28 or fewer days after birth were classified as having "severe"
jaundice.
RESULTS
Asian mothers were older and less likely to smoke than white mothers
(Table 1). The most common ICD-9 code was "neonatal jaundice due to unspecified causes"
(85%). "Neonatal jaundice due to pre-term delivery" was the second most common
jaundice diagnosis (13.5%). A jaundice diagnosis occurred less frequently
among white infants (7.4 per 100 infants) and most often among infants with
2 Asian parents (10.1 per 100 infants) (Table 2). For infants of mixed parentage, the diagnosis of jaundice
differed slightly by whether Asian heritage was maternal (8 per 100 infants)
or paternal (9.3 per 100 infants).
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Table 1. Maternal, Infant, and Pregnancy Characteristics of East Asian,
Mixed Asian/White, and White Study Cohorts*
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Table 2. Incidence of Neonatal Jaundice in East Asian and Asian/White
Infants Relative to White Infants*
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Infants of full Asian parentage were 37% more likely to be diagnosed
with jaundice than white infants (relative risk [RR], 1.37; 95% confidence
interval [CI], 1.16-1.62). Infants with Asian fathers and white mothers had
a 26% greater risk (RR, 1.26; 95% CI, 1.05-1.52), whereas no increased risk
was observed among infants with Asian mothers and white fathers (RR, 1.09;
95% CI, 0.91-1.30). These findings did not change when analyses were restricted
to infants classified as having physiologic jaundice.
Adjustment for maternal age, infant sex, parity, duration of gestation,
diabetes, smoking and alcohol consumption during pregnancy, birth weight,
and preeclampsia did not appreciably change the estimates, nor were marked
differences in risk observed with respect to these variables.
Infants with 2 Asian parents were more likely to be diagnosed with jaundice
regardless of their parents' country of ethnic origin. Relative to white infants,
the RR of diagnosis with neonatal jaundice for infants identified as being
born to Chinese parents was 1.25 (95% CI, 1.00-1.57). For infants of Japanese
parents, the RR was 1.85 (95% CI, 1.34-2.55), and for infants of Filipino
parents, the RR was 1.34 (95% CI, 1.10-1.63). The RR among infants of mixed-heritage
Asian parents was 1.26 (95% CI, 0.81-1.97). When infants with other known
causes of jaundice were excluded, the risks of diagnosis with physiologic
jaundice increased even more for infants in all Asian subgroups, except those
born to Filipino parents.
The risk of severe jaundice significantly increased among infants with
2 Asian parents (RR, 1.70; 95% CI, 1.12-2.58) (Table 3). Infants with Asian mothers/white fathers and white mothers/Asian
fathers had RRs of 1.36 (95% CI, 0.87-2.11) and 1.15 (95% CI, 0.69-1.91),
respectively. Among specific Asian groups, significantly increased risk of
severe jaundice was observed for Japanese (RR, 2.64; 95% CI, 1.27-5.51) and
Filipino (RR, 1.68; 95% CI, 1.02-2.76) infants.
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Table 3. Risk of Severe Jaundice in East Asian and Asian/White Infants,
Relative to White Infants*
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COMMENT
Infants of East Asian parentage were more likely to be diagnosed with
jaundice than white infants. This is consistent with the results of other
studies.3, 6, 10-13
In our study, it is possible that clinicians had a lower threshold for testing
for, and thus diagnosing, jaundice in Asian infants because of awareness of
higher jaundice rates in Asians, or possibly because of skin coloration. To
the extent that a diagnosis of jaundice in our data accurately indicates jaundice,
we found that, among infants with 2 Asian parents, Japanese infants had the
greatest risk, whereas risks for Filipino and Chinese infants were elevated
to a lesser extent. Ho5 found that not all
Asian groups had similar risks of jaundice, and recent investigations provide
evidence of elevated mutation levels in the bilirubin uridine diphosphate–glucuronosyltransferase
gene associated with jaundice in Japanese infants.15-16
The rate of jaundice diagnosis among infants with Asian mothers and
white fathers was not substantially different from that of white infants.
However, infants with Asian fathers and white mothers had a 32% greater risk
relative to white infants, suggesting a stronger paternal influence in determining
an infant's risk of jaundice. At this time, a possible genetic basis for paternal
influence is unknown.
Asian infants were more likely to have severe jaundice requiring phototherapy
and/or blood transfusion, rehospitalization for jaundice, or birth hospitalization
greater than 5 days. The subgroup analysis by Asian ancestry suggests that
infants of full Filipino and Japanese ancestry may be contributing to this
increased risk.
One strength of this analysis is that it was population-based, so infants
are representative of all those born in Washington State from 1987-1995. The
growing Asian population in Washington State permitted us to identify samples
of sufficient size to examine paternal vs maternal Asian influence on risk.
Limitations of this study include reliance on birth certificate and
hospital discharge record coding of race/ethnicity and jaundice, neither of
which we could validate. We also lacked data on other factors, such as family
history of neonatal jaundice,13 genetic traits
that might have varied by race,15-18
medicinal herbs in the diet, breastfeeding,19
or the use of oxytocin to induce or augment labor.15-16,19
Sepsis, preeclampsia, and preterm delivery are also reportedly associated
with jaundice.20-21 However, these
variables were not effect modifiers, nor did their frequency differ among
the 4 cohorts.
Greater knowledge of characteristics associated with risk of jaundice
is helpful, particularly as earlier hospital discharge after birth limits
the opportunity for clinicians to detect progression to more serious disease.
Racial differences have been observed in the time when peak serum bilirubin
concentrations occur,18 with about 6% of Asian
infants diagnosed with jaundice more than 3 days after birth,11
so early discharge may be of particular relevance for these children. As more
is learned about genetic influences for jaundice, these findings may also
be helpful in understanding genetic causes.
| What This Study Adds
Ethnic variation in the rates of neonatal jaundice has been recognized,
and gene mutations associated with hyperbilirubinemia among some Asian groups
have been identified. Greater knowledge of characteristics, including race/ethnicity,
that may be associated with an increased risk of jaundice may be helpful,
particularly as earlier hospital discharge after birth limits opportunity
for clinicians to detect progression to more serious disease.
To our knowledge, this is the first report of levels of jaundice diagnosis
from population-based data in the United States for infants of mixed Asian-white
descent. These population-based findings of increased risks for infants with
Asian parents or one Asian parent and one white parent, may provide useful
information to clinicians and enhance our understanding of potential genetic
causes of jaundice.
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AUTHOR INFORMATION
Accepted for publication November 27, 2001.
This study was presented as a poster at the American Public Health Association
127th Annual Meeting, Chicago, Ill, November 7-11, 1999.
Corresponding author and reprints: Beth A. Mueller, DrPH, 1100 Fairview
Ave N, MP-381, PO Box 19024, Seattle, WA 98109-1024.
From the Department of Epidemiology, University of Washington School
of Public Health and Community Medicine (Mss Setia and Dhillon and Drs Villaveces
and Mueller); and the Public Health Sciences Division, Fred Hutchinson Cancer
Research Center (Ms Dhillon and Dr Mueller), Seattle, Wash.
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