525
Variations in the incidence of intraven-
tricular hemorrhage in very low birth
weight infants have been noted in the
literature.
1-4
Lee et al
1
previously re-
ported large variations in the crude in-
cidence of IVH among Canadian
neonatal intensive care units. In their
analyses of the outcome of infants with
a birth weight ≤1500 g from 36 centers
in 1990, the Vermont-Oxford Trials
Network reported an overall crude
IVH incidence of 26% but with 25th
and 75th percentiles of 18% and 38%,
respectively.
2
The National Institute of
Child Health and Human Develop-
ment Neonatal Network found equally
large variations in IVH incidence
among the 7 participating sites.
3
Oth-
ers
4-5
demonstrated a change in inci-
dence of IVH over time. However,
most previous reports of variation in
IVH rates among NICUs did not ad-
just for severity of illness or examine
reasons for the variation. The aims of
this study were to examine the risk-
and illness severity–adjusted variation
of IVH incidence among NICUs. We
used data from the Canadian NICU
Network,
1
which collected demo-
graphic, severity of illness, outcome,
and treatment data on all admissions
during a 22-month period in 1996-
1997, from 17 NICUs across Canada.
We hypothesized that there were vari-
ations in the incidence of IVH among
Canadian NICUs, that these variations
Variations in intraventricular hemorrhage incidence
rates among Canadian neonatal intensive care units
Anne R. Synnes, MDCM, FRCPC,
MHSc, Li-Yin Chien, MPH, ScD
, Abraham Peliowski, MD,
FRCPC,
Ranjit Baboolal,
MBBCh, FRCPC, Shoo K. Lee,
MBBS, FRCPC, PhD, and the Canadian NICU Network
From the Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada; Centre
for Community Health and Health Evaluation Research, Vancouver, British Columbia, Canada; Department of
Pediatrics, University of Alberta, Edmonton, Alberta, Canada; Department of Pediatrics, University of Toronto,
Toronto, Ontario, Canada.
A complete list of the members of the Canadian NICU Network appears at the end of this article
Supported by Grant 40503 and Grant 00152 from the Medical Research Council of Canada.
Additional funding was provided by the B.C.’s Children’s Hospital Foundation; Calgary Region-
al Health Authority; Dalhousie University Neonatal-Perinatal Research Fund; Division of
Neonatology, Children’s Hospital of Eastern Ontario; Child Health Program, Health Care Cor-
poration of St John’s; The Neonatology Program, Hospital for Sick Children; Lawson Research
Institute; Midland Walwyn Capital Inc; Division of Neonatology, Hamilton Health Sciences
Corporation; Mount Sinai Hospital; North York General Hospital Foundation; Saint Joseph’s
Health Centre; University of Saskatchewan Neonatal Research Fund; and University of West-
ern Ontario; Women’s College Hospital.
Presented in part at the Annual Meeting of the Pediatric Academic societies, Boston, Mass, May
16, 2000.
Submitted for publication June 5, 2000; revision received Sept 7, 2000; accepted Sept 20, 2000.
Reprint requests: Shoo K. Lee, MBBS, FRCPC, PhD, Centre for Community Health and
Health Evaluation Research, 4480 Oak St, Room E-414, Vancouver, BC, V6H 3V4 Canada.
Copyright © 2001 by Mosby, Inc.
0022-3476/2001/$35.00 + 0 9/21/111822
doi:10.1067/mpd.2001.111822
GA Gestational age
IVH Intraventricular hemorrhage
NICU Neonatal intensive care unit
OR Odds ratio
SNAP-II Score for Neonatal Acute Physiology,
Version II
Objectives: To examine the variation in intraventricular hemorrhage
(IVH) incidence among neonatal intensive care units and identify potential-
ly modifiable risk factors.
Study design: Multiple logistic regression analysis was used to examine
variations in ≥grade 3 IVH, adjusting for baseline population risk factors,
admission illness severity, and therapeutic risk factors. Subjects were born
at <33 weeks’ gestational age, admitted within 4 days of life to 1 of 17 par-
ticipating Canadian NICU network sites in 1996-97, and had neuroimaging
in the first 2 weeks of life.
Results: Of 5126 subjects <33 weeks’ gestational age, 3806 had neuroimag-
ing reports. Five of 17 sites had significantly (P < .05) different crude inci-
dence rates of grade 3-4 IVH (odds ratios [OR] 0.2, 3.2, 2.6, 2.1, 1.9) than
the hospital with median incidence. With adjustment for baseline population
risk factors, perinatal risks, and admission illness severity, IVH incidence
rates remained significantly (P < .05) higher at 3 sites (OR 2.9, 2.3 and 2.1).
Inclusion of therapy-related variables (treatment of acidosis and vasopressor
use on the day of admission) in the model eliminated all site differences.
Conclusions: IVH incidence rates vary significantly. Patient characteris-
tics explain some of the variance. Early treatment of hypotension and aci-
dosis and mode of delivery are potentially modifiable factors and warrant
further study in IVH prevention. (J Pediatr 2001;138:525-31)
SYNNES ET AL THE JOURNAL OF PEDIATRICS
APRIL 2001
persisted even after adjusting for
known risk factors and severity of ill-
ness, and that we could identify risk
factors that are potentially modifiable
to reduce the incidence of IVH.
METHODS
Population
The study population comprised all
19,507 infants admitted to 17 NICUs
in the Canadian NICU Network from
January 8, 1996, to October 31, 1997.
The 17 hospitals, except one, are re-
gional tertiary level referral centers
and include 75% of level 3 NICU beds
in Canada. The NICUs ranged in size
from 9 to 70 beds and had an average
of 133 to 1129 admissions annually.
The data were collected as part of a
larger study of practices and outcomes
of NICUs
1
across Canada, which had
a population of nearly 30 million peo-
ple and over 357,000 births in 1996.
6,7
There was no interference in NICU
practices and management. Only in-
fants <33 weeks’ gestational age who
were <4 days old at the time of admis-
sion and who had a cranial sonogram,
computerized tomography, or magnet-
ic resonance imaging (subsequently re-
ferred to collectively as neuroimaging)
were included in the analysis.
Data Collection
Data were collected prospectively by
trained research assistants and entered
directly from patient charts into laptop
computers by using a customized data
entry program with built-in error
checking and a standard manual of
protocols and definitions. Data were
electronically transmitted to the Cen-
tre for Community Health and Health
Evaluation Research at the British Co-
lumbia Research Institute for Chil-
dren’s and Women’s Health. Data
management was conducted by the
Centre for Community Health and
Health Evaluation Research in concert
with a steering committee comprising
experienced researchers and neonatol-
ogists representing each of the 5 geo-
graphic regions (British Columbia,
prairie provinces, Ontario, Quebec,
and the Atlantic provinces) and site in-
vestigators representing each of the
participating hospitals. Patient infor-
mation was collected until death or dis-
charge from the NICU. Patients trans-
ferred to another hospital were tracked
until death or discharge.
Definition of IVH
Abstractors recorded the neuroimag-
ing reports performed within the first 2
weeks after admission using Papile’s
classification system.
8
When there was
more than one report or if there was bi-
lateral IVH, the highest grade was
used. Intraparenchymal hemorrhages
with or without IVH were classified as
grade 4 IVH. All other intracranial
bleeds such as subarachnoid, subdural,
and tentorial bleeds were excluded.
Possible or questionable diagnoses
were excluded.
Variables Analyzed
Variables chosen because they were
known risk factors for IVH were
grouped into patient characteristics, ob-
stetric variables, severity of illness, and
therapy variables. Patient characteris-
tics included (1) sex; (2) GA based on
sonographic and obstetrical data except
when this was unavailable, in which
case the neonatologist’s best estimate
was used; and (3) Apgar score (5-
minute score categorized as low if <4 or
medium if 4-6 or reference if >6). Ob-
stetric variables included (1) use of an-
tenatal steroids, (2) vaginal versus ce-
sarean section delivery, and (3) inborn
versus outborn status. The Score for
Neonatal Acute Physiology, Version
II,
9
recorded within the first 12 hours of
admission, was included as a measure
of the severity of illness. Admission
day therapy-related variables included
(1) treatment of acidosis (sodium bicar-
bonate or tromethamine), (2) vasopres-
sor (any vasoactive infusion such as
dopamine, dobutamine, isoproterenol,
nitroprusside, or epinephrine) use not
associated with a resuscitation, and (3)
surfactant administration.
Analyses
Analyses were performed by using
data for each infant rather than each
admission. For this purpose, data from
re-admissions and inter-hospital trans-
fers for each patient were combined.
Risk factors were analyzed by using
SPSS (version 7.5) software.
10
Crude
incidence rates were calculated for all
sites. When the site with the median
incidence rate was used as a reference,
statistically significant variation was
526
IVH grade
None I II III IV
No. 2685 545 259 152 165
Median birth weight (g) 1244 1162 995 900 830
Median GA (wk) 29 29 27 26 26
Median SNAP-II 9 14 16 21 29
Median Apgar score at 5 min 88877
Inborn (%) 85.9 84.0 71.8 59.9 70.9
Cesarean section (%) 54.7 38.2 30.9 37.5 38.8
Male (%) 54.2 58.4 62.2 60.5 65.9
Antenatal steroids (%) 71.6 71.8 65.0 61.7 53.9
Vasopressors—day 1 (%) 17.1 18.0 33.2 48.0 60.0
Acidosis treatment–day 1 (%) 6.7 6.8 17.2 25.8 36.0
IVH, Intraventricular hemorrhage; GA, gestational age; SNAP-II, Score for Neonatal Acute
Physiology–Version II.
Table. Patient characteristics
THE JOURNAL OF PEDIATRICS SYNNES ET AL
VOLUME 138, NUMBER 4
identified. A P value of <.05 was
deemed to be significant. By means of
multiple logistic regression, the risk
(odds ratio) for IVH at each site was
determined, adjusting stepwise for pa-
tient characteristics, obstetric vari-
ables, and admission illness severity as
defined previously. Admission day
therapy-related risks were then added
to assess their contribution to site vari-
ations in incidence of IVH.
RESULTS
Of the 19,507 infants admitted to the
Canadian NICU Network during the
study period, 5126 were <33 complet-
ed weeks’ GA at birth and <4 days old
at admission. Of these infants, 3806
had neuroimaging performed in the
first 2 weeks of life. Neuroimaging re-
ports were available for 89% of all in-
fants <31 weeks’ GA and 58% of all in-
fants between 31 and 32 weeks’ GA.
Neuroimaging practices differed sig-
nificantly between NICUs (range,
63%-100% among infants <33 weeks’
GA). Infants with neuroimaging (in-
cluded in study) compared with those
infants without neuroimaging (exclud-
ed from study) had lower mean birth
weight (1190 vs 1730 g), lower mean
GA (29 vs 31 weeks), and higher
SNAP-II (14 vs 5). The overall inci-
dence of IVH (any grade) was 29.4%.
Five hundred forty-five (14.3%) in-
fants had a grade 1 IVH, 259 (6.8%)
had a grade 2 IVH, 152 (4.0%) had a
grade 3 IVH, and 165 (4.3%) had a
grade 4 IVH. Characteristics of infants
with different grades of IVH are
shown in the Table.
The variation in the incidence rates of
diagnosed IVH among the 17 NICUs
is shown in Fig 1. The incidence rate
ranged from 14.2% to 57.7% for all
grades of IVH. The ranges of grade-
specific incidence rates of IVH were
6.3% to 29.8% for grade 1, 0% to 25%
for grade 2, 0% to 14.1% for grade 3,
and 0% to 8% for grade 4 IVH. Inci-
dence rates decreased with increasing
GA. The incidence of any grade IVH
(range in parentheses) by GA cate-
gories was 48% (range, 27%–89%),
33% (range, 0%-60%), 23% (range,
8%-50%), and 17% (range, 0% to 30%)
for infants <27 weeks’ GA, 27-28
weeks’ GA, 29-30 weeks’ GA, and 31-
32 weeks’ GA, respectively.
Fig 2 shows the crude ORs and 95%
CIs for each site for severe (grade 3 or
4) IVH in comparison with site H with
the median incidence rate (6.2%). Five
sites had significantly (P < .05) differ-
ent incidence rates; 4 of these sites (C,
F, I, and N) had higher rates, and one
site (M) had a lower rate. After adjust-
ment for patient characteristics (sex,
GA, and Apgar score), obstetric risks
(antenatal steroids, mode of delivery,
inborn vs outborn), and admission ill-
ness severity, only 3 sites (C, F, and N)
had significantly higher incidence rates
than the site with median incidence
(H). The adjusted ORs for IVH by
site, derived from this regression
527
Fig 1. IVH rate by site.
SYNNES ET AL THE JOURNAL OF PEDIATRICS
APRIL 2001
model, are shown in Fig 3. When
therapy-related variables were added
to the model, all the site variations
disappeared.
Significant (P < .05) IVH risk factors
that were included in the final regres-
sion model of site variations were: male
sex (OR 1.4), GA <27 weeks’ (OR
4.2), GA 27-28 weeks’ (OR 2.1),
5-minute Apgar score <4 (OR 2.1),
5-minute Apgar score 4-6 (OR 1.5),
SNAP-II ≥30 (OR 1.6), outborn status
528
Fig 2. IVH crude odds ratios.
Fig 3. IVH adjusted odds ratios.
THE JOURNAL OF PEDIATRICS SYNNES ET AL
VOLUME 138, NUMBER 4
(OR 1.9), vaginal delivery (OR 1.5),
partial antenatal steroid treatment
(OR 0.6), treatment for acidosis (OR
2.1), and treatment with vasopressors
(OR 1.7). Complete antenatal steroid
treatment (OR 0.8) was not significant
(P = .16), but there was significant
collinearity between outborn status
and antenatal steroid use. The latter
variable became highly significant if
outborn status was removed from the
analysis. Surfactant use was not signif-
icantly associated with IVH and was
excluded from the final model.
DISCUSSION
This study demonstrates a statistical-
ly and clinically significant variation in
the incidence of diagnosed IVH in pre-
mature infants (<33 weeks’ GA) admit-
ted to NICUs. This variation existed
across all grades of IVH and all GA
categories. Previous reports of varia-
tions in the incidence of diagnosed
IVH among preterm infants admitted
to NICUs did not adjust for variations
in patient population. In our study, we
found that risk adjustment for baseline
population risk factors and SNAP-II
resulted in a 40% reduction in the
number of NICUs with incidence of
IVH significantly (P < .05) different
from the median incidence. Omission
of adjustment for these factors could
therefore result in inaccurate compar-
isons for a significant number of
NICUs, with important implications if
the results were used for hospital audit
and accreditation purposes.
We identified prematurity, male sex,
5-minute Apgar score, severity of ill-
ness, outborn status, vaginal delivery,
lack of antenatal steroids, and treatment
of acidosis or use of vasopressors on the
day of admission as significant risk fac-
tors for severe (grade 3 or 4) IVH.
Some of these factors are impossible
(eg, male sex) or difficult (eg, prematu-
rity, severity of illness, outborn status)
to modify. Exceptions are choice of ce-
sarean section versus vaginal delivery,
use of antenatal steroids, and vasopres-
sor and sodium bicarbonate use.
Ment et al
11
previously reported an
association between lower IVH rates
and cesarean section delivery and an-
tenatal steroid use. Other studies re-
ported conflicting results as to the ben-
efit of cesarean delivery for very low
birth weight infants,
12-14
but they did
not control for selection bias and ill-
ness severity.
Large variations in antenatal steroid
use persist to this day. Lee et al
1
re-
ported that the incidence of antenatal
steroid use in infants <35 weeks’ gesta-
tion in the study cohort varied from
23% to 76% among Canadian NICUs.
It is possible that increased use of an-
tenatal steroids among Canadian hos-
pitals may further decrease the inci-
dence of IVH. However, antenatal
steroid use may also be a marker for
other risks (eg, outborn delivery). Fur-
ther research is needed to determine
whether cesarean section or antenatal
steroid use can reduce the incidence of
IVH among preterm infants.
Therapy variables (vasopressor use,
treatment for acidosis) were critically
important in explaining the site varia-
tion, and their inclusion in the final re-
gression model eliminated all signifi-
cant site variation. Although our
results do not permit inference of
causal relationships, the association
between IVH and admission day use of
vasopressors and treatment for acido-
sis merits further study. The relation-
ship between vasopressor use, acidosis
treatment, and IVH is consistent with
present concepts of the pathogenesis of
IVH in the preterm infant.
15-17
The
germinal matrix of the preterm infant,
with its friable capillary network and
poor supportive stroma, is especially
susceptible to hemorrhage. Alterations
in arterial blood pressure and cerebral
blood flow appear to be important trig-
gers.
18
In the animal model, IVH is
precipitated either by inducing hy-
potension and then rapidly increasing
the blood pressure by volume infu-
sion
19
or by vasopressors.
20
The rela-
tionship between pathogenesis of IVH
and sodium bicarbonate administra-
tion is not well studied but is likely re-
lated to its hyperosmolarity. Although
further study is needed, our results
suggest that variations in the incidence
of IVH may be reduced by improved
strategies for prevention and treatment
of hypotension and acidosis in preterm
infants. It is also possible that vaso-
pressor use and acidosis treatment are
proxies for other unidentified risk fac-
tors (eg, perinatal infection).
The incidence of IVH may also be af-
fected by other risk factors that were
not examined in our study. Thrombo-
cytopenia and coagulopathy are recog-
nized risk factors but probably do not
play a major role
21
and were not exam-
ined in our study because they were in-
frequent in number. Indomethacin has
been identified as a potential treatment
for prevention of IVH.
22
Because
many of our patients were participants
in a randomized control trial of pro-
phylactic indomethacin treatment, we
were unable to consider indomethacin
prophylaxis in our analysis.
System variables may also have af-
fected IVH rates. Therefore we as-
sessed the effect of the size of the
NICU on IVH risk. The number of ad-
missions at each site was not a signifi-
cant predictor of severe IVH (P = .42),
nor did it alter the size of the therapy
variables effect. The number of admis-
sions of preterm infants <33 weeks’
gestation was a significant predictor of
severe IVH (P = .01), independent of
the use of vasopressors or treatment
for acidosis. These exploratory find-
ings suggest that expertise in caring for
preterm infants may confer benefits in
preventing IVH.
Limitations
We noted a variation between
NICUs in the percentage of patients
who had cranial sonograms or other
neuroimaging. Sites with protocols or
a general consensus generally used a
birth weight of <1500 g and/or a GA of
<32 weeks or <33 weeks as a cutoff for
529
SYNNES ET AL THE JOURNAL OF PEDIATRICS
APRIL 2001
screening. Because neuroimaging was
not performed in all patients, selection
bias may have affected our results.
Inter-rater variability in cranial sono-
graphic diagnosis is well described,
23
and a diagnostic bias may have been
present because we were unable to
have radiologists who were blinded to
risk factors review all subjects’ neu-
roimaging. A residual significant site
variation should have been, but was
not, found if this had been the case.
Only selected admission day therapy-
related risk factors were included in
the analysis. It is possible that other
risks and therapy-related risk factors
beyond the first day of admission could
also be significant predictors of IVH.
However, the elimination of all site
variations by addition of 2 admission
day therapy-related variables suggests
that relevant practice-related risks
occur early in life. Risk factors identi-
fied in our analysis do not infer a
causal relationship, and further study
is needed to determine whether inter-
ventions can be designed to decrease
the risk for IVH.
The incidence of IVH may be re-
duced by improved prevention and/or
treatment for hypotension and acidosis
in preterm infants, and this should be a
priority for research. The role of ante-
natal steroids and cesarean section to
reduce the incidence of IVH in
preterm deliveries also warrants fur-
ther study.
Members of the Canadian NICU Net-
work: Shoo K. Lee, MBBS, FRCPC, PhD
(Coordinator, Canadian NICU Network;
Centre for Community Health and Health
Evaluation Research, Vancouver, BC); Wayne
Andrews, MD, FRCPC (Charles A. Janeway
Child Health Centre, St John’s, NF); Ranjit
Baboolal, MBChB, FRCPC (North York
Hospital, North York, ON); Jill Boulton, MD,
FRCPC (St Joseph’s Health Centre, London,
ON; previously Mt Sinai Hospital, Toronto,
ON); David Brabyn, MBChB, FRACP,
FRCPC (Royal Columbian Hospital, New
Westminster, BC); David S. C. Lee, MBBS,
FRCPC (St Joseph’s Health Centre; London,
ON); Derek Matthew, MRCS, FRCPC, SM
(Victoria General Hospital, Victoria, BC);
Douglas D. McMillan, MD, FRCPC
(Foothill’s Hospital, Calgary, AB); Christine
Newman, MD, FRCPC (Hospital for Sick
Children; Toronto, ON); Arne Ohlsson, MD,
FRCPC, MSc (Mt Sinai Hospital, Toronto,
ON; formerly Women’s College Hospital,
Toronto, ON); Abraham Peliowski, MD,
FRCPC (Royal Alexandra Hospital, Edmon-
ton, AB); Margaret Pendray, MBBS, FRCPC
(Children’s and Women’s Health Centre of
British Columbia, Vancouver, BC); Koravan-
gattu Sankaran, MBBS, FRCPC (Royal
University Hospital, Saskatoon, SK); Bar-
bara Schmidt, MD, FRCPC, MSc (Hamilton
Health Sciences Corporation, Hamilton, ON);
Mary Seshia, MBChB, FRCPC (Health Sci-
ences Centre, Winnipeg, MB); Anne Synnes,
MDCM, FRCPC, MHSc (Children’s and
Women’s Health Centre of British Columbia,
Vancouver, BC; formerly Montreal Children’s
Hospital, Montreal, PQ); Paul Thiessen, MD,
FRCPC (Children’s and Women’s Health
Centre of British Columbia, Vancouver, BC);
Robin Walker, MD, FRCPC (Children’s Hos-
pital of Eastern Ontario and Ottawa General
Hospital, Ottawa, ON); Robin Whyte,
MBBS, FRCPC (IWK-Grace Health Centre
for Women, Children and Families, Halifax,
NS). Coordinating Centre: Centre for Com-
munity Health and Health Evaluation Re-
search (Vancouver, BC): Li-Yin Chien, MPH,
ScD; Joanna Sale, MSc; Herbert Chan, MSc;
Shawn Stewart, BA.
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50 Years Ago in The Journal of Pediatrics
ACUTE GLOMERULONEPHRITIS:I
MPETIGO AS AN ETIOLOGICAL FACTOR
McCullough GC, Coffee JY, Trice PA Jr, Stone JJ, Crandall HL. J Pediatr 1951:38:346-8
Acute glomerulonephritis, a relatively common pediatric disorder, was recognized 50 years ago to follow an
antecedent, usually streptococcal, infection. At that time, the vast majority of cases of post-streptococcal
glomerulonephritis followed pharyngeal infections, and the etiologic mechanism was already presumed to be
the product of an antigen-antibody reaction invoked by a “nephrotoxic substance.” In the mid-1940s, a revo-
lution was occurring in the practice of pediatrics: antibiotics became available to treat streptococcal infections.
McCullough and associates had the opportunity to care for 124 children with acute glomerulonephritis in a
community hospital in Fairfield, Alabama, during the new antibiotic era. These authors carefully reviewed
their 5-year experience, from 1944 to 1949, to reappraise the nature of the preceding infections.
In this group of children, the most common type of infection to precede acute glomerulonephritis was im-
petigo (34% of the patients), with acute tonsillitis being a close second (31%). The average length of hospital-
ization was 19.5 days. There were 2 deaths. All but 4 of the children were admitted to the hospital because of
edema, and 4 presented with convulsions. The authors were surprised that bloody urine was not the original
symptom in most of their patients.
This publication was one of the first to emphasize the importance of streptococcal skin infections as an-
tecedents for acute glomerulonephritis. The authors speculated that their recent access to penicillin for strep-
tococcal infections provided preventative therapy for glomerulonephritis, as it did for acute rheumatic fever.
The authors described skin infections as being considered “innocuous” and not customarily triggering aggres-
sive antibiotic therapy. They urged rapid and more vigorous treatment of impetigo as a means of preventing
acute glomerulonephritis.
In 2001, acute post-streptococcal glomerulonephritis is seen much less frequently in the United States but
remains a significant global problem. Because of the decreased experience with post-infectious glomeru-
lonephritis, the diagnosis is now occasionally missed or delayed. Impetigo continues to be an important cause
of acute glomerulonephritis, particularly in warm climates. Today, the immunologic mechanisms leading to
acute glomerulonephritis are better understood; however, it is still unclear whether early antibiotic therapy
for impetigo can prevent glomerulonephritis. Of greater concern is that with the threat of drug-resistant
streptococci looming, acute post-infectious glomerulonephritis may become familiar to pediatricians once
again, unless effective vaccines are developed.
F. Bruder Stapleton, MD
Ford/Morgan Professor and Chair
Department of Pediatrics
University of Washington School of Medicine
Seattle, WA 98105
9/37/114024
doi:10.1067/mpd.2001.114024
