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ß 2008 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A 146A:312 – 320 (2008)
Hematological Abnormalities During the First Week of
Life Among Neonates With Trisomy 18 and Trisomy 13:
Data From a Multi-Hospital Healthcare System
S.E. Wiedmeier,1,2* E. Henry,1 and R.D. Christensen1
1
Department of Women and Newborns, Intermountain Healthcare, Institute for Health Care Delivery Research,
Salt Lake City, Utah
2
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah
Received 14 June 2007; Accepted 3 September 2007
Limited information is available on the expected hematological values of newborn infants with trisomy 18 or trisomy
13 syndromes. About 50% of patients with these conditions
survive beyond the first week of life, and some have
complete blood counts (CBCs) obtained to assist in medical
management. We tabulated all CBC data that had been
obtained on patients with either trisomy, during their
first week of life, using data from an 18 hospital healthcare
system. We posited that describing the CBC findings would
assist clinicians in providing care for these patients who
survive beyond the first days. During the period of January 1,
2001 through December 31, 2006, 174,480 live births were
recorded at the 18 hospitals. Trisomy 18 was recognized in
28 (prevalence estimate, 1 in 6,231) and trisomy 13 in
22 (prevalence estimate, 1 in 7,931). Twenty-four of these
had one or more CBCs obtained before the seventh day.
Thrombocytopenia was the most common hematological
abnormality detected, occurring in 83% of those with trisomy
18 and 75% of those with trisomy 13. Three patients with
trisomy 18, and 1 with trisomy 13, received platelet
transfusions. The second most commonly detected abnormality was neutrophilia. Eighty-three percent of neonates
with trisomy 13, and 42% with trisomy 18, had neutrophil
concentrations above the upper limit of normal for age.
Abnormal erythrocyte values were the third most common
hematological abnormalities detected. These were much
more common among neonates with trisomy 18. Only 43% of
patients with trisomy 18 had normal erythrocyte values;
anemia was detected in 40% and polycythemia in 17%. Only
one neonate with trisomy 13 had abnormal erythrocyte
findings (polycythemia). These data should assist clinicians
caring for neonates with trisomy 18 or 13, demonstrating
how common hematological abnormalities exist among
these patients. ß 2008 Wiley-Liss, Inc.
Key words: complete blood count; trisomy 18; trisomy 13;
thrombocytopenia; neutrophilia; anemia; polycythemia
How to cite this article: Wiedmeier SE, Henry E, Christensen RD. 2008. Hematological abnormalities
during the first week of life among neonates with trisomy 18 and trisomy 13: Data from
a multi-hospital healthcare system. Am J Med Genet Part A 146A:312–320.
INTRODUCTION
Neonates with trisomy 18 and trisomy 13, are
encountered with regularity in the practice of neonatal intensive care medicine. The prevalence at birth
of trisomy 18 ranges between 1 in 3,600 and 1 in 8,500
live born infants [Root and Carey, 1994; Embleton
et al., 1996; Forrester and Merz, 1999], and the
prevalence of trisomy 13 ranges between 1 in 5,000
and 1 in 29,000 [Goldstein and Nielsen, 1988; Wyllie
et al., 1994; Forrester and Merz, 1999]. Although life
expectancy is short for patients with either trisomy,
some receive hospital care for days or weeks, during
which time they can have laboratory tests drawn to
provide information useful in directing their medical
care [Rasmussen et al., 2003]. However, little
formation is available on the expected hematological
values of newborn infants with these syndromes.
Intermountain Healthcare (IHC) is a not for profit
corporation operating 20 hospitals, 18 with delivery
services, in the western United States. About 30,000
births occur annually in the IHC hospitals. On that
basis we estimated that five to 15 neonates/year in
the IHC system would be identified as having either
trisomy 18 or 13 syndrome. We hypothesized that
most of these patients had CBCs (complete blood
cell counts) performed. We postulated further, that
compiling the CBC data from these patients, during
the most recent 6-year period, would constitute the
*Correspondence to: S.E. Wiedmeier, M.D., Neonatal Intensive Care,
Intermountain Healthcare, LDS Hospital, 8th Ave and C Street, Salt Lake
City, UT 84143. E-mail: ldswiedm@ihc.com
DOI 10.1002/ajmg.a.32107
American Journal of Medical Genetics Part A: DOI 10.1002/ajmg.a
313
HEMATOLOGICAL ABNORMALITIES IN NEONATES WITH TRISOMY 18 AND TRISOMY 13
largest series to date dealing with these issues, and
that such data would be of value to clinicians caring
for neonates with these conditions.
managed and accessed by authorized data analysts.
The Intermountain Healthcare Institutional Review
Board approved this study.
METHODS
RESULTS
Data were collected as a de-identified limited data
set from archived IHC electronic records of all
newborn infants where the diagnosis of either
trisomy 18 or trisomy 13 was made either prenatally
or during the first month after birth. The newborn
services provided within the 18 IHC hospitals with
delivery services include eight Level 1, six Level 2,
and four Level 3 nurseries.
The information collected for analysis was
limited to demographics and the data contained
in the CBCs. Demographic characteristic included
gestational age, birth weight, gender, race, Apgar
score at 5 min, level of neonatal care available at
delivery hospital, in-hospital mortality, length of
initial hospital stay for all patients, and discharge
disposition. Data were collected only for CBCs
obtained <7 days after birth, and only on neonates
with a date of birth from January 1, 2001 through
December 31, 2006, who within the first month of life
had a karyotype analysis confirming the diagnosis of
either trisomy 18 or 13. The program used for data
collection is a modified subsystem of ‘‘clinical workstation.’’ The 3M Company (Minneapolis, MN)
approved the structure and definitions of all data
points for use within the program. The data were
collected from the electronic medical record, case
mix, and laboratory systems. Trained and designated
clinical personnel enter additional data. Data are
Between January 1, 2001 and December 31, 2006,
174,480 live births were recorded at the 18 IHC
hospitals. Twenty-eight of these neonates were
identified as having trisomy 18 (prevalence at birth
estimate, 1/6231) and 22 were identified as having
trisomy 13 (prevalence at birth estimate, 1/7,931).
Twenty-four of these 50 (12 with trisomy 18, and 12
with trisomy 13) had one or more CBCs obtained
during the first 144 hr after birth and recorded in the
IHC electronic database. Karyotype analysis of these
24 included three with an unbalanced Robertsonian
translocation trisomy 13, and 1 with mosaic trisomy
13. The chromosomal abnormality of the remaining
20 was not specified in the electronic records,
although all were stated to have either ‘‘trisomy 18’’
or ‘‘trisomy 13.’’
Demographic features of the 50 neonates are listed
in Table I. The patients with trisomy 18 or 13 who had
a CBC obtained during the first week of life and the
group of patients with trisomy 18 who did not, were
of similar gestational age, term or near-term, and the
majority were small for gestational age (SGA). The
group of patients with trisomy 13 who did not have a
CBC obtained during the first week were slightly
more preterm and a smaller percentage were SGA
compared to the patients in the other three groups.
The distribution of Apgar scores at 1 min was
different for the patient groups. A higher proportion
TABLE I. Demographic Features and Outcomes of 50 Neonates With Trisomy 18 or Trisomy 13
Neonates with trisomy
18 who had one or
more CBCs during
the first week (n ¼ 12)
Gestational age (weeks) SD
Birth weight (g) mean SD
Percent who were SGAa
Gender (% male)
Born in hospital with Level III NICU
Apgar score of <4 at 5 min
Race
White nonhispanic
Hispanic
Other
Outcomes
Died in the hospital—never discharged
home
Died in the hospital within 24 hr of birth
Discharged home from the hospital
Transferred to a non-IHC hospital
Discharged to a long-term care facility
Mean length of the initial hospital
stay—hours
Neonates with trisomy Neonates with trisomy 13
Neonates with
18 who had no CBCs who had one or more
trisomy 13 who
during the first
CBCs during the
had no CBCs during
week (n ¼ 16)
first week (n ¼ 12)
the first week (n ¼ 10)
36.1 3.7
2,007 66
83% (10/12)
25%
50% (6/12)
8% (1/12)
36.8 2.4
1,624 518
100% (16/16)
44%
69% (11/16)
38% (6/16)
37.3 2.1
2,627 704
83% (10/12)
58%
67% (8/12)
8% (1/12)
32.4 6.3
1,752 1,040
40% (4/10)
50%
90% (9/10)
70% (7/10)*
8
2
2
16
0
0
8
3
1
9
0
1
42% (5/12)
81% (13/16)*
50% (6/12)
100% (10/10)*
8% (1/12)
50% (6/12)
8% (1/12)
0%
43.5 (median 11.0)
75% (12/16)*
19% (3/16)
0%
0%
20.8 (median 4.5)
8% (1/12)
42% (5/12)
0%
8% (1/12)
114.5 (median 7.5)
100% (10/10)*
0%*
0%
0%
1.6 (Median 1.0)*
a
SGA, small for gestational age (weight <10th centile).
*P < 0.05 versus ‘‘had CBC’’ group.
American Journal of Medical Genetics Part A: DOI 10.1002/ajmg.a
314
WIEDMEIER ET AL.
of patients with either trisomy who did not have a
CBC during the first week had an Apgar score of less
than 4 recorded at 5 min of age compared to the
group of patients who did have a CBC. In addition,
when compared to patients who did have a CBC, a
significantly higher proportion of neonates with
trisomy 18 or 13 who did not have a CBC died during
their initial hospitalization, most within 24 hr of
delivery. Fifty percent (12/24) of the patients who
had a CBC survived the initial neonatal period and
were ultimately discharged from the hospital. In
contrast only 12% (3/26) of the patients who did not
have a CBC survived long enough to eventually be
discharged (Table I).
The number of CBCs obtained from each of the 50
neonates, during the first week after birth, ranged
from 0 to 9 (median, 2). Blood neutrophil concentrations of the 12 with trisomy 18 and the 12 with
trisomy 13 are shown in Figure 1. Using the criteria of
Manroe et al. [1979], 26% of the blood neutrophil
counts of those with trisomy 18 were in the
neutrophilic range, 54% were in the normal range,
and 20% were in the neutropenic range. Blood
neutrophil counts of those with trisomy 13 included
64% in the neutrophilic range, 33% in the normal
range, and 3% in the neutropenic range.
Platelet counts are shown in Figure 2. Fifty-two
platelet counts were obtained on the 12 neonates
with trisomy 18, with values ranging from 21,000 to
240,000/ml. Seventy-six percent of the counts were in
the thrombocytopenic range (<150,000/ml). Fortyfive percent were in the moderately severe thrombocytopenic range (50,000–100,000/ml), and 6%
were <50,000/ml. Thirty-seven platelet counts were
obtained on the 12 neonates with trisomy 13, with
values ranging from 45,000 to 235,000/ml. Fifty-one
percent of the counts were in the thrombocytopenic
range (<150,000/ml). Twenty-two percent were in
the moderately severe thrombocytopenic range, and
3% were <50,000/ml. The mean platelet volume for
patients with Trisomy 18 was 8.95 fL with 30% of
values above 10 fL and 14% of values below 7.5 fL.
The mean platelet volume for patients with Trisomy
13 was 9.2 fL with 15% of values above 10 fL and 1.5%
of values below 7.5 fL. Three patients with trisomy 18
and 1 patient with trisomy 13 received one or more
platelet transfusions.
Hematocrit and hemoglobin values are shown in
Figure 3 (panels A and B). Polycythemia (hematocrit
>65% or hemoglobin >22g/dl) was identified in 1%
of the CBCs of neonates with trisomy 18. Seventy-five
percent of the hematocrit and hemoglobin values of
neonates with trisomy 18 were normal (40–65% and
13–22 g/dl), while a hematocrit <40% or hemoglobin <13 g/dl was identified in 14%. Polycythemia
was identified in 3% of the CBCs of neonates with
trisomy 13. One underwent a reduction transfusion.
Ninety-five percent of the hematocrit and hemoglobin values of neonates with trisomy 13 were normal,
and no low values were identified.
Nucleated erythrocyte counts (NRBC) ranged from
zero to 584/ml for neonates with trisomy 18 and zero
to 402/ml for those with trisomy 13 (Fig. 3, panel C).
By three days (60 hr) all NRBC concentrations were
<100/ml. As shown in Figure 3 (panel D), the mean
corpuscular volume for neonates with trisomy 18
(109 8 fl) and with trisomy 13 (109 þ 6) were in the
normal range (108 8 fl), [Christensen, 1999].
DISCUSSION
The trisomy 18 and 13 syndromes are two of
the most common multiple congenital anomaly
syndromes in live born infants, with a combined
prevalence of approximately 1 in 4,000 births.
Although numerous reports describe the structural
defects associated with both of these conditions,
there is limited information on the prevalence of
their hematological abnormalities during the neonatal period. The current study was undertaken to
evaluate the CBC findings of neonates with trisomy
18 or 13 in the first week of life, using electronically
archived data from an 18 hospital healthcare system,
in a manner similar to our recent study of the
hematological abnormalities of neonates with Down
syndrome [Henry et al., 2007].
Thrombocytopenia was the most common hematological abnormality identified, having been detected in over 75% of cases (Table II). Smith’s latest
catalog reports that thrombocytopenia occurs in
TABLE II. Hematological Problems Recognized in the First 7 Days After Birth, Among Neonates With
Trisomy 18 or Trisomy 13
Hematological problem
Neutrophiliaa
Thrombocytopeniab
Polycythemiac
Anemia
Neutropenia
a
Trisomy 18 proportion
with this problem
recognized (n ¼ 12)
Trisomy 13 proportion
with this problem
recognized (n ¼ 12)
P-value
(5) 42%
(10) 83%
(2) 17%
(5) 42%
(3) 25%
(10) 83%
(9) 75%
(1) 8%
(0) 0%
(1) 8%
0.040
0.500
0.500
0.019
0.295
Blood neutrophil concentration > upper limit of normal for postnatal age [Manroe et al., 1979].
Platelet concentration <150,000/ml.
Hemoglobin >22 g/dl or hematocrit >65%.
b
c
American Journal of Medical Genetics Part A: DOI 10.1002/ajmg.a
HEMATOLOGICAL ABNORMALITIES IN NEONATES WITH TRISOMY 18 AND TRISOMY 13
315
FIG. 1. Blood concentration of neutrophils during the first 144 hr after birth among 12 neonates with trisomy 18 (squares) and 12 neonates with trisomy 13 (circles).
Heavy lines are drawn to estimate the upper and lower limit of anticipated values for neonates (normal values from Manroe et al. [1979]).
FIG. 2. Blood concentration of platelets, and mean platelet volume, during the first 144 hr after birth among 12 neonates with trisomy 18 (squares) and 12 neonates
with trisomy 13 (circles). Panel A: Platelet concentration per microliter of blood. Heavy lines are drawn at 150,000/ml and 450,000/ml, as estimates of the upper and lower
limits of normal for platelet concentrations of neonates. Panel B: Mean platelet volume (fL).
American Journal of Medical Genetics Part A: DOI 10.1002/ajmg.a
316
WIEDMEIER ET AL.
FIG. 2. (Continued )
FIG. 3. Hematocrit, hemoglobin concentration, nucleated erythrocyte concentration, and mean corpuscular volume, during the first 144 hr after birth among 12
neonates with trisomy 18 (squares) and 12 neonates with trisomy 13 (circles).Panel A: Hematocrit (%). Heavy lines are drawn at 40% and at 65%, as estimates of the
lower and upper limit of normal values in neonates [Christensen, 1999]. Panel B: Hemoglobin (g/dl). Heavy lines are drawn at 13 and 22 g/dl, as estimates of the lower
and upper limit of normal values in neonates [Christensen, 1999]. Panel C: Nucleated erythrocytes (cells/ml). Panel D: Mean corpuscular volume (fL). Heavy lines are
drawn at 100 and 116 fL, as estimates of two standard deviations from the normal mean value of 108 fL among normal neonates [Christensen, 1999].
American Journal of Medical Genetics Part A: DOI 10.1002/ajmg.a
HEMATOLOGICAL ABNORMALITIES IN NEONATES WITH TRISOMY 18 AND TRISOMY 13
FIG. 3. (Continued )
317
American Journal of Medical Genetics Part A: DOI 10.1002/ajmg.a
318
WIEDMEIER ET AL.
FIG. 3. (Continued )
<10% of patients with trisomy 18 and in <50% of
patients with trisomy 13 [Jones, 2006]. Consistent
with our data, Kosho et al. [2006] reported thrombocytopenia in 83% (20/24) of patients with trisomy 18.
In addition, Hohlfeld et al. [1994] reported that 87% of
fetuses with trisomy 18, and 54% of fetuses with
trisomy 13, had platelet counts <150,000/ml. While
collectively these data indicate that thrombocytopenia is common in this group of neonates, we know of
no studies that delineate the responsible mechanism.
Thrombocytopenia is commonly seen in preterm
SGA infants, however it is relatively less common in
term SGA infants [Sola et al., 2000]. In the current
study we noted that while 83% of the neonates who
had one or more CBCs obtained during the first week
after birth were SGA they were all term or near-term
at the time they were delivered making it unlikely
that their SGA status was the single underlying
explanation for their thrombocytopenia. Birth
asphyxia also appears to be a significant risk factor
for neonatal thrombocytopenia [Sola and Christensen, 1999]. Only two of the 24 patients on whom
CBCs were obtained in the current study had an
Apgar score of less that four recorded at 5 min of age
making it unlikely that hypoxia contributed significantly to the pathogenesis of thrombocytopenia in
this group of neonates. Thrombocytopenia also
commonly accompanies systemic infections in neonates. The thrombocytopenia accompanying neonatal sepsis is the kinetic result of accelerated platelet
destruction, and results in a high MPV from a
compensatory release of immature platelets from
the marrow [Patrick and Lazarchick, 1990]. Our
patients with trisomy 18 and 13 did not have a high
MPV, suggesting that the kinetic mechanism in these
patients was not infectious. Decreased platelet
production as a consequence of reduced megakaryocytes or impaired platelet production from megakaryocytes has been identified as the mechanism
responsible for the neonatal thrombocytopenia
associated with a variety of syndromes and congenital disorders. While it is tempting to hypothesize a
similar cause for the thrombocytopenia noted in
neonates with trisomies 18 or 13 much more
investigation will be needed to definitively identify
the responsible mechanism. Potential approaches
might include measuring plasma thrombopoietin
concentrations, reticulated platelet counts, and
marrow biopsies [Sola-Visner et al., 2007].
The second most common hematological abnormality observed was neutrophilia (Table II). Eighty
three percent of neonates with trisomy 13, and 42%
of those with trisomy 18, had blood neutrophil
concentrations above the upper limits of normal
American Journal of Medical Genetics Part A: DOI 10.1002/ajmg.a
HEMATOLOGICAL ABNORMALITIES IN NEONATES WITH TRISOMY 18 AND TRISOMY 13
[Manroe et al. 1979]. Structural anomalies of neutrophils of patients with trisomy 13 have been
reported by several investigator [Huehns et al.,
1964; Salama et al., 2004], but we are unaware of
previous studies documenting the high prevalance of
neutophilia in neonates with trisomy 18 or 13.
Normal neutrophil counts were observed in only
33% of those with trisomy 18 and in fewer than 10% of
those with trisomy 13, suggesting the possibility of
neutrophil dysregulation in these patients.
Abnormal erythrocyte values were the third most
common hematological abnormalities detected
(Table II). These were much more common among
neonates with trisomy 18. In fact, only about 40%
of those with trisomy 18 had normal erythrocyte
values, with anemia present in 40%, polycythemia
in 17%, and an abnormally high or low MCV in
40%. Perhaps, similar to their wide range of neutrophil concentrations, this finding suggests dysregulation of erythropoiesis among patients with
trisomy 18. In contrast, anemia was not detected
in any of the patients with trisomy 13; however one
had polycythemia diagnosed, with a hematocrit
of 69%, and underwent a reduction transfusion.
Werner also reported an increased incidence of
polycythemia in patients with trisomy 18 or 13
[Werner, 1995].
We recognize that our study has several shortcomings. For instance, the results are limited by a
relatively small sample size, and also by the potential
for selection bias, because CBCs were obtained on
only about half of the 50 affected neonates. We were
unable to definitively determine whether fewer CBCs
were obtained if the diagnosis of trisomy had been
made prenatally. One would anticipate that the
medical care provided to neonates in whom the
diagnosis of either trisomy 18 or 13 had been made
prenatally would have been influenced by parenteral
decisions regarding resuscitation and previously
agreed upon therapeutic interventions. We speculate
that this was the case as compared to patients who
had CBCs, a significantly higher proportion of
patients who did not, had Apgar scores of less than
4 at 5 min and died during their initial hospitalization,
most within 24 hr. Another shortcoming is that the
anatomic site of the blood drawn for testing is not
listed in our electronic records, and therefore the
results we report surely contain some venous,
some capillary, and perhaps some arterial sources.
While platelet counts, and determinations of the MPV
and MCV, do not vary significantly with the anatomic
source, capillary values tend to run somewhat higher
than vascular sources when assessing a neonate’s
hemoglobin and hematocrit [Christensen, 1999].
Arterial blood tends to have a lower leukocyte count
than simultaneously obtained venous or capillary
samples [Christensen and Rothstein, 1979].
An additional shortcoming is that we did not
determine the mechanistic explanations for the
319
hematological abnormalities found. Erythropoiesis
and myelopoiesis are multifaceted dynamic processes regulated by cell–cell and cell–matrix interactions, stimulatory and inhibitory cytokines, and an
assortment of transcription factors. Clearly, more
extensive studies will be necessary to determine the
precise impact of genomically unbalanced changes,
such as trisomy 18 or 13, on the developing
hematopoietic system. Despite these limitations,
our findings illustrate that CBC abnormalities are
very common among neonates with trisomy 18 and
13, and if our study is representative, one or more
CBCs are obtained on about half of these patients
during their first week following birth.
Many complex medical and ethical issues arise in
the management of neonates with trisomy 18 or 13
[Carey, 2001]. While the neonatal mortality rates for
patients with either of these conditions is high, it is
important to recognize that a number of these
patients will have longer-term survival [Baty et al.,
1994; Root and Carey, 1994; Brewer et al., 2002;
Rasmussen et al., 2003; Duarte et al., 2004; Kosho
et al., 2006]. We maintain that our present report can
assist clinicians directing the medical care of neonates with trisomy 18 or 13, by heightening their
awareness of the common hematological abnormalities to be anticipated in these neonates.
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