Fetal hydrops and anemia as signs of Down syndrome

Abstract

Before the 20th week of gestation, the most common cause of nonimmune hydrops fetalis is chromosomal abnormalities. Herein, we report a case of fetal hydrops, anemia, and intrauterine growth retardation that presented at 27 weeks of gestation with a negative chromosomal abnormality screening. Cordocentesis and karyotype analysis revealed fetal pancytopenia and Down syndrome. Down syndrome rarely presents with fetal hydrops and anemia. Therefore, when hydrops and anemia are diagnosed, especially in the second trimester of gestation, the possibility of Down syndrome should be kept in mind. In addition, if the pregnancy results in a live birth, the baby should be examined for transient abnormal myelopoiesis.

Full text

CASE REPORT
Fetal hydrops and anemia as signs of Down
syndrome
Yavuz Emre S
‚u
¨ku
¨r*, Murat Go
¨zu
¨ku
¨c¸u
¨k, Vugar Bayramov, Acar Koc¸
Ankara University, Faculty of Medicine, Obstetrics and Gynecology Department, Ankara Universitesi Tip Fakultesi,
Cebeci Hastanesi, Kadin Hastaliklari ve Dogum A.D., Dikimevi, 06100 Ankara, Turkey
Received 28 February 2009; received in revised form 23 April 2009; accepted 30 July 2009
KEYWORDS
Down syndrome;
fetal hydrops;
pancytopenia;
myelopoiesis
Before the 20
th
week of gestation, the most common cause of nonimmune hydrops fetalis is
chromosomal abnormalities. Herein, we report a case of fetal hydrops, anemia, and intra-
uterine growth retardation that presented at 27 weeks of gestation with a negative
chromosomal abnormality screening. Cordocentesis and karyotype analysis revealed fetal
pancytopenia and Down syndrome. Down syndrome rarely presents with fetal hydrops and
anemia. Therefore, when hydrops and anemia are diagnosed, especially in the second
trimester of gestation, the possibility of Down syndrome should be kept in mind. In addition,
if the pregnancy results in a live birth, the baby should be examined for transient abnormal
myelopoiesis.
Copyright ª2011, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.
Introduction
Fetal hydrops may present as a result of any number of
fetal disorders. The incidence of fetal hydrops occurs in
approximately 1 out of 2500e3000 pregancies.
1,2
Rh blood
discordance between the fetus and mother may occur as
a result of this condition, but 87% of the cases have a non-
immunological etiology.
3
The incidence of immunological
fetal hydrops has declined dramatically since the advent of
prophylactic treatment using anti-D immunoglobulin, but it
is still seen on occasion.
The most common etiological factors for nonimmune
hydrops fetalis (NIHF) are structural defects and cardio-
vascular system abnormalities (15e50% of reported
cases).
4,5
The second most common etiological factor for
the development of NIHF is chromosomal abnormalities
(8e16% of cases).
3
The other causes of NIHF include
a variety of other syndromes, including infections, such as
cytomegalovirus (CMV), parvovirus B19, toxoplasmosis, and
syphylis, anemia and various thoracical and genitourinary
disorders.
3
Furthermore, the etiology of 22e35% of NIHF
cases is unknown.
1,6
In the early gestational period, cardiac
failure will generally develop secondary to chromosomal
abnormalities, rather than cardiac abnormalities.
7
* Corresponding author. Ankara University, Faculty of Medicine,
Obstetrics and Gynecology Department, Ankara Universitesi Tip
Fakultesi, Cebeci Hastanesi, Kadin Hastaliklari ve Dogum A.D.,
Dikimevi, 06100 Ankara, Turkey.
E-mail address: yesukur@yahoo.com (Y.E. S
‚u
¨ku
¨r).
0929-6646/$ - see front matter Copyright ª2011, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.
doi:10.1016/j.jfma.2011.09.009
Available online at www.sciencedirect.com
journal homepage: www.jfma-online.com
Journal of the Formosan Medical Association (2011) 110, 716e718

Case
A 28-year-old nulliparous woman, who had not received any
prenatal examinations, was diagnosed with intrauterine
growth retardation (IUGR) and fetal hydrops during the
27
th
week of gestation. Also, because this was her first
visit to an obstetrician, she had not received any nuchal
translucency measurements or the triple test. Her past
medical history included a spontaneous miscarriage at 6
weeks of gestation, but no other diseases or medications
were noted. At her first ultrasonographic examination,
IUGR (compatible with the 24
th
week of gestation), fetal
hydrops, cardiomegaly, pericardial effusion, ascites,
decreased amniotic fluid index (34 mm) and cardiac
arrhythmia were determined (Figs. 1 and 2). The stomach
and bladder of the fetus could not be visualized. The
patient’s blood group was B Rh (þ); therefore, Rh/Rh iso-
immunization was excluded. The presence of toxoplas-
mosis, hepatitis, syphilis, and parvovirus B19 infections
could not be determined on serological screening. Her
complete blood count was used to diagnose here with
maternal anemia (Hb: 9.5 g/dL). Cordocentesis was subse-
quently performed. The fetus’s blood group was A Rh (þ),
and parvovirus B19 IgM was negative. Fetal Hb electro-
phoresis was in normal range (HbF: 81.6%; HbA
2
: 1.7%;
HbA
1
: 16.7%), and no abnormal hemoglobins were detec-
ted. Fetal CBC results were as follows: 7.6 g/dL Hb, 16,200
WBC/mL, and 176,000 thrombocytes/mL. Karyotype analysis
was performed on the blood obtained by cordocentesis.
Because of the diagnosis of fetal supraventricular
tachycardia and anemia, maternal digitalization was per-
formed to determine the possibility of cardiac failure. The
patient was given 0.25 mg digoxin, three times per day, for
the first 24 hours and 0.25 mg digoxin, two times per day,
on the second day. Daily digoxin levels were studied then
studied and ECGs were performed for dose-regulation
purposes.
During the 28
th
week of gestation, cordocentesis was
repeated in order to re-evaluate fetal pancytopenia. The
fetal CBC results were as follows: 4.6 g/dL Hb, 3100
WBC/mL (36.1% polymorphonuclear leucocytes, 56.1%
lymphocytes, 7.8% monocytes), and 28,000 thrombocytes/
mL. Due to the progression of pancytopenia, 75 mL of Rh (e)
blood, compatible with the blood groups of both the
mother and fetus, was slowly transfused via the umbilical
vein.
Serial ultrasonographic measurements were not able to
observe if the fetus was growing, and fetal exitus happened
during the 29
th
week of gestation. The baby was delivered
per vias naturales after induction with misoprostol. Autopsy
established the presence of a cleft lip, simian line in the
right hand, shortened left femur, hepatomegaly, and
extramedullary hematopoiesis. Necrotic and fibrotic areas
were present in the liver. The bone marrow appeared
normal, but hypocellularity was noted. Taken together, the
results of the chromosomal analysis indicated Down
syndrome.
Discussion
When fetal hydrops is established, both the mother and fetus
should be evaluated, both minimally and invasively, using the
appropriate diagnostic tests. After determining the history of
familial diseases, intermarriage, and previous pregnancies,
screening ultrasonography should be performed to determine
plausible etiologies, including congenital, thoracic, and
genitourinary abnormalities. In this case, we determined
cardiomegaly, pericardial effusion, cardiac arrhythmia,
ascites, pleural effusion, fetal growth restriction, and
decreased amniotic fluid. Blood group determination and an
isoimmunization evaluation should be completed when these
conditions present and NIHF is established. Also, parvovirus
and TORCH (toxoplasmosis, rubella, CMV, hepatitis) screen-
ings should be performed using maternal blood samples.
Rarely, special virus and bacterial DNA investigations using
PCR may be necessary.
8
In this case, isoimmunization was not
required and there were no signs of infection.
Down syndrome is the most common autosomal chro-
mosomal abnormality.
9,14
Nuchal translucency thickness,
bowel and cardiac echogenic focuses, shortness of the
extremities, increment in the iliac angle, and pyelectasis
are the ultrasonographic signs of Down syndrome. Also fetal
hydrops, hepatomegaly, and cardiac arrhythmias may be
seen.
10
Figure 1 Fetal pericardial effusion and ascites.
Figure 2 Severe fetal ascites.
Fetal hydrops and anemia as signs of Down syndrome 717

One of the reasons for the development of fetal hydrops
in Down syndrome is transient abnormal myelopoiesis
(TAM). This condition presents in 10% of the babies born
with Down syndrome.
11
In this case, pancytopenia, which is
rarely seen, can be observed on transient abnormal mye-
lopoiesis.
12
The etiological mechanisms for hydrops in cases
of Down syndrome with TAM include heart failure due to
anemia, hepatomegaly, and portal hypertension due to
extramedullary hematopoesis and hypoalbuminemia.
12,13
In
TAM, fetal hydrops has a prognostic value.
12
Another
mechanism for the development of hydrops in babies with
Down syndrome is disseminated lymphatic dysplasia.
14
If
the etiology of hydrops is due to chromosomal abnormali-
ties, the first sign is increased thickness of the nuchal
translucency. Subsequently, depending on the severity of
the dermal edema, pleural effusion and ascites can be
seen.
7
Fetal hydrops has a poor clinical prognosis and mortality
rates are greater than 50%.
1,15
The signs of poor prognosis
include chromosomal abnormalities, structural, cardiac, or
thoracic defects, bradycardia, and symptom onset before
the 24
th
week of gestation.
14,16
Treatment for fetal hydrops
is determined according to its etiology. Possible treatment
methods include transplacental or direct fetal medical
therapies, fetal transfusions, drainage procedures, and
surgery. Transplacental medications are generally applied
via the mother in order to prevent supraventricular tachy-
cardia. In Down syndrome cases, the treatment strategy
should be determined with the family.
The treatment for severe fetal anemia is the use of long-
term blood transfusions. Fetal transfusions are required to
treat fetal hemorrhage, isoimmunization, and parvovirus
B19 infections. The blood used for these transfusions should
be Rh (e), CMV (e), irradiated, and supplemented with
75e85% hematocrit in order to prevent volume overload.
17
Transfusion is done through the umbilical vein using enough
blood to reach the goal of 40e50% hematocrit.
17
The
possible complications of fetal transfusion are death,
infection, and membrane rupture; however, these compli-
cations are much more common in hydropic fetuses.
18
In
this hydropic case, fetal death occurred after the trans-
fusion and the possible mechanism is believed to be cardiac
failure due to anemia secondary to hydrops fetalis.
In conclusion, when NIFH is determined, screening
ultrasonography should first be performed in order to
detect any structural abnormalities. Also, laboratory tests
for parvovirus B19, TORCH, and syphilis should be per-
formed. Subsequently, fetal karyotype analysis should be
performed via amniocentesis or cordocentesis. It should be
determined if anemia, hepatomegaly, and cardiac abnor-
malities are present in addition to NIHF. One of the most
important diagnoses that can be made is Down syndrome,
and this disorder has a poor prognosis.
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