Case Report

A woman, 39 years old, G3P2 was referred to Harapan Kita hospital at gestational age 26 weeks due to
polyhydramnion and cardiomegaly of fetus. The patient denied any complaints such as premature
contraction, genital bleeding, mucus or amniotic fluid during this pregnancy. The mother has history of
thalassemia. Blood type Prior pregnancies were delivered aterm and through Caesarean Section.

Abdominal ultrasound examination revealed the fetus to have cardiomegaly and ascites. USG-guided
cordocentesis, to check fetal haemoglobin and fetal hematocrit levels along with karyotyping, and fetal
ascites reduction was done for this patient. Fetal Hb was xxx and fetal hematocrit was xxx, showing fetal
anemia. Intrauterine Transfusion was planned for this patient and carried at 27 wga. Karyotyping results
showed no chromosomal abnormality and the examination was advised to be repeated after the baby
was born.

Patient came to the hospital 2 days after the first intrauterine transfusion with complaints of uterine
contractions. Pregnancy was currently at 27 wga. Complaints of genital bleeding, discharge, mucus or
amniotic fluid are denied. Patient was admitted to inpatient ward. Further examination showed that the
mother had anemia and hypoalbuminemia.

Abdominal ultrasound was repeated at 27+6 wga and revealed estimated fetal weight (EFW) was 666
grams, CTR >50%, Pi MCA 1,14, and the fetus was diagnosed with hydrops fetalis and IUGR. Intrauterine
transfusion was planned and carried out at 28 wga.

After the second intrauterine transfusion at 28+4 wga, abdominal ultrasound was repeated and showed
EFW 775 grams with hydrops fetalis and IUGR. The examination was repeated at 28+6 wga and EFW was
1178 grams, CTR >50%, and the diagnosis was hydrops fetalis with IUGR.

Ultrasound examination at 33+2 wga showed EFW 1465, CTR 60%, with diagnosis of IUGR,
oligohydramnion, cardiac myopathy and hydops fetalis. Fetal lung maturation was planned and carried
out for this patient.

At 34+6 wga, Abdominal ultrasound examination was repeated and showed EFW of 1532 grams, CTR >
50%, CPR > 1, consistent with previous diagnosis of IUGR and hydrops fetalis. The baby was delivered
through caesarean section at 35+1 wga.

Discussion

Intrauterine transfusion (IUT) should be done urgently if MCA-PSV exceeds 1.5 multiples of median
(MoM) and/or if signs of hydrops are present, as both of them correlate strongly to moderate severe
anemia.(1) IUT is agreed to be done in case of moderate to severe anemia, defined as hemoglobin
concentrations of four to five SD below mean/median for gestational age or a Heoglobin deficit of 5
g/dL or more. (2, 3)
Intrauterine transfusions are carried out with O-negative, washed, irradiated, leukocyte-depleted
blood, negative for antigens against which the mother is immunized (4)
Fetal survival after intrauterine transfusion depends upon the severity of the illness, method of
transfusion, and the skill of the doctor who does the procedure. Overall, the survival rate of fetuses
without hydrops is more than 90% and 75% for fetuses with hydrops. (5)
Possible complications of this procedure are: bleeding from the puncture site, cord occlusion, brady-
or tachycardia and PPROM or preterm labor, along with intrauterine infection (6,7) IUT performed
before 20-22 weeks of gestation carry a higher risk of procedure-related complications compared to
later IUT due to technical difficulties and severity of disease. (8)
There are other noninvasive treatment options has been proposed to postpone IUT in early severe
HDFN, but cannot be used as a sole treatment if fetal anemia is already present. Therapeutic
plasma exchange (TPE), in which patient’s plasma is removed and replaced with albumin-rich fluid
and the the maternal antibodies directed against fetal red cell antigens are then removed. This
procedure may cause decrease in antibody titers as much as 75%. However, the beneficial value of
TPE alone in postponing IUT in early severe HDFN was disappointing. (9)

The effect of IVIG in HDFN may result from various mechanisms such as inhibition of Fc-
mediated antibody passage across the placenta, negative feedback on maternal antibody
production and/or reticuloendothelial Fc-receptor saturation/blockage, resulting in decreased
uptake of opsonized fetal cells by macrophages (10). IVIG may prevent or reduce fetal
hemolysis, but does not treat fetal anemia. (11)

1. Mari G, Deter RL, Carpenter RL, et al. Noninvasive diagnosis by Doppler ultrasonography
of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler
Assessment of the Blood Velocity in Anemic Fetuses. N Engl J Med. 2000;342:9–14. Epub
2000/01/06.
2. Nicolaides KH, Soothill PW, Clewell WH, et al. Fetal haemoglobin measurement in the
assessment of red cell isoimmunisation. Lancet (London, England). 1988;1:1073–1075.
Epub 1988/05/14.
3. Osanan GC, Silveira Reis ZN, Apocalypse IG, et al. Predictive factors of perinatal mortality
in transfused fetuses due to maternal alloimmunization: what really matters? J Maternal-
Fetal Neonatal Med. 2012;25:1333–1337. Epub 2011/11/04.
4. Van Kamp IL, Klumper FJ, Meerman RH, et al. Treatment of fetal anemia due to red-cell
alloimmunization with intrauterine transfusions in the Netherlands, 1988-1999. Acta Obstet
Gynecol Scand. 2004;83:731–737. Epub 2004/07/17.
4x Mari G, Norton ME, Stone J, et al. Society for Maternal-Fetal Medicine (SMFM) clinical
guideline #8: the fetus at risk for anemia–diagnosis and management. Am J Obstet
Gynecol. 2015;212:697–710. Epub 2015/04/01.
4y Zwiers C, Lindenburg IT, Klumper FJ, et al. Complications of intrauterine intravascular
blood transfusions: lessons learned after 1678 procedures. Ultrasound Obstetrics
Gynecology. 2016. doi:10.1002/uog.17319. Epub 2016/10/06.
4z Leveque C, Murat I, Toubas F, et al. Fetal neuromuscular blockade with vecuronium
bromide: studies during intravascular intrauterine transfusion in isoimmunized pregnancies.
Anesthesiology. 1992;76:642–644. Epub 1992/04/01.

5. Branch DW, et al. (2008). Immunologic disorders in pregnancy. In RS Gibbs et al., eds.,
Danforth's Obstetrics and Gynecology, 10th ed., pp. 313-339. Philadelphia: Lippincott Williams
and Wilkins.
6. Van Kamp IL, Klumper FJ, Oepkes D, et al. Complications of intrauterine intravascular
transfusion for fetal anemia due to maternal red-cell alloimmunization. Am J Obstet
Gynecol. 2005;192:171–177. Epub 2005/01/27.
7. Somerset DA, Moore A, Whittle MJ, et al. An audit of outcome in intravascular transfusions
using the intrahepatic portion of the fetal umbilical vein compared to cordocentesis. Fetal
Diagn Ther. 2006;21:272–276. Epub 2006/04/08.
8. Lindenburg IT, Van Kamp IL, Van Zwet EW, et al. Increased perinatal loss after intrauterine
transfusion for alloimmune anaemia before 20 weeks of gestation. BJOG. 2013;120:847–
852. Epub 2013/04/05.
9. Schwartz J, Padmanabhan A, Aqui N, et al. Guidelines on the use of therapeutic apheresis
in clinical practice-evidence-based approach from the writing committee of the American
Society for Apheresis: the seventh special issue. J Clin Apher. 2016;31:149–162. Epub
2016/06/21.
10. Gottvall T, Selbing A. Alloimmunization during pregnancy treated with high dose
intravenous immunoglobulin. Effects on fetal hemoglobin concentration and anti-D
concentrations in the mother and fetus. Acta Obstet Gynecol Scand. 1995;74:777–783.
Epub 1995/11/01.
11. Voto LS, Mathet ER, Zapaterio JL, et al. High-dose gammaglobulin (IVIG) followed by
intrauterine transfusions (IUTs): a new alternative for the treatment of severe fetal
hemolytic disease. J Perinat Med. 1997;25:85–88. Epub 1997/01/01.