Hypertension in Pregnancy, 24:313–317, 2005

Copyright D 2005 Taylor & Francis Inc.

ISSN: 1064-1955 print / 1525-6065 online
DOI: 10.1080/10641950500281100

Temporary Resolution of
Preeclamptic Symptoms
After Intrauterine Death of
One Twin
Frank Bschierl1 and Ernst Beinder, M.D.2,*
1
Department of Internal Medicine, Hospital St. Marien, Erlangen, Germany
2
Department of Obstetrics, University Hospital of Zurich, Zurich, Switzerland
In a 34 year old woman with dichorionic twin pregnancy preeclampsia resolved after
the intrauterine death of one of the HLA-identical twins and recurred with the growth
of the placenta of the surviving twin later in pregnancy. This case gives indirect
evidence that the clinical course of preeclampsia is a dose-dependent phenomenon in
conjunction with vital placental tissue.

Keywords Preeclampsia, Intrauterine death, Twin pregnancy.

INTRODUCTION
Preeclampsia originates in the placenta with a usually progressive clinical
course and is only cured by delivery of the placenta. Redman and Sargent
hypothesized that the continuous release of placental debris into the maternal
circulation provokes a systemic inflammatory response which is exaggerated if
the burden of debris is abnormally high (3). We describe a twin pregnancy
with resolution of preeclamptic symptoms after the intrauterine death of one
of the twins and discuss this observation with respect to the placental theory
of preeclampsia.

*Address correspondence to Ernst Beinder, M.D., Department of Obstetrics, Uni-

versity of Zurich, Frauenklinikstr. 10, Zurich 8091, Switzerland; Fax: 41/1255-4430;
E-mail: ernst.beinder@usz.ch

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314 Bschierl and Beinder
 Temporary Resolution of Preeclamptic Symptoms 315

CASE REPORT
A 34-year-old woman was referred at 27 weeks of a dichorionic twin gestation
with symptoms of preeclampsia. The patient’s first pregnancy had ended in
spontaneous early miscarriage, but otherwise her medical history was
unremarkable. On admission the patient showed arterial hypertension (175/
100 mmHg on repeat measurements) and proteinuria (dipstick + + + ). Her
blood pressure at 12, 18, and 23 weeks of gestation was < 140/90 mmHg. The
blood results (regarding thrombocyte count, liver enzymes, and the global
coagulation parameters) were normal. The quantitative analysis of protein-
uria in a 24-hour urine sample taken after admission showed 1.6 g/day. She
had bilateral slight ankle edema but no headache or visual disturbances.
Ultrasound examination revealed the death of one fetus, which occurred in the
24 hours prior to admission to our hospital, because the referring physician
had demonstrated both fetuses alive by ultrasound examination the previous
day. Ultrasound examination showed a thick intertwin membrane and,
therefore, confirmed the first trimester diagnosis of a dichorionic diamniotic
but single placental mass. While the fetal growth as well as the Doppler
profiles of the surviving twin were normal, the dead fetus appeared growth
restricted [estimated fetal weight below the fifth percentile according to the
curves from Hadlock et al. (1)]. In view of gestational age, it was decided to
prolong the pregnancy under close observation provided maternal and fetal
condition would allow it. The patient received alpha-methyldopa in a dosage of
750 mg daily for blood pressure control. During the following three weeks, a
remarkable improvement was noted: Blood-pressure fell, permitting a gradual
reduction and, finally, the stopping of the antihypertensive treatment.
Proteinuria fell to values below 50 mg/day (sensitivity limit of the
semiquantitative screening test in use) and the body weight decreased from
initially 101 kg to 96 kg (Fig. 1).
Frequent monitoring of twice-daily cardiotocograms and twice-weekly
biophysical profiles with Doppler studies was satisfactory. The biometry
showed a linear growth of the surviving fetus. At 31 + 3 weeks of gestation, 15
days after the preeclamptic symptoms had vanished, a significant proteinuria
reappeared accompanied by an increase in blood pressure. Some days later, a
reduced growth velocity of the surviving fetus was detected, the Doppler
profiles, amniotic fluid index, and cardiotocographic studies continued to
be normal.
At the end of the 34th week of gestation, as the proteinuria had surpassed
4 g/day, labor was induced by local application of prostaglandins. The patient
gave spontaneous vaginal birth to a healthy female infant weighing 1,720 g,
followed by a macerated female fetus of approximately 500 g. The mother

Figure 1: The clinical course (proteinuria in mg/24 h, body weight, and blood pressure) by
gestational age.
316 Bschierl and Beinder

recovered quickly and was discharged from hospital on the fourth day
postpartum. The baby spent another two uneventful weeks under supervision
in a neonatal care unit. The further development of the child was favorable,
and both the mother and her little daughter were still doing well two years
later. Neither an elevated blood pressure nor proteinuria indicating renal
disease or symptoms of immunologic diseases were noted in the mother six
weeks postpartum. The child was developmentally normal in the formal
pediatric assessment at age 2 years.
Human leukocyte antigen (HLA)-genotyping (performed with the permis-
sion of the parents), based on cord blood of the surviving infant and on muscle
biopsies taken from the dead fetus, revealed their HLA identity. Further
comparative genomic studies were impossible due to advanced degradation of
the DNA of the deceased fetus. The placental histology showed extensive
necrotic lesions in the part of the placenta belonging to the intrauterine
deceased fetus. The histology of the placenta of the surviving twin revealed
fibrin deposition on the surface of villi and intervillous thrombosis in distinct
areas of the placenta. Placental bed biopsy was not performed.

DISCUSSION
Zaki et al. (2) described the spontaneous reversal of preeclampsia associated
with parvovirus-induced hydrops. They explain their findings with the
placental theory of preeclampsia as suggested by Redman and Sargent (3):
The placental hydrops leads to an increase in the shedding of placental
debris into the maternal circulation and, hence, to an increased systemic
inflammatory response in the mother inducing the syndrome of preeclamp-
sia. After the spontaneous regression of the hydrops, the preeclamptic
symptoms vanished in their patient, presumably due to a decrease in the
placental volume.
In this respect, we observed an interesting and unusual case, which
supports the placental theory of preeclampsia in a different clinical situation
from that described by Zaki et al: In our patient, preeclampsia resolved after
the intrauterine death of one of HLA-identical twins and recurred with the
growth of the placenta of the surviving twin in later pregnancy. Fetal death
induces necrosis of the corresponding placenta and might therefore alter the
immunogenic maternofetal response.
In general, preeclampsia takes a progressive course without any major
improvement until delivery. One explanation of the resolution of preeclampsia
in our patient is that the death of one fetus and the associated necrosis of the
corresponding placenta reduces the amount of syncytiotrophoblast shedding
into the maternal circulation. This weakens the maternal systemic inflam-
matory response, which is believed to be the cause of endothelial activation
 Temporary Resolution of Preeclamptic Symptoms 317

and preeclampsia. An alternative explanation for the resolution of preeclamp-

sia in our patient is that the debris from a necrotic placenta does not induce
the same inflammatory response in the maternal circulation as placental
debris from a vital placenta.
At 31 weeks of gestation, when the placental volume of the surviving
twin had increased enough with normal fetal growth, preeclampsia recurred
in our patient, supporting the theory that vital placental mass is one
determinant in the occurrence of preeclampsia. We found two published cases
(4, 5) that describe the resolution of preeclampsia in twin pregnancies after
the death of one fetus. Another case report shows resolution of preeclamptic
symptoms after selective fetocide of one twin in a dichorionic twin pregnancy
(6). A later reappearance of the preeclamptic symptoms in twins after the
intrauterine death of one twin was (to our knowledge) never reported in the
international literature.
Our case gives additional evidence that the clinical course of preeclampsia
is a dose-dependent phenomenon in conjunction with vital placental tissue.
However, the nature of the underlying mechanisms leading to endothelial
activation and preeclampsia remains speculative.

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