PRENATAL DIAGNOSIS, VOL.

9,681-682 (1989)

SHORT COMMUNICATION

ANHYDRAMNIOS AND CESSATION OF FETAL

GROWTH IN A PREGNANT MOTHER WITH
POLYCHEMOTHERAPY DURING THE SECOND
TRIMESTER
HERVB FERNANDEZ*, ALPHA DIALLO*, DANIEL B A U M E ~AND EMILE PAPIERNIK*
*Department of Obstetrics and Gynecology, H6pital Antoine Beclere. 92141 Clamart, France;
tDepartment of Medicine and Hematology. Sce Pr Hayat, Institut Gustave Roussy. 94805 Villejuif.
France

SUMMARY
This paper discusses the case of a pregnant woman with poiychemotherapy during the second
trimester of pregnancy for rhabdomyosarcoma of the face and cessation of fetal growth with
disappearance of amniotic fluid after the first course of therapy.

KEY WORDS Anhydramnios Second-trimester pregnancy Chemotherapy

INTRODUCTION
A unique case of anhydramnios and complete intrauterine growth arrest of the fetus
occurred as early as the first course of polychemotherapy for a rhabdomyosarcoma
of the face with metastasis to the bone marrow in a pregnant mother.

CASE REPORT
Mrs P., a 20-year-old primigravida, Caucasian woman, was admitted at 23 weeks of
amenorrhea with a diagnosis of rhabdomyosarcoma of the face with epistaxis,
exophthalmos, bone marrow metastasis, and consumption coagulopathy mani-
fested by a factor V at 30 per cent and a platelet count of 30 x lo9per litre. In view of
the emergency and the critical state of the mother, immediate cancer chemotherapy
was begun by the oncology team and the obstetricians. The following drug schedule
was established: isophosphamide, 5 g per day, on day 1 and day 2; vincristine, 2 mg
per day, on day 1 and day 14; and actinomycin D, 1 mg per day, on day 1 and day 2.
Associated therapy included analgesics (Paracetamol), Uromitexan, Uricozyme,
and Heparin. An initial ultrasound examination performed on the same day, at 23
weeks of amenorrhea, revealed a fetus at the 20th percentile on the growth curve of
Leroy and Lefort, and a normal quantity of amniotic fluid. In addition, the mother
had noted active fetal movements.
Four weeks later, a second course of drug therapy was decided. The ultrasound
revealed a complete absence of amniotic fluid and cessation of fetal growth. During
the ultrasound examination, the fetal bladder was empty. The mother reported no

Adressee for correspondence: Hervt Fernandez, M.D.,

Department of Obstetrics and Gynecology,
HBpital Antoine Beclere, 92141 Clamart, France.

0197-385 1/89/090681-02$05.00 Received I 7 April 1989

0 1989 by John Wiley & Sons, Ltd. Accepted 5 June 1989
682 H. FERNANDEZ ET AL.

further active movements. During the period between the two courses of chemo-
therapy, the mothers weight was stable. Eight days following the second course of
chemotherapy, Mrs P. presented with bone marrow aplasia lasting 8 days. After the
period of aplasia, an ultrasound confirmed the intrauterine fetal growth arrest and
the persistent absence of amniotic fluid. In view of these findings, as well as the
presence of signs of acute fetal hypoxia with non-oscillating fetal heart rate and
late decelerations, an emergency caesarean section was performed at 29 weeks of
amenorrhea. A female infant weighing 720 g was delivered with an Apgar score of
3/7/7 a t 1, 5, and lOmin, respectively, and an umbilical cord blood pH of 7.17.
Despite the ultra-sonographic evidence of two kidneys, anuria persisted in the hours
following postnatal life.
Cerebral ultrasound examination revealed bilateral intraventricular haemor-
rhage and left occipital meningeal hematoma. The infant never passed any urine and
died at day 7.
Autopsy findings included extensive cerebral lesions associated with prematurity
but revealed no discernible renal lesions or chromosome abnormality. In contrast,
examination of the placenta revealed large areas of ischaemic necrosis without
chorioamnionitis. No cancer cells were found either in the placenta or in the fetus.
Viral and bacterial cultures from the infant were negative. The mother died 9
months later.
COMMENT
Up to now, no fetal toxicity, and in particular nothing involving the kidneys which
might explain the anhydramnios, has been reported with any of the drugs used singly
(Nicholson, 1968). The combination of the three chemotherapeutic agents makes it
even more difficult to detect the part played by any of them singly or together.
Among the agents given in association with the anti-cancer drugs, none has been
associated with fetal abnormalities. However, in the adult, isophosphamide has
been found to cause acute renal tubular and glomerular lesions at therapeutic doses
of 5 g per day (Vandyk el al., 1973; De Fronzo et al., 1974). The other two drugs have
not been incriminated in any known renal lesion either in the adult or in the fetus.
However, actinomycin D is a known inhibitor of RNA synthesis and has been used
in trophoblastic disease. One must speculate that the cessation of growth may relate
to the possible effects of actinomycin D on trophoblastic tissue. The fact that the
neonate remained anuric may also be a consequence of fetal or neonatal haemo-
dynamic effects, particularly as it is stated that there was no discernible renal lesion
at autopsy. The transplacental passage of these drugs is unknown. In our case, we
must emphasize the fact that none of the chemotherapeutic agents given is contra-
indicated in the mother especially in emergency situations. However, the severe
consequences for the fetus in this case are worth noting.

REFERENCES
De Fronzo, R.A., Abeloff, M., Braine, H., Humphrey, R.L., Davis, P.J. (1974). Renal dys-
function after treatment with isophosphamide, Cancer Chemother. Rep., 58,375-382.
Nicholson, H.N. (1968). Cytotoxic drugs in pregnancy, J . Obster. Gynaecol. Br. Cwlth., 75,
307-312.
Vandyk, J.J., Falkson, H.C., Van der Merne, A.M., Falkson, G. (1972). Unexpected toxicity
in patients treated with Isophosphamide, Cancer Res., 32,921-924.