Indomethacin therapy in hydramnios.

S Abhyankar, VS Salvi
Department of Obstetrics and Gynaecology, Seth G. S. Medical College and K. E. M.
Hospital, Parel, Mumbai - 400 012, India., India
S Abhyankar Department of Obstetrics and Gynaecology, Seth G. S. Medical
College and K. E. M. Hospital, Parel, Mumbai - 400 012, India. India

:: Abstract

AIM: The use of indomethacin in treatment of hydramnios was evaluated.

SUBJECTS & METHODS: Twelve patients with symptomatic hydramnios
were treated with indomethacin (2.2- 3.0 mg/kg body weight/day).
RESULTS: The treatment was started at a gestational age of 31.17-
/+7.94 weeks and continued for 3.74-/+2.3 weeks. Eleven patients
responded to the therapy both subjectively and objectively and
pregnancies were prolonged by 4.6-/+3.1 weeks (range 0.1-10 weeks).
Five women had term deliveries. Six patients had a favourable perinatal
outcome. Four patients who had a known congenital anomaly in the
foetus, delivered stillborn babies or had an early neonatal death. One
patient who did not follow up after commencing therapy delivered a full-
term stillbirth. One patient delivered within 1 day of starting therapy.
Indomethacin therapy caused no maternal complications. CONCLUSION:
Indomethacin was effective in the management of hydramnios and
preventing it's complications.

Keywords: Adult, Anti-Inflammatory Agents, Non-Steroidal,

administration &dosage,Drug Administration Schedule, Female, Follow-Up
Studies, Gestational Age, Human, Indomethacin, administration
&dosage,Polyhydramnios, drug therapy,ultrasonography,Pregnancy,
Pregnancy Outcome, Severity of Illness Index, Treatment Outcome,
Ultrasonography, Prenatal, methods,
 :: Introduction

Polyhydramnios has been defined as an amniotic fluid volume greater

than 2000 ml.[1] Though, the incidence is less than 1%,[2] it is still a
source of worry for obstetricians as it can jeopardise both maternal and
foetal outcome.[2],[3],[4] The maternal hazards include respiratory
compromise, antepartum haemorrhage, abnormal presentations, uterine
dysfunction, postpartum haemorrhage and increased operative
intervention. The perinatal outcome is compromised due to prematurity,
placental abruption and umbilical cord prolapse. Moreover, the causes of
polyhydramnios such as diabetes mellitus, congenital malformations and
twins are also associated with an adverse perinatal outcome.

No active management may be required in patients with asymptomatic

hydramnios.[3] For patients developing evidence of respiratory
embarrassment, excessive uterine activity or premature opening of os
one of the therapeutic options is decompression by
amniocentesis.[1] However it has a risk of preterm labour and infections.
The medical management of hydramnios utilising indomethacin was first
reported by Cabrol.[5] Though the use of indomethacin is described in
standard literature, there are very few cases of symptomatic hydramnios
requiring therapy. Worldwide only 56 cases have been
reported.[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20] We
report 12 cases of symptomatic hydramnios treated with indomethacin.
 :: Subjects and methods

Twelve cases of symptomatic hydramnios requiring treatment at the KEM

Hospital, Mumbai, over a period of 10 years (1990-1999) are being
reported. Hydramnios was diagnosed clinically and confirmed by
ultrasound. Clinically, the patients had a fundal height greater than the
period of amenorrhoea , foetal parts were not easily palpable, foetal heart
sounds were heard as if coming from a distance and a fluid thrill was
present. At ultrasound examination the largest pocket of amniotic fluid
was measured. Hydramnios was graded as mild, moderate and severe if
the largest vertical pocket of liquor measured 8 to 11cm, 12 to 15 cm and
greater than 16 cm respectively.[2]
The patients received indomethacin only if they had symptoms due to
hydramnios such as respiratory embarrassment, premature opening of os
or presence of uterine activity. Since mild hydramnios is relatively
uncomplicated, indomethacin was utilised only in moderate and severe
hydramnios. The only exception was a patient with mild hydramnios in
both sacs of a twin gestation. Patients were evaluated for determining the
cause of hydramnios such as maternal diabetes, rhesus incompatibility, or
a congenital anomaly in the foetus.
Indomethacin was given in a dose of 2.2-3 mg/kg/day (75 mg twice
daily). The changes in the following parameters were evaluated to
determine the effect of indomethacin therapy a) maternal symptoms and
uterine contractions; b) weekly measurement of fundal height and
abdominal girth at the level of the umbilicus and serial ultrasound (to
monitor foetal growth and amniotic fluid); and c) prolongation of
pregnancy.
 :: Results

The results are depicted in [Table - 1]. All the patients except one had
either moderate or severe hydramnios. All the patients complained of
abdominal discomfort and respiratory embarrassment. Three of the cases
already had premature opening of os. Patient No. 6 had a history of being
tapped in the current pregnancy and 500 ml of amniotic fluid had been
drained. The patients had a gestational age of 31.17?7.95 weeks (range
28-37 weeks). The fundal height was 37.67? 9.96 cm (range 32-48 cm).
Hydramnios was idiopathic in 6 patients, 2 patients had a twin gestation
and 4 foetuses were anomalous. Two patients had concomitant
gestational diabetes. The therapy was given for a period of 3.74?2.32
weeks (range 0.14-8 weeks). All the patients except one (No 9) were
relieved of their abdominal discomfort and respiratory embarrassment.
Patient No 9 went into preterm labour, within a day of starting
indomethacin and the baby expired due to extreme prematurity. In 10
patients, the hydramnios decreased both clinically and on ultrasound
while in patient no 1 the fundal height remained static. Five patients went
to term while the remaining 6 patients could be carried forward to 34 to
36 weeks. Delivery was postponed by 4.6?3.1 weeks (range 0.1-10
weeks). Six cases had a successful perinatal outcome. Case 7 did not
follow up after initiating indomethacin therapy and came directly in labour
with an intrauterine foetal death. All the four babies with congenital
anomalies did not survive. There were no maternal complications except
in case four who had sudden intrapartum bleeding at full dilatation.
 :: Discussion

Indomethacin is an anti-prostaglandin, which acts by reversible inhibition

of the enzyme cyclo-oxygenase. Foetal urination and foetal lung fluid are
major sources of amniotic fluid production and are balanced by fluid
removal through foetal swallowing and intra-membranous absorption
across the foetal surface of the placenta.[21] Indomethacin acts by
decreasing the production of amniotic fluid by reducing the urine output
and also by increasing fluid reabsorption by the lungs secondary to foetal
breathing and increased fluid movement across foetal
membranes.[7] Indomethacin is thought to act by impairing the normal
prostaglandin mediated response of the renal vasculature.

A total of 56 patients[6] have been reported in English literature in whom

indomethacin was used in treatment of polyhydramnios. As in the current
study, all the investigators enrolled patients only if maternal compromise
in the form of cardio-respiratory embarrassment, abdominal pain or
preterm labour were present. Although diagnostic criteria for hydramnios
varied with each investigator, ultrasound was routinely used in all the
patients.

In the 56 reported cases, 19 mothers had diabetes mellitus, 16 cases

were idiopathic and 15 had a multiple gestation. There were two cases of
foetal gastro-intestinal anomalies and one case each of foetal diabetes
insipidus and neuro-muscular disorder. One mother was on haemodialysis
while one had a chorio-angioma of the placenta.

In the current study, indomethacin was used in a dose of 2.2 to 3 mg/kg

body weight, which is the same as that used by Cabrol.[5] The lowest dose
used in other studies was 25 mg 12 hourly[16],[19] and at times the drug
has also been administered per rectally in a few patients.
In the current study, delivery was postponed by 4.6?3.1 weeks and 50%
of the pregnancies had a successful outcome.

In previous studies utilising indomethacin, maternal side effects were

limited to nausea or epigastric discomfort. Rectal dosage produced rectal
irritation. Some studies have shown maternal renal insufficiency after
prolonged treatment. In the current study, there were no gastro-intestinal
side effects. There were no maternal complications attributable to
indomethacin.

Amniocentesis has also been described as therapy for hydramnios but it is

an invasive procedure and multiple taps may be required. Complications
of therapeutic amniocentesis include preterm labour, abruptio placenta,
chorioamnio-nitis.[1] In a study conducted by Elliott et al,[22] of the 94
patients who had undergone therapeutic amniocentesis, 3 patients
developed maternal complications like premature rupture of membranes,
chorioamnionitis and antepartum haemorrhage. The ability of therapeutic
amniocentesis to prolong pregnancy has only been addressed by
Radestad.[23] They utilised this procedure in acute polyhydramnios in twin
pregnancy. Pregnancy was prolonged by 2 weeks in the group managed
by amniocentesis as compared to 1 week in the conservatively managed
group. In the current study, pregnancy was prolonged by 4.6?3.1 weeks
in patients treated with indomethacin.

The use of indomethacin has raised concerns about premature closure of

the ductus arteriosus. Though Moise and colleagues[24] in 1988 reported
that 50% of 14 foetuses whose mothers received indomethacin had ductal
constriction detected by Doppler, persistent constriction was not
demonstrated in the studies described earlier nor has it been described in
the studies in which indomethacin was given for tocolysis.[25] In the study
by Dudley[26] indomethacin was given up to 35 weeks and no foetal
complication was noticed. In Vermillion’s study[27] too, a dramatic
reversal of ductal constriction was noted after stopping indomethacin and
no significant adverse foetal outcome was attributed to indomethacin
therapy. Though, all the cases with morphologically normal foetuses, in
whom therapy was antenatally monitored, delivered healthy normal
neonates, we suggest that indomethacin be used only in cases of
symptomatic hydramnios where maternal well-being overrides concerns
of foetal safety.

In conclusion, indomethacin can be used effectively in the therapeutic

management of hydramnios in pregnancy.

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