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Indomethacin-induced oligohydramnios
Stiller et al.
bones demonstrated continued but minimal growth. Serial sonography of the viable twin noted continued appropriate growth and reassuring biophysical activity until the day of delivery. When a single fetal death in a twin pregnancy is noted on early ultrasonographic examination, resorption of the fetus may occur, as in the "vanishing twin" syndrome. The presence of continued growth of the nonviable twin on subsequent examination should alert the obstetrician to the diagnosis of the twin reversed arterial perfusion syndrome.
May 1989
Am J Obstet Gynecol
REFERENCES I. Van Allen MI, Smith DW, Shepard TH. Twin reversed arterial perfusion (TRAP) sequence: a study of 14 twin pregnancies with acardius. Semin Perinatol 1983;7:285. 2. Twin reversed arterial perfusion. In: Romero R, Pilu G, Jeanty P, et aI., eds. Prenatal diagnosis of congenital anomalies. Norwalk, Connecticut: Appleton and Lange, 1988: 409-11.
Indomethacin-induced oligohydramnios Robert L. Goldenberg, MD, Richard O. Davis, MD, and Rachel C. Baker, RN Birmingham, Alabama A case of reversible indomethacin-induced oligohydramnios is presented. This case suggests a relationship between the dose of indomethacin and the quantity of amniotic fluid. (AM J OBSTET GVNECOL 1989;160:1196-7.)
Key words: Indomethacin, oligohydramnios, prostaglandin synthetase inhibitors Indomethacin appears to be an effective inhibitor of preterm labor. In several case reports, however, its use has been associated with oligohydramnios. Corroborating the effect of indomethacin on amniotic fluid volume are several recent reports of polyhydramnios successfully treated with indomethacin.' To further define this relationship, the case presented shows an effect earlier in pregnancy than previously reported, demonstrates a possible relationship between the indomethacin dose and the quantity of amniotic fluid, and suggests that the effect is reversible by discontinuing the drug.
Case report The patient, a 28-year-old white woman, para 0-2-00, gave a history of two previous neonatal deaths after spontaneous premature labor and delivery at about 21 weeks' gestation. On admission to the hospital at 20 weeks' gestation, contractions were regular with the cerFrom the Perinatal Epidemiology Unit, Division of Maternal-Fetal MedIcine, Department of Obstetncs and Gynecology, UnIVersity of Alabama at Birmingham. ReceIVed for publzcation ju(v 11, 1988; reVISed November 7, 1988; accepted November 22, 1988. Repnnt requests: Robert L. Goldenberg, MD, Pennatal Epidemiology Unit, Division of Maternal-Fetal Medicine, Department of Obstetncs and G.vnecology, The University of Alabama at Binnlngham, Universzty Station, Birmingham, AL 35294.
1196
vix closed but 90% effaced, soft, and anterior. There was a large bulge in the lower uterine segment. She was treated initially with ritodrine and erythromycin, but because there was not an immediate cessation of contractions, indomethacin and ultimately progesterone in oil were added. During the next 12 weeks of hospitalization, she had frequent episodes of contractions ultimately associated with cervical change to 100% effacement and 3 cm dilation. She was treated with various intravenous and oral ~-sympathomimetics, intravenous magnesium sulfate, intramuscular progesterone in oil, and oral erythromycin and indomethacin. She was ultimately delivered at 36 weeks' gestation of a 2905 gm female infant with Apgar scores of9 and 9 at 1 and 5 minutes. Followup of the infant at 1 year of age showed normal development. Fig. 1 shows the relationship of amniotic fluid to the use and dosage of indomethacin. Because of our concern about using 200 mg/day, as soon as the initial contractions were suppressed, the dose was decreased to 100 mg/day. However, with frequent episodes of contractions and cervical change, at 21 weeks' gestation the dose was again increased to 200 mg/ day. Decreasing fundal height led us to perform an ultrasonographic examination, which showed nearly no amniotic fluid. In the twenty-second week, the dose of indomethacin was therefore decreased to 100 mg/day. One week later, the amniotic fluid was described as decreased but
Oligohydramnios
Volume 160 I'\umber 5, Part 1
No .... I
"\./"__ r
•
Amnlottc
fluid
1197
Reduced
~._/
Yol~
Oligo
200
IndOllelhuln 119124hrs
100
18
19
20
21
22
23
24
25
26
27
28
29
30
Gosl.lIon.1 A9. (....h)
Fig. I. Relationship between daily dose of indomethacin and ultrasonographicaUy determined amniotic fluid volume. Oligohydramnios is defined as no pocket ~ I cm in diameter.
with pockets measuring > 1 cm. With this dosage of indomethacin, the quantity of amniotic fluid appeared stable for several weeks. At 25 weeks' gestation, because of increasing contractions and further cervical change, the dosage of indomethacin was increased to 150 mg/day. Seven days later the ultrasonographic report described severe oligohydramnios with no pocket > 1 cm seen. A repeat ultrasonographic examination 1 week later showed no change in fluid. The dosage of indomethacin was decreased to 100 mg. However, at 28 weeks' gestation, because of our concern about the fetal condition and during a period of uterine quiescence, indomethacin was discontinued . Two days later several pockets of amniotic fluid >2 cm were noted, and by 10 days after the discontinuation of indomethacin, the volume of amniotic fluid was described as normal and remained so throughout the pregnancy. Fundal height measurements were noted to vary accordingly with changes in the ultrasonographically determined amniotic fluid volume. Comment Prostaglandin inhibitors such as indomethacin can reduce the volume of amniotic fluid , probably through
a decrease in fetal urinary production.' This case suggests that the amniotic fluid volume is sensitive to indomethacin as early as 21 weeks' gestation. The effect of indomethacin on amniotic fluid volume appeared to be dose related and was reversible with cessation of the drug. In this case episodes of oligohydramnios followed by the reaccumulation of normal quantities of amniotic fluid were not detrimental to the fetus. The role of indomethacin in the treatment of preterm labor is still evolving. However, when indomethacin is used, the volume of amniotic fluid should be carefully monitored. REFERENCES 1. Cabrol D, Landesman R, Muller j, Uzan M, Sureau C, Saxena BB. Treatment of polyhydramnios with prostaglandin synthetase inhibitor (indomethacin). AM j OBSTET GYNECOL 1987; 157:422. 2. Kirshon B, Moise K jr, Wasserstmm N, Ou C, Huhta J. Influence of short-term indomethacin therapy on fetal urine output. Obstet Gynecol 1988;72:5 1.
bones demonstrated continued but minimal growth. Serial sonography of the viable twin noted continued appropriate growth and reassuring biophysical activity until the day of delivery. When a single fetal death in a twin pregnancy is noted on early ultrasonographic examination, resorption of the fetus may occur, as in the "vanishing twin" syndrome. The presence of continued growth of the nonviable twin on subsequent examination should alert the obstetrician to the diagnosis of the twin reversed arterial perfusion syndrome.
May 1989
Am J Obstet Gynecol
REFERENCES I. Van Allen MI, Smith DW, Shepard TH. Twin reversed arterial perfusion (TRAP) sequence: a study of 14 twin pregnancies with acardius. Semin Perinatol 1983;7:285. 2. Twin reversed arterial perfusion. In: Romero R, Pilu G, Jeanty P, et aI., eds. Prenatal diagnosis of congenital anomalies. Norwalk, Connecticut: Appleton and Lange, 1988: 409-11.
Indomethacin-induced oligohydramnios Robert L. Goldenberg, MD, Richard O. Davis, MD, and Rachel C. Baker, RN Birmingham, Alabama A case of reversible indomethacin-induced oligohydramnios is presented. This case suggests a relationship between the dose of indomethacin and the quantity of amniotic fluid. (AM J OBSTET GVNECOL 1989;160:1196-7.)
Key words: Indomethacin, oligohydramnios, prostaglandin synthetase inhibitors Indomethacin appears to be an effective inhibitor of preterm labor. In several case reports, however, its use has been associated with oligohydramnios. Corroborating the effect of indomethacin on amniotic fluid volume are several recent reports of polyhydramnios successfully treated with indomethacin.' To further define this relationship, the case presented shows an effect earlier in pregnancy than previously reported, demonstrates a possible relationship between the indomethacin dose and the quantity of amniotic fluid, and suggests that the effect is reversible by discontinuing the drug.
Case report The patient, a 28-year-old white woman, para 0-2-00, gave a history of two previous neonatal deaths after spontaneous premature labor and delivery at about 21 weeks' gestation. On admission to the hospital at 20 weeks' gestation, contractions were regular with the cerFrom the Perinatal Epidemiology Unit, Division of Maternal-Fetal MedIcine, Department of Obstetncs and Gynecology, UnIVersity of Alabama at Birmingham. ReceIVed for publzcation ju(v 11, 1988; reVISed November 7, 1988; accepted November 22, 1988. Repnnt requests: Robert L. Goldenberg, MD, Pennatal Epidemiology Unit, Division of Maternal-Fetal Medicine, Department of Obstetncs and G.vnecology, The University of Alabama at Binnlngham, Universzty Station, Birmingham, AL 35294.
1196
vix closed but 90% effaced, soft, and anterior. There was a large bulge in the lower uterine segment. She was treated initially with ritodrine and erythromycin, but because there was not an immediate cessation of contractions, indomethacin and ultimately progesterone in oil were added. During the next 12 weeks of hospitalization, she had frequent episodes of contractions ultimately associated with cervical change to 100% effacement and 3 cm dilation. She was treated with various intravenous and oral ~-sympathomimetics, intravenous magnesium sulfate, intramuscular progesterone in oil, and oral erythromycin and indomethacin. She was ultimately delivered at 36 weeks' gestation of a 2905 gm female infant with Apgar scores of9 and 9 at 1 and 5 minutes. Followup of the infant at 1 year of age showed normal development. Fig. 1 shows the relationship of amniotic fluid to the use and dosage of indomethacin. Because of our concern about using 200 mg/day, as soon as the initial contractions were suppressed, the dose was decreased to 100 mg/day. However, with frequent episodes of contractions and cervical change, at 21 weeks' gestation the dose was again increased to 200 mg/ day. Decreasing fundal height led us to perform an ultrasonographic examination, which showed nearly no amniotic fluid. In the twenty-second week, the dose of indomethacin was therefore decreased to 100 mg/day. One week later, the amniotic fluid was described as decreased but
Oligohydramnios
Volume 160 I'\umber 5, Part 1
No .... I
"\./"__ r
•
Amnlottc
fluid
1197
Reduced
~._/
Yol~
Oligo
200
IndOllelhuln 119124hrs
100
18
19
20
21
22
23
24
25
26
27
28
29
30
Gosl.lIon.1 A9. (....h)
Fig. I. Relationship between daily dose of indomethacin and ultrasonographicaUy determined amniotic fluid volume. Oligohydramnios is defined as no pocket ~ I cm in diameter.
with pockets measuring > 1 cm. With this dosage of indomethacin, the quantity of amniotic fluid appeared stable for several weeks. At 25 weeks' gestation, because of increasing contractions and further cervical change, the dosage of indomethacin was increased to 150 mg/day. Seven days later the ultrasonographic report described severe oligohydramnios with no pocket > 1 cm seen. A repeat ultrasonographic examination 1 week later showed no change in fluid. The dosage of indomethacin was decreased to 100 mg. However, at 28 weeks' gestation, because of our concern about the fetal condition and during a period of uterine quiescence, indomethacin was discontinued . Two days later several pockets of amniotic fluid >2 cm were noted, and by 10 days after the discontinuation of indomethacin, the volume of amniotic fluid was described as normal and remained so throughout the pregnancy. Fundal height measurements were noted to vary accordingly with changes in the ultrasonographically determined amniotic fluid volume. Comment Prostaglandin inhibitors such as indomethacin can reduce the volume of amniotic fluid , probably through
a decrease in fetal urinary production.' This case suggests that the amniotic fluid volume is sensitive to indomethacin as early as 21 weeks' gestation. The effect of indomethacin on amniotic fluid volume appeared to be dose related and was reversible with cessation of the drug. In this case episodes of oligohydramnios followed by the reaccumulation of normal quantities of amniotic fluid were not detrimental to the fetus. The role of indomethacin in the treatment of preterm labor is still evolving. However, when indomethacin is used, the volume of amniotic fluid should be carefully monitored. REFERENCES 1. Cabrol D, Landesman R, Muller j, Uzan M, Sureau C, Saxena BB. Treatment of polyhydramnios with prostaglandin synthetase inhibitor (indomethacin). AM j OBSTET GYNECOL 1987; 157:422. 2. Kirshon B, Moise K jr, Wasserstmm N, Ou C, Huhta J. Influence of short-term indomethacin therapy on fetal urine output. Obstet Gynecol 1988;72:5 1.