- Email: [email protected]
Polyhydramnios associated with a ring chromosome and low maternal serum α-fetoprotein levels managed with indomethacin
Polyhydramnios associated with a ring chromosome and low maternal serum a- fetoprotein levels managed with indomethacin Brian Kirshon, MD, and David B. Cotton, MD Houston, Texas A case of polyhydramnios associated with a ring chromosome is described. The condition was also associated with a low maternal serum a-fetoprotein level. The polyhydramnios was managed by Initial therapeutic amniotic fluid decompression followed by indomethacin, which reduced fetal urine output and prevented reaccumulation of polyhydramnios. (AM J OssrET GYNECOL 1988;158:1063-4.)
Key words: Polyhydramnios, indomethacin, ring chromosome
A ring chromosome arises after a break in both the long and short arms of a chromosome. The centromeric ends fuse and the acentric telomeric fragments are lost. In essence, a ring chromosome is a type of deletion chromosome from which both ends have been lost and the broken ends have rejoined to form a ring. Polyhydramnios has been described with trisomy 13, 18, and 21. We report the first case of a ring chromosome with polyhydramnios. In this case indomethacin was used to prevent amniotic fluid production by reducing fetal urine output. Case Report A 33-year-old physician, gravida -3, now P3003, with a negative past medical history was noted to develop symptomatic polyhydramnios and preterm labor at 26 weeks' gestation. Diabetes mellitus was excluded and a level two ultrasound revealed a singleton, structurally normal fetus. The patient had previously declined on religious grounds a genetic amniocentesis at 16 weeks' gestation when a maternal serum a-fetoprotein level <0.4 multiples of the median was noted. She did consent to a chromosomal analysis of the amniotic fluid when a decision was made to perform therapeutic decompression. After removal of 3000 ml of amniotic fluid, indomethacin was started at a dose of 25 mg orally every 4 hours to manage both the preterm labor and to prevent reaccumulation of polyhydramnios by reducing fetal urine output. Fetal echocardiography was performed weekly to ensure that the fetal ductus arteriosus was patent. The karyotype of the amniotic fluid From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine. Received for publication September 24, 1987; accepted November 6, 1987. Reprint requests: Brian Kirshon, MD, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, One Baylor Plaza, Houston, TX 77030.
(confirmed later in the infant) revealed 46 chromosomes and an additional marker chromosome (ring chromosome) in 70% of cells examined. The staining characteristics of the marker indicated it had both C-banded and euchromatic material. Results of cytogenetic studies in both parents were normal, consistent with a spontaneous new mutation marker derivative ring chromosome in the fetus. The origin of the chromosome was unknown. Fetal urine output as determined sonographically declined significantly (<50%) throughout the 9 weeks of indomethacin therapy. The patient did not require any further therapeutic decompression and the ductus remained patent throughout the 9 weeks of indomethacin therapy. At 36 weeks' gestation, a week after discontinuing the indomethacin, the patient went into spontaneous labor and was delivered vaginally of a 2280 gm £emale infant with Apgar scores of 9 at 1 and 5 minutes. The neonate was structurally normal, and at the time of this report the infant was developmentally normal at 3 months of age. Comment Polyhydramnios may be idiopathic or may be associated with multiple pregnancies, diabetes mellitus, neural tube defects, fetal upper gastrointestinal obstruction, hydrops fetalis, and fetal neuromuscular disorders. As chromosomal anomalies may be associated with the above disorders, a karyotype would seem prudent in the work-up of polyhydramnios. Although trisomies have been described with the above entities, we report the association of polyhydramnios with a ring chromosome. Low maternal serum a-fetoprotein levels and trisomies have been described by Mer katz et a!. 1 Our case suggests the addition of ring chromosomal abnormalities to the list of chromosomal anomalies seen in association with low maternal serum a-fetoprotein levels. Indomethacin, a prostaglandin synthetase inhibitor, 1063
Kirshon and Cotton
May 1988
Am J Obstet Gynecol
significantly decreases urine output in adults and newborns.2 Because amniotic fluid volume is largely a product of fetal urine production, any agent decreasing fetal urine output should produce a concomitant decrease in amniotic fluid volume. We used the ultrasound method of Campbell and Wladimiroff' to measure fetal urine output. We were able to decrease significantly the fetal urine output with maternal administration of indomethacin. This therapy prevented the reaccumulation of polyhydramnios after the initial therapeutic decompression. In summary, we wish to emphasize the association of a ring chromosome with polyhydramnios and a low maternal serum a-fetoprotein level. The efficacy of in-
domethacin in managing polyhydramnios after initial decompression by decreasing fetal urine output and preventing reaccumulation of polyhydramnios was also demonstrated. REFERENCES 1. Merkatz IR, Nitowsky HM, Macri JN, Johnson WE. An association between low maternal serum alpha-fetoprotein and fetal chromosomal abnormalities. AM J 0BSTET GvNECOL 1984; 148:886-91. 2. Cifuentes RF, Olley PM, BalfeJW, et al. Indomethacin and renal function in premature infants with persistent patent ductus arteriosus. J Pediatr 1979;95:583-7. 3. Cambell S, Wladimiroff JW, Dewhurst CJ. The antenatal measurement of fetal urine production. J Obstet Gynaecol Br Commonw 1973;80:680-6.
Placental pathology at term associated with elevated midtrimester maternal serum a- fetoprotein concentration Carolyn M. Salafia, MD," Lester Silberman, MD," Nilo E. Herrera, MD," and Maurice J. Mahoney, MD< Danbury and New Haven, Connecticut Reports have supported an association between elevated midtrimester maternal serum a-fetoprotein concentrations (unexplained by fetal anomalies) and intrauterine growth retardation. Our observations show an association between such elevations of maternal serum a-fetoprotein levels and two types of placental pathology at delivery, chronic villitis and placental vascular lesions of infarction or intervillous thrombosis. If chronic villitis was present, the frequency of intrauterine growth retardation was significantly increased, whereas no increase in intrauterine growth retardation was found in the absence of placental pathology. (AM J 0BSTET GYNECOL 1988;158:1064-6.)
Key words: Placenta, a-fetoprotein, intrauterine growth retardation Unexplained elevations of mid trimester maternal serum a-fetoprotein concentrations have identified a group of patients with a two- to threefold increased risk of intrauterine growth retardation (IUGR).' These "idiopathic" elevations are defined after ultrasound to confirm gestational age. In most cases no abnormality of growth is apparent at the time of the elevated maternal serum a-fetoprotein level determination. The cause(s) of the elevation of maternal serum a-fetoprotein in IUGR is at present not understood. One hypothesis
suggests midtrimester fetomaternal transfusion on the basis of chronic decidual-placental separation, resulting in placental insufficiency and poor fetal weight gain in later pregnancy. It also appears that the onset of IUGR early in pregnancy carries a poorer long-term prognosis. If the elevation in maternal serum a-fetoprotein level is a sign of second trimester placental pathology, the group of infants with IUGR might be expected to be among those at increased risk for long-term sequelae.
From the Departments of Laboratory Medicine" and Obstetrics and Gynecology,' Danbury Hospital, Danbury, and Department of Human Genetics,' Yale University School of Medicine, New Haven. Received for publication October 5, 1987; accepted November 16, 1987. Reprint requests: Carolyn M. Salafia, MD, Department ofLaboratory Medicine, Danbury Hospital, 24 Hospital Ave., Danbury, CT 06810.
Material and methods Begun in July 1983, the Danbury Hospital Placental Data Base has permitted the study of many gestatio~al and peripartum conditions. Pathologic study of the placenta is currently performed in 50% to 60% of all deliveries at the Danbury Hospital. All examinations have been performed by a single observer (C.M.S.) with stan-
1064
Key words: Polyhydramnios, indomethacin, ring chromosome
A ring chromosome arises after a break in both the long and short arms of a chromosome. The centromeric ends fuse and the acentric telomeric fragments are lost. In essence, a ring chromosome is a type of deletion chromosome from which both ends have been lost and the broken ends have rejoined to form a ring. Polyhydramnios has been described with trisomy 13, 18, and 21. We report the first case of a ring chromosome with polyhydramnios. In this case indomethacin was used to prevent amniotic fluid production by reducing fetal urine output. Case Report A 33-year-old physician, gravida -3, now P3003, with a negative past medical history was noted to develop symptomatic polyhydramnios and preterm labor at 26 weeks' gestation. Diabetes mellitus was excluded and a level two ultrasound revealed a singleton, structurally normal fetus. The patient had previously declined on religious grounds a genetic amniocentesis at 16 weeks' gestation when a maternal serum a-fetoprotein level <0.4 multiples of the median was noted. She did consent to a chromosomal analysis of the amniotic fluid when a decision was made to perform therapeutic decompression. After removal of 3000 ml of amniotic fluid, indomethacin was started at a dose of 25 mg orally every 4 hours to manage both the preterm labor and to prevent reaccumulation of polyhydramnios by reducing fetal urine output. Fetal echocardiography was performed weekly to ensure that the fetal ductus arteriosus was patent. The karyotype of the amniotic fluid From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine. Received for publication September 24, 1987; accepted November 6, 1987. Reprint requests: Brian Kirshon, MD, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, One Baylor Plaza, Houston, TX 77030.
(confirmed later in the infant) revealed 46 chromosomes and an additional marker chromosome (ring chromosome) in 70% of cells examined. The staining characteristics of the marker indicated it had both C-banded and euchromatic material. Results of cytogenetic studies in both parents were normal, consistent with a spontaneous new mutation marker derivative ring chromosome in the fetus. The origin of the chromosome was unknown. Fetal urine output as determined sonographically declined significantly (<50%) throughout the 9 weeks of indomethacin therapy. The patient did not require any further therapeutic decompression and the ductus remained patent throughout the 9 weeks of indomethacin therapy. At 36 weeks' gestation, a week after discontinuing the indomethacin, the patient went into spontaneous labor and was delivered vaginally of a 2280 gm £emale infant with Apgar scores of 9 at 1 and 5 minutes. The neonate was structurally normal, and at the time of this report the infant was developmentally normal at 3 months of age. Comment Polyhydramnios may be idiopathic or may be associated with multiple pregnancies, diabetes mellitus, neural tube defects, fetal upper gastrointestinal obstruction, hydrops fetalis, and fetal neuromuscular disorders. As chromosomal anomalies may be associated with the above disorders, a karyotype would seem prudent in the work-up of polyhydramnios. Although trisomies have been described with the above entities, we report the association of polyhydramnios with a ring chromosome. Low maternal serum a-fetoprotein levels and trisomies have been described by Mer katz et a!. 1 Our case suggests the addition of ring chromosomal abnormalities to the list of chromosomal anomalies seen in association with low maternal serum a-fetoprotein levels. Indomethacin, a prostaglandin synthetase inhibitor, 1063
Kirshon and Cotton
May 1988
Am J Obstet Gynecol
significantly decreases urine output in adults and newborns.2 Because amniotic fluid volume is largely a product of fetal urine production, any agent decreasing fetal urine output should produce a concomitant decrease in amniotic fluid volume. We used the ultrasound method of Campbell and Wladimiroff' to measure fetal urine output. We were able to decrease significantly the fetal urine output with maternal administration of indomethacin. This therapy prevented the reaccumulation of polyhydramnios after the initial therapeutic decompression. In summary, we wish to emphasize the association of a ring chromosome with polyhydramnios and a low maternal serum a-fetoprotein level. The efficacy of in-
domethacin in managing polyhydramnios after initial decompression by decreasing fetal urine output and preventing reaccumulation of polyhydramnios was also demonstrated. REFERENCES 1. Merkatz IR, Nitowsky HM, Macri JN, Johnson WE. An association between low maternal serum alpha-fetoprotein and fetal chromosomal abnormalities. AM J 0BSTET GvNECOL 1984; 148:886-91. 2. Cifuentes RF, Olley PM, BalfeJW, et al. Indomethacin and renal function in premature infants with persistent patent ductus arteriosus. J Pediatr 1979;95:583-7. 3. Cambell S, Wladimiroff JW, Dewhurst CJ. The antenatal measurement of fetal urine production. J Obstet Gynaecol Br Commonw 1973;80:680-6.
Placental pathology at term associated with elevated midtrimester maternal serum a- fetoprotein concentration Carolyn M. Salafia, MD," Lester Silberman, MD," Nilo E. Herrera, MD," and Maurice J. Mahoney, MD< Danbury and New Haven, Connecticut Reports have supported an association between elevated midtrimester maternal serum a-fetoprotein concentrations (unexplained by fetal anomalies) and intrauterine growth retardation. Our observations show an association between such elevations of maternal serum a-fetoprotein levels and two types of placental pathology at delivery, chronic villitis and placental vascular lesions of infarction or intervillous thrombosis. If chronic villitis was present, the frequency of intrauterine growth retardation was significantly increased, whereas no increase in intrauterine growth retardation was found in the absence of placental pathology. (AM J 0BSTET GYNECOL 1988;158:1064-6.)
Key words: Placenta, a-fetoprotein, intrauterine growth retardation Unexplained elevations of mid trimester maternal serum a-fetoprotein concentrations have identified a group of patients with a two- to threefold increased risk of intrauterine growth retardation (IUGR).' These "idiopathic" elevations are defined after ultrasound to confirm gestational age. In most cases no abnormality of growth is apparent at the time of the elevated maternal serum a-fetoprotein level determination. The cause(s) of the elevation of maternal serum a-fetoprotein in IUGR is at present not understood. One hypothesis
suggests midtrimester fetomaternal transfusion on the basis of chronic decidual-placental separation, resulting in placental insufficiency and poor fetal weight gain in later pregnancy. It also appears that the onset of IUGR early in pregnancy carries a poorer long-term prognosis. If the elevation in maternal serum a-fetoprotein level is a sign of second trimester placental pathology, the group of infants with IUGR might be expected to be among those at increased risk for long-term sequelae.
From the Departments of Laboratory Medicine" and Obstetrics and Gynecology,' Danbury Hospital, Danbury, and Department of Human Genetics,' Yale University School of Medicine, New Haven. Received for publication October 5, 1987; accepted November 16, 1987. Reprint requests: Carolyn M. Salafia, MD, Department ofLaboratory Medicine, Danbury Hospital, 24 Hospital Ave., Danbury, CT 06810.
Material and methods Begun in July 1983, the Danbury Hospital Placental Data Base has permitted the study of many gestatio~al and peripartum conditions. Pathologic study of the placenta is currently performed in 50% to 60% of all deliveries at the Danbury Hospital. All examinations have been performed by a single observer (C.M.S.) with stan-
1064