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Antenatal diagnosis of sacral agenesis syndrome in a pregnancy complicated by diabetes mellitus
Fee et al.
ment by the American College of Obstetricians and Gynecologists emphasizes that to ascribe neurologic deficits to perinatal asphyxia, low Apgar scores alone are insufficient and additional evidence such as seizures and prolonged hypotonia is required. 17 The same stipulation may hold for acidosis identified at birth. Our study suggests that even severe acidosis in umbilical cord blood is insufficient evidence of asphyxia profound enough to cause neurologic damage. Furthermore, most mild neurologic deficits noted in an infant after severe acidosis can be expected to resolve in the first years of life. REFERENCES 1. Beard RW, Rivers RP. Fetal asphyxia in labor. Lancet 1979;2:1117. 2. Niswander K. Asphyxia in the fetus and cerebral palsy. In: Pitkin RM, Ziatnik FJ, eds. Year book of obstetrics and gynecology. Chicago: Year Book, 1983:107-25. 3. Nelson KB, Ellenberg JH. Apgar scores as predictors of chronic neurologic disability. Pediatrics 1981 ;68:36-44. 4. Low JA, Galbraith RS, Muir DW, Killen HL, Pater EA, Karchmar EJ. Motor and cognitive deficits after intrapartum asphyxia in the mature fetus. AM J OB8TET Gv]'o;ECOL 1988; 158:356-61. 5. Dijxhoorn MJ, VisserGHA, Huisjes HJ, Fidler V, Touwen BCL. The relation between umbilical pH values and neonatal neurological morbidity in full term appropriate-fordates infants. Early Human Dev 1985; II :33-42. 6. Ruth VJ. Raivio KO. Perinatal brain damage: predictive
March 1990 Am J Obstet Gynecol
7.
8.
9. 10. II. 12. 13. 14. 15.
16. 17.
value of metabolic acidosis and the Apgar score. Br Med J 1988;297:24. Luthy DA, Shy KK, Strickland D, et al. Status of infants at birth and risk for adverse neonatal events and longterm sequelae: a study in low birth weight infants. AM J OB8TET GVNECOL 1987;157:676-9. Brann AW. Factors during neonatal life that influence brain disorders. In: Freeman JM, ed. Prenatal and perinatal factors associated with brain disorders. (NIH publ no 85-1149). Bethesda, Md: National Institute of Child Health and Human Development, 1985:263. Brazelton TB. Behavioral assessment scale, 2nd ed. London: Spastics International, 1984. Bayley N. The Bayley scales of infant development. New York: The Psychological Corp, 1969. Thomson AJ, Searle M, Russell G. Quality of survIval after severe birth asphyxia. Arch Dis Child 1977;620-6. Scott H. Outcome of very severe birth asphyxia. Arch Dis Child 1976;51:712-6. Nelson KB, Ellenberg JH. The asymptomatic newborn and risk of cerebral palsy. Am J Dis Child 1987; 1333-5. Sexson WR, Sexson SB, RawsonJE, et al. The multisystem involvement of the asphyxiated newborn. Pediatr Res 1976; 10:432-9. Sheldon RE, Peeters LLH, Jones MD Jr, Makowski EL, Meschia G. Redistribution of cardiac output and oxygen delivery in the hypoxemic fetal lamb. AM J OB5TET GvNECOL 1979;135:1071-8. Ellenberg JH, Nelson KB. Cluster of perinatal events identifying infants at high risk for death or disability. J Pediatr 1988;113:546-52. ACOG newsletter: Use and misuse of the Apgar score. Washington, DC: American College of Obstetricians and Gynecologists, Jan 1987, p 8.
Antenatal diagnosis of sacral agenesis syndrome in a pregnancy complicated by diabetes mellitus J.
D. Sonek, MD, S. G. Gabbe, MD, M. B. Landon, MD, L. E. Stempel, MD, M. R. Foley, MD, and K. Shubert-Moell, MD
Columbus, Ohiu The sacral agenesis syndrome is a severe congenital abnormality consisting of agenesis of the lumbar spine, sacrum, and coccyx, as well as hypoplasia of the lower extremities. It is considered the most characteristic of all congenital anomalies associated with maternal diabetes mellitus. We describe the sonographic and radiologic findings of agenesis of the lumbosacrococcygeal spine with lower limb and genital hypoplasia in the offspring of a woman with both diabetic retinopathy and nephropathy. The diagnosis was established at 25 weeks' gestation and was confirmed by radiologic evaluation of the neonate. (AM J OBSTET GVNECOL 1990;162:806-8.)
Key words: Sacral agenesis syndrome, diabetic pregnancy, antenatal diagnosis From the Department of Obstetrics and Gynecology, The OhIO State Univem/'v, and the Mount Carmel Medical Center. Received fo~ publication January 19, 1989; revised June 2, 1989; accepted September 22, 1989. Reprint requests: Jiri Sonek, MD, Medical College of Georgia, Department of Obstetrics and Gynecology, Maternal-Fetal Medicine Section, Augusta, GA 30912-3350. 611116904
806
A case of agenesis of the lumbosacrococcygeal spine with lower limb and genital hypoplasia is described. The diagnosis was made at 25 weeks' gestation.
Case report A 24-year-old white woman, gravida 3, para 0, aborta 2, with proliferative retinopathy and nephropathy, di-
Volume 162 Number 3
Sacral agenesis syndrome
807
Fig. 1. Sonogram demonstrating coronal section of fetus at 28 weeks' gestation. Note absence of spinal vertebrae below mid thorax.
~:: . I"~ . J ~J
2S
:: ~teM ...?S_ . ; .
. w. ·
, ~ .
Fig. 2. Sonogram illustrating transverse section of fetus at 25 weeks' gestation at level of kidneys. Note absence of spine.
agnosed as having White's class FIR diabetes mellitus, was first seen in our clinic at 25 weeks' gestation. She had had sporadic prenatal care before this visit, al· though a first·trimester sonogram had established her expected date of confinement. The hemoglobin Ale level at 25 weeks was 5% (normal 5% to 8%). Diabetes was well controlled on two injections of insulin daily. Her initial physical ex· amination revealed proliferative retinopathy, which required laser therapy. Significant proteinuria (4.1 gm/24 hours) and a creatinine clearance of 118 ml/min were documented. Ultrasonographic examination revealed a single fetus in a cephalic presentation. The amniotic fluid volume appeared normal. The fetal anatomy above the mid· thorax, including the heart and the intracranial struc· tures, was normal. Below this level, however, complete
absence of the vertebrae was noted (Fig. 1). Two kid· neys were identifiable but were closely apposed in the midline (Fig. 2). The fetal bladder was normal in size. The lower extremities were fixed in a "froglike" posi· tion. Measurements of the lower extremities and the feet lagged 3 to 4 weeks behind the head and upper extremities. The fetus was male and the phallus was subjectively small. An amniocentesis was performed and a normal male karyotype, 46,XY, was present. Serial ultrasonographic examinations during the ges· tation revealed normal growth of the fetal head, thorax, and upper extremities. The abdominal circumference, however, was consistently below the 2.5th percentile, and the lower extremities continued to be dispropor· tionately small. The amount of amniotic fluid remained normal. Labor was induced at 35 weeks after uterine tender·
808 Sonek at al.
March 1990
Am J Obstet Gyneco1
ness and low-grade fever (38 C) developed. The patient was delivered of an 1810 gm male infant by cesarean section because of presumed fetal distress evidenced by persistent late decelerations. The infant's Apgar scores were 8 and 9 at 1 and 5 minutes, respectively. Initial examination of the neonate revealed normal respiratory effort and good movement of the upper extremities. The abdomen was slightly distended, and bowel sounds were absent. The lower extremities were hypoplastic and did not move. Cutaneous webs connected the posterior aspect of both calves to the backs of the thighs. Both the scrotum and the phallus were hypoplastic. The testes were not palpable. The urethra and the anus were patent. Radiologic examination of the neonate revealed complete absence of vertebrae below the seventh thoracic vertebra and rib deformities. During the first 3 months of life, the infant's upper body has grown normally and he has had no respiratory difficulties. However, there has been no active movement of the lower torso and the lower extremities. 0
Comment
The congenital abnormalities commonly observed in the offspring of women with insulin-dependent diabetes mellitus are believed to arise during the first 7 weeks of gestation. These include cardiovascular, central nervous system, skeletal, genitourinary, and gastrointestinal abnormalities. None of these malformations is found solely in pregnancies complicated by diabetes mellitus. However, sacral agenesis or the caudal regression syndrome is considered to be the most characteristic abnormality in these patients. Although the relative risk for this rare lesion is increased 200-fold in infants of diabetic women, it has been observed in only 2 per 1000 pregnancies complicated by diabetes mellitus. The caudal regression anomaly may include sacral
agenesis, vertebral and spinal cord agenesis, pelvic deformities and hypoplasia, femoral hypoplasia, talipes equinovarus, muscular atrophy of the lower extremities, and flexion contractu res at the knee with webbing and may be associated with cardiac malformations. Despite intensive investigation, the teratogenic factor(s) in the pregnancy complicated by diabetes mellitus has not been precisely defined. Mills et al. I recently reported that the malformation rate in the offspring of women with diabetes mellitus who were examined before the critical period of organogenesis could not be related to glucose control. However, because the malformation rate in these pregnancies was lower than that in women who were seen later in pregnancy, the authors concluded that attention to glucose control before the pregnancy or early in gestation may be of benefit. The hemoglobin Ale level in this case was not determined until 25 weeks of gestation and does not necessarily reflect the level of glucose control during the initial part of the pregnancy. The case we describe confirms that this rare but major malformation may be detected ante natally by ultrasonography.2 Key findings included absence of the lower thoracic and lumbosacral spine, hypoplasia of the femora, and flexion contractu res of the lower extremities. This case also emphasizes the need for a detailed ultrasonographic examination in midgestation as part of the management of pregnancy complicated by insulin-dependent diabetes mellitus. REFERENCES 1. Mills JL, Knopp RH, Simpson JL, et al. Lack of correlation of increased malformation rate in infants of diabetic mothers to glycemic control during organogenesis. N Engl J Med 1988;318:671-6. 2. Hotston S, Carty H . Lumbosacral agenesis: a report of three new cases and a review of literature. Br J Radiol 1983;55:629-33.
ment by the American College of Obstetricians and Gynecologists emphasizes that to ascribe neurologic deficits to perinatal asphyxia, low Apgar scores alone are insufficient and additional evidence such as seizures and prolonged hypotonia is required. 17 The same stipulation may hold for acidosis identified at birth. Our study suggests that even severe acidosis in umbilical cord blood is insufficient evidence of asphyxia profound enough to cause neurologic damage. Furthermore, most mild neurologic deficits noted in an infant after severe acidosis can be expected to resolve in the first years of life. REFERENCES 1. Beard RW, Rivers RP. Fetal asphyxia in labor. Lancet 1979;2:1117. 2. Niswander K. Asphyxia in the fetus and cerebral palsy. In: Pitkin RM, Ziatnik FJ, eds. Year book of obstetrics and gynecology. Chicago: Year Book, 1983:107-25. 3. Nelson KB, Ellenberg JH. Apgar scores as predictors of chronic neurologic disability. Pediatrics 1981 ;68:36-44. 4. Low JA, Galbraith RS, Muir DW, Killen HL, Pater EA, Karchmar EJ. Motor and cognitive deficits after intrapartum asphyxia in the mature fetus. AM J OB8TET Gv]'o;ECOL 1988; 158:356-61. 5. Dijxhoorn MJ, VisserGHA, Huisjes HJ, Fidler V, Touwen BCL. The relation between umbilical pH values and neonatal neurological morbidity in full term appropriate-fordates infants. Early Human Dev 1985; II :33-42. 6. Ruth VJ. Raivio KO. Perinatal brain damage: predictive
March 1990 Am J Obstet Gynecol
7.
8.
9. 10. II. 12. 13. 14. 15.
16. 17.
value of metabolic acidosis and the Apgar score. Br Med J 1988;297:24. Luthy DA, Shy KK, Strickland D, et al. Status of infants at birth and risk for adverse neonatal events and longterm sequelae: a study in low birth weight infants. AM J OB8TET GVNECOL 1987;157:676-9. Brann AW. Factors during neonatal life that influence brain disorders. In: Freeman JM, ed. Prenatal and perinatal factors associated with brain disorders. (NIH publ no 85-1149). Bethesda, Md: National Institute of Child Health and Human Development, 1985:263. Brazelton TB. Behavioral assessment scale, 2nd ed. London: Spastics International, 1984. Bayley N. The Bayley scales of infant development. New York: The Psychological Corp, 1969. Thomson AJ, Searle M, Russell G. Quality of survIval after severe birth asphyxia. Arch Dis Child 1977;620-6. Scott H. Outcome of very severe birth asphyxia. Arch Dis Child 1976;51:712-6. Nelson KB, Ellenberg JH. The asymptomatic newborn and risk of cerebral palsy. Am J Dis Child 1987; 1333-5. Sexson WR, Sexson SB, RawsonJE, et al. The multisystem involvement of the asphyxiated newborn. Pediatr Res 1976; 10:432-9. Sheldon RE, Peeters LLH, Jones MD Jr, Makowski EL, Meschia G. Redistribution of cardiac output and oxygen delivery in the hypoxemic fetal lamb. AM J OB5TET GvNECOL 1979;135:1071-8. Ellenberg JH, Nelson KB. Cluster of perinatal events identifying infants at high risk for death or disability. J Pediatr 1988;113:546-52. ACOG newsletter: Use and misuse of the Apgar score. Washington, DC: American College of Obstetricians and Gynecologists, Jan 1987, p 8.
Antenatal diagnosis of sacral agenesis syndrome in a pregnancy complicated by diabetes mellitus J.
D. Sonek, MD, S. G. Gabbe, MD, M. B. Landon, MD, L. E. Stempel, MD, M. R. Foley, MD, and K. Shubert-Moell, MD
Columbus, Ohiu The sacral agenesis syndrome is a severe congenital abnormality consisting of agenesis of the lumbar spine, sacrum, and coccyx, as well as hypoplasia of the lower extremities. It is considered the most characteristic of all congenital anomalies associated with maternal diabetes mellitus. We describe the sonographic and radiologic findings of agenesis of the lumbosacrococcygeal spine with lower limb and genital hypoplasia in the offspring of a woman with both diabetic retinopathy and nephropathy. The diagnosis was established at 25 weeks' gestation and was confirmed by radiologic evaluation of the neonate. (AM J OBSTET GVNECOL 1990;162:806-8.)
Key words: Sacral agenesis syndrome, diabetic pregnancy, antenatal diagnosis From the Department of Obstetrics and Gynecology, The OhIO State Univem/'v, and the Mount Carmel Medical Center. Received fo~ publication January 19, 1989; revised June 2, 1989; accepted September 22, 1989. Reprint requests: Jiri Sonek, MD, Medical College of Georgia, Department of Obstetrics and Gynecology, Maternal-Fetal Medicine Section, Augusta, GA 30912-3350. 611116904
806
A case of agenesis of the lumbosacrococcygeal spine with lower limb and genital hypoplasia is described. The diagnosis was made at 25 weeks' gestation.
Case report A 24-year-old white woman, gravida 3, para 0, aborta 2, with proliferative retinopathy and nephropathy, di-
Volume 162 Number 3
Sacral agenesis syndrome
807
Fig. 1. Sonogram demonstrating coronal section of fetus at 28 weeks' gestation. Note absence of spinal vertebrae below mid thorax.
~:: . I"~ . J ~J
2S
:: ~teM ...?S_ . ; .
. w. ·
, ~ .
Fig. 2. Sonogram illustrating transverse section of fetus at 25 weeks' gestation at level of kidneys. Note absence of spine.
agnosed as having White's class FIR diabetes mellitus, was first seen in our clinic at 25 weeks' gestation. She had had sporadic prenatal care before this visit, al· though a first·trimester sonogram had established her expected date of confinement. The hemoglobin Ale level at 25 weeks was 5% (normal 5% to 8%). Diabetes was well controlled on two injections of insulin daily. Her initial physical ex· amination revealed proliferative retinopathy, which required laser therapy. Significant proteinuria (4.1 gm/24 hours) and a creatinine clearance of 118 ml/min were documented. Ultrasonographic examination revealed a single fetus in a cephalic presentation. The amniotic fluid volume appeared normal. The fetal anatomy above the mid· thorax, including the heart and the intracranial struc· tures, was normal. Below this level, however, complete
absence of the vertebrae was noted (Fig. 1). Two kid· neys were identifiable but were closely apposed in the midline (Fig. 2). The fetal bladder was normal in size. The lower extremities were fixed in a "froglike" posi· tion. Measurements of the lower extremities and the feet lagged 3 to 4 weeks behind the head and upper extremities. The fetus was male and the phallus was subjectively small. An amniocentesis was performed and a normal male karyotype, 46,XY, was present. Serial ultrasonographic examinations during the ges· tation revealed normal growth of the fetal head, thorax, and upper extremities. The abdominal circumference, however, was consistently below the 2.5th percentile, and the lower extremities continued to be dispropor· tionately small. The amount of amniotic fluid remained normal. Labor was induced at 35 weeks after uterine tender·
808 Sonek at al.
March 1990
Am J Obstet Gyneco1
ness and low-grade fever (38 C) developed. The patient was delivered of an 1810 gm male infant by cesarean section because of presumed fetal distress evidenced by persistent late decelerations. The infant's Apgar scores were 8 and 9 at 1 and 5 minutes, respectively. Initial examination of the neonate revealed normal respiratory effort and good movement of the upper extremities. The abdomen was slightly distended, and bowel sounds were absent. The lower extremities were hypoplastic and did not move. Cutaneous webs connected the posterior aspect of both calves to the backs of the thighs. Both the scrotum and the phallus were hypoplastic. The testes were not palpable. The urethra and the anus were patent. Radiologic examination of the neonate revealed complete absence of vertebrae below the seventh thoracic vertebra and rib deformities. During the first 3 months of life, the infant's upper body has grown normally and he has had no respiratory difficulties. However, there has been no active movement of the lower torso and the lower extremities. 0
Comment
The congenital abnormalities commonly observed in the offspring of women with insulin-dependent diabetes mellitus are believed to arise during the first 7 weeks of gestation. These include cardiovascular, central nervous system, skeletal, genitourinary, and gastrointestinal abnormalities. None of these malformations is found solely in pregnancies complicated by diabetes mellitus. However, sacral agenesis or the caudal regression syndrome is considered to be the most characteristic abnormality in these patients. Although the relative risk for this rare lesion is increased 200-fold in infants of diabetic women, it has been observed in only 2 per 1000 pregnancies complicated by diabetes mellitus. The caudal regression anomaly may include sacral
agenesis, vertebral and spinal cord agenesis, pelvic deformities and hypoplasia, femoral hypoplasia, talipes equinovarus, muscular atrophy of the lower extremities, and flexion contractu res at the knee with webbing and may be associated with cardiac malformations. Despite intensive investigation, the teratogenic factor(s) in the pregnancy complicated by diabetes mellitus has not been precisely defined. Mills et al. I recently reported that the malformation rate in the offspring of women with diabetes mellitus who were examined before the critical period of organogenesis could not be related to glucose control. However, because the malformation rate in these pregnancies was lower than that in women who were seen later in pregnancy, the authors concluded that attention to glucose control before the pregnancy or early in gestation may be of benefit. The hemoglobin Ale level in this case was not determined until 25 weeks of gestation and does not necessarily reflect the level of glucose control during the initial part of the pregnancy. The case we describe confirms that this rare but major malformation may be detected ante natally by ultrasonography.2 Key findings included absence of the lower thoracic and lumbosacral spine, hypoplasia of the femora, and flexion contractu res of the lower extremities. This case also emphasizes the need for a detailed ultrasonographic examination in midgestation as part of the management of pregnancy complicated by insulin-dependent diabetes mellitus. REFERENCES 1. Mills JL, Knopp RH, Simpson JL, et al. Lack of correlation of increased malformation rate in infants of diabetic mothers to glycemic control during organogenesis. N Engl J Med 1988;318:671-6. 2. Hotston S, Carty H . Lumbosacral agenesis: a report of three new cases and a review of literature. Br J Radiol 1983;55:629-33.