- Email: [email protected]
Severe symmetric intrauterine growth retardation associated with the topical use of triamcinolone
Veille and Cohen
14.
15. 16. 17.
the Eleventh Annual Conference of the Society tor the Study of Fetal Physiology. Oxford, England: Society for the Study of Fetal Physiology, 1984. Arabin B, Berkman P, Saling EZ. Distribution of uteroplacental and fetal blood flow-recent pathophysiological and clinical aspects. In: Kurjak A, ed. Ultrasonic solution to obstetric dilemmas. Amsterdam: Elsevier/Excerpta Medica, 1988. Wladimiroff jW, Tonge HM, Stewart PA. Doppler ultrasound assessment of cerebral blood flow in the human fetus. Br j Obstet Gynaecol 1986;93:471-5. Wladimiroff jW, Wijngood jACW, Degani S, et al. Cerebral and umbilical arterial and growth retarded pregnancies. Obstet Gynecol 1987;69:705-9. Wladimiroff jW, Tonge HM, Stewart PA, et al. Severe intrauterine growth retardation: assessment of its origin
February 1990
Am
18. 19. 20. 21. 22.
J Obstet Gynecol
from fetal arterial flow velocity waveforms. Eur j Obstet Gynecol Reprod Bioi 1986;22:23-9. Busija DW, Heistad DD. Effects of cholinergic nerves on cerebral blood flow in cats. Circ Res 1981 ;48:62-9. Heistad DD, Marcus ML, Ehrhardt jC, Abboud FM. Effect of stimulation of carotid chemoreceptors on total and regional cerebral blood flow. Circ Res 1976;38:20-5. Reivich M, Brannjr. AW, Shapiro H. Reactivity of cerebral vessels to CO 2 in newborn Rhesus monkey. Eur Neurol 1971;6:132-6. Ingvar DH. Functional landscapes of the dominant hemisphere. Brain Res 1976;107:181-97. Mari G, Moise K, Deter RL, et al. Doppler assessment of the pulsatility index in the cerebral circulation of the human fetus. AMj OBSTET GYNECOL 1989;160:698-703.
Severe symmetric intrauterine growth retardation associated with the topical use of triamcinolone Vern L. Katz, MD, John M. Thorp, Jr., MD, and Watson A. Bowes, Jr., MD Chapel Hill, North Carolina Triamcinolone acetonide, a fluorinated glucocorticoid, when given in large parenteral doses has produced structural anomalies and severe growth retardation in nonhuman primates. We present a case report of a gravid patient who applied 40 mg/day of triamcinolone cream because of atopic dermatitis from 12 to 29 weeks' gestation. The infant was symmetrically growth retarded, possibly from exposure to triamcinolone acetonide. There was no evidence of hypoxic, chromosomal, or infectious cause of the growth delay. (AM J OBSTET GVNECOL 1990;162:396-7.)
Key words: Triamcinolone, intrauterine growth retardation Triamcinolone acetonide is a potent fluorinated glucocorticoid commonly used as a topical agent for a variety of dermatologic conditions. Triamcinolone has caused structural defects, growth retardation, and stillbirth in nonhuman primates.' 2 The following is a report of a pregnancy complicated by administration of triamcinolone acetonide and severe growth retardation. Case report The pregnancy of a 28-year-old gravida 3, para I, abortus 1 patient was complicated by atopic dermatitis. The dermatitis was a result of multiple allergens including food additives and preservatives. The patient'S previous term pregnancy was uncomplicated and reFrom the Department of Obstetrics and Gynecology, The UniveTSlty of North Carolina School of MediCine. Received for publicatIOn March 3, 1989; revISed June 16, 1989; accepted June 30,1989. Reprint requests: Vern L. Katz, MD, Department of Obstetrics and Gynecology, DIVision of Maternal and Fetal MediCine, 214 MacNider BUIlding, CB 7570, Chapel Hill, NC 27599-7570.
6/1115018
396
suited in a vaginal delivery of a 3600 gm boy. During the index pregnancy, beginning at 12 weeks' gestation, the patient applied 0.05% triamcinolone acetonide cream to her legs, abdomen, and extremities. She did not smoke, did not take other medications, and was always normotensive. The fundal height was consistent with dates until 29 weeks' gestation. At that time the fundal height was 24 cm. An ultrasonographic examination showed an anatomically normal fetus with dimensions consistent with 24 weeks' gestation. Amniotic fluid was decreased. Umbilical artery Doppler ultrasonography did not show end-diastolic flow. Cordocentesis was performed and umbilical blood gas values were pH 7.39, Peo. 43, and P0 2 32. Fetal karyotype was 46,XX. The medication history was reviewed and the triamcinolone was stopped. The patient'S daily dose was calculated and thought to be approximately 40 mg/day. The patient was admitted for bed rest. Physical examination on admission was remarkable only because of hyper pigmented eczematoid areas over the abdomen and extremities. Laboratory findings included normal liver and renal profiles, normal electrolytes and coagulation studies, negative results of the Veneral Disease
Volume 162 Number 2
Research Laboratory test for syphilis and antinuclear antibody, white blood cell count of 7800 without eosinophilia, hemoglobin of 9.9 mg/dl, and platelet count of 326,000. Maternal cytomegalovirus and toxoplasmosis titers were both < 1: 8. There was no evidence of maternal adrenal suppression. Daily fetal heart rate monitoring was significant because of intermittent decelerations not associated with contractions. After 7 days, ultrasonography showed appropriate amniotic fluid volume and biophysical profile scores of 8 and 8. The patient was discharged home and bed rest was prescribed. One week later ultrasonography showed diminished amnitoic fluid and lack of growth since the first ultrasonogram was obtained. Umbilical artery Doppler ultrasonography again did not show end-diastolic flow. A primary cesarean delivery was performed. The patient's postpartum course was unremarkable. Maternal weight gain during the pregnancy was 8 kg; prepregancy weight was 56 kg. The 700 gm infant had Apgar scores of 6 and 9 at 1 and 5 minutes. The Dubowitz evaluation of 31 weeks' gestation agreed with menstrual dates. The baby was small for gestational age but did not have anomalies, rashes, or organomegaly. Though intubated initially, the baby was breathing room air within 12 hours. Intracranial ultrasonogram and roentgenogram of the chest were normal. Laboratoray evaluations included: hemoglobin, 14.1 mg/dl; white blood cell count, 4100; platelet count, 258,000; total immunoglobulin M <7 mg/dl; negative cytomegalovirus and toxoplasmosis titers. Viral cultures from the urine did not show growth. Electrolyte and coagulation profiles were normal. On day 14 the baby had necrotizing enterocolitis, which necessitated multiple enterostomies. Repeat necrotizing enterocolitis and surgery 5 days later left the infant with 12 cm of intestine. Ten months after delivery the baby was alive but was on total parenteral nutrition. Comment
The large amount of triamcinolone applied by this patient, 40 mg/day, is unusual. In addition, eczematoid
Triamcinolone and growth retardation
397
skin allows for increased absorbtion. We speculate that triamcinolone exposure may have caused the growth retardation as our investigation of more common causes of growth delay failed to identify a source. Triamcinolone is one of the most teratogenic of the glucocorticoids, and is associated with skeletal, neural tube, visceral, and immunologic defects in nonhuman primates. '. 2 Hendrickx et aI.' produced fetal growth delay of 30% to 40% in bonnet and rhesus monkeys with intramuscular triamcinolone. Intramuscular triamcinolone acetonide, 1 to 10 mg/kg, in pregnant rhesus monkeys led to decreased fetal lung volumes and smaller body weight. 2 Extrapolations from animal studies are often misleading because of the doses of medications used and routes of administration. However, the effects of 14 weeks of triamcinolone acetonide in this case are similar to the effects documented in animal studies.' We caution against prolonged or excessive use of topical fluorinated steroids during pregnancy. Addendum Since our initial report, this patient was delivered of a healthy 1660 gm male infant at 34 weeks' gestation (10% weight for gestational age). She did not use steroids during the pregnancy. While this represents mild growth delay, it is much less severe than that of the index pregnancy. REFERENCES 1. Hendrich AG, Sawyer RH, Terrell TG, Osburn BI, Henrickson RV, Steffek AJ. Teratogenic effects of triamcinolone on the skeletal and lymphoid systems in nonhuman primates. Fed Proceed 1975;34:1661-5. 2. Bunton TE, Plopper CG. Triamcinolone-induced structural alterations in the development of the lung of the fetal rhesus macaque. AM] OBSTET GVNECOL 1984;148:203-15.
14.
15. 16. 17.
the Eleventh Annual Conference of the Society tor the Study of Fetal Physiology. Oxford, England: Society for the Study of Fetal Physiology, 1984. Arabin B, Berkman P, Saling EZ. Distribution of uteroplacental and fetal blood flow-recent pathophysiological and clinical aspects. In: Kurjak A, ed. Ultrasonic solution to obstetric dilemmas. Amsterdam: Elsevier/Excerpta Medica, 1988. Wladimiroff jW, Tonge HM, Stewart PA. Doppler ultrasound assessment of cerebral blood flow in the human fetus. Br j Obstet Gynaecol 1986;93:471-5. Wladimiroff jW, Wijngood jACW, Degani S, et al. Cerebral and umbilical arterial and growth retarded pregnancies. Obstet Gynecol 1987;69:705-9. Wladimiroff jW, Tonge HM, Stewart PA, et al. Severe intrauterine growth retardation: assessment of its origin
February 1990
Am
18. 19. 20. 21. 22.
J Obstet Gynecol
from fetal arterial flow velocity waveforms. Eur j Obstet Gynecol Reprod Bioi 1986;22:23-9. Busija DW, Heistad DD. Effects of cholinergic nerves on cerebral blood flow in cats. Circ Res 1981 ;48:62-9. Heistad DD, Marcus ML, Ehrhardt jC, Abboud FM. Effect of stimulation of carotid chemoreceptors on total and regional cerebral blood flow. Circ Res 1976;38:20-5. Reivich M, Brannjr. AW, Shapiro H. Reactivity of cerebral vessels to CO 2 in newborn Rhesus monkey. Eur Neurol 1971;6:132-6. Ingvar DH. Functional landscapes of the dominant hemisphere. Brain Res 1976;107:181-97. Mari G, Moise K, Deter RL, et al. Doppler assessment of the pulsatility index in the cerebral circulation of the human fetus. AMj OBSTET GYNECOL 1989;160:698-703.
Severe symmetric intrauterine growth retardation associated with the topical use of triamcinolone Vern L. Katz, MD, John M. Thorp, Jr., MD, and Watson A. Bowes, Jr., MD Chapel Hill, North Carolina Triamcinolone acetonide, a fluorinated glucocorticoid, when given in large parenteral doses has produced structural anomalies and severe growth retardation in nonhuman primates. We present a case report of a gravid patient who applied 40 mg/day of triamcinolone cream because of atopic dermatitis from 12 to 29 weeks' gestation. The infant was symmetrically growth retarded, possibly from exposure to triamcinolone acetonide. There was no evidence of hypoxic, chromosomal, or infectious cause of the growth delay. (AM J OBSTET GVNECOL 1990;162:396-7.)
Key words: Triamcinolone, intrauterine growth retardation Triamcinolone acetonide is a potent fluorinated glucocorticoid commonly used as a topical agent for a variety of dermatologic conditions. Triamcinolone has caused structural defects, growth retardation, and stillbirth in nonhuman primates.' 2 The following is a report of a pregnancy complicated by administration of triamcinolone acetonide and severe growth retardation. Case report The pregnancy of a 28-year-old gravida 3, para I, abortus 1 patient was complicated by atopic dermatitis. The dermatitis was a result of multiple allergens including food additives and preservatives. The patient'S previous term pregnancy was uncomplicated and reFrom the Department of Obstetrics and Gynecology, The UniveTSlty of North Carolina School of MediCine. Received for publicatIOn March 3, 1989; revISed June 16, 1989; accepted June 30,1989. Reprint requests: Vern L. Katz, MD, Department of Obstetrics and Gynecology, DIVision of Maternal and Fetal MediCine, 214 MacNider BUIlding, CB 7570, Chapel Hill, NC 27599-7570.
6/1115018
396
suited in a vaginal delivery of a 3600 gm boy. During the index pregnancy, beginning at 12 weeks' gestation, the patient applied 0.05% triamcinolone acetonide cream to her legs, abdomen, and extremities. She did not smoke, did not take other medications, and was always normotensive. The fundal height was consistent with dates until 29 weeks' gestation. At that time the fundal height was 24 cm. An ultrasonographic examination showed an anatomically normal fetus with dimensions consistent with 24 weeks' gestation. Amniotic fluid was decreased. Umbilical artery Doppler ultrasonography did not show end-diastolic flow. Cordocentesis was performed and umbilical blood gas values were pH 7.39, Peo. 43, and P0 2 32. Fetal karyotype was 46,XX. The medication history was reviewed and the triamcinolone was stopped. The patient'S daily dose was calculated and thought to be approximately 40 mg/day. The patient was admitted for bed rest. Physical examination on admission was remarkable only because of hyper pigmented eczematoid areas over the abdomen and extremities. Laboratory findings included normal liver and renal profiles, normal electrolytes and coagulation studies, negative results of the Veneral Disease
Volume 162 Number 2
Research Laboratory test for syphilis and antinuclear antibody, white blood cell count of 7800 without eosinophilia, hemoglobin of 9.9 mg/dl, and platelet count of 326,000. Maternal cytomegalovirus and toxoplasmosis titers were both < 1: 8. There was no evidence of maternal adrenal suppression. Daily fetal heart rate monitoring was significant because of intermittent decelerations not associated with contractions. After 7 days, ultrasonography showed appropriate amniotic fluid volume and biophysical profile scores of 8 and 8. The patient was discharged home and bed rest was prescribed. One week later ultrasonography showed diminished amnitoic fluid and lack of growth since the first ultrasonogram was obtained. Umbilical artery Doppler ultrasonography again did not show end-diastolic flow. A primary cesarean delivery was performed. The patient's postpartum course was unremarkable. Maternal weight gain during the pregnancy was 8 kg; prepregancy weight was 56 kg. The 700 gm infant had Apgar scores of 6 and 9 at 1 and 5 minutes. The Dubowitz evaluation of 31 weeks' gestation agreed with menstrual dates. The baby was small for gestational age but did not have anomalies, rashes, or organomegaly. Though intubated initially, the baby was breathing room air within 12 hours. Intracranial ultrasonogram and roentgenogram of the chest were normal. Laboratoray evaluations included: hemoglobin, 14.1 mg/dl; white blood cell count, 4100; platelet count, 258,000; total immunoglobulin M <7 mg/dl; negative cytomegalovirus and toxoplasmosis titers. Viral cultures from the urine did not show growth. Electrolyte and coagulation profiles were normal. On day 14 the baby had necrotizing enterocolitis, which necessitated multiple enterostomies. Repeat necrotizing enterocolitis and surgery 5 days later left the infant with 12 cm of intestine. Ten months after delivery the baby was alive but was on total parenteral nutrition. Comment
The large amount of triamcinolone applied by this patient, 40 mg/day, is unusual. In addition, eczematoid
Triamcinolone and growth retardation
397
skin allows for increased absorbtion. We speculate that triamcinolone exposure may have caused the growth retardation as our investigation of more common causes of growth delay failed to identify a source. Triamcinolone is one of the most teratogenic of the glucocorticoids, and is associated with skeletal, neural tube, visceral, and immunologic defects in nonhuman primates. '. 2 Hendrickx et aI.' produced fetal growth delay of 30% to 40% in bonnet and rhesus monkeys with intramuscular triamcinolone. Intramuscular triamcinolone acetonide, 1 to 10 mg/kg, in pregnant rhesus monkeys led to decreased fetal lung volumes and smaller body weight. 2 Extrapolations from animal studies are often misleading because of the doses of medications used and routes of administration. However, the effects of 14 weeks of triamcinolone acetonide in this case are similar to the effects documented in animal studies.' We caution against prolonged or excessive use of topical fluorinated steroids during pregnancy. Addendum Since our initial report, this patient was delivered of a healthy 1660 gm male infant at 34 weeks' gestation (10% weight for gestational age). She did not use steroids during the pregnancy. While this represents mild growth delay, it is much less severe than that of the index pregnancy. REFERENCES 1. Hendrich AG, Sawyer RH, Terrell TG, Osburn BI, Henrickson RV, Steffek AJ. Teratogenic effects of triamcinolone on the skeletal and lymphoid systems in nonhuman primates. Fed Proceed 1975;34:1661-5. 2. Bunton TE, Plopper CG. Triamcinolone-induced structural alterations in the development of the lung of the fetal rhesus macaque. AM] OBSTET GVNECOL 1984;148:203-15.