456 Vecchi et al. 13. Donzelli GP, Migiiorini MG, Pratesi R, Sbrana G, Vecchi C. Laser-oriented search of optimum light for phototherapy. In: Rubaltelli F, Jori G, eds. Neonatal jaundice: new trends in phototherapy. New York: Plenum Press, 1984:197-214. 14. Sisson TRC, Kendall N, Davies RE, Berger D. Factors influencing the effectiveness of phototherapy in neonatal hyperbilirubinemia. Birth Defects 1970;6:100. 15. Goldberg SM, Kendall S, Sisson TRC. Photodecomposition of bilirubin in vivo. Clin Res 1975;18:110. 16. Ennever JF, Sobel M, McDonagh AF, Speck WT. Phototherapy for neonatal jaundice: in vitro comparison of light sources. Pediatr Res 1984;18:667. 17. Ennever JF, Speck WT. Mechanism of action of phototherapy: new concepts. In: Rubaltelli F, Jori G, eds: Neonatal jaundice: new trends in phototherapy. New York: Plenum Press, 1984:187-196. 18. Ennever JF, Knox 1, Denne SC, Speck WT. Phototherapy for neonatal jaundice: in vivo clearance of bilirubin photoproducts. Pediatr Res 1985;19:205. The Journal o f Pediatrics March 1986 19. Knox 1, Ennever JF, Speck WT. Urinary excretion of an isomer of bilirubin during phototherapy. Pediatr Res 1985; 19:198. 20. Gutcher GR, Yen WM, Odell GB. The in vitro and in vivo photoreactivity of bilirubin. 1. Laser-defined wavelength dependence. Pediatr Res 1983;17:120. 2[. Lightner DA, Linnane WP Ill, Ahlfors CE. Bilirubin photooxidation products in the urine of jaundiced neonates receiving phototherapy. Pediatr Res 1984;18:696. 22. Sisson TRC, Kendall N. Avoidance of undesirable effects of blue light in phototherapy. J~ PEDIATR 1973;82:163. 23. Vogl TP. Introduction to the mechanism of phototherapy of jaundice and related technology. In: Pratesi R, Sacchi CA, eds. Lasers in photomedicine and photobiology. New York: Springer Publishing Co, 1980:136-144. 24. Jacobson ED, Krell K. Genetic effects of fluorescent lamp radiation on eukaryotic cells in culture. Photochem Photobiol 1982;35:875. Clinical and laboratory observations Perinatal cerebral infarction and maternal cocaine use Ira J. Chasnoff, M.D., Mary E. Bussey, M.D., Renate Savich, M.D., and Cynthia M. Stack, M.D. From the Departments of Pediatrics, Obstetrics and Gynecology, Psychiatry and Behavioral Sciences, and Neurology, Northwestern University Medical School and Northwestern Memorial Hospital/institute of Psychiatry, Prentice Women's Hospital and Maternity Center, Chicago The use of cocaine as a recreational drug has increased markedly in the U n i t e d States in the last few years. Concomitantly, more women have used cocaine during pregnancy. I n f o r m a t i o n on the effects of cocaine on the developing fetus, however, is sparse. W e report an infant who developed cerebral infarction after delivery at term to a w o m a n who used a large a m o u n t of cocaine in the 72 hours before delivery. Submitted for publication June 3, 1985; accepted Sept. 4, 1985. Reprint requests: Ira J. Chasnoff, M.D., 1325 W. Howard St., Evanston, IL 60202. CASE REPORT This white male infant was the 3660 gm product of a 40-week gestation born to a 32-year-old G2POAbl (elective), blood type A, Rh-po~ !ve, VDRL-negative mother whose pregnancy was com- See related article p. 459. I CT Computed tomography [ plicated by cocaine use intranasally during the first 5 weeks of pregnancy. She abstained from cocaine until the 3 days before delivery, during which she used 5 gm cocaine intranasally. On the day of delivery, the mother used approximately 1 gm cocaine Volume 108 Number 3 . Clinical and laboratory observations 457 Figure. A, Noncontrast CT scan, 24 hours of age, showing decreased attenuation involving gray and white matter in left frontal parietal region. B, Noncontrast CT scan, 7 days of age, showing gyral type of increased density in region of previously described left parietal infarct and slight increase in ventricular size. C, Noncontrast CT scan, 2V2 months of age, showing discrete area of focal hypodensity in region of previously described infarct, consistent with focal encephalomalacia or porencephaly. intranasally, with the last dose reportedly taken 15 hours before delivery of the infant. Rupture of membranes and onset of Contractions occurred during this period of time. On admission to the labor corridor, the mother was noted to be disoriented and to have slurred speech; she was described by the staff as intoxicated. Her heart rate was 120 beats per minute, and blood pressure was 124/80 mm Hg. Fetal monitoring during the 12 hours before delivery showed the infant to have multiple variable decelerations; the baseline fetal heart rate was 180 to 200 beats per minute. Meconium staining of the amniotic fluid was noted. Maternal urine obtained after delivery was positive on toxicologic screen for cocaine and nicotine. The urine was negative for opiates, alcohol, barbiturates, marijuana, amphetamines, benzodiazepines, propoxyphene, and phencyclidine. Delivery occurred vaginally with epidural anesthesia; Apgar scores were 1 at 1 minute and 7 at 5 minutes. The infant was limp and had a heart rate of 80 beats per minute at birth; thick meconium staining Was noted. The trachea was immediately intubated and suctioned; no meconium was found. Ventilation with 100% Oz was transiently performed, which produced marked improvement. The endotracheal tubes were removed at approximately 5 minutes of age, and the infant remained pink, -wellperfused, and vigorous, without respiratory distress. Arterial cord blood gas values were pH 7.30, Pco2 46 mm Hg, and base deficit - 4 ; venous cord blood gas values were pH 7.32, Pco2 42 mm Hg, and base deficit - 4 . The infant was transferred to the normal newborn nursery, where his initial physical examination was within normal limits except for mild decreased muscle tone of the right upper extremity and tachycardia as high as 180 beats per minute. At approximately 16 hours of age, he had several episodes of apnea and cyanosis. He was transferred to the high-risk nursery, where he was noted to Table. U r i n e c o n c e n t r a t i o n s o f c o c a i n e m e t a b o l i t e s Age (hr) 24 48 60 68 76 82 96 120 Urine toxicology .Cocaine Nicotine Benzoytecgonine Benzoylecgonine Benzoylecgonine Benzoylecgonine Benzoylecgonine Benzoylecgonine Benzoylecgonine Negative Concentration (ng/mL) 1240 240 150 118 89 38 20 have multiple focal seizures involving the right upper and lower extremities and a right parietal cephalohematoma. He had intermittent tachycardia to a rate of 180 beats per minute and a systolic blood pressure of up to 140 mm Hg by palpation. He had marked truncal hypotonia; decreased flexor tone in the right arm, shoulder, and hip; right-sided hyperreflexia; tight cortical thumbs bilaterally; and miotic pupils that dilated in response to noxious stimulation. Diagnostic evaluation of this infant included the following studies. Blood glucose, electrolytes, urea, creatinine, magnesium, calcium and ammonium concentrations, complete blood count with white blood cell differential, and arterial blood gas values were normal. Platelet count was 212,000/1zl. No coagulation studies were performed. Noncontrast computed tomography of the brain, done at 24 hours of age, showed an acute infarction in the distribution of the left middle cerebral artery (Figure). Cerebrospinal fluid evaluation at 21 hours of age showed 1800 red 45$ Clinical and laboratory observations blood cells and five white blood cells per microliter, glucose 81 mg/dl (113 mg/dl in plasma), protein 62 mg/dl, and a negative Gram stain. Urine toxicologic studies at 24 hours of life after treatment with phenobarbital and phenytoin contained cocaine; nicotine, phenobarbital, and phenytoin (Table). This and all subsequent urine specimens Were negative for opiates, amphetamines, benzodiazepines, alcohol, propoxyphen, marijuana, and phencyclidine. Electroencephalography performed at 2 days o f age revealed frequent focal Sharp waves in the left central parietal areas and rarely in the right temporal area, without concurrent clinical seizure activity. The infant initially required phenobarbital 25 mg/kg intravenously and phenytoin 10 mg/kg intravenously to control the right-sided seizure activity. After appropriate cultures were obtained, he was given ampicillin and gentamicin until culture results were available. Blood, urine, and cerebrospinal fluid cultures were negative, and antibiotic therapy was discontinued after 48 hours of age. The infant's blood pressure was extremely labile during the first 24 hours after admission to the high-risk nursery, with systolic levels ranging from 60 to 140 mm Hg. After 48 hours of age, his blood pressure returned to normal without therapy. The infant was given nothing by mouth until the seizures had been controlled for 48 hours. At that time enteral feedings were restarted, and maintenance oral phenobarbital therapy was begun. He remained seizure free with a dosage of 3 mg/kg/day with a serum level of 25.9 ug/ml. A repeat noncontrast CT scan performed at 7 days of age showed persistence of the left-sided infarct and increased gyral density in the region of the previously described infarct (Figure). A pneumogram made before discharge showed a normal respiratory pattern. Serial urine evaluations for cocaine metabolites showed persistence of benzoylecgonine until the infant was 4 days of age (Table). At 1 week of age, his neurologic status was markedly improved, but a mild right-sided hemiparesis persiste d. Auditory screening using behavioral assessment of responses to a high-frequency (3000 Hz) warble tone of 80 and 90 dBHL revealed no evidence for a severe degree of bilateral hearing loss. On the Brazelton Neonatal Behavioral Assessment Scale at 1 week, the infant's interactive capabilities ~}nd sta!e organization were normal for age, but his psychomotor functioning was abnormal as a result of his hemiparesis. A repeat EEG at 2 weeks of age, while he was receiving phenobarbital, was normal in Wake and sleep. Follow-up noncontrast CT scan at 21/2 months Of age showed a persistent area of focal encephalomalacia at the site of the previously noted acute infarction (Figure). Physical examination of the infant at 3 months showed increased deep tendon reflexes in the right biceps and brachiradialis without any other gross asymmetries. He also had persistent mild truncal hypotonia. To date, the baby has hail no recurrence of seizures; and phenobarbital has been discontinued. His head circumference had fallen from the 50th percentile at birth to the 5th percentile at 3 months. He was otherwise an alert, sociable infant. DISCUSSION Cocaine acts centrally in the nervous system as a stimulant and peripherally as an inhibitor of nerve conduction. Reuptake of norepinephrine at the nerve terminals is The Journal of Pediatrics Match 1986 blocked, producing increased norepinephrine levels with subsequent vasoconstriction, tachycardia, and a concomitant acute rise in blood pressure? -3 Deaths in young adults after cocaine use have been attributed to myocardial infarction and cerebrovascular accidents. 4-6 With the large ingestion of cocaine by the pregnant women in the present case, and the subSequent finding of cocaine in the urine of the infant, it appears that the fetal tachycardia and postnatal tachyeardia and hypertension were the result of the in utero exposure of the fetus to cocaine. The CT scan of the neonate at 24 hours of age confirmed the presence of an acute focal cerebral infarction. Possible causes for this infant's cerebral infarction include: thromboembolism (unproved because the placenta was not examined pathologically but was grossly normal in the deliverY room), hypotension and bradycardia with cerebral.hypoperfusion (initial Apgar score was 1, given for heart rate), and intrauterine and postnatal hypertension and subsequent cerebral hemorrhage (the spinal fluid Obtained at 21 hours of age did show 1800 red blood cells without xanthochromia). The initial C T scan showed a wedge-shaped hypodense area in the distribution of the left middle cerebral artery. The follow-up scan at 7 days of age showed gyral hyperdensity in the region of the previous infarct. Diagnostic possibilities for the findings on this second scan included localized subarachnoid hemorrhage, parenehymal hemorrhage, or possibly parenchymal calcification. Because the third C T scan at 21/2 months of age showed no residual hyperdensities, calcification is unlikely. Thus, the focal encephalomalacia seen in the third scan most likely resulted from either a bland infarct, a hemorrhagic infarction, or a small focal parenchymal hemorrhage. As in recently reported series of patients with neonatal eerebrovascular accident, 7-9 our patient's infarction may have been caused by either intrauterine and postnatal hypertension and subsequent cerebral hemorrhage, or by peripartum hypotension and bradycardia with subsequent cerebral hypoperfusion. In subsequent patients with neonatal cerebrovascular accidents, relatively noninvasive diagnostic tests such as digital intravenous angiography may shed light on the anatomic site of pathologic conditions in patients such as ours. The exact timing of the cerebral infarction is not possible to define in the present case, but prenatal occurrence is likely, given the neonate's right-sided upper extremity weakness noted at birth. Cocaine and its metabolites persist in the urine of an adult for up to 27 hours after intranasal use? ~ The persistence of benzoylecgonine, a primary metabolite of cocaine, in the neonate's urine for 4 days is evidence for slow metabolism of cocaine by the neonate, probably related to the immaturity or relative deficiency of plasma cholinesterases in the newborn infant. Drugs of maternal abuse previously investigated by our Volume 108 Number 3 grouplV13 have not produced persistent changes in the heart rate or blood pressure of neonates. Preliminary data from 23 pregnancies complicated by maternal cocaine use revealed an increased incidence of spontaneous abortions and abruptio placentae, as well as impairment of neonatal interactive and state organization abilities on the Brazelton Neonatal Behavioral Assessment Scale. TM Maternal cocaine use also may place the fetus at risk for tachycardia and hypertension, and thus for a cerebrovascular accident. Maternal cocaine use should therefore be considered in the differential diagnosis of neonates with perinatal cerebral infarction, REFERENCES I. Trendelenburg U. Modification of the effects of tyramine by various agents and procedureS. J Pharmacol Exp Ther 1961;134:8-17. 2. Resnick RB, Kestenbaum RS, Schwartz LK. Acute systemic effects Of cocaine in man: a controlled study of intranasal and intravenous routes. Science 1977;195:696-697. 3. BeUchimol A, Bartall H, Desser KB. Accelerated ventricular rhythm and cocaine abuse. Ann Intern Med 1978;88:519520. 4. Westle CV, Wright RK. Death caused by recreational cocaine use. JAMA 1979;241:2519-2522. Clinical and laboratory observations 459 5. Cohen S. The cocaine problems. Drug Abuse and Alcoholism Newsletter 1983;12:1-3. 6. Kossowsky WA, Lyon AF, Cocaine and acute myocardial infarction: probable connection. Chest 1984;86:729-731. 7: Mannino FL, Trauner DA. Stroke in neonates. J PEDIATR 1983; 102:605-610. 8. Ment LR, Duncan CC, Ehrenkranz RA. Perinatal cerebral infarction. Ann Neurol 1984;16:559-568. 9. Voorhies TM Lipper EG, Lee BCP, Vanuci RC, Auld PAM. Occlusive vascular disease in asphyxiated newborn infants. J PEDIATR 1984; 105:92-96. 10. Barnett G, Hawka R, Resnick R. Cocaine pharmocokinetics in humans. J Ethopharmacology 1981 ;3:353. 11. Chasnoff IJ, Hatcher R, Burns WJ. Polydrug- and methadone-addicted newborns: a continuum of impairment? Pediatrics 1982;70:210-213. 12. Chasnoff IJ, Burns W J, Hatcher RP, Schnoll SH. Pentazocine and pyribenzamine ("Ts and Blues"): effects on the fetus and neonate. Dev Pharmacoi Ther 1983;6:162-166. 13. Chasnoff I J, Burns W J, Hatcher RP, Burns KA. Phencyclidine: effects on the fetus and neonate. Dev Pharmacol Ther 1983;6:404-408. 14. Chasnoff IJ, Burns W J, Schnoll SH, Burns KA. Cocaine use in pregnancy. N Engl J Med i985;313:666-669. Neurodevelopmental outcome after neonatal cerebrovascular accident Doris A. Trauner, M.D., a n d Frank L. M a n n i n o , M.D. From the Departments of Neurosciences and Pediatrics, University of California Medical Center, San Diego Recent reports have documented that focal Cerebrovascular accidents occur in the neonatal period TM and can be detected through the use of brain imaging techinques such as computerized tomography and cranial ultrasound. To our knowledge, there have been no reports of long-term follow-up of patients with neonatal CVA. Thus, it is difficult to discuss possibile prognostic implications of such an event with parents. We have identified 10 infants with documented C V A in the neonatal period, and this article describes long-term follow-up in the nine survivors. Submitted for publication Aug. 12, 1985; accepted Oct. 8, 1985. Reprint requests: D. A. Trauner, M.D., Department of Neurology, H-815-B, UCSD Medical Center, 225 W. Dickinson St., San Diego, CA 92103. METHODS Ten infants (Table) were identified as having incurred a focal C V A in the neonatal period on the basis of C T scans of the head. Five of these were previously reported? All but one of these infants were term, and all but the premature See related article, p. 456. CVA CT IVH Cerebrovascular accident Computed t0mography Intraventricular hemorrhage I ] i infant developed focal motor seizures within 24 hours of life. The premature infant had recurrent apneic spells. These problems prompted performance of cranial C T scans, which demonstrated a focal area of lucency in a vascular distribution in each case. Eight of the 10 lesions were in the left hemisphere. N o n e of the infants had