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Placental abruption associated with cocaine use: Case report
ornroducti~'e Toxicology, Vol. I, No. 3, pp. 203-205
0890-6238/87 $3.00 + .00 Copyright9 1988PergamonPressplc
~inted in the U.S.A.
P L A C E N T A L A B R U P T I O N A S S O C I A T E D W I T H C O C A I N E USE: CASE REPORT HELAIN J. LANDY a n d JOANNE HINSON Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, The George Washington University Medical Center, Washington, DC 20037 Abstract -- The medical problems associated with cocaine ingestion, most notably cardiovascular side effects, have become evident as its use has become epidemic in the United States. Its effects on pregnancy and the developing fetus are similarly being recognized as more women of childbearing age are abusing cocaine. A case of placental abruption at 33 weeks' gestation followingcocaine use is reported. A review of the pharmacodynamics, medical complications, teratogenlc potential and effects in pregnancy is included. Key IVords: Cocaine, Placental abruption, Pregnancy.
concern for a possible placental abruption. Tocolysis was stopped. The patient had increasing abdominal tenderness and periumbilical eccymosis was noted. Cesarean section revealed a tense, engorged uterus with hemorrhagic serosa and myometrium near the right uterine cornu. There was no free blood within the peritoneal cavity. A vigorous male infant was delivered from a low segment incision. The anterior placenta delivered spontaneously, almost immediately, and a large retroplacentalclot of approximately 800 ml was noted. Clinically, a 30% abruption was appreciated. During closure of the abdomen, a nonexpanding periumbilicai subfascial hematoma, which had been interpreted as Cullen's sign, was noted. This hematoma was probably a result of superficial bleeding at the needle insertion from amniocentesis. During her postpartum course, the patient was carefully questioned as to antepartum drug ingestion. She ultimately admitted to using intranasal cocaine every few weeks during the pregnancy. On the night prior to admission, she drank two bottles of beer and snorted the usual amount of cocaine, after which she noted the severe abdominal pain that prompted her hospital visit. Her postpartum course was benign. Although the infant was slightly tremulous after birth, this resolved shortly thereafter.
Medical complications with significant consequence are now being recognized in association with cocaine abuse. Reported pregnancy complications include an increased risk of spontaneous abortion and placental abruption. A case of abruption following cocaine use is reported. CASE REPORT A 21-year-old woman, G4P0030, presented to the Labor and Delivery Suite at the Fairfax Hospital in Fairfax, Virginia, at 33 weeks' gestation complaining of severe abdominal pain and cramping. She was found to be contracting every 3 rain. There was no bleeding and membranes were intact. The cervix was l-cm dilated and 50% effaced. Prenatal course had been unremarkable. A sonogram performed at 20 weeks' gestation was normal. She admitted to alcohol, marijuana, and nasal cocaine use only early in pregnancy. She had undergone three voluntary pregnancy terminations and past medical history was benign. Ritodrine tocolysis was begun to treat premature labor. Amniotic fluid gram stain was negative for organisms. The initial hematocrit dropped from 32.1 to 25 vol%. Repeat evaluation showed a further fall to 21.3 vol% within 12 h of admission. Coagulation studies were normal. Urine toxicology screen was positive for cocaine metabolites. Uterine irritability persisted, although the strong, regular contractions had subsided. In light of a falling hematocrit and persistent uterine activity, there was
DISCUSSION As cocaine use in the United States has grown to epidemic proportions in recent years, its associated medical complications, especially cardiovascular problems, are becoming more evident (1). Similarly, cocaine's effects on pregnancy and the devel-
Address correspondence to: tlelain J. Landy, MD, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, The George Washington University Medical Center, 2150 Pennsylvania Avenue, NW, Washington, D.C. 20037. Received 13 October 1987; Accepted 23 October 1987. 203
204
Reproductive Toxicology
oping fetus are being recognized (2-9). Cocaine is an alkaloid prepared from the plant, Erythroxylon coca. Its earliest known use is r e p o r t e d a s 600 A.D. (1). Animal studies suggest that cocaine may be more deleterious to general health than heroin (10). Recent medical reports of significant cardiovascular complications, including acute myocardial infarction, rupture of the ascending aorta, life-threatening cardiac arrhythmias, as well as complications of the central nervous system, confirm these studies (1). The increase in cocaine's availability and purity combined with a decrease in cost have contributed to its recent widespread use. The dangerous clinical effects of cocaine abuse must be recognized, especially since this part of the medical history is often omitted by the patient. The local anesthetic effects of cocaine result from its ability to block initiation and conduction of electrical impulses within neurons, thereby preventing the rapid increase in cell membrane permeability to sodium ions during depolarization (11). Systemic effects appear to result from cocaine's ability to block the presynaptic reuptake of dopamine and norepinephrine, which therefore results in an excess of neurotransmitter at postsynaptic receptor sites (11). The sympathetic nervous system becomes activated with resulting vasoconstriction, acute increase in arterial pressure, tachycardia, and a tendency toward vcntricular arrhythmias and seizures (1). Evidence suggests that with chronic use synapses may become depleted of dopamine (12). The dopamine depletion hypothesis suggests that symptoms of cocaine withdrawal and subsequent craving for more drug are secondary to lack of dopamine at the nerve terminals (12). Cocaine can be used in a variety of ways: intranasally or "snorting," which is the most common route of administration in the United States, injected intramuscularly, subcutaneously or intravenously, orally, sublingually, rectally, or it can be smoked (1). The free alkaloid form ("free base" or "crack") is almost pure cocaine. After absorption, which is slow across mucous membranes and therefore causes a delayed onset and sustained effect, cocaine is metabolized by plasma and liver cholinestereases to water-soluble compounds, benzoylecgonine and ecgonine methyl ester, that are excreted in the urine (I I). Cocaine metabolites can be found in adult urine for up to 24 to 36 h, depending on the individual's cholinesterase activity and route of administration (!). Plasma cholinesterase activity has been shown to be lower during pregnancy, as well as in fetuses and infants (13), resulting in slower cocaine metabolism. Similarly, patients with
Volume l, Number 3, 1987/88
congenital cholinesterase deficiency would be expected to be very sensitive to small amounts of cocaine (1). Cocaine acts as a central nervous system stimulant causing tachycardia, hypertension, and vasoconstriction through sympathetic activation. Vasoconstriction of uteroplacental blood vessels has been demonstrated after cocaine administration (7,8). Acker et al. first reported on two patients who experienced placental abruption after intravenous and intranasal cocaine use (2). The association of cocaine-induced hypertension and vasoconstriction with placental abruption has been suggested by Chasnoff et al. in their review of 28 pregnant cocaine users, which included four cases of placental abruption (3). Bingol et al. recently described three groups of patients: abusers of cocaine only, polydrug abusers, and drug-free women (5). The six stillbirths that occurred in their study, four cases after cocaine use alone and two cases after selfinjection of a "speed ball" (a combination of cocaine and heroin), all resulted from placental abruption. There were no abruptions in the drugfree group of women (5). Vasoconstriction leading to placental abruption may also be the cause of the increased number of spontaneous abortions seen in cocaine-abusing women (3,9). The present case is yet another example of cocaine-associated placental abruption. Cocaine-induced vasoconstriction of uterine arteries can similarly impair fetal oxygenation (7,9). Fetal hypoxia could explain the growth retardation that can be seen in fetuses of cocaine-abusers, both in animal studies (4,10) and in humans (5,9), although growth retardation has not been a consistent finding among all researchers (3,6). Cocaine administration is known to be associated with decreased food consumption (14), and relative maternal malnutrition may also be a factor in fetal growth retardation (4,5). Because of its high water and lipid solubility, low molecular weight and low ionization at physiological pH (15), it might be expected that cocaine would rapidly cross the placenta by simple diffusion. Furthermore, the lower fetal pH would favor higher concentrations of cocaine in the fetal circulation (16). Studying pregnant mice, Shah et al. have shown, however, that relatively low concentrations of cocaine are found in fetal tissues after maternal administration (17). Cocaine's potent vasoconstrictor ability, in causing constriction of uteroplacental vessels, may decrease its own transport across the placenta (4,14). Teratologic information on cocaine is conflict.
Placental abruption and cocaine use * H. J. LANt)V and J. HINSON
itag. In the study by~Mahalik et al. using laboratory rats, skeletal abnormalities were found in association with cocaine use (7). The study by Fantel et al. (4) could not confirm these teratogenic effects in experimental rats and mic~. Mahalik's group also found an association between heavy cocaine use at a distinct gestational age and specific malformations (e.g., cryptorchidism, eye malformations, hydronephrosis) (7). In humans, skull defects (exencephaly and parietal encephalocele) were found in infants of cocaine-abusing mothers in the study by Bingol's group (5). One infant in the review by Chasnoff et al. (3) had prune-belly syndrome (including major genitourinary malformations, bilateral hydronephrosis and bilateral cryptorchidism) and the authors believe that this anomaly was compatible with defective mesodermal development according to Mahalik's experience (7), especially since the mother had used large doses of cocaine at only one point early in the first trimester. One recent small review of eight infants has found no significant teratogenic effects of maternal cocaine use (6). Similarly, a definite withdrawal syndrome has not been consistently described in infants born to cocaine-abusing mothers, although some authors maintain that these infants show irritability and tremulousness (3,9). There appears to be an increased risk of sudden infant death syndrome (SIDS) in infants born to cocaine-using mothers (3,9). In summary, cocaine abuse is becoming a major health problem in the United States and its associated medical complications are becoming apparent. The effects of cocaine use on the pregnant woman primarily relate to sympathetic nervous system stimulation: tachycardia, hypertension, and vasoconstriction. The most notable complications in pregnancy include increased rates of spontaneous abortion and placental abruption, both of which appear to be mediated through uteroplacental vasoconstriction; placental abruption may further lead to stillbirth. For the fetus, growth retardation secondary to relative hypoxia from vasoconstriction and resultant uteroplacental insufficiency may develop, although major malformations are not consis-
205
tent findings. A mild withdrawal syndrome consisting ofjitteriness and irritability may be seen in the neonate, and these infants may be at increased risk for SIDS. In caring for pregnant women, members of the medical community must be suspicious for cocaine abuse and recognize potential lifethreatening situations for both the mother and fetus.
REFERENCES I. Cregler LL, Mark tl. Medical complications of cocaine abuse. N EngI J Med 1986; 15:1495-1500. 2. Acker D, Sachs BP, Tracey K J, et al. Abruptio placentae associated with cocaine use. Am J Obstet Gynecol 1983; 146:220-22 I. 3. Chasnoff IJ, Burns WJ, Schnoll SH, et al. Cocaine use in pregnancy. N Engl J Med 1985; 313:666-669. 4. Fantel AG, MacPhail BJ. The teratogenicity of cocaine. Teratology 1982; 26:17-19. 5. Bingol N, Fuchs M, Diaz V, et al. Tcratogenicity of cocaine in humans. J Pediatr 1987; 110:93-96. 6. Madden JD, Payne TF, Miller S. Maternal cocaine abuse and effect on the newborn. Pediatrics 1986; 77:209-211. 7. Mahalik M, Gautieri RF, Mann DE Je. Mechanisms of cocaine-induced teratogenesis. Res Commun Subst Abuse 1984; 5:279-302. 8. Woods JR Jr, Plessinger MA, Clark KE. Effect of cocaine on uterine blood flow and fetal oxygenation. JAMA 1987; 257:957-961. 9. Chasnoff IF. Perinatal effects of cocaine. Contemp Ob Gyn 1987; 29:163--179. 10. Bozarth MA, Wise RA. Toxicity associated with long-term intravenous heroin and cocaine self-administration in the rat. JAMA 1985; 254:81-83. I I. Ritchie J.M, Greene NM. Local anesthetics. In: Gilman AG, Goodman LS, Rall TW, bdurad F, eds. Tt~epharmacological basis of therapeutics, 7th ed. New York: Macmillan; 1985:309-310. 12. Dackis CA, Gold MS. New concepts in cocaine addiction: the dopamine depletion hypothesis. Neurosci Biobehav Rev 1985; 9:469--477. 13. Pritchard JA. Plasma cholinesterase activity in normal pregnancy and in eclamptogenic toxemia. Am J Obstet Gynecol 1955; 70:1083-1086. 14. Byck R, Van Dyke C. What are the effects of cocaine in man? In: RC Stillmann, RC Petersen, eds. Cocahw 1977, NIDA Monograph #13, Washington, DC: DHEW, 1977:97-118. 15. Wilson JG. Environment and birth defects. New York: 9 Academic Press; 1973:227-284. 16. Brown WU, Bell GC, Alper M. Acidosis, local anesthetics and the newborn. Obstet Gynecol 1976; 48:27-30. 17. Shah NS, May DA, Yates JD. Disposition of levo-[311] cocaine in pregnant and nonpregnant mice. Toxicol Appl Pharmacol 1980; 53:279-284.
0890-6238/87 $3.00 + .00 Copyright9 1988PergamonPressplc
~inted in the U.S.A.
P L A C E N T A L A B R U P T I O N A S S O C I A T E D W I T H C O C A I N E USE: CASE REPORT HELAIN J. LANDY a n d JOANNE HINSON Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, The George Washington University Medical Center, Washington, DC 20037 Abstract -- The medical problems associated with cocaine ingestion, most notably cardiovascular side effects, have become evident as its use has become epidemic in the United States. Its effects on pregnancy and the developing fetus are similarly being recognized as more women of childbearing age are abusing cocaine. A case of placental abruption at 33 weeks' gestation followingcocaine use is reported. A review of the pharmacodynamics, medical complications, teratogenlc potential and effects in pregnancy is included. Key IVords: Cocaine, Placental abruption, Pregnancy.
concern for a possible placental abruption. Tocolysis was stopped. The patient had increasing abdominal tenderness and periumbilical eccymosis was noted. Cesarean section revealed a tense, engorged uterus with hemorrhagic serosa and myometrium near the right uterine cornu. There was no free blood within the peritoneal cavity. A vigorous male infant was delivered from a low segment incision. The anterior placenta delivered spontaneously, almost immediately, and a large retroplacentalclot of approximately 800 ml was noted. Clinically, a 30% abruption was appreciated. During closure of the abdomen, a nonexpanding periumbilicai subfascial hematoma, which had been interpreted as Cullen's sign, was noted. This hematoma was probably a result of superficial bleeding at the needle insertion from amniocentesis. During her postpartum course, the patient was carefully questioned as to antepartum drug ingestion. She ultimately admitted to using intranasal cocaine every few weeks during the pregnancy. On the night prior to admission, she drank two bottles of beer and snorted the usual amount of cocaine, after which she noted the severe abdominal pain that prompted her hospital visit. Her postpartum course was benign. Although the infant was slightly tremulous after birth, this resolved shortly thereafter.
Medical complications with significant consequence are now being recognized in association with cocaine abuse. Reported pregnancy complications include an increased risk of spontaneous abortion and placental abruption. A case of abruption following cocaine use is reported. CASE REPORT A 21-year-old woman, G4P0030, presented to the Labor and Delivery Suite at the Fairfax Hospital in Fairfax, Virginia, at 33 weeks' gestation complaining of severe abdominal pain and cramping. She was found to be contracting every 3 rain. There was no bleeding and membranes were intact. The cervix was l-cm dilated and 50% effaced. Prenatal course had been unremarkable. A sonogram performed at 20 weeks' gestation was normal. She admitted to alcohol, marijuana, and nasal cocaine use only early in pregnancy. She had undergone three voluntary pregnancy terminations and past medical history was benign. Ritodrine tocolysis was begun to treat premature labor. Amniotic fluid gram stain was negative for organisms. The initial hematocrit dropped from 32.1 to 25 vol%. Repeat evaluation showed a further fall to 21.3 vol% within 12 h of admission. Coagulation studies were normal. Urine toxicology screen was positive for cocaine metabolites. Uterine irritability persisted, although the strong, regular contractions had subsided. In light of a falling hematocrit and persistent uterine activity, there was
DISCUSSION As cocaine use in the United States has grown to epidemic proportions in recent years, its associated medical complications, especially cardiovascular problems, are becoming more evident (1). Similarly, cocaine's effects on pregnancy and the devel-
Address correspondence to: tlelain J. Landy, MD, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, The George Washington University Medical Center, 2150 Pennsylvania Avenue, NW, Washington, D.C. 20037. Received 13 October 1987; Accepted 23 October 1987. 203
204
Reproductive Toxicology
oping fetus are being recognized (2-9). Cocaine is an alkaloid prepared from the plant, Erythroxylon coca. Its earliest known use is r e p o r t e d a s 600 A.D. (1). Animal studies suggest that cocaine may be more deleterious to general health than heroin (10). Recent medical reports of significant cardiovascular complications, including acute myocardial infarction, rupture of the ascending aorta, life-threatening cardiac arrhythmias, as well as complications of the central nervous system, confirm these studies (1). The increase in cocaine's availability and purity combined with a decrease in cost have contributed to its recent widespread use. The dangerous clinical effects of cocaine abuse must be recognized, especially since this part of the medical history is often omitted by the patient. The local anesthetic effects of cocaine result from its ability to block initiation and conduction of electrical impulses within neurons, thereby preventing the rapid increase in cell membrane permeability to sodium ions during depolarization (11). Systemic effects appear to result from cocaine's ability to block the presynaptic reuptake of dopamine and norepinephrine, which therefore results in an excess of neurotransmitter at postsynaptic receptor sites (11). The sympathetic nervous system becomes activated with resulting vasoconstriction, acute increase in arterial pressure, tachycardia, and a tendency toward vcntricular arrhythmias and seizures (1). Evidence suggests that with chronic use synapses may become depleted of dopamine (12). The dopamine depletion hypothesis suggests that symptoms of cocaine withdrawal and subsequent craving for more drug are secondary to lack of dopamine at the nerve terminals (12). Cocaine can be used in a variety of ways: intranasally or "snorting," which is the most common route of administration in the United States, injected intramuscularly, subcutaneously or intravenously, orally, sublingually, rectally, or it can be smoked (1). The free alkaloid form ("free base" or "crack") is almost pure cocaine. After absorption, which is slow across mucous membranes and therefore causes a delayed onset and sustained effect, cocaine is metabolized by plasma and liver cholinestereases to water-soluble compounds, benzoylecgonine and ecgonine methyl ester, that are excreted in the urine (I I). Cocaine metabolites can be found in adult urine for up to 24 to 36 h, depending on the individual's cholinesterase activity and route of administration (!). Plasma cholinesterase activity has been shown to be lower during pregnancy, as well as in fetuses and infants (13), resulting in slower cocaine metabolism. Similarly, patients with
Volume l, Number 3, 1987/88
congenital cholinesterase deficiency would be expected to be very sensitive to small amounts of cocaine (1). Cocaine acts as a central nervous system stimulant causing tachycardia, hypertension, and vasoconstriction through sympathetic activation. Vasoconstriction of uteroplacental blood vessels has been demonstrated after cocaine administration (7,8). Acker et al. first reported on two patients who experienced placental abruption after intravenous and intranasal cocaine use (2). The association of cocaine-induced hypertension and vasoconstriction with placental abruption has been suggested by Chasnoff et al. in their review of 28 pregnant cocaine users, which included four cases of placental abruption (3). Bingol et al. recently described three groups of patients: abusers of cocaine only, polydrug abusers, and drug-free women (5). The six stillbirths that occurred in their study, four cases after cocaine use alone and two cases after selfinjection of a "speed ball" (a combination of cocaine and heroin), all resulted from placental abruption. There were no abruptions in the drugfree group of women (5). Vasoconstriction leading to placental abruption may also be the cause of the increased number of spontaneous abortions seen in cocaine-abusing women (3,9). The present case is yet another example of cocaine-associated placental abruption. Cocaine-induced vasoconstriction of uterine arteries can similarly impair fetal oxygenation (7,9). Fetal hypoxia could explain the growth retardation that can be seen in fetuses of cocaine-abusers, both in animal studies (4,10) and in humans (5,9), although growth retardation has not been a consistent finding among all researchers (3,6). Cocaine administration is known to be associated with decreased food consumption (14), and relative maternal malnutrition may also be a factor in fetal growth retardation (4,5). Because of its high water and lipid solubility, low molecular weight and low ionization at physiological pH (15), it might be expected that cocaine would rapidly cross the placenta by simple diffusion. Furthermore, the lower fetal pH would favor higher concentrations of cocaine in the fetal circulation (16). Studying pregnant mice, Shah et al. have shown, however, that relatively low concentrations of cocaine are found in fetal tissues after maternal administration (17). Cocaine's potent vasoconstrictor ability, in causing constriction of uteroplacental vessels, may decrease its own transport across the placenta (4,14). Teratologic information on cocaine is conflict.
Placental abruption and cocaine use * H. J. LANt)V and J. HINSON
itag. In the study by~Mahalik et al. using laboratory rats, skeletal abnormalities were found in association with cocaine use (7). The study by Fantel et al. (4) could not confirm these teratogenic effects in experimental rats and mic~. Mahalik's group also found an association between heavy cocaine use at a distinct gestational age and specific malformations (e.g., cryptorchidism, eye malformations, hydronephrosis) (7). In humans, skull defects (exencephaly and parietal encephalocele) were found in infants of cocaine-abusing mothers in the study by Bingol's group (5). One infant in the review by Chasnoff et al. (3) had prune-belly syndrome (including major genitourinary malformations, bilateral hydronephrosis and bilateral cryptorchidism) and the authors believe that this anomaly was compatible with defective mesodermal development according to Mahalik's experience (7), especially since the mother had used large doses of cocaine at only one point early in the first trimester. One recent small review of eight infants has found no significant teratogenic effects of maternal cocaine use (6). Similarly, a definite withdrawal syndrome has not been consistently described in infants born to cocaine-abusing mothers, although some authors maintain that these infants show irritability and tremulousness (3,9). There appears to be an increased risk of sudden infant death syndrome (SIDS) in infants born to cocaine-using mothers (3,9). In summary, cocaine abuse is becoming a major health problem in the United States and its associated medical complications are becoming apparent. The effects of cocaine use on the pregnant woman primarily relate to sympathetic nervous system stimulation: tachycardia, hypertension, and vasoconstriction. The most notable complications in pregnancy include increased rates of spontaneous abortion and placental abruption, both of which appear to be mediated through uteroplacental vasoconstriction; placental abruption may further lead to stillbirth. For the fetus, growth retardation secondary to relative hypoxia from vasoconstriction and resultant uteroplacental insufficiency may develop, although major malformations are not consis-
205
tent findings. A mild withdrawal syndrome consisting ofjitteriness and irritability may be seen in the neonate, and these infants may be at increased risk for SIDS. In caring for pregnant women, members of the medical community must be suspicious for cocaine abuse and recognize potential lifethreatening situations for both the mother and fetus.
REFERENCES I. Cregler LL, Mark tl. Medical complications of cocaine abuse. N EngI J Med 1986; 15:1495-1500. 2. Acker D, Sachs BP, Tracey K J, et al. Abruptio placentae associated with cocaine use. Am J Obstet Gynecol 1983; 146:220-22 I. 3. Chasnoff IJ, Burns WJ, Schnoll SH, et al. Cocaine use in pregnancy. N Engl J Med 1985; 313:666-669. 4. Fantel AG, MacPhail BJ. The teratogenicity of cocaine. Teratology 1982; 26:17-19. 5. Bingol N, Fuchs M, Diaz V, et al. Tcratogenicity of cocaine in humans. J Pediatr 1987; 110:93-96. 6. Madden JD, Payne TF, Miller S. Maternal cocaine abuse and effect on the newborn. Pediatrics 1986; 77:209-211. 7. Mahalik M, Gautieri RF, Mann DE Je. Mechanisms of cocaine-induced teratogenesis. Res Commun Subst Abuse 1984; 5:279-302. 8. Woods JR Jr, Plessinger MA, Clark KE. Effect of cocaine on uterine blood flow and fetal oxygenation. JAMA 1987; 257:957-961. 9. Chasnoff IF. Perinatal effects of cocaine. Contemp Ob Gyn 1987; 29:163--179. 10. Bozarth MA, Wise RA. Toxicity associated with long-term intravenous heroin and cocaine self-administration in the rat. JAMA 1985; 254:81-83. I I. Ritchie J.M, Greene NM. Local anesthetics. In: Gilman AG, Goodman LS, Rall TW, bdurad F, eds. Tt~epharmacological basis of therapeutics, 7th ed. New York: Macmillan; 1985:309-310. 12. Dackis CA, Gold MS. New concepts in cocaine addiction: the dopamine depletion hypothesis. Neurosci Biobehav Rev 1985; 9:469--477. 13. Pritchard JA. Plasma cholinesterase activity in normal pregnancy and in eclamptogenic toxemia. Am J Obstet Gynecol 1955; 70:1083-1086. 14. Byck R, Van Dyke C. What are the effects of cocaine in man? In: RC Stillmann, RC Petersen, eds. Cocahw 1977, NIDA Monograph #13, Washington, DC: DHEW, 1977:97-118. 15. Wilson JG. Environment and birth defects. New York: 9 Academic Press; 1973:227-284. 16. Brown WU, Bell GC, Alper M. Acidosis, local anesthetics and the newborn. Obstet Gynecol 1976; 48:27-30. 17. Shah NS, May DA, Yates JD. Disposition of levo-[311] cocaine in pregnant and nonpregnant mice. Toxicol Appl Pharmacol 1980; 53:279-284.