Preliminary evidence for a cocaine-induced embryopathy in mice

Finnell, Richard H.; Toloyan, S.; Waes, Michael Van; Kalivas, Peter W.

doi:10.1016/0041-008x(90)90226-k

Cited by 53 publications

(11 citation statements)

References 30 publications

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“…Some studies report no increases in congenital abnormalities in rats or mice. 40 -42 Other studies in both species, however, have indicated that prenatal cocaine exposure may be teratogenic in a dose-dependent manner, resulting in abnormalities of the limbs, [43][44][45] cardiovascular, 43,46 genitourinary, 43,44,47,48 and central nervous systems. 43,44,46,47,49 Some human reports have likewise noted anomalies of the genitourinary 3,10,11,13,20,21 and cardiovascular systems, 1,8,14 -16 skull defects, 14 limb defects and intestinal atresias, 6,13,20,21,50 and a variety of central nervous system lesions 4,5,7,9,13,[51][52][53][54][55][56] in infants exposed to cocaine in utero.…”

Section: Discussionmentioning

confidence: 99%

The Search for Congenital Malformations in Newborns With Fetal Cocaine Exposure

et al. 2001

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ABSTRACT. Context. The association between prenatal cocaine exposure and congenital anomalies is not definitive.Objective. To determine whether prenatal cocaine exposure results in an increased number or identifiable pattern of abnormalities.Design. A prospective, longitudinal cohort enrolled between 1991 and 1993.Setting. Rural public health population delivering at a regional tertiary medical center.Patients. Two hundred seventy-two offspring of 154 prenatally identified crack/cocaine users and 154 nonusing controls were matched on race, parity, location of prenatal care (that related to level of pregnancy risk), and socioeconomic status. Drug use was determined through repeated in-depth histories and urine screens. Infants not examined within 7 days of birth were excluded.Outcome Measures. Assessments were made by experienced examiners masked to maternal drug history. Included were 16 anthropometric measurements and a checklist of 180 physical features defined and agreed upon in advance.Results. There were no differences on major risk variables between the included and excluded infants. There were significantly more premature infants in the cocaineexposed group. Cocaine-exposed infants were significantly smaller in birth weight, length, and head circumference but did not differ on remaining anthropometric measurements. There was no difference in type or number of abnormalities identified between the exposed and nonexposed groups. There was no relationship between amount or timing of exposure and any of the outcomes.Conclusions. This prospective, large-scale, blinded, systematic evaluation for congenital anomalies in prenatally cocaine-exposed children did not identify an increased number or consistent pattern of abnormalities. A search for congenital malformations related to prenatal cocaine exposure has been underway since physicians became aware of the epidemic of prenatal use in the mid-1980s. Concern has been aroused because of a variety of case reports, small patient series, and retrospective studies reporting abnormalities of the skull, heart, skeleton, gastrointestinal tract, and genitourinary tract in infants born to women who used cocaine during pregnancy. [1][2][3][4][5][6][7][8][9][10][11][12][13] Over the years, the results of prospective studies have yielded somewhat conflicting outcomes. 14 -28 Methodologic concerns in many of these studies have precluded widespread acceptance of their findings, either positive or negative, leaving unanswered the question regarding the association between prenatal cocaine exposure and congenital anomalies.The most commonly identified mechanism of the effects of prenatal exposure involves the vasoconstrictive properties of cocaine. The proper growth and development of the fetus depend on a wellfunctioning vascular system. Vasoconstriction resulting in disruption of blood flow to the fetus could result in the development of structural abnormalities throughout gestation. 29,30 The purpose of this study was to determine whether prenatal cocaine exposure was associat...

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Section: Discussionmentioning

confidence: 99%

The Search for Congenital Malformations in Newborns With Fetal Cocaine Exposure

et al. 2001

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“…Certainly the vulnerable window for malformation varies by species [44] and a strategically timed co caine dose might result in a malformation unique to that species. Further, cocaine me tabolism differs by species [45] and could become apparent that teratogenesis can oc cur in the absence of overt effects on mater nal and fetal weight, implantation and re sorption [43], Our studies indicate that the direct effects of cocaine maintained at a plasma concentration compatible with hu man use [48] do not reproduce the sequelae observed in humans. These results suggest that the direct effects alone do not account for the altered perinatal and postnatal out come.…”

Section: Discussionmentioning

confidence: 68%

“…injection on gestational days 14-19 with potentiation of effects when 2 daily doses were given. Finneh et al [43] have utilized a mouse model exposed to 40-60 mg/kg i.p. cocaine to dem onstrate neural, cardiovascular, and urinary tract deformity, though limb and gastroin testinal defects were sporadic.…”

Section: Discussionmentioning

confidence: 99%

Effects of Prenatal Cocaine Exposure on Perinatal Morbidity and Postnatal Growth in the Rabbit

Weese‐Mayer¹,

Klemka-Walden²,

Chan³

et al. 1991

Dev Pharmacol Ther

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Prenatal cocaine (CC) exposure may result in increased fetal loss, growth retardation, altered neurodevelopment, and sudden infant death syndrome (SIDS). We sought to establish an animal model for prenatal cocaine exposure which (1) would allow us to distinguish the direct effects from the indirect and nutritional effects of the drug, and (2) might be used to address questions of cocaine’s toxicity, specifically to the developing respiratory control system. The study design included 38 New Zealand White rabbit does among CC, pair-fed (PF), and free-fed (FF) groups. Miniosmotic pumps were implanted in each doe on day 10 of timed gestation providing continuous subcutaneous administration of either 30 mg/kg/day of cocaine HCl in H(2)O (CC) or sterile H(2)O alone (PF and FF). Mean (SEM) plasma cocaine concentration was 1.71 ± 0.21 μmol/l (519.4 ± 64.4 ng/ml). Pregnancy outcome compared for incidence of stillbirth, maternal death, spontaneous abortion, and gross malformation among 211 pups was significant only for increased stillbirths among CC pups (18%, p < 0.04) as compared to PF (6%) and FF pups (7%). External and renal malformation and postnatal weight, crown-rump length, and snout-occiput head circumference for pups aged 4 and 5 days of age did not differ among groups. The direct effects of prenatal cocaine evaluated in our model do not reproduce the altered perinatal outcome observed among humans. However, our results do not determine if physiologic function has been altered. Investigation of the physiologic and pathologic abnormalities that are relevant to this human condition, specifically to the developing respiratory control system, should add clarity to the mechanism of action of cocaine during pregnancy.

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“…Limb reduction defects,44, 45 p h~c o m e l i a ,~~ polydactyly, and syndactyly have also been reported.22, 30 Ileal atresia was described in the fetuses of cocaine-exposed mice. 43 In human studies, 3 of 10 infants had nonduodenal intestinal atresia or i n f a r~t i o n ,~~ and 2 of 75 had ileal atresia. "…”

Section: Other Malformationsmentioning

confidence: 99%

“…The findings of animal studies using several species of mice and rats are conflicting. Some researchers found no evidence of cocaine-induced terat~genicity,~', 41 whereas others described a variety of congenital malformation~.~'~ 43 The major anomalies reported in animal models are ileal atresia, and urogenital, cardiac, ocular, skeletal, and cerebral defects.…”

Section: Teratogenicitymentioning

confidence: 99%

Cocaine: Its Effects on Maternal and Child Health

Young,

Vosper,

Phillips

1992

Pharmacotherapy

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Cocaine abuse has become one of America's leading public health problems. Its use throughout pregnancy is associated with an increased risk of abruptio placentae, stillbirth, and preterm labor. Cocaine‐associated neonatal complications include congenital malformations, decreased fetal growth, seizures, cerebral infarction and hemorrhage, auditory system deficits, sudden infant death syndrome, cardiac arrhythmias, necrotizing enterocolitis, and behavioral changes. Children followed throughout the first year of life continue to show developmental delay. Infants and children growing up in cocaine‐abusing families are at risk for drug‐related injuries. Accidental and intentional intoxication has occurred in infants and children from the smoke of freebase cocaine. The drug has also caused intoxication in breast‐feeding infants. Adolescents experimenting with cocaine are at risk, with an apparently high frequency of seizures and loss of consciousness, as well as behavioral changes and psychosocial dysfunction.

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Preliminary evidence for a cocaine-induced embryopathy in mice

Cited by 53 publications

References 30 publications

The Search for Congenital Malformations in Newborns With Fetal Cocaine Exposure

The Search for Congenital Malformations in Newborns With Fetal Cocaine Exposure

Effects of Prenatal Cocaine Exposure on Perinatal Morbidity and Postnatal Growth in the Rabbit

Cocaine: Its Effects on Maternal and Child Health

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