Teratogenic potential of cocaine hydrochloride in CF-1 mice

Mahalik, Michael P.; Gautieri, Ronald F.; Mann, David E.

doi:10.1002/jps.2600690625

Cited by 146 publications

(24 citation statements)

References 10 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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“…Thus, except for a reduction in fetal weight and an in creased frequency of fetal resorption, Fantel and MacPhail [18] did not document a significant increase in congenital malformations in rodents exposed to as much as 60 mg/kg of cocaine during the time of organo genesis. In contrast, Mahalik et al [19] reported an in creased incidence in CF-1 mice of malformations which resembled the abnormalities reported in human infants, e.g. skeletal defects, exencephaly, ocular malforma tions, hydronephrosis, cryptorchidism and delayed os sification.…”

Section: Teratogenicitymentioning

confidence: 77%

Effect of Maternal Cocaine Use on the Fetus and Newborn: Review of the Literature

Roland

Volpe

1989

Pediatr Neurosurg

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The recent epidemic of cocaine abuse, especially among young individuals, has caused increasing concern about the potential hazards of prenatal cocaine exposure on the developing fetus and newborn. Although large-scale epidemiologic studies and long-term data are lacking, a review of the literature suggests strongly that the popular belief about the relative safety of cocaine is unfounded and that maternal cocaine abuse during pregnancy may be associated with increased perinatal morbidity and mortality.

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“…Maternal fatality in excess of 30% occurred at this dose. Mahalik et al [36] noted increased fetal resorption among CF-1 mice exposed to 60 mg/kg s.c. on day 10 only of a 19 day gestation. Fantel and MacPhail [37] reported increased resorption frequen cies and fetal edema in Sprague-Dawley rats but not Swiss-Webster mice given 60 mg/kg cocaine by intraperitoneal injection on days 8-12 of a 20-day gestation and days 7-16 of an 18-day gestation, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…and no defects in mice at a similar dose. Mahalik et al [36] reported eye, skeletal, and genitouri nary defects in mice after 60 mg/kg s.c. dur ing days 7-12 of a 19-day gestation. Church et al [35] reported only 1 case each of unilat eral anophthalmia and microcephaly among rat fetuses exposed to 40 and 90 mg/kg co caine s.c., respectively.…”

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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Teratogenic potential of cocaine hydrochloride in CF-1 mice

Cited by 146 publications

References 10 publications

The Search for Congenital Malformations in Newborns With Fetal Cocaine Exposure

The Search for Congenital Malformations in Newborns With Fetal Cocaine Exposure

Effect of Maternal Cocaine Use on the Fetus and Newborn: Review of the Literature

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

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