Teratogenicity of cocaine in humans

doi:10.1016/S0022-3476(87)80297-4

The Journal of Pediatrics

Volume 110, Issue 1, January 1987, Pages 93-96

https://doi.org/10.1016/S0022-3476(87)80297-4 Get rights and content

To study teratogenicity of cocaine in humans, we studied three groups of pregnant women and their offspring: group 1, 50 women who abused cocaine only; group 2, 110 women who were polydrug abusers; and group 3, 340 who were drug free. All three groups were similar for socioeconomic status, cigarette smoking, and ethnicity. Maternal age of group 1 was similar to that of group 3, but group 2 mothers were significantly older. Gravidity was significantly higher in groups 1 and 2 compared with group 3. No statistical difference was found in spontaneous abortion rate among the three groups, but the stillbirth rate was significantly higher in group 1 (ξ²=6.89, P≤0.01). All stillbirths were related to abruptio placentae. Birth weight, length, and head circumference were significantly decreased in infants in groups 1 and 2 compared with group 3 (P≤0.0001), but no statistical difference was found between groups 1 and 2. The congenital malformation rate was significantly higher in group 1 compared with group 3 (ξ²=7.07, P≤0.01). We conclude that cocaine abuse in humans significantly reduces weight of the fetus, increases the stillbirth rate related to abruptio placentae, and is associated with a higher malformation rate.

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Drugs can exert major effects on the developing central nervous system (CNS). In the broadest sense, drugs may disturb specific developmental events in the brain and, in turn, produce teratogenic effects. In addition, maternal ingestion of certain drugs can result in passive addiction of the fetus and postnatally lead to a neonatal withdrawal or abstinence syndrome. Although some effects may be transient, most are likely to persist in some form into childhood and adolescence with multiple systems affected spanning cognition, motor function, language, and behavior. This chapter provides a comprehensive overview of the neurological effects of a range of licit and illicit drugs on the infant and growing child. Drugs reviewed include fetal exposure to alcohol, antiepileptic drugs, stimulants, opioids, selective serotonin reuptake inhibitors (SSRIs), sedatives, anesthetics, and marijuana. Clinical considerations in the evaluation and care of the drug-exposed neonate are also discussed.
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Cardiovascular consequences of cocaine use
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It is presumed that such issues occur as a result of the vasoconstrictive effects of cocaine exposure on the maternal cardiovascular system and uteroplacental blood flow [63]. A five-fold increase in the risk of congenital malformations has been observed in cocaine-exposed pregnancies compared to cocaine-negative controls [63,64]. Recognizing cocaine as the cause of cardiovascular events is important for optimal patient management due to some of the treatment differences described below.
The cardiovascular consequences of cocaine use are numerous and can be severe, with mechanisms of cardiotoxicity unique to cocaine that include sympathomimetic effects, blockade of sodium and potassium channels, oxidative stress and mitochondrial damage, and disruption of excitation–contraction coupling. In combination, these effects increase myocardial oxygen demand while simultaneously decreasing oxygen supply. Cocaine-associated chest pain is particularly common and, in some instances, associated with a more severe cardiac syndrome, such as myocardial infarction, myocardial ischemia, arrhythmia, cardiomyopathy, aortic dissection, or endocarditis. Therapy for cocaine-associated chest pain and myocardial infarction is similar to treatment in non-cocaine users, except for differences in the use of benzodiazepines and phentolamine and avoidance of beta-blockers in the acute setting. In this review, we discuss the most up-to-date literature regarding the mechanisms of cocaine-associated cardiotoxicity and clinical consequences, diagnosis, and treatment; we also discuss relevant controversies while proposing several important areas for future research.
Recreational drugs
2015, Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment: Third Edition
Use of recreational drugs and other substances in women of childbearing potential is common and enquiries regarding the fetal risks following inadvertent exposure during early pregnancy are therefore also frequent. Misuse of drugs throughout or in later pregnancy may also impact on fetal well-being, and in some cases confer a risk of potentially serious effects in the neonate, such as neonatal withdrawal. Data demonstrating the extensive and lifelong problems associated with in utero exposure to alcohol are now vast and have been fundamental in informing the development of programs to reduce maternal alcohol use in pregnancy, and to improve diagnosis of fetal alcohol spectrum disorders in exposed individuals to enable early assessment and intervention. Unfortunately, the full fetal effects of drugs such as cannabis, opiates, amphetamines, cocaine and hallucinogens remain to be determined and use in pregnancy is therefore not advisable. This chapter summarizes the published literature regarding the fetal risks associated with maternal use of recreational drugs, cigarettes, caffeine and alcohol during pregnancy, the latter in the context of both regular and binge-drinking. Where applicable, recommendations regarding additional fetal monitoring or interventions are provided.
MOTHERISK ROUNDS: Cocaine Abuse During Pregnancy
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Citation Excerpt :
However, when this analysis was completed with comparison of mothers who were abusing only cocaine with the drug-free control group, the effect was no longer observed.24 Early reports by Bingol and colleagues suggested that cocaine may act as a teratogen.4 However, this study was limited in its assessment of confounding factors and had some methodological limitations.25,26
Cocaine abuse during pregnancy is a significant public health problem but is infrequently discussed between physicians and patients. The impact of in utero cocaine exposure on pregnancy and the baby has received significant media attention in preceding decades because of fears of teratogenicity, long-term health consequences, and poor cognitive and neurodevelopmental outcomes. We sought to review the medical literature examining these phenomena. We identified risks to the pregnancy and baby in women abusing cocaine during pregnancy. These include preterm birth, placenta-associated syndromes (e.g., placental abruption, preeclampsia, and placental infarction), and impaired fetal growth. Long-term neurodevelopmental and cognitive deficits include (but are not limited to) poorer language development, learning and perceptual reasoning, behavioural problems, and adverse effects on memory and executive function. However, these results should be interpreted cautiously because cocaine abuse may be accompanied by many other maternal and sociodemographic risk factors, so it is difficult to ascertain the effect of cocaine alone. Therefore, it is critical to counsel patients about potential risk, and perhaps more importantly, to treat addiction and to better understand, and advocate for improvements to, these patients’ high-risk environment.
Bien que la consommation de cocaïne pendant la grossesse constitue un problème de santé publique considérable, elle ne fait que peu fréquemment l’objet de discussions entre les médecins et leurs patientes. Les effets de l’exposition in utero à la cocaïne sur la grossesse et l’enfant se sont mérités une attention médiatique considérable au cours des dernières décennies, en raison de préoccupations au sujet de la tératogénicité de la cocaïne, de ses conséquences à long terme sur la santé et de son influence sur l’obtention de piètres issues cognitives et neurodéveloppementales. Nous avons cherché à analyser la littérature médicale examinant ces phénomènes. Nous avons identifié des risques pour la grossesse et l’enfant attribuables à la consommation de cocaïne pendant la grossesse. Parmi ces risques, on trouve l’accouchement préterme, des syndromes associés au placenta (p. ex. décollement placentaire, prééclampsie et infarctus placentaire) et l’altération de la croissance fœtale. Parmi les déficits cognitifs et neurodéveloppementaux à long terme, on trouve (entre autres) des difficultés quant au développement langagier, à l’apprentissage et au raisonnement perceptif, des problèmes comportementaux et des effets indésirables sur la mémoire et la fonction exécutive. Toutefois, ces résultats devraient être interprétés avec prudence, puisque la consommation de cocaïne pourrait s’accompagner de nombreux autres facteurs de risque maternels et sociodémographiques; il est donc difficile de déterminer l’effet qui est seulement attribuable à la cocaïne. Ainsi, il est d’une importance cruciale de conseiller les patientes au sujet des risques potentiels d’une telle pratique et, ce qui est peut-être encore plus important, d’assurer la prise en charge de l’assuétude et de mieux comprendre les conditions de vie à risque élevé de ces patientes (et de promouvoir la mise en œuvre de mesures permettant de les améliorer).
The manifestation of cocaine-induced midline destructive lesion in bone tissue and its identification in human skeletal remains
2013, Forensic Science International
Citation Excerpt :
Although pups born to mothers administered 100 mg of cocaine daily during pregnancy did not show the same significant effects, they did generally show higher rates of intrauterine and postnatal death prior to measurement than any other group in the study and higher rates of osteopenia than pair-fed controls. Prenatal cocaine exposure is also associated with delayed ossification of paws and the skull in mice and rat pups [109] and with developmental limb and digit anomalies, cranial bone defects (including exencephaly and interparietal encephalocele, and parietal bone defects without herniation), and delayed calvarial ossification in human infants [110,111]. These findings further suggest reduced/impaired osteoblastic activity associated with cocaine use.
Cocaine-induced midline destructive lesion (CIMDL) is a condition that may arise in response to chronic insufflation (“snorting”) of cocaine. It is clinically diagnosed when the nasal septum, lateral nasal walls, and/or hard palate show signs of destruction in association with cocaine use. Although its true incidence is unknown, CIMDL is not an uncommon clinical finding amongst intranasal cocaine abusers and is likely to be encountered by forensic anthropologists and medical examiners working worldwide. Given the preponderance of drug abusers amongst the subjects of forensic casework, the ability to diagnose CIMDL in dry bone may provide crucial insight into an investigation and even help confirm an individual identification.
This paper aims to make practicing forensic anthropologists aware of CIMDL. Through the analysis of existing clinical literature, patient CT scans, and histology sections, it works toward the establishment of formal diagnostic criteria for identifying CIMDL in human skeletal remains. Lytic destruction regularly involves the vomer and frequently extends to the perpendicular plate of the ethmoid, the palatal process of the maxillae or the palatine bones, and the inferior nasal conchae. The middle nasal conchae, medial walls of the maxillary sinuses, ethmoid sinuses, and cribriform plate are often damaged. Destruction may also implicate the superior nasal conchae, the orbit, and the sphenoid. Bones affected by CIMDL may contain necrotic lesions or may be absent entirely. Lesions show minimal, if any, signs of repair. The author proposes that this lack of new bone formation may be mediated by potentially elevated leptin levels in cocaine abusers and CIMDL patients and may be the key to differentiating CIMDL from other lytic processes of the midface.

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View full text

Teratogenicity of cocaine in humans

J Pharm Sci

South Am J Obstet Gynecol

Toxicol Appl Pharmacol

Am J Obstet Gynecol

Cocaine: a growing public health problem in cocaine. Pharmacology, effects and treatment of abuse

Drug use and abuse in arrestees: new findings from a study of arrestees in Manhattan

The danger of cocaine

JAMA

Cocaine use in pregnancy

N Engl J Med