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Cocaine Abuse During Pregnancy

      Abstract

      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.

      Résumé

      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).

      Key Words

      BACKGROUND

      Canadian prevalence data are unavailable, but estimates from a 2012 survey conducted in the United States suggest that illicit drug use occurs in 5.9% of all pregnancies, with rates as high as 18.3% in 15- to 17-year-olds and 12.4% among 18- to 25-year-olds.
      • Substance Abuse and Mental Health Services Administration
      Of these drugs, cocaine abuse has received media attention since the mid-1980s because of fears of teratogenicity, long-term health effects, and poor neurodevelopmental outcomes from in utero cocaine exposure.
      • Behnke M.
      • Smith V.C.
      Prenatal substance abuse: short- and long-term effects on the exposed fetus.
      • Chasnoff I.J.
      • Burns W.J.
      • Schnoll S.H.
      • Burns K.A.
      Cocaine use in pregnancy.
      • Bingol N.
      • Fuchs M.
      • Diaz V.
      • Stone R.K.
      • Gromisch D.S.
      Teratogenicity of cocaine in humans.
      Cocaine is a highly addictive substance and is most often abused intranasally, but may also be smoked or injected. Abuse of cocaine is associated with a large number of health complications, including infectious disease, psychiatric illness, gastrointestinal complications, respiratory disease, and acute cardiovascular disease.
      • Bhargava S.
      • Arora R.R.
      Cocaine and cardiovascular complications.
      • Glauser J.
      • Queen J.R.
      An overview of non-cardiac cocaine toxicity.
      Self-reported survey data from the United States suggest that cocaine use occurs in 1.1% of young adults aged 18 to 25 years.
      • Substance Abuse and Mental Health Services Administration
      However, Canadian, United States, and European studies that have examined meconium and hair for cocaine and its metabolites suggest that rates of in utero cocaine exposure may be substantially higher (nearly 4- to 10-fold).
      • Ostrea Jr., E.M.
      • Brady M.
      • Gause S.
      • Raymundo A.L.
      • Stevens M.
      Drug screening of newborns by meconium analysis: a large-scale, prospective, epidemiologic study.
      • Pichini S.
      • Puig C.
      • Zuccaro P.
      • Marchei E.
      • Pellegrini M.
      • Murillo J.
      • et al.
      Assessment of exposure to opiates and cocaine during pregnancy in a Mediterranean city: preliminary results of the “Meconium Project.”.
      • Forman R.
      • Klein J.
      • Barks J.
      • Mehta D.
      • Greenwald M.
      • Einarson T.
      • et al.
      Prevalence of fetal exposure to cocaine in Toronto, 1990-1991.
      Given that approximately 50% of all pregnancies are unplanned,
      • Finer L.B.
      • Zolna M.R.
      Unintended pregnancy in the United States: incidence and disparities, 2006.
      fetal exposure may occur inadvertently before a woman knows she is pregnant. Cocaine rapidly crosses the human placenta
      • Schenker S.
      • Yang Y.
      • Johnson R.F.
      • Downing J.W.
      • Schenken R.S.
      • Henderson G.I.
      • et al.
      The transfer of cocaine and its metabolites across the term human placenta.
      and the fetal blood-brain barrier, and exhibits pharmacological activity in the developing fetal brain, where it is thought to interfere with neurotransmission and synaptic development.
      • Behnke M.
      • Smith V.C.
      Prenatal substance abuse: short- and long-term effects on the exposed fetus.
      • Benveniste H.
      • Fowler J.S.
      • Rooney W.D.
      • Scharf B.A.
      • Backus W.W.
      • Izrailtyan I.
      • et al.
      Cocaine is pharmacologically active in the nonhuman primate fetal brain.
      Notably, women who abuse cocaine may have other risk factors that contribute to adverse pregnancy and infant outcomes, including (but not limited to) lower socioeconomic status, inadequate prenatal care, polysubstance abuse, maternal infections, maternal psychopathology, and a history of partner violence (Table).
      • Bendersky M.
      • Alessandri S.
      • Gilbert P.
      • Lewis M.
      Characteristics of pregnant substance abusers in two cities in the northeast.
      • Bauer C.R.
      • Shankaran S.
      • Bada H.S.
      • Lester B.
      • Wright L.L.
      • Krause-Steinrauf H.
      • et al.
      The Maternal Lifestyle Study: drug exposure during pregnancy and short-term maternal outcomes.
      • Richardson G.A.
      • Goldschmidt L.
      • Larkby C.
      Effects of prenatal cocaine exposure on growth: a longitudinal analysis.
      • Bada H.S.
      • Bann C.M.
      • Whitaker T.M.
      • Bauer C.R.
      • Shankaran S.
      • Lagasse L.
      • et al.
      Protective factors can mitigate behavior problems after prenatal cocaine and other drug exposures.
      • Nair P.
      • Schuler M.E.
      • Black M.M.
      • Kettinger L.
      • Harrington D.
      Cumulative environmental risk in substance abusing women: early intervention, parenting stress, child abuse potential and child development.
      • Bada H.S.
      • Das A.
      • Bauer C.R.
      • Shankaran S.
      • Lester B.
      • Wright L.L.
      • et al.
      Gestational cocaine exposure and intrauterine growth: maternal lifestyle study.
      • Lambert B.L.
      • Bauer C.R.
      Developmental and behavioral consequences of prenatal cocaine exposure: a review.
      Maternal cocaine abuse and in utero cocaine exposure therefore represent significant public health problems for both mother and fetus.

      EFFECT OF MATERNAL COCAINE ABUSE ON PREGNANCY OUTCOMES

      Maternal cocaine abuse has been associated with a number of adverse pregnancy outcomes, including preterm birth, premature rupture of membranes, and a number of other placenta-associated syndromes (e.g., placental abruption, placental infarction, and preeclampsia).
      • Gouin K.
      • Murphy K.
      • Shah P.S.
      Knowledge Synthesis group on Determinants of Low Birth Weight and Preterm Births. Effects of cocaine use during pregnancy on low birthweight and preterm birth: systematic review and metaanalyses.
      • Addis A.
      • Moretti M.E.
      • Ahmed Syed F.
      • Einarson T.R.
      • Koren G.
      Fetal effects of cocaine: an updated meta-analysis.
      • Mbah A.K.
      • Alio A.P.
      • Fombo D.W.
      • Bruder K.
      • Dagne G.
      • Salihu H.M.
      Association between cocaine abuse in pregnancy and placenta-associated syndromes using propensity score matching approach.
      It has also been associated with intrauterine growth restriction leading to low birth weight and small for gestational age infants.
      • Bada H.S.
      • Das A.
      • Bauer C.R.
      • Shankaran S.
      • Lester B.
      • Wright L.L.
      • et al.
      Gestational cocaine exposure and intrauterine growth: maternal lifestyle study.
      • Gouin K.
      • Murphy K.
      • Shah P.S.
      Knowledge Synthesis group on Determinants of Low Birth Weight and Preterm Births. Effects of cocaine use during pregnancy on low birthweight and preterm birth: systematic review and metaanalyses.
      • Addis A.
      • Moretti M.E.
      • Ahmed Syed F.
      • Einarson T.R.
      • Koren G.
      Fetal effects of cocaine: an updated meta-analysis.
      An increased risk of miscarriage has been noted,
      • Ness R.B.
      • Grisso J.A.
      • Hirschinger N.
      • Markovic N.
      • Shaw L.M.
      • Day N.L.
      • et al.
      Cocaine and tobacco use and the risk of spontaneous abortion.
      but this association remains controversial. In a meta-analysis by Motherisk, polysubstance abusers who were also abusing cocaine had an increased risk of miscarriage compared with the reference group of drug-free mothers. 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.
      • Lutiger B.
      • Graham K.
      • Einarson T.R.
      • Koren G.
      Relationship between gestational cocaine use and pregnancy outcome: a meta-analysis.

      COCAINE IS NOT A GROSS STRUCTURAL TERATOGEN

      Early reports by Bingol and colleagues suggested that cocaine may act as a teratogen.
      • Bingol N.
      • Fuchs M.
      • Diaz V.
      • Stone R.K.
      • Gromisch D.S.
      Teratogenicity of cocaine in humans.
      However, this study was limited in its assessment of confounding factors and had some methodological limitations.
      • Bauchner H.
      • Zuckerman B.
      • Amaro H.
      • Frank D.A.
      • Parker S.
      Teratogenicity of cocaine.
      • Koren G.
      Cocaine and the human fetus: the concept of teratophilia.
      The contribution of other sociodemographic and environmental risk factors to the observed association was suggested as early as in 1987,
      • Bauchner H.
      • Zuckerman B.
      • Amaro H.
      • Frank D.A.
      • Parker S.
      Teratogenicity of cocaine.
      amid growing fears of a potential epidemic of harm due to in utero cocaine exposure. In subsequent and more methodologically sound studies, no specific pattern of gross congenital anomalies or syndromes has been identified.
      • Addis A.
      • Moretti M.E.
      • Ahmed Syed F.
      • Einarson T.R.
      • Koren G.
      Fetal effects of cocaine: an updated meta-analysis.
      • Behnke M.
      • Eyler F.D.
      • Garvan C.W.
      • Wobie K.
      The search for congenital malformations in newborns with fetal cocaine exposure.
      • Minnes S.
      • Robin N.H.
      • Alt A.A.
      • Kirchner H.L.
      • Satayathum S.
      • Salbert B.A.
      • et al.
      Dysmorphic and anthropometric outcomes in 6-year-old prenatally cocaine-exposed children.
      Therefore, it is thought that cocaine does not act independently as a gross structural teratogen.
      Tabled 1Factors thought to confound the relationship between in utero cocaine exposure and pregnancy outcomes, infant growth, and long-term neurodevelopmental and cognitive deficits
      Confounding factors
      Ethnic minority status
      Lower socioeconomic status
      Polysubstance abuse
      Criminal history
      Homelessness
      Inadequate prenatal care
      Maternal undernutrition
      Maternal infections during pregnancy
      Maternal or childhood stress
      Parental or caregiver psychopathology
      Parental or partner violence
      Low birth weight
      Prematurity
      Residing in foster versus maternal care
      Low maternal intelligence
      Low maternal language ability
      Lower quality home and/or community environment
      Amount and duration of in utero cocaine exposure

      IN UTERO COCAINE EXPOSURE: GROWTH, COGNITIVE, AND NEURODEVELOPMENTAL OUTCOMES

      Whether there is an effect of in utero cocaine exposure on long-term child growth remains uncertain. Studies have reported evidence of slower growth rates among prenatally exposed children up to the age of 10 years after other factors associated with child growth have been controlled for.
      • Richardson G.A.
      • Goldschmidt L.
      • Larkby C.
      Effects of prenatal cocaine exposure on growth: a longitudinal analysis.
      • Minnes S.
      • Robin N.H.
      • Alt A.A.
      • Kirchner H.L.
      • Satayathum S.
      • Salbert B.A.
      • et al.
      Dysmorphic and anthropometric outcomes in 6-year-old prenatally cocaine-exposed children.
      • Covington C.Y.
      • Nordstrom-Klee B.
      • Ager J.
      • Sokol R.
      • Delaney-Black V.
      Birth to age 7 growth of children prenatally exposed to drugs: a prospective cohort study.
      Some studies have reported that children exposed to cocaine prenatally had adverse neurodevelopmental outcomes. Reported outcomes include, but are not limited to, poorer adolescent functioning,
      • Buckingham-Howes S.
      • Berger S.S.
      • Scaletti L.A.
      • Black M.M.
      Systematic review of prenatal cocaine exposure and adolescent development.
      poorer perceptual reasoning,
      • Singer L.T.
      • Nelson S.
      • Short E.
      • Min M.O.
      • Lewis B.
      • Russ S.
      • et al.
      Prenatal cocaine exposure: drug and environmental effects at 9 years.
      impairment in procedural learning,
      • Mayes L.
      • Snyder P.J.
      • Langlois E.
      • Hunter N.
      Visuospatial working memory in school-aged children exposed in utero to cocaine.
      internalizing, externalizing, and total behaviour problems,
      • Bada H.S.
      • Das A.
      • Bauer C.R.
      • Shankaran S.
      • Lester B.
      • LaGasse L.
      • et al.
      Impact of prenatal cocaine exposure on child behavior problems through school age.
      more symptoms of oppositional defiant disorder and attention deficit hyperactivity disorder,
      • Linares T.J.
      • Singer L.T.
      • Kirchner H.L.
      • Short E.J.
      • Min M.O.
      • Hussey P.
      • et al.
      Mental health outcomes of cocaine-exposed children at 6 years of age.
      impairment of executive function,
      • Lambert B.L.
      • Bauer C.R.
      Developmental and behavioral consequences of prenatal cocaine exposure: a review.
      adverse effects on short-term memory,
      • Betancourt L.M.
      • Yang W.
      • Brodsky N.L.
      • Gallagher P.R.
      • Malmud E.K.
      • Giannetta J.M.
      • et al.
      Adolescents with and without gestational cocaine exposure: longitudinal analysis of inhibitory control, memory and receptive language.
      and poorer language development.
      • Landi N.
      • Crowley M.J.
      • Wu J.
      • Bailey C.A.
      • Mayes L.C.
      Deviant ERP response to spoken non-words among adolescents exposed to cocaine in utero.
      • Nulman I.
      • Rovet J.
      • Greenbaum R.
      • Loebstein M.
      • Wolpin J.
      • Pace-Asciak P.
      • et al.
      Neurodevelopment of adopted children exposed in utero to cocaine: the Toronto Adoption Study.
      However, recent systematic reviews and meta-analyses suggest that sociodemographic, environmental, and other factors such as those listed in the Table may make a contribution to these adverse neurodevelopmental outcomes that is equal to or even greater than cocaine.
      • Lambert B.L.
      • Bauer C.R.
      Developmental and behavioral consequences of prenatal cocaine exposure: a review.
      • Ackerman J.P.
      • Riggins T.
      • Black M.M.
      A review of the effects of prenatal cocaine exposure among school-aged children.
      • Frank D.A.
      • Augustyn M.
      • Knight W.G.
      • Pell T.
      • Zuckerman B.
      Growth, development, and behavior in early childhood following prenatal cocaine exposure: a systematic review.
      Further, a recent study showed that environmental “protective factors,” such as resilience, caretaker involvement, higher family socioeconomic status, and family support and resources reduce the trajectory of behavioural problems from in utero cocaine exposure.
      • Bada H.S.
      • Bann C.M.
      • Whitaker T.M.
      • Bauer C.R.
      • Shankaran S.
      • Lagasse L.
      • et al.
      Protective factors can mitigate behavior problems after prenatal cocaine and other drug exposures.

      COUNSELLING PATIENTS ON MATERNAL COCAINE ABUSE DURING PREGNANCY

      Cocaine abuse has been associated with adverse pregnancy and fetal outcomes, but it most often occurs within the context of other social and environmental risk factors found in disadvantaged populations. Interventions aimed at managing maternal addiction and understanding the context in which drug abuse takes place, providing comprehensive prenatal care, reducing or discontinuing drug use, and improving the social determinants of health and environment in which pregnancy and infant development occur may help reduce risk to maternal and child health.
      Importantly, infants and children of cocaine-addicted mothers are at substantially higher risk for neglect and different types of abuse, and they need to be followed intensively to decide whether they can be adequately cared for by their biological parents.

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        Impact of prenatal cocaine exposure on child behavior problems through school age.
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