Langzeitkonsequenzen der intrauterinen Drogenexposition

Zusammenfassung

Obschon die intrauterine Exposition gegenüber Drogen vom Typ Opioide, Cannabinoide sowie Kokain eine nicht ganz seltene Entität ist, liegen nur wenige systematische Arbeiten zu deren langfristigen Konsequenzen für die Entwicklung Betroffener vor. Wesentliche Konsequenzen der Exposition gegenüber Opioiden sind innerhalb der ersten 2 Lebensjahre eine Reduktion der motorischen Entwicklungs-Scores, die sich bis zum Schulkindesalter und Adoleszenz verbessern. In diesen Altersabschnitten finden sich für kognitive und Verhaltensuntersuchungen in Metaanalysen deutliche, allerdings nicht signifikante Trends zu verminderten Leistungen nach Exposition. Die Nachuntersuchungen nach intrauteriner Exposition gegenüber Cannabinoiden zeigen in einem Teil der Studien verminderte kognitive Leistungen und eine verschlechterte Lesefunktion sowie Störungen der Exekutivfunktionen der komplexen Planung. Bei Jungen zeigen sich in der Verhaltensanalyse vermehrt externalisierende Störungen. Die pränatale Kokainexposition führt hinsichtlich der Variablen Kognition, Sprache sowie Verhalten zu einer schwach signifikanten Verminderung der Leistungen Betroffener bis zur Adoleszenz. Insgesamt ist bei der Interpretation der Nachsorgedaten zu beachten, dass widersprüchliche Resultate publiziert wurden, die zumindest partiell durch differente Umgebungsbedingungen während der Kindheit zu erklären sind. Die aufgeführten Daten sollten ein Grund mehr sein, primäre und sekundäre Präventivbemühungen zu intensivieren.

Abstract

Although prenatal exposure to opioids, cannabinoids and cocaine is a frequent problem, only scarce data have been published on the long-term outcome in affected children and adolescents. While opioid-exposed children up to the age of 2 years show a reduced motor developmental pattern, data from meta-analyses up to adolescence show a strong trend for reduced performance with regard to cognitive function and behavior. Follow-up data after intrauterine cannabinoid exposure indicate reduced cognitive and reading abilities as well as abnormal findings in complex planning tests. Externalizing pathologies have been observed more frequently in boys. Prenatal cocaine exposure results in reduced cognitive and verbal development up to adolescence; however, differences are small but significant in meta-analyses. Interpretation of follow-up data with partially contradictory results may reflect methodological differences and a number of modifying co-factors, e.g., social conditions during the childhood period. These data should encourage further primary and secondary preventive attempts.

Schlüsselwörter

intrauterine Exposition - Opioide - Cannabinoide - Kokain - Langzeitentwicklung

Key words

prenatal exposure - opioids - cannabinoids - cocaine - long-term development

• Literatur

• 1 Majewski F. On certain embryopathies induced by teratogenic agents (author’s transl. Monatsschr Kinderheilkd 1977; 125: 609-620
• 2 Clarren SK, Alvord Jr. EC, Sumi SM. et al. Brain malformations related to prenatal exposure to ethanol. J Pediatr 1978; 92: 64-67
• 3 Hoyme HE, Kalberg WO, Elliott AJ et al. Updated Clinical Guidelines for Diagnosing Fetal Alcohol Spectrum Disorders. Pediatrics 2016; 138: (2). pii: e20154256
• 4 Ko JY, Patrick SW, Tong VT. et al. Incidence of Neonatal Abstinence Syndrome - 28 States, 1999–2013. MMWR Morb Mortal Wkly Rep 2016; 65: 799-802
• 5 Tolia VN, Patrick SW, Bennett MM. et al. Increasing incidence of the neonatal abstinence syndrome in U.S. neonatal ICUs. N Engl J Med 2015; 372: 2118-2126
• 6 Pryor JR, Maalouf FI, Krans EE. et al. The opioid epidemic and neonatal abstinence syndrome in the USA: a review of the continuum of care. Archives of disease in childhood Fetal and neonatal edition 2017; 102: F183-F187
• 7 Davies H, Gilbert R, Johnson K. et al. Neonatal drug withdrawal syndrome: cross-country comparison using hospital administrative data in England, the USA, Western Australia and Ontario, Canada. Archives of disease in childhood Fetal and neonatal edition 2016; 101: F26-F30
• 8 Tsang TW, Lucas BR, Carmichael Olson H. et al. Prenatal Alcohol Exposure, FASD, and Child Behavior: A Meta-analysis. Pediatrics 2016; 137: e20152542
• 9 Feldmann R, Girke N. Mental and Motor Development of Children with Preterm Birth and Children with Fetal Alcohol Syndrome. Klin Padiatr 2015; 227: 259-263
• 10 Kandall SR, Albin S, Gartner LM. et al. The narcotic-dependent mother: fetal and neonatal consequences. Early Hum Dev 1977; 1: 159-169
• 11 Fujinaga M, Mazze RI. Teratogenic and postnatal developmental studies of morphine in Sprague-Dawley rats. Teratology 1988; 38: 401-410
• 12 Kaltenbach K, Finnegan LP. Developmental outcome of children born to methadone maintained women: a review of longitudinal studies. Neurobehav Toxicol Teratol 1984; 6: 271-275
• 13 Behnke M, Eyler FD, Warner TD. et al. Outcome from a prospective, longitudinal study of prenatal cocaine use: preschool development at 3 years of age. J Pediatr Psychol 2006; 31: 41-49
• 14 Konijnenberg C, Sarfi M, Melinder A. Mother-child interaction and cognitive development in children prenatally exposed to methadone or buprenorphine. Early Hum Dev 2016; 101: 91-97
• 15 Jaeger DA, Suchan B, Scholmerich A. et al. Attention Functioning in Children with Prenatal Drug Exposure. Infant Ment Health J 2015; 36: 522-530
• 16 Steinhausen HC, Eschmann S, Metzke CW. Continuity, psychosocial correlates, and outcome of problematic substance use from adolescence to young adulthood in a community sample. Child Adolesc Psychiatry Ment Health 2007; 1: 12
• 17 Baldacchino A, Arbuckle K, Petrie DJ. et al. Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis. BMC Psychiatry 2014; 14: 104
• 18 Behnke M, Smith VC. Committee on Substance A et al. Prenatal substance abuse: short- and long-term effects on the exposed fetus. Pediatrics 2013; 131: e1009-e1024
• 19 Nygaard E, Moe V, Slinning K. et al. Longitudinal cognitive development of children born to mothers with opioid and polysubstance use. Pediatr Res 2015; 78: 330-335
• 20 Nygaard E, Slinning K, Moe V. et al. Behavior and Attention Problems in Eight-Year-Old Children with Prenatal Opiate and Poly-Substance Exposure: A Longitudinal Study. PLoS One 2016; 11: e0158054
• 21 Hall ES, Isemann BT, Wexelblatt SL. et al. A Cohort Comparison of Buprenorphine versus Methadone Treatment for Neonatal Abstinence Syndrome. J Pediatr 2016; 170: 39-44 e31
• 22 Mucke S, Nagel M, Siedentopf J. et al. Neonatal Abstinence Syndrome: Twelve Years of Experience at a Regional Referral Center. Klin Padiatr 2017; 229: 32-39
• 23 Konijnenberg C, Melinder A. Executive function in preschool children prenatally exposed to methadone or buprenorphine. Child Neuropsychol 2015; 21: 570-585
• 24 Kraft WK, Adeniyi-Jones SC, Chervoneva I. et al. Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome. N Engl J Med 2017; 376: 2341-2348
• 25 Huybrechts KF, Bateman BT, Desai RJ. et al. Risk of neonatal drug withdrawal after intrauterine co-exposure to opioids and psychotropic medications: cohort study. BMJ (Clinical research ed) 2017; 358: j3326
• 26 Mactier H, McLaughlin P, Gillis C. et al. Variations in Infant CYP2B6 Genotype Associated with the Need for Pharmacological Treatment for Neonatal Abstinence Syndrome in Infants of Methadone-Maintained Opioid-Dependent Mothers. Am J Perinatol 2017; 34: 918-921
• 27 de Salas-Quiroga A, Diaz-Alonso J, Garcia-Rincon D. et al. Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons. Proc Natl Acad Sci U S A 2015; 112: 13693-13698
• 28 Mounteney J, Griffiths P, Sedefov R. et al. The drug situation in Europe: an overview of data available on illicit drugs and new psychoactive substances from European monitoring in 2015. Addiction 2016; 111: 34-48
• 29 Fried PA. The Ottawa Prenatal Prospective Study (OPPS): methodological issues and findings–it’s easy to throw the baby out with the bath water. Life Sci 1995; 56: 2159-2168
• 30 Richardson GA, Day NL, Goldschmidt L. Prenatal alcohol, marijuana, and tobacco use: infant mental and motor development. Neurotoxicol Teratol 1995; 17: 479-487
• 31 Calvigioni D, Hurd YL, Harkany T. et al. Neuronal substrates and functional consequences of prenatal cannabis exposure. Eur Child Adolesc Psychiatry 2014; 23: 931-941
• 32 Hofman A, Jaddoe VW, Mackenbach JP. et al. Growth, development and health from early fetal life until young adulthood: the Generation R Study. Paediatr Perinat Epidemiol 2004; 18: 61-72
• 33 Rhodes T, Bernays S, Houmoller K. Parents who use drugs: accounting for damage and its limitation. Soc Sci Med 2010; 71: 1489-1497
• 34 Smith AM, Mioduszewski O, Hatchard T. et al. Prenatal marijuana exposure impacts executive functioning into young adulthood: An fMRI study. Neurotoxicol Teratol 2016; 58: 53-59
• 35 Webster WS, Brown-Woodman PD, Lipson AH. et al. Fetal brain damage in the rat following prenatal exposure to cocaine. Neurotoxicol Teratol 1991; 13: 621-626
• 36 Martin MM, Graham DL, McCarthy DM. et al. Cocaine-induced neurodevelopmental deficits and underlying mechanisms. Birth Defects Res C Embryo Today 2016; 108: 147-173
• 37 Bateman DA, Chiriboga CA. Dose-response effect of cocaine on newborn head circumference. Pediatrics 2000; 106: E33
• 38 Singer LT, Minnes S, Short E. et al. Cognitive outcomes of preschool children with prenatal cocaine exposure. JAMA 2004; 291: 2448-2456
• 39 Lester BM, Bagner DM, Liu J. et al. Infant neurobehavioral dysregulation: behavior problems in children with prenatal substance exposure. Pediatrics 2009; 124: 1355-1362
• 40 Buckingham-Howes S, Berger SS, Scaletti LA. et al. Systematic review of prenatal cocaine exposure and adolescent development. Pediatrics 2013; 131: e1917-e1936
• 41 Chiriboga CA, Kuhn L, Wasserman GA. Neurobehavioral and developmental traiectories associated with level of prenatal cocaine exposure. J Neurol Psychol 2014; 2: 12
• 42 Richardson GA, Goldschmidt L, Larkby C. et al. Effects of prenatal cocaine exposure on adolescent development. Neurotoxicol Teratol 2015; 49: 41-48
• 43 Aiken CE, Ozanne SE. Sex differences in developmental programming models. Reproduction 2013; 145: R1-13
• 44 Messinger DS, Bauer CR, Das A. et al. The maternal lifestyle study: cognitive, motor, and behavioral outcomes of cocaine-exposed and opiate-exposed infants through three years of age. Pediatrics 2004; 113: 1677-1685
• 45 Ornoy A, Daka L, Goldzweig G. et al. Neurodevelopmental and psychological assessment of adolescents born to drug-addicted parents: effects of SES and adoption. Child Abuse Negl 2010; 34: 354-368
• 46 Ornoy A, Finkel-Pekarsky V, Peles E. et al. ADHD risk alleles associated with opiate addiction: study of addicted parents and their children. Pediatr Res 2016; 80: 228-236