The age-related particular susceptibility of developing brain tissue to injury from drugs, alcohol, and exposure to environmental toxins has long been known (for review see Larson 1989). The teratogenic effect of individual drugs and alcohol on embryonic growth and the brain's general vulnerability are described in Chap. 16-20. It should be pointed out here that mercury can cause cytoarchitectonic abnormalities; alcohol abuse (see p. 383) and the use of drugs such as phenytoin (hydantoin) and warfarin (coumarin) can lead to microcephaly with polymicrogyria and mental retardation. Ionizing radiation (pp. 257 ff) as well as cytostatic treatment of the mother during pregnancy (p. 359) interferes with neuronal proliferation and migration and is also capable of inducing microcephaly with mental retardation.

Growth processes susceptible to chemicals and drugs have been analyzed by Barone et al. (2000). These authors highlight the following temporally and regionally dependent processes contributing to cerebral development: proliferation, migration, differentiation, synaptogenesis, gliogenesis, myelina-tion, apoptosis, and neurotrophic factors.

The morphological changes engendered by these substances closely resemble those described above (Sect. 21.1). Here we deal only with the consequences of illicit drug consumption by mothers during pregnancy, which can have a major impact on the practice of obstetrics and pediatrics in urban areas the world over. The newborn exhibits withdrawal symptoms including staring, sneezing, excessive sweating, depressed respiratory status or mitotic pupils. In such cases, death may result from the deleterious effects

Fig. 21.4a-e. Hypoxic-ischemic encephalopathy. a, b The brain hemorrhage is seen (c, d), as well as a bilateral subdural hemor-surface still is smooth without gyri in a child born in the 24th rhage along the falx cerebri (e) week of gestation, while on the frontal sections a subependymal

of drugs on the placenta or on the fetus. Premature birth, perinatal hypoxia, and meconium aspiration are all known causes of death in the newborn offspring of drug-dependent mothers.

Respiratory distress is an early consequence of the presence of various other drugs in the mother (and fetus) and may lead to death. The incidence of sudden infant death syndrome (SIDS) is estimated to be 5 to 10 times greater in these babies (Chavez et al. 1979). Drug-addicted parents are responsible for an alarming number of deaths attributable to physical abuse or neglect (Mayor's Task Force on Child Abuse and Neglect 1985; for review Larson 1989; Bays and Feldman 2001).

21.3.1 Cocaine

Death can occur from intracerebral hemorrhage in infants whose mothers have taken a large dose of cocaine just prior to precipitous and premature delivery (Chasnoff et al. 1986). Cocaine intoxication is known to cause microinfarcts in adult brains and it is thought that fibrosis of the germinal matrix region of the brain can occur in infants and children born to mothers who have consumed large doses of cocaine periodically during pregnancy. A number of cocaine-related congenital malformations are known, including amniotic band syndrome, cerebro-hepato-renal syndrome (Zellweger) and generalized anasarca (hydrops). Skull defects, including exencephaly, parietal bone defects and ossification center delays and interparietal encephalocele, have been documented in addition to intracerebral hemorrhage and infarction (Bingol et al. 1987).

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