Teratogenic Effects of Benzodiazepine Use during Pregnancy

Department of Pediatrics II, Gothenburg University, Sweden.
Journal of Pediatrics (Impact Factor: 3.79). 02/1989; 114(1):126-31. DOI: 10.1097/00006254-198910000-00012
Source: PubMed


Eight children exposed in utero to benzodiazepines had characteristic dysmorphic features, growth aberrations, and central nervous system abnormalities from birth. Their dysmorphic characteristics resembled those of the fetal alcohol syndrome, although they had greater focal involvement of cranial nerves, with a sullen and expressionless face, and they more often had impairment of vitality at birth. One infant died and at autopsy had varying degrees of distortion of neuronal migration, with concomitant heterotopias. Five of the eight mothers had regularly consumed benzodiazepines, and the three remaining mothers had blood samples during pregnancy revealing benzodiazepine concentrations indicative of regular use. Our findings indicate that maternal consumption of benzodiazepines may be teratogenic in humans.

20 Reads
  • Source
    • "Endoscopy should be done with minimal sedation. Meperidine, FDA class B followed by small doses of midazolam FDA class C. (Qureshi, 2005) Benzodiazepines (D) should be avoided in the first trimester since they have been associated with congenital cleft palate and when used late in pregnancy with neurobehavioral disorders (Ornoy, 1998; Dolovich, et al 1998; Laegreid et al,1989). Propofol, FDA class B, should be administered by an anaesthetist; its safety as yet in first trimester has not been studied (Gin, 1994). "

    Inflammatory Bowel Disease - Advances in Pathogenesis and Management, 01/2012; , ISBN: 978-953-307-891-5
  • Source
    • "However, two others of their patients were tested biochemically and did not show accumulation of very long and branched-chain fatty acids, a biochemical hallmark of ZS. One of these two died at 11 weeks of age, and upon autopsy was found to have slight cortical dysplasia and single-cell neuronal heterotopias in white matter [48]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Zellweger syndrome (ZS) is a fatal inherited disease caused by peroxisome biogenesis deficiency. Patients are characterized by multiple disturbances of lipid metabolism, profound hypotonia and neonatal seizures, and distinct craniofacial malformations. Median live expectancy of ZS patients is less than one year. While the molecular basis of peroxisome biogenesis and metabolism is known in considerable detail, it is unclear how peroxisome deficiency leads to the most severe neurological symptoms. Recent analysis of ZS mouse models has all but invalidated previous hypotheses. We suggest that a regulatory rather than a metabolic defect is responsible for the drastic impairment of brain function in ZS patients. Using microarray analysis we identify diazepam binding inhibitor/acyl-CoA binding protein (DBI) as a candidate protein that might be involved in the pathogenic mechanism of ZS. DBI has a dual role as a neuropeptide antagonist of GABA(A) receptor signaling in the brain and as a regulator of lipid metabolism. Repression of DBI in ZS patients could result in an overactivation of GABAergic signaling, thus eventually leading to the characteristic hypotonia and seizures. The most important argument for a misregulation of GABA(A) in ZS is, however, provided by the striking similarity between ZS and "benzodiazepine embryofetopathy", a malformation syndrome observed after the abuse of GABA(A) agonists during pregnancy. We present a tentative mechanistic model of the effect of DBI misregulation on neuronal function that could explain some of the aspects of the pathology of Zellweger syndrome.
    BMC Pediatrics 04/2004; 4(1):5. DOI:10.1186/1471-2431-4-5 · 1.93 Impact Factor
  • Source
    • "Assessing the effects of in utero alcohol and other drug exposure is often limited by difficulties in specifying and measuring the various dosage levels of alcohol and drugs consumed by the mother ( Chasnoff 1991; Zuckerman 1991c). Examinations of prenatal exposure are further complicated by differences in chemical properties of the substances, in teratogenic potential, and in the timing of fetal development ( Laengreid et al. 1989; Silverman 1989; Streissguth 1989; Bingol et al. 1987; Chasnoff et al. 1983; Abel 1980; Wilson, Desmond & Verniaud 1973). Zuckerman (1991b) warns that there are several criteria that must be met in order to draw firm conclusions regarding the effect of a particular substance on an infant. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Children are affected by alcohol and other drug use along three primary paths: in utero through the mother's use, environmentally through both family and community influences, and through their own use. Children who are prenatally exposed are put at risk both through physiological insults and through caregiving deficits in their immediate family. The number of cases of Fetal Alcohol Syndrome (FAS) in the western world has been estimated at 0.33 cases per 1,000 live births; 200 babies are born with FAS per year in California. The National Institute on Drug Abuse (NIDA) estimates that 7.62 million babies (18.6%) were exposed to alcohol during gestation. Current prevalence estimates show about 28.6 million children of alcoholics in the United States, while in California it is estimated that about 17.6% of children lived with a parent who used illegal substances during the past year. Although all the prenatal effects of alcohol are not known, it is clear that there is no safe amount of alcohol to be consumed during pregnancy. There is little consensus, however, on long-term effects from in utero exposure alone because of the influence of adverse environmental factors; prenatal exposure is usually not the final influence, but is reinforced by years of neglect, deprivation, negative behavioral models, and other adverse conditions. And although society places most emphasis upon the negative effects of illicit substances, use of alcohol is strongly associated with crime and family violence. The consequences of use of alcohol and tobacco are more costly to society in terms of health care, accidents, days of work lost, and other social costs.
    Journal of psychoactive drugs 03/1997; 29(1):23-42. DOI:10.1080/02791072.1997.10400168 · 1.10 Impact Factor
Show more