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      Effects of Nicotine During Pregnancy: Human and Experimental Evidence

      research-article
      *
      Current Neuropharmacology
      Bentham Science Publishers Ltd.
      Newborn, perinatal, intrauterine, programming, developmental, NRT, snuff.

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          Abstract

          Prenatal exposure to tobacco smoke is a major risk factor for the newborn, increasing morbidity and even mortality in the neonatal period but also beyond. As nicotine addiction is the factor preventing many women from smoking cessation during pregnancy, nicotine replacement therapy (NRT) has been suggested as a better alternative for the fetus. However, the safety of NRT has not been well documented, and animal studies have in fact pointed to nicotine per se as being responsible for a multitude of these detrimental effects. Nicotine interacts with endogenous acetylcholine receptors in the brain and lung, and exposure during development interferes with normal neurotransmitter function, thus evoking neurodevelopmental abnormalities by disrupting the timing of neurotrophic actions. As exposure to pure nicotine is quite uncommon in pregnant women, very little human data exist aside from the vast literature on prenatal exposure to tobacco smoke.

          The current review discusses recent findings in humans on effects on the newborn of prenatal exposure to pure nicotine and non-smoke tobacco. It also reviews the neuropharmacological properties of nicotine during gestation and findings in animal experiments that offer explanations on a cellular level for the pathogenesis of such prenatal drug exposure.

          It is concluded that as findings indicate that functional nAChRs are present very early in neuronal development, and that activation at this stage leads to apoptosis and mitotic abnormalities, a total abstinence from all forms of nicotine should be advised to pregnant women for the entirety of gestation.

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          Most cited references136

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          Cholinergic systems in brain development and disruption by neurotoxicants: nicotine, environmental tobacco smoke, organophosphates.

          Acetylcholine and other neurotransmitters play unique trophic roles in brain development. Accordingly, drugs and environmental toxicants that promote or interfere with neurotransmitter function evoke neurodevelopmental abnormalities by disrupting the timing or intensity of neurotrophic actions. The current review discusses three exposure scenarios involving acetylcholine systems: nicotine from maternal smoking during pregnancy, exposure to environmental tobacco smoke (ETS), and exposure to the organophosphate insecticide, chlorpyrifos (CPF). All three have long-term, adverse effects on specific processes involved in brain cell replication and differentiation, synaptic development and function, and ultimately behavioral performance. Many of these effects can be traced to the sequence of cellular events surrounding the trophic role of acetylcholine acting on its specific cellular receptors and associated signaling cascades. However, for chlorpyrifos, additional noncholinergic mechanisms appear to be critical in establishing the period of developmental vulnerability, the sites and type of neural damage, and the eventual outcome. New findings indicate that developmental neurotoxicity extends to late phases of brain maturation including adolescence. Novel in vitro and in vivo exposure models are being developed to uncover heretofore unsuspected mechanisms and targets for developmental neurotoxicants.
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            Behavioral and neural consequences of prenatal exposure to nicotine.

            To review evidence for the neurodevelopmental effects of in utero exposure to nicotine. Concerns about long-term cognitive and behavioral effects of prenatal exposure to nicotine arise from reports of increased rates of disruptive behavioral disorders in children whose mothers smoked during pregnancy. The relatively high rate of tobacco smoking among pregnant women (25% of all pregnancies in the U.S.) underlines the seriousness of these concerns. This review examines the largest and most recent epidemiological and clinical studies that investigated the association of prenatal nicotine exposure with health, behavioral, and cognitive problems. Because of the numerous potential confounding variables in human research, findings from animal studies, in which environmental factors are strictly controlled, are also discussed. Finally, neural and molecular mechanisms that are likely to underlie neurodevelopmental disruptions produced by prenatal nicotine exposure are outlined. A dose-response relationship between maternal smoking rates and low birth weight (potentially associated with lower cognitive ability) and spontaneous abortion is consistently found, whereas long-term developmental and behavioral effects in the offspring are still controversial, perhaps because of the difficulty of separating them from other genetic and environmental factors. Despite the wide variability of experimental paradigms used in animal studies, common physical and behavioral effects of prenatal exposure to nicotine have been observed, including low birth weight, enhanced locomotor activity, and cognitive impairment. Finally, disturbances in neuronal pathfinding, abnormalities in cell proliferation and differentiation, and disruptions in the development of the cholinergic and catecholaminergic systems all have been reported in molecular animal studies of in utero exposure to nicotine. Prenatal exposure to nicotine may lead to dysregulation in neurodevelopment and can indicate higher risk for psychiatric problems, including substance abuse. Knowledge of prenatal exposure to nicotine should prompt child psychiatrists to closely monitor at-risk patients.
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              Multiple serotonergic brainstem abnormalities in sudden infant death syndrome.

              The serotonergic (5-hydroxytryptamine [5-HT]) neurons in the medulla oblongata project extensively to autonomic and respiratory nuclei in the brainstem and spinal cord and help regulate homeostatic function. Previously, abnormalities in 5-HT receptor binding in the medullae of infants dying from sudden infant death syndrome (SIDS) were identified, suggesting that medullary 5-HT dysfunction may be responsible for a subset of SIDS cases. To investigate cellular defects associated with altered 5-HT receptor binding in the 5-HT pathways of the medulla in SIDS cases. Frozen medullae from infants dying from SIDS (cases) or from causes other than SIDS (controls) were obtained from the San Diego Medical Examiner's office between 1997 and 2005. Markers of 5-HT function were compared between SIDS cases and controls, adjusted for postconceptional age and postmortem interval. The number of samples available for each analysis ranged from 16 to 31 for SIDS cases and 6 to 10 for controls. An exploratory analysis of the correlation between markers and 6 recognized risk factors for SIDS was performed. 5-HT neuron count and density, 5-HT(1A) receptor binding density, and 5-HT transporter (5-HTT) binding density in the medullary 5-HT system; correlation between these markers and 6 recognized risk factors for SIDS. Compared with controls, SIDS cases had a significantly higher 5-HT neuron count (mean [SD], 148.04 [51.96] vs 72.56 [52.36] cells, respectively; P<.001) and 5-HT neuron density (P<.001), as well as a significantly lower density of 5-HT(1A) receptor binding sites (P
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                Author and article information

                Journal
                Curr Neuropharmacol
                CN
                Current Neuropharmacology
                Bentham Science Publishers Ltd.
                1570-159X
                1875-6190
                September 2007
                : 5
                : 3
                : 213-222
                Affiliations
                []Neonatal Research Unit, Department of Women and Child Health, Karolinska Institutet, Sweden
                Author notes
                [* ]Address correspondence to this author at Neonatal Research Unit, Q2:07, ALB, Karolinska University Hospital, 171 76 Stockholm, Sweden; E-mail: Ronny.Wickstrom@ 123456ki.se
                Article
                CN-5-213
                10.2174/157015907781695955
                2656811
                19305804
                0764b0ff-1ca3-43ed-a818-9d3a5992af81
                ©2007 Bentham Science Publishers Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.5/) which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 December 2006
                : 6 February 2007
                : 7 February 2007
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                newborn,snuff.,programming,nrt,perinatal,intrauterine,developmental
                Pharmacology & Pharmaceutical medicine
                newborn, snuff., programming, nrt, perinatal, intrauterine, developmental

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