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4. Nicotine and the Unborn Fetus

Exposure to nicotine through maternal cigarette smoking during pregnancy has harmful effects upon the offspring (Kinney, O’Donnell, Kriger, & White, 1993). Harmful effects to children include neurological abnormalities, developmental delays, and attention deficit hyperactivity disorder. Other harmful effects of maternal smoking are related to the combined effects of nicotine, tar and carbon monoxide contained in smoke which cause chronic fetal hypoxia (Spinillo et al., 1995). Cigarette smoking is associated with increases in perinatal mortality and morbidity rates.

In a study by Spinillo, Ometto, Stronati, Piazzi, Iasci and Rondini (1995), they found that heavy cigarette smoking during the latter half of pregnancy increases the risk of mild intracranial hemorrhage in pre-term infants. It was hypothesized that chronic fetal hypoxemia and hypercapnia associated with heavy maternal smoking may affect susceptibility of the vessels of the germinal matrix to postnatal fluctuations in cerebral hemodynamics. Nicotine exerts significant hemodynamic effects in the mother by increasing arterial blood pressure and heart rate. The hypertensive effect of nicotine on the fetal circulation could further explain the increased risk of periventricular-intraventricular hemorrhage in pre-term infants of heavy smokers.

In order to differentiate harm to the fetus related to potential teratogens in cigarette smoke from nicotine, continuous subcutaneous infusion models of nicotine were developed that eliminated the hypoxic/ischemic components of nicotine exposure (Levitt, 1998). The effects of prenatal nicotine exposure result in a pattern of altered development. There is a complex combination of delays in developmental maturation, followed by recovery and then late-expressed alterations.

Nicotine may be directly toxic to the developing brain. Nicotine directly interacts with endogenous nicotinic acetylcholine receptors (nAChRs) in the brain (Kinney, O’Donnell, Kriger, & White, 1993). This interaction can profoundly affect CNS function and development. One mechanism of nicotine toxicity in the fetal brain involves altered development of cholinergic pathways via nicotinic receptor-mediated interactions.

A strong and significant positive association between maternal smoking and attention deficit hyperactivity disorder (ADHD) in children was found in a study (Milberger, Biederman, Faraone, Chen, & Jones, 1996). The results could not be attributed to socioeconomic status, parental ADHD, and parental IQ. On the basis of animal studies, it has been hypothesized that catecholaminergic pathways play an important role in the etiology of ADHD. Though the exact mechanism of stimulant therapy is unknown, evidence shows that the dopaminergic system is involved. It has been shown that nicotine freely crosses the placenta and it is believed that the human fetus is actually exposed to a higher nicotine concentration than the smoking mother. Nicotinic receptors modulate dopaminergic activity and dopaminergic dysregulation is believed to be involved in the underlying pathophysiology of ADHD.

Maternal smoking causes statistically significant, though modest changes in general brain size, protein/DNA and RNA/DNA content, and ornithine decarboxylase activity on the fetal nervous system (Levitt, 1998). Nicotine exposure appeared to generate inconsistent changes in biochemical markers. The rapid and often paradoxical changes in particular markers strong suggest viewing specific nicotine effects with great caution because ontogenetic events, such as cell fate decisions, cell migration, neuronal polarity, or synapse formation have not been measured directly.

Nicotine shrinks the placenta’s blood vessels and hampers oxygenation and feeding of the fetus (Frydman, 1996). The development of the fetus depends upon the quantity of oxygen provided by the mother and this is affected by both nicotine and carbon monoxide that crosses the placenta. Many studies of effects of maternal smoking do not differentiate nicotine from the components of cigarette smoke.

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