Triadas Aeropuerto Matecaña (128)

Carbon monoxide and nicotine are two o f the major components in cigarette smoke and the adverse effects of these toxins on the fetus have been studied by a number of authors (Mochizuki et al. 1984; Koren, 1995; Aubard Y and Magne I, 2000).

Carbon monoxide has an affinity for haemoglobin 250 times greater than oxygen. It readily dissolves in the plasma thereby perturbing oxygen exchange in the tissues (Aubard Y and Magne I, 2000). The dissolved carbon monoxide in maternal plasma crosses the placental barrier by passive diffusion and as fetal haemoglobin has a higher affinity for carbon monoxide than adult haemoglobin, the unborn child is exposed to higher risk from this gas than the mother. In pregnant smokers, the concentration o f carboxyhaemoglobin in the blood is about 3%, while the level in the blood o f a newborn infant o f a non-smoking mother is 2%, which increases to 6 - 9% if the mother is a smoker (Aubard Y and Magne I, 2000). Thus chronic exposure to carbon monoxide during pregnancy and post delivery may produce significant growth restriction as a result of the adverse effects on oxygenation by carboxyhaemoglobin (Lambers and Clark, 1996).

Nicotine is a weak base, and as fetal blood is more acidic than maternal blood, the alkaloid is more ionised in the fetal circulation, creating a driving force o f movement from mother to fetus (Koren, 1995). Thus, nicotine readily gains access to the fetal compartment via the placenta, with fetal concentrations generally 15% higher than maternal levels (Koren, 1995; Lambers and Clark, 1996). In a recent study, Jauniaux et al. reported that cotinine, a derivative o f nicotine, was found in coelomic and amniotic fluid as early as seven weeks’ gestation in both active and passive smokers (Jauniaux et al. 1999). In addition, cotinine levels from newborn infants’ first urine were shown to be significantly higher than those not exposed to in-utero smoke (Etzel et al. 1985) and were comparable with levels found in active adult smokers (Hoo et al. 1998). Thus, throughout gestation, the fetus is exposed to increasing concentrations o f nicotine through maternal blood and via gastrointestinal and skin absorption o f nicotine from the amniotic fluid (Koren, 1995). The physiological effects o f nicotine on fetal growth appear to be primarily vasoconstrictive effects on the uterine and potentially the umbilical artery, hence causing abnormal placental development (Genbacev et al. 2000) and impaired placental function through reduction in placental blood flow (Lambers and Clark, 1996).

The potential effects o f smoking during pregnancy on lung and airway development may include structural alterations, interference with ventilatory response to hypoxia and alterations to the developing immune system (Collins et al. 1985; Milerad et al. 1995; Ji et al. 1998; Wisborg et al. 1999). Animal studies have shown that maternal cigarette smoke exposure during pregnancy is characterised by fetal growth retardation and lung hypoplasia with decreased airspaces and a reduction in the length o f elastin in the saccule walls (Collins et al. 1985; Sekhon et al. 1999). Maritz and Thomas reported alveolar fenestrations, blebbing and rupturing o f the blood-air barrier in the alveolar epithelial cells o f smoke exposed neonatal rats (Maritz et al. 1993). Sekhon et al. reported that prenatal nicotine increases a? nicotinic receptor expression in the developing lung o f rhesus monkeys and that the increased collagen deposition around airways was stimulated by the interaction o f nicotine with the a? nicotinic cholinergic receptor-bearing fibroblasts (Sekhon et al.

1999). In addition, absolute and specific (per lOOg body weight) lung weight were significantly lower (16% and 14%) respectively) in the nicotine-exposed group compared to the controls, suggesting that prenatal nicotine exposure decreases lung

growth. Peak tidal expiratory flow and FEV0.2 was significantly lower, but pulmonary resistance and specific pulmonary resistance (corrected for lung volume) were significantly increased in monkeys exposed to prenatal nicotine (Sekhon et al. 2001). Furthermore, maternal exposure to environmental smoke was found to alter the normal development o f the Clara cell in the fetal rat lung and to increase the size of neuroepithelial bodies in the fetal lung (Chen et al. 1987; Ji et al. 1998). Thus it has been suggested that these changes may alter airway defence in early life and contribute to the pathophysiology of sudden infant death syndrome (SIDS) (Nicholl and O'Cathain, 1992; Cutz et al. 1996).

Milerad and colleagues also suggested that nicotine alters peripheral chemoreceptor oxygen sensitivity and affects central processing o f the chemoreceptor input. Hence they hypothesised that the observed associations between parental smoking and SIDS is mediated by adverse effects o f nicotine on central control of breathing (Milerad et al. 1995). Similar findings were reported by Lewis and Bosque who observed that infants o f mothers who smoked during pregnancy have deficient hypoxic awakening responses, which may contribute to the increased risk o f SIDS in such infants (Lewis and Bosque, 1995). Recently, Hubbard et al. suggested that infants exposed to in- utero smoke have an altered arousal response (Hubbard et al. 2000) but Poole and colleagues did not find an independent effect o f maternal smoking on respiratory control (Poole et al. 2000).

The association o f maternal smoking during pregnancy with increased childhood respiratory illnesses has been well documented (Strachan and Cook, 1997; Strachan and Cook, 1998). Infant lung function studies have shown changes in the pattern of breathing and diminished airflow in infants whose mothers smoked in pregnancy (Hanrahan et al. 1992; Brown et al. 1995). Martinez et al. also reported an increased incidence o f asthma in children o f smoking mothers and observed that children o f lower socio-economic status may be at considerable risk o f developing asthma if their mothers smoked more than 10 cigarettes per day (Martinez et al. 1992). Thus it has been hypothesised that maternal smoking in pregnancy may cause a reduction in airway size as well as alterations in the growth and maturation of the mechanical properties o f the respiratory system in the newborn. In a study o f preterm infants, these changes are evident at least seven weeks prior to their expected

date o f delivery, suggesting that the adverse effects o f prenatal exposure to tobacco are not limited to the last weeks o f pregnancy (Hoo et al. 1998). Furthermore, among term infants, specific airway conductance during end expiration was significantly diminished at one year of age in those exposed to maternal smoking (Dezateux et al. 2000).