The effects of antenatal smoking on lung function and respiratory symptoms in infants and children
Introduction
The association between parental smoking and increased respiratory illness in children was first reported by Colley in 1974 [1]. He noted that the incidence of pneumonia and bronchitis was 7.8% in those born to non smokers, 11.4% if one parent smoked and 17.6% if both parents smoked. More recently, Cook et al. [2] summarised the results of case controlled studies reported up to the late 1990s. They found that the odds ratio (OR) for lower respiratory illness in those under two years of age was 1.57 if either parent smoked, but 1.72 if the mother smoked. The increase in risk was lower in older children, such that the OR for asthma was 1.31 in children under the age of 6 years and 1.13 for older children [2]. Despite the reduction in risk with age it has been calculated that parental smoking accounts for approximately 20% of all asthma in childhood. Parental smoking also adversely affects lung function in school aged children [3].
The first suggestion that antenatal smoking exposure might be as, if not more, important than exposure to tobacco smoke after delivery was made by Taylor and Wadsworth in 1987 [4]. Analysing the British Births Survey data bank, they found that the incidences of admission to hospital for a lower respiratory tract infection in the firs t five years after birth and of episodes of bronchitis occurred in 2.3% and 14.1% respectively of infants born to non smokers and 3.1% and 18.2% of infants whose mothers smoked only after birth, but in 5.9% and 18.9% of infants whose mothers smoked only during pregnancy. Interest in the possible role of antenatal smoking in increasing respiratory problems in infants and children was further stimulated by the findings that reduced lung function in early infancy is associated with increased risks of admission to hospital with acute bronchiolitis and of episodes of wheezing in the first three years of life [5]. In addition, maternal smoking affects fetal growth in a dose dependent fashion. Smoking in excess of 20 cigarettes a day has been associated with a reduction in birth weight of approximately 250 g [6] i.e. similar to that observed in infants born to starving mothers in Northern Europe at the end of the last war.
There have been four approaches to explore the possible adverse effects of antenatal smoking exposure on respiratory outcome in infants and children. Firstly, the effect of nicotine on lung growth and function in animals has been studied. Secondly, population studies have been undertaken, with large enough numbers of mothers who smoked either only during pregnancy or after delivery to allow meaningful analysis of the differential effects of antenatal and postnatal smoking exposure. Thirdly, lung function in children has been measured in similarly large populations. Fourthly, lung function has been assessed in early infancy to limit or avoid the possible adverse effects of exposure to passive smoking postnatally.
Antenatal nicotine exposure results in pulmonary hypoplasia in a variety of animal models. In the rat model, antenatal nicotine exposure resulted in the offspring in a reduction in elastin synthesis [7] and fewer, but larger alveoli suggestive of emphysema. New born guinea pigs had fewer alveolar attachment points and increased airway responsiveness after antenatal nicotine exposure [8]. Exposure of the fetal monkey to nicotine infusion from day 26 to 134 of pregnancy resulted in the offspring having enlarged air spaces, reduction in alveolar surface area, altered airway morphology and function and lung hypoplasia [9]. Those effects were partially prevented by giving the pregnant monkeys vitamin C [10]. Prenatal nicotine exposure also produced in the newborn a breathing pattern suggestive of increased resistance and/or reduced compliance, that is, shallower and faster breaths than seen in controls. The animal data showing that antenatal nicotine exposure results in pulmonary hypoplasia could be explained by the suppressant effect of nicotine on fetal breathing. It is well documented that absence or reduction in fetal breathing leads to pulmonary hypoplasia.
A study including 10,683 infants born in Avon (United Kingdom), demonstrated that antenatal smoking exposure was associated with an odds ratio for infant wheezing in the first six months after birth of 1.30 (95% confidence intervals (CI) 1.09–1.56) [11]. A stronger effect (OR 2.2, 95% CI, 1.3–3.6) was noted in a study of 4089 children up to two years of age born in Sweden [12]. Although, the prospective Tucson Children’s Respiratory Study [13] failed to show a significant effect of antenatal smoking exposure on respiratory symptoms in children older than three years of age, other studies [14], [15] have found effects. In children aged 9 to 11 years, antenatal smoking exposure was associated with an OR of 1.6 (95% CI 1.1–2.5) for episodes of dyspnoea [14] and in a Californian study, involving 5762 school children up to the age of 15 years, ORs of 1.8 for diagnosed asthma and 3.1 for persistent wheezing were found [15]. In another study [16], an excess of respiratory symptoms in young adults aged 20 to 44 years was argued to be due to antenatal, rather than postnatal environmental, tobacco smoke exposure.
Gilliland et al. [17] measured lung function in 5933 Californian children aged 7 to 18 years , whose histories of antenatal and passive smoking were obtained retrospectively. They found that antenatal smoking exposure was associated with a reduction in airway function. The forced expiratory volume in one second/forced vital capacity (FEV1/FVC) was reduced by 1.3% and the mean expiratory flow from 25 to 75% of FVC (FEF25–75) by 1.3% in boys and by 4.6% in girls. The adverse effects on lung function were doubled in those children who had been exposed to antenatal smoking and had early, but not late onset asthma. They [17] did not show any significant adverse effects of either exposure to environmental tobacco smoke (ETS) alone or in association with antenatal smoke exposure. In a larger international study, spirometry data were obtained from children aged 6 to 12 years [18]. Satisfactory data were obtained on 22,712 children. The researchers [18] found that antenatal smoking exposure was associated in the children with a mean reduction of 0.9% in FEV1 and 5.1% reduction in FEF25 (the expiratory flow after 75% of the vital capacity has been expired). FEF25 is one of the best measures of small, rather than large, airway abnormality. Unlike, the findings of the Californian study [17], both current and first year ETS exposure were also associated with significant reductions in airway function, but the effects were smaller than those following antenatal smoking exposure [18]. It has also been suggested that there may be a link between in utero exposure and asthma in adult life [19].
There are now at least 22 reports examining the effects of in antenatal smoking exposure on lung function, using a variety of techniques, in children between the ages of two days and 93 weeks. These have been well reviewed by Stocks and Dezateux [20] (Table 1).
Section snippets
Tidal breathing assessment
The simplest assessment which has been used is the time to peak expiratory flow as a ratio of expiratory time (tPTEF;tE) during quiet tidal breathing; the lower the ratio, the worse the lung function. TtPTEF;tE is obtained using either devices which measure flow, for example thermisters or pneumotachographs, or by differentiating the volume signal provided by inductance plethysmography (Respitrace) to obtain flow. Of the eight groups [21], [22], [23], [24], [25], [26], [27], [28] who used this
Assessment of bronchial hyperreactivity
Four of the “Vmax.FRC” studies included measurements before and after a histamine challenge [26], [27], [33], [37], to determine whether antenatal smoking was associated with increased bronchial hyperreactivity. No such association was found. In one study, the measurements were also repeated after inhaled salbutamol [23]. The investigators found that only the controls showed a significant increase in Vmax.FRC after salbutamol inhalation, suggesting reduced rather than increased bronchial
Key guidelines
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Maternal smoking is associated with increased respiratory morbidity and lung function abnormalities in childhood.
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Antenatal smoking exposure has a greater adverse effect than postnatal smoking exposure.
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Women should, therefore, be encouraged to stop smoking before becoming pregnant.
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Prenatal nicotine exposure alters pulmonary function in newborn rhesus monkeys
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Vitamin C prevents the effects of prenatal nicotine on pulmonary function in newborn monkeys
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Pre-and postnatal parental smoking and wheeze in infancy: cross cultural differences. Avon Study of Parents and Children (ALSPAC) Study Team1 and European Longitudinal Study of Pregnancy and Childhood (ELSPAC) Co-ordinating Centre
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2012, Early Human DevelopmentCitation Excerpt :Hanrahan et al. [7] found that forced expiratory flow rates in infants born to smoking mothers were significantly lower than those found in infants whose mothers did not smoke during pregnancy. Moshammer et al. [8] and Milner et al. [9] demonstrated that antenatal smoking exposure exacerbated the number of respiratory symptoms and reduced lung function in infants and children. These studies have suggested that maternal smoking during pregnancy might impair in utero airway development, although the exact mechanisms underlying these changes remain to be determined.