Читать книгу Clinical Obesity in Adults and Children - Группа авторов - Страница 54

Recent epidemiologic and experimental data have elucidated the role of environmental chemicals on the risk for obesity and related metabolic diseases. These organic and inorganic pollutants of human and natural origin have been termed “environmental obesogens” or “metabolism‐disrupting chemicals.”

Maternal smoking during pregnancy is one well‐characterized example of an environmental exposure that appears to persistently influence offspring body weight. While prenatal smoking causes reduced fetal growth, analyses from dozens of studies have consistently found associations with later offspring obesity. One meta‐analysis of 14 studies estimated that maternal smoking during pregnancy conferred 50% increased odds (adjusted OR 1.50; 95% CI: 1.36, 1.65) for offspring obesity across an age range of 3–33 years [64]. Adjustment for factors related to social and economic position did not markedly affect estimates, and publication bias did not appear to explain the finding, but residual confounding is still possible. A more recent independent patient data meta‐analysis included 26 identified studies, including a total of 238,340 mother–child‐pairs [65]. A linear positive association was observed between the number of cigarettes smoked and offspring overweight for up to 15 cigarettes per day with an OR increased per cigarette of 1.03 (95% CI: 1.02, 1.03); the OR flattened with higher cigarette use (Fig. 3.4) [65].

A similar pattern of association as for maternal prenatal smoking, with both lower fetal growth and rapid postnatal weight gain, is seen with traffic‐related air pollution [66], supporting the smoking‐obesity relationship by analogy. Further, animal studies have observed similar findings; one in rats indicated that nicotine administration in the puerperal period led to higher adiposity through early adulthood despite no differences in maternal weight gain or size at birth [67]. Nicotine‐exposed offspring had phenotypes similar to those associated with human obesity, including higher blood pressure and impaired glucose metabolism [68,69]. Interestingly, limited data suggest that these effects may be transgenerational – F2 offspring of F1 dams exposed to nicotine during their own intrauterine development had higher blood pressure, higher fasting insulin, and greater insulin response to a glucose load [70].

Figure 3.4 Association of maternal number of cigarettes smoked per day and risk of offspring overweight (including obesity), and obesity only stratified by sex. From Albers et al. [65] ©Nature Publishing Group.

Reproduced with permission. ____ = OR for the association between maternal number of cigarettes and offspring overweight/obesity; _ _ _ = 95% CI of the OR; the vertical dashes above the x axis indicate the density of the observations underlying the model.

Per‐ and polyfluorinated substances (PFAS) are another class of chemicals that have been studied in relation to programming of obesity [71]. PFAS are man‐made fluorinated chemicals used in stain‐resistant and water‐resistant coatings for textiles, non‐stick cookware, food containers, floor polish, fire‐fighting foam, and industrial surfactants. The strong carbon‐fluorine chemical bond makes PFAS extremely resistant to thermal, chemical, and biological degradation, which results in bioaccumulation and persistence in human tissues for years. Four PFAS – perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) – are almost universally detected in the serum of pregnant women, neonates, and children worldwide, which indicates that exposure is ubiquitous. Furthermore, these chemicals can cross the placenta [71]. A substantial body of evidence exists suggesting that prenatal exposure to PFAS could adversely affect fetal growth. In a systematic review and meta‐analysis, greater prenatal PFOA exposure was associated with a 19 g decrement in birth weight (95% CI: −8 to −30 g) [72]. These results in humans are similar to those observed in rodent studies [73]. Some human observational studies indicate an association of higher circulating concentrations of certain PFAS with weight gain or obesity in children and adults [74,75]. Additionally, some prospective cohort data show that prenatal PFAS exposure is associated with alterations in infant or child growth, increased adiposity during childhood and adulthood [76–78], although others have not shown associations [79,80].