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Evaluation of the association between maternal smoking, childhood obesity, and metabolic disorders: a national toxicology program workshop review.

Behl M, Rao D, Aagaard K, Davidson TL, Levin ED, Slotkin TA, Srinivasan S, Wallinga D, White MF, Walker VR, Thayer KA, Holloway AC - Environ. Health Perspect. (2012)

Bottom Line: This conclusion is supported by findings from laboratory animals exposed to nicotine during development.The existing literature on human exposures does not support an association between maternal smoking during pregnancy and type 1 diabetes in offspring.Too few human studies have assessed outcomes related to type 2 diabetes or metabolic syndrome to reach conclusions based on patterns of findings.

View Article: PubMed Central - PubMed

Affiliation: Kelly Government Solutions, Research Triangle Park, North Carolina, USA.

ABSTRACT

Background: An emerging literature suggests that environmental chemicals may play a role in the development of childhood obesity and metabolic disorders, especially when exposure occurs early in life.

Objective: Here we assess the association between these health outcomes and exposure to maternal smoking during pregnancy as part of a broader effort to develop a research agenda to better understand the role of environmental chemicals as potential risk factors for obesity and metabolic disorders.

Methods: PubMed was searched up to 8 March 2012 for epidemiological and experimental animal studies related to maternal smoking or nicotine exposure during pregnancy and childhood obesity or metabolic disorders at any age. A total of 101 studies-83 in humans and 18 in animals-were identified as the primary literature.

Discussion: Current epidemiological data support a positive association between maternal smoking and increased risk of obesity or overweight in offspring. The data strongly suggest a causal relation, although the possibility that the association is attributable to unmeasured residual confounding cannot be completely ruled out. This conclusion is supported by findings from laboratory animals exposed to nicotine during development. The existing literature on human exposures does not support an association between maternal smoking during pregnancy and type 1 diabetes in offspring. Too few human studies have assessed outcomes related to type 2 diabetes or metabolic syndrome to reach conclusions based on patterns of findings. There may be a number of mechanistic pathways important for the development of aberrant metabolic outcomes following perinatal exposure to cigarette smoke, which remain largely unexplored.

Conclusions: From a toxicological perspective, the linkages between maternal smoking during pregnancy and childhood overweight/obesity provide proof-of-concept of how early-life exposure to an environmental toxicant can be a risk factor for childhood obesity.

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Animal studies of prenatal or prenatal + lactational exposure to nicotine or cigarette smoking and adiposity-related end points. The primary grouping of studies is based on whether the end point was related to adiposity or body weight. Within each end point category, main findings are grouped by whether the exposure was to nicotine or cigarette smoke. Within each exposure category, main findings were sorted based on specific end point (A to Z). Abbreviations: AUC, area under the curve; BAT, brown adipose tissue; BW, body weight; eWAT, epididymal white adipose tissue; GD, gestational day; inhal, inhalation; inj, injection; MCS, mainstream cigarette smoke; PND, postnatal day; sc, subcutaneous; w, weeks. aValue was assumed or estimated based on data presented in publication. bIn Ng et al. (2009) animals were exposed via whole body inhalation to mainstream cigarette smoke (smoke inhaled by an active smoker) at a particle concentration of 15 mg/m3; in Chen et al. (2011) dams were exposed to exposed to cigarette smoke via a perspex chamber for 30 min 5 days/week (2 cigarettes/day, nicotine ≤ 1.2 mg, carbon monoxide ≤ 15 mg). cDose level summarized in graph. *Statistically significant effect at specified dose level as reported in publication. In some cases statistical significance of percent control response differs from author’s interpretation (e.g., author’s statistical analysis considered multiple comparisons, i.e., analysis of variance).
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f4: Animal studies of prenatal or prenatal + lactational exposure to nicotine or cigarette smoking and adiposity-related end points. The primary grouping of studies is based on whether the end point was related to adiposity or body weight. Within each end point category, main findings are grouped by whether the exposure was to nicotine or cigarette smoke. Within each exposure category, main findings were sorted based on specific end point (A to Z). Abbreviations: AUC, area under the curve; BAT, brown adipose tissue; BW, body weight; eWAT, epididymal white adipose tissue; GD, gestational day; inhal, inhalation; inj, injection; MCS, mainstream cigarette smoke; PND, postnatal day; sc, subcutaneous; w, weeks. aValue was assumed or estimated based on data presented in publication. bIn Ng et al. (2009) animals were exposed via whole body inhalation to mainstream cigarette smoke (smoke inhaled by an active smoker) at a particle concentration of 15 mg/m3; in Chen et al. (2011) dams were exposed to exposed to cigarette smoke via a perspex chamber for 30 min 5 days/week (2 cigarettes/day, nicotine ≤ 1.2 mg, carbon monoxide ≤ 15 mg). cDose level summarized in graph. *Statistically significant effect at specified dose level as reported in publication. In some cases statistical significance of percent control response differs from author’s interpretation (e.g., author’s statistical analysis considered multiple comparisons, i.e., analysis of variance).

Mentions: Body weight and adiposity. Most animal studies have reported that rats exposed to nicotine during perinatal development tended to have a higher body weight and more fat mass compared with controls (Figure 4), with the effect typically first apparent at weaning and persisting through adulthood (Gao et al. 2005; Newman et al. 1999; Oliveira et al. 2009, 2010; Somm et al. 2008). However, there are exceptions to this pattern (Gao et al. 2008; Holloway et al. 2007), which do not appear to be attributable to strain differences, dosing, or the timing of exposure. Food intake was unaffected in studies that evaluated it as an end point (Oliveira et al. 2009, 2010; Somm et al. 2008). The potential interaction between perinatal nicotine exposure and postnatal diet has been explored in only one study, which examined whether a high-fat diet (HFD) postnatally would exacerbate the weight gain in nicotine-exposed animals (Somm et al. 2008). Although the nicotine-treated animals that were fed an HFD did not consume more kilocalories than controls fed the same diet, they were heavier. The nicotine-treated animals were less physically active than control animals that consumed the same diet. There were no differences in oxygen consumption or respiratory exchange ratio, suggesting that increased weight gain in HFD animals with the same caloric intake was perhaps attributable to the dysregulation of adipose tissue development, thereby leading to higher amounts of fat storage.


Evaluation of the association between maternal smoking, childhood obesity, and metabolic disorders: a national toxicology program workshop review.

Behl M, Rao D, Aagaard K, Davidson TL, Levin ED, Slotkin TA, Srinivasan S, Wallinga D, White MF, Walker VR, Thayer KA, Holloway AC - Environ. Health Perspect. (2012)

Animal studies of prenatal or prenatal + lactational exposure to nicotine or cigarette smoking and adiposity-related end points. The primary grouping of studies is based on whether the end point was related to adiposity or body weight. Within each end point category, main findings are grouped by whether the exposure was to nicotine or cigarette smoke. Within each exposure category, main findings were sorted based on specific end point (A to Z). Abbreviations: AUC, area under the curve; BAT, brown adipose tissue; BW, body weight; eWAT, epididymal white adipose tissue; GD, gestational day; inhal, inhalation; inj, injection; MCS, mainstream cigarette smoke; PND, postnatal day; sc, subcutaneous; w, weeks. aValue was assumed or estimated based on data presented in publication. bIn Ng et al. (2009) animals were exposed via whole body inhalation to mainstream cigarette smoke (smoke inhaled by an active smoker) at a particle concentration of 15 mg/m3; in Chen et al. (2011) dams were exposed to exposed to cigarette smoke via a perspex chamber for 30 min 5 days/week (2 cigarettes/day, nicotine ≤ 1.2 mg, carbon monoxide ≤ 15 mg). cDose level summarized in graph. *Statistically significant effect at specified dose level as reported in publication. In some cases statistical significance of percent control response differs from author’s interpretation (e.g., author’s statistical analysis considered multiple comparisons, i.e., analysis of variance).
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3569686&req=5

f4: Animal studies of prenatal or prenatal + lactational exposure to nicotine or cigarette smoking and adiposity-related end points. The primary grouping of studies is based on whether the end point was related to adiposity or body weight. Within each end point category, main findings are grouped by whether the exposure was to nicotine or cigarette smoke. Within each exposure category, main findings were sorted based on specific end point (A to Z). Abbreviations: AUC, area under the curve; BAT, brown adipose tissue; BW, body weight; eWAT, epididymal white adipose tissue; GD, gestational day; inhal, inhalation; inj, injection; MCS, mainstream cigarette smoke; PND, postnatal day; sc, subcutaneous; w, weeks. aValue was assumed or estimated based on data presented in publication. bIn Ng et al. (2009) animals were exposed via whole body inhalation to mainstream cigarette smoke (smoke inhaled by an active smoker) at a particle concentration of 15 mg/m3; in Chen et al. (2011) dams were exposed to exposed to cigarette smoke via a perspex chamber for 30 min 5 days/week (2 cigarettes/day, nicotine ≤ 1.2 mg, carbon monoxide ≤ 15 mg). cDose level summarized in graph. *Statistically significant effect at specified dose level as reported in publication. In some cases statistical significance of percent control response differs from author’s interpretation (e.g., author’s statistical analysis considered multiple comparisons, i.e., analysis of variance).
Mentions: Body weight and adiposity. Most animal studies have reported that rats exposed to nicotine during perinatal development tended to have a higher body weight and more fat mass compared with controls (Figure 4), with the effect typically first apparent at weaning and persisting through adulthood (Gao et al. 2005; Newman et al. 1999; Oliveira et al. 2009, 2010; Somm et al. 2008). However, there are exceptions to this pattern (Gao et al. 2008; Holloway et al. 2007), which do not appear to be attributable to strain differences, dosing, or the timing of exposure. Food intake was unaffected in studies that evaluated it as an end point (Oliveira et al. 2009, 2010; Somm et al. 2008). The potential interaction between perinatal nicotine exposure and postnatal diet has been explored in only one study, which examined whether a high-fat diet (HFD) postnatally would exacerbate the weight gain in nicotine-exposed animals (Somm et al. 2008). Although the nicotine-treated animals that were fed an HFD did not consume more kilocalories than controls fed the same diet, they were heavier. The nicotine-treated animals were less physically active than control animals that consumed the same diet. There were no differences in oxygen consumption or respiratory exchange ratio, suggesting that increased weight gain in HFD animals with the same caloric intake was perhaps attributable to the dysregulation of adipose tissue development, thereby leading to higher amounts of fat storage.

Bottom Line: This conclusion is supported by findings from laboratory animals exposed to nicotine during development.The existing literature on human exposures does not support an association between maternal smoking during pregnancy and type 1 diabetes in offspring.Too few human studies have assessed outcomes related to type 2 diabetes or metabolic syndrome to reach conclusions based on patterns of findings.

View Article: PubMed Central - PubMed

Affiliation: Kelly Government Solutions, Research Triangle Park, North Carolina, USA.

ABSTRACT

Background: An emerging literature suggests that environmental chemicals may play a role in the development of childhood obesity and metabolic disorders, especially when exposure occurs early in life.

Objective: Here we assess the association between these health outcomes and exposure to maternal smoking during pregnancy as part of a broader effort to develop a research agenda to better understand the role of environmental chemicals as potential risk factors for obesity and metabolic disorders.

Methods: PubMed was searched up to 8 March 2012 for epidemiological and experimental animal studies related to maternal smoking or nicotine exposure during pregnancy and childhood obesity or metabolic disorders at any age. A total of 101 studies-83 in humans and 18 in animals-were identified as the primary literature.

Discussion: Current epidemiological data support a positive association between maternal smoking and increased risk of obesity or overweight in offspring. The data strongly suggest a causal relation, although the possibility that the association is attributable to unmeasured residual confounding cannot be completely ruled out. This conclusion is supported by findings from laboratory animals exposed to nicotine during development. The existing literature on human exposures does not support an association between maternal smoking during pregnancy and type 1 diabetes in offspring. Too few human studies have assessed outcomes related to type 2 diabetes or metabolic syndrome to reach conclusions based on patterns of findings. There may be a number of mechanistic pathways important for the development of aberrant metabolic outcomes following perinatal exposure to cigarette smoke, which remain largely unexplored.

Conclusions: From a toxicological perspective, the linkages between maternal smoking during pregnancy and childhood overweight/obesity provide proof-of-concept of how early-life exposure to an environmental toxicant can be a risk factor for childhood obesity.

Show MeSH
Related in: MedlinePlus