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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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Related in: MedlinePlus

Animal studies of prenatal or prenatal + lactational exposure to nicotine and pancreatic end points. The primary grouping of studies is based on the type of pancreatic effect. Within the effect category, main findings were sorted based on whether treatment occurred only during prenatally (black) or prenatal + lactational (green). Abbreviations: GD, gestational day; PND, postnatal day; sc, subcutaneous; w, weeks. aValue was assumed or estimated based on data presented in publication. *Statistically significant effect at specified dose level as reported in publication.
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f6: Animal studies of prenatal or prenatal + lactational exposure to nicotine and pancreatic end points. The primary grouping of studies is based on the type of pancreatic effect. Within the effect category, main findings were sorted based on whether treatment occurred only during prenatally (black) or prenatal + lactational (green). Abbreviations: GD, gestational day; PND, postnatal day; sc, subcutaneous; w, weeks. aValue was assumed or estimated based on data presented in publication. *Statistically significant effect at specified dose level as reported in publication.

Mentions: Pancreatic effects. Changes in pancreatic weight, morphology, and function have been reported in animals that were treated with nicotine during gestation alone or during gestation and lactation (Bruin et al. 2007, 2008a, 2008b; Grove et al. 2001; Holloway et al. 2005; Somm et al. 2008) (Figure 6). These pancreatic effects include increased β-cell apoptosis and decreased β-cell mass in rodents (Bruin et al. 2007; Holloway et al. 2005; Somm et al. 2009). Other findings include decreased pancreatic weight in infant rhesus monkeys (Grove et al. 2001). As noted earlier, the treatment protocols used in the rodent studies result in maternal serum cotinine levels that are considered relevant to women who smoke or use nicotine patches as cigarette substitutes. The pancreatic effects are hypothesized to occur as a direct effect of nicotine binding to nicotinic acetylcholine receptors in the developing pancreas, leading to oxidative stress and mitochondrial damage and eventual β-cell apoptosis (Bruin et al. 2007, 2008a, 2008b, 2008c). Pancreatic tissue is considered to be especially susceptible to oxidative stress–mediated tissue damage due to low levels of antioxidant enzyme expression (Lenzen et al. 1996; Tiedge et al. 1997).


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 and pancreatic end points. The primary grouping of studies is based on the type of pancreatic effect. Within the effect category, main findings were sorted based on whether treatment occurred only during prenatally (black) or prenatal + lactational (green). Abbreviations: GD, gestational day; PND, postnatal day; sc, subcutaneous; w, weeks. aValue was assumed or estimated based on data presented in publication. *Statistically significant effect at specified dose level as reported in publication.
© Copyright Policy - public-domain
Related In: Results  -  Collection

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

f6: Animal studies of prenatal or prenatal + lactational exposure to nicotine and pancreatic end points. The primary grouping of studies is based on the type of pancreatic effect. Within the effect category, main findings were sorted based on whether treatment occurred only during prenatally (black) or prenatal + lactational (green). Abbreviations: GD, gestational day; PND, postnatal day; sc, subcutaneous; w, weeks. aValue was assumed or estimated based on data presented in publication. *Statistically significant effect at specified dose level as reported in publication.
Mentions: Pancreatic effects. Changes in pancreatic weight, morphology, and function have been reported in animals that were treated with nicotine during gestation alone or during gestation and lactation (Bruin et al. 2007, 2008a, 2008b; Grove et al. 2001; Holloway et al. 2005; Somm et al. 2008) (Figure 6). These pancreatic effects include increased β-cell apoptosis and decreased β-cell mass in rodents (Bruin et al. 2007; Holloway et al. 2005; Somm et al. 2009). Other findings include decreased pancreatic weight in infant rhesus monkeys (Grove et al. 2001). As noted earlier, the treatment protocols used in the rodent studies result in maternal serum cotinine levels that are considered relevant to women who smoke or use nicotine patches as cigarette substitutes. The pancreatic effects are hypothesized to occur as a direct effect of nicotine binding to nicotinic acetylcholine receptors in the developing pancreas, leading to oxidative stress and mitochondrial damage and eventual β-cell apoptosis (Bruin et al. 2007, 2008a, 2008b, 2008c). Pancreatic tissue is considered to be especially susceptible to oxidative stress–mediated tissue damage due to low levels of antioxidant enzyme expression (Lenzen et al. 1996; Tiedge et al. 1997).

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