Limits...
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.

Show MeSH

Related in: MedlinePlus

Animal studies of prenatal or prenatal + lactational exposure to nicotine and glucose homeostasis-related end points. The primary grouping of studies is based on whether the end point was based on glucose or insulin. Within the end point category, main findings were sorted based on specific end point (A to Z). Abbreviations: AUC, area under the curve; GD, gestational day; ipGTT, intraperitoneal glucose tolerance test; inj, injection; OGTT, oral glucose tolerance test; 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. **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
getmorefigures.php?uid=PMC3569686&req=5

f5: Animal studies of prenatal or prenatal + lactational exposure to nicotine and glucose homeostasis-related end points. The primary grouping of studies is based on whether the end point was based on glucose or insulin. Within the end point category, main findings were sorted based on specific end point (A to Z). Abbreviations: AUC, area under the curve; GD, gestational day; ipGTT, intraperitoneal glucose tolerance test; inj, injection; OGTT, oral glucose tolerance test; 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. **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: Glucose homeostasis and insulin sensitivity. There are several reports in the literature on impaired glucose homeostasis in the male offspring of rats that were treated with nicotine during gestation (Somm et al. 2008), lactation (Oliveira et al. 2010), or gestation and lactation (Bruin et al. 2007, 2008c; Holloway et al. 2005) (Figure 5). Administered doses ranged from 1 to 6 mg/kg-day delivered to the mother either via an osmotic minipump implanted under the skin or via daily subcutaneous injections. These dosing protocols resulted in maternal serum cotinine levels considered relevant to women who smoke or use nicotine patches as cigarette substitutes (Bruin et al. 2007; Hackman et al. 1999; Somm et al. 2009). The most consistent findings from these studies were indications of insulin resistance in adulthood based on increased insulin area under the curve (AUC) following an oral or intraperitoneal glucose challenge (Bruin et al. 2007, 2008c; Holloway et al. 2005; Somm et al. 2008) or on an increased insulin resistance index (Oliveira et al. 2010). These effects were seen across studies despite the use of different doses of nicotine, different administration protocols, and different windows of developmental exposure within the perinatal period (i.e., gestation and/or lactation). A study by Holloway et al. (2007), reported increased insulin resistance in 15-week-old F2 generation male offspring of dams that were treated with nicotine only during gestation and lactation compared with untreated controls. Impairments in glucose tolerance also have been reported following nicotine exposure (Bruin et al. 2007, 2008c; Holloway et al. 2005; Somm et al. 2008). Effects on fasting insulin levels have been less consistent, with some studies showing no effect (Bruin et al. 2007; Somm et al. 2008) and others reporting increased levels in adult rodents compared with untreated controls (Holloway et al. 2005, 2007; Oliveira et al. 2010). At low dose levels (1 mg/kg-day) permanent changes in glucose homeostasis were observed only when exposure occurred during both fetal and neonatal life (i.e., pregnancy and lactation); however, when dams were exposed to 3 mg/kg-day (Somm et al. 2008) or 6 mg/kg-day (Oliveira et al. 2010), then either fetal or lactational exposure was sufficient to affect glycemic control. Importantly, no effects on glucose homeostasis were observed in Wistar rats (Jose et al. 2009) or in a series of studies (Jose et al. 2009; Swislocki 2003; Swislocki and Fakiri 2008; Swislocki et al. 1997) in Sprague-Dawley rats treated with nicotine after weaning. Taken together, these data suggest that cigarette smoke or nicotine exposure during gestation and lactation is the critical window of exposure.


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 glucose homeostasis-related end points. The primary grouping of studies is based on whether the end point was based on glucose or insulin. Within the end point category, main findings were sorted based on specific end point (A to Z). Abbreviations: AUC, area under the curve; GD, gestational day; ipGTT, intraperitoneal glucose tolerance test; inj, injection; OGTT, oral glucose tolerance test; 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. **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

f5: Animal studies of prenatal or prenatal + lactational exposure to nicotine and glucose homeostasis-related end points. The primary grouping of studies is based on whether the end point was based on glucose or insulin. Within the end point category, main findings were sorted based on specific end point (A to Z). Abbreviations: AUC, area under the curve; GD, gestational day; ipGTT, intraperitoneal glucose tolerance test; inj, injection; OGTT, oral glucose tolerance test; 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. **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: Glucose homeostasis and insulin sensitivity. There are several reports in the literature on impaired glucose homeostasis in the male offspring of rats that were treated with nicotine during gestation (Somm et al. 2008), lactation (Oliveira et al. 2010), or gestation and lactation (Bruin et al. 2007, 2008c; Holloway et al. 2005) (Figure 5). Administered doses ranged from 1 to 6 mg/kg-day delivered to the mother either via an osmotic minipump implanted under the skin or via daily subcutaneous injections. These dosing protocols resulted in maternal serum cotinine levels considered relevant to women who smoke or use nicotine patches as cigarette substitutes (Bruin et al. 2007; Hackman et al. 1999; Somm et al. 2009). The most consistent findings from these studies were indications of insulin resistance in adulthood based on increased insulin area under the curve (AUC) following an oral or intraperitoneal glucose challenge (Bruin et al. 2007, 2008c; Holloway et al. 2005; Somm et al. 2008) or on an increased insulin resistance index (Oliveira et al. 2010). These effects were seen across studies despite the use of different doses of nicotine, different administration protocols, and different windows of developmental exposure within the perinatal period (i.e., gestation and/or lactation). A study by Holloway et al. (2007), reported increased insulin resistance in 15-week-old F2 generation male offspring of dams that were treated with nicotine only during gestation and lactation compared with untreated controls. Impairments in glucose tolerance also have been reported following nicotine exposure (Bruin et al. 2007, 2008c; Holloway et al. 2005; Somm et al. 2008). Effects on fasting insulin levels have been less consistent, with some studies showing no effect (Bruin et al. 2007; Somm et al. 2008) and others reporting increased levels in adult rodents compared with untreated controls (Holloway et al. 2005, 2007; Oliveira et al. 2010). At low dose levels (1 mg/kg-day) permanent changes in glucose homeostasis were observed only when exposure occurred during both fetal and neonatal life (i.e., pregnancy and lactation); however, when dams were exposed to 3 mg/kg-day (Somm et al. 2008) or 6 mg/kg-day (Oliveira et al. 2010), then either fetal or lactational exposure was sufficient to affect glycemic control. Importantly, no effects on glucose homeostasis were observed in Wistar rats (Jose et al. 2009) or in a series of studies (Jose et al. 2009; Swislocki 2003; Swislocki and Fakiri 2008; Swislocki et al. 1997) in Sprague-Dawley rats treated with nicotine after weaning. Taken together, these data suggest that cigarette smoke or nicotine exposure during gestation and lactation is the critical window of exposure.

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