Evaluation of the Association between Maternal Smoking, Childhood Obesity, and Metabolic Disorders: A National Toxicology Program Workshop Review

Mamta Behl,^1,2 Deepa Rao,³ Kjersti Aagaard,⁴ Terry L. Davidson,⁵ Edward D. Levin,⁶ Theodore A. Slotkin,⁷ Supriya Srinivasan,⁸ David Wallinga,⁹ Morris F. White,¹⁰ Vickie R. Walker,¹¹ Kristina A. Thayer,¹¹ and Alison C. Holloway¹²


¹Kelly Government Solutions, Research Triangle Park, North Carolina, USA; ²Division of National Toxicology Program, National Institute of Environmental Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina, USA; ³Integrated Laboratory Systems Inc., Research Triangle Park, North Carolina, USA; ⁴Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas, USA; ⁵Department of Psychological Sciences, Purdue University, West Lafayette, Indiana, USA; ⁶Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA; ⁷Department of Pharmacology and Cancer Biology, Duke University, Durham, North Carolina, USA; ⁸Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA; ⁹Food and Health Program, Institute for Agriculture and Trade Policy, Minneapolis, Minnesota, USA; ¹⁰Howard Hughes Medical Institute, Division of Endocrinology, Children’s Hospital Boston, Boston, Massachusetts, USA;¹¹Division of National Toxicology Program, Office of Health Assessment and Translation, NIEHS, NIH, DHHS, Research Triangle Park, North Carolina, USA; ¹²Reproductive Biology Division, Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada


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.


Key words: animal, chemically induced/epidemiology, diabetes, environmental epidemiology, glucose, insulin, maternal smoking toxicity, metabolism, nicotine toxicity, obesity. 


Environ Health Perspect 121:170–180 (2013). http://dx.doi.org/10.1289/ehp.1205404 [Online 11 December 2012]


Address correspondence to A. Holloway, Department of Obstetrics and Gynecology, McMaster University, HSC 3N52, 1280 Main St. West, Hamilton, ON, Canada L8S 4K1. Telephone: (905) 525-9140 ext 22130. E-mail: hollow@mcmaster.ca


Supplemental Material is available online (http://dx.doi.org/10.1289/ehp.1205404).


This review is based on deliberations that occurred at an 11–13 January 2011 workshop sponsored by the National Institute of Environmental Health Sciences/National Toxicology Program (NIEHS/NTP), U.S. Environmental Protection Agency (EPA), and the Food and Drug Administration National Center for Toxicological Research (FDA/NCTR) (http://ntp.niehs.nih.gov/go/36433). 


We gratefully acknowledge the contributions of S. Holmgren (NIEHS) for developing the literature search strategy, and J. Stevens (GLP Support Services) and K. Taylor (NTP/NIEHS) for assistance in preparing the background literature review document. We also acknowledge the invaluable assistance of the staff at the U.S. EPA National Center for Computation Toxicology (NCCT), particularly D. Reif, D. Dix, K. Houck, and R. Judson. We also thank J. Heindel and M. Longnecker (NIEHS) for their excellent review of the manuscript.


This article is the work product of a group of employees of the NIEHS, NIH; however, the statements, opinions, or conclusions contained therein do not necessarily represent the statements, opinions or conclusions of NIEHS, NIH, or the U.S. government.


M. Behl is employed by Kelly Government Solutions; D. Rao is employed by Integrated Laboratory Systems Inc.; D. Wallinga is employed by Food and Health Program, Institute for Agriculture and Trade Policy. The authors declare they have no actual or potential competing financial interests.


Received 30 April 2012; Accepted 4 December 2012; Online 11 December 2012.