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

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.

A study of the consequences of early gestational ethanol and/or nicotine exposure in the mouse

“…Children whose mothers smoked during their pregnancies are at increased risk of reduced birth weight (Butler et al, 1972;Lieberman et al, 1994;Ward et al, 2007), cognitive impairments (Julvez et al, 2007), behavioural problems (Weitzman et al, 1992), asthma (Jaakkola and Gissler, 2004), altered immune function (Noakes et al, 2006), aberrant metabolic profiles (reviewed in Behl et al, 2013), offspring nicotine dependence (Buka et al, 2003), spontaneous abortion (Kline et al, 1977), stillbirth (reviewed in Marufu et al, 2015), and Sudden Infant Death Syndrome (Anderson et al, 2005).…”

“…At 17.5 dpc, there was no difference in fetal weight ( Exposure to cigarette smoke or nicotine during gestation has been associated with increased risk of later obesity in various animal studies (reviewed in Behl et al, 2013). To investigate whether the nicotine-exposed and dual ethanol/nicotine-exposed mice in our models were at increased risk of obesity, a new cohort of mice (cohort D) were generated from which offspring were weaned onto either a high-fat diet (23.50% total fat, Specialty Feeds SF04-001), or a low-fat diet (5.30 % total fat, Specialty Feeds SF13-081) and body weight assayed at regular intervals until 24 weeks of age.…”

“…Furthermore, both maternal ethanol consumption (Kaminen-Ahola et al, 2010a) and maternal smoking (Delpisheh et al, 2008) have also been reported to result in microcephaly. Despite maternal tobacco smoking during gestation being associated with reduced birth weight (Butler et al, 1972;Lieberman et al, 1994;Ward et al, 2007), these exposures have also been associated with increased adiposity later in life in both humans and experimental animal studies (recently extensively reviewed in Behl et al, 2013). Many of the experimental animal studies which have previously reported these associations used models in which the exposures occurred either in late gestation (Wang et al, 2008), for the majority of gestation (Rowell and Clark, 1982;Somm et al, 2008;Wang et al, 2009), or lactation as well as gestation (Gao et al, 2005;Holloway et al, 2005).…”

Adverse effects of perinatal nicotine exposure on reproductive outcomes

“…Nicotine also accumulates in breast milk, placental tissue, amniotic fluid, and fetal blood (Luck & Nau 1984, Dahlstrom et al 1990), leading to significant fetal and neonatal exposure. Research in animal models have clearly demonstrated that fetal and neonatal exposure to nicotine results in a wide range of short-and long-term health consequences for the offspring, including deficits in postnatal reproductive function (Bruin et al 2010, Behl et al 2013.…”

“…For example, obesity and type 2 diabetes mellitus (DM) have been strongly associated with detrimental reproductive outcomes, including decreased fertility, impaired sex hormone levels, and reduced sperm quality in human and animal studies (Jangir & Jain 2014, Kawwass et al 2015. Interestingly, prenatal nicotine exposure leads to an increased risk of postnatal obesity and DM in animal studies (Behl et al 2013), raising the possibility that nicotine-induced obesity and/or DM may contribute to the reproductive health deficits in nicotineexposed offspring. However, it is important to note that currently none of the randomized controlled trials of NRT use during pregnancy have investigated the effects of nicotine exposure during fetal life on either metabolic or reproductive outcomes in the offspring.…”