Prenatal cocaine exposure and childhood obesity at nine years

Abstract

Little is known about the association between prenatal cocaine exposure and obesity. We tested whether prenatal cocaine exposure increases the likelihood of obesity in 561 9-year-old term children from the Maternal Lifestyle Study (MLS). Overall, 21.6% of children met criterion for obesity (body mass index [BMI] ≥ 95th percentile, age and sex-specific). While there was no overall cocaine effect on obesity, multivariate logistic analysis revealed that children exposed to cocaine but not alcohol were 4 times more likely to be obese (OR 4.11, CI 2.04–9.76) than children not exposed to either drug. No increase in obesity prevalence was found in children exposed to alcohol but not cocaine (OR 1.08, CI .59–1.93) or both (OR 1.21, CI 0.66–2.22). Alcohol exposure may attenuate the effect of cocaine exposure on obesity. Increased obesity associated with cocaine but not alcohol exposure was first observed at 7 years. BMI was also elevated from 3 to 9 years in children exposed to cocaine but not alcohol, due to increasing weight but normal height. Prenatal exposure to cocaine may alter the neuroendocrine system and metabolic processes resulting in increased weight gain and childhood obesity.

Introduction

Studies of perinatal growth in children with prenatal cocaine exposure have generally reported deficits in birth weight, length and head circumference (Bada et al., 2002, Lumeng et al., 2007, Richardson et al., 2007) with increased prevalence of small for gestational age (Lumeng et al., 2007, Shankaran et al., 2006) and rapid early weight gain (Jacobson et al., 1994, Lumeng et al., 2007). Reports of exposure effects on long term growth up to 10 years of age are inconsistent including no effects (Lumeng et al., 2007, Nordstrom-Klee et al., 2002), increased weight (Jacobson et al., 1994) and deficits in height but not weight gain (Covington et al., 2002, Minnes et al., 2006). The one study that tested and found no effects of cocaine exposure on obesity (≥ 95th percentile, age and sex-specific) did not have enough power to adjust for confounding factors including other drugs of abuse likely to co-occur (Lumeng et al., 2007). Of the other drugs of abuse commonly used with cocaine, increased obesity in children has only been reported with prenatal nicotine exposure (Dubois and Girard, 2006, Li et al., 2007, Salsberry and Reagan, 2005). In other studies, the association of prenatal nicotine exposure and standard growth parameters vary from increased body mass index (BMI) (Hill et al., 2005, Leary et al., 2006) to no differences in weight or height (Lumeng et al., 2007, Richardson et al., 2007). Prenatal alcohol exposure, on the other hand, has been generally associated with long-term growth deficits (Hill et al., 2005, Lumeng et al., 2007, Nordstrom-Klee et al., 2002). No long term growth deficits or increases have been associated with prenatal marijuana exposure (Fried et al., 2001, Richardson et al., 2007). In our large sample, we found evidence that cocaine exposure was associated with increased BMI and hypertension in 9-year-old term children (Shakaran et al., 2010) with adjustment for confounding factors. The prevalence of obesity per se is not apparent by evaluation of BMI. Thus the current study examines prenatal cocaine exposure and obesity directly in the context of other prenatal exposures, early growth and behavioral factors, some of which are also associated with prenatal cocaine exposure.

Obesity in children is a serious problem related to increased metabolic risk factors in childhood (Cook et al., 2008, Messiah et al., 2008) as well as increased likelihood of adult obesity, which is a key risk factor for type 2 diabetes and cardiovascular disease, the leading causes of death, disease and disability in the US (Ogden et al., 2003, Reilly et al., 2003). The increased prevalence of childhood obesity from 1980 to 2004 is well-documented (Ogden et al., 2006). Recent analyses show no further overall increase in obesity from 2003–2006. Relevant to this study, Black girls were more likely to be obese than White girls, but no differences were found between Black and White boys (Ogden et al., 2008). Also alarming are indicators that most children of all races identified as obese by the ≥ 95th percentile would also meet the higher cutoff of ≥ 97th percentile, suggesting that the heaviest children are getting heavier (Ogden et al., 2008). Poverty which affects many minority children as well as children in the current study has been associated with conditions that contribute to obesity in children as young as 6 years such as high caloric diet, inadequate exercise and sedentary behavior (excessive television watching) (Vandewater et al., 2004, Wang and Beydoun, 2007, Wang and Zhang, 2006).

Early identification of children at risk for obesity is important to the development of effective interventions with impact on current and long term public health. BMI and obesity in middle childhood has been related to higher birth weight (Hui et al., 2008, Simmons, 2008) and rapid early weight gain during the first year (Agras and Mascola, 2005, Gardner et al., 2009, Stettler et al., 2002), but not intrauterine growth retardation or small for gestational age (SGA). Studies of children ages 6 and 9 years reported that children with SGA continue to be smaller than children with normal weight (Chakraborty et al., 2007, Shankaran et al., 2006). On the other hand, SGA has been associated with increased prevalence of hypertension at 6 years (Shankaran et al., 2006) as well as obesity and metabolic syndrome in adults (Simmons, 2008). These findings have been explained as a consequence of fetal programming that alters metabolic pathways (Simmons, 2008). Although original studies on fetal programming focused on low birth weight as the precipitating condition, it is generally accepted that low birth weight per se is not at the heart of these disorders, but a proxy for other factors that influence intrauterine growth (Lester and Padbury, 2009, Welberg and Seckl, 2001), one of which could be prenatal cocaine exposure (Lester and Padbury, 2009, Welberg and Seckl, 2001).

The mechanisms of action of cocaine have been well described in terms of neurochemical and vasoconstrictive effects. However, there may be a ‘third pathophysiology’ in which cocaine acts as an intrauterine stressor that alters fetal programming (Lester and Padbury, 2009). Stress hormones such as catecholamines and glucocorticoids, which are elevated in the fetus exposed to cocaine, can alter regulation of the neuroendocrine environment by acting on the hypothalamic–pituitary–adrenal axis which results in an altered set point for physiologic and metabolic outcomes including obesity (Barat et al., 2007). As a stressor that alters the neuroendocrine environment, prenatal cocaine exposure could reprogram metabolic pathways of the fetus increasing the likelihood of rapid early weight gain and childhood obesity.

The goal of this study was to test the hypothesis that prenatal cocaine exposure is associated with increased prevalence of obesity at 9 years of age.