Pregnancy endocrine disruption and obesity-related outcomes in the third generation

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Background/Aims Childhood obesity has become a global epidemic, with 1 in 3 children in the United States affected. The etiology of obesity is multifactorial, including genetic, perinatal, dietary, psychosocial, and environmental factors. One of the potential modifiable environmental risk factors for childhood obesity is endocrine disrupting chemicals. Diethylstilbestrol (DES) is a synthetic estrogen that was prescribed to pregnant women to prevent pregnancy loss between the 1940s and 1970s, but banned for its unexpected adverse health effects. Previous research has linked in utero exposure to DES with increased risk for obesity among those exposed prenatally, but whether such effects extend to the third generation—independently from any effect on the second generation—are not known despite emerging evidence of multigenerational effects of DES on other outcomes.Methods We investigated the association between DES use during pregnancy and risk of both overweight (BMI>25 kg/m2) and diagnosis of high cholesterol (2011) in the grandchildren by linking the data from three interconnected cohort studies (Nurses’ Health Study II (NHS II), Nurses’ Mothers’ Cohort Study (NMCS), and Growing Up Today Study (GUTS)). Grandmothers reported their use of DES and other potential confounding factors in the NMCS and anthropometric data were provided by participants in both NHS II and GUTS. Data were analyzed using cluster-weighted generalized estimating equations.Results Among 3,837 grandmother (G0)-mother (G1) pairs the prevalence of G0 use of DES during pregnancy was 2.6%. Among 5,431 children (G2), 1,749 (32.2%) were overweight or obese, and 135 (2.5%) had high cholesterol. Grandmother (G0) use of DES during pregnancy was associated with an increased risk of having a diagnosis of high cholesterol (adjusted odds ratio [aOR]=2.82; 95% CI: 1.37-5.78), but not with overweight/obesity among grandchildren (G2).Conclusion DES use during pregnancy is associated with an elevated risk of grandchildren being diagnosed with high cholesterol.