In Utero Exposure to Maternal Obesity and Diabetes: Animal Models That Identify and Characterize Implications for Future Health
Peter W. Nathanielsz, MD, PhD, ScD, FRCOGa,*, Lucilla Poston, PhD, FRCOGb, Paul D. Taylor, PhDb
Department of Obstetrics & Gynecology, Center for Pregnancy and Newborn Research, The University of Texas of HealthScience Center, 7703 Floyd Curl Drive, MSC 7836, San Antonio, TX 78229, USA b Maternal & Fetal Unit, Department of Women’s Health, Division of Reproduction and Endocrinology, King’s College London, 10th Floor, North Wing, St. Thomas’ Hospital, London SE1, 7EH, UK
The developed and developing worlds are experiencing an epidemic of obesity and associated predisposition to diabetes. This epidemic placesa major drain on health care resources. In the United States, estimates suggest that one third of adult women are clinically obese . This increased incidence of obesity and diabetes includes women of child-bearing age [2–4]. It is now clear that maternal obesity and gestational diabetes have major adverse eﬀects on the developing fetus that lead to increased neonatal morbidity and mortality,as discussed elsewhere in this issue. Obesity in pregnancy and gestational diabetes represent a special problem, not only as a result of their immediate adverse eﬀects on maternal health and pregnancy outcome, but also because of growing evidence for their persistent and deleterious eﬀects on the developing child. Recent human epidemiologic observations and experimental studies in rodents and sheep[5–10] show that the nutrient environment in which the fetus and neonate develop can alter the trajectory of development of multiple organ systems in ways that permanently impair their function and predispose the oﬀspring to chronic diseases that only emerge in later life. The persistent eﬀects of a suboptimal fetal and neonatal development have been called
NICHD HD 21350. * Correspondingauthor. E-mail address: firstname.lastname@example.org (P.W. Nathanielsz). 0889-8545/07/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.ogc.2007.03.006 obgyn.theclinics.com
developmental programming. Developmental programming can be deﬁned as the response to a speciﬁc challenge to the mammalian organism during a critical developmental timewindow that alters the trajectory of development qualitatively and/or quantitatively with resulting persistent eﬀects on phenotype. The fundamental principles of developmental programming are laid out in Box 1. The nutritional environment experienced during fetal and early postnatal life is proposed to aﬀect susceptibility to the development of cardiovascular disease and glucose intolerance later inlife . Numerous human cohort studies have demonstrated an association of low weight at birth with facets of metabolic syndrome, including hypertension, glucose intolerance, and obesity [12–14]. Catch-up growth in early postnatal life or childhood seems to further increase the risk of developing these predisposing conditions, which have strong associations with cardiovascular disease [15–18].Maternal obesity and consequences for the developing child In view of the rising birth weight in developed countries, the prevalence of obesity in pregnancy, and the association with gestational diabetes, there is increasing interest in the potentially detrimental inﬂuence of a maternal hypernutritional status and associated raised birth weight on the risk of disease in the child [19–23]. Though thelink between obesity, gestational diabetes and heavier weight at birth is recognized, it is increasingly clear that obesity per se may also contribute. Indeed weight gain between ﬁrst and second pregnancies has recently been recognized as a factor that increases the risk of the second baby being large for gestational age, even amongst women who are not clinically obese . Prolonged eﬀects of...