The Long-Term Effects of Prenatal Development on Growth and Metabolism

Medical Research Council Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom.
Seminars in Reproductive Medicine (Impact Factor: 2.35). 05/2011; 29(3):257-65. DOI: 10.1055/s-0031-1275518
Source: PubMed

ABSTRACT People who were small at birth and had poor infant growth have an increased risk of adult cardiovascular disease, osteoporosis, and type 2 diabetes, particularly if their restricted early growth was followed by increased childhood weight gain. These relations extend across the normal range of birth size in a graded manner, so reduced size is not a prerequisite. In addition, larger birth size is associated with risks of obesity and type 2 diabetes. The associations appear to reflect developmental plastic responses made by the fetus and infant based on cues about the environment, influenced by maternal characteristics including diet, body composition, stress, and exercise levels. These responses involve epigenetic processes that modify the offspring's phenotype. Vulnerability to ill health results if the environment in infancy, childhood, and later life is mismatched to the phenotype induced in development, informed by the developmental cues. This mismatch may arise through unbalanced diet or body composition of the mother or a change in lifestyle factors between generations. These insights offer new possibilities for the early diagnosis and prevention of chronic disease.

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    • "Limitation of intrauterine growth has important consequences for infant, child and adult health. Associations have been reported between intrauterine growth restriction and the incidence of several chronic conditions in later life such as type 2 diabetes mellitus [1] or cardiovascular diseases [2]. It has been hypothesized that variations in birth weight are among the most visible manifestations of a broader set of biological changes setting grounds for the development of non-communicable diseases in later life and that such biological changes may be caused, noticeably, by environmental factors [3]. "
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    ABSTRACT: Background Exposure to air pollution is frequently associated with reductions in birth weight but results of available studies vary widely, possibly in part because of differences in air pollution metrics. Further insight is needed to identify the air pollution metrics most strongly and consistently associated with birth weight. Methods We used a hospital-based obstetric database of more than 70,000 births to study the relationships between air pollution and the risk of low birth weight (LBW, <2,500 g), as well as birth weight as a continuous variable, in term-born infants. Complementary metrics capturing different aspects of air pollution were used (measurements from ambient monitoring stations, predictions from land use regression models and from a Gaussian dispersion model, traffic density, and proximity to roads). Associations between air pollution metrics and birth outcomes were investigated using generalized additive models, adjusting for maternal age, parity, race/ethnicity, insurance status, poverty, gestational age and sex of the infants. Results Increased risks of LBW were associated with ambient O3 concentrations as measured by monitoring stations, as well as traffic density and proximity to major roadways. LBW was not significantly associated with other air pollution metrics, except that a decreased risk was associated with ambient NO2 concentrations as measured by monitoring stations. When birth weight was analyzed as a continuous variable, small increases in mean birth weight were associated with most air pollution metrics (<40 g per inter-quartile range in air pollution metrics). No such increase was observed for traffic density or proximity to major roadways, and a significant decrease in mean birth weight was associated with ambient O3 concentrations. Conclusions We found contrasting results according to the different air pollution metrics examined. Unmeasured confounders and/or measurement errors might have produced spurious positive associations between birth weight and some air pollution metrics. Despite this, ambient O3 was associated with a decrement in mean birth weight and significant increases in the risk of LBW were associated with traffic density, proximity to roads and ambient O3. This suggests that in our study population, these air pollution metrics are more likely related to increased risks of LBW than the other metrics we studied. Further studies are necessary to assess the consistency of such patterns across populations.
    Environmental Health 02/2013; 12(1):18. DOI:10.1186/1476-069X-12-18 · 3.37 Impact Factor
    • "Nutrient restriction during pregnancy, leading to so-called intrauterine growth restriction (IUGR), is associated with an increased risk of developing infl ammation, obesity, and metabolic syndrome in later life (Godfrey et al., 2011). Intrauterine growth restriction is also a production problem in farm animals (Wu et al., 2006). "
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    ABSTRACT: The Developmental Origins of Health and Disease hypothesis formulated in the early 1990s has stimulated research on long-term effects of early nutrition and environment over the last decades. Longterm is understood in this review as physiologically relevant periods such as after weaning, around sexual maturity, and in adulthood, as opposed to early developmental periods. The small and large intestines as targets for the study of long-term effects have received little attention until recent years and the stomach has been considered very rarely. Data have accumulated for laboratory animal models but they are still scarce in the swine species. Following the epidemics of metabolic diseases and obesity in western countries, experimental evidence has been published showing that nutritional factors, including energy, fat and fatty acids, protein, and micronutrients impact various facets of gut function. These include alterations in intestinal digestive, absorptive, secretory, barrier, and defense systems, often in a way potentially detrimental to the host. Environmental factors with long-term influence include stress (e. g., maternal deprivation, neonatal gut irritation), chemical pollutants (e. g., bisphenol A), and gut microbiota disturbances (e. g., by antibiotics). Examples of such long-term effects on the gut are provided in both laboratory animals and pigs together with underlying physiological mechanisms whenever available. Experimental evidence for the involvement of underlying epigenetic modifications (e. g., genomic DNA methylation) in long-term studies has just started to emerge with regard to the gastrointestinal tract. Also, interactions between the microbiota and the host are being considered pivotal in the early programming of gut functions. Finally, suggestions for future research are provided in order to better understand and then control early programming as an attempt to optimize vital functions of the gastrointestinal tract throughout adult life.
    Journal of Animal Science 01/2013; 90(Supplement 4):421-429. DOI:10.2527/jas.53904 · 2.11 Impact Factor
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    • "Impaired placental function leads to fetal malnutrition and deprivation of oxygen and nutrition supply. It is meanwhile well accepted that undernutrition results in intrauterine growth restriction which seems to program coronary heart disease and hypertension later in life [3–5]. Strikingly the human placenta is only a transient organ, but its effect on the offspring is conserved throughout life. "
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    ABSTRACT: Preeclampsia is one of the leading causes of maternal and fetal morbidity and mortality. New molecular insights offer new possibilities of early diagnosis of elevated maternal risk. Maternal risk factors, biophysical parameters like Doppler examination of the uterine arteries and biochemical parameters allow early risk calculation. Preventive and effective therapeutic agents like acetylsalicylacid can be started in the early second trimester. This article reviews the diagnostic possibilities of early risk calculation to detect women having high risk for preeclampsia and the potential benefits for them, the offspring and health care systems. We provide risk calculation for preeclampsia as an important and sensible part of first trimester screening.
    ISRN obstetrics and gynecology 07/2012; 2012:172808. DOI:10.5402/2012/172808
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