3 minute read

Genetics: Parental Influence

Maternal Nutrition

The study of long-term effects of maternal nutrition on offspring has a rich and extensive history. The hypothesis, referred to as fetal origins, fetal programming, or metabolic imprinting, addresses the permanent effect that maternal undernutrition may have on physiological systems in the offspring, reportedly affecting glucose regulation, lipid metabolism, cardiovascular disease, blood pressure, and obesity. Human studies on the imprinting effect have been conducted retrospectively, utilizing records to establish vital statistics on newborns. Aspects of health, physiological fitness, and mortality in newborns were followed up many years later, during adulthood. Studies on men born in Herefordshire, England, demonstrated that those with the lowest birth weights were more likely to have higher mortality rates from coronary heart disease. Similarly, low-birth-weight males were more likely to develop noninsulin-dependent diabetes and impaired glucose tolerance, inferring that low-birth-weight babies were deprived nutritionally during development. Data from the Dutch famine of World War II, which resulted in maternal malnutrition, more directly tested gestational malnutrition and demonstrated that glucose tolerance was indeed decreased years later in surviving adults.

Epidemiological studies are limited by their retrospective nature, especially over issues of controls, sampling bias, and concerns over adjustment for confounding factors. In attempts to address some of these concerns, animal studies have been conducted, and in some cases they have supported the fetal origins hypothesis on issues of body composition, cardiovascular disease, and glucose tolerance. However, animal studies must be interpreted with caution, due to questions of species differences in the expression of pathology. Given the large collection of human and animal data on the subject, the fetal origins hypothesis remains topical, though it requires additional research to test its accuracy.

While many of these hypotheses will require elucidation through future study, new technology will greatly assist in the process. Previous studies have also suggested areas of research to help test fetal programming, such as permanent modification of gene expression and alterations in cell number. Epigenetic mechanisms, where heritable changes in gene function occur without changes in DNA sequence, provide another interesting mechanism by which fetal programming can occur. Finally, the techniques of in vitro fertilization with gametes from older parents, as well as cloning of differentiated adult cells, may provide new information on the effect of early development on aging in successive generations and help discern the role of genetics and environment on these complex issues.



CROW, J. F. "Spontaneous Mutation in Man." Mutation Research 437 (1999): 5–9.

GAVRILOV, L. A.; GAVRILOVA, N. S.; KROUTKO, V. N.; EVDOKUSHKINA, G. A.; SEMYONOVA, V. G.; GAVRILOVA, A. L.; LAPSHIN, E. V.; EVDOKUSHKINA, N. N.; and KUSHNAREVA Y. E. "Mutation Load and Human Longevity." Mutation Research 377 (1997): 61–62.

HEMMINKI, K., and KYYRONEN, P. "Parental Age and Risk of Sporadic and Familial Cancer in Offspring: Implications for Germ Cell Mutagenesis." Epidemiology 10 (1999): 747–751.

JOSEPH, K. S., and KRAMER, M. S. "Review of the Evidence of Fetal and Early Childhood Antecedents of Adult Chronic Disease." Epidemiologic Reviews 18 (1996): 158–174.

MCINTOSH, G. C.; OLSHAN, A. F.; and BAIRD, P. A. "Paternal Age and the Risk of Birth Defects in Offspring." Epidemiology 6 (1995): 282–288.

NICOLAIDIS, P., and PETERSEN, M. B. "Origin and Mechanisms of Non-disjunction in Human Autosomal Trisomies." Human Reproduction 13 (1998): 313–319.

TARIN, J. J.; BRINES, J.; and CANO, A. "Long-Term Effects of Delayed Parenthood." Human Reproduction 13 (1998): 2371–2376.

WATERLAND, R. A., and GARZA, C. "Potential Mechanisms of Metabolic Imprinting That Lead to Chronic Disease." American Journal of Clinical Nutrition 69 (1999): 179–197.

ZHANG, Y.; KREGER B. E.; DORGAN, J. F.; CUPPLES, L. A.; MYERS, R. H.; SPLANSKY, G. L.; SCHATZKIN, A.; and ELLISON, R. C. "Parental Age at Child's Birth and Son's Risk for Prostate Cancer: The Framingham Study." American Journal of Epidemiology 150 (1999): 1208–1212.

Additional topics

Medicine EncyclopediaAging Healthy - Part 2Genetics: Parental Influence - Parental Age, Maternal Nutrition