Prenatal Programming

Life in the Womb: The Origin of Health and Disease.
Peter W. Nathanielsz.
Promethean Press, 1999.
363 pages, $27.50.
 

For any woman who is currently pregnant or contemplating pregnancy, this book is both enlightening and frightening. It summarizes the effects of the maternal environment on the long-term health of the offspring. To quote from the book: ". . . it is clear that pre-natal growth is critical to health throughout life. It is important to focus on health rather than disease." There is a tendency to explain all health problems--high blood pressure, weight gain, fecundity or longevity--in terms of the genetic attributes inherited from our parents. Genetic determinism, or, as Dr. Nathanielsz calls it, "genetic myopia," is a way of denying responsibility for the development of the unborn and newborn child. At one extreme, it is argued that our whole life is genetically pre-determined.

This book takes issue with such notions and clearly identifies the difference between genetic and congenital disorders of health. Thus, the genetic potential provided at the time of conception can be modified during prenatal development and life. We are all now aware of the consequences of prenatal exposure to toxic compounds including cigarette smoke, alcohol, and environmental toxins. We are less aware of the fact that the maternal environment during gestation can have a profound effect not only on organ development (the creation of overt deformities at birth) but also on the long-term health of the offspring.

The thalidomide tragedy is one example of the modification of the intrauterine environment in early gestation. Another is fetal alcohol syndrome, the consequence of excess alcohol ingestion during pregnancy, typically changing the physical characteristics of the newborn. Although recognized in 1968, it was not until 1981 that warnings were issued about this condition. Likewise, it was recognized that smoking is also teratogenic and that drug addiction of the mother will often lead to an addicted neonate. In the 1960s it was recognized that when mothers took estrogen in the form of the synthetic diethylstilbestrol (DES), their female children appeared normal but, in later life, often developed cancer of the cervix and vagina. Only now is it being recognized that there are other perturbations that may alter the processes of growth and development.

One of the most interesting studies that Dr. Nathanielsz quotes involves the effects of malnourishment of the mother during pregnancy on the subsequent development of the offspring. The Dutch famine occurred in the Second World War, when the retreating Germans deliberately deprived the population of food during the harsh winter of 1944-1945. There were, in the affected population, women at various stages of pregnancy, and the studies of their offspring demonstrated some unexpected outcomes. Babies whose mothers were deprived of food in the first six months of pregnancy became obese in later years. Body composition and body weight are thought mainly to be a genetically determined parameter, but this observation suggested that the control of body composition was disordered during maturation of the brain. Longevity may also be altered by maternal malnutrition. Studies from the West African country of Gambia demonstrated that babies born in the "hungry" season have a shorter life span than those born in the "harvest" season. The survival of the two groups was identical up to age 20, but at age 45, only 45% of the "hungry season" cohort were alive, whereas the "harvest season" group showed a 65% survival rate.

It is tantalizing to speculate about why the outcome depends on the time of gestation at which the insult occurs. It is easy to understand that disturbances during organ development would lead to gross malformation. Major alterations in adult health not manifested until late in life are more difficult to understand. During the last four or five weeks of pregnancy and even in the early months of life, the final development of the fetus involves not only organ growth, but the formation of complex control systems, especially within the central nervous and endocrine systems. These involve the assembly of neural networks and the generation of molecules within membranes and cells. In other words, the system is "fine-tuned" for life and it seems that dislocation during this period of development compromises the successful completion of development.

The evidence which Dr. Nathanielsz summarizes is a triumph for the discipline of epidemiology. By analyzing large amounts of data, epidemiology draws certain conclusions when certain comparisons are made. There are many pitfalls in such an analysis of cause and effect. For example, a statistical analysis would clearly demonstrate that most men that wear kilts are Scotsmen, and that most men that eat porridge are also from Scotland, but it does not necessarily mean that all men who wear the kilt and eat porridge are Scotsmen. There are many variable factors that could lead to an erroneous conclusion regarding the relationship between cause and effect. The epidemiological process provides the experimental scientist with clues about problems worthy of investigation. The experimental scientist then has to decide whether or not the epidemiological evidence has been rigorously analyzed to prevent false interpretation.

It is to be hoped that the agencies that fund biological research, especially the National Institutes of Health, will be alerted by this book. An unfavorable uterine environment can result in much more than overt malformation; there is already enough evidence to suggest that adult health may be adversely impacted in ways not yet completely understood. Periods of war, famine and pestilence affect the unborn as well as children, although recognition of their injuries may not become apparent for several decades.

Life in the Womb, unlike most science texts aimed at the lay public, contains a lengthy final section which refers to additional material for the topics discussed in each chapter with a brief description of the articles. They will stimulate the reader who is interested in this topic to read more widely. Dr. Nathanielsz has also written a companion book, Life Before Birth, which traces fetal development and focuses on the factors that lead to normal birth and the difficulties and causes of premature birth. Life in the Womb complements and extends the enthralling saga of the first book.

David Robertshaw is a professor of physiology at the Department of Biomedical Sciences of Cornell University.