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Abstract & commentary
Synopsis: Maternal nutritional deprivation (starvation) appears to be associated with antisocial personality disorder in resultant offspring.
Source: Neugebauer R, et al. JAMA 1999;282:455-462.
Between october 1944 and may 1945, the german army severely restricted the flow of food supplies to the western area of The Netherlands. Because other studies have recently shown that restricting the nutritional intake of pregnant women may result in offspring with more psychiatric disorders than are seen in the general population, Neugebauer and colleagues use the famine conditions occurring in this geographic area to attempt to determine whether caloric restriction causes an increase in antisocial personality disorder (ASPD).
Upon reaching 18 years of age, Dutch men born in the 1944-1946 time frame were required to undergo psychiatric examination as part of their military induction process. Neugebauer et al used the results of these examinations as well as the known availability of food in the various regions in The Netherlands to compare the occurrence of ASPD between men who were exposed to famine conditions while in utero as opposed to those who were not so exposed.
Those males who were exposed to famine conditions (less than 1000 calories food ration per day) during the first and/or second trimester had more than a two-fold increased risk of ASPD compared to males who were not so exposed. Neugebauer et al carefully selected their methodology such that the most likely explanation for the increase in psychiatric illness was the lack of maternal nutrition.
Comment By kenneth L. noller, md
The reason I have chosen this article for review is to provide me with the opportunity to discuss an area of growing interest in the field of disease etiology—namely, that the intrauterine milieu may be responsible for diseases that occur many years later in life.
It has been known for a long time that insults such as infections can cause fetal maldevelopment and lifelong disease. Examples would include such things as maternal toxiplasmosis and German measles infections. Maternal nutritional deficiencies such as folate deficiency have now been shown to cause an increase in congenital anomalies. However, it is not nearly as well recognized that some diseases of adults might be the result of intrauterine exposures. The obvious and best example is the association between vaginal clear-cell cancer and maternal ingestion of DES.
Many other diseases are now being linked to maternal conditions. Although not yet proven, it is likely that women who have higher naturally occurring levels of estrogen predispose their female offspring to higher rates of breast cancer. Decreased nutritional intake during pregnancy has been linked to a variety of psychiatric illnesses including schizophrenia and, now with the publication of this paper, ASPD.
Some years ago, we reported the association of eating disorders occurring in adults with exposure before birth to DES. Thus, it appears that a disease need not be evident at the time of birth to be linked to the intrauterine milieu. This area of research is just beginning to blossom. I strongly suspect that we will see many more associations between maternal health and diseases in offspring that occur decades later.
a. antisocial personality disorder.
b. spina bifida.
d. regional enteritis.