Magnesium Research (1993) 6, 3, 297-298
Commentary on recent clinical advances:
Key words: Magnesium deficiency, pregnancy, birth weight, birth length, head circumference, sudden infant death syndrome, cardiovascular risk factors, maternal undernutrition.
Higher incidence rates of sudden infant death syndrome (SIDS) have been observed in infants of diminished birth weight. Several analytical studies, for example the NICHD cooperative study1 controlling a variety of confounders of birth size have estimated the likelihood of SIDS deaths in relation to the four variables of birth size: birth weight, birth length, head circumference and gestational age. SIDS may be associated with symmetrical intrauterine growth retardation because of reduction in both birth weight and length even after controlling for gestational age and sex of the infant. This suggests that mechanisms responsible for growth retardation in this situation begin early in pregnancy1. Various subtle morphological differences between SIDS and controls support the notion of early intrauterine injury as playing some part in the genesis of SIDS2.
Several English surveys have indicated that reduction in fetal growth which begins early in gestation is followed by increased mortality from cardiovascular disease in adult life. One of them, concerning 1586 men born in a maternity hospital in Sheffield between 1907 and 1925 showed that death rates from cardiovascular diseases fell progressively with increasing weight, head circumference and weight/length ponderal index at birth3. In another one, dealing with 5694 men born in Hertfordshire between 1911 and 1930, examination of men and women showed that lower birth weight is associated with a higher incidence of known risk factors for cardiovascular disease, including raised blood pressure, plasma glucose and basal insulin concentrations, plasma fibrinogen and factor VII concentrations4. The studies in Preston have shown that babies who have small head circumferences and are thin at birth tend as adults to develop a "syndrome X": a combination of hypertension, non-insulin dependent diabetes, disordered lipids, hyperinsulinaemia, obesity and abdominal fatness5.
It has been argued that people whose growth has been impaired in utero may continue to be exposed to an adverse environment in infancy, childhood and adult life and it may be this later environment that produces the effects being attributed to programming. But the associations with cardiovascular risk factors are independent of known influences in lifestyle: they occur in each social class, and at each level of cigarette smoking, alcohol consumption and obesity4.
Fetal growth can also be constrained by maternal size. But a baby's birth measurements, however, are predictive of adult disorders independent of maternal pelvic size3, 4.
These very interesting studies, mainly by the MRC Environmental Epidemiology Unit of Southampton directed by D.J.P. Barker, suggested that cardiovascular disease and non-insulin dependent diabetes may begin early in gestation. Maternal nutrition may have an important influence on programming of the body structure and physiology. Persisting changes in the levels of hormone secretion and in the sensitivity of tissue to them may link fetal undernutrition with abnormal structure, function and disease in life3-5.
Among the multiple variables of maternal undernutrition which may induce frequently early symmetrical intrauterine growth retardation, experimental and clinical data have highlighted the importance of marginal magnesium deficiency2, 6-8. Several prospective double-blind studies in Germany and in Hungary on the effects of the control of chronic marginal maternal magnesium deficiency by oral physiological magnesium supplementation have shown their beneficial effects on all the stigmata of diminished development of the baby at birth: such as birth weight, crown-heel length, and head circumference2, 9. Therefore maternal magnesium intake appears to be one of the factors of nutrition in pregnancy which induces reduced fetal growth and may have an influence during the entire life on programming.
The classical studies of magnesium supplementation only analyse its effects on the mother, the fetus and the neonate at birth9. The main consequence of the magnesium-dependent thermal dysregulation theory of SIDS is to follow up the baby over the first year in order to check the validity of this important hypothesis2. But now--after the seminal epidemiological studies by Barker--the protocol of the multicentre trials of maternal magnesium supplementation should be followed up not only during the first year but throughout life. This notion should be borne in mind during the development of this protocol to get the best of it in the future.
1. Van Belle, G., Hoffman, H. & Peterson, D. (1988): Intra-uterine growth retardation and the sudden infant death syndrome. In: Sudden infant death syndrome: risk factors and basic mechanisms. eds. R.M. Harper & H.J. Hoffman, pp. 203-219. New York: PMA Publishing Corporation.
2. Durlach, J., Durlach, V., Rayssiguier, Y., Ricquier, D., Goubern, M., Bertin, R., Bara, M., Guiet-Bara, A., Olive, G. & Mettey, R. (1991): Magnesium and thermoregulation. I. Newborn and infant. Is sudden infant death syndrome a magnesium-dependent disease of the transition from chemical to physical thermoregulation? Magnes. Res. 4, 137-152.
3. Barker, D.J.P., Osmond, C., Simmonds, S.J. & Wield, G.A. (1993): The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life. BMJ 306, 422-426.
4. Barker, D.J.P., Gluckman, P.D., Godfrey, K.M., Harding, J.E., Owens, J.A. & Robinson, J.S. (1993): Fetal nutrition and cardiovascular disease in adult life. Lancet 341, 938-941.
5. Barker, D.J.P., Hales, C.N., Osmond, C., Phipps, K. & Clark, P.M.S. (1993): Type 2 (non-insulin dependent) diabetes mellitus, hypertension and hyperlipemia (syndrome X): relation to reduced fetal growth. Diabetologia 36, 62-67.
6. Kubena, K.S. & Durlach, J. (1990): Historical review of the effects of marginal intake of magnesium in chronic experimental magnesium deficiency. Magnes. Res. 3, 219-226.
7. Durlach, J. (1989): Recommended dietary amounts of magnesium: Mg RDA. Magnes. Res. 2, 195-203.
8. Durlach, J. & Mareschi, J.P. (1991): Recommended dietary amounts for magnesium: updated European Consensus and future prospects. In: Magnesium: a relevant ion, eds. B. Lasserre & J. Durlach, pp. 39-49, London: John Libbey.
9. Spatling, L., Disch, G. & Classen, H.-G. (1989): Magnesium in pregnant women and the newborn. Magnes. Res. 2, 271-280.
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