magnesium ( mg ) is an important cofactor for the enzymes that are involved in carbohydrate metabolism : an important role of mg in insulin action has been reported [ 1 , 2 ] ; low serum and intracellular mg ( [ mg]i ) concentrations are associated with insulin resistance , impaired glucose tolerance , and decreased insulin secretion [ 3 , 4 ] . furthermore , lower dietary mg intake could cause insulin resistance both in children and adults [ 5 , 6 ] . based on these findings , we studied whether low [ mg]i in the fetus would be one of the critical abnormalities associated with small for gestational age ( sga ) . in addition , several studies have shown the association of size at birth or indices in poor fetal growth with later development of metabolic syndrome and insulin resistance . proposed that impaired glucose tolerance and type 2 diabetes might arise as a result of programming . programming is a term used to describe persistent changes in organ structure and function caused by exposure to adverse environmental influences during critical periods of development . hypothesis , which proposes that fetal adaptation to an adverse intrauterine environment affecting fetal growth may program life - long physiological changes . it has been proposed that various fetal growth patterns and intrauterine growth retardation ( iugr ) arise as a result of an early stimulus or insult . since both fetal weight and length gains are closely related , there is much overlap between sga and iugr . sga is defined as birth weight and/or length at least 2 standard deviations below the mean for gestational age .   in this review , we discuss the potential contribution of aberrant mg regulation to sga and to the pathogenesis of metabolic syndrome later in life . it is reported that the amount of maternal mg intake is not only associated with pregnancy outcome but also with infant outcome . the mean daily intake of mg ( 284.3  mg / day ) during pregnancy was found to be lower than recommended . for example , mg deficiency is reported to occur in 44% of pregnant indian women . another study has demonstrated that mothers who drink water containing high amounts of mg have a reduced risk of having very low birth weight infants ( less than 1,500  g of birth weight ) . by the end of a normal pregnancy , the fetus is believed to have acquired approximately 28  g of calcium , 16  g of phosphorous , and 0.7  g of mg , mostly during the third trimester , also the time when 80% of fetal accretion of mg occurs . the fetal circulation contains higher levels of total calcium , ionized calcium , and mg compared to maternal blood . in the placental membrane , copper and selenium share the same transport pathway along a concentration gradient in the maternal - fetal direction , while mg and iron use predominantly an active transport pathway . in fact , evidence for an active transport mechanism for mg in the placenta has been demonstrated in cultured trophoblast cells in which low [ mg]i is maintained by the function of a na / mg exchanger . mg levels in umbilical cord blood are the lowest in preterm low birth weight babies , followed by term low birth weight babies and are the highest in term controls ( p < .05 ) . calcium and mg have an immediate effect on placental vascular flow . reduced placental vascular flow is at least , in part , responsible for placental insufficiency and fetal growth retardation ( fgr ) . a variety of hormones , cytokines , and growth factors produced by fetal membranes and the placenta can act locally on the myometrium . the ability of the uterine artery to dilate during pregnancy may be specifically related to the upregulation of multiple pathways for the production of nitric oxide . the activity of constitutive nitric oxide synthase is dependent on calcium and is inhibited by a reduction in the concentration of mg . blood mg levels were reportedly lower in women with severe pre - eclampsia than in healthy pregnant women ( 1.63    0.05  mg / dl versus 1.87    0.05  mg / dl ; p < .001 ) . therapeutic levels of mg have also been found to produce specific placental effects such as vasodilation . from an in vitro study of human umbilical artery resistance , mg sulfate was found to exert a relaxant effect on umbilical arterial tone attenuating the vasoconstrictor effect of angiotensin ii and endothelin-1 in the fetal - placental vasculature . mg sulfate used for the treatment of pre - eclampsia or hypertensive disease in pregnancy may have beneficial effects on the fetoplacental circulation . prenatal treatment with mg sulfate may influence calcium homeostasis and nonenzymatic antioxidant reserve in erythrocytes of preterm newborns . it is well known that plasma mg falls in pregnancy because of accumulation of ion in the placenta and fetus . mg is therefore widely given as a supplement during pregnancy , particularly in cases of preterm labor . there are several reports that oral mg supplementation in pregnancy is safe and that it has a positive effect on fetal morbidity . patients in preterm labor have significantly depressed serum mg levels , while in patients with pre - eclampsia , mg levels are not significantly different from that of the controls . mg supplementation was found to decrease the rate of fgr , premature rupture of membranes , and premature delivery in risk pregnancies treated with betamimetics . oral mg supplementation given before the 25th week of gestation is associated with a lower frequency of preterm births , a lower frequency of low birth weight , and fewer sga infants compared with the placebo . mg intake in 513 women who were near the end of their first trimester of pregnancy was determined from records of food consumption . mg intake correlated with weight , length , and head circumference at birth as well as length of gestation up to a threshold of around 3,200  g of birth weight . on the other hand , mg supplements ( 100  mg / day ) taken during the second and third trimesters had no effect on the outcome of the pregnancy . the effect of mg compared with placebo in a randomized double - blind controlled study of patients with pregnancy - induced hypertension was investigated . mg supplementation was found to be beneficial in the management of pregnancy - induced hypertension . at present , there is insufficient high - quality evidence to show that dietary mg supplementation during pregnancy is beneficial . it is important to determine the timing and dose of mg supplementation as both factors may alter the pregnancy outcome . we have previously reported that intracellular magnesium ( [ mg]i ) is lower in children with diabetes mellitus and in children who are obese . in the type 2 diabetes mellitus and obese groups , platelets responded well to insulin . under insulin - resistant states , [ mg]i decreases before the poor reactivity to insulin occurs in platelets . from these findings , we hypothesize that [ mg]i is decreased earlier than when poor reactivity to insulin develops in platelets exposed to an insulin resistant environment . this suggests that low [ mg]i may be an intrinsic abnormality in infants with low birth weight . to test this hypothesis , we studied the relationship of [ mg]i   in cord blood platelets to birth weight . we found that mean basal [ mg]i , but not plasma magnesium , is lower in sga than in the appropriate for gestational age ( aga ) groups ( 323    162  mol / l versus 488    132  mol / l , p = .004 ) . mg]i significantly correlates with birth weight ( p < .0001 ) as well as cord plasma leptin ( p = .031 ) and igf-1 ( p < .001 ) . [ mg]i as well as leptin and igf-1 reflects the extent of fetal growth . also , [ mg]i significantly correlates with the quantitative insulin sensitivity check index ( quicki ) ) ( p < .001 ) . decreased [ mg]i in sga might underlie the initial pathophysiological events that lead to insulin resistance . for example , hyperglycemia may have an effect on mg transport and induce a decline of [ mg]i . reported that responses to hyperglycemia in vitro were blunted in adult hypertensive subjects and that these responses were closely linked to basal [ mg]i   levels . in our study , we found no correlation between cord plasma glucose and basal [ mg]i   levels . in addition , we did not find any significant difference in plasma glucose levels between the sga and aga groups . intrauterine glucose levels may have less of an effect on inducing sga or low [ mg]i . as [ mg]i plays a promotive role in fetal growth , low [ mg]i may partly be responsible for sga . as low [ mg]i is an intrinsic abnormality seen in infants with low birth weight , it is considered that fetal mg deficiency is an important determinant of insulin resistance in later life . in fact , our data was supported by a recent animal study demonstrating that maternal mg restriction irreversibly increases body fat and induces insulin resistance in pups by 6  months of age . the fetal origin hypothesis by barker et al . [ 810 ] states that fetal undernutrition in middle to late gestation leads to disproportionate fetal growth programs and later metabolic diseases . fetal programming is a phenomenon in which alterations in fetal growth and development in response to the prenatal environment have long - term or permanent effects . this theory was further established in the category of developmental origins of health and disease ( dohad ) . the mechanisms thought to be responsible for fetal programming include the direct effects on cell number , altered stem cell function , and the resetting of regulatory hormonal axes : hypothalamic - pituitary - adrenal axis [ 39 , 40 ] and growth hormone insulin - like growth factor axis . one of the underlying mechanisms for the postulated early - life programming is that of epigenetics . altered epigenetic regulation of genes in phenotype induction could possibly give rise to interventions that modify long - term disease risk associated with unbalanced nutrition in early life . reported that fasting insulin and homeostasis model assessment - insulin resistance ( homa - ir ) increased in offspring from mg - restricted dams at 6  months of age . maternal and postnatal mg status is important in the long - term programming of body adiposity and insulin secretion in rat offspring . although low birth weight and poor prenatal nutrition are strongly associated with metabolic syndrome in later life , postnatal catch - up growth was recently considered to also be a pivotal element associated with the development of various pathological conditions . the concept of a sensitive or crucial period that operates to cause long - term changes in development and adverse outcomes later in life is an intriguing one and should be the focus of more studies in the future . birth weight is only a crude index of early growth and indicates nothing about the success of a fetus in achieving its growth potential . [ mg]i may be a marker of early growth restriction , which may be of future diagnostic use as an early predictor of adult diseases . low [ mg]i , which may represent the prenatal programming of insulin resistance , has lifelong effects on metabolic regulation . a biological interpretation of the association between birth size and risk of insulin - resistant diseases should emphasize the possible underlying roles of [ mg]i .