Il efects of maternal obsity on foetus and on adult life of her siblings .

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Foetal outcome in obese women? How obesity adversely affect the foetus?? Ans:-- Obesity in pregnancy is linked to a multitude of short- and long-term adverse fetal outcomes. For example, obese women are more likely to give birth to a 1) macrosomic infant, which is associated with increased perinatal morbidity and 2) in  later life  risk of developing obesity and  3) these foetus will have propensity to develop in  later life  risk metabolic syndrome later in life. Glucose is the primary energy substrate for placenta and the fetus and fetoplacental glucose needs are met entirely by uptake from the maternal circulation. Approximately 55% of the glucose taken up from the uteroplcental circulation is metabolized by the placental and the remaining 45% is transferred to the fetus. Glucose stimulates fetal secretion of insulin and insulin- like growth factor-I(IGF-I), the two  primary fetal growth hormones, providing a direct link between fetal glucose availability and fetal growth. In addition, 4)  glucose can be converted to fat consistent with the possibility that increased glucose availability could increase fetal adiposity. Fetal growth is highly dependent on the availability of nutrients such as glucose; however, the mechanisms underlying fetal overgrowth in nondiabetic pregnancies of obese women remain to be fully established.

Fetal growth is highly dependent on the availability of nutrients such as glucose; however, the mechanisms underlying fetal overgrowth in nondiabetic pregnancies of obese women remain to be fully established.

Glucose transports (GLUT) mathematical modeling of placental glucose transport:- Placental glucose transport occurs via facilitated diffusion, mediated by glucose transports (GLUT). GLUT-I is highly expressed in the two plasma membranes of the a) syncytiotrophoblast (microvillous membrane,MVM] and b) basal membrane, [BM], These two mm are the   transporting epithelium of the human placenta. Because basal membrane  has been shown to have a much lower expression of GLUT-I than MVM(micro villous membrane) , the transfer across BM has been suggested to be the rate limiting step in maternofetal glucose transport. This model is supported by recent mathematical modeling of placental glucose transport and studies in in vitro perfused placenta.

basal membrane,of placenta ( BM) & its  GLUT-I expression and glucose transporter activity are increased in pregnancies complicated by diabetes, in particular in association to increased fetal growth. In addition, GLUT-9 is also expressed in term placentas and microvillous membrane(,MVM)- and basal membrane, (BM) GLUT-9 expression has been reported to be increased in pregnancies complicated by diabetes.

HAPO study makes a warning signal:__Increased fetal glucose availability could contribute to fetal overgrowth in obese women without diabetes. Because of the facilitated nature of maternal-fetal glucose transfer even a modest increase in maternal glucose levels may enhance glucose supply to the fetus, which is consistent with the continuous association between maternal glucose levels (below those diagnostic of diabetes) and increased birthweight reported by the HAPO study.

Obese women are at greater risk for glucose intolerance pregnancy because of their markedly lower insulin sensitivity as compared with lean control and intermittent minor elevations of maternal blood glucose cold contribute to stimulate fetal growth in these women. We hypothesized that (1) umbilical vein glucose and insulin levels and (2) placental glucose transporter expression and activity are positively correlated with early pregnancy maternal BMI and infant birthweight. To address this hypothesis we collected maternal and placentas form pregnancies of women with varying BMI giving birth to infants across the growth spectrum, from appropriate for their gestational age to large infants with birthweights greater than 4000 g. we determined maternal and fetal plasma glucose levels and studies GLUT-1 and GLUT-9 protein expression and glucose transport activity in isolated MVM and BM.

The impact of maternal BMI>-25 on placental glucose transporter activity appears on distinct from the effect of diabetes on placental glucose transport capacity. Specifically, BM glucose transport activity and GLUT-1 expression have been reported to be increased in large infants born to mothers with type-1 diabetes. Furthermore, the protein expression of GLUT-9 is increased in MVM and BM isolated from placentas of women with diabetes. The reason for these differences remains to be established but may be related to the more abnormal glucose metabolism in pregnant women with diabetes as compared with Ow/Ob women without diabetes.

Our study confirms previous reports that placental weight is increased in women with BMI>-25 and that fetal  glucose positively correlates to placental weight. Although we did not measure plausible that women with BMI>-25 with heavier placentas also had larger surface areas compared with placentas of normal BMI women, allowing for increased transport of glucose over the length of gestation would thus produce a heavier infant and would not be detectable by measuring glucose transporter activity in isolated plasma membrane vesicles.

Other possible explanations for fetal hyperglycemia of obese mothers in the absence of changes in placental glucose transport activity include a decreased metabolism of glucose in their placentas thus allowing for more glucose to be available to be transported to the fetus. Yet another possible explanation is that fetuses born to women with BMI>-25 may already exhibit a certain degree of insulin resistance at birth explaining their elevated fetal glucose and increasing umbilical vein insulin with birthweight. This hypothesis is supported by a recent study of insulin sensitivity in newborns of obese mothers.

The impact on maternal obesity on the placenta may show ethnic differences. For example, in a cohort of predominantly African- American women, maternal obesity was reported to be associated with placental macrophage accumulation and inflammation, whereas, a similar study in white women failed to find infiltration of immune cells in the placentas of obese women. Thus, it is possible that our findings in a predominantly Hispanic group of women may differ from other ethnic groups. Limitations of the study include using umbilical vein glucose and insulin as a surrogate for fetal glucose and insulin because this does not take into account fetal metabolism.