Obesity is the most common medical condition in women of reproductive age. Obesity during pregnancy has short term and long term adverse consequences for both mother and child. Obesity causes problems with infertility, and in early gestation it causes spontaneous pregnancy loss and congenital anomalies. Metabolically, obese women have increased insulin resistance in early pregnancy, which becomes manifest clinically in late gestation as glucose intolerance and fetal overgrowth. At term, the risk of cesarean delivery and wound complications is increased. Postpartum, obese women have an increased risk of venous thromboembolism, depression, and difficulty with breast feeding. Because 50-60% of overweight or obese women gain more than recommended by Institute of Medicine gestational weight guidelines, postpartum weight retention increases future cardiometabolic risks and prepregnancy obesity in subsequent pregnancies. Neonates of obese women have increased body fat at birth, which increases the risk of childhood obesity. Although there is no unifying mechanism responsible for the adverse perinatal outcomes associated with maternal obesity, on the basis of the available data, increased prepregnancy maternal insulin resistance and accompanying hyperinsulinemia, inflammation, and oxidative stress seem to contribute to early placental and fetal dysfunction. We will review the pathophysiology underlying these data and try to shed light on the specific underlying mechanisms.

OBJECTIVE: Offspring of obese mothers have an increased risk for obesity and diabetes. The purpose of this study was to determine whether fetuses of obese women have increased obesity, insulin resistance, and markers of inflammation, supporting the concept of fetal programming. RESEARCH DESIGN AND METHODS: Fifty-three lean and 68 obese women with singleton term pregnancies were evaluated at elective cesarean delivery. Maternal and umbilical cord blood was obtained for measures of insulin resistance and cytokines. Neonatal body composition was estimated using anthropometric measurements within 24 h of delivery. RESULTS: The fetuses of obese mothers had greater percent body fat (13.1 ± 3.4 vs. 11.6 ± 2.9%, P = 0.02), homeostasis model assessment of insulin resistance (1.51 ± 0.86 vs. 1.06 ± 0.70, P = 0.003), cord leptin (14.5 ± 13.5 vs. 8.2 ± 4.7 ng/ml, P = 0.001), and interleukin-6 (3.5 ± 2.3 vs. 2.4 ± 1.4 pg/ml, P = 0.02) than fetuses of lean women. There was a strong positive correlation between fetal adiposity and insulin resistance (r = 0.32, P = 0.0008) as well as maternal pregravid BMI and fetal insulin resistance (r = 0.31, P = 0.007) even with adjustment for potential confounders. Cord leptin had a significant correlation with fetal insulin resistance (r = 0.30, P = 0.001), but there was no significant correlation between any other umbilical cord cytokines and fetal insulin resistance. CONCLUSIONS: These data suggest that maternal obesity creates a significant risk for the next generations with metabolic compromise already apparent at birth. Therefore, if prevention of obesity is the goal rather than treatment, the perinatal period may be an important focus of future research.

Background: Childhood obesity has increased significantly in recent decades.Objective: The objective was to examine the perinatal risk factors relate

Women with normal glucose tolerance pre‐gravid and developing gestational diabetes in late gestation have subclinical metabolic dysfunction prior to conception compared with women with normal glucose tolerance. Because of the 60% decrease in insulin sensitivity with normal pregnancy, these women develop clinical hyperglycaemia/gestational diabetes in late gestation. The metabolic dysfunction includes impaired insulin response, decreased hepatic suppression of glucose production during insulin infusion and decreased insulin‐stimulated glucose uptake in skeletal muscle, i.e. peripheral insulin resistance. The insulin resistance in normal glucose tolerance pregnancy is related to a decrease in the post‐receptor insulin signalling cascade, specifically decreased insulin receptor substrate 1 tyrosine phosphorylation. In women with normal glucose tolerance this is reversed post‐partum. In contrast, in gestational diabetes, in addition to the decrease in insulin receptor substrate 1 tyrosine phosphorylation, there is an additional decrease in tyrosine phosphorylation of the intracellular portion of the insulin receptor that is not related to the insulin receptor protein content. Post‐partum women with gestational diabetes, who had retention of gestational weight gain, had no significant improvement in insulin sensitivity and increased inflammation expressed as increased plasma and skeletal muscle tumour necrosis factor alpha. The increased inflammation or meta‐inflammation is a hallmark of obesity and during pregnancy develops in both white adipose tissue and placenta. Last gene array studies of placenta were associated with alterations in gene expression relating primarily to lipid in contrast to glucose metabolic pathways in gestational diabetes compared with Type 1 diabetes. Future studies are directed at decreasing inflammation prior to and during pregnancy using various lifestyle and nutritional interventions.

There has been a significant increase over the past few decades in the number of reproductive age women who are either overweight or obese. Overweight and obese women are at increased risk for having decreased insulin sensitivity as compared with lean or average weight women. The combination of obesity and decreased insulin sensitivity increases the long-term risk of these individuals developing the metabolic syndrome and associated problems of diabetes, hypertension, hyperlipidemia, and cardiovascular disorders. Because of the metabolic alterations during normal pregnancy, particularly the 60% decrease in insulin sensitivity, overweight and obese women are at increased risk of metabolic dysregulation in pregnancy, i.e. gestational diabetes, preeclampsia, and fetal overgrowth. Hence, pregnancy can be considered as a metabolic stress test for the future risk of the metabolic syndrome. In this review, we will review the underlying pathophysiology related to these disorders. Most importantly, an understanding of these risks provides an opportunity for prevention. For example, a planned pregnancy offers an opportunity to address weight control prior to conception. At the very least, by avoiding excessive weight gain during pregnancy, this may prevent excessive weight retention post partum. Finally, based on the concept of in utero programming, these lifestyle measures may not only have short- and long-term benefits for the woman but also for her offspring as well. Abstract There has been a significant increase over the past few decades in the number of reproductive age women who are either overweight or obese. Overweight and obese women are at increased risk for having decreased insulin sensitivity as compared with lean or average weight women. The combination of obesity and decreased insulin sensitivity increases the long-term risk of these individuals developing the metabolic syndrome and associated problems of diabetes, hypertension, hyperlipidemia, and cardiovascular disorders. Because of the metabolic alterations during normal pregnancy, particularly the 60% decrease in insulin sensitivity, overweight and obese women are at increased risk of metabolic dysregulation in pregnancy, i.e. gestational diabetes, preeclampsia, and fetal overgrowth. Hence, pregnancy can be considered as a metabolic stress test for the future risk of the metabolic syndrome. In this review, we will review the underlying pathophysiology related to these disorders. Most importantly, an understanding of these risks provides an opportunity for prevention. For example, a planned pregnancy offers an opportunity to address weight control prior to conception. At the very least, by avoiding excessive weight gain during pregnancy, this may prevent excessive weight retention post partum. Finally, based on the concept of in utero programming, these lifestyle measures may not only have short- and long-term benefits for the woman but also for her offspring as well.