Objective We sought to evaluate inadequate gestational weight gain and fetal growth among overweight and obese women. Study Design We conducted an analysis of prospective singleton term pregnancies ...in which 1053 overweight and obese women gained >5 kg (14.4 ± 6.2 kg) or 188 who either lost or gained ≤5 kg (1.1 ± 4.4 kg). Birthweight, fat mass, and lean mass were assessed using anthropometry. Small for gestational age (SGA) was defined as ≤10th percentile of a standard US population. Univariable and multivariable analysis evaluated the association between weight change and neonatal morphometry. Results There was no significant difference in age, race, smoking, parity, or gestational age between groups. Weight loss or gain ≤5 kg was associated with SGA, 18/188 (9.6%) vs 51/1053 (4.9%); (adjusted odds ratio, 2.6; 95% confidence interval, 1.4–4.7; P = .003). Neonates of women who lost or gained ≤5 kg had lower birthweight (3258 ± 443 vs 3467 ± 492 g, P < .0001), fat mass (403 ± 175 vs 471 ± 193 g, P < .0001), and lean mass (2855 ± 321 vs 2995 ± 347 g, P < .0001), and smaller length, percent fat mass, and head circumference. Adjusting for diabetic status, prepregnancy body mass index, smoking, parity, study site, gestational age, and sex, neonates of women who gained ≤5 kg had significantly lower birthweight, lean body mass, fat mass, percent fat mass, head circumference, and length. There were no significant differences in neonatal outcomes between those who lost weight and those who gained ≤5 kg. Conclusion In overweight and obese women weight loss or gain ≤5 kg is associated with increased risk of SGA and decreased neonatal fat mass, lean mass, and head circumference.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective The purpose of this study was to estimate the association of pregravid body mass index (BMI), independent of 3-hour oral glucose tolerance test (OGTT) results, with pregnancy outcome. Study ...Design In this secondary analysis of a cohort of women with untreated mild gestational glucose intolerance, which was defined as a 50-g glucose loading test between 135 and 199 mg/dL and fasting glucose level of <95 mg/dL, we modeled the association between pregravid BMI, OGTT results, and both pregnancy complications and neonatal adiposity. Results Among 1250 participants, both pregravid BMI and glucose at hour 3 of the OGTT were associated with increased risk of gestational hypertension. Maternal pregravid BMI also was associated positively with large-for-gestational-age infants; both maternal BMI and fasting glucose were associated with birthweight z-score and neonatal fat mass. Conclusion Among women with untreated mild gestational glucose intolerance, pregravid BMI is associated with increased gestational hypertension, birthweight, and neonatal fat mass, independent of OGTT values.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The Pedersen hypothesis was formulated more than 50 years ago. Jorgen Pedersen primarily cared for women with type 1 diabetes. He suggested that fetal overgrowth was related to increased ...transplacental transfer of glucose, stimulating the release of insulin by the fetal beta cell and subsequent macrosomia. Optimal maternal glucose control decreased perinatal mortality and morbidity. However, over the ensuing decades, there have been increases in maternal obesity and subsequently gestational diabetes mellitus (GDM) and type 2 diabetes. The underlying pathophysiology of type 1 and GDM/type 2 diabetes are fundamentally different, type 1 diabetes being primarily a disorder of beta cell failure and type 2 diabetes/GDM including both insulin resistance and beta cell dysfunction. As such the metabolic milieu in which the developing fetus is exposed may be quite different in type 1 diabetes and obesity. In this review we examine the metabolic environment of obese diabetic women and lipid metabolism affecting fetal adiposity. The importance of understanding these issues relates to the increasing trends of obesity worldwide with perinatal programming of metabolic dysfunction in the offspring.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective The purpose of this study was to investigate the effects of insulin on human placental transcriptome and biological processes in first-trimester pregnancy. Study Design Maternal plasma and ...placenta villous tissue were obtained at the time of voluntary termination of pregnancy (7-12 weeks) from 17 lean (body mass index, 20.9 ± 1.5 kg/m2 ) and 18 obese (body mass index, 33.5 ± 2.6 kg/m2 ) women. Trophoblast cells were immediately isolated for in vitro treatment with insulin or vehicle. Patterns of global gene expression were analyzed using genome microarray profiling after hybridization to Human Gene 1.1 ST and real time reverse transcription–polymerase chain reaction. Results The global trophoblast transcriptome was qualitatively separated in insulin-treated vs untreated trophoblasts of lean women. The number of insulin-sensitive genes detected in the trophoblasts of lean women was 2875 ( P < .001). Maternal obesity reduced the number of insulin-sensitive genes recovered by 30-fold. Insulin significantly impaired several gene networks regulating cell cycle and cholesterol homeostasis but did not modify pathways related to glucose transport. Obesity associated with high insulin and insulin resistance, but not maternal hyperinsulinemia alone, impaired the global gene profiling of early gestation placenta, highlighting mitochondrial dysfunction and decreased energy metabolism. Conclusion We report for the first time that human trophoblast cells are highly sensitive to insulin regulation in early gestation. Maternal obesity associated with insulin resistance programs the placental transcriptome toward refractoriness to insulin with potential adverse consequences for placental structure and function.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The global epidemic of obesity has led to an increasing number of obese women of reproductive age. Obesity is associated with reduced fertility, and pregnancies complicated by maternal obesity are ...associated with adverse outcomes, including increased risk of gestational diabetes, pre-eclampsia, preterm birth, instrumental and caesarean births, infections, and post-partum haemorrhage. The medical and obstetric management of obese women is focused on identifying, addressing, and preventing some of these associated complications, and is a daunting challenge given the high percentage of patients with obesity and few therapeutic options proven to improve outcomes in this population. The UK's National Institute for Health and Care Excellence guidelines and the American College of Obstetricians and Gynecologists recommend that all pregnant women follow a healthy diet, and consider at least half an hour of moderate physical activity per day during pregnancy. However, although obese women are often directed to seek the advice of a nutritionist and to limit gestational weight gain, guidelines for the management of pregnancy and delivery in this high-risk group are lacking. The post-partum period represents an important opportunity to optimise maternal health before the next pregnancy. As many of the physiological changes of pregnancy associated with maternal obesity are present from early pregnancy onward, reducing maternal obesity before conception is probably the best strategy to decrease the health burden associated with maternal obesity.
Objective We evaluated whether improvements in pregnancy outcomes after treatment of mild gestational diabetes mellitus differed in magnitude on the basis of fetal gender. Study Design This is a ...secondary analysis of a masked randomized controlled trial of treatment for mild gestational diabetes mellitus. The results included preeclampsia or gestational hypertension, birthweight, neonatal fat mass, and composite adverse outcomes for both neonate (preterm birth, small for gestational age, or neonatal intensive care unit admission) and mother (labor induction, cesarean delivery, preeclampsia, or gestational hypertension). After stratification according to fetal gender, the interaction of gender with treatment status was estimated for these outcomes. Results Of the 469 pregnancies with male fetuses, 244 pregnancies were assigned randomly to treatment, and 225 pregnancies were assigned randomly to routine care. Of the 463 pregnancies with female fetuses, 233 pregnancies were assigned randomly to treatment, and 230 pregnancies were assigned randomly to routine care. The interaction of gender with treatment status was significant for fat mass ( P = .04) and birthweight percentile ( P = .02). Among women who were assigned to the treatment group, male offspring were significantly more likely to have both a lower birthweight percentile (50.7 ± 29.2 vs 62.5 ± 30.2 percentile; P < .0001) and less neonatal fat mass (487 ± 229.6 g vs 416.6 ± 172.8 g; P = .0005,) whereas these differences were not significant among female offspring. There was no interaction between fetal gender and treatment group with regard to other outcomes. Conclusion The magnitude of the reduction of a newborn's birthweight percentile and neonatal fat mass that were related to the treatment of mild gestational diabetes mellitus appears greater for male neonates.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Pregnancy and obesity Yogev, Yariv; Catalano, Patrick M
Obstetrics and gynecology clinics of North America,
06/2009, Volume:
36, Issue:
2
Journal Article
Peer reviewed
Obesity has become a worldwide epidemic: it is associated with increased rate of infertility and with many pregnancy complications. Moreover, it is associated with gestational diabetes mellitus, ...which increases the risk of these complications. As the prevalence of obesity is increasing, so is the number of women in the reproductive age who are overweight and obese. This article addresses issues concerning pregravid obesity and weight gain during pregnancy and their implication on gestational diabetes and pregnancy outcome.
Objective Changes in metabolic homeostasis in pregnant diabetic women are potential determinants of increased adiposity of the fetus. The aim of this study was to characterize diabetes ...mellitus-induced changes in genes for fetoplacental energy metabolism in relation to fetal adiposity. Study Design Placentas of women with type 1 diabetes mellitus, gestational diabetes mellitus (GDM), or no complications were analyzed by microarray profiling. The pattern of gene expression was assessed in primary placental cell cultures. Results Diabetes mellitus was associated with 49 alterations in gene expression at key steps in placental energy metabolism, with 67% of the alterations related to lipid pathways and 9% of the alterations related to glucose pathways. Preferential activation of lipid genes was observed in pregnancy with GDM. Type 1 diabetes mellitus induced fewer lipid modifications but an enhancement of glycosylation and acylation pathways. Oleate enhanced expression of genes for fatty acid esterification and the formation of lipid droplets 3 times as much as glucose in cultured placental cells. Conclusion These results point to fatty acids as preferential lipogenic substrates for placental cells and suggest that genes for fetoplacental lipid metabolism are enhanced selectively in GDM. The recruited genes may be instrumental in increasing transplacental lipid fluxes and the delivery of lipid substrates for fetal use.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background Weight gain in pregnancy is an essential physiologic adaptation that supports growth and development of a fetus and is distributed among lean mass that includes total body water and fat ...mass gains. Although gestational weight gain provides a source of energy for the mother and fetus, excess gestational weight gain may underlie reported associations between parity and future metabolic disorders and is linked to postpartum weight retention and insulin resistance. Although weight gain often is proposed as a modifiable variable to mitigate adverse maternal and offspring health outcomes, our knowledge of specific maternal body composition changes with weight gain and the potential metabolic consequences is limited. Furthermore, although gestational weight gain alters maternal body composition, the impact of excess weight gain on fat and lean mass is not well-studied. Understanding the accrual of fat and lean body mass may improve our understanding of the role of excessive gestational weight gain and metabolic dysfunction. Objective The purpose of our study was to quantify the relationship between gestational weight gain and maternal fat and lean body mass accrual and to compare fat and lean body mass accrual according to the 2009 Institute of Medicine Guidelines for Gestational Weight Gain in Pregnancy adherence. We hypothesized that exceeding current weight gain guidelines would be associated with greater fat, compared with lean body, mass accrual. Study Design This is a secondary analysis of a randomized controlled trial of 49 overweight/obese women; all 49 are included in this secondary analysis. Maternal weight and body composition were collected in early (13 0/6 to 16 6/7 weeks gestation) and late (34 0/7 to 36 6/7 weeks gestation) pregnancy with the use of air densitometry. Correlations were drawn between gestational weight gain and change in fat and lean body mass. We compared change in fat and lean body mass by adherence to the 2009 Institute of Medicine Guidelines for Gestational Weight Gain in Pregnancy. Nonparametric tests and chi-square analyses were performed; a probability value of <.05 was significant. Results Early pregnancy body mass index was 30.3 kg/m2 (interquartile range IQR, 28.5–35.2 kg/m2 ); women gained 9.0 kg (IQR, 5.3-13.2 kg). Overweight and obese women were equally likely to gain excess weight (48% vs 35%; P = .6). Weight gain correlated strongly with fat mass change ( r = 0.87; P < .001); women with excess vs adequate vs inadequate weight gain had greater fat mass change overall (5.2 IQR, 4.2-8.1 vs 0.2 IQR, –0.4-2.2 vs -2.7 IQR, –5.2- –0.7 kg, respectively; P < .001) and in all pairwise comparisons. Weight gain also correlated with lean body mass change ( r = 0.52; P = .001), but women with excess vs adequate weight gain had similar lean body mass change (8.4 IQR, 7.2–10.1 vs 7.8 IQR, 6.0–8.7 kg; P = .1). Conclusion Excess gestational weight gain is associated primarily with maternal fat, but not with lean body mass accrual. Our results may help explain the reason that excess gestational weight gain or fat mass accrual is associated with long-term obesity, metabolic dysfunction, and cardiovascular disease risk.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective The purpose of this study was to examine the association between gestational age (GA) at the time of treatment initiation for gestational diabetes mellitus (GDM) and maternal and perinatal ...outcomes. Study Design We conducted a secondary analysis of a multicenter randomized treatment trial of mild GDM in which women with mild GDM were assigned randomly to treatment vs usual care. The primary outcome of the original trial, as well as this analysis, was a composite perinatal adverse outcome that included neonatal hypoglycemia, hyperbilirubinemia, hyperinsulinemia, and perinatal death. Other outcomes that were examined included the frequency of large for GA, birthweight, neonatal intensive care unit admission, gestational hypertension/preeclampsia, and cesarean delivery. The interaction between GA at treatment initiation (stratified as 24-26, 27, 28, 29, and ≥30 weeks of gestation) and treatment group (treated vs routine care), with the outcomes of interest, was used to determine whether GA at treatment initiation was associated with outcome differences. Results Of 958 women whose cases were analyzed, those who initiated treatment at an earlier GA did not gain an additional treatment benefit compared with those who initiated treatment at a later GA (probability value for interaction with the primary outcome, .44). Similarly, there was no evidence that other outcomes were improved significantly by earlier initiation of GDM treatment (large for GA, P = .76; neonatal intensive care unit admission, P = .8; cesarean delivery, P = .82). The only outcome that had a significant interaction between GA and treatment was gestational hypertension/preeclampsia ( P = .04), although there was not a clear cut GA trend where this outcome improved with treatment. Conclusion Earlier initiation of treatment of mild GDM was not associated with stronger effect of treatment on perinatal outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK