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Objective: We aimed to explore: (i) the association of sedentary time (ST) and physical activity (PA) during pregnancy with the placental expression of genes related to glucose and lipid metabolism in pregnant women who are obese; (ii) maternal metabolic factors mediating changes in these placental transcripts; and (iii) cord blood markers related to the mRNAs mediating neonatal adiposity. Design: Multicentre randomised controlled trial. Setting: Hospitals in nine European countries. Population: A cohort of 112 pregnant women with placental tissue. Methods: Both ST and moderate‐to‐vigorous PA (MVPA) levels were measured objectively using accelerometry at three time periods during pregnancy. Main outcome measures: Placental mRNAs (FATP2, FATP3, FABP4, GLUT1 and PPAR‐γ) were measured with NanoString technology. Maternal and fetal metabolic markers and neonatal adiposity were assessed. Results: Longer periods of ST, especially in early to middle pregnancy, was associated with lower placental FATP2 and FATP3 expression (P < 0.05), whereas MVPA at baseline was inversely associated with GLUT1 mRNA (P = 0.02). Although placental FATP2 and FATP3 expression were regulated by the insulin–glucose axis (P < 0.05), no maternal metabolic marker mediated the association of ST/MVPA with placental mRNAs (P > 0.05). Additionally, placental FATP2 expression was inversely associated with cord blood triglycerides and free fatty acids (FFAs; P < 0.01). No cord blood marker mediated neonatal adiposity except for cord blood leptin, which mediated the effects of PPAR‐γ on neonatal sum of skinfolds (P < 0.05). Conclusions: In early to middle pregnancy, ST is associated with the expression of placental genes linked to lipid transport. PA is hardly related to transporter mRNAs. Strategies aimed at reducing sedentary behaviour during pregnancy could modulate placental gene expression, which may help to prevent unfavourable fetal and maternal pregnancy outcomes. Reducing sedentary behaviour in pregnancy might modulate placental expression of genes related to lipid metabolism in women who are obese. Reducing sedentary behaviour in pregnancy might modulate placental expression of genes related to lipid metabolism in women who are obese. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is a common finding in overweight/obese pregnant women and is associated with increased risk for adverse pregnancy outcome. Both maternal vitamin D deficiency and maternal obesity contribute to metabolic derangements in pregnancy. We aimed to assess the effects of vitamin D3 supplementation in pregnancy versus placebo on maternal and fetal lipids. Main inclusion criteria were: women <20 weeks’ gestation, BMI ≥ 29 kg/m2. Eligible women (n = 154) were randomized to receive vitamin D3 (1600 IU/day) or placebo. Assessments were performed <20, 24−28 and 35−37 weeks and at birth. Linear regression models were used to assess effects of vitamin D on maternal and cord blood lipids. In the vitamin D group significantly higher total 25-OHD and 25-OHD3 levels were found in maternal and cord blood compared with placebo. Adjusted regression models did not reveal any differences in triglycerides, LDL-C, HDL-C, free fatty acids, ketone bodies or leptin between groups. Neonatal sum of skinfolds was comparable between the two groups, but correlated positively with cord blood 25-OH-D3 (r = 0.34, p = 0.012). Vitamin D supplementation in pregnancy increases maternal and cord blood vitamin D significantly resulting in high rates of vitamin D sufficiency. Maternal and cord blood lipid parameters were unaffected by Vitamin D3 supplementation.

Studies on the relationship between vitamin D (VitD) and glucose homeostasis usually consider either total VitD or 25OHD3 but not 25OHD2 and epimers. We aimed to evaluate the cross-sectional association of VitD compounds with glucose homeostasis measurements in pregnant women with overweight/obesity participating in the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus Prevention study. Methods: The analysis included 912 women. Inclusion criteria: <20 weeks gestation, body mass index ≥29 kg/m2 and information on exposure and outcome variables at baseline. Measurements: A 75 g OGTT at <20, 24−28 and 35−37 weeks gestation (except if previous diabetes diagnosis). Exposure variables: 25OHD2, 25OHD3 and C3-epimer. Outcome variables: fasting and post-challenge insulin sensitivity and secretion indices, corresponding disposition indices (DI), plasma glucose at fasting and 1 and 2 h, hyperglycemia in pregnancy (HiP). Statistics: Multivariate regression analyses with adjustment. Results: Baseline VitD sufficiency was 66.3%. Overall, VitD compounds did not show strong associations with any glucose homeostasis measures. 25OHD3 showed direct significant associations with: FPG at <20 and 24−28 weeks (standardized β coefficient (β) 0.124, p = 0.030 and 0.111, p = 0.026 respectively), 2 h plasma glucose at 24−28 weeks (β 0.120, p = 0.018), and insulin sensitivity (1/HOMA-IR, β 0.127, p = 0.027) at 35−37 weeks; it showed an inverse association with fasting DI (QUCKI*HOMA-β) at <20 and 24−28 weeks (β −0.124, p = 0.045 and β −0.148, p = 0.004 respectively). 25OHD2 showed direct associations with post-challenge insulin sensitivity (Matsuda, β 0.149, p = 0.048) at 24−28 weeks) and post-challenge DI (Matsuda*Stumvoll phase 1) at 24−28 and 35−37 weeks (β 0.168, p = 0.030, β 0.239, p = 0.006). No significant association with C3-epimer was observed at any time period. Conclusions: In these women with average baseline VitD in sufficiency range, VitD compounds did not show clear beneficial associations with glucose homeostasis measures.

Gestational weight gain is necessary for the normal fetus development, in fact a series of studies have evidenced that both low and excessive gestational weight gain is associated with negative fetal-neonatal outcomes. So, evidences on the optimal gestational weight gain across the ranges of the pre-pregnancy maternal body mass index are necessary. In this context, while for normal weight and underweight the recommendations of IOM are clearly stated and supported by well designed and conducted clinical studies, those for the obese pregnant women are even today debated. Pre-pregnancy obesity is associated with high risk to develop hypertension, gestational diabetes, cesarean section and high birth weight. The Institute of Medicine guidelines, in 2009, recommended that women with obesity gain 11-20 lb at a rate of 0.5 lb/week during the second and third trimesters of pregnancy. Successively, taking into account a series of meta-analysis, the American College of Obstetricians and Gynecologists emphasized that the IOM weight gain targets for obese pregnant women are too high. However the high risk to have babies small for gestational age, related to a low weight gain or a losing of weight during pregnancy, has also been demonstrated. More recent studies have taken into consideration the maternal and fetal outcomes of obese pregnant women with different obesity class (I,II,III) and different weight gain during pregnancy. The analysis of these studies, discussed in this narrative review, show that the appropriate gestational weight gain should be personalized considering the three obesity class; furthermore both an upper and lower limit of gestational weight gain should be reconsidered in order to prevent the negative maternal and fetal outcomes in these women., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: We aimed to explore: (i) the association of sedentary time (ST) and physical activity (PA) during pregnancy with the placental expression of genes related to glucose and lipid metabolism in pregnant women who are obese; (ii) maternal metabolic factors mediating changes in these placental transcripts; and (iii) cord blood markers related to the mRNAs mediating neonatal adiposity., Design: Multicentre randomised controlled trial., Setting: Hospitals in nine European countries., Population: A cohort of 112 pregnant women with placental tissue., Methods: Both ST and moderate-to-vigorous PA (MVPA) levels were measured objectively using accelerometry at three time periods during pregnancy., Main Outcome Measures: Placental mRNAs (FATP2, FATP3, FABP4, GLUT1 and PPAR-γ) were measured with NanoString technology. Maternal and fetal metabolic markers and neonatal adiposity were assessed., Results: Longer periods of ST, especially in early to middle pregnancy, was associated with lower placental FATP2 and FATP3 expression (P < 0.05), whereas MVPA at baseline was inversely associated with GLUT1 mRNA (P = 0.02). Although placental FATP2 and FATP3 expression were regulated by the insulin-glucose axis (P < 0.05), no maternal metabolic marker mediated the association of ST/MVPA with placental mRNAs (P > 0.05). Additionally, placental FATP2 expression was inversely associated with cord blood triglycerides and free fatty acids (FFAs; P < 0.01). No cord blood marker mediated neonatal adiposity except for cord blood leptin, which mediated the effects of PPAR-γ on neonatal sum of skinfolds (P < 0.05)., Conclusions: In early to middle pregnancy, ST is associated with the expression of placental genes linked to lipid transport. PA is hardly related to transporter mRNAs. Strategies aimed at reducing sedentary behaviour during pregnancy could modulate placental gene expression, which may help to prevent unfavourable fetal and maternal pregnancy outcomes., Tweetable Abstract: Reducing sedentary behaviour in pregnancy might modulate placental expression of genes related to lipid metabolism in women who are obese., (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Aims: To describe the metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes., Methods: We performed a post hoc analysis using data from the Vitamin D And Lifestyle Intervention for gestational diabetes prevention (DALI) trial conducted across nine European countries (2012-2014). In women with a BMI ≥29 kg/m 2 , insulin resistance and secretion were estimated from the oral glucose tolerance test values performed before 20 weeks, using homeostatic model assessment of insulin resistance and Stumvoll first-phase indices, respectively. Women with early gestational diabetes, defined by the International Association of Diabetes and Pregnancy Study Groups criteria, were classified into three groups: GDM-R (above-median insulin resistance alone), GDM-S (below-median insulin secretion alone), and GDM-B (combination of both) and the few remaining women were excluded., Results: Compared with women in the normal glucose tolerance group (n = 651), women in the GDM-R group (n = 143) had higher fasting and post-load glucose values and insulin levels, with a greater risk of having large-for-gestational age babies [adjusted odds ratio 3.30 (95% CI 1.50-7.50)] and caesarean section [adjusted odds ratio 2.30 (95% CI 1.20-4.40)]. Women in the GDM-S (n = 37) and GDM-B (n = 56) groups had comparable pregnancy outcomes with those in the normal glucose tolerance group., Conclusions: In overweight and obese women with early gestational diabetes, higher degree of insulin resistance alone was more likely to be associated with adverse pregnancy outcomes than lower insulin secretion alone or a combination of both., (© 2020 Diabetes UK.)

Background/objectives: Obese pregnant women are at high risk of developing gestational diabetes mellitus (GDM), which might be reduced by sufficient physical activity (PA) and reduced sedentary time (ST). We assessed whether PA and ST are longitudinally associated with the glucose-insulin axis in obese pregnant women., Subjects/methods: In this secondary analysis of the DALI (vitamin D And Lifestyle Intervention for gestational diabetes mellitus prevention) study, pregnant women, <20 weeks gestation, with a pre-pregnancy body mass index (BMI) ≥ 29 kg/m 2 , without GDM on entry were included. Time spent in moderate-to-vigorous PA (MVPA) and ST were measured objectively with accelerometers at <20 weeks, 24-28 weeks and 35-37 weeks of gestation. Fasting glucose (mmol/l) and insulin (mU/l), insulin resistance (HOMA-IR) and first-phase and second-phase insulin release (Stumvoll first and second phase) were assessed at the same time. Linear mixed regression models were used to calculate between-participant differences and within-participant changes over time. Analyses were adjusted for gestational age, randomisation, pre-pregnancy BMI, education and age. MVPA, Insulin, HOMA-IR and Stumvoll first and second phase were log-transformed for analyses due to skewness., Results: 232 women were included in the analysis. Concerning differences between participants, more ST was associated with higher fasting glucose (Estimate: 0.008; 95% CI: 0.002, 0.014), fasting insulin (0.011; 0.002, 0.019), HOMA-IR (0.012; 0.004, 0.021) and Stumvoll first and second phase (0.008; 0.001, 0.014 and 0.007; 0.001, 0.014). Participants with more MVPA had lower Stumvoll first and second phase (-0.137; -0.210, -0.064 and -0.133; -0.202, -0.063). Concerning changes over time, an increase in ST during gestation was associated with elevated Stumvoll first and second phase (0.006; 0.000, 0.011)., Conclusions: As the glucose-insulin axis is more strongly associated with ST than MVPA in our obese population, pregnant women could be advised to reduce ST in addition to increasing MVPA. Moreover, our findings suggest that behaviour change interventions aiming at GDM risk reduction should start in early or pre-pregnancy.

Background: Although previous studies evaluated the association of maternal health parameters with neonatal adiposity, little is known regarding the complexity of the relationships among different maternal health parameters throughout pregnancy and its impact on neonatal adiposity., Objectives: To evaluate the direct and indirect associations between maternal insulin resistance during pregnancy, in women with obesity, and neonatal adiposity. In addition, associations between maternal fasting glucose, triglycerides (TG), non-esterified fatty acids (NEFA), and neonatal adiposity were also assessed., Methods: This is a longitudinal, secondary analysis of the DALI study, an international project conducted in nine European countries with pregnant women with obesity. Maternal insulin resistance (HOMA-IR), fasting glucose, TG, and NEFA were measured three times during pregnancy (<20, 24-28, and 35-37 weeks of gestation). Offspring neonatal adiposity was estimated by the sum of four skinfolds. Structural equation modelling was conducted to evaluate the direct and indirect relationships among the variables of interest., Results: Data on 657 mother-infant pairs (50.7% boys) were analysed. Neonatal boys exhibited lower mean sum of skinfolds compared to girls (20.3 mm, 95% CI 19.7, 21.0 vs 21.5 mm, 95% CI 20.8, 22.2). In boys, maternal HOMA-IR at <20 weeks was directly associated with neonatal adiposity (β = 0.35 mm, 95% CI 0.01, 0.70). In girls, maternal HOMA-IR at 24-28 weeks was only indirectly associated with neonatal adiposity, which implies that this association was mediated via maternal HOMA-IR, glucose, triglycerides, and NEFA during pregnancy (β = 0.26 mm, 95% CI 0.08, 0.44)., Conclusions: The timing of the role of maternal insulin resistance on neonatal adiposity depends on fetal sex. Although the association was time-dependent, maternal insulin resistance was associated with neonatal adiposity in both sexes., (© 2020 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Aims: To investigate the performance of early pregnancy HbA 1c for predicting gestational diabetes mellitus (GDM) and adverse pregnancy outcomes in obese women., Methods: Post hoc analysis using data from the Vitamin D And Lifestyle Intervention for GDM prevention trials conducted across 9 European countries (2012-2014). Pregnant women (BMI ≥ 29 kg/m 2 ) underwent a baseline HbA 1c and oral glucose tolerance tests at < 20 weeks, 24-28 weeks, and 35-37 weeks. Women with GDM were referred for treatment., Results: Among the 869 women tested, the prevalence of GDM was 25.9% before 20 weeks, with a further 8.6% at 24-28 weeks. The areas under the curves for HbA 1c at the two time points were 0.55 (0.50-0.59) and 0.54 (0.47-0.61), respectively. An early HbA 1c  ≥ 5.7% (39 mmol/mol) (N = 111) showed low sensitivity (18.2%) with 89.1% specificity for GDM before 20 weeks, at 24-28 weeks (sensitivity of 8.0% and specificity of 88.6% after excluding early GDM), and throughout gestation (sensitivity of 15.9% and specificity of 89.4%). The ≥ 5.7% (39 mmol/mol) threshold was significantly associated with concurrent GDM before 20 weeks (adjusted OR (aOR) 2.77(1.39-5.51)) and throughout gestation (aOR 1.72 (1.02-2.89)), but not adverse pregnancy outcomes., Conclusions: Early pregnancy HbA 1c is of limited use for predicting either GDM or adverse outcomes in overweight/obese European women., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: To investigate the importance of time in pregnancy and neonatal sex on the association between maternal metabolic parameters and neonatal sum of skinfolds., Methods: This was a longitudinal, secondary analysis of the vitamin D and lifestyle intervention for gestational diabetes mellitus study, conducted in nine European countries during 2012 to 2015. Pregnant women with a pre-pregnancy body mass index (BMI) of ≥29 kg/m 2 were invited to participate. We measured 14 maternal metabolic parameters at three times during pregnancy: <20 weeks, 24 to 28 weeks, and 35 to 37 weeks of gestation. The sum of four skinfolds assessed within 2 days after birth was the measure of neonatal adiposity., Results: In total, 458 mother-infant pairs (50.2% female infants) were included. Insulin resistance (fasting insulin and HOMA-index of insulin resistance) in early pregnancy was an important predictor for boys' sum of skinfolds, in addition to fasting glucose and maternal adiposity (leptin, BMI and neck circumference) throughout pregnancy. In girls, maternal lipids (triglycerides and fatty acids) in the first half of pregnancy were important predictors of sum of skinfolds, as well as fasting glucose in the second half of pregnancy., Conclusions: Associations between maternal metabolic parameters and neonatal adiposity vary between different periods during pregnancy. This time-dependency is different between sexes, suggesting different growth strategies., (© 2020 The Authors. Pediatric Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background & Aims: As vitamin D deficiency is associated with an increased risk of gestational diabetes mellitus (GDM), we aimed to test vitamin D supplementation as a strategy to reduce GDM risk (evaluated after fasting plasma glucose (FPG), insulin resistance and weight gain) in pregnant overweight/obese women., Methods: The DALI vitamin D multicenter study enrolled women with prepregnancy body mass index (BMI) ≥ 29 kg/m 2 , ≤19 + 6 weeks of gestation and without GDM. Participants were randomized to receive 1600 IU/day vitamin D3 or placebo (each with or without lifestyle intervention) on top of (multi)vitamins supplements. Women were assessed for vitamin D status (sufficiency defined as serum 25-hydroxyvitamin D (25(OH)D) ≥ 50 nmol/l), FPG, insulin resistance and weight at baseline, 24-28 and 35-37 weeks. Linear or logistic regression analyses were performed to assess intervention effects., Results: Average baseline serum 25(OH)D was ≥50 nmol/l across all study sites. In the vitamin D intervention arm (n = 79), 97% of participants achieved target serum vitamin 25(OH)D (≥50 nmol/l) at 24-28 weeks and 98% at 35-37 weeks vs 74% and 78% respectively in the placebo arm (n = 75, p < 0.001). A small but significantly lower FPG (-0.14 mmol/l; CI95 -0.28, -0.00) was observed at 35-37 weeks with the vitamin D intervention without any additional difference in metabolic status, perinatal outcomes or adverse event rates., Conclusion: In the DALI vitamin D trial, supplementation with 1600 IU vitamin D3/day achieved vitamin D sufficiency in virtually all pregnant women and a small effect in FPG at 35-37 weeks. The potential of vitamin D supplementation for GDM prevention in vitamin D sufficient populations appears to be limited., Trial Registration Number: ISRCTN70595832., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objective: In our randomized controlled trial, we investigated the impact of healthy eating (HE) aiming for restricted gestational weight gain (GWG) and physical activity (PA) interventions on maternal and neonatal lipid metabolism., Research Design and Methods: Obese pregnant women ( n = 436) were included before 20 weeks' gestation and underwent glucose testing (oral glucose tolerance test) and lipid profiling at baseline and 24-28 and 35-37 gestational weeks after an at least 10-h overnight fast. This secondary analysis had a factorial design with comparison of HE ( n = 221) versus no HE ( n = 215) and PA ( n = 218) versus no PA ( n = 218). Maternal changes in triglycerides (TG), LDL cholesterol, HDL cholesterol, free fatty acids (FFAs), and leptin from baseline to end of pregnancy and neonatal outcomes were analyzed using general linear models with adjustment for relevant parameters., Results: At 24-28 weeks' gestation, FFAs (mean ± SD, 0.60 ± 0.19 vs. 0.55 ± 0.17 mmol/L, P < 0.01) were increased after adjustment for FFA at baseline, maternal age, BMI at time of examination, gestational week, insulin resistance, self-reported food intake, self-reported physical activity, and maternal smoking, and GWG was lower (3.3 ± 2.6 vs. 4.3 ± 2.8 kg, P < 0.001, adjusted mean differences -1.0 [95% CI -1.5; -0.5]) in HE versus no HE. Fasting glucose levels (4.7 ± 0.4 vs. 4.6 ± 0.4 mmol/L, P < 0.05) and 3-β-hydroxybutyrate (3BHB) (0.082 ± 0.065 vs. 0.068 ± 0.067 mmol/L, P < 0.05) were higher in HE. Significant negative associations between carbohydrate intake and FFA, 3BHB, and fasting glucose at 24-28 weeks' gestation were observed. No differences between groups were found in oral glucose tolerance test or leptin or TG levels at any time. Furthermore, in PA versus no PA, no similar changes were found. In cord blood, elevated FFA levels were found in HE after full adjustment (0.34 ± 0.22 vs. 0.29 ± 0.16 mmol/L, P = 0.01)., Conclusions: HE intervention was associated with reduced GWG, higher FFAs, higher 3BHB, and higher fasting glucose at 24-28 weeks of gestation, suggesting induction of lipolysis. Increased FFA was negatively associated with carbohydrate intake and was also observed in cord blood. These findings support the hypothesis that maternal antenatal dietary restriction including carbohydrates is associated with increased FFA mobilization., (© 2019 by the American Diabetes Association.)

Aims/hypothesis: Offspring of obese women are at increased risk of features of the metabolic syndrome, including obesity and diabetes. Lifestyle intervention in pregnancy might reduce adverse effects of maternal obesity on neonatal adiposity., Methods: In the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus (GDM) Prevention (DALI) lifestyle trial, 436 women with a BMI ≥29 kg/m 2 were randomly assigned to counselling on healthy eating (HE), physical activity (PA) or HE&PA, or to usual care (UC). In secondary analyses of the lifestyle trial, intervention effects on neonatal outcomes (head, abdominal, arm and leg circumferences and skinfold thicknesses, estimated fat mass, fat percentage, fat-free mass and cord blood leptin) were assessed using multilevel regression analyses. Mediation of intervention effects by lifestyle and gestational weight gain was assessed., Results: Outcomes were available from 334 neonates. A reduction in sum of skinfolds (-1.8 mm; 95% CI -3.5, -0.2; p = 0.03), fat mass (-63 g; 95% CI -124, -2; p = 0.04), fat percentage (-1.2%; 95% CI -2.4%, -0.04%; p = 0.04) and leptin (-3.80 μg/l; 95% CI -7.15, -0.45; p = 0.03) was found in the HE&PA group, and reduced leptin in female neonates in the PA group (-5.79 μg/l; 95% CI -11.43, -0.14; p = 0.05) compared with UC. Reduced sedentary time, but not gestational weight gain, mediated intervention effects on leptin in both the HE&PA and PA groups., Conclusions/interpretation: The HE&PA intervention resulted in reduced adiposity in neonates. Reduced sedentary time seemed to drive the intervention effect on cord blood leptin. Implications for future adiposity and diabetes risk of the offspring need to be elucidated., Trial Registration: ISRCTN70595832.

A better understanding of what drives behaviour change in obese pregnant overweight women is needed to improve the effectiveness of lifestyle interventions in this group at risk for gestational diabetes (GDM). Therefore, we assessed which factors mediated behaviour change in the Vitamin D and Lifestyle Intervention for GDM Prevention (DALI) Lifestyle Study. A total of 436 women, with pre-pregnancy body mass index ≥29 kg/m², ≤19 + 6 weeks of gestation and without GDM, were randomised for counselling based on motivational interviewing (MI) on healthy eating and physical activity, healthy eating alone, physical activity alone, or to a usual care group. Lifestyle was measured at baseline, and at 24⁻28 and 35⁻37 weeks of gestation. Outcome expectancy, risk perception, task self-efficacy and social support were measured at those same time points and considered as possible mediators of intervention effects on lifestyle. All three interventions resulted in increased positive outcome expectancy for GDM reduction, perceived risk to the baby and increased task self-efficacy. The latter mediated intervention effects on physical activity and reduced sugared drink consumption. In conclusion, our MI intervention was successful in increasing task self-efficacy, which was related to improved health behaviours.

Excess gestational weight gain (GWG) is associated with the development of gestational diabetes mellitus (GDM). Lifestyle trials have not achieved much GWG limitation, and have largely failed to prevent GDM. We compared the effect of substantial GWG limitation on maternal GDM risk. Pregnant women with a body mass index (BMI) ≥29 kg/m² <20 weeks gestation without GDM ( n = 436) were randomized, in a multicenter trial, to usual care (UC), healthy eating (HE), physical activity (PA), or HE and PA lifestyle interventions. GWG over the median was associated with higher homeostasis model assessment insulin resistance (HOMA-IR) and insulin secretion (Stumvoll phases 1 and 2), a higher fasting plasma glucose (FPG) at 24⁻28 weeks (4.66 ± 0.43 vs. 4.61 ± 0.40 mmol/L, p < 0.01), and a higher rate of caesarean section (38% vs. 27% p < 0.05). The GWG over the median at 35⁻37 weeks was associated with a higher rate of macrosomia (25% vs. 16%, p < 0.05). A post hoc comparison among women from the five sites with a GWG difference >3 kg showed no significance difference in glycaemia or insulin resistance between HE and PA, and UC. We conclude that preventing even substantial increases in GWG after the first trimester has little effect on maternal glycaemia. We recommend randomized controlled trials of effective lifestyle interventions, starting in or before the first trimester.

Objective: Risk factors are widely used to identify women at risk for gestational diabetes mellitus (GDM) without clear distinction by pregnancy period or oral glucose tolerance test (OGTT) time points. We aimed to assess the clinical risk factors for Hyperglycemia in pregnancy (HiP) differentiating by these two aspects., Design and Methods: Nine hundred seventy-one overweight/obese pregnant women, enrolled in the DALI study for preventing GDM. OGTTs were performed at ≤19 + 6, 24-28 and 35-37 weeks (IADPSG/WHO2013 criteria). Women with GDM or overt diabetes at one time point did not proceed to further OGTTs. Potential independent variables included baseline maternal and current pregnancy characteristics., Statistical Analysis: Multivariate logistic regression., Results: Clinical characteristics independently associated with GDM/overt diabetes were at ≤19 + 6 weeks, previous abnormal glucose tolerance (odds ratio (OR): 3.11; 95% CI: 1.41-6.85), previous GDM (OR: 2.22; 95% CI: 1.20-4.11), neck circumference (NC) (OR: 1.58; 95% CI: 1.06-2.36 for the upper tertile), resting heart rate (RHR, OR: 1.99; 95% CI: 1.31-3.00 for the upper tertile) and recruitment site; at 24-28 weeks, previous stillbirth (OR: 2.92; 95% CI: 1.18-7.22), RHR (OR: 3.32; 95% CI: 1.70-6.49 for the upper tertile) and recruitment site; at 35-37 weeks, maternal height (OR: 0.41; 95% CI: 0.20-0.87 for upper tertile). Clinical characteristics independently associated with GDM/overt diabetes differed by OGTT time point (e.g. at ≤19 + 6 weeks, NC was associated with abnormal fasting but not postchallenge glucose)., Conclusion: In this population, most clinical characteristics associated with GDM/overt diabetes were non-modifiable and differed by pregnancy period and OGTT time point. The identified risk factors can help define the target population for future intervention trials., (© 2018 European Society of Endocrinology.)

Background: Gestational diabetes mellitus (GDM) is associated with perinatal health risks to both mother and offspring, and represents a large economic burden. The DALI study is a multicenter randomized controlled trial, undertaken to add to the knowledge base on the effectiveness of interventions for pregnant women at increased risk for GDM. The purpose of this study was to evaluate the cost-effectiveness of the healthy eating and/or physical activity promotion intervention compared to usual care among pregnant women at increased risk of GDM from a societal perspective., Methods: An economic evaluation was performed alongside a European multicenter-randomized controlled trial. A total of 435 pregnant women at increased risk of GDM in primary and secondary care settings in nine European countries, were recruited and randomly allocated to a healthy eating and physical activity promotion intervention (HE + PA intervention), a healthy eating promotion intervention (HE intervention), or a physical activity promotion intervention (PA intervention). Main outcome measures were gestational weight gain, fasting glucose, insulin resistance (HOMA-IR), quality adjusted life years (QALYs), and societal costs., Results: Between-group total cost and effect differences were not significant, besides significantly less gestational weight gain in the HE + PA group compared with the usual care group at 35-37 weeks (-2.3;95%CI:-3.7;-0.9). Cost-effectiveness acceptability curves indicated that the HE + PA intervention was the preferred intervention strategy. At 35-37 weeks, it depends on the decision-makers' willingness to pay per kilogram reduction in gestational weight gain whether the HE + PA intervention is cost-effective for gestational weight gain, whereas it was not cost-effective for fasting glucose and HOMA-IR. After delivery, the HE + PA intervention was cost-effective for QALYs, which was predominantly caused by a large reduction in delivery-related costs., Conclusions: Healthy eating and physical activity promotion was found to be the preferred strategy for limiting gestational weight gain. As this intervention was cost-effective for QALYs after delivery, this study lends support for broad implementation., Trial Registration: ISRCTN ISRCTN70595832 . Registered 2 December 2011.