Elisabetta Petrella

Myo-inositol Supplementation for Prevention of Gestational Diabetes in Obese Pregnant Women: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether myo-inositol supplementation, an insulin sensitizer, reduces the rate of gestational diabetes mellitus (GDM) and lowers insulin resistance in obese pregnant women. METHODS: In an open-label, randomized trial, myo-inositol (2 g plus 200 micrograms folic acid twice a day) or placebo (200 micrograms folic acid twice a day) was administered from the first trimester to delivery in pregnant obese women (prepregnancy body mass index 30 or greater. We calculated that 101 women in each arm would be required to demonstrate a 65% GDM reduction in the myo-inositol group with a statistical power of 80% (&agr;=0.05). The primary outcomes were the incidence of GDM and the change in insulin resistance from enrollment until the diagnostic oral glucose tolerance test. RESULTS: From January 2011 to April 2014, 220 pregnant women at 12–13 weeks of gestation were randomized at two Italian university hospitals, 110 to myo-inositol and 110 to placebo. Most characteristics were similar between groups. The GDM rate was significantly reduced in the myo-inositol group compared with the control group, 14.0% compared with 33.6%, respectively (P=.001; odds ratio 0.34, 95% confidence interval 0.17–0.68). Furthermore, women treated with myo-inositol showed a significantly greater reduction in the homeostasis model assessment of insulin resistance compared with the control group, −1.0±3.1 compared with 0.1±1.8 (P=.048). CONCLUSION: Myo-inositol supplementation, started in the first trimester, in obese pregnant women seems to reduce the incidence in GDM through a reduction of insulin resistance. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01047982.

Gestational weight gain in overweight and obese women enrolled in a healthy lifestyle and eating habits program

Abstract Objectives: To determine whether changes in lifestyle in women with BMI > 25 could decrease gestational weight gain and unfavorable pregnancy outcomes. Methods: Women with BMI > 25 were randomized at 1st trimester to no intervention or a Therapeutic Lifestyle Changes (TLC) Program including diet (overweight: 1700 kcal/day, obese: 1800 kcal/day) and mild physical activity (30 min/day, 3 times/week). At baseline and at the 36th week women filled-in a Food Frequency Questionnaire. Outcomes: gestational weight gain, gestational diabetes mellitus, gestational hypertension, preterm delivery. Data stratified by BMI categories. Results: Socio-demographic features were similar between groups (TLC: 33 cases, Controls: 28 cases). At term, gestational weight gain in obese women randomized to TLC group was lower (6.7 ± 4.3 kg) versus controls (10.1 ± 5.6 kg, p = 0.047). Gestational diabetes mellitus, gestational hypertension and preterm delivery were also significantly lower. TLC was an independent factor in preventing gestational weight gain, gestational diabetes mellitus, gestational hypertension. Significant changes in eating habits occurred in the TLC group, which increased the number of snacks, the intake of fruits–vegetables and decreased the consumption of sugar. Conclusions: A caloric restriction associated to changes in eating behavior and constant physical activity, is able to reduce gestational weight gain and related pregnancy complications in obese women.

Effects of antenatal diet and physical activity on maternal and fetal outcomes: Individual patient data meta-analysis and health economic evaluation

BACKGROUND Diet- and physical activity-based interventions in pregnancy have the potential to alter maternal and child outcomes. OBJECTIVES To assess whether or not the effects of diet and lifestyle interventions vary in subgroups of women, based on maternal body mass index (BMI), age, parity, Caucasian ethnicity and underlying medical condition(s), by undertaking an individual patient data (IPD) meta-analysis. We also evaluated the association of gestational weight gain (GWG) with adverse pregnancy outcomes and assessed the cost-effectiveness of the interventions. DATA SOURCES MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects and Health Technology Assessment database were searched from October 2013 to March 2015 (to update a previous search). REVIEW METHODS Researchers from the International Weight Management in Pregnancy Collaborative Network shared the primary data. For each intervention type and outcome, we performed a two-step IPD random-effects meta-analysis, for all women (except underweight) combined and for each subgroup of interest, to obtain summary estimates of effects and 95% confidence intervals (CIs), and synthesised the differences in effects between subgroups. In the first stage, we fitted a linear regression adjusted for baseline (for continuous outcomes) or a logistic regression model (for binary outcomes) in each study separately; estimates were combined across studies using random-effects meta-analysis models. We quantified the relationship between weight gain and complications, and undertook a decision-analytic model-based economic evaluation to assess the cost-effectiveness of the interventions. RESULTS Diet and lifestyle interventions reduced GWG by an average of 0.70 kg (95% CI -0.92 to -0.48 kg; 33 studies, 9320 women). The effects on composite maternal outcome [summary odds ratio (OR) 0.90, 95% CI 0.79 to 1.03; 24 studies, 8852 women] and composite fetal/neonatal outcome (summary OR 0.94, 95% CI 0.83 to 1.08; 18 studies, 7981 women) were not significant. The effect did not vary with baseline BMI, age, ethnicity, parity or underlying medical conditions for GWG, and composite maternal and fetal outcomes. Lifestyle interventions reduce Caesarean sections (OR 0.91, 95% CI 0.83 to 0.99), but not other individual maternal outcomes such as gestational diabetes mellitus (OR 0.89, 95% CI 0.72 to 1.10), pre-eclampsia or pregnancy-induced hypertension (OR 0.95, 95% CI 0.78 to 1.16) and preterm birth (OR 0.94, 95% CI 0.78 to 1.13). There was no significant effect on fetal outcomes. The interventions were not cost-effective. GWG, including adherence to the Institute of Medicine-recommended targets, was not associated with a reduction in complications. Predictors of GWG were maternal age (summary estimate -0.10 kg, 95% CI -0.14 to -0.06 kg) and multiparity (summary estimate -0.73 kg, 95% CI -1.24 to -0.23 kg). LIMITATIONS The findings were limited by the lack of standardisation in the components of intervention, residual heterogeneity in effects across studies for most analyses and the unavailability of IPD in some studies. CONCLUSION Diet and lifestyle interventions in pregnancy are clinically effective in reducing GWG irrespective of risk factors, with no effects on composite maternal and fetal outcomes. FUTURE WORK The differential effects of lifestyle interventions on individual pregnancy outcomes need evaluation. STUDY REGISTRATION This study is registered as PROSPERO CRD42013003804. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Dietary interventions in overweight and obese pregnant women: a systematic review of the content, delivery, and outcomes of randomized controlled trials.

CONTEXT Interventions targeting maternal obesity are a healthcare and public health priority. OBJECTIVE The objective of this review was to evaluate the adequacy and effectiveness of the methodological designs implemented in dietary intervention trials for obesity in pregnancy. DATA SOURCES A systematic review of the literature, consistent with PRISMA guidelines, was performed as part of the International Weight Management in Pregnancy collaboration. STUDY SELECTION Thirteen randomized controlled trials, which aimed to modify diet and physical activity in overweight and obese pregnant women, were identified. DATA SYNTHESIS There was significant variability in the content, delivery, and dietary assessment methods of the dietary interventions examined. A number of studies demonstrated improved dietary behavior in response to diet and/or lifestyle interventions. Nine studies reduced gestational weight gain. CONCLUSION This review reveals large methodological variability in dietary interventions to control gestational weight gain and improve clinical outcomes in overweight and obese pregnant women. This lack of consensus limits the ability to develop clinical guidelines and apply the evidence in clinical practice.

Study protocol: differential effects of diet and physical activity based interventions in pregnancy on maternal and fetal outcomes-individual patient data (IPD) meta-analysis and health economic evaluation

BackgroundPregnant women who gain excess weight are at risk of complications during pregnancy and in the long term. Interventions based on diet and physical activity minimise gestational weight gain with varied effect on clinical outcomes. The effect of interventions on varied groups of women based on body mass index, age, ethnicity, socioeconomic status, parity, and underlying medical conditions is not clear. Our individual patient data (IPD) meta-analysis of randomised trials will assess the differential effect of diet- and physical activity-based interventions on maternal weight gain and pregnancy outcomes in clinically relevant subgroups of women.Methods/designRandomised trials on diet and physical activity in pregnancy will be identified by searching the following databases: MEDLINE, EMBASE, BIOSIS, LILACS, Pascal, Science Citation Index, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Health Technology Assessment Database. Primary researchers of the identified trials are invited to join the International Weight Management in Pregnancy Collaborative Network and share their individual patient data. We will reanalyse each study separately and confirm the findings with the original authors. Then, for each intervention type and outcome, we will perform as appropriate either a one-step or a two-step IPD meta-analysis to obtain summary estimates of effects and 95% confidence intervals, for all women combined and for each subgroup of interest. The primary outcomes are gestational weight gain and composite adverse maternal and fetal outcomes. The difference in effects between subgroups will be estimated and between-study heterogeneity suitably quantified and explored. The potential for publication bias and availability bias in the IPD obtained will be investigated. We will conduct a model-based economic evaluation to assess the cost effectiveness of the interventions to manage weight gain in pregnancy and undertake a value of information analysis to inform future research.Systematic review registrationPROSPERO 2013:CRD42013003804

Myo-inositol may prevent gestational diabetes onset in overweight women: a randomized, controlled trial

Abstract Objective: To evaluate whether myo-inositol supplementation may reduce gestational diabetes mellitus (GDM) rate in overweight women. Methods: In an open-label, randomized trial, myo-inositol (2 g plus 200 μg folic acid twice a day) or placebo (200 μg folic acid twice a day) was administered from the first trimester to delivery in pregnant overweight non-obese women (pre-pregnancy body mass index ≥ 25 and < 30 kg/m2). The primary outcome was the incidence of GDM. Results: From January 2012 to December 2014, 220 pregnant women were randomized at two Italian University hospitals, 110 to myo-inositol and 110 to placebo. The incidence of GDM was significantly lower in the myo-inositol group compared to the placebo group (11.6% versus 27.4%, respectively, p = 0.004). Myo-inositol treatment was associated with a 67% risk reduction of developing GDM (OR 0.33; 95% CI 0.15–0.70). Conclusions: Myo-inositol supplementation, administered since early pregnancy, reduces GDM incidence in overweight non-obese women.

Effect of diet and physical activity based interventions in pregnancy on gestational weight gain and pregnancy outcomes: meta-analysis of individual participant data from randomised trials

Abstract Objective To synthesise the evidence on the overall and differential effects of interventions based on diet and physical activity during pregnancy, primarily on gestational weight gain and maternal and offspring composite outcomes, according to women’s body mass index, age, parity, ethnicity, and pre-existing medical condition; and secondarily on individual complications. Design Systematic review and meta-analysis of individual participant data (IPD). Data sources Major electronic databases from inception to February 2017 without language restrictions. Eligibility criteria for selecting studies Randomised trials on diet and physical activity based interventions in pregnancy. Data synthesis Statistical models accounted for clustering of participants within trials and heterogeneity across trials leading to summary mean differences or odds ratios with 95% confidence intervals for the effects overall, and in subgroups (interactions). Results IPD were obtained from 36 randomised trials (12 526 women). Less weight gain occurred in the intervention group than control group (mean difference −0.70 kg, 95% confidence interval −0.92 to −0.48 kg, I2=14.1%; 33 studies, 9320 women). Although summary effect estimates favoured the intervention, the reductions in maternal (odds ratio 0.90, 95% confidence interval 0.79 to 1.03, I2=26.7%; 24 studies, 8852 women) and offspring (0.94, 0.83 to 1.08, I2=0%; 18 studies, 7981 women) composite outcomes were not statistically significant. No evidence was found of differential intervention effects across subgroups, for either gestational weight gain or composite outcomes. There was strong evidence that interventions reduced the odds of caesarean section (0.91, 0.83 to 0.99, I2=0%; 32 studies, 11 410 women), but not for other individual complications in IPD meta-analysis. When IPD were supplemented with study level data from studies that did not provide IPD, the overall effect was similar, with stronger evidence of benefit for gestational diabetes (0.76, 0.65 to 0.89, I2=36.8%; 59 studies, 16 885 women). Conclusion Diet and physical activity based interventions during pregnancy reduce gestational weight gain and lower the odds of caesarean section. There is no evidence that effects differ across subgroups of women.

Dietary interventions, lifestyle changes, and dietary supplements in preventing gestational diabetes mellitus: a literature review.

&NA; Gestational diabetes mellitus (GDM) is associated with increased rates of fetal morbidity and mortality, both during the pregnancy and in the postnatal life. Current treatment of GDM includes diet with or without medications, but this management is expensive and poorly cost-effective for the health care systems. Strategies to prevent such condition would be preferable with respect to its treatment. The aim of this literature review was to evaluate studies reporting the efficacy of the most used approaches to prevent GDM as well as evidences of efficacy and safety of dietary supplementations. Systematic literature searches were performed in electronic databases, covering the period January 1983 to April 2014. Randomized controlled clinical trials were included. Quality of the articles was evaluated with the Jadad scale. We did not evaluate those articles that were already entered in the most recent systematic reviews, and we completed the research with the trials published thereafter. Of 55 articles identified, 15 randomized controlled trials were eligible. Quality and heterogeneity of the studies cannot allow firm conclusions. Anyway, trials in which only intake or expenditure has been targeted mostly reported negative results. On the contrary, combined lifestyle programs including diet control (orienting food intake, restricting energy intake) associated with moderate but continuous physical activity exhibit better efficacy in reducing GDM prevalence. The results from dietary supplements with myo-inositol or probiotics are promising. The actual evidences provide enough arguments for implementing large-scale, high-quality randomized controlled trials looking at the possible benefits of these new approaches for preventing GDM. Target Audience Obstetricians and gynecologists, family physicians Learning Objectives After completing this CME activity, physicians should be better able to summarize the benefits of myo-inositol during pregnancy because it is a safe insulin sensitizer substance able to improve glucose homeostasis and insulin sensitivity, also during pregnancy; therefore, it seems reasonable to implement its assumption starting, if possible, in the preconceptional period (ie, in women with polycystic ovary syndrome); to take into account the possibility of supplying probiotics for preventing GDM in women at risk for GDM development; as well as to encourage preconceptional weight loss in obese women focused to decrease weight-related infertility and pregnancy complications.

Adherence to a lifestyle programme in overweight/obese pregnant women and effect on gestational diabetes mellitus: a randomized controlled trial

This study aims to determine whether the prescription of a detailed lifestyle programme in overweight/obese pregnant women influences the occurrence of gestational diabetes (GDM), and if this kind of prescription increases the adherence to a healthier lifestyle in comparison to standard care. The study was designed as a randomized controlled trial, with open allocation, enrolling women at 9-12 weeks of pregnancy with a BMI ≥ 25 kg/m2 . The women assigned to the Intervention group (I = 96) received a hypocaloric, low-glycaemic, low-saturated fat diet and physical activity recommendations. Those assigned to the Standard Care group (SC = 95) received lifestyle advices regarding healthy nutrition and exercise. Follow-up was planned at the 16th , 20th , 28th and 36th weeks. A total of 131 women completed the study (I = 69, SC = 62). The diet adherence was higher in the I (57.9%) than in the SC (38.7%) group. GDM occurred less frequently in the I (18.8%) than in the SC (37.1%, P = 0.019) group. The adherent women from either groups showed a lower GDM rate (12.5% vs. 41.8%, P < 0.001). After correcting for confounders, the GDM rate was explained by allocation into the I group (P = 0.034) and a lower BMI category (P = 0.039). The rates of hypertension, preterm birth, induction of labour, large for gestational age babies and birthweight > 4000 g were significantly lower in I group. The incidence of small for gestational age babies was not different. These findings demonstrate that the adherence to a personalized, hypocaloric, low-glycaemic, low-saturated fat diet started early in pregnancy prevents GDM occurrence, in women with BMI ≥ 25 kg/m2 .

The l-arginine/nitric oxide pathway is impaired in overweight/obese pregnant women.

OBJECTIVE To evaluate the l-arginine/NO system and its role in insulin signaling and endothelial function during the pregnancy of women of different BMI categories. STUDY DESIGN Twelve women with BMI⩾25 were compared with 10 normal-weight women in a fasting condition after the infusion of l-arginine (20g in 3h) and after the evaluation of the flow-mediated vasodilation (FMD) of the brachial artery between the 9th-12th and 24th-27th weeks. Blood samples for insulin and nitrite/nitrate (NOx) were collected at baseline and after 1, 2 and 3h after initiating the infusion. RESULTS In both trimesters, the baseline NOx levels were similar among groups. In the 1st trimester of the lean women, there was a NOx increase in response to l-Arg (AUC: 1328; 3, 3173), which had increased by the 2nd trimester (AUC: 3884; 1905, 7686); in overweight/obese women, no responses to l-Arg were found in the 1st or 2nd trimesters. In the 1st trimester, the insulin levels were significantly reduced in both groups after l-Arg infusion. Although the insulin levels in all BMI categories were higher in the 2nd trimester, such levels during weeks 24-27 were suppressed only in normal-weight women after l-Arg infusion. The FMD was higher during both trimesters in the lean controls and was impaired in the overweight/obese subjects. CONCLUSIONS NO availability is impaired in overweight/obese women during pregnancy, which affects endothelial functioning and interferes with insulin regulation. These mechanisms could be involved in the development of hypertensive disorders and glucose intolerance in this population.