The importance of maternal insulin resistance throughout pregnancy on neonatal adiposity

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

The Weak Relationship between Vitamin D Compounds and Glucose Homeostasis Measures in Pregnant Women with Obesity : An Exploratory Sub-Analysis of the DALI Study

Altres ajuts: Netherlands Organization for Health Research and Development (ZonMw, 200310013); Polish Ministry of Science (2203/7, PR/2011/2); Odense University Free Research Fund; NIHR Clinical Research Network: Eastern; In Spain (CAIBER 1527-B-226); Spanish Diabetes Society (SED) XI Grant for clinical research projects in diabetes.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/m 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

Correction to: Reldesemtiv in Patients with Spinal Muscular Atrophy: a Phase 2 Hypothesis-Generating Study (Neurotherapeutics, (2021), 18, 2, (1127-1136), 10.1007/s13311-020-01004-3)

This article has been updated to add the author Richard S. Finkel. The original article has been corrected

Temporal relationships between maternal metabolic parameters with neonatal adiposity in women with obesity differ by neonatal sex : Secondary analysis of the DALI study

To investigate the importance of time in pregnancy and neonatal sex on the association between maternal metabolic parameters and neonatal sum of skinfolds. 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 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. 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. 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

Temporal relationships between maternal metabolic parameters with neonatal adiposity in women with obesity differ by neonatal sex : secondary analysis of the DALI study

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/m2 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

Mediators of lifestyle behaviour changes in obese pregnant women. Secondary analyses from the DALI lifestyle randomised controlled trial

Altres ajuts: The project described has received funding from the European Community's 7th Framework Programme (FP7/2007-2013) under grant agreement no. 242187. In the Netherlands, additional funding was provided by the Netherlands Organization for Health Research and Development (ZonMw) (grant no. 200310013). In Poland, additional funding was obtained from Polish Ministry of Science (grant no. 2203/7. PR/2011/2). In Denmark, additional funding was provided by the Odense University Free Research Fund. In the United Kingdom, the DALI team acknowledge the support received from the NIHR Clinical Research Network: Eastern, especially the local diabetes clinical and research teams based in Cambridge. In Spain, additional funding was provided by CAIBER 1527-B-226. The funders had no role in any aspect of the study beyond funding.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/m , ≤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

A reduction in sedentary behaviour in obese women during pregnancy reduces neonatal adiposity : the DALI randomised controlled trial

Altres ajuts: Funding The project described has received funding from the European Community's 7th Framework Programme (FP7/2007-2013) under grant agreement no. 242187. In the Netherlands, additional funding was provided by the Netherlands Organisation for Health Research and Development (ZonMw) (grant no. 200310013). In Poland, additional funding was obtained from the Polish Ministry of Science (grant no. 2203/7, PR/2011/2). In Denmark, additional funding was provided by Odense University Free Research Fund. In the UK, the DALI team acknowledges the support received from the National Institute for Health Research Clinical Research Network Eastern, especially the local diabetes clinical and research teams based in Cambridge. In Spain, additional funding was provided by CAIBER (Consorcio de Apoyo a la Investigación Biomédica en Red; 1527-B-226). The funders had no role in any aspect of the study beyond funding.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 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

Consensus Guidelines for Perioperative Care in Neonatal Intestinal Surgery: Enhanced Recovery After Surgery (ERAS\u3csup\u3e®\u3c/sup\u3e) Society Recommendations

Background: Enhanced Recovery After Surgery (ERAS®) Society guidelines integrate evidence-based practices into multimodal care pathways that have improved outcomes in multiple adult surgical specialties. There are currently no pediatric ERAS® Society guidelines. We created an ERAS® guideline designed to enhance quality of care in neonatal intestinal resection surgery. Methods: A multidisciplinary guideline generation group defined the scope, population, and guideline topics. Systematic reviews were supplemented by targeted searching and expert identification to identify 3514 publications that were screened to develop and support recommendations. Final recommendations were determined through consensus and were assessed for evidence quality and recommendation strength. Parental input was attained throughout the process. Results: Final recommendations ranged from communication strategies to antibiotic use. Topics with poor-quality and conflicting evidence were eliminated. Several recommendations were combined. The quality of supporting evidence was variable. Seventeen final recommendations are included in the proposed guideline. Discussion: We have developed a comprehensive, evidence-based ERAS guideline for neonates undergoing intestinal resection surgery. This guideline, and its creation process, provides a foundation for future ERAS guideline development and can ultimately lead to improved perioperative care across a variety of pediatric surgical specialties

Temporal relationships between maternal metabolic parameters with neonatal adiposity in women with obesity differ by neonatal sex: Secondary analysis of the DALI study

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/m2 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