Gestational diabetes mellitus and offspring's carotid intima-media thickness at birth: MySweetHeart Cohort study.

OBJECTIVE Hyperglycaemia during pregnancy is associated with cardiometabolic risks for the mother and the offspring. Mothers with gestational diabetes mellitus (GDM) have signs of subclinical atherosclerosis, including increased carotid intima-media thickness (CIMT). We assessed whether GDM is associated with increased CIMT in the offspring at birth. DESIGN AND SETTING MySweetHeart Cohort is a prospective cohort study conducted in Switzerland. PARTICIPANTS, EXPOSURE AND OUTCOME MEASURES This work included pregnant women with and without GDM at 24-32 weeks of gestation and their singleton live-born offspring with data on the primary outcome of CIMT. GDM was diagnosed based on the criteria of the International Association of Diabetes and Pregnancy Study Groups. Offspring's CIMT was measured by ultrasonography after birth (range 1-19 days). RESULTS Data on CIMT were available for 99 offspring of women without GDM and 101 offspring of women with GDM. Maternal age ranged from 18 to 47 years. Some 16% of women with GDM and 6% of women without GDM were obese. Smoking during pregnancy was more frequent among women with GDM (18%) than among those without GDM (4%). Neonatal characteristics were comparable between the two groups. The difference in CIMT between offspring of women with and without GDM was of 0.00 mm (95% CI -0.01 to 0.01; p=0.96) and remained similar on adjustment for potential confounding factors, such as maternal prepregnancy body mass index, maternal education, smoking during pregnancy, family history of diabetes, as well as offspring's sex, age, and body surface area (0.00 mm (95% CI -0.02 to 0.01; p=0.45)). CONCLUSIONS We found no evidence of increased CIMT in neonates exposed to GDM. A longer-term follow-up that includes additional vascular measures, such as endothelial function or arterial stiffness, may shed further light on the cardiovascular health trajectories in children born to mothers with GDM. TRIAL REGISTRATION NUMBER NCT02872974; Pre-results

Interventions to Decrease Carotid-Intima Media Thickness in Children and Adolescents With Type 1 Diabetes: A Systematic Review and Meta-Analysis.

INTRODUCTION Hyperglycemia is associated with a higher cardiovascular risk, as evidenced by increased carotid-intima media thickness (CIMT) in youth with diabetes. We conducted a systematic review and meta-analysis to assess the effect of pharmacological or non-pharmacological interventions on CIMT in children and adolescents with prediabetes or diabetes. METHODS We conducted systematic searches of MEDLINE, EMBASE, and CENTRAL, together with supplementary searches in trial registers and other sources for studies completed up to September 2019. Interventional studies assessing ultrasound CIMT in children and adolescents with prediabetes or diabetes were considered for inclusion. Where appropriate, data were pooled across studies using random-effect meta-analysis. Quality was assessed using The Cochrane Collaboration's risk-of-bias tool and a CIMT reliability tool. RESULTS Six studies involving 644 children with type 1 diabetes mellitus were included. No study involved children with prediabetes or type 2 diabetes. Three randomized controlled trials (RCTs) evaluated the effects of metformin, quinapril, and atorvastatin. Three non-randomized studies, with a before-and-after design, evaluated the effects of physical exercise and continuous subcutaneous insulin infusion (CSII). The mean CIMT at baseline ranged from 0.40 to 0.51 mm. The pooled difference in CIMT was -0.01 mm (95% CI: -0.04 to 0.01) for metformin compared to placebo (2 studies; 135 participants; I2: 0%). The difference in CIMT was -0.01 mm (95% CI: -0.03 to 0.01) for quinapril compared to placebo (1 study; 406 participants). The mean change from baseline in CIMT was -0.03 mm (95% CI: -0.14 to 0.08) after physical exercise (1 study; 7 participants). Inconsistent results were reported for CSII or for atorvastatin. CIMT measurement was rated at a higher quality on all reliability domains in 3 (50%) studies. The confidence in results is limited by the low number of RCTs and their small sample sizes, as well as the high risk of bias in before-and-after studies. CONCLUSIONS Some pharmacological interventions may decrease CIMT in children with type 1 diabetes. However, there is great uncertainty with respect to their effects and no strong conclusions can be drawn. Further evidence from larger RCTs is required. SYSTEMATIC REVIEW REGISTRATION PROSPERO, CRD42017075169

Consequences of gestational diabetes mellitus on neonatal cardiovascular health: MySweetHeart Cohort study.

BACKGROUND Hyperglycaemic disorders of pregnancy are associated with offspring cardiovascular alterations. METHODS MySweetHeart cohort study aimed to assess the effect of maternal gestational diabetes (GDM) on offsprings' cardiovascular health. Newborns underwent clinical and echocardiographic examinations between 2016 and 2020. RESULTS Compared to mothers without GDM (n = 141), mothers with GDM (n = 123) were more likely to have had GDM in previous pregnancies and had higher weight, BMI, blood glucose, and HbA1c. Newborns of both groups showed similar clinical characteristics. Echocardiography was performed on the 3rd (interquartile range, IQR, 2nd-4th) day of life in 101 offsprings of mothers without and 116 offsprings of mothers with GDM. Left ventricular (LV) mass was similar. Children born to mothers with GDM had a thicker posterior LV wall (z-score +0.15, IQR -0.38/0.62, versus +0.47, IQR -0.11/+1.1, p = 0.004), a smaller end-systolic (1.3 mL, IQR 1.0-1.5 mL, versus 1.4 mL, IQR 1.2-1.8 mL, p = 0.044) but a similar end-diastolic LV volume. They also had shorter tricuspid valve flow duration and aortic valve ejection time, lower tricuspid E-wave and pulmonary valve velocities. CONCLUSIONS Newborns of mothers with or without GDM had similar clinical characteristics and LV mass. However, some echocardiographic differences were detected, suggesting an altered myocardial physiology among infants of mothers with GDM. REGISTRATION ClinicalTrials.gov (NCT02872974). IMPACT Hyperglycaemic disorders of pregnancy are known to be associated with offspring cardiovascular alterations. Clinical characteristics and estimated left ventricular (LV) mass were similar in children issued from mothers with and without gestational diabetes (GDM). Children born to mothers with GDM had a thicker posterior LV wall and a smaller end-systolic LV volume. Although LV mass is not different, myocardial physiology may be altered in these infants. Further studies should investigate the endothelial function of this population and the cardiovascular evolution of these children over time

Consequences of gestational diabetes mellitus on neonatal cardiovascular health: MySweetHeart Cohort study

Hyperglycaemic disorders of pregnancy are associated with offspring cardiovascular alterations. MySweetHeart cohort study aimed to assess the effect of maternal gestational diabetes (GDM) on offsprings' cardiovascular health. Newborns underwent clinical and echocardiographic examinations between 2016 and 2020. Compared to mothers without GDM (n = 141), mothers with GDM (n = 123) were more likely to have had GDM in previous pregnancies and had higher weight, BMI, blood glucose, and HbA1c. Newborns of both groups showed similar clinical characteristics. Echocardiography was performed on the 3rd (interquartile range, IQR, 2nd-4th) day of life in 101 offsprings of mothers without and 116 offsprings of mothers with GDM. Left ventricular (LV) mass was similar. Children born to mothers with GDM had a thicker posterior LV wall (z-score +0.15, IQR -0.38/0.62, versus +0.47, IQR -0.11/+1.1, p = 0.004), a smaller end-systolic (1.3 mL, IQR 1.0-1.5 mL, versus 1.4 mL, IQR 1.2-1.8 mL, p = 0.044) but a similar end-diastolic LV volume. They also had shorter tricuspid valve flow duration and aortic valve ejection time, lower tricuspid E-wave and pulmonary valve velocities. Newborns of mothers with or without GDM had similar clinical characteristics and LV mass. However, some echocardiographic differences were detected, suggesting an altered myocardial physiology among infants of mothers with GDM. ClinicalTrials.gov (NCT02872974). Hyperglycaemic disorders of pregnancy are known to be associated with offspring cardiovascular alterations. Clinical characteristics and estimated left ventricular (LV) mass were similar in children issued from mothers with and without gestational diabetes (GDM). Children born to mothers with GDM had a thicker posterior LV wall and a smaller end-systolic LV volume. Although LV mass is not different, myocardial physiology may be altered in these infants. Further studies should investigate the endothelial function of this population and the cardiovascular evolution of these children over time

Early life determinants of cardiovascular health in children

CONTEXTE : L'épaisseur intima-média carotidienne (EIMC) est associée au risque de maladie cardiovasculaire (MCV) chez les adultes. Les 1000 premiers jours de la vie, de la conception à l'âge de 2 ans, pourraient être une période critique pour le développement du risque cardiovasculaire, et c'est pourquoi la prévention des MCV dès le début de la vie est conseillée. Les objectifs de cette thèse étaient de 1) identifier les facteurs de risque dans les 1000 premiers jours de vie associés à une augmentation de l'EIMC de la naissance à l'adolescence, 2) évaluer si le traitement améliore l'EIMC chez les enfants et adolescents avec diabète, et 3) évaluer l'effet de diabète gestationnel (DG) sur l'EIMC à la naissance. MÉTHODES : Nous avons mené 2 revues systématiques {RS) avec des méta-analyses pour répondre aux 2 premiers objectifs et une étude prospective de cohorte pour répondre au troisième objectif. RÉSULTATS : Notre première RS a révélé que la petite taille pour l'âge gestationnel, la conception grâce aux technologies de procréation assistée ou l'exposition au tabagisme maternel pendant la grossesse pourraient entraîner une augmentation de l'EIMC. La petite taille pour l'âge gestationnel est le plus fortement associée à une augmentation de l'EIMC de la naissance à l'adolescence. Notre deuxième RS a révélé que la metformine ou le quinapril entraînent peu, voire pas, de différence pour l'amélioration de l'EIMC chez les enfants avec diabète de type 1. Notre étude de cohorte n'a pas trouvé de différence à la naissance entre l'EIMC des enfants de mères avec et sans DG. CONCLUSIONS: Nos résultats suggèrent que plusieurs facteurs dans les 1000 premiers jours de la vie et en particulier une faible croissance fœtale, mais pas le DG, peuvent déterminer une augmentation de l'EIMC et, donc possiblement du risque cardiovasculaire déjà au début de la vie. L'incertitude reste importante sur comment intervenir pour atténuer le risque cardiovasculaire chez les enfants avec diabète. D'autres données probantes de haute qualité sur la façon d'améliorer la santé cardiovasculaire au début de la vie sont nécessaires. -- BACKGROUND: Carotid intima-media thickness (CIMT) is associated with the risk of cardiovascular disease (CVD) in adults. The first 1,000 days of lite, i.e., from conception to age 2 years, could be a critical period for cardiovascular risk development, hence CVD prevention starting early in lite is advocated. The objectives of this thesis were to 1) identify risk factors in the first 1,000 days of lite associated with an increased CIMT from birth to adolescence, 2) assess whether treatment improves CIMT in children and adolescents with diabetes, and 3) assess the effect of gestational diabetes mellitus (GDM) on CIMT at birth. METHODS: We conducted 2 systematic reviews (SR) with meta-analyses to address the first 2 objectives and a prospective cohort study to address the third objective. RESULTS: Our first SR found that small size for gestational age, conception through assisted reproductive technologies, or exposure to maternai smoking during pregnancy may result in increased CIMT. Small size for gestational age has the strongest association with increased CIMT from birth to adolescence. Our second SR found that metformin or quinapril result in little to no difference in improving CIMT in children with type 1 diabetes. Our cohort study found no difference in CIMT at birth in offspring of women with and without GDM. CONCLUSIONS: Our findings suggest that several factors in the first 1000 days of lite and in particular poor fetal growth, but not GDM, may increase CIMT and, hence, cardiovascular risk already in early lite. Uncertainty remains high with respect on how to intervene to mitigate CVD risk in children and adolescents with diabetes. Further high-quality evidence on how to improve early lite cardiovascular health is needed

Caesarean section and obesity in young adult offspring: Update of a systematic review with meta-analysis.

As compared with vaginal delivery (VD), caesarean section (CS) birth could be associated with increased risk of obesity in young adult offspring. We aimed to evaluate this association by updating data from a systematic review with meta-analysis of observational studies. From 3774 records identified in PubMed and Embase, we retained six studies and added five studies from the last systematic review, for a total of 11 studies. Crude estimates of the association were retrieved from nine cohort studies (n = 143,869), and maximally adjusted estimates were retrieved from eight cohort studies. Young adults born by CS had higher risk of obesity (body mass index [BMI] ≥ 30 kg/m2 ) than young adults born by VD, corresponding to a crude pooled risk ratio (RR) of 1.30 [95% confidence interval (CI) 1.13 to 1.50] and a maximally adjusted pooled RR of 1.22 [95% CI 1.02 to 1.46]. In a sensitivity analysis pooling, five studies that included maternal prepregnancy BMI, a major potential confounding factor, in the set of controlled covariates, the RR was 1.08 [95% CI 0.92 to 1.27]. We concluded that the association between CS and obesity in young adulthood was mostly explained by confounding from maternal prepregnancy BMI

Effect of covering perinatal health-care costs on neonatal outcomes in Switzerland: a quasi-experimental population-based study.

BACKGROUND Low birthweight and preterm birth are associated with an increased risk of neonatal death and chronic conditions across the life course. Reducing these adverse birth outcomes is a global public health priority and requires strategies to improve health care during pregnancy. We aimed to assess the effect of a Swiss health policy expansion fully covering illness-related costs during pregnancy on health outcomes in newborn babies. METHODS We implemented a quasi-experimental difference in regression discontinuity design to assess the effect of expansion of Swiss health insurance (on March 1, 2014), to fully cover health-care costs during pregnancy and 8 weeks postpartum, on neonatal outcomes. Before this reform, only costs specific to the standard monitoring of a normal pregnancy were covered. Babies born before March 1, 2014, and their mothers were assigned to the unexposed group, and babies born on or after March 1, 2014, and their mothers were assigned to the exposed group. We included nearly all children born 2011-19 in Switzerland within a period of 9 months around the date March 1, 2014, and control years 2012, 2016, and 2018. Outcomes were birthweight, low birthweight, very low birthweight, gestational age, preterm or extremely preterm birth, and neonatal death. We estimated the intention-to-treat effect of the policy using parametric regression models. FINDINGS 61 910 children were born 9 months before and 63 991 were born 9 months after March 1, 2014. 382 861 children were born in the same time period around the three control dates. In the period before policy implementation, mean birthweight was 3289 g, gestational age was 275 days, and 6·5% of children had low birthweight, 1·0% very low birthweight, 7·1% were preterm, 0·4% were extremely preterm, and 0·3% died within the first 28 days of life. After initiation of the policy (vs before) mean birthweight increased by 23 g (95% CI 5 to 40) and the predicted proportion of low birthweight births decreased by 0·81% (0·14 to 1·48) and of very low birthweight births decreased by 0·41% (0·17 to 0·65). The effect on very low birthweight was not robust in sensitivity analyses. The policy had a negligible effect on gestational age (mean difference 1 day, 95% CI 0 to 1) and no clear effects on the other examined outcomes. The change in predicted proportion for preterm births was -0·39% (95% CI -1·2 to 0·38), for extremely preterm births was -0·09% (-0·27 to 0·08), and for neonatal death was -0·07% (-0·2 to 0·07). INTERPRETATION Free access to prenatal care in Switzerland reduced the risk of some adverse health outcomes in newborn babies. Expanding health-care coverage is a relevant health system intervention to reduce the risk of adverse health outcomes in the newborn baby and, potentially, across the life course. FUNDING Swiss National Science Foundation

Effect of covering perinatal health-care costs on neonatal outcomes in Switzerland: a quasi-experimental population-based study

BACKGROUND: Low birthweight and preterm birth are associated with an increased risk of neonatal death and chronic conditions across the life course. Reducing these adverse birth outcomes is a global public health priority and requires strategies to improve health care during pregnancy. We aimed to assess the effect of a Swiss health policy expansion fully covering illness-related costs during pregnancy on health outcomes in newborn babies. METHODS: We implemented a quasi-experimental difference in regression discontinuity design to assess the effect of expansion of Swiss health insurance (on March 1, 2014), to fully cover health-care costs during pregnancy and 8 weeks postpartum, on neonatal outcomes. Before this reform, only costs specific to the standard monitoring of a normal pregnancy were covered. Babies born before March 1, 2014, and their mothers were assigned to the unexposed group, and babies born on or after March 1, 2014, and their mothers were assigned to the exposed group. We included nearly all children born 2011-19 in Switzerland within a period of 9 months around the date March 1, 2014, and control years 2012, 2016, and 2018. Outcomes were birthweight, low birthweight, very low birthweight, gestational age, preterm or extremely preterm birth, and neonatal death. We estimated the intention-to-treat effect of the policy using parametric regression models. FINDINGS: 61 910 children were born 9 months before and 63 991 were born 9 months after March 1, 2014. 382 861 children were born in the same time period around the three control dates. In the period before policy implementation, mean birthweight was 3289 g, gestational age was 275 days, and 6·5% of children had low birthweight, 1·0% very low birthweight, 7·1% were preterm, 0·4% were extremely preterm, and 0·3% died within the first 28 days of life. After initiation of the policy (vs before) mean birthweight increased by 23 g (95% CI 5 to 40) and the predicted proportion of low birthweight births decreased by 0·81% (0·14 to 1·48) and of very low birthweight births decreased by 0·41% (0·17 to 0·65). The effect on very low birthweight was not robust in sensitivity analyses. The policy had a negligible effect on gestational age (mean difference 1 day, 95% CI 0 to 1) and no clear effects on the other examined outcomes. The change in predicted proportion for preterm births was -0·39% (95% CI -1·2 to 0·38), for extremely preterm births was -0·09% (-0·27 to 0·08), and for neonatal death was -0·07% (-0·2 to 0·07). INTERPRETATION: Free access to prenatal care in Switzerland reduced the risk of some adverse health outcomes in newborn babies. Expanding health-care coverage is a relevant health system intervention to reduce the risk of adverse health outcomes in the newborn baby and, potentially, across the life course. FUNDING: Swiss National Science Foundation