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.

Risk factors during first 1,000 days of life for carotid intima-media thickness in infants, children, and adolescents: A systematic review with meta-analyses.

BACKGROUND: The first 1,000 days of life, i.e., from conception to age 2 years, could be a critical period for cardiovascular health. Increased carotid intima-media thickness (CIMT) is a surrogate marker of atherosclerosis. We performed a systematic review with meta-analyses to assess (1) the relationship between exposures or interventions in the first 1,000 days of life and CIMT in infants, children, and adolescents; and (2) the CIMT measurement methods. METHODS AND FINDINGS: Systematic searches of Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), and Cochrane Central Register of Controlled Trials (CENTRAL) were performed from inception to March 2019. Observational and interventional studies evaluating factors at the individual, familial, or environmental levels, for instance, size at birth, gestational age, breastfeeding, mode of conception, gestational diabetes, or smoking, were included. Quality was evaluated based on study methodological validity (adjusted Newcastle-Ottawa Scale if observational; Cochrane collaboration risk of bias tool if interventional) and CIMT measurement reliability. Estimates from bivariate or partial associations that were least adjusted for sex were used for pooling data across studies, when appropriate, using random-effects meta-analyses. The research protocol was published and registered on the International Prospective Register of Systematic Reviews (PROSPERO; CRD42017075169). Of 6,221 reports screened, 50 full-text articles from 36 studies (34 observational, 2 interventional) totaling 7,977 participants (0 to 18 years at CIMT assessment) were retained. Children born small for gestational age had increased CIMT (16 studies, 2,570 participants, pooled standardized mean difference (SMD): 0.40 (95% confidence interval (CI): 0.15 to 0.64, p: 0.001), I2: 83%). When restricted to studies of higher quality of CIMT measurement, this relationship was stronger (3 studies, 461 participants, pooled SMD: 0.64 (95% CI: 0.09 to 1.19, p: 0.024), I2: 86%). Only 1 study evaluating small size for gestational age was rated as high quality for all methodological domains. Children conceived through assisted reproductive technologies (ART) (3 studies, 323 participants, pooled SMD: 0.78 (95% CI: -0.20 to 1.75, p: 0.120), I2: 94%) or exposed to maternal smoking during pregnancy (3 studies, 909 participants, pooled SMD: 0.12 (95% CI: -0.06 to 0.30, p: 0.205), I2: 0%) had increased CIMT, but the imprecision around the estimates was high. None of the studies evaluating these 2 factors was rated as high quality for all methodological domains. Two studies evaluating the effect of nutritional interventions starting at birth did not show an effect on CIMT. Only 12 (33%) studies were at higher quality across all domains of CIMT reliability. The degree of confidence in results is limited by the low number of high-quality studies, the relatively small sample sizes, and the high between-study heterogeneity. CONCLUSIONS: In our meta-analyses, we found several risk factors in the first 1,000 days of life that may be associated with increased CIMT during childhood. Small size for gestational age had the most consistent relationship with increased CIMT. The associations with conception through ART or with smoking during pregnancy were not statistically significant, with a high imprecision around the estimates. Due to the large uncertainty in effect sizes and the limited quality of CIMT measurements, further high-quality studies are needed to justify intervention for primordial prevention of cardiovascular disease (CVD).

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.

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.

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.

Antibiotics administration during last trimester of pregnancy is associated with atopic dermatitis - a cross-sectional study.

INTRODUCTION: Studies regarding antibiotics administration during pregnancy and atopic dermatitis (AD) in children are only few. In this context, the objective of our study was to investigate the potential association between the timing of intrauterine exposure to antibiotics or prenatal antibiotic administration in general and AD occurrence in children. METHODS: This was a cross-sectional study in 1046 subjects. The exposure to antibiotics during pregnancy was initially evaluated using simple logistic regressions. Then, each period of antibiotics administration was adjusted with the other periods of antibiotics exposure (model 1) and with the other variables associated with AD in our database (model 2). RESULTS: In simple logistic regression analysis, the administration of antibiotics during pregnancy, as a whole period, presented a trend of association with AD (OR = 1.28, %CI: 0.99 - 1.65). When we analyzed antibiotic administration during each trimester of pregnancy, only antibiotherapy during the 3rd trimester was associated with AD (OR = 2.94, %CI: 1.21 - 7.12). After adjusting with all the other important risk factors associated with AD in the database, antibiotics administration during the 3rd trimester of pregnancy was still independently associated with AD (OR=2.64, %CI: 1.01 - 6.91). CONCLUSION: Antibiotic administration during the 3rd trimester of pregnancy was independently associated with AD in children.

Corona Immunitas: study protocol of a nationwide program of SARS-CoV-2 seroprevalence and seroepidemiologic studies in Switzerland.

OBJECTIVES: Seroprevalence studies to assess the spread of SARS-CoV-2 infection in the general population and subgroups are key for evaluating mitigation and vaccination policies and for understanding the spread of the disease both on the national level and for comparison with the international community. METHODS: Corona Immunitas is a research program of coordinated, population-based, seroprevalence studies implemented by Swiss School of Public Health (SSPH+). Over 28,340 participants, randomly selected and age-stratified, with some regional specificities will be included. Additional studies in vulnerable and highly exposed subpopulations are also planned. The studies will assess population immunological status during the pandemic. RESULTS: Phase one (first wave of pandemic) estimates from Geneva showed a steady increase in seroprevalence up to 10.8% (95% CI 8.2-13.9, n = 775) by May 9, 2020. Since June, Zurich, Lausanne, Basel City/Land, Ticino, and Fribourg recruited a total of 5973 participants for phase two thus far. CONCLUSIONS: Corona Immunitas will generate reliable, comparable, and high-quality serological and epidemiological data with extensive coverage of Switzerland and of several subpopulations, informing health policies and decision making in both economic and societal sectors. ISRCTN Registry: https://www.isrctn.com/ISRCTN18181860 .

Risk factors and determinants of carotid intima-media thickness in children: protocol for a systematic review and meta-analysis.

INTRODUCTION: Carotid intima-media thickness (CIMT) is a surrogate marker of atherosclerosis that is measured in adults and children to better understand the natural history of cardiovascular disease (CVD). In adults, CIMT is predictive of myocardial infarction and stroke. In children and adolescents, CIMT is used to assess vascular changes in the presence of CVD risk factors (obesity, hypertension, smoking, etc) or clinical conditions associated with a high risk for premature CVD. However, there is no comprehensive overview, in a life-course epidemiology perspective, of the risk factors and determinants of CIMT in children. It is also important to evaluate between-study differences in CIMT measurement methods and take them into consideration when drawing conclusions. Our objective is to systematically review the evidence on the relationship between CIMT and prenatal and postnatal exposures or interventions in children, as well as documenting and discussing the CIMT measurement methods. METHODS AND ANALYSIS: Systematic searches of the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica (EMBASE)and Central Register of Controlled Trials (CENTRAL) databases will be conducted. The reference lists and other literatures sources will be browsed. Observational and experimental studies in children from birth up to 18 years will be included. Prenatal and postnatal exposures or interventions assessed in relationship with CIMT will be considered for inclusion. Examples might include gestational age, obesity, hypertension, tobacco exposure, specific at-risk conditions (chronic kidney disease, diabetes, etc) or statin treatment. The outcome will be CIMT assessed by ultrasonography. The setting, scanning and measurement methods for each included study will be described in detail. Results will be synthesised descriptively and, if appropriate, will be pooled across studies to perform meta-analyses. Separate meta-analyses for each exposure or intervention type will be conducted. ETHICS AND DISSEMINATION: This systematic review will be published in a peer-reviewed journal. A report will be prepared for clinicians and other healthcare decision-makers. PROSPERO REGISTRATION NUMBER: CRD42017075169.

Assessing the consequences of gestational diabetes mellitus on offspring's cardiovascular health: MySweetHeart Cohort study protocol, Switzerland.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a state of glucose intolerance with onset during pregnancy. GDM carries prenatal and perinatal risks as well as long-term risks for the mother and her child. GDM may be involved in the foetal programming of long-term cardiovascular health. However, evidence is sparse and the effect of GDM on cardiovascular health is unknown. To address these issues, we will conduct MySweetHeart Cohort study. The objectives are to assess the effect of GDM on offspring's cardiovascular health early in life by using surrogate markers of cardiovascular disease and atherosclerosis. METHODS AND ANALYSIS: This is a cohort study of 100 offspring of women with GDM and 100 offspring of women without GDM. At inclusion, a baseline assessment of the mothers will be conducted through means of self-report questionnaires, a researcher-administrated interview, blood pressure and anthropometric measurements, and a maternal blood sampling. Between the 30th and 34th weeks of gestation, a foetal echography will be performed to assess the foetal cardiac structure and function, the fetomaternal circulation and the hepatic volume. At birth, maternal and neonatal characteristics will be assessed. An echocardiography will be performed to assess cardiac structure and function 2-7 days after birth; carotid intima-media thickness will be also measured to assess vascular structure. MySweetHeart Cohort is linked to MySweetHeart Trial (clinicaltrials.gov/ct2/show/NCT02890693), a randomised controlled trial assessing the effect of a multidimensional interdisciplinary lifestyle and psychosocial intervention to improve the cardiometabolic and mental health of women with GDM and their offspring. A long-term follow-up of children is planned. ETHICS AND DISSEMINATION: Ethical approval has been obtained through the state Human Research Ethics Committee of the Canton de Vaud (study number 2016-00745). We aim to disseminate the findings through regional, national and international conferences and through peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (clinicaltrials.gov/ct2/show/NCT02872974).