Lifestyle intervention in obese pregnancy and cardiac remodelling in 3-year olds: children of the UPBEAT RCT

Background/Objectives: Obesity in pregnancy has been associated with increased childhood cardiometabolic risk and reduced life expectancy. The UK UPBEAT multicentre randomised control trial was a lifestyle intervention of diet and physical activity in pregnant women with obesity. We hypothesised that the 3-year-old children of women with obesity would have heightened cardiovascular risk compared to children of normal BMI women, and that the UPBEAT intervention would mitigate this risk. Subjects/Methods: Children were recruited from one UPBEAT trial centre. Cardiovascular measures included blood pressure, echocardiographic assessment of cardiac function and dimensions, carotid intima-media thickness and heart rate variability (HRV) by electrocardiogram. Results: Compared to offspring of normal BMI women (n = 51), children of women with obesity from the trial standard care arm (n = 39) had evidence of cardiac remodelling including increased interventricular septum (IVS; mean difference 0.04 cm; 95% CI: 0.018 to 0.067), posterior wall (PW; 0.03 cm; 0.006 to 0.062) and relative wall thicknesses (RWT; 0.03 cm; 0.01 to 0.05) following adjustment. Randomisation of women with obesity to the intervention arm (n = 31) prevented this cardiac remodelling (intervention effect; mean difference IVS −0.03 cm (−0.05 to −0.008); PW −0.03 cm (−0.05 to −0.01); RWT −0.02 cm (−0.04 to −0.005)). Children of women with obesity (standard care arm) compared to women of normal BMI also had elevated minimum heart rate (7 bpm; 1.41 to 13.34) evidence of early diastolic dysfunction (e prime) and increased sympathetic nerve activity index by HRV analysis. Conclusions: Maternal obesity was associated with left ventricular concentric remodelling in 3-year-old offspring. Absence of remodelling following the maternal intervention infers in utero origins of cardiac remodelling. Clinical trial registry name and registration number: The UPBEAT trial is registered with Current Controlled Trials, ISRCTN89971375

Sequencing and Comparative Genome Analysis of Two Pathogenic Streptococcus gallolyticus Subspecies: Genome Plasticity, Adaptation and Virulence

Streptococcus gallolyticus infections in humans are often associated with bacteremia, infective endocarditis and colon cancers. The disease manifestations are different depending on the subspecies of S. gallolyticus causing the infection. Here, we present the complete genomes of S. gallolyticus ATCC 43143 (biotype I) and S. pasteurianus ATCC 43144 (biotype II.2). The genomic differences between the two biotypes were characterized with comparative genomic analyses. The chromosome of ATCC 43143 and ATCC 43144 are 2,36 and 2,10 Mb in length and encode 2246 and 1869 CDS respectively. The organization and genomic contents of both genomes were most similar to the recently published S. gallolyticus UCN34, where 2073 (92%) and 1607 (86%) of the ATCC 43143 and ATCC 43144 CDS were conserved in UCN34 respectively. There are around 600 CDS conserved in all Streptococcus genomes, indicating the Streptococcus genus has a small core-genome (constitute around 30% of total CDS) and substantial evolutionary plasticity. We identified eight and five regions of genome plasticity in ATCC 43143 and ATCC 43144 respectively. Within these regions, several proteins were recognized to contribute to the fitness and virulence of each of the two subspecies. We have also predicted putative cell-surface associated proteins that could play a role in adherence to host tissues, leading to persistent infections causing sub-acute and chronic diseases in humans. This study showed evidence that the S. gallolyticus still possesses genes making it suitable in a rumen environment, whereas the ability for S. pasteurianus to live in rumen is reduced. The genome heterogeneity and genetic diversity among the two biotypes, especially membrane and lipoproteins, most likely contribute to the differences in the pathogenesis of the two S. gallolyticus biotypes and the type of disease an infected patient eventually develops

Modifiable early life exposures associated with adiposity and obesity in 3-year old children born to mothers with obesity

Background: children born to mothers with obesity are at increased risk of obesity. Influences underlying this predisposition include in-utero exposures, genetic predisposition and a shared family environment. Effective intervention strategies are needed to prevent obesity in these high-risk children; this requires evaluation of modifiable pregnancy and early-life risk factors. Objectives: to assess the individual and cumulative contributions of maternal and early-life modifiable exposures on childhood adiposity and obesity outcomes in 3-year-old children born to women with obesity.Methods: we used adjusted regression to assess the individual and cumulative contributions of six exposures (early pregnancy BMI, excessive gestational weight gain, mode of infant feeding and three measures of childhood eating habits (food responsiveness, slowness in eating and a processed/snacking dietary pattern score)) on body composition in 495 three-year-old children. Outcomes included BMI z-score, arm circumference and overweight/obesity (BMI≥25.0kg/m2). Results: While the UPBEAT intervention did not influence adiposity outcomes in 3-year-old children, the six modifiable exposures combined incrementally to increase childhood adiposity and obesity. For each additional exposure, children had a higher BMI z-score (β=0.35SD (95% confidence interval: 0.23, 0.47)), arm circumference (β=0.59cm (0.40, 0.79)) and risk of overweight/obesity (relative risk 1.49 (1.26, 1.77)). Compared to no exposures, children with four or more exposures had a higher BMI z-score (1.11SD (0.65, 1.58)), arm circumference (2.15cm (1.41, 2.89)) and risk of overweight/obesity (3.01 (1.67, 5.41)) (all p<0.001).Conclusion: our findings suggest that complex interventions targeting preconception, pregnancy, perinatal and early childhood exposures offer a potential strategy for prevention of pre-school obesity

Interventions in preconception and pregnant women at risk of gestational diabetes; a systematic review and meta-analysis of randomised controlled trials

\ua9 2024, The Author(s).Background: Women at risk of gestational diabetes mellitus (GDM) need preventative interventions. Objective: To evaluate targeted interventions before and during pregnancy for women identified as being at risk of developing GDM. Methods: Systematic review and meta-analysis conducted following PRISMA guidelines. MEDLINE, EMBASE and the Cochrane Library in addition to reference and citation lists were searched to identify eligible randomised controlled trials (RCTs) utilising risk stratification during the preconception period or in the first/early second trimester. Screening and data extraction were carried out by the authors independently. Quality assessment was conducted based on the Cochrane risk-of-bias tool. Random effects meta-analysis and narrative synthesis were performed. Results: Eighty-four RCTs were included: two during preconception and 82 in pregnancy, with a pooled sample of 22,568 women. Interventions were behavioural (n = 54), dietary supplementation (n = 19) and pharmacological (n = 11). Predictive factors for risk assessment varied; only one study utilised a validated prediction model. Gestational diabetes was reduced in diet and physical activity interventions (risk difference − 0.03, 95% CI 0.06, − 0.01; I2 58.69%), inositol (risk difference − 0.19, 95% CI 0.33, − 0.06; I2 92.19%), and vitamin D supplements (risk difference − 0.16, 95% CI 0.25, − 0.06; I2 32.27%). Subgroup analysis showed that diet and physical activity interventions were beneficial in women with ≥ 2 GDM risk factors (risk difference − 0.16, 95% CI 0.25, − 0.07; I2 11.23%) while inositol supplementation was effective in women with overweight or obesity (risk difference − 0.17, 95% CI 0.22, − 0.11; I2 0.01%). Effectiveness of all other interventions were not statistically significant. Conclusions: This review provides evidence that interventions targeted at women at risk of GDM may be an effective strategy for prevention. Further studies using validated prediction tools or multiple risk factors to target high-risk women for intervention before and during pregnancy are warranted