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

Abstract

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.

Made in the Womb: Maternal Programming of Offspring Cardiovascular Function by an Obesogenic Womb

“…Exercise before and during gestation in combination with an adequate and balanced diet resulted in lower male offspring’s blood glucose concentration, insulin levels, and plasma triglyceride levels, and alterations in gut microbiota diversity, such as enriched operational taxonomic units (OTUs) affiliated with Bacteroides and Blautia [ 201 ]. The UK Pregnancies Better Eating and Activity Trial (UPBEAT), consisting of an 8-week intensive lifestyle intervention in human offspring’s diet and physical activity, prevented the concentric cardiac remodeling observed in 3-year-old offspring of obese women subjected to standard antenatal care, including the increased interventricular septum, posterior wall, and relative wall thickness [ 202 ].…”

Early life impacts of maternal obesity: a window of opportunity to improve the health of two generations

“…Physical activity is a modifiable factor that reduces insulin resistance and has the potential to reduce GWG and GDM incidence [ 59 ]. UPBEAT, a trial in the UK that provided a combined approach of dietary and exercise intervention in obese pregnancies, was successful in limiting GWG [ 60 ] and preventing cardiac remodelling in offspring at 3 years of age [ 61 ]. Although the exercise intervention was effective in reducing offspring adiposity at 6 months of age [ 62 ], this effect was no longer visible in offspring at 3 years of age [ 63 ].…”

Sulforaphane induced NRF2 activation in obese pregnancy attenuates developmental redox imbalance and improves early-life cardiovascular function in offspring

“…Maternal oxidative stress coincides with abnormal uterine artery perfusion and/or placental maladaptation [ 4 , 5 ] altering maternal:fetal transfer to influence fetal growth and development [ 6 , 7 ]. Pathological early life changes in cardiac development have been reported, including fetal ventricular hypertrophy, interventricular septal thickening, impaired myocardial function and increased heart rate in human [ [8] , [9] , [10] , [11] ] and animal models of obesity and glucose dysregulation in pregnancy [ [12] , [13] , [14] ]. Moreover, vascular reactivity is compromised, with early-life vascular dysfunction and increases in systolic blood pressure leading to adult-onset hypertension and/or cardiovascular related death [ [15] , [16] , [17] , [18] , [19] , [20] ], with perturbations in redox homeostasis influencing the phenotype of developing cardiac and vascular tissues [ 21 , 22 ].…”