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Issue 148 Summer 2023

Endocrinologist > Summer 2023 > Features


IMPROVED DIET AND EXERCISE IN PREGNANCY PROTECTS BABY’S HEART DEVELOPMENT

PAUL D TAYLOR, SAMUEL J BURDEN, KATHRYN DALRYMPLE AND PABLO LAMATA | Features



Maternal obesity is known to increase the risk of congenital abnormalities and alter growth of the offspring.1 However, little is known about the impact of maternal obesity on baby’s cardiac development in the womb. Controversy remains over the relative roles of adverse nutritional exposures during pregnancy, inherited genes from mum, and a shared postnatal environment of similar diet and lifestyle habits, in explaining relationships between maternal obesity and risk of later heart complications in the child.2

However, our recent analysis of cardiac imaging techniques suggests that maternal obesity causes remodelling of baby’s heart and decreases heart chamber size,3 implicating a direct effect of maternal obesity on fetal cardiovascular development during pregnancy. An observation consistent with our extensive preclinical studies in rodent models of obesity in pregnancy.4 This overview will discuss recent findings supporting the in utero developmental programming of the fetal heart in pregnancies complicated by obesity.

'The UPBEAT lifestyle intervention in obese pregnancy may be protective of longer-term heart health in infants born to obese pregnant women.'

Well-conducted randomised control trials in the antenatal period provide the opportunity to discriminate between pregnancy and postnatal influences on heart health in children born to women with obesity. The UK Pregnancy Better Eating and Activity Trial (UPBEAT)5 was a study of 1,555 pregnant women with obesity (body mass index (BMI)>30kg/m2; mean BMI 36.3 kg/m2, SD 4.8) who were randomised in early pregnancy to either a ‘lifestyle’ intervention (involving professional dietary advice and planned physical activity during pregnancy) or standard antenatal care. Remarkably, in neonates born to women with obesity, resting heart rate (when asleep) was approximately 10bpm higher than in infants born to mothers of a healthy BMI <25kg/m2).3 Heart rate variability (HRV) of the normal beat-to-beat interval, a measure of central nervous system function, was significantly lower in infants born to obese versus healthy weight mothers, suggesting increased sympathetic activity (fight or flight response) as a potential underlying cause.3 At six months, resting heart rate was markedly lower in infants of mothers randomised to the intervention, after controlling for other maternal influences such as parity, ethnicity, smoking status, maternal age, years spent in full time education, and infant birthweight.6 This provided the first indication that the UPBEAT lifestyle intervention in obese pregnancy may be protective of longer-term heart health in infants born to obese pregnant women.

Evidence for persistent effects of maternal obesity on infant cardiac structure and function is provided by a recent echocardiography imaging study of the hearts of three-year-olds from UPBEAT.7 Compared to children of women with a normal weight, children born to women with obesity in the standard care arm demonstrated thickening of the walls of the heart, specifically the left ventricular septal wall, after controlling for potential confounders. Evidence of specific remodelling around the left ventricle of the heart included higher left ventricular mass indexed to the child’s size and an increase in the ratio of left ventricular mass to ventricular end-diastolic volume, a marker of cardiac remodelling that is well established in hypertension and obesity. There was also evidence of contractile dysfunction with lower ejection fraction and indications of impaired left ventricular relaxation. By contrast, those children whose mothers were in the intervention arm of the study did not show evidence of cardiac remodelling; rather there was a significant reduction in heart wall thickness and heart mass compared to children of women in the standard care arm.

Children in the UPBEAT standard care arm, at three years of age, continued to show elevated resting heart rate compared to children of mothers with a normal BMI, even after adjustment for confounders. HRV analysis revealed a decrease in variability (more variability is typically healthier), and an increased ‘fight or flight’ response relative to the group with normal weight. The UPBEAT intervention tended to improve all parameters of autonomic nervous system function but were not statistically significant, suggesting that a larger sample size may be needed to see the effect of the intervention on the autonomic nervous system.7

'Maternal obesity may adversely impact the fetal autonomic nervous system and heart development that is apparent up to three years of age.'

Most recently, to further investigate the impact of maternal obesity on fetal heart development, we employed novel heart atlasing techniques8 and 3D computer modelling to evaluate ‘cardiac shape’ by magnetic resonance imaging (MRI).9 Newborn babies underwent imaging in the first 48 hours of life using a ‘feed and wrap’ technique to encourage babies to sleep during the 30-minute scan. Infants born to mothers with obesity had a markedly different heart shape at end-diastole with significantly reduced ‘sphericity’ (left ventricular volume/length) compared to infants born to lean women (see Figure). Reduced sphericity of the heart, or cardiac remodelling, is commonly seen in various adult cardiovascular diseases, including hypertension, and can result in reduced contractility of heart and reduced cardiac output. It is important to note that this may not be pathophysiological at a young age and so further longitudinal studies will be needed to determine risk. However, a decreased sphericity might predispose the infant left ventricle to increased wall stress, which could activate pathways linked with left ventricular hypertrophy (thickening of the myocardium), as evident in our three-year-old data. If sustained, this could lead to the deterioration of cardiac function.

In conclusion, maternal obesity may adversely impact the fetal autonomic nervous system and heart development that is apparent up to three years of age. The extent to which increased fetal/neonatal heart rate, secondary to maternal obesity, impacts on neonatal cardiac development and function remains to be established. We can hypothesise that these sub-clinical changes in a child’s heart structure and function may amplify over time, as evidenced by overt clinical disease in young people born to women with obesity,2 and the increased cardiovascular mortality and morbidity observed in adults born to obese women in the Scottish cohort study.10 The UPBEAT complex antenatal lifestyle intervention in obese pregnancy appears to protect against elevated infant heart rate, limits changes in cardiac structure and function in childhood, and infers the in utero origins of cardiac remodelling in obese pregnancy.

PAUL D TAYLOR
Women and Children’s Health, School of Life Course & Population Sciences, King’s College London

SAMUEL J BURDEN
Women and Children’s Health, School of Life Course & Population Sciences, King’s College London

KATHRYN DALRYMPLE
Women and Children’s Health and Department of Population Health, School of Life Course & Population Sciences, King’s College London

PABLO LAMATA
Professor in Computational Cardiology, Department of Biomedical Engineering, King’s College London

REFERENCES

1. Mitanchez D & Chavatte-Palmer P 2018 Acta Paediatrica 107 1156–1165.
2. Razaz N et al. 2020 The Lancet Diabetes & Endocrinology 8 572–581.
3. Groves AM et al. 2021 Archives of Diseases in Childhood. Fetal and Neonatal Edition 107 481–487.
4. Taylor PD et al. 2014 Acta Physiologica 210 508–523.
5. Briley AL et al. 2014 BioMed Central Pregnancy and Childbirth 14 74.
6. Dalrymple KV et al. 2020 Pediatric Obesity 16 e12725.
7. Taylor PD et al. 2022 International Journal of Obesity 46 2145–2155.
8. Marciniak M et al. 2022 European Heart Journal – Cardiovascular Imaging 23 1645–1653.
9. Cox DJ et al. 2019 Pediatric Research 85 807–815.
10. Reynolds RM et al. 2013 The British Medical Journal 347 f4539.




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