Effects of Maternal Obesity On Cardiac Development An Offspring Study in Human Neonates and Minipigs

The results of a fascinating study conducted by Dr. Patricia Iozzo and her colleagues at the Institute of Clinical Physiology, in Pisa, Italy showed that neonatal changes in cardiac morphology were explained by late-trimester maternal body mass index; myocardial glucose overexposure seen in minipigs could justify early human findings. Moreover, long-term effects in minipigs consisted of myocardial insulin resistance, enzymatic alterations, and hyperdynamic systolic function, according to the publication in JACC: Cardiovascular Imaging.

The epidemic of obesity involves pregnant women. The uterine environment affects organ development, modulating disease susceptibility. Offspring of obese mothers have higher rates of cardiovascular events and mortality. In the light of this, the aim of this study was to investigate the consequences of maternal obesity on cardiac development in offspring in infants (short-term) and minipigs (short and longer term). Echocardiography was performed in infants born to lean and overweight mothers at birth and at 3, 6, and 12 months of age. In minipigs born to mothers fed a high-fat diet or a normal diet, cardiac development (echocardiography, histology), glucose metabolism and perfusion (positron emission tomography), triglyceride and glycogen content, and myocardial enzymes regulating metabolism (mass spectrometry) were determined from birth to adulthood.

The findings of the study portrayed that in neonates, maternal obesity, especially in the last trimester, predicted a thicker left ventricular posterior wall at birth (4.1 ± 0.3 vs. 3.3 ± 0.2 mm; p < 0.05) and larger end-diastolic and stroke volumes at 1 year. Minipigs born to mothers fed a high-fat diet showed greater left ventricular mass (p ¼ 0.0001), chambers (+100%; p < 0.001), stroke volume (+75%; p ¼ 0.001), cardiomyocyte nuclei (+28%; p ¼ 0.02), glucose uptake, and glycogen accumulation at birth (+100%; p < 0.005), with lower levels of oxidative enzymes, compared with those born to mothers fed a normal diet. Subsequently, they developed myocardial insulin resistance and glycogen depletion. Late adulthood showed an elevated heart rate (111 ± 5 vs. 84 ± 8 beats/min; p < 0.05) and ejection fraction and deficient fatty acid oxidative enzymes.

The investigators concluded that in humans, neonatal changes were explained by late-trimester maternal BMI. The animal model demonstrated that the elevation in myocardial glucose uptake, leading to glycogen accumulation and inhibition of glucose oxidative pathways, could explain cardiac findings in the newborn human. Lifespan data in minipigs showed that these cardiac changes subside, and later ages were characterized by myocardial insulin resistance, enzymatic alterations, and hyperdynamic systolic function. Speaking of future research in this field, the investigators acknowledged, “Although our minipig data reproduced infants’ results and we could follow minipigs through adulthood, which showed vulnerabilities, findings of myocardial insulin resistance and hyperdynamic function should be investigated and confirmed in adult humans. More research is required to validate molecular mechanisms and targets. In addition, studies preventing or reverting maternal obesity to demonstrate prevention potential are warranted.” Expressing his enthusiasm on the matter, Dr. Heinrich Taegtmeyer, Cardiologist at McGovern Medical School at The University of Texas Health Science Center at Houston, Texas remarked, “In summary, the work by Guzzardi et al.  reveals that maternal-fetal parabiosis combined with maternal metabolic stress results in structural and functional remodeling of the fetal heart. This remodeling continues and is sustained post-partum. Collectively, these observations expose unexpected and still incompletely understood mechanisms of cardiac growth and metabolism. This study also highlights the power of contemporary cardiac imaging and molecular techniques as tools with which to generate new and exciting hypotheses.”