Isolating adverse effects of glucocorticoids on the embryonic cardiovascular system

Teulings, Noor E. W. D.; Garrud, Tessa A. C.; Niu, Youguo; Skeffington, Katie L.; Beck, Christian; Itani, Nozomi; Conlon, Fiona G.; Botting, Kimberley J.; Nicholas, Lisa M.; Ashmore, Tom; Blackmore, Heather L.; Tong, Wen Ting; Camm, Emily J.; Derks, Jan; Logan, Angela; Murphy, Michael P.; Ozanne, Susan E.; Giussani, Dino A.

doi:10.1096/fj.202000697r

Cited by 9 publications

(40 citation statements)

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“…Reported effects include a premature switch from tissue accretion to differentiation, increased oxidative stress, alterations in mitochondrial fatty acid oxidation and activation of cellular senescence in fetal cardiomyocytes. Long‐term adverse effects of synthetic steroids on cardiac function in offspring reported in preclinical experimental studies include weakened systolic function, an impaired cardiac functional reserve and left ventricular hypertrophy 5,6,7,46,47,48,49,50,51,52,53,54,55,56 . An interesting study by Kuo et al.…”

Section: Discussionmentioning

confidence: 99%

The effect of antenatal corticosteroid use on offspring cardiovascular function: A systematic review

Sacco

Cornish

Marlow

et al. 2022

BJOG

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Background: Antenatal corticosteroids (ACS) are recommended in threatened preterm labour to improve short-term neonatal outcome. Preclinical animal studies suggest detrimental effects of ACS exposure on offspring cardiac development; their effects in humans are unknown. Objectives: To systematically review the human clinical literature to determine the effects of ACS on offspring cardiovascular function. Search strategy: A systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines in MEDLINE, EMBASE and Cochrane databases.Selection criteria: Offspring who had been exposed to ACS during fetal life, in comparison with those not receiving steroids, those receiving a placebo or population data, were included. Studies not performed in humans or that did not assess cardiovascular function were excluded.Data collection and analysis: Two authors independently screened the studies, extracted the data and assessed the quality of the studies. Results were combined descriptively and analysed using a standardised Excel form.

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Section: Discussionmentioning

confidence: 99%

The effect of antenatal corticosteroid use on offspring cardiovascular function: A systematic review

Sacco

Cornish

Marlow

et al. 2022

BJOG

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“…It is possible that the synthetic rise in corticosteroids due to the maternal administration of betamethasone may also accelerate fetal cardiomyocyte growth and maturation in preparation for postnatal life and hence influenced the number of cardiomyocytes. 55 , 56 Importantly, the number of cardiomyocytes within the LV + S reduced consequent to prematurity, which is likely attributed to smaller body size. Given the limited replicative capacity of cardiomyocytes postnatally, the reduced endowment of LV + S cardiomyocytes following preterm birth may adversely impact lifelong functional reserve and the adaptive (structural and functional) capabilities of the myocardium for physiological hypertrophy in those individuals born preterm.…”

Section: Discussionmentioning

confidence: 99%

Intrauterine inflammation exacerbates maladaptive remodeling of the immature myocardium after preterm birth in lambs

et al. 2022

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Background Antenatal conditions that are linked with preterm birth, such as intrauterine inflammation, can influence fetal cardiac development thereby rendering the heart more vulnerable to the effects of prematurity. We aimed to investigate the effect of intrauterine inflammation, consequent to lipopolysaccharide exposure, on postnatal cardiac growth and maturation in preterm lambs. Methods Preterm lambs (~129 days gestational age) exposed antenatally to lipopolysaccharide or saline were managed according to contemporary neonatal care and studied at postnatal day 7. Age-matched fetal controls were studied at ~136 days gestational age. Cardiac tissue was sampled for molecular analyses and assessment of cardiac structure and cardiomyocyte maturation. Results Lambs delivered preterm showed distinct ventricular differences in cardiomyocyte growth and maturation trajectories as well as remodeling of the left ventricular myocardium compared to fetal controls. Antenatal exposure to lipopolysaccharide resulted in further collagen deposition in the left ventricle and a greater presence of immune cells in the preterm heart. Conclusions Adverse impacts of preterm birth on cardiac structure and cardiomyocyte growth kinetics within the first week of postnatal life are exacerbated by intrauterine inflammation. The maladaptive remodeling of the cardiac structure and perturbed cardiomyocyte growth likely contribute to the increased vulnerability to cardiac dysfunction following preterm birth. Impact Preterm birth induces maladaptive cardiac remodeling and adversely impacts cardiomyocyte growth kinetics within the first week of life in sheep. These effects of prematurity on the heart are exacerbated when preterm birth is preceded by exposure to intrauterine inflammation, a common antecedent of preterm birth. Inflammatory injury to the fetal heart coupled with preterm birth consequently alters neonatal cardiac growth and maturation and thus, may potentially influence long-term cardiac function and health.

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“…Although this work by Liggins and Howie has improved outcomes and saved the lives of countless preterm neonates, there remains interest in exploring alternative means of ensuring adequate lung development in the preterm population (Moisiadis & Matthews, 2014; McGowan & Matthews, 2018; Teulings et al . 2020). The concept of an artificial placenta to extend gestation and maintain fetal development ex utero has been of interest for many years (Westin et al .…”

Section: Introductionmentioning

confidence: 99%

“…The discovery that maternal glucocorticoid administration accelerated fetal surfactant production and improved neonatal outcomes is possibly the most successful example of preclinical research transforming clinical practice (Liggins, 1969;Liggins & Howie, 1972). Although this work by Liggins and Howie has improved outcomes and saved the lives of countless preterm neonates, there remains interest in exploring alternative means of ensuring adequate lung development in the preterm population (Moisiadis & Matthews, 2014;McGowan & Matthews, 2018;Teulings et al 2020). The concept of an artificial placenta to extend gestation and maintain fetal development ex utero has been of interest for many years (Westin et al 1958;Callaghan et al 1963;Rochow et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Haemodynamics and cerebral oxygenation of neonatal piglets in the immediate ex utero period supported by mechanical ventilation or ex utero oxygenator

Darby

Berry

Quinn

et al. 2021

The Journal of Physiology

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Key points The margin of human viability has extended to the extremes of gestational age (<24 weeks) when the lungs are immature and ventilator‐induced lung injury is common. Artificial placenta technology aims to extend gestation ex utero in order to allow the lungs additional time to develop prior to entering an air‐breathing environment. We compared the haemodynamics and cerebral oxygenation of piglets in the immediate period post‐oxygenator (OXY) transition against both paired in utero measures and uniquely against piglets transitioned onto mechanical ventilation (VENT). Post‐transition, OXY piglets became hypotensive with reduced carotid blood flow in comparison with both paired in utero measures and VENT piglets. The addition of a pump to the oxygenator circuit may be required to ensure haemodynamic stability in the immediate post‐transition period. Abstract Gestational age at birth is a major predictor of wellbeing; the lower the gestational age, the greater the risk of mortality and morbidity. At the margins of human viability (<24 weeks gestation) immature lungs combined with the need for early ventilatory support means lung injury and respiratory morbidity is common. The abrupt haemodynamic changes consequent on birth may also contribute to preterm‐associated brain injury, including intraventricular haemorrhage. Artificial placenta technology aims to support oxygenation, haemodynamic stability and ongoing fetal development ex utero until mature enough to safely transition to a true ex utero environment. We aimed to characterize the impact of birth transition onto either an oxygenator circuit or positive pressure ventilation on haemodynamic and cerebral oxygenation of the neonatal piglet. At 112 days gestation (term = 115 days), fetal pigs underwent instrumentation surgery and transitioned onto either an oxygenator (OXY, n = 5) or ventilatory support (VENT, n = 8). Blood pressure (BP), carotid blood flow and cerebral oxygenation in VENT piglets rose from in utero levels to be significantly higher than OXY piglets post‐transition. OXY piglet BP, carotid blood flow and carotid oxygen delivery (DO2) decreased from in utero levels post‐transition; however, cerebral regional oxygen saturation (rSO2) was maintained at fetal‐like levels. OXY piglets became hypoxaemic and retained CO2. Whether OXY piglets are able to maintain cerebral rSO2 under these conditions for a prolonged period is yet to be determined. Improvements to OXY piglet oxygenation may lie in maintaining piglet BP at in utero levels and enhancing oxygenator circuit flow.

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Isolating adverse effects of glucocorticoids on the embryonic cardiovascular system

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 9 publications

References 50 publications

The effect of antenatal corticosteroid use on offspring cardiovascular function: A systematic review

The effect of antenatal corticosteroid use on offspring cardiovascular function: A systematic review

Intrauterine inflammation exacerbates maladaptive remodeling of the immature myocardium after preterm birth in lambs

Haemodynamics and cerebral oxygenation of neonatal piglets in the immediate ex utero period supported by mechanical ventilation or ex utero oxygenator

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