Antenatal corticosteroids not associated with long-term effects on BP in exposed offsprings
Over the last 40 years, the administration of antenatal corticosteroids (ACS) has become routine practice in mothers with threatened preterm labour between 24 and 34 weeks of gestation. In this circumstance, ACS are proven to reduce short-term neonatal morbidity-especially that caused by respiratory distress syndrome, intraventricular haemorrhage, necrotising enterocolitis and sepsis-and mortality. Prophylactic treatment with ACS is designed to mimic the maturational effects of the normal endogenous, prepartum increase in fetal plasma cortisol concentration that occurs close to term in humans and other species. Glucocorticoids are known to switch tissue accretion to differentiation. Therefore, ACS accelerate the maturation of many fetal organs and systems, enhancing the preterm baby's successful transition to neonatal life.
Despite the clear life-saving benefits of ACS, there is an increasing awareness of possible adverse off-target effects. The developing cardiovascular system is also affected by glucocorticoid signalling. Preclinical animal studies have suggested that ACS may have long-term adverse effects on the heart and the circulation but much less is known about the cardiovascular consequences of ACS exposure in humans. Therefore, the aim of this study by Sacco A, Cornish EF, Marlow N et al was to systematically review the human clinical literature to determine the effects of ACS on offspring cardiovascular function.
A systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines in MEDLINE, EMBASE and Cochrane databases. 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. Two authors independently screened the studies, extracted the data and assessed the quality of the studies.
Twenty-six studies including 1921 patients were included, most of which were cohort studies of mixed quality. The type of ACS exposure, gestational age at exposure, dose and number of administrations varied widely. Offspring cardiovascular outcomes were assessed from 1 day to 36 years postnatally. The most commonly assessed parameter was arterial blood pressure (18 studies), followed by echocardiography (eight studies), heart rate (five studies), electrocardiogram (ECG, three studies) and cardiac magnetic resonance imaging (MRI, one study). There were no clinically significant effects of ACS exposure on offspring blood pressure. However, there were insufficient studies assessing cardiac structure and function using echocardiography or cardiac MRI to be able to determine an effect.
This systematic review identified 26 studies in humans assessing cardiovascular function following ACS exposure, where appropriate controls such as no exposure, placebo or population norms were included. The majority of these studies focused solely on the assessment of arterial BP. Such studies reported either no effect or, in the neonatal period specifically, an increase in the MAP of the infant. This was seen as either clinically beneficial, reducing the need for vasopressor BP support, or clinically irrelevant.
Maternal ACS are administered to women at risk of preterm birth so as to reduce the risk of serious illness and death in newborns. It is estimated that ACS reduce perinatal death, reduce neonatal death and reduce respiratory distress syndrome. Importantly, the evidence demonstrates improved outcomes in preterm infants (24–34 weeks) delivered between 1 and 7 days after the administration of a single course of ACS. Often women in threatened preterm labour do not deliver within this short time frame following ACS administration, however, and more go on to deliver after 34 weeks of gestation, when ACS are not recommended.
This systematic review found that the administration of ACS is not associated with long-term effects on BP in exposed human offspring. The human data on other adverse long-term cardiovascular consequences of ACS exposure are insufficient to exclude important harmful effects. Given the evidence from animal and human studies, the administration of ACS should be limited to clinical settings where there is a high degree of certainty that preterm birth is imminent, to reduce the risk that as yet poorly understood adverse effects might outweigh the known clinical benefits. Ascertaining the potential direct long-term effects of ACS on cardiovascular function in exposed children should be a clinical priority going forward. Authors would therefore recommend further clinical research on the effects of ACS specifically on cardiac structure and function in children born both preterm and at term.
Source: Sacco A, Cornish EF, Marlow N, David AL, Giussani DA. The effect of antenatal corticosteroid use on offspring cardiovascular function: A systematic review. BJOG: Int J Obstet Gy. 2022;00:1–9. https://doi.org/10.1111/1471-0528.17316
