Antenatal glucocorticoids: where are we after forty years?

Abstract

Since their introduction more than forty years ago, antenatal glucocorticoids have become a cornerstone in the management of preterm birth and have been responsible for substantial reductions in neonatal mortality and morbidity. Clinical trials conducted over the past decade have shown that these benefits may be increased further through administration of repeat doses of antenatal glucocorticoids in women at ongoing risk of preterm and in those undergoing elective cesarean at term. At the same time, a growing body of experimental animal evidence and observational data in humans has linked fetal overexposure to maternal glucocorticoids with increased risk of cardiovascular, metabolic and other disorders in later life. Despite these concerns, and somewhat surprisingly, there has been little evidence to date from randomized trials of longer-term harm from clinical doses of synthetic glucocorticoids. However, with wider clinical application of antenatal glucocorticoid therapy there has been greater need to consider the potential for later adverse effects. This paper reviews current evidence for the short- and long-term health effects of antenatal glucocorticoids and discusses the apparent discrepancy between data from randomized clinical trials and other studies.

Glucocorticoids as regulatory signals during intrauterine development

“…Clinically, synthetic glucocorticoids are given to pregnant women to treat asthma, arthritis and adrenal insufficiency and to improve neonatal viability in threatened preterm delivery (McKinlay et al 2014). These drugs are also given to mares to treat laminitis and to cattle to induce delivery at or near term (Johnson et al 2002;Mansell et al 2006).…”

“…However, the effects of F0 glucocorticoid treatment do not persist to the F3 generation never exposed to glucocorticoid excess, which indicates that any glucocorticoid-induced epigenetic marks are not stably inherited (Drake et al 2005). In humans, prenatal treatment with synthetic glucocorticoids also alters blood pressure and indices of insulin resistance postnatally, but the adult physiological outcomes of early-life glucocorticoid overexposure in humans appear to be less pronounced than in experimental animals and, to date, have unknown intergenerational consequences (Harris & Seckl 2011;McKinlay et al 2014); this relates to the longer human lifespan, because the majority of infants clinically exposed to synthetic glucocorticoids in utero are still relatively young adults. The outcomes of clinical glucocorticoid treatment of pregnant women for their infants are also likely to depend on the type and dose of synthetic glucocorticoid given, its route of administration and on the timing and duration of treatment during pregnancy (Brownfoot et al 2013;Aiken et al 2014;Romejko-Wolniewicz et al 2014).…”

Fetal and neonatal outcomes after term and preterm delivery following betamethasone administration in twin pregnancies

“…The administration of glucocorticoids in singleton pregnancies at risk of preterm birth to induce fetal lung maturation and reduce neonatal morbidity and mortality is common practice [1]. However, despite the beneficial effects, evidence is accumulating that higher doses of prenatal glucocorticoids result in impaired fetal growth and that exposure to high levels of glucocorticoids in utero is among the proposed mechanisms of perinatal programming [2,3].…”

Antenatal corticosteroid therapy for foetal maturation in women with eclampsia and severe pre-eclampsia in a rural hospital in Western Tanzania

“…ACT for foetal maturation has been undisputed since the publication by Liggins and Howie in 1972 [7], although long-term health effects have been less well studied [8]. In the most recent Cochrane systematic review of 18 trials the effect there was a 34 % reduction of respiratory distress syndrome, a 46 % reduction of intraventricular haemorrhage and a 31 % reduction in neonatal mortality [9].…”