Repeat doses of antenatal betamethasone and risk factors for cardiometabolic disease at early school age.

Abstract

Commentary on: McKinlay CJ, Cutfield WS, Battin MR, Dalziel SR, Crowther CA, Harding JE, ACTORDS Study Group. Cardiovascular risk factors in children after repeat doses of antenatal glucocorticoids: an RCT. Pediatrics 2015; 135: e405–15. McKinlay et al. 1 provides new evidence regarding some aspects of long-term safety with the use of repeated courses of antenatal corticosteroids. The original aim of the ACTORDS study was to evaluate short-term outcomes, and it has shown reduced neonatal morbidity after repeated courses of antenatal corticosteroids without an associated increase in neurologic disability at two years of corrected age or at mid-childhood 2. In the context of cardiometabolic health, the associations between preterm birth and later hypertension, diabetes, stroke and even death from cardiovascular disease 3 – boosted by animal data – have generated worries about glucocorticoid exposure in foetal life, especially if repeated. The central worry is that this glucocorticoid exposure might be in the causal pathway towards cardiometabolic disease in adult life. Previously, there had been some conflicting observational data 4-9. The long-term evaluation by McKinlay et al. carries an important message; that is, there were no adverse cardiovascular and metabolic outcomes in children exposed to repeat dose(s) of antenatal betamethasone. Although reassuring, there are some, as always, remaining questions and limitations. First, extremely preterm infants were few in the ACTORDS study. The average gestational age at study entry was >28 weeks. It cannot be excluded that extremely low gestational age at exposure may exert long-standing effects on glucose metabolism. Secondly, although six to eight years of follow-up most be considered as long term from a neonatologist's perspective, it may be too short for the outcomes addressed. Finally, the authors state that they will report other outcomes separately. These include neurologic function, lung function, general intellectual ability, specific cognitive skills, behaviour, general health and health-related quality of life. I look forward to coming reports. So what should the attending obstetrician and neonatologist recommend? The latest Cochrane review of 10 randomised trials comparing single and repeat courses of antenatal glucocorticoids for neonatal morbidity favours repeat courses. And although repeated courses have been associated with lower birthweight and small reductions in head circumference, data on long-term safety outcomes are so far generally reassuring 2. According to ACOG present guidelines, a single rescue course of antenatal corticosteroids may be considered if the antecedent treatment was given more than two weeks prior, the gestational age is less than 32 weeks and the women are judged by the clinician to be likely to give birth within the next week. The ACTORDS follow-up studies – the one reviewed herein and others 2 – add further support for such recommendation. https://ebneo.org/2015/05/repeat-doses-of-antenatal-betamethasone-and-risk-factors-for-cardio-metabolic-disease-at-early-school-age/ None. None.