Both antenatal and postnatal steroids have the capacity to influence neurodevelopment and outcome. We will review the latest evidence regarding the most controversial issues.
Steroids have been used in the treatment of respiratory problems in preterm infants since the 1950s and the relationship between neonatologists and steroids has swung like a pendulum ever since.1 The earliest rationale for trying steroids was the observation that they accelerate lung development, and particularly surfactant synthesis. Despite this theoretical basis, studies in the 1970s of postnatal steroids (PNS) in infants ventilated for respiratory distress syndrome (RDS) failed to show
In 35 of the 38 trials of corticosteroids, the study drug was dexamethasone and 4056 infants were enrolled. These studies were highly varied in design. The duration of therapy varied from a mini pulse of two doses to a full six weeks' tapering course. The start of therapy varied the day of birth to three to four weeks. There was overlap in combinations of duration and timing such that the early studies group included studies of just two doses together with studies with a course of therapy from
The most extensive analyses are the Cochrane reviews that were most recently updated in 2003 and included all published RCTs (n = 37) of preterm infants at risk for BPD that compared intravenous or oral steroids with placebo. The primary factor by which the studies were categorized was the age at the start of therapy. This aimed to reflect the clinical intention of the investigators as therapy in the first week of life aims hopefully to prevent BPD, in the second week a combination of prevention
In recent years, a number of additional trials have reported long-term follow-up data and one important additional RCT has been reported. In order to enhance this discussion, we have conducted a new meta-analysis of the RCTs that compared dexamethasone with placebo and that have reported long-term follow-up.5, 28, 29, 30, 31, 32, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45 These studies were identified by review of previous analyses together with an updated Medline search. The data were
The combined evidence of RCTs, meta-analyses and cohort and case–control studies demands that find a better and safer treatment for BPD than dexamethasone.
Antenatal corticosteroids (ACS) are generally thought to be beneficial (reduced mortality and respiratory and neurologic morbidity). However, any potent therapy administered to the fetus has the potential to alter normal development. In a recent large cohort study, ACS treatment was highly associated with favorable outcome in infants born at 22–25 weeks of gestation.47 However, until recently, relatively little information has been available regarding their short- and long-term effects on the
Perinatal corticosteroids represent a potent intervention for both the fetus and preterm infant. Although widely used, many issues remain unclear and more research is required to understand how to gain the optimal benefits with minimal harm. Updated meta-analysis shows postnatal dexamethasone to be clearly related to risk for neurodevelopmental impairment. Lower doses of dexamethasone are as yet of unproven safety. Antenatal steroids: betamethasone is preferred and repeat coursesPractice points
We had not expected such large numbers to score so poorly in several domains. Several studies reported that high doses of postnatal steroids are associated with an increased risk of neurodevelopmental impairments, especially motor impairments [4,22–24]. To the best of our knowledge, however, there are only a few studies on the use of low-dose DXM and none report any significant abnormal neurological outcomes [10,11,25].
This results in increased target gene expression such as for anti-inflammatory-proteins (transactivation), or reduced production of pro-inflammatory proteins (transrepression) (Rhen and Cidlowski, 2005). The therapeutic effects of CSs as anti–inflammatory and immunosuppressive drugs have been employed since the 1950s (Chari, 2014; Shinwell and Eventov-Friedman, 2009) to treat diverse pathologies such as asthma, allergies and rheumatoid arthritis (Rhen and Cidlowski, 2005). In neural cell transplantation therapy, the use of anti-inflammatory and immunosuppressive drugs such as CSs is essential to improve transplant survival and limit rejection by host tissue (Mazzini et al., 2015; Skardelly et al., 2013).
Corticosteroids are therefore useful in the management of women who are at immediate risk of preterm birth before 34 weeks of gestation (with or without PPROM). However, based on this finding and results from some other studies [18,19], further investigation of the possible adverse effects of antenatal corticosteroids on brain development is needed. In this study, hypoglycemia was associated with a significantly increased risk of an abnormal ASQ outcome.
A systematic review reported that high-dose DXM after the first week of life facilitated extubation, reduced the rate of BPD, and reduced neonatal mortality [2]. Evidence also hints at DXM having detrimental effects on the developing central nervous system as illustrated by reduced brain growth [3], and an increased risk of cerebral palsy (CP) [4]. Regarding cognition and behavior, outcome studies of DXM-treated children are sparse and report predominantly on pre-school age outcome [5,6].
This cautious approach to the use of postnatal steroid therapy is adopted in our NICU, too, where this treatment, restricted to the most severe cases, is used in around 12%, a rate slightly higher than that reported by the VON (9.9%).39 In our sample, in agreement with the literature,40 neonatal steroid treatment emerged as a significant and independent risk factor for a poor outcome. Another risk factor found in our sample was surgical closure of PDA, again confirming the findings of others.41
