Association between gestational age at birth, antenatal corticosteroids, and outcomes at 5 years: multiple courses of antenatal corticosteroids for preterm birth study at 5 years of age (MACS-5)

Abstract

BackgroundThe Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS) showed no benefit in the reduction of major neonatal mortality/morbidity or neurodevelopment at 2 and 5 years of age. Using the data from the randomized controlled trial and its follow-up, the aim of this study was to evaluate the association between gestational ages at birth in children exposed to single versus multiple courses of antenatal corticosteroid (ACS) therapy in utero and outcomes at 5 years of age.MethodA total of 1719 children, with the breakdown into groupings of <30, 30–36, and ≥ 37 weeks gestation at birth, contributed to the primary outcome: death or survival with a disability in one of the following domains: neuromotor, neurosensory, and neurobehavioral/emotional disability and were included in this analysis.ResultsGestational age at birth was strongly associated with the primary outcome, p < 0.001. Overall, the interaction between ACS groups and gestational age at birth was not significant, p = 0.064. Specifically, in the 2 preterm categories, there was no difference in the primary outcome between single vs. multiple ACS therapy. However, for infants born ≥37 weeks gestation, there was a statistically significant increase in the risk of the primary outcome in multiple ACS therapy, 48/213 (22.5%) compared to 38/249 (15.3%) in the single ACS therapy; OR = 1.69 [95% CI: 1.04, 2.77]; p = 0.037.ConclusionPreterm birth (<37 weeks gestation) remained the primary factor contributing to an adverse outcome regardless of the number of courses of ACS therapy. Children born ≥ 37 weeks and exposed to multiple ACS therapy may have an increased risk of neurodevelopmental/neurosensory impairment by 5 years of age. To optimize outcomes for infants/children, efforts in reducing the incidence of preterm birth should remain the primary focus in perinatal research.Trial registrationThis study has been registered at (identifier NCT00187382)Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2393-14-272) contains supplementary material, which is available to authorized users.

Antenatal Dexamethasone Exposure in Preterm Infants Is Associated with Allergic Diseases and the Mental Development Index in Children

“…This may explain the correlation between the use of antenatal corticosteroids and mental development. However, Asztalos et al demonstrated that, in preterm infants, the neurodevelopmental outcome remained the primary factor (such as gestational age at birth), which was contributory regardless of the number of courses of antenatal synthetic corticosteroid therapy [33]. Dexamethasone is not only used to promote fetus lung maturation but also to prevent further intraventricular hemorrhaging in preterm births before 34 weeks’ gestation [34].…”

Effects of antenatal glucocorticoids on the developing brain

“…Recommended treatment courses include two doses of 12mg betamethasone administered intramuscularly 24 hours apart or four doses of 6mg dexamethasone administered intramuscularly every 12 hours. This treatment is not standardized across the United States and treatment courses may be administered multiple times 6 , despite recent evidence that suggests that multiple doses of antenatal sGC do not significantly improve clinical outcomes 7 . In fact, the Multiple Courses of antenatal corticosteroids for preterm birth study at 5 years of age (MACS-5 study) indicated that multiple courses of antenatal sGC may have an increased risk for neurodevelopmental and neuropsychiatric conditions at the age of five years providing evidence against the use of multiple courses 7 .…”

Antenatal corticosteroids beyond 34 weeks gestation: What do we do now?

“…38 A rescue dose of steroids is often used in these situations; however, multiple courses of ANCS are not recommended due to poor fetal head growth and increased risk of neurodevelopmental impairment by 5 years. [39][40][41] To fully implement ANCS to the greatest benefit of the preterm pregnancies at risk of imminent delivery, improved methods of preterm birth prediction are needed. 42,43 Furthermore, if ANCS treatment is extended from 34 to <37 weeks and many of these fetuses deliver at term, the effects are unknown.…”