Antenatal Corticosteroids for Fetal Lung Maturity - Too Much of a Good Thing?

Abstract

Background: Between 5-15% of babies are born prematurely worldwide, with preterm birth defined as delivery before 37 completed weeks of pregnancy (term is at 40 weeks of gestation). Women at risk of preterm birth receive antenatal corticosteroids as part of standard care to accelerate fetal lung maturation and thus improve neonatal outcomes in the event of delivery. As a consequence of this treatment, the entire fetal organ system is exposed to the administered corticosteroids. The implications of this exposure, particularly the long-term impacts on offspring health, are poorly understood. Aims: This review will consider the origins of antenatal corticosteroid treatment and variations in current clinical practices surrounding the treatment. The limitations in the evidence base supporting the use of antenatal corticosteroids and the evidence of potential harm to offspring are also summarised. Results: Little has been done to optimise the dose and formulation of antenatal corticosteroid treatment since the first clinical trial in 1972. International guidelines for the use of the treatment lack clarity regarding the recommended type of corticosteroid and the gestational window of treatment administration. Furthermore, clinical trials cited in the most recent Cochrane Review have limitations which should be taken into account when considering the use of antenatal corticosteroids in clinical practice. Lastly, there is limited evidence regarding the long-term effects on the different fetal organ systems exposed in utero, particularly when the timing of corticosteroid administration is sub-optimal. Conclusion: Further investigations are urgently needed to determine the most safe and effective treatment regimen for antenatal corticosteroids, particularly regarding the type of corticosteroid and optimal gestational window of administration. A clear consensus on the use of this common treatment could maximise the benefits and minimise potential harms to offspring.

Maternal-Fetal Circadian Communication During Pregnancy

“…Additionally, some of these hormones are exogenously administered during pregnancy, but without consideration of their normal diurnal variation. For example, women at risk of preterm birth receive antenatal corticosteroids as part of standard care to improve neonatal outcomes (90). Knowing the appropriate daily profile and roles of glucocorticoids (e.g., in entraining the fetus) could inform the best times of day and doses for steroid treatment to promote fetal development and circadian entrainment.…”

Antenatal Betamethasone Every 12 Hours in Imminent Preterm Labour

“…More than 50% of pregnant women who received prenatal corticosteroids continue their pregnancy beyond day 7 from maturity or go to term [ 10 ]. It is also estimated that 15% of pregnant women who received prenatal corticosteroids finish their pregnancy before 48 h from the start of regimen, sometimes without having received the two doses of betamethasone or four doses of dexamethasone, which complete the course [ 11 ]. In these cases of imminent delivery, international guidelines recommend an administration of at least one dose of prenatal corticosteroid.…”

The effects of betamethasone on clinical outcome of the late preterm neonates born between 34 and 36 weeks of gestation

“…Taking corticosteroids between 34 to 36 weeks of gestation promotes fetal lung development, increases neonatal Apgar score, and reduces the likelihood of RDS [ 4 , 5 ]. Additionally, treatment with glucocorticoids in such pregnancies can reduce neonatal mortality and morbidity due to reducing the risk for intraventricular hemorrhage, necrotizing enterocolitis, decrease the need for intensive care unit cares, and increase the risk of sepsis in the first 48 h of neonatal life [ 6 – 8 ]. Human studies have also shown that betamethasone used during pregnancy can potentially affect placental function, fetal growth, hypothalamic-pituitary-adrenal axis development, and endocrine stress responses during infancy [ 9 – 12 ].…”