Antenatal corticosteroids in Singapore: a clinical and scientific assessment

Abstract

Preterm birth (PTB; delivery prior to 37 weeks' gestation) is the leading cause of early childhood death in Singapore today. Approximately 9% of Singaporean babies are born preterm; the PTB rate is likely to increase given the increased use of assisted reproduction technologies, changes in the incidence of gestational diabetes/high body mass index and the ageing maternal population. Antenatal administration of dexamethasone phosphate is a key component of the obstetric management of Singaporean women who are at risk of imminent preterm labour. Dexamethasone improves preterm outcomes by crossing the placenta to functionally mature the fetal lung. The dexamethasone regimen used in Singapore today affords a very high maternofetal drug exposure over a brief period of time. Drawing on clinical and experimental data, we reviewed the pharmacokinetic profile and pharmacodynamic effects of dexamethasone treatment regimen in Singapore, with a view to creating a development pipeline for optimising this critically important antenatal therapy.

Figure 1

Chart shows increasing survival of premature babies born at 24, 25 and 26 weeks of gestation over the last two decades at National University Hospital, Singapore.

Figure 2

Chart shows neurodevelopmental impairments at 18–24 months among survivors born at 23–25 weeks: (National University Hospital 2015–2020; n = 33/36). None/mild = no hearing or visual impairment, no cerebral palsy (CP), and Bayley Scale of Infant Development cognitive composite score >85; moderate = ≥1 mild/moderate CP, Gross Motor Function Classification System (GMFCS) score 2–3, cognitive composite score 70–85, unilateral hearing loss or bilateral loss not requiring aids, visual impairment requiring glasses at 2 years; severe = severe CP, GMFCS score 4–5, cognitive composite score <70, blindness or deafness.

Figure 3

Chart shows comparative maternal and fetal drug level projections for the following antenatal steroid treatment regimens: (1) two 12-mg maternal intramuscular injections of dexamethasone phosphate spaced by 12 hours (Singapore regimen); (2) four 6-mg maternal intramuscular injections of dexamethasone phosphate spaced by 12 hours (WHO regimen used predominantly in low-resource jurisdictions; (3) two 12-mg maternal intramuscular injections of combined betamethasone phosphate and betamethasone acetate spaced by 24 hours (regimen proposed by Liggins and Howie and used in Australia and the USA); and (4) putative low-dose dexamethasone regimen, consisting of four 1.5-mg maternal intramuscular injections of dexamethasone phosphate spaced by 12 hours.