AFJOG

REVIEW analysis of seven RCTs, (n = 4144) mainly from low-and middle- income countries examined the use of ACS at late preterm gestations and found a reduced need for neonatal resuscitation at birth and respiratory support (RR = 0.68 CI=0.47–0.98), but worryingly, a higher risk of neonatal hypoglycaemia (RR = 1.61 CI=1.38–1.87), and thus called for studies with long term follow up to assess the neurodevelopmental outcomes. 10 Repeat Antenatal Corticosteroid doses It remains uncertain whether a repeat course of ACS should be administered in women who remain at risk of preterm birth below 34 weeks and in women with a previous course of ACS administered more than 7 days earlier, with a renewed high risk of imminent preterm labour. Most authorities recommend that a repeat course can be considered if the individual woman remains at risk of PTB in the next 7 days, and the previous administration was 7-14 days prior. 2, 14 This is regarded as a conditional recommendation because the evidence for its use is of low quality. The concerns in respect of repeat dose(s) of ACS arise from the studies which indicate the possibility of reduced head circumference, low birth weight, as well as the possibility of cerebral palsy. 15,16 Interestingly, another review of three clinical trials reported that a follow-up of children exposed to multiple doses of ACS showed no difference in neurodevelopment compared to those exposed to a single dose. 14 However, a meta-analysis of women at risk of preterm births who had multiple doses of ACS led to neurodevelopmental variations noted in children between the ages of two to three years. 15 Getting the Balance Right Given the increasing concerns of the potential long-term harms of the use of ACS, experts have suggested strategies which could be considered to balance the benefits of ACS against the potential long-term harms. 11, 12 One strategy suggested, is to ensure accurate pregnancy dating as the gestational age threshold for antenatal corticosteroid administration is clinically relevant. Estimating gestational age by use of clinical decision support tools is essential for the appropriate administration and timing of these drugs. In 2022, the WHO updated guidelines based on evidence from 27 efficacy trials including the WHO Action-1 trial, and re-iterated its recommendation that antenatal steroids should be used under the following conditions: only when gestational age can be accurately assessed (<33 weeks plus 6 days gestational age), preterm birth is considered imminent, there is no clinical evidence of maternal infection, adequate neonatal care is available and the preterm neonate can receive adequate care for complications if needed (resuscitation, thermal support, feeding support, infection treatment and safe oxygen use). 2 Another strategy to reduce potential long-term harms is to use the most appropriate dose of antenatal corticosteroids. 13 Liggins and Howie based their dosage on the results from preclinical studies in foetal sheep. 1 Recently, animal studies indicated that half of the current betamethasone dose might be as effective as a full dose. 11 In a recent article, Schmitz et al., tested the hypothesis that half a dose of antenatal betamethasone is non-inferior to a full dose in women at risk of preterm birth in a double-blind, placebo controlled non-inferiority trial. 12 These findings did not support a change to a half dose of betamethasone. The researchers suggest that the current dose of betamethasone is unlikely to change in the near future and that there is a need for further studies. 13 The appropriate dose to reduce the adverse effects of foetal exposure to ACS has not been established yet, but a study conducted in sheep suggested that it is the duration of low dosages and not necessarily high dosages of ACS exposure that promotes lung maturation. 16 The current variability between users with regards the duration of administration (24 versus 48 hours from first dose), the frequency and the interval in between the doses, needs further clarification. The emerging potential harms obviously need further investigation on all human organ systems as steroids have pleiotropic activities, and in particular the developing brain contains a high level of steroid receptors. 17 Key Points • ACS should be judiciously administered to women at a gestational age between 24 weeks +6 days and 33weeks +6 days when preterm birth is anticipated within the next 7 days. 18 • Administration between 34 and 36 weeks should be considered and discussed with the families concerned. 18 • Administration in pregnancies beyond 37 weeks is not advocated even for elective caesarean births, as current evidence does not suggest benefit, and there may be potential long term developmental problems in children. 18 • Either Betamethasone or dexamethasone maybe used. • Further studies should consider ACS doses based on maternal weight, as women with low body mass index may develop severe hyperglycaemia, and this may potentially limit undesired long-term effects in the offspring. 19 Conclusion The judicious use of ACS in women who are in imminent preterm labour (between 24-34 weeks) is not disputed, and a single repeat course can be considered in pregnancies which remain at risk of premature delivery, 7-days after a previous course in a pregnancy below 34 weeks gestational age, as multiple doses may affect neonatal development negatively. REFERENCES ® § ¥ ¤ ½ ¤ · African Journal of Obstetrics and Gynaecology | Volume 1 | Issue 2 | 2023 | 18