REMARKS Q This recommendation applies to all other recommendations relating to the use of antenatal corticosteroid therapy in this guideline (i.e. Recommendations 1.1 to 1.10). Q High likelihood of preterm birth within 7 days may be assessed using the following criteria: preterm membrane rupture without preterm labour, spontaneous preterm labour with intact membranes (where preterm labour is defined as at least six regular uterine contractions/hour and at least one of the following: cervix ≥3 cm dilated or ≥75% effaced), or planned preterm birth by induction or caesarean section. Q The recommendation is largely based on evidence derived from settings where the certainty of gestational age estimation is reasonably high. Therefore, accurate and standardized gestational age assessment (ideally from first trimester ultrasound, or an ultrasound performed at the time of presentation in situations where an early ultrasound of reasonable quality is not available) is essential to ensure that all eligible women receive corticosteroid therapy while avoiding unnecessary treatment of ineligible women. Antenatal corticosteroids should not be routinely administered in situations where ultrasound for gestational age assessment cannot be performed. Q In defining the upper limit of gestational age for antenatal corticosteroid therapy, the GDG placed its emphasis on study populations where there is convincing evidence that the benefits of antenatal corticosteroid therapy outweigh the potential harms. The GDG acknowledged the overlap in the populations of the subgroups considered (≤35 weeks and ≥34 weeks) and that the overall benefits of antenatal corticosteroid therapy probably extend up to 35 weeks. Nonetheless, the GDG specified 34 weeks 0 days as the upper limit because of the uncertainties in the balance between benefits and harms that clearly exist in the ≥34 weeks subgroup (respiratory morbidity benefits versus increased risk of neonatal hypoglycaemia), that is largely based on evidence derived from studies conducted in high-income settings. Additionally, the GDG considered 34 weeks (rather than 35 weeks) as a reasonable safeguard to prevent the use of corticosteroids in women at risk of preterm birth later in gestation, given the limitations in accuracy of gestational age assessment during the final weeks of the third trimester. Q The GDG agreed that while the lower limit of gestational age for antenatal corticosteroid therapy was based on available trial evidence, corticosteroids may be associated with substantial clinical benefits among infants born at <24 weeks who were exposed to corticosteroids antenatally, based on evidence from observational studies. The GDG noted that the probability of survival without long-term residual morbidity (“intact survival”) at <24 weeks is low, even in high-resource settings, and therefore shared decision-making among women and health care professionals on the immediate and long-term risks of extreme prematurity even in the context of antenatal corticosteroid therapy is warranted. Q The GDG acknowledged that the recommendation conditions listed above may not be operationalized in a standard and consistent manner across settings. However, the GDG placed its emphasis on the new evidence of mortality and morbidity reduction from antenatal corticosteroid therapy in lowresource countries where these conditions were reasonably and consistently met (20), against the background of previous evidence suggestive of harms in low-resource countries where these conditions were not prioritized (18). The GDG agreed that the possibility of harms from antenatal corticosteroid therapy cannot be excluded in settings where these conditions cannot be met such as lower-level health facilities and at the community level. To successfully operationalize these conditions, further details are provided under the implementation considerations section. Q The GDG acknowledged evidence of possible benefit to neonates born at 34 weeks to <37 weeks as well as potential increased risks of harm (neonatal hypoglycaemia) and noted that further trials are required to improve understanding of the balance of harms and benefits, particularly in low-resource settings.

Implementation considerations outlined in Table 2.