A study by Poggi Davis et al reinforces these concerns.18 They studied 54 children, aged 6 to 10, who had received a single course of betamethasone at a mean gestational age of 29.3 weeks (+/- 3 weeks), delivered at term, and matched 1:2 to term infants not exposed to ACS. There were very concerning findings with ACS exposure: widespread differences in cortical thickness associated with significant thinning of the cortex, particularly the rostral anterior cingulate cortex (rACC), which is strongly associated with development of affective disorders, as well as HPA axis dysregulation.
These findings are consistent with every animal model of ACS exposure that has been studied.12 In particular, they mirror the findings of Uno et al who used different dexamethasone dosing regimens administered similarly to ACS to preterm macaques.19 In unpublished data, they demonstrated significant changes in the hippocampus, and neural damage in the cere tarded growth of the cerebellum. The finding on the cerebellum has been confirmed.20
Before endorsing the use of ACS at gestational ages when severe morbidity and mortality is low, the onus is on clinician-scientists and policy-makers to require long-term follow-up studies. ACS administration has always been enigmatic. We have gone from under-using it to abusing it with prophylactic weekly administration, to salvage therapy. Clinicians should avoid elective late-term deliveries and delay elective cesareans whenever possible to 39 weeks to reduce the morbidity associated with these deliveries.
In 2013, SMFM published recommendations regarding early delivery for multiple maternal, fetal, and obstetrical complications.21 These recommendations were largely determined by consensus and not high-quality data.
What are clinicians to do? Are we to deliver an increasing number of women late preterm to reduce the potential risks of expectant management and expose them to a single course of ACS all in an effort to avoid admission to the NICU and reduce short-term respiratory morbidity? Or should we avoid iatrogenic delivery prior to 39 weeks and thus obviate the need for ACS exposure but possibly increase fetal and maternal risk from continuing the pregnancy?
If parents were informed of the low risk of severe respiratory complications in the majority of late preterm or term infants and the unknown risk for irreversible changes in the brain and the hypopituitary axis, the majority would likely choose to avoid ACS therapy.
ACS therapy should not be expanded until we fully understand the potential risk-benefit ratio of treatment, and better understand the long-term consequences of exposure to ACS late preterm or at term. <
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