Safety of antenatal predniso(lo)ne and dexamethasone on fetal, neonatal and childhood outcomes: a systematic review
Context
Due to ethical considerations, antenatal dose finding for prednisolone and dexamethasone in pregnant women is limited, leading to a knowledge gap. In order to guide the clinician in weighing benefits versus risks, the aim is to systematically review the current literature on the side-effects of antenatal predniso(lo)ne and dexamethasone use on the foetus, newborn and (pre)pubertal child and to review whether there is a relationship between the dose and risk of these side-effects.
Evidence Acquisition
The search was performed in PubMed/MEDLINE and EMBASE using prespecified keywords and Medical Subject Headings (MeSH). This systematic review investigated studies published until August 2022 with the following inclusion criteria: studies were conducted in humans and assessed side-effects of long-term antenatal predniso(lo)ne and dexamethasone use during at least one of the trimesters on the child during the foetal period, neonatal phase and during childhood. Exclusion criteria were 1) studies not conducted in humans, 2) abstracts, 3) reviews, 4) retracted papers and 5) papers not written in English. Critical appraisal tools of the Joanna Briggs Institute (JBI) were used to assess bias.
Evidence Synthesis
In total, 328 papers in PubMed and 193 in EMBASE were identified. Fifteen studies were eligible for inclusion. Seven records were added through references. Antenatal predniso(lo)ne use may be associated with lower gestational age, but was not associated with miscarriages and stillbirths, congenital abnormalities, differences in blood pressure or low blood glucose levels at birth, or with low bone mass, long-term elevated cortisol and cortisone or high blood pressure at prepubertal age. Increased risks of antenatal dexamethasone use include association with miscarriages and stillbirths, and from age sixteen years, associations with disturbed insulin secretion, higher glucose and cholesterol levels. The quality of reporting of the studies was high. However, part of the cohort studies lack of a control group.
Conclusions
Based on the limited evidence found in this systematic review, predniso(lo)ne may have less side-effects compared to dexamethasone in short- and long-term outcomes. Current literature shows minimal risk of side-effects in the newborn by administration of a prenatal predniso(lo)ne dose of up to 10 mg per day.