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.

OBJECTIVE: In order to guide the clinician in weighing benefits vs risks, the aim is to systematically review the current literature on the side effects of antenatal predniso(lo)ne and dexamethasone use on the fetus, newborn, and (pre)pubertal child.

EVIDENCE ACQUISITION: The search was performed in PubMed/MEDLINE and Embase using prespecified keywords and Medical Subject Headings. 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 fetal period, neonatal phase, and during childhood.

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 16 years, associations with disturbed insulin secretion and higher glucose and cholesterol levels.

CONCLUSIONS: Based on the limited evidence found, predniso(lo)ne may have less side effects compared with dexamethasone in short- and long-term outcomes. Current literature shows minimal risk of side effects in the newborn from administration of a prenatal predniso(lo)ne dose of up to 10 mg per day.