USE OF SYSTEMIC CORTICOSTEROIDS IN PREGNANCY

Systemic corticosteroids available in the UK include prednisolone, prednisone, hydrocortisone, betamethasone, dexamethasone, deflazacort, methylprednisolone and triamcinolone.

Corticosteroids are used to reduce inflammation, suppress the immune system, and replace hormones where a deficiency exists. The British Society for Rheumatology (BSR) states that prednisolone is compatible with pregnancy and is the preferred corticosteroid for treatment of rheumatological disease in pregnancy. Guidelines from the Royal College of Obstetricians and Gynaecologists (RCOG) state that where premature delivery is anticipated, intramuscular dexamethasone or betamethasone should be offered to women to reduce the risk of neonatal respiratory distress syndrome. Systemic corticosteroids are also used in the treatment of severe COVID-19 infection, including during pregnancy.

Systemic administration of corticosteroids during organogenesis has been associated with an increase in rates of cleft lip and palate in some animal models. Although the majority of human data do not demonstrate that gestational exposure to systemic corticosteroids increases the risk of orofacial clefts, a small number of studies have suggested an association and further research is therefore required. The available data do not support an association between in utero exposure to systemic corticosteroids and cardiac defects in the offspring. Data on other specific malformations are too limited to confirm or refute associations. Studies assessing birth weight outcomes following gestational exposure to systemic corticosteroids (low birth weight, intrauterine growth restriction, small for gestational age) do not provide robust evidence of an association but are limited. The currently available data suggest that preterm delivery may be associated with gestational exposure to systemic corticosteroids. However, they do not rule out that this may be due to confounding as a consequence of the underlying maternal illness, rather than to steroid exposure itself, and further well-controlled studies are required to address this question. Due to limited data, it is not currently possible to conduct an evidence-based assessment of the risks of miscarriage or intrauterine death following corticosteroid use but prescribers should be aware that uncontrolled inflammation has been linked to fetal demise. The data on neurodevelopmental outcomes in the child following gestational exposure to systemic corticosteroids are generally highly confounded by the fact that these drugs are commonly used in the setting of premature rupture of membranes and/or preterm or very preterm delivery.

It should also be noted that many of the studies reporting pregnancy outcomes following gestational exposure to systemic corticosteroids are limited by a lack of stratification to account for differing doses, treatment duration, and steroid potencies. An increased risk of adverse fetal effects following use of high dose/potency corticosteroids, or use for extended periods, can therefore not be ruled out.

Where use of systemic corticosteroids is clinically indicated for the mother or fetus, treatment should not be withheld on account of pregnancy. Exposure to corticosteroids at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy or any additional fetal monitoring. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments.