Does the dose of Corticosteroid (corticosteroid) cause cleft palate?

From the Guidelines

Corticosteroids taken during pregnancy, particularly during the first trimester, can increase the risk of cleft palate in developing fetuses, with a dose-dependent relationship and higher doses posing greater risk, as noted in a study published in 2020 1. The risk is highest when these medications are taken between weeks 7-12 of pregnancy, which is the critical period for palate formation.

• Systemic corticosteroids like prednisone, prednisolone, and dexamethasone are of particular concern, especially when doses exceed 20mg per day of prednisone or equivalent.
• The mechanism involves corticosteroids interfering with normal facial development by affecting cell migration, proliferation, and differentiation in the developing palate.
• Pregnant women requiring corticosteroid treatment should discuss the risks with their healthcare provider, as the benefits of treatment may outweigh the risks in certain medical conditions.
• When possible, using the lowest effective dose, topical rather than systemic administration, or alternative medications may help reduce this risk, as suggested by a study published in 2021 1.
• Women with conditions requiring ongoing corticosteroid therapy who are planning pregnancy should consult with their healthcare provider about medication management before conception, and consider the potential risks and benefits of corticosteroid use during pregnancy, as outlined in a study published in 2024 1.
• A study published in 2020 1 also recommended that oral corticosteroids in short bursts may be safe after the first trimester, but consultation with the patient's obstetrician is recommended.
• Overall, the decision to use corticosteroids during pregnancy should be made on a case-by-case basis, taking into account the potential risks and benefits, as well as the severity of the underlying medical condition, and considering the most recent and highest quality evidence available, such as the study published in 2020 1.

From the FDA Drug Label

Pregnancy Teratogenic Effects Pregnancy Category C Prednisolone has been shown to be teratogenic in many species when given in doses equivalent to the human dose. Animal studies in which prednisolone has been given to pregnant mice, rats, and rabbits have yielded an increased incidence of cleft palate in the offspring.

The dose of corticosteroid may cause cleft palate in the offspring, as shown in animal studies 2. However, it is essential to note that there are no adequate and well-controlled studies in pregnant women. Therefore, prednisolone sodium phosphate oral solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Key points:
  • Cleft palate has been observed in animal studies.
  • No adequate and well-controlled studies in pregnant women.
  • Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

From the Research

Corticosteroid Use and Cleft Palate Risk

• The relationship between corticosteroid use during pregnancy and the risk of cleft palate in newborns has been investigated in several studies 3, 4, 5, 6, 7.
• A case-control study published in 1998 found a significant association between exposure to corticosteroids during the first trimester of pregnancy and an increased risk of cleft lip (with or without cleft palate) in newborn infants, with an odds ratio of 6.55 (95% CI = 1.44-29.76, P = 0.015) 3.
• However, a study published in 2014 found no association between maternal corticosteroid use and cleft lip and palate in offspring, with an odds ratio of 1.0 (95% CI = 0.7-1.4) 4.
• Another study published in 2007 suggested a moderately increased risk of cleft lip and palate among women who use corticosteroids during early pregnancy, with a crude odds ratio of 1.7 (95% CI = 1.1-2.6) for cleft lip and palate, and 0.5 (95% CI = 0.2-1.3) for cleft palate only 5.
• A case-control study published in 2003 found a significant increase in prevalence of maternal use of topical corticosteroids in the first trimester of pregnancy among children with nonsyndromic cleft lip or palate, with an odds ratio of 13.154 (95% CI = 1.67-586, P = 0.0049) 6.
• A nationwide cohort study published in 2011 found no statistically significant increased risk of orofacial clefts associated with the use of corticosteroids during pregnancy, with prevalence odds ratios of 1.05 (95% CI = 0.80-1.38) for cleft lip with or without cleft palate, and 1.23 (95% CI = 0.83-1.82) for cleft palate alone 7.

Study Findings

• The studies suggest inconsistent findings regarding the association between corticosteroid use during pregnancy and the risk of cleft palate in newborns 3, 4, 5, 6, 7.
• Some studies found a significant association between corticosteroid use and an increased risk of cleft lip and palate 3, 5, 6, while others found no association 4, 7.
• The findings of these studies should be considered when evaluating the potential risks and benefits of corticosteroid use during pregnancy 3, 4, 5, 6, 7.