Is there a relationship between maternal bronchial asthma treated with corticosteroids (steroids) and the risk of fetal cleft palate?

From the Guidelines

The use of systemic corticosteroids by mothers with bronchial asthma during pregnancy has a small but increased risk of causing cleft palate in the developing fetus, particularly when used during the first trimester, as supported by recent studies such as 1 and 1. The risk appears to be dose-dependent, with higher doses and longer durations of treatment posing greater risk. For pregnant women with asthma requiring treatment, inhaled corticosteroids like budesonide (preferred during pregnancy) are generally considered safer alternatives with minimal systemic absorption and lower risk of fetal malformations, as stated in 1 and 1. Some key points to consider include:

• The benefits of treating severe maternal asthma typically outweigh the small increased risk of cleft palate, as uncontrolled asthma poses significant risks to both mother and fetus including preeclampsia, preterm birth, and low birth weight, as mentioned in 1 and 1.
• The mechanism behind this association involves corticosteroids potentially interfering with palatal shelf migration and fusion during weeks 6-9 of embryonic development.
• Pregnant women with asthma should work closely with both pulmonologists and obstetricians to maintain optimal asthma control while minimizing potential risks to the developing fetus. It is essential to weigh the risks and benefits of treatment and consider the individual patient's circumstances, as recommended in 1 and 1. In general, the preferred treatment for long-term-control medication in pregnant women with asthma is daily low-dose inhaled corticosteroid, such as budesonide, due to its strong effectiveness data and reassuring safety profile, as stated in 1 and 1.

From the FDA Drug Label

Subcutaneous studies in the mouse and rat at 45 and 100 mcg/kg, respectively (approximately equivalent to and 4 times, respectively, the maximum recommended daily intranasal dose in adults on a mcg/m basis) revealed fetal toxicity characteristic of potent corticosteroid compounds, including embryonic growth retardation, omphalocele, cleft palate, and retarded cranial ossification Corticosteroids have been shown to be teratogenic in many species when given in doses equivalent to the human dose Animal studies in which corticosteroids have been given to pregnant mice, rats, and rabbits have yielded an increased incidence of cleft palate in the offspring.

Relationship between maternal steroid use and fetal cleft palate:

• There is evidence from animal studies that corticosteroids, including fluticasone and prednisone, may increase the risk of fetal cleft palate when used during pregnancy 2 3.
• The FDA drug labels for fluticasone and prednisone indicate that these medications should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
• Key points:
  • Corticosteroids have been shown to be teratogenic in animal studies.
  • Fetal cleft palate is a potential risk associated with maternal corticosteroid use.
  • The safety of corticosteroids during pregnancy has not been established in humans.

From the Research

Relationship Between Maternal Bronchial Asthma and Fetal Cleft Palate

• There is no direct evidence in the provided studies to support a relationship between maternal bronchial asthma, steroid use, and fetal cleft palate.
• The studies primarily focus on the treatment of asthma using corticosteroids, comparing different dosages, and types of corticosteroids, as well as their effects on asthma symptoms and lung function 4, 5, 6, 7, 8.
• None of the studies mention fetal cleft palate as an outcome or discuss the potential effects of maternal asthma or steroid use on fetal development.
• Therefore, there is no conclusive evidence to support or refute a relationship between maternal bronchial asthma, steroid use, and fetal cleft palate based on the provided studies.

Corticosteroid Use in Asthma Treatment

• Corticosteroids are a common treatment for asthma, with studies comparing the efficacy of different types and dosages of corticosteroids 4, 5, 6, 7, 8.
• The studies suggest that inhaled corticosteroids, such as fluticasone propionate and budesonide, are effective in improving lung function and reducing asthma symptoms 6, 7, 8.
• Oral corticosteroids, such as prednisolone, are also used to treat acute asthma exacerbations, but their use needs to be balanced against potential side effects 4, 5.

Limitations of the Studies

• The studies have limitations, including variability in study design, outcome measures, and interventions, which limit the ability to draw firm conclusions 4, 5, 6, 7, 8.
• The studies primarily focus on adult populations, with limited data on pediatric populations 4, 5, 6, 7, 8.
• Further research is needed to fully understand the effects of corticosteroids on asthma treatment and potential fetal outcomes.