Answer:
In August 2004, the FDA upgraded intranasal budesonide, which is an intranasal corticosteroid, to (then) pregnancy category B based on a review of 3 Swedish Birth Register studies containing pregnancy and neonatal outcomes from Sweden from 1995 to 2001. All other intranasal corticosteroids used for the treatment of AR remained (then) pregnancy category C because of insufficient human data. Additionally, the use of Budesonide has been extensively studied regarding the safety in children.
Thorrson, et al (1) found that systemic absorption of Aqueous Budesonide has a 21% bio-availability. The authors went on to state that the low figures of systemic availability claimed for FP and MF may also be related to difficulties in determining the systemic availability correctly due to plasma concentrations below the lower limit of quantification (LOQ). That plasma concentrations are below the lower LOQ does not exclude that the GCS is associated with a significant systemic activity. For instance, a clinical dose of 200 μg day−1 of nasal FP was recently found to produce a significant suppression (43%) of overnight urinary cortisol, indicating a systemic absorption of FP. The systemic availability of MF after nasal administration remains to be investigated.
A Cochrane Review (2) looked at interventions managing asthma in pregnancy and stated fluticasone and budesonide have been regarded as ’preferred’ inhaled corticosteroids for use in pregnancy, with the most gestational safety data for budesonide. Beclomethasone was found inferior.
It was concluded that it is important that the agents assessed are either those commonly utilized or recommended in current clinical practice (for example, considering inhaled corticosteroids, budesonide, rather than beclomethasone.
The data from the unique study of Berard et al (3) are generally reassuring regarding exposure to intranasal corticosteroids and important perinatal outcomes. Notably, previously demonstrated relationships between corticosteroids and oral clefts were not confirmed in this study. However, the authors report that intranasal triamcinolone use was associated with an increased risk (adjusted odds ratio, 2.71; 95% CI, 1.11-6.64) of respiratory system defects. Triamcinolone acetonide was reported to have potential to have a potent teratogenic effect on various mammalian fetal tissues, as well as a steroid effect on the lung, fetal growth retardation, and cleft palate anomalies. At present, no human pregnancy data are available for intranasal triamcinolone.
In sensitivity analyses they found that even if intranasal budesonide has a pregnancy category B, it was associated with the malformation, respiratory defects, though was not statistically significant. The authors reported that the lack of statistical power could partly explain the nonstatistical findings, although these could also be due to chance.
Based on these reports, Triamcinolone and Beclomethasone should be avoided in pregnancy. While Budesonide dose has a reported higher degree of bio-availability, this may not have significant clinical relevance. While Fluticasone is reported to have lower bio-availability, this may be more related to ability to measure accurately, since Fluticasone is metabolized into other components; and despite “low bio-availability”, Thorrson reported significant suppression (43%) of overnight urinary cortisol, indicating higher systemic absorption of Fluticasone.
Except for Triamcinolone and Beclomethasone, the other intranasal steroids appear to have minimal clinical risk among pregnant mothers and the fetus. I was unable to identify a study that specially recommended Fluticasone or Mometasone over Budesonide. As discussed above bio-availability measure may not be complete and may not necessarily correlate with systemic effects.
As it currently stands, the FDA continues to identify Budesonide as the preferred agent. Your thoughts are certainly are valid, and it is important that you make medication decisions that you feel would provide the best outcome for your patients.
1) Thorsson L, Borgâ O, Edsbäcker S. Systemic availability of budesonide after nasal administration of three different formulations: pressurized aerosol, aqueous pump spray, and powder.
Br J Clin Pharmacol. 1999;47(6):619–624. doi:10.1046/j.1365-2125.1999.00956.x
2) Bain E, Pierides KL, Clifton VL, et al.
Interventions for managing asthma in pregnancy. Cochrane Database Syst Rev. 2014;2014(10):CD010660. Published 2014 Oct 21. doi:10.1002/14651858.CD010660.pub2
3) Bérard A, Sheehy O, Kurzinger ML, Juhaeri J. Intranasal triamcinolone use during pregnancy and the risk of adverse pregnancy outcomes.
J Allergy Clin Immunol. 2016;138(1):97–104.e7. doi:10.1016/j.jaci.2016.01.021
I hope this has been helpful.
Respectfully submitted,
Jeffrey G Demain, MD, FAAAAI