Respiratory Drug (Corticosteroid)
PREGNANCY RECOMMENDATION: Compatible
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
In a position statement from a joint committee of the American College of Obstetricians and Gynecologists (ACOG) and the American College of Allergy, Asthma, and Immunology (ACAAI) published in 2000, either beclomethasone or budesonide were considered the inhaled steroids of choice for use during pregnancy (1).
FETAL RISK SUMMARY
Beclomethasone dipropionate is given by inhalation for the chronic treatment of bronchial asthma in patients requiring corticosteroid therapy for the control of symptoms. It is also available for intranasal use and, outside of the United States, for topical application.
Beclomethasone was embryocidal (increased fetal resorption) and teratogenic when administered by SC injection to mice and rabbits at approximately 10 times the human dose (HD) (2,3). Congenital malformations observed included cleft palate, agnathia, microstomia, absence of the tongue, delayed ossification, and agenesis of the thymus. Similar toxic effects in both species were observed with SC injections that were approximately one-half the maximum recommended adult daily inhalation dose based on BSA (4). In the rat, no embryo or fetal harm was found with inhaled (at 10 times the HD) or oral (at 1000 times the HD) beclomethasone (2,3).
No human reports associating the use of beclomethasone with human congenital anomalies have been found. A 1975 report briefly mentioned seven healthy babies born from mothers who had used beclomethasone aerosol for >6 months (5). In another report, beclomethasone was used during 45 pregnancies in 40 women (6). Dosage ranged between 4 and 16 inhalations/day (mean 9.5), with each inhalation delivering 42 mcg of drug. Three of the 33 prospectively studied pregnancies ended in abortion that was not thought to be caused by the maternal asthma. Forty-three living infants resulted from the remaining 42 pregnancies. Six infants had low birth weights, including two of the three premature newborns (<37 weeks’ gestation). There was no evidence of neonatal adrenal insufficiency. One full-term infant had cardiac malformations (double ventricular septal defect, patent ductus arteriosus, and subaortic stenosis). However, the mother’s asthma was also treated with prednisone, theophylline, and epinephrine. In addition, she had schizophrenia and diabetes mellitus for which she took fluphenazine and insulin (6). Cardiac malformations are known to occur with diabetes mellitus (see Insulin).
In a surveillance study of Michigan Medicaid recipients involving 229,101 completed pregnancies conducted between 1985 and 1992, 395 newborns had been exposed to beclomethasone during the 1st trimester (F. Rosa, personal communication, FDA, 1993). A total of 16 (4.1%) major birth defects were observed (16 expected). Specific information was not available on the defects, but no anomalies were observed in six categories (cardiovascular defects, oral clefts, spina bifida, polydactyly, limb reduction defects, and hypospadias). These data do not support an association between the drug and congenital defects.
A 2004 prospective, double-blind, double placebo-controlled, randomized study compared inhaled beclomethasone (194 women) with theophylline (191 women) for the treatment of moderate asthma during pregnancy (7). The mean gestational age at randomization was about 20 weeks in both groups. There was no significant difference in the rate of asthma exacerbations between the groups, but significantly fewer discontinued beclomethasone because of adverse effects. There also were no differences in maternal or perinatal outcomes (7).
A 2004 study examined the effect of inhaled corticosteroids on low birth weight, preterm births, and congenital malformations in pregnant asthmatic patients (8). The inhaled steroids with the number of patients were beclomethasone (N = 277), fluticasone (N = 132), triamcinolone (N = 81), budesonide (N = 43), and flunisolide (N = 25). Compared with the general population, the study found no increased incidence of small-for-gestational-age infants (<10th percentile for gestational age), low birth weight (<2500 g), preterm births, and congenital malformations (8).
A 2006 meta-analysis on the use of inhaled corticosteroids during pregnancy was published in 2006 (9). The analysis included five agents: beclomethasone, budesonide, flunisolide, fluticasone, and triamcinolone. The results showed that these agents do not increase the risk of major congenital defects, preterm delivery, low birth weight, and pregnancy-induced hypertension. Thus, they could be used during pregnancy (9).
A 2007 report described the use of inhaled beclomethasone in 29 pregnant women (10). No effects on fetal growth or pregnancy outcomes were observed. Beclomethasone was metabolized by placental enzymes (10).
BREASTFEEDING SUMMARY
It is not known whether beclomethasone is excreted into breast milk. Other corticosteroids are excreted into milk in low concentrations (see Prednisone), and the passage of beclomethasone into milk should be expected. One report mentioned three cases of maternal beclomethasone use during breastfeeding (5). Effects on the nursing infants were not mentioned.
References
1.Joint Committee of the American College of Obstetricians and Gynecologists (ACOG) and the American College of Allergy, Asthma, and Immunology (ACAAI). Position statement. The use of newer asthma and allergy medications during pregnancy. Ann Allergy Asthma Immunol 2000;84:475–80.
2.Product information. Beconase. Glaxo Wellcome, 2000.
3.Product information. Vancenase; Vanceril. Schering, 2000.
4.Product information. Beclovent. Glaxo Wellcome, 2000.
5.Brown HM, Storey G. Treatment of allergy of the respiratory tract with beclomethasone dipropionate steroid aerosol. Postgrad Med J 1975;51(Suppl 4):59–64.
6.Greenberger PA, Patterson R. Beclomethasone dipropionate for severe asthma during pregnancy. Ann Intern Med 1983;98:478–80.
7.Dombrowski MP, Schatz M, Wise R, Thom EA, Landon M, Mabie W, Newman RB, McNellis D, Hauth JC, Lindheimer M, Caritis SN, Leveno KJ, Meis P, Miodovnik M, Wapner RJ, Varner MW, O’Sullivan MJ, Conway DL, for the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network, and the National Heart, Lung, and Blood Institute. Randomized trial of inhaled beclomethasone dipropionate versus theophylline for moderate asthma during pregnancy. Am J Obstet Gynecol 2004;190:737–44.
8.Namazy J, Schatz M, Long L, Lipkowitz M, Lillie M, Voss M, Deitz RJ, Petitti D. Use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth. J Allergy Clin Immunol 2004;113:427–32.
9.Rahimi R, Nikfar S, Abdollahi M. Meta-analysis finds use of inhaled corticosteroids during pregnancy safe: a systematic meta-analysis review. Hum Exp Toxicol 2006;25:447–52.
10.Murphy VE, Fittock RJ, Zarzycki PK, Delahunty MM, Smith R, Clifton VL. Metabolism of synthetic steroids by the human placenta. Placenta 2007;28:39–46.