Safety of leukotriene receptor antagonists in pregnancy

doi:10.1016/j.jaci.2006.12.618

Journal of Allergy and Clinical Immunology

Volume 119, Issue 3, March 2007, Pages 618-625

https://doi.org/10.1016/j.jaci.2006.12.618 Get rights and content

Background

Asthma is a chronic disorder that affects about 8% of pregnant women and may complicate pregnancy. Adequate asthma therapy in pregnancy is crucial but challenging because of safety concerns for the fetus.

Objective

To evaluate the safety of gestational asthma therapy with leukotriene receptor antagonists (LTRAs) for the mother and fetus/newborn.

Methods

Subjects were participants of the Organization of Teratology Information Specialists Asthma Medications in Pregnancy Study. Perinatal outcomes among 96 women who took LTRAs (montelukast or zafirlukast) were compared with women who exclusively took short-acting β₂-agonists (n = 122) and women without asthma (n = 346).

Results

Use of LTRAs was not associated with an increased risk of pregnancy loss, gestational diabetes, preeclampsia, low maternal weight gain, preterm delivery, low Apgar scores, or reduced measures of birth length and head circumference in infants (P > .05). Slightly decreased birth weight in infants born to LTRA users could be attributed to maternal asthma severity/control. The birth prevalence of major structural defects in the LTRA group (5.95%) was significantly higher compared with controls without asthma (P = .007), but not different from the comparison group with asthma (P = .524). Furthermore, the defects observed in the LTRA group did not represent a consistent pattern.

Conclusions

Use of LTRAs in pregnancy was not associated with a specific pattern of major structural anomalies in offspring or a large risk of other adverse perinatal outcomes.

Clinical implications

This study suggests that LTRAs do not appear to be a major human teratogen; however, results should be interpreted with caution because of limited sample size.

Section snippets

Study population

Subjects were participants of the Asthma Medications in Pregnancy Study conducted by the Organization of Teratology Information Specialists (OTIS) from 1998 to 2003. The detailed methodology of this study has been described elsewhere.11, 12 Briefly, OTIS is a nonprofit organization of teratology information services located across North America that receives calls from approximately 100,000 women a year with questions about various exposure factors in pregnancy. The Asthma Medications in

Results

In the OTIS Asthma Medications in Pregnancy Study, 96 women took LTRAs (72, montelukast; 22, zafirlukast; and 2, both) sometime during pregnancy. The majority of subjects had a first trimester exposure (89.6%), and 50% of women used LTRAs throughout the pregnancy. More than 85% of subjects took the recommended adult doses: 10 mg daily for montelukast and 20 mg twice a day for zafirlukast. Because LTRAs are often taken in combination with other controller and/or rescue medications, 99% of

Discussion

This study evaluated the safety of LTRAs in pregnancy relative to a wide array of perinatal outcomes. Because of a limited sample size, the study was able to rule out only large risks associated with exposure to LTRAs in pregnancy. In our sample, use of LTRAs was not associated with an increased risk of any evaluated maternal complications, including pregnancy loss, gestational diabetes, preeclampsia/PIH, or low maternal weight gain. In addition, no association was found with preterm delivery,

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Supported by a grant from Aventis Pharmaceutical.

Disclosure of potential conflict of interest: K. L. Jones has consulting arrangements with Merck and has received grant support from Sanofi-Aventis, Sanofi-Pasteur, Abbott Laboratories, Amgen, Apotex, Barr Laboratories, Kali Laboratories, Sandoz Pharmaceutical, and Teva Pharmaceutical. M. Schatz has received grant support from GlaxoSmithKline and Sanofi-Aventis and has received honoraria from GlaxoSmithKline, Genentech, and Merck. C. D. Chambers has consulting arrangements with Cephalom Pharmaceutical and has received grant support from Sanofi-Aventis, Sanofi-Pasteur, Abbott Laboratories, Amgen, Apotex, Barr Laboratories, Kali, Laboratories, Sandoz Pharmaceutical, and Teva Pharmaceutical. The rest of the authors have declared that they have no conflict of interest.

^∗: The following members of the OTIS Collaborative Research Group contributed to this study: Arizona Teratogen Information Program, University of Arizona, Tucson: D. Quinn, D. Vogt; California Pregnancy Risk Information, University of California, San Diego: K. Kao; Connecticut Pregnancy Exposure Information Service, University of Connecticut Health Center, Farmington: S. Lavigne, J. Brochu; Nebraska Teratogen Project, University of Nebraska Medical Center, Omaha: Dr B. Buehler, E. Conover; Illinois Teratogen Information Service, Chicago: K. Ormond, C. Chou; Michigan Teratogen Information Service. Children's Hospital of Michigan, Detroit: Dr Y. Johnson, S. Swerc; Missouri Teratogen Information Service, University of Missouri Hospital and Clinics, Columbia: Dr S. Braddock, P. Slusher; Pregnancy Risk Network, University of Buffalo: Dr L. Robinson, S. Gangell; Motherisk Program, Hospital for Sick Children, Toronto, Ontario: Dr G. Koren, M. Morreti; Texas Teratogen Information Service, University of North Texas, Denton: L. Wolfe; Pregnancy RiskLine Project, Utah Department of Health, Salt Lake City: Dr J. Carey; J. Robertson; Counseling and Advice on Reproductive Exposures Northwest, University of Washington, Seattle: Dr J. Polifka, Dr E. Rudy.

View full text

Asthma diagnosis and treatmentSafety of leukotriene receptor antagonists in pregnancy

Background

Objective

Methods

Results

Conclusions

Clinical implications

Section snippets

Study population

Results

Discussion

Immunol Allergy Clin North Am

J Allergy Clin Immunol

Am J Obstet Gynecol

Obstet Gynecol

Ann Allergy Asthma Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Immunol Allergy Clin North Am

J Allergy Clin Immunol

Am J Obstet Gynecol

Ann Allergy Asthma Immunol

Am J Obstet Gynecol

Int J Gynaecol Obstet

Am J Obstet Gynecol

Effect of bronchial asthma on the course of pregnancy, labour and perinatal outcome

J Obstet Gynaecol

Asthma exacerbations during pregnancy: incidence and association with adverse pregnancy outcomes

Thorax

Drug facts and comparisons

NAEPP expert panel report: managing asthma during pregnancy: recommendations for pharmacologic treatment: 2004 update

J Allergy Clin Immunol

Four factor index of social status

Asthma diagnosis and treatment
Safety of leukotriene receptor antagonists in pregnancy