Risk of congenital malformations associated with treatment of asthma during early pregnancy

doi:10.1016/S0140-6736(99)02542-8

The Lancet

Volume 355, Issue 9198, 8 January 2000, Page 119

https://doi.org/10.1016/S0140-6736(99)02542-8 Get rights and content

Summary

Studies assessing the risk of congenital malformations associated with the treatment of asthma during the first trimester of pregnancy are few, have limited power and support continuation of treatment.

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Cited by (16)

Effect of maternal asthma and asthma control on pregnancy and perinatal outcomes
2007, Journal of Allergy and Clinical Immunology
Citation Excerpt :
Black women were 1.6 (95% CI, 1.5-1.7) times more likely than white women to receive care for exacerbated asthma during pregnancy. Our findings add another report to the literature that confirms maternal asthma was not associated with birth defects,3,7,26,27,32 which should be reassuring to expectant mothers. However, birth defects are rare events, and even this large study has insufficient power to detect moderate effects between specific treatments and defects.
Asthma is a common condition during pregnancy.
We sought to determine the effect of asthma on the rates of adverse pregnancy and fetal outcomes.
We identified pregnancies among black and white women age 15 to 44 with singleton gestations enrolled in the Tennessee Medicaid program over a period of 9 consecutive years, from 1995to 2003, and used claims data to determine the relationship of maternal asthma and asthma exacerbations on pregnancy and infant outcomes.
Among the 140,299 pregnancies, 6.5% were in women with asthma. Among women with asthma, 23% had a hospital or emergency department visit (exacerbated asthma); 40% of black and 23% of white women received hospital or emergency department care for asthma during pregnancy. After controlling for race and other covariates, birth weights among infants of women with asthma were, on average, 38 g lower, and among infants of women with exacerbated asthma they were, on average, 56 g lower. There were moderate, dose-dependent relationships between asthma alone and exacerbated asthma with hypertensive disorders of pregnancy, membrane-related disorders, preterm labor, antepartum hemorrhage, and cesarean delivery. Maternal asthma was not associated with preterm birth or birth defects.
Asthma is a risk factor for several common adverse outcomes of pregnancy, and poorly controlled asthma during pregnancy increases these risks.
It is possible that both maternal and infant outcomes could be improved in this population with appropriate asthma care, especially among black women.
Outcome of pregnancy in a randomized controlled study of patients with asthma exposed to budesonide
2005, Annals of Allergy, Asthma and Immunology
Budesonide is the only inhaled corticosteroid to be given a category B pregnancy rating by the US Food and Drug Administration, based on observational data from the Swedish Medical Birth Registry. However, data from large randomized controlled trials are lacking.
To compare pregnancy outcomes among patients with recent-onset mild-to-moderate persistent asthma receiving low-dose budesonide vs placebo.
In a randomized, double-blind, placebo-controlled trial, 7,241 patients aged 5 to 66 years with mild-to-moderate persistent asthma for less than 2 years and no previous regular corticosteroid therapy received once-daily budesonide or placebo via dry powder inhaler in addition to their usual asthma medication for 3 years. This trial was followed by a 2-year open-label treatment period. The daily dose of budesonide was 400 μg for adults. The study included 2,473 females aged 15 to 50 years at randomization. Pregnancy was not an exclusion criterion (except for US patients).
Of 319 pregnancies reported, 313 were analyzed. Healthy children were delivered in 81% and 77% of all pregnancies in the budesonide and placebo groups, respectively. Of the 196 pregnancies reported by participants taking budesonide, 38 (19%) had adverse outcomes: 23 (12%) had miscarriages, 3 (2%) had congenital malformations, and 12 (6%) had other outcomes. Of the 117 pregnancies reported in the placebo group, 27 (23%) had adverse outcomes: 11 (9%) had miscarriages, 4 (3%) had congenital malformations, and 12 (10%) had other outcomes.
Treatment with low-dose inhaled budesonide in females with mild-to-moderate persistent asthma does not seem to affect the outcome of pregnancy.
Asthma and pregnancy - Efficacy and safety of medication during pregnancy
2004, Revista Portuguesa de Pneumologia
A asma é um dos problemas médicos que mais frequentemente complica a gravidez, com uma prevalência que se estima entre 4 a 7 %. O curso da asma durante a gravidez é variável, verificando-se um agravamento dos sintomas em cerca de um terço das grávidas. O período mais crítico situa-se entre a 24.ª e a 36.ª semanas. Após o parto, a tendência é para a remissão dos sintomas nos três meses seguintes, sendo de esperar nas sucessivas gravidezes um padrão de comportamento idêntico. O controlo da asma durante a gravidez baseia-se na educação da grávida e na prescrição de uma medicação segura, preferencialmente por via inalatória, que previna o aparecimento das crises. Na asma crónica, os fármacos actualmente existentes — corticóides inalados — previnem de forma eficaz o aparecimento das crises de asma, sem riscos para o feto (beclometasona e budesonido). Aos corticóides inalados existe uma sucessão de fármacos a associar — broncodilatadores agonistas beta de acção curta ou retardada — de acordo com o grau de obstrução brônquica existente e frequência das crises. No tratamento farmacológico da asma aguda, as recomendações terapêuticas não devem ser subestimadas, pois numa asma não controlada aumenta o risco de aparecimento de complicações (aumento da incidência de baixo peso e prematuros) em número superior ao eventual risco de uma medicação.
REV PORT PNEUMOL 2004; X (5): 405-419
Bronchial asthma is one of the most common medical problems in pregnancy, with prevalance around 4-7 %. Asthma clinical course is variable, with worsening of symptoms in one third of the cases. The most critical period occurs between the 24th and 36th week of gestation. Symptoms usually regress completely after delivery during the following three months and they are expected to recur, with the same pattern, in subsequent pregnancies. Asthma control during pregnancy depends on pregnant patient education and safe medication, preferably inhaled, that prevents crises. In chronic asthma, usually prescribed drugs (inhaled corticosteroids: beclometasone and budesonide) are effective and safe to the fetus. There are several drugs to be added to inhaled steroids - beta agonists bronchodilators: short and long acting – according to the severity of bronchial constriction and frequency of crises. Treatment of acute asthma should follow recommended guidelines, since uncontrolled asthma increases more the risk of pregnancy complications (low birth weight and premature delivery) than the eventual medication risks to pregnancy.
REV PORT PNEUMOL 2004; X (5): 405-419
Normal pregnancy outcomes in a population-based study including 2968 pregnant women exposed to budesonide
2003, Journal of Allergy and Clinical Immunology
Background: Inhaled corticosteroids are recommended as first-line therapy for pregnant women with moderate to severe asthma, although the effects on pregnancy outcome are uncertain. A low compliance with the recommendations might lead to inadequate control of asthma, which has been associated with adverse outcomes both for the mother and the infant. Objective: To investigate whether the reported use of inhaled budesonide (Pulmicort) during pregnancy influences birth outcome. Methods: Data were derived from the Swedish Medical Birth Register, which includes 99% of births in Sweden. During 1995 to 1998, 293,948 newborn infants were identified. Pregnancy outcomes were compared for mothers in Sweden reporting asthma medication usage with those reporting no asthma medication usage. Results: The 2968 mothers who reported use of inhaled budesonide during early pregnancy gave birth to infants of normal gestational age, birth weight, and length, with no increased rate of stillbirths or multiple births. The rate of caesarean births was higher among mothers who used asthma medication during their pregnancy than among the control group. Conclusions: The use of inhaled budesonide in Sweden is not linked with any clinically relevant effects associated with pregnancy outcome.
Use of intranasal cromolyn sodium for allergic rhinitis
2002, Mayo Clinic Proceedings
Citation Excerpt :
Cromolyn is classified as category B in pregnancy by the FDA because teratogenicity has not been observed. Few studies have evaluated the risk of teratogenicity in patients treated with antiasthmatic agents such as cromolyn during the first trimester of pregnancy, but they support continuation of treatment.36 In a study of 824 pregnant women with asthma and 678 pregnant women without asthma, cromolyn (inhaled, intranasal, and ophthalmic), β-agonists (inhaled or oral), theophylline, corticosteroids (oral, inhaled, or intranasal), antihistamines, or decongestants were not associated with occurrence of major congenital malformations.37
Allergic rhinitis affects 10% to 20% of Americans. It frequently coexists with other conditions, such as allergic conjunctivitis, sinusitis, and asthma, and is associated with impaired occupational function and performance in school, decreased quality of life, and increased health care costs. An efficacious agent with minimal adverse effects and a lack of drug interactions is needed to help simplify treatment of allergic rhinitis, especially in patients with comorbidities. Controlled studies of intranasal cromolyn sodium therapy for patients with seasonal and perennial allergic rhinitis are reviewed, and appropriate candidates for treatment with this agent are discussed. Cromolyn inhibits the degranulation of sensitized mast cells, thereby blocking the release of inflammatory and allergic mediators. It reduces symptoms of allergic rhinitis, and, when used prophylactically, cromolyn can prevent symptoms from occurring. Controlled studies comparing cromolyn with placebo, intranasal corticosteroids, and antihistamines have shown the efficacy of cromolyn in relieving rhinitis symptoms. In addition, because cromolyn is poorly absorbed systemically, it is well tolerated and not associated with drug interactions. Intranasal cromolyn has an excellent safety record, is available as an over-the-counter medication, and has been proved to be efficacious in patients with allergic rhinitis.
Asthma in pregnancy
2000, American Journal of Medicine
Citation Excerpt :
The most recent British (48) and American (49) guidelines on the general management of asthma offer no specific advice about its treatment during pregnancy. Little is known about the effects of treatment on congenital malformations (50). However, the American College of Allergy, Asthma and Immunology’s Registry for Allergic, Asthmatic Pregnant Patients will collect data on 800 women who require inhaled corticosteroids during pregnancy (51).
Although about 1% of pregnant women have asthma, it is often underrecognized and suboptimally treated. The course of asthma during pregnancy varies; it improves, remains stable, or worsens in similar proportions of women. The risk of an asthma exacerbation is high immediately postpartum, but the severity of asthma usually returns to the preconception level after delivery and often follows a similar course during subsequent pregnancies. Changes in β₂-adrenoceptor responsiveness and changes in airway inflammation induced by high levels of circulating progesterone have been proposed as possible explanations for the effects of pregnancy on asthma. Good control of asthma is essential for maternal and fetal well-being. Acute asthmatic attacks can result in dangerously low fetal oxygenation. Chronically poor control is associated with pregnancy-induced hypertension, preeclampsia, and uterine hemorrhage, as well as greater rates of cesarian section, preterm delivery, intrauterine growth retardation, low birth weight, and congenital malformation. Women with well-controlled asthma during pregnancy, however, have outcomes as good as those in their nonasthmatic counterparts. Inhaled therapies remain the cornerstone of treatment; most appear to be safe in pregnancy.

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Research LettersRisk of congenital malformations associated with treatment of asthma during early pregnancy

Summary

Lancet

J Allergy Clin Immunol

Research Letters
Risk of congenital malformations associated with treatment of asthma during early pregnancy