Use of anti-asthmatic drugs during pregnancy. 2. Infant characteristics excluding congenital malformations

Tornblad Institute, University of Lund, Biskopsgatan 7, 223 62, Lund, Sweden.
European Journal of Clinical Pharmacology (Impact Factor: 2.7). 05/2007; 63(4):375-81. DOI: 10.1007/s00228-006-0258-0
Source: PubMed

ABSTRACT To study the characteristics of the infants born to women who have used anti-asthmatic drugs during pregnancy.
Various characteristics of infants with mothers who had reported the use of anti-asthmatic drugs in early pregnancy (n=24,750) or had such drugs prescribed later during pregnancy by a maternity health care centre (n=763) were identified from the Swedish Medical Birth Register and compared to those of all infants. Risks estimated with Mantel-Haenszel technique were expressed as odds ratios (OR) with 95% confidence intervals after adjustment for a number of putative confounders. The severity of maternal asthma was assessed on the basis of the number of anti-asthmatic drugs used.
An increased risk for preterm birth, low birth weight and small for gestational age was found, which increased with the number of anti-asthmatic drugs used by the mother during pregnancy (OR=1.46, 1.67, and 1.70, respectively, when three or more drugs had been used). An increased risk for large for gestational age could be explained by the effect of gestational diabetes and high body mass index. An increased risk for neonatal icterus was mainly an effect of preterm birth, while an increased risk for respiratory problems and/or low Apgar score (OR=1.43) was only slightly reduced in full-term infants. An increased risk for hyperglycaemia (OR=1.62) was not explained by confounding from maternal diabetes. No risk increase was found for neonatal convulsions or cerebral haemorrhage. Mortality was increased only among infants whose mother had used three or more anti-asthmatic drugs (OR=1.52).
Infants whose mothers had asthma had a number of manifestations of poor outcome which appeared to be linked with the severity of the asthma.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: L’asthme est connu comme l’une des maladies chroniques les plus fréquentes chez la femme enceinte avec une prévalence de 4 à 8%. La prévalence élevée de l’asthme fait en sorte qu’on se préoccupe de l’impact de la grossesse sur l’asthme et de l’impact de l’asthme sur les issus de la grossesse. La littérature présente des résultats conflictuels concernant l’impact de l’asthme maternel sur les issus périnatales comme les naissances prématurées, les bébés de petit poids et les bébés de petit poids pour l’âge gestationnel (PPGA). De plus, les données scientifiques sont rares concernant l’impact de la sévérité et de la maîtrise de l’asthme durant la grossesse sur les issus périnatales. Donc, nous avons mené cinq études pour réaliser les objectifs suivants: 1. Le développement et la validation de deux indexes pour mesurer la sévérité et la maîtrise de l’asthme. 2. L’évaluation de l’impact du sexe du fœtus sur le risque d’exacerbation de l’asthme maternel et l’utilisation de médicaments antiasthmatiques durant la grossesse; 3. L’évaluation de l’impact de l’asthme maternel sur les issus périnatales; 4. L’évaluation de l’impact de la sévérité de l’asthme maternel durant la grossesse sur les issus périnatales; 5. L’évaluation de l’impact de la maîtrise de l’asthme maternel durant la grossesse sur les issus périnatales. Pour réaliser ces projets de recherche, nous avons travaillé avec une large cohorte de grossesse reconstruite à partir du croisement de trois banques de données administratives du Québec recouvrant la période entre 1990 et 2002. Pour les trois dernières études, nous avons utilisé un devis de cohorte à deux phases d’échantillonnage pour obtenir, à l’aide d’un questionnaire postal, des informations complémentaires qui ne se trouvaient pas dans les banques de données, comme la consommation de cigarettes et d’alcool pendant la grossesse. Nous n’avons trouvé aucune différence significative entre les mères de fétus féminins et de fétus masculins pour les exacerbations de l’asthme pendant la grossesse (aRR=1.02; IC 95%: 0.92 to 1.14). Par contre, nous avons trouvé que le risque de bébé PPGA (OR: 1.27, IC 95%: 1.14-1.41), de bébé de petit poids (OR: 1.41, IC 95%:1.22-1.63) et de naissance prématurée (OR: 1.64, IC 95%:1.46-1.83) était significativement plus élevés chez les femmes asthmatiques que chez les femmes non asthmatiques. De plus, nous avons démontré que le risque d’un bébé PPAG était significativement plus élevé chez les femmes avec un asthme sévère (OR:1.48, IC 95%: 1.15-1.91) et modéré (OR: 1.30, IC 95%:1.10-1.55) que chez les femmes qui avaient un asthme léger. Nous avons aussi observé que les femmes qui avaient un asthme bien maîtrisé durant la grossesse étaient significativement plus à risque d’avoir un bébé PPAG (OR:1.28, IC 95%: 1.15-1.43), un bébé de petit poids (OR: 1.42, IC 95%:1.22-1.66), et un bébé prématuré (OR: 1.63, IC 95%:1.46-1.83) que les femmes non asthmatiques. D’après nos résultats, toutes les femmes asthmatiques même celles qui ont un asthme bien maîtrisé doivent être suivies de près durant la grossesse car elles courent un risque plus élevé d’avoir des issus de grossesses défavorables pour leur nouveau-né. Asthma is known as one of the most frequent chronic diseases encountered during pregnancy with prevalence estimated between 4 and 8%. The high prevalence of asthma during pregnancy results in some concerns about the impact of pregnancy on maternal asthma and also the impact of maternal asthma on perinatal outcomes. The literature presents conflicting results concerning the impact of maternal asthma during pregnancy on perinatal outcomes, such as preterm birth, low-birth-weight (LBW) infant and small-for-gestational-age (SGA) infant. Also, scientific evidence is scarce regarding the impact of asthma severity and control during pregnancy on these perinatal outcomes. We thus conducted a research project composed of five studies to achieve the following objectives: 1. to develop and validate two database indexes, one to measure the control of asthma and the other to measure asthma severity; 2. to evaluate the effect of fetal gender on maternal asthma exacerbations and the use of asthma medications during pregnancy; 3. to evaluate the impact of maternal asthma on adverse perinatal outcomes; 4. to evaluate the impact of the severity of asthma during pregnancy on adverse perinatal outcomes; 5. to evaluate the impact of adequately controlled maternal asthma during pregnancy on adverse perinatal outcomes. A large population-based cohort was reconstructed through the linking of three of Quebec’s (Canada) administrative databases covering the period between 1990 and 2002. A two-stage sampling cohort design was used to collect additional information on the women’s life-style habits by way of a mailed questionnaire for the three last studies. We have observed no significant differences between mothers of a female and male fetus as to the occurrence of asthma exacerbations (aRR=1.02; 95% CI: 0.92 to 1.14). We have found that the risk of SGA (OR: 1.27, 95% CI: 1.14-1.41), LBW (OR: 1.41, 95% CI:1.22-1.63) and preterm delivery (OR: 1.64, 95%CI:1.46-1.83) was significantly higher among asthmatic than non-asthmatic women. Moreover, our results showed that the risk of SGA was significantly higher among severe (OR:1.48, 95%CI: 1.15-1.91) and moderate asthmatic women (OR: 1.30, 95%CI:1.10-1.55) than mild asthmatic women. Also, mothers with adequately controlled asthma during pregnancy were found to be at higher risk of adverse perinatal outcomes than non-asthmatic women (SGA (OR:1.28, 95%CI: 1.15-1.43), LBW (OR: 1.42, 95%CI:1.22-1.66), and preterm deliveries (OR: 1.63, 95%CI:1.46-1.83)). According to our results, all asthmatic women even those with adequately controlled asthma should be closely monitored during pregnancy because they are at increased risk of adverse perinatal outcomes.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The prevalence of asthma among pregnant women varies among studies from 4 to 8%, making it by far the most common respiratory disorder complicating pregnancy. Controversy exists among the numerous retrospective and prospective studies regarding pregnancy outcomes of asthmatic patients. Overall, the literature indicates that women with severe asthma are at an increased risk for preterm delivery, low birth weight, preeclampsia and Caesarean delivery, especially in the absence of inhaled corticosteroid therapy. Asthmatic women carrying a female fetus may particularly be at increased risk of these adverse outcomes. On the other hand, mild or moderate, well-controlled asthma is associated with favorable pregnancy and perinatal outcomes. Pregnancy also influences the course of asthma. Recently published data indicate that the real risk for an exacerbation during pregnancy may be underestimated. There is no question, however, that the risk of having an exacerbation correlates closely with the severity of asthma. The mechanisms responsible for these changes are not fully understood. Maternal hypoxia or inflammatory processes have been suggested and could explain reduced fetal growth through alterations in placental function. The goal of asthma therapy is to maintain adequate oxygenation of the fetus by prevention of exacerbations. Optimal management of asthma during pregnancy should include scheduled monitoring of objective lung function tests, avoiding triggers, patient education and tailored pharmacologic therapy. Inhaled corticosteroids are the treatment of choice for all levels of persistent asthma, yet other drug classes, such as beta(2)-agonists and theophylline, are effective and safe for use during pregnancy.
    Expert Review of Respiratory Medicine 02/2008; 2(1):97-107. DOI:10.1586/17476348.2.1.97
  • [Show abstract] [Hide abstract]
    ABSTRACT: In order to evaluate the previously published association between maternal use of selective serotonin re-uptake inhibitors (SSRI) and persistent pulmonary hypertension in the neonate (PPHN), we used data from the Swedish Medical Birth Register for the years 1997–2005. Infants were identified from discharge diagnoses, and maternal exposure to drugs from interviews performed in early pregnancy and from prescriptions from the antenatal care service. Putative confounders were studied: an increased risk for PPHN was indicated for high maternal age, for first parity, for maternal BMI, and possibly for maternal smoking. Adjusting for these variables and year of birth, an association between maternal use of SSRI and PPHN in births after 34 completed weeks was identified with a risk ratio of 2.4, 95%CI 1.2–4.3 when based on women who reported the drug use in early pregnancy. When a subgroup of the women were studied who also had prescriptions for SSRI from the antenatal care later in pregnancy, the risk estimate was 3.6, 95%CI 1.2–8.3. The risk estimates were lower than that described previously in the literature, but both estimates could come from the same about 4–5 times increased risk. The mechanism behind the association between SSRI and PPHN is unclear but an increased risk for respiratory problems after maternal use of SSRI is well known, and PPHN could be a rare part of this association. Copyright © 2008 John Wiley & Sons, Ltd.
    Pharmacoepidemiology and Drug Safety 08/2008; 17(8):801 - 806. DOI:10.1002/pds.1570 · 3.17 Impact Factor
Show more