Maternal Asthma Medication Use and the Risk of Selected Birth Defects
ABSTRACT Approximately 4% to 12% of pregnant women have asthma; few studies have examined the effects of maternal asthma medication use on birth defects. We examined whether maternal asthma medication use during early pregnancy increased the risk of selected birth defects.
National Birth Defects Prevention Study data for 2853 infants with 1 or more selected birth defects (diaphragmatic hernia, esophageal atresia, small intestinal atresia, anorectal atresia, neural tube defects, omphalocele, or limb deficiencies) and 6726 unaffected control infants delivered from October 1997 through December 2005 were analyzed. Mothers of cases and controls provided telephone interviews of medication use and additional potential risk factors. Exposure was defined as maternal periconceptional (1 month prior through the third month of pregnancy) asthma medication use (bronchodilator or anti-inflammatory). Associations between maternal periconceptional asthma medication use and individual major birth defects were estimated by using adjusted odds ratios (aOR) and 95% confidence intervals (95%CI).
No statistically significant associations were observed for maternal periconceptional asthma medication use and most defects studied; however, positive associations were observed between maternal asthma medication use and isolated esophageal atresia (bronchodilator use: aOR = 2.39, 95%CI = 1.23, 4.66), isolated anorectal atresia (anti-inflammatory use: aOR = 2.12, 95%CI = 1.09, 4.12), and omphalocele (bronchodilator and anti-inflammatory use: aOR = 4.13, 95%CI = 1.43, 11.95).
Positive associations were observed for anorectal atresia, esophageal atresia, and omphalocele and maternal periconceptional asthma medication use, but not for other defects studied. It is possible that observed associations may be chance findings or may be a result of maternal asthma severity and related hypoxia rather than medication use.
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ABSTRACT: Anorectal malformations (ARMs) comprise a broad spectrum of anomalies, including anal atresia, congenital anal fistula and persistence of the cloaca. Research suggests that genetic factors play an important role in ARM development. However, few genetic variants have been identified. Embryogenesis is orchestrated by crosstalk of the wingless-type MMTV integration site family (WNT) and fibroblast growth factor (FGF) signaling pathways in a process that involves several intracellular cascades. Studies in mice have implicated several genes from these pathways in the etiology of ARMs. We performed sequencing analysis of seven of these previously reported genes in 78 patients with ARMs occurring within the context of at least one additional congenital anomaly. No associations were identified with variants in WNT3A, WNT5A, WNT11, DACT1, FGF10 or the T gene. In the FGFR2 gene, three novel heterozygous nucleotide substitutions were identified. Further investigations, including the study of family members, revealed that these variants were not causally related to the phenotype in the present ARM cohort. Mutations in the seven investigated genes may nonetheless be a cause of ARMs in rare cases. However, further studies should consider genes encoding other proteins in the WNT/FGF signaling pathways as possible candidates.International Journal of Molecular Medicine 09/2012; 30(6). DOI:10.3892/ijmm.2012.1124 · 1.88 Impact Factor
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ABSTRACT: BACKGROUND: The effects of maternal use of medicines during pregnancy on tooth development has scarcely been studied; only negative effects of tetracycline on tooth germs are known (irreversible tooth discoloration and enamel hypoplasia). OBJECTIVE: The aim of this study was to investigate whether antibacterials and anti-allergic and anti-asthma medicines, being the most frequently used medicines during pregnancy, are associated with deciduous molar hypomineralisation (DMH) and, if so, which specific medicines. MATERIALS AND METHODS: To clarify this possible association, the participants of the Generation R Study, a population-based prospective cohort study from fetal life until young adulthood, were studied. Data on medicine use during pregnancy were retrieved from pharmacies. Clinical photographs of the second primary molars, which were scored for DMH, were taken with an intra-oral camera in 6,690 children (mean age 6.2 years, standard deviation [SD] ± 0.53; 49.9 % girls). RESULTS: During pregnancy, 20.3 % of the mothers used antibacterials, 12.3 % anti-asthma medicines and 5.4 % anti-allergic medicines. The prevalence of DMH was 9.0 % in the study group. There was no association between the use of anti-asthma medicines, anti-allergic medicines (odds ratio [OR]: 0.97 [95 % CI 0.61-1.54]; OR: 1.04 [0.54-2.03]) or antibacterials (OR: 0.73 [0.49-1.09]) during pregnancy and DMH (all p-values >0.05). The study had sufficient power (80 %) to detect significant associations. CONCLUSION: Maternal use of antibacterials, anti-allergic medicines or anti-asthma medicines during pregnancy is not associated with the development of DMH in the offspring.Drug Safety 06/2013; 36(8). DOI:10.1007/s40264-013-0078-y · 2.62 Impact Factor
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ABSTRACT: Asthma is a common medical condition complicating pregnancy with potentially serious effects on pregnancy outcome. The aim of this review is to provide an update on efficacy and safety of asthma medications, primarily bronchodilators and corticosteroids, used during pregnancy with focus on pregnancy outcome, and, furthermore, to discuss limitations of available studies and point to possible improvements in future studies. A planned series of systematic searches was conducted using the PubMed database. Use of short-acting β2-agonists has generally been established as safe, and the few studies stating otherwise appear to have, perhaps critical, methodological limitations. The safety of long-acting β2-agonists remains to be further investigated, and the few available studies have methodological limitations and, therefore, provide no definite answers, although a very recent study supports the safety of add-on long-acting β2-agonists to inhaled corticosteroids. Inhaled corticosteroids are generally found to be safe, although further research is needed to investigate both the efficacy and safety of high dose therapy with inhaled corticosteroids. Studies have reported associations between the use of systemic corticosteroids and adverse perinatal outcomes, such as preterm birth, low birth weight, and pre-eclampsia. This must, however, be weighed against the potential serious impact of severe, uncontrolled asthma itself on pregnancy outcome. The main obstacle to a valid interpretation of several of the available studies is the inadequate stratification for asthma severity and control. Overall, asthma in itself and not just poor asthma control poses a greater risk to pregnancy outcomes than asthma medication. Nonetheless, more studies focusing on disentangling the effects of asthma alone and asthma medications are needed. Increased use of stratified risk assessments, taking the concept of asthma severity into greater consideration, is much warranted in future studies.Journal of Asthma and Allergy 11/2013; 6:117-125. DOI:10.2147/JAA.S52592