Risk of Hypospadias in Offspring of Women Using Loratadine during Pregnancy

Division of General Internal Medicine, Department of Medicine, Center for Research on Health Care, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
Drug Safety (Impact Factor: 2.82). 02/2008; 31(9):775-88. DOI: 10.2165/00002018-200831090-00006
Source: PubMed


Loratadine, a second-generation antihistamine, is commonly used to treat seasonal allergies. Some studies have suggested that use of loratadine by pregnant women increases the risk of hypospadias in male offspring.
This meta-analysis was designed to assess the strength of the association between loratadine and hypospadias.
To locate pertinent articles published in any language from January 1989 until August 2007, we searched electronic databases (MEDLINE, OVID, EMBASE, SCOPUS, TOXLINE Special, ReproTox, TERIS, CINAHL and others), conference proceedings and bibliographies. Studies were eligible for this analysis if they were cohort, case-control or case series studies that reported the incidence of hypospadias in the offspring of women who were or were not exposed to loratadine during pregnancy. Two authors independently extracted information on study design, participant characteristics, measures of outcome, control for potential confounding factors and risk estimates using a standardized data collection form. The Newcastle-Ottawa Scale was then used to assess the quality of each study. We used a random-effects meta-analysis model to combine the risk data.
In 1402 potentially relevant titles, we found three case-control studies and seven cohort studies that reported the incidence of hypospadias or other congenital malformations in offspring of women who did or did not use loratadine during pregnancy. Together the studies in our meta-analysis provided information about 453 053 male births in Brazil, Canada, Denmark, Israel, Italy, Sweden, the UK and the US.Of 2694 male infants born to women using loratadine, 39 (1.4%) had hypospadias. Of 450 413 male infants born to women not using loratadine, 4231 (0.9%) had hypospadias. Women who used loratadine during pregnancy were not significantly more likely to have a son with hypospadias (unadjusted odds ratio [OR] 1.27, 95% CI 0.73, 2.23; adjusted OR 1.28, 95% CI 0.69, 2.39).
The results of our systematic review and meta-analysis of controlled observational studies indicate that the use of loratadine during pregnancy does not significantly increase the risk of hypospadias in male offspring.

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    • "The use of second-generation antihistamines (sgAH) for example is widely used for the treatment of allergic disease. In pregnancy, it is recommended to limit the use of sgAH to loratadine (16), and possibly desloratadine, because of best available evidence. Nowadays, several AH are OTC (over-the-counter) products in many countries and it can be assumed that these drugs are frequently used by pregnant women – at least before they knew to be pregnant. "
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    ABSTRACT: During pregnancy, the maternal organism is under the influence of tremendous endocrine as well as immunological changes as an adaptation to the implanted and developing fetus. In most cases, the maternal adaptations to pregnancy ensure both, the protection against harmful pathogens and the tolerance toward the growing semi-allogeneic fetus. However, under certain circumstances the unique hormonal milieu during pregnancy is causative of a shift into an unfavorable direction. Of particular importance are cellular disorders previous to pregnancy that involve cell types known for their susceptibility to hormones. One interesting cell type is the mast cell (MC), one of the key figures in allergic disorders. While physiological numbers of MCs were shown to positively influence pregnancy outcome, at least in mouse models, uncontrolled augmentations in quantity, and/or activation can lead to pregnancy complications. Women that have the desire of getting pregnant and been diagnosed with MC mediated disorders such as urticaria and mastocytosis or chronic inflammatory diseases in which MCs are involved, including atopic dermatitis, asthma, or psoriasis, may benefit from specialized medical assistance to ensure a positive pregnancy outcome. In the present review, we address the course of pregnancy in women affected by MC mediated or associated disorders.
    Frontiers in Immunology 05/2014; 5:231. DOI:10.3389/fimmu.2014.00231
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    • "Of note, many of the drugs that are prescribed and considered safe to use during pregnancy are in fact P-gp or BCRP substrates, like Loratadine and H2 blockers (i.e., Ranitidine and Cimetidine) (Collett et al., 1999; Chen et al., 2003; Li et al., 2008; Schwarz et al., 2008; Dahan & Amidon, 2009; Gill, O’Brien & Koren, 2009; Matok et al., 2010). Our finding may have clinical implications, suggesting that the use of cannabis during gestation may alter drug transport through the trophoblast and lead to the absence of a functional placental barrier during the first trimester, leaving the developing embryo unprotected at this vulnerable period of pregnancy. "
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    ABSTRACT: Objectives. Marijuana is the most commonly used illicit drug during pregnancy. Due to high lipophilicity, cannabinoids can easily penetrate physiological barriers like the human placenta and jeopardize the developing fetus. We evaluated the impact of cannabidiol (CBD), a major non-psychoactive cannabinoid, on P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) expression, and P-gp function in a placental model, BeWo and Jar choriocarcinoma cell lines (using P-gp induced MCF7 cells (MCF7/P-gp) for comparison). Study design. Following the establishment of the basal expression of these transporters in the membrane fraction of all three cell lines, P-gp and BCRP protein and mRNA levels were determined following chronic (24–72 h) exposure to CBD, by Western Blot and qPCR. CBD impact on P-gp efflux function was examined by uptake of specific P-gp fluorescent substrates (calcein-AM, DiOC2(3) and rhodamine123(rh123)). Cyclosporine A (CsA) served as a positive control. Results. Chronic exposure to CBD resulted in significant changes in the protein and mRNA levels of both transporters. While P-gp was down-regulated, BCRP levels were up-regulated in the choriocarcinoma cell lines. CBD had a remarkably different influence on P-gp and BCRP expression in MCF7/P-gp cells, demonstrating that these are cell type specific effects. P-gp dependent efflux (of calcein, DiOC2(3) and rh123) was inhibited upon short-term exposure to CBD. Conclusions. Our study shows that CBD might alter P-gp and BCRP expression in the human placenta, and inhibit P-gp efflux function. We conclude that marijuana use during pregnancy may reduce placental protective functions and change its morphological and physiological characteristics.
    PeerJ 09/2013; 1(1):e153. DOI:10.7717/peerj.153 · 2.11 Impact Factor
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    ABSTRACT: V. Piette, P. Demoly Introduction Many pregnant women are asthmatics and maternal asthma is a source of questions and complications concerning both the progress of the pregnancy itself and the impact on the fœtus. In this situation good asthma control is essential as the disease can deteriorate with acute exacerbations, possibly precipitated by reduction or even withdrawal of treatment on account of fear of teratogenicity. Background Even though asthma treatments are not totally harmless during pregnancy, their use has been validated by several studies and guidelines. To help clinicians, we undertake here a review of the complications induced by maternal asthma and its medications, and then suggest management guidelines according to the most recent publications. Conclusions The risks and benefits of asthma treatments should be explained in a real partnership between the patient and her general practioner and specialists (obstetrician, chest physician or allergist). In order to reduce complications to both mother and child, perfect control of asthma is required and inhaled steroids remain the treatment of choice for partially or uncontrolled asthma in the pregnant woman.
    Revue des Maladies Respiratoires 04/2009; 26(4):482-482. DOI:10.1016/S0761-8425(09)74067-7 · 0.62 Impact Factor
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