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      Association of Asthma Diagnosis and Medication Use with Fecundability: A Prospective Cohort Study

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          Abstract

          Purpose

          Asthma has been positively associated with irregular menses and infertility in some studies, but data are limited on the relation between asthma medication use and fecundability (i.e., average per-cycle probability of conception among non-contracepting couples). This study examines the extent to which a history of asthma, asthma medication use, and age at first asthma diagnosis are associated with fecundability among female pregnancy planners.

          Participants and Methods

          Pregnancy Study Online (PRESTO) is an ongoing, web-based preconception cohort study of couples aged 21–45 years from North America. Between July 2013 and July 2019, a total of 10,436 participants enrolled in PRESTO, and 8286 were included in the present analysis. At study enrollment, women reported whether they had ever been diagnosed with asthma and, if so, the year they were first diagnosed. Women who reported ever being diagnosed with asthma were asked about medication use, including medication type and frequency of use. Participants completed follow-up questionnaires every 8 weeks for up to 12 months or until pregnancy. Proportional probabilities regression models were used to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for potential confounders. Fecundability ratios below 1.00 indicate reduced probability of conception.

          Results

          There was little association between a history of asthma diagnosis or asthma medication use and fecundability. Compared with no history of asthma, the FR for ever-diagnosis of asthma with medication use was 1.02 (95% CI: 0.91–1.15) and for ever-diagnosis of asthma without medication use was 1.00 (95% CI: 0.91–1.09). Highest intensity asthma medication use (daily plus extra dosing for symptoms), combination inhaled corticosteroid and long-acting beta-agonist inhaler use, and a first diagnosis of asthma after age 17 years were associated with small reductions in fecundability.

          Conclusion

          The present study provides little evidence that asthma or asthma medication use is adversely associated with fecundability.

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          Most cited references15

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          Design and Conduct of an Internet-Based Preconception Cohort Study in North America: Pregnancy Study Online.

          We launched the Boston University Pregnancy Study Online (PRESTO) to assess the feasibility of carrying out an Internet-based preconception cohort study in the US and Canada.
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            Expression of intracellular Th1 and Th2 cytokines in women with recurrent spontaneous abortion, implantation failures after IVF/ET or normal pregnancy.

            We aimed to investigate absolute counts of intracellular T helper 1 (Th1) and Th2 cytokine expressing T-cell subpopulations in women with three or more recurrent spontaneous abortions (RSA), multiple implantation failures after in-vitro fertilization and embryo transfer (IVF/ET) (three or more) or during normal pregnancy. Absolute cell counts and percentages of CD3+, CD3+/CD4+, and CD3+/CD8+ T-cell populations expressing intracellular cytokines [interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-4 and IL-10] was studied by four-color flow cytometry in 15 RSA and 13 implantation failure patients. Eighteen fertile non-pregnant and 47 normal pregnant women were also compared with regard to intracellular cytokine expression. Interleukin-10 producing CD3+/CD8+ T-cell counts were significantly lower in women with RSA (P < 0.05) and implantation failures (P < 0.05), and TNF-alpha producing CD3+/CD4+ T-cell counts were higher in women with RSA (P < 0.05) and implantation failures (P < 0.005) than those of non-pregnant fertile controls. During normal pregnancies, first trimester IL-4 expressing CD3+, CD3+/CD4+ T-cell counts (P < 0.05) and IFN-gamma expressing CD3+ T-cell counts (P < 0.05) were significantly higher than those of third trimester (P < 0.05). First trimester TNF-alpha expressing CD3+/CD8+ T-cell counts were significantly higher than those of second and third trimester women (P < 0.05). However, there are no differences in cytokine expression between non-pregnant and first trimester pregnant women. Absolute counts of IFN-gamma, IL-4, and TNF-alpha expressing T cells decrease with the progress of gestation (third trimester) during normal pregnancies. In women with implantation failures, absolute cell counts of TNF-alpha expressing CD3+/ 4- cells reflects the presence of dominant Th1 immune response. A significantly increased Th1 cytokine expression may be the underlying immune etiology for reproductive failures.
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              Reduced fecundability in women with prenatal exposure to cigarette smoking.

              Animal studies have suggested that fertility may be impaired by transplacental exposures, but little is known about human prenatal exposures and subsequent adult reproduction. A possible relation between prenatal exposure to cigarette smoking and adult fecundability in women was explored, with the use of data from a prospective study of 221 North Carolina couples. These couples were recruited during 1983-1985, at the time they stopped using birth control in order to become pregnant. The relative fecundability of exposed compared with unexposed women was estimated by applying a discrete-time proportional probabilities model to the cycle-by-cycle conception rates. Women with prenatal exposure to their mother's cigarette smoking had reduced fecundability. The fecundability ratio associated with prenatal exposure to mother's smoking, adjusted for age, frequency of intercourse, current smoking status, age at menarche, and childhood exposure to cigarette smoking, was 0.5 (95% confidence interval 0.4-0.8). This association was not changed by further adjustment for other possible confounding variables, including educational level, reproductive history, body weight, and consumption of alcohol and caffeine. Thus, women whose mothers smoked while pregnant with them may be on average substantially less fecund than women whose mothers did not smoke during pregnancy.
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                Author and article information

                Journal
                Clin Epidemiol
                Clin Epidemiol
                CLEP
                clinepid
                Clinical Epidemiology
                Dove
                1179-1349
                08 June 2020
                2020
                : 12
                : 579-587
                Affiliations
                [1 ]Department of Epidemiology, Boston University School of Public Health , Boston, MA 02118, USA
                [2 ]RTI International , Raleigh, NC 27709, USA
                [3 ]Department of Clinical Epidemiology, Aarhus University , Aarhus N 8200, Denmark
                [4 ]Boston University School of Medicine , Boston, MA 02118, USA
                Author notes
                Correspondence: Holly Michelle Crowe Email hcrowe@bu.edu
                Author information
                http://orcid.org/0000-0001-9164-532X
                http://orcid.org/0000-0003-2138-3752
                http://orcid.org/0000-0003-4299-7040
                http://orcid.org/0000-0003-4685-6894
                Article
                245040
                10.2147/CLEP.S245040
                7292257
                32606983
                f42781dd-75e9-4023-b4ad-a732e20307c2
                © 2020 Crowe et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 07 January 2020
                : 24 April 2020
                Page count
                Tables: 2, References: 29, Pages: 9
                Categories
                Original Research

                Public health
                corticosteroid,beta agonist,time to pregnancy,fertility
                Public health
                corticosteroid, beta agonist, time to pregnancy, fertility

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