WEUSRTP4850: Phase II: ICS/LABA Use in Pregnancy and Outcomes
Condition: Asthma
MeSH terms: Asthma
Study type: Observational

Summary: 
      Asthma is reported to affect between 3-14% of pregnancies making asthma medicines one of the
      most commonly used classes of medicines during pregnancy. Maternal asthma and in particular
      poorly controlled asthma has been found to be associated with a number of adverse perinatal
      outcomes including preterm delivery, low birth weight and pre-eclampsia. At present little is
      known about the safety in humans of many anti-asthma medicines when used during pregnancy. As
      a result all inhaled corticosteroids, with the exception of budesonide which is category B,
      have an FDA pregnancy category C, indicative of the fact there are no adequate and well
      controlled studies in humans.

      Fluticasone propionate is an inhaled corticosteroid used for the treatment of asthma, often
      in combination with the long-acting β-agonist salmeterol. Owing to small numbers of pregnancy
      exposures in the past, little is known about the safety of fluticasone propionate when used
      during pregnancy. A recent feasibility study, however, has shown that there are sufficient
      numbers of first trimester exposed pregnancies on the General Practice Research Database
      (GPRD) to allow the overall risk of major congenital malformations (MCMs) to be evaluated.
      This study also demonstrated that using data from the GPRD it is possible to determine an
      individual's exposure to anti-asthma medicines during pregnancy and to classify her treatment
      in terms of the British Thoracic Society treatment steps based on linked prescription and
      primary care data.

      The aims of this study are to 1) evaluate the safety profile of fluticasone propionate (FP)
      compared with exposure to all other inhaled corticosteroids with all major congenital
      malformations combined as the primary endpoint, whilst taking into account potential
      confounders and exposure to other anti-asthma medicine; and 2) test the null hypothesis that
      exposure to fluticasone propionate during the first trimester of pregnancy is not associated
      with increased overall risk of all major congenital malformations when compared to the risk
      in those exposed to other inhaled corticosteroids during the first trimester of pregnancy.

      The study will be a retrospective cohort study and will use data from the United Kingdom's
      General Practice Research Database (GPRD). The GPRD contains longitudinal medical records
      collected within UK primary care. All medical symptoms and diagnoses are recorded in the
      database, including those relating to pregnancy, in the form of Read Codes. In addition to
      coded data GPs have the option of recording un-coded comments ('free text'), such as more
      detailed descriptions of diagnoses or treatments along with information provided to them via
      hospital letters, referrals and discharge summaries.

      As the recording of stillbirths, neonatal deaths and pre-term births on the GPRD has not been
      verified, a verification exercise will be carried out. This will involve requesting and
      reviewing free text comments for 100 stillbirths, 100 neonatal deaths and 100 pre-term
      births. Free text comments will be requested if they are associated with a medical code
      related to pregnancy, delivery, post natal visits, death, post mortem, hospital letters and
      other forms of communication. If the free text is not found to be informative we will send
      questionnaires to the woman's GP.

      All outcomes will be identified and verified blinded to asthma treatment and severity levels.
    


Intervention name(s): Fluticasone propionate (with and without concurrent salmeterol)
Intervention type(s): Drug
Intervention description(s): Fluticasone propionate is an inhaled corticosteroid used for the treatment of asthma, often in combination with the long-acting β-agonist salmeterol. For the primary endpoint, exposure status will be determined based on the individual receiving a prescription for the drug of interest (fluticasone propionate or another inhaled corticosteroid) in the 2 weeks immediately before the LMP date or during the first trimester of pregnancy.
Sensitivity analysis will be carried out categorising exposure based on mapping the duration of prescriptions based on the number of inhalers, number of puffs within an inhaler and the prescribed daily dose.
Intervention MeSH terms: Fluticasone; Xhance; Salmeterol Xinafoate
Observational model: Cohort
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        The study population will consist of all eligible pregnancies identified from the source
        population where the female is considered to have asthma. The source population will be all
        pregnancies identified on the GPRD that started and ended between 1 January 2000 and 31
        December 2010.
      
Keywords: fluticasone propionate; asthma; pregnancy; major congenital malformations