Grant: Knowledge Synthesis Grant

<html> <body>Many new mothers face breastfeeding difficulties, and a range of approaches are used to improve milk supply. Domperidone is a dopamine antagonist approved in Canada to increase gastrointestinal (GI) motility and prevent treatment-related GI symptoms in Parkinson&rsquo;s disease. Domperidone is also increasingly being used off-label to stimulate lactation. In British Columbia, 20% of postpartum women were dispensed domperidone in 2011, up from 8% in 2002. Domperidone has been subject to safety advisories due to QT interval prolongation and epidemiological evidence of serious arrhythmias and sudden death. Evidence of harm is mainly in older patients, and questions exist about applicability to women of reproductive age.<br> <br> An up-to-date systematic review is needed on domperidone&rsquo;s effects on maternal and infant health, as compared with non-drug approaches, no treatment, and other galactagogues, in order to better guide treatment decisions. We are addressing two related research questions : <br> <br> 1. In randomized controlled trials (RCTs), does postpartum domperidone use lead to better infant and/or maternal health and quality of life, and to improved milk volume and breastfeeding rates, as compared with non-drug approaches, no treatment, placebo or other galactagogues? Are there differences in treatment outcomes by dose or duration?<br> <br> 2. Is domperidone use associated with QT prolongation, cardiac arrhythmias (torsade de pointes, ventricular fibrillation, ventricular tachycardia, flutter), or sudden cardiac death in women of reproductive age and infants?<br> <br> We are addressing Question 2 separately because of the need to include a broader evidence base to assess the potential for serious, infrequent harm. <br> <br> Question 1 includes RCTs in women with pre-term or full-term births. Domperidone is first assessed versus placebo, no treatment, and non-drug treatments; drug-drug comparisons, and dose/duration comparisons are evaluated separately. Outcomes include infant weight, growth and development; maternal and infant serious and non-serious adverse events; quality of life, milk volume and composition, and breastfeeding rates. <br> <br> For question 2, we will include RCTs that assess QT interval length and that compare domperidone with placebo and compare domperidone doses. Cohort and case-control studies are included if they assess cardiac arrhythmias and/or sudden death. All ages and both sexes are included, but we will contact authors for sex and age-disaggregated data. Case reports and case series in infants (0-2 years) and women of reproductive age will also be included.<br> <br>We will use Cochrane review methods, with duplicate independent screening, data entry, coding and risk of bias evaluations, and integration of quality assessment into analysis and interpretation. <br> <br> The project team includes independent researchers and knowledge users in midwifery, general practice and pediatrics; a perinatal epidemiologist; a consumer breastfeeding activist; expertise in systematic review methods, pharmacology, library science. We are using an integrated knowledge translation (KT) approach, including clinician and consumer perspectives in question and protocol development. This is combined with end-of-grant KT to meet with a range of stakeholders and discuss study results and implications for care, as well as more traditional publications and conference presentations. Ultimately the aim is to improve the evidence base for care and informed treatment choices for new mothers.</body> </html>