Calcium and vitamin D supplementation and/or periodontal therapy in the treatment of periodontitis among Brazilian pregnant women: protocol of a feasibility randomised controlled trial (the IMPROVE trial)
Authors: Cocate Paula Guedes , Kac Gilberto , Heitmann Berit L. , Nadanovsky Paulo , da Veiga Soares Carvalho Maria Cláudia , Benaim Camila , Schlüssel Michael Maia , de Castro Maria Beatriz Trindade , Alves-Santos Nadya Helena , Baptista Amanda Farnum , Holick Michael F. , Mokhtar Rana R. , Bomfim Alessandra Raymundo , Adegboye Amanda Rodrigues Amorim 
Published: March 2019

Abstract
Background
Periodontitis is a common oral inflammation, which is a risk factor for adverse pregnancy outcomes. Intakes of vitamin D and calcium are inversely associated with occurrence and progression of periodontitis. This study aims to assess the feasibility of a multi-component intervention, including provision of milk powder supplemented with calcium and vitamin D and periodontal therapy (PT), for improving maternal periodontal health and metabolic and inflammatory profiles of low-income Brazilian pregnant women with periodontitis.

Methods
The IMPROVE trial is a feasibility randomised controlled trial (RCT) with a 2 × 2 factorial design with a parallel process evaluation. Pregnant women with periodontitis, aged 18–40 years and with < 20 gestational weeks (n = 120) were recruited and randomly allocated into four groups: (1) fortified sachet (vitamin D and calcium) and powdered milk plus PT during pregnancy, (2) placebo sachet and powdered milk plus PT during pregnancy, (3) fortified sachet (vitamin D and calcium) and powdered milk plus PT after delivery and (4) placebo sachet and powdered milk plus PT after delivery. Dentists and participants are blinded to fortification. Acceptability of study design, recruitment strategy, random allocation, data collection procedures, recruitment rate, adherence and attrition rate will be evaluated. Data on serum levels of vitamin D, calcium and inflammatory biomarkers; clinical periodontal measurements; anthropometric measurements; and socio-demographic questionnaires are collected at baseline, third trimester and 6–8 weeks postpartum. Qualitative data are collected using focus group, for analysis of favourable factors and barriers related to study adherence.

Discussion
Oral health and mineral/vitamin supplementation are much overlooked in the public prenatal assistance in Brazil and of scarcity of clinical trials addressing these issues in low and middle-income countries,. To fill this gap the present study was designed to assess the feasibility of a RCT on acceptability of a multi-component intervention combining conventional periodontal treatment and consumption of milk fortified with calcium-vitamin D for improving periodontal conditions and maternal metabolic and inflammation status, among Brazilian low-income pregnant women with periodontitis. Thus, we hope that this relatively low-cost and safe multicomponent intervention can help reduce inflammation, improve maternal periodontal health and metabolic profile and consequently prevent negative gestational outcomes.

Trial registration
NCT, NCT03148483. Registered on May 11, 2017.