Periodontal Disease and Small Vulnerable Newborns: A Cluster Randomized Trial - In 2022, 2.3 million newborns died in their first 28 days of life. Over half of these deaths occurred among small vulnerable newborns (SVN), who are born preterm (<37 weeks’ gestation), small-for-gestational-age (SGA, <10% centile), and/or low birth weight (LBW, <2,500g). The highest rates of SVNs occur in South Asia, where 52.1% of newborns are affected, and global and regional progress in reducing these outcomes has stagnated over the last decade. Periodontal disease has been implicated in observational studies as a factor associated with preterm, SGA, and LBW births. Yet randomized controlled trials evaluating the impact of periodontal interventions on incidence of SVN types have produced inconsistent results. Meta-analyses of previous trials have reported that many studies failed to eliminate the periodontal disease exposure or suffered from methodological flaws that threatened their internal validity, and some only delivered interventions later in gestation, potentially too late to disrupt hypothesized pathways. The study proposed in this application offers an opportunity to address such issues in innovative ways, including by 1) enrolling a large sample, 2) identifying participants in the 1st trimester for early intervention initiation, and 3) utilizing a low-cost package of interventions, including an antiseptic oral rinse, to reduce gingival inflammation. The study area, located in Nepal’s Terai region, has high rates of SVN types and neonatal mortality and is broadly representative of rural settings in much of South Asia. The study is a cluster-randomized controlled trial (n=2,280) to evaluate a package of oral health interventions delivered early in the first trimester until delivery on the incidence of SVNs in rural Sarlahi District, Nepal. The intervention package will include an oral health examination, daily antiseptic oral rinse, intensive oral hygiene education and instruction, and provision of a manual toothbrush, toothpaste, and dental floss. The trial will map and census the area, randomize clusters to intervention or control, establish surveillance to identify incident pregnancies, collect baseline data in both arms on a range of factors, deliver the intervention package until the pregnancy outcome, and visit participants within 72 hours of birth to assess incidence of SVNs and other outcomes. In a biospecimen sub-study (n=200), we will collect venous blood, gingival crevicular fluid, and plaque in early and late pregnancy to explore relationships between subgingival inflammation, circulating inflammation, and SVN types. The specific aims are to: 1) Determine the effect of a package of oral health interventions in pregnancy on the incidence of SVNs at birth and preterm birth, SGA birth, and LBW birth; 2) Explore relationships between subgingival inflammation, circulating inflammation, and incidence of SVNs.
