Nutrition Supplements, Oral Health and Adverse Pregnancy Outcomes in Malawi

Every year, 32 million infants are born preterm (PTB) or with intrauterine growth restriction (IUGR), predisposing them to a high risk of mortality and morbidity. Most of these infants are born in low-income countries. Maternal malnutrition and infections are among the most important interlinked risk factors for adverse pregnancy outcomes. Therefore, nutritional supplementation with multiple micronutrients during pregnancy is increasingly recommended in low-resource settings. Periodontitis, i.e. infection in the tooth-supporting tissues, has been extensively investigated as a risk for poor pregnancy outcomes, but the role of dental caries and its sequel, periapical infection (PAI), is almost unknown. As with periodontitis, the pathway between PAI and adverse pregnancy outcomes is biologically plausible. The aim of this thesis was to investigate the interlinkage between nutrition supplementation, oral diseases and pregnancy outcomes in a rural Malawian population. The thesis was based on three studies: Study I assessed whether supplementation with multiple micronutrients (MMN) or lipid-based nutrient supplement (LNS) influence dental caries development or periodontal health when compared with commonly used iron and folic-acid supplementation (IFA). Study II investigated the associations between maternal caries, PAI or periodontitis and pregnancy duration and birth size of the infant. Study III explored two possible causal mechanisms underlying the association between PAI and adverse pregnancy outcomes detected in Study II: spread of periapical bacteria to the fetoplacental unit (direct pathway) and systemic inflammation (indirect pathway). For the study, 1391 pregnant women were enrolled before their twentieth gestational week. They were provided with a daily capsule of IFA or MMN or a sachet of LNS containing proteins, carbohydrates, essential fatty acids and 21 micronutrients. Maternal blood and salivary samples were collected at enrollment and at 36 gestational weeks, and placental tissue after delivery. Infant weight, length and head circumference were measured after birth. Of the enrolled participants, 1024 underwent clinical and radiological oral health examination within six weeks after delivery and were included in the analysis. When comparing the nutrition supplement groups, the prevalence of caries was significantly higher in the MMN and LNS groups than in the IFA group (69.1%, 63.3% and 56.7% respectively; P = 0.004). When assessing the birth outcomes by infection group, the mean (95% CI) pregnancy duration was 0.4 weeks (0.1–0.8) shorter and infants’ mean birth weight 79 g (13–145) lower and length 0.5 cm (0.2– 0.9) shorter in women who had PAI compared to those without. PTB incidence was 3.5% (95%; CI 1.1–8.1%) and prevalence of stunting 9.0% higher (95% CI 2.7– 15.2%) in women who had PAI. No significant differences in the periodontal disease parameters were seen between supplementation groups or in birth outcomes between groups of women with or without periodontitis. PAI was associated with creactive protein (CRP), alpha-1-acid glycoprotein (AGP) and cortisol concentrations in a dose-dependent manner at 36 gestation weeks. When CRP, AGP or cortisol concentration was added into regression models, the association between PAI and duration of pregnancy or infant birth weight and length was attenuated, suggesting that AGP, CRP and cortisol were on the causal pathway between PAI and birth outcomes. In conclusion, maternal diet supplementation with multiple micronutrients during pregnancy in low-resource environments in which malnutrition and oral diseases are common may enhance caries development. PAI, the common sequel of caries, elevates systemic inflammation, which can lead to PTB and IUGR. This study thus suggests that PAI is a common, previously unidentified and relatively easily modifiable risk factor for adverse pregnancy outcomes. Caries prevention should be considered, especially when planning nutrient intervention programs for pregnant women in low-resource environments.