Maternal inflammatory and microbial drivers of low birthweight in low- and middle-income countries.

Background: Low birthweight (LBW) is when an infant is born too soon or too small, and it affects one in seven infants in low- and middle-income countries. LBW has a significant impact on short-term morbidity and mortality, and it impairs long-term health and human capital. Antenatal microbial and inflammatory exposure may contribute to LBW.

Methods: Ovid-Medline, Embase and Cochrane databases were searched for English-language articles evaluating inflammatory, microbial or infective causes of LBW, small-for-gestational age, intra-uterine growth restriction or prematurity. Inclusion criteria were human studies including published data; conference abstracts and grey literature were excluded. A narrative synthesis of the literature was conducted.

Results: Local infections may drive the underlying causes of LBW: for example, vaginitis and placental infection are associated with a greater risk of prematurity. Distal infection and inflammatory pathways are also associated with LBW, with an association between periodontitis and preterm delivery and environmental enteric dysfunction and reduced intra-uterine growth. Systemic maternal infections such as malaria and HIV are associated with LBW, even when infants are exposed to HIV but not infected. This latter association may be driven by chronic inflammation, co-infections and socio-economic confounders. Antimicrobial prophylaxis against other bacteria in pregnancy has shown minimal impact in most trials, though positive effects on birthweight have been found in some settings with a high infectious disease burden.

Conclusion: Maternal inflammatory and infective processes underlie LBW, and provide treatable pathways for interventions. However, an improved understanding of the mechanisms and pathways underlying LBW is needed, given the impact of LBW on life-course.