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.

Mycoplasma genitalium in pregnancy, including specific co-infections, is associated with lower birthweight: A prospective cohort study.

BACKGROUND: Mycoplasma genitalium infection in pregnancy is increasingly reported at similar frequencies to other sexually transmitted infections (STIs). Knowledge on its contribution to adverse pregnancy outcomes is very limited, especially relative to other STIs or bacterial vaginosis (BV). Whether M. genitalium influences birthweight remains unanswered. METHODS: Associations between birthweight and M. genitalium and other STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis) and BV in pregnancy were examined in 416 maternal-newborn pairs from a prospective cohort study in Papua New Guinea. FINDINGS: Compared to uninfected women, M. genitalium (-166.9 g, 95% confidence interval [CI]: -324.2 to -9.7 g, p = 0.038) and N. gonorrhoeae (-274.7 g, 95% CI: -561.9 to 12.5 g, p = 0.061) infections were associated with lower birthweight in an adjusted analysis. The association for C. trachomatis was less clear, and T. vaginalis and BV were not associated with lower birthweight. STI prevalence was high for M. genitalium (13.9%), N. gonorrhoeae (5.0%), and C. trachomatis (20.0%); co-infections were frequent. Larger effect sizes on birthweight occurred with co-infections of M. genitalium, N. gonorrhoeae, and/or C. trachomatis. CONCLUSION: M. genitalium is a potential contributor to lower birthweight, and co-infections appear to have a greater negative impact on birthweight. Trials examining the impact of early diagnosis and treatment of M. genitalium and other STIs in pregnancy and preconception are urgently needed. FUNDING: Funding was received from philanthropic grants, the National Health and Medical Research Council, and the Burnet Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Impact of an integrated health, nutrition, and early child stimulation and responsive care intervention package delivered to preterm or term small for gestational age babies during infancy on growth and neurodevelopment: study protocol of an individually randomized controlled trial in India (Small Babies Trial).

BACKGROUND: Preterm and term small for gestational age (SGA) babies are at high risk of experiencing malnutrition and impaired neurodevelopment. Standalone interventions have modest and sometimes inconsistent effects on growth and neurodevelopment in these babies. For greater impact, intervention may be needed in multiple domains-health, nutrition, and psychosocial care and support. Therefore, the combined effects of an integrated intervention package for preterm and term SGA on growth and neurodevelopment are worth investigating. METHODS: An individually randomized controlled trial is being conducted in urban and peri-urban low to middle-socioeconomic neighborhoods in South Delhi, India. Infants are randomized (1:1) into two strata of 1300 preterm and 1300 term SGA infants each to receive the intervention package or routine care. Infants will be followed until 12 months of age. Outcome data will be collected by an independent outcome ascertainment team at infant ages 1, 3, 6, 9, and 12 months and at 2, 6, and 12 months after delivery for mothers. DISCUSSION: The findings of this study will indicate whether providing an intervention that addresses factors known to limit growth and neurodevelopment can offer substantial benefits to preterm or term SGA infants. The results from this study will increase our understanding of growth and development and guide the design of public health programs in low- and middle-income settings for vulnerable infants. TRIAL REGISTRATION: The trial has been registered prospectively in Clinical Trial Registry - India # CTRI/2021/11/037881, Registered on 08 November 2021.