Preterm birth (before 37 completed weeks of gestation) is a significant global health problem, with Bangladesh having the highest prevalence (19.1%). Preterm birth leads to various short- and long-term health issues for infants, contributing significantly to neonatal and under-five mortality. Several socioeconomic and demographic factors, such as low socioeconomic status, multiple pregnancies, and child marriage (marriage before age 18), are associated with increased preterm birth risk. Environmental exposure to heavy metals is another contributing factor. Studies have linked specific metals (arsenic, lead, chromium, copper) to preterm birth, but fewer have explored the causal relationship between socioeconomic factors and metal exposure leading to preterm birth. This study utilized a well-established birth cohort in rural Bangladesh to investigate this relationship, measuring 19 metals in maternal serum during the first and second trimesters using inductively coupled plasma mass spectrometry (ICP-MS). The aim was to identify novel metal biomarkers, critical exposure windows, and upstream socioeconomic factors affecting metal exposure and preterm birth risk, informing future interventions.

Existing literature highlights the global burden of preterm birth and its associated morbidity and mortality. Studies have established links between various socioeconomic and demographic factors, including child marriage, and preterm birth risk. The impact of environmental metal exposure on birth outcomes has also been explored, with several metals individually implicated in increased preterm birth risk. However, a limited number of studies have comprehensively investigated the causal pathway linking socioeconomic factors, maternal metal exposure, and preterm birth risk. This research gap underscores the need for a prospective study examining the interplay between these factors in a high-risk population like rural Bangladesh.

This prospective cohort study included 780 mother-offspring pairs recruited in rural Bangladesh (2008-2011). Inclusion criteria included maternal age ≥18 years, singleton pregnancy ≤16 weeks gestation, use of groundwater as the primary drinking water source, and intention to reside at the current location throughout pregnancy. Maternal serum samples were collected during the first and second trimesters, and 19 metals were analyzed using ICP-MS. Preterm birth was defined as delivery before 37 completed weeks of gestation, determined by ultrasonography. Demographic and socioeconomic data were collected using structured questionnaires. Statistical analyses included t-tests, Mann-Whitney U tests, chi-square tests, Pearson and Spearman correlations, mixed-effects logistic regression models (to assess the impact of metal exposure on preterm birth, adjusting for covariates), and mediation analysis (to evaluate the role of metal exposure in the relationship between marriage age and preterm birth).

The study population (780 mothers) had a mean marriage age of 17.46 years, with 44.4% married before 18. Of the live births, 22.4% were preterm. Mothers of preterm infants were more likely to be younger at marriage, experience secondhand smoke exposure, and have lower baseline weight, parental education level, and household income. Mixed-effects logistic regression revealed significant associations between preterm birth and early pregnancy serum levels of zinc (OR = 0.28), arsenic (OR = 1.49), and strontium (OR = 0.39), and mid-pregnancy serum barium (OR = 1.25). Mediation analysis demonstrated that these four metals mediated 30.2% of the effect of marriage age on preterm birth risk. The association between younger marriage age and preterm birth risk followed an exponential dose-response relationship, with women married after 18 years having a considerably lower risk.

The findings support the hypothesis that maternal serum metal exposure mediates the effect of child marriage on preterm birth risk. The identified metals (zinc, arsenic, strontium, barium) represent potential biomarkers and highlight critical exposure windows during pregnancy. The significant mediation effect of these metals suggests a causal pathway where child marriage may indirectly increase preterm birth risk through altered metal exposure. This is plausible given that younger mothers may experience nutritional deficiencies and have higher exposure to environmental pollutants. The study contributes to understanding the complex interplay between socioeconomic factors and environmental exposures in influencing preterm birth outcomes. The identified metal biomarkers can be further investigated for their utility in developing targeted interventions.

This study provides evidence that maternal serum metal exposure plays a mediating role in the association between child marriage and increased preterm birth risk in rural Bangladesh. The identification of specific metals and their critical exposure windows offers valuable insights for developing targeted interventions aimed at reducing preterm birth rates. Future research could focus on the specific mechanisms by which these metals influence preterm birth, exploring the interactions with other environmental exposures and nutritional factors. Further investigation into interventions aimed at improving nutritional status and reducing metal exposure in young mothers is warranted.

The study's cross-sectional nature limits the ability to definitively establish causality. Residual confounding from unmeasured factors cannot be completely ruled out. The sample size, while substantial, might limit the power to detect subtle effects of less prevalent metals. Generalizability to other populations may be limited by the specific context of rural Bangladesh.