Maternal blood biomarkers and adverse pregnancy outcomes: a systematic review and meta-analysis

Background: Pregnancy is a vulnerable period for the mother and the infant and exposures to environmental chemicals in utero can influence neonatal morbidity and mortality. There is a momentum toward understanding and exploring the current maternal biological mechanisms specific to in utero effects, to improve birth outcomes. This study aims to examine the current understanding of the role of biomarkers that may be associated with term of pregnancy, infant birth weights and infant development in utero. Methods: Electronic searches were conducted in PubMed, Embase, OvidMD, and Scopus databases; and all relevant research articles in English were retrieved. Studies were selected if they evaluated maternal blood plasma/serum biomarkers proposed to influence adverse birth outcomes in the neonate. Data were extracted on characteristics, quality, and odds ratios from each study and meta-analysis was conducted. Results: A total of 54 studies (35 for meta-analysis), including 43,702 women, 50 plasma markers and six descriptors of birth outcomes were included in the present study. The random effect point estimates for risk of adverse birth outcomes were 1.61(95%CI: 1.39-1.85, p < 0.0001) for inflammation-related biomarkers and 1.65(95%CI: 1.22-2.25, p = 0.0013) for growth factor/hormone-related biomarkers. All subgroups of plasma markers showed significant associations with adverse birth outcomes with no apparent study bias. Conclusions: The two subsets of plasma markers identified in this study (inflammation-related and growth factor/hormone-related) may serve as potentially valuable tools in the investigation of maternal molecular mechanisms, especially select pathways underlying inflammatory and immunological mediation in terms of modulating adverse infant outcomes. Future large, prospective cohort studies are needed to validate the promising plasma biomarkers, and to examine other maternal biological matrices such as cervicovaginal fluid and urine.