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Association between inflammatory indicators derived from preconception complete blood count and specific adverse
Yue Jiang1, Shuaihua Song1, Hanze Du1
1Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Translational Medicine Center, State Key Laboratory of Complex Severe and Rare Diseases, National Health Commission Key Laboratory of Endocrinology, Beijing, China.
Insights
Preconception inflammation markers like NLR, PLR, and SII show outcome-specific associations with adverse pregnancy outcomes, but have limited individual clinical use. These findings offer population-based insights for rural preconception risk stratification.
Area of Science:
- Reproductive Medicine
- Immunology
- Public Health
Background:
- Adverse fetal and neonatal outcomes (SGA, LGA, LBW) pose significant risks to maternal and infant health.
- Limited population-based cohort evidence exists on preconception immune-inflammatory status and specific adverse pregnancy outcomes.
Purpose of the Study:
- To systematically analyze the associations between preconception immune-inflammatory indicators and adverse fetal, neonatal, and pregnancy outcomes.
- To investigate the role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) in pregnancy complications.
Main Methods:
- Large-sample cohort study using data from China's National Free Preconception Health Examination Program (2010-2012).
- Inclusion of 49,855 rural women of childbearing age.
- Multivariate logistic regression and restricted cubic spline (RCS) models to analyze CBC-derived inflammatory markers.
Main Results:
- Distinct outcome-specific associations were observed for NLR, PLR, and SII.
- Moderate NLR increased SGA risk; moderate NLR and SII reduced LGA risk; high PLR elevated LGA risk; moderate NLR decreased preterm birth risk.
- U-shaped nonlinear associations were confirmed for NLR, PLR, and SII with LGA, and for PLR and SII with preterm birth, indicating threshold effects.
Conclusions:
- Preconception NLR, PLR, and SII demonstrate outcome-specific threshold associations with adverse fetal and neonatal outcomes.
- Unmeasured confounders may influence correlations; effect sizes are modest, limiting individual clinical utility.
- Results require validation in diverse urban and multicenter cohorts.
Background:
Adverse fetal and neonatal outcomes, including small for gestational age (SGA), large for gestational age (LGA), and low birth weight (LBW), seriously endanger maternal and infant health. Currently, the associations between preconception baseline immune-inflammatory status and the above specific adverse pregnancy outcomes still lack systematic population-based cohort evidence.
Methods:
Based on the National Free Preconception Health Examination Program in China from 2010 to 2012, this large-sample cohort study recruited rural women of childbearing age in China. Multivariate logistic regression and restricted cubic spline (RCS) models were used to systematically analyze the associations between preconception complete blood count (CBC)-derived inflammatory indicators, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and adverse fetal, neonatal, and pregnancy outcomes.
Results:
A total of 49,855 preconception participants were enrolled in this study, among whom 16,105 cases experienced adverse fetal and neonatal outcomes. Quartile analysis revealed distinct outcome-specific associations of inflammatory indicators. Moderate levels of NLR increased the risk of SGA, while moderate NLR and SII levels reduced the risk of LGA; the highest quartile of PLR elevated the risk of LGA, and moderate NLR decreased the risk of preterm birth. Only high levels of NLR exerted a protective effect against HBW. Further RCS analyses confirmed significant U-shaped nonlinear associations of NLR, PLR, and SII with LGA, as well as U-shaped correlations of PLR and SII with preterm birth, indicating obvious threshold effects of preconception inflammation on pregnancy outcomes.
Conclusion:
After adjusting available covariates, preconception NLR, PLR, and SII exhibited outcome-specific threshold associations with adverse fetal and neonatal outcomes, yet unmeasured confounders (preconception infection, maternal nutrition, etc.) may overestimate these correlations. Owing to the large sample, many significant results carry modest effect sizes with limited individual clinical utility; these markers merely offer population-based epidemiological references instead of standalone screening indicators for rural preconception risk stratification. Our results require validation in modern urban and multicenter cohorts due to the historical rural-only study population.
