Association of maternal prenatal copper concentration with gestational duration and preterm birth: a multi-country meta-analysis
Bibliographic record
Abstract
ABSTRACT Background Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). We aimed to determine the association of maternal plasma/serum Cu concentrations during pregnancy with PTB risk and gestational duration in a large multi-cohort study including diverse populations. Methods Gestational duration data and maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal plasma or serum Cu concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS) analysis. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute phase reactants (APRs), malaria, and HIV infection were analyzed in 1239 samples from the Malawi cohort. Findings The maternal prenatal Cu concentration in our study samples followed a normal distribution with a mean of 1.92 μg/ml and a standard deviation of 0.43 μg/ml, and Cu concentrations increased with gestational age up to 20 weeks. The random effect meta-analysis across the 18 cohorts revealed that 1 μg/ml increase in maternal Cu concentration before the third trimester was associated with a higher risk of PTB with an OR of 1.30 (95% CI: 1.08 to 1.57) and shorter gestational duration of 1.64 days (95% CI: 0.56 to 2.73). The estimated effects were generally consistent across all sites. In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. Interpretation Our study supports a robust negative association between maternal mid-gestation Cu concentration and gestational duration and a positive association with risk for preterm birth. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as a potential marker of the integrated inflammatory pathways during pregnancy and risk for preterm birth.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.010 | 0.017 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.009 | 0.038 |
| Bibliometrics | 0.003 | 0.005 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".