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Association of maternal prenatal copper concentration with gestational duration and preterm birth: a multicountry meta-analysis.

Monangi NK, Xu H, Fan YM, Khanam R, Khan W, Deb S, Pervin J, Price JT, Kaur L; INTERBIO-21st Study Consortium, Mahmud AA, Thanh LQ, Care A, Landero JA, Combs GF, Belling E, Chappell J, Chen J, Kong F, Lacher C, Ahmed S, Chowdhury NH, Rahman S, Kabir F, Nisar I, Hotwani A, Mehmood U, Nizar A, Khalid J, Dhingra U, Dutta A, Ali SM, Aftab F, Juma MH, Rahman M, Ahmed T, Islam MM, Vwalika B, Musonda P, Ashorn U, Maleta K, Hallman M, Goodfellow L, Gupta JK, Alfirevic A, Murphy SK, Rand L, Ryckman KK, Murray JC, Bahl R, Litch JA, Baruch-Gravett C, Sopory S, Natchu UCM, Kumar PV, Kumari N, Thiruvengadam R, Singh AK, Kumar P; GARBH-Ini Study Team, Alfirevic Z, Baqui AH, Bhatnagar S, Hirst JE, Hoyo C, Jehan F, Jelliffe-Pawlowski L, Rahman A, Roth DE, Sazawal S, Stringer JSA, Ashorn P, Zhang G, Muglia LJ.

  • Published 01 Jan 2024

  • Volume 119

  • ISSUE 1

  • Pagination 221-231



Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB).


This study aimed to determine the association of maternal Cu concentration during pregnancy with PTB risk and gestational duration in a large multicohort study including diverse populations.


Maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal Cu concentrations were determined using inductively coupled plasma mass spectrometry. 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) and infection status were analyzed in 1239 samples from the Malawi cohort.


The maternal prenatal Cu concentration in our study samples followed normal distribution with mean of 1.92 μg/mL and standard deviation of 0.43 μg/mL, and Cu concentrations increased with gestational age up to 20 wk. The random-effect meta-analysis across 18 cohorts revealed that 1 μg/mL increase in maternal Cu concentration was associated with higher risk of PTB with odds ratio of 1.30 (95% confidence interval [CI]: 1.08, 1.57) and shorter gestational duration of 1.64 d (95% CI: 0.56, 2.73). 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.


Our study supports robust negative association between maternal Cu and gestational duration and positive association with risk for PTB. 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 potential marker of integrated inflammatory pathways during pregnancy and risk for PTB.