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

Nagendra K Monangi, Huan Xu, Yue-Mei Fan, Rasheeda Khanam, Waqasuddin Khan, Saikat Deb, Jesmin Pervin, Joan T Price, Lovejeet Kaur, INTERBIO-21st Study Consortium, Abdullah Al Mahmud, Le Quang Thanh, Angharad Care, Julio A Landero, Gerald F Combs, Elizabeth Belling, Joanne Chappell, Jing Chen, Fansheng Kong, Craig LacherSalahuddin Ahmed, Nabidul Haque Chowdhury, Sayedur Rahman, Furqan Kabir, Imran Nisar, Aneeta Hotwani, Usma Mehmood, Ambreen Nizar, Javairia Khalid, Usha Dhingra, Arup Dutta, Said Mohamed Ali, Fahad Aftab, Mohammed Hamad Juma, Monjur Rahman, Tahmeed Ahmed, M Munirul Islam, Bellington Vwalika, Patrick Musonda, Ulla Ashorn, Kenneth Maleta, Mikko Hallman, Laura Goodfellow, Juhi K Gupta, Ana Alfirevic, Susan K Murphy, Larry Rand, Kelli K Ryckman, Jeffrey C Murray, Rajiv Bahl, Per Ashorn

Research output: Contribution to journalArticleScientificpeer-review

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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).

OBJECTIVES: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)221-231
Number of pages11
JournalAmerican Journal of Clinical Nutrition
Volume119
Issue number1
Early online date27 Oct 2023
DOIs
Publication statusPublished - Jan 2024
Publication typeA1 Journal article-refereed

Keywords

  • Pregnancy
  • Female
  • Humans
  • Infant, Newborn
  • Premature Birth
  • Copper
  • Gestational Age
  • Live Birth
  • Inflammation
  • Risk Factors

Publication forum classification

  • Publication forum level 3

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