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Meta-Analysis
. 2024 Jan;119(1):221-231.
doi: 10.1016/j.ajcnut.2023.10.011. Epub 2023 Oct 27.

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

Nagendra K Monangi  1 , Huan Xu  2 , Yue-Mei Fan  3 , Rasheeda Khanam  4 , Waqasuddin Khan  5 , Saikat Deb  6 , Jesmin Pervin  7 , Joan T Price  8 , Lovejeet Kaur  9 ; INTERBIO-21st Study Consortium; Abdullah Al Mahmud  10 , Le Quang Thanh  11 , Angharad Care  12 , Julio A Landero  13 , Gerald F Combs  14 , Elizabeth Belling  15 , Joanne Chappell  15 , Jing Chen  16 , Fansheng Kong  15 , Craig Lacher  17 , Salahuddin Ahmed  18 , Nabidul Haque Chowdhury  18 , Sayedur Rahman  18 , Furqan Kabir  5 , Imran Nisar  5 , Aneeta Hotwani  5 , Usma Mehmood  5 , Ambreen Nizar  5 , Javairia Khalid  5 , Usha Dhingra  19 , Arup Dutta  19 , Said Mohamed Ali  6 , Fahad Aftab  6 , Mohammed Hamad Juma  6 , Monjur Rahman  10 , Tahmeed Ahmed  10 , M Munirul Islam  10 , Bellington Vwalika  20 , Patrick Musonda  21 , Ulla Ashorn  22 , Kenneth Maleta  23 , Mikko Hallman  24 , Laura Goodfellow  12 , Juhi K Gupta  12 , Ana Alfirevic  12 , Susan K Murphy  25 , Larry Rand  26 , Kelli K Ryckman  27 , Jeffrey C Murray  28 , Rajiv Bahl  29 , James A Litch  30 , Courtney Baruch-Gravett  30 , Shailaja Sopory  9 , Uma Chandra Mouli Natchu  31 , Pavitra V Kumar  32 , Neha Kumari  9 , Ramachandran Thiruvengadam  9 , Atul Kumar Singh  32 , Pankaj Kumar  32 ; GARBH-Ini study team  9 ; Zarko Alfirevic  12 , Abdullah H Baqui  4 , Shinjini Bhatnagar  9 , Jane E Hirst  33 , Cathrine Hoyo  34 , Fyezah Jehan  35 , Laura Jelliffe-Pawlowski  36 , Anisur Rahman  7 , Daniel E Roth  37 , Sunil Sazawal  38 , Jeffrey S A Stringer  8 , Per Ashorn  39 , Ge Zhang  40 , Louis J Muglia  41
Collaborators, Affiliations
Meta-Analysis

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

Nagendra K Monangi et al. Am J Clin Nutr. 2024 Jan.

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.

Keywords: acute-phase reactants; copper; gestational duration; inflammation; low- and middle-income countries; nutrition; pregnancy; preterm birth.

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Figures

FIGURE 1
FIGURE 1
Geographic location of study sites.
FIGURE 2
FIGURE 2
Flow chart of the study illustrating the total number of subjects and inclusion/exclusion criteria. The boxes on the left side list the exclusion criteria applied at different stages, and the boxes on the right side describe the experiment and data analyses performed at different stages.
FIGURE 3
FIGURE 3
Copper concentration at each gestational week of sampling from 5 to 41 wk (N = 10,432).
FIGURE 4
FIGURE 4
Meta-analysis of the association of maternal copper concentration with PTB (A) and gestational duration (B). This analysis was performed in 10,017 pregnancies with samples collected before 28 wk.
FIGURE 5
FIGURE 5
Correlogram of copper (Cu) concentration, acute-phase reactants (APRs), and phenotype measured in the Malawi (iLiNS-DYAD) cohort. Associations between maternal Cu and APRs, infection status were analyzed in 1239 samples from the Malawi cohort.
See this image and copyright information in PMC

References

    1. Liu L., Oza S., Hogan D., Chu Y., Perin J., Zhu J., et al. Global, regional, and national causes of under-5 mortality in 2000-15: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet. 2016;388(10063):3027–3035. doi: 10.1016/S0140-6736(16)31593-8. - DOI - PMC - PubMed
    1. Blencowe H., Cousens S., Chou D., Oestergaard M., Say L., Moller A.B., et al. Born too soon: the global epidemiology of 15 million preterm births. Reprod. Health. 2013;10(suppl 1):S2. doi: 10.1186/1742-4755-10-S1-S2. - DOI - PMC - PubMed
    1. DiNicolantonio J.J., Mangan D., O’Keefe J.H. Copper deficiency may be a leading cause of ischaemic heart disease. Open Heart. 2018;5(2) doi: 10.1136/openhrt-2018-000784. - DOI - PMC - PubMed
    1. Kelley D.S., Daudu P.A., Taylor P.C., Mackey B.E., Turnlund J.R. Effects of low-copper diets on human immune response. Am. J. Clin. Nutr. 1995;62(2):412–416. doi: 10.1093/ajcn/62.2.412. - DOI - PubMed
    1. Festa R.A., Thiele D.J. Copper: an essential metal in biology. Curr. Biol. 2011;21(21):R877–R883. doi: 10.1016/j.cub.2011.09.040. - DOI - PMC - PubMed

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