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, Abdullah Al Mahmud, Le Quang Thanh, Angharad Care, Julio A Landero, Gerald F Combs, Elizabeth Belling, Joanne Chappell, Jing Chen, Fansheng Kong, Craig Lacher, Salahuddin 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, James A Litch, Courtney Baruch-Gravett, Shailaja Sopory, Uma Chandra Mouli Natchu, Pavitra V Kumar, Neha Kumari, Ramachandran Thiruvengadam, Atul Kumar Singh, Pankaj Kumar, Zarko Alfirevic, Abdullah H Baqui, Shinjini Bhatnagar, Jane E Hirst, Cathrine Hoyo, Fyezah Jehan, Laura Jelliffe-Pawlowski, Anisur Rahman, Daniel E Roth, Sunil Sazawal, Jeffrey S A Stringer, Per Ashorn, Ge Zhang, Louis J Muglia

Journal: The American journal of clinical nutrition 2024;119(1):221-231

PMID: 37890672

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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.

Address: Division of Neonatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center and March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, Ohio, United States; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States. Electronic address: [email protected].; Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center and March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, Ohio, United States; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.; Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland. Electronic address: [email protected].; International Center for Maternal and Newborn Health, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States.; Biorepository and Omics Research Group, Department of Pediatrics and Child Health, Faculty of Health Sciences, Medical College, Aga Khan University, Karachi, Sindh, Pakistan.; Research Division, Public Health Laboratory, Center for Public Health Kinetics, Chake Chake, Tanzania.; Maternal and Child Health Division, International Centre for Diarrheal Disease Research, Bangladesh, Dhaka District, Bangladesh.; Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States.; Child and Maternal Health Program, Translational Health Science and Technology Institute (THSTI), Faridabad, India.; Nutrition and Clinical Services Division, International Centre for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh.; Tu Du Hospital, Ho Chi Ming City, Vietnam.; Department of Women's and Children's Health, The University of Liverpool, Liverpool, United Kingdom.; Department of Chemistry, University of Cincinnati, Cincinnati, OH, United States.; Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, United States.; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States.; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: [email protected].; USDA-ARS, Grand Forks Human Nutrition Research Center, Grand Forks, ND, United States.; Projahnmo Research Foundation, Dhaka, Bangladesh.; Center for Public Health Kinetics, New Delhi, India.; School of Medicine, University of Zambia, Lusaka, Zambia.; School of Public Health, University of Zambia, Lusaka, Zambia.; Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.; School of Public Health and Family Medicine, University of Malawi College of Medicine, Blantyre, Malawi.; School of Public Health and Family Medicine, University of Malawi College of Medicine, Blantyre, Malawi; Medical Research Centre Oulu, PEDEGO Research Unit, University of Oulu, Oulu, Pohjois-Pohjanmaa, Finland.; Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, NC, United States.; Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco School of Medicine, San Francisco, CA, United States.; Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, United States.; Department of Pediatrics, University of Iowa, Iowa City, IA, United States.; Department of Maternal, Newborn, Child and Adolescent Health, World Health Organization, Geneva, Switzerland.; Global Alliance to Prevent Prematurity and Stillbirth, Lynnwood, WA, United States.; St. John's Research Institute (SJRI), Bangladore, India.; Geochronology Group, Inter University Accelerator Centre (IUAC), Delhi, India.; Tu Du Hospital, Ho Chi Ming City, Vietnam; Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, United Kingdom.; Department of Biological Sciences and Center for Human Health and the Environment, North Carolina State University, Raleigh, North Carolina, United States.; Department of Pediatrics and Child Health, Aga Khan University, Karachi, Pakistan.; Department of Epidemiology and Biostatistics, University of California San Francisco School of Medicine, San Francisco, CA, United States.; Centre for Global Child Health, Hospital for Sick Children, University of Toronto, Toronto, Canada; Department of Pediatrics, University of Toronto, Toronto, Canada.; Research Division, Public Health Laboratory, Center for Public Health Kinetics, Chake Chake, Tanzania; Center for Public Health Kinetics, New Delhi, India.; Center for Child, Adolescent and Maternal Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Pediatrics, Tampere University Hospital, Tampere, Finland.; Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center and March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, Ohio, United States; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States. Electronic address: [email protected].; Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center and March of Dimes Prematurity Research Center Ohio Collaborative, Cincinnati, Ohio, United States; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Burroughs Wellcome Fund, Research Triangle Park, NC, United States.

DOI: 10.1016/j.ajcnut.2023.10.011

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MeSH Terms: Pregnancy, Female, Humans, Infant, Newborn, Premature Birth, Copper, Gestational Age, Live Birth, Inflammation, Risk Factors