Skip to main content
SpringerLink
Log in

Umbilical Serum Copper Status and Neonatal Birth Outcomes: a Prospective Cohort Study

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Our study aimed to assess the distribution of copper (Cu) in umbilical cord serum and estimated the association between umbilical serum Cu status and neonatal birth outcomes in a Chinese population. Through the Ma’anShan Birth Cohort Study, 2689 maternal-singleton pairs with detailed birth records and available serum samples were identified. The tertile levels of ln-transformed Cu were used to define low, medium, and high levels for serum Cu. The median for umbilical cord serum Cu was 298.2 μg/L with a range of 123.1–699.6 μg/L in this study population. Our study found a positive association between the concentration of serum Cu in the umbilical cord and the duration of gestation. Compared with medium Cu levels, we found that infants with low Cu levels had a significant higher risk of preterm birth (OR = 5.06, 95% CI 2.74, 9.34) and early-term birth (OR = 1.36, 95% CI 1.10, 1.69) in the crude model. We also found that infants with high Cu levels had a significant higher risk of late- or post-term birth (OR = 1.47, 95% CI 1.11, 1.95). A significant higher risk of preterm, early-term, and late- or post-term birth still remained, even after adjustment for potential confounding factors. Our findings suggested that both Cu deficiency and Cu overload had an adverse effect on neonatal birth outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Blencowe H, Cousens S, Oestergaard MZ, Chou D, Moller AB, Narwal R, Adler A, Vera Garcia C, Rohde S, Say L, Lawn JE (2012) National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 379(9832):2162–2172. https://doi.org/10.1016/S0140-6736(12)60820-4

    Article  PubMed  Google Scholar 

  2. Romero R, Dey SK, Fisher SJ (2014) Preterm labor: one syndrome, many causes. Science 345(6198):760–765. https://doi.org/10.1126/science.1251816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. American College of Obstetricians and Gynecologists (2013) ACOG committee opinion no 579: definition of term pregnancy. Obstet Gynecol 122(5):1139–1140. https://doi.org/10.1097/01.AOG.0000437385.88715.4a

    Article  Google Scholar 

  4. Reddy UM, Bettegowda VR, Dias T, Yamada-Kushnir T, Ko CW, Willinger M (2011) Term pregnancy: a period of heterogeneous risk for infant mortality. Obstet Gynecol 117(6):1279–1287. https://doi.org/10.1097/AOG.0b013e3182179e28

    Article  PubMed  PubMed Central  Google Scholar 

  5. Tita AT, Landon MB, Spong CY, Lai Y, Leveno KJ, Varner MW, Moawad AH, Caritis SN, Meis PJ, Wapner RJ, Sorokin Y, Miodovnik M, Carpenter M, Peaceman AM, O'Sullivan MJ, Sibai BM, Langer O, Thorp JM, Ramin SM, Mercer BM (2009) Timing of elective repeat cesarean delivery at term and neonatal outcomes. N Engl J Med 360(2):111–120. https://doi.org/10.1056/NEJMoa0803267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Uriu-Adams JY, Scherr RE, Lanoue L, Keen CL (2010) Influence of copper on early development: prenatal and postnatal considerations. Biofactors 36(2):136–152. https://doi.org/10.1002/biof.85

    Article  CAS  PubMed  Google Scholar 

  7. Araya M, Koletzko B, Uauy R (2003) Copper deficiency and excess in infancy: developing a research agenda. J Pediatr Gastroenterol Nutr 37(4):422–429

    Article  CAS  Google Scholar 

  8. Gonzalez-Tarancon R, Calvo-Ruata L, Aramendia M, Ortega C, Garcia-Gonzalez E, Rello L (2017) Serum copper concentrations in hospitalized newborns. J Trace Elem Med Biol 39:1–5. https://doi.org/10.1016/j.jtemb.2016.06.010

    Article  CAS  PubMed  Google Scholar 

  9. Harvey LJ, McArdle HJ (2008) Biomarkers of copper status: a brief update. Br J Nutr 99(Suppl 3):S10–S13. https://doi.org/10.1017/s0007114508006806

    Article  CAS  PubMed  Google Scholar 

  10. Marriott LD, Foote KD, Kimber AC, Delves HT, Morgan JB (2007) Zinc, copper, selenium and manganese blood levels in preterm infants. Arch Dis Child Fetal Neonatal Ed 92(6):F494–F497. https://doi.org/10.1136/adc.2006.107755

    Article  PubMed  PubMed Central  Google Scholar 

  11. Gambling L, McArdle HJ (2004) Iron, copper and fetal development. Proc Nutr Soc 63(4):553–562

    Article  CAS  Google Scholar 

  12. Bermudez L, Garcia-Vicent C, Lopez J, Torro MI, Lurbe E (2015) Assessment of ten trace elements in umbilical cord blood and maternal blood: association with birth weight. J Transl Med 13:291. https://doi.org/10.1186/s12967-015-0654-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lewis SS, Keller SJ (2009) Identification of copper-responsive genes in an early life stage of the fathead minnow Pimephales promelas. Ecotoxicology 18(3):281–292. https://doi.org/10.1007/s10646-008-0280-3

    Article  CAS  PubMed  Google Scholar 

  14. Alebic-Juretic A, Frkovic A (2005) Plasma copper concentrations in pathological pregnancies. J Trace Elem Med Biol 19(2–3):191–194. https://doi.org/10.1016/j.jtemb.2005.08.002

    Article  CAS  PubMed  Google Scholar 

  15. Jauniaux E, Poston L, Burton GJ (2006) Placental-related diseases of pregnancy: involvement of oxidative stress and implications in human evolution. Hum Reprod Update 12(6):747–755. https://doi.org/10.1093/humupd/dml016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Vukelic J, Kapamadzija A, Petrovic D, Grujic Z, Novakov-Mikic A, Kopitovic V, Bjelica A (2012) Variations of serum copper values in pregnancy. Srp Arh Celok Lek 140(1–2):42–46

    Article  Google Scholar 

  17. Ge X, Tao FB, Huang K, Mao LJ, Huang SH, Niu Y, Hao JH, Sun YL, Rutayisire E (2016) Maternal snoring may predict adverse pregnancy outcomes: a cohort study in China. PLoS One 11(2):e0148732. https://doi.org/10.1371/journal.pone.0148 732

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wang SF, Ge X, Zhu BB, Xuan YJ, Huang K, Rutayisire E, Mao LJ, Huang SH, Yan SQ, Tao FB (2016) Maternal continuing folic acid supplementation after the first trimester of pregnancy increased the risk of large-for- gestational-age birth: a population-based birth cohort study. Nutrients 8(8). https://doi.org/10.3390/nu8080493

    Article  Google Scholar 

  19. Huebert D (2017) Definition of baseline chemistry: box plots of data are information rich. Integr Environ Assess Manag 13(2):446–448. https://doi.org/10.1002/Ieam.1872

    Article  PubMed  Google Scholar 

  20. Zhang Z, Yuan EW, Liu JJ, Lou XF, Jia LT, Li XF, Zhang LL (2013) Gestational age-specific reference intervals for blood copper, zinc, calcium, magnesium, iron, lead, and cadmium during normal pregnancy. Clin Biochem 46(9):777–780. https://doi.org/10.1016/j.clinbiochem.2013.03.004

    Article  CAS  PubMed  Google Scholar 

  21. Baqui AH, Rosen HE, Lee AC, Applegate JA, El Arifeen S, Rahman SM, Begum N, Shah R, Darmstadt GL, Black RE (2013) Preterm birth and neonatal mortality in a rural Bangladeshi cohort: implications for health programs. J Perinatol 33(12):977–981. https://doi.org/10.1038/jp.2013.91

    Article  CAS  PubMed  Google Scholar 

  22. Wang H, Hu YF, Hao JH, Chen YH, Wang Y, Zhu P, Zhang C, Xu YY, Tao FB, Xu DX (2016) Maternal serum zinc concentration during pregnancy is inversely associated with risk of preterm birth in a Chinese population. J Nutr 146(3):509–515. https://doi.org/10.3945/jn.115.220632

    Article  CAS  PubMed  Google Scholar 

  23. Carey JC, Klebanoff MA, Hauth JC, Hillier SL, Thom EA, Ernest JM, Heine RP, Nugent RP, Fischer ML, Leveno KJ, Wapner R, Varner M (2000) Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med 342(8):534–540. https://doi.org/10.1056/nejm200002243420802

    Article  CAS  PubMed  Google Scholar 

  24. Liang CM, Li ZJ, Xia X, Wang QN, Tao RW, Tao YR, Xiang HY, Tong SL, Tao FB (2017) Determine multiple elements simultaneously in the sera of umbilical cord blood samples—a very simple method. Biol Trace Elem Res 177(1):1–8. https://doi.org/10.1007/s12011-016-0853-6

    Article  CAS  PubMed  Google Scholar 

  25. Wells EM, Jarrett JM, Lin YH, Caldwell KL, Hibbeln JR, Apelberg BJ, Herbstman J, Halden RU, Witter FR, Goldman LR (2011) Body burdens of mercury, lead, selenium and copper among Baltimore newborns. Environ Res 111(3):411–417. https://doi.org/10.1016/j.envres.2010.12.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Jones EA, Wright JM, Rice G, Buckley BT, Magsumbol MS, Barr DB, Williams BL (2010) Metal exposures in an inner-city neonatal population. Environ Int 36(7):649–654. https://doi.org/10.1016/j.envint.2010.04.007

    Article  CAS  PubMed  Google Scholar 

  27. El Marroun H, Zeegers M, Steegers EA, van der Ende J, Schenk JJ, Hofman A, Jaddoe VW, Verhulst FC, Tiemeier H (2012) Post-term birth and the risk of behavioural and emotional problems in early childhood. Int J Epidemiol 41(3):773–781. https://doi.org/10.1093/ije/dys043

    Article  PubMed  Google Scholar 

  28. Yang J, Huo W, Zhang B, Zheng T, Li Y, Pan X, Liu W, Chang H, Jiang M, Zhou A et al (2016) Maternal urinary cadmium concentrations in relation to preterm birth in the Healthy Baby Cohort Study in China. Environ Int 94:300–306. https://doi.org/10.1016/j.envint.2016.06.003

    Article  CAS  PubMed  Google Scholar 

  29. Brown HK, Speechley KN, Macnab J, Natale R, Campbell MK (2014) Neonatal morbidity associated with late preterm and early term birth: the roles of gestational age and biological determinants of preterm birth. Int J Epidemiol 43(3):802–814. https://doi.org/10.1093/ije/dyt251

    Article  PubMed  Google Scholar 

  30. Sengupta S, Carrion V, Shelton J, Wynn RJ, Ryan RM, Singhal K, Lakshminrusimha S (2013) Adverse neonatal outcomes associated with early-term birth. JAMA Pediatr 167(11):1053–1059. https://doi.org/10.1001/jamapediatrics.2013.2581

    Article  PubMed  Google Scholar 

  31. Edwards MO, Kotecha SJ, Lowe J, Richards L, Watkins WJ, Kotecha S (2015) Early-term birth is a risk factor for wheezing in childhood: a cross-sectional population study. J Allergy Clin Immunol 136(3):581–7.e2. https://doi.org/10.1016/j. jaci.2015.05.005

    Article  PubMed  Google Scholar 

  32. Bruckner TA, Cheng YW, Caughey AB (2008) Increased neonatal mortality among normal-weight births beyond 41 weeks of gestation in California. Am J Obstet Gynecol 199(4):421.e1–421.e\. https://doi.org/10.1016/j.ajog.2008.05.015

    Article  Google Scholar 

  33. Frank R, Garfinkle J, Oskoui M, Shevell MI (2016) Clinical profile of children with cerebral palsy born term compared with late- and post-term: a retrospective cohort study. BJOG. https://doi.org/10.1111/1471-0528.14240

    Article  Google Scholar 

  34. Perveen S, Altaf W, Vohra N, Bautista ML, Harper RG, Wapnir RA (2002) Effect of gestational age on cord blood plasma copper, zinc, magnesium and albumin. Early Hum Dev 69(1–2):15–23. https://doi.org/10.1016/s0378-3782(02)000 24-5

    Article  CAS  PubMed  Google Scholar 

  35. Schulpis KH, Karakonstantakis T, Gavrili S, Chronopoulou G, Karikas GA, Vlachos G, Papassotiriou I (2004) Maternal--neonatal serum selenium and copper levels in Greeks and Albanians. Eur J Clin Nutr 58(9):1314–1318. https://doi.org/10.1038/sj.ejcn.1601967

    Article  CAS  PubMed  Google Scholar 

  36. Algerwie MH, Khatri PC (1998) Serum copper in newborns and their mothers. Indian J Pediatr 65(6):899–903

    Article  CAS  Google Scholar 

  37. Galinier A, Periquet B, Lambert W, Garcia J, Assouline C, Rolland M, Thouvenot JP (2005) Reference range for micronutrients and nutritional marker proteins in cord blood of neonates appropriated for gestational ages. Early Hum Dev 81(7):583–593. https://doi.org/10.1016/j.earlhumdev.2005.01.007

    Article  CAS  PubMed  Google Scholar 

  38. Tsuzuki S, Morimoto N, Hosokawa S, Matsushita T (2013) Associations of maternal and neonatal serum trace element concentrations with neonatal birth weight. PLoS One 8(9):e75627. https://doi.org/10.1371/journal.pone.0075627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Maia PA, Figueiredo RC, Anastácio AS, Porto da Silveira CL, Donangelo CM (2007) Zinc and copper metabolism in pregnancy and lactation of adolescent women. Nutrition 23(3):248–253. https://doi.org/10.1016/j.nut.2007.01.003

    Article  CAS  PubMed  Google Scholar 

  40. Izquierdo Alvarez S, Castañón SG, Ruata ML, Aragüés EF, Terraz PB, Irazabal YG, González EG, Rodríguez BG (2007) Updating of normal levels of copper, zinc and selenium in serum of pregnant women. J Trace Elem Med Biol 21:49–52. https://doi.org/10.1016/j.jtemb.2007.09.023

    Article  CAS  PubMed  Google Scholar 

  41. O'Brien KO, Zavaleta N, Caulfield LE, Wen J, Abrams SA (2000) Prenatal iron supplements impair zinc absorption in pregnant Peruvian women. J Nutr 130(9):2251–2255

    Article  CAS  Google Scholar 

  42. Hawk SN, Lanoue L, Keen CL, Kwik-Uribe CL, Rucker RB, Uriu-Adams JY (2003) Copper-deficient rat embryos are characterized by low superoxide dismutase activity and elevated superoxide anions. Biol Reprod 68(3):896–903

    Article  CAS  Google Scholar 

  43. Uriu-Adams JY, Keen CL (2005) Copper, oxidative stress, and human health. Mol Asp Med 26(4–5):268–298. https://doi.org/10.1016/j.mam.2005.07.015

    Article  CAS  Google Scholar 

  44. Sultana Z, Maiti K, Aitken J, Morris J, Dedman L, Smith R (2017) Oxidative stress, placental ageing-related pathologies and adverse pregnancy outcomes. Am J Reprod Immunol. https://doi.org/10.1111/aji.12653

    Article  Google Scholar 

  45. Zadrozna M, Gawlik M, Nowak B, Marcinek A, Mrowiec H, Walas S, Wietecha-Posluszny R, Zagrodzki P (2009) Antioxidants activities and concentration of selenium, zinc and copper in preterm and IUGR human placentas. J Trace Elem Med Biol 23(2):144–148. https://doi.org/10.1016/j.jtemb.2009.02.005

    Article  CAS  PubMed  Google Scholar 

  46. Challis JR, Lockwood CJ, Myatt L, Norman JE, Strauss JF 3rd, Petraglia F (2009) Inflammation and pregnancy. Reprod Sci 16(2):206–215. https://doi.org/10.1177/1933719108329095

    Article  CAS  Google Scholar 

  47. Tao XY, Huang K, Yan SQ, Zuo AZ, Tao RW, Cao H, Gu CL, Tao FB (2016) Pre-pregnancy BMI, gestational weight gain and breast-feeding: a cohort study in China. Public Health Nutr:1–8. https://doi.org/10.1017/s1368980016003165

    Article  Google Scholar 

  48. Ziaei S, Janghorban R, Shariatdoust S, Faghihzadeh S (2008) The effects of iron supplementation on serum copper and zinc levels in pregnant women with high-normal hemoglobin. Int J Gynaecol Obstet 100(2):133–135. https://doi.org/10.1016/j.ijgo.2007.07.026

    Article  CAS  PubMed  Google Scholar 

  49. Huang SH, Weng KP, Lin CC, Wang CC, Lee CT, Ger LP, Wu MT (2016) Maternal and umbilical cord blood levels of mercury, manganese, iron, and copper in southern Taiwan: a cross-sectional study. J Chin Med Assoc. https://doi.org/10.1016/j.jcma.2016.06.007

    Article  Google Scholar 

Download references

Acknowledgments

Funding was provided by the National Natural Science Foundation of China (No. 81330068, Beijing, People’s Republic of China) and the National Natural Science Foundation of China (No. 81573168, Beijing, People’s Republic of China).

Author information

Authors and Affiliations

  1. Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China

    Zhijuan Li, Chunmei Liang, Kun Huang, Ruiwen Tao, Xun Xia, Yiran Tao, Haiyun Xiang, Jiahu Hao, Beibei Zhu, Peng Zhu, Shilu Tong & Fangbiao Tao

  2. Anhui Provincial Key Laboratory of Population Health and Aristogenics, Hefei, Anhui, China

    Chunmei Liang, Kun Huang, Jie Sheng, Jiahu Hao, Beibei Zhu, Qunan Wang, Peng Zhu, Shilu Tong & Fangbiao Tao

  3. Ma’anshan Maternal and Child Health (MCH) Center, Ma’anshan, China

    Shuangqin Yan & Weijun Pan

  4. School of Public Health and Social Work and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia

    Shilu Tong

  5. Shanghai Children’s Medical Center, Shanghai Jiao Tong University, Shanghai, China

    Shilu Tong

Authors
  1. Zhijuan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chunmei Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kun Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shuangqin Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ruiwen Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jie Sheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Weijun Pan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xun Xia
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yiran Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Haiyun Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jiahu Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Beibei Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Qunan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Peng Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Shilu Tong
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Fangbiao Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Shilu Tong or Fangbiao Tao.

Ethics declarations

All experimental procedures were approved by the institutional ethics committee of Anhui Medical University.

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Zhijuan Li and Chunmei Liang are the equal first authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, Z., Liang, C., Huang, K. et al. Umbilical Serum Copper Status and Neonatal Birth Outcomes: a Prospective Cohort Study. Biol Trace Elem Res 183, 200–208 (2018). https://doi.org/10.1007/s12011-017-1144-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-017-1144-6

Keywords

Search

Navigation