Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Congenital heart defects and maternal fever: systematic review and meta-analysis

Journal of Perinatology volume 34, pages 677–682 (2014)Cite this article

Subjects

Abstract

OBJECTIVE:

To systematically review and meta-analyze the relation between maternal fever in the first trimester and congenital heart defect (CHD) in offspring.

STUDY DESIGN:

We searched PubMed (1977–2012), Embase (1974–2012) and the Cochrane Library (2012) databases to identify relevant articles. Random effects model were performed, with the conduction of subgroup analysis.

RESULT:

Meta-analysis yielded a pooled odds ratio of 1.53 (95% confidence interval=1.36 to 1.73) for the magnitude of the relation between maternal fever in the first trimester and CHD in offspring. As to subgroup analysis, it is associated with ventricular septal defects (VSDs) and right obstructive defects.

CONCLUSION:

Our analysis suggests that maternal fever in the first trimester is the risk factor of congenital heart diseases in offspring. Through the subgroup analysis, we find that exposure to maternal fever is the risk factor of VSD and right obstructive defects.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Rosamond W, Flegal K, Friday G, Furia K, Go A, Greenlund K et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee Heart disease and stroke statistics-2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2007; 115 (5) 169–171.

    Article  Google Scholar 

  2. Zhang YL, Riehle-Colarusso T, Correa A, Li S, Feng X, Gindler J et al. Observed prevalence of congenital heart defects from a surveillance study in china. J Ultrasound Med 2011; 30 (7): 989–995.

    Article  Google Scholar 

  3. Tikkanen J, Heinonen OP . Risk factors for cardiovascular malformations in Finland. Eur J Epidemiol 1990; 6 (4): 348–356.

    Article  CAS  Google Scholar 

  4. Shaw GM, Malcoe LH, Swan SH, Cummins SK, Schulman J . Congenital cardiac anomalies relative to selected maternal exposures and conditions during early pregnancy. Eur J Epidemiol 1992; 8 (5): 757–760.

    Article  CAS  Google Scholar 

  5. Frohn-Mulder IM, Meilof JF, Szatmari A, Stewart PA, Swaak TJ, Hess J . Clinical significance of maternal Anti-Ro/SS-A antibodies in children with isolated heart block. J Am College Cardiol 1994; 23 (7): 1677–1681.

    Article  CAS  Google Scholar 

  6. Jenkins KJ, Correa A, Feinstein JA, Botto L, Britt AE, Daniels SR et al. Non-inherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation 2007; 115 (23): 2995–3014.

    Article  Google Scholar 

  7. Nora JJ, Nora AH . The evolution of specific genetic and environmental counseling in congenital heart diseases. Circulation 1987; 57 (2): 205–213.

    Article  Google Scholar 

  8. Moretti ME, Bar-Oz B, Fried S, Koren G . Maternal hyperthermia and the risk for neural tube defects in offspring: systematic review and meta-analysis. Epidemiol 2005; 16 (2): 216–229.

    Article  Google Scholar 

  9. Edwards MJ . Review: hyperthermia and fever during pregnancy. Birth Defects Res A Clin Mol Teratol 2006; 76 (7): 507–516.

    Article  CAS  Google Scholar 

  10. Shahrukh Hashmi S, Gallaway MS, Waller DK, Langlois PH, Hecht JT . Maternal fever during early pregnancy and the risk of oral clefts. Birth Defects Res A Clin Mol Teratol 2010; 88 (3): 186–194.

    CAS  PubMed  Google Scholar 

  11. Botto LD, Lynberg MC, Erickson JD . Congenital heart defects, maternal febrile illness, and multivitamin use: a population-based study. Epidemiol 2001; 12 (5): 485–490.

    Article  CAS  Google Scholar 

  12. Oster ME, Riehle-Colarusso Tiffany, Alverson CJ, Correa A . Associations between maternal fever and influenza and congenital heart defects. J Pediatr 2011; 158 (6): 990–995.

    Article  Google Scholar 

  13. Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses http://www.lri.ca 2000.

  14. Adams MM, Mulinare J, Dooley K . Risk factors for conotruncal cardiac defects in Atlanta. J Am Coll Cardiol 1989; 14 (2): 432–442.

    Article  CAS  Google Scholar 

  15. Tikkanen J, Heinonen OP . Maternal hyperthermia during pregnancy and cardiovascular malformations in the offspring. Eur J Epidemiol 1991; 7 (6): 628–635.

    Article  CAS  Google Scholar 

  16. Zhang J, Cai WW . Association of the common cold in the first trimester of pregnancy with birth defects. Pediatrics 1993; 92 (4): 559–563.

    CAS  PubMed  Google Scholar 

  17. Acs N, Banhidy F, Puho E, Czeizel AE . Maternal influenza during pregnancy and risk of congenital abnormalities in offspring. Birth Defects Res A Clin Mol Teratol 2005; 73 (12): 989–996.

    Article  CAS  Google Scholar 

  18. Cleves MA, Malik S, Yang S, Carter TC, Hobbs CA . Maternal urinary tract infections and selected cardiovascular malformations. Birth Defects Res A Clin Mol Teratol 2008; 82 (6): 464–473.

    Article  CAS  Google Scholar 

  19. Lynberg MC, Khoury MJ, Lu X, Cocian T . Maternal flu, fever, and the risk of neural tube defects: A population based case-control study. Am J Epidemiol 1994; 140 (3): 244–255.

    Article  CAS  Google Scholar 

  20. Miyake T, Shinohara T, Inoue T, Marutani S, Takemura T . Spontaneous closure of muscular trabecular ventricular septal defect: comparison of defect position. Acta Paediatr 2011; 100 (10): e158–e162.

    Article  Google Scholar 

  21. Edwards MJ . Hyperthermia as a teratogen: a review of experimental studies and their clinical significance. Teratogenesis Carcinog Mutagen 1986; 6 (6): 563–582.

    Article  CAS  Google Scholar 

  22. Mirkes PE, Cornel LM, Park HW, Cunningham ML . Induction of thermotolerance in early postimplantation rat embryos is associated with increased resistance to hyperthermia-induced apoptosis. Teratol 1997; 56 (3): 210–219.

    Article  CAS  Google Scholar 

  23. Edwards MJ . Apoptosis, the heat shock response, hyperthermia, birth defects, disease and cancer: where are the common links? Cell Stress Chaperones 1998; 3 (4): 213–220.

    Article  CAS  Google Scholar 

  24. Roulston A, Marcellus RC, Branton PE . Viruses and apoptosis. Annu Rev Microbiol 1999; 53: 577–628.

    Article  CAS  Google Scholar 

  25. Nilsen NO . Vascular abnormalities due to hyperthermia in chick embryos. Teratol 1984; 30 (2): 237–251.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the grants from National Natural Science Foundation of China (No. 21003077), the Open Project of Key Laboratory of Advanced Energy Materials Chemistry (No. KLAEMC-OP201101)

Author Contributions

YL Zhang, QY Shi and JB Zhang were involved in the conceptualization, research design, execution and write-up of the first draft of the manuscript. YQ Mi, Y Song and J Ma advised on the design of the study, and the analysis and interpretation of the results. All authors were involved in the preparation of the manuscript.

Author information

Author notes

  1. Q Y Shi and J B Zhang: These authors contributed equally to this work.

  2. J Ma and Y L Zhang: These authors contributed equally to this work.

Authors and Affiliations

  1. Tianjin Second People’s Hospital, School of Graduate, Tianjin Medical University, Tianjin, China

    Q Y Shi

  2. Tianjin Teda International Cardiovascular Disease Hospital, Clinical College of Cardiovascular, Tianjin Medical University, Tianjin, China

    J B Zhang

  3. Depanment of Chinese Integrative Medicine, Tianjin Second People’s Hospital, Tianjin Medical University, Tianjin, China

    Y Q Mi

  4. Coronary Care Unit, Tianjin Teda International Cardiovascular Disease Hospital, Clinical College of Cardiovascular, Tianjin Medical University, Tianjin, China

    Y Song

  5. Department of Health Statistics, College of Public Health, Tianjin Medical University, Tianjin, China

    J Ma

  6. Institute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health, School of Public Health, Peking University Health Science Center, Beijing, China

    Y L Zhang

  7. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China

    Y L Zhang

Authors
  1. Q Y Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J B Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Y Q Mi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Y L Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to J Ma or Y L Zhang.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Journal of Perinatology website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shi, Q., Zhang, J., Mi, Y. et al. Congenital heart defects and maternal fever: systematic review and meta-analysis. J Perinatol 34, 677–682 (2014). https://doi.org/10.1038/jp.2014.76

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jp.2014.76

Search

Advanced search

Quick links