Skip to main content

Advertisement

SpringerLink
Log in

Association Between Maternal Infections and Preeclampsia: A Systematic Review of Epidemiologic Studies

  • Published:
Maternal and Child Health Journal Aims and scope Submit manuscript

Abstract

Objectives

A growing body of evidence suggests an association between maternal infection and preeclampsia. To examine the strength of this association, we conducted a comprehensive review of studies published in peer-reviewed journals.

Methods

Data collection for this review involved Medline, Embase, and Cochrane data base searches of published studies since 1964 on the relationship between maternal infection and preeclampsia. Data were abstracted according to predefined inclusion and exclusion criteria. Study population included women with preeclampsia and normotensive mothers with and without bacterial or viral infections. Altogether, thirty two original studies were identified and evaluated for methodological quality, preeclampsia diagnosis and adjustment for well-known preeclampsia confounders. Pooled odds ratios and 95% confidence intervals, according to infection status, were calculated using DerSimonian-Laird random-effects models. Publication bias was assessed with a funnel plot and Egger’s regression asymmetry test.

Results

Sixteen of the 32 studies evaluated were selected for inclusion in the meta-analysis. These studies showed that women with either a bacterial or viral infection were at higher risk of developing preeclampsia, compared to women without infection. Combined results for the 16 studies yielded an OR of 2.1 (95% CI 1.6–2.7). Separate pooled estimates for prospective (OR 2.3, 95% CI 1.7–3.0), case control and retrospective studies combined (OR 2.0, 95% CI 1.4–2.9) yielded similar results. Heterogeneity was significant across overall pooled estimates, case control and retrospective studies (Qdf=20 of 45.7, P = .001; Qdf=10 of 38.7, P < .005, respectively), but not prospective studies (Qdf=9 of 6.5 P = .69).

Conclusions

In our analysis, any infection (bacterial or viral) was associated with a two-fold higher risk of preeclampsia. This association may provide a potential explanation for preeclampsia-related inflammation.

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
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. WHO international collaborative study of hypertensive disorders of pregnancy (1988). Geographic variation in the incidence of hypertension in pregnancy. American Journal of Obstetrics and Gynecology, 158, 80–83.

    Google Scholar 

  2. Roberts, J. M., & Redman, C. W. (1993). Preeclampsia: more than pregnancy-induced hypertension. Lancet, 342, 619.

    Google Scholar 

  3. Saftlas, A. F., Olson, D. R., Franks, A. L., Atrash, H. K., & Pokras, R. (1990). Epidemiology of preeclampsia and eclampsia in the United States, 1979–1986. American Journal of Obstetrics and Gynecology, 163(2), 460–465.

    PubMed  CAS  Google Scholar 

  4. Roberts, J. M., Taylor, R. N., Musci, T. J., Rodgers, G. M., Hubel, C. A., & McLaughlin, M. K. (1989). Preeclampsia: an endothelial cell disorder. American Journal of Obstetrics and Gynecology, 161, 1200–1204.

    PubMed  CAS  Google Scholar 

  5. Redman, C. W. G., Sacks, G. P., & Sargent, I. L. (1999). Preeclampsia: An excessive maternal inflammatory response to pregnancy. American Journal of Obstetrics and Gynecology, 180, 499–506.

    Article  PubMed  CAS  Google Scholar 

  6. Sacks, G. P., Studena, K., Sargent, I. L., & Redman, C. W. G. (1998). Normal pregnancy and preeclampsia both produce inflammatory changes in peripheral blood leukocytes akin to those of sepsis. American Journal of Obstetrics and Gynecology, 197, 80–86.

    Article  Google Scholar 

  7. Rinehart, B. K., Terrone, D. A., Lagoo-Deenadayalan, S., Barber, W. H., Hale, E. A., Martin, J. N. Jr, & Benett, W. A. (1999). Expression of the placental cytokines tumor necrosis factor-α, interleukin 1-ß, and interleukin 10 is increased in preeclampsia. American Journal of Obstetrics and Gynecology, 181(4), 915–920.

    Article  PubMed  CAS  Google Scholar 

  8. Visser, W., & Wallenburg, H. C. (1999). Prediction and prevention of pregnancy-induced hypertensive disorders. Baillière’s Best Practice & Research. Clinical Obstetrics & Gynaecology, 13, 131–156.

    Article  CAS  Google Scholar 

  9. Sanchez, S. E., Zhang, C., Williams, M. A., Ware-Jauregui, S., Larrabare, G., Bazul, V., & Farrand, A. (2000). Tumor necrosis factor-α soluble p55(sTNFp55) and risk of preeclampsia in Peruvian women. Journal of Reproductive Immunology, 47, 49–63.

    Article  PubMed  CAS  Google Scholar 

  10. Amory, J. H., Hitti, J., Lawler, R., & Eschenbach, D. A. (2001). Increased tumor necrosis factor-α production after lipopolysaccharide stimulation of whole blood in patients with previous preterm delivery complicated by intraamniotic infection or inflammation. American Journal of Obstetrics and Gynecology, 185, 1064–1067.

    Article  PubMed  CAS  Google Scholar 

  11. Benyo, D. F., Smarason, A., Redman, C. W. G., Sims, C., & Conrad, K. P. (2001). Expression of inflammatory cytokines in placentas from women with preeclampsia. The Journal of clinical endocrinology and metabolism, 86, 2505–2512.

    Article  PubMed  CAS  Google Scholar 

  12. Luppi, P., Haluszczak, C., Betters, D., Richard, C. A. H., Trucco, M., & DeLoia, J. A. (2002). Monocytes are progressively activated in the circulation of pregnant women. The Journal of clinical endocrinology and metabolism, 72, 874–884.

    CAS  Google Scholar 

  13. Paternoster, D. M., Fantinato, S., Stella, A., Nanhorngue, K. N., Milani, M., Plebani, M., Nicolini, U., & Girolami, A. (2006). C-reactive protein in hypertensive disorders in pregnancy. Clinical & Applies Thrombosis/Hemostasis, 12, 330–337.

    Article  CAS  Google Scholar 

  14. Gordis, L. (1996). Meta-analysis. In: L. McGrew (Ed.), Epidemiology. (p. 253). Philadelphia: WB Saunders Company.

    Google Scholar 

  15. Stroup, D. F., Berlin, J. A., Morton, S. C., & et al. (2000). Meta-analysis of observational studies in epidemiology: A proposal for reporting – Meta-analysis of Observational Studies in Epidemiology (MOOSE) Group. JAMA, 283, 2008–2012.

    Article  PubMed  CAS  Google Scholar 

  16. Trogstad, L. I., Eskild, A., Bruu, A. L., Jeansson, S., & Jenum, P. A. (2001). Is preeclampsia an infectious disease? Acta Obstetricia et Gynecologica , 80, 1036–1038.

    Article  CAS  Google Scholar 

  17. Jüni, P., Witschi, A., Bloch, R., & Matthias, E. (1999). The hazards of scoring the quality of clinical trials for meta-analysis. JAMA, 282, 1054–1060.

    Article  PubMed  Google Scholar 

  18. Greenland, S., & O’Rourke, K. (2001). On the bias produced by quality scores in meta-analysis, and a hierarchical review of proposed solutions. Biostatistics, 2, 463–471.

    Article  PubMed  CAS  Google Scholar 

  19. Whiting, P., Harbord, R., & Kleijnen, J. (2005). No role for quality scores in systematic reviews of diagnostic accuracy studies. BMC Medical Research Methodology, 5, 19.

    Article  PubMed  Google Scholar 

  20. Laird, N. M., & Mosteller, F. (1990). Some statistical methods for combining experimental results. International Journal of Technology Assessment in Health Care, 6, 5–30.

    PubMed  CAS  Google Scholar 

  21. DerSimonian, R., & Laird, N. (1986). Meta-analysis in clinical trials. Controlled Clinical Trials, 7, 177–188.

    Article  PubMed  CAS  Google Scholar 

  22. Higgins, J. P. T., & Thompson, S. G. (2002). Quantifying heterogeneity in a meta-analysis. Statistics in Medicine, 21, 1539–1558.

    Article  PubMed  Google Scholar 

  23. Berkey, C. S., Hoaglin, D. C., Mosteller, F., & Colditz, G. A. (1995). A random-effects regression model for meta-analysis. Statistics in Medicine, 14, 395–411.

    Article  PubMed  CAS  Google Scholar 

  24. Sterne J. A. C., & Egger, M. (2001). Funnel plots for detecting bias in meta-analysis: Guidelines on choice of axis. Journal of Clinical Epidemiology, 54, 1046–1055.

    Article  PubMed  CAS  Google Scholar 

  25. Egger, M., Smith, G. D., & Phillips, A. N. (1997). Meta-analysis: principles and procedures. BMJ, 315, 1533–1537.

    PubMed  CAS  Google Scholar 

  26. Stata\({\texttrademark}\) 9.2 Stata Corporation, 4905 Lakeway Drive, College Station, Texas 77845 USA.

  27. Stuart, K. L., Cummins, G. T. M., & Chin, W. A. (1965). Bacteriuria, prematurity, and the hypertensive disorders of pregnancy. British Medical Journal, 5434, 554–556.

    Google Scholar 

  28. Kincaid-Smith, P., & Bullen, M. (1965). Bacteriuria in pregnancy. Lancet, 191, 7382–7399.

    Google Scholar 

  29. Tarjan, G. (1967). Frequency of bacteriuria in women with late toxemias of pregnancy. Zentralblatt für Gynäkologie, 89, 646–646 (Article in German).

    Google Scholar 

  30. Wimalasundera, R. C., Larbalestier, N., Smith, J. H., de Ruiter A., McG Thom, S. A., Hughes, A. D., Poulter, N., Regan, L., & Taylor, G. P. (2002). Preeclampsia, antiretroviral therapy, and immune reconstitution. Lancet, 360, 1152–1154.

  31. Castaldi, J. L., Bertin, M. S., Gimenez, F., & Lede, R. (2006). Periodontal disease: is it a risk factor for premature labor, low birth weight or preeclampsia? Rev Panam Salud Publica, 19, 253–258 (Article in Spanish).

    Article  PubMed  Google Scholar 

  32. Sartelet, H., Rogier, C., Milko, S.I., Angel, G., & Michel, G. (1996). Malaria associated preeclampsia in Senegal. Lancet, 347, 1121.

    Article  PubMed  CAS  Google Scholar 

  33. Teran, E., & Escudero, C. (2003). Seroprevalence of antibodies to Chlamydia pneumoniae in women with preeclampsia. Obstetrics and Gynecology, 102, 198–199.

    Article  PubMed  Google Scholar 

  34. Mattar, R., Amed, A. M., Lindsey, P. C., Sass, N., & Daher, S. (2004). Preeclampsia and HIV infection. Obstetrics and Gynecology, 117, 240–241.

    Google Scholar 

  35. Oettinger-Barak, O., barak Shlomi, Ohel, G., Oettinger, M., Kreutzer, H., Peled, M., & machtei, E. E. (2005). Severe pregnancy complication (preeclampsia) is associated with greater periodontal destruction. Journal of Periodontology, 76, 134–137.

    Article  PubMed  Google Scholar 

  36. Aral, M., Guven, M. A., & Kocturk, S. A. (2005). Chlamydia pneumoniae seropositivity in women with preeclampsia. International Journal of Gynaecology and Obstetrics, 92, 77–78.

    Article  PubMed  Google Scholar 

  37. Belfort, M., Cortes, J., Bowles, N., Saade, G., Dorman, K., Abadajos, P., & Towbin J. (1998). Placental Cytomegalovirus infection and preeclampsia: Are they related? Journal of the Society for Gynecologic Investigation, 5, 136A–T403.

    Article  Google Scholar 

  38. Rustveld, L., Ness, R., Costantino, J., & Roberts, J. (2003). Serological association between primary infections with Herpes Simplex Virus Types 1 and 2 (HSV-1 and HSV-2), Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) and the risk of preeclampsia. American Journal of Epidemiology, 157(suppl), 296-S.

    Google Scholar 

  39. Blaauw, J., Kunnen, A., Van Pampus, M. G., Van Doormaal, J. J., Van Winkelhoff, A. J., Abbas, F., & Aarnoudse, J. G. (2005). Periodontal disease in recently preeclamptic women. American Journal of Obstetrics and Gynecology, 193, S69.

    Google Scholar 

  40. Chang, E., Armstrong, M. D., Ebeling, M., Hulsey, T., & Newman R. (2006). Urinary tract infections are associated with an increased risk of preeclampsia. American Journal of Obstetrics and Gynecology, 193(suppl), S71–214.

    Google Scholar 

  41. Herrera, J. A., Chaudhuri, G., & Lopez-Jaramillo, P. (2001). Is infection a major risk factor for preeclampsia. Medical Hypotheses, 57, 393–397.

    Article  PubMed  CAS  Google Scholar 

  42. Riche, E. L., Boggess, K. A., Lieff, S., Murtha, A. P., Beck, J. D., & Offenbacher, S. (2002). Periodontal disease increases the risk of preterm delivery among preeclamptic women. Annals of Periodontology, 7, 95–101.

    Article  PubMed  Google Scholar 

  43. Bogess, K. A., Lieff, S., Murtha, A., Moss, K., Beck, J., & Offenbacher, S. (2003). Maternal periodontal disease is associated with an increased risk for preeclampsia. Obstetrics and Gynecology, 101, 227–231.

    Article  Google Scholar 

  44. Contreras, A., Herrera, J. A., Soto, J. E., Arce, R. M., Jaramillo, A., & Botero, J. E. (2006). Periodontitis is associated with preeclampsia in pregnant women. Journal of Periodontology, 77, 182–188.

    Article  PubMed  CAS  Google Scholar 

  45. Frank, K. A., Buchmann, E. J., & Schackis, R. C. (2004). Does Human Immunodeficiency Virus infection protect against preeclampsia-eclampsia? Obstet Gynecol, 104, 238–242.

    PubMed  CAS  Google Scholar 

  46. Suy, A., Martinez, E., Coll, O., Lonca, M., Palacio, M., de Lazzari, E., Larrousse, M., Milinkovic, A., Hernandez, S., Blanco, J. L., Mallolas, J., Leon, A., Vanrell, J. A., & Gatell, J. M. (2006). Increased risk of preeclampsia and fetal death in HIV-infected pregnant women receiving highly active antiretroviral therapy. AIDS, 20, 59–66.

    Article  PubMed  Google Scholar 

  47. Wimalasundera, R. C., Larbalestier, N., Smith, J. H., de Ruiter A., Thom, SA. MCG., Hughes, A .D., Poulter N., Regan L., & Taylor, G. P. (2002). Preeclampsia, antiretroviral therapy, and immune reconstitution. Lancet, 360, 1152–1154.

    Article  PubMed  CAS  Google Scholar 

  48. American College of Obstetrics and Gynecologist (ACOG) (2002) Hypertension in pregnancy. ACOG Educational Bulletin 33.

  49. Hsu, C. D., & Witter, F. R. (1995). Urogenital infection in preeclampsia. Journal of Obstetrics and Gynaecology, 49, 271–275.

    CAS  Google Scholar 

  50. Mittendorf, R., Lain, K. Y., Williams, M. A., & Walker, C. K. (1996). Preeclampsia: A nested, case control study for risk factors and their interactions. The Journal of Reproductive Medicine, 41, 491–496.

    PubMed  CAS  Google Scholar 

  51. Heine, R. P., Ness, R. B., & Roberts, J. M. (2003). Seroprevalence of antibodies to Chlamydia pneumoniae in women with preeclampsia. Obstetrics and Gynecology, 101, 221–226.

    Article  PubMed  Google Scholar 

  52. Canakci, V., Canakci, C. F., Canakci, H., Canakci, E., Cicek, Y., Ingec, M., Ozgoz, M., Demir, T., Dilsiz, A., Yagiz, H. (2004). Periodontal disease as a risk factor for preeclampsia: A case contol study. Australian and New Zealand Journal of Obstetrics and Gynaecology, 44, 568–573.

    Google Scholar 

  53. Von Dadelszen, P., & Magee, L. A. (2002). Could an infectious tiger explain the differential maternal response to the shared placental pathology of preeclampsia and normotensive intrauterine growth restriction? Acta Obstetricia et Gynecologica Scandinavica, 81, 642–648.

    Article  PubMed  Google Scholar 

  54. Raynor, D. B., Bonney, E. A., Jang, K. T., Coto, W., & Garcia, M. S. (2004). Preeclampsia and Chlamydia pneumoniae: Is there a link? Hypertension in Pregnancy, 23, 129–133.

    Article  PubMed  CAS  Google Scholar 

  55. Todros, T., Verdiglione, P., Ogge, G., Paladini, D., Vergani, P., Cardaropoli, S. (2006). Low incidence of hypertensive disorders of pregnancy in women treated with spiramycin for toxoplasma infection. British Journal of Clinical Pharmacology, 61(3), 336–340.

    Article  PubMed  CAS  Google Scholar 

  56. Arechavaleta-Velasco, F., Ma, Y., Zhang, J., McGrath, C. M., & Parry, S. (2006). Adeno-Associated Virus-2 (AAV-2) causes trophoblast dysfunction, and placental AAV-2 infection is associated with preeclampsia. The American Journal of Pathology , 168, 1951–1959.

    Article  PubMed  CAS  Google Scholar 

  57. Gilbert, G. L., Garland, S. M., Fairley, K. F., & McDowall, D. M. (1986). Bacteriuria due to ureaplasmas and other fastidious organisms during pregnancy: prevalence and significance. Pediatric Infectious Disease, 5(6Suppl), S239–243.

    PubMed  CAS  Google Scholar 

  58. Hill, J. A., Devoe, L. D., & Bryans, C. I. Jr (1986). Frequency of asymptomatic bacteriuria in preeclampsia. Obstetrics and Gynecology, 67, 529–532.

    PubMed  CAS  Google Scholar 

  59. Carreiras, M., Montagnani, S., & Layrisse, Z. (2002). Preeclampsia: A multifactorial disease resulting from the interaction of the feto-maternal HLA genotype and HCMV infection. AJRI, 48, 176–183.

    PubMed  CAS  Google Scholar 

  60. Goulis, D. G., Chappell, L., Gibbs, R. G. J., Williams, D., Dave, J. R., Taylor, P., de Swiet, M., Poston, L., & Williamson, C. (2005). Association of raised titres of antibodies to Chlamydia pneumoniae with a history of pre-eclampsia. BJOG : An International Journal of Obstetrics and Gynaecology, 112, 299–305.

    Article  Google Scholar 

  61. Dowell, S. F., Peeling, R. W., Boman, J., Carlone, G. M., Fields, B. S., Guarner, J., Hammerschlag, M. R., Jackson, L. A., Kuo, C. C., Maass M., Messmer T. O., Talkington D. F., Tondella M. L., & Zaki S. R. (2001). Standardizing Chlamydia pneumoniae Assays: Recommendations from the Centers for Disease Control and Prevention (USA) and the Laboratory Centre for Disease Control (Canada). Clinical Infectious Diseases, 33, 492–503.

    Article  PubMed  CAS  Google Scholar 

  62. Dickersin, K. (1990). The existence of publication bias and risk factors for its occurrence. JAMA, 263, 1385–1389.

    Article  PubMed  CAS  Google Scholar 

  63. Hubel, C. A. (1999). Oxidative stress in the pathogenesis of preeclampsia. Proceedings of the Society for Experimental Biology and Medicine, 222, 222–234.

    Article  PubMed  CAS  Google Scholar 

  64. Kalayoglu, M. V., & Byrne, G. I. (1998). Induction of macrophage foam cell formation by Chlamydia pneumoniae. The Journal of Infectious Diseases , 177, 725–729.

    PubMed  CAS  Google Scholar 

  65. Ross, R. (1999). Atherosclerosis: an inflammatory disease. The New England Journal of Medicine, 340, 115–226.

    Article  PubMed  CAS  Google Scholar 

  66. Brown, M., & Goldstein, J. (1983). Lipoprotein metabolism in the macrophage. Annual Review of Biochemistry, 52, 223–261.

    Article  PubMed  CAS  Google Scholar 

  67. Lindberg, G., Rastam, L., Lundblad, A., & et al. (1997). ARIC Study Investigators. The association between serum sialic acid and asymptomatic carotic atherosclerosis is not related to antibodies to Herpes type viruses of Chlamydia pneumoniae. International Journal of Epidemiology, 26, 1386–1391.

    Article  PubMed  CAS  Google Scholar 

  68. Sibai, B., Dekker, G., & Kupferminc, M. (2005). Preeclampsia. Lancet, 365, 785–799.

    PubMed  Google Scholar 

  69. Sacks, G., Sargent, I., & Redman, C. W. G. (1999). An innate view of human pregnancy. Immunology Today, 20, 114–118.

    Article  PubMed  CAS  Google Scholar 

  70. Genco, R., Offenbacher, S., & Beck, J. (2002). Periodontal disease and cardiovascular disease: Epidemiology and possible mechanisms. JADA, 133, 14S–22S.

    PubMed  Google Scholar 

  71. Mattila, K. J., Nieminen, M. S., & Valtonen, V. V. (1989). Association between dental health and acute myocardial infarction. BMJ, 298, 779–781.

    Article  PubMed  CAS  Google Scholar 

  72. Marcus, A. J., & Hajjar, D. P. (1993). Vascular transcellular signaling. Journal of Lipid Research, 34, 2017–2031.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Family and Community Medicine, Baylor College of Medicine, 3701 Kirby Drive, Suite 600, Houston, TX, 77098-3926, USA

    Luis O. Rustveld

  2. Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, A525, Pittsburgh, PA, 15261, USA

    Sheryl F. Kelsey

  3. Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA

    Ravi Sharma

Authors
  1. Luis O. Rustveld
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sheryl F. Kelsey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ravi Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luis O. Rustveld.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rustveld, L.O., Kelsey, S.F. & Sharma, R. Association Between Maternal Infections and Preeclampsia: A Systematic Review of Epidemiologic Studies. Matern Child Health J 12, 223–242 (2008). https://doi.org/10.1007/s10995-007-0224-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10995-007-0224-1

Keywords

Search

Navigation