Obstetrics & Gynecology Track the topics, authors and articles important to you
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Obstetrics & Gynecology 2005;106:73-80
© 2005 by The American College of Obstetricians and Gynecologists
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Karinen, L.
Right arrow Articles by Hartikainen, A.-L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Karinen, L.
Right arrow Articles by Hartikainen, A.-L.
Related Collections
Right arrow Immunology
Right arrow Infectious disease
Right arrow Obstetric complications of pregnancy

ORIGINAL RESEARCH

Serum C-reactive Protein and Chlamydia trachomatis Antibodies in Preterm Delivery

Liisa Karinen, MD, Anneli Pouta, MD, PhD, Aini Bloigu, BSc, Pentti Koskela, PhD, Mika Paldanius, MNSc, Maija Leinonen, PhD, Pekka Saikku, MD, PhD, Marjo-Riitta Jêrvelin, MD, PhD and Anna-Liisa Hartikainen, MD, PhD

From the Department of Obstetrics and Gynecology, University Hospital of Oulu, Oulu, Finland; Department of Public Health Science and General Practice, University of Oulu, Oulu, Finland; National Public Health Institute, Oulu, Finland; Department of Medical Microbiology, University of Oulu, Oulu, Finland; and Department of Epidemiology and Public Health, Imperial College of London, London, United Kingdom.

Address reprint requests to: Address correspondence to: Liisa Karinen, Department of Obstetrics and Gynecology, University Hospital of Oulu, PO Box 24, FIN-90029 OYS, Finland; e-mail: Liisa.Karinen{at}oulu.fi.


   ABSTRACT
TOP
ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
OBJECTIVE: To assess the association between Chlamydia trachomatis antibodies, antibodies to C trachomatis heat shock proteins 60 and 10, and C-reactive protein (CRP) levels in maternal serum measured by highly sensitive CRP assay during the first trimester and spontaneous preterm delivery before 37 weeks of gestation.

Methods: This was a nested case–control study of 104 spontaneous preterm singleton deliveries (cases) and 402 term singleton deliveries, as controls, of mothers belonging to the population-based Northern Finland 1966 Birth Cohort. Data on 2,309 first deliveries were available from the Finnish Medical Birth Register. Serum C trachomatis and C pneumoniae antibodies were measured by the microimmunofluorescence test and chlamydial heat shock proteins 60 and 10 antibodies by enzyme immunoassay using recombinant proteins as antigens, and highly sensitive CRP levels were quantified with highly sensitive immunoenzymometric assay.

Results: Highly sensitive CRP levels were higher and C trachomatis immunoglobulin G levels (pools and individual serotypes) were more often present (thought not nominally significantly in all cases) in the women with preterm compared with term deliveries. Elevated immunoglobulin G levels of C trachomatis antibodies or elevated highly sensitive CRP levels alone, however, did not increase the estimated risk for preterm delivery, but when they were present simultaneously, the estimated risk for preterm delivery was 4-fold (odds ratio 4.3, 95% confidence interval 2.0–9.3). Among the women delivered at or before 34 weeks of gestation, the estimated risk was even more evident (odds ratio 5.6, 95% confidence interval 2.1–14.5). The preterm delivery rate was 26.5% for those with C trachomatis antibodies and 18.8% for those without C trachomatis antibodies.

Conclusion: The results of the present study suggest that chlamydial infection in the first trimester is associated with preterm delivery.

Level of Evidence: II-2

Preterm birth is one of the most important problems in modern obstetrics and the leading cause of neonatal mortality and morbidity. Approximately 5–10% of all births are premature, and the frequency has not decreased over the past 20–30 years.1,2 In 2003, the rate of preterm deliveries including stillbirths (22–37 weeks of gestation) was 5.7% in Finland.3 Approximately 30–40% of preterm deliveries are thought to be due to different infections. Chlamydia trachomatis infections in women are mostly asymptomatic, and the reported prevalence of C trachomatis infection during pregnancy ranges from 2% to 21%.2,4 In pregnant women, acute C trachomatis infection is associated with premature rupture of membranes, chorioamnionitis, premature delivery, and puerperal and neonatal infections, but the evidence is still mainly indirect.

It has been hypothesized that inflammation of decidual tissue or chorioamnion leads to prostaglandin production, cervical ripening, and subsequent uterine contractions.7 It is not known exactly when this inflammatory process begins, or how long a latency period is required for symptoms to manifest. A preexisting subclinical intrauterine inflammatory process in early gestation has been proposed as a possible condition leading to preterm delivery.8,9 We investigated the association between C trachomatis and C pneumoniae antibodies, chlamydial heat shock proteins 60 and 10 antibodies, and highly sensitive C-reactive protein levels in maternal serum obtained during the first trimester as markers of low-grade systemic chronic inflammation and spontaneous preterm delivery before 37 gestational weeks.


   MATERIALS AND METHODS
TOP
ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
The nested case-control study population was derived from the Northern Finland 1966 Birth Cohort followed up since the sixth month of their mother’s pregnancy until the offspring’s age of 31 years. In 1966, 5,964 females were born, 5,889 of them alive. In 1997–1998, 5,608 of them were alive and traced for the 31-year follow-up study, and a postal questionnaire was sent to all these women. Women still living in the original target or capital city area (n = 4,074) were invited for a clinical examination. Of these, 3,077 women gave a blood sample and written consent and filled in the postal questionnaire on socioeconomic position, smoking, and reproductive history.

Of the female cohort, 2,309 women with a history of at least 1 delivery and data on their first pregnancy (obtained from the Finnish Medical Birth Register) were eligible for the present study and gave written consent. This register covers all deliveries in Finland from 1987 onward, including prospective information on pregnancies.

Gestational age was determined by menstrual history and confirmed by second trimester ultrasonographic measurement for 75% of the participants. Multifetal pregnancies were excluded. Data on previous spontaneous abortions, previous induced abortions, and serious bleeding during the pregnancy were collected from the Hospital Discharge Register. The final cohort of cases consisted of 104 women with spontaneous preterm singleton (< 37 gestational weeks) deliveries and first-trimester serum samples. A 4-fold number of age- and parity-matched controls were randomly selected from the same female cohort (n = 402, term singleton delivery at or after 37 completed weeks of gestation, Fig. 1). A prestudy calculation indicated that if 20% occurrence of C trachomatis antibodies in the general female population is assumed, this study has 85% power to find a 15% difference between the cases and the controls at a 5% significance level.



View larger version (30K):
[in this window]
[in a new window]
  		Fig. 1. Flow chart for nested case–control study on the first singleton deliveries in the Northern Finland 1966 birth cohort. Karinen. CRP, Chlamydial Antibodies, and Preterm Birth. Obstet Gynecol 2005.

 

The first-trimester (mean 10.4 gestational weeks) serum samples for the enrolled women were obtained from the serum bank of the Finnish Maternity Cohort in the National Public Health Institute and were available for 98.5% of the study population. Such samples have been collected and stored (at –25°C) from all (98.5%) pregnant women in Finland since 1983.

C trachomatis-specific immunoglobulins G (IgG), A (IgA), and M (IgM) antibodies were first screened by the microimmunofluorescence test10 using the serovar pools GFK (intermediate complex), BED (B complex), and CJHI (C complex) obtained from the University of Washington (Seattle, WA) as antigen, and the positive findings were further analyzed using the serotype-specific antigens B, E, D, G, F, K, C, J, H, and I (University of Washington).11 Sera were tested in serial 2-fold dilutions from 1:8 to the end point. Chlamydia pneumoniae-specific IgG, IgA, and IgM antibodies were measured by an in-house microimmunofluorescence test10 using the purified elementary bodies (EB) of the Finnish strain Kajaani 6 as antigen12 and fluorescein-conjugated anti-human IgG, IgA, and IgM (Dako, Glostrup, Denmark) as conjugates.13 Purified recombinant chlamydial heat shock proteins 60 and 10 were kindly provided by Dr. G. I. Byrne for antigens.14,15 Immunoglobulin G and IgA antibodies to chlamydial heat shock proteins 60 and 10 were measured by our in-house enzyme immunoassay (EIA) method,13 and the results were expressed as EIA units (optical density x serum dilution). The highly sensitive CRP levels were determined by Immunoenzymometric Assay test (Medix Biochemical, Kauniainen, Finland).16 The enzymatic reaction was proportional to the amount of CRP in the sample. The sensitivity of the test was 0.08 mg/L.

Student t tests were used to compare age and body mass index between the study groups. Variables representing chlamydial heat shock proteins 60 and 10 antibody levels and highly sensitive CRP concentration were skewed, and the nonparametric Mann-Whitney U test was therefore used to compare the variables. Categorical variables were compared by {chi}2 test or Fisher exact test as appropriate. The Spearman correlation coefficient was used for an analysis of correlations. When the joint effect of C trachomatis IgG antibodies and highly sensitive CRP levels was studied, a new categorical variable was constructed to represent the different combinations of the original variables. To estimate the relative risk of preterm delivery associated with these combinations, odds ratios with 95% confidence intervals were calculated using logistic regression analysis. Informed consent was obtained from all participants. The study was approved by the Ethics Committee of the University of Oulu and by the Finnish Maternity Cohort steering group.


   RESULTS
TOP
ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
In our study, the mean gestational age of preterm births was 34.4 weeks (range 26–36 weeks). Among the cases, 89 (85.6%) women delivered after the 32nd week of gestation and 62 (59.6%) after the 34th week of gestation. There were 8 very preterm or extremely preterm births: 5 women (4.8%) delivered at 29–31 weeks of gestation (very preterm birth) and 3 women (2.9%) before the 28th week of gestation (extremely preterm birth). Maternal age, previous induced abortions, previous spontaneous abortions, serious bleeding during the pregnancy, and history of smoking did not differ significantly between the cases and controls. There were more blue-collar employees but fewer workers among the women with preterm deliveries compared with the controls (Table 1).


View this table:
[in this window]
[in a new window]
  		Table 1. Background Characteristics of the Women Delivered Before (Cases) and at or After (Controls) the 37th Gestational Week

 

The highly sensitive CRP levels (mg/L) in the sera collected in early pregnancy were significantly higher in the women delivered preterm than in those delivered at term (median 2.7 [interquartile range 1.1–5.8] compared with 2.0 [0.7–4.1], P = .007). The percentage of subjects at or above the upper quartile (4.3 mg/L) was also higher among the cases than the controls, (34.6% compared with 22.4%, P = .010) (Table 2).


View this table:
[in this window]
[in a new window]
  		Table 2. Percentage of Subjects Above the Upper Quartile of Highly Sensitive C-Reactive Protein Concentrations and Frequencies of Chlamydia trachomatis Immunoglobulin G Antibody Against Serovar Pools Measured by Microimmunofluorescence in Women Delivered Before (Cases) and at or After (Controls) the 37th Gestational Week

 

Immunoglobulin G antibodies to C trachomatis serovar pools and individual serotypes were more often present in the first trimester in the women with preterm delivery compared with those delivered at term (any pool positive 28.8% compared with 20.6%, P = .074), the difference being nominally significant only for serotype I (Table 2). Immunoglobulin A antibodies to C trachomatis were equally often (4%) detected in the maternal sera in both groups. Immunoglobulin M antibodies to C trachomatis were not detected in any of the sera. Serum IgA and IgG antibody levels against chlamydial heat shock proteins 60 and 10 were lower in the maternal first trimester sera among the women with preterm delivery than in those delivered at term, but the difference was not statistically significant.

The possible joint effect between the presence of C trachomatis antibodies (IgG titer ≥ 8) and elevated highly sensitive CRP (≥ 4.3, upper quartile) on the risk of preterm delivery was analyzed (Table 3). The risk was regarded as 1.0 when no antibodies were present and highly sensitive CRP was less than 4.3. The presence of C trachomatis antibodies alone without elevated highly sensitive CRP did not increase the estimated risk at all (odds ratio [OR] 1.0, 95% confidence interval [CI] 0.5–2.0), and when elevated highly sensitive CRP was present without C trachomatis antibodies, the estimated risk increased slightly but was not statistically significantly (OR 1.3, 95% CI 0.7–2.3). The simultaneous presence of these factors increased the estimated risk 4.3-fold (95% CI 2.0–9.3). Among the cases with delivery at or before 34 weeks of gestation, the estimated risk was even more evident (OR 5.6, 95% CI 2.1–14.5).


View this table:
[in this window]
[in a new window]
  		Table 3. Odds Ratios With 95% confidence intervals of Preterm Delivery Associated With Elevated Chlamydia trachomatis Immunoglobulin G Antibody Levels and Elevated Highly Sensitive C-Reactive Protein Concentration

 

No correlation between C pneumoniae IgG antibodies and C trachomatis IgG antibodies measured by microimmunofluorescence (Spearman correlation coefficient rs –0.042, P = .35) was found in the whole study population (n = 506). There were no significant differences in the prevalence rates or the levels of C pneumoniae antibodies between the cases and controls, either.


   DISCUSSION
TOP
ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Our study demonstrated a positive association between elevated first-trimester maternal blood highly sensitive CRP levels in early pregnancy and preterm delivery. We were also able to show that IgG antibodies against C trachomatis (pools and individual serotypes) were more often, although not nominally significantly, present in the mothers with preterm delivery than in those with term delivery. Interestingly, in the joint effect analysis, not even highly elevated highly sensitive CRP levels (≥ 4.3mg/L) alone or C trachomatis antibodies alone predicted the risk for preterm delivery, whereas the simultaneous presence of both elevated highly sensitive CRP and C trachomatis antibodies increased the estimated risk more than 4-fold. These findings suggest that neither past C trachomatis infection (serological scar without inflammation) nor systemic inflammation unrelated to C trachomatis infection is associated with preterm delivery. Further, these findings point to the possibility that chronic C trachomatis infection may lead to systemic low-grade inflammation, as indicated by the elevated highly sensitive CRP levels, contributing to the pathogenetic process leading to preterm delivery in our study population. The lack of IgM antibodies and CRP levels only measurable by highly sensitive method also excludes the role of acute C trachomatis infection in this process.

The relationship between intrauterine infection and preterm birth is not consistent across all gestational ages. In 1979, Russell,17 using histologic chorioamnionitis as a marker of infection, showed that virtually all births at 21 to 24 gestational weeks were associated with an intrauterine infection, compared with only about 10% of the preterm births between 33 and 36 gestational weeks. Similar findings were also reported by Chellam and Rushton,18 Myller-Heubach et al,19 and Andrews et al.20 In 1992, Watts et al21 studied amniotic fluid cultures of women in labor with clinically intact membranes and showed that at 23–24 weeks of gestation, more than 60% of the women in labor had infectious organisms in their amniotic fluid, whereas the corresponding percentage for women in labor at 33–34 weeks was less than 20%. In addition, Hauth et al22 showed that women in early preterm labor had organisms in their membranes before membrane rupture, and the authors regarded this association as the likely cause of preterm birth. They further emphasized that intrauterine infections leading to preterm birth are often chronic, the organisms are usually of low virulence, and they are mostly associated with preterm births occurring before 30 weeks of gestation. In addition, intrauterine infections have been documented weeks or even months before preterm birth.23,24 Using interleukin (IL)-6 as a marker of infection, it has also been shown that women undergoing routine genetic amniocentesis at 16 to 18 weeks and having high amniotic fluid IL-6 levels frequently deliver before the 32nd gestational week.8,25

Earlier studies have shown that elevated CRP levels as acute-phase reactants are associated with chorioamnionitis.26,27 C-reactive protein is produced by hepatocytes primarily in response to IL-6 and is uniformly distributed in the vascular compartment. C-reactive protein levels may rise many-fold in the presence of acute infection or trauma. Recently, it has been suggested that even a very small rise of the CRP level above the baseline may be a useful predictor of low-grade inflammation.28

In the present study, we demonstrated that serum highly sensitive CRP levels were already higher in the first trimester in the women with preterm deliveries. There are only 2 previous prospective studies on the association between maternal serum highly sensitive CRP and preterm delivery. Hvilsom et al9 found high midterm maternal highly sensitive CRP to be associated with a nearly 2-fold risk of preterm delivery. However, Ghezzi et al29 found no relationship between midterm maternal blood highly sensitive CRP levels and preterm delivery.

Maternal infections caused by various vaginal organisms, especially sexually transmitted ones, have been associated with preterm birth.2,4 Because women with such infections are also more likely to have several other risk factors, it is difficult to determine whether it is the infection or some other risk factor that is responsible for the preterm birth. In this study, preterm delivery was not associated with low socioeconomic status, and no differences in the history of smoking were seen between the cases and controls.

In the present study, only C trachomatis IgG antibodies were associated with preterm delivery. Immunoglobulin A antibodies were very rare both in cases and in controls, and no significant differences in their presence were found between the groups. Interestingly, no IgM antibodies were found, suggesting that IgG seropositivity indicates a past or possibly persistent or reactivated C trachomatis infection. As regards all sexually transmitted infections, the evidence showing C trachomatis to be a causative agent for preterm birth is most powerful, and this infection has been reported to be associated with prematurity in several studies.2,4 Chlamydia trachomatis may occur in endometrial tissue without obvious serological responses30 or manifest clinical symptoms,31 and it may also spread to the placenta and fetus.1,2,32 Harrison et al33 showed that C trachomatis IgM-positive women more often had low-birth-weight infants and more often experienced premature rupture of membranes than either IgM-negative or C trachomatis culture–negative women. In addition, Gencay et al34 showed recently that C trachomatis IgG antibodies as markers of past infection were more often detected in the sera of mothers with stillbirth, whereas mothers with very preterm delivery (< 30 weeks of gestation) more often had serum IgM antibodies as a marker of acute infection compared with those with term delivery. In our study, 85.6% of preterm deliveries occurred at gestational ages of more than 32 weeks, and the absence of IgM antibodies in our cases may thus indicate that chronic C trachomatis infection plays a more important role than acute infection in this group. No correlation between C trachomatis and C pneumoniae antibodies was found here, indicating the species specificity of the microimmunofluorescence method used.35 Furthermore, the presence of C pneumoniae antibodies was similar in our cases and controls, which further points to the pathogenic role of C trachomatis in the development of pregnancy complications.

Heat shock proteins are evolutionary highly conserved proteins that absorb stressful stimuli and are produced by both host and microbial cells in stressful conditions, eg, during infection, and their continuous presence during chronic infection may lead to autoimmune responses and tissue damage.36 Plenty of evidence has accumulated on the role of chlamydial heat shock proteins, especially chlamydial heat shock proteins 60 and 10, in the development of immunopathological damage after C trachomatis infections.14,15,37 We have shown earlier in the same Finnish Birth Cohort study that antibodies to chlamydial heat shock proteins 60 and 10 are associated with female subfertility.11 However, the role of chlamydial heat shock protein 60 and 10 in the pathogenesis of preterm deliveries has not been clarified yet. The presence of heat shock proteins in different tissues relevant to human reproduction has been demonstrated: human heat shock protein 60 is expressed during the early stages of pregnancy by glandular epithelial cells in deciduae and in follicular fluids of women with failed in vitro fertilization cycles and also in mammalian embryos.38 In previous studies, the presence of placental heat shock protein has been shown to be similar in both preterm and term pregnancies, indicating that their production is part of the physiological pregnancy process.39,40 However, immune complexes between IgG antibodies and heat shock proteins 60 and 70 were detected only in the placentas of women delivered preterm,40 suggesting that autoimmunity to heat shock protein might be involved in immune-mediated preterm labor. In women previously sensitized to chlamydial heat shock protein 60, its expression during the early stages of pregnancy may reactivate the chlamydial heat shock protein 60–sensitized lymphocytes. The resulting activation of the immune system could lead to a failure of the pregnancy to progress.38,41 In addition, Witkin et al42 have shown that a previous infection with C trachomatis and the resulting immune sensitization to chlamydial heat shock protein epitopes were associated with a poor prognosis for reproductive outcome. Interestingly, in the present study, IgG antibody levels against chlamydial heat shock proteins 60 and 10 were lower in maternal first-trimester sera in the mothers with preterm delivery than in those with term delivery, suggesting that the highly cross-reactive serum antibodies, chlamydial heat shock protein proteins, might have been bound as immune complexes to placental tissue expressing both human heat shock protein and chlamydial heat shock protein antigens.

In conclusion, the results of the present study suggest that chlamydial infection in the first trimester is associated with preterm delivery. When elevated C trachomatis IgG levels were present simultaneously with elevated highly sensitive CRP level, the risk for preterm delivery was significantly increased. Our findings indicate the need for further studies on pathogenetic mechanisms of chronic infections in this important problem of pregnancy.


   Footnotes
 
Reprints are not available.

Funded by the Academy of Finland.

doi:10.1097/01.AOG.0000164464.11979.5d


   REFERENCES
TOP
ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
1. Kramer MS, Demissic K, Yang H, Platt RW, Sauve R, Liston R. The contribution of mild and moderate preterm birth to infant mortality. JAMA 2000;284:843–9.[Abstract/Free Full Text]

2. Andrews WW, Hauth JC, Goldenberg RL. Infection and preterm birth. Am J Perinatol 2000;17:357–65.[Medline]

3. Welfare and Health Care Statistics, Finland, 2003 [in Finnish]. Available at: http://www.stakes.info/files/pdf/Tilastotiedotteet/Tt26_04.pdf. Retrieved October 1, 2004.

4. Goldenberg RL, Andrews WW, Yuan AC, MacKay HT, St Louis ME. Sexually transmitted diseases and adverse outcomes of pregnancy. Clin Perinatol 1997;24:23–41.[Medline]

5. Yost NP, Cox SM. Infection and preterm labor. Clin Obstet Gynecol 2000;43:759–67.[Medline]

6. Challis JR. Mechanism of parturition and preterm labor. Obstet Gynecol Surv 2000;55:650–60.[Medline]

7. Romero R, Mazor M, Wu YK, Sirtori M, Oyarzun E, Mitchell MD, et al. Infection in the pathogenesis of preterm labor. Semin Perinatol 1988;12:262–79.[Medline]

8. Wenstrom KD, Andrews WW, Hauth JC, Goldenberg RL, Cliver SP. Elevated second-trimester amniotic fluid interleukin-6 levels predict preterm delivery. Am J Obstet Gynecol 1998;178:546–50.[Medline]

9. Hvilsom G, Thorsen P, Jeune B, Bakketeig L. C-reactive protein: a serological marker for preterm delivery. Acta Obstet Gynecol Scand 2002;81:424–9.[Medline]

10. Wang SP, Grayston JT. Immunologic relationship between genital TRIC, lymphogranuloma venereum, and related organisms in a new microtiter indirect immunofluorescence test. Am J Ophthalmol 1970;70:367–74.[Medline]

11. Karinen L, Pouta A, Hartikainen A-L, Bloigu A, Paldanius M, Leinonen M, et al. Antibodies to Chlamydia trachomatis heat shock proteins Hsp60 and Hsp10 and subfertility in general population at age 31. Am J Reprod Immunol 2004;52:291–7.

12. Ekman MR, Leinonen M, Syrjala H, Linnanmaki E, Kujala P, Saikku P. Evaluation of serological methods in the diagnosis of Chlamydia pneumoniae pneumonia during an epidemic in Finland. Eur J Clin Microbiol Infect Dis 1993;12:756–60.[Medline]

13. Paldanius M, Bloigu A, Leinonen M, Saikku P. Measurement of Chlamydia pneumoniae-specific immunoglobulin A (IgA) antibodies by the microimmunofluorescence (MIF) method: comparison of seven fluorescein-labeled anti-human IgA conjugates in an in-house MIF test using one commercial MIF and one enzyme immunoassay kit. Clin Diagn Lab Immunol 2003;10:8–12.[Abstract/Free Full Text]

14. LaVerda D, Byrne GI. Use of monoclonal antibodies to facilitate identification, cloning, and purification of Chlamydia trachomatis hsp10. J Clin Microbiol 1997;35:1209–15.[Abstract]

15. LaVerda D, Albanese LN, Ruther PE, Morrison SG, Morrison RP, Ault KA, et al. Seroreactivity to Chlamydia trachomatis Hsp10 correlates with severity of human genital tract disease. Infect Immun 2000;68:303–9.[Abstract/Free Full Text]

16. Taponen S, Martikainen H, Jarvelin MR, Sovio U, Laitinen J, Pouta A, et al. Metabolic cardiovascular disease risk factors in women with self-reported symptoms of oligomenorrhea and/or hirsutism: Northern Finland Birth Cohort 1966 Study. J Clin Endocrinol Metab 2004;89:2114–8.[Abstract/Free Full Text]

17. Russell P. Inflammatory lesions of the human placenta. I. Clinical significance of acute chorioamnionitis. Am J Diagn Gynecol Obstet 1979;1:127–37.

18. Chellam VG, Rushton DI. Chorioamnionitis and funiculitis in the placentas of 200 births weighing less than 2.5 kg. Br J Obstet Gynaecol 1985;92:808–14.[Medline]

19. Meuller-Heubach E, Rubinstein DN, Schwarz SS. Histologic chorioamnionitis and preterm delivery in different patient populations. Obstet Gynecol 1990;75:622–6.[Abstract/Free Full Text]

20. Andrews WW, Goldenberg RL, Hauth JC Preterm labor: emerging role of genital tract infection. Infect Agents Dis 1995;4:196–211.[Medline]

21. Watts DH, Krohn MA, Hiller SL, Eschenbach DA. The association of occult amniotic fluid infection with gestational age and neonatal outcome among women in preterm labor. Obstet Gynecol 1992;79:351–7.[Medline]

22. Hauth JC, Andrews WW, Goldenberg RL. Infection-related risk factor predictive of spontaneous labor and birth. Prenat Neonatal Med 1998;3:86–90.

23. Cassell G. Ureaplasma infection. In: Hitchcock PJ, MacKay HT, Waisserheit JN, Binder R, editors. Sexually transmitted diseases and adverse outcomes of pregnancy. Washington (DC): ASM Press; 1999. p. 175–93.

24. Horowitz S, Mazor M, Romero R, Horowitz J, Glezerman M. Infection of the amniotic cavity with Ureaplasma urealyticum in the midtrimester of pregnancy. J Reprod Med 1995;40:375–9.[Medline]

25. Ghidini A, Jenkins CB, Spong CY, Pezzullo JC, Salafia CM, Eglinton GS. Elevated amniotic fluid interleukin-6 levels during the early second trimester are associated with greater risk of subsequent preterm delivery. Am J Reprod Immunol 1997;37:227–31.

26. Yoon BH, Jun JK, Park KH, Syn HC, Gomez R, Romero R. Serum C-reactive protein, white blood cell count and amniotic fluid white blood cell count in women with premature rupture of membranes. Obstet Gynecol 1996;88:1034–40.[Abstract]

27. Burrus DR, Ernest JM, Veille J Fetal fibronectin, interleukin-6 and C-reactive protein are useful in establishing prognostic subcategories of idiopathic preterm labor. Am J Obstet Gynecol 1995;173:1258–62.[Medline]

28. Ablij HC, Meinders AE. C-reactive protein: history and revival. Eur J Intern Med 2002;13:412–22.[Medline]

29. Ghezzi F, Massimo F, Raio L, Di Naro E, Bossi G, D’Eril G, et al. Elevated amniotic fluid C-reactive protein at the time of genetic amniocentesis is a marker for preterm delivery. Am J Obstet Gynecol 2002;186:268–73.[Medline]

30. Ersbak V, Soegaard H, Moeller BR. Detection of Chlamydia trachomatis in formalin-fixed endometrial tissue. Eur J Obstet Gynecol Reprod Biol 1990;36:147–51.[Medline]

31. Wiesenfeld HC, Hillier SL, Krohn MA, Amortegui AJ, Heine RP, Landers DV, et al. Lower genital tract infection and endometritis: insight into subclinical pelvic inflammatory disease. Obstet Gynecol 2002;100:456–63.[Abstract/Free Full Text]

32. Gencay M, Puolakkainen M, Wahlstrom T, Ammala P, Mannonen L, Vaheri A, et al. Chlamydia trachomatis detected in human placenta. J Clin Pathol 1997;50:852–5.[Abstract/Free Full Text]

33. Harrison HR, Alexander ER, Weinstein L, Lewis M, Nash M, Sim DA. Cervical Chlamydia trachomatis and mycoplasmal infections in pregnancy: epidemiology and outcomes. JAMA 1983;250:1721–7.[Abstract]

34. Gencay M, Koskiniemi M, Ammala P, Fellman V, Narvanen A, Wahlstrom T, et al. Chlamydia trachomatis seropositivity is associated both with stillbirth and preterm delivery. APMIS 2000;108:584–8.[Medline]

35. Grayston JT, Golubjatnikov R, Hagiwara T, Hahn DL, Leinonen M, Persson K, et al. Serologic tests for Chlamydia pneumoniae. Pediatr Infect Dis J 1993;12:790–1.

36. Kaufmann SH. Heat shock proteins and the immune response. Immunol Today 1990;11:129–36.[Medline]

37. Peeling RW, Patton DL, Cosgrove Sweeney YT, Cheang MS, Lichtenwalner AB, Brunham RC, et al. Antibody response to chlamydial heat shock protein 60 in an experimental model of chronic pelvic inflammatory disease in monkeys (Macaca nemestrina). J Infect Dis 1999;180:774–9.[Medline]

38. Neuer A, Spandorfer SD, Giraldo P, Dieterle S, Rosenwaks Z, Witkin SS. The role of heat shock proteins in reproduction. Hum Reprod Update 2000;6:149–59.[Abstract/Free Full Text]

39. Divers MJ, Bulmer JN, Miller D, Lilford RJ. Placental heat shock proteins: no immunohistochemical evidence for a differential stress response in preterm labour. Gynecol Obstet Invest 1995;40:236–43.[Medline]

40. Ziegert M, Witkin SS, Sziller I, Alexander H, Brylla E, Hartig W. Heat shock proteins and heat shock protein-antibody complexes in placental tissues. Infect Dis Obstet Gynecol 1999;7:180–5.[Medline]

41. Witkin SS. Immunological aspects of genital Chlamydia infections. Best Pract Res Clin Obstet Gynaecol 2002;16:865–74.[Medline]

42. Witkin SS, Jeremias J, Neuer A, David S, Kligman I, Toth M, et al. Immune recognition of the 60 kD heat shock protein: implications for subsequent fertility. Infect Dis Obstet Gynecol 1996;4:152–8.[Medline]





This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Karinen, L.
Right arrow Articles by Hartikainen, A.-L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Karinen, L.
Right arrow Articles by Hartikainen, A.-L.
Related Collections
Right arrow Immunology
Right arrow Infectious disease
Right arrow Obstetric complications of pregnancy

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS