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Context: Intra-amniotic infection (IAI) is commonly associated with preterm birth and adverse neonatal sequelae. Early diagnosis of IAI, however, has been hindered by insensitive or nonspecific tests., Objective: To identify unique protein signatures in rhesus monkeys with experimental IAI, a proteomics-based analysis of amniotic fluid was used to develop diagnostic biomarkers for subclinical IAI in amniotic fluid and blood of women with preterm labor., Design, Setting, and Participants: Surface-enhanced laser desorption-ionization/time-of-flight mass spectrometry, gel electrophoresis, and tandem mass spectrometry were used to characterize amniotic fluid peptides in 19 chronically instrumented pregnant rhesus monkeys before and after experimental IAI. Candidate biomarkers were determined by liquid chromatography-tandem mass spectrometry. Polyclonal antibodies were generated from synthetic peptides for validation of biomarkers of IAI. Amniotic fluid peptide profiles identified in experimental IAI were subsequently tested in a cohort of 33 women admitted to Seattle, Wash, hospitals between June 25, 1991, and June 30, 1997, with preterm delivery at 35 weeks or earlier associated with subclinical IAI (n = 11), preterm delivery at 35 weeks or earlier without IAI (n = 11), and preterm contractions with subsequent term delivery at later than 35 weeks (n = 11)., Main Outcome Measures: Identification of peptide biomarkers for occult IAI., Results: Protein expression profiles in amniotic fluid showed unique signatures of overexpression of polypeptides in the 3- to 5-kDa and 10- to 12-kDa molecular weight ranges in all animals after infection and in no animal prior to infection. In women, the 10- to 12-kDa signature was identified in all 11 patients with subclinical IAI, in 2 of 11 with preterm delivery without IAI, and in 0 of 11 with preterm labor and term delivery without infection (P<.001). Peptide fragment analysis of the diagnostic peak in amniotic fluid identified calgranulin B and a unique fragment of insulinlike growth factor binding protein 1, which were also expressed in maternal serum. Mapping of other amniotic fluid proteins differentially expressed in IAI identified several immunoregulators not previously described in amniotic fluid., Conclusions: This proteomics-based characterization of the differential expression of amniotic fluid proteins in IAI identified a distinct proteomic profile in an experimental primate chorioamnionitis model that detected subclinical IAI in a human cohort with preterm labor. These diagnostic protein expression signatures, complemented by immunodetection of specific biomarkers in amniotic fluid and in maternal serum, might have application in the early detection of IAI.

Objective: --To examine available data regarding optimal antimicrobial therapy for pelvic inflammatory disease (PID) and to address selected treatment issues confronting clinicians caring for women with PID., Data Sources: --Studies evaluated to help establish the Centers for Disease Control's 1989 Sexually Transmitted Diseases Treatment Guidelines and other reports published since 1985. A MEDLINE search of English-language literature was conducted using the indexing terms "pelvic inflammatory disease" or "pelvic infections" or "salpingitis" and "treatment". In addition, abstracts and bibliographies of articles and books were reviewed., Study Selection: --Studies were selected for detailed review if they evaluated the effectiveness of an antimicrobial regimen for treatment of PID., Data Extraction: --All studies were evaluated to determine the numbers of women treated and the percentage with clinical or microbiologic evidence of cure., Data Synthesis: --A variety of combination antimicrobial regimens are highly effective in providing clinical and microbiologic evidence of cure; few data are available to assess optimal therapy for prevention of late sequelae. Because PID is polymicrobial in cause, recommended antimicrobial regimens are broad-spectrum in coverage., Conclusions: --No single agent that provides sufficient coverage is currently available. Several combination regimens appear highly effective clinically even among women with tubo-ovarian abscess formation. Uncertainties regarding the effectiveness of antimicrobial therapy for prevention of late sequelae complicate decisions regarding the choice among regimens and the appropriateness of ambulatory treatment of women with PID. Pending better data, hospitalization should be strongly considered, where feasible, particularly for those women with PID desiring further childbearing. Sex partners of all women with PID should be treated.

The vaginal douching habits of 100 consecutive municipal hospital patients with verified pelvic inflammatory disease (cases) were compared with those of 762 randomly selected controls (random controls) and 119 women thought to have pelvic inflammatory disease but in whom the diagnosis was not confirmed by laparoscopy and/or endometrial biopsy specimen (internal controls). Because patients had been symptomatic for no more than 3 weeks, current douching was arbitrarily defined as any douching during the previous 2 months. Current douching was more common among those with pelvic inflammatory disease than among random controls or internal controls. Among current douchers, pelvic inflammatory disease was significantly related to frequency of douching. For example, when cases were compared with random controls, those who douched three or more times per month were 3.6 times more likely than those who douched less than once per month to have confirmed pelvic inflammatory disease. A logistic regression model was used to adjust for demographic, behavioral, and other possible confounding variables. Even after adjustments, douching during the previous 2 months remained associated with pelvic inflammatory disease. These data suggest that among these women vaginal douching may be a risk factor for pelvic inflammatory disease.

Studies have shown that oral contraceptive use may protect against pelvic inflammatory disease (PID), but it is not known whether oral contraceptives protect against the disease among women already infected with Chlamydia trachomatis or Neisseria gonorrhoeae. The relationship between oral contraceptive use and PID was analyzed in a case-control study of 141 women with verified PID and 739 randomly selected, sexually active women with no clinical evidence of the disease. Case and control subjects were stratified on the basis of infection with C trachomatis, N gonorrhoeae, or neither organism. Among women infected with C trachomatis alone, those with PID were less likely than control subjects to use oral contraceptives. The association was significant when oral contraceptive use was compared with nonuse (odds ratio, 0.22; 95% confidence interval, 0.08 to 0.64) and with noncontraception (odds ratio, 0.17; 95% confidence interval, 0.06 to 0.53) and remained so after adjusting for potential confounding variables by logistic regression analysis. Among women infected with N gonorrhoeae alone, no association was found between use of oral contraceptives and PID. These data suggest that oral contraceptive use protects against symptomatic PID among women infected with C trachomatis but not among those infected with N gonorrhoeae.

In a prospective study of morbidity associated with Chlamydia trachomatis infections during pregnancy, we isolated C trachomatis from the endocervix of 18 (6.7%) of 268 women examined before 19 weeks' gestation. Infected women were significantly younger than noninfected women, and significantly more often unmarried, supported by public assistance, and pregnant for the first time. Among women followed up from 19 weeks' gestation until delivery, the mean duration of gestation was significantly shorter for those with antepartum chlamydial infection. Stillbirth or neonatal death occurred in six (33%) of the 18 pregnancies of infected women compared with eight (3.4%) of the 238 pregnancies of noninfected women followed up from the 19th week of gestation through delivery. Stillbirth or neonatal death occurred ten times more often among Chlamydia-infected women than among uninfected controls matched for age, marital status, socioeconomic status, pregnancy order, and race.

We prospectively studied the relationship of pregnancy outcome to bacterial vaginosis, an anaerobic vaginal condition, and to other selected genital pathogens among 534 gravid women. Bacterial vaginosis was presumptively diagnosed by gas-liquid chromatographic identification of microbial organic acid metabolites in 102 women (19%), and cervical infection with Chlamydia trachomatis was found in 47 (9%) of the women. Although women with and without bacterial vaginosis had similar demographic and obstetric factors, neonates born to women with bacterial vaginosis had lower mean birth weight than did neonates born to women without bacterial vaginosis (2960 +/- 847 g vs 3184 +/- 758 g). Bacterial vaginosis was significantly associated with preterm premature rupture of the membranes (odds ratio [OR], 2.0; 95% confidence interval [Cl], 1.1 to 3.7), preterm labor (OR, 2.0; Cl, 1.1 to 3.5), and amniotic fluid infection (OR, 2.7; Cl, 1.1 to 6.1), but not with birth weight below 2500 g (OR, 1.5; Cl, 0.8 to 2.0). Cervical infection with C trachomatis was independently associated with preterm premature rupture of the membranes, preterm labor, and low birth weight (OR, 1.5; Cl, 0.8 to 2.0).

We compared the efficacy of erythromycin ophthalmic ointment vs 1% silver nitrate drops for the prevention of neonatal conjunctivitis or respiratory tract infection from Chlamydia trachomatis. The organism was isolated from the cervix of 67 (12%) of 572 pregnant women. They gave birth to 559 infants who were randomly assigned to either prophylaxis immediately after birth. Thirty-six of 60 infants born to Chlamydia-positive women received silver nitrate; 24 received erythromycin. Twelve (33%) of the 36 infants who received silver nitrate had chlamydial conjunctivitis, but none of the 24 infants who received erythromycin did. Ten (29%) of 36 infants receiving silver nitrate had chlamydial nasopharyngeal infection (three later had pneumonia), as opposed to five (21%) of 24 who received erythromycin (one had pneumonia). Thus, erythromycin ointment is effective in prevention of chlamydial conjunctivitis, but it may not reduce nasopharyngeal infection or subsequent pneumonia.