OBSTETRICS
Diagnosis of Subclinical Amniotic Fluid Infection Prior to Rescue Cerclage Using Gram Stain and Glucose Tests: An Individual Patient Meta-Analysis

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Abstract

Objectives

Microbial invasion of the amniotic cavity (MIAC) can affect outcomes following rescue cerclage. We carried out a study to compare the diagnostic performance of the Gram stain and glucose tests for detecting subclinical MIAC.

Methods

We used individual-level data from published studies on Gram stain, glucose, and amniotic fluid culture among women with preterm labour. We calculated the sensitivity, specificity, area under the curve (AUC) and other indices, with amniotic fluid culture results used as the gold standard. The probability of infection using both tests as predictors was also estimated using logistic regression.

Results

The rate of culture-confirmed MIAC was 11.8% (34 of 288 women). The Gram stain test yielded a sensitivity of 65% (95% CI 46% to 78%) and a specificity of 99% (95% CI 98% to 100%). A positive Gram stain or glucose test had a sensitivity of 88% (95% CI 72% to 96%) and a specificity of 87% (95% CI 82% to 90%), while a positive Gram stain and a positive glucose test had a sensitivity of 62% (95% CI 44% to 77%) and a specificity of 100% (95% CI 98% to 100%). The AUC for the tests were Gram stain 0.82 (95% CI 0.74 to 0.90), glucose 0.86 (95% CI 0.80 to 0.93), and combined Gram stain and glucose 0.92 (95% CI 0.86 to 0.98). Using the tests, singly or in combination, provided greater clinically important calibration, risk-stratification, and classification accuracy than using no tests.

Conclusion

Amniotic fluid Gram stain and/or glucose testing provides substantially improved performance for the diagnosis of subclinical MIAC compared with no testing.

Résumé

Objectifs

L’invasion microbienne de la cavité amniotique (IMCA) peut affecter les issues à la suite d’un cerclage d’urgence. Nous avons mené une étude visant à comparer le rendement diagnostique de la coloration de Gram à celui de la concentration en glucose pour ce qui est du dépistage d’une IMCA subclinique.

Méthodes

Nous avons utilisé des données personnelles issues d’études publiées ayant porté sur l’utilisation de la coloration de Gram, de la concentration en glucose et de la mise en culture du liquide amniotique chez des femmes connaissant un travail préterme. Nous avons calculé la sensibilité, la spécificité, la surface sous la courbe (SSC) et d’autres indices, les résultats de la mise en culture du liquide amniotique étant utilisés à titre de test de référence. La probabilité de constater une infection à la suite de l’utilisation des deux tests à titre de facteurs prédictifs a également été estimée au moyen d’une régression logistique.

Résultats

Le taux d’IMCA confirmée par mise en culture était de 11,8 % (34 femmes sur 288). Le test par coloration de Gram a présenté une sensibilité de 65 % (IC à 95 %, 46 % - 78 %) et une spécificité de 99 % (IC à 95 %, 98 % - 100 %). L’obtention d’un résultat positif à la suite d’une coloration de Gram ou de la mesure de la concentration en glucose présentait une sensibilité de 88 % (IC à 95 %, 72 % - 96 %) et une spécificité de 87 % (IC à 95 %, 82 % - 90 %), tandis que l’obtention d’un résultat positif à la suite d’une coloration de Gram et de la mesure de la concentration en glucose présentait une sensibilité de 62 % (IC à 95 %, 44 % - 77 %) et une spécificité de 100 % (IC à 95 %, 98 % - 100 %). Les SSC étaient de 0,82 (IC à 95 %, 0,74 - 0,90) pour la coloration de Gram, de 0,86 (IC à 95 %, 0,80 - 0,93) pour la concentration en glucose et de 0,92 (IC à 95 %, 0,86 - 0,98) pour la combinaison « coloration de Gram-concentration en glucose ». L’utilisation de ces tests, de façon isolée ou en combinaison, offrait une meilleure (importante sur le plan clinique) capacité d’étalonnage, capacité de stratification du risque et précision en matière de classification que l’utilisation d’aucun de ces tests.

Conclusion

La coloration de Gram et/ou la mesure de la concentration en glucose du liquide amniotique offrent un rendement substantiellement accru pour ce qui est du diagnostic de l’IMCA subclinique, par comparaison avec l’absence de tests.

Section snippets

INTRODUCTION

Cervical insufficiency during the second trimester of pregnancy increases the risk of preterm delivery and presents a management challenge.1., 2., 3. While a rescue/emergency cerclage in the absence of clinical chorioamnionitis can potentially prolong pregnancy, the success of this intervention depends largely on the absence of subclinical infection.3., 4., 5., 6., 7., 8., 9., 10. In the presence of microbial invasion of the amniotic cavity, cervical cerclage can lead to increased maternal

METHODS

We used data available in the published literature, specifically using studies with individual-level information about amniotic fluid Gram stain, glucose concentration, and culture results following a second trimester amniocentesis. Additional criteria for study selection included those based on homogenous populations with preterm labour and intact membranes. Two studies satisfied these conditions: the first study13 included 168 consecutive patients, and the second study included 120 patients.16

RESULTS

The study population included 288 women who underwent amniocentesis during the second trimester to detect MIAC. The overall prevalence of culture confirmed MIAC was 11.8% (34/288). The test results for the Gram stain, glucose, and amniotic fluid culture tests are presented in Figure 1. The sensitivity and specificity of the Gram stain test were 65% and 99%, respectively, and the positive and negative predictive values were 92% and 95%, respectively (Table 1). The sensitivity of the glucose

DISCUSSION

Our study showed that the amniotic fluid Gram stain and glucose concentration tests diagnosed microbial infection of the amniotic cavity with reasonable accuracy when used singly or in combination. These tests provide a substantial advantage over no testing for diagnosing subclinical infection. For example, if used to aid clinical decision-making before rescue cerclage, Gram stain testing alone would identify 65% of women with MIAC and deny intervention to only 8% of women (92% of whom would

CONCLUSION

Our study showed that the use of Gram stain and glucose testing, either singly or in combination, can help diagnose subclinical MIAC; this may be, for instance, in women with cervical insufficiency considering a rescue cerclage. Details of test performance dictate whether a single test or both tests in combination is preferable. The choice of specific test or the specific combination of the two tests to be used depends on the value placed on detecting all cases of MIAC versus keeping

ACKNOWLEDGEMENTS

This study was supported by a Canadian Institutes of Health Research Team grant in severe maternal morbidity (MAH-115445). Yasser Sabr is supported by a scholar award from the King Saud University, Saudi Arabia. K.S. Joseph holds a Canadian Institutes of Health Research Chair in maternal, fetal and infant health services research and is also supported by the Child and Family Research Institute.

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    Competing Interests: None declared.

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