Cervical length measurement for the prediction of preterm birth in multiple pregnancies: a systematic review and bivariate meta-analysis.

OBJECTIVES: To review the literature on cervical length as a predictor of preterm birth in asymptomatic women with a multiple pregnancy. METHODS: We searched MEDLINE, Embase and reference lists of included articles to identify all studies that reported on the accuracy of cervical length for predicting preterm birth in asymptomatic women with a multiple pregnancy. We scored study characteristics and study quality, and extracted data in order to construct two-by-two tables cross-classifying cervical length and preterm delivery. Meta-analysis using a bivariate model was performed. Summary receiver-operating characteristics (ROC) curves were generated for various test characteristics and outcome definitions. RESULTS: We found 21 studies reporting on 2757 women. There was a large variation in gestational age at measurement, cut-off point for cervical length and definition of preterm birth. The summary ROC curve indicated a good predictive capacity of short cervical length for preterm birth. Summary estimates of sensitivity and specificity for preterm birth before 34 weeks' gestation were 78% and 66%, respectively, for 35 mm, 41% and 87% for 30 mm, 36% and 94% for 25 mm and 30% and 94% for 20 mm. CONCLUSIONS: In women with a multiple pregnancy, second-trimester cervical length is a strong predictor of preterm birth. In the absence of effective preventive strategies, there is currently no place in clinical practice for cervical length measurement in this population. However, future studies should evaluate preventive interventions in women with multiple pregnancies and a short cervix, and cervical length should be measured in any trial studying preventive strategies in multiple pregnancies.

Liposome-encapsulated dexamethasone attenuates ventilator-induced lung inflammation.

BACKGROUND AND PURPOSE: Systemic glucocorticoid therapy may effectively attenuate lung inflammation but also induce severe side-effects. Delivery of glucocorticoids by liposomes could therefore be beneficial. We investigated if liposome-encapsulated dexamethasone inhibited ventilator-induced lung inflammation. Furthermore, we evaluated whether targeting of cellular Fcγ-receptors (FcγRs) by conjugating immunoglobulin G (IgG) to liposomes, would improve the efficacy of dexamethasone-liposomes in attenuating granulocyte infiltration, one of the hallmarks of lung inflammation. EXPERIMENTAL APPROACH: Mice were anaesthetized, tracheotomized and mechanically ventilated for 5 h with either 'low' tidal volumes ∼7.5 mL·kg(-1) (LV(T) ) or 'high' tidal volumes ∼15 mL·kg(-1) (HV(T) ). At initiation of ventilation, we intravenously administered dexamethasone encapsulated in liposomes (Dex-liposomes), dexamethasone encapsulated in IgG-modified liposomes (IgG-Dex-liposomes) or free dexamethasone. Non-ventilated mice served as controls. KEY RESULTS: Dex-liposomes attenuated granulocyte infiltration and IL-6 mRNA expression after LV(T) -ventilation, but not after HV(T) -ventilation. Dex-liposomes also down-regulated mRNA expression of IL-1ß and KC, but not of CCL2 (MCP-1) in lungs of LV(T) and HV(T) -ventilated mice. Importantly, IgG-Dex-liposomes inhibited granulocyte influx caused by either LV(T) or HV(T) -ventilation. IgG-Dex-liposomes diminished IL-1ß and KC mRNA expression in both ventilation groups, and IL-6 and CCL2 mRNA expression in the LV(T) -ventilated group. Free dexamethasone prevented granulocyte influx and inflammatory mediator expression induced by LV(T) or HV(T) -ventilation. CONCLUSIONS AND IMPLICATIONS: FcγR-targeted IgG-Dex-liposomes are pharmacologically more effective than Dex-liposomes particularly in inhibiting pulmonary granulocyte infiltration. IgG-Dex-liposomes inhibited most parameters of ventilator-induced lung inflammation as effectively as free dexamethasone, with the advantage that liposome-encapsulated dexamethasone will be released locally in the lung thereby preventing systemic side-effects.