Abstract

Background:An elevated sFlt-1 indicates soluble Fms-like tyrosine kinase-1 (sFlt-1)/ placental growth factor (PlGF) ratio has recently been validated as significant predictor of preeclampsia (PE)(1). However, raised sFlt-1 levels due to inflammation are observed in patients with rheumatoid arthritis (RA)(2). The use of the sFlt-1/PlGF ratio for the prediction of PE has not been evaluated in pregnant women with diseases that are characterized by high levels of inflammation, such as RAObjectives:We investigated whether sFlt-1 and/or PlGF are altered in pregnant women with RA according to disease activity, and evaluated whether a sFlt-1/PlGF ratio of ≤38 could be used to predict the absence of PE in pregnant RA-patients.Methods:This study was embedded in a nationwide, observational, prospective cohort study on pregnant women with RA (PARA-study). sFlt-1 and PlGF levels were measured, using automated analyzer (Cobas-6000, e-module; Roche-Diagnostics), in the third trimester of pregnancy.Results:A total of 221 women, aged 21–42 years, were included. Values of sFlt-1, PlGF and sFlt-1/PlGF ratio were not significantly correlated with the DAS28-CRP (Figure 1). CRP correlated weakly with PlGF (r=-0.14, p=0.03), while no correlation was found with sFlt-1 or the sFlt-1/PlGF ratio.Preeclampsia occurred in four out of 214 women with a ratio ≤38 (2%) in contrast to three out of seven women with a ratio >38 (43%), p<0.001 (Table 1). When stratified to a sFlt-1/PlGF ratio of ≤38 only 2% of women developed preeclampsia, compared to 43% of the women with a ratio >38. The observed sensitivity and specificity for a sFlt-1/PlGF ratio cut-off of ≤38 were 42.1% and 98.1%, respectively, with a negative predictive value (NPV) of 98%. All women that developed PE, developed PE >4 weeks after collecting of blood samples in the 3rd trimester, therefore the observed NPV could be even higher.Table 1.Pregnancy Outcome according to sFlt-1/PlGF ratio with a cut-off value of 38.ParameterRatio ≤38Ratio >38P-valueN2147GA at birth, weeks39 (38 - 40)37 (36 - 40)0.05<342 (1)0(0)1.0034 - 3718 (8)2 (29)0.12Male, n (%)113 (53)5 (71)0.45Birth weight, grams3420 (2998 - 3800)2620 (2360 - 2850)<0.01Maternal OutcomeGestational Hypertension15 (7)2 (29)0.09Preeclampsia4 (2)3 (43)<0.001Time to delivery, days66 (52 - 75)52 (44 - 66)0.08Fetal OutcomeBirth weight percentile <1033 (15)5 (71)<0.01Fetal/Neonatal Death1 (1)0 (0)1.00Data are reported as median (interquartile range) or number (percentage). sFlt-1 indicates soluble Fms-like tyrosine kinase-1; PlGF, placental growth factor; GA, gestational age. Time to delivery is defined as the amount of days between blood sampling and delivery.Conclusion:Our study shows that in pregnant women with RA, the sFlt-1/PlGF ratio is not altered due to disease activity, and a cut-off of ≤38 of this ratio can be used to exclude preeclampsia.

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