Quantitative cervicovaginal fluid fetal fibronectin: A liquid biopsy for intra-amniotic inflammation.

INTRODUCTION: Intra-amniotic inflammation is causally linked to spontaneous preterm labor. The gold standard for the diagnosis of intra-amniotic inflammation is the determination of an amniotic fluid profile obtained from transabdominal amniocentesis, which is invasive. Cervicovaginal fluid fetal fibronectin (fFN) is a widely-used predictive biomarker for spontaneous preterm labor. The aims of this study are to determine (1) whether a quantitative cervicovaginal fluid fFN test can be used to identify the presence of intra-amniotic inflammation; and (2) an appropriate cut-off value of a cervicovaginal fluid fFN concentration for the identification of intra-amniotic inflammation. MATERIAL AND METHODS: This prospective cohort study included 78 patients with preterm labor and intact membranes who had a sample collected for quantitative cervicovaginal fluid fFN measurement and underwent transabdominal amniocentesis. Intra-amniotic inflammation was defined as an amniotic fluid interleukin-6 concentration ≥2.6 ng/mL. Clinicians were masked from the results of cervicovaginal fluid fFN and amniotic fluid interleukin-6 concentrations. Logistic regression analysis was used to determine which factors were significant predictors of intra-amniotic inflammation. The diagnostic indices of the cervicovaginal fluid fFN test for the identification of intra-amniotic inflammation were calculated. RESULTS: (1) Frequency of intra-amniotic inflammation was 26.9% (21/78); (2) the higher the cervicovaginal fluid fFN concentration, the greater the risk of intra-amniotic inflammation (p < 0.001); (3) cervicovaginal fluid fFN concentration ≥125 ng/mL had an area under the curve of 0.91 (95% confidence interval: 0.83-0.96) for the identification of intra-amniotic inflammation with 100% sensitivity, 100% negative predictive value, 82.46% specificity and a positive likelihood ratio of 5.7; and (4) cervicovaginal fluid fFN cut-off of 125 ng/mL had a significant higher predictive performance than the traditional cut-off (50 ng/mL) for the identification of intra-amniotic inflammation. CONCLUSIONS: Quantitative cervicovaginal fluid fFN with a cut-off of 125 ng/mL had a high sensitivity and a negative predictive value as well as a positive likelihood ratio for the identification of intra-amniotic inflammation. Its high sensitivity and negative predictive value can be used to decrease an index of suspicion of intra-amniotic inflammation. This test may be useful as an initial assessment test to select appropriate patients for amniocentesis to determine intra-amniotic inflammation.

Anaphylaxis-induced premature uterine contractions: a case report and literature review.

BACKGROUND: Preterm labor is caused by multiple etiologies, including intra-amniotic infection and/or intra-amniotic inflammation, vascular disorders, cervical disease, decidual senescence, and breakdown of maternal-fetal tolerance. Accumulating evidence in vivo and in vitro has shown that an allergic reaction, including anaphylaxis, can induce preterm uterine contractions. This report describes a case of a pregnant woman who developed anaphylaxis and regular uterine contractions after the ingestion of a strawberry-coated biscuit. We also review the mechanism of allergic reaction (hypersensitivity)-induced preterm labor. Case presentation A 31-year-old woman (gravida 1, para 0) at 30+2 weeks of gestation was admitted to the labor and delivery unit with regular uterine contractions and anaphylactic symptoms after she ingested a strawberry-coated biscuit as a snack. The uterine contractions resolved after the treatment of anaphylaxis by administering antihistamines and epinephrine. The patient subsequently delivered at 39+3 weeks of gestation. The amniotic fluid profile showed no infection or inflammation. A postpartum skin-prick test confirmed a positive type 1 hypersensitivity reaction to the strawberry-coated biscuit. CONCLUSIONS: We report a case of anaphylaxis-induced uterine contractility in which uterine contractions subsided after the treatment of anaphylaxis. The absence of intra-amniotic infection and/or intra-amniotic inflammation and the cause of the anaphylaxis were confirmed. Our findings indicate that maternal allergic reactions may be one of the mechanisms of preterm labor.

Pharmacogenomics of Preeclampsia therapies: Current evidence and future challenges for clinical implementation.

Preeclampsia is a pregnancy-specific disorder, and it is a leading cause of maternal and perinatal morbidity and mortality. The application of pharmacogenetics to antihypertensive agents and dose selection in women with preeclampsia is still in its infancy. No current prescribing guidelines from the clinical pharmacogenetics implementation consortium (CPIC) exist for preeclampsia. Although more studies on pharmacogenomics are underway, there is some evidence for the pharmacogenomics of preeclampsia therapies, considering both the pharmacokinetic (PK) and pharmacodynamic (PD) properties of drugs used in preeclampsia. It has been revealed that the CYP2D6*10 variant is significantly higher in women with preeclampsia who are non-responsive to labetalol compared to those who are in the responsive group. Various genetic variants of PD targets, i.e., NOS3, MMP9, MMP2, TIMP1, TIMP3, VEGF, and NAMPT, have been investigated to assess the responsiveness of antihypertensive therapies in preeclampsia management, and they indicated that certain genetic variants of MMP9, TIMP1, and NAMPT are more frequently observed in those who are non-responsive to anti-hypertensive therapies compared to those who are responsive. Further, gene-gene interactions have revealed that NAMPT, TIMP1, and MMP2 genotypes are associated with an increased risk of preeclampsia, and they are more frequently observed in the non-responsive subgroup of women with preeclampsia. The current evidence is not rigorous enough for clinical implementation; however, an institutional or regional-based retrospective analysis of audited data may help close the knowledge gap during the transitional period from a traditional approach (a "one-size-fits-all" strategy) to the pharmacogenomics of preeclampsia therapies.