Chorioamnionitis Occurring in Women With Preterm Rupture of the Fetal Membranes Is Associated With a Dynamic Increase in mRNAs Coding Cytokines in the Maternal Circulation

Abstract

Background: Preterm prelabor rupture of the fetal membranes (PPROM) is a significant contributor to the morbidity and mortality of preterm birth, particularly in the setting of chorioamnionitis. No sensitive or specific diagnostic or predictive test currently exists for the accurate diagnosis of chorioamnionitis. Our aim was to measure messenger RNA (mRNA) coding cytokines in the maternal blood and examine whether they were increased in association with chorioamnionitis at delivery. Methods/Results: We performed a prospective cohort study of women recruited with PPROM at a mean gestational age of 28.9 weeks at risk of developing chorioamnionitis. Blood was sampled from participants, and the expression of mRNA coding for proinflammatory genes was measured in women with and without chorioamnionitis at the time of delivery as well as gestationmatched healthy controls. Expression was measured using quantitative polymerase chain reaction (PCR) and also digital PCR. Interleukin 1b (IL1B) mRNA expression in maternal blood was elevated in women with chorioamnionitis compared to gestation-matched controls. Importantly, among women admitted with PPROM, digital PCR confirmed a significant increase in IL1B expression in maternal blood in women with chorioamnionitis compared to women without chorioamnionitis. Polymerase chain reaction array revealed that CD14, nuclear factor of k light polypeptide gene enhancer in B-cells 1 (NFKB1), and tumor necrosis factor receptor super family-interacting serine-threonine kinase 1 mRNA were significantly increased in women with chorioamnionitis compared to controls. Digital PCR confirmed that NFKB1 mRNA was significantly increased in patients with chorioamnionitis compared to controls and that CD14 levels increased over time in patients with PPROM having chorioamnionitis. Conclusion: Measuring circulating proinflammatory mRNA in women with PPROM may distinguish those with chorioamnionitis from those without, in turn providing better targeted therapies and appropriate timing of delivery.

Measuring circulating placental RNAs to non-invasively assess the placental transcriptome and to predict pregnancy complications

“…Preterm birth is often preceded by premature rupture of membranes and chorioamnionitis. In a study by Stock et al , cpRNA coding interleukin 1 β in maternal blood was increased in pregnancies with ruptured membranes complicated by chorioamnionitis compared with those without chorioamnionitis and may be a potential biomarker to identify pregnancies, which may benefit from early delivery to prevent complications of infection …”

Prolonged latency of preterm prelabour rupture of membranes and neurodevelopmental outcomes: a secondary analysis

“…Although neurodevelopmental delay has a multifactorial etiology and its pathophysiology is not entirely understood, prematurity and neonatal or fetal infection and inflammation are important associated risk factors . Preterm prelabour rupture of membranes (PPROM), a common cause of spontaneous preterm birth that affects approximately 3% of pregnancies, is frequently associated with inflammation and infection . PPROM occurs when the fetal membranes, which represent an anatomical and physiological barrier, rupture, thereby allowing uterine infections from the vagina to ascend and increasing the risk for chorioamnionitis, as found both clinically and upon pathology analysis .…”

“…[2][3][4][5] Preterm prelabour rupture of membranes (PPROM), a common cause of spontaneous preterm birth that affects approximately 3% of pregnancies, is frequently associated with inflammation and infection. 6,7 PPROM occurs when the fetal membranes, which represent an anatomical and physiological barrier, rupture, thereby allowing uterine infections from the vagina to ascend and increasing the risk for chorioamnionitis, as found both clinically and upon pathology analysis. 7 The management approach to PPROM for women at <34 weeks of gestation includes administering antibiotics to increase latency and expectant management, to reduce risks from prematurity, until a fetal or maternal condition arises that mandates delivery.…”

“…6,7 PPROM occurs when the fetal membranes, which represent an anatomical and physiological barrier, rupture, thereby allowing uterine infections from the vagina to ascend and increasing the risk for chorioamnionitis, as found both clinically and upon pathology analysis. 7 The management approach to PPROM for women at <34 weeks of gestation includes administering antibiotics to increase latency and expectant management, to reduce risks from prematurity, until a fetal or maternal condition arises that mandates delivery. 8,9 Given that PPROM and neurodevelopmental delay are both associated with inflammation and infection, it is plausible that prolonged PPROM could be an independent risk factor for this condition; however, it is unknown whether extended latency in the setting of PPROM confers additional risk beyond delivery at the same gestational age with shorter latency.…”

Cefotaxime vs Ceftriaxone for the Management of Preterm Premature Rupture of Membranes

“…The incidence of PPROM is not only a problem when it causes preterm labor. Women with prolonged PPROM are at higher risk for developing chorioamnionitis, which can be obtained from an increase in bacterial colonization before membrane rupture (causing PPROM) or after membrane rupture (PPROM complications) [3,4]. The risk of infection increases with the decreasing gestational age when membrane rupture and the increasing duration of the ruptured membrane [3].…”