Assessment of fetal inflammatory syndrome by “classical” markers in the management of preterm labor: a possible lesson from metabolomics and system biology

Abstract

There exists a huge gap between protocols issued by scientific bodies and evidence derived by system biology studies on the multifactorial origin of threatened preterm delivery and their different associations with neonatal outcome. The objective of this prospective study was the analysis obstetrical and neonatal outcome in a cohort of pregnant patients treated for the risk of preterm delivery according to maternal and fetal assessment determined by amniotic fluid samples. Methods. Threatened preterm delivery and premature rupture of membranes between 24 + 1 and 32 + 6 weeks of gestation were treated by prolonged tocolytic regimens and if necessary by antibiotics for maternal infections when intra-amniotic inflammation (IAI) was excluded on the basis of negative white blood cell count in the amniotic fluid, or opposite, by delivery after a course of betamethasone and 48 hours maintenance tocolysis. Twenty-three cases were compared with 22 historical controls treated by the same teams according to the 48 hours treat and wait criteria. In addition to this, cases with normal and abnormal amniotic fluid white blood cell were compared. Results. Maternal and fetal conditions at admission were not significantly different between the study and control cohort for all maternal and fetal variables. Clinical indices were significantly improved as regard to latency from admission to delivery, number of newborns admitted to neonatal intensive care unit and length of stay in neonatal intensive care unit. Not any perinatal death or sepsis occurred in the study cohort. Overall, improved neonatal outcomes were observed in the study cohort. Composite major neonatal eventful outcomes occurred in 26% of cases vs. 50% in controls. The limited number of cases was not powered enough to reach a statistical significance for these variables. Continued tocolysis on demand and full regimen of mono or combined antibiotic regimen for maternal infection achieved significantly longer delay between admission to delivery with improved in neonatal outcome in cases negative for IAI: only 2 of 14 newborns suffered of major neonatal complications vs. 4 of 9 newborns delivered for IAI. Conclusions. Fetuses without IAI can be treated conservatively and their stay in utero prolonged without harm. However, we confirmed that when IAI is already active in utero a worse neonatal outcome is already partly predetermined. These positive findings must be interpreted with cautions given the limited number of cases considered by this study.

Serum Amyloid A and Haptoglobin Concentrations are Increased in Plasma of Mares with Ascending Placentitis in the Absence of Changes in Peripheral Leukocyte Counts or Fibrinogen Concentration

“…However, the finding that placentitis induces changes in APP (i.e., SAA and Hp) concentrations opens a new field of investigation on the inflammatory response in mares with placentitis. In humans, APP (e.g., C‐reactive protein; CRP and Hp) have been focus of numerous publications involving infection of the placental and fetal tissues . Changes in concentrations of CRP in the systemic circulation of women suffering with chorioamnionitis have been demonstrated by several studies .…”

“…However, we believe that a controlled study was warranted to confirm clinical observations. In humans, controversy exists whether peripheral WBC and Fb are useful markers to assess placental diseases . Some reports suggest that WBC can also be assessed in the amniotic fluid in combination with cytokines to diagnose chorioamnionitis …”

“…Haptoglobin (Hp), a moderate APP, is constantly present in plasma of health horses, and concentrations are increased upon inflammation . Recent studies, involving human neonates, suggested that Hp is a useful marker for neonatal sepsis . In horses, Hp appeared to be a useful marker to evaluate acute–chronic conditions (i.e., >4‐day duration) .…”

A Bayesian Stepwise Discriminant Model for Predicting Risk Factors of Preterm Premature Rupture of Membranes

“…The etiologies of genital infection include Chlamydia trachomatis (CT), Ureaplasma urealyticum (UU), Candida albicans , syphilis, Neisseria gonorrhoea (NG), group B streptococci (GBS), herpes simplex virus (HSV), and bacterial vaginosis (BV). [ 1 2 ]…”

Infección materna, preeclampsia temprana y sepsis neonatal: ¿Secuencia o casualidad?

“…El diagnóstico clínico de la infección intrauterina es difícil y a menudo requiere laboratorio especializado para su evaluación. 36 Es conocido el alto riesgo de displasia broncopulmonar, hemorragia intraventricular y parálisis cerebral en esta población y aunque se considera la corioamnionitis como un fenómeno agudo, hay algunos estudios sugestivos de que podría tratarse de un proceso crónico. 37 Algunos investigadores han procurado identificar temprano las repercusiones neurológicas agudas de los pacientes expuestos a infección intrauterina 38 , pero no se dispone de un método de evaluación fiable, tampoco es posible predecir los efectos en el neurodesarrollo desde el período neonatal temprano.…”