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 eventuful 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 acheived significnatly 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.

Keywords::

• Preterm delivery
• fetal inflammatory syndrome
• metabolomics
• amniocentesis
• intra amniotic inflammation
• tocolysis

Declaration of Interest: The authors received funding from Giorgio Pardi Reasearch Fundation to carry out the study, no other commercial relationships were relevant to the subject matter of the article. All participating authors declare no conflicts of interest relevant to the study.