Background The arsenal of maternal and amniotic fluid (AF) immune response to local or systemic infection includes among others the acute-phase reactants IL-6, C-reactive protein (CRP) and procalcitonin (PCT). If these molecules can be used as non-invasive biomarkers of intra-amniotic infection (IAI) in the subclinical phase of the disease remains incompletely known. Methods We used time-matched maternal serum, urine and AF from 100 pregnant women who had an amniocentesis to rule out IAI in the setting of preterm labor, PPROM or systemic inflammatory response (SIR: pyelonephritis, appendicitis, pneumonia) to infection. Cord blood was analyzed in a subgroup of cases. We used sensitive immunoassays to quantify the levels of inflammatory markers in the maternal blood, urine and AF compartment. Microbiological testing and placental pathology was used to establish infection and histological chorioamnionits. Results PCT was not a useful biomarker of IAI in any of the studied compartments. Maternal blood IL-6 and CRP levels were elevated in women with subclinical IAI. Compared to clinically manifest chorioamnionitis group, women with SIR have higher maternal blood IL-6 levels rendering some marginal diagnostic benefit for this condition. Urine was not a useful biological sample for assessment of IAI using either of these three inflammatory biomarkers. Conclusions In women with subclincal IAI, the large overlapping confidence intervals and different cut-offs for the maternal blood levels of IL-6, CRP and PCT likely make interpretation of their absolute values difficult for clinical decision-making.

Objective-To test the hypothesis that inflammation modulates fetal erythroblastosis and/or the release of NRBCs independent of hypoxia or fetal stress. We sought to determine if fetal inflammation is associated with an elevation in neonatal NRBC count in the setting of inflammation-associated preterm birth.Study Design-The relationships between peripheral NRBC count, histological chorioamnionitis, umbilical cord interleukin-6 (IL-6), erythropoietin (EPO), cortisol and acid-base status were analyzed in 68 preterm singletons, born to mothers who had an amniocentesis to rule out infection. Proteomic profiling of amniotic fluid identified presence of intra-amniotic inflammation according to established parameters. NRBC counts were assessed within 1-hour of birth. Early-onset neonatal sepsis (EONS) was established based on hematological and microbiological indices. IL-6, EPO and cortisol levels were measured by immunoassays. Fetal acid-base status was determined within 10 minutes of delivery. Parametric or nonparametric statistics was employed.Results-Fetuses with EONS (n=19) were delivered at earlier gestational ages (mean±SD: 27.1±2.8 weeks, P=0.001) and more often by mothers with intra-amniotic inflammation (P=0.022) and histological chorioamnionitis (P<0.001). Neonates with EONS had higher absolute NRBCs Condensation:In inflammation-associated preterm birth and in the absence of hypoxia, elevated neonatal nucleated red blood cell counts may be a direct response to inflammatory mediators. Authors' Contributions:Antonette Dulay is the principal investigator and responsible author. Antonette Dulay, Irina Buhimschi and Catalin Buhimschi designed the study, generated, interpreted the data and wrote the initial draft of the manuscript. Guomao Zhao participated with processing of biological samples, performed immunoassays, revised critically the manuscript and approved the final version. Vineet Bhandari participated with aspects of data analysis and interpretation, revised critically the manuscript and approved the final version. Guoyang Luo; Sonya Abdel-Razeq; Michael Cackovic, Victor Rosenberg, Christian Pettker Stephen Thung and Mert Ozan Bahtiyar participated with patient enrollment, acquisition of demographic and clinical data, critical revision of the manuscript and approved the final version. NIH Public AccessAuthor Manuscript Am J Obstet Gynecol. Author manuscript; available in PMC 2014 May 16. Published in final edited form as: Am J Obstet Gynecol. 2008 April ; 198(4): 426.e1-426.e9. doi:10.1016/j.ajog.2008 NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript counts (P=0.011). NRBC counts were directly correlated with cord blood IL-6 levels (P<0.001) but not with EPO, cortisol or parameters of acid-base status levels regardless of EONS status. These relationships remained following correction for gestational age, diabetes, intrauterine growth restriction (IUGR) and steroid exposure.Conclusion-In the setting of inflammation-associated preterm birth and in the absence of hypoxia,...

We sought to define the risk of neonatal respiratory distress syndrome (RDS) as a function of both lecithin/sphingomyelin (L/S) ratio and gestational age. Amniotic fluid L/S ratio data were collected from consecutive women undergoing amniocentesis for fetal lung maturity at Yale-New Haven Hospital from January 1998 to December 2004. Women were included in the study if they delivered a live-born, singleton, nonanomalous infant within 72 hours of amniocentesis. The probability of RDS was modeled using multivariate logistic regression with L/S ratio and gestational age as predictors. A total of 210 mother-neonate pairs (8 RDS, 202 non-RDS) met criteria for analysis. Both gestational age and L/S ratio were independent predictors of RDS. A probability of RDS of 3% or less was noted at an L/S ratio cutoff of ≥3.4 at 34 weeks, ≥2.6 at 36 weeks, ≥1.6 at 38 weeks, and ≥1.2 at term. Under 34 weeks of gestation, the prevalence of RDS was so high that a probability of 3% or less was not observed by this model. These data describe a means of stratifying the probability of neonatal RDS using both gestational age and the L/S ratio and may aid in clinical decision making concerning the timing of delivery.

Background: Several meta analyses have concluded n-3 fatty acids, including docosahexaenoic acid (DHA), reduce early preterm birth (EPB, < 34 weeks), however, the amount of DHA required is unclear. We hypothesized that 1000 mg DHA per day would be superior to 200 mg, the amount in most prenatal supplements. Methods: This randomised, multicentre, double-blind, adaptive-design, superiority trial was conducted in three USA medical centres. Women with singleton pregnancies and 12 to 20 weeks gestation were eligible. randomization was generated in SAS Ò by site in blocks of 4. The planned adaptive design periodically generated allocation ratios favoring the better performing dose. Managing study personnel were blind to treatment until 30 days after the last birth. The primary outcome was EPB by dose and by enrolment DHA status (low/high). Bayesian posterior probabilities (pp) were determined for planned efficacy and safety outcomes using intention-to-treat. The study is registered with ClinicalTrials.gov (NCT02626299) and closed to enrolment.

OBJECTIVE Pro-inflammatory cytokines of placental or systemic origin are thought to play a central role in the pathophysiology of preeclampsia. We sought to estimate the fractional excretion of tumor necrosis factor (TNF)-α in relationship to proteinuria in women with severe preeclampsia. METHODS In a cross-sectional study, we evaluated the serum and urine levels of TNF-α in 45 women diagnosed with severe preeclampsia (mean±SEM, gestational age: 29.1±0.5 weeks). Forty-five healthy pregnant control women matched for parity, maternal and gestational age at recruitment (30.1±0.4 weeks) served as control. Urinary concentrations were normalized to creatinine. The fractional excretion of the TNF-α was interpreted in relationship to those of total proteins and that of soluble fms-like tyrosine kinase-1 (sFlt-1). RESULTS We found that preeclamptic women had significantly higher serum TNF-α concentrations compared to controls (mean ± SEM, preeclampsia: 1.39±0.09 vs. control: 0.93±0.07 pg/mL, P<0.001). In contrast, urinary levels of TNF-α were significantly decreased in preeclampsia compared with healthy controls (median [interquartile range], preeclampsia: 0.26 [0.10–0.91] vs. control: 0.58 [0.21–1.29] pg/mg creatinine, P=0.003), even though the hypertensive women had higher levels of proteinuria. In contrast to sFlt-1, urinary TNF-α did not correlate with the degree of proteinuria. Additionally, in preeclampsia the fractional excretion of TNF-α was significantly lower (preeclampsia: 1.92 [0.46–4.20] vs. control: 7.2 [2.44–12.07] percent, P<0.001). CONCLUSION The fractional excretion of TNF-α is significantly reduced in women with severe preeclampsia, despite proteinuria. The decreased clearance and altered renal excretion of this cytokine may contribute to the exaggerated inflammatory response observed in preeclampsia.