Cord Blood Interleukin-6 Research Articles

Two cases of Leukemoid reaction in premature infants caused by fetal inflammatory response syndrome

BackgroundFetal inflammatory response syndrome (FIRS) is a systemic inflammatory response caused by the activation of the fetal immune system. The serological diagnostic criterion for fetal inflammatory response syndrome is a cord blood interleukin-6 concentration that exceeds 11 pg/mL, while pathologic evidence indicates the presence of funisitis or chorionic vasculitis. It can affect all systems of the fetus. Alterations in patients’ hematopoietic system are primarily reflected by changes in peripheral blood leukocyte and neutrophil counts.Case presentationWe performed placental pathology to identify FIRS and showed two cases of neonatal leukemoid reaction caused by FIRS. These two babies’ alterations in hematopoietic system resolves spontaneously with the inflammation relief, without specific interventions. During the 16‑month and14- month follow‑up period, their motor and intellectual development was normal.Conclusions . Neonatal leukemoid reaction is a reactive disease characterized by abnormal blood parameters similar to those of leukemia, but not leukemia. It is an aberrant hematopoietic response that typically resolves spontaneously with cause relief without requiring specific interventions.

Soluble urokinase plasminogen activator receptor in vaginally collected amniotic fluid predicting fetal inflammatory response syndrome: a prospective cohort study

BackgroundImproving noninvasive antenatal diagnosis of fetal inflammatory response syndrome (FIRS) can assist in the evaluation of prenatal risk and reduce perinatal outcomes. This study aimed to determine whether soluble urokinase-type plasminogen activator receptor (suPAR) in vaginally collected amniotic fluid is significant in identifying FIRS after preterm premature rupture of membranes before 34 weeks of gestation.MethodsThis was a prospective cohort study of 114 pregnant women and their newborns after preterm premature rupture of membranes at 22–34+6 weeks of gestation. SuPAR was evaluated using an enzyme-linked immunosorbent assay in vaginally collected amniotic fluid. Patients were classified according to the presence or absence of FIRS. FIRS was defined by umbilical cord blood interleukin-6 level > 11 pg/mL or histological funisitis. The data were analyzed using the R package (R–4.0.5).ResultsSuPAR was detected in all amniotic fluid samples with a median of 26.23 ng/mL (interquartile range (IQR), 15.19–51.14). The median level of suPAR was higher in the FIRS group than in the non-FIRS group, 32.36 ng/mL (IQR, 17.27–84.16) vs. 20.46 ng/mL (IQR, 11.49–36.63) (P = 0.01), respectively. The presence of histological chorioamnionitis significantly increased the suPAR concentration in the FIRS group (P < 0.001). The areas under the curve for FIRS and FIRS with histological chorioamnionitis were 0.65 and 0.74, respectively, with an optimum cutoff value of 27.60 ng/mL. Controlling for gestational age, the cutoff of suPAR more than 27.60 ng/mL predicted threefold higher odds for FIRS and sixfold higher odds for FIRS with histologic chorioamnionitis.ConclusionSoluble urokinase-type plasminogen activator receptor in vaginally obtained amniotic fluid may assist in evaluating prenatal risk of FIRS in patients after preterm premature rupture of membranes before 34 weeks of gestation.

Machine learning predictive models for grading bronchopulmonary dysplasia: umbilical cord blood IL-6 as a biomarker.

This study aimed to analyze the predictive value of umbilical cord blood Interleukin-6 (UCB IL-6) for the severity-graded BPD and to establish machine learning (ML) predictive models in a Chinese population based on the 2019 NRN evidence-based guidelines. In this retrospective analysis, we included infants born with gestational age <32 weeks, who underwent UCB IL-6 testing within 24 h of admission to our NICU between 2020 and 2022. We collected their medical information encompassing the maternal, perinatal, and early neonatal phases. Furthermore, we classified the grade of BPD according to the 2019 NRN evidence-based guidelines. The correlation between UCB IL-6 and the grades of BPD was analyzed. Univariate analysis and ordinal logistic regression were employed to identify risk factors, followed by the development of ML predictive models based on XGBoost, CatBoost, LightGBM, and Random Forest. The AUROC was used to evaluate the diagnostic value of each model. Besides, we generated feature importance distribution plots based on SHAP values to emphasize the significance of UCB IL-6 in the models. The study ultimately enrolled 414 preterm infants, with No BPD group (n = 309), Grade 1 BPD group (n = 73), and Grade 2-3 BPD group (n = 32). The levels of UCB IL-6 increased with the grades of BPD. UCB IL-6 demonstrated clinical significance in predicting various grades of BPD, particularly in distinguishing Grade 2-3 BPD patients, with an AUROC of 0.815 (95% CI: 0.753-0.877). All four ML models, XGBoost, CatBoost, LightGBM, and Random Forest, exhibited Micro-average AUROC values of 0.841, 0.870, 0.851, and 0.878, respectively. Notably, UCB IL-6 consistently appeared as the most prominent feature across the feature importance distribution plots in all four models. UCB IL-6 significantly contributes to predicting severity-graded BPD, especially in grade 2-3 BPD. Through the development of four ML predictive models, we highlighted UCB IL-6's importance.

Diagnostic accuracy of amniotic fluid interleukin‐6 for fetal inflammatory response syndrome

This study aimed to clarify the diagnostic accuracy of amniotic fluid interleukin-6 for fetal inflammatory response syndrome (FIRS). This retrospective cohort study was conducted in a single institution and targeted cases of preterm birth within 24 h after amniocentesis among singleton cases that underwent amniocentesis at our hospital for suspected intraamniotic inflammation (IAI) from gestational ages of 22-36 weeks between August 2014 and March 2020. FIRS was defined as >11.0pg/mL of umbilical cord blood interleukin-6. The analysis included 158 pregnant women. There was a strong correlation between amniotic fluid interleukin-6 and umbilical cord blood interleukin-6 (r=0.70, p < 0.001). The area under the receiver operating characteristic curve of amniotic fluid interleukin-6 for FIRS was 0.93, with a cutoff value of 15.5ng/mL, and showed high sensitivity and specificity (0.91 and 0.88, respectively). An amniotic fluid interleukin-6 cutoff value of ≥15.5ng/mL was associated with a significant risk of FIRS (adjusted odds ratio: 27.9; 95% confidence interval: 6.3-123.0; p < 0.001). The results of this study show that amniotic interleukin 6 alone can be used to diagnose FIRS prenatally. While there is a need for validation, it may be possible to treat IAI while preventing damage to the central nervous and respiratory systems in the uterus by keeping the amniotic fluid interleukin-6 below the cutoff value.

Antepartum periodontitis treatment and risk of offspring screening positive for autism spectrum disorder.

To evaluate if treating maternal periodontal disease, a pro-inflammatory condition, during pregnancy (intervention) compared to after pregnancy (control) reduces the likelihood of offspring screening positive for autism spectrum disorder (ASD). In a follow-up study to the MOTOR randomized trial, we compared rates of positive screens on the Modified Checklist for Autism in Toddlers (M-CHAT) among n = 306 two-year-old toddlers and correlated findings to maternal and cord blood pro-inflammatory interleukin-6 (IL-6). Toddlers in the intervention group had decreased risk of a positive M-CHAT screen (adjusted RR = 0.53, 95% CI 0.29-0.99). Toddlers screening positive compared to negative had higher mean IL-6 in cord blood (1.58 ± 1.14 vs. 1.09 ± 0.72 p = 0.001) and maternal IL-6 change from baseline (1.30 ± 0.61 vs 0.96 ± 0.62 p = 0.03). Treating periodontal disease during pregnancy reduced risk of a positive ASD screen. M-CHAT positivity was associated with increased IL-6 in maternal and cord blood. Trial Registration numbers: Clinicaltrials.gov NCT03423836.

Umbilical cord blood interleukin-6 level as a predictor of early-onset neonatal sepsis

&#x0D; &#x0D; Background Neonatal sepsis is a global health problem contributing significantly to neonatal morbidity and mortality. It is difficult to clinically distinguish neonates with and without sepsis. Interleukin-6 (IL-6) concentration in neonates has high sensitivity and specificity to predict neonatal sepsis in infants at risk.&#x0D; Objective To determine the utility of umbilical cord blood IL-6 as a predictor of early-onset neonatal sepsis.&#x0D; Methods This prospective cohort study was conducted in neonates born to mothers with sepsis risk factors from December 2020 to January 2021. We measured IL-6 from umbilical cord blood taken after placental expulsion. IL-6 ³16.4 pg/ml was considered to be elevated. Subjects were monitored for signs of clinical sepsis until 72 hours after birth. We also recorded the presence of other maternal and infant risk factors of sepsis and assessed association between IL-6 and other risk factors with the occurrence of sepsis, expressed as relative risk (RR) with 95% confidence interval (95%CI).&#x0D; Results During the study period, 40 neonates were born to mothers with sepsis risk factors; 13 (32.5%) developed clinical sepsis. Significantly more infants with elevated IL-6 developed neonatal sepsis (55.5%) than those with normal IL-6 (13.6%). After multivariate analysis incorporating other significant variables, the risk factors predictive of clinical early-onset neonatal sepsis were IL-6 [RR 5.54 (95%CI 1.68-18.25); P=0.016], prematurity [RR 4.92 (95%CI 1.66-14.59); P=0.014], and initial Apgar score [RR 3.38 (95%CI 1.34-3.38); P=0.046].&#x0D; Conclusion In neonates with maternal risk factors, an IL-6 level of ³16.4 pg/ml is associated with an increased risk of early-onset neonatal sepsis.

The significance of TNF-α and MMP-8 concentrations in non-invasively obtained amniotic fluid predicting fetal inflammatory response syndrome.

To determine the significance of tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-8 (MMP-8) in vaginally obtained amniotic fluid predicting fetal inflammatory response syndrome (FIRS) after preterm premature rupture of membranes (PPROM). In this prospective case-control study, TNF-α and MMP-8 concentrations were evaluated in vaginally obtained amniotic fluid from women with PPROM at 22-34 weeks of pregnancy. Biomarkers' concentrations were determined using an enzyme-linked immunosorbent assay. Patients were divided into two groups: the FIRS group (cord blood interleukin-6> 11 pg/ml or histological funisitis) and the non-FIRS group (without these findings). The data were analyzed using R package (R-4.0.5). The median TNF-α and MMP-8 concentrations in amniotic fluid from the 145 women included in the study were higher in the FIRS group than in the non-FIRS group. The area under the curve of TNF-α and MMP-8 was 0.77 and 0.75, respectively. The TNF-α concentration cut-off predicting FIRS was 89.20 pg/ml and was 170.76 pg/ml for MMP-8. In regression analysis, MMP-8 concentration was an independent predictor for FIRS. An MMP-8 concentration greater than 170 ng/ml and a TNF-α concentration greater than 89 pg/ml increased the odds of FIRS 7.62 and 14.92 times, respectively. MMP-8 and TNF-α concentrations in vaginally obtained amniotic fluid may be good predictors for FIRS after PPROM before 34 weeks of pregnancy. The non-invasive amniotic fluid analysis could be an alternative method to invasive amniocentesis.

Cord blood antimicrobial peptide LL37 levels in preterm neonates and association with preterm complications

BackgroundCathelicidin/LL-37 plays a significant role in the human immune defense reaction. Preterm human immature organs being exposed to inflammation-induced injury was the critical denominator leading to the common preterm associated complications. Previous study showed LL37 concentration in preterm neonates was lower in tracheal aspirates and breast milk as compared to term infants. An adults study showed decreased LL-37 levels was a risk factor for patients in developing severe chronic obstructive pulmonary disease (COPD). However, little is known about the regulation of human cord blood LL37 in preterm neonates and the association with preterm complications. This study was designed to investigate the concentration of LL37 in cord blood of preterm infants and correlation with preterm complications.MethodsSingleton infants born in June 2017 to August 2021 in the study hospital were enrolled. Maternal and neonatal clinical characteristics were collected. LL37 levels, pro-inflammatory factor interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in cord blood and LL37 levels in serum 48–72 hours after birth were measured by enzyme-linked immunosorbent assay. The serum level of LL37 in preterm and term neonates were compared, the perinatal factors possibly affecting the LL37 levels were investigated and the relationship between LL37 level and preterm outcomes were analyzed.ResultsCord blood LL37 levels in preterm infants were lower than that in term neonates. Cord blood LL37 level was positively correlated with gestational age in preterm. Prenatal steroid administration in preterm neonates decreased cord blood LL37 level. LL37 level was obviously lower in patients with bronchopulmonary dysplasia (BPD). Multiple line regression analysis showed higher LL37 level in cord blood was an independent protective factor for BPD. The concentration of pro-inflammatory factor IL-6 was negatively correlated with LL37.ConclusionCord blood LL37 levels increased during gestation and decreased after perinatal steroid usage. Very preterm infants who displayed higher cord blood LL37 level had reduced risk of developing BPD. Regulation of pro-inflammatory cytokine IL-6 may be associated with the protective effect of LL37 on BPD.

Reduced fetal urine production rate-An early marker of fetal inflammatory response syndrome in preterm premature rupture of membranes: Prospective cohort study.

To find association between fetal urine production rate (FUPR) and fetal inflammatory response syndrome (FIRS) in preterm premature rupture of membranes (PPROM). A prospective cohort study of 70 pregnant women with PPROM at 28-34weeks of pregnancy was conducted. FUPR was calculated by performing serial fetal bladder volume measurements ultrasonographically and was repeated weekly until delivery. After delivery, cord blood interleukin-6 (IL-6) levels were measured. Placental tissue histopathology was performed and neonatal outcomes were noted. Out of 70 recruited patients with PPROM, 44 had evidence of FIRS (62.86%). Mean FUPR at the time of delivery was significantly reduced in neonates with evidence of FIRS compared with the Non-FIRS group (13.89±8.06ml/h vs. 25.89±4.94ml/h). Out of 41 patients with reduced FUPR, 39 neonates had FIRS whereas only five out of 29 neonates with normal FUPR had FIRS (P<0.001). Severe neonatal morbidity was found in 24 out of 41 (58.54%) neonates with reduced FUPR prenatally. The occurrence of respiratory distress syndrome, necrotizing enterocolitis, and sepsis was significantly high in neonates with reduced FUPR. Reduced FUPR is strongly associated with FIRS in cases of PPROM and hence can be used as an early predictor of adverse neonatal outcomes.

Does maternal SARS-CoV-2 infection or SARS-CoV-2 vaccination trigger an inflammatory response in the fetus?

SARS-CoV-2 infection triggers a significant maternal inflammatory response. There is a dearth of data regarding whether maternal SARS-CoV-2 infection or SARS-CoV-2 vaccination triggers an inflammatory response in the fetus. Fetal Inflammatory Response Syndrome (FIRS) has been described in other clinical conditions such as intraamniotic infection and has been defined as a cord blood Interleukin-6 (IL-6) level > 11 pg/ml. The objective of the study is to evaluate Il-6 levels in the cord blood of three delivering women: SARS-CoV-2 infection group, SARS-CoV-2 vaccinated group, and a control group.

Maternal psychiatric status and infant wheezing: The role of maternal hormones and cord blood cytokines.

Maternal psychosocial stress might be associated with development of allergic diseases in the offspring. To evaluate the association of maternal depression and anxiety with ever wheezing and recurrent wheezing among infants and to assess the role of maternal hypothalamo-pituatary-adrenal axis changes and fetal immune response in this association. This study encompasses two designs; cohort design was developed to evaluate the association of prenatal depression with development of wheezing in infants while nested case-control design was used to assess the role of maternal cortisol and tetranectin and cord blood interleukin 13and interferon γ. We enrolled 697 pregnant women. Elementary school graduate mother (odds ratio [OR] = 1.5, p = .06), maternal smoking during pregnancy (OR = 3.4, p = .001), familial history of asthma (OR = 2.7, p < .001) increased the risk of ever wheezing. Elementary school graduate mother (OR = 2.6, p = .002), maternal smoking during pregnancy (OR = 4.8, p < .001) and familial history of asthma (OR = 1.7, p = .01) increased the risk of recurrent wheezing. Maternal previous psychiatric disease, or Edinburgh Postnatal Depression Scale or Spielberger State-Trait Anxiety Inventory scores were not associated with wheezing. Maternal tetranectin levels were significantly higher among never wheezers compared to the ever wheezers (264.3 ± 274.8 vs. 201.6 ± 299.7, p = .04). In conclusion, the major risk factors for ever wheezing and recurrent wheezing were maternal smoking, level of education and family history of asthma. However, maternal depression and anxiety were not determined as risk factors for wheezing. Maternal tetranectin carries potential as a biomarker for wheezing in the infant.

IL-6 Predicts Poor Early Post-Natal Growth in Very Low-Birth-Weight Infants in a Low-Middle Income Setting.

Extra-uterine growth restriction (EUGR) is common in preterms and may be associated with elevated pro-inflammatory cytokines. Describe postnatal growth in a cohort of very low-birth-weight (VLBW) infants and determine the association of interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) in umbilical cord blood with growth at 40 weeks and 12 months postmenstrual age (PMA). Single-centre, prospective cohort study conducted from 1 June 2017 to 31 January 2019 with follow-up to 31 March 2020. Infants <1500 g at birth were enrolled, cord blood collected for IL-6 and TNF-α assays and postnatal care, including anthropometry, provided to 12 months PMA. Informed consent and ethics approval were obtained. In total, 279 patients were enrolled; 84 (30.1%) died before 12 months and 91 (32.6%) lost to follow-up. Anthropometry was available for 151 infants at 40 weeks and 105 at 12 months. Z-Scores at 40 weeks for males and females combined were -2.5, -2.1 and -1.2 for weight, length and head circumference. EUGR occurred in 103/113 (91.2%), 98/107 (91.6%) and 70/109 (64.2%) participants for weight, length and head circumference. Elevated IL-6 was associated with restricted weight (56.0 vs. 14.5 pg/ml, p = 0.02) and length (60.4 vs. 7.3 pg/ml, p = 0.01) at 40 weeks. There was no difference in IL-6 at 12 months and no difference in TNF-α at 40 weeks or 12 months. The study reports significant EUGR. Elevated IL-6 was associated with growth restriction at 40 weeks but not 12 months PMA.

Increased Levels of Umbilical Cord Blood Interleukin-6 (IL-6) and Serum C-Reactive Protein (CRP) in Premature Infants of Vitamin D Deficient Mothers

Objective: Increased levels of inflammatory factors in newborns are often associated with lower maternal vitamin D levels. This study aimed to find out the relationship between maternal and umbilical cord vitamin D serum levels on umbilical cord Interleukin-6 (IL-6) and serum C-Reactive Protein (CRP) levels in premature infants.Methods: The study was an observational analytic, cross-sectional design in mothers who underwent preterm birth at 28-34 weeks' gestation due to premature rupture of membranes (PROM) and their infants at Dr. Cipto Mangunkusumo General Hospital (RSCM), Jakarta and Persahabatan General Hospital, Jakarta, from January 2017 to August 2018. Levels of serum vitamin D of the maternal and umbilical cord, umbilical cord IL-6 and serum CRP in premature infants were recorded. Vitamin D level was divided into deficiency (&lt;10 ng/mL), insufficiency (10–29 ng/mL), and normal (&gt;30 ng/mL) groups. The relationship of vitamin D levels with IL-6 and CRP was carried out using Kruskal Wallis test.Results: A total of 70 subjects met the research criteria. Umbilical cord IL-6 and serum CRP levels in premature infants of vitamin D deficient mothers were higher (20.31 pg/mL and 0.50 mg/L) compared to insufficient (3.34 pg/mL and 0.45 mg/L) and normal mothers (3.29 pg/mL and 0.30 mg/L), although not statistically significant (IL-6 p = 0.665, CRP p = 0.89). Referring to the umbilical cord blood vitamin D levels, the results were different and not as expected, in which the umbilical cord IL-6 and serum CRP levels of preterm infants in the deficiency (3.76 pg/mL and 0.35 mg/L) and insufficiency (3.37 pg/mL and 0.40 mg/L) groups were lower (IL-6) and not different (CRP) than the normal group (9.41 pg/mL and 0.40 mg/L).Conclusion: There were an increasing tendency for umbilical cord IL-6 and serum CRP levels in premature infants of vitamin D deficient mothers although these were not statistically significant. Based on the levels of vitamin D umbilical cord blood, the CRP levels in the serum of premature infants were not different, while the IL-6 levels in the deficiency and insufficiency group were lower than in the normal group.Keywords: CRP, IL-6, maternal vitamin D, umbilical cord vitamin D.&#x0D; &#x0D; Abstrak&#x0D; Tujuan: Peningkatan kadar faktor inflamasi pada bayi baru lahir sering dikaitkan dengan rendahnya kadar vitamin D ibu. Penelitian ini bertujuan untuk mengetahui hubungan kadar serum vitamin D ibu dan tali pusat, dengan kadar IL-6 tali pusat dan serum C-Reactive Protein (CRP) bayi prematur.Metode: Studi observasional analitik dengan desain potong lintang pada subjek ibu yang mengalami kelahiran prematur di usia 28–34 minggu kehamilan disebabkan ketuban pecah dan bayi yang dilahirkannya, di Rumah Sakit Umum Pusat Nasional dr. Cipto Mangunkusumo (RSCM) dan Rumah Sakit Umum Pusat Persahabatan, Jakarta, pada bulan Januari 2017 sampai Agustus 2018. Variabel data adalah kadar serum vitamin D ibu dan tali pusat, kadar serum IL-6 tali pusat dan kadar CRP darah bayi. Kadar vitamin D (25(OH)D) dibagi menjadi defisiensi (&lt;10 ng/mL), insufisiensi (10–29 ng/mL) dan normal (&gt;30 ng/mL) dan dicari hubungannya dengan kadar IL-6 tali pusat dan serum CRP bayi prematur, menggunakan uji Kruskal Wallis. Hasil: Sebanyak 70 subjek telah memenuhi kriteria penelitian. Kadar IL-6 tali pusat dan serum CRP bayi prematur dari kelompok ibu defisiensi vitamin D (20,31 pg/ml dan 0,50 mg/L) lebih tinggi dibandingkan kelompok ibu insufisiensi vitamin D (3,34 pg/mL dan 0,45 mg/L) maupun kelompok ibu normal vitamin D (3,29 pg/mL dan 0,30 mg/L) tetapi perbedaan tersebut tidak bermakna (IL-6 p=0,665 dan CRP p = 0,899). Mengacu pada kadar vitamin D darah tali pusat didapatkan hasil yang berbeda dan tidak sesuai harapan, dimana tali pusat IL-6 dan serum CRP bayi prematur mengalami defisiensi (3,76 pg / mL dan 0,35 mg / L) dan insufisiensi. (3,37 pg / mL dan 0,40 mg / L) kelompok lebih rendah (IL-6) dan tidak berbeda (CRP) dibandingkan kelompok normal (9,41 pg / mL dan 0,40 mg / L).Kesimpulan: Didapat kecenderungan peningkatan kadar IL-6 darah tali pusat dan serum CRP bayi prematur dari ibu dengan defisiensi kadar vitamin D walaupun secara statistik tidak signifikan. Berdasarkan kelompok vitamin D darah tali pusat, kadar CRP serum bayi prematur tidak berbeda, sedangkan kadar IL-6 pada kelompok defisiensi dan insufisiensi lebih rendah dibandingkan pada kelompok normal.Kata kunci: CRP, IL-6, vitamin D ibu, vitamin D tali pusat. &#x0D;

Maternal risk score for the prediction of fetal inflammatory response syndrome after preterm premature rupture of membranes.

Preterm premature rupture of membranes (PPROM) is common in preterm births. Fetal inflammatory response syndrome (FIRS) is present in nearly 50% of PPROM cases. We created a risk score to predict FIRS using maternal factors after PPROM. We conducted a retrospective study of singleton pregnancies complicated by PPROM that resulted in delivery at 23-35 weeks of gestation. Antepartum maternal factors and umbilical cord blood interleukin-6 (IL-6) data were analyzed. FIRS was defined as IL-6 > 11 pg/mL. Umbilical cord blood IL-6 and maternal blood data within 24 h before parturition were available for 158 cases; 66 were diagnosed with FIRS (41.8%; median IL-6, 57.55 pg/mL). We created a risk score (FIRS score) comprising expected delivery weeks (≤30 weeks), maternal C-reactive protein (≥1.2 mg/dL), maternal white blood cell count (≥13 000/μL), corticosteroid use (none) and PROM latency period (≥3 days) from the multivariate logistic regression model predicting FIRS. Receiver operating characteristic curve analysis of the score produced the following results: area under the curve, 0.82; 95% CI, 0.76-0.89; cut-off value, 7.5; sensitivity, 89%; specificity, 63%; positive predictive value, 63% and negative predictive value, 89%. The probability of FIRS according to the categories of the FIRS score was 11% for those with a score of 0-7, 50% for a score of 8-15, and 88% for a score of 16-22. The devised maternal risk score could predict FIRS and be helpful to decide the delivery timing for the cases of PPROM.

Fetal Inflammatory Response Syndrome and Cerebral Oxygenation During Immediate Postnatal Transition in Preterm Neonates.

Introduction: Fetal inflammatory response syndrome (FIRS), defined as elevated umbilical cord blood interleukin-6 (IL-6) values > 11 pg/ml, is associated with an increased risk of neonatal morbidity and mortality. The primary aim of the present study was to evaluate a potential influence of FIRS on cerebral oxygen saturation (crSO2) and fractional tissue oxygen extraction (cFTOE) during immediate postnatal transition in preterm neonates. The secondary aim was to analyze the potential influence of FIRS on cerebral injury and mortality.Methods: Secondary outcome parameters of prospective observational studies were analyzed. Preterm neonates with measured IL-6 values from umbilical cord blood and cerebral near-infrared spectroscopy (NIRS) measurements during immediate transition after birth were included. Preterm neonates with FIRS (FIRS group) were matched 1:1 for gestational age (± 1 week) to preterm neonates without FIRS (non-FIRS group). crSO2, cFTOE, arterial oxygen saturation (SpO2), heart rate (HR), and fraction of inspired oxygen (FiO2) were compared between both groups. In addition, cerebral injury and mortality were compared between both groups.Results: A total of 46 preterm neonates were included. Twenty-three neonates in the FIRS group [median gestational age 32.1 (IQR 30.3–33.0) weeks; median IL-6 19.7 (IQR 12.2–37.0) pg/ml] were compared to 23 neonates in the non-FIRS group [gestational age: 32.0 (30.4–33.1) weeks; IL-6: 5.4 (3.0–6.7) pg/ml]. cFTOE showed significantly lower values within the first 4 min and a trend toward lower values in minute 5 after birth in the FIRS group. There were no significant differences in crSO2 within the first 15 min after birth between the two groups. SpO2 was significantly lower in minutes 5 and 6 and HR was significantly lower in minutes 2 and 4 after birth in the FIRS group compared to the non-FIRS group. Survival without cerebral injury was similar in both groups.Conclusion: In preterm neonates with FIRS the crSO2 was similar despite significantly lower cFTOE values during the first minutes after birth. This observation may be a result of compromised oxygen consumption and delivery in the first minutes after birth in neonates with FIRS.

Umbilical Blood Levels of IL-6 and TNF-α as Predictors of the Central Nervous System Damage and Retinopathy in Preterm Infants.

The aim was to identify the critical levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor-A in umbilical cord blood that could be used as markers for predicting the central nervous system (CNS) damage and retinopathy of prematurity (ROP) in preterm infants. A total of 158 preterm infants, born at 22 to 34 weeks of gestation, were evaluated in the first week after birth and at 36 to 37 weeks of postconceptual age. A significant relationship between CNS changes and concentrations of IL-6 (p < 0.001) and TNF-α (p < 0.001) in umbilical cord blood at 22 to 34 weeks of gestation was determined. The concentration of IL-6 >13.0 pg/mL predicts significant CNS damages in 36 to 37-week infants (p = 0.013). ROP was diagnosed in 24.8% infants (n = 149). It was detected that the levels of TNF-α >116.4 pg/mL (p < 0.001) and IL-6 >13.0 pg/mL (p < 0.05) in umbilical cord blood could predict 2 to 3/3 to 4 stages of ROP. Critical values of IL-6 and TNF-α in predicting ≥grade III intraventricular hemorrhage in the early adaptation and in predicting marked CNS damages and severe ROP stages in the later adaptation of preterm infants were determined.

Cord blood interleukin-6 as a predictor of early-onset sepsis in preterm babies

Cord blood interleukin-6 as a predictor of early-onset sepsis in preterm babies

Cord Blood Interleukin-6 as a Predictor of Early Onset Sepsis in High Risk Neonates

Introduction: The purpose of this study was to evaluate accuracy of cord blood interleukin-6 (IL-6) as an early marker of early onset neonatal sepsis (EOS) in neonates with maternal risk factors..Objectives: To evaluate accuracy of cord blood IL-6 as a predictor of early onset neonatal sepsis (EONS) in neonates with prenatal risk factors for sepsis.Patients and methods: The study included 80 neonates divided into two groups. Group(I) included 25 full-term and 25 preterm neonates. Group (II) included thirty healthy age and sex matched controls with mean gestational age 35.2±3.8. All patients were subjected to adequate history taking, full clinical examination, complete blood count, blood culture, cord blood interleukin-6 and serum high sensitive CRP for elevated IL-6 level.Results: IL-6 level was significantly higher in the group (I) compared with group(II). No significant correlation between gestational age and level of IL-6. The best cutoff value for serum interleukin-6 as a marker for early detection of neonatal sepsis is ≥50 pg/ml with sensitivity 96 % and specificity 100%.Conclusion: Cord blood IL-6 can be a sensitive predictor of early onset sepsis for neonates with high risk of sepsis.

Components of the antepartum, intrapartum, and postpartum exposome impact on distinct short-term adverse neonatal outcomes of premature infants: A prospective cohort study.

We aimed to test the hypothesis that determinants of the perinatal clinical exposome related to the underlying etiology of premature birth (PTB) impact differently on select neonatal outcomes. We conducted a prospective longitudinal study of 377 singleton preterm neonates [gestational age (GA) at birth: 23–34 weeks] separated into three distinct contemporaneous newborn cohorts: i) spontaneous PTB in the setting of intra-amniotic infection/inflammation (yes-IAI, n = 116); ii) spontaneous PTB in the absence of IAI (no-IAI, n = 130), and iii) iatrogenic PTB for preeclampsia (iPTB-PE, n = 131). Newborns (n = 372) were followed until death or discharge. Amniotic fluid defensins 1&2 and calgranulins A&C were used as biomarkers of IAI. An algorithm considering cord blood interleukin-6 (IL-6) and haptoglobin (Hp switch-on) was used to assess fetal exposure to IAI. Intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), early-onset neonatal (EONS) and late-onset (LOS) sepsis, death. Independent risk factors for adverse outcomes were: i) IVH (n = 53): histologic chorioamnionitis, GA, fetal growth restriction, male sex, Hp switch-on; ii) PVL (n = 11): cord blood IL-6; iii) NEC (n = 25), GA; iv) BPD (n = 53): ventilator support, need for surfactant, GA; v) ROP (n = 79): ventilator support, Hp switch-on, GA; vi) fetal and neonatal death (n = 31): GA, amniotic fluid IL-6; vii) suspect EONS (n = 92): GA, Hp switch-on; viii) LOS (n = 81): GA. Our findings are applicable to pregnancies delivered between 23 and 34 weeks’ gestation in the setting of IAI and PE, and suggest that GA and inflammatory intrauterine environment play key roles in occurrence of IVH, PVL, ROP, death, EONS and LOS. Postnatal determinants seem to play major role in NEC and BPD.

Maternal Epidural Steroids to Prevent Neonatal Exposure to Hyperthermia and Inflammation.

Epidural analgesia is associated with a fourfold increased rate of intrapartum fever. The likely pathophysiology is a noninfectious maternal inflammatory activation. Safe interventions to reduce maternal and neonatal exposures to intrapartum fever and inflammation are needed. The purpose of this study was to determine if prophylactic epidural steroids decrease fetal exposure to hyperthermia and inflammatory cytokines following epidural analgesia. This is a randomized, double-blinded, placebo controlled trial. Term nulliparous women requesting epidural analgesia received 80 mg methylprednisolone or preservative-free normal saline via the epidural catheter at placement. The primary outcome was maternal temperature >100.4°F. Secondary outcomes included fetal exposure to inflammation as assessed by cord blood interleukin-6 (IL-6) levels and rates of funisitis. Power analysis estimated a sample size requirement of 276, but new Food and Drug Administration (FDA) recommendations advising a black box warning on epidural steroids resulted in early study termination. A total of 116 subjects were enrolled: 58 treatments and 58 placebos. There was no difference in the rate of maternal intrapartum fever or cord blood IL-6 levels between treatment arms. No complications listed in the FDA warning occurred. Prophylactic epidural methylprednisolone was not effective in reducing intrapartum fever or neonatal inflammation following epidural analgesia. Alternate mechanisms and preventative strategies should be considered.