Amniotic fluid interleukin-18 at mid-trimester genetic amniocentesis: relationship to intraamniotic microbial invasion and preterm delivery

Objective  To determine the value of amniotic fluid interleukin-18 (AF IL-18) in the diagnosis of microbial invasion of the amniotic cavity and prediction of preterm delivery (PTD).
Design  Analysis of the results of AF collected prospectively following genetic amniocentesis between February 2006 and September 2007.
Setting  A tertiary referral centre for fetal medicine.
Methods  Following amniocentesis, a sample of amniotic fluid was transferred to the laboratory for aerobic and anaerobic bacterial cultures, Ureaplasma urealyticum culture and IL-18 assays. All women who delivered preterm (<37 weeks of gestation) formed the study group. The control group consisted of the two subsequent women who also underwent amniocentesis during the same time period and delivered a normal neonate at term, matched for maternal age, parity and indication for amniocentesis.
Main outcome measures  The relationship between AF IL-18 levels and the risk of both microbial invasion of the amniotic cavity and PTD.
Results  Forty-eight women who delivered preterm (<37 weeks) were matched with 96 controls. The preterm delivery group had significantly higher concentrations of IL-18 (median = 609 pg/ml, interquartile range: 445.7–782.7) compared to controls (median = 322.1 pg/ml, interquartile range: 277.7–414.4), ( P  < 0.001). IL-18 level was also significantly higher ( P  < 0.001) in cases with positive amniotic fluid cultures (median = 697.7, interquartile range: 609.0–847.2) compared to those with negative ones (median = 330.9 pg/ml, interquartile range: 235.2–440.8).
Conclusions  Elevated mid-trimester concentrations of AF IL-18 can identify women at risk for intraamniotic infection and spontaneous PTD.     

Elevated amniotic fluid ferritin levels are associated with inflammation-related pregnancy loss following mid-trimester amniocentesis

Objective: Occult infection accounts for up to 12% of pregnancy losses following genetic amniocentesis. Elevated serum and cervical fluid levels of ferritin, an acute-phase reactant, have been associated with spontaneous preterm delivery. We determined the association between amniotic fluid (AF) ferritin levels and post-amniocentesis pregnancy loss. Methods: We performed a case-control study involving 66 women with a non-anomalous fetus who had a spontaneous pregnancy loss within 30 days following genetic amniocentesis and 66 term controls matched for maternal age, gestational age, time of test and indication for amniocentesis. Amniotic fluid ferritin and interleukin-6 (IL-6) levels were measured using commercially available kits. Results: Mean (± SD) AF ferritin levels were similar between the cases (19.3 ± 21.4 ng/ml) and the controls (19.8 ± 22.7 ng/ml) (p = 0.9). Mean (± SD) AF IL-6 levels were significantly higher in the women with post-amniocentesis pregnancy loss (4.0 ± 13.1 ng/ml) than in controls (0.5 ± 0.7 ng/ml) (p = 0.04). A significant proportion (12.1%, 8/66) of the women with postamniocentesis pregnancy loss had elevated amniotic fluid IL-6 levels (> 3 SD, 2.5 ng/ml) indicating inflammation, as compared to none in the control group (p = 0.01). In this subgroup of women with pregnancy loss and elevated IL-6 levels, AF ferritin levels were significantly elevated (52.0 ± 45.5 ng/ml) compared to the level in women who had a term delivery (19.8 ± 22.7 ng/ml) (p = 0.002), and were strongly correlated with IL-6 levels among the cases (r = 0.67, p < 0.001). Conclusion: The strong correlation of AF ferritin with IL-6 levels, along with the high ferritin values in cases with high AF IL-6, indicates that ferritin is a marker of inflammation in asymptomatic women destined to have an early pregnancy loss.     

A rapid interleukin-6 bedside test for the identification of intra-amniotic inflammation in preterm labor with intact membranes

Objective: Preterm birth is associated with 5–18% of pregnancies and is the leading cause of neonatal morbidity and mortality. Amniotic fluid (AF) interleukin-6 (IL-6) is a key cytokine for the identification of intra-amniotic inflammation, and patients with an elevated AF IL-6 are at risk for impending preterm delivery. However, results of the conventional method of measurement (enzyme-linked immunosorbent assay; ELISA) are usually not available in time to inform care. The objective of this study was to determine whether a point of care (POC) test or lateral-flow-based immunoassay for measurement of AF IL-6 concentrations can identify patients with intra-amniotic inflammation and/or infection and those destined to deliver spontaneously before term among women with preterm labor and intact membranes.

Methods: One-hundred thirty-six women with singleton pregnancies who presented with symptoms of preterm labor and underwent amniocentesis were included in this study. Amniocentesis was performed at the time of diagnosis of preterm labor. AF Gram stain and AF white blood cell counts were determined. Microbial invasion of the amniotic cavity (MIAC) was defined according to the results of AF culture (aerobic and anaerobic as well as genital mycoplasmas). AF IL-6 concentrations were determined by both lateral flow-based immunoassay and ELISA. The primary outcome was intra-amniotic inflammation, defined as AF ELISA IL-6?≥?2600?pg/ml.

Results: (1) AF IL-6 concentrations determined by a POC test have high sensitivity (93%), specificity (91%) and a positive likelihood ratio of 10 for the identification of intra-amniotic inflammation by using a threshold of 745?pg/ml; (2) the POC test and ELISA for IL-6 perform similarly in the identification of MIAC, acute inflammatory lesions of placenta and patients at risk of impending spontaneous preterm delivery.

Conclusion: A POC AF IL-6 test can identify intra-amniotic inflammation in women who present with preterm labor and intact membranes and those who will subsequently deliver spontaneously before 34 weeks of gestation. Results can be available within 20?min – this has important clinical implications and opens avenues for early diagnosis as well as treatment of intra-amniotic inflammation/infection.     

Maternal cytokines and disease severity influence pregnancy outcomes in women with rheumatoid arthritis

Objectives: To assess the influence of maternal cytokine levels, disease activity and severity on preterm delivery, small for gestational age (SGA) and cesarean delivery in pregnant women with rheumatoid arthritis (RA).

Methods: A prospective study in 47 pregnant women with RA and 22 healthy pregnant controls. The main outcome measures were birth weight in relation to maternal serum levels of interleukin-6 (IL-6), interleukin-10 (IL-10), and RA activity and severity at three different time points: preconception and during the first and third trimesters.

Results: During the third trimester, IL-10 was detectable in 23.4% of patients with RA, IL-6 in 76.6%. Mean birth weight born to mothers with RA was higher when IL-10 level was high compared with low (p?=?0.001), and lower when IL-6 was high compared with low (p?=?0.035). Also increase in disease activity score-28 (in 60.1%, p?=?0.001), Health Assessment Questionnaire–Disability Index (in 87.5%, p?=?0.013), and pain score (56.9?±?11.4, p?=?0.003) associated with increased risk of SGA. High patient’s global scale was associated with unfavorable pregnancy outcome (preterm, SGA, and cesarean).

Conclusion: High maternal IL-10 levels are associated with higher birth weight and high IL-6 levels are associated with lower birth weight (SGA). Among women with RA, disease activity and severity are predictive of unfavorable pregnancy outcomes suggesting that better disease management early in the pregnancy could improve pregnancy outcomes.     

Evaluation of amniotic fluid cytokines in preterm labor and intact membranes.

OBJECTIVE: To compare the amniotic fluid (AF) concentration of pro-inflammatory cytokines between women with preterm labor and intact membranes that delivered within 7 days, with those that delivered after 7 days of the amniocentesis according to the result of the AF culture. METHODS: Fifty-two women with preterm labor and intact membranes between 21 and 35 weeks of gestation were included in the study. Transabdominal amniocentesis was performed to rule out intra-amniotic infection, and AF concentrations of interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor (TNF) were determined with sensitive and specific enzyme-linked immunosorbent assays. Amniotic fluid was cultured for aerobic and anaerobic bacteria, Ureaplasma urealyticum, and Mycoplasma hominis. Exclusion criteria included preterm premature rupture of membranes, vaginal bleeding, multiple gestations, uterine anomalies, fetal congenital anomalies, ominous fetal heart rate tracings and fetal deaths. Proportions were compared using chi2 or Fisher's exact test. Receiver operator characteristic (ROC) curve analysis was performed for each cytokine for the prediction of delivery within 7 days. RESULTS: Sixty-two percent (32/52) of women delivered within 7 days and 38% (20/52) delivered after 7 days of amniocentesis. All women that delivered after 7 days of the procedure had negative AF cultures. In contrast, 28% (9/32) of women that delivered within 7 days had positive AF cultures and 72% (23/32) had negative AF cultures. Women that delivered within 7 days regardless of AF cultures had a lower birth weight and a shorter amniocentesis-to-delivery interval than those that delivered after 7 days of amniocentesis. Among women that delivered within 7 days, those with positive AF cultures had a lower gestational age at delivery and a higher frequency of histologic chorioamnionitis than those with negative AF cultures. The AF concentrations of all cytokines were significantly higher in women that delivered within 7 days with positive AF cultures than in those with negative AF cultures. Similarly, the AF concentrations of IL-1alpha, IL-6, and IL-8 were significantly higher in women that delivered within 7 days than those that delivered after 7 days of the amniocentesis, regardless of the AF culture results. Diagnostic indexes were calculated for all cytokines using critical values derived from ROC curve analysis for the prediction of delivery within 7 days. CONCLUSIONS: Women with preterm labor and intact membranes that delivered within 7 days had higher AF concentrations of pro-inflammatory cytokines than those who delivered after 7 days of the amniocentesis regardless of the AF culture results.     

Will cervicovaginal interleukin-6 combined with fetal fibronectin testing improve the prediction of preterm delivery?

Objective: We sought to investigate if determination of cervicovaginal interleukin-6 (IL-6) levels would enhance the positive predictive value of fetal fibronectin (fFN) for preterm birth.

Methods: A prospective cohort study was undertaken of 135 women between 24 and 34 weeks gestation with symptoms of suspected preterm labor. Cervicovaginal secretions were collected for both IL-6 and fFN and measured by immunoassay and ELISA, respectively. Outcome variables included preterm delivery in less than 48 h, within 7 days, and prior to 37 weeks. Statistical analysis was performed with Fisher's exact test, regression for logarithmic transform levels, and multivariate logistic regression. ROC curves were created for IL-6 levels.

Results: IL-6 and fFN levels were both elevated in cervicovaginal secretions of women with symptoms of preterm labor. IL-6 values > 100 pg/ml resulted in a odds ratio for delivery at < 37 weeks of 1.57 (95%CI = 0.89–2.75, P =. 11), whereas fFN values > 50 ng/ml resulted in a preterm delivery risk of 4.58 (95%CI = 154–13.35, P =. 003). Combining IL-6 and fFN results did not improve upon the predictive value of fFN alone for preterm birth [odds ratio 4.00 (95%CI = 1.31–12.17, P =. 015)].

Conclusion: Cervicovaginal IL-6 levels did not provide any additional, independent effect on the prediction of preterm birth beyond that of fFN testing alone.     

The negative predictive value of cervical interleukin-6 for the risk assessment of preterm birth

Abstract

Objective: To determine the potential clinical use of cervical interleukin-6 (IL-6) as a negative predictor of preterm birth in symptomatic women.

Study design: Observational prospective study carried out in a tertiary hospital.

Patients and methods: We studied 100 singleton pregnant women with threatened preterm delivery and intact membranes, between 24 and 34 weeks, recruited during the period 2006–2008. A cervical swab for IL-6 detection was taken and a transvaginal ultrasound scan was performed for measuring the cervical length.

Results: Five women delivered within 2?d and six women within 7?d. A high cervical IL-6 concentration was found in these women. The area under the ROC curve for cervical IL-6 was 0.97 for deliveries within 2?d after the test, and 0.85 for deliveries within 7?d. The optimal cut-off point was a cervical IL-6 concentration of 210?pg/ml. The negative predictive value (NPV) was 100% for deliveries within 2?d, and 98.5% for deliveries within 7?d (when considering a prevalence of preterm birth of 8%). Cervical IL-6 and sonographic measurement of cervical length showed similar NPV.

Conclusion: A low-cervical IL-6 concentration can accurately identify symptomatic women with a very low chance to progress to preterm birth within 2–7?d.     

Second-trimester amniotic fluid interleukin-10 concentration predicts preterm delivery

Objective: Interleukin-6 (IL-6) is an inflammatory cytokine that has been shown to be elevated in the amniotic fluid of patients with preterm labor. On the other hand, interleukin-10 (IL-10) is an anti-inflammatory cytokine that has been shown to inhibit the synthesis of other cytokines. We hypothesized that amniotic fluid IL-10 in the early second trimester is low in patients who subsequently develop preterm labor, and because of its deficiency, excessive inflammatory responses associated with IL-6 elevation lead to preterm labor and delivery.

Study design: Amniotic fluid IL-6 and IL-10 levels were measured in 96 women who underwent genetic amniocentesis between 15 and 23 weeks' gestation. Levels of IL-6 and IL-10 were measured by immunoassay and correlated with demographic and pregnancy outcome information.

Results: Fifteen patients delivered at or before 36 weeks and 81 patients delivered after 36 weeks. There was an inverse correlation between amniotic fluid IL-10 concentration and gestational age at delivery. Similarly, an inverse correlation also existed between amniotic fluid IL-6 concentration and gestational age at delivery.

Conclusions: Both IL-10 and IL-6 levels in second-trimester amniotic fluid obtained at the time of genetic amniocentesis appeared to be higher in patients who subsequently developed preterm delivery. Therefore, low amniotic fluid IL-10 production during the second trimester does not seem to be an etiology for preterm labor.     

Interleukin-6 and Mycoplasma hominis as markers of preterm birth and related brain damage: Our experience

Objective.?The aim of this study is to investigate whether a high concentration of interleukin-6 (IL)-6 in the amniotic fluid is associated to a higher risk of preterm delivery, premature rupture of the membranes (PROM), and periventricular leucomalacia (PVL) in preterm infants; we have further investigated whether the levels of IL-6 are related to the presence of vaginal infection by mycoplasms.

Methods. One hundred eight patients were screened by vaginal swab, sonography, amniocentesis, and dosage of IL-6 in the amniotic fluid during the second trimester of pregnancy.

Results.?High levels of IL-6 and vaginal mycoplasms are related to preterm birth and PROM. We had no case of PLV.

Conclusion.?In order to achieve a good therapeutic purpose and get to an efficient strategy, the patients have to be elected by a number of criteria, which may include anamnesis elements, vaginal swab, then cytokines dosage in selected women, thus excluding the low-risk cases. Further studies are expected in order to plan guidelines including the dosage of ILs and principally of IL-6 as a main marker of preterm birth, above all during the second trimester.     

Predictive value of intra-amniotic and serum markers for inflammatory lesions of preterm placenta

Objective

To compare the relative predictive values of amniotic fluid (AF) matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), and serum C-reactive protein (CRP) for histologic chorioamnionitis and intra-amniotic infection in women with preterm labor or preterm premature rupture of membranes (PROM).

Study design

This retrospective cohort study included 99 consecutive women with preterm labor or preterm PROM (21–35 weeks’ gestation) who delivered within 72 h of transabdominal amniocentesis. The AF was cultured for aerobic and anaerobic bacteria and for genital mycoplasmas and was assayed for MMP-9 and IL-6 levels. Maternal serum CRP was measured immediately after amniocentesis. The placentas were examined histologically.

Main outcome measures

histologic chorioamnionitis and intra-amniotic infection.

Results

The prevalence of histologic chorioamnionitis and a positive AF culture was 44% (44/99) and 28% (28/99), respectively. In predicting intra-amniotic infection, AF MMP-9 had a significantly higher area under the curve (AUC: 0.94 [95% CI, 0.87–0.98]) than AF IL-6 (0.87 [95% CI, 0.78–0.84]; P < 0.05) and serum CRP (0.76 [95% CI, 0.66–0.84]; P < 0.001) and a higher sensitivity and specificity than serum CRP (P < 0.01, respectively). However, in predicting histologic chorioamnionitis, there were no significant differences in AUCs among the three tests (AF MMP-9: 0.78 [95% CI, 0.68–0.85]; AF IL-6: 0.76 [95% CI, 0.66–0.84]; serum CRP: 0.76 [95% CI, 0.66–0.84]). In a sub-analysis of 71 women without intra-amniotic infection, histologic chorioamnionitis was associated with an elevated serum CRP level (P < 0.05), but not with the level of AF IL-6 or MMP-9 (P = 0.232 and P = 0.402, respectively).

Conclusions

The AF MMP-9 has a better overall diagnostic performance than the AF IL-6 and maternal serum CRP in predicting intra-amniotic infection. However, the serum CRP level obtained up to 72 h before delivery appears to be an important marker for early identification of histologic chorioamnionitis in women without intra-amniotic infection.     

The possible preterm birth preventive effect of ampicillin during pregnancy

Objective: To study the possible association between oral ampicillin treatment during pregnancy and pregnancy complications, in addition to birth outcomes, particularly preterm birth. Methods: We evaluated newborn infants without congenital abnormalities born to mothers with or without ampicillin treatment during pregnancy in the population-based large data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities. Results: Of 38,151 newborn infants, 2,630 (6.9%) had mothers with ampicillin treatment during pregnancy. Some pregnancy complications, particularly preeclampsia, showed a higher prevalence in pregnant women with ampicillin treatment. Mean gestational age was slightly longer (0.2 week) but it resulted in a significant reduction in the prevalence of preterm birth (7.1 vs 9.3%; adjusted POR with 95% CI: 0.8, 0.7–0.9). The preterm birth preventive effect of ampicillin was most obvious after the use of the drug in the first trimester of pregnancy. Similar difference was not seen in the reduction of low birth weight. The rate of preterm birth was lower in newborn infants born to mothers with acute infectious diseases of both the genitourinary and respiratory systems if they were treated by ampicillin. Conclusions: Ampicillin treatment, particularly in the first trimester of gestation, can reduce the proportion of preterm birth in pregnant women with acute infectious diseases of the genitourinary and respiratory system.     

IL-17, A Possible Salivary Biomarker for Preterm Birth in Females with Periodontitis

BackgroundPrevious studies have suggested that chronic periodontal infection may be associate with preterm births and low birth weight. The present study was conducted to evaluate the levels of interleukin-17 (IL-17) in saliva samples of pregnant females as a possible marker in determining whether or not an association exists between chronic periodontitis and preterm labor.AimThe aim of the study is to assess the relation between the periodontal health status and preterm low birth weight of the new born on the basis of salivary IL-17 levels.Materials and MethodsThis case–control study included a random sample of 40 female patients, aged 18 to 35 years, who were in their second trimester, assigned to two groups, Group 1 consisted of 20 pregnant females without periodontitis, Group 2 included 20 pregnant females with periodontitis. Saliva samples were obtained in the second trimester and postpartum. Saliva samples were measured by using ELISA for IL-17 levels.ResultsIL-17 levels in saliva were significantly higher in Group 2 than that of Group 1(p < 0.001). There was no significant difference found between the preterm and low birth weight cases and periodontitis.ConclusionThis study did not find any association between the periodontitis and preterm deliveries and low birth weight cases on the basis of IL-17 levels in saliva.     

Identifying the potential protein biomarkers of preterm birth in amniotic fluid

ObjectivePreterm birth severely threatens neonatal health and life. Although the detailed mechanism of preterm birth is not well understood, accurately predicting preterm birth can help people make preparations in advance, greatly reducing the subsequent health risk of neonates. Therefore, in this study, we aimed to identify potential protein biomarkers of preterm birth in amniotic fluid (AF).Materials and methodsWe first enrolled pregnant subjects and collected their AF samples when they underwent amniocentesis at the second trimester of gestation. After delivery, the collected AF samples were classified into a full-term birth (sample size n = 21) set or preterm birth (n = 36) set, followed by 2-D DIGE and MS/MS assays.ResultsBy doing so, we identified seven potential protein biomarkers of preterm birth, three of which were further validated in all samples with ELISA, including Apolipoprotein A-IV (Apoa4), Lumican (Lum) and Kininogen-1 (Kng1). As a result, all three potential biomarkers were significantly differently expressed between preterm and full-term birth AF samples. Furthermore, without prior classification, we found that these three biomarkers were positively correlated with gestation age (correlation coefficient ranging from 0.25 to 0.38) and were able to predict the occurrence of preterm birth.ConclusionIn this study, by examining amniotic fluid, we identified three biomarker proteins that may facilitate the identification of preterm birth. There three proteins were never reported to be related to preterm birth. Their pathogenesis roles in preterm birth deserve further investigations by using in vitro cell model or in vivo animal model assays.     

Inflammatory biomarkers and spontaneous preterm birth among obese women

Objective: To identify associations between second-trimester serum inflammatory biomarkers and preterm birth among obese women.

Methods: In this nested case-control study, we compared 65 serum inflammatory biomarkers in obese women whose pregnancies resulted in early spontaneous preterm birth (<32 weeks gestation, n?=?34) to obese women whose pregnancies resulted in term birth (n?=?34). These women were selected from a larger population-based California cohort. Random forest and classification and regression tree techniques were employed to identify biomarkers of importance, and adjusted odds ratios (aORs) and 95% confidence intervals (CI) were estimated using logistic regression.

Results: Random forest and classification and regression tree techniques found that soluble vascular endothelial growth factor receptor-3 (sVEGFR3), soluble interleukin-2 receptor alpha-chain (sIL-2RA) and soluble tumor necrosis factor receptor-1 (sTNFR1) were related to preterm birth. Using multivariable logistic regression to compare preterm cases and term controls, decreased serum levels of sVEGFR3 and increased serum levels of sIL-2RA and sTNFR1 were associated with increased risk of preterm birth among obese women, aOR?=?3.2 (95% CI: 1.0–9.9), aOR?=?2.8 (95% CI: 0.9–9.0), and aOR?=?4.1 (95% CI: 1.2–14.1), respectively.

Conclusions: In this pilot study, we identified three serum biomarkers indicative of inflammation to be associated with spontaneous preterm birth among obese women: sVEGFR3, sIL-2RA and sTNFR1.     

Do the first,second and third trimester maternal serum hepcidin concentrations clarify obstetric complications?

Objective: To evaluate whether first, second, and third-trimester maternal serum hepcidin levels are different in pregnancies with and without adverse pregnancy outcomes (APO).

Methods: A 165 nullipar pregnant women were included in this prospective cohort study. Serum hepcidin, ferritin, IL-6, C-reactive protein (CRP) and Hb values were measured at 11–14, 24–28, and 30–34 weeks of gestation. The relation between these parameters and APO and neonatal outcomes were investigated. Preterm delivery, intrauterine growth restriction, pre-eclampsia, gestational hypertension and placental abruption were determined as adverse pregnancy outcomes.

Results: The risk of APO was three times higher in women with high IL-6 levels in the second trimester. High hepcidin levels in the second trimester were associated with a 1.6 times increased risk of APO. Newborns of women with high IL-6 levels in the third trimester had a 1.6-fold increased risk of neonatal complications. High ferritin levels in the third trimester were associated with minimally increased risk of neonatal complications.

Conclusions: Mean serum hepcidin levels were similar in all pregnant women, however, elevated second trimester serum hepcidin and IL-6 levels were associated with a higher risk of APO and high third trimester hepcidin, ferritin and IL-6 levels were associated with higher risk of neonatal complications.     

Association between vaginal 70-kd heat shock protein, interleukin-1 receptor antagonist, and microbial flora in mid trimester pregnant women

OBJECTIVE: This study investigated the association among the inducible 70-kd heat shock protein, cytokines, and microbial flora in the vagina in mid trimester pregnant women and subsequent preterm delivery. STUDY DESIGN: Vaginal samples from 205 pregnant women, which were collected at 18 to 22 weeks of gestation, were analyzed for qualitative and quantitative vaginal microflora and for 70-kd heat shock protein, interleukin-1beta, interleukin-1 receptor antagonist, and tumor necrosis factor-alpha by enzyme-linked immunosorbent assay. Pregnancy outcome data were obtained subsequently. RESULTS: The 70-kd heat shock protein was detected in 38 vaginal samples (18.5%). Its presence was associated with elevated vaginal pH, a diagnosis of bacterial vaginosis, and elevated interleukin-1 receptor antagonist levels (P < .001). Among women with bacterial vaginosis, 70-kd heat shock protein-positive subjects had a >80% increase in median vaginal concentration of interleukin-1 receptor antagonist (P < .05). CONCLUSION: Vaginal 70-kd heat shock protein expression is associated with the down-regulation of the proinflammatory immune response to abnormal vaginal flora in mid trimester pregnant women.     

The relationship between amniotic and newborn gastric fluid inflammatory mediators

Abstract

Objective: To determine whether the levels of inflammatory mediators in gastric fluid (GF) of a premature newborn are associated with those in amniotic fluid (AF) of the newborn’s mother.

Patients: Twenty-three pairs of pregnant women and their premature newborns <35 weeks gestation, born by Cesarean sections.

Methods: Amniotic fluids and newborn gastric fluids were obtained from women during Cesarean section procedure. The mother-premature newborn dyads were retrospectively assessed to analyze the clinical and laboratory data. Concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α) and mannose-binding lectin (MBL) were compared between amniotic and newborn gastric fluids in each dyad.

Results: Premature newborns and their mothers with funisitis had significantly higher median AF IL-6, TNF-α and GF IL-8 concentrations than those without funisitis (p?=?0.022 for AF IL-6; p?=?0.023 for AF TNF-α; p?=?0.022 for GF IL-8). The concentrations of IL-6, IL-8, TNF-α and MBL in newborn GF were significantly correlated with those in AF in each dyad (p?<?0.001, r?=?0.872 for IL-6; p?<?0.001, r?=?0.851 for IL-8; p?<?0.001, r?=?0.768 for TNF-α; p?<?0.001, r?=?0.845 for MBL, respectively).

Conclusion: The levels of inflammatory mediators in GF of a premature newborn immediately after birth are strongly associated with those in AF of the newborn’s mother.     

Second-trimester amniotic fluid interleukin-10 concentration predicts preterm delivery.

OBJECTIVE: Interleukin-6 (IL-6) is an inflammatory cytokine that has been shown to be elevated in the amniotic fluid of patients with preterm labor. On the other hand, interleukin-10 (IL-10) is an anti-inflammatory cytokine that has been shown to inhibit the synthesis of other cytokines. We hypothesized that amniotic fluid IL-10 in the early second trimester is low in patients who subsequently develop preterm labor, and because of its deficiency, excessive inflammatory responses associated with IL-6 elevation lead to preterm labor and delivery. STUDY DESIGN: Amniotic fluid IL-6 and IL-10 levels were measured in 96 women who underwent genetic amniocentesis between 15 and 23 weeks' gestation. Levels of IL-6 and IL-10 were measured by immunoassay and correlated with demographic and pregnancy outcome information. RESULTS: Fifteen patients delivered at or before 36 weeks and 81 patients delivered after 36 weeks. There was an inverse correlation between amniotic fluid IL-10 concentration and gestational age at delivery. Similarly, an inverse correlation also existed between amniotic fluid IL-6 concentration and gestational age at delivery. CONCLUSIONS: Both IL-10 and IL-6 levels in second-trimester amniotic fluid obtained at the time of genetic amniocentesis appeared to be higher in patients who subsequently developed preterm delivery. Therefore, low amniotic fluid IL-10 production during the second trimester does not seem to be an etiology for preterm labor.     

The preterm prediction study: elevated cervical ferritin levels at 22 to 24 weeks of gestation are associated with spontaneous preterm delivery in asymptomatic women

OBJECTIVE: Low serum ferritin levels correlate with low iron stores, whereas high levels are associated with an acute-phase reaction. Our objective was to determine whether elevated levels of ferritin in the genital tract may be a potent marker to identify patients at risk for spontaneous preterm delivery. STUDY DESIGN: We performed a nested case-control study involving 182 women who had spontaneous preterm delivery and 182 term control subjects matched for race, parity, and recruitment center, and selected from 2929 women enrolled in the Preterm Prediction Study of the National Institute of Child Health and Development Maternal-Fetal Medicine Units Network. Cervical fluid ferritin was measured by use of radioimmunoassay. RESULTS: Cervical ferritin levels were significantly higher in women who subsequently had spontaneous early preterm delivery (<32 weeks, mean +/- SD, 37.7 +/- 31.1 vs 21.5 +/- 24.1 ng/mL, P =.002; and <35 weeks, 43.2 +/- 62.7 vs 28.2 +/- 36.7 ng/mL, P =.004) than in term controls. A cervical ferritin of >75th percentile in the controls (>35.5 ng/mL) was found in 52.9% (9/17) of the women delivered <29 weeks vs 17.7% (3/17) of the controls (odds ratio [OR] 5.3 [95% CI 1.1-25.2]) and in 43.5% (20/46) of the women delivered <32 weeks versus 10.9% (5/46) of the controls (OR 6.3, 95% CI 2.1-18.9). Cervical ferritin levels had a weaker association with spontaneous preterm delivery <35 weeks (OR 2.8 [95% CI 1.5-5.1]) and <37 weeks (OR 1.6, 95% CI 1.0-2.5]). Cervical ferritin levels correlated significantly with cervical lactoferrin, interleukin-6 (IL-6), and defensin levels. CONCLUSIONS: Elevated cervical ferritin levels at 22 to 24 weeks of gestation in asymptomatic women are associated with subsequent spontaneous preterm birth. The strong correlation of cervical ferritin with other inflammatory markers provides support for the hypothesis of infection as a mediator of preterm delivery.     

The effect of maternal soluble FMS-like tyrosine kinase 1 during pregnancy on risk of preterm delivery

Objective: Soluble fms-like tyrosine kinase 1 (sFlt1) is an antiangiogenic protein that is associated with a number of disorders of placental angiogenesis. It has been hypothesized that disruption of placental angiogenesis may contribute to the pathophysiology of preterm delivery (PTD). However, the relationship of PTD risk to variation in sFlt1 levels is not well known. We investigate the relationship between longitudinal variation in maternal serum concentrations of sFlt1 and risk of PTD. Methods: Data were collected in a longitudinal cohort study involving 278 pregnant women. Maternal serum sFlt1 concentrations were measured at 6–10, 10–14, 16–20, 22–26, and 32–36 weeks gestation. Data analyses used longitudinal regression models using repeated measures that allow robust inferences from our modest sample size. The outcome was birth prior to 37 weeks gestation. Results: sFlt1 concentrations were higher in first trimester for preterm compared to term deliveries. This relationship reversed in second trimester because sFlt1 concentrations increased more rapidly across gestation for term deliveries. In Cox proportional hazards analyses, a 2?ng higher sFlt1 concentration across gestation was associated with a hazard ratio of 1.3 (95% CI: 1.1, 1.5) for PTD suggesting the importance of levels in early pregnancy. Conclusion: Elevated maternal serum sFlt1 concentration during pregnancy is associated with increased risk of PTD.