Differences in the fetal interleukin-6 response to microbial invasion of the amniotic cavity between term and preterm gestation

Background/objective: Fetal inflammatory response has been implicated as a mechanism of multi-system organ injury in preterm and term neonates. Microbial invasion of the amniotic cavity (MIAC) is frequently associated with a fetal inflammatory response. However, there are no studies comparing the fetal response to MIAC in term and preterm gestations. The purpose of this study was to compare the umbilical cord plasma interleukin-6 (IL-6) concentrations in term and preterm neonates in the presence or absence of MIAC. Study design: Umbilical cord blood was obtained at birth from 252 neonates whose mothers had an amniocentesis within 48 h of delivery (preterm delivery, n = 62; term delivery, n = 190). MIAC was defined as a positive amniotic fluid culture for bacteria or genital mycoplasmas. IL-6 was measured by a sensitive and specific immunoassay. Results: The median IL-6 concentration in umbilical cord plasma was significantly higher in preterm neonates than in term neonates (median 13.4 pg/ml, range 0.1-676 pg/ml vs. median 3.2 pg/ml, range 0.1-408 pg/ml; p < 0.0001). In the context of MIAC, the median umbilical cord plasma IL-6 concentration was significantly higher in preterm than in term neonates (median 31.6 pg/ml, range 1.4-676 pg/ml vs. median 11.7 pg/ml, range 1.3-82 pg/ml, respectively; p < 0.05). Neonates born to mothers with a positive amniotic fluid culture had a significantly higher median IL-6 concentration than neonates born to mothers with a negative amniotic fluid culture (preterm: median 31.6, range 1.4-676 pg/ml vs. median 8.0, range 0.1-656 pg/ml; p < 0.05 and term: median 11.7, range 1.3-82 pg/ml vs. median 3.1, range 0.1-408 pg/ml; p < 0.01, respectively). Conclusions: The preterm fetus is capable of mounting a systemic cytokine response as measured by IL-6 in its peripheral blood. In the setting of MIAC, a fetal IL-6 response is higher in preterm than in term gestation.     

Funisitis and chorionic vasculitis: the histological counterpart of the fetal inflammatory response syndrome

Objective: To determine whether there is a relationship between the presence of histological signs of inflammation in the extraplacental membranes and umbilical cord and the concentrations of fetal plasma interleukin-6 (IL-6). Methods: The study examined a cohort of patients who were admitted with preterm labor or preterm premature rupture of the membranes (PROM) and who underwent cordocentesis. Inclusion criteria included fetal plasma available for IL-6 determination, histological examination of the umbilical cord and placenta, and delivery within 48 h of the procedure. This last criterion was used to preserve a meaningful temporal relationship between fetal plasma IL-6 and the results of histological examination of the placenta. Fetal plasma IL-6 was determined by a high sensitivity ELISA. Forty-five patients were available for study: 18 patients had preterm labor with intact membranes and 27 had preterm PROM. Results: The incidence of funisitis was 44.4% (20/45): 27.8% (5/18) in patients with preterm labor and intact membranes and 55.6% (15/27) in patients with preterm PROM. The median values of fetal plasma IL-6 in patients with funisitis, chorioamnionitis without funisitis, and non-inflamed membranes were 51.4, 18.4 and 5.2 pg/ml, respectively. After log transformation of the fetal plasma IL-6 concentration, the means differed significantly from each other (ANOVA, p < 0.02). There was no difference in log fetal plasma IL-6 concentration between patients with funisitis and those with chorioamnionitis without funisitis. The difference in mean concentration of log fetal plasma IL-6 between patients with funisitis or chorionic vasculitis and those without inflammation was highly significant (post-hoc test, p = 0.01 and p < 0.01, respectively). Fetuses with fetal plasma IL-6 > 11 pg/ml had a significantly higher rate of histological signs of inflammation in the extraplacental membranes and umbilical cord than those with fetal plasma IL-6 < 11 pg/ml (funisitis: 55.6% (15/27) vs. 27.8% (5/18), p < 0.05; chorionic vasculitis: 55.6% (15/27) vs. 12.5% (2/16), p < 0.01; chorioamnionitis only: 25.9% (7/27) vs. 16.7% (3/18), p < 0.05; no inflammation: 18.5% (5/27) vs. 55.6% (10/18), p < 0.05, respectively). Fetuses with funisitis had significantly higher rates of clinical and histological chorioamnionitis, and neonatal infectious morbidity (proven + suspected sepsis) than fetuses without funisitis (40% (8/20) vs. 8% (2/25), 90% (18/20) vs. 36% (9/25), and 40% (8/20) vs. 4% (1/25), respectively; p < 0.01 for each). Fetuses with chorionic vasculitis had significantly higher rates of clinical and histological chorioamnionitis as well as neonatal infectious morbidity (proven + suspected sepsis) than fetuses without chorionic vasculitis (100% (17/17) vs. 42.3% (11/26), p < 0.01; 82.4% (14/17) vs. 50.0% (13/26), p = 0.05; and 41.2% (7/17) vs. 7.7% (2/26), p = 0.01). Conclusion: Fetal plasma IL-6 concentration is significantly associated with the presence of inflammatory lesions in the extraplacental membranes and umbilical cord. Fetuses with fetal plasma IL-6 > 11 pg/ml had a significantly higher rate of funisitis and/or chorionic vasculitis than fetuses with fetal plasma IL-6 < 11 pg/ml. These findings suggest that funisitis/chorionic vasculitis is the histological manifestation of the fetal inflammatory response syndrome.     

Interleukin-19 in fetal systemic inflammation

Objective: The fetal inflammatory response syndrome (FIRS) is considered the fetal counterpart of the systemic inflammatory response syndrome (SIRS), which can be caused by infection and non-infection-related insults. Although the initial response is mediated by pro-inflammatory signals, the control of this response is achieved by anti-inflammatory mediators which are essential for the successful outcome of the affected individual. Interleukin (IL)-19 is capable of stimulating the production of IL-10, a major anti-inflammatory cytokine, and is a potent inducer of the T-helper 2 (Th2) response. The aim of this study was to determine if there is a change in umbilical cord plasma IL-19 and IL-10 concentrations in preterm neonates with and without acute funisitis, the histologic counterpart of FIRS. Methods: A case-control study was conducted including 80 preterm neonates born after spontaneous labor. Neonates were classified according to the presence (n?=?40) or absence of funisitis (n?=?40), which is the pathologic hallmark of FIRS. Neonates in each group were also matched for gestational age. Umbilical cord plasma IL-19 and IL-10 concentrations were determined by ELISA. Results: 1) The median umbilical cord plasma IL-19 concentration was 2.5-fold higher in neonates with funisitis than in those without funisitis (median 87 pg/mL; range 20.6–412.6 pg/mL vs. median 37 pg/mL; range 0–101.7 pg/mL; p?<?0.001); 2) newborns with funisitis had a significantly higher median umbilical cord plasma IL-10 concentration than those without funisitis (median 4 pg/mL; range 0–33.5 pg/mL vs. median 2 pg/mL; range 0–13.8 pg/mL; p?<?0.001); and 3) the results were similar when we included only patients with funisitis who met the definition of FIRS by umbilical cord plasma IL-6 concentrations ≥ 17.5 pg/mL (p?<?0.001). Conclusion: IL-19 and IL-10 are parts of the immunologic response of FIRS. A subset of fetuses with FIRS had high umbilical cord plasma IL-19 concentrations. In utero exposure to high systemic concentrations of IL-19 may reprogram the immune response.     

Soluble ST2 in the fetal inflammatory response syndrome: in vivo evidence of activation of the anti-inflammatory limb of the immune response

Abstract

Objective: Inflammation is a mechanism of host response to infection, which can be harmful when inappropriately modulated. Soluble ST2 (sST2) is a decoy receptor of interleukin (IL)-33, and this complex modulates the balance in the Th1/Th2 immune response. Moreover, sST2 inhibits the production of pro-inflammatory cytokines in cooperation with an anti-inflammatory cytokine, IL-10. The objectives of this study were to: (1) determine whether umbilical cord plasma sST2 concentration differs between preterm neonates with and without funisitis and between those with and without the fetal inflammatory response syndrome (FIRS); and (2) evaluate the relationship between sST2 and IL-10 among neonates with funisitis and/or FIRS.

Methods: Umbilical cord plasma was collected from neonates delivered prematurely due to preterm labor or preterm prelabor rupture of membranes with (n?=?36), and without funisitis (n?=?30). FIRS (umbilical cord IL-6 concentration ≥17.5?pg/mL) was identified in 29 neonates. Plasma sST2 and IL-10 concentrations were determined by enzyme linked immune sorbent assay.

Results: The median umbilical cord plasma sST2 concentration was 6.7-fold higher in neonates with FIRS than in those without FIRS (median 44.6?ng/mL, interquartile range (IQR) 13.8–80.3?ng/mL versus median 6.7?ng/mL, IQR 5.6–20.1?ng/mL; p?<?0.0001). Similarly, the median umbilical cord plasma sST2 concentration was 2.7-fold higher in neonates with funisitis than in those without funisitis (median 19.1?ng/mL; IQR 7.1–75.0?ng/mL versus median 7.2?ng/mL; IQR 5.9–23.1?ng/mL; p?=?0.008). There was a strong positive correlation between sST2 and IL-10 in neonates with funisitis and/or FIRS (Spearman’s Rho?=?0.7, p?<?0.0001).

Conclusion: FIRS and funisitis are associated with an elevation of umbilical cord plasma concentrations of soluble ST2. This protein represents an important mediator of the immune response in neonates diagnosed with FIRS by promoting an anti-inflammatory effect in association with IL-10.     

The expression of cytokines IFN-γ, IL-4, IL-17A,and TGF-β1 in peripheral blood and follicular fluid of patients testing positive for anti-thyroid autoantibodies and its influence on in vitro fertilization and embryo transfer pregnancy outcomes

Abstract

The aim of this work was to study the expression of the cytokines IFN-γ, IL-4, IL-17?A, and TGF-β1 in peripheral blood and follicular fluid (FF) of patients positive for antithyroid autoantibodies (ATA⁺) with normal thyroid gland function and the influence of these autoantibodies on in vitro fertilization and embryo transfer (IVF-ET) pregnancy outcomes. Nineteen patients were in the ATA⁺ group, and 27 patients tested negative for anti-thyroid autoantibody (ATA^?). Blood samples were drawn from the two groups of patients on the oocyte retrieval day and the 5th and 14th days of transplantation; in addition, FF was extracted on the oocyte retrieval day from both groups of patients and tested through enzyme-linked immunosorbent assay (ELISA) for IFN-γ, IL-4, IL-17?A, and TGF-β1. For the ATA⁺ group, the concentration of IFN-γ increased whereas the concentration of TGF-β1 decreased in peripheral blood on the oocyte retrieval day (p?<?.05); the concentration of IL-4 decreased in peripheral blood on the 5th and 14th days of transplantation for the ATA⁺ group (p?<?.05); further, the concentration of IL-17?A increased whereas that of TGF-β1 decreased in FF (p?<?.05). The ratio of IL-17?A/TGF-β1 in the ATA⁺ group significantly increased in FF and peripheral blood on the oocyte retrieval day and the 14th day of transplantation (p?<?.05). The ratio of IL-17?A/TGF-β1 in FF of the pregnant patients was significantly lower than in the non-pregnant patients (p?<?.05). The findings suggested that the ratio between pro-inflammatory and anti-inflammatory cytokines was adversely affected; therefore, adverse pregnancy outcomes of patients with ATA⁺ undergoing IVF-ET treatment may be attributed to immunological mechanisms.     

Umbilical blood gas analysis in preeclamptic versus healthy pregnancies with preterm birth

Objective: Comparing the value of umbilical cord arterial blood gas (UC-ABG) analysis in the prediction of neonatal mortality and morbidity in the preeclamptic versus healthy pregnancies with preterm birth.

Methods: Eight hundred sixteen preterm (born at?<37 gestational weeks) neonates with no other morbidities who were born by cesarean section were evaluated. Immediately after delivery, UC-ABG analysis was performed and the neonates were followed.

Results: Preeclamptic women had lower umbilical cord blood (UCB) pH (7.2 4?±?0.1 versus 7.2 7?±?0.08, p?=?0.008) and higher UCB base deficit (BD) (3.5?±?3.7 versus 2.2?±?3.4, p?=?0.005) compared with controls. In the preeclamptic group, UCB metabolic acidosis (pH?<?7.15 and B.D?>?8) was not independently associated with neonatal morbidity or mortality, while in the control group UCB metabolic acidosis was independently associated with low 10-min Apgar (OR, 4.9; 95%CI 1.37–18.03), respiratory distress syndrome (OR, 2.37; 95%CI 1.05–6.17), intraventricular hemorrhage (OR, 3.01; 95%CI 1.13–7.99), and neonatal mortality (OR, 17.33; 95%CI 4.51–66.53).

Conclusions: The preterm neonates born to preeclamptic mothers have lower UCB pH and higher BD. In these neonates, UCB acidosis is not independently associated with any adverse neonatal outcomes. In contrast, in the preterm neonates born to healthy mothers, UCB metabolic acidosis is independently associated with neonatal mortality and morbidity.     

Changes in circulating levels of carboxymethyllysine,soluble receptor for advanced glycation end products (sRAGE), and inflammation markers in women during normal pregnancy

Abstract

Objective: To determine the circulating levels of insulin, Nε-carboxymethyllysine (CML), soluble receptor for advanced glycation end products (sRAGE), and markers of inflammation and oxidative stress (OS) in maternal and umbilical cord blood in a cohort of healthy women with normal pregnancy.

Methods: We conducted an observational longitudinal study in a group of women (n?=?31; age range 18–39 years) with healthy pregnancy starting at 30 weeks of gestation and finishing at the time of delivery. We collected weight and height in the participants and their neonates and calculated body mass index (BMI). Blood from each patient was collected at 30th week of pregnancy and at delivery when a sample of cord blood was also obtained. Glucose, lipid profile, CML, sRAGE, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), highly sensitivity C-reactive protein (hsPCR), and insulin were determined. The study was approved by the University of Guanajuato Institutional Ethics Committee.

Results: All pregnancies reached term (mean gestational time 38.9?±?0.83 weeks) and there were no maternal complications. Mean age was 27.6 years. Lipid profile values were higher in the group compared with our values in nonpregnant women. During pregnancy, levels of insulin increased (p?<?.0006), CML (p?<?.0001) and sRAGE (p?<?.01) decreased, levels of MDA did not change, while those of TNF-α and hsPCR tended to increase. In the neonates, we found lower levels of CML (p?<?.003), hsPCR (p?<?.004), and insulin (p?<?.004) and higher levels of sRAGE (p?<?.013) and TNF-α (p?<?.022) compared to their mothers at delivery. In the total group, we found association of CML of the mother at baseline with the CML (p?<?.0006) and MDA (p?<?.002) in neonates, while maternal sRAGE at the end of pregnancy was associated with CML (p?<?.004) of their neonates.

Conclusions: Our study confirms that normal pregnancy is accompanied by insulin resistance (IR) and significant increase in lipid profile, and demonstrates that circulating levels of CML and sRAGE decreased significantly at the end of pregnancy. The lack of association between the course of insulin levels and those of CML probably results from the predominant role of placental factors in the pathogenesis of IR in pregnancy. sRAGE levels in the neonates are markedly increased compared to their mothers suggesting a placental origin of this compound which may have a protective effect on the fetus since sRAGE restricts Advanced glycation end product (AGE) effects and may exert anti-inflammatory effects.     

Assessment of maternal–fetal status of some essential trace elements in pregnant women in late gestation: relationship with birth weight and placental weight

Objective: The status of the essential trace elements copper (Cu), iron (Fe), zinc (Zn), selenium (Se) and molybdenum (Mo) has been investigated in maternal and umbilical cord blood in control, uncomplicated pregnancies at term, and the possibility assessed of a relationship between blood levels of these trace elements and newborn weight and placental weight. Fetal–maternal ratios of the elements were also computed to establish baseline values for the Kuwaiti obstetric population.

Methods: Blood samples were collected from a maternal vein, the umbilical artery and umbilical vein of normal pregnant women at the time of spontaneous delivery or Cesarean section, and the concentrations of various trace elements determined by atomic absorption spectrophotometry.

Results: The concentration of Cu, Fe, Mo, Se and Zn averaged 2406.1, 3252.1, 11.6, 107.3 and 696.2?μg/l, respectively, in maternal venous blood in the pregnant women (n?=?39) at term. Umbilical venous/maternal venous ratios of Cu, Fe, Mo, Se and Zn averaged 0.32, 1.96, 1.03, 0.83 and 1.55, respectively. Neonatal birth weight did not correlate with maternal blood levels of the trace elements (p?>?0.05) in the mother–child pairs studied. However, neonatal weight correlated negatively (p?<?0.05) with umbilical venous Cu level. Placental weight correlated positively (p?<?0.05) with Fe and Mo levels and negatively with Zn level in umbilical venous blood.

Conclusions: Our results indicate an active placental transport for Fe and Zn, while Cu, Mo and Se appear to be exchanged passively between mother and fetus. Evaluation of Fe, Mo, Se and Zn levels in maternal and umbilical cord blood does not appear to be useful in the assessment of fetal growth.     

Inducible nitric oxide inhibitor aminoguanidine,ameliorated oxidative stress,interleukin-6 concentration and improved brain-derived neurotrophic factor in the brain tissues of neonates born from titanium dioxide nanoparticles exposed rats

Abstract

Introduction: An interaction between oxidative stress, neuroinflammation, and nitric oxide (NO) has been suggested to have a role neurotoxicity. The aim of current research was to investigate the effect of aminoguanidine (AG) as an inducible NO synthase (iNOS) inhibitor, on brain-derived neurotrophic factor (BDNF), oxidative stress, and interleukin-6 (IL-6) concentrations in the brain tissues of neonates born from the rats exposed to titanium dioxide nanoparticles (TiO2 NPs) during gestation.

Methods: The pregnant rats were grouped into three and received: (1) saline, (2) TiO2 (200?mg/kg, gavage), and (3) TiO2-AG [200?mg/kg intraperitoneal (IP)]. The treatment was started since the second gestation day up to the delivery time. The neonates born from the rats were deeply anesthetized, sacrificed, and the brains were collected for biochemical evaluations.

Results: The neonates born from the rats exposed to TiO₂ showed a lower BDNF (p?<?.001) but a higher IL-6 (p?<?.01) concentrations in their hippocampal tissue. TiO₂ exposure also increased malondialdehyde (MDA) (p?<?.001) and NO metabolites (p?<?.001), while diminished thiol (p?<?.001), superoxide (SOD) (p?<?.001), and catalase (CAT) (p?<?.001) in all hippocampal, cortical, and cerebellar tissues. Administration of AG improved BDNF (p?<?.01) but attenuated IL-6 (p?<?.01) concentrations in the hippocampal tissue. AG also decreased MDA (p?<?.001) and NO metabolites (p?<?.01–p?<?.001), while increased thiol (p?<?.01–p?<?.001), SOD (p?<?.001), and CAT (p?<?.05–p?<?.001) in all cerebellar, hippocampal, cortical, and tissues.

Conclusion: The results of the current research revealed that iNOS inhibitor AG, ameliorated oxidative stress, IL-6 concentration, and improved BDNF in the brain tissues of neonates born from TiO₂ NPs exposed rats.     

Maternal and neonatal circulating visfatin concentrations in patients with pre-eclampsia and a small-for-gestational age neonate

Objective.?Maternal circulating visfatin concentrations are higher in patients with a small-for-gestational-age (SGA) neonate than in those who delivered an appropriate-for-gestational age (AGA) neonate or in those with pre-eclampsia. It has been proposed that enhanced transfer of visfatin from the foetal to maternal circulation may account for the high concentrations of maternal visfatin observed in patients with an SGA neonate. The aims of this study were: (1) to determine whether cord blood visfatin concentrations differ between normal neonates, SGA neonates and newborns of pre-eclamptic mothers; and (2) to assess the relationship between maternal and foetal circulating visfatin concentrations in patients with an SGA neonate and those with pre-eclampsia.

Study design.?This cross-sectional study included 88 pregnant women and their neonates, as well as 22 preterm neonates in the following groups: (1) 44 normal pregnant women at term and their AGA neonates; (2) 22 normotensive pregnant women and their SGA neonates; (3) 22 women with pre-eclampsia and their neonates; and (4) 22 preterm neonates delivered following spontaneous preterm labour without funisitis or histologic chorioamnionitis, matched for gestational age with infants of pre-eclamptic mothers. Maternal plasma and cord blood visfatin concentrations were determined by ELISA. Non-parametric statistics were used for analyses.

Results.?(1) The median visfatin concentration was lower in umbilical cord blood than in maternal circulation, in normal pregnancy, SGA and pre-eclampsia groups (p?<?0.001 for all comparisons); (2) the median cord blood visfatin concentrations did not differ significantly between term AGA or SGA neonates, infants of mothers with pre-eclampsia and their gestational-age-matched preterm AGA neonates; (3) maternal and cord blood visfatin concentrations correlated only in the normal term group (r?=?0.48, p?=?0.04).

Conclusion.?Circulating visfatin concentrations are lower in the foetal than in the maternal circulation and did not significantly differ between the study groups. Thus, it is unlikely that the foetal circulation is the source of the high maternal visfatin concentrations reported in patients with an SGA neonate.     

Cytokine concentrations during the first days of life

OBJECTIVE: To evaluate the cytokine concentration patterns during the first 5 days of life by measuring serum concentrations of type-1 cytokines, like interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) and type-2 cytokines, like IL-4, as well as the receptors of IL-2 (sIL-2R) and IL-4 (sIL-4R) during the early neonatal period. SUBJECTS AND METHODS: Forty-two healthy term neonates were included in the study. Cytokine concentrations were measured in umbilical cord, in the 1st and 5th day after birth and compared with those in serum of 30 healthy adults. RESULTS: IL-2 concentrations presented a decrease trend from umbilical cord to 5th day, while sIL-2R showed a significant elevation from umbilical cord to 5th day after birth. IL-4 concentrations did not differ significantly among umbilical cord, the 1st and the 5th day, while the sIL-4R showed the highest values in the 1st day after birth. Both IL-4 and sIL-4R concentrations in neonatal samples were elevated compared to adults. IFN-gamma concentrations increased significantly from umbilical cord to 5th day of life. CONCLUSION: Our findings indicate a dysregulation among IL-2, IL-4 and IFN-gamma concentrations during the 1st day after birth, favoring a more precocious expression of IL-2 and IL-4 against IFN-gamma that seems to be ameliorated in the end of the 1st week of life.     

Evaluation of inflammatory mediators in the deciduas of pregnant women with pre-eclampsia/eclampsia

Objective: The objective was to evaluate some inflammatory mediators, i.e. cytokines that induce and inhibit nitric oxide (NO) synthase, in pregnant women with pre-eclampsia/eclampsia (PE/E) compared to clinically normal patients.

Methods: Placental fragments were collected from 46 pregnant patients, including 30 clinically normal subjects and 16 women with PE/E, and stored in NP40-containing phosphate buffer in a freezer at ?70?°C until the time of solubilization. Cytokines IL-4, IL-10, IL-13, TNF-α and IFN-γ were assayed by ELISA and NO was estimated by the Griess reaction after reduction.

Results: Patients with PE/E presented significantly lower placental levels of IL-10 and IL-3 than the control group (p?<?0.05). On the other hand, IL-4, TNF-α and IFN-γ levels were similar on the two groups, whereas nitrite/nitrate levels were significantly lower in the PE/E group. A higher inflammatory balance was observed in patients with PE/E compared to normal subjects (p?<?0.05).

Conclusion: Patients with PE/E present lower levels of Th2 cytokines associated with a pro-inflammatory balance as evaluated by the IL-10/TNF-α ratio, as well as lower nitrite/nitrate levels, than controls.     

Umbilical cord blood concentrations of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) in neonates developing hypoxic-ischemic encephalopathy

Objective: To compare ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) concentrations in umbilical cord blood of neonates who develop Sarnat stage II–III hypoxic-ischemic encephalopathy (HIE) to healthy controls, and to relate the concentrations to the severity of neurology and long-time outcomes.

Material and methods: Cord sera of 15 neonates with HIE II–III and 31 matched controls were analyzed for UCH-L1 and GFAP. Comparisons were performed for cord artery pH, amplitude-integrated electroencephalography (aEEG), stage of HIE, and death or sequelae up to an age of 6 years. Parametric and non-parametric statistics were used with a two-sided p?<?0.05 considered significant.

Results: Among controls no associations between biomarker concentrations and gestational age, birthweight, length of storage of cord sera and degree of hemolysis were found. No significant differences in biomarker concentrations were found between HIE neonates and controls, and no differences were found with regard to HIE stage, cord acidemia, severity of aEEG changes, or persistent sequelae or death.

Conclusions: No differences in cord blood UCH-L1 and GFAP concentrations were found between HIE neonates and controls, and no associations were found between the biomarker concentrations and the severity of disease, or whether the condition developed into a permanent or fatal injury.     

新生儿IL-18对Th1/Th2类细胞免疫平衡的作用与HBV宫内感染相关性研究

目的:探讨新生儿IL-18对Th1/Th2类细胞免疫平衡的作用与HBV宫内感染的相关性。方法:选择HBsAg、HBeAg双阳性但肝功能正常孕产妇分娩的新生儿157例,以其中胎儿宫内感染21例为研究组,无宫内感染136例为对照组。用流式细胞仪检测两组脐血白细胞介素-18(IL-18)、γ-干扰素(IFN-γ)、白细胞介素-4(IL-4)的表达水平。结果:(1)研究组IL-18及IFN-γ表达水平明显低于对照组,差异有显著性(P<0.05;P<0.05);研究组IL-4表达水平百分数高于对照组,但差异无显著性(P>0.05);研究组IFN-γ/IL-4高于对照组,差异有显著性(P<0.05);(2)研究组IL-18与IFN-γ、IL-4、IFN-γ/IL-4均呈显著正相关(P均<0.05)。结论:IL-18是Th1/Th2网络平衡的更高层次的调控者;IL-18水平下调,导致新生儿Th1/Th2细胞因子比例下降,以致不利于HBV的清除,IL-18水平下调可能是HBV宫内感染的危险因素之一。     

Umbilical cord vitamin D,ionized calcium and myocardial oxygen demand

Abstract

Objective: Systemic blood vitamin D and total calcium are correlates of birthweight and cardiovascular disease but whether umbilical cord blood vitamin D and ionized calcium are correlates of birthweight and cardiovascular function is not known. This cross-sectional study correlates umbilical cord vitamin D, ionized calcium and birthweight with the heart rate-systolic pressure product (RPP), an indicator of myocardial oxygen demand.

Methods: Cord blood vitamin D and ionized calcium concentrations were compared for vitamin D normal (≥50?nM, 20?ng/mL) and vitamin D deficiency (<50?nM, 20?ng/mL) in normal weight (≥2500?g) and low birthweight (LBW, <2500?g) newborns. Heart rate and blood pressure were measured during postnatal transition and RPP was computed.

Results: RPP was positively correlated with birthweight (r?=?+0.52, p?<?0.001) and with cord ionized calcium level (r?=?+0.42, p?<?0.01) in the normal and LBW newborns. RPP was positively correlated with cord vitamin D level in the LBW newborns (raw r?=?+0.50, p?<?0.05, normalized for birthweight r?=?+0.73, p?<?0.01).

Conclusions: Small RPP, an indicator of low myocardial oxygen demand, in LBW newborns appears to correlate with low umbilical cord vitamin D and ionized calcium levels, suggestive of pathological heart development.     

Differences in levels of oxidative stress in mothers and neonate: the impact of mode of delivery

Abstract

Objective: To determine there are differences in the production levels of oxygen free radical between mothers and neonates by the mode of delivery, we measured oxygen free radical concentrations in maternal vein and umbilical artery.

Methods: Forty-four women with singleton term pregnancies were prospectively recruited and classified into two groups: those who had a spontaneous uncomplicated vaginal delivery (VD group; n?=?21), and those who had an elective cesarean delivery (CD group; n?=?23). We determined maternal and fetal oxidative stress levels by measuring concentrations of derivatives of reactive oxygen metabolites (d-ROMs) in maternal vein before delivery and on postnatal day 5, and in umbilical artery at delivery. We also measured the pH, partial pressure of oxygen (PaO₂), partial pressure of carbon dioxide (PaCO₂) and base excess (BE) in umbilical artery blood collected at delivery.

Results: The concentrations of d-ROMs in maternal vein on postnatal day 5 were significantly decreased in the VD group, but were significantly increased in the CD group, compared to before delivery. The concentrations of d-ROMs in umbilical artery were significantly higher in the VD group than the CD group. Compared to the CD group, umbilical artery pH tended to be lower (p?=?0.07), and BE significantly lower (p?<?0.005), in the VD group. There were no significant differences in umbilical artery PaO₂ and PaCO₂ between the two groups.

Conclusion: Our findings indicate that those production levels of oxygen free radical in mothers are greater by CD than by VD, while those in neonates are greater by VD than by CD.     

Cervical IL-6 and pIGFBP-1 and the prediction of neonatal outcome in symptomatic preterm labour

Abstract

Objective: To evaluate the use of cervical Interleukin 6 (IL-6) and phosphorylated Insulin Growth Binding Protein 1 (pIGFBP1) in the prediction of adverse neonatal outcome.

Methods: Prospective observational study including women between 24 and 34 weeks of gestation. One hundred and twelve cervical samples for IL-6 and pIFBP1 were taken. Neonatal outcome variables were birth weight, Apgar scores at 1st/5th minute, gestational age at delivery, admission to neonatal unit (NNU) and to neonatal intensive care unit (NICU), composite neonatal morbidity (NCM) and neonatal mortality.

Results: Cervical IL-6 concentrations (pg/ml) were higher in neonates admitted to NNU and NICU versus non-admission, and women developing chorioamnionitis versus non-chorioamnionitis (mean?±?standard deviation: 168.1?±?205.2 versus 62.3?±?72.4, p?<?0.01; 262.1?±?298 versus 92?±?127.6, p?<?0.01, and 564?±?213 versus 93.4?±?126.4, p?<?0.05, respectively). In the NCM group, the IL-6 concentrations were higher compared to the non-NCM (181.7?±?224 versus 84.1?±?117.7, p?<?0.05). In the preterm births <37 weeks, no differences were found for NCM, admission to NICU/NNU. The logistic regression analysis, showed cervical IL-6 and examination-to-delivery interval as predictors of NCM in the univariate analysis. However, the only independent marker of adverse neonatal outcome was the examination-to-delivery interval.

Conclusions: Adverse neonatal outcome is associated with increased cervical IL-6 concentrations.     

The relationship between serum visfatin,adiponectin, and insulin sensitivity markers in neonates after birth

Aim.?The aim of this study was to assess the adiponectin and visfatin concentrations in small-for-gestational age (SGA), appropriate-for-gestational age (AGA), and large-for-gestational age (LGA) newborns and their mothers. Sixty parturients giving birth to 20 term AGA singleton infants, 20 term singleton SGA infants, and 20 term singleton LGA infants were included into the study.

Results.?Mean visfatin levels were found significantly higher in the SGA (p?<?0.001) and LGA (p?<?0.001) groups, and adiponectin levels were found significantly lower in the SGA group (p?<?0.001) when compared with the AGA group. The SGA and LGA groups had higher insulin concentrations and HOMA-IR in comparison with the AGA group. The visfatin, glucose levels, and HOMA-IR (p?<?0.001, p?<?0.001, and p: 0.002, respectively) were higher in the LGA group than SGA group.

Conclusion.?We found significantly higher insulin and visfatin levels in LGA neonates and lower adiponectin levels in SGA neonates. We concluded that the relationship between adiponectin and visfatin and insulin sensitivity (metabolic disturbances) is very complex with little evidence of correlation in SGA and LGA neonates.     

Oxidative stress status in umbilical cord blood from neonates born to mothers with atopic asthma

Abstract

Objective: Our objective was to assess the oxidative stress status and analyse the relationship between an oxidant/antioxidant imbalance and the mediator release properties of cord blood basophils from neonates born to mothers with atopic asthma.

Methods: Cord blood was collected from the neonates of 16 asthmatic mothers and 18 healthy mothers Basophils were purified and stimulated by Dermatophagoides farinae (Df), hyperosmotic mannitol or peptidoglycan (PGN). Immunoblotting detected nuclear factor κB (NFκB) as a measure of functional receptor response. The linear correlations between IL-4 levels in the supernatants and 3-nitrotyrosine (3-NT), glutathione peroxidase (GSH-Px) in the serum were evaluated.

Results: Compared with the healthy group, the levels of 3-NT in maternal blood and cord blood were significantly higher in allergic asthma group, whereas the GSH-Px activity were lower. After stimulation, cord blood basophils from the neonates born to atopic mothers produced more IL-4 involving NF-κB pathways. There was a significant relationship between the IL-4 levels produced by basophils and 3-NT (or GSH-Px) in cord blood from allergic asthma group.

Conclusion: In asthma, mediator release properties of human basophils induced by environmental allergens and irritants are associated with oxidative stress, which may be one of the pathogenesis of allergic diseases.     

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.