Maternal irisin level in last trimester isolated intrauterine growth-restriction

Objective: Intrahepatic cholestasis of pregnancy (ICP), the most common liver disease in pregnancy, is characterized by elevated serum total bile acid levels and pruritus. It has become clear that bile acids are no longer labeled as simple detergent-like molecules, but also represent complex hormonal metabolic regulators. ICP has also been associated with increased incidence rates of gestational diabetes mellitus. Irisin is a newly discovered myokine that is able to regulate glucose and lipid levels, thus improving insulin sensitivity. In this study, maternal serum irisin levels were analyzed in order to provide a new perspective on the pathogenesis of ICP.Materials and methods: In this controlled cross-sectional study, 58 consecutive pregnant women with ICP (30 with mild and 28 with severe disease) and 30 healthy women with uncomplicated pregnancies (as the control group) were examined. The maternal irisin, fasting blood glucose, fasting insulin and homeostatic model assessment of insulin resistance levels of the two groups were compared.Results: Serum irisin levels were significantly higher in the severe ICP group than in the mild ICP and control groups (p = 0.005 and p < 0.001, respectively). At the best cut-off level of 908.875 pg/ml, irisin accurately predicted ICP [AUC = 0.827 (95% CI: 0.745–0.909; p < 0.001)] with sensitivity and specificity rates of 72.5 and 86.8%, respectively. There was a significant negative correlation between irisin and fasting blood glucose levels (r = −0.399; p = 0.021).Conclusion: The results of this study indicate that serum irisin levels were significantly higher in women with ICP compared to healthy pregnant controls. However, it is difficult to infer whether high irisin level is a cause or effect of ICP.

Background: The aim of our study was to find out whether exercise of the pelvic muscles during vaginal delivery increases maternal and cord blood irisin levels. Methods: This prospective study included 20 patients who vaginally delivered their babies and 20 patients that underwent elective cesarean section. In the vaginal delivery group, delivery occured either spontaneously or by induction. In the other group, the patients were electively operated before uterine contractions started. We compared serum irisin levels of the two groups and cord blood irisin levels of the babies of these mothers. Results: There was no statistically significant difference in maternal serum irisin levels between the two groups (p&gt;0.05). We also found no statistically significant difference in cord blood irisin levels (p&gt;0.05). The positive correlation between maternal and cord blood irisin levels was found to be statistically significant (p&lt;0.05). We also detected a significant positive correlation between maternal irisin levels and BMI in our study (p&lt;0.05). Conclusions: Irisin is a challenging molecule. Although we did not find a significant difference in the irisin levels of women according to the method of delivery, we feel that further investigations are warranted.

Intrauterine growth restriction is associated with persistent aortic wall thickening and glomerular proteinuria during infancy

Effects of delivery on maternal & neonatal irisin levels in normal and preeclamptic pregnant women.

Pregnancies complicated by late-onset fetal growth restriction (FGR) are at increased risk of short- and long-term morbidities. Despite this, identification of cases at higher risk of adverse perinatal outcome, at the time of FGR diagnosis, is challenging. The aims of this study were to elucidate the strength of association between fetoplacental Doppler indices at the time of diagnosis of late-onset FGR and adverse perinatal outcome, and to determine their predictive accuracy. This was a prospective study of consecutive singleton pregnancies complicated by late-onset FGR. Late-onset FGR was defined as estimated fetal weight (EFW) or abdominal circumference (AC) < 3rd centile, or EFW or AC < 10th centile and umbilical artery (UA) pulsatility index (PI) > 95th centile or cerebroplacental ratio (CPR) < 5th centile, diagnosed after 32 weeks. EFW, uterine artery PI, UA-PI, fetal middle cerebral artery (MCA) PI, CPR and umbilical vein blood flow normalized for fetal abdominal circumference (UVBF/AC) were recorded at the time of the diagnosis of FGR. Doppler variables were expressed as Z-scores for gestational age. Composite adverse perinatal outcome was defined as the occurrence of at least one of emergency Cesarean section for fetal distress, 5-min Apgar score < 7, umbilical artery pH < 7.10 and neonatal admission to the special care unit. Logistic regression analysis was used to elucidate the strength of association between different ultrasound parameters and composite adverse perinatal outcome, and receiver-operating-characteristics (ROC)-curve analysis was used to determine their predictive accuracy. In total, 243 consecutive singleton pregnancies complicated by late-onset FGR were included. Composite adverse perinatal outcome occurred in 32.5% (95% CI, 26.7-38.8%) of cases. In pregnancies with composite adverse perinatal outcome, compared with those without, mean uterine artery PI Z-score (2.23 ± 1.34 vs 1.88 ± 0.89, P = 0.02) was higher, while Z-scores of UVBF/AC (-1.93 ± 0.88 vs -0.89 ± 0.94, P ≤ 0.0001), MCA-PI (-1.56 ± 0.93 vs -1.22 ± 0.84, P = 0.004) and CPR (-1.89 ± 1.12 vs -1.44 ± 1.02, P = 0.002) were lower. On multivariable logistic regression analysis, Z-scores of mean uterine artery PI (P = 0.04), CPR (P = 0.002) and UVBF/AC (P = 0.001) were associated independently with composite adverse perinatal outcome. UVBF/AC Z-score had an area under the ROC curve (AUC) of 0.723 (95% CI, 0.64-0.80) for composite adverse perinatal outcome, demonstrating better accuracy than that of mean uterine artery PI Z-score (AUC, 0.593; 95% CI, 0.50-0.69) and CPR Z-score (AUC, 0.615; 95% CI, 0.52-0.71). A multiparametric prediction model including Z-scores of MCA-PI, uterine artery PI and UVBF/AC had an AUC of 0.745 (95% CI, 0.66-0.83) for the prediction of composite adverse perinatal outcome. While CPR and uterine artery PI assessed at the time of diagnosis are associated independently with composite adverse perinatal outcome in pregnancies complicated by late-onset FGR, their diagnostic performance for composite adverse perinatal outcome is low. UVBF/AC showed better accuracy for prediction of composite adverse perinatal outcome, although its usefulness in clinical practice as a standalone predictor of adverse pregnancy outcome requires further research. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

The aim of the study was to investigate whether plasma irisin concentrations differ between uncomplicated, early-onset and late-onset pre-eclamptic pregnancies. This cross-sectional study was conducted on 27 women with early-onset, 27 women with late-onset pre-eclampsia (PE) and 26 healthy pregnant women. Maternal levels of serum irisin were measured with the use of an enzyme-linked immunosorbent assay kit. The mean maternal serum irisin level of early-onset PE was significantly lower than late-onset PE (1.14 ± 0.56 vs. 1.46 ± 0.59, p < .05) and control subjects (1.14 ± 0.56 vs. 3.14 ± 0.81, p < 0.001). The mean maternal serum irisin level of late-onset PE was significantly lower than the control group (1.46 ± 0.59 vs. 3.14 ± 0.81, p < 0.001). Maternal serum irisin levels are decreased in pre-eclamptic pregnancies. Low levels of irisin may be the result or the cause of pathologic changes in PE.Impact statementWhat is already known on this subject? There are only two studies in the literature evaluating maternal serum irisin levels in pre-eclamptic pregnancies. One study demonstrated decreased maternal serum irisin levels in pre-eclamptic patients and the other found no significant difference between pre-eclamptic and control pregnancies.What do the results of this study add? The present study demonstrates that serum irisin levels were significantly lower in pre-eclampsia than normotensive pregnancies. Furthermore, we have also demonstrated for the first time that women with EO-PE had significantly lower levels of serum irsin than women with LO-PE.What are the implications of these findings for clinical practice and/or further research? Low levels of irisin may be the result or the cause of pathologic changes in pre-eclampsia. More studies are needed to evaluate the relationship between irisin and pre-eclampsia.

To evaluate maternal and cord blood irisin levels in pregnant women with gestational diabetes mellitus (GDM) and in obese pregnant women without GDM. The study included 109 patients, with 34 patients in the GDM group, 40 in the obese non-GDM group, and 35 in the control group. Maternal serum irisin levels at the time of delivery were measured by an enzyme-linked immunosorbent assay kit. The correlation of serum irisin levels with metabolic parameters and anthropometric measurements was analyzed. There were significant differences between the study groups in terms of cord arterial, cord venous, and maternal serum irisin levels (P < 0.001, P < 0.01, P < 0.001, respectively). Cord arterial, cord venous, and maternal serum irisin levels were higher in the obese group compared to the control (P < 0.01, P < 0.01, P < 0.01, respectively) and the GDM group (P < 0.001, P < 0.001, P < 0.001, respectively). Elevation in irisin levels of women who have pregnancies complicated with obesity may be explained as part of the compensation mechanism against disturbed metabolic functions. Pregnant individuals with GDM have lower serum irisin levels in comparison to healthy pregnant women. In this regard, it is possible that the measurement of serum irisin levels may be utilized in the future for prediction, prevention, and treatment of GDM.

To determine whether a single elevated myocardial performance index (MPI) value in the third trimester of pregnancy is a marker for later adverse obstetric outcomes in stable placental-mediated disease, defined as well-controlled pre-eclampsia (PE) on a single agent and/or uncompensated intra-uterine growth restriction (IUGR). Fifty-five foetuses whose mothers had stable placental-mediated disease, either mild pre-eclampsia controlled on a single agent, and/or uncompensated IUGR in the third trimester, attending the Foetal Unit at Inkosi Albert Luthuli Hospital, Durban, South Africa were prospectively recruited with 55 matched controls. Recorded data for the subjects included demographic data of maternal age and parity, sonographic data of estimated foetal weight (EFW) and amniotic fluid index (AFI), myocardial performance index (MPI), and foetal Doppler data of the umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV). The mean gestational age in the controls, the IUGR and any PE cases was 31.4, 31.8 and 31.0 weeks, respectively. The distribution of MPI values was significantly lower in the controls compared to all other groups. The highest standardised MPI values were observed in the PE-IUGR group, where a median of 5.62 was observed. The only significant differences observed between the PE and IUGR groups was the UA resistance index (p = 0.01), where the IUGR cases tended to have higher UA values compared to the combined PE group. Borderline statistical significance was observed for the MCA resistance index values ( p = 0.05) between these groups. The overall adverse event rate in the cases was 49%. The highest rate was observed in the PE + IUGR group, where eight out of 12 (67%) experienced adverse events. MPI z-scores served as a good marker of adverse events, as evidenced by the total area under the curve (AUC) of 0.90 on the ROC curve. A cut-off value of 4.5 on the MPI z-score conferred a sensitivity of 89% and specificity of 68% for an adverse event later in pregnancy. In univariate logistic regression, MPI z-score, AFI, EFW, UA Doppler, CPR category, DV Doppler and MCA Doppler were assessed separately as potential predictors of adverse outcome. The only significant predictor of adverse outcome was MPI z-score. A single elevated value of the MPI ( z-score > 4.5) in the third trimester in stable placental-mediated disease was a strong indicator of adverse obstetric outcomes later in pregnancy. This has the potential to be incorporated in conjunction with standard monitoring models in stable placental-mediated disease to predict an adverse event later in pregnancy and thus to reduce perinatal morbidity and mortality.

The aim of this study is to examine the maternal serum and cord blood irisin and preptin levels in gestational diabetes mellitus (GDM) and correlate their levels with demographic and biochemical parameters. A total of 21 pregnant women with GDM and 21 BMI and age-matched pregnant women without GDM were included in the study. They underwent 50 g glucose challenge test (GCT) between 24-28th gestational weeks. Women with a GCT result higher than 140 mg/dl received 100 g oral glucose tolerance test (OGTT). Detection of one of the following criteria after OGTT was accepted as GDM: fasting plasma glucose level 92 mg/dL; 1-h plasma glucose level 180 mg/dL; and 2-h plasma glucose 153 mg/dL. Correlation between metabolic parameters and cord blood and maternal serum preptin and irisin levels in GDM and non-GDM subjects were analyzed. Maternal serum preptin values of GDM subjects were similar to the serum preptin values of non-GDM control subjects (123.12±34.3 pg/mL vs. 112.02±12.0 pg/mL, p<0.23). Cord blood preptin levels of GDM (64.3±1.09 pg/mL vs. 123.12±34.3 pg/mL, p<0.03) and non-GDM subjects (59.2±021 pg/mL vs. 112.02±12.0 pg/mL, p<0.02) were significantly lower than the maternal serum preptin values. Serum preptin levels of GDM group were positively correlated with HOMA-IR (r=0.33, p<0.04), but not with other parameters. Maternal serum irisin levels in the GDM group were lower than the non-GDM control group (5.32±0.44 µg/mL vs. 7.74±4.52 µg/mL, p<0.01). Cord blood irisin concentrations were found similar in women with GDM and non-GDM subjects (4.91±3.12 µg/mL vs. 5.01±2.14 µg/mL, p<0.14). Cord blood irisin levels of GDM subjects were similar to maternal serum irisin levels (4.91±3.12 µg/mL vs. 5.32±0.44 µg/mL, p<0.57). We found positive correlation between irisin concentration and fasting insulin, HOMA-IR, and BMI in women with GDM. In subgroup analysis of 6 patients using insulin treatment, serum and cord blood irisin and preptin levels were similar to those that did not use insulin. Maternal serum and cord blood preptin and irisin concentrations are regulated independently in women with GDM.

Objective: To prospectively investigate maternal concentrations of the myokine irisin in large for gestational age (LGA) and intrauterine growth restricted (IUGR) versus appropriate for gestational age (AGA) normal pregnancies and associate them with various perinatal parameters.Methods: Plasma irisin and insulin concentrations were measured by enzyme-linked immunosorbent assay (ELISA) and immunoradiometric assay (IRMA), respectively, in a cohort of 80 mothers delivering LGA (n = 30), IUGR (n = 30) and AGA (n = 20) singleton full-term infants.Results: Maternal irisin concentrations were similar among LGA, IUGR and AGA groups and did not correlate with respective insulin ones or maternal body mass index. In a combined group, maternal irisin concentrations decreased with advancing gestational age (p < 0.001) and were lower in multi-, compared to nulliparous women (p = 0.004). In the IUGR group, maternal irisin concentrations were higher in cases of smoking (p = 0.006).Conclusions: Irisin may not be differentially regulated in insulin resistance-associated pregnancy disorders resulting in fetal macrosomia and IUGR. Maternal irisin down-regulation with advancing gestation could possibly contribute to the observed maternal fat accumulation and progressive insulin resistance towards term. Similarly, lower maternal irisin concentrations in multiparous women may reflect the documented positive association between parity and fat deposition. Irisin up-regulation in cases of smoking may indicate the need for enhanced oxygen consumption to maintain energy production under conditions of hypoxia.

Abstract- The objective of this project was investigating and comparing changes of serum irisin, and trace levels of the elements (Zn, Cu, Mg) in pregnant women with gestational diabetes mellitus GDM in addition to wholesome pregnant group, examining the correlation among (Zn, Cu, Mg) levels and irisin insulin impedance in GDM pregnant women. Sixty GDM pregnant women and thirty wholesome pregnant women were examined. The pair groups were matched for age, and maternal serum irisin. Insulin levels and gestational age were calculated by the assay for enzyme-linked immune sorbent kit at gestation at 24-28 weeks. The confederation between clinical and biochemical parameters and maternal serum irisin levels were predestined. Serum levels of glucose, body mass index, insulin, OGTT, HOMA IR, HOMAβ, HbA1c, Hb%, irisin, Zn, Cu and Mg were investigated and analyzed for the examined collection as well as control samples. Pregnant women with GDM disease had noteworthy rising fast blood glucose FBG (P=0.004), first-hour OGTT glucose (P=0.001), second-hour OGTT glucose (P=0.001), fasting insulin FI (P=0.001) levels, HOMA IR (P=0.001), HOMAβ (P=0.001), HbA1C (P=0.001), Hb% (P=0.017), as contrasted to healthy women. Levels of irisin serum were significantly minimizing (P=0.001) in women, and sequentially more advanced GDM (mean±SD=71.65±8.03) than healthy pregnant controls (mean±SD 136.54±22.56). Analyses among irisin levels of anthropometric and biochemical values in gestational diabetes patients disclosed that none of the scrupulousness values were remediated with serum irisin level. His present outcomes indicate that the levels of serum irisin might be presented as an incoming GDM marker with decreased irisin levels being GDM symptomatic.

The aim of the present study was to compare maternal serum and cord blood irisin levels in females whose pregnancies were or were not complicated by idiopathic foetal growth restriction. A total of 30 subjects participated. The study group consisted of 15 female patients who were referred to our perinatology clinic for delivery because of foetal growth restriction developing in the third trimester. Fifteen females with uncomplicated singleton pregnancies constituted the control group. Irisin levels were assessed in maternal serum, as well as in serum from the umbilical vein and artery. The demographic features of the two groups were similar (p > 0.05). Gestational age at delivery and birth weight were higher in females with uncomplicated pregnancies (p = 0.001). Umbilical artery irisin levels were significantly lower in pregnancies complicated by foetal growth restriction compared to controls (p = 0.003). Umbilical artery irisin levels were positively correlated with foetal weight (p = 0.01) and foetal abdominal circumference (measured by ultrasonography) (p = 0.01). Maternal and umbilical vein irisin levels did not differ between the two groups (p > 0.05). The data suggest that umbilical artery irisin levels were lower in pregnancies complicated by foetal growth restriction. Such lower irisin levels may contribute to the pathogenesis of this common condition, and metabolic syndrome may be a long-term consequence of idiopathic FGR.

ABSTRACTObjectives: Intrauterine growth restriction (IUGR) is one of the common conditions that interfere with the growth of the fetus accounting for 10-15%of pregnant woman. Literature explores a wide range of incidence of perinatal complication including mortality among IUGR pregnancies. Limiteddata available on these complications confined to coastal Karnataka and its association with abnormal arterial Doppler flow pattern. To study theperinatal complications associated with IUGR pregnancies and its prevalence in comparison to healthy controls of comparable gestational age.Methods: This cohort study screened 53 IUGR fetuses by an antenatal scan at gestational age of 27 weeks or more. The diagnosis of IUGR was madeaccording to established criteria from SOGC clinical practice guidelines August 2013. The data also included 48 appropriate for gestational age fetuseswith healthy mothers with the comparable gestational week. Experienced cardiac sonographer and gynecologist performed fetal echocardiography(ECHO) using Vivid 7, GE health-care system ECHO machine with the convex transducer of frequency 1.7-2.4 MHz. The study was conducted at southIndian tertiary care center.Results: This study included 53 IUGR cases and 48 non-IUGR controls. The mean age was 27±4.37 and 26.88±3.14 years in IUGR and non-IUGRgroups, respectively. Fetal Doppler study variables showed a significant decrease in peak aortic velocity and velocity time integral which was notevident on other valves, though mitral antegrade flow during atrial contraction was found to be lower among IUGR group. In two-dimensional chamberquantification of IUGR group revealed significant increase in pulmonary artery dimension, right ventricular (RV) dimension and RV thickness than thecontrol group (p&lt;0.05). The anthropometric parameters such as weight and length; abdomen circumference was significantly lower in IUGR group,whereas head circumference found to be more in IUGR group (p&lt;0.001). The gestational weeks at delivery was significantly different among twogroups with IUGR group depicting the early delivery group. p&lt;0.001(35.58±2.92 and 38.5±0.96 in IUGR and non-IUGR groups, respectively). IUGRgroup also had prolonged neonatal intensive care unit stay when compared to controls (p&lt;0.001).Conclusions: IUGR carries profound course in altered Doppler indices and cardiac function which explore its prediction on mortality and adverseperinatal outcome. This study showed significant perinatal mortality accounting for 5.6% among IUGR cases when compared to normal. Althoughtissue Doppler indices show normal variants, IUGR possesses significant adverse perinatal outcome, however with lesser incidence compared tosevere form of IUGR subsets who show altered tissue annular velocities.Keywords: Intrauterine growth restriction, Echocardiography, Doppler, Perinatal.

PurposeWe aimed to provide diagnostic models based on different parameters of placental magnetic resonance imaging (MRI) to detect intrauterine growth restriction (IUGR), as well as the severity of placental insufficiency.Material and methodsWe included 44 foetuses with appropriate weight for gestational age (AGA) and 46 foetuses with documented IUGR, defined as the estimated foetal weight (EFW) below the 10th centile. Using Doppler ultrasound, IUGR cases were divided into 2 groups: 1) IUGR with severity signs: EFW < 3rd centile, or cerebroplacental ratio < 5th centile, or abnormal umbilical/uterine artery pulsatility index; and 2) non-severe IUGR without any of this criterion. For all these participants, placental MRI was performed in the third gestational trimester, and its parameters were compared between AGA and IUGR, as well as between the severe and non-severe IUGR groups. Two diagnostic models consisting of significant predictors were developed, and their performance was investigated with accuracy metrics.ResultsThe severity signs were detected in 25 (54.3%) IUGR cases. The diagnostic model for the differentiation of IUGR from AGA revealed an acceptable performance (area under the curve [AUC] of 0.749) and consisted of 2 variables: 1) the largest size of infarct ≥ 25 mm (odds ratio [OR] = 5.01, p = 0.001), and 2) thickness : volume ratio ≥ 0.043 (OR = 3.76, p = 0.027); while, the logistic regression model for detection of the severity signs was even better, with AUC = 0.862, and comprised of 2 predictors: 1) placental infarct percent ≥ 10% (OR = 26.73, p = 0.004), and 2) placental globular shape (OR = 5.40, p = 0.034).ConclusionsPlacental MRI parameters can differentiate IUGR from AGA, and more precisely, assess the severity of placental insufficiency in IUGR foetuses.

Objectives Intrauterine growth restriction (IUGR) is diagnosed when the estimated fetal weight remains below the 10th percentile of gestational age based on pathological restriction of growth and/or accompanying Doppler abnormalities. Endothelial dysfunction is a common pathogenetic pathway underlying IUGR etiology. Endocan (ESM-1) is a novel marker of endothelial dysfunction and inflammation found in the maternal circulation. This study was designed to compare plasma endocan levels between pregnancies complicated with IUGR and a control group. Study design Forty-four pregnancies complicated with IUGR and 47 healthy pregnancies were included. Maternal plasma endocan levels were detected by ELISA. Parametric data was studied by Student’s t-test. Mann–Whitney U-test was used in analyzing non-parametric data. Categorical variables underwent chi-square test. ROC analysis was performed to define the cutoff value of endocan in detecting IUGR. Spearman correlation test was performed. Results Maternal plasma endocan level varied significantly between IUGR and healthy pregnancies and was 1.8 fold higher in the IUGR group (793.0 (IQR:544.4–1896.0) ng/L vs. 441.8 (IQR: 408.3–512.4) ng/L, p < .001). There was a weak negative correlation between endocan level and 5th and 10th minute APGAR Scores (r = −0.256; p = .015 and r = −0.215; p = .042, respectively), a weak positive correlation with umbilical artery pulsatility index, and a moderate negative correlation with cerebroplacental ratio (r = 0.394; p < .001 and r = −0.459; p < .001, respectively). Conclusions There was a significant difference between endocan levels of IUGR and healthy pregnancies. Further studies might be designed to investigate the performance of endocan in predicting neonatal outcomes for pregnancies complicated with IUGR.