Antibody microarray analysis of the amniotic fluid proteome for predicting the outcome of rescue cerclage in patients with cervical insufficiency

Little is known about the biomarkers that can identify patient candidates suitable for rescue cerclage procedure. The purpose of the study was to identify novel biomarkers in amniotic fluid (AF) that can predict the outcome of rescue cerclage in patients with cervical insufficiency by using an antibody microarray. This case–control study was conducted using AF samples collected from singleton pregnant women who underwent rescue cerclage following a diagnosis of cervical insufficiency (19–25 weeks). Patients were divided into case (n=20) and control (n=20) groups based on the occurrence of spontaneous preterm delivery (SPTD) at <34 weeks of gestation after cerclage placement. The AF proteomes were analyzed using an antibody microarray for biomarker discovery work. Ten candidate biomarkers of interest were validated by enzyme-linked immunosorbent assay (ELISA). Thirty-one molecules studied showed significant intergroup differences (≥two-fold change in signal intensity). Validation by ELISA confirmed significantly higher levels of a proliferation-inducing ligand (APRIL), S100 calcium-binding protein A8/A9 complex (S100 A8/A9), tissue inhibitors of metalloproteinase-1 (TIMP-1), macrophage inflammatory protein-1α (MIP-1α), and interleukin-8 (IL-8) in women who had SPTD at <34 weeks. Of these, AF S100 A8/A9 and TIMP-1 levels were independent of other potentially confounding factors (e.g., cervical dilatation). S100 A8/A9 had the highest area under the curve (AUC) at 0.857. Using protein–antibody microarray technology, we identified differentially expressed proteins (DEPs) and several novel biomarkers (APRIL, IL-8, MIP-1α, S100 A8/A9, and TIMP-1) in AF from women who had SPTB at <34 weeks after cerclage for cervical insufficiency. These data can provide an insight into the molecular mechanisms underlying SPTD after rescue cerclage in patients with cervical insufficiency.     

Association between the Lipid Levels and Single Nucleotide Polymorphisms of ABCA1, APOE and HMGCR Genes in Subjects with Spontaneous Preterm Delivery

Spontaneous preterm delivery (SPTD) with gestational age between 28 and 37 complete weeks was reported to have a genetic predisposition in lipids metabolism. This study aimed to investigate the association between the lipid levels and gene polymorphisms of ABCA1 (rs2422493), APOE (rs7412) and HMGCR (rs12916) in Chinese pregnant women with SPTD. A case-control study was conducted at the baseline randomization in 200 SPTD and 178 healthy full term delivery (FTD) women. Maternal blood lipids were detected close to delivery of fetus in SPTD group and in FTD group with gestational age-matched. Cord blood lipids were detected after delivery in two groups. Three genotypes both in maternal and cord blood were determined by real time PCR. The results showed that the levels of total cholesterol (TCHO), triglyceride (TG), high density lipoprotein (HDL), and low-density lipoprotein cholesterol (LDL) in the maternal blood in the SPTD group were significantly lower than those in the FTD group, while the levels of TCHO, HDL, and LDL in the cord blood in the SPTD group were significantly higher than those in the FTD group. In the SPTD subjects, the levels of TG and LDL in the maternal blood were associated with different genotypes of HMGCR gene rs12916 loci. These results indicate that abnormal lipid metabolism may exist in SPTD women and the premature fetus and the HMGCR gene may be a susceptible gene for SPTD.     

Total matrix metalloproteinase-8 serum levels in patients labouring preterm and patients with threatened preterm delivery

Preterm labour and prematurity are still a main cause of perinatal morbidity nowadays. The aim of our study was to assess the role of MMP-8 as a predictive marker of preterm delivery. Four groups of patients were involved to the study: I - pregnant women at 24-34 weeks of gestation with any symptoms of threatened preterm labour; II - threatened preterm labour patients between 24-34 weeks of gestation; III - preterm vaginal delivery patients; IV - healthy term vaginal delivery patients. Serum concentration of total MMP-8 was measured using two enzyme-linked immunosorbent assays. There were no significant differences in the median concentrations of total MMP-8 between physiological pregnancy and threatened preterm labour patients with existing uterine contractility. No significant differences of total MMP-8 were either found between healthy term and preterm labouring patients. The studies on a larger population are needed to reject the hypothesis that preterm labour is connected with increased MMP-8 plasma concentrations of women in preterm labour and threatened preterm delivery.     

MicroRNA‐transcriptome networks in whole blood and monocytes of women undergoing preterm labour

Preterm birth is attributed to neonatal morbidity as well as cognitive and physiological challenges. We have previously identified significant differences in mRNA expression in whole blood and monocytes, as well as differences in miRNA concentration in blood plasma, extracellular vesicles (EV) and EV‐depleted plasma in women undergoing spontaneous preterm labour (sPTL). The goal of this analysis was to identify differences in miRNA expression within whole blood (WB) and peripheral monocytes (PM) from the same population of women undergoing sPTL compared with non‐labouring controls matched by gestational age. We performed single‐end small RNA sequencing in whole blood and peripheral monocytes from women undergoing sPTL with active contractions (24‐34 weeks of gestation, N = 15) matched for gestational age to healthy pregnant non‐labouring controls (>37 weeks gestation, N = 30) who later delivered at term as a part of the Ontario Birth Study (Toronto, Ontario CA). We identified significant differences in expression of 16 miRNAs in PMs and nine miRNAs in WB in women undergoing sPTL. In PMs, these miRNAs were predicted targets of 541 genes, including 28 previously associated with sPTL. In WB, miRNAs were predicted to target 303 genes, including nine previously associated with sPTL. These genes were involved in a variety of immune pathways, including interleukin‐2 signalling. This study is the first to identify changes in miRNA expression in WB and PMs of women undergoing sPTL. Our results shed light on potential mechanisms by which miRNAs may play a role in mediating systemic inflammatory response in pregnant women that deliver prematurely.     

Limited Relationship between Cervico-Vaginal Fluid Cytokine Profiles and Cervical Shortening in Women at High Risk of Spontaneous Preterm Birth

Objective

To determine the relationship between high vaginal pro-inflammatory cytokines and cervical shortening in women at high risk of spontaneous preterm labor and to assess the influence of cervical cerclage and vaginal progesterone on this relationship.

Methods

This prospective longitudinal observational study assessed 112 women with at least one previous preterm delivery between 16 and 34 weeks’ gestation. Transvaginal cervical length was measured and cervico-vaginal fluid sampled every two weeks until 28 weeks. If the cervix shortened (<25 mm) before 24 weeks’ gestation, women (cases) were randomly assigned to cerclage or progesterone and sampled weekly. Cytokine concentrations were measured in a subset of cervico-vaginal fluid samples (n = 477 from 78 women) by 11-plex fluid-phase immunoassay.

Results

All 11 inflammatory cytokines investigated were detected in cervico-vaginal fluid from women at high risk of preterm birth, irrespective of later cervical shortening. At less than 24 weeks’ gestation and prior to intervention, women destined to develop a short cervix (n = 36) exhibited higher cervico-vaginal concentrations than controls (n = 42) of granulocyte-macrophage colony-stimulating factor [(GM-CSF) 16.2 fold increase, confidence interval (CI) 1.8–147; p = 0.01] and monocyte chemotactic protein-1 [(MCP-1) 4.8, CI 1.0–23.0; p = 0.05]. Other cytokines were similar between cases and controls. Progesterone treatment did not suppress cytokine concentrations. Interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor (G-CSF), interferon (IFN)-γ and tumour necrosis factor (TNF)-α concentrations were higher following randomization to cerclage versus progesterone (p<0.05). Cerclage, but not progesterone treatment, was followed by a significant increase in cervical length [mean 11.4 mm, CI 5.0–17.7; p<0.001].

Conclusions

Although GM-CSF and MCP-1 cervico-vaginal fluid concentrations were raised, the majority of cervico-vaginal cytokines did not increase in association with cervical shortening. Progesterone treatment showed no significant anti-inflammation action on cytokine concentrations. Cerclage insertion was associated with an increase in the majority of inflammatory markers and cervical length.     

Placental hCG immunohistochemistry and serum free-Beta-hCG at 11–13 weeks’ gestation in intrauterine fetal demise

Intrauterine fetal demise (IUFD) is a continuing problem that can result in severe psychosocial trauma for expecting parents. Our aim was to analyze placental human chorionic gonadotropin (hCG) expression at the third trimester and free-Beta-hCG levels measured at 11–13 weeks in cases of IUFD that occurred after 34 weeks’ gestation, alongside a parallel analysis of a set of controls. In this retrospective study we present immunohistochemical data of a tissue microarray that included the following: 12 placentas where IUFD occurred (24 samples); 28 control placentas from first and early second trimester (56 samples); and 30 control placentas at term of pregnancy (60 samples). We used immunohistochemistry to analyze the expression of hCG. Data are also presented from 3,240 first trimester trisomies screening tests, of which 21 pregnancies resulted in IUFD (15 after 22 weeks’ gestation and 6 after 34 weeks). All pregnancies took place between 2001 and 2010. For each case, our analysis took account of pregnancy-related data that we gathered from the relevant clinical files. Small for gestational age (SGA) was defined as neonatal weight <10th centile. Our results show that full-term placentas displayed a decreased immunohistochemical expression of hCG in comparison with those at the first trimester (p < 0.05). Moreover, low hCG expression in placentas at the third trimester was shown to be an independent risk factor for IUFD after 34 weeks’ gestation (under multivariate analysis with p < 0.05). When we reviewed first trimester screening results, free-Beta-HCG was found to be lower for the group of IUFD after 34 weeks’ gestation than in the group of live births (p < 0.05). This difference was heavily weighted by non small for gestational age (non-SGA) associated cases of IUFD: these presented a free-Beta-hCG MoM log of ?0.27 (±0.09) in contrast to just ?0.01 (±0.03) in SGA-associated IUFD (p < 0.05). Our results show that low hCG is an independent risk factor for IUFD after 34 weeks’ gestation, and that levels of the hormone are significantly lower in non-SGA associated cases of IUFD.     

The Effect of Gestational Age and Labour on Markers of Lipid and Protein Oxidation in Cord Plasma

There are many potential sources of reactive oxidants around the time of birth and pre-term infants are considered to be particularly vulnerable to oxidative injury. To gain insight into these processes, we have measured biomarkers of lipid and protein oxidation in umbilical cord plasma and related concentrations to mode of delivery and gestational age. Protein carbonyls were measured by ELISA and malondialdehyde (MDA) by HPLC after reaction with thiobarbituric acid, for 54 pre-term (≤36 weeks gestational age) and 43 term infants. Protein carbonyls were significantly lower in pre-term (median for <32 weeks gestational age 0.048?nmol/mg protein) than in term infants (0.105?nmol/mg, p=0.004), and were unrelated to mode of delivery. In contrast, MDA concentrations were higher in the very pre-term (<32 weeks gestation) group (2.47 compared with 1.83?μM for term infants, p<0.0001). MDA concentrations were higher in infants who were born with labour compared with elective caesarean section. Pre-eclampsia in the mother was associated with higher cord blood MDA concentrations. The MDA results are consistent with other studies of this marker and could be interpreted as indicating increased oxidative stress associated with prematurity and labour. However, the lower protein carbonyls in pre-term infants would lead to an opposite interpretation. More information is needed on the source and fate of these and other biomarkers before drawing strong conclusions on how they reflect oxidative stress in this and other clinical situations.     

The patterns of changes in the electrohysterogram amplitude characteristics in healthy pregnant women during the third trimester

The patterns of changes in the amplitude characteristics of the bioelectrical activity of the uterus were studied on the basis of the external multichannel electrohysterography data in healthy pregnant women with physiological pregnancy at weeks 28 to 40 of gestation using electrophysiological methods. Three groups of women were identified, according to the term of pregnancy. The first group included 12 women at 26–28 weeks of gestation; the second group, 49 women at 29–37 weeks of gestation; and the third group, 48 women at 38–40 weeks of gestation. The preliminary norms of the electrohysterogram amplitude characteristics were obtained. The average electrohysterogram amplitude was revealed to increase with the term of the pregnancy.     

Long noncoding RNA expression in the cervix mid-pregnancy is associated with the length of gestation at delivery

Infants born preterm are at increased risk of multiple morbidities and mortality. Why some women deliver preterm remains poorly understood. Prior studies have shown that cervical microRNA expression and DNA methylation are associated with the length of gestation. However, no study has examined the role of long noncoding RNAs (lncRNAs) in the cervix during pregnancy. To determine whether expression of lncRNAs is associated with length of gestation at delivery, we analyzed RNA from cervical swabs obtained from 78 women during pregnancy (mean 15.5, SD 5.0, weeks of gestation) who were participating in the Spontaneous Prematurity and Epigenetics of the Cervix (SPEC) Study in Boston, MA, USA. We used a PCR-based platform and found that 9 lncRNAs were expressed in at least 50% of the participants. Of these, a doubling of the expression of TUG1, TINCR, and FALEC was associated with shorter lengths of gestation at delivery [2.8 (95% CI: 0.31, 5.2); 3.3 (0.22, 6.3); and 4.5 (7.3, 1.6) days shorter respectively]. Of the lncRNAs analyzed, none was statistically associated with preterm birth, but expression of FALEC was 2.6-fold higher in women who delivered preterm vs. term (P = 0.051). These findings demonstrate that lncRNAs can be measured in cervical samples obtained during pregnancy and are associated with subsequent length of gestation at delivery. Further, this study supports future work to replicate these findings in other cohorts and perform mechanistic studies to determine the role of lncRNAs in the cervix during pregnancy.     

Vaginal sonography of the cervix for the prediction of "time to delivery" in ART twins gestations.

The present study aimed to determine a reliable tool to estimate the interval time to delivery in assisted conception twin pregnancies. Mid-gestation cervical length was prospectively measured using transvaginal sonography (TVS) during routine antenatal care. Fifty-seven of 101 suitable women were longitudinally followed and two TVS measurements of their cervical length were obtained, first at approximately 24 weeks gestation and then at approximately 27 weeks gestation. The mean cervical length decreased from 37 +/- 12mm at first measurement to 34 +/- 11mm at the second one. A linear regression model was found between the time interval of the first (R = 0.656, p < 0.001) and the second (R = 0.435, p < 0.001) assessments and the week of delivery. The current data confirm that the length of the preserved segment of the cervix is an important indicator of its competence. A simple equation using the cervical length (mm) divided by 3 can predict mid gestation scan-to-delivery interval in twin gestation.     

Cervical length as a predictor of pre-term birth in twin gestations.

The aim of this study was to determine the predictive value of cervical length as a risk factor for spontaneous pre-term birth in twin gestations. A retrospective chart review was carried out on patients with twin pregnancies referred to our multiples' clinic. Cervical length was measured by transvaginal ultrasonography. Patients with an indicated pre-term delivery or intervention were excluded from the analysis. Outcomes included preterm delivery < 28 and < 35 weeks gestation. After extracting the data, 2 x 4 tables were constructed. Likelihood ratios were then generated for cervical lengths < or = 2.0 cm, < or = 2.5 cm, < or = 3.0 cm, and > 3.0 cm. Because of the limited number of measurements taken < 25 weeks gestation, we elected to collapse the tables, thereby achieving more meaningful results. For measurements taken before 30 weeks gestation, a shorter cervix did predict delivery < 28 weeks gestation (likelihood ratios for cervical lengths < or = 2.0 cm, < or = 2.5 cm, < or = 3.0 cm, and > 3.0 cm were 4.43, 1.94, 0.97, and 1.02, respectively). The probability of preterm delivery < 35 weeks gestation increased with decreasing cervical length (likelihood ratios for cervical length < or = 2.0 cm, < or = 2.5 cm, < or = 3.0 cm, and > 3.0 cm were 2.58, 1.66, 1.38, and 0.81, respectively). A shorter cervix measured before 30 weeks gestation was a stronger predictor of preterm delivery < 28 weeks compared to < 35 weeks gestation. Cervical length was not predictive of preterm delivery if measured after 30 weeks. Cervical length is predictive of preterm delivery < 28 weeks and < 35 weeks gestation when measured before 30 weeks gestation. No trend was seen when measured after 30 weeks gestation. A prospective study is currently underway to confirm these results.     

Corticotropin-releasing hormone, its binding protein and receptors in human cervical tissue at preterm and term labor in comparison to non-pregnant state

Background  

Preterm birth is still the leading cause of neonatal morbidity and mortality. The level of corticotropin-releasing hormone (CRH) is known to be significantly elevated in the maternal plasma at preterm birth. Although, CRH, CRH-binding protein (CRH-BP), CRH-receptor 1 (CRH-R1) and CRH-R2 have been identified both at mRNA and protein level in human placenta, deciduas, fetal membranes, endometrium and myometrium, no corresponding information is yet available on cervix. Thus, the aim of this study was to compare the levels of the mRNA species coding for CRH, CRH-BP, CRH-R1 and CRH-R2 in human cervical tissue and myometrium at preterm and term labor and not in labor as well as in the non-pregnant state, and to localize the corresponding proteins employing immunohistochemical analysis.     

Preterm Birth Prevention Post-Conization: A Model of Cervical Length Screening with Targeted Cerclage

Women with a history of excisional treatment (conization) for cervical intra-epithelial neoplasia (CIN) are at increased risk of preterm birth, perinatal morbidity and mortality in subsequent pregnancy. We aimed to develop a screening model to effectively differentiate pregnancies post-conization into low- and high-risk for preterm birth, and to evaluate the impact of suture material on the efficacy of ultrasound indicated cervical cerclage. We analysed longitudinal cervical length (CL) data from 725 pregnant women post-conization attending preterm surveillance clinics at three London university Hospitals over a ten year period (2004–2014). Rates of preterm birth <37 weeks after targeted cerclage for CL<25mm were compared with local and national background rates and expected rates for this cohort. Rates for cerclage using monofilament or braided suture material were also compared. Of 725 women post-conization 13.5% (98/725) received an ultrasound indicated cerclage and 9.7% (70/725) delivered prematurely, <37weeks; 24.5% (24/98) of these despite insertion of cerclage. The preterm birth rate was lower for those that had monofilament (9/60, 15%) versus braided (15/38, 40%) cerclage (RR 0.7, 95% CI 0.54 to 0.94, P = 0.008). Accuracy parameters of interval reduction in CL between longitudinal second trimester screenings were calculated to identify women at low risk of preterm birth, who could safely discontinue surveillance. A reduction of CL <10% between screening timepoints predicts term birth, >37weeks. Our triage model enables timely discharge of low risk women, eliminating 36% of unnecessary follow-up CL scans. We demonstrate that preterm birth in women post-conization may be reduced by targeted cervical cerclage. Cerclage efficacy is however suture material-dependant: monofilament is preferable to braided suture. The introduction of triage prediction models has the potential to reduce the number of unnecessary CL scan for women at low risk of preterm birth.     

Changes in Interleukin 1 Levels in Human Amniotic Fluid with Gestational Ages and Delivery

In order to understand the role of interleukin 1 (IL-1) in pregnancy, the amount of IL-1 in normal human amniotic fluid (AF) from various gestational ages and delivery was measured using an ELISA. AF samples were divided into three groups of varying gestational ages. Group 1 of AF was collected by amniocentesis from gestational ages <24 weeks (n = 13). Group 2 was collected transvaginally during delivery following labor ≥36 weeks (n = 36). Group 3 was transabdominally collected from elective cesarean section without labor ≥36 weeks (n ?8). IL-1α was present in AF of early gestational age, 19.2±21.7 pg/ml, in group 1, and appeared to increase with gestational age, 63.4±50.1 pg/ml, in group 3. In contrast, IL-1β was not detectable in either group 1 or 3. However, the concentration of IL-1 in group 2 was extremely high (IL-lα, 233.1±351.9 pg/ml; IL-1β, 1,093.5±1,369.7 pg/ml) compared to the other groups. Moreover, these concentrations tended to increase with the duration of labor. IL-1α and IL-1β concentrations in AF were intimately related. These findings suggest that IL-1 has some roles during pregnancy and especially during labor.     

Serum reference levels of selenium,zinc and copper in healthy pregnant women at a prenatal screening program in southeastern mediterranean region of Turkey

ProjectThe aim of the study was to investigate the serum reference range for Selenium (Se), Zinc (Zn) and Copper (Cu) levels in women of 10–14 (group I) and 16–20 (group II) weeks of gestation and compare them with those in non-pregnant healthy women and healthy men.ProcedureThis cross-sectional study was performed in 351 pregnant women [group I (n: 177) and group II (n: 174)], 30 non-pregnant women and 30 men as controls. The levels of Se, Zn and Cu levels were determined on flame and furnace atomic absorption spectrophotometer using Zeeman background correction.ResultsIn the 10–14 weeks of gestation Se, Zn and Cu serum levels were 44.85±9.23, 81.30±31.94 and 132.33±38.24 ug/dl, in 16–20 weeks of gestation were 47.18±10.92, 74.25±22.47 and 164.86±39.69 ug/dl, in non-pregnant women were 55.38±8.81, 121.41±29.22 and 104.75±39.14 ug/dl also in men 72.24±9.28, 134.85±15.95 and 78.29±20.90 ug/dl, respectively.ConclusionA significant low level of serum Se, Zn and a high level of Cu in the pregnant women in the 10–14 and 16–20 weeks of gestation were detected when compared with that of non-pregnant women and men.     

Gestation Dependant Changes in Angiogenic Factors and Their Associations with Fetal Growth Measures in Normotensive Pregnancy

Background

Earlier studies indicate that altered angiogenesis at birth is associated with poor birth outcome in women with preeclampsia. Now, we hypothesize that the progressive gestation dependant changes in markers of angiogenesis will be more useful to predict birth weight early even in a normotensive pregnancy. This study for the first time examines the association of gestation dependant changes in the levels of maternal angiogenic factors in addition to their levels in cord with birth weight.

Method

Ninety two pregnant women were followed at three different time points: 16–20 weeks, 26–30 weeks and at delivery during pregnancy. Plasma levels of angiogenic and anti angiogenic factors were determined by commercial enzyme-linked immunosorbent assay (ELISA) kits.

Results

Maternal plasma VEGF levels increased (p<0.01) till the second time point and decreased (p<0.05) up to delivery while plasma sFlt-1 levels increased (p<0.01) at delivery. PlGF levels peaked (p<0.01) at second time point and decreased (p<0.01) at delivery. Cord plasma VEGF levels were higher (p<0.01) and sFlt-1 levels were lower (p<0.01) as compared to maternal values at all time points. Maternal plasma VEGF levels at first time point and PlGF levels at delivery were positively (p<0.05 and p<0.01 respectively), while sFlt-1/PlGF ratio at delivery was negatively associated (p<0.05) with birth weight.

Conclusion

Levels of pro- and anti-angiogenic factors may be differentially regulated across gestation. Maternal VEGF levels at early gestation (16–20 weeks) may be predictive of birth weight in healthy term pregnancies.     

mRNA expression and localization of bNOS,eNOS and iNOS in human cervix at preterm and term labour

Background  

Preterm birth is the primary cause of the neonatal mortality and morbidity. There will be no preterm birth without a cervical softening. Nitric oxide (NO) is shown to be a mediator of term cervical ripening. The aim of this study was to investigate mRNA expression of the three isomers of NO synthases (NOS) and to identify them by immunohistochemistry in the human cervix at preterm birth compared to term.     

Identification of bactenecin-1 in cervicovaginal fluid by two-dimensional electrophoresis in an ovine model of preterm labour

Preterm labour is a major problem in obstetrics. Timely intervention with available treatments is hampered by the lack of a reliable test of imminent preterm delivery. Current methods of diagnosis are based on the detection of breakdown products of foetal membranes or structural changes to the cervix when preterm labour is well established. The aim of this study was to screen the cervicovaginal fluid (CVF) proteome to identify labour-associated proteins that could be used as markers of imminent preterm delivery. Labour was induced in sheep at 135 days of gestation (term 147 days) by foetal infusion of dexamethasone (1 mg/24 h). CVF samples were collected before and 28 h after the start of infusion as well as at delivery (58.7 +/- 1.9 after the start of infusion, n = 5). One protein that was upregulated eight-fold, was bactenecin-1, a member of the cathelicidin family of antimicrobial proteins. This antimicrobial protein warrants further investigation as a marker of preterm labour, particularly during the period after the initiation of labour but before there is marked cervical connective tissue breakdown.     

Peptidome analysis of human skim milk in term and preterm milk

The abundant proteins in human milk have been well characterized and are known to provide nutritional, protective, and developmental advantages to both term and preterm infants. Due to the difficulties associated with detection technology of the peptides, the expression of the peptides present in human milk is not known widely. In recent years, peptidome analysis has received increasing attention. In this report, the analysis of endogenous peptides in human milk was done by mass spectrometry. A method was also developed by our researchers, which can be used in the extraction of peptide from human milk. Analysis of the extracts by LC–MS/MS resulted in the detection of 1000–3000 Da peptide-like features. Out of these, 419 peptides were identified by MS/MS. The identified peptides were found to originate from 34 proteins, of which several have been reported. Analysis of the peptides’ cleavage sites showed that the peptides are cleaved with regulations. This may reflect the protease activity and distribution in human body, and also represent the biological state of the tissue and provide a fresh source for biomarker discovery. Isotope dimethyl labeling analysis was also used to test the effects of premature delivery on milk protein composition in this study. Differences in peptides expression between breast milk in term milk (38–41 weeks gestation) and preterm milk (28–32 weeks gestation) were investigated in this study. 41 Peptides in these two groups were found expressed differently. 23 Peptides were present at higher levels in preterm milk, and 18 were present at higher levels in term milk.     

Comparison of Misoprostol and Dinoprostone for elective induction of labour in nulliparous women at full term: A randomized prospective study

Background  

The objective of this randomized prospective study was to compare the efficacy of 50 mcg vaginal misoprostol and 3 mg dinoprostone, administered every nine hours for a maximum of three doses, for elective induction of labor in a specific cohort of nulliparous women with an unfavorable cervix and more than 40 weeks of gestation.