The use of PAMG-1 testing in patients with preterm labor, intact membranes and a short sonographic cervix reduces the rate of unnecessary antenatal glucocorticoid administration.

OBJECTIVES: To assess the frequency of antenatal corticosteroid (ACS) administration in cases with shortened cervical length by addition of placental alpha-microglobulin-1 (PAMG-1) testing to sonographic examination. METHODS: Single centre retrospective cohort study. Rate of ACS administration was compared between cases with cervical length between 15 and 25 mm and cases with positive PAMG-1 testing and cervical length between 15 and 25 mm. We evaluated the following outcome parameters: Rate of ACS administration, gestational age at delivery, time to delivery, delivery within seven days, delivery <34 and <37 weeks' gestation, rate of admission to neonatal intensive care unit (NICU). RESULTS: In total, 130 cases were included. "PAMG-1 group" consisted of 68 women, 62 cases built the "historical control group". ACS administration was performed less frequently in the "PAMG-1 cohort" (18 (26%) vs. 46 (74%); p<0.001). The rate of delivery within seven days did not differ (2 (3%) vs. 4 (6.5%); p=0.4239). The rates of delivery <34 weeks' gestation (7 (10%) vs. 9 (15%); p=0.4643) and <37 weeks' gestation (19 (28%) vs. 26 (42%); p=0.0939) did not differ. Time to delivery interval was longer in the PAMG-1 group (61.5 vs. 43 days, p=0.0117). NICU admission occurred more often in the "historical control group" (22 (38%) vs. 28 (60%); p=0.0272). CONCLUSIONS: Addition of biomarker testing can help to avoid unnecessary ACS administrations in women with shortened cervical length.

Biomarker Modulation Study of Celecoxib for Chemoprevention in Women at Increased Risk for Breast Cancer: A Phase II Pilot Study.

In preclinical studies, celecoxib has been associated with reduced risk of breast cancer. In this study, the aim was to assess the biomodulatory effect of celecoxib on blood and benign breast tissue biomarkers in women at increased risk for breast cancer. Women at increased risk for breast cancer [5-year Gail risk score of >1.67%, history of atypical hyperplasia, lobular carcinoma in situ, or previous estrogen receptor (ER)-negative breast cancer] were treated with celecoxib at 400 mg orally twice daily for 6 months. Participants underwent random periareolar fine needle aspiration and blood draw at baseline and at 6 months for analysis of biomarkers: serum levels of insulin-like growth factor 1 (IGF-1), IGF-binding protein 1 (IGFBP-1), and IGFBP-3; tissue expression of Ki-67 and ER; as well as cytology. Forty-nine patients were eligible for analysis. Median IGFBP-1 levels increased significantly from 6.05 ng/mL at baseline to 6.93 ng/mL at 6 months (P = 0.04), and median IGFBP-3 levels decreased significantly from 3,593 ng/mL to 3,420 ng/mL (P = 0.01). We also detected favorable changes in cytology of 52% of tested sites after 6 months of celecoxib therapy. No changes in tissue Ki-67 and ER expression levels were observed. No grade 3 or 4 toxicity was recorded. Celecoxib was well tolerated and induced favorable changes in serum biomarkers as well as cytology in this pilot phase II trial. A phase IIb placebo-controlled study with celecoxib could be considered for women at increased risk for breast cancer.

The effects of physical activity on physiological markers in breast cancer survivors: A meta-analysis.

BACKGROUND: To systematically evaluate the effects of physical activity on physiological markers in breast cancer survivors. METHODS: A systematic search of the PubMed, Wed of Science, Medline, CNKI and Wanfang Database was performed to identify eligible randomized controlled trials to explore physical activity on physiological markers in breast cancer survivors. STATA version 13.0 (Stata Corp LP, College Station, TX) was used for all statistical analyses. RESULTS: A total of 11 articles with 941 cases were eligible in this meta-analysis. The results of the meta-analysis showed that physical activity could decrease the levels of insulin (SMD = -1.90, 95%CI: -3.2 to -0.60; I = 92.3%, P < .001), insulin-like growth factor 1 (IGF-I) (WMD = -4.67, 95%CI: -23.14 to 13.79; I = 96.2%, P < .001), insulin-like growth factor binding protein-3 (IGFBP-3) (WMD = -20.09, 95%CI: -47.15 to 6.97; I = 93.3%, P < .001). However, compared with the control group, there was not the significant change of insulin-like growth factor 2 (IGF-II), insulin-like growth factor binding protein-1 (IGFBP-1), leptin, adiponectin, glucose, C-reactive protein (CRP), Interleukin-6 (IL-6), Interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-ɑ) levels after the intervention. CONCLUSIONS: Physical activity could improve the insulin function that might be associated with decreasing the levels of IGF-I, IGFBP-3 and insulin in breast cancer survivors.

The levonorgestrel-releasing intrauterine device induces endometrial decidualisation in women on tamoxifen.

There is conflicting literature on whether the levonorgestrel-releasing intrauterine system (LNG-IUS; Mirena®) induces decidualisation in the tamoxifen-treated endometrium. The expression of the decidualisation marker IGFBP-1 was measured using immunohistochemistry in endometrial biopsies and in serum (using ELISA) of 20 postmenopausal women at the start of tamoxifen-treatment for breast cancer. Ten women were then fitted with LNG-IUS and the other ten received tamoxifen-treatment only and acted as controls. Samples were taken at baseline and after 12 months. At baseline, all endometrial samples were negative for IGFBP-1 and at 12 months, IGFBP-1 was only expressed in the endometria of women fitted with the LNG-IUS, confirming the observed histological features of decidualisation. By contrast, serum IGFBP-1 concentrations were increased by tamoxifen, but not in the group receiving LNG-IUS. In conclusion, tamoxifen induces a rise in serum IGFBP-1 suggesting a systemic, possibly hepatic effect, whilst LNG abrogates this in both the liver and endometrium. Impact statement What is already known on this subject? Previous reports of the use of LNG-IUS in women on tamoxifen have provided conflicting evidence as to whether the endometrium exhibited decidualisation or not. These reports were however based solely on histological examination and lacked supporting biochemical data. What do the results of this study add? After 12 months of treatment with LNG-IUS, the endometria of women on tamoxifen show histological features of decidualisation and the presence of the decidualisation marker IGFBP-1, suggesting that levonorgestrel protects the tamoxifen-treated uterus from additional pathology by causing decidualisation. Serum levels of IGFBP-1 were expected to be a reflection of uterine production, but contrary to expectations, higher levels were identified in women on tamoxifen alone. These data suggest that an inhibition of tamoxifen-induced serum IGFBP-1 production (possibly from a hepatic source) by LNG-IUS occurred and indicates independent systemic effects of both drugs in post menopausal breast cancer patients. What are the implications of these findings for clinical practice and/or further research? This research demonstrated a mechanism for endometrial protection in women on tamoxifen. It also alerts clinicians to the fact that both tamoxifen and LNG-IUS exert systemic effects in this patient group.

Evaluation of the quantitative fetal fibronectin test and PAMG-1 test for the prediction of spontaneous preterm birth in patients with signs and symptoms suggestive of preterm labor.

Objective: The objective of this study is to compare the qualitative fFN test at 50 ng/ml threshold to novel methods for assessing risk of imminent sPTB in women with symptoms of preterm labor (PTL): (1) quantitative fetal fibronectin (qfFN) at four thresholds: 10, 50, 200, and 500 ng/ml; and (2) qualitative PAMG-1 test. Study design: Consecutive patients presenting with singleton pregnancies, signs of PTL, gestational age 23.1-34.6, intact membranes, no coitus within 24 h, and cervical dilation ≤3 cm. fFN was performed as standard of care, while clinicians were blinded to the qfFN and PAMG-1 test results. qfFN accuracy was evaluated at four thresholds of 10, 50, 200, and 500 ng/ml for its ability to predict imminent spontaneous preterm delivery (sPTD) ≤ 7 and ≤14 d from the time of sample collection. The PAMG-1 test was evaluated based on its qualitative result for the same delivery endpoints. Results: Seventy-two patients were analyzed. Fifty-seven percent of patients had an fFN concentration of <10 ng/ml fFN; 75% < 50 ng/ml; 92% < 200 ng/ml; 97% < 500 ng/ml. The SN, SP, PPV, and NPV for fFN at each of the four cutoffs for sPTB ≤7 d: 10 ng/ml: 67%, 58%, 6%, 98%; 50 ng/ml: 67%, 77%, 11%, 98%; 200 ng/ml: 33%, 93%, 17%, 97%; 500 ng/ml: 0%, 97%, 0%, 96%. The PAMG-1 test was positive in 7% of patients. SN, SP, PPV, and NPV for PAMG-1 for sPTD ≤7 d were 67%, 96%, 40%, and 99%, respectively. Conclusion: Compared with qfFN, the PAMG-1 test is a better predictor of spontaneous delivery within 7 d while maintaining a very high negative predictive value. The PAMG-1 test is an easy-to-use bedside test that provides rapid results, does not require a speculum examination, can be used after vaginal exam and coitus and does not require specialized equipment to analyze results. As to be expected, compared with the conventional cutoff of fFN (50 ng/ml), a higher fFN cutoff of 200 ng/ml does seem to increase the PPV of the test, but this comes at a cost to the fFN test's SN and NPV, rendering it of little to no advantage in clinical practice.

Increased Insulin-like Growth Factor Binding Protein-1 Phosphorylation in Decidualized Stromal Mesenchymal Cells in Human Intrauterine Growth Restriction Placentas.

Intrauterine growth restriction (IUGR) is often caused by placental insufficiency, which is believed to be associated with decreased delivery of oxygen and nutrients to the placental barrier. We recently reported that hypoxia and/or leucine deprivation triggered hyperphosphorylation of insulin-like growth factor binding protein-1 (IGFBP-1) in decidualized human immortalized endometrial stromal cells (HIESCs), resulting in decreased insulin-like growth factor-1 (IGF-1) bioactivity. To test the hypothesis that human IUGR is associated with increased decidual IGFBP-1 phosphorylation at discrete sites, we used IUGR and gestational age matched appropriate for gestational age (AGA) placentas ( n=5 each). We performed dual immunofluorescence immunohistochemistry (IHC) using IGFBP-1 and vimentin as decidual and mesenchymal markers, respectively. Employing a unique strategy with imaging software, we extracted signal intensity of IGFBP-1 expressed specifically from truly decidualized cells of the placenta. Relative IGFBP-1 was increased (85%; p=0.0001) and using custom phospho-site-specific antibodies, we found that IGFBP-1 phosphorylation (pSer101; +40%, p=0.0677/pSer119; +60%, p=0.0064/pSer169; +100%, p=0.0021) was markedly enhanced in IUGR. Together, our data links for the first time, increased decidual IGFBP-1 phosphorylation at discrete sites with human IUGR. These novel findings suggest that hyperphosphorylation of IGFBP-1 in decidualized stromal mesenchymal decidua basalis contributes to potentially elevated levels of phosphorylated IGFBP-1 in maternal circulation in IUGR pregnancies.

Delayed Diagnosis of Acromegaly in the Context of Post-Traumatic Stress Disorder due to Symptoms Mimicking Known Psychotropic Medication Side Effects.

BACKGROUND: Acromegaly is caused by elevated secretion of human growth hormone, which is frequently because of intracranial tumors. This diagnosis is fairly uncommon with an incidence of 3 to 4 cases per million patients per year. We are presenting a case of acromegaly diagnosed in an active duty Chief Petty Officer. MATERIALS AND METHODS: A 38-year-old male Chief Petty Officer with no previous mental health diagnosis experienced post-traumatic stress disorder (PTSD)-like symptoms in early 2012 after deploying to Iraq and Afghanistan from 2010 to 2011. Initially he self-managed his symptoms, but in July 2012 he required a reduction mammoplasty because of gynecomastia. The metabolic workup revealed elevated prolactin, but this was not further investigated. His recovery from anesthesia was complicated by intensified PTSD-like symptoms, which continued to worsen after the surgery. On self-referral to mental health, he was diagnosed with PTSD and managed for 6 months with cognitive behavioral therapy. Because of persistent and worsening symptoms, his therapy was augmented to include continued cognitive behavioral therapy, alpha-blockers, antidepressants, antihistamines, and sleep aids. Because of night sweats, the selective serotonin reuptake inhibitors doses were modified. Night sweats persisted, and the patient was re-evaluated for other potential etiologies. On evaluation, the patient endorsed a history of obstructive sleep apnea, cervicalgia, visual changes, depressed mood, as well as multiple physical symptoms including coarsened facial features, large hands/feet, and increased interdental distance. On laboratory analysis, insulin-like growth factor 1 was noted to be 3 times the upper limit of normal, and a prolactin level was five times the upper limit of normal. A brain magnetic resonance imaging revealed a cystic pituitary lesion with suprasellar extension, compression of the infundibulum without invasion of the cavernous sinus, or displacement of the optic chiasm. Based on clinical history, physical examination, laboratory data, and the pituitary lesion, this patient was diagnosed with acromegaly. He was referred to neurosurgery for further evaluation and management. RESULTS AND CONCLUSION: This case shows that side effects of medications can easily mimic some medical conditions. The possibility of unrecognized disease should not be overlooked simply because a patient's symptoms that develop after starting a medication correspond well the side effect profile of the prescribed medications. This is especially true if side effects do not stop with alteration of medication dose, cessation of the medication, or changing to another medication. Pituitary adenomas are rare in patients treated for PTSD. However, attribution of PTSD patient's symptoms to the side effects of selective serotonin reuptake inhibitors therapy without considering a broader differential may lead to a missed diagnosis of an endocrine disease. In this case, the presence of an undiagnosed pituitary lesion resulted in ineffective medical management of PTSD in the patient. Mental health providers should remain allied with their primary care counterparts and consider directing patients to primary care for periodic physical re-evaluation to provide the most effective approach to symptom evaluation and management.

Accuracy of a combined insulin-like growth factor-binding protein-1/interleukin-6 test (Premaquick) in predicting delivery in women with threatened preterm labor.

PURPOSE: To determine values of combinations of interleukin-6 (IL-6)/cervical native insulin-like growth factor-binding protein-1 (IGFBP-1)/total IGFBP-1 (Premaquick©) in predicting spontaneous deliveries and spontaneous exclusive preterm deliveries in women with threatened preterm labor. METHODS: Women with singleton pregnancies between gestation age (GA) of 24 weeks and 36 weeks and 6 days with preterm labor were recruited during a prospective multicenter study. Premaquick© was positive when at least two of three biomarkers were positive. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were estimated for both prediction of spontaneous deliveries and spontaneous exclusive preterm deliveries. RESULTS: Ninety-seven (99.0%) out of 98 women enrolled were analyzed. Based on delivery status 7/14 days post-enrollment of general study population, Premaquick© had a sensitivity of 87.1/85.7%, a specificity of 92.4/96.8%, a PPV of 84.4/93.8% and a NPV of 93.9/92.3% for prediction of spontaneous delivery. Predictive accuracy of Premaquick© test in relation to days of enrollment were: 90.7% (≤7 days) and 92.8% (≤14 days). For women enrolled at GA <35 weeks, Premaquick© had a sensitivity of 100.0/87.5%, a specificity of 94.1/96.9%, a PPV of 70.5/87.5%, a NPV of 100.0/96.9% and an accuracy of 95.0/95.0% for prediction of preterm delivery within 7/14 days of enrollment, respectively. PPV was most significantly different in both groups when outcomes were compared between 2 days and 14 days post-enrollment (P<0.001). CONCLUSION: This novel triple biomarker model of native and total IGFBP-1 and IL-6 appears to be an accurate test in predicting spontaneous deliveries and spontaneous exclusive preterm deliveries in threatened preterm labor in singleton pregnancies.

Agreement between circulating IGF-I, IGFBP-1 and IGFBP-3 levels measured by current assays versus unavailable assays previously used in epidemiological studies.

OBJECTIVE: Levels of insulin-like growth factor (IGF) proteins are associated with the risk of cancer and mortality. IGF assays produced by Diagnostic Systems Laboratories (DSL) were widely used in epidemiological studies, were not calibrated against recommended standards and are no longer commercially available. DESIGN: In a split sample study among 1471 adults participating in the Cardiovascular Health Study, we compared values obtained using DSL assays with alternative assays for serum IGF-I (Immunodiagnostic Systems, IDS), IGFBP-1 (American Laboratory Products Company, ALPCO) and IGFBP-3 (IDS). RESULTS: Results were compared using kernel density estimation plots, quartile analysis with weighted kappa statistics and linear regression models to assess the concordance of data from the different assays. Participants had a mean age of 77years. Results between alternative assays were strongly correlated (IGF-I, r=0.93 for DSL versus IDS; log-IGFBP-1, r=0.90 for DSL versus ALPCO; IGFBP-3, r=0.92 for DSL versus IDS). Cross tabulations showed that participants were usually in the same quartile categories regardless of the assay used (overall agreement, 74% for IGF-I, 64% for IGFBP-1, 71% for IGFBP-3). Weighted kappa also showed substantial agreement between assays (kw, 0.78 for IGF-I, 0.69 for IGFBP-1, 0.76 for IGFBP-3). Regressions of levels obtained with DSL assays (denoted X) to alternative assays were, IGF-I: 0.52X+15.2ng/ml, log-IGFBP-1: 1.01X-1.73ng/ml IGFBP-3: 0.87X+791.1ng/ml. Serum values of IGF-I, IGFBP-1 and IGFBP-3 measured using alternative assays are moderately correlated. CONCLUSIONS: Care is needed in the interpretation of data sets involving IGF analytes if assay methodologies are not uniform.

[Insulin-like growth factor-1 (IGF-1) - structure and the role in the human body]. / Insulinopodobny czynnik wzrostu-1 (IGF-1) - budowa i rola w organizmie czlowieka.

In the recent years, managed to broadly explore the structure and role of insulin-like growth factors type 1 and 2 (IGF1 I 2). They belong to the structure of polypeptide hormones homologous to proinsulin. They are characterized by a wide range of activities. IGF-1 is a key mediator of most tissue effects of growth hormone (GH). In addition to effects on growth processes of the body, is also an important factor for cell homeostasis, is subject to both endocrine and tissue-specific auto- and paracrine regulation. In this paper, the current, general knowledge on the structure, function and mechanism of biological effects of IGF-1 in the human body was presented. Attention was also drawn to the directions of use of IGf-1 in the treatment of other diseases than the diseases of the hypothalamic-pituitary and growth disorders in children.

Proliferation and decidualization of endometrial stromal cells during embryo-attachment stage in bonnet monkeys (Macaca radiata).

We report embryo-induced alterations occurring in endometrial stromal cells (ESCs) during the embryo-attachment stage in bonnet monkeys (Macaca radiata). Laser micro-dissected ESCs obtained from pregnant and non-pregnant animals were compared for levels of selected proliferation and decidualization-associated factors by analysis with quantitative real-time polymerase chain reaction or immunohistochemistry. Stromal cells exhibited extensive cellular proliferation, as indicated by cellular compaction and significantly higher (P < 0.05) levels of proliferating cell nuclear antigen and of estrogen receptor 1, c-Myc, and Cyclin D1 transcripts in pregnant animals as compared with non-pregnant animals. A significant decrease (P < 0.05) was observed in the transcript levels of stromal interleukin-6 (IL-6) in pregnant animals. Cell proliferation was accompanied by a significant increase (P < 0.001) in the levels of decidualization-associated molecules such as IL-1ß in the luminal and glandular epithelium and of stromal insulin-like growth-factor-binding protein-1 (IGFBP-1) and prostaglandin-endoperoxide synthase-2 (PTGS-2) proteins. In pregnant animals, proliferation was evident throughout the gestational stroma, whereas decidualization was more pronounced in the embryo-attachment zone than in the non-attachment zone. To our knowledge, this is the first report of alterations in the endometrial stroma during the embryo-attachment stage in a non-human primate model.

Effect of blood on ROM diagnosis accuracy of PAMG-1 and IGFBP-1 detecting rapid tests.

Vaginal bleeding may be present in up to 30% of patients presenting with signs and symptoms of a rupture of the fetal membranes (ROM). The presence of blood may lead to false positive results with biochemical markers. The data presented in this study came from a multi-centric prospective observational clinical study that, for the first time, systematically evaluated the performance of placental alpha microglobulin-1 (PAMG-1) and insulin-like growth factor binding protein-1 (IGFBP-1) detecting tests in 151 women with vaginal bleedings as well as signs and symptoms indicative of ROM. Our data showed better performance for the PAMG-1 compared with the IGFBP-1 detecting tests in all quality parameters evaluated. In detail, sensitivity (SN) was 97.8% (91.0%), specificity (SP) was 91.5% (75.0%), positive predictive value (PPV) was 94.6% (83.5%) and negative predictive value (NPV) was 96.4% (85.7%) for PAMG-1 tests (and IGFBP-1 tests, respectively). A major difference between both tests was related to the number of non-evaluable test results (e.g., hidden bands due to blood smear on the test strips). While 2% of all results were not evaluable for PAMG-1 tests, this artifact appeared in 11% of the results obtained with IGFBP-1 tests. This difference and also those in Specificity and PPV were statistically significant, demonstrating superiority of PAMG-1 over IGFBP-1 detecting tests. In conclusion, the PAMG-1 detecting test was significantly less susceptible to interference by blood than the IGFBP-1 detecting test.

Can preterm labour be predicted in low risk pregnancies? Role of clinical, sonographic, and biochemical markers.

BACKGROUND AND OBJECTIVES: This is a prospective nested cohort study conducted over a period of 3 years. 2644 women were recruited, out of which final analysis was done for 1884 women. METHODS: Cervicovaginal and blood samples were collected for all recruited women. Out of these, 137 women who delivered before 35 weeks were treated as cases and equal number of matched controls were chosen. Analysis of samples for serum G-CSF, AFP, ferritin, and cervicovaginal interleukin-6 and IGFBP-1 was done. RESULTS: Poor orodental hygiene, which can be a social marker, was significantly more common in women who delivered preterm (P = 0.008). Serum alkaline phosphatase and serum ferritin were found to be significantly associated with preterm deliveries. The 90th percentile value of these parameters was considered as cut-off as there is no specific cut-off. CONCLUSIONS: Our study did not prove usefulness of any predictive marker. Serum ferritin and alkaline phosphatase were found to have correlation but their values are affected in many conditions and need to be elucidated with caution. Larger studies are needed for predicting preterm labour in asymptomatic women.

Relationship between use of proton pump inhibitors and IGF system in older subjects.

OBJECTIVES: to investigate the effects of proton pump inhibitors (PPIs) on the insulin-like-growth factor 1(IGF-1) system in the elderly. DESIGN: cross-sectional. SETTING: InCHIANTI study. PARTICIPANTS: 938 older subjects (536 women, 402 men, mean age 75.7±7.4 years). MEASUREMENTS: complete data on age, sex, BMI, liver function, medications, dietary intake, IGF-1, IGF-binding protein-1 and -3 (IGFBP-1, IGFBP-3). RESULTS: Participants were categorized by PPI use, identifying 903 PPI non users and 35 users. After adjusting for age, male PPI users (107.0 ± 69.6 vs. 127.1 ± 55.8, p<0.001) and female PPI users (87.6 ± 29.1 vs. 107.6 ± 52.3, p=0.03) had lower IGF-1 levels than non-users. IGFBP-1 levels were similar in the two groups in both sexes. In whole population, after adjustment for age and sex, PPI users had lower IGF-1 levels 81.9 [61.1-113.8] than non-users 110 [77.8-148.6], p=0.02. After further adjustment for BMI, albumin, liver function, C-reactive protein, Interleukin-6, number of medications, ACE-inhibitors use, caloric intake, protein intake, physical activity, glycemia, and IGFBP-1, the use of PPIs remained significantly and negatively associated with IGF-1 levels (ß±SE = -19.60±9.83, p=0.045). CONCLUSION: Use of PPIs was independently and negatively associated with IGF-1 levels.

Insulin-like growth factor binding protein-1 (Actim PROM test) for detection of premature rupture of fetal membranes.

AIM: This study was designed to detect the accuracy of the insulin-like growth factor binding protein-1 (IGFBP-1) in diagnosing premature rupture of fetal membranes. MATERIALS AND METHODS: A total of 150 pregnant women after 37 weeks' gestation were included in this study and divided into two groups according to presence or absence of premature rupture of the membranes (PROM); 75 patients with PROM were included in group I and 75 patients without PROM were included in group II as controls. The diagnosis of PROM was based on patient's history of sudden gush of water, pooling of amniotic fluid, positive Ferning pattern, positive Nitrazine test, confirmed by visualization of fluid passing from the cervical canal during sterile speculum examination and transabdominal ultrasound to measure the amniotic fluid index. RESULTS: In this study, the sensitivity and the specificity of IGFBP-1 (Actim PROM test) in diagnosing PROM were 89.3% and 82.7%, respectively, as compared with 84% sensitivity and 78.7% specificity for Ferning test, and 86.7% sensitivity and 81.3% specificity for Nitrazine test. The positive predictive value (PPV) and negative predictive value (NPV) of IGFBP-1 were 83.8% and 88.6%, respectively, as compared with 79.7% PPV and 83.1% NPV for the Ferning test, and 82.2% PPV and 85.9% NPV for the Nitrazine test. The IGFBP-1 was more accurate (86%) for detection of PROM than the Ferning (81.3%) or Nitrazine (84.0%) tests. CONCLUSION: The Actim PROM test for detection of IGFBP-1 in the vaginal fluid is a simple bedside test and can be used as a complimentary test to confirm the clinical diagnosis of PROM.

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

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.

Placental alpha microglobulin-1 (AmniSure test) versus insulin-like growth factor binding protein-1 (Actim PROM test) for detection of premature rupture of fetal membranes.

AIM: This study was designed to compare the accuracy of placental alpha microglobulin-1 (PAMG-1) versus insulin-like growth factor binding protein-1 (IGFBP-1) to diagnose premature rupture of fetal membranes (PROM). MATERIAL AND METHODS: This comparative prospective study was carried out over 3 years in Al-Rashid Maternity and Ahmadi Hospitals, Kuwait. One hundred and fifty pregnant women after 37 weeks gestation were included in this study for induction of labor and divided into two groups according to presence or absence of PROM. RESULTS: In this study, the sensitivity and specificity (97.3% and 98.7%) of PAMG-1 to diagnose PROM were statistically insignificant compared with the sensitivity and specificity (89.3% and 82.7%) of IGFBP-1. The PPV and NPV (98.6% and 97.4%) of PAMG-1 were also statistically insignificant compared with the PPV and NPV (83.8% and 88.6%) of IGFBP-1. Also, the accuracy (98%) of PAMG-1 was statistically insignificant compared with the accuracy (86%) of IGFBP-1 (P > 0.05). CONCLUSION: Although AmniSure test seems to be the most accurate test to diagnose rupture of the fetal membranes with high sensitivity and specificity, in this study the sensitivity, specificity and accuracy of AmniSure test to diagnose PROM were statistically insignificant compared with the sensitivity, specificity and accuracy of Actim PROM test.

Early pregnancy vaginal fluid phosphorylated insulin-like growth factor binding protein-1 predicts preterm delivery.

OBJECTIVE: We aimed to study vaginal fluid phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) testing in early pregnancy to predict spontaneous preterm delivery (PTD). METHODS: Vaginal and cervical swab samples were collected from 5180 unselected women during the first-trimester (mean gestational age 13.1 weeks) ultrasound screening. PhIGFBP-1 was measured in vaginal and cervical fluid by an immunoenzymometric assay. Concentrations of ≥10 µg/L were considered elevated. The outcome measure was spontaneous PTD at <32 or <37 weeks gestation. RESULTS: The median concentrations of first-trimester vaginal and cervical phIGFBP-1 were higher in women with spontaneous PTD at <32 and <37 weeks gestation. When 10 µg/L of phIGFBP-1 was used as a cut-off level, the OR in predicting PTD at <32 weeks gestation was 8.6 (95% CI 3.6-20.7) for vaginal samples and 3.6 (95% CI 1.7-7.9) for cervical samples. At <37 weeks gestation, the OR in predicting PTD was 3.0 (95% CI 1.9-3.9) for vaginal samples and 1.9 (95% CI 1.4-2.5) for cervical samples. In multiple logistic regression analysis, both elevated vaginal and cervical fluid phIGFBP-1 levels were independent predictors of PTD both at <32 and <37 weeks gestation. CONCLUSION: First-trimester vaginal phIGFBP-1 performed better than cervical phIGFBP-1 in the prediction of spontaneous PTD.

The Actim Partus test to predict pre-term birth in asymptomatic high-risk women.

The Actim Partus test has been shown to be a useful predictor of pre-term birth in symptomatic women, but limited research has been carried out in high-risk asymptomatic women. This is a pilot study to evaluate the use of this test as a direct comparator with the fetal fibronectin test. All asymptomatic high-risk women attending a pre-term surveillance clinic over a 9-month period, took an Actim Partus and fetal fibronectin test, between 23(+0)-24(+6) weeks' gestation. A total of 45 women were eligible. The positive and negative predictive values of the Actim Partus test for delivery at ≤ 37 weeks' gestation were 0% and 70%, respectively, compared with the fetal fibronectin test, with values of 67% and 79%, respectively. It was concluded that the Actim Partus test did not perform well as a predictor of pre-term birth in high-risk asymptomatic women.

Combination of biochemical markers in predicting pre-term delivery.

PURPOSE: The aim of this study was to evaluate the predictive performances of some biochemical markers in predicting pre-term delivery in asymptomatic women. METHODS: We included 491 asymptomatic women at 24 weeks' gestation, who underwent the endocervical phosphorylated insulin-like growth factor binding protein (phIGFBP-1) test, cervico-vaginal interleukins 6 (IL-6) and 8 (IL-8), and serum C-reactive protein (CRP). A receiver-operating characteristics (ROC) curve was used to determine the most useful cut off point. A multivariate logistic regression model was used in order to analyze the combination of significant predictive variables for pre-term delivery following univariate analysis. RESULTS: ROC curves indicated that 33 µg/l was the optimal cut off value for phIGFBP-1 test, 21.3 ng/l for IL-6, 324 ng/l for IL-8, and 8.42 mg/l for CRP in predicting pre-term delivery. The univariate logistic regression analyses revealed an odds ratio of 3.04 for phIGFBP-1 test, 4.82 for IL-6, and 3.08 for CRP. The multivariate analysis of phIGFBP-1 test, IL-6, and CRP showed that they were independent variables and therefore useful in combination for predicting pre-term delivery. CONCLUSIONS: The phIGFBP-1 test, the cervico-vaginal IL-6, and the serum CRP are independent variables that can be used together to predict pre-term delivery in asymptomatic women.