Value of cervical phosphorylated insulinlike growth factor binding protein-1 in the prediction of preterm labor

OBJECTIVE: To determine the value of cervical phosphorylated insulinlike growth factor binding protein-1 (IGFBP-1) in the prediction of preterm labor. STUDY DESIGN: In this prospective study, 77 pregnant women, gestational age 24-36 weeks, were enrolled in the study. Twenty women with completely healthy pregnancies formed the control group. Fifty-seven women with signs and symptoms of preterm labor formed the study group. Phosphorylated IGFBP-1 in cervical secretions was assessed in all patients by using a qualitative, immunochromatographic, 1-step dipstick test. Cervical length was measured by transvaginal sonography. RESULTS: The IGFBP-1 test was negative in all patients in the control group (n = 20), and all of them delivered after 37 weeks, while the test was positive in 15 of 45 (33.3%) patients in the study group. The correlation between cervical length and gestational age at the time of delivery in patients with a positive phosphorylated IGFBP-1 test (n = 15) was significant (r = .553, P = .03). The sensitivity, specificity, positive predictive value and negative predictive value for the phosphorylated IGFBP-1 test were 78%, 87%, 73% and 90%, respectively. CONCLUSION: Use of a 1-step dipstick test for detecting phosphorylated IGFBP-1 in cervical secretions is of value in the prediction of preterm labor. The high negative predictive value of the test may be useful in avoiding unnecessary medical interventions.     

Insulin-like growth factor binding protein-1 in female reproductive functions.

Multiple lines of evidence suggest that growth factors and related proteins are involved in the regulation of reproductive functions. It appears that hormones and local regulators control each other's production and action. Thus, the same regulatory factor may have different effects depending on the context in which it acts. Insulin-like growth factor-binding protein-1 (IGEBP-1) is a member of the family of soluble proteins that bind insulin-like growth factors (IGF-I and IGF-II) and modulate their biological actions at the cellular level. In the reproductive tract, endometrium and ovarian granulosa-luteal cells express IGFBP-1 mRNA and secrete the protein at a certain stage of differentiation. During pregnancy, IGFBP-1 is a major secretory product of decidualized endometrium. This report summarizes the current views on IGFBP-1 with special regard to its synthesis, regulation and potential role in female reproductive tissues.     

IGFBP-1的测定及宫颈结构的变化在早产预测中的价值

目的探讨宫颈结构变化及IGFBP-1的测定在早产预测中的价值。方法阴超检测先兆早产者宫颈长度、内口形态及宫颈指数,并结合IGFBP-1的测定,来作为预测早产的指标。设立随机和自身对照研究。结果①先兆早产组宫颈长度（2.56±0.62）cm,明显短于对照组正常孕妇宫颈长度（3.74±0.71）cm,差异有高度统计学意义（t=4.659,P〈0.001）。其中9例早产的宫颈长度（1.61±0.22）cm,明显短于未发生早产的53例宫颈长度（2.69±0.51）cm,差异有高度统计学意义（t=6.221,P〈0.001）。先兆早产组宫颈指数（0.68±0.21）,明显高于正常孕妇宫颈指数（0.35±0.23）,差异有高度统计学意义（t=8.762,P〈0.001）。9例早产的宫颈指数（0.85±0.26）明显高于未发生早产的53例宫颈指数（0.63±0.24）,差异有统计学意义（t=2.513,P〈0.05）;②宫颈内口形态：62例先兆早产中宫颈内口漏斗型11例,其中发生早产9例（占81.82%）。正常组宫颈内口均成“T”型;③IGFBP-1：62例先兆早产中IGFBP-1阳性27例（占43.55%）,经保胎治疗后先兆早产症状消失。有9例于入院后1-3 d内发生早产（占14.52%）。正常组78例IGFBP-1均为阴性;④疗效：先兆早产IGFBP-1阳性27例;经治疗症状消失,2周后复查IGFBP-1有18例转为阴性（占66.67%）。另外先兆早产治疗后宫颈长度有所增长,平均增长0.56 cm。结论宫颈结构及IGFBP-1的测定与早产密切相关;可以作为预测早产的客观可靠的指标;也可作为早产疗效判断的可靠指标。宫颈长度≤2.5 cm,宫颈指数≥0.5,宫颈内口有漏斗形成,宫颈阴道分泌物IGFBP-1阳性,则发生早产的特异性为100%。值得临床医生重视。     

New rapid bed-side test to predict preterm delivery: phosphorylated insulin-like growth factor binding protein-1 in cervical secretions

BACKGROUND: Phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) is secreted by decidual cells and leaks into cervical secretions when fetal membranes detach from decidua. Our aim was to assess whether detection of phIGFBP-1 in cervical secretions by a rapid bed-side test could be used to predict preterm delivery in patients with regular uterine contractions. STUDY DESIGN: In our prospective study, 36 women between 20 and 36 weeks of gestation with regular, persistent contractions (> 10/h) and 18 women between 20 and 36 weeks gestation without symptoms of preterm labor were assessed for the presence of cervical phIGFBP-1. Dacron swabs were applied to the cervix and assayed in 5 min by using immunochromotography, a new rapid bed-side test (actim partus test, Medix Biochemica, Kauniainen, Finland). Data analysis included one-way variance analysis (ANOVA), Student's t-test, chi-square and Fisher's exact test. RESULTS: Of the 36 patients with regular uterine contractions, 18 had a positive actim partus test and 18 had a negative test. Among the 18 patients with a positive test, only one delivered term and the other 17 patients delivered preterm (< 37 weeks). Among the 18 women with a negative test, only two delivered preterm (p < 0.05). Mean gestational age at delivery for patients with a positive and a negative test was 34.4 +/- 3.0 and 37.9 +/- 2.3 weeks, respectively (p < 0.05). Sensitivity, specificity, positive and negative predictive values of the rapid phIGFBP-1 test for preterm delivery was 89.5, 94.1, 94.4 and 88.9%, respectively. For delivery < 37 weeks, positive likelihood ratio was 15.2 (+/- 95% CI; range 2.6-102.5). When cervical phIGBP-1 assay was used to predict delivery within 7 days, sensitivity, specificity, positive and negative predictive values were 93.8, 85%, 83.3 and 94.1%, respectively. Positive likelihood ratio with +/- 95% CI was 6.25 (range 2.2-17.8). When patients were categorized according to cervical dilatation, the positive likelihood ratio of the test when the cervix was closed at 2 cm were 8.3 (1.3-55.3), 13.6 (2-91.4), 15.8 (2.3-106.3) and 1.5 (0.2-11.5), respectively, CONCLUSION: The presence of cervical phIGFBP-1 is predictive of preterm delivery < 37 weeks of gestation. Our study shows that cervical detection of phIGFBP-1 by immunochromotography is a rapid and easily applicable test that highly anticipates preterm delivery in patients at risk.     

Cervical phosphorylated insulin-like growth factor binding protein-1 in prediction of preterm delivery

Background  The aim of this study was to evaluate the phosphorylated isoform of insulin-like growth factor binding protein-1 (phIGFBP-1) in endocervical secretions as a predictor of preterm delivery in symptomatic and asymptomatic pregnant women. Methods  The study included 105 patients between 24 and 34 weeks’ gestation with uterine contractions and 73 controls. Ph IGFBP-1 in cervical secretions was assessed in all patients by using a qualitative, immunochromatographic one-step dipstick test. Data analysis included Student’s test, Chi-Square, Fisher’s exact test and Kruskal Wallis variance analysis. Results  Preterm birth rate was 19.04% (20/105) in the study group. Of the 25 patients with a positive phIGFBP-1 test, mean gestational age at delivery was 32.8 ± 3.8, whereas of the 80 patients with a negative phIGFBP-1 test mean gestational age at delivery was 37.8 ± 2.5, in the study group (P < 0.05). The sensitivity, specificity, positive predictive value and negative predictive value for phIGFBP-1 in symptomatic patients were 70, 87.05, 56 and 92.5%, respectively, while in asymptomatic patients they were 40, 82.35, 14.28 and 94.91%, respectively. Conclusions  The phIGFBP-1 in cervical secretions is a potential specific marker for preterm delivery occurring before 37 weeks. Also cervical detection of phIGFBP-1 by immunochromotography is a rapid and easily applicable test that highly predicts preterm delivery.     

Fragmented forms of insulin-like growth factor binding protein-1 in amniotic fluid of patients with preterm labor and intact membranes

To determine the clinical significance of an increase in various fragmented forms of insulin-like growth factor binding protein-1 (IGFBP-1) in amniotic fluid (AF), a retrospective cohort study was conducted in 103 consecutive patients with preterm labor and intact membranes. Amniotic fluid samples were cultured for aerobic and anaerobic bacteria, and mycoplasmas, and then assayed for matrix metalloproteinase-8. Fragmented-to-intact IGFBP-1 ratios were evaluated by densitometric analysis of Western blot assays. Intact IGFBP-1 (30 kDa) and 21, 17, and 12 kDa fragments were detected in AF. Median ratios of fragmented-to-intact IGFBP-1 were higher in patients whose neonates had significant morbidity than in those whose neonates did not (P < .05), in patients spontaneously delivered within 2 and 7 days from amniocentesis than in those delivered after 2 and 7 days (P < .05), and in patients with intra-amniotic infection/inflammation than in those without (P < .001). Collectively, fragmented IGFBP-1 in AF may be indicators for adverse perinatal outcomes.     

Insulin-like growth factor-binding protein-1 in cervical secretion as a predictor of preterm delivery

BACKGROUND: The aim of the study was to evaluate whether the phosphorylated isoforms of insulin-like growth factor-binding protein-1 (IGFBP-1), a protein produced by the decidua, can be detected in cervical secretions of pregnant women with preterm uterine contractions, and whether their presence predicts an increased risk of preterm delivery. METHODS: A prospective analysis of sixty-three women who presented with preterm labor but intact fetal membranes at weeks 22-36+6 days of gestation at the Antenatal clinic at the Department of Obstetrics and Gynecology, Helsinki University Central Hospital. Phosphorylated IGFBP-1 (phIGFBP-1) was measured in cervical swab samples obtained at presentation, using an immunoenzymometric assay. The values > or =10 microg/L were considered as positive. In addition, 58 asymptomatic women at the same gestational stage were studied as controls. Multiple logistic regression was applied to control for confounding variables and to obtain adjusted odds ratios. RESULTS: The concentration of phIGFBP-1 in cervical samples ranged from undetectable to 95 microg/L. In 17 of the 63 (27%) women with preterm labor it was > or =10 microg/L. Seven of these 17 (41%) women with a positive phIGFBP-1 result delivered preterm, all before 35 weeks of gestation. Among the women with preterm labor and a negative phIGFBP-1 result, three of the 46 (7%) delivered before 37 weeks of gestation (adjusted OR 24, 95% CI 1.2-487), but all after 35 weeks of gestation. In the asymptomatic control population three out of 58 (5%) women had a positive cervical phIGFBP-1 test result but none delivered preterm. Among the controls with a negative cervical phIGFBP-1 test result (55 of 58, 95%), one woman delivered preterm (1 of 55, 2%). CONCLUSIONS: Pregnant women who are in preterm labor with intact fetal membranes and who have a positive phIGFBP-1 test result in cervical secretion have an increased risk of preterm delivery.     

Regulation of insulin-like growth factor-I and insulin-like growth factor binding protein-1 concentrations in preterm fetuses

OBJECTIVE: Our purpose was to evaluate which factors regulate insulin-like growth factor-I and insulin-like growth factor binding protein-1 concentrations in preterm fetuses. STUDY DESIGN: We studied 76 singleton births between 25 and 36 weeks of gestation. Forty-nine pregnancies were complicated by hypertensive disease; 24 pregnancies were complicated by preterm labor or preterm rupture of membranes; and antenatal glucocorticoids were given in 49 pregnancies. Pathology reports showed infarct(s) or hematoma(s) in 31 of 69 placentas. We recorded blood gas values in umbilical artery and vein and measured glucose, C-peptide, and insulin-like growth factor-I and insulin-like growth factor binding protein-1 concentrations in umbilical vein. RESULTS: Birth weight correlated with umbilical vein insulin-like growth factor-I (r = 0.68, P <.0001) and inversely with insulin-like growth factor binding protein-1 (r = -0.26, P =.02). Babies with birth weight of 25th percentile. Two-factor analysis of variance showed that umbilical vein insulin-like growth factor-I was determined by gestational age (P =.0004) and birth weight percentile (P <.0001), whereas insulin-like growth factor binding protein-1 was not affected by gestational age. Umbilical vein C-peptide was highly correlated with insulin-like growth factor binding protein-1 (r = -0.55, P <.0001), but not insulin-like growth factor-I, levels. Blood gas values in umbilical artery and vein, particularly umbilical artery PO (2), were correlated with umbilical vein insulin-like growth factor-I and insulin-like growth factor binding protein-1 (r = 0.51 and -0.48, respectively; P <.0001); changes in insulin-like growth factor-I and insulin-like growth factor binding protein-1 occurred at umbilical artery PO (2) <14.8 mm Hg. Multiple regression analysis showed that umbilical vein insulin-like growth factor-I was predicted by umbilical artery PO (2), gestational age, and the presence of placental infarcts/hematomas (R (2) of model = 0.58, P <.0001), and umbilical vein insulin-like growth factor binding protein-1 by umbilical vein C-peptide, umbilical artery PO (2), and placental infarcts/hematomas (R (2) = 0.49, P <.0001). CONCLUSION: In the preterm fetus, circulating insulin-like growth factor-I is related to gestational age and the in utero growth potential, whereas insulin-like growth factor binding protein-1 is related only to the in utero growth potential. The PO (2) is a robust determinant of both insulin-like growth factor-I and insulin-like growth factor binding protein-1 levels; hypoxia may restrain fetal growth through its effects on the insulin-like growth factor/insulin-like growth factor binding protein axis. Insulin is a powerful determinant of insulin-like growth factor binding protein-1, but not insulin-like growth factor-I, concentrations in the preterm fetus.     

Insulin-like growth factor-binding protein-1 (IGFBP-1) in cervical secretions as a predictor of preterm delivery.

OBJECTIVE: The objective of this study was to investigate the level of insulin-like growth factor-binding protein-1 (IGFBP-1) in cervical secretions and Bishop score as predictors of preterm delivery in asymptomatic pregnant women. METHODS: This was a prospective study at the Clinic for Gynecology and Obstetrics at the University Clinical Center in Tuzla, on a sample of 80 healthy pregnant women at between 24 and 34 gestational weeks. After interview every woman underwent IGFBP-1 concentration measurement by the 'Actim Partus' test. The Bishop score was determined by the author (A.L) during vaginal examination. Rates among groups were compared using arithmetic mean and standard deviation, Student's t-test, Mann-Witney U-test, and Spearman-Rank correlation test. Statistical importance was determined at the variation levels of 5% and 1%. RESULTS: Eight (10.00%) women in the study group had a positive Actim Partus test and six (7.50%) of them had a preterm delivery. The positive predictive value was 44.44% and negative predictive value was 98.59%. The specificity of the Bishop score in the study group was 83.78% and the sensitivity was 50.00%. The positive predictive value of the Bishop score in this group was 20.00% and the negative predictive value was 95.36%. There was no correlation between the Bishop score and Actim Partus test (p = 0.15). CONCLUSIONS: If the concentration of IGFBP-1 is <10 microg/L (negative Actim Partus test) in asymptomatic pregnant women, the risk of preterm delivery is low. The Actim Partus test could be used as a screening test for preterm delivery in asymptomatic pregnant women.     

Fetal fibronectin detection in preterm labor: Evaluation of a prototype bedside dipstick technique and cervical assessment

Objective: The aims of this study were to evaluate a prototype bedside test for fetal fibronectin detection in women with symptoms of preterm labor, to compare the efficacy of obtaining fetal fibronectin swabs with and without a speculum, and to assess the value of combining the fetal fibronectin test with cervical dilatation for predicting delivery within 10 days. Study Design: This investigation prospectively studied a cohort of women with symptoms of preterm labor (n = 121), gestational age between 24 and 33 6/7 weeks, and cervical dilatation ≤3 cm. Vaginal swabs for fibronectin testing with the bedside dipstick Fetal Fibronectin Membrane Immunoassay test (Adeza Biomedical, Sunnyvale, Calif) were obtained with and without a speculum. Results were not available to the clinicians. Results: Twenty-two percent of the fetal fibronectin samples collected with a speculum (27/121) yielded positive results. The incidence of delivery within 10 days of testing was 14% (17/121). Fetal fibronectin detection predicted delivery within 10 days with sensitivity, specificity, and positive and negative predictive values of 65%, 85%, 41%, and 94%, respectively. The positive and negative likelihood ratios were 4.3 and 0.41, respectively. There was substantial association between samples obtained with and without a speculum (Cohen κ statistic 0.65, 95% confidence interval 0.44-0.87). Cervical dilatation ≥1 cm predicted delivery within 10 days with sensitivity, specificity, and positive and negative predictive values of 71%, 87%, 46%, and 95%, respectively, with positive and negative likelihood ratios of 5.5 and 0.33, respectively. Combination of fetal fibronectin testing with cervical dilatation ≥1 cm did not significantly improve the fetal fibronectin test characteristics. After exclusion of women with slight vaginal bleeding, cervical dilatation ≥1 cm and fetal fibronectin status remained the only independent variables associated with delivery within 10 days. Conclusion: Fetal fibronectin testing according to this prototype may have a limited role in clinical decision analysis. In this study a cervical dilatation ≥1 cm had predictive values equivalent to those of the fetal fibronectin test, and it should be evaluated further in a clinical setting. (Am J Obstet Gynecol 1998;179:1553-8.)     

Insulin-like growth factor-1 and insulin-like growth factor binding protein-1 and 3 in the follicular fluid of infertile patients submitted to in vitro fertilization

Purpose: In the present article we propose to evaluate IGF-1, IGFBP-1 and 3 in the follicular fluid of infertile patients submitted to in vitro fertilization.Methods: We performed a case-control study with 53 infertile patients submitted to the first in vitro fertilization attempt. We compared their follicular fluid concentration of IGF-1, IGFBP-1 and IGFBP-3 between the patients who became pregnant (n = 11) versus those nonpregnant (n = 42).Results: The clinical characteristics of patients from the two groups were similar in terms of age and body mass index. Data related to the analysis of ovulation induction was not different regarding length of induction in days, number of retrieved oocytes, fertilization rate, and number of transferred embryos. Furthermore, the number of FSH units required for ovarian induction was also similar between the studied groups.IGF-1 and IGFBP-1 were not significantly different between the groups (p > 0.05). However, those patients that became pregnant presented a lower follicular fluid concentration of IGFBP-3, 2237.10 ± 582.73 pg/ml and 2657.64 ± 584.15 ng/ml, respectively (p = 0.038).Conclusions: We demonstrated an association of a lower follicular fluid IGFBP-3 in individuals that became pregnant compared to subjects that did not after in vitro fertilization.     

Maternal serum insulin-like growth factor binding protein-1 in pregnancy at high altitude

OBJECTIVE: To investigate the effect of environmental hypoxia at 4300-m altitude on the maternal serum concentration of insulin-like growth factor binding protein-1 (IGFBP-1). METHODS: We conducted a cross-sectional study of 108 pregnant women in Peru, 62 from high altitude (4300 m, 14100 ft) and 46 from sea level at 14-42 weeks' gestation. For comparison, 20 healthy nonpregnant women (ten from high altitude and ten from sea level) were also examined. Total and nonphosphorylated IGFBP-1 were measured in maternal serum. RESULTS: Both total and nonphosphorylated IGFBP-1 were higher at high altitude than at sea level in the pregnant groups (ratio = 1.28, P =.008, and ratio = 1.45, P =.003, respectively), and there was significant interaction between high altitude and sea level (P =.037 and P =.043, respectively). The threshold model showed that the difference became significant from 25 weeks' gestation onwards. CONCLUSION: Before 25 weeks of pregnancy, there was no significant difference in IGFBP-1 between women living at high or low altitude, suggesting that the increased IGFBP-1 at high altitude is unlikely to be related to inadequate trophoblast invasion resulting in placental hypoxia. In the second half of pregnancy, the maternal and fetal demands increase dramatically, and low atmospheric oxygen with resulting maternal systemic hypoxemic hypoxia may cause placental hypoxia. This stimulates increased production of IGFBP-1, which in turn restricts the insulin-like growth factor-mediated fetal growth as an adaptive mechanism to prevent worsening of the fetoplacental hypoxia.     

Significance of detecting insulin-like growth factor binding protein-1 in cervicovaginal secretions: comparison with nitrazine test and amniotic fluid volume assessment

OBJECTIVES: The diagnosis of premature rupture of membranes (PROM) is sometimes challenging, and common diagnostic tests are of limited value in the diagnosis. We aimed to study the accuracy of detecting insulin-like growth factor binding protein-1 (IGFBP-1) in vaginal fluid by a rapid dipstick method in comparison with the nitrazine test and amniotic fluid index (AFI) and we studied the predictivity of these methods on the latency of pregnancy in patients with suspected PROM. MATERIAL AND METHOD: One hundred and fifty-one patients (36 definite PROM, 35 no PROM and 80 suspected PROM) at 20-42 weeks' gestation were included in the study. Patients with preterm labor and PROM, patients at <20 gestational weeks, and those with multiple pregnancies were excluded. IGFBP-1 in the cervicovaginal fluid was measured by a rapid dipstick method (PROM test). AFI was measured by the four-quadrant method and an AFI of <80 mm was considered as oligohydroamnios. RESULTS: The sensitivity, specificity and accuracy of the nitrazine test, the PROM test and AFI were 97, 16 and 56%, 97, 97 and 97% and 94, 91 and 92%, respectively. The nitrazine test results were affected by vaginal discharge but the PROM test results were not affected. Only a positive PROM test was associated with delivery within 7 days [odds ratio (OR) 12; 95% confidence interval (CI) 4.2-35, p < 0.001]. CONCLUSION: The dipstick method of detecting IGFBP-1 in the vaginal fluid is a rapid, reliable and noninvasive method. The PROM test is the most accurate diagnostic test and predictor of latency in patients with suspected PROM.     

Insulin-like growth factor 1 and its binding protein 1 during normal and diabetic pregnancies.

Investigations of circulating insulin-like growth factor 1, hPL, and infant size during pregnancy in normal and insulin-dependent diabetic women have yielded conflicting results and have not been analyzed longitudinally. We studied serial changes in maternal serum insulin-like growth factor 1 levels (measured by radioimmunoassay after acid ethanol extraction) throughout pregnancy in 22 normal women and in 38 with insulin-dependent diabetes. The diabetic women had significantly lower serum insulin-like growth factor 1 concentrations than normal women throughout pregnancy and after delivery, although the rates of change in both groups of women were similar. Within-patient analysis showed a significant decrease in serum insulin-like growth factor 1 between 6-12 weeks' gestation and a significant increase between 24-32 weeks, followed by a significant decrease from 36 weeks' gestation to 12 weeks after delivery. Incremental changes in insulin-like growth factor 1 between 24-32 weeks' gestation correlated significantly with incremental changes in hPL (r = 0.40; P less than .001) and with birth weight (r = 0.37; P less than .01), but not with ultrasound measurements of fetal growth. The correlation of increments in insulin-like growth factor 1 and birth weight became nonsignificant when the association of hPL with both insulin-like growth factor 1 and birth weight was taken into account. Neither insulin-like growth factor binding protein 1 (placental protein 12) nor its ratio to insulin-like growth factor 1 showed any association with infant size. The physiologic changes in maternal serum insulin-like growth factor 1 in pregnant diabetic women do not appear related to the increased birth weight of their infants.     

Insulin-like growth factor, insulin-like growth factor–binding protein-4, and pregnancy-associated plasma protein-A gene expression in human granulosa cell tumors

The insulin-like growth factor (IGF) system plays an important role in folliculogenesis. It is also thought to contribute to the pathogenesis of many cancers, including those of the ovarian epithelium. In the human follicle, the predominant IGF is IGF-II and its actions are modulated by insulin-like growth factor-binding protein-4 (IGFBP-4), the IGFBP-4 protease, and the pregnancy-associated plasma protein-A (PAPP-A). These peptide components are synthesized by the granulosa cells of the developing follicle. The aim of this study was to characterize the expression of these components of the IGF system in granulosa cell tumors (GCT) of the ovary. IGF-I, IGF-II, IGFBP-4, and PAPP-A gene expression was determined in a panel of GCT and compared to the levels in normal ovary and in epithelial ovarian tumors. Although both the IGF-I and IGF-II genes were expressed in the GCT, the levels were lower than in the other tissue groups. IGFBP-4 expression was also low in the GCT, whereas PAPP-A gene expression was highest in the GCT. These findings were unexpected given the prominent role this signaling system plays in normal granulosa cells. In conclusion, these observations suggest that the IGF system may have a limited role in the pathogenesis of GCT with PAPP-A subserving a function other than IGFBP-4 proteolysis.     

Serum insulin-like growth factor binding protein-1 at 16 weeks and subsequent preeclampsia

OBJECTIVE: To determine whether serum concentrations of insulin-like growth factor-binding protein-1 (IGFBP-1), a major decidual protein, at 16 weeks' gestation differ between women who later develop pregnancy-related hypertension and normotensive women. METHODS: Concentrations of IGFBP-1 were measured using immunoenzymometric assay in serum samples collected for alpha-fetoprotein (AFP) and free beta subunit of hCG (free beta-hCG) determinations in a Down syndrome screening program at 16 weeks' gestation in a population-based cohort of 1049 nulliparous women. After exclusion of subjects with multiple pregnancies, insulin-dependent diabetes, major fetal malformations, and incomplete data, 917 subjects remained eligible. RESULTS: The mean levels (+/- standard deviation) of IGFBP-1 were significantly lower in 34 women who later developed preeclampsia (73 +/- 43 microg/L, P < .01) and in 80 women with White A diabetes (84.7 +/- 53 microg/L, P < .01) compared with controls (103 +/- 58 microg/L). In seven women with White A diabetes and subsequent preeclampsia IGFBP-1 levels were especially low (41 +/- 34 microg/L). The concentrations of AFP and free beta-hCG in the subgroups with hypertensive disorders were not significantly different from those of normotensive women. CONCLUSION: Decreased IGFBP-1 levels at 16 weeks' gestation in women who develop preeclampsia might indicate impaired decidual function. Hyperinsulinemia, a known risk factor for preeclampsia, might contribute to decreased concentrations of serum IGFBP-1. However, due to low sensitivity, assay of serum IGFBP-1 was not clinically valuable for predicting preeclampsia.     

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

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

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

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

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