A C TA Obstetricia et Gynecologica
AOGS M A I N R E SE A RC H A R TI C LE
Usefulness of the insulin-like growth factor binding protein-1 bedside test for ruptured fetal membranes HANNA KALLIONIEMI, LEENA RAHKONEN, OSKARI HEIKINHEIMO, VEDRAN STEFANOVIC & JORMA PAAVONEN Department of Obstetrics and Gynecology, University Central Hospital, Helsinki, Finland
Key words Insulin-like growth factor binding protein-1, phosphorylated insulin-like growth factor binding protein-1, rupture of fetal membranes, bleeding, amniotic fluid, preterm delivery Correspondence Hanna Kallioniemi, Department of Obstetrics and Gynecology, University Central Hospital, Haartmaninkatu 2, 00029 HUS Helsinki, Finland. E-mail: [email protected] Conflict of interest Hanna Kallioniemi, Leena Rahkonen, Oskari Heikinheimo and Jorma Paavonen declare no conflict of interest. Vedran Stefanovic has received travel and congress fee grant from Medix Biochemica in 2012 and 2013. Please cite this article as: Kallioniemi H, Rahkonen L, Heikinheimo O, Stefanovic V, Paavonen J. Usefulness of the insulin-like growth factor binding protein-1 bedside test for ruptured fetal membranes. Acta Obstet Gynecol Scand 2014; 93: 1282–1289. Received: 9 February 2014 Accepted: 14 August 2014 DOI: 10.1111/aogs.12481
Abstract Objective. We evaluated whether phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) in blood or from other sources interferes with the vaginal IGFBP-1 dipstick test in rupture of fetal membranes (ROM). Design. Cross-sectional study. Setting. Antenatal Clinic, University Hospital. Population. A total of 247 pregnant women consulting the emergency obstetric unit with self-reported amniotic fluid leakage. Methods. Vaginal samples were tested with the IGFBP-1 dipstick test and the concentrations of different IGFBP1 isoforms were measured by two immunoenzymometric assays. Main outcome measure. IGFBP-1 dipstick test result in the presence or absence of blood and different phosphoisoforms of IGFBP-1. Results. The dipstick test was positive in 37.2% of women and negative in 62.8% of women. Vaginal bleeding was present in 19.4%. In women with a positive test and clinical evidence of ROM, both IGFBP-1 and phIGFBP-1 concentrations in vaginal fluid were lower in women with than in women without bleeding (p = 0.025 and p = 0.031, respectively). No difference was found in concentrations of IGFBP-1 and phIGFBP-1 in women with a positive dipstick test without ROM, with or without vaginal bleeding. In women with a negative test the concentrations of IGFBP-1 and phIGFBP-1 remained below the cut-off for the test, regardless of bleeding. IGFBP-1 concentration did not differ by cervical status, but phIGFBP-1 concentration was higher in women with a ripe cervix (p = 0.001). Conclusions. Rapid vaginal dipstick test can be used in the detection of ROM irrespective of the presence or absence of blood. Positive tests near term indicate either ROM or leakage of less phIGFBP-1 associated with onset of delivery. IEMA, immunoenzymometric assay; IGFBP-1, insulin-like growth factor binding protein-1; phIGFBP-1, phosphorylated insulin-like growth factor binding protein-1; PPROM, preterm premature rupture of fetal membranes; PROM, premature rupture of fetal membranes; ROM, rupture of fetal membranes.
Abbreviations:
Key Message Introduction Premature rupture of fetal membranes (PROM) complicates about 10% of all pregnancies (1), and preterm PROM (PPROM) is responsible for approximately one-third of all preterm births (2). Diagnosis of rupture of fetal membranes (ROM) in the presence of bleeding is
1282
Diagnosis of rupture of membranes in the presence of bleeding is challenging, because the therapeutic measures differ depending on whether the membranes are intact or not. The insulin-like growth factor binding protein-1 bedside test can be used for detection of rupture of membranes in patients with vaginal bleeding.
ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 93 (2014) 1282–1289
H. Kallioniemi et al.
challenging, because therapeutic measures often differ depending on whether the membranes are intact. Insulinlike growth factor binding protein-1 (IGFBP-1) is a major protein in human decidua and amniotic fluid. Amniotic fluid contains nonphosphorylated and less phosphorylated isoforms (referred as IGFBP-1), whereas in decidua and maternal serum highly and less phosphorylated isoforms (referred as phIGFBP-1) predominate (3,4). The presence of IGFBP-1 in cervicovaginal secretions is consistent with ROM when the clinical diagnosis is uncertain (5–7). An immunochromatographic strip test, with monoclonal antibody to IGFBP-1 (ActimProm; Medix Biochemica, Kauniainen, Finland), has been developed to detect amniotic fluid in the vagina (5,6). The monoclonal antibody used in the test detects non- and less phosphorylated amniotic fluid isoforms, but not the highly phosphorylated IGFBP-1 (4). The sensitivity of the IGFBP-1 dipstick test varies from 95 to 100% and specificity from 89 to 98% (6,8–12). It has been suggested that the presence of blood interferes with the diagnosis of ROM. We wanted to evaluate whether blood of maternal, fetal or decidual origin or different phosphoisoforms of IGFBP-1 interfere with the dipstick test by measuring the concentrations of different phosphoisoforms of IGFBP-1 in vaginal samples.
Material and methods This cross-sectional study was conducted at the Department of Obstetrics and Gynecology, University Central Hospital, Helsinki, Finland between March 2011 and December 2011. The study was approved by the local Institutional Ethics Committee (Reg. no. 246/13/03/03/ 2011). A total of 247 pregnant women between 24 and 42 weeks of gestation, consulting the obstetric emergency unit with self-reported amniotic fluid leakage were enrolled in the study. Vaginal secretion was collected from 247 women. Of the 247 women, 50 (20.2%) were preterm (
AOGS M A I N R E SE A RC H A R TI C LE
Usefulness of the insulin-like growth factor binding protein-1 bedside test for ruptured fetal membranes HANNA KALLIONIEMI, LEENA RAHKONEN, OSKARI HEIKINHEIMO, VEDRAN STEFANOVIC & JORMA PAAVONEN Department of Obstetrics and Gynecology, University Central Hospital, Helsinki, Finland
Key words Insulin-like growth factor binding protein-1, phosphorylated insulin-like growth factor binding protein-1, rupture of fetal membranes, bleeding, amniotic fluid, preterm delivery Correspondence Hanna Kallioniemi, Department of Obstetrics and Gynecology, University Central Hospital, Haartmaninkatu 2, 00029 HUS Helsinki, Finland. E-mail: [email protected] Conflict of interest Hanna Kallioniemi, Leena Rahkonen, Oskari Heikinheimo and Jorma Paavonen declare no conflict of interest. Vedran Stefanovic has received travel and congress fee grant from Medix Biochemica in 2012 and 2013. Please cite this article as: Kallioniemi H, Rahkonen L, Heikinheimo O, Stefanovic V, Paavonen J. Usefulness of the insulin-like growth factor binding protein-1 bedside test for ruptured fetal membranes. Acta Obstet Gynecol Scand 2014; 93: 1282–1289. Received: 9 February 2014 Accepted: 14 August 2014 DOI: 10.1111/aogs.12481
Abstract Objective. We evaluated whether phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) in blood or from other sources interferes with the vaginal IGFBP-1 dipstick test in rupture of fetal membranes (ROM). Design. Cross-sectional study. Setting. Antenatal Clinic, University Hospital. Population. A total of 247 pregnant women consulting the emergency obstetric unit with self-reported amniotic fluid leakage. Methods. Vaginal samples were tested with the IGFBP-1 dipstick test and the concentrations of different IGFBP1 isoforms were measured by two immunoenzymometric assays. Main outcome measure. IGFBP-1 dipstick test result in the presence or absence of blood and different phosphoisoforms of IGFBP-1. Results. The dipstick test was positive in 37.2% of women and negative in 62.8% of women. Vaginal bleeding was present in 19.4%. In women with a positive test and clinical evidence of ROM, both IGFBP-1 and phIGFBP-1 concentrations in vaginal fluid were lower in women with than in women without bleeding (p = 0.025 and p = 0.031, respectively). No difference was found in concentrations of IGFBP-1 and phIGFBP-1 in women with a positive dipstick test without ROM, with or without vaginal bleeding. In women with a negative test the concentrations of IGFBP-1 and phIGFBP-1 remained below the cut-off for the test, regardless of bleeding. IGFBP-1 concentration did not differ by cervical status, but phIGFBP-1 concentration was higher in women with a ripe cervix (p = 0.001). Conclusions. Rapid vaginal dipstick test can be used in the detection of ROM irrespective of the presence or absence of blood. Positive tests near term indicate either ROM or leakage of less phIGFBP-1 associated with onset of delivery. IEMA, immunoenzymometric assay; IGFBP-1, insulin-like growth factor binding protein-1; phIGFBP-1, phosphorylated insulin-like growth factor binding protein-1; PPROM, preterm premature rupture of fetal membranes; PROM, premature rupture of fetal membranes; ROM, rupture of fetal membranes.
Abbreviations:
Key Message Introduction Premature rupture of fetal membranes (PROM) complicates about 10% of all pregnancies (1), and preterm PROM (PPROM) is responsible for approximately one-third of all preterm births (2). Diagnosis of rupture of fetal membranes (ROM) in the presence of bleeding is
1282
Diagnosis of rupture of membranes in the presence of bleeding is challenging, because the therapeutic measures differ depending on whether the membranes are intact or not. The insulin-like growth factor binding protein-1 bedside test can be used for detection of rupture of membranes in patients with vaginal bleeding.
ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 93 (2014) 1282–1289
H. Kallioniemi et al.
challenging, because therapeutic measures often differ depending on whether the membranes are intact. Insulinlike growth factor binding protein-1 (IGFBP-1) is a major protein in human decidua and amniotic fluid. Amniotic fluid contains nonphosphorylated and less phosphorylated isoforms (referred as IGFBP-1), whereas in decidua and maternal serum highly and less phosphorylated isoforms (referred as phIGFBP-1) predominate (3,4). The presence of IGFBP-1 in cervicovaginal secretions is consistent with ROM when the clinical diagnosis is uncertain (5–7). An immunochromatographic strip test, with monoclonal antibody to IGFBP-1 (ActimProm; Medix Biochemica, Kauniainen, Finland), has been developed to detect amniotic fluid in the vagina (5,6). The monoclonal antibody used in the test detects non- and less phosphorylated amniotic fluid isoforms, but not the highly phosphorylated IGFBP-1 (4). The sensitivity of the IGFBP-1 dipstick test varies from 95 to 100% and specificity from 89 to 98% (6,8–12). It has been suggested that the presence of blood interferes with the diagnosis of ROM. We wanted to evaluate whether blood of maternal, fetal or decidual origin or different phosphoisoforms of IGFBP-1 interfere with the dipstick test by measuring the concentrations of different phosphoisoforms of IGFBP-1 in vaginal samples.
Material and methods This cross-sectional study was conducted at the Department of Obstetrics and Gynecology, University Central Hospital, Helsinki, Finland between March 2011 and December 2011. The study was approved by the local Institutional Ethics Committee (Reg. no. 246/13/03/03/ 2011). A total of 247 pregnant women between 24 and 42 weeks of gestation, consulting the obstetric emergency unit with self-reported amniotic fluid leakage were enrolled in the study. Vaginal secretion was collected from 247 women. Of the 247 women, 50 (20.2%) were preterm (
