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A transcervical amniotic fluid collector: a new medical device for the assessment of amniotic fluid in patients with ruptured membranes

  • Seung Mi Lee , Roberto Romero EMAIL logo , Joong Shin Park , Piya Chaemsaithong , Jong Kwan Jun and Bo Hyun Yoon EMAIL logo
Published/Copyright: November 5, 2014
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Journal of Perinatal Medicine
From the journal Journal of Perinatal Medicine Volume 43 Issue 4

Abstract

Aim: To describe a new device for the transcervical collection of amniotic fluid (AF) in patients with ruptured membranes, and to compare the concentration of proteins in fluid retrieved by transabdominal amniocentesis and the transcervical AF collector.

Study design: Paired AF samples were collected in patients with preterm prelabor rupture of membranes (PROM) (n=11) by transabdominal amniocentesis and with the transcervical AF collector (Yoon’s AF Collector™). Three proteins known to have high concentrations in AF [α-fetoprotein (AFP), β-human chorionic gonadotrophin (β-hCG), and prolactin] were measured.

Results: (1) There was a significant correlation between the concentrations of analytes in AF obtained by transabdominal amniocentesis and by the transcervical AF collector (r=0.94, P<0.001 for AFP; r=0.96, P<0.001 for β-hCG; r=0.72, P<0.05 for prolactin); (2) Bland-Altman plots showed no evidence of heteroscedasticity between transabdominal or transcervical AF concentrations of these markers.

Conclusions: There was a strong correlation between the concentrations of proteins in AF collected by amniocentesis or with the transcervical device.

Keywords: Amniocentesis; α-fetoprotein; β-human chorionic gonadotrophin; premature rupture of membranes; prolactin; PROM; pPROM; transcervical amniotic fluid collector; Yoon’s AF Collector™

Introduction

Rupture of membranes (ROM) occurs spontaneously during the course of labor [1]. Prelabor rupture of membranes (PROM) is defined as chorioamniorrhexis prior to the onset of labor and complicates 10% of all pregnancies [2–20]; in 2% of the cases, it occurs in preterm gestations [1, 21–37]. Preterm PROM accounts for 30–35% of all preterm births [21, 24, 38].

Amniotic fluid analysis is used to assess the likelihood of intra-amniotic infection, intra-amniotic inflammation [32, 39–79], and fetal lung maturity [73, 80–95] in preterm PROM. Amniotic fluid can be retrieved with amniocentesis; however, this procedure is technically demanding in the context of rupture of membranes due to the decreased volume of amniotic fluid frequently observed in these cases [37, 96, 97].

We report herein a novel device designed for transcervical collection of amniotic fluid. The purpose of this article is to describe the device and to report the concentration of proteins in amniotic fluid collected transabdominally, as well as that obtained transcervically with the use of the device. For this, we measured α-fetoprotein (AFP), beta-human chorionic gonadotropin (β-hCG), and prolactin, which are known to be present in high concentrations in amniotic fluid [98–102].

Materials and methods

Study design

Eleven women with singleton pregnancies admitted to the Seoul National University Hospital, Seoul National University Bundang Hospital, or Dongguk University Hospital, Korea, were included in the study. All patients had the diagnosis of preterm PROM (≤35 weeks of gestation). Amniotic fluid was collected using the new medical device described herein. Transabdominal amniocentesis was also performed to examine the presence or absence of intra-amniotic infection and/or inflammation and is part of the standard of practice in our institution.

The retrieval of amniotic fluid was performed after obtaining written informed consent from the patients, and the Institutional Review Boards of the Seoul National University Hospital, Seoul National University Bundang Hospital, and Dongguk University Hospital approved the collection and use of these samples and information for research purposes.

Collection of amniotic fluid

Transcervical amniotic fluid collection was performed with the transcervical amniotic fluid collector (Yoon’s AF Collector™), which was developed and patented by the authors (patent number: Korea 10-1170053-0000). The collector was placed against the cervix during a sterile speculum exam and fixed with a silicon balloon. Amniotic fluid that leaked through the cervix pooled into the collector (Figure 1). Transabdominal amniotic fluid was obtained after transcervical amniotic fluid collection by amniocentesis under ultrasonographic guidance as previously described [78, 103, 104]. Amniotic fluid was centrifuged for 10 min, and stored in polypropylene tubes at –70°C until assayed.

Figure 1 (A) The transcervical amniotic fluid collector (Yoon’s AF Collector™). (B) Schematic drawing of Yoon’s AF Collector™ placed in the vagina.
Figure 1

(A) The transcervical amniotic fluid collector (Yoon’s AF Collector™). (B) Schematic drawing of Yoon’s AF Collector™ placed in the vagina.

Amniotic fluid analysis

Amniotic fluid was assayed for AFP, β-hCG, and prolactin by immunoradiometric assays (IRMA) with commercially available kits (AFP: Immunotech, Prague, Czech Republic; β-hCG: Shinjin, Seoul, Korea; prolactin: Shinjin, Seoul, Korea).

Statistical analysis

The concentrations of amniotic fluid proteins in samples retrieved either by transabdominal amniocentesis or using the transcervical amniotic fluid collector were compared using Spearman’s correlation and Passing and Bablok regression analysis. Bland-Altman plots were used to evaluate the differences between protein concentrations obtained from transabdominal amniotic fluid and those retrieved transcervically. We used SPSS version 20.0 for Windows (SPSS Inc., Chicago, IL, USA) and MedCalc version 12.7.1.0 (MedCalc Software, Mariaherke, Belgium). A P-value<0.05 was considered significant.

Results

The clinical characteristics of patients enrolled in the study are summarized in Table 1. None of the patients developed clinical chorioamnionitis.

Table 1

Clinical characteristics of the study population.

n=11
Agea33 (29–36)
Nulliparity6 (55%)
Gestational age at amniocentesisa30.1 (27.3–34.1)
Positive AF culture2 (18%)
Intra-amniotic infection and/or inflammation3 (27%)
Gestational age at deliverya32.6 (27.4–34.4)
Cesarean delivery2 (18%)
Birthweighta1956 (1080–2800)
Histologic chorioamnionitis6/10 (60%)
Funisitis3/10 (30%)

AF=amniotic fluid. aMedian (range).

Figure 2 shows the distribution of protein concentrations in fluid collected either by transabdominal amniocentesis or using the transcervical amniotic fluid collector. The transcervical collector was effective in collecting amniotic fluid from all patients. There was a significant correlation between the concentrations of analytes in transabdominal and transcervical amniotic fluid (Spearman correlation coefficients: r=0.936, P<0.001 for AFP; r=0.964, P<0.001 for β-hCG; r=0.718, P<0.05 for prolactin; Figure 3 and Table 2). Bland-Altman plots showed no evidence of heteroscedasticity between transabdominal and transcervical amniotic fluid concentrations of these markers (Figure 4). Passing-Bablok regression analysis revealed neither constant distance (with intercept including 0 for all of proteins) nor proportional difference (with slope including 1) for all three proteins (Table 2).

Figure 2 Protein concentrations in transabdominal amniotic fluid and those in transcervical amniotic fluid, with means and 95% confidence interval presented in solid line. (A) α-Fetoprotein (AFP) (IU/mL); (B) β-human chorionic gonadotrophin (β-hCG) (mIU/mL); (C) prolactin (ng/mL).
Figure 2

Protein concentrations in transabdominal amniotic fluid and those in transcervical amniotic fluid, with means and 95% confidence interval presented in solid line. (A) α-Fetoprotein (AFP) (IU/mL); (B) β-human chorionic gonadotrophin (β-hCG) (mIU/mL); (C) prolactin (ng/mL).

Figure 3 Scatter plot of correlation between protein concentrations in transabdominal amniotic fluid and those in transcervical amniotic fluid. (A) α-Fetoprotein (AFP) (IU/mL); (B) β-human chorionic gonadotrophin (β-hCG) (mIU/mL); (C) prolactin (ng/mL).
Figure 3

Scatter plot of correlation between protein concentrations in transabdominal amniotic fluid and those in transcervical amniotic fluid. (A) α-Fetoprotein (AFP) (IU/mL); (B) β-human chorionic gonadotrophin (β-hCG) (mIU/mL); (C) prolactin (ng/mL).

Table 2

The protein concentrations in transabdominal amniotic fluid and those in transcervical amniotic fluid.

Concentrations [mean (SD)]α-Fetoprotein (IU/mL)β-hCG (mIU/mL)Prolactin (ng/mL)
Transabdominal AFTranscervical AFTransabdominal AFTranscervical AFTransabdominal AFTranscervical AF
2006 (1771)1997 (1575)1190 (1122)1322 (1220)784 (400)829 (592)
Wilcoxon signed rank test (P-value)0.930.821.00
Spearman correlation coefficients (P-value)0.94 (P<0.001)0.96 (P<0.001)0.72 (P<0.05)
Passing-Bablok regression analysis
 Intercept [95% CI]176.9 [–415.2 to 629.9]75.6 [–989.7 to 260.7]–48.5 [–989.6 to 372.7]
 Slope [95% CI]0.86 [0.62 to 1.46]0.89 [0.67 to 2.50]1.05 [0.39 to 2.26]

SD=standard deviation, AF=amniotic fluid, AFP=α-fetoprotein, β-hCG=β-human chorionic gonadotropin.

Figure 4 Bland-Altman plots of protein concentrations in transabdominal amniotic fluid and those in transcervical amniotic fluid. (A) α-Fetoprotein (AFP) (IU/mL); (B) β-human chorionic gonadotrophin (β-hCG) (mIU/mL); (C) prolactin (ng/mL).
Figure 4

Bland-Altman plots of protein concentrations in transabdominal amniotic fluid and those in transcervical amniotic fluid. (A) α-Fetoprotein (AFP) (IU/mL); (B) β-human chorionic gonadotrophin (β-hCG) (mIU/mL); (C) prolactin (ng/mL).

Discussion

Principal findings of the study

(1) We describe a new device for the transcervical collection of amniotic fluid from patients with ruptured membranes; and (2) a strong and significant relationship was observed between the concentration of proteins in amniotic fluid obtained by the transabdominal and transcervical method.

Amniotic fluid analysis in the assessment of patients with ruptured membranes

Amniotic fluid analysis has been used to study fetal lung maturity [80–82, 84, 85, 89–92, 94, 105], karyotype, intra-amniotic inflammation, and microorganisms (bacteria and viruses) [32, 39–79] in patients with preterm PROM. Fluid obtained from the vaginal pool has been employed to assess fetal lung maturity [73, 80–95, 105]. However, this fluid cannot be used for the assessment of microbial invasion of the amniotic cavity or the assessment of intra-amniotic inflammation, because bacteria are normally present in the vagina, and vaginal fluid contains a high concentration of inflammatory mediators [44, 51, 54, 56, 59–61, 75, 76]. Therefore, we devised a method to obtain amniotic fluid noninvasively, by collecting this biological material directly through the cervix before it reached the vaginal canal. Ultrasound images demonstrate that this fluid is present in the cervix of patients who have ruptured membranes, and can be seen with color Doppler in the endocervical canal [106]. Obtaining amniotic fluid noninvasively can allow assessment of patients with severe oligohydramnios in which amniocentesis is not possible. Moreover, it allows serial evaluation of patients with preterm PROM without repeat amniocentesis.

Collection of amniotic fluid by a transcervical amniotic fluid collector

We obtained amniotic fluid using a transcervical amniotic fluid collector designed for this specific purpose. This device has the following features: (1) it allows collection at the level of the external cervical os, and thereby reduces the likelihood of dilution of amniotic fluid with vaginal discharge; (2) it prevents leakage of amniotic fluid into the vagina, and therefore, fluid can be obtained even in patients with scant vaginal pooling; and (3) placement of the device for a short period of time (60 min) allowed collection of enough fluid for analysis. Patients did not report discomfort during collection of fluid with this device (Figure 1). Importantly, there was an excellent correlation between the concentration of a set of analytes in fluid retrieved by transabdominal amniocentesis and the use of the transcervical amniotic fluid collector, suggesting that this method may be useful in assessing the composition of amniotic fluid in patients with preterm PROM. Future studies are required to determine if this material can be used to assess the likelihood of intra-amniotic inflammation and fetal lung maturity.

This was a feasibility study; therefore, the sample size was small. We measured AFP, prolactin, and hCG, all of which are known to be present in high concentrations in amniotic fluid. It would be important to assess other components of amniotic fluid, including “omics” characterization (proteomics, metabalomics, lipidomics, etc.).

Conclusion

We describe a new device for the collection of amniotic fluid from patients with ruptured membranes. The transcervical amniotic fluid collector might be useful in the evaluation of amniotic fluid in patients with ruptured membranes.

Corresponding authors: Roberto Romero, MD, D. Med. Sci, Perinatology Research Branch, NICHD/NIH/DHHS, Wayne State University/Hutzel Women’s Hospital, 3990 John R, Box 4, Detroit, MI 48201, USA, Tel.: +1-313-993-2700, Fax: +1-313-993-2694, E-mail: ; and Bo Hyun Yoon, MD, PhD, Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, 110-744, Korea, Tel.: +82-2-2072-2826, Fax: +82-2-742-2028, E-mail:

Acknowledgments

The participation of Roberto Romero in this research is funded by the Division of Intramural Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and, in part, by NICHD Contract No. HHSN275201300006C and by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI12C0768). All patients were recruited in South Korea under IRB approved protocols, and assays were performed at the Seoul National University Hospital, Seoul National University Bundang Hospital or Dongguk University Hospital.

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The authors stated that there are no conflicts of interest regarding the publication of this article.

Article note

The device described in this article was patented by the Seoul National University in Seoul, Korea. Dr. BH Yoon, Dr. JS Park, and Dr. SM Lee are inventors.

Received: 2014-8-15
Accepted: 2014-10-6
Published Online: 2014-11-5
Published in Print: 2015-7-1

©2015 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Erich Saling – The Father of Prenatal and Perinatal Medicine—Dedication to his 90th birthday
  4. Original articles - Obstetrics
  5. A transcervical amniotic fluid collector: a new medical device for the assessment of amniotic fluid in patients with ruptured membranes
  6. Advanced cervical dilatation and spontaneous preterm labor: a comparison between twin and singleton gestations
  7. Comparison of a novel test for placental alpha microglobulin-1 with fetal fibronectin and cervical length measurement for the prediction of imminent spontaneous preterm delivery in patients with threatened preterm labor
  8. Does recent sexual intercourse during pregnancy affect the results of the fetal fibronectin rapid test? A comparative prospective study
  9. Usefulness of maternal serum C-reactive protein with vaginal Ureaplasma urealyticum as a marker for prediction of imminent preterm delivery and chorioamnionitis in patients with preterm labor or preterm premature rupture of membranes
  10. Effect of blood on ROM diagnosis accuracy of PAMG-1 and IGFBP-1 detecting rapid tests
  11. Single versus combination tocolytic regimen in the prevention of preterm births in women: a prospective cohort study
  12. Recommendations of activity restriction in high-risk pregnancy scenarios: a Danish national survey
  13. Is pharmacologic research on pregnant women with psychoses ethically permissible?
  14. Women’s knowledge and attitude towards pregnancy in a high-income developing country
  15. Impact of maternal body mass index on the cesarean delivery rate in Germany from 1990 to 2012
  16. Justified skepticism about Apgar scoring in out-of-hospital birth settings
  17. The effect of the use of oxytocin on blood loss during different postpartum periods
  18. Original articles - Fetus
  19. The T/QRS ratio values in pregnancies complicated by threatened preterm labour treated with intravenous infusions of fenoterol
  20. Cardiotocography patterns and risk of intrapartum fetal acidemia
  21. Combined spinal epidural analgesia for labor using sufentanil epidurally versus intrathecally: a retrospective study on the influence on fetal heart trace
  22. Original articles - Newborn
  23. Predicting fetal growth deviation in parous women: combining the birth weight of the previous pregnancy and third trimester ultrasound scan
  24. Letter to the Editor
  25. A cerclage is not a modified total cervical occlusion!
  26. Letter Reply
  27. Reply to: a cerclage is not a modified Total Cervical Occlusion!
  28. Congress Calendar
  29. Congress Calendar
https://doi.org/10.1515/jpm-2014-0276
Keywords for this article
Amniocentesis; α-fetoprotein; β-human chorionic gonadotrophin; premature rupture of membranes; prolactin; PROM; pPROM; transcervical amniotic fluid collector; Yoon’s AF Collector™

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Erich Saling – The Father of Prenatal and Perinatal Medicine—Dedication to his 90th birthday
  4. Original articles - Obstetrics
  5. A transcervical amniotic fluid collector: a new medical device for the assessment of amniotic fluid in patients with ruptured membranes
  6. Advanced cervical dilatation and spontaneous preterm labor: a comparison between twin and singleton gestations
  7. Comparison of a novel test for placental alpha microglobulin-1 with fetal fibronectin and cervical length measurement for the prediction of imminent spontaneous preterm delivery in patients with threatened preterm labor
  8. Does recent sexual intercourse during pregnancy affect the results of the fetal fibronectin rapid test? A comparative prospective study
  9. Usefulness of maternal serum C-reactive protein with vaginal Ureaplasma urealyticum as a marker for prediction of imminent preterm delivery and chorioamnionitis in patients with preterm labor or preterm premature rupture of membranes
  10. Effect of blood on ROM diagnosis accuracy of PAMG-1 and IGFBP-1 detecting rapid tests
  11. Single versus combination tocolytic regimen in the prevention of preterm births in women: a prospective cohort study
  12. Recommendations of activity restriction in high-risk pregnancy scenarios: a Danish national survey
  13. Is pharmacologic research on pregnant women with psychoses ethically permissible?
  14. Women’s knowledge and attitude towards pregnancy in a high-income developing country
  15. Impact of maternal body mass index on the cesarean delivery rate in Germany from 1990 to 2012
  16. Justified skepticism about Apgar scoring in out-of-hospital birth settings
  17. The effect of the use of oxytocin on blood loss during different postpartum periods
  18. Original articles - Fetus
  19. The T/QRS ratio values in pregnancies complicated by threatened preterm labour treated with intravenous infusions of fenoterol
  20. Cardiotocography patterns and risk of intrapartum fetal acidemia
  21. Combined spinal epidural analgesia for labor using sufentanil epidurally versus intrathecally: a retrospective study on the influence on fetal heart trace
  22. Original articles - Newborn
  23. Predicting fetal growth deviation in parous women: combining the birth weight of the previous pregnancy and third trimester ultrasound scan
  24. Letter to the Editor
  25. A cerclage is not a modified total cervical occlusion!
  26. Letter Reply
  27. Reply to: a cerclage is not a modified Total Cervical Occlusion!
  28. Congress Calendar
  29. Congress Calendar
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