Comment and reply on: The clinical significance of a positive Amnisure test in women with term labor with intact membranes

Lee et al. reported that among term women in labor without clinically apparent rupture of membranes, those patients with a positive Amnisure have a shorter admission-to-delivery interval than those patients with a negative result [1]. The median interval in the positive group was 6.88 h versus 9.79 h in the negative group (range 1.18–15.98 h and 2.32–33.07 h, respectively; p < 0.05). Although this was found to be a statistically significant result, we suggest that it is not clinically significant given the stated gestational age.

We were surprised that the mean cervical dilatation in the laboring groups at time of entry into the study was 2.2 cm in group 2 (labor without clinical rupture of membranes [ROM], Amnisure negative), 2.4 cm in group 3 (labor without clinical ROM, Amnisure positive), and 2.1 cm in group 4 (labor with clinical ROM). Friedman's classic description of labor curves in 500 nulliparous patients documented an increase in rate of dilatation between 4 and 5 cm [2] and a more recent examination of over 1300 nulliparous women reported that most enter the active phase between 3 and 5 centimeters [3].

Table I of the manuscript reports four items with statistically significant results. Three of the items simply reflect that group 1 patients were admitted for induction, whereas the patients in the other three groups presented in labor. This group's cervical dilatation was less, estimated gestation age was greater and use of oxytocin was greater. The fourth significant finding of questionable relevance was a difference in pre-pregnancy body mass index between groups 3 and 4.

The authors suggest that positive Amnisure may be associated with labor itself. Uterine contractions increase intraamniotic pressure, which may lead to microperforations of the chorioamniotic membrane and disruption of the decidual interface. This may lead to seepage of markers of impending labor through the cervix and into the vagina. Accurate and timely diagnosis of preterm labor will allow treatments to prolong pregnancy and enhance fetal lung maturity. The detection of minute concentrations of PAMG-1 must not be assumed to indicate impending labor. We support further clinical research between weeks 22 and 34 to clarify the role of PAMG-1 testing in predicting preterm labor and delivery.

References

• Lee SM, Lee J, Seong HS, Lee SE, Park JS, Romero R, Yoon BH. The clinical significance of a positive Amnisure test in women with term labor with intact membranes. J Matern Fetal Neonatal Med 2009;22:305–310.
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• Freidman EA. Primigravid labor; a graphicostatistical analysis. Obstet Gynecol 1955;6:567–589.
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• Zhang J, Troendle JF, Yancey MK. Reassessing the labor curve in nulliparous women. Am J Obstet Gynecol 2002;187:824–828.
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Author's reply

Seung Mi Lee and Bo Hyun Yoon

Department of Obstetrics and Gynecology Seoul National University College of Medicine Seoul, Republic of Korea

Roberto Romero

Perinatology Research Branch, NICHD/NIH/DHHS Detroit, Michigan, USA

Correspondence: 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: [phone]. E-mail: [email protected]

Author's reply

We thank Drs. Kurt Martinuzzi and Federico Mariona for their interest in our findings [1], and we are glad to reply to their Letter to the Editor.

The point of our article was to report that women with intact membranes in labor at term can have a positive Amnisure test. This is important because this test is being offered as a new method to diagnose rupture of membranes. Our study was intended to alert clinicians that a positive Amnisure test may be observed in women in labor at term and the discussion intended to explore the reasons for this and its potential implications.

We wish to emphasize to readers of the journal that 30% (25/81) of women in spontaneous labor at term with intact membranes had a positive test, while this occurred only in 4.8% (6/125) of women who were not in labor and had no evidence of ruptured membranes. These findings suggest that in the context of labor, a positive test cannot be interpreted to indicate rupture of membranes, which is the claim of those advocating for the test.

Table I in our manuscript describes the clinical and demographical characteristics of the study groups. We found that the median interval-to-delivery in patients with intact membranes and a positive Amnisure test was shorter than that of patients with intact membranes and a negative Amnisure test. However, our results reflect what actually happened with these patients. We did not claim that the difference between 6.8 h and 9.7 h is clinically significant, and hence, we are unclear as to why Drs. Martinuzzi and Mariona think that this is clinically meaningful. The results are reported because these data were collected and they hint that the parturitional process may have been more advanced in patients with a positive Amnisure test than in those with a negative Amnisure test. We think that an attempt to seek clinical significance in this difference is misplaced and we are puzzled by this effort.

The second point in the Letter to the Editor is the surprise that Drs. Martinuzzi and Mariona expressed that patients admitted in labor would have a cervical dilatation of 2.2 cm and 2.4 cm. This was the cervical dilatation at which patients were admitted in labor. It would seem that Drs. Martinuzzi and Mariona have an expectation that patients would not be admitted to the labor and delivery unit until they are in active labor. This is not the practice of obstetrics, either in Korea or most institutions in the US. Indeed, we doubt that this will be the practice in most hospitals in Michigan where Drs. Martinuzzi and Mariona reside. Friedman described the latent phase of labor as the period of time elapsed between the onset of regular uterine contractions and the active phase of labor [2]. In the study of Vahratian et al., the median cervical dilatation at admission was 3 cm [3]. This confirms that 50% of patients are admitted with a cervical dilatation of 3 cm or less. This is consistent with the findings in our report. We are not clear what relationship this issue (the cervical dilatation at which patients are admitted or whether they are admitted in active labor or not) could have with a positive Amnisure test. If there was any relation, we would expect that the more advanced the cervical dilatation, the more likely a positive result would be. Thus, the fact that our patients were not in active labor strengthens the importance of our findings. Most physicians would perform this test before patients enter the active phase of labor. Performing the test after patients enter the active phase of labor would have dubious value.

The final point in the Letter to the Editor is that we reported that women admitted for elective cesarean section or induction of labor had a higher body mass index (BMI) than those admitted in labor. Our observation is consistent with that of others who have reported that the BMI in cases of labor induction or elective cesarean section is higher than in women in spontaneous labor at term [4,5]. Table I, where these findings were reported, contains these data because it was collected and describes the patient population. We have not attributed clinical significance or claim relevance of BMI to the likelihood of a positive or negative Amnisure test. Thus, we are unclear as to the point the authors are making.

The message of our article is simple: a positive Amnisure test in women in labor at term does not necessarily indicate rupture of membranes. This is the standard interpretation of a positive test. Studies are now in progress to determine whether a positive Amnisure test is a risk factor for preterm delivery in women with preterm labor with intact membranes. We believe that such a finding would be of interest and agree with Drs. Martinuzzi and Mariona that further studies are warranted to test whether this is the case.