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Letters to the Editors
Reply To the Editors: We are grateful to Dr. Ghosh et al for their comments. Indeed, it is impossible to rule out completely all of the etiologies for intrauterine fetal death in each and every case, and overall the etiology remains unknown in as much as 50% of subjects.1,2 In our study we did our best to exclude all of the subjects with maternal or fetal risk factors for fetal death. Moreover, we reviewed the autopsy report in 92% of case subjects and exclude all of the subjects with anomalies or evidence of fetal infection. Accordingly, we excluded approximately 40% of the stillbirths that occurred during the study period. Frankly we were quite surprised not to find inherited thrombophilia as a major etiologic factor a in the remaining 37 subjects of unexplained thirdtrimester intrauterine fetal death. As noted by Dr. Ghosh et al, one would expect that with recurrent unexplained fetal loss, the role of genetic factors, such as inherited thrombophilia, would be more prominent than with a single case of intrauterine fetal death. Consequently, the lack of association between thrombophilia and recurrent fetal loss, as reported by Dr. Ghosh et al, further corroborates our results. However, one should regard with caution their results because their study group included subjects with 2 or more fetal losses at any gestational age, whereas our study was restricted to the third trimester. Early pregnancy loss has multiple etiologies, which may differ
from the etiologies of third-trimester fetal death.3 Grouping together early and late fetal loss may by itself dilute the impact of any specific etiology. We certainly agree that only a large multicenter study with predetermined inclusion and exclusion criteria may help to solve the current controversy with regard to this issue. Ron Gonen, MD* *Department of Obstetrics and Gynecology Bnai Zion Medical Center Faculty of Medicine TechnioneIsrael Institute of Technology 47 Golomb Street Haifa 31048, Israel E-mail:
[email protected]
References 1. Incerpi MH, Miller DA, Samadi R, Settlage RH, Goodwin TM. Stillbirth evaluation: what tests are needed? Am J Obstet Gynecol 1998;178:1121-5. 2. Shyken JM. Fetal demise. In: Winn HN, Hobbins JC, editors. Clinical maternal-fetal medicine. New York, London: The Parthenon Publishing Group; 2000. p. 683-9. 3. Abortion. In: Cunningham FG, Gant NF, Leveno KJ, Gilstrap LC, Hauth JC, Wenstrom KD, editors. Williams obstetrics. 21st ed. New York, NY: McGraw-Hill; 2001. p. 855-82.
0002-9378/$ - see front matter Ó 2006 Mosby, Inc. All rights reserved. doi:10.1016/j.ajog.2005.07.031
A short cervix in women with preterm labor and intact membranes: A risk factor for microbial invasion of the amniotic cavity To the Editors: The study by Gomez et al1 that demonstrated that decreasing cervical length in women diagnosed with preterm labor was associated with an increased risk of a positive amniotic fluid culture was both interesting and novel. Although this was a commendable study, there were a few methodologic issues with the study and analytic design; and typical of some of the most interesting studies, this paper raised as many questions as it answered. The first methodologic question raised was the diagnosis of preterm labor. As with any study assessing
patients with this diagnosis, rigorous criteria should be utilized. The authors state that the diagnosis was made ‘‘in the presence of regular uterine contractions of at least 3 in 30 minutes.’’1 However, most studies of preterm labor incorporate a finding of either cervical change or advanced cervical exam into their diagnosis2; were such findings also included? Given that, on average, patients achieved 5 additional weeks of pregnancy after admission, one must consider that only a minority of these patients actually had preterm labor. Could the authors stratify the rates of
902 microbial invasion by weeks from presentation until delivery? Analytically, in the multivariate model, the authors state they added cervical exam, contraction frequency, and ‘‘others’’1 to their model without finding significant contributions. What were the other potential predictors the authors examined? In particular, did they examine parity, previous preterm delivery, and socioeconomic status? Furthermore, because cervical length and dilation are unlikely to be independent variables, how was the interaction between these 2 predictors examined? One might posit a different effect of the interrelationship between cervical length and dilation between nulliparous and multiparous women. Finally, although the estimated risk table (Table IV) is interesting, how do the authors suggest clinicians use it? Considering the authors well-justified point that a randomized, control trial of antibiotic use versus placebo is not likely to be soon forthcoming, is there some risk above which the authors would recommend
Letters to the Editors an amniocentesis, routine antibiotic use, or even delivery? Aaron B. Caughey, MD, MPP, MPH* *Department of Obstetrics, Gynecology, and Reproductive Sciences University of California, San Francisco 505 Parnassus Avenue, Box 0132 San Francisco, CA 94143 E-mail:
[email protected]
References 1. Gomez R, Romero R, Nien JK, Chaiworapongsa T, Medina L, Kim YM, et al. A short cervix in women with preterm labor and intact membranes: a risk factor for microbial invasion of the amniotic cavity. Am J Obstet Gynecol 2005;192:678-89. 2. Carr DB, Clark AL, Kernek K, Spinnato JA. Maintenance oral nifedipine for preterm labor: a randomized clinical trial. Am J Obstet Gynecol 1999;181:822-7.
0002-9378/$ - see front matter Ó 2006 Mosby, Inc. All rights reserved. doi:10.1016/j.ajog.2005.07.029
Reply To the Editors: We thank Dr Caughey for the interest in our work on the relationship between sonographic cervical length and the frequency of microbial invasion of the amniotic cavity and intra-amniotic inflammation. First, Dr Caughey asked why we did not include cervical changes as part of the criteria for entry into our study when the standard definition of preterm labor calls for the combination of increased uterine contractility and cervical changes. The reason is that we have substantial reservations concerning the scientific basis of the conventional definition of preterm labor. Indeed, there is evidence that women admitted with increased uterine contractility and without the degree of cervical change required by the standard definition can stop contracting, be discharged from the hospital, and still deliver a preterm neonate. Dr Caughey infers that if patients with increased contractility did not deliver preterm, then they did not have preterm labor. This assumes that the only course of preterm labor is a progressive one, leading to preterm delivery. We do not agree with this position. If that were the case, why bother with the diagnosis of preterm labor? Our view is that activation of the common terminal pathway of parturition (uterine contractility, cervical ripening, and membrane/decidual activation) can be synchronous or asynchronous and reversible or irreversible.1
Much of the confusion about the diagnosis of preterm labor stems from an incomplete grasp of the definition of activation of each component as well as an inadequate understanding of the probability of spontaneous preterm delivery as a function of the cumulative activation of the different components of the common terminal pathway of parturition. In response to the question of whether we can provide the rates of microbial invasion according to the admission-to-delivery interval, our results indicate that the shorter the interval to delivery, the higher the rate of microbial invasion of the amniotic cavity (0-14 days: 22.1%; 14-28 days: 6.1%; 28-42 days: 0%; 42-56 days: 0%; 56-70 days: 0%; and more than 70 days: 2.3%). This means that patients who have an intraamniotic infection deliver sooner than those who have a sterile amniotic cavity. This is neither surprising nor new. We reported these findings more than 15 years ago,2 and this has been confirmed by many investigators since that time. Dr Caughey asked what variables were included in the multivariate model reported in our study. Such variables were cervical length, gestational age at admission, cervical dilatation assessed by digital examination, parity, and frequency of uterine contractions. We thank Dr Caughey for giving us the opportunity to clarify