Current Measures to Prevent Late Abortion Or Prematurity

Perinatology, edited by Erich Saling, Nestle" Nutrition Workshop Series, Vol. 26, Nestec, Ltd., Vevey/Raven Press, Ltd., New York © 1992. Current Measures to Prevent Late Abortion or Prematurity Erich Saling Department of Obstetrics, Berlin-Neukolln and Institute of Perinatal Medicine, Free University of Berlin, Mariendorfer Weg 28, D-I000 Berlin 44, Germany During the past few years it has been recognized more and more that ascending genital infection is an important factor in the etiology of prematurity. This is con- firmed in a number of reports in the literature. Recent reviews have been published by Romero et al. (1) and in this volume (see chapters by Eschenbach and Hobel). In a retrospective study by Schmitz, Riedewald, Schmeling, and myself (unpub- lished) we have tried to determine the cause of prematurity in 195 cases from our unit with delivery of an infant with a birth weight of less than 2,000 g and gestation less than 37 weeks. The results (Fig. 1) show that in 76% of the cases there was evidence of an infection. This means that there was direct evidence of organisms in the vagina or cervix which are known to be pathogenic or facultative pathogenic, and/or one or more of the following: raised C-reactive protein, IgA against chlamydia (never as a single parameter), leukocytosis, left shift of granulocytes, bacteriuria, abnormal placental histology, or (in several cases) manifest infections in the newborn. In 29% there was evidence of organisms as well as other signs of infection. In 47% the above-mentioned signs of infection were present but we could not find direct evidence of organisms. In cases where infection was only suspected the incidence of premature rupture of the membranes (PROM) was, as expected, very high, at between 60 and 70%. We think our results show that infection plays a considerable role in causing prematurity. In principle the course of events is as follows: a functional defect of the cervical barrier and the subsequent ascension of pathogenic organisms leads to local inflammation and prostaglandin release. For example, Bejar and coworkers (2) were able to show that pathogenic organisms like Bacteroides fragilis and Streptococcus vir- idans produce phospholipase A2. This stimulates the arachidonic acid metabolism in the amnion cells and prostaglandin is formed (3). It is also possible that the mi- gration of leukocytes which produces the picture of chorioamnionitis, is also able to induce intrauterine prostaglandin metabolism. According to Romero and coworkers, leukocytes are also able to induce prostaglandin synthesis through the effect of interleukin (4). 141 142 PREVENTION OF LATE ABORTION AND PREMATURITY Suspected infection without evidence of organisms 47% Only parameters of infection Additional other than infection causes PROM 62% I No cause detected Suspected infection with evidence of organisms Insufficient diagnostics 29% Only parameters of infection Other than infection causes PROM 68% 1 Additional other than infection causes |PROM33%| FIG. 1. Causes of premature labor in 195 cases (<37/0 gestational weeks and <2,000 g weight), 1988/89. Data by C. Schmitz, S. Riedewald, S. Schmeling, and E. Saling. Ascending infections reaching the membranes and decidua can, via the metabolic products of bacteria or local changes due to inflammation, lead to a lessening of the breaking strength of the lower egg pole (5) and, by stimulating prostaglandin synthesis, to premature rupture of the membranes and/or to premature contractions. At the beginning of the 1990s—and before infection was considered to be so important in the pathogenesis of premature labor—we were able to find the first con- crete evidence that a barrier to the ascension of organisms provided much better chances of preventing late abortions or prematurity. To achieve this, since 1981 we have been using the operative early total occlusion of the external os uteri (ETCO), which provides an excellent barrier against the ascension of organisms (6,7). As this measure is only indicated in a small group of high-risk cases with a bad history, we have to search for practicable strategies to prevent dangerous ascending bacterio- logical infection that can be applied in every pregnancy. On the basis of present knowledge we have elaborated a relatively simple program suitable for daily routine use to prevent late abortions and prematurity in the future and to achieve better overall results (8). The first important step in our new program is shown in Fig. 2 as Stage I of the routine diagnostic procedures. In the very early stages of pregnancy and then at every subsequent consultation in the antenatal outpatient clinic it is possible—by PREVENTION OF LATE ABORTION AND PREMATURITY 143 Routln.: | STAGE In UN Dlractad apacial maaauraa t [STAGE 111 <3> ® © Diagnosis DIM to pravtoua I* critical ofbactorla Caryl x CRP- I (found by © kitnaeanlx, dlagnoatlca datarmi nation tha vagina, by vaginal n matarnal critical finding* aaiaallaaurtna aonography aarum ® Dlagnoala of chlamydla antlbodlaa FIG. 2. Diagnostic measures in the prematurity prevention program. simply measuring the local pH—to find out whether normal, i.e., undisturbed, con- ditions prevail in the ascending area, particularly in the vagina, so that the ascension of pathogenic organisms can be prevented by the defense mechanisms naturally present—i.e., the vagina must have a relatively high acidity. According to examinations made by our coworker I. M. Kreutzmann, the pH level—measured in the posterior fornix—should be 4.3 or even less (9). The importance of a normal acidity of the vaginal milieu has been convincingly shown by Ernest and coworkers (10). They found that patients with a mean vaginal pH above 4.5 had a threefold increased risk of premature rupture of the membranes compared with those with a mean pH of 4.5 or lower. There are three practical ways of measuring the intravaginal pH; all three can be used depending on expected accuracy and on the prevailing situation. The simplest and most precise method is to insert a pH electrode directly into the vagina and to read the pH level using a portable pH meter. The only disadvantage of this method is that the pH electrode must be disinfected after use. This takes about 15 min. The second possibility involves measuring the pH level in a vaginal smear. For this a small but nevertheless adequate amount of vaginal smear must be left on the with- drawn speculum. When the substrate is too small the measurement can be incorrect or even impossible to do. The advantage is that the pH-electrode does not have to be disinfected after use, only cleaned in tap water. The third possibility is to assess the pH level using test paper. This procedure is inexpensive and simple but unfor- tunately is not so precise as the other two more direct methods. If the routinely measured pH levels—or other factors—indicate an increased risk, then the measures shown in Stage II (Fig. 2, lower part) should be performed. These are specific diagnostic measures and are necessarily more expensive. A greater risk is present (on the left of Fig. 2): a. When indicated by past history, such as previous late abortion or premature birth, and/or when certain critical factors are present in the current pregnancy, such as 144 PREVENTION OF LATE ABORTION AND PREMATURITY poor social status, serious difficulties in professional or family life, multiple pregnancy, uterine anomalies, etc. b. When the vaginal pH level is increased c. When the cervix is in a critical state (found by conventional vaginal examination) d. When premature contractions exist. When such indications are present, the following diagnostic measures are recommended (on the right of Fig. 2): 1. Bacterial cultures of the cervix and the vagina as well as of the urine 2. Examination of maternal serum for chlamydia antibodies (still controversial) 3. Assessment of the cervix by vaginal sonography 4. Determination of C-reactive protein in maternal serum. With regard to item 2, it must be said that positive chlamydia IgG and IgA results are naturally not pathognomonic for cervicitis. When there is no direct evidence of a chlamydia infection in the cervix, positive IgA may be the result of a chlamydia infection located in another region. However, when symptoms of threatened premature labor are present and chlamydia antibody tests are positive, it would be careless not to treat because of uncertainty about the precise backgrounds. For this reason we think that antibiotic therapy should be used in such cases. According to a study made by our coworker E. Hansel (11), cervical assessment by vaginal sonography recommended in point 3 of Stage II appears to be more reliable than the traditional vaginal digital examination alone. If one assumes that a sono- graphically measured cervical canal length of less than 3 cm can be considered as critical, then it has been shown (Fig. 3) that when the findings on digital examination were normal, with a length of 2 cm or more, nevertheless in almost 20% (left columns) of these cases a shortened cervical canal was measured by vaginal sonography. Such shortening is often due to a three-cornered or sack-shaped hernia-like sacculation of the lower egg pole into the cervical canal in the region of the former inner os uteri. On the other hand in 46% of the cases (Fig. 3, right columns) normal cervical canal lengths were measured by vaginal sonography when short lengths of 1 cm or less had been found by palpation. C-reactive protein determination can help us in the following ways: 1. It indicates the presence of an overall reaction of the body to a bacteriologically proven ascending infection or urogenital infection and enables an assessment to be made of its degree of severity.

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