British Journal of Obstetrics and Gynaecology July 1992, Vol. 99, pp. 625-627
CORRESPONDENCE
Prenatal microbiological risk factors associated with preterm birth Dear Sir, We found the study by McDonald et a/. (1992) interesting and a valuable contribution to our understanding of the aetiology of preterm labour. Bacterial vaginosis has been considered to be important in the aetiology of preterm labour for some time and studies conducted by Saling (1 99 1) have shown that early detection and correction of disturbances in the vaginal flora can reduce the occurrence of early preterm delivery. The two groups of micro-organisms hypothesized are interesting. The direct production of phospholipase by Gardnerella vaginalis and Ureaplasma urealyticum would result in a general increase in prostaglandin production (PGE, and PGF,,). The response to the enteropharyngeal organisms, however, would depend on the bacterial toxin composition of the particular organism. Bacterial toxins or lipoteichoic acid have been shown to act on uterine decidua to cause increased formation of cytokines (Casey et al. 1989; Romero et al. 1989). Cachetin/tumour necrosis factor-a ;TNF-a) is synthesized and secreted by human decidual cells in response to lipoteichoic acid and may also cause an increase in PGF,, production. In addition, in amnion cells in monolayer culture, TNF-a, has been shown to stimulate PGE, formation (Casey et al. 1989). Therefore, both PGF,, and PGE, may be released in response to a bacterial challenge. PGF,, is known primarily to stimulate myometrial activity, whilst the main effect of PGE, is to change the physical properties of the cervix by an alteration in its composition. Depending on the effect of the infecting organism on the decidua, varying quantities of both PGF,, and PGE, would be released. Where there is a predominance of PGF?, contractions would be stimulated, but as long as there was no change in the state of the cervix, labour would not progress (OIBh & Gee 1992). This may explain the association of U. urealyticum with preterm labour and the lack of an association with preterm delivery (Minkoff et al. 1984). However, if the release of PGE, predominates, then cervical change is possible, and in such cases little myometrial activity is required to effect delivery. Therefore, where cervical change is significant, delivery is inevitable ( O M & Gee 1992). It is with such cases that an impact will be made in the prevention of preterm delivery if correct identification of at-risk pregnancies can be made. A more comprehensive understanding of the complex biomolecular events that lead to the formation of the prostaglandins, and their relative production in response to various micro-organisms may lead to a better understanding of the pathophysiology of idiopathic preterm labour and delivery. Further studies on the infective aetiology of idiopathic preterm labour are required. Karl S. Olah Clinical Research Fellow
Harry Gee Senior Lecturer Department of Fetal Medicine Birmingham University Birmingham Maternity Hospital Edghaston Birmingham B15 2TG
References Casey M. L., Cox S. M., Beutler B., Milewich L. & McDonald P. C. (1989) Cachetin/tumor necrosis factor-A formation in human decidua. J Clin Invest 83.430436.
McDonald H. M., O’Loughlin J. A., Jolley P., Vigneswaran R., McDonald P. J. &McDonald P. J. (1992) Prenatal microbiological risk factors associated with preterm birth. Br J Ohstet Gynaecol 99, 190-196. Minkoff H., Grunebaum A. N., Schwartz R. H. et al. (1984) Risk factors for prematurity and premature rupture of membranes. A prospective study of the vaginal floral in pregnancy. Am J Ohstet Gynecol 150,965-972. Ollh K. S. &Gee H. (1992) The prevention of preterm deliverydan we afford to continue to ignore the cervix? (Commentary) Br J Ohstet Gynaecol99,278-280. Romero R., Brody T., Oyarzun E., Mazor M., King Wu Y., Hobbins J. C. & Durum S. K. (1989) Infection and labour. 111. Interleukin-I: A signal for the onset of parturition. Am J Ohstet Gynecol 160, 11 17-1 123. Saling E. (1991) Effective measures for prevention of late abortions and early premature births. J Perinat Med 19 (supplement 2), 10.
The implications of introducing the symphysealfundal height-measurement. A prospective randomized controlled trial Dear Sir, There is a serious weakness in most of the research on symphysisfundus height measurements and the paper by Lindhard et al. (1990) illustrates this very well. How can you test a method’s validity if it is not given the opportunity to show its full potential? In this paper only three S-F measurements were taken during the whole pregnancy and in 21% only one or two. With so few measurements it is not worth doing it at all! The Oxford Clinical Trial Data Base Editor’s conclusion regarding this paper was ‘It would seem unwise to abandon the use of symphysis fundal height measurement unless a much larger trial likewise suggests that it is unhelpful’. Galbraith et al. (1979) commented ‘The clinical prediction of IUGR in . . . low risk patients is heavily dependent on the serial measurement of fundal height in order to demonstrate plateauing or static fetal growth’. At this hospital SF measurements have been used on every pregnant woman at every antenatal visit since 1976. Our original method was rather rough but, since 1981, we have used the method described by Westin (1977). Since 1984, the method has also been used nationally in all government antenatal clinics. Perinatal mortality covering about 8000 deliveries at Ramotswa has fallen to a record low level of 18/1000 at a time when the perinatal mortality rate at most district hospitals in Africa is at least 30/1000 and often as much as 60/1000. What is most noteworthy about these figures is that since 1981, the stillbirth and neonatal death rate had been consistently low although the figure elsewhere is in the region of 2.5 to 3. Of the only two stillbirths which occurred after admission to hospital last year, both showed clear failure of fetal growth on their flat S-F graphs. The problem was not whether the graph indicated fekd growth impairment or not but when was the best moment to intervene? Both babies died inutero suddenly and unexpectedly, and we clearly waited far too long. Those who have never used the graph regularly in woman after woman throughout pregnancy are not in any position to make useful comments on its value, even after elegant research and apparently significant statistics. None of the doctors who have worked here and who
625
CORRESPONDENCE
Prenatal microbiological risk factors associated with preterm birth Dear Sir, We found the study by McDonald et a/. (1992) interesting and a valuable contribution to our understanding of the aetiology of preterm labour. Bacterial vaginosis has been considered to be important in the aetiology of preterm labour for some time and studies conducted by Saling (1 99 1) have shown that early detection and correction of disturbances in the vaginal flora can reduce the occurrence of early preterm delivery. The two groups of micro-organisms hypothesized are interesting. The direct production of phospholipase by Gardnerella vaginalis and Ureaplasma urealyticum would result in a general increase in prostaglandin production (PGE, and PGF,,). The response to the enteropharyngeal organisms, however, would depend on the bacterial toxin composition of the particular organism. Bacterial toxins or lipoteichoic acid have been shown to act on uterine decidua to cause increased formation of cytokines (Casey et al. 1989; Romero et al. 1989). Cachetin/tumour necrosis factor-a ;TNF-a) is synthesized and secreted by human decidual cells in response to lipoteichoic acid and may also cause an increase in PGF,, production. In addition, in amnion cells in monolayer culture, TNF-a, has been shown to stimulate PGE, formation (Casey et al. 1989). Therefore, both PGF,, and PGE, may be released in response to a bacterial challenge. PGF,, is known primarily to stimulate myometrial activity, whilst the main effect of PGE, is to change the physical properties of the cervix by an alteration in its composition. Depending on the effect of the infecting organism on the decidua, varying quantities of both PGF,, and PGE, would be released. Where there is a predominance of PGF?, contractions would be stimulated, but as long as there was no change in the state of the cervix, labour would not progress (OIBh & Gee 1992). This may explain the association of U. urealyticum with preterm labour and the lack of an association with preterm delivery (Minkoff et al. 1984). However, if the release of PGE, predominates, then cervical change is possible, and in such cases little myometrial activity is required to effect delivery. Therefore, where cervical change is significant, delivery is inevitable ( O M & Gee 1992). It is with such cases that an impact will be made in the prevention of preterm delivery if correct identification of at-risk pregnancies can be made. A more comprehensive understanding of the complex biomolecular events that lead to the formation of the prostaglandins, and their relative production in response to various micro-organisms may lead to a better understanding of the pathophysiology of idiopathic preterm labour and delivery. Further studies on the infective aetiology of idiopathic preterm labour are required. Karl S. Olah Clinical Research Fellow
Harry Gee Senior Lecturer Department of Fetal Medicine Birmingham University Birmingham Maternity Hospital Edghaston Birmingham B15 2TG
References Casey M. L., Cox S. M., Beutler B., Milewich L. & McDonald P. C. (1989) Cachetin/tumor necrosis factor-A formation in human decidua. J Clin Invest 83.430436.
McDonald H. M., O’Loughlin J. A., Jolley P., Vigneswaran R., McDonald P. J. &McDonald P. J. (1992) Prenatal microbiological risk factors associated with preterm birth. Br J Ohstet Gynaecol 99, 190-196. Minkoff H., Grunebaum A. N., Schwartz R. H. et al. (1984) Risk factors for prematurity and premature rupture of membranes. A prospective study of the vaginal floral in pregnancy. Am J Ohstet Gynecol 150,965-972. Ollh K. S. &Gee H. (1992) The prevention of preterm deliverydan we afford to continue to ignore the cervix? (Commentary) Br J Ohstet Gynaecol99,278-280. Romero R., Brody T., Oyarzun E., Mazor M., King Wu Y., Hobbins J. C. & Durum S. K. (1989) Infection and labour. 111. Interleukin-I: A signal for the onset of parturition. Am J Ohstet Gynecol 160, 11 17-1 123. Saling E. (1991) Effective measures for prevention of late abortions and early premature births. J Perinat Med 19 (supplement 2), 10.
The implications of introducing the symphysealfundal height-measurement. A prospective randomized controlled trial Dear Sir, There is a serious weakness in most of the research on symphysisfundus height measurements and the paper by Lindhard et al. (1990) illustrates this very well. How can you test a method’s validity if it is not given the opportunity to show its full potential? In this paper only three S-F measurements were taken during the whole pregnancy and in 21% only one or two. With so few measurements it is not worth doing it at all! The Oxford Clinical Trial Data Base Editor’s conclusion regarding this paper was ‘It would seem unwise to abandon the use of symphysis fundal height measurement unless a much larger trial likewise suggests that it is unhelpful’. Galbraith et al. (1979) commented ‘The clinical prediction of IUGR in . . . low risk patients is heavily dependent on the serial measurement of fundal height in order to demonstrate plateauing or static fetal growth’. At this hospital SF measurements have been used on every pregnant woman at every antenatal visit since 1976. Our original method was rather rough but, since 1981, we have used the method described by Westin (1977). Since 1984, the method has also been used nationally in all government antenatal clinics. Perinatal mortality covering about 8000 deliveries at Ramotswa has fallen to a record low level of 18/1000 at a time when the perinatal mortality rate at most district hospitals in Africa is at least 30/1000 and often as much as 60/1000. What is most noteworthy about these figures is that since 1981, the stillbirth and neonatal death rate had been consistently low although the figure elsewhere is in the region of 2.5 to 3. Of the only two stillbirths which occurred after admission to hospital last year, both showed clear failure of fetal growth on their flat S-F graphs. The problem was not whether the graph indicated fekd growth impairment or not but when was the best moment to intervene? Both babies died inutero suddenly and unexpectedly, and we clearly waited far too long. Those who have never used the graph regularly in woman after woman throughout pregnancy are not in any position to make useful comments on its value, even after elegant research and apparently significant statistics. None of the doctors who have worked here and who
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