19
Inr J Gynecol Obstet, 1992, 38: 19-24 International Federation of Gynecology and Obstetrics
Adjunctive antibiotic treatment of women with preterm rupture of membranes or preterm labor J.F. McCaul, KG. Perry, Jr., J.L. Moore, J.C. Morrison Department
of Obstetrics
and Gynecology,
University of Mississippi
Jr., R.W. Martin,
E.T. Bucovaz
and
Medical Center, Jackson, MS (USA)
(Received September 3rd, 1991) (Revised and accepted October 22nd, 1991)
Abstract
Introduction
Subclinical infection is associated with preterm rupture of the membranes (PROM) and preterm labor (PTL) in many cases. It was hypothesized that antibiotic treatment might delay delivery and/or decrease infectious morbidity in those with PROM or PTL. Patients from I9 to 34 weeks with PROM and no labor or PTL with intact membranes (but not both) were separately randomized to receive ampicillin versus placebo in addition to usual therapy. There were 36 women with PTL (21 ampicillin/l5 placebo) and 84 with preterm PROM (41 ampicillini43 placebo). Demographically, the treatment and placebo groups were similar. Outcome variables analyzed included delivery delay after treatment, maternal chorioamnionitis/endometritis, Apgar score, neonatal infection, or respiratory distress, and hospital stay. There were no significant dif ferences between the ampicillin and placebo groups in those with PTL or preterm PROM as it concerned outcome parameters. Adjunctive ampicillin usedfor treatment of idiopathic PTL or preterm PROM was not beneficial in this study.
Preterm birth affects 8-10% of all newborns and as many as 15-20% may die in the first month of life [4]. As many as 20% of the early deliveries are indicated because of obstetric and medical factors necessitating early birth [lo]. Another 40-50% appear to be due to idiopathic preterm labor (PTL) which has most recently been related to infection [8]. Finally, the remaining 30-40% are related to preterm rupture of the membranes (PROM), which may be related to subclinical infection [3,12]. Although there is substantial evidence that infections play a major role in preterm birth, there is a paucity of well defined studies assessing the effectiveness of prophylactic antibiotic treatment in patients with preterm PROM or PTL [7]. Most commonly, studies involving patients with PTL have selected either ampicillin, erythromycin, or clindamycin as supportive treatment for those with idiopathic PTL [6-l 11. Of these investigations, two demonstrated a positive effect with such treatment but the studies either had a small number of patients in each group or received other drugs such as tocolytics or steroids as concomitant treatment [6,10]. The other authors found that the early delivery rate or birthweight was not favorably affected by such treatment ]5,111.
Keywords
Preterm branes; Antibiotics.
labor;
Ruptured
mem-
0020-7292/92/$05.00 0 1992 International Federation of Gynecology and Obstetrics Printed and Published in Ireland
Article
The issue is even more complex when one assays studies involving antibiotic treatment in women with preterm PROM. In these studies, ampicillin or various cephalosporins have been utilized by several authors in an effort to prolong the latency period from rupture to delivery and to reduce the incidence of maternal/neonatal infection [ 1,2,9]. These studies likewise are plagued with small numbers [1,2] or with concominant treatments [9], which make interpretation of the data difficult. In addition, studies involving both preterm PROM and PTL are further compromised by the inability to sort out the meaning of conflicting culture results; as in some studies a positive culture dictated delivery whereas in others, clinical signs of infection alone indicated termination of the study. The purpose of the current study was to assess the ability of a broad spectrum antibiotic (versus placebo) to prolong pregnancy and/or reduce the incidence of clinical infection in patients with preterm PROM but not in labor or in those with idiopathic PTL with intact membranes when studied longitudinally. Materials and methods Over a 16-month period, patients with preterm PROM or idiopathic PTL were offered enrollment in this study which was approved by the Institutional Review Board. During this time period 195 patients with PTL and 172 women with preterm PROM were available for inclusion. Preterm labor was defined as recurrent, persistent uterine contractions (usually > 12/h) with concominant cervical dilatation > 1 cm (but ~4 cm) or cervical change from a previous examination. Preterm PROM was documented by maternal history and visualization of fluid flowing from the cervical OS and/or by arborization of amniotic fluid on a slide mount (fern test). Inclusion criteria also included 14-45 years of age and > 18 weeks but I 33 weeks gestation (confirmed by dates and/or ultrasound). All
patients signed informed consent forms prior to enrollment. Prior to enrollment, during screening, patients were excluded if they had known reasons for early labor or rupture of the membranes (multiple gestation, urinary tract infection, nonvertex presentation, uterine anomalies, etc.). In the PROM group, women were also excluded if the cervix was more than 2 cm dilated or obvious intrauterine infection was present (by speculum or amniocentesis, respectively). In the PTL group, membranes were intact. Patients in both groups were cultured for group B streptococcus and for Neisseria gonorrhoeae (cervix). If the results were positive they were treated and removed from the study. Obstetric conditions such as fetal distress, abruptio placenta, cord prolapse, which could bias study outcome, were eliminated from the study. Finally, all patients with a history of penicillin allergy were likewise not candidates for the study. At enrollment the pharmacy was notified that a study candidate with either preterm PROM (n = 112) or idiopathic PTL (n = 75) was available for randomization. Pharmacy personnel consulted the appropriate randomization schedule (one for preterm PROM, one for PTL) which had been generated from a random number table. It is important to emphasize that patients were randomized to one of two groups (preterm PROM or PTL) rather than stratifying the subjects into two groups after randomization. They sent to the labor and delivery area an infusion set that contained either 2 g of ampicillin or a placebo (which appeared similar to the ampicillin). This was infused over a 4-h period. The pharmacy likewise, in the same patient, sent 28 capsules which either contained 500 mg of ampicillin or a placebo. The placebo and ampicillin capsules were similar in appearance. The patients took medication four times per day and usually completed the entire course while in hospital. If they were discharged prior to finishing the 7 days of therapy, they were issued the remaining capsules to con-
Antihiotks
tinue 4 times per day at home. On the first prenatal visit after their discharge, the bottle was returned by the patient and assessed by the pharmacy to ensure all of the capsules had been taken. The standard treatment regimen for patients in PTL included intravenous magnesium sulfate until uterine quiescence was obtained followed by oral magnesium gluconate for 3-7 days and then discharge on oral medication (2 g every 4 h). For patients with preterm PROM, clinical care included assessment of fluid level by ultrasound and observation for signs of amnionitis (CBC, temperature, uterine tenderness, labor). Patients were managed with bedrest the first 2 days and then limited activity (bathroom privileges) for 3-7 days. Subjects in both groups were monitored for uterine activity by palpation and tocodynamometry. If Iabor did not develop, most patients were discharged by 7 days. Patients in both groups were followed in the Obstetric Complication Clinic on a weekly basis. The group with PTL received pelvic examinations each week while the group with preterm PROM received visual examination of the cervix using a sterile speculum. In each group, demographic data were collected as were outcome statistics. These included the interval from treatment to delivery, the number of subjects with chorioamnionitis, birthweight, and infant parameters such as neonatal sepsis, respiratory distress syndrome, and the number of hospital days.
do 11of v[fw/
prcrrrr~~ lohor
Statistical analysis was performed using the Student’s t-test, chi-square analysis and analysis of variance, where indicated. Differences were considered significant if the P value was 1000 patients in each group would be needed to reveal a potential difference in favor of
Preterm labor with intact membranes: outcome statistics.
Group
No. of patients
Antibiotic Placebo
21 19
Treatment to delivery interval
Chorioamnionitis
Birthweight (g)
Respiratory distress syndrome
Neonatal sepsis
Neonatal hospital days
0 1
2403.3 zt 850.3 2462.6 f 617.5
0 1
1 1
27.7~ 161.3 24.4 f 52.6
(days)
B~SD.
35.2 f 29.6a 34.7 f 21.1
A~!/ihio/ic~
antibiotic treatment. Therefore, it does not appear that such treatment has a salutary effect in either group of patients. Specifically patients with idiopathic PTL in our study offer similar results to those of Newton et al. [I 11. In a group of women between 24 and 34 weeks who received intravenous ampicillin plus oral erythromycin, the frequency of preterm births, time to delivery, birthweight and episodes of recurrent labor were not different from the placebo group. While McCormack et al. found erythromycin treatment of women in preterm labor (if they were colonized with Ureuplusma ureulyticum, A4yopZusmu hominis, or both) to be effective in lowering the low birthweight rate, erythromycin had to be begun in the third trimester I51. McGregor et al. [6] used only erythromycin in treating 58 women with this drug or with placebo. He found that among women I 1 cm at the initiation of treatment of PTL, the mean time to delivery was 32.5 days with antibiotic versus only 22.4 days with placebo (P = 0.027). This allowed more women in the erythromycin treated group to deliver at term versus those who received placebo (P = 0.035). Morales likewise revealed a benefit to antibiotic treatment because it extended the treatment to delivery interval from 17 days in the placebo group to 30 days in the antibiotic group. In this study, patients were managed with steroid administration and subjects who had positive fluid cultures in the antibiotic group were less likely to receive benefit when these patients were separately stratified. These investigations did not use antibiotic combination treatment (infusion/oral administration) and/or had confounding variables (steroids) in the study population. Among those with preterm PROM and no uterine activity, Morales et al. [9] revealed that the ampicillin treated patients had less clinical chorioamnionitis (4% versus 26%) and less neonatal sepsis (5% versus 10%). Interestingly they found this reduction in infectious morbidity was noted only in that portion of the study population (approximately
do r~oi c//w/
/nx’lr~~r ltrhor
23
one-fourth) who were colonized with group B streptococcus. Unfortunately, subjects were frequently treated with drugs which were confounding variables such as steroids or tocolytic agents. Fortunato et al. [2] found a considerable increase in the latency period from rupture of the membranes to delivery if a cephalosporin or ampicillin were utilized versus a control group which was given no antibiotic treatment. There was, however, no significant difference in postpartum infections between the two groups. He did not find any differences between ceftizozime versus cefoxitin, cefazolin or ampicillin as all were used in the study and increased the latency period. However, the data in the current investigation agree with those of Amon et al. [l] who studied 82 patients receiving either ampicillin or no medication. There was no significant difference in the duration of membrane rupture to delivery interval, gestational age at birth, or postpartum infection. They did show, however, that the risk of early delivery (< 12 h) was lower in the patients receiving prophylactic ampicillin as was the rate of neonatal infection (P = 0.04) [I]. The question of whether idiopathic preterm labor and preterm rupture of the membranes are caused by subclinical infection remains unanswered. Clearly several of the studies in the literature appear to support the use of antibiotics in such women as a method of suppressing the infectious morbidity and thus increasing the interval to delivery. In the current study, we could not prove this hypothesis. It is possible that small numbers hindered our ability to assess a change in outcome parameters. On the other hand, it is also possible that other studies finding benefit are swayed by multiple confounding variables having little to do with the microbacteriologic flora. Finally, the microbacteriologic flora of our patients may be different than those in other studies published in the literature. However, our study design eliminated those with infection at the time of entry and speaks against this explanation for the difference between the current study and others in the
24
Md’ird
CI trl.
literature. In conclusion, in our population the use of the broad spectrum antibiotic ampicillin is not associated with prologation of pregnancy, and did not offer benefit to the mother or infant. Perhaps a larger trial with different antibiotics might prove fruitful. Acknowledgment Supported in part by the Vicksburg Hospital Medical Foundation References Amon E, Lewis SV, Sibai BM, Villar MA, Arheart KL: Ampicillin prophylaxis in preterm premature rupture of the membranes: A prospective randomized study. Am J Obstet Gynecol 159: 539, 1988. Fortunato SJ, Welt SI, Eggleston M, Cole J, Bryant EC, Dodson MG: Prolongation of the latency period in preterm premature rupture of the membranes using prophylactic antibiotics and tocolysis. J Perinatol IO: 252, 1990. Gravett MG, Hummel D, Eschenbach DA, Holmes KK: Preterm labor associated with subclinical amniotic fluid infection and with bacterial vaginosis. Obstet Gynecol67: 229, 1986. Institute of Medicine: Preventing Low Birthweight. National Academy Press, Washington, DC, 1985. McCormack WM, Rosner B, Lee YH, Munoz A, Charles D, Kass EH: Effect on birth weight of erythromycin treatment of pregnant women. Obstet Gynecol69: 202, 1987.
6
McGregor JA, French JI, Reller LB, Todd JK, Makowski EL: Adjunctive erythromycin treatment for idiopathic preterm labor: results of a randomized, double-blinded, placebo-controlled trial. Am J Obstet Gynecol 154: 98, 1986. 7 McGregor JA, French JI, Richter R, France-Buff A, Johnson A, Hillier S, Judson FN, Todd JK: Antenatal microbiologic and maternal risk factors associated with prematurity. Am J Obstet Gynecol 163: 1465, 1990. 8 Minkoff I-I Prematurity: Infection as an etiologic factor. Obstet Gynecol 62: 137, 1983. 9 Morales WJ, Angel JL, O’Brien WF, Knuppel RA: Use. of ampicillin and corticosteroids in premature rupture of membranes: a randomized study. Obstet Gynecol73: 721, 1989. 10 Morales NJ, Angel JL, O’Brien WF, Knuppel RA, Finazzo M: A randomized study of antibiotic therapy in idiopathic preterm labor. dbstet Gynecol 72: 829, 1988. 11 Newton ER, Dinsmoor MJ, Gibbs RS: A randomized, blinded, placebo-controlled trial of antibiotics in idiopathic preterm labor. Obstet Gynecol 74: 562, 1989. 12 Sbarra AJ, Thomas GB, Cetrulo CL, Shakr C, Chaudhury A, Paul B: Effect of bacterial growth on the bursting pressure of fetal membranes in vitro. Obstet Gynecol 70: 107, 1987.
Address for reprints:
J.C.
Morrison
Department
of Obstetrics
and Gynecology
University of Mississippi Medical 2500 North State Street Jackson,
MS 39216405,
USA
Center
Inr J Gynecol Obstet, 1992, 38: 19-24 International Federation of Gynecology and Obstetrics
Adjunctive antibiotic treatment of women with preterm rupture of membranes or preterm labor J.F. McCaul, KG. Perry, Jr., J.L. Moore, J.C. Morrison Department
of Obstetrics
and Gynecology,
University of Mississippi
Jr., R.W. Martin,
E.T. Bucovaz
and
Medical Center, Jackson, MS (USA)
(Received September 3rd, 1991) (Revised and accepted October 22nd, 1991)
Abstract
Introduction
Subclinical infection is associated with preterm rupture of the membranes (PROM) and preterm labor (PTL) in many cases. It was hypothesized that antibiotic treatment might delay delivery and/or decrease infectious morbidity in those with PROM or PTL. Patients from I9 to 34 weeks with PROM and no labor or PTL with intact membranes (but not both) were separately randomized to receive ampicillin versus placebo in addition to usual therapy. There were 36 women with PTL (21 ampicillin/l5 placebo) and 84 with preterm PROM (41 ampicillini43 placebo). Demographically, the treatment and placebo groups were similar. Outcome variables analyzed included delivery delay after treatment, maternal chorioamnionitis/endometritis, Apgar score, neonatal infection, or respiratory distress, and hospital stay. There were no significant dif ferences between the ampicillin and placebo groups in those with PTL or preterm PROM as it concerned outcome parameters. Adjunctive ampicillin usedfor treatment of idiopathic PTL or preterm PROM was not beneficial in this study.
Preterm birth affects 8-10% of all newborns and as many as 15-20% may die in the first month of life [4]. As many as 20% of the early deliveries are indicated because of obstetric and medical factors necessitating early birth [lo]. Another 40-50% appear to be due to idiopathic preterm labor (PTL) which has most recently been related to infection [8]. Finally, the remaining 30-40% are related to preterm rupture of the membranes (PROM), which may be related to subclinical infection [3,12]. Although there is substantial evidence that infections play a major role in preterm birth, there is a paucity of well defined studies assessing the effectiveness of prophylactic antibiotic treatment in patients with preterm PROM or PTL [7]. Most commonly, studies involving patients with PTL have selected either ampicillin, erythromycin, or clindamycin as supportive treatment for those with idiopathic PTL [6-l 11. Of these investigations, two demonstrated a positive effect with such treatment but the studies either had a small number of patients in each group or received other drugs such as tocolytics or steroids as concomitant treatment [6,10]. The other authors found that the early delivery rate or birthweight was not favorably affected by such treatment ]5,111.
Keywords
Preterm branes; Antibiotics.
labor;
Ruptured
mem-
0020-7292/92/$05.00 0 1992 International Federation of Gynecology and Obstetrics Printed and Published in Ireland
Article
The issue is even more complex when one assays studies involving antibiotic treatment in women with preterm PROM. In these studies, ampicillin or various cephalosporins have been utilized by several authors in an effort to prolong the latency period from rupture to delivery and to reduce the incidence of maternal/neonatal infection [ 1,2,9]. These studies likewise are plagued with small numbers [1,2] or with concominant treatments [9], which make interpretation of the data difficult. In addition, studies involving both preterm PROM and PTL are further compromised by the inability to sort out the meaning of conflicting culture results; as in some studies a positive culture dictated delivery whereas in others, clinical signs of infection alone indicated termination of the study. The purpose of the current study was to assess the ability of a broad spectrum antibiotic (versus placebo) to prolong pregnancy and/or reduce the incidence of clinical infection in patients with preterm PROM but not in labor or in those with idiopathic PTL with intact membranes when studied longitudinally. Materials and methods Over a 16-month period, patients with preterm PROM or idiopathic PTL were offered enrollment in this study which was approved by the Institutional Review Board. During this time period 195 patients with PTL and 172 women with preterm PROM were available for inclusion. Preterm labor was defined as recurrent, persistent uterine contractions (usually > 12/h) with concominant cervical dilatation > 1 cm (but ~4 cm) or cervical change from a previous examination. Preterm PROM was documented by maternal history and visualization of fluid flowing from the cervical OS and/or by arborization of amniotic fluid on a slide mount (fern test). Inclusion criteria also included 14-45 years of age and > 18 weeks but I 33 weeks gestation (confirmed by dates and/or ultrasound). All
patients signed informed consent forms prior to enrollment. Prior to enrollment, during screening, patients were excluded if they had known reasons for early labor or rupture of the membranes (multiple gestation, urinary tract infection, nonvertex presentation, uterine anomalies, etc.). In the PROM group, women were also excluded if the cervix was more than 2 cm dilated or obvious intrauterine infection was present (by speculum or amniocentesis, respectively). In the PTL group, membranes were intact. Patients in both groups were cultured for group B streptococcus and for Neisseria gonorrhoeae (cervix). If the results were positive they were treated and removed from the study. Obstetric conditions such as fetal distress, abruptio placenta, cord prolapse, which could bias study outcome, were eliminated from the study. Finally, all patients with a history of penicillin allergy were likewise not candidates for the study. At enrollment the pharmacy was notified that a study candidate with either preterm PROM (n = 112) or idiopathic PTL (n = 75) was available for randomization. Pharmacy personnel consulted the appropriate randomization schedule (one for preterm PROM, one for PTL) which had been generated from a random number table. It is important to emphasize that patients were randomized to one of two groups (preterm PROM or PTL) rather than stratifying the subjects into two groups after randomization. They sent to the labor and delivery area an infusion set that contained either 2 g of ampicillin or a placebo (which appeared similar to the ampicillin). This was infused over a 4-h period. The pharmacy likewise, in the same patient, sent 28 capsules which either contained 500 mg of ampicillin or a placebo. The placebo and ampicillin capsules were similar in appearance. The patients took medication four times per day and usually completed the entire course while in hospital. If they were discharged prior to finishing the 7 days of therapy, they were issued the remaining capsules to con-
Antihiotks
tinue 4 times per day at home. On the first prenatal visit after their discharge, the bottle was returned by the patient and assessed by the pharmacy to ensure all of the capsules had been taken. The standard treatment regimen for patients in PTL included intravenous magnesium sulfate until uterine quiescence was obtained followed by oral magnesium gluconate for 3-7 days and then discharge on oral medication (2 g every 4 h). For patients with preterm PROM, clinical care included assessment of fluid level by ultrasound and observation for signs of amnionitis (CBC, temperature, uterine tenderness, labor). Patients were managed with bedrest the first 2 days and then limited activity (bathroom privileges) for 3-7 days. Subjects in both groups were monitored for uterine activity by palpation and tocodynamometry. If Iabor did not develop, most patients were discharged by 7 days. Patients in both groups were followed in the Obstetric Complication Clinic on a weekly basis. The group with PTL received pelvic examinations each week while the group with preterm PROM received visual examination of the cervix using a sterile speculum. In each group, demographic data were collected as were outcome statistics. These included the interval from treatment to delivery, the number of subjects with chorioamnionitis, birthweight, and infant parameters such as neonatal sepsis, respiratory distress syndrome, and the number of hospital days.
do 11of v[fw/
prcrrrr~~ lohor
Statistical analysis was performed using the Student’s t-test, chi-square analysis and analysis of variance, where indicated. Differences were considered significant if the P value was 1000 patients in each group would be needed to reveal a potential difference in favor of
Preterm labor with intact membranes: outcome statistics.
Group
No. of patients
Antibiotic Placebo
21 19
Treatment to delivery interval
Chorioamnionitis
Birthweight (g)
Respiratory distress syndrome
Neonatal sepsis
Neonatal hospital days
0 1
2403.3 zt 850.3 2462.6 f 617.5
0 1
1 1
27.7~ 161.3 24.4 f 52.6
(days)
B~SD.
35.2 f 29.6a 34.7 f 21.1
A~!/ihio/ic~
antibiotic treatment. Therefore, it does not appear that such treatment has a salutary effect in either group of patients. Specifically patients with idiopathic PTL in our study offer similar results to those of Newton et al. [I 11. In a group of women between 24 and 34 weeks who received intravenous ampicillin plus oral erythromycin, the frequency of preterm births, time to delivery, birthweight and episodes of recurrent labor were not different from the placebo group. While McCormack et al. found erythromycin treatment of women in preterm labor (if they were colonized with Ureuplusma ureulyticum, A4yopZusmu hominis, or both) to be effective in lowering the low birthweight rate, erythromycin had to be begun in the third trimester I51. McGregor et al. [6] used only erythromycin in treating 58 women with this drug or with placebo. He found that among women I 1 cm at the initiation of treatment of PTL, the mean time to delivery was 32.5 days with antibiotic versus only 22.4 days with placebo (P = 0.027). This allowed more women in the erythromycin treated group to deliver at term versus those who received placebo (P = 0.035). Morales likewise revealed a benefit to antibiotic treatment because it extended the treatment to delivery interval from 17 days in the placebo group to 30 days in the antibiotic group. In this study, patients were managed with steroid administration and subjects who had positive fluid cultures in the antibiotic group were less likely to receive benefit when these patients were separately stratified. These investigations did not use antibiotic combination treatment (infusion/oral administration) and/or had confounding variables (steroids) in the study population. Among those with preterm PROM and no uterine activity, Morales et al. [9] revealed that the ampicillin treated patients had less clinical chorioamnionitis (4% versus 26%) and less neonatal sepsis (5% versus 10%). Interestingly they found this reduction in infectious morbidity was noted only in that portion of the study population (approximately
do r~oi c//w/
/nx’lr~~r ltrhor
23
one-fourth) who were colonized with group B streptococcus. Unfortunately, subjects were frequently treated with drugs which were confounding variables such as steroids or tocolytic agents. Fortunato et al. [2] found a considerable increase in the latency period from rupture of the membranes to delivery if a cephalosporin or ampicillin were utilized versus a control group which was given no antibiotic treatment. There was, however, no significant difference in postpartum infections between the two groups. He did not find any differences between ceftizozime versus cefoxitin, cefazolin or ampicillin as all were used in the study and increased the latency period. However, the data in the current investigation agree with those of Amon et al. [l] who studied 82 patients receiving either ampicillin or no medication. There was no significant difference in the duration of membrane rupture to delivery interval, gestational age at birth, or postpartum infection. They did show, however, that the risk of early delivery (< 12 h) was lower in the patients receiving prophylactic ampicillin as was the rate of neonatal infection (P = 0.04) [I]. The question of whether idiopathic preterm labor and preterm rupture of the membranes are caused by subclinical infection remains unanswered. Clearly several of the studies in the literature appear to support the use of antibiotics in such women as a method of suppressing the infectious morbidity and thus increasing the interval to delivery. In the current study, we could not prove this hypothesis. It is possible that small numbers hindered our ability to assess a change in outcome parameters. On the other hand, it is also possible that other studies finding benefit are swayed by multiple confounding variables having little to do with the microbacteriologic flora. Finally, the microbacteriologic flora of our patients may be different than those in other studies published in the literature. However, our study design eliminated those with infection at the time of entry and speaks against this explanation for the difference between the current study and others in the
24
Md’ird
CI trl.
literature. In conclusion, in our population the use of the broad spectrum antibiotic ampicillin is not associated with prologation of pregnancy, and did not offer benefit to the mother or infant. Perhaps a larger trial with different antibiotics might prove fruitful. Acknowledgment Supported in part by the Vicksburg Hospital Medical Foundation References Amon E, Lewis SV, Sibai BM, Villar MA, Arheart KL: Ampicillin prophylaxis in preterm premature rupture of the membranes: A prospective randomized study. Am J Obstet Gynecol 159: 539, 1988. Fortunato SJ, Welt SI, Eggleston M, Cole J, Bryant EC, Dodson MG: Prolongation of the latency period in preterm premature rupture of the membranes using prophylactic antibiotics and tocolysis. J Perinatol IO: 252, 1990. Gravett MG, Hummel D, Eschenbach DA, Holmes KK: Preterm labor associated with subclinical amniotic fluid infection and with bacterial vaginosis. Obstet Gynecol67: 229, 1986. Institute of Medicine: Preventing Low Birthweight. National Academy Press, Washington, DC, 1985. McCormack WM, Rosner B, Lee YH, Munoz A, Charles D, Kass EH: Effect on birth weight of erythromycin treatment of pregnant women. Obstet Gynecol69: 202, 1987.
6
McGregor JA, French JI, Reller LB, Todd JK, Makowski EL: Adjunctive erythromycin treatment for idiopathic preterm labor: results of a randomized, double-blinded, placebo-controlled trial. Am J Obstet Gynecol 154: 98, 1986. 7 McGregor JA, French JI, Richter R, France-Buff A, Johnson A, Hillier S, Judson FN, Todd JK: Antenatal microbiologic and maternal risk factors associated with prematurity. Am J Obstet Gynecol 163: 1465, 1990. 8 Minkoff I-I Prematurity: Infection as an etiologic factor. Obstet Gynecol 62: 137, 1983. 9 Morales WJ, Angel JL, O’Brien WF, Knuppel RA: Use. of ampicillin and corticosteroids in premature rupture of membranes: a randomized study. Obstet Gynecol73: 721, 1989. 10 Morales NJ, Angel JL, O’Brien WF, Knuppel RA, Finazzo M: A randomized study of antibiotic therapy in idiopathic preterm labor. dbstet Gynecol 72: 829, 1988. 11 Newton ER, Dinsmoor MJ, Gibbs RS: A randomized, blinded, placebo-controlled trial of antibiotics in idiopathic preterm labor. Obstet Gynecol 74: 562, 1989. 12 Sbarra AJ, Thomas GB, Cetrulo CL, Shakr C, Chaudhury A, Paul B: Effect of bacterial growth on the bursting pressure of fetal membranes in vitro. Obstet Gynecol 70: 107, 1987.
Address for reprints:
J.C.
Morrison
Department
of Obstetrics
and Gynecology
University of Mississippi Medical 2500 North State Street Jackson,
MS 39216405,
USA
Center
