Miscarriages Associated with Group B Strep

CAPSULE

Women presenting with recurrent pregnancy losses and positive genital tract cultures for Group B Streptococcus infection were successfully managed with pre and post-conceptional antibiotic therapy.  An infectious etiology of these miscarriages is suggested.

ABSTRACT

OBJECTIVE: To offer antibiotics as a valued treatment option for patients with group B streptococcus colonization and recurring first trimester pregnancy losses.

DESIGN: Case reports.

SETTING: Private infertility clinic with New York State licensed microbiology laboratory.

PATIENTS: Six couples who visited The MacLeod Laboratory for the evaluation of recurring first trimester miscarriages during an eighteen months period.

INTERVENTION: All couples underwent routine fertility evaluation and detailed bacteria testing of seminal fluid, cervix and endometrial samples. Based on culture results, all couples received antibiotics as the only fertility therapy. After the next pregnancy was achieved all the wives were retreated with intravenous Ampicillin.

RESULTS: All six women revealed positive post - conceptional cervical culture for group B streptococcus. Following a post conceptional IV Ampicillin therapy only two patients remained culture positive during the second trimester and were treated with additional oral Penicillin for the remainder of pregnancy. All six women experienced term deliveries.

CONCLUSIONS: It appears that in addition to causing infectious complications and pregnancy loss during the second and third trimester, group B streptococcus is also associated with first trimester pregnancy losses. We also suggest revising the recommended dose of antibiotics in this group of patients.

INTRODUCTION

Group B streptococcus is readily recovered from human sources, both in symptomatic and asymptomatic conditions, most notably from the vaginal canal in postpartum women suffering from endometritis (1,2).  The bacterium is known to be one of the chief causes of neonatal sepsis and meningitis (3) Recently group B streptococcus infection has been reported in association with preterm delivery (4), suspected as one of the major causes of still birth (5) and as the key pathogen in asymptomatic intrauterine infections associated with spontaneous mid-trimester abortions (6).  During the past few years, we observed certain patients with histories of multiple first trimester miscarriages and heavy cervical and endometrial colonization with group B streptococcus.  Since some patients, in addition, have experienced adverse pregnancy outcomes identical to those associated with group B streptococcus, without finding any other cause for the pregnancy losses, we elected to use antibiotics as the single therapeutic regimen in this group of patients.

 CASE REPORTS

Between June of 1999 and December of 2000 six couples were evaluated at our center for recurring adverse pregnancy outcomes and positive group B streptococcus isolates from genital secretions.  They ranged in age from 29 to 37 and except for one (Patient 1) all suffered from secondary infertility of two to five years’ duration. Patient 6 was an only child, the others all had siblings with live children.  Detailed histories did not reveal autoimmune disease, arthritis, Raynaud’s phenomenon or thyroid condition in any of the couples.  A search for genetically abnormal offspring in any of the close or distant relatives was negative.  Patients 4 and 6 underwent complete genetic testing with negative results.  Patient 1 underwent a complex immunological evaluation and during a failed pregnancy, prednisone, aspirin and heparin were administered to counteract elevated killer cells. All five patients who had suffered from secondary infertility had received multiple courses of clomiphene citrate and four patients, at least during two cycles, received Pergonal stimulation.  One patient underwent a failed IVF cycle.

Our evaluation, to determine the cause of the recurrent abortions, included testing for the following conditions: structural abnormalities were ruled out on all patients by hysterosalpingography.  In addition, three patients had hysteroscopy and laparoscopy with negative findings.  On cycle day three of the cycle all patients underwent FSH, LH and Estradiol testing and a mid luteal phase endometrial biopsy and serum Progesterone determination was performed to rule out luteal phase defect.  The results of these tests were all within the normal range. All husbands had normal semen analyses.  Seminal fluid, vaginal, cervical and endometrial biopsy specimens were cultured for Mycoplasma, aerobic, anaerobic bacteria and yeast.  Syva Micro-Tract system was used to identify Chlamydia trachomatis elementary bodies.  Table 1 summarizes the clinical features of these patients, the culture findings, the therapy administered and the clinical outcome.

The finding of group B streptococcus in cervical/endometrial specimens was thecommon factor among all the women.  The seminal fluid of three husbands, patients 1, 2 and 5 exhibited the organism at the time of the first testing.  The results of the microbiological studies and the subsequently administered antibiotic regimens are also listed in Table 1.  No further therapeutic recommendations were made.  Two to four months following the completion of the antibiotic therapy all six patients reported spontaneous pregnancies.  Within ten days of the missed period, cervical specimens were tested and found to be positive for group B streptococcus in all six patients.  Intravenous ampicillin therapy was initiated immediately on all patients, 6 grams daily on five, while patient 2 received 2 grams daily for ten days duration.  A follow up cervical culture between the 20th and 24th week of gestation remained positive for patients 1 and 2.  These patients were prescribed Pen VK 250 mgs daily intermittently for the remainder of the pregnancy.  The total length of this oral therapy for both patients was six weeks.  Because of her previous history of a mid trimester pregnancy loss, patient 1 underwent a Shirodkar procedure, with removal at 38 wks followed by spontaneous rupture of membranes and a normal vaginal delivery. All the other pregnancies were managed expectantly and delivered at term.  Patient 4 was delivered by elective repeat Cesarean section at 39 weeks.

DISCUSSION

Factors determining the implantation of an intrauterine pregnancy, the course of the pregnancy, events surrounding the delivery and maternal and fetal complications during or after delivery are largely unknown.  There is, however, a growing body of evidence showing that bacterial colonization of the genital tract is a significant factor in certain instances of pregnancy loss and premature rupture of membranes followed by premature delivery with maternal and fetal infectious complications.  We presented the case histories of six patients who all suffered from a variety of pregnancy-related complications, including first trimester pregnancy losses.  The common feature in all the patients was a group B streptococcal genital tract infection that persisted despite an initial comprehensive antibiotic therapy.  Though all patients achieved spontaneous pregnancy within four months of the therapy, postconceptionally, group B streptococcus was isolated from the cervical culture of all patients and, in two, the colonization persisted even after the administration of ten additional days of intravenous ampicillin therapy.  Recently, antibiotic resistance became a major concern in treating third trimester group B streptococcal infections (7).  We are unaware of studies linking antibiotic resistance with pathogenicity, though prophylactic antibiotic therapy is advocated for recurring second trimester group B streptococcus chorioamnionitis (8).  We suggest that asymptomatic infection with group B streptococcus can affect the course of the pregnancy in any trimester and a first trimester pregnancy loss can be an early manifestation of the infection.  Since asymptomatic group B streptococcus carrier rate in the general population can vary as much as 5 to 40% (2), there are no firm guidelines for the eradication or suppression of this organism. Though the ideal dose of antibiotics and the length of therapy are still debated, the benefit of prophylactic ampicillin or penicillin during the third trimester is well documented in the literature (9, 10).  Since the only common variable distinguishing our studied patients was the persisting group B streptococcal infection, we chose a length of therapy and a dose of antibiotics well beyond the questionable effectiveness.  The persistence of group B streptococcus in two of our treated patients however makes us wonder if any reasonable dose could be recommended for the purpose of routine eradication of this organism.  The successful pregnancy outcome in these patients seems to suggest suppression therapy as a viable alternative.

TABLE 1

 

REFERENCES

1. Gordon JS, Sbarra AJ. Incidence, technique of isolation and treatment of group B streptococci. Am J Obstet Gynecol. 1976;126:1023-1026.

2. Anthony BF, Eisenstadt R, Carter J, et al. Genital and intestinal carriage of group B streptococci during pregnancy. J Infect Dis. 1981;143:761-766

3. Pass MA. Gray BM, Khare S, et al. Prospective studiesof group B streptococcal infections in infants. J Pediatr, 1979;95:437-443

4. Regan JA, Klebanoff MA, Nugent RP, et al. Colonization with group B streptococci in pregnancy and adverse outcome. Am J Obstet Gynecol. 1996;174:1354-1360

5. Tolockiene E, Morsing E, Holst E, et al. Intrauterine infection may be a major cause of stillbirth in Sweden. Acta Obstet Gynecol Scand 2001;6:511-518

6. McDonalds HM, Chambers HM. Intrauterine infection and spontaneous midgestation abortion: is the spectrum of microorganisms similar to that in preterm labor? Infect Dis Obstet Gynecol 2000;8:220-2207
7. Bland ML, Vermillion ST, Soper DE, Austin M. Antibiotic resistance pattern of group B streptococci in late third-trimester rectovaginal culteres. Am J Obstet Gynecol 2001;184:1125-1126

8. Marinoff DN, Chinn A. Prevention of recurrent second trimester group B streptococcus chorioamnionitis by intermittent prophylactic ampicillin. Obstet Gynecol 2001;98:918-919.

9. Johnson JR, Colombo DF, Gardner D, Cho E, Fan-Havard P, Shellhas CS. Optimal dosing of penicillin G in the third trimester of pregnancy for prophylaxis against group B Streptococcus. Am J Obstet Gynecol. 2001;185:850-853.

10. Gilson GJ, Christensen F, Romero H, Bekes K, Silva L, Qualls CR. Prevention of group B streptococcus early-onset neonatal sepsis: comparison of Center for Disease Control and prevention screening-based protocol to a risk-based protocol in infants at greater than 37 weeks’ gestation. J Perinatol 2000;20:491-495.