Obstetrics & Gynecology:
Risk Factors for Recurrence of Group B Streptococcus Colonization in a Subsequent Pregnancy
Cheng, Po-Jen MD1; Chueh, Ho-Yen MD1; Liu, Ching-Ming MD1; Hsu, Jenn-Jeih MD2; Hsieh, T'sang-T'ang MD2; Soong, Yung-Kuei MD1
From the 1Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Linkou Medical Center, Taoyuan, Taiwan; and 2Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taipei, Taiwan.
Supported by research grant NSC 96-2314-B-182A-066-MY2 from the National Science Council, Taiwan, Republic of China.
Corresponding author: Dr. Po-Jen Cheng, Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, 5, Fu-Shin Street, Kwei-Shan, TaoYuan, 333, Taiwan, R.O.C; e-mail: firstname.lastname@example.org.
Financial Disclosure The authors have no potential conflicts of interest to disclose.
OBJECTIVE: To document rates of recurrent group B streptococci (GBS) colonization in women with previous GBS colonization in an initial pregnancy and to assess maternal risk factors associated with recurrence.
METHODS: A retrospective, longitudinal study was performed in a teaching hospital on women with GBS colonization who were pregnant between 2002 and 2006 and had at least one subsequent pregnancy during the same time period. When only the index and first subsequent pregnancy were analyzed, the cohort included 251 women. The rate of recurrence was estimated for GBS colonization in the pregnancy after the index pregnancy for GBS colonization. Multivariable regression models were constructed to model recurrence of GBS colonization in a subsequent pregnancy as functions of potential predictors to estimate relative risks and confidence intervals.
RESULTS: The rate of recurrence of GBS colonization in the pregnancy subsequent to the index pregnancy was 38.2% (95% confidence interval 33.5–42.9%). Multivariable regression models showed that the time interval between the two pregnancies and the intensity of GBS colonization from the index pregnancy were predictive of recurrent GBS colonization.
CONCLUSION: More than one third of women had recurrent GBS colonization in a subsequent pregnancy. These findings should assist clinicians in counseling women with GBS colonization about their risk for recurrence, the importance of appropriate prenatal GBS screening in a subsequent pregnancy, and intrapartum antibiotic prophylaxis for unknown GBS status.
LEVEL OF EVIDENCE: II
Infection by Streptococcus agalactiae (group B streptococci [GBS]) is still the most frequent cause of neonatal diseases such as pneumonia, septicemia, and meningitis.1 It is generally accepted that GBS colonization of the fetus during passage through the genital tract may lead to early-onset infections (those among neonates aged less than 7 days), which remain a major cause of neonatal death and disability.2,3 Universal bacteriological screening of mothers for vaginal or rectal GBS colonization at 35 to 37 weeks of gestation, followed by selective intrapartum antibiotic prophylaxis for all screen-positive women, is the strategy currently recommended to reduce incidence of colonization in neonates and prevent early-onset GBS-related diseases.4–6
Although our previous study demonstrated that women with GBS colonization did not have a sustained increase in anxiety and they were strongly positive about being screened for GBS in the current pregnancy and any subsequent pregnancy,7 there is a paucity of data providing information regarding recurrence rates in a subsequent pregnancy and evaluating factors predictive for recurrent maternal GBS colonization among these women. Using a retrospective, longitudinal design, we conducted hospital medical record reviews during the period 2002–2006 to document rates of recurrent GBS colonization in women with previous GBS colonization during an initial pregnancy and to assess maternal risk factors associated with recurrence.
MATERIALS AND METHODS
Since 2002, the Chang Gung Memorial Hospital in Linkou and Taipei, Taiwan, has offered routine screening for GBS colonization to all pregnant women. Prenatal GBS screening culture is performed between 35 and 37 weeks of gestation under guidelines published by the U.S. Centers for Disease Control and Prevention8 and the American College of Obstetricians and Gynecologists (ACOG)9 in 2002. Vaginal and rectal swab specimens from each woman are collected separately, with both swabs placed into the same container with Amies transport medium (Copan Italia, Brescia, Italy) to be cultured within 36 hours in nonenriched and selective LIM broth medium (PML Microbiologicals, Wilsonville, OR) at 36±1°C in ambient air. After 18–24 hours of incubation in selective broth medium, an aliquot is plated onto 5% sheep blood agar. After another 24 hours, potential GBS colonies are evaluated according to morphology and the presence of hemolysis. If GBS is not identified after this time period, the plate will be reincubated and inspected at 48 hours. Mueller Hinton agar (Oxoid, Unipath Ltd., Basingstoke, UK) supplemented with 5% defibrinated sheep blood is used for antimicrobial susceptibility testing. Minimum inhibitory concentrations of penicillin, ampicillin, cefotaxime, tetracycline, erythromycin, and clindamycin are evaluated according to the National Committee for Clinical Laboratory Standards guidelines. Intensity of GBS colonization growth is evaluated quantitatively as follows (study analysis used same threshold standards): Over 80 colony-forming units (CFUs) is defined as heavy colonization, between 80 and 20 CFUs is defined as moderate, and under 20 CFUs is defined as light.10 The full screening test report is available to clinicians within 72 hours; pregnant women are informed of the GBS colonization and antimicrobial susceptibility test results during a routine clinic appointment 1 week later. At the time of labor or rupture of membranes, intrapartum chemoprophylaxis is given to all pregnant women identified as GBS carriers. For intrapartum chemoprophylaxis, the specific regimen for each colonized woman reflects history of penicillin allergy, report of antimicrobial susceptibility testing, and result of antimicrobial challenge test.
This study was performed between January 2002 and December 2006. Data were abstracted from hospital medical records by trained health records personnel from the Chang Gung Memorial Hospital in Linkou, Taiwan. The database includes extensive information on maternal medical conditions, prenatal and labor and delivery events, neonatal outcomes, and some information on maternal life-style and demographic factors. Women included in this study had a pregnancy with a diagnosis of GBS colonization and at least one subsequent pregnancy in the study time period. Women with clinical GBS bacterial infection during the index or subsequent pregnancy, as well as those with previous delivery of an infant with early-onset GBS disease, were excluded from analysis. Information pertaining to all pregnancies subsequent to the pregnancies with initial diagnosis of GBS colonization (eg, the index pregnancy) was collected. The research protocol was approved by the Chang Gung Memorial Hospital Research and Ethics Committee.
All statistical analysis was performed using SPSS 11.0 (SPSS Inc., Chicago, IL). Possible predictors were initially analyzed in univariable fashion by estimating relative risks (RRs) and 95% confidence intervals. Next, potential predictors were modeled using stepwise logistic regression. Variables from the index pregnancy included maternal age, marital status, prepregnancy weight, weight gain during pregnancy, infant birth weight, breastfeeding, result of gestational diabetes mellitus (GDM) screening, and intensity of GBS colonization. From the subsequent pregnancy, prepregnancy weight, smoking, and GDM screening were considered. The time interval between the two pregnancies (defined as the number of months between the date of delivery of the index pregnancy and the date of delivery of the subsequent pregnancy) and ethnicity were also evaluated. Pairwise comparisons among those who had recurrent GBS colonization and those who did not were made using χ2 tests for dichotomous variables and the Student t test for continuous variables. Because the estimated recurrent rate of GBS colonization would be more than 30%, log-odds ratios will overestimate the RR. Finally, odds ratios were converted to RRs under the use of log-linear models with a binary error term.
This study included 251 women who had documented GBS colonization during an index pregnancy and then had a subsequent pregnancy. The vast majority (72%) of women had GBS colonization (index pregnancy) with their first pregnancy; for 19% of women, the index pregnancy was their second pregnancy. Of the total of 251 women in this study, 96 (38.2%) had GBS colonization during the subsequent pregnancy (95% confidence interval 33.5–42.9%).
A comparison of potential risk factors among women who had recurrent GBS colonization and those who did not is shown in Table 1. In univariable analysis, all variables related to maternal weight did not differ among those who had recurrent GBS colonization and those who did not, regardless of whether data pertained to the index or subsequent pregnancy. In addition, there was no difference in maternal age, marital status, ethnicity, breastfeeding, and birth weight for both pregnancies between women with and those without recurrent GBS colonization. Four factors—GDM screening results for either the index pregnancy or subsequent pregnancy, intensity of GBS colonization for the index pregnancy, smoking during subsequent pregnancy, and time interval between the two pregnancies—were significantly associated with recurrent GBS colonization. When all potential predictors were analyzed in a logistic model, only the intensity of GBS colonization during the index pregnancy and the time interval between index and subsequent pregnancies significantly contributed to the fit of the model predicting recurrence of GBS colonization. As shown in Table 2, women who had heavy GBS colonization during their index pregnancy were 70% more likely to have recurrent GBS colonization than women with light GBS colonization. Women whose time interval between pregnancies was less than 12 months were 60% more likely to have recurrent GBS colonization compared with women whose interval was longer than 36 months. A statistically significant difference was seen with both time interval between pregnancies and intensity of GBS colonization during index pregnancy when these factors were modeled as continuous variables.
This study describes rates of recurrent GBS colonization among women in Taiwan who had documented GBS colonization during an initial index pregnancy. Rates found in this study were double the incidence rate of maternal colonization found in our institutions (18.3%)11 and much higher then the maternal GBS colonization rate reported in the other study of Chinese women (11.1%).12 Our results demonstrate that previous intrapartum GBS colonization is a major risk factor for maternal GBS colonization in the subsequent pregnancy.
Group B streptococcus was first recognized as a significant cause of neonatal sepsis and meningitis.1 Multiple clinical trials have demonstrated that universal prenatal screening for vaginal and rectal GBS colonization at 35–37 weeks of gestation and use of intrapartum antibiotic prophylaxis for affected women reduces the rate of neonatal colonization with GBS and the incidence of early-onset neonatal GBS-related diseases.2–6 Multiple epidemiologic studies have shown that the overall rate of GBS colonization among pregnant women ranges from 10% to 30%.13 The various rates of GBS colonization seen in different studies may reflect differences in the underlying population or in ethnicity.14 In addition, other factors have been shown to increase risk for maternal GBS colonization in studies of different communities. These include black race, Hispanic ethnicity, health care workers, history of sexually transmitted disease, and women with high body mass index.15–17 However, none of these risk factors has predictive value for identifying pregnant women with GBS colonization. Of note, reports suggest that women with one of these risk factors but who have negative prenatal screening cultures are at relatively low risk for neonatal early-onset GBS-related disease compared with women who were colonized prenatally but had none of the risk factors.2–6 Previous studies showed that delivery of an infant with invasive GBS-related disease may increase risk of early-onset disease in subsequent deliveries,18,19 and intrapartum treatment of such women during the subsequent pregnancies has been promoted. By contrast, colonization with GBS in a previous pregnancy is not currently considered an indication for intrapartum prophylaxis in subsequent pregnancies; rather, women require evaluation for prenatal colonization with each pregnancy. However, it is not clear whether or not previous GBS colonization has an impact on subsequent pregnancies. We searched the MEDLINE/PubMed database using the terms “pregnancy,” “risk factors,” “group B streptococcus,” “colonization,” and “recurrent” to look for articles on the topic of recurrent GBS colonization in a subsequent pregnancy in English language journals published from January 1996 to December 2006. We also used the Google Scholar search engine to look for Internet articles on this topic published since 1987. We could not find any previous study to evaluate the recurrent rate in such a population.
Our report is the first to show that a mother with previous positive GBS colonization is at significant risk for recurrent GBS colonization in a subsequent pregnancy. The predictive factors for recurrent colonization identified in this study include shorter time interval between pregnancies (less than 12 months) and heavy GBS colonization status during the index pregnancy.
Previous longitudinal investigation of GBS genital tract colonization in pregnant women has shown persistence of colonization for weeks to months.20,21 It is plausible that mothers with prenatal GBS colonization continue to carry the organism after delivery. Anthony et al22 did not find any significant variation in prevalence of GBS colonization during pregnancy and during the intrapartum and postpartum periods. Hansen et al23 found that GBS colonization status was relatively stable over a long period of time for most women: Only 18% of GBS carriers and noncarriers among pregnant women had changed carrier status 1 year after delivery. Boyer et al24 demonstrated that the ability of antenatal culture to predict GBS colonization at time of delivery varies inversely with the duration between specimen collection and delivery. With a colonization rate of 21%, Regan et al25 reported that GBS colonization obtained at 23–26 weeks of gestation had a positive predictive value of only 53% for identifying colonization at delivery. Late colonization, confirmed at 31–36 weeks, improved the positive predictive value to 69%. Our study showed that women with a shorter interval between pregnancies were more likely to have recurrent GBS colonization during the subsequent pregnancy, with a 60% difference of adjusted relative risk. Our observation is consistent with reports on concordance of prenatal GBS colonization status with colonization at time of delivery despite the difference in follow-up period.
Our study also shows that women with heavy GBS colonization were more likely to have recurrent colonization during the subsequent pregnancy. One possible explanation for this phenomenon relates to alteration of local immune or host cellular factors in the female genital microenvironment. It is known that GBS is an organism whose presence in the female genital organs does not elicit a significant host inflammatory response.26 Actually, detection of GBS in the female genital organs is typically considered to denote colonization rather than infection because bacterial isolation does not appear to be causally related to the presence of vulvovaginal symptoms.27,28 However, pregnant women with heavy vaginal GBS colonization at 23–26 weeks of gestation have a significantly increased risk for preterm labor and for delivery of a low birth weight infant compared with pregnant women with either no or light GBS colonization.25 This finding suggests that, although GBS colonization does not typically produce overt genitalia-related symptoms, alterations in the vaginal microenvironment may occur and larger quantities of GBS may be more likely to create these alterations.
According to the 2002 U.S. Centers for Disease Control and Prevention revised guidelines, women in labor with an unknown GBS status (culture not done, incomplete, or results unknown) should receive intrapartum antibiotic prophylaxis in the presence of one or more of the following risk factors: delivery at gestation less than 37 weeks, duration of amniotic membrane rupture for 18 hours or more, or intrapartum temperature of 100.4ºF (38.0ºC) or higher.8 Based on the high recurrent rate of GBS revealed in our study, we recommend that intrapartum antibiotics treatment should also be considered in those pregnancies whose GBS status is unknown at the time of labor but with either shorter time interval between pregnancies (less than 12 months) or heavy GBS colonization status during the index pregnancy.
In conclusion, the present study demonstrates an association between either shorter interpregnancy interval or heavy GBS intensity with recurrent GBS colonization in a subsequent pregnancy. The specific pathophysiologic mechanisms responsible for this association await elucidation, but they may include microenvironmental changes in either local genital tract immunity or physiology. The information on risk factors for recurrent GBS colonization will assist health care providers in counseling women with GBS colonization about their risk for recurrence, the importance of appropriate prenatal GBS screening, and intrapartum antibiotics treatment for unknown GBS status in any subsequent pregnancy.
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© 2008 The American College of Obstetricians and Gynecologists
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