The course of hepatitis C viraemia in transfusion recipients prior to availability of antiviral therapy.

Knowing the likely distribution of intervals from hepatitis C infection to first RNA-negativity is important in deciding about therapeutic intervention. Prospectively collected sera and data from the Transfusion-transmitted Viruses Study (1974-1980) provide specific dates of infection and pattern of alanine aminotransferase (ALT) elevations. We examined frequency, timing and correlates of spontaneous resolution for 94 acutely infected transfusion recipients followed for a median of 9.5 months. Later, follow-up sera (>10 years) were available for 27 of the 94 cases from a Veterans Administration (VA) Study (1989-1990). Twenty-five (27%) of the 94 cases were classified as probably resolved during the episode itself. First RNA negativity occurred at 6-50 weeks (median, 19.5 weeks) after infection, and 5-43 weeks (median, 11 weeks) after ALT elevation. Thirteen of the 25 cases remained RNA-negative subsequently; 12 others had 1-6 RNA-positive sera intercalated between first and last RNA-negative results. RNA negativity, therefore, began variably and was interrupted in 12 cases of 25 (48%) by transient RNA-positive sera. Five of these 25 patients who were RNA-negative in the last study specimen had late, Veterans Administration Study follow-up; none showed viraemia. Of the remaining 69 transfusion transmitted virus study recipients, whose last serum was RNA-positive, two cleared viraemia after the last study serum but before late follow-up. Eleven (16%) had 23 intercalated RNA-negative sera before last positivity. RNA status, therefore, needs monitoring for many months before judging the spontaneous outcome as transient negativity may occur. Resolution was significantly more common in women and symptomatic cases; it was not associated with viral load in the infectious donation, HCV genotype, or the recipient's age.

Intrapartum chlorhexidine vaginal irrigation and chorioamnion and placental microbial colonization.

OBJECTIVES: To determine whether intrapartum chlorhexidine vaginal irrigation reduces microbial colonization of the chorioamnion or placenta. METHODS: Secondary analysis was made of a randomized trial. Cultures for aerobic and anaerobic bacteria, Mycoplasma species and Ureaplasma urealyticum were performed using standard isolation techniques. RESULTS: The placentas of 83 trial participants allocated to chlorhexidine and 93 allocated to placebo underwent evaluation. These two groups were statistically balanced for risk factors for infection. Aerobic bacteria were isolated from 47% of the chlorhexidine placentas vs. 51% of the placebo placentas (relative risk 0.9, 95% confidence interval 0.7-1.3), anaerobic bacteria from 30% and 35%, respectively (0.8, 0.5-1.3), group B streptococcus from 12% and 15% (0.8, 0.4-1.7), U. urealyticum from 18% and 29% (0.6, 0.4-1.1), Mycoplasma species from 6% and 11% (0.6, 0.2-1.6), and any organism from 57% and 67%, respectively (0.8, 0.7-1.1). CONCLUSIONS: Intrapartum chlorhexidine vaginal irrigation was associated with non-significant reductions in the rates of placental microbial isolation.

Elevated amniotic fluid ferritin levels are associated with inflammation-related pregnancy loss following mid-trimester amniocentesis.

OBJECTIVE: Occult infection accounts for up to 12% of pregnancy losses following genetic amniocentesis. Elevated serum and cervical fluid levels of ferritin, an acute-phase reactant, have been associated with spontaneous preterm delivery. We determined the association between amniotic fluid (AF) ferritin levels and post-amniocentesis pregnancy loss. METHODS: We performed a case-control study involving 66 women with a non-anomalous fetus who had a spontaneous pregnancy loss within 30 days following genetic amniocentesis and 66 term controls matched for maternal age, gestational age, time of test and indication for amniocentesis. Amniotic fluid ferritin and interleukin-6 (IL-6) levels were measured using commercially available kits. RESULTS: Mean (+/- SD) AF ferritin levels were similar between the cases (19.3 +/- 21.4 ng/ml) and the controls (19.8 +/- 22.7ng/ml) (p = 0.9). Mean (+/- SD) AF IL-6 levels were significantly higher in the women with post-amniocentesis pregnancy loss (4.0 +/- 13.1 ng/ml) than in controls (0.5 +/- 0.7 ng/ml) (p = 0.04). A significant proportion (12.1%, 8/66) of the women with post-amniocentesis pregnancy loss had elevated amniotic fluid IL-6 levels (> 3 SD, 2.5 ng/ml) indicating inflammation, as compared to none in the control group (p = 0.01). In this subgroup of women with pregnancy loss and elevated IL-6 levels, AF ferritin levels were significantly elevated (52.0 +/- 45.5 ng/ml) compared to the level in women who had a term delivery (19.8 +/- 22.7 ng/ml) (p = 0.002), and were strongly correlated with IL-6 levels among the cases (r = 0.67, p < 0.001). CONCLUSION: The strong correlation of AF ferritin with IL-6 levels, along with the high ferritin values in cases with high AF IL-6, indicates that ferritin is a marker of inflammation in asymptomatic women destined to have an early pregnancy loss.

Midtrimester vaginal Mycoplasma genitalium in women with subsequent spontaneous preterm birth.

OBJECTIVE: We sought to determine the midtrimester prevalence of Mycoplasma genitalium in women who had subsequent spontaneous preterm birth. STUDY DESIGN: In a prospective study of lower genital tract infections, we identified 127 women who subsequently had spontaneous preterm birth. Vaginal samples were obtained between 21 and 25 weeks' gestation for pH, for bacterial vaginosis Gram stain, and cultures that yielded Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. M genitalium was identified by using validated polymerase chain reaction (PCR) primers, and the results were compared to pregnancy outcomes. RESULTS: Of 124 women with spontaneous preterm births, only five (3.9%) had PCR assays positive forM genitalium. The mean +/- SD delivery gestational age was similar for women with a positive PCR (34.6 +/- 2.2 weeks) and a negative PCR (34.0 +/- 2.7 weeks) (P =.62). None of the women with positive PCR results tested positive for any other sexually transmitted disease, whereas 36 (30%) women with negative PCR results tested positive. CONCLUSIONS: The occurrence of M genitalium in the vagina at midtrimester is infrequent in women with subsequent spontaneous preterm birth.

The Preterm Prediction Study: association between cervical interleukin 6 concentration and spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: The aim of this study was to determine the interrelationship between cervical concentration of interleukin 6 and detection of fetal fibronectin and other risk factors for spontaneous preterm birth. STUDY DESIGN: All patients with spontaneous preterm birth at <35 weeks' gestation (case patients; n = 125) and subjects matched for race, parity, and center delivered at > or = 37 weeks' gestation (n = 125; control subjects) were selected from women enrolled in the National Institute of Child Health and Human Development's Preterm Prediction Study. Interleukin 6 concentrations were determined by enzyme-linked immunosorbent assay in cervical swabs obtained at 22 weeks' to 24 weeks 6 days' gestation. Cutoffs to define an elevated interleukin 6 concentration included the 90th and 95th percentiles for control subjects (>305 and >538 pg/mL, respectively). RESULTS: The mean (+/-SD) interleukin 6 concentration was significantly higher in case patients than in control subjects (212 +/- 339 vs 111 +/- 186 pg/mL; P = .008). With either cutoff value elevated interleukin 6 concentration was significantly associated with spontaneous preterm birth (90th percentile, 20% vs 9.6%; P = .02; 95th percentile, 12% vs 4.8%; P = .04). Cervical interleukin 6 levels were highest within 4 weeks of delivery, and the trend continued until term. Elevated interleukin 6 concentration was not significantly associated with bacterial vaginosis, maternal body mass index <19.8 kg/m2, or a short cervix (< or = 25 mm), but it was significantly associated with a positive cervicovaginal fetal fibronectin test result (90th percentile, odds ratio, 5.5; 95% confidence interval, 2.6-11.9; 95th percentile, odds ratio, 5.3, 95% confidence interval, 2.1-12.9). The mean interleukin 6 concentration among women with a positive fibronectin test result was 373 +/- 406 pg/mL; that among women with a negative fetal fibronectin test result was 130 +/- 239 pg/mL (P = .001). In a regression analysis that adjusted for risk factors significantly associated with spontaneous preterm birth in this population (positive fetal fibronectin test result, body mass index <19.8 kg/m2, vaginal bleeding in the first or second trimester, previous spontaneous preterm birth, and short cervix) elevated cervical interleukin 6 concentration was not independently associated with spontaneous preterm birth (odds ratio, 1.8; 95% confidence interval, 0.8-4.3). CONCLUSIONS: At 24 weeks' gestation cervical interleukin 6 concentration in women who subsequently had a spontaneous preterm birth at <35 weeks' gestation was significantly elevated relative to those who were delivered at term. The association was particularly strong within 4 weeks of testing. A positive fetal fibronectin test result was strongly associated with elevated cervical interleukin 6 concentration, but bacterial vaginosis was not.

Vaginal fetal fibronectin levels and spontaneous preterm birth in symptomatic women.

OBJECTIVE: To relate vaginal fetal fibronectin levels in women with symptoms of preterm labor to subsequent spontaneous preterm birth. METHODS: Quantitative fetal fibronectin values were calculated from women who participated in two prospective multicenter trials relating fetal fibronectin to subsequent spontaneous preterm birth. The study populations consisted of women who presented with symptoms of preterm labor between 24(0)/(7) and 34(6)/(7) weeks, a singleton pregnancy, intact membranes, no prior tocolysis, and cervical dilation less than 3 cm. RESULTS: The characteristics of the two study populations were similar. In both populations, the rates of delivery within 7, 14, and 21 days after sampling were clustered into three distinct fetal fibronectin groups (less than 40, 40-100, and 100 ng/mL or more). As fetal fibronectin values increased, the risk of subsequent spontaneous preterm birth also increased. Delivery within 7 days of sampling was 0.4%, 3.3%, and 18.2% (trial A) and 1.4%, 8.0%, 30.0% (trial B) as the fetal fibronectin levels increased from less than 40 ng/mL, to 40-100 ng/mL, and to at least 100 ng/mL, respectively. CONCLUSION: In women with symptoms of preterm labor, an increase in fetal fibronectin from under 40 ng/mL, to 40-100 ng/mL, to at least 100 ng/mL was associated with a progressive increase in the risk of subsequent spontaneous preterm birth. The use of a single fetal fibronectin cutoff of 50 ng/mL for defining a positive test in women with symptoms of preterm labor should be reevaluated.

The Preterm Prediction Study: association of second-trimester genitourinary chlamydia infection with subsequent spontaneous preterm birth.

OBJECTIVE: This study was undertaken to determine the association between genitourinary tract infection with Chlamydia trachomatis and spontaneous preterm birth. STUDY DESIGN: Genitourinary tract infection with C trachomatis was determined with a ligase chain reaction assay of voided urine samples collected at 24 weeks' gestation (22 weeks' to 24 weeks 6 days' gestation) and 28 weeks' gestation (27 weeks' to 28 weeks 6 days' gestation). Case patients (spontaneous preterm birth at <37 weeks' gestation; n = 190) and control subjects (delivery at >/=37 weeks' gestation, matched for race, parity, and center; n = 190) were selected from 2929 women enrolled in the Preterm Prediction Study of the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. RESULTS: Genitourinary C trachomatis infection (11% overall) was significantly more common among the case patients than among the control subjects at 24 weeks' gestation (15.8% vs 6.3%; P =.003) but not at 28 weeks' gestation (12.6% vs 10.9%; P =.61). Women with chlamydia infection were more likely to have bacterial vaginosis (57.1% vs 32.9%; P =.002) and a short cervical length (

Puerperal infection after cesarean delivery: evaluation of a standardized protocol.

OBJECTIVE: Our goal was to evaluate an antibiotic protocol for treatment of postcesarean endometritis. STUDY DESIGN: Endometritis was diagnosed as a persistent fever > or =100.4 degrees F beyond 24 hours after cesarean delivery and one or more of the following: uterine tenderness, tachycardia, foul lochia, or leukocytosis. Antibiotic therapy included gentamicin plus clindamycin and ampicillin (or vancomycin) as a triple antimicrobial in 148 women. Antibiotic failure was defined as persistent fever after 5 days of antibiotics and 72 hours of triple antibiotics. RESULTS: Between 1993 and 1996, 322 of 1643 (20%) women were diagnosed with postcesarean endometritis. One hundred seventy-four patients (54%) were cured with clindamycin-gentamicin, and 129 who additionally received ampicillin or vancomycin (40%) were cured. Nineteen of the 322 (6%) women had persistent fever despite triple antibiotics. Of these, 6 had a wound complication, 12 were suspected to have antimicrobial resistance, and 1 had an infected hematoma. CONCLUSION: A prospective protocol consisting of clindamycin-gentamicin plus the selective addition of ampicillin or vancomycin cured 303 of 322 (94%) women with postcesarean endometritis.

The preterm prediction study: cervical lactoferrin concentration, other markers of lower genital tract infection, and preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: This study was undertaken to determine the relationship among cervical lactoferrin concentration, other cervical markers potentially related to infection, and spontaneous preterm birth. STUDY DESIGN: Cervical lactoferrin concentrations obtained at 22 to 24 weeks' gestation among 121 women who had a spontaneous preterm birth <35 weeks' gestation were compared with cervical lactoferrin concentrations among 121 women matched for race, parity, and center who were delivered at >/=37 weeks' gestation. Results were compared against levels of cervical interleukin 6, fetal fibronectin, and sialidase, against cervical length according to ultrasonography, and according to the bacterial vaginosis Gram stain score. RESULTS: Cervical lactoferrin concentrations ranged from not measurable (19% of the concentrations were below the threshold for this assay) to a titer of >/=1:64. There was no significant difference in the overall distributions of lactoferrin concentrations between the case patients and control subjects (P =.18). Only when the highest titers of lactoferrin were considered were there more women in the spontaneous preterm birth group (6/121 vs 0/121; P =.03). According to Spearman correlation analyses the cervical lactoferrin concentrations were strongly related to interleukin 6 concentration (r =.51; P =.0001), sialidase activity (r =.38; P =.0001), and bacterial vaginosis (r =.38; P =.0001), were weakly related to fetal fibronectin (r =. 16; P =.01), and were not related to cervical length. With the 90th percentile (a dilution of 1:32) used as a cutoff to establish a dichotomous variable, lactoferrin concentration had the following odds ratios and 95% confidence intervals for associations with other potential markers of infection: bacterial vaginosis odds ratio, 4.8 (95% confidence interval, 2.2-10.3); interleukin 6 concentration odds ratio, 2.8 (95% confidence interval, 1.2-6.5); sialidase activity odds ratio, 5. 5 (95% confidence interval, 2.2-13.7); fetal fibronectin concentration odds ratio, 0.6 (95% confidence interval, 0.2-2.0); chlamydiosis odds ratio, 2.3 (95% confidence interval, 0.8-6.9); and short cervix odds ratio, 0.5 (95% confidence interval, 0.2-1.4). CONCLUSIONS: Lactoferrin found in the cervix correlated well with other markers of lower genital tract infection. High lactoferrin levels were associated with spontaneous preterm birth but had a very low predictive sensitivity.

The preterm prediction study: granulocyte colony-stimulating factor and spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

OBJECTIVE: Granulocyte colony-stimulating factor is elevated in the amniotic fluid and plasma of women with chorioamnionitis and active preterm labor. We investigated the relationship between plasma granulocyte colony-stimulating factor and subsequent spontaneous preterm birth in pregnant women without symptoms. STUDY DESIGN: We performed a nested case-control study involving 194 women who had a singleton spontaneous preterm birth and 194 matched term control subjects from the patient pool (n = 2929) enrolled in the Preterm Prediction Study. Plasma collected at 24 and 28 weeks' gestation was analyzed for granulocyte colony-stimulating factor, and the results were compared with subsequent spontaneous preterm birth. RESULTS: Compared with term control subjects, women who were delivered of their infants spontaneously at <28 weeks' gestation had increased mean granulocyte colony-stimulating factor values at 24 weeks' gestation (84.7 +/- 38.4 vs 67.7 +/- 28.6 pg/mL; P =.049), and women who were delivered of their infants at <32 weeks' gestation had increased mean plasma granulocyte colony-stimulating factor values at 28 weeks' gestation (80.4 +/- 24.1 vs 55.9 +/- 16.5 pg/mL; P =. 001). At 24 weeks' gestation a granulocyte colony-stimulating factor value >75th percentile in control subjects (approximately 80 pg/mL) was found in 48.9% (23/47) of all women delivered of their infants at <32 weeks' gestation versus 14.9% (7/47) of the term control subjects (adjusted odds ratio, 6.2; 95% confidence interval, 1.8-20. 8). At 28 weeks' gestation a granulocyte colony-stimulating factor value >75th percentile was found in 36.8% (7/19) of women delivered of their infants at <32 weeks' gestation versus 5.3% (1/19) of term control subjects (adjusted odds ratio, 25.7; 95% confidence interval, 1.5-470.4). When measured at 24 or 28 weeks' gestation, granulocyte colony-stimulating factor did not predict spontaneous preterm birth at 32 to 34 weeks' gestation or at 35 to 36 weeks' gestation. CONCLUSION: In pregnant women without symptoms at 24 and 28 weeks' gestation, elevated plasma granulocyte colony-stimulating factor levels are associated with subsequent early (<32 weeks' gestation) spontaneous preterm birth, especially within the next 4 weeks, but not with late spontaneous preterm birth. These data provide further evidence that early spontaneous preterm birth is associated with an inflammatory process that is identifiable by the presence of a cytokine in maternal plasma several weeks before the early spontaneous preterm birth; however, later spontaneous preterm birth is not associated with this process.

Second-trimester cervical ultrasound: associations with increased risk for recurrent early spontaneous delivery.

OBJECTIVE: To determine whether short cervical length or internal os funneling before 20 weeks' gestation predicts early preterm birth or pregnancy loss in women with at least one prior spontaneous early preterm birth. METHODS: Transvaginal cervical ultrasound examinations were done every 2 weeks on 69 women with singleton gestations and histories of at least one prior spontaneous birth between 16 and 30 weeks' gestation. The results of those examinations were correlated with gestational age at delivery. RESULTS: Among 53 women who had ultrasound examinations before 20 weeks' gestation, those with cervical lengths at or below the tenth percentile for the study population (22 mm, n = 4) or funneling of the internal os (n = 5) were more likely than women without those factors to have spontaneous preterm births within 2 weeks (33% versus 0%, P = .01) or 4 weeks from the ultrasound examination (67% versus 0%, P < .001) or before 35 weeks' gestation (100% versus 19%, P < .001). Short cervical length or funneling between 20-24 and 25-29 weeks was also associated with increased risk of spontaneous preterm birth before 35 weeks' gestation (P < or = .05 and P = .002, respectively) but not with increased risk of spontaneous preterm birth within 2 or 4 weeks of ultrasound examination. CONCLUSION: Women with prior early spontaneous preterm births who have short cervical lengths or funneling of the internal cervical os before 20 weeks' gestation are at increased risk of subsequent spontaneous preterm birth.

Infection and preterm birth.

Preterm birth complicates 11% of all pregnancies in the United States and remains a leading cause of infant mortality and long-term neurological handicap. The majority of this morbidity and mortality is concentrated among the small subset of infants born before 32 weeks' gestational age and that have birth weights < 1500 g. Although the survival of these preterm infants has improved over the last 20 years, the rate of long-term handicap has not. Despite widespread use of preventive strategies, the rate of preterm birth is increasing. Therefore, the prevalence of long-term handicap attributed to preterm birth also is increasing. Considerable data implicate a clinically silent upper genital tract infection as a key component of the pathophysiology of a majority of early spontaneous preterm births, but a minority of preterm births that occur near term. This report reviews the current status of our understanding of the relationship between genital tract microbial infection and spontaneous preterm birth, the availability and usefulness of markers to identify women with such infections, and the results of recent prospective randomized clinical trials of antibiotic therapy to prevent preterm birth. Strengths and limitations of the trials are reviewed in relationship to their value for guidance in clinical management strategies and directions for future research are discussed.

The association of interleukin 6 with clinical and laboratory parameters of acute pelvic inflammatory disease.

OBJECTIVE: We sought (1) to determine whether interleukin 6 levels are increased in plasma and cervical secretions and endometrial tissue obtained from women with a clinical diagnosis of pelvic inflammatory disease, (2) to determine whether interleukin 6 levels in these sample sites reflected the clinical severity of acute infection, and (3) to determine whether interleukin 6 levels in endometrial tissue obtained from these women were higher in the presence of histologic endometritis. STUDY DESIGN: We performed a prospective pilot study on 20 women with a clinical diagnosis of pelvic inflammatory disease (patients) and then compared them with 20 women presenting to the gynecology clinic without pelvic complaints (control subjects). Interleukin 6 levels were measured by enzyme-linked immunologic testing in plasma, cervical secretions, and endometrial biopsy specimens. RESULTS: Cervical interleukin 6 levels were higher in patients than control subjects (median, 317 vs 111 pg/mL; P =.003). Among women with pelvic inflammatory disease, statistically significant positive correlations were noted between the clinical severity score and the erythrocyte sedimentation rate (r = 0.45; P =.04), the clinical severity score and the white blood cell count (r = 0.49; P =.03), the plasma interleukin 6 levels and the erythrocyte sedimentation rate (r = 0.55; P =.02), and the plasma interleukin 6 levels and the white blood cell count (r = 0.54, P =.01). Endometrial tissue interleukin 6 levels were also higher in patients with versus those without histologic endometritis (median, 427 vs 17 pg/mL; P =.004). CONCLUSION: In this pilot study interleukin 6 levels in cervical secretions were significantly higher in women with pelvic inflammatory disease versus those without pelvic inflammatory disease. In women with pelvic inflammatory disease, endometrial tissue samples with histologic evidence of endometritis were observed to have higher levels of interleukin 6. Interleukin 6 may be a useful adjunct to the clinical diagnosis of pelvic inflammatory disease.

The preterm prediction study: failure of midtrimester cervical sialidase level elevation to predict subsequent spontaneous preterm birth.

OBJECTIVE: Our objective was to determine any associations among midtrimester cervical fluid sialidase activity, bacterial vaginosis, and subsequent spontaneous preterm birth. STUDY DESIGN: In this nested case-control study all patients (n = 126) with spontaneous preterm birth at <35 weeks' gestation and selected control subjects delivered at >/=37 weeks' gestation (n = 126, matched for race, parity, and center) were derived from women enrolled in the multicenter National Institute of Child Health and Human Development Preterm Prediction Study. Sialidase activity and presence of bacterial vaginosis according to Gram stain were determined in cervical swabs and vaginal smears, respectively, obtained at 22 weeks' to 24 weeks 6 days' gestation. RESULTS: The mean +/- SD sialidase activities were similar in case patients and control subjects (0.64 +/- 1.60 vs 0.41 +/- 0.94 nmol. mL-1. min-1, P =.21). Neither sialidase activity above the 90th percentile (10.3% vs 9.5%, P =.8) nor sialidase activity above the 95th percentile (7.9% vs 4. 8%, P =.3) of control specimens (>1.43 and >2.23 nmol. mL-1. min-1, respectively) was associated with spontaneous preterm birth. The frequency of combinations of bacterial vaginosis and elevated sialidase activity was similar (P >/=.63 with either cutoff) in case patients and control subjects. Sialidase activity was significantly higher among women with bacterial vaginosis than among those without bacterial vaginosis (1.35 +/- 1.87 vs 0.03 +/- 0.14 nmol. mL-1. min-1, P <.0001). CONCLUSIONS: Elevated cervical fluid sialidase activity at 22 to 24 weeks' gestation did not distinguish women at increased risk for spontaneous preterm birth, nor did it discriminate a subgroup of patients who had bacterial vaginosis associated with spontaneous preterm birth.

Syphilis, gonorrhoea, and drug abuse among pregnant women in Jefferson County, Alabama, US, 1980-94: monitoring trends through systematically collected health services data.

OBJECTIVE: To assess the association between self reported drug abuse and syphilis and gonorrhoea among pregnant women, Jefferson County, Alabama, United States, 1980-94. STUDY DESIGN: We analysed a prenatal care database and assessed the association of self reported drug use with seropositive syphilis and gonorrhoea using prevalence rates, multiple logistic regression models, and the Pearson correlation coefficient (r) for trends. RESULTS: Overall, 5.5% of the women acknowledged drug abuse, 1.4% had seropositive syphilis, and 4.8% had gonorrhoea. In a multivariate analysis, drug abuse was associated with syphilis (odds ratio 2.9, 95% confidence interval 1.6, 5.3) but not with gonorrhoea. Trends in the annual prevalence of drug abuse closely paralleled trends in the annual prevalence of syphilis, including simultaneous peaks in 1992 (drug abuse, 9.1%; syphilis, 3.2%). There was no such parallel trend between drug abuse and gonorrhoea. Annual prevalence of drug abuse correlated with the prevalence of syphilis (r = 0.89, p = 0.001) more than with the prevalence of gonorrhoea (r = 0.45, p = 0.201). CONCLUSION: Among pregnant women, an increase in drug abuse was closely associated with an epidemic of syphilis, but not of gonorrhoea. Systematically collected prenatal care data can usefully supplement surveillance of diseases and behavioural risk factors associated with them.

Antibiotic susceptibility profile of group B streptococcus acquired vertically.

OBJECTIVE: To determine the contemporary antibiotic susceptibility profile of vertically acquired group B streptococcal isolates. METHODS: Susceptibility to ampicillin, penicillin G, erythromycin, clindamycin, cefazolin, and gentamicin was assessed by two methods, minimal inhibitory concentration and disc diffusion. RESULTS: The susceptibility profiles of 119 colonizing and eight invasive strains of group B streptococcus isolated from January 1996 to September 1997 at two hospitals in Birmingham, Alabama-University of Alabama at Birmingham and Cooper Green-were studied. Minimal inhibitory concentration determinations indicated that all colonizing strains were susceptible or moderately susceptible to ampicillin and penicillin G. Resistance was noted by at least one strain to each of the other antibiotics; all were resistant to gentamicin, whereas 27 (21%) were resistant to erythromycin, five (4%) to clindamycin, and one (1%) to cefazolin. All of the eight invasive strains were susceptible or moderately susceptible to ampicillin, penicillin G, clindamycin, and cefazolin; one (13%) was resistant to erythromycin, and all were resistant to gentamicin. Disc diffusion results generally were concordant with minimal inhibitory concentration results, although by disc diffusion fewer isolates were classified as susceptible, and more as moderately susceptible, to ampicillin and penicillin G than by minimal inhibitory concentration. CONCLUSION: Universal susceptibility of group B streptococcus to members of the penicillin family supports the continued use of penicillin G or ampicillin for early onset neonatal group B streptococcal disease prevention. For patients allergic to beta-lactam agents, clindamycin (4% resistance) may be a better alternative than erythromycin (21% resistance).

Choriodecidual inflammation: a potentially preventable cause of perinatal HIV-1 transmission?

The obstetric risk factors for perinatal transmission of HIV-1 include preterm birth, prolonged rupture of the chorioamniotic membranes, and clinical and histological bacterial chorioamnionitis. A chronic chorioamnionitis precedes many cases of preterm labour and spontaneous rupture of membranes, whereas an acute chorioamnionitis is more common after rupture of the membranes at term. Amniotic fluid cytokines are raised in the presence of term and preterm intrauterine bacterial infections, and various cytokines seem able to attract HIV-1-infected leucocytes into the amniotic cavity and to increase replication of HIV-1. We postulate that the association of preterm birth and prolonged rupture of membranes with perinatal transmission of HIV-1 may result from an associated chronic or acute bacterial chorioamnionitis marked by the migration of HIV-1-infected maternal leucocytes into the amniotic cavity. Antibiotic treatment could prevent this sequence of events.

Pharmacokinetics of oral valacyclovir and acyclovir in late pregnancy.

OBJECTIVE: The objective was to obtain preliminary pharmacokinetic data for acyclovir from gravid women receiving herpes simplex virus suppressive therapy with the acyclovir prodrug valacyclovir. STUDY DESIGN: In a prospective, double-blind trial, 20 women with a history of recurrent genital herpes simplex virus infection and positive herpes simplex virus 2 serologic results were randomly assigned at 36 weeks' gestation to receive oral valacyclovir (500 mg twice daily) or acyclovir (400 mg 3 times daily). Acyclovir pharmacokinetic profiles were obtained after the initial dose (36 weeks) and at steady state (38 weeks). Amniotic fluid samples were obtained during labor and simultaneous umbilical cord and maternal plasma samples were collected at delivery. Laboratory studies were performed to screen for laboratory evidence of toxicity in mothers and infants. RESULTS: Peak acyclovir plasma concentrations (mean +/- standard deviation) were higher in valacyclovir recipients than in acyclovir recipients after the initial dose (3.14 +/- 0.7 microg/mL vs 0.74 +/- 0.6 microg/mL, P < .0001) and at steady state (3.03 +/- 1.0 microg/mL vs 0.94 +/- 0.7 microg/mL, P < .001). The daily area under the curve values were higher in valacyclovir recipients than acyclovir recipients after the initial dose (17.8 +/- 3.6 h x microg/mL vs 7.71 +/- 2.5 h x microg/mL, P < .001) and at steady state (19.65 +/- 6.4 h x microg/mL versus 11.0 +/- 4.5 h x microg/mL, P = .009). There was no significant difference in drug elimination half-life or in time to peak concentration between valacyclovir and acyclovir recipients at either sampling interval. Acyclovir was concentrated in the amniotic fluid; however, there was no evidence of preferential fetal drug accumulation (mean maternal/umbilical vein plasma ratios at delivery were 1.7 for valacyclovir and 1.3 for acyclovir). Valacyclovir was well tolerated, and no significant laboratory or clinical evidence of toxicity was detected. CONCLUSION: In this phase I trial maternal valacyclovir therapy resulted in higher plasma acyclovir levels, with significantly higher peak concentrations and daily area under the curve values, than did acyclovir therapy. Additional trials are needed to further evaluate the safety and efficacy of suppressive valacyclovir therapy during late pregnancy.

Bacterial vaginosis: association with adverse pregnancy outcome.

Bacterial vaginosis is the most common lower genital tract infection encountered among women of reproductive age. This condition can best be considered as a vaginal syndrome associated with an alteration of the normal vaginal flora rather than an infection specific to any one microorganism. Bacterial vaginosis is a clinical condition with a complex microbiology that is characterized by a reduced concentration of a normally abundant Lactobacillus species along with high concentrations of gram-negative and anaerobic bacteria, particularly, Gardnerella vaginalis and Mobiluncus, Bacteroides, Prevotella, and Mycoplasma species. The exact make up of the microorganisms and their relative concentration vary among women who have this condition. Although it was previously regarded as a harmless condition, recent work has linked bacterial vaginosis to numerous upper genital tract complications such as preterm labor and preterm delivery, preterm premature rupture of the membranes, chorioamnionitis, and postpartum endometritis. The findings from recent prospective randomized trials suggest that treatment of bacterial vaginosis in certain women who are at high risk for preterm delivery decreases the rate of preterm birth.