A randomized controlled trial of interleukin-1 receptor antagonist in a rabbit model of ascending infection in pregnancy.

OBJECTIVE: To determine whether treatment with interleukin-1 receptor antagonist (IL1-ra) would affect amniotic fluid concentrations of tumor necrosis factor alpha (TNF-alpha) and prostaglandins or clinical or microbiological outcomes in a model of ascending bacterial infection in pregnancy. METHODS: Timed pregnant New Zealand white rabbits at 70% of gestation underwent endoscopic inoculation of the cervices with 10(6) - 10(7) cfu Escherichia coli. Animals were randomly assigned in a blinded manner to a 5-h intravenous infusion of human IL1-ra (10 mg/kg) or placebo beginning 1-2 h after inoculation. Blood was drawn from the does for assay of serum IL1-ra concentration before inoculation, at mid-infusion, after the infusion ended and at necropsy. At necropsy, temperature and cultures were taken, and aspirated amniotic fluid was pooled for assays of TNF-aalpha, prostaglandin E2 (PGE2) and ILI-ra. RESULTS: Serum IL1-ra concentrations rose to a mean of 2 microg/ml at mid-infusion and fell markedly after the infusion to concentrations barely detectable at necropsy. Between the two groups, there were no significant differences in the rates of fever or positive cultures or in amniotic fluid concentrations of PGE2 or TNF-alpha. One unique finding was the demonstration that administration of human IL1-ra to the does resulted in measurable concentrations of human IL1-ra in the amniotic fluid. CONCLUSIONS: Treatment with an intravenous infusion of human IL1-ra after cervical inoculation with E. coli did not affect clinical or microbiological outcomes or amniotic fluid concentrations of TNF-alpha or PGE2. This experiment providesthefirstdemonstration of passage of human IL1-ra from the maternal bloodstream to the amniotic fluid.

Histologic inflammation in the maternal and fetal compartments in a rabbit model of acute intra-amniotic infection.

OBJECTIVE: This study was undertaken to determine the course of acute inflammation in the maternal and fetal compartments during experimentally induced ascending intra-amniotic infection. STUDY DESIGN: Forty pregnant rabbits at 70% gestation were inoculated endocervically with 10(5) colony-forming units of Escherichia coli. Does were killed at 0, 4, 8, 16, 24, and 30 hours after inoculation. At necropsy, blood, peritoneal fluid, amniotic fluid, and uterine tissue were cultured. Fetal brain, lung, heart, gut, and kidney were collected for histologic examination. Necrosis, infiltrates, congestion, and edema were each assessed semiquantitatively, and mean composite histologic-inflammation scores were compared with analysis of variance. Inflammation, mitotic activity, and apoptosis were evaluated in the fetal brain, and groups were compared with analysis of variance. RESULTS: Twenty-six animals were evaluated after 14 were excluded (lack of fever or positive culture results). A significant increase in histologic inflammation score was seen in the uterus (P<.001), placenta(P = .011), and fetal lung (P = .001) but not in other fetal tissues. These changes were seen earlier in the uterus and placenta and later in the fetal lung. Mitotic activity in the fetal brain decreased significantly by 8 hours after cervical inoculation. There was no inflammation in the fetal brain, and apoptosis in the fetal brain did not increase with time. CONCLUSIONS: Histologic inflammation occurs early in both the uterus and the placenta and later in the fetal lung in the rabbit model of acute intra-amniotic infection. This contrasts with the previously reported chronic model of intra-amniotic infection in the rabbit.

Acute intrauterine infection results in an imbalance between pro- and anti-inflammatory cytokines in the pregnant rabbit.

PROBLEM: Intrauterine infection results in an increase in cytokines. This study compared the time courses for the pro- and anti-inflammatory cytokine responses in 33 pregnant rabbits at 70% gestation. Pro-inflammatory markers were activated nuclear factor-kappa B (NF-kappaB) in placenta and tumor necrosis factor-alpha (TNF-alpha) in amniotic fluid. These were compared to the anti-inflammatory cytokine, interleukin-1 receptor antagonist (IL-1ra), in placenta and uterus. METHOD OF STUDY: Does were endoscopically inoculated with Escherichia coli through their cervices and sacrificed at six intervals between 0 and 30 hr post-inoculation. RESULTS: Activated NF-kappaB, determined by electromobility gel shift assay, increased significantly 16 hr after bacterial inoculation (P < or = 0.05). This was directly mirrored by TNF-alpha concentrations, determined by bioassay, in the amniotic fluid. However, IL-1ra levels, determined by enzyme-linked immunosorbent assay, did not increase in response to infection. CONCLUSIONS: Intrauterine infection results in an imbalance between pro- and anti-inflammatory cytokines that may potentiate infection-induced preterm delivery.

A randomized trial of conjugated group B streptococcal type Ia vaccine in a rabbit model of ascending infection.

OBJECTIVE: Maternal vaccination may become a central strategy in the prevention of early-onset group B Streptococcal sepsis. Unlike earlier group B streptococcal polysaccharide vaccines that were poorly immunogenic, newer vaccines conjugated to tetanus toxoid have been developed and have improved immunogenicity. We sought to evaluate a conjugated vaccine using our rabbit model of ascending infection. STUDY DESIGN: Rabbit does were randomized to receive either conjugated group B streptococcal type Ia (Ia-tetanus toxoid) or conjugated group B streptococcal type III (III-tetanus toxoid) vaccine. Does were vaccinated 7 days before conception and 7 and 21 days after conception. On days 28 to 30 of a 30-day gestation, does were inoculated intracervically with 10(6) colony-forming units of type Ia group B Streptococcus. Labor was induced if does were undelivered after 72 hours. Does were observed up to 7 days after inoculation. Offspring were observed up to 4 days. We obtained maternal cultures from the uterus, peritoneum, and blood and offspring cultures from the mouth, anus, and blood. Antibody levels were also determined. RESULTS: Offspring survival was significantly improved in the group receiving Ia-tetanus toxoid (P =.047). Outcomes such as maternal sepsis and severe illness, although not reaching statistical significance, showed a trend toward improved outcomes in the Ia-tetanus toxoid group. CONCLUSIONS: This is the first study to evaluate the conjugated group B streptococcal vaccine by using any model of ascending infection. The Ia-tetanus toxoid vaccine led to improved survival and was immunogenic but fell short of its expected efficacy in preventing ascending group B streptococcal disease under these experimental conditions.

Fetal meconium peritonitis after maternal hepatitis A.

Hepatitis A virus has rarely been implicated in congenital infections. After maternal hepatitis A at 13 weeks' gestation, ultrasonographic examinations revealed fetal ascites (20 weeks) and meconium peritonitis (33 weeks). After delivery, a perforated distal ileum was resected. Elevated levels of hepatitis A immunoglobulin G persisted in the infant 6 months after delivery.

Oral quinolone in the treatment of experimental polymicrobial puerperal infection in rabbits.

OBJECTIVE: To evaluate the efficacy of oral levofloxacin in the treatment of experimental polymicrobial puerperal infection in the rabbit. METHODS: Timed pregnant rabbits were anesthetized on day 29 or 30 of a 31-day gestation and 106 colony-forming units each of Escherichia coli, group B streptococcus, and Staphylococcus saccharolyticus were inoculated endoscopically in the cervices. Labor was induced with intramuscular oxytocin 16 hours later if it had not occurred spontaneously. The animals then were observed every 3 hours for fever; when a temperature of 104F was reached, treatment was begun. Animals were assigned randomly in a blinded, placebo-controlled manner to received oral levofloxacin (10 mg/kg/day) or placebo and were treated twice daily for 4-5 days. The animals were killed and necropsy was performed 4-6 hours after the last dose. Specimens for culture were taken from uterine horns, peritoneum, and blood. Levofloxacin concentrations were determined from blood samples at necropsy. Clinical cure of fever, eradication of microbes, and presence of uterine abscesses at necropsy were assessed. RESULTS: Compared with placebo-treated rabbits, levofloxacin-treated animals had a significantly greater number of clinical cures (nine of 11 versus four of 12, P=.027) and significantly more eradication of E coli (ten of 11 versus five of 12, P=.022). Four uterine abscesses were seen in 12 placebo-tested animals, compared with none of 11 levofloxacin-tested animals (P=.093). There was no difference in eradication of group B streptococcus between the two groups. No blood cultures were positive for organisms in any animal. Levofloxacin was detected in all treated animals, but at low levels (less than 1 microg/mL). CONCLUSION: Treatment of experimental puerperal infection with oral levofloxacin in rabbits resulted in significantly more clinical cures and eradication of E coli compared with treatment with placebo.

Does reducing the number of prenatal office visits for low-risk women result in increased use of other medical services?

OBJECTIVE: To determine whether a schedule of fewer prenatal visits than traditional for women with low-risk pregnancies lead to additional medical services outside prescribed prenatal care. METHODS: In a randomized, controlled trial conducted within a group-model health maintenance organization, we studied 2328 pregnant women judged to be a low risk of adverse perinatal outcomes. After risk assessment and consent, women were assigned to an experimental (nine visits) or a control (14 visits) schedule, with additional visits if requested either by providers after identifying risks or by women seeking additional services. We recorded whether women underwent maternal serum alpha-fetoprotein screening, obstetric ultrasound examinations at 15-24 weeks' gestation, hematocrit testing after 20 weeks, and diabetic screening. We also noted visits to nonobstetric care providers or our emergency care center, telephone calls, and hospitalizations. RESULTS: We found no significant differences between the two groups for prenatal blood tests, visits to nonobstetric providers or to the emergency care center, telephone calls from patients, or hospital admissions. A significantly greater percentage of women underwent ultrasound examinations at 15-24 weeks in the control group compared with the experimental group (57.3% and 53.1%, respectively; P = .045). CONCLUSION: The reduction in prenatal visits achieved using the experimental schedule was not accompanied by an increase in the use of other medical services compared with the routine schedule. The use of the schedule proposed by the Expert Panel on the Content of Prenatal Care improved the efficiency of delivery of prenatal care to low-risk women.

A randomized controlled trial of a new fetal acoustic stimulation test for fetal well-being.

OBJECTIVES: Our purpose was to determine (1) whether a fetal acoustic stimulation test results in more palpable fetal movement compared with a mock test (control) and (2) whether palpated fetal movements after a fetal acoustic stimulation test are accompanied by a reactive nonstress test. STUDY DESIGN: In a randomized controlled trial we studied women seen in the labor and delivery suite for various indications. Women were excluded for multiple gestation, < 31 weeks' gestational age, treatment with magnesium sulfate or narcotics, or ruptured membranes. Informed consent was obtained from eligible women, who were then randomized to a test or control group. We placed an acoustic stimulator on the abdomen of each woman, but only the test group was stimulated. We assessed fetal movement by a grading system: 0 = no fetal movement felt by patient or tester, 1 = fetal movement felt by patient only, 2 = fetal movement felt by tester, 3 = visual movement seen by tester. A positive fetal acoustic stimulation test result was defined as one with any fetal movement felt or seen by the tester (grades 2 or 3). We then performed a nonstress test. We compared rates of a positive fetal acoustic stimulation test in the test and control groups with the chi 2 test. A p value < 0.05 was considered significant. RESULTS: We randomized 297 women to the test group and 280 women to the control (mock test) group. Of women tested with the fetal acoustic stimulation test. 81% had fetal movement by palpation or visualization (grades 2 or 3) compared with 19% of the control group (p < 0.0001, odds ratio 19.29, 95% confidence interval 12.42 to 30.07). Of the test group, 283 (95%) had a reactive nonstress test and 14 (5%) had nonreactive tests; the control group had 267 (95%) reactive and 13 (5%) nonreactive nonstress tests. Of 242 patients in the test group with a positive fetal acoustic stimulation test, 236 (98%) had a reactive nonstress test. Of those in the test group with fewer than three contractions per 10 minutes. 164 (89%) had a positive fetal acoustic stimulation test. Of these, 162 (99%) had a reactive nonstress test. CONCLUSION: The fetal acoustic stimulation test evokes significantly more palpated or visualized fetal movement than in controls. Palpated or visualized fetal movement after acoustic stimulation was almost always accompanied by a reactive nonstress test.

Compliance with a risk-factor-based guideline for the prevention of neonatal group B streptococcal sepsis.

OBJECTIVE: The purpose of this study was to determine the compliance rate with a maternal risk-factor-based guideline for the prevention of neonatal group B streptococcal (GBS) sepsis. METHODS: In August 1994, a risk-factor-based guideline for selective intrapartum prophylaxis against neonatal GBS was adopted by a group model health maintenance organization. This guideline identified the following maternal risk factors for neonatal GBS sepsis: preterm delivery, rupture of membranes for >18 h, fever/chorioamnionitis, and history of a previous GBS-affected child. Patients with one or more risk factors were to receive intrapartum antibiotic prophylaxis consisting of either ampicillin, erythromycin, or clindamycin. We conducted a retrospective chart review to record risk factors and use of antibiotics. We hypothesized that >90% of patients with risk factors would receive intrapartum chemoprophylaxis. RESULTS: A total of 805 maternal charts were reviewed. Of these, 105 (13%) were candidates for intrapartum prophylaxis. We found an overall compliance rate of 65%. Compliance rates by risk factor were preterm delivery (51%), prolonged rupture of membranes (73%), fever/chorioamnionitis (87%), and previous affected child (100%). CONCLUSIONS: Our results show unexpectedly low compliance rates with a risk-factor-based guideline for the prevention of neonatal GBS sepsis. Only 65% of women with any risk factor for neonatal GBS sepsis received intrapartum antibiotic prophylaxis appropriately. Educational efforts to improve compliance with a risk-factor-based guideline should specifically address mothers delivering at 34-36 weeks gestation and mothers with prolonged rupture of membranes.

Randomized, placebo-controlled trial of transplacental antibiotic prophylaxis of neonatal group B streptococcal colonization and bacteremia in rabbits.

OBJECTIVE: We evaluated the effect of maternal administration of ampicillin/sulbactam on colonization and bacteremia in newborn rabbits after intracervical inoculation of mothers with group B streptococci (GBS). METHODS: New Zealand white rabbits on day 30 of a 31-day gestation were inoculated intracervically with 10(4)-10(5) colony forming units (cfu) GBS. Two hours after inoculation mothers received ampicillin/sulbactam (50 mg/kg) or saline (control) intramuscularly as a single dose, in a randomized double-blinded manner. We induced labor 4 h later with intramuscular oxytocin. At delivery, cultures for GBS were taken from neonatal oropharynx. Thereafter, cultures were taken from neonatal oropharynx and anorectum daily and from neonatal heart at death or after 96 h. Sample size analysis showed a need for 17 pups in each group. RESULTS: In the control group, induction failed in one animal that was excluded from analysis. At birth, 0 of 39 pups of treated does had positive oropharyngeal cultures compared to 26 of 27 (96%) pups of saline-treated does (P < 0.0001). Pups treated with antibiotic in utero were also significantly less likely to have positive oropharyngeal cultures at 24, 48, and 72 h after birth compared to controls (24 h, 0% vs. 100%, P < 0.0001; 48 h, 8% vs. 100%, P < 0.0001; 72 h, 16% vs. 100%, P < 0.0001). Treated pups were significantly less likely to have positive anorectal cultures at 24, 48, and 72 h after birth compared to control animals (24 h, 0% vs. 100%, P < 0.0001; 48 h, 0% vs. 95%, P < 0.0001; 72 h, 0% vs. 92%, P < 0.0001). Treated pups were significantly less likely to have positive heart cultures at 72 h after birth compared to controls (11% vs. 92%, P < 0.0002). Cumulative neonatal survival was higher in treated pups compared to controls at 72 and 96 h after birth (72 h, 32% vs. 0%, P = 0.0003; 96 h, 26% vs. 0%, P = 0.015). CONCLUSIONS: Single dose transplacental prophylaxis given 4 h before delivery resulted in decreased neonatal GBS colonization and bacteremia and improved neonatal survival in rabbits.

The effect of timing of single-dose transplacental ampicillin-sulbactam therapy for prevention of neonatal group B streptococcal colonization and bacteremia in a rabbit model.

OBJECTIVE: Our purpose was to evaluate the effect of maternal administration of ampicillin-sulbactam on group B streptococcal colonization and bacteremia in newborn rabbits. STUDY DESIGN: Before induction of labor, timed pregnant New Zealand White rabbits on day 29 of a 31-day gestation received no therapy or ampicillin-sulbactam 50 mg/kg intramuscularly as a single dose 2 to 8 hours before delivery. Labor was induced with oxytocin. After delivery, the oropharynx of each pup was inoculated with 10(9) cfu of type la group B Streptococcus. Cultures of each pup were taken from the oropharynx and anorectum daily and from the heart at death or after 96 hours. Ampicillin-sulbactam concentrations were determined at delivery in both mothers and pups. RESULTS: Thirteen animals were assigned to no therapy and 14 animals to ampicillin-sulbactam. Untreated pups had 100% oropharyngeal colonization at 24 hours. Pups treated with antibiotic were significantly less likely to have positive oropharyngeal cultures at 24 and 48 hours after birth than did untreated pups (24 hours 47% vs 100%, p < 0.0001; 48 hours 68% vs 91%, p = 0.0006). For anorectal cultures treated pups were significantly less likely to have positive culture results. Heart cultures were also less likely to have positive results for treated animals at 48 and 72 hours than for untreated animals (48 hours 30% vs 96%, p = 0.0001; 72 hours 31% vs 71%, p = 0.03). Treated pups had higher rates of survival at 48 hours (89% vs 62%, p < 0.0001). When neonatal oropharyngeal colonization at 24 hours after birth was compared with length of time from maternal antibiotic injection to delivery, there was a significant polynomial relationship (r = 0.78, p < 0.05). Ampicillin-sulbactam serum concentrations were highest 3 to 5 hours after injection. An inverse relationship existed between the rate of neonatal oropharyngeal colonization with group B streptococci at 24 hours after birth and neonatal ampicillin serum concentrations near birth (r = 0.733). CONCLUSION: Transplacental treatment with a single intramuscular dose of ampicillin-sulbactam significantly decreased neonatal colonization and bacteremia after oral inoculation with type la group B Streptococcus. An effect of ampicillin-sulbactam was evident as early as 2 hours but maximal 3 to 5 hours after injection.

Ascending group B streptococcal genital infection in the rabbit model.

OBJECTIVE: We investigated in a pregnant rabbit model the effects of intravaginal inoculation of type la group B streptococci and antibiotic intervention. STUDY DESIGN: We inoculated 10(4) to 10(6) cfu of type la group B streptococci into the upper vagina hysteroscopically at day 21 to 27 of a 31-day gestation. Initially we studied the natural history in 23 animals and then allocated the next 31 animals to receive either no therapy or ampicillin-sulbactam intramuscularly beginning immediately after inoculation. Outcomes were delivery, fever, positive cultures for group B streptococci, any live fetuses, and maternal death. RESULTS: Without antibiotic treatment upper vaginal inoculation led to frequent complications, namely, fever in 44% (15/34), delivery in 41% (14/34), positive endometrial cultures in 47% (15/32), and positive blood cultures in 26% (7/27). Live fetuses were present in only 53% (18/34). Animals treated with antibiotics were significantly less likely to have fever (p < 0.01), positive endometrial cultures (p < 0.01), or positive blood cultures (p = 0.03) and were more likely to have a live fetus (p = 0.04) than untreated animals were. CONCLUSION: Upper vaginal inoculation with type la group B streptococci in the rabbit led to an ascending infection of the upper genital tract, causing serious adverse outcomes in 40% with bacteremia in 26%. Early antibiotic intervention significantly improved outcomes. The susceptibility of the rabbit to ascending perinatal group B streptococci infection makes it an appealing model for further work pertinent to human disease.

Newborn screening for HLA markers associated with IDDM: diabetes autoimmunity study in the young (DAISY).

Autoimmunity causing insulin-dependent diabetes mellitus (IDDM) begins in early childhood due to interactions between genes and unknown environmental factors that may be identified through follow-up of a large cohort of genetically susceptible children. Such a cohort has been established using a simple and rapid cord blood screening for HLA alleles. The DRB1 and DQB1 second exon sequences were co-amplified using the polymerase chain reaction and hybridized with single and pooled sequence-specific oligonucleotide probes. Four individual probes were used to detect the susceptibility alleles DRB1*03, DRB1*04, and DQB1*0302 as well as the usually protective DRB1*15/16 (DR2) alleles. In addition, pooled probes allow the distinction of DR3/3 from the DR3/x genotype (where x is neither DR2, 3, nor 4) and DR4/4 from DR4/x. Among 5000 newborns from the general Denver population, we have found the high-risk genotype (DRB1*03/ DRB1*04, DQB1*0302) to be present in 2.4% of non-Hispanic whites, 2.8% of Hispanics, and 1.6% of African Americans. The moderate-risk genotypes (DRB1*04, DQB1*0302/DRB1*04, DQB1*0302, DRB1*04, DQB1*0302/x, or DRB1*03/DRB1*03) are present in 17% of American non-Hispanic whites, 24% of Hispanics and in 10% of African Americans. These results demonstrate the feasibility of a large-scale newborn screening for genes associated with IDDM. The ultimate role for such a screening in future routine prediction and prevention of IDDM will depend on the availability of an effective and acceptable form of clinical intervention.

Beta-cell autoantibodies in infants and toddlers without IDDM relatives: diabetes autoimmunity study in the young (DAISY).

Little is known concerning the natural history of beta-cell autoimmunity in infants and toddlers, especially in those without a first degree IDDM relative. A population-based cohort of Colorado infants at increased IDDM risk due to their HLA genotype has been identified through a PCR-based HLA screening of cord blood and is being prospectively studied. We report the distribution of insulin (IAA), GAD65 (GAA), and ICA512 autoantibody levels in 312 children aged 9 months and in 131 children aged 15 months from this cohort, without family history of IDDM. The levels of IAA, GAA and ICA512 did not differ by the HLA genotype (DR3/4,DQB1*0302 vs. DR3/3, vs. DR2/DR4,DQB1*0302 vs. DRx/4,DQB1*0302, where x is not DR3 or DR2), by ethnicity (non-Hispanic whites vs. other ethnic groups), or by age (9 vs. 15 months). The 95th and 99th percentiles of the IAA distribution were respectively 40 and 61 nU/ml at the age of 9 months and 38 and 59 nU/ml at the age of 15 months. The 95th and 99th percentiles of the GAA distribution were respectively 0.020 and 0.046 at the age of 9 months and 0.022 and 0.098 at the age of 15 months. We propose to use IAA levels greater than 60 nU/ml and GAA index greater than 0.05 to define the presence of beta-cell autoimmunity in children younger than 2 years.

Prenatal screening using maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol: two-year experience in a health maintenance organization.

The objective of this study was to evaluate a 2-year experience in a health maintenance organization with mid-trimester maternal serum screening with alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and unconjugated estriol (UE) as a screen for fetal Down's syndrome. Women at 15-20 weeks gestation were offered triple marker screening. A patient-specific second trimester risk of 1:295 for Down's syndrome was used as a threshold for referral. Women at risk for trisomy 18 were identified by a protocol with fixed low cutoffs. The AFP threshold for referral for neural tube defects (NTD) was 2.0 multiples of the median (MoM). Patients at risk were offered ultrasonography, genetic counseling, and prenatal diagnosis. A total of 6,474 samples were drawn. The initial screen positive rate for Down's syndrome was 7.1%. After ultrasound evaluation, 351 (5.7%) of the remaining 6,197 women were still at risk for Down's syndrome. After genetic counseling, 292 (4.7%) women underwent prenatal diagnosis. Overall, 12 of 16 (75%) cases of Down's syndrome were detected antenatally by triple marker screening. Using AFP alone, only 3 of 14 (21%) cases of Down's syndrome in women under 35 years would have been detected. We detected 1 abnormal karyotype (including one 45, X) for every 22 amniocenteses performed for abnormal Down's syndrome screening. For trisomy 18, 13 women (0.2%) were at risk and, of these, 3 cases were diagnosed. All 6 cases of NTD during the study period were detected by AFP after identifying 3.8% of women as at risk. In conclusion, in the setting of a health maintenance organization where abnormal screening tests were managed by a single referral center, triple marker screening was effective not only for screening for fetal Down's syndrome, but also for trisomy 18 and NTD.

Effect of frequency of prenatal care visits on perinatal outcome among low-risk women. A randomized controlled trial.

OBJECTIVES: In 1989, the Expert Panel on the Content of Prenatal Care established guidelines on the timing and content of prenatal care, including a schedule consisting of fewer prenatal visits than traditionally provided, for women at low risk of adverse perinatal outcomes. We tested the hypothesis that there are no significant increases in adverse perinatal outcomes when low-risk women are seen in a prenatal care visit schedule of fewer visits than routinely advised. DESIGN: Randomized controlled trial. SETTING: Group-model health maintenance organization. PATIENTS: A total of 2764 pregnant women, judged to be at low risk of adverse perinatal outcomes. INTERVENTIONS: Following risk assessment, participants were randomly assigned to an experimental schedule (nine visits) or a control schedule (14 visits) with additional visits as indicated or as desired by the patient. MAIN OUTCOME MEASURES: Preterm delivery, preeclampsia, cesarean delivery, low birth weight and patient's satisfaction with care. RESULTS: On average, there were 2.7 fewer visits observed in the experimental group than in the control group. There were no significant increases in the main outcomes of the experimental group; preterm delivery (relative risk [RR], 1.08; 95% confidence interval [CI], 0.92 to 1.27; P = .19), preeclampsia (RR, 0.94; 95% CI, 0.78 to 1.14, P = .74), cesarean delivery (RR, 1.04; 95% CI, 0.93 to 1.17; P = .25), and low birth weight (RR, 0.94; 95% CI, 0.78 to 1.12; P = .76). There were no differences between the two groups in patients' satisfaction with quality of prenatal care. CONCLUSION: In this study, good perinatal outcomes and patient satisfaction were maintained when the prenatal visit schedule proposed by the Expert Panel on the Content of Prenatal Care was observed.

A comparison of aztreonam and two regimens of gentamicin in a rabbit model of intra-amniotic infection and sepsis.

OBJECTIVE: To compare aztreonam in a standard dose with two gentamicin doses in the early treatment of experimental intra-amniotic infection in rabbits induced by intracervical inoculation with Escherichia coli. METHODS: Timed pregnant rabbits on day 21 (70% of gestation) were inoculated intracervically with 10(4)-10(5) colony-forming units of E coli. After inoculation, the animals were treated with one of three regimens: 1) aztreonam at 90 mg/kg/day ("standard" dose in humans), 2) gentamicin at 4.5 mg/kg/day ("standard" dose in humans), or 3) higher-dose gentamicin at 6.0 mg/kg/day, each given in three divided doses daily. Outcomes included fever, delivery, and presence of a live fetus. At necropsy, cultures were taken from endometrium, amniotic fluid, and blood. Data were analyzed by Fisher exact test because the expected cell size was fewer than five. RESULTS: Compared with rabbits treated with aztreonam, those treated with gentamicin 4.5 mg/kg/day delivered significantly more often (P = .002), had more positive cultures (P < .001), and had significantly fewer live fetuses (P < .001). Compared with rabbits treated with gentamicin 6.0 mg/kg/day, those treated with gentamicin 4.5 mg/kg/day delivered more often (P = .003), had fewer live fetuses (P = .02), and had more positive cultures (P = .02). There were no significant differences between the aztreonam and gentamicin 6.0 mg/kg/day groups. CONCLUSIONS: This study demonstrates in an animal model that aztreonam and gentamicin at 6.0 mg/kg/day are more effective than gentamicin at 4.5 mg/kg/day (a dose that is widely used empirically in humans) in the early treatment of experimental intra-amniotic infection in rabbits. Aztreonam was as effective as gentamicin at 6.0 mg/kg/day. In this rabbit model, in which intra-amniotic infection is accompanied by maternal sepsis, 4.5 mg/kg/day of gentamicin was not adequate for the treatment of severe maternal infection.

Neonatal group B streptococcal sepsis during 2 years of a universal screening program.

OBJECTIVE: To assess the feasibility and efficacy of a protocol for universal screening for group B streptococci combined with selective intrapartum prophylaxis at a teaching hospital. METHODS: This is a descriptive study of experience with a standardized protocol in which patients were screened at 26-28 weeks with a rectal and genital culture placed directly in selective media. As risk factors, we used clinical chorioamnionitis, preterm birth, and rupture of the membranes greater than 12 hours. Participants were all women receiving prenatal care at our hospital. Major outcomes were compliance and neonatal sepsis due to group B streptococci. RESULTS: The prevalence of rectal and genital group B streptococci was 18.5% of 3721 screened women. Of culture-positive women, 35% developed risk factors (9% chorioamnionitis, 13% preterm birth, and 13% membrane rupture greater than 12 hours at term). With strict application of criteria, the compliance rate in administering indicated prophylaxis was 80.3%. Of women receiving prophylaxis, 42% had the first dose for 4 hours or less before delivery. There were five cases of group B streptococcal neonatal sepsis, resulting from either protocol violations, protocol failures, or both. Compared to the historic rate of group B streptococcal sepsis of 1.5 per 1000 births at our hospital, the rate in these 2 years was 1.0 per 1000 (1.6 per 1000 in the first year and 0.5 per 1000 in the second). CONCLUSIONS: It is feasible to conduct such a protocol, but compliance is only moderately good because the algorithm is complex. The protocol is not foolproof in preventing neonatal group B streptococcal sepsis, as there are protocol failures and violations.

Midtrimester hemoperitoneum caused by placenta percreta in association with elevated maternal serum alpha-fetoprotein level.

We report a case of hemoperitoneum in the second trimester due to placenta percreta which was associated with an elevated maternal serum alpha-fetoprotein. A 29-year-old woman, gravida 4, para 1-0-2-1, was seen at 17 weeks' gestation with an acute abdomen. Maternal serum alpha-fetoprotein in a sample drawn 1 week previously revealed a value of 5.0 multiples of the median. At laparotomy, placenta percreta was discovered. This case of placenta percreta diagnosed in the second trimester was associated with an elevated maternal serum alpha-fetoprotein level. Physicians counseling patients with unexplained elevated maternal serum alpha-fetoprotein levels should include placenta accreta or percreta in the differential diagnosis and should maintain an awareness of its existence in patients with acute abdomen in pregnancy.