Efficacy of polymeric encapsulated C5a peptidase-based group B streptococcus vaccines in a murine model.

OBJECTIVE: The purpose was to examine in mice the efficacy of various polymeric-encapsulated C5a peptidase vaccine formulations in eliciting a long-term immune response and preventing group B streptococcus (GBS) infection. STUDY DESIGN: C5a peptidase was encapsulated in semipermeable microspheres of poly(lactide-coglycolide) (PLGA). Female ICR mice were immunized with 0, 10, or 30 µg of encapsulated C5a peptidase within 2 different formulations of PLGA polymers. Booster doses were given at weeks 4 and 8. Antibody responses were measured by enzyme-linked immunosorbent assay at weeks 4, 8, 11, and 40. Vaginal challenges with GBS types 1a, III, and V were performed at week 12. RESULTS: Thirty microgram doses of the 75:25 and 50:50 PLGA formulations generate the highest and most sustained C5a peptidase-specific immune responses. Mice that received encapsulated C5a peptidase were significantly protected from vaginal colonization compared with mice that received empty microspheres. CONCLUSION: Encapsulated C5a peptidase elicited significant immune responses and protection against a GBS challenge. C5a peptidase microsphere encapsulation has potential as a GBS vaccine.

Cord gas analysis, decision-to-delivery interval, and the 30-minute rule for emergency cesareans.

OBJECTIVE: Our primary objective was to examine the relationship between umbilical arterial gas analysis and decision-to-delivery interval for emergency cesareans performed for nonreassuring fetal status to determine if this would validate the 30-minute rule. STUDY DESIGN: For this retrospective cohort study, all cesarean deliveries performed for nonreassuring fetal status from September 2001 to January 2003 were reviewed. A synopsis of clinical information that would have been available to the clinician at the time of delivery and the last hour of the electronic fetal heart rate tracing prior to delivery were reviewed by three different maternal-fetal medicine specialists masked to outcome, who classified each delivery as either emergent (delivery as soon as possible) or urgent (willing to wait up to 30 minutes for delivery) since immediacy of the fetal condition is the key factor affecting the type of anesthesia used. RESULTS: Of 145 cesareans performed for nonreassuring fetal status during this period, 117 patients met criteria for entry, of which 34 were classified as emergent and 83 as urgent. Kappa correlation was 0.35, showing only fair/moderate agreement between reviewers. In the emergent group, general anesthesia was more common (35.3%, 10.8%, p=0.003), and the decision-to-delivery interval was 14 minutes shorter (23.0+/-15.3, 36.7+/-14.9 minutes, p<0.001). Linear regression showed a statistically significant relationship between increasing decision-to-delivery interval and umbilical arterial pH (r=0.22, p=0.02) and base excess (r=0.33, p<0.001) showing that delivery proceeded sooner for most of those with the worst cord gases, with a gradual improvement over time. For the 13 (11%) neonates with cord gases placing them at increased risk for long-term neurologic sequelae, the decision-to-delivery interval was 24.7+/-14.6 minutes (range 6 to 50 minutes), and 3/13 (23%) were classified as urgent rather than emergent. CONCLUSION: Electronic fetal monitoring shows considerable variation in interpretation among maternal-fetal medicine specialists and is not a sensitive predictor of the fetus developing metabolic acidosis. There is no deterioration in cord gas results after 30 minutes, and most neonates delivered emergently or urgently for nonreassuring fetal status even when born after 30 minutes have normal cord gases. The 30-minute rule is a compromise that reflects the time it takes the fetus to develop severe metabolic acidosis, our imprecision in its identification, and its rarity in the presence of nonreassuring fetal monitoring.

Neonatal cerebral white matter injury in preterm infants is associated with culture positive infections and only rarely with metabolic acidosis.

OBJECTIVE: Neonatal cerebral white matter injury represents a major precursor for neurological impairment and cerebral palsy. Our objective was to identify risk factors associated with its development. STUDY DESIGN: This retrospective case-control study of all births between 23 and 34 weeks gestation at a single university hospital between May 1994 and September 2001 identified 150 cases with white matter injury characterized by periventricular leukomalacia or ventricular dilatation from white matter atrophy that were chromosomally normal and did not have other congenital anomalies. Cases were matched to controls without brain injury by the next delivery within 7 days of their gestational age. RESULTS: There were small differences between controls and cases in gestational age (27.5 +/- 2.7, 27.4 +/- 2.6 weeks, P = .01) and birth weight (1053 +/- 402, 966 +/- 285 g, P = .002) that were statistically but not clinically significant. There was no difference in the percentage of controls and cases delivered by cesarean (45%, 49%, P = .64). There were no differences between controls and cases in umbilical arterial pH (7.27 +/- 0.11, 7.25 +/- 0.15, P = .19), base excess (-2.1 +/- 2.7, -3.0 +/- 4.1 mmol/L, P = .28), pH less than 7.0 (2/122 [2%], 3/107 [3%], P = 1.0), or base excess less than -12 mmol/L (4/121 [3%], 6/106 [6%], P = .75). The cases had a significant increase in positive blood (19%, 29%, P = .036), cerebrospinal fluid (6%, 17%, P = .002), and tracheal (9%, 22%, P = .003) cultures during the neonatal period. Conditional logistic regression showed a significant association among multiple gestations ( P = .02), intraventricular hemorrhage ( P < .001), and positive tracheal cultures ( P = .02) with cerebral white matter injury. CONCLUSION: Culture-positive infection was associated with an increased risk of cerebral white matter injury in preterm neonates. Intrapartum hypoxia-ischemia as manifested by metabolic acidosis was rarely associated with white matter injury and was not different from the incidence in premature neonates without injury.

Nulliparity and duration of pregnancy in multiple gestation.

OBJECTIVE: We sought to test the hypothesis that nulliparous women with multiple gestations would be more likely to have shorter gestational durations, a higher frequency of previable deliveries, and fewer pregnancy complications when compared with parous women. METHODS: We reviewed the medical records of women who delivered a multiple gestation at 15 or more weeks at 2 institutions between January 1, 1990 and June 30, 2002 (n = 1,035). We recorded demographic data, medical complications, and pregnancy outcomes and analyzed these using paired t tests for continuous variables, chi(2) for categorical variables, and linear regression analysis for the effect of multiple variables on the primary outcome variable, gestational age at delivery. RESULTS: There was a statistically significant difference in mean gestational age at delivery (34 versus 34.9 weeks, P =.006) between the nulliparous and multiparous groups after excluding women with a history of previous preterm birth and/or midtrimester loss. There were no differences between groups in the likelihood of delivering before 20, 24, or 28 weeks. In linear regression analysis, ongoing fetal number (P <.001), premature rupture of membranes (PROM; P <.001), cerclage (P =.002), and death of 1 or more fetuses (P <.001) were associated with shorter gestation. Cesarean delivery was associated with longer gestation (P <.001). Nulliparous women were significantly more likely to have a pregnancy complicated by hypertension (20.8% versus 9.2%, P <.001), diabetes (7% versus 4%, P =.03), or PROM (24.4% versus 17.3%, P =.006). CONCLUSION: Nulliparous women with a multiple gestation deliver their pregnancies, on average, 0.9 weeks earlier than parous women and more frequently experience hypertension, diabetes, and PROM. They are not, however, more likely to deliver before 24 weeks of gestation.