Emily Ling

Biochemical mediators of meningeal inflammatory response to group B streptococcus in the newborn piglet model

ABSTRACT: The meningeal inflammatory response to a heat-killed mutant unencapsulated strain of type III group B Streptococcus (GBS) was studied in a newborn piglet model. GBS (109 colony-forming unit equivalents) or saline (control) was inoculated intraventricularly. Serial cerebrospinal fluid measurements were done at baseline and over the course of the next 24 h for cytochemical changes and production of tumor necrosis factor (TNF) and prostaglandins. In separate experiments, we defined the time course of early changes during the first 6 h and dose response relationship over a range of inocula 106 to 109 colony-forming unit equivalents. The intraventricular inoculation of the heat-killed unencapsulated GBS induced marked leukocytosis and increased protein by 6 h. These changes were preceded by a several hundredfold increase in TNF (maximum at 2 h) and prostaglandins (maximum at 2–4 h). The early and sharp rise in TNF suggests its pivotal role in initiating the inflammatory cascade. The magnitude of the inflammatory response increased with increasing bacterial dose over the range studied. To study the effect of encapsulation of GBS in the induction of meningeal inflammation, we compared the response to the unencapsulated mutant strain with that to the encapsulated parent strain. The encapsulated strain produced much smaller inflammatory changes, and only with high doses of bacteria. The GBS cell wall appeared to be the primary bacterial product triggering inflammation. Intraventricular injection of the heat-killed unencapsulated GBS with exposed cell wall can serve as a valid model for studying neonatal meningitis.

Neonatal autoimmune thrombocytopenia: role of high-dose intravenous immunoglobulin G therapy.

SummaryHigh-dose intravenous immunoglobulin G (IVIgG) therapy results in a rapid reversal of thrombocytopenia in over 80% of children with acute immune thrombocytopenic purpura (ITP). Comparable results were observed in eleven infants with an analogous condition, neonatal autoimmune thrombocytopenia (NATP), who received IVIgG (2 g/kg body weight) administered alone (n=6) or in combination with steroids (n=5). The median platelet count pre-IVIgG therapy was 25×109/l (range 5 to 74×109/l). The overall response rate to IVIgG therapy, administered alone or in combination with steroids was 75% (12 of 16 treatment episodes). A good response to therapy was defined as an increase in the platelet count to ⪖ 50×109/l and at least twice the pre-treatment value at 48 h after completion of the IVIgG infusion. The rapid and generally excellent response to IVIgG therapy in infants with NATP suggests that this treatment approach should be considered as first-line therapy for severely thrombocytopenic infants with this self-limiting but potentially serious disorder.

HAS THE 18-MONTH OUTCOME FOR EXTREMELY LOW GESTATIONAL AGE (ELGA) INFANTS OF 23-25 WEEKS GESTATION IMPROVED? † 1614

Our purpose was to examine the neurodevelopmental outcome at 18 months corrected age of surviving ELGA infants of 23-25 weeks gestation born in 1991-3, and to compare the results with those from an earlier cohort born in 1983-9 (Synnes A et al J Pediatr 1994:125:952-60). ELGA infants delivered in British Columbias tertiary perinatal center had their gestational age (GA) ascertained as accurately as possible by early ultrasound and dates using predetermined criteria. There were no survivors at <23 weeks in the two time periods. The results of multidisciplinary assessments performed at a corrected age of 18 months were reviewed for survivors of 23-25 weeks GA. Major impairment was defined as a Bayley MDI below -2 s.d., definite signs of cerebral palsy (CP), visual acuity in the better eye with optimal refractive correction worse than 20/200, or sensorineural hearing loss requiring amplification. Of 111 live births, 48 survived to 18 months corrected age and follow-up data was available in 35 (73%). 4 of 12 infants with major impairment, had multiple impairments. The recent cohort was smaller in size(3-year vs 7-year period) and the follow-up rate was lower (73% vs 93%), with a sampling bias toward the lower birthweight infants. Survival rate (to discharge) for 23-25 weeks GA has not improved (44% vs 44%) and the survivors had comparable incidence of major impairment at 18 months (34%; vs 36% resp.). Of children with impairments, multiple impairments were present in 33% (vs 38% in earlier cohort). As there were so few 23 week babies, the results were re-analyzed for infants 24-25 weeks GA. Survival (53% vs 50%) and impairment rate (32% vs 34%) remained not statistically different. There is no evidence in this survey that the introduction of recent innovations such as surfactant therapy has produced any improvement in outcomes for the smallest babies.Table

CEREBROVASCULAR PROSTANOID PRODUCTION IN NEONATAL GROUP B STREPTOCOCCAL MENINGITIS. † 1777

Group B Streptococcal (GBS) meningitis impairs cerebral blood flow (CBF) autoregulation in newborn piglets. We determined whether the early impairment could be related to increased prostaglandin (PG) production and if dexamethasone and ibuprofen alter PG production in the early phase (1st 6 hrs) of GBS meningitis. Net cerebrovascular PG production (calculated as total CBF× (sagittal-arterial plasma PG concentration) of 6-keto-PGF1α (stable metabolite of prostacyclin), TXB2(thromboxane B2) and PGE2 were measured in 4 groups of piglets given either 1) saline 0.5 ml intracerebroventrically (icv, control grp, n=9), 2) GBS alone (109 cfu/0.5 ml GBS icv, n=7), or 3) GBS icv plus dexamethasone (DEX) 1 mg/kg intraarterial, ia, n=8) or 4) GBS icv plus ibuprofen (IBU) 30 mg/kg ia,n=7) during periods of normotension (MABP= 50-90 mmHg), hypotension (MABP 90mmHg). MABP was randomly adjusted by balloon tipped catheters in the aortic root and descending aorta. CBF was measured by radioactive microsphere technique and PGs were measured by radioimmunoassay. Results show that within each treatment group there was a decrease in cerebrovascular production of 6 keto-PGF1α, TXB2 and PGE2 (p < 0.05) during hypotension possibly due to relative depletion in tissue oxygen for cyclo-oxygenation of arachidonate. However, between treatment groups (Control, GBS alone, GBS+DEX, and GBS+IBU) PG production did not change with BP adjustments except for increased PGE2 during cerebral hypertension(mean±SD, PGE2=250±25 ng/min/100 g brain tissue) compared to hypotension in GBS alone (PGE2=325±30 ng/min/100 g brain, p< 0.05). Irrespective of MABP, cerebral PG production is highest for PGE2, followed by 6-keto PGF1α with no production of TXB2. Since cerebral PG production is minimally influenced by GBS with or without DEX or IBU over a wide range of cerebral perfusion pressures, we suggest that vasoactive mediators other than PGs may mediate CBF impairment in early meningitis. Thus, treatment directed to PGs may not prevent CBF impairment in neonatal GBS meningitis.

Ethical Impact of Changing Trends in Management and Outcomes of Infants at the Limit of Viability |[diams]| 159

Ethical Impact of Changing Trends in Management and Outcomes of Infants at the Limit of Viability ♦ 159

HYALINE MEMBRANE DISEASE AS AN EARLY PREDICTOR OF THE NEED FOR DEXAMETHASONE IN THE TREATMENT OF BRONCHOPULMONARY DYSPLASIA † 1077

Dexamethasone (Dex) is an effective drug in the treatment of bronchopulmonary dysplasia (BPD) and there is some evidence that early Dex may be better at reducing inflammation and minimizing lung damage. However Dex is a potent drug with potential serious side effects. We wished to identify which babies develop severe BPD and would therefore be potential candidates for early Dex. We retrospectively studied all babies 30%.

PREVALENCE OF IN-UTERO DRUG USE IN VANCOUVER BY MECONIUM TESTING † 1201

Accurate Canadian prevalence data on drug use in pregnancy is lacking as self reporting is likely to be unreliable and urine screening detects only recent drug exposure. The purposes of this epidemiologic study were to assess:(1) prevalence of drug use in pregnancy, using meconium testing (2) correlation with self-reporting (3) demographics of pregnant drug users.

INCIDENCE OF CONGENITAL ANOMALIES IN A NEONATAL INTENSIVE CARE UNIT (NICU)

A one-year study (1985) review showed a high proportion of infants with congenital anomalies admitted to the NICU of our perinatal center. Congenital anomalies were present in 79 (10%) out of 790 admissions.Classification of the congenital anomalies fell into two groups. 1) Single defect (51%): Deformation-2; Malformation-38 (CSV 12, GU 10, Pulm.7, CNS 6, GI 3). II) Multiple anomalies (49%): Chromosomal-13; Monogenic-11, Unknown-15 (i.e. about 40% of the multiple congenital anomalies could not be diagnosed).Clinical profile of these infants will be presented in percentage and compared to the overall NICU admission in brackets. 1) Gestational age, range 25-42 wks: preterm 73% [76%]; full-term 27% [24%]. 2) Intrauterine growth retardation in 22% [6%]. 3) Multiple births in 6% [16%]. 4) Fetal anomalies were suspected antenatally in 65%. 5) Delivery by cesarean section occurred in 43% [38%] and was performed primarily for fetal reasons in 74%. Of these, 64% had lethal congenital anomalies, chromosomal disorders or recognized syndromes with grave outcome. 6) Mortality in NICU was 25% [10%]; all of these deaths were attributed to congenital anomalies, none to prematurity. Another 10% [1%] died within the first year after discharge/transfer. 7) These cases accounted for 2580 patient-days (13% of NICU workload).These findings raise concerns about the perinatal diagnosis and management of neonates with congenital anomalies, particularly those suspected antenatally.