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OBJECTIVE: To confirm previous known relationships between Fetal Inflammatory Response Syndrome (FIRS) and neonatal bronchopulmonary dysplasia (BPD) and to present information on previously unknown special relationships between inflammatory variables and BPD. STUDY DESIGN: At delivery, we obtained biological specimens including umbilical cord venous blood for plasma interleukin-6 levels, as well as placental histology and bacteriology. Among other neonatal outcomes, we collected prospective information on BPD. RESULTS: Of 141 newborns in the study, 16 had BPD; 79% of these had antecedent FIRS, 27% of those without FIRS had BPD. By multivariable regression, only very low birth weight (adjusted [adj] odds ratio [OR] 32.0, 95% Confidence Interval [CI] 5.0 to positive infinity) and FIRS (adj OR 5.7, 95% CI 1.1 to 42.3) remained significant risk factors. Escherichia coli, perhaps due to its pyogenic nature (strongly elicits inflammatory responses), may have had a special relationship with BPD. CONCLUSIONS: In our data, FIRS and neonatal BPD are highly associated. It is possible that certain pyogenic bacteria in the chorioamnion space may be implicated more often than others. CONDENSATION: Neonates having Fetal Inflammatory Response Syndrome at delivery may later develop BPD. Pyogenic bacteria, such as Escherichia coli, may be implicated more frequently. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether there is an unconfounded association between neonatal intraventricular hemorrhage (IVH) and lenticulostriate vasculopathy (LSV (also known as thalamostriate or mineralizing vasculopathy))., Study Design: During the conduct of the Magnesium and Neurologic Endpoints Trial (MagNET), a randomized controlled trial involving maternal, hence fetal, exposure to antenatal magnesium sulfate in the context of preterm labor, head ultrasounds were obtained for each of the surviving neonates. Because of our previous experience in the diagnosis of LSV, when ascertaining the presence of IVH, as called for by the research protocol of our study, the presence or absence of LSV was also determined., Results: We found LSV to be relatively prevalent (10% (14 of 140) among surviving babies). More importantly, it was significantly associated with the occurrence of neonatal IVH, even when controlled for possible confounding (adjusted OR 9.8, 95% confidence interval 1.3 to 73.1; p=0.03)., Conclusion: Given the known relationships between IVH and neonatal morbidity and mortality, the finding of a statistically significant association between neonatal IVH and LSV may suggest more substantial implications for the latter than previously believed.

Objective: To find out whether there is an association between cultures positive for coagulase negative staphylococci (CONS) taken from babies in the Neonatal Intensive Care Unit (NICU) and a subsequent outcome of cerebral palsy., Study Design: At delivery, we obtained cultures from the chorioamnion space and, when medically indicated, we obtained bacterial cultures from children in the NICU. Surviving neonates underwent final examination for cerebral palsy at age 18 months., Results: Of six children in the Magnesium and Neurologic Endpoints Trial who had cerebral palsy, chorioamnion cultures had been obtained for five of six. Four of these five children (80%) had CONS-positive cultures, whereas 26 of 102 (25%) children without cerebral palsy were CONS positive (p = 0.02). In the NICU, of children with cerebral palsy, the prevalence of culture-proven CONS was 80% (4/5); for those without cerebral palsy, the prevalence was 17% (15/86) (p = 0.01). Using multivariable logistic regression to control for confounding, CONS in the chorioamnion remained significant (adjusted odds ratio [OR] 37.7, 95% confidence interval [CI] 3.0 to +infinity; p = 0.003). However, when controlled for extremely low birth weight, nonvertex presentation, and being on a ventilator > or = 20 days, the association between culture-proven CONS in the NICU and cerebral palsy became insignificant (adjusted OR 3.0, 95% CI 0.2 to +infinity; p = 0.42)., Conclusion: CONS in the chorioamnion space are associated with cerebral palsy, but in these data, CONS in the NICU are not found to be associated with cerebral palsy.

To determine whether common carotid artery blood flow measured with an ultrasonic flow transducer would predict brain blood flow in fetal sheep, we measured unilateral common carotid artery blood flow and compared this to simultaneous measurements of total brain blood flows made by radioisotope-labelled microsphere techniques. We studied anaesthetized, exteriorized fetal sheep with intact umbilical circulation after ligation of extracranial, extracerebral arteries and placement of a common carotid artery flow transducer; five fetuses at 120 d gestation had 19 total comparison measurements. As measured by microsphere technique, mean basal blood flow during undisturbed conditions to regional brain areas were similar to normal values reported for the exteriorized ovine fetus; these flows were highly correlated to fetal PaCO2 and successfully varied over a wide range (total brain 9.1-200.4 ml/min/100g and total cortex 6.1-153.1 ml/min/100g) in subsequent experimental conditions of hypercapnia or occluded blood flow. Blood flow as measured by flow transducer significantly correlated (P < or = 0.01) with microsphere measurements of blood flow to total brain (r = 0.56) and total cortex (r = 0.62); regional flow to cerebellum (r = 0.70) and thalamus (r = 0.60) also correlated to transducer measurements. Stronger correlations were observed at low-flow conditions to total brain (r = 0.83) and to total cortex (r = 0.90). As measured by microsphere technique, right and left cortical blood flows were highly correlated (P = 0.0001, r = 0.97), indicating that the flow transducer or surgical manipulation did not disturb the distribution of cerebral blood flow. The mean values for zero flow reference of the transducer were < 1.5% of mean basal flow values. It is concluded that the common carotid artery flow transducer technique developed in this study provides an accurate prediction of blood flow to total brain and total cortex over a wide range of values in fetal sheep. This technique provides a methodologic advantage to sequential experimental interventions and may prove advantageous to studies of fetal sheep cerebral circulation.

To describe the clinical causes of fetal death in black women, we performed a record review of the primary causes of fetal deaths (n = 315, > or = 500 g or > or = 24 weeks' gestation) occurring over an 11-year period in a population of 26,852 black women who delivered at the Chicago Lying-in Hospital, University of Chicago Hospitals, Chicago, IL. The over-all fetal death rate (FDR) per 1,000 total births was 11.7, consistent with U.S. vital statistics data for blacks. The FDR per 10,000 births attributed to hypertension was nine times greater in our population than in a historical comparison population of Canadian white women: 19.5 (95% CI = 13.7, 25.4) versus 2.2 (P < .0001), respectively, although the prevalence of hypertension was only 1.2 times greater in the population of black women. Furthermore, hypertension in pregnancy accounted for 15% of the excess fetal mortality in our population of urban black women as compared to the population of Canadian white women. Health care providers should be aware of the risk of fetal death in hypertensive, innercity, U.S. black women.

Drugs, such as cocaine, which may alter monoamine neurotransmitter responsiveness, could adversely affect the regulation of cerebral vasculature. Cocaine exhibits at least two mechanisms that may alter vascular responsiveness: synaptic uptake inhibition, which may augment response to stimulation, and Na+ channel inhibition, which may attenuate response. To help elicit the concentration-dependent effects of cocaine, the effects of cocaine on monoamine neurotransmitter responsiveness were studied in vitro on fetal sheep cerebral arteries (120 days gestation). The changes in diameter of segments of cannulated, pressurized fetal sheep cerebral artery were measured with a videomicroscaler system. Cumulative concentration-response curves (10(-10) to 10(-4)M) were generated for two monoamines, norepinephrine and serotonin, alone and in the presence of cocaine (10(-5) or 10(-4)M). Cocaine caused concentration-dependent alteration of response. At 10(-4)M, cocaine attenuated mean maximal norepinephrine-induced vasoconstriction 46.2% (P < 0.05). At 10(-5)M, cocaine increased sensitivity to norepinephrine (log EC50 decreased -6.63 +/- 0.09 to -7.11 +/- 0.03) and to serotonin (log EC50 decreased -7.24 +/- 0.04 to -7.81 +/- 0.09) (P < 0.05). The higher concentration of cocaine (10(-4)M) did not significantly decrease log EC50 norepinephrine. Cocaine (10(-4)M) also attenuated the response to single doses of norepinephrine (10(-6)M) and serotonin (10(-6)M) by 26.5% and 40.0%, respectively (P < or = 0.05). It is concluded that cocaine has concentration-dependent effects on vasoconstriction of the fetal sheep cerebral artery in vitro. This cocaine-induced alteration of cerebral vascular responsiveness to monoamines may be important in the regulation of fetal cerebral blood flow.

alpha-Chloralose is a commonly used anesthetic agent in cardiovascular research despite a paucity of information whether it may have important pharmacologic interaction with subsequently given adrenergic drugs. To assess any potential pharmacologic interaction, we studied the cardiovascular response to beta-adrenergic receptor antagonism (propranolol, 1 mg/kg i.v.) after either chloralose (30 mg/kg i.v.) or saline control in paired studies in 10 chronically instrumented neonatal lambs. Chloralose increased heart rate by 46% as compared to control (283 +/- 37 vs. 194 +/- 48 beats/min, p = 0.0002) and had no significant effect on cardiac output; chloralose also increased mean pulmonary arterial pressure by 45% (27 +/- 13 vs. 19 +/- 6 mm Hg, p = 0.050) and pulmonary vascular resistance by 79% (0.211 +/- 0.13 vs. 0.118 +/- 0.04 mm Hg/ml/kg/min, p = 0.050). The group pretreated with chloralose had significantly elevated heart rate (186 +/- 23 vs. 157 +/- 31 beats/min, p = 0.03), mean pulmonary arterial pressure (29 +/- 9 vs. 22 +/- 6 mm Hg, p = 0.03) and pulmonary vascular resistance (0.228 +/- 0.13 vs. 0.130 +/- 0.05 mm Hg/ml/kg/min, p = 0.05) after propranolol as compared to the conscious saline-treated group. We conclude that pretreatment with chloralose as an anesthetic agent may produce important pharmacologic interaction with subsequent adrenergic drugs in neonatal lambs. While anesthesia may be necessary in animal research, investigators should be aware that the anesthetic agent may also qualitatively and quantitatively influence measured outcome variables.

Although group B beta-hemolytic streptococcus (GBS) causes pathologic hemodynamic alterations in both human neonates and neonatal animal models of sepsis, little is known about strain-dependent differences in hemodynamic responses to GBS. This study compared pulmonary and systemic hemodynamic dose-response profiles in conscious neonatal lambs with three different strains of heat-killed GBS originally isolated from infected human neonates (group 1: serotype Ib, early-onset sepsis; group 2: serotype Ib, necrotizing enterocolitis; and group 3: serotype III, meningitis). Regression models of hemodynamic responses were characterized after lambs were injected with heat-killed GBS (dose range 0.1-6.0 x 10(9) colony-forming units, i.v.). All three GBS strains caused dose-dependent increases in mean pulmonary arterial pressure and pulmonary and systemic vascular resistances and decreases in cardiac output and heart rate. The GBS strain used in group 1 caused a greater effect on mean pulmonary arterial pressure and systemic vascular resistance than those used in groups 2 and 3 and was the only strain to cause an increase in mean systemic arterial pressure. The GBS strains used in groups 1 and 2 had a greater effect on pulmonary vascular resistance than that used in group 3. No group differences were observed in cardiac output and heart rate responses, which were, however, influenced by age, gender, and duration of postoperative recovery of the lambs. No attenuation or augmentation of hemodynamic effect was observed after sequential doses of 10(9) colony-forming units of GBS given in a single day. This study demonstrates strain-dependent quantitative differences in pulmonary vascular response and qualitative differences in systemic vascular response to heat-killed GBS.

We conducted a prospective cohort study of 323 consecutively born very low birth weight infants (< or = 1499 gm) to determine any association between prenatal cocaine exposure and (1) intracranial ultrasonographic abnormalities and (2) other adverse perinatal outcomes. The infants were assigned to either a cocaine-exposed group (n = 86) or a cocaine-nonexposed group (n = 146) on the basis of combined detection methods for prenatal maternal cocaine abuse including maternal history, maternal and infant urine immunoassay (Emit), and meconium analysis (high-performance liquid chromatography and gas chromatography-mass spectrometry). Ninety-one infants were not assigned because of early death before complete testing (n = 80) or missed tests (n = 11). The detected incidence of cocaine exposure in the assigned population was 37% (86/232). Meconium testing with high-performance liquid chromatography and gas chromatography-mass spectrometry was the sole means of detection in 30% (26/86) of cases. The cocaine-nonexposed infants did not differ from the cocaine-exposed infants in the incidence of intraventricular hemorrhage (36% vs 35%), grades III and IV intraventricular hemorrhage (14% vs 14%), or periventricular leukomalacia (4% vs 2%). Adverse outcomes increased by cocaine exposure were abruptio placentae (8% vs 18%; p = 0.046), surgical ligation of a patent ductus arteriosus (1% vs 7%; p = 0.02), and seizures (5% vs 17%; p = 0.004). We conclude that prenatal cocaine exposure does not increase the incidence or severity of intracranial hemorrhage or periventricular leukomalacia but does increase the risk of abruptio placentae, surgical ligation of a patent ductus arteriosus and seizures in very low birth weight infants.

alpha-Chloralose is an anesthetic commonly used in cardiovascular research. Using a chronically instrumented neonatal lamb model, we previously determined that chloralose has important effects on basal hemodynamics and arterial oxygen tension as compared with those of paired conscious control lambs. We wished to determine whether beta-adrenergic receptor stimulation accounted for chloralose-induced hemodynamic effects and to investigate the influence of chloralose and beta-adrenergic receptor antagonism on oxygen metabolism. In paired studies, five lambs were given chloralose intravenously (30 mg/kg i.v.) after propranolol (1 mg/kg i.v.) or saline control. The group pretreated with propranolol had reduced heart rate (HR 206 +/- 12 vs. 244 +/- 10 beats/min, p = 0.04) and cardiac output (CO 253 +/- 29 vs. 302 +/- 40 ml/min/kg, p = 0.005) 30 min after chloralose as compared with control; pretreatment with propranolol also attenuated the systemic hypertensive response to chloralose (77 +/- 8 vs. 89 +/- 5 mm Hg, p = 0.055). No difference in the response of stroke volume (SV), atrial or pulmonary arterial pressures, or pulmonary and systemic vascular resistances (PVR, SVR) were observed between treatment groups. No differences between propranolol and saline treatment groups were observed in arterial and mixed venous oxygen contents, arteriovenous (A-V) oxygen difference, oxygen extraction, or oxygen consumption; a reduction in oxygen delivery observed after propranolol as compared with saline was not altered by chloralose. We conclude that tachycardia and increase in CO induced by chloralose in lambs probably are mediated by beta-adrenergic receptor stimulation, which may be direct or indirect.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophylline, a methyl xanthine, has been used for many years in the treatment of apnea of prematurity and bronchospasm. Aminophylline relaxes smooth muscle through several proposed mechanisms. We hypothesized that aminophylline might be effective in relaxing preconstricted pulmonary vascular smooth muscle and would be ideally suited for clinical trial in babies with pulmonary hypertension. To test this hypothesis, the haemodynamic response of chronically instrumented newborn lambs to injections of heat-killed Group B beta-hemolytic Streptococcus (GBS) and leukotriene (LT) D4, potent pulmonary vasoconstrictors was compared before and after pretreatment with a clinically therapeutic dose of intravenous aminophylline. GBS (10(9)cfu) significantly increased pulmonary arterial pressure 130%. LTD4 (1.0 microgram/kg) significantly increased pulmonary arterial pressure 142% and systemic arterial pressure 23% and decreased cardiac output 47%. Aminophylline did not significantly affect the baseline variables or alter the pulmonary or systemic haemodynamic response to either stimuli. Therefore, it is unlikely that aminophylline will be clinically useful in the treatment of babies with persistent pulmonary hypertension whose etiology is infectious or leukotriene-mediated.

A solid-phase extraction method was developed for the extraction of first-day meconium samples from premature infants of cocaine-dependent mothers. Extracts were analysed by high-performance liquid chromatography and gas chromatography-mass spectrometry for cocaine and its metabolites. Control stools showed no drug. Meconium from cocaine-dependent mothers showed cocaine in the range 0.1-0.78 micrograms/g. Benzoylecgonine, ecgonine and ecognine methyl ester were not present in the samples, which suggests that the metabolism of cocaine in the premature neonate is limited.

Anesthetic agents are required when restraining animals in most forms of animal research. In particular, alpha-chloralose is a widely used anesthetic for respiratory and cardiovascular research despite limited controlled studies investigating whether chloralose could represent a variable influencing cardiorespiratory reflexes in acute animal studies. We previously used a chronically-instrumented neonatal lamb model to determine that chloralose had important effects on oxygen delivery and on basal hemodynamics. To investigate the influence of chloralose on oxygen metabolism and catecholamine secretion in relation to these hemodynamic changes, we studied 12 lambs before and after infusion of chloralose (30 mg/kg, i.v.) or control saline vehicle. Chloralose caused no differences in arterial or mixed venous oxygen contents, arterio-venous oxygen difference, or oxygen delivery, consumption, or extraction.(ABSTRACT TRUNCATED AT 250 WORDS)