Immature fetal sheep exposed to LPS had profound reductions in placental blood flow and cerebral O(2) delivery, which could contribute to fetal brain injury. Reduced O(2) delivery to white matter was similar to that in other brain regions. Mechanisms that enable fetal CBF to increase in hypoxemic conditions were apparently ineffective in the presence of LPS.

Fetal exposure to maternal alcohol intake can be harmful to the developing brain but the effects of acute exposures are less well documented. Our objective was to determine the effects of acute alcohol exposure on developing white matter and to investigate the potential role of pro-inflammatory cytokines. Fifteen pregnant ewes underwent surgery at 110.0+/-1.0 days of the 147 day gestation for fetal catheterization. Ethanol (1g/kg maternal weight) was administered intravenously to 8 ewes for 1h on 3 consecutive days at 116.0+/-1.0 days of gestation (0.8 of full term); 7 pregnant control ewes received saline. Fetal brains were collected at necropsy 5 days after the initial ethanol exposure and processed for structural analysis. Maternal and fetal blood ethanol concentrations reached maximal values (0.11+/-0.01 g/dL) 1h after infusions commenced, declining to zero thereafter. Ethanol exposure did not cause fetal hypoxemia, acidemia, hypercapnia, hypoglycemia or hypotension. Subcortical white matter injury, defined as microglia/macrophage infiltration, axonal disruption, increased apoptosis, astrogliosis and altered glial cell morphology, was observed in 4 of the 8 ethanol-exposed fetuses. The injury occupied 6.6-18.3% of the cross-sectional area of cerebral white matter examined and was substantial in 2/8 and modest in 2/8 ethanol-exposed fetuses. Three remaining fetuses exhibited astrogliosis and elevated levels of apoptosis in cerebral white matter. There was a positive correlation between maternal and fetal blood ethanol concentrations and the extent of brain damage. There was no significant elevation in concentrations of the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta and interleukin-6 in fetal plasma. Developing white matter in the late gestation fetus is vulnerable to acute alcohol exposure, but mechanisms remain unclear.

Immature fetal sheep exposed to LPS had profound reductions in placental blood flow and cerebral O(2) delivery, which could contribute to fetal brain injury. Reduced O(2) delivery to white matter was similar to that in other brain regions. Mechanisms that enable fetal CBF to increase in hypoxemic conditions were apparently ineffective in the presence of LPS.

Background: Controversy exists whether early adrenal insufficiency is present in preterm infants (PIs) or not. Urinary cortisol production rates (CPRs) provides an integrated index of adrenal function. The aim of this prospective study was to compare CPRs between well and ill PIsϽ 30 weeks gestational age.Methods: PIs were classified according to clinical criteria and the score for neonatal acute physiology (SNAP). All major neonatal glucocorticoid metabolites (GMs) (nϭ14) were profiled by gas chromatography-mass spectrometry in 24-h urinary samples. Excretion rates of GMs were summed to calculate CPRs (g/kg/d/mg creatinine). We developed an own non invasive urine collection procedure using specially manufactured cellulose nappies and extraction by hydraulic press. Results: CPRs were determined in 17 well (27.9 Ϯ 1.8 wk; 1078 Ϯ 321g) and 44 ill (27.3 Ϯ 1.6; 984 Ϯ 257) PIs. Medians of SNAP and CPRs of ill (well) PIs were given in the Bult, Neonatology, Hannover, Germany; 4 Olgahospital, Neonatology, Stuttgart, Germany; 5 Hannover, Screeninglabor, Hannover, Germany Background: A systemic perinatal inflammatory response is known to be a risk factor of severe intraventricular hemorrhage (IVH) in preterm infants. Molecular markers predicting susceptibility to cerebral morbidity in premature infants are missing. Genetic polymorphisms in the tumor necrosis factor (TNF) -gene are known to modify TNF expression. ASSOCIATION OF TWO TUMOR NECROSIS FACTOR POLYMORPHISMS WITH THE INCIDENCE OF SEVERE INTRAVENTRICULAR HEMORRHAGE IN PRETERM IN-FANTSAims: To study the incidence of biallelic polymorphisms of the TNF alpha promoter region and NcoI polymorphism of the TNF beta gene in premature infants with severe IVH.Methods: Study subjects: A double blinded retrospective cohort study was carried out on stored Guthrie blood spot cards. 27 premature infants Ͻ32 weeks of gestational age with sonographic finding of severe IVH at day 7 postnatal age (grade III IVH or IVH with apparent periventricular hemorrhagic infarction) and 102 healthy newborn infants (Ͼ32ϩ0 weeks of gestation, no signs of severe IVH on ultrasound examination at 7 days postnatal age) were included in the study. TNF allele distribution of the study population was also compared to cohorts of healthy adult volunteers. Laboratory investigation: To detect microsatellite nucleotide polymorphism in the TNF gene, polymorphism of the TNF alpha promoter-308 region and NcoI polymorphism of TNF beta gene was assessed using polymerase chain reaction (PCR) followed by melting curve analysis or NcoI digestion.Results: The overall allele frequency and genotype distribution of the -308 TNF-alpha polymorphism were comparable with values found in controls and no difference was found with regards to gender. The overall incidence of the TNF beta 2 allele was higher in the IVH group compared to the control group (81.5% vs.63.2%; pϭ0.01). Allele distribution of a polymorphic site within the TNF beta locus in the male patient group significantly differed from the distribution in the c...