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Background: Childhood infections are common and Bacillus Calmette-Guérin (BCG) vaccination at birth may prevent these via nonspecific effects. Methods: A randomized, clinical multicenter trial. All women planning to give birth (n = 16,521) at the three study sites were invited during the recruitment period. Participating children were randomized to receive BCG within 7 d of birth or to a no intervention control group. Parent-reported infections (events) were collected using telephone interviews at 3 and 13 mo. Data collectors were blinded to allocation. Results: The analyses included 4,224/4,262 (99%) and 4,192/4,262 (98%) children at 3 and 13 mo. From 0 to 3 mo, there were 291 events in the BCG group vs. 336 events in the control group, incidence rate ratio (IRR) = 0.87 (95% confidence interval (CI): 0.72 to 1.05). In this age group, the IRR was 0.62 (95% CI: 0.39 to 0.98) if the mother was BCG vaccinated. From 3 to 13 mo, there were 7,028 vs. 6,791 events, IRR = 1.02 (95% CI: 0.97 to 1.07). Conclusion: This study did not find a nonspecific public health benefit of BCG on parent-reported infections. BCG may have reduced the incidence of infections in children of BCG-vaccinated mothers during the first 3 mo.

Carbon dioxide-induced changes in near infrared spectrophotometry recordings were compared with changes in cerebral blood flow estimated by 133Xenon clearance (global cerebral blood flow (infinity)) at serial measurements in 24 mechanically ventilated preterm infants (mean gestational age 30.2 wk). In all infants, three measurements were taken at different arterial carbon dioxide tension levels (mean 4.4 kPa, range 2.1-7.8) obtained by adjustment of the ventilator settings. Mean arterial blood pressure changed spontaneously, whereas arterial oxygen tension was kept within normal range. At all wavelengths (904, 845, 805, and 775 nm), the OD increased at higher arterial carbon dioxide tension levels, indicating cerebral vasodilation. This conclusion was supported by conversion of the data to changes in oxygenated and deoxygenated Hb concentration. A parallel increase in cerebral blood volume index and global cerebral blood flow (infinity) was found (p less than 0.0001). The oxygenation level of cytochrome aa3 increased with increases in oxygen delivery (p less than 0.0001). This observation, however, may have been artifactual due to cross-talk between the oxidized cytochrome aa3 and the oxygenated Hb signals, as these signals were closely interrelated in the present experimental design. We suggest that near infrared spectrophotometry may be used for estimation of the cerebral blood volume index/cerebral blood flow-CO2 reactivity within a wide range of arterial carbon dioxide tension. Knowledge of the light path length would put this estimation on a quantitative basis.

Background and aims: Hypovolaemia constitutes a stress to systemic circulation. The place of volume expansion in ill newborn infants with low arterial blood pressure (ABP) is uncertain. Our hypothesis was that hypovolaemia would further reduce cerebral autoregulatory capacity (CA-capacity) at low ABP. Methods: Piglets (n=7, age 1-2 days) were anaesthetized with propofol and randomized to normovolaemia- hypovolaemia or hypovolaemia- normovolaemia. Hypovolaemia was induced by removal of $${\raise0.7ex\hbox{$1$} \!\mathord{\left/ {\vphantom {1 3}}\right.\kern-\nulldelimiterspace} \!\lower0.7ex\hbox{$3$}}$$ of the estimated blood volume. Normovolaemia was re-established by re-infusing the removed blood volume. A resting period of 30 minutes was interpolated after removal and re-infusion of the blood volume to enable recovery of cerebral autoregulation. CA-capacity was estimated from changes in cortical flux (laser-Doppler probe) to induced rises in ABP by inflation of a thoracic aorta balloon for 30 seconds. Subsequently, CA-capacity was calculated as %ΔCVR/%ΔABP (i.e. percentage of full autoregulatory capacity), where CVR was estimated as ABP/Doppler flux. Results: A total of 104 and 94 rises in ABP were analyzed during normo-and hypovolaemia, respectively. Hypovolaemia reduced mean ABP from 54±4 to 39±5 mmHg (P=0.02) and CA-capacity from 62±9 to 37±8% (P=0.05) (mean±SEM). CA-capacity was 56±3 at ABP above 40 mmHg compared to 33± 3 below 40 mmHg (P=0.00005). Analysis of variance demonstrated an interaction between hypovolaemia and ABP such that hypovolaemia reduced CA-capacity by 32% at ABP below 40 mmHg but not above (P=0.03). Conclusions: In newborn piglets CA-capacity appears to be reduced by hypovolaemia in itself. In this experiment, however, the level of ABP was the dominating determinant of CA-capacity.

BACKGROUND AND Aims: Impaired cerebral autoregulation (CA) is common and associated with brain damage in sick neonates. Frequency analysis between spontaneous changes in arterial blood pressure (ABP) and cerebral NIRS has been used to detect the presence and estimate the magnitude of this impairment. Coherence (i.e. correlation in the frequency-domain) detects its presence. Gain estimates its magnitude by analysing the magnitude of ABP-variability passing from systemic to cerebral circulation. We aimed to validate this dynamic method by comparing it with a static measurement of CA-capacity in piglets. Methods: Piglets (n=7, age 1-2 days) were anaesthetized and monitored during normo- and hypovolaemia. In both states, dynamic CA was estimated with analysis of coherence and gain between spontaneous changes in ABP and cerebral oxygenation (NIRS) in four 10-minutes epochs. Both before and after this dynamic period, static CA-capacity was estimated from changes in cortical flux (laser-Doppler probe) to induced rises in ABP by repeated inflations of a thoracic aorta balloon for 30 seconds. Subsequently, CA-capacity was calculated as %ΔCVR/%ΔABP (i.e. percentage of full autoregulatory capacity), where CVR (i.e. cerebral vascular resistance) was estimated as ABP/Doppler flux. Results: Linear regression demonstrated an inverse relationship between coherence and static CA-capacity (R2=38%, P=0.02). Likewise, linear regression indicated an inverse, however weak, relationship between gain and static CA-capacity, with R2 increasing from 1% (P=0.72) to 55% (P=0.09) when measurements with insignificant coherence were excluded. Conclusions: Frequency analysis of spontaneous changes in ABP and cerebral NIRS is associated with cerebral autoregulation as measured with laser-Doppler during ABP-challenge.

BACKGROUND AND Aims: Dopamine is widely used to treat hypotension in newborns. Data regarding its effect on the circulation in the brain, however, are ambiguous. To test for a direct effect on the brain, we estimated the magnitude of variability in arterial blood pressure (ABP) passing from systemic to cerebral circulation (i.e. frequency gain) during an ABP-challenge with dopamine in piglets. Methods: Piglets (n=7, age 1-2 days) were anaesthetized and monitored with NIRS (cerebral oxygenation) during normo- and hypovolaemia. In both states, ABP was challenged with dopamine during a 20-minute stepwise dose-increment (20, 30, 40 and 50 μg/kg/min). Each infusion lasted 2½ minutes. Pauses lasting 2½ minutes were interpolated. Before and after the dopamine-challenge, ABP was challenged with six inflations of a thoracic aorta balloon. Each inflation lasted 30 seconds and pauses lasting 30 seconds were interpolated. Subsequently, frequency gain between ABP and cerebral oxygenation was calculated (frequency range: 0.003-0.04 Hz). Results: Mean variability in ABP was 36±4.3 mm Hg during balloon challenge and 17±3.2 mm Hg during dopamine challenge (mean ±SEM). Mean gain between ABP and cerebral NIRS was 0.11±0.019 during ABP-challenge with the aorta balloon and 0.12±0.029 μM/mm Hg during ABP-challenge with dopamine (P=0.86). The mean difference was 0.01 [95%-CI: -0.07 to +0.09] Conclusions: ABP-variability induced by dopamine and by inflating an aortic balloon had similar effects on cerebral oxygenation. This suggests that dopamine has no direct constricting or dilating effect on the cerebral blood vessels or that such effects are counterbalanced by changes in cerebral oxygen uptake.

The peak amplitude of pulsatile cerebral electrical impedance (delta Zp) was compared with simultaneous 133xenon clearance estimations of cerebral blood flow (CBF infinity) on 28 occasions in nine infants receiving assisted ventilation who had changes in PaCO2 and thereby presumably in cerebral blood flow. Percentage changes from one measurement to the next in each infant were compared. Using linear regression the relationship was delta Zp = 0.5 CBF infinity-1.5 with r = 0.67. The 95% confidence interval for the regression coefficient was 0.2-0.8 and the mean residual was 28%. Changes in cerebral blood flow in these clinical conditions were similarly detected by the two methods but delta Zp underestimated the magnitude of the change in comparison with CBF infinity and its accuracy was insufficient to allow conclusions about the magnitude of small changes in cerebral blood flow in individual infants.

Central blood flow (CBF) was estimated by an intravenous 133-xenon technique in six preterm infants before and after administration of indomethacin for closure of patent ductus arteriosus. CBF fell in all infants (range 12%-40%), the mean fall was 24% (P less than 0.005). Though none of the infants showed signs of impaired cerebral function during or following the injections, the results do not indicate whether or not the use of indomethacin is a potential hazard.

Cerebral lesions in premature infants are usually found in the periventricular area, closely related to the optic tracts. Therefore, we have developed a simple set-up which allows repetive measurements of visual evoked potentials (VEP) during the first hours of life leaving the infants undisturbed in the incubator. Stimulation by single flashes during periods of quiet spontaneous EEG activity results in distinct VEPs. In 20 “healthy” newborns (27-34 gw) the latency decreased over a few hours coinciding with the increase in core temperature and with the recovery from slight respiratory- and/or metabolic acidosis. No changes in VEPs were observed in 4 infants with arterial hypotension (m-BP down to 20 mmHg) nor in 5 infants with hypocarbia (pCO2 down to 1.3 KPa). However, in 4 hypoxic infants (a-pO2 down to 2.5 KPa) the latency increased and the amplitude decreased markedly. Finally, in 9 premature infants with asymptomatic hypoglycemia (0.0-1.3; median 0.7 mmol/1) no effects on VEPs were detectable.