Cerebrovascular autoregulation in preterm fetal growth restricted neonates.

OBJECTIVE: To investigate the effect of fetal growth restriction (FGR) on cerebrovascular autoregulation in preterm neonates during the first 3 days of life. DESIGN: Case-control study. SETTING: Neonatal intensive care unit of the Wilhelmina Children's Hospital, The Netherlands. PATIENTS: 57 FGR (birth weight <10th percentile) and 57 appropriate for gestational age (AGA) (birth weight 20th-80th percentiles) preterm neonates, matched for gender, gestational age, respiratory and blood pressure support. METHODS: The correlation between continuously measured mean arterial blood pressure and regional cerebral oxygen saturation was calculated to generate the cerebral oximetry index (COx). Mean COx was calculated for each patient for each postnatal day. The percentage of time with impaired autoregulation (COx>0.5) was also calculated. RESULTS: FGR neonates had higher mean COx values than their AGA peers on day 2 (0.15 (95% CI 0.11 to 0.18) vs 0.09 (95% CI 0.06 to 0.13), p=0.029) and day 3 (0.17 (95% CI 0.13 to 0.20) vs 0.09 (95% CI 0.06 to 0.12), p=0.003) of life. FGR neonates spent more time with impaired autoregulation (COx value >0.5) than controls on postnatal day 2 (19% (95% CI 16% to 22%) vs 14% (95% CI 12% to 17%), p=0.035) and day 3 (20% (95% CI 17% to 24%) vs 15% (95% CI 12% to 18%), p=0.016). CONCLUSION: FGR preterm neonates more frequently display impaired cerebrovascular autoregulation compared with AGA peers on days 2 and 3 of life which may predispose them to brain injury. Further studies are required to investigate whether this impairment persists beyond the first few days of life and whether this impairment is linked to poor neurodevelopmental outcome.

Effects of caffeine on the preterm brain: An observational study.

BACKGROUND AND AIM: Caffeine improves neurodevelopmental outcome of preterm infants. This study analyses the effects of caffeine on the neonatal brain. We hypothesized that caffeine has a neuroprotective effect through an increase in oxygen metabolism; reflected by increased cerebral oxygen extraction, electrical function, and perfusion. METHODS: Preterm infants <32 weeks gestation (GA) receiving their primary dose caffeine-base (10 mg/kg) were included. Ten minutes of stable monitoring were selected before, during, and every hour up to 6 h after caffeine. Near-infrared spectroscopy monitored regional cerebral oxygenation (rScO2) and extraction (FTOE). Amplitude-integrated electroencephalogram (aEEG) monitored minimum, mean and maximum amplitudes. Spontaneous activity transients (SAT) rate and the interval between SATs (ISI) were calculated. Mean arterial blood pressure (MABP), heart rate (HR) and arterial oxygen saturation (SaO2) were monitored. Arterial pCO2's were collected before and 4 h after caffeine. Brain perfusion was assessed 1 h before and 3 h after caffeine by Doppler-measured resistance-index (RI), peak systolic velocity (PSV) and end-diastolic velocity (EDV), in the anterior cerebral artery (ACA) and internal carotid artery (ICA). Results were presented in mean ±â€¯SD. RESULTS: 34 infants, mean GA 28.8 ±â€¯2.1 wk, were included. rScO2 significantly decreased from 69 ±â€¯11 to 63 ±â€¯12 1 h after caffeine, and recovered at 6 h (66 ±â€¯10). FTOE increased correspondingly. MABP and HR increased significantly. PSV in the ACA decreased slightly. Other Doppler variables, aEEG parameters, and SaO2 were unaffected. CONCLUSION: Caffeine increases oxygen extraction, suggesting a (transient) stimulating effect on brain metabolism. However, no substantial changes were found in brain perfusion and in electrical brain activity.

Carbon Dioxide Fluctuations Are Associated with Changes in Cerebral Oxygenation and Electrical Activity in Infants Born Preterm.

OBJECTIVES: To evaluate the effects of acute arterial carbon dioxide partial pressure changes on cerebral oxygenation and electrical activity in infants born preterm. STUDY DESIGN: This retrospective observational study included ventilated infants born preterm with acute fluctuations of continuous end-tidal CO2 (etCO2) as a surrogate marker for arterial carbon dioxide partial pressure, during the first 72 hours of life. Regional cerebral oxygen saturation and fractional tissue oxygen extraction were monitored with near-infrared spectroscopy. Brain activity was monitored with 2-channel electroencephalography. Spontaneous activity transients (SATs) rate (SATs/minute) and interval between SATs (in seconds) were calculated. Ten-minute periods were selected for analysis: before, during, and after etCO2 fluctuations of ≥5 mm Hg. RESULTS: Thirty-eight patients (mean ± SD gestational age of 29 ± 1.8 weeks) were included, with 60 episodes of etCO2 increase and 70 episodes of etCO2 decrease. During etCO2 increases, brain oxygenation increased (regional cerebral oxygen saturation increased, fractional tissue oxygen extraction decreased; P < .01) and electrical activity decreased (SATs/minute decreased, interval between SATs increased; P < .01). All measures recovered when etCO2 returned to baseline. During etCO2 decreases, brain oxygenation decreased (regional cerebral oxygen saturation decreased, fractional tissue oxygen extraction decreased; P < .01) and brain activity increased (SATs/minute increased, P < .05), also with recovery after return of etCO2 to baseline. CONCLUSION: An acute increase in etCO2 is associated with increased cerebral oxygenation and decreased brain activity, whereas an acute decrease is associated with decreased cerebral oxygenation and slightly increased brain activity. Combining continuous CO2 monitoring with near-infrared spectroscopy may enable the detection of otherwise undetected fluctuations in arterial carbon dioxide partial pressure that may be harmful to the neonatal brain.

Reduction in Cerebral Oxygenation due to Patent Ductus Arteriosus Is Pronounced in Small-for-Gestational-Age Neonates.

BACKGROUND: A haemodynamically significant patent ductus arteriosus (hsPDA) reduces cerebral oxygenation in appropriate-for-gestational-age (AGA) preterm neonates. Reduced cerebral oxygenation has been associated with brain injury. Preterm small-for-gestational-age (SGA) neonates show higher cerebral oxygenation than AGA peers throughout the first postnatal days. To date, no studies have investigated the effect of hsPDA on cerebral oxygenation in preterm SGA neonates. OBJECTIVE: We aimed to assess the effect of hsPDA on cerebral oxygenation in preterm SGA neonates compared to AGA peers. We hypothesised that higher baseline cerebral oxygenation would reduce the impact of hsPDA on cerebral oxygenation in preterm SGA neonates. METHODS: We monitored regional cerebral oxygen saturation (rScO2) with near-infrared spectroscopy and calculated the cerebral fractional tissue oxygen extraction (cFTOE) for 72 h after birth. Retrospective analysis compared 36 preterm SGA neonates (birth weight <10th percentile, 18 with hsPDA) to 36 preterm AGA neonates (birth weight 20th to 80th percentile, 18 with hsPDA). RESULTS: In contrast to the other groups, SGA-hsPDA neonates demonstrated a significant fall in rScO2 [69% (SEM 2.5) at 4-8 h to 61% (2.7) at 68-72 h, p < 0.001] with a concurrent rise in cFTOE [0.26 (0.026) at 4-8 h to 0.34 (0.030) at 68-72 h, p < 0.001]. CONCLUSIONS: Contrary to our hypothesis, hsPDA had a significant negative effect on cerebral oxygenation in preterm SGA neonates. Future studies should explore the potential benefits of early screening and treatment for hsPDA on long-term neurodevelopmental outcome in preterm SGA neonates.

Growth restriction and gender influence cerebral oxygenation in preterm neonates.

OBJECTIVE: To investigate the effect of fetal growth restriction and gender on cerebral oxygenation in preterm neonates during the first 3 days of life. DESIGN: Case-control study. SETTING: Neonatal Intensive Care Unit of the Wilhelmina Children's Hospital, The Netherlands. PATIENTS: 68 (41 males) small for gestational age (SGA) (birth weight <10th percentile) and 136 (82 males) appropriate for gestational age (AGA) (birth weight 20th-80th percentile) neonates, matched for gender, gestational age, ventilatory and blood pressure support. METHODS: Regional cerebral oxygen saturation (rScO2) and cerebral fractional tissue oxygen extraction (cFTOE) as measured by near-infrared spectroscopy throughout the first 72 h of life were compared between SGA and AGA neonates. The effect of gender was also explored within these comparisons. RESULTS: SGA neonates demonstrated higher rScO2 (71% SEM 0.2 vs 68% SEM 0.2) and lower cFTOE (0.25 SEM 0.002 vs 0.29 SEM 0.002) than AGA neonates. There was an independent effect of gender on rScO2 and cFTOE, resulting in the finding that SGA males displayed highest rScO2 and lowest cFTOE (73% SEM 0.3 respectively 0.24 SEM 0.003). AGA males and SGA females showed comparable rScO2 (69% SEM 0.2 vs 69% SEM 0.4) and cFTOE (0.28 SEM 0.002 vs 0.28 SEM 0.004). AGA females showed lowest rScO2 and highest cFTOE (66% SEM 0.2 respectively 0.30 SEM 0.002). CONCLUSIONS: Growth restriction and gender influence cerebral oxygenation and oxygen extraction in preterm neonates throughout the first 3 days of life.

Brain-Sparing in Intrauterine Growth Restriction: Considerations for the Neonatologist.

Intrauterine growth restriction (IUGR) is most commonly caused by placental insufficiency, in response to which the fetus adapts its circulation to preserve oxygen and nutrient supply to the brain ('brain-sparing'). Currently, little is known about the postnatal course and consequences of this antenatal adaptation of the cerebral circulation. The altered cerebral haemodynamics may persist after birth, which would imply a different approach with regard to cerebral monitoring and clinical management of IUGR preterm neonates than their appropriately grown peers. Few studies are available with regard to this topic, and the small body of evidence shows controversy. This review discusses the cerebral circulatory adaptations of IUGR fetuses and appraises the available literature on their postnatal cerebral circulation with potential clinical consequences.

Perfusion Index in Preterm Infants during the First 3 Days of Life: Reference Values and Relation with Clinical Variables.

BACKGROUND: The perfusion index (PI) derived from pulse oximetry readings represents the ratio of pulsatile (arterial blood) and nonpulsatile contributors to infrared light absorption. PI has been shown to correlate with cardiac performance. In theory, PI is readily available on every pulse oximeter; therefore, no additional sensors or infant handling are required. Currently, reference values are lacking in (preterm) neonates and the association with common clinical conditions is unclear. OBJECTIVES: To establish reference values for the PI in premature infants and at the same time determine the influence of common clinical conditions. METHODS: PI was prospectively monitored on the lower limb for 72 h in 311 neonates born with a gestational age <32 weeks between January 2011 and December 2013. Longitudinal mixed-effects modeling was used. Linear, quadratic, and cubic models were explored. Main effects and interactions were investigated. RESULTS: A squared model (0-24 h) followed by a linear model (24-72 h) provided the best fit of the data. PI was lowest around 12-18 h after birth and showed a steady increase thereafter. PI was positively related with female gender, gestational age, and pulse pressure. Negative associations were found with SIMV/HFOV ventilation, dopamine administration, mean arterial blood pressure, and arterial oxygen saturation. Although more complex, the general association with a patent ductus arteriosus was positive. CONCLUSION: PI varied according to several clinical conditions. The association with common clinical factors suggests that PI might be used for monitoring neonatal hemodynamics and possibly as an additional guidance for interventions.

Hypotension in preterm neonates: low blood pressure alone does not affect neurodevelopmental outcome.

OBJECTIVE: To compare neurodevelopmental outcome, mean arterial blood pressure (MABP), and regional cerebral oxygenation (rSco2) between preterm neonates treated for hypotension and controls. STUDY DESIGN: Preterm neonates (N = 66) with a gestational age (GA) ≤32 weeks, without a patent ductus arteriosus, treated for hypotension (dopamine ≥5 µg/kg/min) were included. Neonates were matched to controls for GA, birth weight, sex, and year of birth. The rSco2 was determined by using near-infrared spectroscopy. Monitoring of MABP, rSco2, and arterial saturation was started at admission and continued for at least 72 hours. Neurodevelopmental outcome was assessed at 18 and 24 months' corrected age by using the Griffiths Mental Development Scales or the Bayley Scales of Infant and Toddler Development, Third Edition. RESULTS: Infants treated for hypotension spent more time with an MABP less than GA (median 9% vs 0%, P < .001) and time with an MABP/rSco2 correlation >0.5 (27% vs 17%, P < .001). Time spent with an rSco2 <50% and neurodevelopmental outcome at 18 and 24 months' corrected age were not significantly different between infants treated for hypotension and controls. The 26 neonates with an rSco2 <50% for >10% of time had a lower neurodevelopmental outcome at 18 months (median 99 vs 104, P = .02). CONCLUSION: An MABP less than GA (in weeks) was not associated with lower rSco2 or with lower neurodevelopmental outcome scores. However, regardless of MABP, low rSco2 was associated with lower neurodevelopmental outcome scores. Perfusion/oxygenation variables could be of additional value in neonatal intensive care.

Tocolytic indomethacin: effects on neonatal haemodynamics and cerebral autoregulation in the preterm newborn.

BACKGROUND: Indomethacin has vasoactive properties in cerebral and systemic vascular beds, and it improves cerebral autoregulatory ability. We speculated that tocolytic indomethacin will improve cerebral autoregulatory ability in the very preterm infant in early postnatal life. METHODS: Eighteen stable preterm infants gestational age (GA) 25.3-29.6 weeks, birth weight (BW) 660-1430 grams), whose mothers had received 50-150 mg of tocolytic indomethacin within 24 h before birth, and 18 individually matched controls (GA 25.0-29.7 weeks, BW 700-1390 grams) were studied four times for 15 min in the first 24 h of life. Autoregulation was assessed by determining correlations between mean arterial blood pressure (MABP (mm Hg)) and near-infrared spectroscopy-monitored cerebral oxygenation (rScO2). RESULTS: MABPs were significantly higher in the indomethacin infants than in the control infants (p=0.03). A decreased ability to autoregulate was found in four of the indomethacin infants, and in six of the control infants, which is not significantly different. CONCLUSIONS: Prenatally administered indomethacin, given as a tocolytic in doses of 50-150 mg per day, improved transitional circulation in very preterm infants by significantly raising the MABP. It did not have an effect on the ability to autoregulate the cerebral circulation. In this study, no differences in short-term outcomes, like haemorrhagic or ischaemic cerebral lesions, were observed.

Cerebral oxygenation, extraction, and autoregulation in very preterm infants who develop peri-intraventricular hemorrhage.

OBJECTIVE: To test the hypothesis that near-infrared spectroscopy (NIRS)-determined patterns of regional cerebral oxygen saturation (rScO2), cerebral fractional tissue oxygen extraction (cFTOE), and autoregulatory ability can identify neonates at risk for developing peri-intraventricular hemorrhage (PIVH). STUDY DESIGN: This case-control study is a subanalysis of 30 neonates who developed PIVH >12 hours after admission as part of a lager prospective observational cohort study comprising 650 preterm neonates born at ≤32 weeks' gestational age. PIVH was diagnosed by cranial ultrasound, performed at least once daily. Mean arterial blood pressure (MABP), NIRS-determined rScO2, cFTOE, and MABP-rScO2 correlation were monitored from birth to 72 hours of age. RESULTS: Infants with PIVH received more inotropic drugs before being diagnosed with PIVH. Significantly more infants with severe PIVH needed treatment for patent ductus arteriosus. The MABP-rScO2 correlation was >0.5 significantly more often before mild/moderate PIVH and after severe PIVH compared with controls. rScO2 was higher and cFTOE lower in infants before severe PIVH. CONCLUSION: NIRS-monitored rScO2 and cFTOE suggest cerebral hyperperfusion in infants with severe PIVH. Moreover, MABP-rScO2 correlation indicates more blood pressure-passive brain perfusion in infants with PIVH. Continuous assessment of patterns of cerebral oxygenation and arterial blood pressure may identify those preterm infants at risk for severe PIVH and prompt consideration of preventive measures.

Cerebral oxygenation and oxygen extraction in the preterm infant during desaturation: effects of increasing FiO(2) to assist recovery.

BACKGROUND: In the clinical setting, episodes of desaturation in newborn infants are often treated by increasing the fraction of inspired oxygen (FiO(2)). OBJECTIVES: To study the effect of an increase in FiO(2) on cerebral oxygenation during recovery from desaturation, as measured by near-infrared spectroscopy (NIRS). METHODS: Peripheral arterial saturation (SaO(2)), NIRS-monitored cerebral saturation (rScO(2)), and fractional cerebral oxygen extraction (cFTOE) were analyzed in the first 3 days of life during 6 episodes of desaturation (SaO(2) <75%, >30 s) in each of 24 otherwise stable spontaneously breathing preterm infants (gestational age 29.8 ± 1.5 weeks, birth weight 1,215 ± 280 g; mean ± SD), during 3 episodes without and 3 episodes with increased FiO(2) during recovery from desaturation. RESULTS: Post-recovery SaO(2) with increased FiO(2) was significantly higher than post-recovery SaO(2) without increased FiO(2). Post-recovery SaO(2) and rScO(2) were significantly increased over baseline saturations when FiO(2) was increased. Post-recovery rScO(2) was very high for several minutes in some cases, while cFTOE was highly suggestive of oxygen delivery that exceeded consumption. CONCLUSIONS: Assuming that NIRS-measured rScO(2) is an indicator of cerebral oxygen content, an increase in FiO(2) to assist recovery from desaturation may cause hyperoxygenation of the brain in relatively stable preterm infants. This procedure may be particularly harmful in the sick very preterm infant with limited regulation of brain circulation and poorly developed antioxidant defenses.