Gunnar Naulaers

Monitoring Neonatal Regional Cerebral Oxygen Saturation in Clinical Practice: Value and Pitfalls

This review focuses on the clinical use of near infrared spectroscopy (NIRS) to assess brain oxygenation by the tissue oxygenation index (TOI), and monitoring regional cerebral oxygen saturation (rScO2), cerebral fractional tissue oxygen extraction (cFTOE), which is derived from rScO2, and systemic oxygen saturation. Its precision and pitfalls are discussed. At this stage, it is clear that NIRS-monitored oxygenation of the brain by rScO2 or TOI lacks the precision required to be used as a robust quantitative variable to monitor cerebral oxygenation. Intra- and especially interpatient variability are too large for this aim. On the other hand, when used merely as a trend monitor in the individual patient, substantial changes in rScO2 or TOI and consequently of cFTOE, larger than the limits of agreement, can yield important clinical information that suggest an intervention. Since neonatal intensive care is for a substantial part ‘brain orientated’ this approach seems conceivable. This gives rise to the conclusion that NIRS-monitored TOI, rScO2 and cFTOE increasingly will have a role in clinical practice as semiquantitative indicators of changes in cerebral oxygenation and oxygen extraction. Combination with other (cerebral) parameters such as amplitude-integrated EEG and blood pressure seems promising for further optimization of monitoring the immature brain.

Use of Tissue Oxygenation Index and Fractional Tissue Oxygen Extraction as Non-Invasive Parameters for Cerebral Oxygenation

Objective: To evaluate the relation between cerebral tissue oxygenation index (TOI), measured with spatially resolved spectroscopy (SRS), and the different oxygenation parameters. To evaluate the relation between a new parameter named fractional tissue oxygen extraction (FTOE) and the cerebral fractional oxygen extraction (FOE). Methods: Six newborn piglets were measured at 33, 35, and 37°C and in hypocapnia. Mean arterial blood pressure (MABP), haemoglobin (Hb), peripheral oxygen saturation (S_aO₂) and P_aCO₂ were measured at each step. Cerebral blood flow (CBF) was measured by injection of coloured microspheres into the left atrium. Jugular bulb oxygen saturation (JVS), cerebral arterial and venous oxygen content (C_aO₂ and C_vO₂) and FOE were calculated. TOI of the brain was calculated and FTOE was introduced as (S_aO₂ – TOI)/S_aO₂. The correlation was calculated with an ANCOVA test. Results: There was a positive correlation (R = 0.4 and p = 0.011) between TOI and JVS. No correlation was found with CBF, MABP or Hb. There was a positive correlation between P_aCO₂ and cerebral TOI (R = 0.24 and p = 0.03). FTOE correlated well with FOE (R = 0.4 and p = 0.016) and there was a negative correlation between FTOE and P_aCO₂ (R = 0.24, p = 0.03). Conclusion: The measurement of TOI and FTOE by SRS correlated well with the cerebral venous saturation and FOE, respectively.

Effect of Treatment of Subclinical Neonatal Seizures Detected With aEEG: Randomized, Controlled Trial

OBJECTIVES: The goals were to investigate how many subclinical seizures in full-term neonates with hypoxic-ischemic encephalopathy (HIE) would be missed without continuous amplitude-integrated electroencephalography (aEEG) and whether immediate treatment of both clinical and subclinical seizures would result in a reduction in the total duration of seizures and a decrease in brain injury, as seen on MRI scans. METHODS: In this multicenter, randomized, controlled trial, term infants with moderate to severe HIE and subclinical seizures were assigned randomly to either treatment of both clinical seizures and subclinical seizure patterns (group A) or blinding of the aEEG registration and treatment of clinical seizures only (group B). All recordings were reviewed with respect to the duration of seizure patterns and the use of antiepileptic drugs (AEDs). MRI scans were scored for the severity of brain injury. RESULTS: Nineteen infants in group A and 14 infants in group B were available for comparison. The median duration of seizure patterns in group A was 196 minutes, compared with 503 minutes in group B (not statistically significant). No significant differences in the number of AEDs were seen. Five infants in group B received AEDs when no seizure discharges were seen on aEEG traces. Six of 19 infants in group A and 7 of 14 infants in group B died during the neonatal period. A significant correlation between the duration of seizure patterns and the severity of brain injury in the blinded group, as well as in the whole group, was found. CONCLUSIONS: In this small group of infants with neonatal HIE and seizures, there was a trend for a reduction in seizure duration when clinical and subclinical seizures were treated. The severity of brain injury seen on MRI scans was associated with a longer duration of seizure patterns.

L-Thyroxine Treatment of Preterm Newborns: Clinical and Endocrine Effects

Preterm newborns have low serum thyroxine (T4) levels compared with late-gestational fetuses. Low thyroid hormone levels are associated with increased severity of neonatal illness and neurodevelopmental dysfunction. We assessed the endocrine and clinical effects of increasing serum T4 levels in preterm newborns with a gestational age <31 wk. Forty newborns were randomized in a double blind protocol: 20 infants received a daily dose of 20 μg/kg l-T4 for 2 wk, whereas 20 control infants received saline. Serum concentrations of T4, triiodothyronine (T3), reverse T3 (rT3), thyroglobulin (TG), and TSH were measured weekly as well as serum levels of GH, prolactin, and IGF-I. After 2 wk, a TSH-releasing hormone (TRH) test was performed. Neonatal illness and outcome was evaluated by noting heart rate, oxygen requirement, duration of ventilation, development of chronic lung disease, oral fluid intake, and weight gain; a Bayley score was done at the corrected age of 7 mo. l-T4 administration induced a marked increase in serum T4 without apparent change in T3 levels, whereas the postnatal decline in serum rT3 was more gradual. l-T4 treatment was associated with a decrease in serum TG and TSH levels. TRH injection induced a definite rise in serum TSH and T3 in controls, but not in L-T4 treated newborns. Neither l-T4 treatment, nor TRH administration appeared to alter circulating levels of prolactin, GH, or IGF-I. In contrast to the pronounced endocrine effects, no clinical effects of l-T4 administration were detected.

Pediatric Outcome after Maternal Cancer Diagnosed during Pregnancy.

BACKGROUND Data on the long-term outcome of children who are exposed to maternal cancer with or without treatment during pregnancy are lacking. METHODS In this multicenter case-control study, we compared children whose mothers received a diagnosis of cancer during the pregnancy with matched children of women without a cancer diagnosis. We used a health questionnaire and medical files to collect data regarding neonatal and general health. All children were prospectively assessed (by means of a neurologic examination and the Bayley Scales of Infant Development) at 18 months, 36 months, or both. A cardiac assessment was performed at 36 months. RESULTS A total of 129 children (median age, 22 months; range, 12 to 42) were included in the group whose mother had cancer (prenatal-exposure group) with a matching number in the control group. During pregnancy, 96 children (74.4%) were exposed to chemotherapy (alone or in combination with other treatments), 11 (8.5%) to radiotherapy (alone or in combination), 13 (10.1%) to surgery alone, 2 (1.6%) to other drug treatments, and 14 (10.9%) to no treatment. Birth weight was below the 10th percentile in 28 of 127 children (22.0%) in the prenatal-exposure group and in 19 of 125 children (15.2%) in the control group (P=0.16). There was no significant between-group difference in cognitive development on the basis of the Bayley score (P=0.08) or in subgroup analyses. The gestational age at birth was correlated with the cognitive outcome in the two study groups. Cardiologic evaluation among 47 children at 36 months of age showed normal cardiac findings. CONCLUSIONS Prenatal exposure to maternal cancer with or without treatment did not impair the cognitive, cardiac, or general development of children in early childhood. Prematurity was correlated with a worse cognitive outcome, but this effect was independent of cancer treatment. (Funded by Research Foundation-Flanders and others; ClinicalTrials.gov number, NCT00330447.).

Maturational pharmacokinetics of single intravenous bolus of propofol

Background:  Our aim was to document propofol pharmacokinetics in preterm and term neonates following a single intravenous bolus and compare these estimates with pharmacokinetics findings in toddlers and young children.

Cerebral tissue oxygenation index in very premature infants

Aim: To describe normal values of the cerebral tissue oxygenation index (TOI) in premature infants. Methods: TOI was measured by spatially resolved spectroscopy in preterm infants on the first 3 days of life. Infants with an abnormal cranial ultrasound were excluded. Other simultaneously measured variables were Pao2, Paco2, pH, mean arterial blood pressure, heart rate, haemoglobin, glycaemia, and peripheral oxygen saturation. Results: Fifteen patients with a median postmenstrual age of 28 weeks were measured. There was a significant increase in median TOI over the first 3 days of life: 57% on day 1, 66.1% on day 2, and 76.1% on day 3. Multiple regression analysis showed no correlation between TOI and postmenstrual age, peripheral oxygen saturation, mean arterial blood pressure, Pao2, Paco2, and haemoglobin concentration. Conclusion: Cerebral TOI increases significantly in the first 3 days of life in premature babies. This increase probably reflects the increase in cerebral blood flow at this time.

Perinatal growth characteristics and associated risk of developing threshold retinopathy of prematurity.

PURPOSE To document perinatal growth characteristics in infants who developed threshold retinopathy of prematurity (ROP) in an attempt to describe prenatal and postnatal growth-related risk factors for threshold ROP. METHODS To document birth weight as well as absolute and relative weight gain (g/d and g/kg/d) in the first 6 weeks of life in infants who developed threshold ROP and who were admitted to a single tertiary neonatal intensive care unit between 1996 and 2000. These data were compared (case-control approach) with infants of the same gestational age (GA) who did not developed threshold ROP. RESULTS Small for gestational age (SGA; ie, weight <10th percentile for a given GA) and growth restriction (<25th percentile for a given GA) are risk factors for threshold ROP (relative risk = 3.7 and 4.5, respectively). Absolute weight gain (g/d) is also associated with an increased risk of developing threshold ROP (P<.05). In contrast, relative weight gain (g/kg/d) is not significantly different between threshold ROP infants and GA-matched controls. CONCLUSIONS SGA and a birth weight below the 25(th) percentile are risk factors for threshold ROP. Postnatal weight and absolute weight gain (g and g/d, respectively) in the first 6 weeks of life are statistically significant but of less clinical relevance because smaller infants at birth stay relatively smaller during the first 6 weeks of life. Even with normal (ie, same weight as control infants) postnatal relative weight gain (g/kg/d), growth retarded or restricted infants at birth still have an increased risk of developing threshold ROP.

Hepatic tolerance of repeated intravenous paracetamol administration in neonates.

Introduction:  An intravenous (i.v.) formulation of paracetamol is available, but reports on its hepatic tolerance in neonates are limited. We therefore assessed hepatic tolerance of i.v. paracetamol in neonates.

Guidelines for the Management of Extremely Premature Deliveries: A Systematic Review.

BACKGROUND AND OBJECTIVES: Available data on survival rates and outcomes of extremely low gestational age (GA) infants (22–25 weeks’ gestation) display wide variation by country. Whether similar variation is found in statements by national professional bodies is unknown. The objectives were to perform a systematic review of management from scientific and professional organizations for delivery room care of extremely low GA infants. METHODS: We searched Embase, PubMed, and Google Scholar for management guidelines on perinatal care. Countries were included if rated by the United Nations Development Programme’s Human Development Index as “very highly developed.” The primary outcome was rating of recommendations from “comfort care” to “active care.” Secondary outcomes were specifying country-specific survival and considering potential for 3 biases: limitations of GA assessment; bias from different definitions of stillbirths and live births; and bias from the use of different denominators to calculate survival. RESULTS: Of 47 highly developed countries, 34 guidelines from 23 countries and 4 international groups were identified. Of these, 3 did not state management recommendations. Of the remaining 31 guidelines, 21 (68%) supported comfort care at 22 weeks’ gestation, and 20 (65%) supported active care at 25 weeks’ gestation. Between 23 and 24 weeks’ gestation, much greater variation was seen. Seventeen guidelines cited national survival rates. Few guidelines discussed potential biases: limitations in GA (n = 17); definition bias (n = 3); and denominator bias (n = 7). CONCLUSIONS: Although there is a wide variation in recommendations (especially between 23 and 24 weeks’ GA), there is general agreement for comfort care at 22 weeks’ GA and active care at 25 weeks’ GA.