Kurt von Siebenthal

Postnatal growth in VLBW infants: Significant association with neurodevelopmental outcome

OBJECTIVE To study the significance of growth status at birth and postnatal growth on neurodevelopmental outcome in very low birth weight (VLBW) infants. STUDY DESIGN Growth and neurodevelopment were examined in 219 VLBW (<1250 g) children, 94 small for gestational age (SGA) (<10th percentile) and 125 appropriate for gestational age (AGA) (>10th percentile). Outcome at age 2 was assessed with the Bayley Scales of Infant Development (Mental Developmental Index [MDI], Psychomotor Developmental Index [PDI]) and a standardized neurologic examination. RESULTS SGA status was not associated with poor neurodevelopmental outcome. However, after adjustment for covariables including cerebral palsy (CP), SGA children with weight <10th percentile at age 2 had lower mean PDI than SGA children with catch-up growth to weight >10th percentile (mean [SD], 89.9 [17.4] versus 101.8 [14.5]; P<.001). AGA children with catch-down growth (weight <10th percentile at age 2) were, independent of CP, more likely to have lower mean MDI (94.9 vs 101.7, P=.05) and PDI (81.9 vs 95.1; P<.001) than AGA children remaining >10th percentile at age 2. They also more frequently had severe CP (22.9% vs 1.2%; P=.008). CONCLUSIONS In VLBW children, the course of postnatal growth rather than the appropriateness of weight for gestational age at birth determines later neurodevelopmental outcome.

Sucrose reduces pain reaction to heel lancing in preterm infants: a placebo-controlled, randomized and masked study.

ABSTRACT: In term infants sucrose given by mouth has been reported to reduce duration of crying after a heel prick. This study was designed primarily to investigate the effect of sucrose administered orally immediately before heel lancing on the nociceptive reaction in preterm infants as assessed by change in heart rate and duration of crying. A secondary objective was to document changes in cerebral blood volume during acute pain. We used a randomized, masked, placebo-controlled, crossover trial in a neonatal intermediate care unit in a level 3 perinatal center. The patients studied were 16 preterm infants; birth weight, 900–1900 g; gestational wk, 27–34; corrected postmenstrual age at time of investigation, 33–36 wk. Each infant was assessed twice receiving 2 mL of sucrose 50% or 2 mL of distilled water in random order immediately before heel lance. Heart rate, thoracic movements, and transcutaneous blood gases were monitored continuously. Crying during the procedure was documented by a video-camera. A change in cerebral blood volume was assessed by near-infrared spectroscopy. We found the heart rate increased by a mean of 35 beats/min (bpm) after sucrose and 51 bpm after placebo (median difference 16 bpm, interquartile range 1–30 bpm, p = 0.005). Infants cried 67% of time after sucrose and 88% after placebo (median difference 10%, interquartile range 3–33%, p = 0.002). Cerebral blood volume decreased in 5 of 14 infants after sucrose and in 6 of 14 infants after placebo (difference not significant). We concluded that sucrose administered orally before a heel lance reduces the pain reaction in preterm infants. Response of cerebral blood volume to pain does not seem to be altered by sucrose.

The Influence of the Timing of Cord Clamping on Postnatal Cerebral Oxygenation in Preterm Neonates: A Randomized, Controlled Trial

OBJECTIVE. Our goal was to investigate the effect of placentofetal transfusion on cerebral oxygenation in preterm infants by near-infrared spectroscopy. SUBJECTS. A total of 39 preterm infants with a median gestational age of 30.4 weeks were randomly assigned to an experiment group (n = 15) and a control group (n = 24). INTERVENTIONS. The delivery of the infants in the experiment group was immediately followed by maternal administration of syntocinon, the infant was placed 15 cm below the placenta, and cord clamping was delayed by 60 to 90 seconds. The infants in the control group were delivered conventionally. At the ages of 4 and 24 hours, cerebral hemoglobin concentrations, cerebral blood volume, and regional tissue oxygenation were measured by near-infrared spectroscopy. RESULTS. Cerebral blood volume was not different between the 2 groups at the age of 4 hours (6.1 vs 5.8 mL/100 g of tissue) nor at the age of 24 hours (6.2 vs 6.2 mL/100 g of tissue). Mean regional tissue oxygenation of the experiment group was higher at the ages of 4 hours (69.9% vs 65.5%) and of 24 hours (71.3% vs 68.1%). CONCLUSION. Delayed clamping of the umbilical cord improves cerebral oxygenation in preterm infants in the first 24 hours.

The influence of a clear layer on near-infrared spectrophotometry measurements using a liquid neonatal head phantom

It is difficult to test near-infrared spectrophotometry instruments in vivo. Therefore we constructed a liquid phantom which mimics the neonatal head. It consists of a spherical 3.5 mm thick layer of silicone rubber simulating skin and bone and a 0.5 mm thick clear layer of polypropylene imitating cerebrospinal fluid. It acts as container for a liquid solution with Intralipid, 60 micromol l(-1) haemoglobin and yeast. The solution was oxygenated using oxygen and then deoxygenated by the yeast. From the instrumental (Critikon 2020) algorithm, we found that with increasing scattering (0.5%, 1%, 1.5% and 2% Intralipid concentration) the reading was increasingly offset from the expected value of 0 micromol l(-1) by 55.7, 68.6, 76.5 and 80.4 micromol l(-1) (oxyhaemoglobin) and 16.0, 24.4, 29.6 and 31.7 micromol l(-1) (deoxyhaemoglobin). This reduced the range of the oxygen saturation reading from the expected 100% to 31.5, 21.1, 14.3 and 11.5%. Haemoglobin concentration changes were increasingly underestimated by a factor of two to four. For a second algorithm based on the diffusion approximation the offsets were smaller: oxyhaemoglobin 11.4, 17.8, 22.5 and 25.1 micromol l(-1) and deoxyhaemoglobin 1.3, 3.4, 5.2 and 6.0 micromol l(-1). The range of the oxygen saturation reading was higher: 41.3, 29.2, 23.4 and 16.6%. Concentration changes were underestimated by a factor of six to ten. This study demonstrates the need to develop algorithms which take into consideration anatomical structures.

Cyclical fluctuations in blood pressure, heart rate and cerebral blood volume in preterm infants

Many recently published papers describe cyclical changes of cerebral circulatory variables, mainly in cerebral blood flow velocity (CBFV) performed with Doppler sonography. In this paper we focus on another important variable of cerebral circulation: on cerebral blood volume (CBV) measured by near infrared spectrophotometry (NIRS). In a retrospective analysis of NIRS measurements in 20 preterm infants (median 27 3/7 weeks of gestation), the dominating frequencies and prevalence of cyclical changes of CBV and its possible correlation with peripheral circulatory variables (mean arterial pressure and heart rate) was examined. In 19 out of the 20 infants cyclical changes of CBV were found within a frequency range of 2-4.7 cycles/min which is comparable to the results of the Doppler studies describing fluctuations in CBFV. A dominating frequency of heart rate (HR), was found only in 12 out of 20 infants, and it was with 2.1-3.8 cycles/min in a similar range compared to CBV. In mean arterial blood pressure (MABP), however we detected cycles with longer periods every 1-2.5 min in 14 out of 20 infants. There was a significant coherence between MABP/CBV and HR/CBV. The area under the coherence curve, however, was significantly larger between MABP and CBV as compared to HR and CBV (P = 0.0007, Wilcoxon signed-rank test).

Differences in Movement Quality at Term among Preterm and Term Infants

Significant differences in movement quality at term are reported in high-risk preterm (n = 18), low-risk preterm (n = 21) and term (n = 20) infants. Movement quality was judged using 2-minute video collection of general movements; three parameters of movement quality could be assessed reliably in a semiquantitative way: fluency, spatiotemporal variability and sequencing. The parameters fluency and variability correlated highly with each other (r = 0.47-0.99) while their correlations with sequencing were less (r = 0.42-0.67). Significant differences on all quality parameters were noted between term, low-risk preterm and high-risk preterm infants (p < 0.001-0.05). The findings indicate a significant impact of prematurity per se and brain damage on movement quality.

Impact of Central, Obstructive and Mixed Apnea on Cerebral Hemodynamics in Preterm Infants

The objective of this study was to evaluate the effect of central, obstructive and mixed apnea on cerebral total hemoglobin concentration (tHb), which is analogous to cerebral blood volume, and to investigate whether tHb alterations correlate with bradycardia and arterial desaturation. Measurements were carried out on 17 preterm infants (gestational age 26-30 weeks) with frequent apneic events. Near infrared spectrophotometry (NIRS) was used to quantify changes in tHb. Respiration was monitored by chest movements using impedance pneumography and by nasal airflow using a thermistor. In addition, heart rate, arterial oxygen saturation, in each infant and esophageal pressure in 3 babies were continuously recorded. 130 apneic episodes of > 10 s duration showed four different patterns of tHb alterations: (1) no change in tHb (28%); (2) isolated decrease (35%); (3) isolated increase (12%), or (4) both combined, an initial decrease followed by an increase over the previous baseline level (25%). Obstructive apneic episodes were associated with a significantly greater maximum fall in tHb (median 11.5; 5th percentile 0 and 95th percentile 30.5 mumol/l) compared to mixed (4.9, 0 and 26.4 mumol/l) and central events (3.0, 0 and 14.0 mumol/l). Changes in tHb correlated with heart rate only in purely central apnea and were not reflected in arterial oxygen saturation in any type of apnea. Obstructive apnea was observed to have the strongest impact on tHb. As these tHb alterations may exacerbate or cause intraventricular hemorrhage, efforts must be made to prevent obstruction of upper airways and to focus monitoring on cerebral perfusion.

Comparison of three methods to measure absolute cerebral hemoglobin concentration in neonates by near-infrared spectrophotometry.

Three methods by which to determine absolute total cerebral hemoglobin concentration (tHb in micromol/L) by near-infrared spectrophotometry (NIRS) have evolved: (1) tHbo, requiring oxygenation changes and arterial oxygen saturation measurements as a reference using a relative NIRS algorithm, (2) tHbg, using a geometrical multidistance principle and (3) tHbgo, a combination of both. The aim of this study was to compare the three methods quantitatively. Sixteen clinically stable preterm infants with a mean gestational age of 29.6 (range of 25.1-36.4) weeks, birthweight of 1386 (680-2820) g and a postnatal age of 2.5 (0.5-6) days, who needed supplemental oxygen, were enrolled. The mean+/-standard deviation tHbg was 150.2+/-41.8 micromol/L (range of 61.6-228.9 micromol/L), the tHbo was 62.1+/-27.2 micromol/L (26.0-110.8 micromol/L) and the tHbgo was 89.3+/-45.6 micromol/L (26.5-195.9 micromol/L). The correlation coefficient among the three methods were tHbg and tHbgo r=0.736; tHbo and tHbgo r=0.938; tHbg and tHbo r=0.598. A multiple regression with variable selection by Mellows C(p) showed, that tHbg was correlated to the birthweight, the postnatal age, the heart rate and the pCO2 (r(2)=0.588), tHbo and tHbgo were associated with the hemoglobin concentration in the blood, the mean arterial blood pressure and the pCO2 (r(2)=0.493 and 0.406, respectively). The three methods (tHbg, tHbo, and tHbgo) give systematically different tHb readings and large intersubject variability.

CO2 Reactivity of the Cerebral Hemoglobin Concentration in Healthy Term Newborns Measured by Near Infrared Spectrophotometry

CO2 reactivity of cerebral hemoglobin concentration was studied in 16 healthy term neonates on days 1 and 4 after birth using the near infrared spectrophotometry (NIRS) technique. The aim was to establish data on the physiological range of CO2 reactivity in healthy newborns and to investigate the influence of postnatal age on it. The CO2 reactivity measured by NIRS is expressed as the change of the total cerebral hemoglobin concentration (tHbR) per change of CO2 tension in µmol/l/kPa. We evaluated CO2 reactivity during increases and decreases of transcutaneous CO2 partial pressure and found in our methodological setting the data of the increases more reliable. In all infants but 1 we found a tHbR on day 1 with a mean value of 8.19 µmol/l/kPa (–1.39 to 18.87), in all infants on day 4 with a mean value of 9.54 µmol/l/kPa (2.76–25.88). There is a trend to higher values between day 1 and day 4 (difference = 2.25 µmol/l/kPa; p = 0.08). The noninvasive NIRS technique enabled us to test the cerebrovascular CO2 reactivity of the tHbR for the first time in healthy term newborns. Data on its physiologic range and variability are presented and compared to findings from ventilated infants and other age groups. As the CO2 reactivity might be an indicator for infants at risk of cerebral damage, it is necessary to have data on the physiological range of this parameter.

Body proportionality in growth-retarded VLBW infants

The aim of this study was to investigate how intrauterine growth retardation affects body proportions in VLBW infants. The cohort consisted of 135 surviving and 80 deceased preterm infants weighing less than 1250 grams at birth. Gestational age varied between 24 and 36 weeks (mean age 29.7 and 27.5 weeks, respectively). Birth weight was more than 2 SD below the mean birth standard values in 32% of the surviving, and in 27% of the deceased infants. Reduction of weight, length and head circumference at birth was analysed using Z scores based on Swedish birth standards. Z scores of weight, length and head circumference were highly correlated in the surviving and the deceased infants (r = 0.78 to 0.94 and 0.65 to 0.97, respectively). Length was significantly more affected by growth retardation than weight. Weight and head circumference were proportionately reduced. Intrauterine growth retardation influences body proportions in VLBW infants differently than in larger preterm and term infants.