Hans Daniels

Oxygen-Induced Retinopathy in Mice: Amplification by Neonatal IGF-I Deficit and Attenuation by IGF-I Administration

In preterms, low serum levels of IGF (IGF-I) correlate with retinopathy of prematurity (ROP). In mice, IGF-I is a prerequisite for normal retinal development. We further explored the link between IGF-I and oxygen-induced retinopathy (OIR). To assess the role of endogenous IGF-I, pups were redistributed into smaller versus larger litters at birth; in one subgroup, we measured body weight and circulating IGF-I; in another, we applied hyperoxia and assessed retinal neovascularization (NV). To screen for the potential role of exogenous IGF-I, we administered a single bolus of rhIGF-I on postnatal day (P) 4 to pups in normal litters, and applied hyperoxia; body weight and IGF-I were measured; maturation and NV were assessed. Neonatal mice in larger litters had a lower body weight than mice in smaller litters; they had lower levels of circulating IGF-I, and developed more OIR (p = 0.002). Mice who had received rhIGF-I, weighed more and had higher endogenous IGF-I levels; they matured faster and developed less OIR (p = 0.00001). These findings in mice are the first to support the notion that higher availability of endogenous or exogenous IGF-I reduces OIR risk, and thus sharpen the perspective that ROP may be preventable by briefly up-regulating IGF-I after birth.

Feeding behaviour in preterm neonates

In 100 bottle-fed preterm infants feeding efficiency was studied by quantifying the volume of milk intake per minute and the number of teat insertions per 10 ml of milk intake. These variables were related to gestational age and to number of weeks of feeding experience. Feeding efficiency was greater in infants above 34 weeks gestational age than in those below this age. There was a significant correlation between feeding efficiency and the duration of feeding experience at most gestational ages between 32 and 37 weeks. A characteristic adducted and flexed arm posture was observed during feeding: it changed along with feeding experience. A neonatal feeding score was devised that allowed the quantification of the early oral feeding behavior. The feeding score correlated well with some aspects of perinatal assessment, with some aspects of the neonatal neurological evaluation and with developmental assessment at 7 months of age. These findings are a stimulus to continue our study into the relationships between feeding behaviour and other aspects of early development, especially of neurological development.

Prognostic value of early somatosensory evoked potentials for adverse outcome in full-term infants with birth asphyxia

SEPs were examined during the first weeks of life in 34 infants with mild to severe birth asphyxia, in an attempt to provide a more accurate prediction of neurodevelopmental outcome. Normal, delayed and absent responses were compared with the infants acute clinical condition, imaging findings using different imaging techniques and neurodevelopmental outcome. All infants with normal SEPs were normal at follow-up. All but two of the infants with a delayed or absent response died or suffered from severe neurological sequelae. A delayed or absent N1 latency carried a risk for death or severe handicap of 71 and 100%, respectively, compared with 25 and 89% for moderate or severe encephalopathy on neurological assessment, and 29 and 85% for moderate or severe changes seen using different imaging techniques. SEPs may provide useful additional information when assessing the infant with birth asphyxia.

Upper limits of brain blood flow autoregulation in stable infants of various conceptional age

In healthy adults cerebral blood flow is autoregulated and kept constant over a wide range of mean arterial blood pressures (MAP) between 60 and 150 mmHg. In 27 stable infants with different conceptional ages ranging from 33 to 50 weeks, Doppler measurements of mean flow velocity at the anterior cerebral artery have been recorded simultaneously with mean arterial blood pressures (MAP) during a period of 6 h. The range of autoregulation and its upper limit could thus be determined. The upper limit was found to increase with advancing age. In the infants with conceptional ages between 33 and 35 weeks, the upper limit of autoregulation varied between 45 and 60 mmHg, while the upper limit shifted to a MAP of 100 mmHg at 47 weeks conceptional age. A significant positive linear relationship existed between the upper limit of autoregulation and conceptional age.

Mechanisms of feeding efficiency in preterm infants

Nutritive sucking was studied in 18 preterm infants. Differences in feeding efficiency could not be explained by differences in sucking rate. Quick efficient drinking, however, was characterized by long sucking bursts and by a large amount of milk intake during each sucking movement. Slow inefficient drinking was characterized by short sucking bursts and by a small amount of milk intake during each sucking movement.

Prediction of neurodevelopmental outcome in the preterm infant: short latency cortical somatosensory evoked potentials compared with cranial ultrasound.

One hundred and twenty six preterm infants, with a gestational age of 34 weeks or less, were studied to compare the predictive value of somatosensory evoked potentials (SEPs) with that of cranial ultrasound. A normal N1 latency was no guarantee of a normal outcome, nor did a persistently delayed N1 latency always correlate with a poor outcome. As a predictor of cerebral palsy, SEPs had a sensitivity of 44% and a specificity of 92%. The presence of a large haemorrhage (grade IIb/III) or cystic leukomalacia on cranial ultrasound predicted cerebral palsy with a sensitivity of 73.6% and a specificity of 83.1%. These results demonstrate that the role of SEPs recorded after median nerve stimulation is limited in preterm infants.

Characteristics of respiratory syncytial virus‐related apnoea in three infants

Apnoea is a common sign in respiratory syncytial virus (RSV) infections in young infants and can be the first presentation of an acquired RSV infection. We describe polysomnographic recordings of three infants revealing prolonged RSV‐related apnoea before RSV infection was diagnosed. The apnoeas were of central origin. The caregivers had not noted any apparent life‐threatening events (ALTE) prior to the polysomnography. Cardiorespiratory monitoring after the acute infection did not reveal any further apnoeas.

Polysomnography and home documented monitoring of cardiorespiratory pattern.

Polysomnographic findings were compared with data obtained subsequently from home documented monitoring in order to study the diagnostic value of both techniques. Polysomnography was performed in 1274 infants born prematurely and in 422 patients admitted because of apparent life threatening events (ALTEs). In 72 of the infants, home documented monitoring of the cardiorespiratory pattern, including QRS complexes, was performed. Subsequent documented episodes of heart rate < 50 beats/min were considered as “serious life threatening events”. It was confirmed that polysomnographic findings correlated well with subsequent events as registered by home documented monitoring. Especially in the ALTE group where both infants with and without abnormal polysomnography were home monitored, the single polysomnography significantly predicted subsequent life threatening events. Home documented monitoring of the cardiorespiratory pattern has a distinctive advantage over simple cardiorespiratory monitoring as a means to identify and document life threatening events, in addition to its value as a rescue device.

Effects of non-nutritive sucking on heart rate, respiration and oxygenation: a model-based signal processing approach.

Several studies support the idea that the use of pacifiers can reduce the risk of Sudden Infant Death Syndrome. To investigate the effect of non-nutritive sucking (NNS), we measured heart rate, abdominal respiration, EMG and arterial oxygen saturation of 20 neonates. Also, in 10 of these neonates, changes in cerebral hemoglobin concentrations were acquired by means of near-infrared spectroscopy. Using a parametric technique to model the heart rate as a sum of exponentially damped sinusoids, two main frequency components were found in the heart rate during NNS: a frequency of approximately 0.08 Hz due to the alternation of sucking bursts and pauses, and a frequency of approximately 0.8 Hz that reflects the influence of the respiration. Our analysis shows that it is the alternation of bursts and pauses itself that causes the increased heart rate variability, and that this is not due to increased effort. This suggests that the neuronal mechanism regulating NNS also stimulates the heart rate. From our measurements, no effect of NNS on cerebral or peripheral oxygenation could be found. Furthermore, we show that our model-based signal processing technique is well suited for the analysis of non-stationary biomedical signals.

POSTURE OF LOW-RISK PRETERM INFANTS BETWEEN 32 AND 36 WEEKS POSTMENSTRUAL AGE

The supine posture of 15 low‐risk preterm infants was studied to establish whether they have a preferred posture and, if so, whether it changes with age. No over‐all preferred posture was found. Almost always one posture was adopted most frequently, but often a great variety of other postures were adopted almost as frequently. There was no correlation between postmenstrual age and preferred posture, the number of different postures, or the duration of longest uninterrupted posture.