Morphine pharmacokinetics and pain assessment in premature newborns.

OBJECTIVES: To determine morphine pharmacokinetics in premature neonates varying in postconceptional age (PCA) and evaluate behavioral pain response in relationship to serum morphine concentrations. METHODS: Premature neonates (n = 48), stratified by weeks of PCA (group 1 = 24-27 weeks, group 2 = 28-31 weeks, group 3 = 32-35 weeks, and group 4 = 36-39 weeks) received morphine infusions. Blood samples were drawn at 48, 60, and 72 hours and at discontinuation of morphine, followed by 3 samples obtained during the next 24 hours. Newborns were videotaped during heel lances and restful states, with morphine at steady-state concentrations and without morphine. Pain was assessed by using the Neonatal Facial Coding System (NFCS). Statistical analysis included regression between NFCS score changes from baseline to painful procedure with and without morphine. RESULTS: Morphine clearance for groups 1, 2, 3, and 4 was calculated as 2.27 +/- 1.07, 3.21 +/- 1.57, 4.51 +/- 1.97, and 7.80 +/- 2.67 mL/kg/min, respectively, and correlated with PCA (r = 0.63, P <.001). Pain measured by facial expression was diminished; however, it did not correlate with morphine concentrations. CONCLUSION: Morphine clearance in premature neonates is less than reported, increasing with PCA. Facial activity discloses morphine analgesia; however, it is unrelated to morphine concentrations.

Extremely premature (< or = 800 g) schoolchildren: multiple areas of hidden disability.

AIM: To examine the functional abilities of extremely low birthweight (ELBW, < or = 800 g) children at school age compared with full term children. METHODS: ELBW children (n = 115) in a geographically defined regional cohort born between 1974 and mid-1985 (comprising 96% of 120 survivors of 400 ELBW infants admitted to the Provincial Tertiary neonatal intensive care unit), were compared with (n = 50) children of comparable age and sociodemographic status. Each child was categorised by the pattern and degree of disability, using a system derived from the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM IV). Psycho-educational, behavioural, and motor results for ELBW children free of severe/multiple neurosensory disabilities (n = 90; 91% return rate) were compared with the term children. RESULTS: Severe/multiple neurosensory disabilities were present in 16 ELBW children (14%), and 15 (13%) had borderline intelligence. ELBW children of global IQ > or = 85 scored significantly lower in standardised tests of fine and gross motor control, visuo-motor pencil output, visual memory, and academic achievement (reading, arithmetic, written language). ELBW survivors were three times more likely to have learning disorders (47% vs 18%) and 22 (41%) of the 54 ELBW children with learning disorders had multiple areas of learning difficulty. Of the ELBW group, 30 (26%) were not disabled compared with 41 (82%) of the term group. Only five (12%) of the ELBW boys were not disabled, compared with 25 (35%) of the ELBW girls. Finally, ELBW children had significantly worse scores on ratings of behaviour during testing by the psychologist and behaviour by parental report. CONCLUSION: The most likely outcome for ELBW survivors at school age is a learning disorder, often multiple, or borderline intellectual functioning, combined with behavioural and motor risk factors rather than severe/multiple disability. Mean scores on psycho-educational testing showed poorer performance of the ELBW children, but grossly understated the complex nature of the individual degree of educational difficulty faced by these children.

Issues of assessment of pain and discomfort in neonates.

Pain assessment in neonates often presents problems. The problem of inadequate or inaccurate assessment is complicated by issues related to the nature, consistency, and variability of the infant's physiologic and behavioral responses; the reliability, validity, specificity, sensitivity, and practicality of existing neonatal pain measures or measurement approaches; ethical questions about pain research in infants; and uncertainty about the responsibilities of health care professionals in managing pain in clinical settings. Despite these many issues, neonates need to be comfortable and as free of pain as possible to grow and develop normally. Valid and reliable assessment of pain is the major prerequisite for attaining this goal. Issues embodied in neonatal pain responses, measurement, ethical, and clinical considerations are explored. Suggestions for resolving some of these problems are presented.

Judging pain in newborns: facial and cry determinants.

Explored the facial and cry characteristics that adults use when judging an infant's pain. Sixteen women viewed videotaped reactions of 36 newborns subjected to noninvasive thigh rubs and vitamin K injections in the course of routine care and rated discomfort. The group mean interrater reliability was high. Detailed descriptions of the infants' facial reactions and cry sounds permitted specification of the determinants of distress judgments. Several facial variables (a brow bulge, eyes squeezed shut, and deepened nasolabial fold constellation, and taut tongue) accounted for 49% of the variance in ratings of affective discomfort after controlling for ratings of discomfort during a noninvasive event. In a separate analysis not including facial activity, several cry variables (formant frequency, latency to cry) also accounted for variance (38%) in ratings. When the facial and cry variables were considered together, cry variables added little to the prediction of ratings in comparison to facial variables. Cry would seem to command attention, but facial activity, rather than cry, can account for the major variations in adults' judgments of neonatal pain.

A comparison of two measures of facial activity during pain in the newborn child.

Facial activity is strikingly visible in infants reacting to noxious events. Two measures that reduce this activity to composite events, the Neonatal Facial Coding System (NFCS) and the Facial Action Coding System (FACS), were used to examine facial expressions of 56 neonates responding to routine heel lancing for blood sampling purposes. The NFCS focuses upon a limited subset of all possible facial actions that had been identified previously as responsive to painful events, whereas the FACS is a comprehensive system that is inclusive of all facial actions. Descriptions of the facial expressions obtained from the two measurement systems were very similar, supporting the convergent validity of the shorter, more readily applied system. As well, the cluster of facial activity associated with pain in this sample, using either measure, was similar to the cluster of facial activity associated with pain in adults and other newborns, both full-term and preterm, providing construct validity for the position that the face encodes painful distress in infants and adults.

Language development at 3 years in pre-term children of birth weight below 1000 g.

Language development at 3 years of pre-term children born below 1000 g birth weight was compared with full-term controls matched for social background. The pre-term group used less complex expressive language and showed lower receptive understanding, auditory memory and verbal reasoning. Language outcome was related to intraventricular haemorrhage but not to global indication of postnatal illness such as number of days on the ventilator. Average verbal intelligence in environmentally low risk, extremely low birth weight children is an insufficient indicator of complex language functioning.

Cognitive and task-related EEG correlates of arithmetic performance in adolescents.

Cognitive and neurophysiological correlates of arithmetic calculation, concepts, and applications were examined in 41 adolescents, ages 12-15 years. Psychological and task-related EEG measures which correctly distinguished children who scored low vs. high (using a median split) in each arithmetic subarea were interpreted as indicative of processes involved. Calculation was related to visual-motor sequencing, spatial visualization, theta activity measured during visual-perceptual and verbal tasks at right- and left-hemisphere locations, and right-hemisphere alpha activity measured during a verbal task. Performance on arithmetic word problems was related to spatial visualization and perception, vocabulary, and right-hemisphere alpha activity measured during a verbal task. Results suggest a complex interplay of spatial and sequential operations in arithmetic performance, consistent with processing model concepts of lateralized brain function.

Neurological, psychological and educational sequelae of low birth weight.

In a prospective study of 501 infants of low birth weight (LBW) who mostly weighed 2,041 g (4 1/2 lb) or less, and of 203 control infants of full birth weight (FBW > 2,500 g), 335 LBW and 139 FBW children were followed beyond the age of 6 years and 6 months. The incidence of neurological defects was negatively correlated with birth weight, and the mean "global" IQ of different birth weight groups retained a direct relationship. While the relationship of birth weight to IQ gradually became less marked, the effect of social class was increasingly evident from the age of 2 years and 6 months. The preterm children whose birth weight was appropriate for gestational age (AGA) attained a slightly higher mean IQ and significantly better grade placement in the third school year than the children who were unduly light for their gestational age. Details of the neurological and ophthalmological defects are given, and the predictive significance of neonatal variables is analyzed.