Michael F. Whitfield

Pain in the preterm neonate: behavioural and physiological indices

&NA; The impact of invasive procedures on preterm neonates has received little systematic attention. We examined facial activity, body movements, and physiological measures in 56 preterm and full‐term newborns in response to heel lancing, along with comparison preparatory and recovery intervals. The measures were recorded in special care and full‐term nurseries during routine blood sampling. Data analyses indicated that in all measurement categories reactions of greatest magnitude were to the lancing procedure. Neonates with gestational ages as short as 25–27 weeks displayed physiological responsivity to the heel lance, but only in the heart rate measure did this vary with gestational age. Bodily activity was diminished in preterm neonates in general, relative to full‐term newborns. Facial activity increased with the gestational age of the infant. Specificity of the response to the heel lance was greatest on the facial activity measure. Identification of pain requires attention to gestational age in the preterm neonate.

Neonatal procedural pain exposure predicts lower cortisol and behavioral reactivity in preterm infants in the NICU

Data from animal models indicate that neonatal stress or pain can permanently alter subsequent behavioral and/or physiological reactivity to stressors. However, cumulative effects of pain related to acute procedures in the neonatal intensive care unit (NICU) on later stress and/or pain reactivity has received limited attention. The objective of this study is to examine relationships between prior neonatal pain exposure (number of skin breaking procedures), and subsequent stress and pain reactivity in preterm infants in the NICU. Eighty‐seven preterm infants were studied at 32 (±1 weeks) postconceptional age (PCA). Infants who received analgesia or sedation in the 72 h prior to each study, or any postnatal dexamethasone, were excluded. Outcomes were infant responses to two different stressors studied on separate days in a repeated measures randomized crossover design: (1) plasma cortisol to stress of a fixed series of nursing procedures; (2) behavioral (Neonatal Facial Coding System; NFCS) and cardiac reactivity to pain of blood collection. Among infants born ≤28 weeks gestational age (GA), but not 29–32 weeks GA, higher cumulative neonatal procedural pain exposure was related to lower cortisol response to stress and to lower facial (but not autonomic) reactivity to pain, at 32 weeks PCA, independent of early illness severity and morphine exposure since birth. Repeated neonatal procedural pain exposure among neurodevelopmentally immature preterm infants was associated with down‐regulation of the hypothalamic–pituitary–adrenal axis, which was not counteracted with morphine. Differential effects of early pain on development of behavioral, physiologic and hormonal systems warrant further investigation.

Bedside application of the Neonatal Facial Coding System in pain assessment of premature neonates

&NA; Assessment of infant pain is a pressing concern, especially within the context of neonatal intensive care where infants may be exposed to prolonged and repeated pain during lengthy hospitalization. In the present study the feasibility of carrying out the complete Neonatal Facial Coding System (NFCS) in real time at bedside, specifically reliability, construct and concurrent validity, was evaluated in a tertiary level Neonatal Intensive Care Unit (NICU). Heel lance was used as a model of procedural pain, and observed with n=40 infants at 32 weeks gestational age. Infant sleep/wake state, NFCS facial activity and specific hand movements were coded during baseline, unwrap, swab, heel lance, squeezing and recovery events. Heart rate was recorded continuously and digitally sampled using a custom designed computer system. Repeated measures analysis of variance (ANOVA) showed statistically significant differences across events for facial activity (P<0.0001) and heart rate (P<0.0001). Planned comparisons showed facial activity unchanged during baseline, swab and unwrap, then increased significantly during heel lance (P<0.0001), increased further during squeezing (P<0.003), then decreased during recovery (P<0.0001). Systematic shifts in sleep/wake state were apparent. Rise in facial activity was consistent with increased heart rate, except that facial activity more closely paralleled initiation of the invasive event. Thus facial display was more specific to tissue damage compared with heart rate. Inter‐observer reliability was high. Construct validity of the NFCS at bedside was demonstrated as invasive procedures were distinguished from tactile. While bedside coding of behavior does not permit raters to be blind to events, mechanical recording of heart rate allowed for an independent source of concurrent validation for bedside application of the NFCS scale.

Neonatal pain, parenting stress and interaction, in relation to cognitive and motor development at 8 and 18 months in preterm infants

ABSTRACT Procedural pain in the neonatal intensive care unit triggers a cascade of physiological, behavioral and hormonal disruptions which may contribute to altered neurodevelopment in infants born very preterm, who undergo prolonged hospitalization at a time of physiological immaturity and rapid brain development. The aim of this study was to examine relationships between cumulative procedural pain (number of skin‐breaking procedures from birth to term, adjusted for early illness severity and overall intravenous morphine exposure), and later cognitive, motor abilities and behavior in very preterm infants at 8 and 18 months corrected chronological age (CCA), and further, to evaluate the extent to which parenting factors modulate these relationships over time. Participants were N = 211 infants (n = 137 born preterm ⩽32 weeks gestational age [GA] and n = 74 full‐term controls) followed prospectively since birth. Infants with significant neonatal brain injury (periventricular leucomalacia, grade 3 or 4 intraventricular hemorrhage) and/or major sensori‐neural impairments, were excluded. Poorer cognition and motor function were associated with higher number of skin‐breaking procedures, independent of early illness severity, overall intravenous morphine, and exposure to postnatal steroids. The number of skin‐breaking procedures as a marker of neonatal pain was closely related to days on mechanical ventilation. In general, greater overall exposure to intravenous morphine was associated with poorer motor development at 8 months, but not at 18 months CCA, however, specific protocols for morphine administration were not evaluated. Lower parenting stress modulated effects of neonatal pain, only on cognitive outcome at 18 months.

Early pain experience, child and family factors, as precursors of somatization: a prospective study of extremely premature and fullterm children

&NA; In a prospective study of 36 children who were extremely low birthweight (ELBW: < 1000 g) preterm infants and 36 matched full‐term controls, differences were found in somatization at age Symbol years. Only children who had been extremely premature, and thereby experienced prolonged hospitalization and repeated medical intervention in infancy, had clinically high somatization scores on the Personality Inventory for Children. The combination of family relations at age Symbol years, neonatal intensive care experience, poor maternal sensitivity to child cues in mother‐child interaction observed at age 3 years, and child avoidance of touch or holding at age 3. predicted somatization scores, prior to school entry. Due to the known higher incidence of actual medical problems among children with a history of extreme prematurity, the high somatization ELBW children were compared with the normal somatization ELBW children. There were no differences in prevalence of actual medical problems between the 2 ELBW groups, and the importance of maternal factors in relation to somatization was confirmed. Child temperament at age 3, but not personality at Symbol, was related to somatization. The etiology of recurrent physical complaints of no known medical cause appears to be a multi‐dimensional problem. Non‐optimal parenting may contribute to the development of inappropriate strategies for coping with common pains of childhood, or of chronic pain patterns, in some children who have experienced prolonged or repeated pain as neonates. Symbol. No caption available Symbol. No caption available Symbol. No caption available

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

AIM To examine the functional abilities of extremely low birthweight (ELBW, ⩽ 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 theDiagnostic 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 ⩾ 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.

Pain sensitivity and temperament in extremely low-birth-weight premature toddlers and preterm and full-term controls

&NA; High‐technology medical care of extremely low‐birth‐weight (ELBW) infants (< 1001 g) involves repeated medical interventions which are potentially painful and may later affect reaction to pain. At 18 months corrected age (CCA), we examined parent ratings of pain sensitivity and how pain sensitivity ratings related to child temperament and parenting style in 2 groups of ELBW children (49 with a birth weight of 480–800 g and 75 with a birth weight of 801–1000 g) and 2 control groups (42 heavier preterm (1500–2499 g) and 29 full‐birth‐weight (FBW) children (> 2500 g)). Both groups of ELBW toddlers were rated by parents as significantly lower in pain sensitivity compared with both control groups. The relationships between child temperament and pain sensitivity rating varied systematically across the groups. Temperament was strongly related to rated pain sensitivity in the FBW group, moderately related in the heavier preterm and ELBW 801–1000 g groups, and not related in the lowest birth‐weight group (< 801 g). Parental style did not mediate ratings of pain sensitivity. The results suggest that parents perceive differences in pain behavior of ELBW toddlers compared with heavier preterm and FBW toddlers, especially for those less than 801 g. Longitudinal research into the development of pain behavior for infants who experience lengthy hospitalization is warranted.

Developmental Coordination Disorder in Extremely Low Birth Weight Children at Nine Years

ABSTRACT. Developmental coordination disorder (DCD) is defined as an impairment in the development of motor coordination that interferes with academic achievement or activities of daily living (DSM-IV). DCD has been reported to affect 5% to 9% of children in the normal population. This study describes the prevalence of DCD in a cohort of extremely low birth weight children (ELBW, ≤800 g) at 8.9 years of age, from which were excluded children with major impairments. Seventy-three children were included in the study group, along with 18 term-born, socially matched controls. Of the 73 ELBW children, 37 (51%) were classified as having DCD. ELBW children with DCD also had significantly lower Performance IQ (PIQ) scores and were more likely (43%) to have a learning difficulty in arithmetic than ELBW children who did not have DCD. This study found that DCD is a common problem in school-aged ELBW children.

BEHAVIOR, PAIN PERCEPTION, AND THE EXTREMELY LOW-BIRTH WEIGHT SURVIVOR

This article explores the literature concerning responses to pain of both premature and term-born newborn infants, the evidence for short-term and long-term effects of pain, and behavioral sequelae in individuals who have experienced repeated early pain in neonatal life as they mature. There is no doubt that pain causes stress in babies and this in turn may adversely affect long-term neurodevelopmental outcome. Although there are methods for assessing dimensions of acute reactivity to pain in an experimental setting, there are no very good measures available at the present time that can be used clinically. In the clinical setting repeated or chronic pain is more likely the norm rather than infrequent discrete noxious stimuli of the sort that can be readily studied. The wind-up phenomenon suggests that, exposed to a cascade of procedures as happens with clustering of care in the clinical setting in an attempt to provide periods of rest for stressed babies, an infant may in fact perceive procedures that are not normally viewed as noxious, as pain. Pain exposure during lifesaving intensive medical care of ELBW neonates may also affect subsequent reactivity to pain in the neonatal period, but behavioral differences are probably not likely to be clinically significant in the long term. Prolonged and repeated untreated pain in the newborn period, however, may produce a relatively permanent shift in basal autonomic arousal related to prior NICU pain experience, which may have long-term sequelae. In the long run, the most significant clinical effects of early pain exposure may be on neurodevelopment, contributing to later attention, learning, and behavior problems in these vulnerable children. Although there is considerable evidence to support a variety of adverse effects of early pain, there is less information about the long-term effects of opiates and benzodiazepines on the developing central nervous system. Current evidence reviewed suggests that judicious use of morphine for adjustment to mechanical ventilation may ameliorate the altered autonomic response. It may be very important, however, to distinguish stress from pain. Animal evidence suggests that the neonatal brain is affected differently when exposed to morphine administered in the absence of pain than in the presence of pain. Pain control may be important for many reasons but overuse of morphine or benzodiazepines may have undesirable long-term effects. This is a rapidly evolving area of knowledge of clear relevance to clinical management likely to affect long-term outcomes of high-risk children.

Perinatal outcomes of a large cohort of extremely low gestational age infants (twenty-three to twenty-eight completed weeks of gestation)

OBJECTIVES To determine gestational age (GA)-specific mortality rates; the effects of GA, birth weight, sex, and multiple gestation on mortality rates; short-term morbidity for infants born at 23 to 28 weeks GA; and impairment rates at a corrected chronologic age of 18 months for those born at 23 to 25 weeks GA. METHODS A data base analysis was performed with a linked obstetric and a neonatal database. GA was determined by obstetric data and confirmed by early ultrasonography (available in 88%) on all births < 30 weeks GA at British Columbias tertiary perinatal center from 1983 to 1989. RESULTS Of 1024 births occurring between 23 and 28 weeks GA, 911 were live born. The mortality rate decreased with increasing GA: 84% at 23 weeks; 57% at 24 weeks; 45% at 25 weeks; 37% at 26 weeks; 23% at 27 weeks; and 13% at 28 weeks GA. For each GA, mortality rate versus birth weight plots showed a decreasing mortality rate with increasing birth weight, except for infants who were large for GA. Male infants had a higher mortality rate than female infants (odds ratio, 1.8; confidence interval, 1.4 to 2.5). Twins fared worse than singletons with a decreasing effect from 24 weeks GA (odds ratio, 10.3) to no effect at 28 weeks GA. The median number of days supported by mechanical ventilation and the length of stay in the neonatal intensive care unit decreased markedly with increasing GA. Eighteen-month outcome of survivors between 23 and 25 weeks GA with 93% follow-up rate revealed an overall impairment rate of 36%, but 6 of the 9 surviving 23-week infants had major impairments. CONCLUSIONS The GA-specific perinatal outcome results of this large cohort provide information to assist in perinatal management decision making and for counseling parents prenatally.