Pain behaviours in Extremely Low Gestational Age infants

BACKGROUND: To date, there are over 40 infant pain measures. Despite this plethora of measures, only 8 have included preterm infants and only 2 have included Extremely Low Gestational Age (ELGA; infants <28 weeks GA) in their development. Without reliable, valid and clinically useful indicators for procedural pain in ELGA infants, clinicians have no means to interpret the responses from an immature infant who may respond differently from infants of older GA. OBJECTIVE: To examine the physiological, behavioural and biochemical responses to painful and non-painful procedures in ELGA infants and the influence of GA and sex. DESIGN/METHODS: A prospective crossover design with 50 ELGA infants from one Canadian tertiary level NICU was conducted. Infants were assessed in random order during standardized painful (heel lance) and non-painful (diaper change) procedures. Physiological (heart rate, oxygen saturation) and behavioural (facial and body movement) indicators were continuously collected during 4 phases of the procedures. Biochemical (salivary cortisol) indicators were collected immediately before and 20 min following the procedures. RESULTS: Four facial actions (brow bulge, eye squeeze, nasolabial furrow, vertical mouth stretch) increased immediately following the heel lance. There were no specific changes in physiological, body movement or cortisol indicators following the heel lance. ELGA infants demonstrated greater body movements during the diaper change, which may reflect immature motor coordination. No differences in pain responses were found for infants born between 23-25 6/7 weeks GA and those between 26-28 weeks GA. Similarly, no gender differences were found. CONCLUSIONS: Changes in 4 facial actions were the most sensitive indicators of pain in ELGA infants. This finding is consistent with existing measures where facial actions are the most prominent pain indicators. Specific body movements such as those included in NIDCAP, may provide more information about pain in ELGA infants. Movements such as hand-on-face, finger splaying, fisting, arching or yawning need to be examined in future research.     

Neurological outcome at 6 and 12 months corrected age in hospitalised late preterm infants -a prospective study

Late preterm infants (34-0/7 to 36-6/7 weeks“ gestation) account for 10–20% of NICU admissions and are at increased risk for morbidity and mortality. Although they are prone to developmental delays, reports on neurological outcome during the first 2 years of life are scarce.The aim of the study was to assess neurological/neuromotor outcome in high risk late preterm infants at 6 and 12 months corrected age and the change in neurological scores over time, and to identify factors associated with the neurological outcome.The Hammersmith Infant Neurological Examination was performed in a cohort of 157 late preterm infants admitted in the NICU. The infants were examined at 6 and 12 months corrected age respectively and scored with the optimality score system including 26 items assessing cranial nerve function, posture, movements, tone and reflexes. Also parents reported neurological milestones in the follow up visit.Infants at 6 months had a global score of 59 (47–76) and optimal scores achieved in 25.4%. At 12 months they had a global score of 70 (58–78) and achieved optimal scores in 63.2%. The subscores of posture, tone and reflexes gradually increased from 6 to 12 months corrected age. Being born small for gestational age was the only factor that adversely influenced HINE score at 6 and 12 months. At 12 months 58.5% achieved independent walking. High risk late preterm infants have suboptimal HINE scores at 6 and 12 months of age, suggesting a need for closer follow up and early intervention programs.     

Skin conductance compared to a combined behavioural and physiological pain measure in newborn infants

AIM: To assess the ability of galvanic skin response (GSR) to differentiate between tactile and painful stimulation in newborn infants, and to compare this with the ability of the premature infant pain profile (PIPP). METHODS: Thirty-two healthy full-term infants undergoing routine blood sampling were recruited. In a randomized order they were subjected to tactile and painful stimulation. The three GSR variables conductance baseline level, number of waves per second and mean amplitude of the waves were recorded together with the behavioural and physiological variables of PIPP. RESULTS: The GSR variables number of waves and amplitude of the waves increased more during painful stimulation than during tactile stimulation, as did also the PIPP score. Receiver operating characteristic curves analysis revealed no significant differences between the studied methods. CONCLUSION: GSR can differentiate painful from tactile stimulation, but more research is needed to achieve a clinically useful application.     

Neonatal behavioural profile and crying in premature infants at term age

Aim : To analyse behavioural characteristics of infants who cried more versus those who cried less, in a sample of low-risk premature infants. Methods : Participants were 63 low-risk healthy premature infants. At term age, the Neonatal Behavioral Assessment Scale (NBAS) was administered, and a 1-d diary for crying was recorded starting on the following day. Infants were categorized into two groups: those with "high level of crying" (≥75th percentile) and those with "less crying" (<75th percentile), based on the total amount of crying time. Results : Some individual NBAS scores and "habituation" and "regulation of state" cluster scores were lower in the high-level-of-crying group. Infants in the group with a high level of crying had lower thresholds for response in the "peak of excitement", "rapidity of build-up", "irritability" and "general irritability" items. Logistic regression analysis revealed that lower "habituation" and "regulation of state" cluster scores were significantly associated with lower thresholds for crying.
Conclusion : These results suggest that neonatal behavioural characteristics, such as hyperresponsivity and poor state regulation, are associated with high levels of crying. Clinical assessments based on the NBAS may help parents elucidate their infant's level of tolerance for stimuli, and identify strategies to minimize their crying.     

Brain positron emission tomography in preterm and term newborn infants

Objective

To study the clinical values of positron emission tomography (PET) in preterm and term newborn infants through observing brain glucose metabolism by ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET.

Method

To observe the brain ¹⁸F-FDG PET imaging in 9 term and 7 preterm newborn infants in the same condition after administration of 0.1 mCi/kg ¹⁸F-FDG.

Result

The brain ¹⁸F-FDG PET imaging showed that the uptake of ¹⁸F-FDG was relatively more in the thalamus, and less in the cerebral cortex in preterm and term newborn infants. The uptake of ¹⁸F-FDG of cerebral cortex in preterm infants was less than that in term infants, so the structure of brain ¹⁸F-FDG PET imaging was a little fainter in preterm neonates as compared with that in term newborns.

Conclusion

¹⁸F-FDG PET imaging could show different glucose metabolisms of brain in preterm and term infants. Brain ¹⁸F-FDG PET imaging might be a useful tool for estimating the brain function in newborn infants, and its clinical values need further investigation.     

The behavioral pain response to heelstick in preterm neonates studied longitudinally: Description, development, determinants, and components

Objectives

Preterm infants often experience multiple painful procedures during their stay in neonatal intensive care units (NICUs). The objectives of this study were to evaluate behavioral responses to heelstick in preterm newborns, characterize developmental changes and the effects of other demographic and clinical variables on the pain response, and estimate the contributions of individual Neonatal Infant Pain Scale (NIPS) behaviors to the summary pain score.

Methods

A longitudinal study was conducted to evaluate the behavioral responses of 35 preterm newborns to multiple heelstick procedures during their stay in the NICU. Sixty-one video recordings of blood collection by heel lance were evaluated for behavioral pain response using the NIPS. Generalized linear mixed models were calculated to address the study objectives.

Results

The increases in NIPS scores from the baseline to the blood draw were highly significant (mean baseline score = 3.34, mean blood draw score = 5.45, p < 0.001). The newborns' pain responses increased an average of 0.23 points on the NIPS scale each week (p = 0.002). Lower NIPS scores during the heelstick procedure were associated with four clinical variables: younger post-menstrual age at birth, lower birthweight, mechanical ventilation, and longer length of stay in the NICU. Crying, arousal state, and facial grimace contributed more than 85% of the increase in NIPS scores during the heelstick procedure.

Discussion

While behavioral responses to pain are attenuated in young, severely ill preterm newborns, they can be reliably detected. The most robust pain behaviors are crying, changes in arousal state, and facial grimacing.     

Urinary S-100B concentrations in term and preterm infants at risk for brain damage

BACKGROUND: Elevated serum concentrations of S-100B, a 21-kDa protein expressed in astroglial cells, has been used to assess cerebral damage after head trauma, infection, ischemia, and perinatal asphyxia. OBJECTIVE: As S-100B is eliminated by the kidneys, we investigated the feasibility of measuring S-100B in urine of newborns with severe perinatal asphyxia, and in very low birth weight (VLBW) preterm infants at risk for neurodevelopmental impairment. METHODS: We first analyzed urine samples of 8 term or near-term newborns without major medical problems, followed by urine samples of 2 term newborns with severe birth asphyxia, and finally urine samples of 8 VLBW (gestational age 24-28 weeks) infants collected every 4 h for up to 10 days. RESULTS: Urinary S-100B concentrations in 8 term or near-term newborns without major medical problems were consistently <1 microg/l. In 2 term newborns with severe asphyxia (Apgar 0/0/0 and 0/2/4) who subsequently had widespread cerebral damage on magnetic resonance imaging, peak urinary S-100B concentrations on the first day of life were 28.1 and 28.4 microg/l, respectively. In 5/8 VLBW infants, urinary S-100B was> microg/l in samples obtained on the first day of life (range 1.2-44.9 microg/l, median 6.8 microg/l). Peak S-100B in urine samples collected during the first 12 h of life were negatively related to gestational age (R(s)=-0.882, p=0.009). Three of the 8 preterm infants had peak urinary concentrations>0 microg/l but neither ultrasound signs of brain damage nor neurodevelopmental delay at 1 year corrected age. CONCLUSIONS: The determination of urinary S-100B concentrations might be helpful in term infants with severe asphyxia, while high urinary S-100B concentrations in preterm infants are to be attributed to immaturity.     

Skin conductance as a measure of pain and stress in hospitalised infants

BACKGROUND: Reliable and valid methods of measuring pain responses in infants continue to be sought as a means of evaluating the effectiveness of pain reduction strategies. Skin conductance has recently been shown to be a promising physiological indicator of pain and stress in premature and term infants. AIM: To evaluate changes in skin conductance in hospitalised infants under different environmental conditions and during both painful and non-painful procedures. METHODS: Measurements of skin conductance activity were made in infants under three different environmental temperature conditions (open cot, incubator and overhead radiant heater), during the routine non-painful nursing procedure of either nappy change or oral feeding, and whilst undergoing the painful procedure of heel lancing for blood sampling. RESULTS: Skin conductance activity in 21 infants was studied on 43 separate occasions. Skin conductance activity was highly variable between infants but did not differ significantly under the three environmental conditions. Routine nursing care did not result in a significant increase in skin conductance activity above baseline; however, on cessation of care there was a significant reduction to levels below baseline (p < 0.05). Conversely, during the heel lance procedure, skin conductance activity significantly increased upon lance (p < 0.05) and remained elevated following completion of the procedure. There were no statistically significant differences between skin conductance activity changes from baseline as a result of routine nursing care compared to that of the heel lance procedure. CONCLUSION: Due to large variability in skin conductance activity further studies are needed before this technology can be recommended as a clinically useful indicator of pain and stress in neonates.     

Early prediction of neurological outcome by term neurological examination and cranial ultrasound in very preterm infants

Aim: To assess the value of term neurological examination and cranial ultrasound in the early prediction of neurological outcome at 12 months corrected age in a cohort of very preterm infants.
Methods: A cohort of 102 preterm infants born at <32 weeks gestation or with a birth weight of <1500 g were assessed using the Hammersmith Term Neurological Examination. They underwent cranial ultrasound examinations according to local guidelines. The Hammersmith Infant Neurological Examination was performed at 12 months corrected age. Scores for the term examinations were compared with scores derived from healthy infants born at term and with scores from low-risk preterm infants at term equivalent age. Term neurological scores and cranial ultrasound findings were compared in the prediction of 12-month neurological outcome.
Results: Seventy-eight (76.5%) preterm infants had suboptimal total neurological scores at term when compared to healthy infants born at term. However, most went on to have optimal neurological scores at 12 months corrected age. When our cohort was compared with low-risk preterm infants at term equivalent age only 14 (13.7%) scored outside the normal range. Neither system of scoring predicted neurological outcome at 12 months corrected age as reliably as cranial ultrasound (sensitivity 0.83, specificity 0.87).
Conclusion: Neurological examination of preterm babies at term may be unreliable in the prediction of neurological outcome at 12 months corrected age. For early prediction of neurological outcome cranial ultrasound examination was found to be more reliable.     

Postnatal and postprandial changes in plasma concentrations of glicentin in term and preterm infants

Aim: To examined the changes in basal plasma concentrations of glicentin in developing children and the postnatal and postprandial changes in plasma glicentin levels in infants. Methods: Glicentin, an active component of enteroglucagon, is considered to have a significant trophic action on the intestinal mucosa. Fasting plasma concentrations of glicentin in healthy children and in term and preterm infants were measured before and 30 min after feeding during the first 14 d of life. Results: Plasma basal concentrations of glicentin in children under 1 y of age were significantly higher than those in children aged 1 to 15 y. Plasma basal concentrations of glicentin at 5 or 6 d (2496 and 2190 pg/ml) and at 14 d (2987 and 2817 pg/ml) after birth were significantly higher than those at 1 or 2 d (1098 and 1240 pg/ml) after birth in normal birthweight (NBW) and low-birthweight (LBW) infants. There was no significant difference in the glicentin level between infants at 1 or 2 d (1864 pg/ml) and at 5 or 6 d (1910 pg/ml) after birth in very-low birthweight (VLBW) infants, but the levels at 14 d (3310 pg/ml) after birth were significantly higher than either of those levels. Plasma glicentin concentrations after feeding were significantly higher than those before feeding at 1 or 2 d and at 5 or 6 d after birth in NBW and LBW infants, but a significant increase in the plasma glicentin level after feeding was first observed at 14 d after birth in VLBW infants. There were no significant differences in the basal plasma (2401 and 2718 pg/ml) and postprandial (3007 and 3912 pg/ml) glicentin levels between breastfed and formula-fed infants.

Conclusion: The results of the study suggest that glicentin may play an important role in intestinal mucosal growth in the early period of life, although its role in VLBW infants should be further investigated.     

影响早产儿肺透明膜病机械通气短期预后的危险因素分析

目的探讨影响早产儿肺透明膜病(HMD)机械通气短期预后的危险因素。方法将47例HMD早产儿分为死亡组和存活组,用单因素χ2检验和多因素Logistic回归分析判定影响机械通气短期预后的危险因素。结果胎龄≤30周、院外出生、出生时窒息、严重酸中毒、生后未应用PS、HMD III~IV级、HMD自身及机械通气并发症、机械通气>3 d与机械通气短期预后有关(P<0.05或P<0.01)。Logistic回归分析发现HMD自身及机械通气并发症、院外出生、HMD III~IV级为机械通气短期预后的独立影响因素(OR=6.773、8.809、9.290,P均<0.05)。结论HMD自身及机械通气并发症、院外出生、HMD III~IV级是影响早产儿HMD机械通气短期预后的重要危险因素,应重视并针对危险因素加以预防。     

早产儿404例脑损伤发生率及相关因素分析

目的调查我院住院早产儿脑损伤发生率及影响因素。方法对2003年8月至2005年10月我院收治的404例早产儿应用ABR4000S/L B超诊断仪在生后3~7d内常规进行床边头颅B超检查。结果150例早产儿存在脑损伤,平均胎龄为(33·27±1·99)周;平均出生体重(1993±505)g。总的脑室内出血发生率35·2%(142/404),脑室周围白质软化的发生率3·5%(14/404),轻度脑损伤发生率23·5%(95/404),重度脑损伤发生率13·6%(55/404)。胎龄越小,体重越低,脑损伤发生率越高,但与颅内出血程度无关。妊高征、宫内窘迫、胎龄、高频振荡通气治疗、出生时窒息、出生体重可使早产儿脑损伤发生率增高。结论早产儿脑损伤的发生及严重程度与多因素有关,头颅B超可对早产儿脑损伤作出早期诊断,为早期干预提供依据。     

早产儿404例脑损伤发生率及相关因素分析

目的 调查我院住院早产儿脑损伤发生率及影响因素.方法 对2003年8月至2005年10月我院收治的404例早产儿应用ABR4000S/L B超诊断仪在生后3～7 d内常规进行床边头颅B超检查.结果 150例早产儿存在脑损伤,平均胎龄为(33.27±1.99)周;平均出生体重(1 993±505)g.总的脑室内出血发生率35.2%(142/404),脑室周围白质软化的发生率3.5%(14/404),轻度脑损伤发生率23.5%(95/404),重度脑损伤发生率13.6%(55/404).胎龄越小,体重越低,脑损伤发生率越高,但与颅内出血程度无关.妊高征、宫内窘迫、胎龄、高频振荡通气治疗、出生时窒息、出生体重可使早产儿脑损伤发生率增高.结论 早产儿脑损伤的发生及严重程度与多因素有关,头颅B超可对早产儿脑损伤作出早期诊断,为早期干预提供依据.     

Reliability, sensitivity and responsiveness of the Infant Behavioral Assessment in very preterm infants

Aim: The aim of this study is to investigate the reliability, sensitivity and responsiveness of the Infant Behavioral Assessment (IBA) to evaluate neurobehavioural organization in very preterm infants. Methods: Videotaped assessments of very preterm infants participating in a recent trial served to evaluate a standardized IBA observation. Inter‐rater reliability was based on 40 videos scored by two independent observers, using percentage agreement and weighted Kappa’s. Sensitivity was evaluated by comparing the IBA results of 169 infants at 35–38 weeks postmenstrual age, dichotomized according to two developmental risk factors. For responsiveness, the effect size (ES) was calculated between 0 and 6 months corrected age in all intervention and control infants and in subgroups of high‐risk intervention and control infants with oxygen dependency ≥28 days. Results: Inter‐rater agreement was 93% in the total assessment; Kappa agreement was moderate to good in the behavioural categories. Significant differences were found between groups with or without risk factors. Larger differences between ESs in the randomized groups with oxygen dependency ≥28 days than in the total randomized groups reflect the responsiveness of the IBA. Conclusion: In this study, we found satisfactory to good clinimetric characteristics of the IBA in very preterm born infants.     

Prediction of developmental performance in preterm infants at two years of corrected age: contribution of the neurological assessment at term age

Background

The population of preterm infants is increasing and resources available for follow-up are limited. Early markers are needed to identify children who will show major as well as more subtle neurodevelopmental impairments. Such a challenge could be achieved with the Amiel-Tison Neurological Assessment at Term (ATNAT).

Aims

This study assesses the usefulness of the ATNAT in the prediction of developmental problems at two years of corrected age (CA) in infants born between 29 and 37 weeks of gestation.

Method

Inclusion criteria were: gestational age between 29^0/7 and 36^6/7 weeks inclusively, birth weight below 2500 g and minimal 24-hour stay in the Neonatal Intensive Care Unit of Sainte-Justine Hospital. A sample of 147 was prospectively recruited and assessed at two ages: at term with the ATNAT and at 24 months CA with Bayley Scales of Infant Development-II.

Results

No major impairment such as cerebral palsy and no neurosensory impairment were observed. Developmental delay defined by an index < 70 on the mental or psychomotor scale was reported respectively in 6.2% and 5.4% of the cohort. Significant differences in mental, psychomotor and behavioral performances were found according to neurological status. Neurological status was the only variable to enter the predictive model for psychomotor and behavioral indexes. Gender and neurological status remained in the predictive model for mental performance.

Conclusion

This study supports the inclusion of the ATNAT among the eligibility criteria for systematic neurodevelopmental surveillance as it allows early identification of infants at higher risk of low developmental performances at 24 months CA.     

早产儿动脉导管未闭危险因素临床分析

目的探讨早产儿动脉导管未闭(PDA)发生的有关危险因素。方法对2008年1～12月在我院新生儿科住院751例早产儿进行回顾性分析,其中133例行超声心动图检查,48例诊断PDA为病例组,85例非PDA为对照组,对两组临床资料进行对照研究,应用Logistic回归模型分析。结果单因素分析显示,胎龄、出生体重、母亲产前用激素、胎儿宫内窘迫、吸氧、出生窒息、呼吸衰竭、肺透明膜病、败血症、液体摄入、超声心动图检查时机与早产儿PDA的发生有关联,其OR值分别为2.636、2.755、0.311、12、0.431、3.692、3.038、7.085、2.282、2.581、1.026、0.474;Logistic回归分析表明小胎龄、低出生体重、出生窒息、败血症是主要危险因素,其OR值分别是2.517、2.957、13.770、3.493,而母亲产前用激素、吸氧是主要保护因素,其OR值是0.208和0.127。结论早产儿发生PDA与围生期多种因素有关,有针对性开展围生期保健是降低早产儿PDA的有效措施。     

Magnetic resonance imaging at term and neuromotor outcome in preterm infants

In order to evaluate the value of neonatal brain magnetic resonance imaging (MRI) for predicting neuromotor outcome in very low birthweight (VLBW) preterm infants, 51 such infants with gestational age <34 wk underwent brain MRI at term age. Myelination, parenchymal lesions (haemorrhage, leukomalacia, infarction, reduction of white matter), parenchymal lesions without subependymal haemorrhage, ventricular/brain ratios and widths of the extracerebral spaces were assessed. The MRI findings were compared with cranial ultrasound (US) performed at term. Infants' neuromotor development was followed up until 18 mo corrected age. Parenchymal lesions seen in MRI at term predicted cerebral palsy (CP) with 100% sensitivity and 79% specificity, the corresponding figures for US being 67% and 85%, respectively.
Parenchymal lesions in MRI, excluding subependymal haemorrhages, predicted CP with a sensitivity of 82% and a specificity of 97%, the corresponding figures for US being 58% and 100%, respectively. Delayed myelination, ventricular/brain ratios and widths of the extracerebral spaces failed to predict CP. Term age is a good time for neuroradiological examinations in prematurely born high-risk infants. Parenchymal lesions seen in MRI are reliable predictors for CP.