Pain and distress reactivity and recovery as early predictors of temperament in toddlers born preterm

Background

Pain reactivity may reflect underlying mechanisms of constitutional aspects of temperament.

Aim

To examine whether the neonatal biobehavioral reactivity and recovery responses from pain and distress, as well as the gestational age, the illness severity and the amount of painful procedures undergone the Neonatal Intensive Care Unit (NICU) stay, predict temperament later in toddlerhood, in vulnerable children born preterm.

Study design

Prospective-longitudinal study.

Subjects

Twenty-six preterm and very low birth weight infants followed from birth to toddlerhood.

Outcome measures

Illness severity was assessed with the Clinical Risk Index for Babies (CRIB) score. The medical charts were reviewed prospectively for obtaining the amount of pain exposure in NICU. For assessing the behavioral and cardiac reactivity and recovery from pain and distress, the neonates were evaluated during routine blood collection in the NICU in the first 10 days of life. Pain and distress reactivity and recovery was measured using the Neonatal Facial Coding System score, the duration of crying, and the magnitude of average heart rate. At toddlerhood, mothers answered the Early Childhood Behavior Questionnaire.

Results

Higher biobehavioral reactivity to pain and distress predicted higher temperamental Negative Affect, above and beyond gestational age, illness severity and amount of pain exposure in NICU. However, we did not find a predictive relation between gestational age, CRIB score and number of painful procedures undergone NICU and toddler's temperament.

Conclusions

The findings highlight the relevance of the neonatal individual characteristics of reactivity for identifying more vulnerable infants for future problems in biobehavioral regulation.     

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.     

Promoting shorter duration of ventilator treatment decreases the number of painful procedures in preterm infants

Aim:  To investigate whether promoting shorter ventilator treatment decreases the number of painful procedures and the use of analgesics in preterm infants.
Methods:  Retrospective patient chart review of all preterm infants in one Neonatal Intensive Care Unit (NICU) was carried out in 2000 (n = 240) and 2005 (n = 206). Between these cohorts, early nasal continuous positive airway pressure (nCPAP) application and early extubation policy were introduced.
Results:  Fewer infants were intubated (22 vs. 32%, p = 0.03), the duration of ventilator treatment decreased (6.7 SD 11.3 vs. 9.0 SD 11.1 days, p < 0.001) and nCPAP treatment became more common (41 vs. 25%, p < 0.001) in 2005 than in 2000. Similarly, the infants' exposure to painful procedures did not decrease significantly (61.9 SD 98.5 vs. 67.1 SD 104.3 procedures, p = 0.32) but the procedures related to respiratory support were fewer (45.2 SD 79.5 vs. 68.9 SD 91.1 procedures, p < 0.001) in 2005 than in 2000. In addition, the amount of pain medication used was significantly lower in 2005 than in 2000. One day on a ventilator included more painful procedures than a day on nCPAP (11.2 95% CI: 11.0–11.5 vs. 4.2 95% CI: 4.1–4.4 procedures, p < 0.001) during both study years.
Conclusion:  Early nCPAP and early extubation policies were successfully implemented in an NICU resulting in less invasive respiratory support. This was associated with fewer painful procedures and less pain medication in the preterm infants who required respiratory support. Despite this positive effect, the number of painful procedures in all preterm infants stayed at the same level. Our results provide further support for the use of nCPAP in preterm infants.     

Analgesia in preterm newborns: the comparative effects of sucrose and glucose

The aim of this study was to evaluate the effectiveness of different oral carbohydrate solutions for alleviation of pain in healthy preterm babies. Thirty-one preterm infants who were having blood drawn by heel prick were given 2 ml of solution A (20% sucrose), solution B (20% glucose) or solution C (placebo, sterile water) into the mouth, 2 min before lancing. Behavioural responses to this painful stimulus were measured by duration of crying and facial expressions (Neonatal Facial Coding System, NFCS) and physiological responses were measured by heart rate (HR), respiratory rate (RR), and oxygen saturation changes (SaO₂). Infants had a mean birth weight (±SD) of 1,401 g (406), gestational age of 30.5 weeks (2.7); at the time of the procedure the postmenstrual age was 32.3 weeks (1.5). There was no significant difference in the time spent squeezing the heel between the three groups (P = 0.669). After the heel prick of both the sucrose and glucose groups the duration of first cry and total crying time was significantly reduced (P = 0.005 and P = 0.007). When the babies received placebo they showed a significantly higher NFCS score at 4 and 5 min after the heel prick (P = 0.009 and 0.046 respectively). Following painful stimulus HR increased significantly in the first 3 min compared with baseline, and at the first minute the mean of the HR was found to be significantly higher in the placebo group than in the sucrose and glucose groups (P = 0.007). We concluded that both sucrose and glucose administered orally before a heel prick reduce the pain response in preterm infants.     

早产儿低血压诊治进展

低血压是新生儿重症监护室的常见疾病,早产儿更容易出现低血压.目前,对早产儿低血压的定义、何时开始治疗及如何治疗仍存在争议,治疗上除扩容外,主要的药物有多巴胺、多巴酚丁胺、肾上腺素、氢化可的松、米力农等,这些药物能否改善早产儿预后需要更多的临床研究加以证实.     

Stool pH and sugar in preterm neonates

The stool pH and sugar were examined in 76 breast fed and 38 formula fed premature infants. The stool pH decreased gradually till 5th day of life and then increased again. Stool sugar was not more than 0.75 percent in breast fed and 0.5 percent in formula fed during first seven days of life. A premature infant with stool pH<6 and sugar>0.5 percent after seventh day of life needs to be investigated for pathological sugar malabsorption.     

Prevention and treatment of necrotising enterocolitis in preterm neonates

Prevention and treatment of NEC has become an area of priority for research due to the increasing number of preterm survivors at risk, and the significant mortality and morbidity related to the illness. Probiotic supplementation appears to be a promising option for primary prevention of NEC but further large trials are necessary for documenting their safety in terms of sepsis as well as long-term neurodevelopmental outcomes and immune function. As new frontiers including immunomodulating agents like pentoxifylline continue to be explored, the impact of well-established simple strategies like antenatal glucocorticoid therapy, and early and preferential use of breast milk must not be forgotten. Clinical research on manifestations of ileus of prematurity, and feeding in the presence of common risk factors such as IUGR is needed. Safety of minimal enteral feeds in terms of NEC and benefits of standardised feeding regimens need to be confirmed. Association of common clinical practices such as red cell transfusions, H2 receptor blockade, and thickening of feeds with NEC warrants attention. An approach utilising a package of potentially better practices seems to be the most appropriate strategy for the prevention and treatment of NEC.     

Inflation time in mechanical ventilation of preterm neonates

The importance of the preterm infant's inspiratory time in determining the optimum inflation time during mechanical ventilation was investigated. The optimum inflation time was defined as that which was most commonly associated with synchronous respiration and maximum minute volume. Twelve preterm infants were studied on 14 occasions. They were ventilated at rates of 60, 75, 90, 105 and 120 breaths/min, with an inspiratory: expiratory ratio of 11.2. These rates were chosen as they resulted in inflation times approximating to the spontaneous inspiratory time measured during a brief period of disconnection, on continuous positive airways pressure (CPAP), and greater than that measured on CPAP. Inspiratory time during disconnection was always shorter than that measured on CPAP (P<0.01). Synchrony was most commonly provoked and minute volume greatest at the shortest inflation time (P<0.01). We conclude fast ventilator rates are most efficacious for preterm neonates. As previously shown, this rate can be estimated by examining the standard reference range of rates in relation to gestational age.     

Current management of transitional feeding issues in preterm neonates born in Queensland, Australia

Background

Many preterm neonates display difficulty establishing suck-feeding competence in the weeks following birth. Ineffective management of transitional feeding issues may cause patient complications, and can contribute to increased length of stay.

Aims

Given that many neonatal nurseries appear to vary in their neonatal feeding management practices, the aim of this study was to investigate and document the routine level of support and intervention currently provided for preterm neonates with transitional feeding issues across the various level II (special care) nurseries (SCNs) in Queensland, Australia.

Methods

A questionnaire was mailed to all Queensland SCNs in 2005 (n = 36). The questionnaire contained a series of closed-choice and short-answer questions designed to obtain information from each SCN regarding their current practices for managing transitional feeding issues in preterm neonates. Results were confirmed during a follow-up phone call.

Results

Responses were obtained from 29 SCNs (80.6%). None of these nurseries reported having any formal, written policies regarding the management of transitional feeding issues in preterm neonates. Wide variations were reported in relation to the suck-feeding assessments and interventions used by staff within the various SCNs. Of the 29 nurseries, 4 (13.8%) reported using checklists or assessments to judge readiness for suck-feeds, and 5 (17.2%) reported using pulse oximetry to judge tolerance of suck-feeding attempts. Eighteen SCNs (62.1%) reported offering some form of active intervention to assist neonates with transitional feeding issues, with the most common intervention techniques reported being non-nutritive sucking during tube feeds, pre-feeding oral stimulation, and actively pacing suck-feeds. Twenty-two SCNs (75.4%) reported having access to a lactation consultant to assist mothers with breastfeeding issues.

Conclusions

Differences were reported in the routine management of transitional feeding issues in preterm neonates across the various SCNs in Queensland. It is suggested that evidence based guidelines need to be developed, and that, in order to do this, further research studies are required to determine current best practice, as well as to answer remaining questions.     

Acute symptomatic neonatal seizures in preterm neonates: etiologies and treatments

Acute symptomatic neonatal seizures in preterm newborns are a relevant clinical challenge due to the presence of many knowledge gaps. Etiology-wise, acute symptomatic seizures have an age-specific epidemiology, with intraventricular hemorrhage and its complications representing the first cause in extremely and very preterm neonates, whereas other etiologies have similar occurrence rates as in full-term infants. Specific treatment strategies for the premature neonates are not yet available. Studies suggest a similarly low response rate with even more unfavorable prognosis than in full-term infants. Pharmacodynamic and pharmacokinetic changes are likely under way during the preterm period, with the potential to affect both effectiveness and safety of antiepileptic drugs in these patients. However, due to the lack of clear evidence to guide prioritization of second-line drugs, off-label medications are frequently indicated by review papers and flow-charts, and are prescribed in clinical practice. We therefore conclude by exploring potential future lines of research.     

Assessment of jaundice in preterm neonates: comparison between clinical assessment, two transcutaneous bilirubinometers and serum bilirubin values

Aim: 1) To compare the clinical assessment of craniocaudal progression of jaundice and two transcutaneous bilirubinometers with serum bilirubin values in preterm neonates; 2) to identify factors affecting the difference between non-invasive bilirubin estimation and serum bilirubin. Methods: Serum bilirubin was clinically estimated in healthy preterm newborn infants (34 to 36.9 gestational weeks) independently by a primary investigator and by nurses, and subsequently compared with separate measures of two transcutaneous bilirubinometers. Results: A total of 107 measurements were performed on 69 infants. Minolta JM-102 showed the best performance, with ROC area under the curve of 0.96, followed by BiliCheck™ over the sternum (0.89) and over the forehead (0.88), clinical assessment by nurses (0.73) and by a physician (0.70). Serum bilirubin >190 μmol/l can be detected with 95% sensitivity with Minolta JM-102 ≥19 units, with BiliCheck™ ≥145 μmol/l over the sternum and ≥165 μmol/l over the forehead and with jaundice progression to the trunk or further (Kramer zone ≥2). Gestational age affects all non-invasive methods in the estimation of serum bilirubin, whereas skin colour affects both BiliCheck™ and clinical assessment. Ambient light affects only clinical assessment.

Conclusion: Minolta JM-102 showed the best performance, closely followed by BiliCheck™, with clinical assessment performing far worse than either transcutaneous method. None of the three methods are recommended as complete substitutes for serum bilirubin values in jaundiced preterm infants.     

Analgosedation with low-dose morphine for preterm infants with CPAP: risks and benefits

BACKGROUND: CPAP is widely used in preterm infants on NICUs but it poses a stressful stimulus to the patient, sometimes requiring the use of analgosedative drugs. AIM: The aim of this study is to evaluate the risks and benefits associated with the use of low-dose morphine in preterm infants with CPAP, especially apnea. METHODS: Sixty-four CPAP-treated preterm infants, who received a low single dose of morphine (recommended 0.01 mg/kg), were included in this prospective study. Observation-time was 4 h prior to injection, directly before injecting, until 15 min and 15-30 min, 30 min-1 h, 1-2 h, 2-3 h, 3-4 h, 4-5 h and 5-6 h after injection. For all observation periods incidence of apnea, heart rate, respiratory rate and a score for analgesia and for sedation were recorded. RESULTS: Sixty-four preterm infants (29.6+/-3.3 weeks gestational age (GA), birth weight 1401+/-735 g) received 0.025+/-0.012 mg/kg morphine i.v. on the day 10-13 of life. The decrease in heart and respiratory rate, scores for analgesia and sedation were significant. The overall incidence of apnea did not increase compared to the 4 h pre-morphine period. Six patients (9.3%) experienced considerable delayed apnea. This group was significantly younger in GA (p<0.001) and lighter in birth weight (p=0.002). CONCLUSION: Morphine in dosage less than half of recommended dosage has a high analgetic and sedative potential. The danger of delayed severe apnea has to be taken into consideration in the clinical situation, especially in patients<28 weeks.     

Alternative female kangaroo care for procedural pain in preterm neonates: a pilot study

Aim: To determine the feasibility and effect size of kangaroo care (KC) for pain from heel lance in preterm neonates provided by either the infant’s mother (MKC) or an unrelated alternate female (AFKC). Methods: Using a randomized crossover design, preterm neonates (n = 18) between 28 and 37 weeks gestational age within 10 days of life from two university‐affiliated level III NICU’s undergoing routine heel lance were assigned to receive KC 30 min before and during the procedure from either their mother (MKC) or an unrelated woman. In the second heel lance procedure at least 24 h later but within 10 days, the infants were crossed over to the other condition. Results: There was a 48% participation rate, with only 40 of 82 eligible cases having maternal consent. The main reason for refusal was discomfort with another woman providing kangaroo care. The effect sizes on the pain scores (PIPP) were small, ranging from .23 to .43 across the first 2 min of procedure. Conclusion: The difference between nonrelated females and the mother in decreasing pain response is small, although not negligible. Given the high refusal rate, nonrelated females are a less desirable alternative to mothers than fathers.     

Comparison of the transcutaneous bilirubinometers BiliCheck and Minolta JM‐103 in preterm neonates

Aim: To investigate the trueness and uncertainty of two transcutaneous bilirubinometers BiliCheck and Minolta JM‐103 in preterm infants; establish cut‐off values for the transcutaneous bilirubin (TcB) level, indicating the need for total serum bilirubin (TsB) measurement; and estimate how many blood samples could be saved. Methods: In 133 neonates with gestational ages 28⁺⁰–34⁺⁶ weeks, 239 measurements of TcB by BiliCheck (TcB(B)) and JM‐103 (TcB(M)) and of TsB were performed. Results: Median TsB of the first samples was 160 (range, 53–293) μmol/L, whereas median TcB(B) was 12 μmol/L (8%) lower and TcB(M) 67 μmol/L (40%) lower. TcB(B) underestimated TsB for TsB ≥180μmol/L. All TcB(M) values, except one, underestimated TsB. The underestimation increased with increasing TsB. Multiple regression analysis showed that post‐natal age and ethnicity were confounding factors for TcB(M); none were found for TcB(B). The uncertainty was the same for the two instruments. By using cut‐off values of 70% of the phototherapy limit for TcB(B) and 35% for TcB(M), the sensitivity of the screening would be 95% and 97%, and 36% and 24% of the blood samples could be saved, respectively. Conclusion: TcB determined with JM‐103 gave values much lower than those obtained with BiliCheck. The underestimation of TsB increased with increasing concentrations. By using transcutaneous bilirubinometers in preterm neonates, 24–36% of the blood samples could be saved.     

Perinatal and socioeconomic determinants of breastfeeding duration in very preterm infants

AIM: To describe the impact of prematurity, size at birth, neonatal disorders and the families' socioeconomic status (SES) on breastfeeding duration in mothers of very preterm infants. METHODS: Prospective population-based cohort study. Data on breastfeeding, registered in databases in two Swedish counties in 1993-2001, were matched with data from two national registries: the Medical Birth Registry and Statistics Sweden. Mothers of 225 very preterm singleton infants were identified and included. RESULTS: Seventy-nine percent of the mothers breastfed at 2 months, 62% at 4 months, 45% at 6 months, 22% at 9 months and 12% at 12 months. Prematurity, size at birth and neonatal disorders did not show an effect on breastfeeding duration. Being adversely exposed to any of the SES factors (maternal education, unemployment benefit, social welfare and equivalent disposable income in the household) was significantly associated with earlier weaning up to 6 months of infants' postnatal age. CONCLUSIONS: This study shows new and noteworthy results concerning breastfeeding duration in mothers of very preterm infants, which was not influenced by degree of prematurity, size at birth or neonatal disorders but was affected by SES. This highlights the need for improved support of socioeconomically disadvantaged mothers, during and after the hospital stay.     

Correlation of grading and duration of periventricular echodensities with neurodevelopmental outcome in preterm infants

Background Transient periventricular echodensities (PVE) in preterm infants affect neurodevelopmental outcome.Objective To correlate the duration and grading of PVE with neurodevelopmental outcome.Materials and methods A retrospective, single-centre cohort study of infants with PVE diagnosed by ultrasonography from 1995 to 2000 with blinded grading and recognition of duration of PVE.Results A total of 72 infants (median gestational age 32 weeks, median birth weight 1,668 g) were diagnosed as having PVE. Minor neurological abnormalities were diagnosed in seven (10%), cerebral palsy in six (8%), developmental delay in seven (10%), and mild mental retardation in two (3%) of the infants. Differences regarding adverse outcome were not significant between infants with severity grade 1 compared to severity grade 2 (16% and 22%, respectively). There was a significant increase in adverse neurodevelopmental outcome with increasing duration of PVE. Of 33 infants with duration of PVE <7 days, 1 (3%) had an adverse neurodevelopmental outcome, compared to 6 (24%) of 25 infants with a duration of PVE of 7–14 days, and 6 (43%) of 14 infants with a duration of PVE >14 days (P<0.002, RR 7.920, 95% CI 1.017–61.661; P<0.001, RR 14.143, 95% CI 1.871–106.895, respectively).Conclusion The duration, but not the grading, of transient PVE was significantly correlated with neurodevelopmental outcome.