Food intake and oral sucrose in preterms prior to heel prick

To investigate the soothing effect of feeding on infants in distress, the effects of 2 mL 15% and 1 mL 25% sucrose given orally 2 min before heel prick in fasting preterms to reduce the pain response were assessed. The effects of milk intake by nasogastric tube were also assessed once during the last hour before heel prick, and the effects of milk intake by nasogastric tube once during the last hour before heel prick together with 1 mL 25% sucrose given orally 2 min before heel prick. The pain response was measured as changes in crying time, behavioural state, skin conductance and heart rate. Each group included 12 healthy preterm infants with a median gestational age of 32 wk and a median postnatal age of 14 d. These infants were randomly studied twice; one in connection with the intervention and once after being given sterilized water. Differences in the measured variables before and during heel prick showed that only the crying time was reduced when the infants received milk or 25% sucrose prior to heel prick (p < 0.05). If the infants received milk and 25% sucrose before heel prick, the crying time and the level of behavioural state were reduced (p < 0.05). The increase from before to during heel prick in skin conductance (number and amplitude of the waves) and heart rate correlated with the crying time (p < 0.01).     

Skin conductance and the stress response from heel stick in preterm infants

AIM: To evaluate whether spontaneous skin conductance activity is an objective method for measuring the stress response to painful stimuli in premature infants. The number and amplitude of the waves and the baseline increase with the activity of the sympathetic nervous system. METHODS: In 20 preterm infants of gestational age >/= 29 weeks, behavioural state and spontaneous skin conductance activity variables were measured for three minutes before, during, and for three minutes after heel stick. RESULTS: The number of waves (p < 0.001), the amplitude of the waves (p = 0.001), and the level of the behavioural state (p < 0.001) increased during heel stick, and then decreased to levels found before the procedure. The baseline increased both during (p < 0.001) and after heel stick (p < 0.001), compared with levels before. CONCLUSION: Spontaneous skin conductance activity reflects the stress response to heel stick in premature infants from at least 29 weeks of gestational age.     

Development of emotional sweating in the newborn infant.

Sweating from the palm and sole occurs independently of ambient temperature but is influenced by emotional factors. It thus provides a useful objective measure of emotional state. The development of this emotional sweating in the newborn was investigated by measuring palmar water loss and relating it to the infant''s state of arousal. Although 433 individual measurements were made on 124 babies of gestational age 25 to 41 weeks and postnatal age 15 hours to 9 weeks. Palmar water loss was also recorded continuously in 22 infants undergoing heel prick for routine blood sampling. In babies of 37 weeks'' gestation or more, there was a clear relationship between palmar water loss and arousal from the day of birth, and by the third week levels on vigorous crying were comparable with those of an anxious adult. Less mature babies did not show emotional sweating at birth; it was first seen at the equivalent of 36 to 37 weeks'' gestation regardless of maturity. Continuous recordings confirmed the cross-sectional data and illustrated the abrupt nature of the response. Emotional sweating could be a useful tool for the assessment of emotional state of the newborn.     

Behavioural response to pain in healthy neonates.

A bedside technique for evaluating the behavioural response of healthy neonates to pain was assessed. Thirty six term infants (median gestational age 40 weeks; median postnatal age 4 days) and 31 preterm infants (median gestational age 34 weeks; median postnatal age 4 days) were assessed at the cotside for their response to heel preparation and heel lance for routine blood sampling. The facial actions of brow bulge, eye squeeze, nasolabial furrow, and open mouth were noted, and also the presence or absence of crying. Thirty five (97%) term and 26 (84%) preterm infants showed an increase in the number of behaviours in response to heel lance. Brow bulge and nasolabial furrow were seen most often, and occurred more often than crying in the two groups. There was good interobserver agreement (94%). The consistency of response and the high degree of interobserver agreement makes this method of behavioural assessment of acute pain of use in healthy neonates.     

Pain-relieving effect of sucrose in newborns during heel prick

We assessed the effect of sucrose as a pain reliever in a population of newborns when cuddled and comforted during heel prick for diagnosis of phenylketonuria. In addition, the influences of gender, gestational age, postnatal age, ponderal index and behavioural state of the infant before the heel prick were studied, as judged by the neonatal infant pain scale (NIPS) score, on crying time (CT) and subsequent NIPS score. 100 healthy full-term infants were enrolled in this double-blind, randomized controlled trial. Before the heel prick, the newborns, when cuddled by the parent(s), were either given 2 ml 50% sucrose solution or 2 ml sterile water. The sessions were videotaped and analyzed for determination of CT and NIPS scores. The frequency distribution of CT showed a bimodal pattern in both the sucrose and the placebo groups. Sucrose significantly reduced CT and NIPS scores after the heel prick. No influence of gender, gestational age, postnatal age or ponderal index on CT was found. NIPS scores before the heel prick correlated significantly and positively with CT and subsequent NIPS scores in both the sucrose and the placebo groups. Intra-orally administered sucrose given before heel prick can be recommended as a useful pain reliever. Furthermore, the findings indicate that factors calming the newborn and creating low NIPS scores before the procedure can reduce the pain reaction equivalently and additively to sucrose administration.     

Skin conductance and behaviour during sensory stimulation of preterm and term infants

Aim: To investigate the responses to painful and tactile stimulation in preterm and term infants in terms of changes in the plantar skin conductance activity (SCA) and behavioural state. Plantar SCA reflects activity in the sympathetic nervous system. Design: The plantar SCA and behavioural state in response to nociceptive (the heel prick for blood samples, or immunization) and tactile (routine nursery handling) simulation was recorded in four different groups of infants (n=71): Preterm and term neonatal infants (defined here as up to 1 week old), and preterm and term infants in the postneonatal period. Results: The preterm infants had significant increases in all skin conductance variables during both tactile and nociceptive stimulation (p<0.02), except for wave amplitude when newborns were heel pricked. The term infants displayed a more varied picture, but both the number and amplitude of the waves increased significantly during both procedures in the newborn groups, while the postneonatal groups only showed significant increases in wave amplitude during nociceptive stimulation (p<0.05). Tactile stimulation of the preterm newborn infants produced significantly higher increases in SCA than nociceptive stimulation (p<0.01), while the behavioural state was highest during nociceptive stimulation (p<0.05). A gradual change in this relation was seen with advancing total age. Conclusion: Non-painful sensory stimulation of infants, especially the newborn and preterm ones, can produce equal or higher levels of physiological stress activation than painful stimulation. Repeated nociceptive stimulation probably sensitises the infants to pain.     

Influences on heart rate variability in spontaneously breathing preterm infants.

To investigate the influence of maturational and physiological factors on heart rate variability in spontaneously breathing very preterm infants (n = 29) a multiparametric study was performed during the first 3 days of life in infants born at a gestational age below 33 weeks. Four times a day, RR-intervals, respiration curve and rate, transcutaneously measured blood gases and observed body movements were recorded while the infants were asleep. All data were stored simultaneously in a micro-computer. Non-invasively measured blood pressure and patency of the ductus arteriosus were documented as well. Four sets of short- (STV) and long term variability (LTV) indices were calculated. Both STV and LTV appeared to be significantly influenced by conceptional and postnatal age in the appropriate for gestational age infants. LTV was influenced by the behavioural state and body movements. During state coincidence 2 ('active sleep') LTV was influenced by respiratory rate and the variations in transcutaneous PO2. An effect of blood pressure or ductus patency could not be demonstrated.     

Does change in skin perfusion provide a good index to monitor the sympathetic response to a noxious stimulus in preterm newborns?

Skin perfusion was measured using laser Doppler fluximetry (LDF) in 16 preterm babies undergoing a standardised heel prick procedure. Although there was a significant reduction in skin blood flow following the heel prick, this was variable and dependent on basal skin blood flow. This, together with loss of data due to movement artefact, makes this technique unreliable in quantifying the sympathetic response to a noxious stimulus in preterm infants.     

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.     

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.     

Skin conductance measurements as pain assessment in newborn infants born at 22-27 weeks gestational age at different postnatal age

Background

To assess pain or stress in newborn infants submitted to intensive care is important but difficult, as different observational pain scales are not always reliable in premature infants. As an indicator of pain, skin conductance (SC) measurements have detected increased sweating in newborn infants > 28 gestational age (GA) submitted to heel lancing.

Objective

To measure SC during heel lancing and routine care in newborn infants, born at 22 to 27 GA, with special relation to postnatal age (PNA).

Methods

In six infants < 28 + 0 GA and 4 infants ≥ 28 + 0 GA spontaneous SC activity and behavioural state (Neonatal Pain Agitation and Sedation Scale (N-PASS)) was measured before, during and after each intervention. Measurements were repeated in each patient at different PNA.

Results

Baseline SC prior to intervention took longer time to stabilise and was higher in < 28 than in ≥ 28 + 0 PNA. The combination of heel lancing and squeezing gave an increased SC in < 28 PNA, whereas heel lancing alone gave the same SC response in ≥ 28 + 0 PNA. A possibly continued immature response in SC measurements was not observed. Oral glucose admission prior to heel lancing increased SC. Routine care did not give any changes in SC. Except during orogastric tube placement no signs of discomfort or pain could be detected by the neonatal pain, agitation and sedation scale (N-PASS) in < 28 PNA.

Conclusion

Changes in SC could be detected in infants at < 28 + 0 PNA and related to the combination of heel lancing and squeezing. A maturational development of the SC was observed in infants born < 28 GA. SC seems to be able to differentiate between pain and discomfort.     

Percutaneous lignocaine absorption in newborn infants

The permeability of the skin of newborn infants to lignocaine was examined in vitro using excised skin. Samples were studied from 24 infants of gestational age 25 to 40 weeks and postnatal age 0 to 7 days. Mature skin was relatively impermeable to lignocaine, but the more premature infants showed a marked increase in absorption. There was a strong inverse correlation between gestational age and skin permeability. These findings suggest that topical lignocaine would be an effective local anaesthetic in preterm infants. Calculations indicate that there is negligible risk of toxicity due to systemic absorption.     

Variations of the skin permeability in premature newborn infants. Value of the skin vasoconstriction test with neosynephrine]

BACKGROUND. The skin of preterm infants is defective as a barrier and does not function like that of mature until about 2 weeks of age. METHODS. Percutaneous drug absorption was studied by observing the blanching response to aqueous solutions of 10% Neosynephrin applied to a small area of skin on the internal surface of the thigh. The subjects, 10 preterm infants born at gestational ages 29 to 32 weeks (mean: 31 weeks 2 days), were tested when they were aged from day 0 to 7. The controls were 8 normal newborns aged 2 days. All preterm infants were tested a second time at the age 7 to 17 days (mean: 10 days). The blanching response was measured after 5 minutes, and graded on a scale of 0 to 4. RESULTS. The first test was positive grade 2 to 4 in all the preterm babies, while it was negative in the normal newborns. The second test was negative in 7 of the 10 preterm infants; in other 3, the grade was at least 50% lower. Infants nursed under radiant heaters were not different from the other infants. CONCLUSION. Skin permeability is increased in immature infants, but falls steadily until about the age of 10 days. The results of the Neosynephrin test could be useful in predicting the response to topically administered drug.     

Percutaneous lignocaine absorption in newborn infants

The permeability of the skin of newborn infants to lignocaine was examined in vitro using excised skin. Samples were studied from 24 infants of gestational age 25 to 40 weeks and postnatal age 0 to 7 days. Mature skin was relatively impermeable to lignocaine, but the more premature infants showed a marked increase in absorption. There was a strong inverse correlation between gestational age and skin permeability. These findings suggest that topical lignocaine would be an effective local anaesthetic in preterm infants. Calculations indicate that there is negligible risk of toxicity due to systemic absorption.     

The influence of respiratory distress syndrome on heart rate variability in very preterm infants.

In a multi-parametric study the influence of pathological neonatal conditions on heart rate variability was investigated in 60 preterm infants born at a gestational age below 33 weeks. Measurements were performed during the first 3 days of life. Four times a day, RR-intervals, respiration curve and rate, transcutaneously measured blood gases and observed body movements were recorded while the infants were asleep. All data were stored simultaneously in a micro-computer. Severity of respiratory distress syndrome (RDS), patency of ductus arteriosus and periventricular haemorrhage were documented as well. Four sets of short- (STV) and long-term variability (LTV) indices were calculated. Severe RDS was associated with a significant decrease in LTV. The influence of RDS on LTV persisted after correction for conceptional age, postnatal age, behavioural state and variations in respiratory rate and in transcutaneous PO2. Infants with a symptomatic patent ductus arteriosus had lower LTV than controls with the same severity of RDS. STV was predominantly influenced by postnatal and conceptional age, and tended to be lower in infants with periventricular haemorrhage.     

Absorption of chlorhexidine from the intact skin of newborn infants.

34 newborn infants who had been bathed in a standard manner with Hibiscrub were studied to find out whether it was absorbed percutaneously. Low levels of chlorhexidine were found in the blood of all 10 babies sampled by heel prick, and 5 of 24 from whom venous blood was taken. The detection of chlorhexidine varied greatly with the method and timing of sampling, and no correlation was found between gestational or postnatal age and chlorhexidine levels.     

Free-radical-induced lipid peroxidation during the early neonatal period

The effect of gestational age on postnatal free-radical-mediated lipid peroxidation was studied in 19 term (gestational age 37–42 weeks) and 21 healthy preterm (gestational age 31–36 weeks) infants by measurement of expired ethane and pentane during the first 7 days of life. Ethane (11.9 versus 5.7 pmol/kg/min; p = 0.0001) and pentane (11.4 versus 7.5 pmol/kg/min; p = 0.01) were significantly higher in preterm than in term infants. Correlations were found between gestational age and ethane ( r = 0.60, p = 0.0001) for days 1–7 and pentane ( r = 0.54, p = 0.0003) for days 3–7; and between birth weight and ethane ( r = 0.58, p = 0.0001) and pentane (r = 0.55, p = 0.0003). These results indicate that during the postnatal period, immaturity is a major factor determining the rate of free-radial-mediated lipid peroxidation.     

Blood pressure,heart rate,and skin temperature in preterm infants: associations with periventricular haemorrhage.

The mean arterial blood pressure (MABP), heart rate, and skin temperature were monitored every 15 minutes in the first 10 days after birth in 34 preterm infants, gestational age 24 to 33 weeks. Ultrasound brain scans carried out daily showed that a periventricular haemorrhage (PVH) occurred in a subgroup of infants (n = 15) of lower birthweight and gestational age. In infants without PVH the daily median of MABP increased with birthweight and postnatal age; that of heart rate was not affected by postnatal age, body weight, or gestational age; and that of skin temperature showed a slight fall with postnatal age. In infants with PVH, on or before the day of PVH, daily medians of MABP and skin temperature were not significantly different from those of infants without PVH, but the daily median of heart rate tended to be slightly higher. The percentage of positive correlations between the 96 15 minute values per day for heart rate and MABP increased with postnatal age and with birthweight, but did not differ in infants who developed a PVH. The coefficient of variation (CV) of the 96 15 minute values for MABP tended to be higher in infants on the day of PVH, and a similar trend was apparent on the day before. The processes of development of blood pressure, heart rate, and skin temperature are similar in infants with or without PVH but at lower gestational ages altered blood pressure control may cause brain haemorrhage.     

Circulating insulin-like growth factor I levels in newborn premature and full-term infants followed longitudinally

Longitudinal circulating levels of insulin-like growth factor I (IGF-I) were measured by radioimmunoassay after acid/ethanol extraction of serum or plasma in 44 appropriate-for-gestational age (AGA) premature infants, 7 small-for-gestational age (SGA) premature infants and 9 AGA full-term infants. The subjects were divided into cohorts with gestational age at birth 26-29 weeks, 30-33 weeks, 34-37 weeks and 38-42 weeks (full-term). The premature infants in this study exhibited diminished growth as compared with normal intrauterine growth. In all but the earliest premature infant cohort there was an immediate fall from the mean fetal IGF-I level, as reflected by the cord value, to a basal postnatal circulating level of IGF-I. The basal level of circulating IGF-I in premature infants was related only to gestational age. It increased slowly from 25 weeks gestation until four weeks after full-term equivalent and was independent of time of birth. Full-term infants were distinguished from early premature infants by the occurrence of a prominent postnatal surge in circulating IGF-I levels that was characterised by a significant (P less than 0.02) increase between day 1 and days 10-15. The SGA and AGA infants in the 34-37 week cohort showed similar profiles of circulating IGF-I with no significant difference in cord values between the two groups.     

Cardiovascular changes in preterm infants nursed under radiant warmers

Radiant heat is known to increase insensible water loss and, to a certain extent, oxygen consumption. Little is known about its cardiovascular effects. We measured cardiac output, stroke volume, heart rate, and lower limb and skin blood flow in 20 preterm newborn infants nursed in an incubator and under a radiant warmer at an abdominal skin temperature of 36.5 degrees C. Mean (+/- SEM) birth weight was 1.57 (0.06) kg, gestational age 31.7 (0.4) weeks, and weight at examination 1.69 (0.02) kg; median postnatal age was 15 days. Skin and limb blood flow measurements increased by 44% to 55% with radiant heat (P less than .001 and P less than .01, respectively). Cardiac output increased by 5.4% (P less than .02) under the radiant warmer secondary to a small but significant (P less than .05) increase in heart rate. The changes in cardiac output during radiant heat administration are comparable to those reported for oxygen consumption.