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Objectives: Cobedding of preterm twin infants provides tactile, olfactory, and auditory stimulation and may affect pain reactivity. We carried out a randomized trial to assess the effect of cobedding on pain reactivity and recovery in preterm twin neonates., Methods: Stable preterm twins (n = 67 sets) between 28 and 36 weeks of gestational age were randomly assigned to a cobedding group (cared for in the same incubator or crib) or a standard care group (cared for in separate incubators or cribs). Pain response (determined by the Premature Infant Pain Profile [PIPP]) and time to return to physiologic baseline parameters were compared between groups with adjustment for the nonindependence of twin infants., Results: Maternal and infant characteristics were not significantly different between twin infants in the cobedding and standard care groups except for 5-minute Apgar <7 and postnatal age and corrected gestational age on the day of the heel lance. Mean PIPP scores were not different between groups at 30, 60, or 120 seconds. At 90 seconds, mean PIPP scores were higher in the cobedding group (6.0 vs 5.0, P = .04). Recovery time was shorter in the cobedding group compared with the standard care group, (mean = 75.6 seconds versus 142.1 seconds, P = .001). No significant adverse events were associated with cobedding. Adjustment for nonindependence between twins and differences in baseline characteristics did not change the results., Conclusions: Cobedding enhanced the physiologic recovery of preterm twins undergoing heel lance, but did not lead to lower pain scores.

Objective: The purpose of this trial was to investigate whether breast milk (either breastfed or bottle-fed) has a better analgesic effect than sucrose in newborns born at a postmenstrual age between 32 and 37 weeks., Methods: We conducted a randomized controlled trial at a secondary care neonatal unit in the Netherlands on 71 preterm neonates (postmenstrual age at birth 32-37 weeks), undergoing heel lance with an automated piercing device. Newborns were randomly assigned to breast milk (either breastfed or bottle-fed) administered during heel lance or oral sucrose administered before heel lance. We assessed the Premature Infant Pain Profile (PIPP) score (range, 0-21) to investigate whether there was a difference in pain score between neonates receiving breast milk and those receiving sucrose solution., Results: There was no significant difference in mean PIPP score between neonates receiving breast milk (6.1) and those receiving sucrose (5.5), with a mean difference of 0.6 (95% confidence interval -1.6 to 2.8; P = .58)., Conclusions: From this study, it cannot be concluded that breast milk has a better analgesic effect than sucrose in late preterm infants. From the results, it follows with 95% confidence that the analgesic effect of breast milk is not >1.6 points better and not > 2.8 points worse on the PIPP scale (SD 3.7) than the analgesic effect of sucrose in late preterm infants.

Objective: Pain experience can alter clinical outcome, brain development, and subsequent behavior in newborns, primarily in preterm infants. The aims of this study were (1) to evaluate several simple, commonly used methods for pain control in newborns and (2) to evaluate the concordance between behavioral and autonomic cardiac reactivity to pain in term neonates during heel-lancing., Methods: A prospective study was conducted of 180 term newborn infants who were undergoing heel-lancing for routine neonatal screening of phenylketonuria and hypothyroidism. Newborns were assigned to 6 groups: (1) control (no pain relief intervention); (2) nonnutritive sucking; (3) holding by mother; (4) oral glucose solution; (5) oral formula feeding; or (6) breastfeeding. Outcome measures included the Neonatal Facial Coding System score; cry duration; and autonomic variables obtained from spectral analysis of heart rate variability before, during, and after heel-lancing., Results: Infants with no pain control showed the highest pain manifestation compared with newborns to whom pain control was provided. Infants who breastfed or received an oral formula showed the lowest increase in heart rate (21 and 23 beats per minute, respectively, vs 36; P < .01), lowest neonatal facial score (2.3 and 2.9, respectively, vs 7.1; P < .001), lowest cry duration (5 and 13 seconds, respectively, vs 49; P < .001), and lowest decrease in parasympathetic tone (-2 and -2.4, respectively, vs 1.2; P < .02) compared with the other groups., Conclusions: Any method of pain control is better than none. Feeding and breastfeeding during heel-lancing were found to be the most effective methods of pain relief.

Objective: The purpose of this work was to compare the efficacy of breastfeeding versus orally administered sucrose solution in reducing pain response during blood sampling through heel lance. METHODS; We conducted an open-label, randomized, controlled trial at a neonatal unit of a public hospital in northern Italy on 101 term neonates undergoing heel lance with an automated piercing device for routine neonatal screening for congenital disorders. Newborn infants were randomly assigned to breastfeeding during blood sampling or to the oral administration of 1 mL of 25% sucrose solution. We validated the multidimensional acute pain rating scale of the Premature Infant Pain Profile, heart rate increase, oxygen saturation decrease, crying behavior (duration of first cry, cry percentage in 2 minutes, and during blood sampling), duration of sampling, and the number of performed heel lances., Results: Median Premature Infant Pain Profile scores were lower in the breastfeeding group (3.0) than in the sucrose-solution group (8.5), and the median group difference was -5.0. The median heart rate increase, oxygen saturation decrease, and duration of first cry for the breastfeeding group were, respectively, 13.0, -1, and 3 and for sucrose group were 22, -3, and 21. Medians were significantly different between the groups. There were no significant differences in the sampling duration and numbers of heel lances., Conclusions: This study suggests that breastfeeding provides superior analgesia for heel lance compared with oral sucrose in term neonates.

Background: Morphine alleviates prolonged pain, reduces behavioral and hormonal stress responses induced by surgery among term neonates, and improves ventilator synchrony and sedation among ventilated preterm neonates, but its analgesic effects on the acute pain caused by invasive procedures remain unclear., Objective: To investigate the analgesic efficacy of intravenously administered morphine on heel stick-induced acute pain among preterm neonates., Design: This study was nested within a prospective, randomized, double-blind, multicenter, placebo-controlled trial (the NEOPAIN Trial)., Setting: A tertiary-care NICU in a teaching hospital., Participants: Forty-two preterm neonates undergoing ventilation., Interventions: Neonates were randomized to either the morphine (loading dose of 100 microg/kg, followed by infusions of 10-30 microg/kg per hour according to gestation, N = 21) or placebo (5% dextrose infusions, N = 21) group. Pain responses to 3 heel sticks were evaluated, ie, before the loading dose (T1), 2 to 3 hours after the loading dose (T2), and 20 to 28 hours after the loading dose (T3)., Main Outcomes Measures: Pain was assessed with the Douleur Aiguë Nouveau-né (DAN) scale (behavioral pain scale) and the Premature Infant Pain Profile (PIPP) (multidimensional pain scale); plasma morphine levels were measured at T3., Results: Infants in the placebo and morphine groups had similar gestational ages (mean +/- SD: 27.2 +/- 1.7 vs 27.3 +/- 1.8 weeks) and birth weights (972 +/- 270 vs 947 +/- 269 g). Mean +/- SD DAN pain scores at T1, T2, and T3 were 4.8 +/- 4.0, 4.6 +/- 2.9, and 4.7 +/- 3.6, respectively, for the placebo group and 4.5 +/- 3.8, 4.4 +/- 3.7, and 3.1 +/- 3.4 for the morphine group. The within-group factor (pain at T1, T2, and T3) was not statistically different over time. The between-group analysis (infants receiving placebo versus those receiving morphine) showed no significant differences. Mean +/- SD PIPP pain scores at T1, T2, and T3 were 11.5 +/- 4.8, 11.1 +/- 3.7, and 9.1 +/- 4.0, respectively, for the placebo group and 10.0 +/- 3.6, 8.8 +/- 4.9, and 7.8 +/- 3.6 for the morphine group. The within-group factor was statistically different over time. The between-group analysis showed no significant differences. Mean +/- SD plasma morphine levels at T3 were 0.44 +/- 1.79 ng/mL and 63.36 +/- 33.35 ng/mL for the placebo and morphine groups, respectively. There was no correlation between plasma morphine levels and pain scores at T3 (DAN, R = -0.05; PIPP, R = -0.02)., Conclusions: Despite its routine use in the NICU, morphine given as a loading dose followed by continuous intravenous infusions does not appear to provide adequate analgesia for the acute pain caused by invasive procedures among ventilated preterm neonates.

Context: This study identifies a behavioral and nonpharmacologic means of preventing newborn pain., Objective: To determine whether breastfeeding is analgesic in newborn infants undergoing heel lance-a routine, painful, hospital procedure., Design: A prospective, randomized, controlled trial., Setting: Hospital maternity services at Boston Medical Center, Boston, Massachusetts, and Beverly Hospital, Beverly, Massachusetts., Participants: A random sample of 30 full-term, breastfed infants., Interventions: Infants in the intervention group were held and breastfed by their mothers during heel lance and blood collection procedures for the Newborn Screening Program Blood Test. Infants in the control group experienced the same blood test while receiving the standard hospital care of being swaddled in their bassinets., Outcomes Measures: Crying, grimacing, and heart rate differences were analyzed between the breastfeeding and the control infants before, during, and after blood collection., Results: Crying and grimacing were reduced by 91% and 84%, respectively, from control infant levels during the blood collection. Heart rate was also substantially reduced by breastfeeding., Conclusions: Breastfeeding is a potent analgesic intervention in newborns during a standard blood collection.

Background: Management of pain in very low birth weight infants is limited by a lack of empiric knowledge about the multiple determinants of biobehavioral reactivity in infants receiving neonatal intensive care., Objective: To examine relationship of early neonatal factors and previous medication exposure to subsequent biobehavioral reactivity to acute pain of blood collection., Design: Prospective cohort study. Methods. One hundred thirty-six very low birth weight (

Objective: Because blood loss attributable to laboratory testing is the primary cause of anemia among preterm infants during the first weeks of life, we quantified blood lost attributable to phlebotomy overdraw, ie, excess that might be avoided. We hypothesized that phlebotomy overdraw in excess of that requested by the hospital laboratory was a common occurrence, that clinical factors associated with excessive phlebotomy loss would be identified, and that some of these factors are potentially correctable. DESIGN, OUTCOME MEASURES, AND ANALYSIS: Blood samples drawn for clinical purposes from neonates cared for in our 2 neonatal special care units were weighed, and selected clinical data were recorded. The latter included the test performed; the blood collection container used; the infant's location (ie, neonatal intensive care unit [NICU] and intermediate intensive care unit); the infant's weight at sampling; and the phlebotomist's level of experience, work shift, and clinical role. Data were analyzed by univariate and multivariate procedures. Phlebotomists included laboratory technicians stationed in the neonatal satellite laboratory, phlebotomists assigned to the hospital's central laboratory, and neonatal staff nurses. Phlebotomists were considered experienced if they had worked in the nursery setting for >1 year. Blood was sampled from a venous or arterial catheter or by capillary stick from a finger or heel. Blood collection containers were classified as tubes with marked fill-lines imprinted on the outside wall, tubes without fill-lines, and syringes. Infants were classified by weight into 3 groups: <1 kg, 1 to 2 kg, and >2 kg. The volume of blood removed was calculated by subtracting the weight of the empty collection container from that of the container filled with blood and dividing by the specific gravity of blood, ie, 1.050 g/mL. The volume of blood withdrawn for individual laboratory tests was expressed as a percentage of the volume requested by the hospital laboratory., Results: The mean (+/- standard error of the mean) volume of blood drawn for the 578 tests drawn exceeded that requested by the hospital laboratory by 19.0% +/- 1.8% per test. The clinical factors identified as being significantly associated with greater phlebotomy overdraw in the multiple regression model included: 1) collection in blood containers without fill-lines; 2) lighter weight infants; and 3) critically ill infants being cared for in the NICU. Because the overall R(2) of the multiple regression for these 3 clinical factors was only.24, the random factor of individual phlebotomist was added to the model. This model showed that there was a significant variation in blood overdraw among individual phlebotomists, and as a result, the overall R(2) increased to.52. An additional subset analysis involving 2 of the 3 groups of blood drawers (ie, hospital and neonatal laboratory phlebotomists) examining the effect of work shift, demonstrated that there was significantly greater overdraw for blood samples obtained during the evening shift, compared with the day shift when drawn using unmarked tubes for the group of heavier infants cared for in the NICU., Conclusion: Significant volumes of blood loss are attributable to overdraw for laboratory testing. This occurrence likely exacerbates the anemia of prematurity and may increase the need for transfusions in some infants. Attempts should be made to correct the factors involved. Common sense suggests that blood samples drawn in tubes with fill-lines marked on the outside would more closely approximate the volumes requested than those without. Conversely, the use of unmarked tubes could lead to phlebotomy overdraw because phlebotomists may overcompensate to avoid having to redraw the sample because of an insufficient volume for analysis. We were surprised to observe that the lightest and most critically ill infants experienced the greatest blood overdraw. (ABSTRACT TRUNCATED)

Objective: To compare biobehavioral responses to acute pain at 4 months' corrected age between former extremely low birth weight (ELBW) infants and term-born controls., Methodology: Measures of facial behavioral and cardiac autonomic reactivity in 21 former ELBW infants (mean birth weight = 763 g) were compared with term-born infants (n = 24) during baseline, lance, and recovery periods of a finger-lance blood collection. Further, painful procedures experienced during neonatal care were quantified in both groups., Results: Overall, behavioral and cardiac autonomic responses to the lance were similar between groups. However, the ELBW group seemed to have a less intense parasympathetic withdrawal in the lance period and a more sustained sympathetic response during recovery than the control group. Further, in the recovery period, two behavioral patterns (early recovery and a late recovery) were apparent among the ELBW group., Conclusions: Biobehavioral pain responses were similar overall between both groups of infants. Subtle differences were observed in cardiac autonomic responses during the lance period and in behavioral recovery among ELBW infants. Whether these findings represent a long-term effect of early pain experience or a developmental lag in pain response remains unclear. The lack of an overall difference runs counter to previously reported findings of reduced behavioral response in former ELBW infants. biobehavioral pain response, premature infants, repetitive pain, heart rate variability.

Objectives: To determine whether skin-to-skin contact between mothers and their newborns will reduce the pain experienced by the infant during heel lance., Design: A prospective, randomized, controlled trial., Setting: Boston Medical Center, Boston, Massachusetts., Participants: A total of 30 newborn infants were studied., Interventions: Infants were assigned randomly to either being held by their mothers in whole body, skin-to-skin contact or to no intervention (swaddled in crib) during a standard heel lance procedure., Outcome Measures: The effectiveness of the intervention was determined by comparing crying, grimacing, and heart rate differences between contact and control infants during and after blood collection., Results: Crying and grimacing were reduced by 82% and 65%, respectively, from control infant levels during the heel lance procedure. Heart rate also was reduced substantially by contact., Conclusion: Skin-to-skin contact is a remarkably potent intervention against the pain experienced during heel stick in newborns.

Objective: Heel lancing has hitherto been the method of choice for screening tests of inborn errors of metabolism in neonates. Eutectic mixture of local anesthetic has little, if any, analgesic effect when applied to the heel of pre- and full-term infants. Today there seems to be no practical method that effectively alleviates the pain caused by heel lancing. The aim of this study was to investigate whether other methods, such as venipuncture of the dorsal side of the hand, are less painful and more efficient than heel lancing in neonates., Methods: One hundred twenty healthy, full-term infants who underwent testing for phenylketonuria (PKU) were included in the study. They were randomized into three groups: a venipuncture group (VP) (n = 50), a heel-lance group with a small lancet (SL) (n = 50), or a large lancet (LL) (n = 20). Pain reactions were assessed by the Neonatal Facial Coding System (NFCS). The latency and duration of the first cry as well as the total screaming time was analyzed. The efficacy of the method was assessed by the time taken to complete the PKU test and number of times the skin had to be punctured., Results: Nociceptive response. The NFCS scores after the first skin puncture were: VP, 247; SL, 333; and LL, 460. The NFCS scores were significantly lower in the VP than in the groups subjected to heel lancing. During the first 60 seconds after skin puncture, 44% of the infants cried in the VP group, compared with 72% and 85% in the SL and LL groups, respectively. Efficacy. A successful PKU test with only one skin puncture was performed in 86% of the VP group, but in only 19% in the SL group and 40% in the LL group. The total time needed to obtain the PKU blood sample was 191 seconds (median) in the VP group, 419 seconds in the SL group, and 279 seconds in the LL group., Conclusion: Venipuncture is more effective and less painful than heel lancing for blood tests in neonates.

The effectiveness of sucrose as an analgesic agent for newborn infants was assessed during two standard painful hospital procedures: blood collection via heel lance and circumcision. Infants who drank 2 mL of a 12% sucrose solution prior to blood collection cried 50% less during the blood collection procedure than did control infants who had received 2 mL of sterile water. Crying of infants who ingested sucrose returned to baseline levels within 30 to 60 seconds after blood collection whereas control infants required 2.5 to 3.0 minutes to return to baseline. Like findings were obtained for infants who received sucrose on a pacifier prior to and during circumcision. Specifically, control infants who underwent a standard circumcision procedure without intervention cried 67% of the time. A water-moistened pacifier reduced crying to 49% (P less than .01). Crying was reduced further to 31% (P less than .05) by providing infants with a sucrose-flavored pacifier to suck. These findings, which parallel results obtained in studies of pain in infant rats, provide a potent yet simple, benign intervention to help alleviate stress and pain routinely experienced by human infants.