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February 2001

Consensus Statement for the Prevention and Management of Pain in the Newborn

K. J. S. Anand, MBBS, DPhil; and the International Evidence-Based Group for Neonatal Pain
Author Affiliations

Participants (listed alphabetically) of the International Evidence-Based Group for Neonatal Pain are the following: Huda Huijer Abu-Saad, Maastricht, the Netherlands; K. J. S. Anand, Little Rock, Ark (chair); Albert Aynsley-Green, London, England; Eduardo Bancalari, Miami, Fla; Franca Benini, Padova, Italy; G. David Champion, Darlinghurst, Australia; Kenneth D. Craig, Vancouver, British Columbia; Tomasz S. Dangel, Warszawa, Poland; Elisabeth Fournier-Charrière, Kremlin-Bicetre, France; Linda S. Franck, London, England; Ruth Eckstein Grunau, Vancouver, British Columbia; Steen A. Hertel, Copenhagen, Denmark; Evelyne Jacqz-Aigrain, Paris, France; Gerhard Jorch, Magdeburg, Germany; Benjamin I. Kopelman, São Paulo, Brazil; Gideon Koren, Toronto, Ontario; Björn Larsson, Stockholm, Sweden; Neil Marlow, Nottingham, England; Neil McIntosh, Edinburgh, Scotland; Arne Ohlsson, Toronto, Ontario; Gunnar Olsson, Stockholm, Sweden; Fran Porter, St Louis, Mo; Renate Richter, Erlangen, Germany; Bonnie Stevens, Toronto, Ontario; and Anna Taddio, Toronto, Ontario.

Arch Pediatr Adolesc Med. 2001;155(2):173-180. doi:10.1001/archpedi.155.2.173

Objective  To develop evidence-based guidelines for preventing or treating neonatal pain and its adverse consequences. Compared with older children and adults, neonates are more sensitive to pain and vulnerable to its long-term effects. Despite the clinical importance of neonatal pain, current medical practices continue to expose infants to repetitive, acute, or prolonged pain.

Design  Experts representing several different countries, professional disciplines, and practice settings used systematic reviews, data synthesis, and open discussion to develop a consensus on clinical practices that were supported by published evidence or were commonly used, the latter based on extrapolation of evidence from older age groups. A practical format was used to describe the analgesic management for specific invasive procedures and for ongoing pain in neonates.

Results  Recognition of the sources of pain and routine assessments of neonatal pain should dictate the avoidance of recurrent painful stimuli and the use of specific environmental, behavioral, and pharmacological interventions. Individualized care plans and analgesic protocols for specific clinical situations, patients, and health care settings can be developed from these guidelines. By clearly outlining areas where evidence is not available, these guidelines may also stimulate further research. To use the recommended therapeutic approaches, clinicians must be familiar with their adverse effects and the potential for drug interactions.

Conclusion  Management of pain must be considered an important component of the health care provided to all neonates, regardless of their gestational age or severity of illness.

NEWBORNS routinely experience pain associated with invasive procedures such as blood sampling, immunization, vitamin K injection, or circumcision. The sick or preterm infant may experience repetitive or prolonged pain resulting from many diagnostic, surgical, or therapeutic procedures.1-4

Multiple lines of evidence suggest an increased sensitivity to pain in neonates compared with older age groups.5,6 This pain sensitivity is further accentuated in preterm neonates, and may not be clinically evident.5-8 Critically ill and preterm neonates do not mount vigorous behavioral responses to pain, and therefore require particularly detailed assessment.6-8 The pain modulation systems that operate in older children and adults do not appear to be fully functional in newborns9-11 or may function only during maternal contact in healthy newborns.12 Even the most immature preterm neonates mount increasing responses to the pain caused by mild, moderate, or highly invasive procedures, and the magnitude of their responses increase with postnatal age.6,7,13 Compared with older children, neonates exhibit greater hormonal, metabolic, and cardiovascular responses to surgical operations, and may require relatively higher doses of anesthetics and analgesics for adequate pain control.5,14-17 The metabolism and clearance rates of most analgesic agents in preterm neonates are slower than in term neonates, but increase rapidly with age.18,19

Management of pain in the newborn is hampered by the lack of awareness among health care professionals that the neonate is capable of experiencing pain, and by fears about the adverse effects associated with analgesic use. Current evidence supports the general principles listed in Table 1 for the routine management of neonates using safe and effective environmental, behavioral, and pharmacological interventions for relieving pain and for preventing its adverse consequences.20

Table 1. 
General Principles for the Prevention and Management of Pain in Newborns
General Principles for the Prevention and Management of Pain in Newborns


These guidelines were developed from 2 consensus development meetings (in April 1998 and August 1999). A detailed search of the published literature on neonatal pain was conducted to identify the experts who were invited to these meetings. Databases searched were MEDLINE, Embase, and PubMed using the following terms: pain, nociception, stress, infant-newborn, and infant-premature. Faculty members were selected by the chairman (K.J.S.A.) based on their expertise in specific topics related to neonatal pain, coupled with a concerted effort to include professionals trained in different disciplines and representing different countries and distinct practice settings (eg, children's hospitals, general hospitals, office practices). The disciplines represented were pediatrics, neonatology, child psychology, anesthesiology, neuroscience, endocrinology, neonatal nursing, pharmacy/pharmacology, rehabilitation medicine, critical care medicine, rheumatology/immunology, and others. At the time of these meetings, faculty members were affiliated to academic institutions in Australia, Brazil, Canada, Denmark, France, Germany, Israel, Italy, Poland, Sweden, Switzerland, the Netherlands, United Kingdom, and the United States.

Faculty members performed a systematic review of the published literature on their specific topic, critically evaluated the quality of published data, and synthesized these findings. Data from all relevant studies were presented at these meetings and were discussed by the experts present. Other faculty members were encouraged to present additional data and ample time was allowed for detailed discussion. Guidelines were developed after reaching a consensus on the clinical practices that were prevalent in most countries. As such, these guidelines were based on a combination of published evidence (from randomized controlled trials, systematic reviews, or meta-analyses of trials) and its critical evaluation by the faculty members. Between September 1999 and April 2000, 3 separate draft versions of this statement were circulated and modified by all members of the participating faculty. Approval of all faculty members was obtained for the final version of the consensus statement, which is organized around broad general principles (Table 1) and evidence-based guidelines for neonatal pain management. The pharmacological interventions recommended in these guidelines are not the exclusive products of the pharmaceutical company that funded these meetings, and the representatives of this company have had no input in the format or content of these guidelines.


Evidence-based guidelines for the management of neonatal pain

Recognition of the Sources of Pain

Some of the painful procedures commonly performed on neonates in the neonatal intensive care unit (NICU) include heel lancing, venipuncture, venous or arterial catheter insertion, chest tube placement, tracheal intubation or suctioning, lumbar puncture, and subcutaneous or intramuscular injections (see Table 2 for additional procedures).1-4 Other sources of pain may include areas of inflammation and hyperalgesia around previous tissue injury, postoperative pain, localized infection or inflammation, and skin burns or abrasions caused by transcutaneous probes, monitoring leads, or topical agents.

Table 2. 
Painful Procedures Commonly Performed in the Neonatal Intensive Care Unit
Painful Procedures Commonly Performed in the Neonatal Intensive Care Unit

Assessment of Pain

  • Concomitantly with the vital signs, assessment of neonatal pain must be undertaken and documented every 4 to 6 hours or as indicated by the pain scores or clinical condition of the neonate.21-24

  • Standardized pain assessment methods with evidence of validity, reliability, and clinical utility should be used25-32 (Table 3).

  • Pain assessment instruments should be sensitive and specific for infants of different gestational ages and/or with acute, recurrent, or continuous pain.13,32,33 Examples of ongoing, continuous pain may include postoperative pain or inflammatory conditions.1,3,33

  • Pain assessment should be comprehensive and multidimensional, including contextual, behavioral, and physiological indicators.8,13,21-23

  • Pain assessment must be performed after each potentially painful clinical intervention and to evaluate the efficacy of behavioral, environmental, and pharmacological agents.21,23,33,34

Table 3. 
Commonly Used Methods for Assessment of Pain in Newborns
Commonly Used Methods for Assessment of Pain in Newborns

Management of Pain in the Newborn

  • Strategies for prevention, particularly by avoiding recurrent painful stimuli.20,33

  • Use of environmental interventions to reduce stress in the NICU.33,35,36

  • Behavioral methods, including sucrose and nonnutritive sucking.12,20,37-56

  • Pharmacological agents for preemptive analgesia20,57-76 (Table 4).

  • Pharmacological therapy for ongoing pain17,19,34,58,71-80 (Table 4).

Table 4. 
Recommended Analgesic Doses for Neonates*
Recommended Analgesic Doses for Neonates*

Suggested management approaches for neonatal pain

In the following sections, an asterisk indicates that evidence from studies in neonates is available to support the proposed intervention. The combined use of multiple interventions may have additive or synergistic clinical effects.

Heel Lance

  • Consider use of venipuncture instead of heel lance in full-term neonates and more mature preterm neonates* (because it is less painful, more efficient and requires less resampling).62,81-87 This approach may not apply to the care of extremely preterm infants.

  • Use a pacifier* with sucrose* (concentration 12%-24%) given 2 minutes before the procedure.39-48,51-55

  • Use swaddling, containment,* or facilitated tucking.37,38

  • Consider skin-to-skin contact with the mother.*12

  • Use a mechanical spring-loaded lance, eg, Autolance.*62,85,86

EMLA (a eutectic mixture of local anesthetics: lidocaine and prilocaine hydrochloride in an emulsion base), acetaminophen, and warming the heel are ineffective for heel lancing*; squeezing for blood collection is the most painful part of the procedure.70,81-85,87

Percutaneous Venous Catheter Insertion

  • Use a pacifier* with sucrose.*39,41,70,81-84

  • Use swaddling, containment, or facilitated tucking.37,38

  • Apply EMLA* to the proposed site (when nonurgent).60,82,88,89

  • Consider opioid dose(s),* if intravenous access is available.58,73

  • Consider a similar approach for venipuncture.88,89

Percutaneous Arterial Catheter Insertion

  • Use a pacifier* with sucrose.39,41

  • Use swaddling, containment, or facilitated tucking.37,38

  • Apply EMLA to the proposed site.60,70

  • Consider subcutaneous infiltration of lidocaine.58,70

  • Consider a similar approach for arterial puncture.

Peripheral Arterial or Venous Cutdown

  • Use a pacifier with sucrose.39,41

  • Use swaddling, containment, or facilitated tucking.37,38

  • Apply EMLA to the proposed site.58,60,70

  • Consider subcutaneous infiltration of lidocaine; avoid intravascular injection.58,70

  • Consider opioid dose(s), if intravenous access is available.15,58,76

Central Venous Line Placement

  • Use a pacifier* with sucrose.39,41

  • Use swaddling, containment, or facilitated tucking.37,38

  • Apply EMLA to the proposed site, if nonurgent.60,90

  • Consider subcutaneous infiltration of lidocaine.58,70

  • Consider slow intravenous opioid infusion (morphine sulfate* or fentanyl citrate*).73,76

  • Consider using general anesthesia for the procedure.15,70,76,91

Umbilical Catheter Insertion (Umbilical Arterial/Umbilical Venous)

  • Consider the use of a pacifier with sucrose.39,41

  • Use swaddling, containment, or facilitated tucking.37,38

  • Avoid the placement of sutures or hemostat clamps on the skin around the umbilicus.

Peripherally Inserted Central Catheter Placement

  • Use a pacifier with sucrose.39,41

  • Use swaddling, containment, or facilitated tucking.37,38

  • Apply EMLA* to the proposed site (when nonurgent).58,60,90

  • Consider opioid dose(s), if intravenous access is available.58,76,91

Lumbar Puncture

  • Use a pacifier* with sucrose.39,41

  • Apply EMLA to the proposed site.60

  • Consider subcutaneous infiltration of lidocaine.58,70

  • Because containment is not possible, careful physical handling is advised.

Subcutaneous or Intramuscular Injection

  • Avoid subcutaneous and intramuscular injections; give drugs intravenously whenever possible.

    If necessary:

  • Use a pacifier with sucrose.39,41

  • Use swaddling, containment, or facilitated tucking.37,38

  • Apply EMLA to the proposed site (evidence for this approach is available from studies in children, but not from studies in neonates).92-94

Endotracheal Intubation

Many variations in clinical approach have been noted; the superior efficacy of any one technique is not supported by current evidence33,58,70,95-97:

  • Use combination of atropine sulfate and ketamine hydrochloride*95

  • Use combination of atropine, thiopental sodium,* and succinylcholine chloride.97

  • Use combination of atropine, morphine, or fentanyl, and nondepolarizing muscle relaxant (pancuronium, vercuronium, rorcuronium).15,58

  • Consider using a topical lidocaine spray, if available.98,99

  • Other drug combinations are frequently used.58,70

Tracheal intubation without the use of analgesia or sedation should be performed only for resuscitation in the delivery room or for other life-threatening situations associated with the unavailability of intravenous access.95-97

Endotracheal Suction

This is considered a stressful procedure and may be associated with the same physiological responses that accompany other painful procedures71,100-104:

  • Use a pacifier; may consider giving sucrose.39,41

  • Use swaddling, containment, or facilitated tucking.37,38

  • Consider continuous intravenous infusion of opioids (morphine*)71 or slow injection of intermittent opioid doses (fentanyl,* meperidine,* or alfentanil*).100-104

Nasogastric or Orogastric Tube Insertion

  • Use a pacifier with sucrose.39,41

  • Use swaddling, containment, or facilitated tucking.37,38

  • Use a gentle technique and appropriate lubrication.105

Chest Tube Insertion

  • Anticipate the need for intubation and ventilation in neonates breathing spontaneously.58

  • Use a pacifier with sucrose.39,41

  • Consider subcutaneous infiltration of lidocaine.58,70

  • Consider slow intravenous opioid infusion (morphine or fentanyl; see Table 4 for dosages).15,58

  • Other approaches may include the use of short-acting anesthetic agents.15,58,76

The use of intravenous midazolam is not recommended.106,107


If deemed necessary108,109:

  • Use an appropriate clamp (Mogen clamp preferred over Gomco*).110,111

  • Apply EMLA* to the proposed site.57,60,111

  • Place a dorsal penile nerve block,*64,111,112 ring block,*65,66 or caudal block,67,68,113-116 using plain or buffered lidocaine.*117-119

  • Use a pacifier* with sucrose.*39,41,56,111,118

  • Consider acetaminophen for postoperative pain.*69

Analgesics can be combined for maximum efficacy,67,110,111,118 although the addition of sodium bicarbonate to lidocaine does not alter the neonatal responses to lidocaine injection.117-119

Ongoing Analgesia for Routine NICU Care and Procedures

  • Use swaddling, containment, or facilitated tucking.37,38

  • Use a pacifier; may consider giving sucrose.39,41

  • Low-dose continuous infusion of morphine* or fentanyl* if patient is ventilated.71-75

    There is no evidence to show that neonates can be safely sedated for several weeks or months20,71,72,74,75 and the use of midazolam is not recommended.71,106,107

  • Consider acetaminophen therapy.

    The efficacy and safety of repeated acetaminophen doses is unknown, rectal absorption is variable, and intravenous propacetamol is not available in the United States.77-80,87

  • Reduce acoustic, thermal, and other environmental stresses.33,35,36


Recognition of the clinical importance of neonatal pain and stress has been delayed5,20 by outdated professional attitudes (that newborns are less sensitive to pain),120-126 lack of education,127,128 need for accurate assessment methods, and lack of evidence for the safety and efficacy of management approaches that can be applied to the routine care of neonates. This is a preliminary attempt to present the available evidence so that it may be useful to the clinicians at the bedside. We hope to stimulate further research by clearly outlining the areas where current evidence is not available for defining the efficacy of specific therapeutic approaches. Although these management approaches are mainly applicable for established NICUs that provide advanced medical and nursing care for critically ill neonates, they can be adapted for management of neonatal pain in other clinical settings or geographical locations.

Adverse effects that may result from these therapies are listed in Table 5,129-158 and all clinicians using these guidelines must be familiar with the safe use of analgesic agents in healthy or critically ill, term and preterm neonates. Professionals working with neonates are expected to be knowledgeable about the current assessment and management approaches through participation in ongoing pain education, interaction with pain experts, attention to the most recent research evidence, and adherence to professional standards and clinical guidelines.159 We strongly support the initiative taken by national professional organizations for the prevention and management of neonatal pain20,108,109 and for the development of standards for health care professionals and institutions. This consensus statement provides evidence-based protocols for developing neonatal pain management guidelines that can be uniquely designed for various clinical situations and diverse practice settings. Adherence to such guidelines will not only improve the clinical care provided to all neonates, but may also have a positive impact on their subsequent health and behaviors during childhood and adolescence.160

Table 5. 
Adverse Effects of Analgesic Agents in Neonates
Adverse Effects of Analgesic Agents in Neonates

Accepted for publication October 16, 2000.

These efforts were supported by an unrestricted educational grant from Astra Pharmaceuticals (now AstraZeneca Inc, London, England) and were developed at 2 meetings of the International Evidence-Based Group for Neonatal Pain (Nice, France, April 21-23, 1998, and Baden, Austria, August 20-22, 1999).

The group gratefully acknowledges Jonas Nylander, Nadia Hammouda (AstraZeneca, Inc), Brian Parsons, Anna Welsh (Colwood Healthworld, London, England), Sarah Knott, and Daphne Steptoe (Wells Medical, Royal Tunbridge Wells, Kent, England) for helping in the development of these guidelines.

Corresponding author and reprints: K. J. S. Anand, MD, Arkansas Children's Hospital, S-431, 800 Marshall St, Little Rock, AR 72202 (e-mail: anandsunny@exchange.uams.edu).

Fernandez  CVRees  EP Pain management in Canadian level 3 neonatal intensive care units.  CMAJ. 1994;150499- 504Google Scholar
Barker  DPRutter  N Exposure to invasive procedures in neonatal intensive care unit admissions.  Arch Dis Child Fetal Neonatal Ed. 1995;72F47- F48Google ScholarCrossref
Johnston  CCCollinge  JMHenderson  SJAnand  KJS A cross-sectional survey of pain and pharmacological analgesia in Canadian neonatal intensive care units.  Clin J Pain. 1997;13308- 312Google ScholarCrossref
Porter  FLAnand  KJS Epidemiology of pain in neonates.  Res Clin Forums. 1998;209- 18Google Scholar
Anand  KJS Clinical importance of pain and stress in preterm newborn infants.  Biol Neonate. 1998;731- 9Google ScholarCrossref
Johnston  CCStevens  BJYang  FHorton  L Differential response to pain by very premature neonates.  Pain. 1995;61471- 479Google ScholarCrossref
Johnston  CCStevens  BJFranck  LSJack  AStremler  RPlatt  R Factors explaining lack of response to heel stick in preterm newborns.  J Obstet Gynecol Neonatal Nurs. 1999;28587- 594Google ScholarCrossref
Craig  KDWhitfield  MFGrunau  RVELinton  JHadjistavropoulos  HD Pain in the pre-term neonate: behavioral and physiological indices.  Pain. 1993;52201- 299Google ScholarCrossref
Marti  EGibson  SJPolak  JM  et al.  Ontogeny of peptide and amino-containing neurons in motor, sensory and autonomic regions of rat and human spinal cord.  J Comp Neurol. 1987;266332- 359Google ScholarCrossref
Jennings  EFitzgerald  M C-fos can be induced in the neonatal rat spinal cord by both noxious and innocuous peripheral stimulation.  Pain. 1996;68301- 306Google ScholarCrossref
Boucher  TJennings  EFitzgerald  M The onset of diffuse noxious inhibitory controls in postnatal rat pups: a C-fos study.  Neurosci Lett. 1998;2579- 12Google ScholarCrossref
Gray  LWatt  LBlass  EM Skin-to-skin contact is analgesic in healthy newborns.  Pediatrics [serial online]. 2000;105e14Google Scholar
Porter  FLWolf  CMMiller  JP Procedural pain in newborn infants: the influence of intensity and development.  Pediatrics [serial online]. 1999;104e13Google Scholar
Anand  KJSBrown  MJCauson  RC  et al.  Can the human neonate mount an endocrine and metabolic response to surgery?  J Pediatr Surg. 1985;2041- 48Google ScholarCrossref
Yaster  M The dose response of fentanyl in neonatal anesthesia.  Anesthesiology. 1987;56433- 435Google ScholarCrossref
Greeley  WJde Broijn  NP Changes in sufentanil pharmacokinetics within the neonatal period.  Anesth Analg. 1988;5786- 90Google Scholar
Chay  PCWDuffy  BJWalker  JS Pharmacokinetic:pharmacodynamic relationships of morphine in neonates.  Clin Pharmacol Ther. 1992;51334- 342Google ScholarCrossref
Olkkola  KTHamunen  K Pharmacokinetics and pharmacodynamics of analgesic drugs. Anand  KJSStevens  BJMcGrath  PJeds. Pain in Neonates. 2nd ed. Amsterdam, the Netherlands Elsevier Science2000;135- 158Google Scholar
Scott  CSRiggs  KWLing  EW  et al.  Morphine pharmacokinetics and pain assessment in premature newborns.  J Pediatr. 1999;135423- 429Google ScholarCrossref
American Academy of Pediatrics and Canadian Paediatric Society, Prevention and management of pain and stress in the newborn.  Pediatrics. 2000;105454- 461 Paediatr Child Health. 2000;531- 3839- 47Google ScholarCrossref
Chiswick  ML Assessment of pain in neonates.  Lancet. 2000;3556- 8Google ScholarCrossref
Abu-Saad  HHBours  GJStevens  BHamers  JP Assessment of pain in the neonate.  Semin Perinatol. 1998;22402- 416Google ScholarCrossref
Stevens  BJohnston  CGibbins  S Assessment of pain in the neonate. Anand  KJSStevens  BMcGrath  PJeds. Pain in Neonates. 2nd ed. Pain Research and Clinical Management. 10 Amsterdam, the Netherlands Elsevier Science2000;101- 134Google Scholar
Franck  LSGreenberg  CSStevens  B Pain assessment in infants and children.  Pediatr Clin North Am. 2000;47487- 512Google ScholarCrossref
Krechel  SWBildner  J CRIES: a new neonatal postoperative pain measurement score: initial testing of validity and reliability.  Paediatr Anaesth. 1995;553- 61Google ScholarCrossref
Sparshott  M The development of a clinical distress scale for ventilated newborn infants: identification of pain and distress based on validated behavioural scores.  J Neonatal Nurs. 1996;25- 11Google Scholar
Stevens  BJohnston  CCPetryshen  PTaddio  A Premature infant pain profile: development and initial validation.  Clin J Pain. 1996;1213- 22Google ScholarCrossref
Grunau  RVEOberlander  TFHolsti  L  et al.  Bedside application of the Neonatal Facial Coding System in pain assessment of premature neonates.  Pain. 1998;76277- 286Google ScholarCrossref
Lawrence  JAlcock  DMcGrath  PKay  JMacMurray  SBDulberg  C The development of a tool to assess neonatal pain.  Neonatal Network. 1993;1259- 66Google Scholar
Blauer  TGerstmann  D A simultaneous comparison of three neonatal pain scales during common NICU procedures.  Clin J Pain. 1998;1439- 47Google ScholarCrossref
Ballantyne  MStevens  BMcAllister  M  et al.  Validation of the Premature Infant Pain Profile in the clinical setting.  Clin J Pain. 1999;15297- 303Google ScholarCrossref
Guinsburg  RBerenguel  RCXavier  RCAlmeida  MFBKopelman  BI Are behavioral scales suitable for preterm and term pain assessment? Jensen  TSTurner  JAWiesenfeld-Hallin  Zeds. Proceedings of the 8th World Congress on Pain. Seattle, Wash International Association for the Study of Pain1997;893- 902Google Scholar
McIntosh  N Pain in the newborn, a possible new starting point.  Eur J Pediatr. 1997;156173- 177Google ScholarCrossref
Guinsburg  RKopelman  BIAnand  KJSAlmeida  MFBPeres  CAMiyoshi  MH Physiological, hormonal and behavioral responses to a single fentanyl dose in intubated and ventilated preterm neonates.  J Pediatr. 1998;132954- 959Google ScholarCrossref
Sauve  RedSaigal  Sed Optimizing the neonatal intensive care environment.  Report of the 10th Canadian Ross Conference in Pediatrics. Montreal, Quebec GCI Communications1995;Google Scholar
American Academy of Pediatrics, Committee on Environmental Health, Noise: a hazard for the fetus and the newborn.  Pediatrics. 1997;100724- 727Google ScholarCrossref
Corff  KE An effective comfort measure for minor pain and stress in preterm infants: facilitated tucking.  Neonatal Network. 1993;1274Google Scholar
Corff  KSeideman  RVenkataraman  PLutes  LYates  B Facilitated tucking: a nonpharmacologic comfort measure for pain in preterm infants.  J Obstet Gynecol Neonatal Nurs. 1995;24143- 147Google ScholarCrossref
Stevens  BOhlsson  A Sucrose for analgesia in newborn infants undergoing painful procedures [Cochrane Review on CD-ROM].  Oxford, England Cochrane Library2000;2CD001069
Stevens  BJohnston  CFranck  L  et al.  The efficiency of developmentally sensitive interventions and sucrose for relieving pain in VLBW neonates.  Nurs Res. 1999;4835- 43Google ScholarCrossref
Stevens  BTaddio  AOhlsson  AEinarson  T The efficacy of sucrose for relieving pain in neonates: a systematic review and meta-analysis.  Acta Paediatr. 1997;86837- 842Google ScholarCrossref
Abad  FDiaz  NDomenech  ERobayna  MRico  J Oral sweet solution reduces pain-related behavior in preterm infants.  Acta Paediatr. 1996;85854- 858Google ScholarCrossref
Barr  RGPantel  MSYoung  SNWright  JHHendricks  LAGravel  R The response of crying newborns to sucrose: is it a "sweetness" effect?  Physiol Behav. 1999;66409- 417Google ScholarCrossref
Blass  EMHoffmeyer  LB Sucrose as an analgesic for newborn infants.  Pediatrics. 1991;87215- 218Google Scholar
Bucher  HUMoser  Tvon Siebenthal  KKeel  MWolf  MDuc  G Sucrose reduces pain reaction to heel lancing in preterm infants: a placebo-controlled, randomized and masked study.  Pediatr Res. 1995;38332- 335Google ScholarCrossref
Haouari  NWood  CGriffiths  GLevene  M The analgesic effect of sucrose in full term infants: a randomised controlled trial.  BMJ. 1995;3101498- 1500Google ScholarCrossref
Ramenghi  LWood  CGriffeth  GLevene  M Reduction of pain response in premature infants using intraoral sucrose.  Arch Dis Child Fetal Neonatal Ed. 1996;74F126- F128Google ScholarCrossref
Ramenghi  LEvans  DJLevene  M "Sucrose analgesia": absorptive mechanism or taste perception?  Arch Dis Child Fetal Neonatal Ed. 1999;80F146- F147Google ScholarCrossref
Gormally  SMBarr  RGYoung  SNAlhawaf  RWersheim  L Combined sucrose and carrying reduces newborn pain response more than sucrose or carrying alone.  Arch Pediatr Adolesc Med. 1996;15047Google Scholar
Johnston  CCStremler  RStevens  RHorton  L Effectiveness of oral sucrose and simulated rocking on pain response in preterm neonates.  Pain. 1997;72193- 199Google ScholarCrossref
Overgaard  CKnudsen  A Pain-relieving effect of sucrose in newborns during heel prick.  Biol Neonate. 1999;75279- 284Google ScholarCrossref
Carbajal  RChauvet  XCouder  SOlivier-Martin  M Randomised trial of analgesic effects of sucrose, glucose, and pacifiers in term neonates.  BMJ. 1999;3191393- 1397Google ScholarCrossref
Barker  DRutter  N Analgesic effect of sucrose: heel pricks were unnecessarily painful.  BMJ. 1995;311747Google ScholarCrossref
Johnston  CCStremler  RHorton  L  et al.  Effect of repeated doses of sucrose during heel stick procedure in preterm neonates.  Biol Neonate. 1999;75160- 166Google ScholarCrossref
Mellah  DGourrier  EMerbouche  S  et al.  Analgesia with saccharose during heel capillary prick: a randomized study in 37 newborns of over 33 weeks of amenorrhea [French].  Arch Pediatr. 1999;6610- 616Google ScholarCrossref
Herschel  MKnoshnood  BEllman  C  et al.  Neonatal circumcision: randomized trial of a sucrose pacifier for pain control.  Arch Pediatr Adolesc Med. 1998;152279- 284Google ScholarCrossref
Taddio  AStevens  BCraig  K Efficacy and safety of lidocaine-prilocaine cream for pain during neonatal circumcision.  N Engl J Med. 1997;3361197- 1201Google ScholarCrossref
Menon  GAnand  KJSMcIntosh  N Practical approach to analgesia and sedation in the neonatal intensive care unit.  Semin Perinatol. 1998;22417- 424Google ScholarCrossref
Larsson  BAJylli  LLagercrantz  HOlsson  GL Does a local anaesthetic cream (EMLA) alleviate pain from heel lancing in neonates?  Acta Anaesthesiol Scand. 1995;391028- 1031Google ScholarCrossref
Taddio  AOhlsson  AStevens  BEinarson  TRKoren  G A systematic review of lidocaine-prilocaine cream EMLA in the treatment of acute pain in neonates.  Pediatrics [serial online]. 1998;101e1Google Scholar
Brisman  MLjung  BMOtterbom  ILarsson  LEAndreasson  SE Methaemoglobin formation after the use of EMLA cream in term neonates.  Acta Paediatr. 1998;871191- 1194Google ScholarCrossref
McIntosh  NVan Veen  LBrameyer  H Alleviation of the pain of heel prick in preterm infants.  Arch Dis Child Fetal Neonatal Ed. 1994;70F177- F181Google ScholarCrossref
Essink-Tebbes  CMWuis  EWLiem  KD  et al.  Safety of lidocaine-prilocaine cream application four times a day in premature infants: a pilot study.  Eur J Pediatr. 1999;158421- 423Google ScholarCrossref
Holliday  MAPinckert  TLKiernan  SC  et al.  Dorsal penile nerve block vs topical placebo for circumcision in low-birth-weight neonates.  Arch Pediatr Adolesc Med. 1999;153476- 480Google ScholarCrossref
DeJonge  MH Ring block for neonatal circumcision.  Obstet Gynecol. 1998;92891- 892Google ScholarCrossref
Hardwick-Smith  SMastrobattista  MWallace  PA  et al.  Ring block for neonatal circumcision.  Obstet Gynecol. 1998;91930- 934Google ScholarCrossref
Mohan  CGRisucci  DACasimir  MGulrajani-LaCorte  M Comparison of analgesics in ameliorating the pain of circumcision.  J Perinatol. 1998;1813- 19Google Scholar
Shechet Rabbi  JFried  SMTanenbaum  B  et al.  Local anesthesia for infants undergoing circumcision.  JAMA. 1998;2791170- 1171Google Scholar
Howard  CRHoward  FMWeitzman  ML Acetaminophen analgesia in neonatal circumcision: the effect on pain.  Pediatrics. 1994;93641- 646Google Scholar
Larsson  BA Strategies to reduce procedural pain in the newborn.  Res Clin Forums. 1998;2063- 71Google Scholar
Anand  KJSMcIntosh  NLagercrantz  H  et al.  Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN trial.  Arch Pediatr Adolesc Med. 1999;153331- 338Google ScholarCrossref
Quinn  MWWild  JDean  HG  et al.  Randomised double-blind controlled trial of effect of morphine on catecholamine concentrations in ventilated preterm babies.  Lancet. 1993;342324- 327Google ScholarCrossref
Moustogiannis  ANRaju  TNKRoohey  TMcCulloch  KM Intravenous morphine attenuates pain induced changes in skin blood flow in newborn infants.  Neurol Res. 1996;18440- 444Google Scholar
Dyke  MPKohan  REvans  S Morphine increases synchronous ventilation in preterm infants.  J Paediatr Child Health. 1995;31176- 179Google ScholarCrossref
Orsini  AJLeef  KHCostarino  ADettorre  MDStefano  JL Routine use of fentanyl infusions for pain and stress reduction in infants with respiratory distress syndrome.  J Pediatr. 1996;129140- 145Google ScholarCrossref
Cordero  LGardner  DKO'Shaughnessy  R Analgesia versus sedation during Broviac catheter placement.  Am J Perinatol. 1991;8284- 287Google ScholarCrossref
van Lingen  RADeinum  JTQuak  JM  et al.  Pharmacokinetics and metabolism of rectally administered paracetamol in preterm neonates.  Arch Dis Child Fetal Neonatal Ed. 1999;80F59- F63Google ScholarCrossref
Lin  YCSussman  HHBenitz  WE Plasma concentrations after rectal administration of acetaminophen in preterm neonates.  Paediatr Anaesth. 1997;7457- 459Google ScholarCrossref
van Lingen  RADeinum  HTQuak  CMOkken  ATibboel  D Multiple-dose pharmacokinetics of rectally administered acetaminophen in term infants.  Clin Pharmacol Ther. 1999;66509- 515Google ScholarCrossref
Autret  EDutertre  JPBreteau  MJonville  APFuret  YLaugier  J Pharmacokinetics of paracetamol in the neonate and infant after administration of propacetamol chlorhydrate.  Dev Pharmacol Ther. 1993;20129- 134Google Scholar
Larsson  BATannfeldt  GLagercrantz  HOlsson  GL Venipuncture is more effective and less painful than heel lancing for blood tests in neonates.  Pediatrics. 1998;101882- 886Google ScholarCrossref
Larsson  BATannfeldt  GLagercrantz  HOlsson  GL Alleviation of the pain of venipuncture in neonates.  Acta Paediatr. 1998;87774- 779Google ScholarCrossref
Shah  VSTaddio  ABennett  SSpeidel  BD Neonatal pain response to heel stick vs venepuncture for routine blood sampling.  Arch Dis Child Fetal Neonatal Ed. 1997;77F143- F144Google ScholarCrossref
Shah  VOhlsson  A Venepuncture versus heel lance for blood sampling in term neonates [Cochrane Review on CD-ROM].  Oxford, England Cochrane Library2000;2CD001452
Ohlsson  ATaddio  AJadad  ARStevens  BJ Evidence-based decision making, systematic reviews and the Cochrane collaboration: implications for neonatal analgesia. Anand  KJSStevens  BJMcGrath  PJeds. Pain in Neonates. 2nd ed. Pain Research & Clinical Management 10 Amsterdam, the Netherlands Elsevier Science2000;251- 268Google Scholar
Harpin  VARutter  N Making heel pricks less painful.  Arch Dis Child. 1983;58226- 228Google ScholarCrossref
Shah  VTaddio  AOhlsson  A Randomised controlled trial of paracetamol for heel prick pain in neonates.  Arch Dis Child Fetal Neonatal Ed. 1998;79F209- F211Google ScholarCrossref
Gourrier  EKaroubi  PEl-Hanache  A  et al.  Utilisation de la crème EMLA chez le nouveau-ne a terme et premature: etude d'efficacite et de tolerance.  Arch Pediatr. 1995;21041- 1046Google ScholarCrossref
Acharya  ABBustani  PCPhillips  JDTaub  NABeattie  RM Randomised controlled trial of eutectic mixture of local anaesthetics cream for venepuncture in healthy preterm infants.  Arch Dis Child Fetal Neonatal Ed. 1998;78F138- F142Google ScholarCrossref
Garcia  OCReichberg  SBrion  LPSchulman  M Topical anesthesia for line insertion in very low birth weight infants.  J Perinatol. 1997;17477- 480Google Scholar
Smith  MF Internal jugular venous cannulation in children under 5 years of age.  Can J Anaesth. 1990;37 (4 pt 2) S102Google ScholarCrossref
Walsh  ZBertilson  SO Topical anaesthetic cream provides pain relief in tetanus vaccination.  Lakartidningen. 1987;84611- 612Google Scholar
Uhari  M A eutectic mixture of lidocaine and prilocaine for alleviating vaccination pain in infants.  Pediatrics. 1993;92719- 721Google Scholar
Taddio  ANulman  IGoldbach  MIpp  MKoren  G Use of lidocaine-prilocaine cream for vaccination pain in infants.  J Pediatr. 1994;124643- 648Google ScholarCrossref
Friesen  RHHonda  ATThieme  RE Changes in anterior fontanel pressure in preterm neonates during tracheal intubation.  Anesth Analg. 1987;66874- 878Google Scholar
Pokela  MLKoivisto  M Physiological changes, plasma beta-endorphin and cortisol responses to tracheal intubation in neonates.  Acta Paediatr. 1994;83151- 156Google ScholarCrossref
Bhutada  ASahni  RRastogi  SWung  JT Randomised controlled trial of thiopental for intubation in neonates.  Arch Dis Child Fetal Neonatal Ed. 2000;82F34- F37Google ScholarCrossref
Mostafa  SMMurthy  BVBarrett  PJMcHugh  P Comparison of the effects of topical lidocaine spray applied before or after induction of anaesthesia on the pressor response to direct laryngoscopy and intubation.  Eur J Anaesthesiol. 1999;167- 10Google ScholarCrossref
Lehtinen  AMHovorka  JWidholm  O Modification of aspects of the endocrine response to tracheal intubation by lignocaine, halothane and thiopentone.  Br J Anaesth. 1984;56239- 246Google ScholarCrossref
Durand  MSangha  BCabal  LAHoppenbrouwers  THodgman  JE Cardiopulmonary and intracranial pressure changes related to endotracheal suctioning in preterm infants.  Crit Care Med. 1989;17506- 510Google ScholarCrossref
Greisen  GSFrederiksen  PSHertel  MChristensen  NJ Catecholamine response to chest physiotherapy and endotracheal suctioning in preterm infants.  Acta Paediatr Scand. 1985;74525- 529Google ScholarCrossref
Pokela  ML Pain relief can reduce hypoxemia in distressed neonates during routine treatment procedures.  Pediatrics. 1994;93379- 383Google Scholar
Saarenmaa  EHuttunen  PLeppaluoto  JFellman  V Alfentanil as procedural pain relief in newborn infants.  Arch Dis Child Fetal Neonatal Ed. 1996;75F103- F107Google ScholarCrossref
Hickey  PRHansen  DDWessel  DLLang  PJonas  RAElixson  EM Blunting of stress responses in the pulmonary circulation of infants by fentanyl.  Anesth Analg. 1985;641137- 1142Google Scholar
Haxhija  EQRosegger  HPrechtl  HF Vagal response to feeding tube insertion in preterm infants: has the key been found?  Early Hum Dev. 1995;4115- 25Google ScholarCrossref
Ng  ETaddio  AOhlsson  A Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit. [Cochrane Review on CD-ROM].  Oxford, England Cochrane Library2000;2CD002052
Jacqz Aigrain  EDaoud  PBurtin  P  et al.  Placebo-controlled trial of midazolam sedation in mechanically ventilated newborn infants.  Lancet. 1994;344646- 650Google ScholarCrossref
American Academy of Pediatrics, Task Force on Circumcision, Circumcision policy statement.  Pediatrics. 1999;103686- 693Google ScholarCrossref
Canadian Paediatric Society, Fetus and Newborn Committee, Neonatal circumcision revisited.  CMAJ. 1996;154769- 780Google Scholar
Kurtis  PSDeSilva  HNBernstein  BAMalakh  LSchechter  NL A comparison of the Mogen and Gomco clamps in combination with dorsal penile nerve block in minimizing the pain of neonatal circumcision.  Pediatrics [serial online]. 1999;103e23Google Scholar
Taddio  APollock  NGilbert-MacLeod  COhlsson  KKoren  G Combined analgesia and local anesthesia to minimize pain during circumcision.  Arch Pediatr Adolesc Med. 2000;154620- 623Google ScholarCrossref
Butler-O'Hara  MLeMoine  CGuillet  R Analgesia for neonatal circumcision: a randomized controlled trial of EMLA cream versus dorsal penile nerve block.  Pediatrics [serial online]. 1998;101e5Google Scholar
Hassan  SZ Caudal anesthesia in infants.  Anesth Analg. 1977;56686- 689Google ScholarCrossref
Lunn  JN Postoperative analgesia after circumcision: a randomized comparison between caudal analgesia and intramuscular morphine in boys.  Anaesthesia. 1979;34552- 554Google ScholarCrossref
May  AEWandless  JJames  RH Analgesia for circumcision in children: a comparison of caudal bupivacaine and intramuscular buprenorphine.  Acta Anaesth Scand. 1982;6331- 333Google ScholarCrossref
Spear  RM Dose-response in infants receiving caudal anaesthesia with bupivacaine.  Paediatr Anaesth. 1991;147- 52Google ScholarCrossref
Newton  CWMulnix  NBaer  LBovee  T Plain and buffered lidocaine for neonatal circumcision.  Obstet Gynecol. 1999;93350- 352Google ScholarCrossref
Stang  HJSnellman  LWCondon  LM  et al.  Beyond dorsal penile nerve block: a more humane circumcision.  Pediatrics [serial online]. 1997;100e3Google Scholar
Fatovich  DMJacobs  IG A randomized controlled trial of buffered lidocaine for local anesthetic infiltration in children and adults with simple lacerations.  J Emerg Med. 1999;17223- 228Google ScholarCrossref
Anand  KJSHickey  PR Pain and its effects in the human neonate and fetus.  N Engl J Med. 1987;3171321- 1329Google ScholarCrossref
Franck  LS A national survey of the assessment and treatment of pain and agitation in the neonatal intensive care unit.  J Obstet Gynecol Neonatal Nurs. 1987;16387- 393Google ScholarCrossref
Purcell-Jones  GDormon  FSumner  E Paediatric anaesthetists' perceptions of neonatal and infant pain.  Pain. 1988;33181- 187Google ScholarCrossref
Wellington  NRieder  MJ Attitudes and practices regarding analgesia for newborn circumcision.  Pediatrics. 1993;92541- 543Google Scholar
McLaughlin  CRHull  JGEdwards  WHCramer  CPDewey  WL Neonatal pain: a comprehensive survey of attitudes and practices.  J Pain Symptom Manag. 1993;87- 16Google ScholarCrossref
Porter  FLWolf  CMGold  JLotsoff  DMiller  JP Pain and pain management in newborn infants: a survey of physicians and nurses.  Pediatrics. 1997;100626- 632Google ScholarCrossref
Salantera  S Finnish nurses' attitudes to pain in children.  J Adv Nurs. 1999;29727- 736Google ScholarCrossref
Howard  CRHoward  FMGarfunkel  LCde Blieck  EAWeitzman  M Neonatal circumcision and pain relief: current training practices.  Pediatrics. 1998;101423- 428Google ScholarCrossref
Rana  SR Pain: a subject ignored.  Pediatrics. 1987;79309Google Scholar
Kart  TChristrup  LLRasmussen  M Recommended use of morphine in neonates, infants and children based on a literature review, part 2: clinical use.  Paediatr Anaesth. 1997;793- 101Google ScholarCrossref
Barker  DPSimpson  JPawula  MBarrett  DAShaw  PNRutter  N Randomised, double blind trial of two loading dose regimens of diamorphine in ventilated newborn infants.  Arch Dis Child Fetal Neonatal Ed. 1995;73F22- F26Google ScholarCrossref
Campbell  NNReynolds  GJPerkins  G Postoperative analgesia in neonates: an Australia-wide survey.  Anaesth Intensive Care. 1989;17487- 491Google Scholar
Gill  AMCousins  ANunn  AJChoonara  IA Opiate-induced respiratory depression in pediatric patients.  Ann Pharmacother. 1996;30125- 129Google Scholar
Partridge  JCWall  SN Analgesia for dying infants whose life support is withdrawn or withheld.  Pediatrics. 1997;9976- 79Google ScholarCrossref
Tholl  DAWager  MSSajous  CHMyers  TF Morphine use and adverse effects in a neonatal intensive care unit.  Am J Hosp Pharm. 1994;512801- 2803Google Scholar
Saarenmaa  EHuttunen  PLeppaluoto  JMeretoja  OFellman  V Advantages of fentanyl over morphine in analgesia for ventilated newborn infants after birth: a randomized trial.  J Pediatr. 1999;134144- 150Google ScholarCrossref
Sabatino  GQuartulli  LDi Fabio  SRamenghi  LA Hemodynamic effects of intravenous morphine infusion in ventilated preterm babies.  Early Hum Dev. 1997;47263- 270Google ScholarCrossref
Goldstein  RFBrazy  JE Narcotic sedation stabilizes arterial blood pressure fluctuations in sick premature infants.  J Perinatol. 1991;11365- 371Google Scholar
Farrington  EAMcGuinness  GAJohnson  GFErenberg  ALeff  RD Continuous intravenous morphine infusion in postoperative newborn infants.  Am J Perinatol. 1993;1084- 87Google ScholarCrossref
Rasch  DKWebster  DEPollard  TGGurkowski  MA Lumbar and thoracic epidural analgesia via the caudal approach for postoperative pain relief in infants and children.  Can J Anaesth. 1990;37359- 362Google ScholarCrossref
Vaughn  PRTownsend  SFThilo  EHMcKenzie  SMoreland  SDenver  KK Comparison of continuous infusion of fentanyl to bolus dosing in neonates after surgery.  J Pediatr Surg. 1996;311616- 1623Google ScholarCrossref
Burtin  PDaoud  PJacqz-Aigrain  E  et al.  Hypotension with midazolam and fentanyl in the newborn.  Lancet. 1991;3371545- 1546Google ScholarCrossref
Irazuzta  JPascucci  RPerlman  NWessel  D Effects of fentanyl administration on respiratory system compliance in infants.  Crit Care Med. 1993;211001- 1004Google ScholarCrossref
Lemmen  RJSemmekrot  BA Muscle rigidity causing life-threatening hypercapnia following fentanyl administration in a premature infant [letter].  Eur J Pediatr. 1996;1551067Google ScholarCrossref
Lindemann  R Respiratory muscle rigidity in a preterm infant after use of fentanyl during caesarean section.  Eur J Pediatr. 1998;1571012- 1013Google ScholarCrossref
Bolisetty  SKitchanan  SWhitehall  J Generalized muscle rigidity in a neonate following intrathecal fentanyl during caesarean delivery [letter].  Intensive Care Med. 1999;251337Google ScholarCrossref
Pokela  MLRyhanen  PTKoivisto  MEOlkkola  KTSaukkonen  AL Alfentanil-induced rigidity in newborn infants.  Anesth Analgesia. 1992;75252- 257Google ScholarCrossref
Okada  YPowis  MMcEwan  APierro  A Fentanyl analgesia increases the incidence of postoperative hypothermia in neonates.  Pediatr Surg Int. 1998;13508- 511Google ScholarCrossref
Anand  KJSSippell  WGAynsley-Green  A Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: effects on the stress response.  Lancet. 1987;1243- 248Google ScholarCrossref
Resar  LMHelfaer  MA Recurrent seizures in a neonate after lidocaine administration.  J Perinatol. 1998;18193- 195Google Scholar
Garner  LStirt  JAFinholt  DA Heart block after intravenous lidocaine in an infant.  Can Anaesth Soc J. 1985;32425- 428Google ScholarCrossref
Calobrisi  SDDrolet  BAEsterly  NB Petechial eruption after the application of EMLA cream.  Pediatrics. 1998;101471- 473Google ScholarCrossref
Frey  BKehrer  B Toxic methaemoglobin concentrations in premature infants after application of a prilocaine-containing cream and peridural prilocaine.  Eur J Pediatr. 1999;158785- 788Google ScholarCrossref
Law  RMHalpern  SMartins  RFReich  HInnanen  VOhlsson  A Measurement of methemoglobin after EMLA analgesia for newborn circumcision.  Biol Neonate. 1996;70213- 217Google ScholarCrossref
Cotsen  MRDonaldson  JSUejima  TMorello  FP Efficacy of ketamine hydrochloride sedation in children for interventional radiologic procedures.  AJR Am J Roentgenol. 1997;1691019- 1022Google ScholarCrossref
Tashiro  CMatsui  YNakano  SUeyama  HNishimura  MOka  N Respiratory outcome in extremely premature infants following ketamine anaesthesia.  Can J Anaesth. 1991;38287- 291Google ScholarCrossref
Green  SMClark  RHostetler  MACohen  MCarlson  DRothrock  SG Inadvertent ketamine overdose in children: clinical manifestations and outcome.  Ann Emerg Med. 1999;34492- 497Google ScholarCrossref
Parker  RIMahan  RAGiugliano  DParker  MM Efficacy and safety of intravenous midazolam and ketamine as sedation for therapeutic and diagnostic procedures in children.  Pediatrics. 1997;99427- 431Google ScholarCrossref
Goldberg  RNMoscoso  PBauer  CR  et al.  Use of barbiturate therapy in severe perinatal asphyxia: a randomized controlled trial.  J Pediatr. 1986;109851- 856Google ScholarCrossref
Anand  KJSStevens  BJMcGrath  PJ Pain in neonates.  Pain Research and Clinical Management 2nd ed.10 Amsterdam, the Netherlands Elsevier Science2000;Google Scholar
Anand  KJS Pain, plasticity, and premature birth: a prescription for permanent suffering?  Nat Med. 2000;6971- 973Google ScholarCrossref