Pain Relief for Newborns Gets a Blueprint: New Guidelines Tackle the Distress of Vascular Access Procedures

Every day in neonatal intensive care units around the world, thousands of newborn babies, many of them born months too early, undergo the insertion of vascular access devices. These thin catheters, threaded into peripheral veins or deep central vessels, are the lifelines of modern neonatal medicine: they deliver nutrition, antibiotics, and life-saving medications to infants who cannot yet feed or absorb drugs reliably. Yet the very procedures that sustain these fragile patients are among the most painful and distressing experiences they will ever encounter. A new set of expert recommendations, published in the journal Pediatric Research by an international consortium of neonatologists, nurses, anesthesiologists, and parent advocates, aims to change that by providing a structured, evidence-informed framework for assessing, managing, and alleviating the pain and distress associated with vascular access device placement in neonates.

The recommendations come from the Pediatric and Neonatal Vascular Access Special Interest Group of the European Society for Paediatric Research, working together with NEVAT, a multidisciplinary vascular access network. Led by first author Tobias Werther of the Medical University of Vienna and corresponding author Robin van der Lee of Radboud University Medical Center in the Netherlands, the group spans institutions across Europe and beyond, from Lisbon and Treviso to Brussels, Sofia, and London. Their motivation is blunt: vascular access is a pervasive facet of contemporary neonatal practice, yet it lacks standardization, and some common practices lack supporting evidence. In other words, the procedures are universal, but the way clinicians prepare babies for them varies enormously from unit to unit, and not always in ways supported by data.

The scientific case for taking neonatal pain seriously has grown dramatically over the past two decades. Preterm infants in intensive care are exposed to a remarkable number of painful procedures during their hospital stay, and repeated early-life pain is no longer regarded as a transient inconvenience. Recent research cited by the group links cumulative early pain exposure in premature infants to atypical cerebellar development and later neurodevelopmental deficits, suggesting that unmanaged procedural pain may leave lasting traces in the developing brain. The developing nervous system of a newborn, and especially that of a very preterm infant, processes nociceptive signals with heightened sensitivity, and immature descending inhibitory pathways mean that pain signals arrive essentially unfiltered. The long-standing assumption that newborns barely feel pain, or that any distress is quickly forgotten, has been thoroughly dismantled by modern neuroscience.

A central pillar of the new recommendations is the principle of assessing pain before attempting to treat it. Because preverbal infants cannot report their experiences, clinicians must rely on validated behavioral and physiological indicators: facial expression, body movement, crying, changes in heart rate, and oxygen saturation. The authors emphasize the use of structured pain and sedation scales designed specifically for neonatal and pediatric patients in preverbal stages of development, noting that systematic reviews have evaluated the validity and reliability of such instruments, including for preterm infants. Without consistent measurement, the group argues, pain management becomes arbitrary, and the effectiveness of any intervention, whether pharmacological or non-pharmacological, cannot be judged. Assessment is framed not as a bureaucratic step but as the foundation on which every subsequent decision rests.

On the pharmacological side, the recommendations draw on a substantial evidence base. For minor procedures, oral sucrose has become one of the most widely studied analgesic interventions in neonatology, with Cochrane reviews confirming its effectiveness for procedural pain relief in newborns undergoing painful procedures, and subsequent trials working to identify the minimally effective dose. Sucrose appears to activate endogenous opioid pathways, and its effect can be amplified when combined with non-nutritive sucking, such as a pacifier. Breastfeeding and expressed breast milk also carry evidence for procedural pain relief, offering a natural alternative that combines analgesia with nutrition and maternal contact. Topical anesthetics such as lidocaine-prilocaine cream have been evaluated for needle-related pain, although the evidence in neonates remains more limited than in older children.

For more invasive procedures, particularly the ultrasound-guided placement of central venous catheters, the recommendations acknowledge that simple sweet-tasting solutions are not enough. Here the group points to analgosedation protocols, the deliberate combination of analgesic and sedative agents to keep infants comfortable and still during longer procedures. Randomized controlled trials have examined remifentanil for percutaneous intravenous central catheter placement in preterm infants, and more recent prospective studies have tested structured analgosedation protocols for ultrasound-guided catheterization in the neonatal intensive care unit, including combinations such as ketamine with fentanyl. Population pharmacokinetic studies have clarified how fentanyl exposure in preterm and term newborns depends on pre- and postnatal maturation, underscoring that dosing in this population is a precision exercise rather than a simple weight-based calculation. Intranasal routes for analgosedation have also been systematically reviewed as a practical option for infants in intensive care, while the evidence for intravenous midazolam infusion as a sedative in this population has been critically appraised by Cochrane reviewers.

Perhaps the most striking technical shift reflected in the recommendations is the rise of ultrasound as a routine tool in neonatal vascular access. Structured pre-procedural ultrasound assessment protocols, with acronyms such as Rasuva for superficial veins, Raceva for central veins before catheterization, and Rafeva for the femoral veins of the lower limb, allow clinicians to map vessel anatomy, diameter, and patency before the first needle stick. Structured protocols for ultrasound-based tip navigation and tip location during central venous access device placement further reduce the guesswork. The logic connecting this technology to pain relief is straightforward: every failed insertion attempt is an additional painful procedure, so improving first-attempt success through better planning directly reduces the cumulative pain burden. This philosophy was crystallized in the Abba Project, Assess Better before Access, a retrospective cohort study of neonatal intravascular device outcomes that demonstrated the value of careful pre-procedural assessment.

Alongside drugs and devices, the recommendations give prominent weight to non-pharmacological and family-centered strategies. Systematic reviews and meta-analyses have found that non-pharmacological methods reduce neonatal pain, and the group highlights interventions such as swaddling, facilitated tucking, and skin-to-skin care, for which Cochrane evidence supports a role in procedural pain relief. Notably, one reported practice involves maintaining parent-infant skin-to-skin contact even during peripheral intravenous catheter insertion, a departure from the traditional separation of baby and parent for any sterile procedure. Family integrated care models, in which parents are trained and empowered as partners in their infant’s care rather than visitors, are supported by emerging clinical trial evidence, including nonrandomized trials of close collaboration with parents interventions in neonatal intensive care units. The involvement of the European Foundation for the Care of Newborn Infants and the Global Foundation for the Care of Newborn Infants in the drafting process signals that parent perspectives were built into the recommendations from the start, not appended afterward.

The recommendations also confront an uncomfortable implementation gap. National guidelines for procedural pain in newborns have existed for years, for example in Italy, where audits of their implementation revealed uneven adherence across units. The American Academy of Pediatrics issued an update on the prevention and management of procedural pain in the neonate nearly a decade ago, and pediatric clinical practice guidelines for acute procedural pain have been systematically reviewed, yet translation into bedside practice remains inconsistent. By focusing specifically on vascular access, the procedures that generate much of the procedural pain burden in neonatal care, the new document aims to close the distance between guideline and practice with concrete, procedure-specific recommendations rather than general exhortations.

For clinicians, the practical message is a sequence: assess the infant’s pain and distress with validated tools, plan the vascular access strategy with ultrasound before touching the patient, choose the appropriate combination of non-pharmacological comfort measures and pharmacological analgesia or analgosedation for the specific procedure, involve parents wherever possible, and reassess afterward to confirm that the strategy worked. For parents, the message is that their presence, touch, and breast milk are not sentimental extras but measurable components of pain care. The authors declare no competing interests and note that the work received no external funding, positioning it as a consensus effort by a community of specialists who see, daily, what unrelieved pain does to the smallest patients. As neonatal intensive care continues to push survival boundaries earlier and earlier, the group’s recommendations make the case that how these babies are treated matters as much as whether they survive, and that a needle inserted with skill, preparation, and compassion is a fundamentally different experience from one inserted without them.

Subject of Research: Management of pain and distress in neonates during vascular access device placement

Article Title: Neonatal vascular access: management of pain and distress during vascular access device placement

Article References: Werther, T., Marçal, M., Tuna, M. L., Salazar, A., van der Lee, R., Lago, P., Mader, S., Piersigilli, F., Van Eenoo, S., Hugill, K., van Rens, M., on behalf of the Pediatric and Neonatal Vascular Access SIG of the ESPR and NEVAT, Van der Lee, R., Van Eenoo, S., van Rens, M., Yousef, N., Schwaberger, B., De Bisschop, B., Ouwehand, T., … Van Delft, B. (2026). Neonatal vascular access: management of pain and distress during vascular access device placement. Pediatric Research. https://doi.org/10.1038/s41390-026-05482-7

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05482-7

Keywords: neonatal pain, vascular access, preterm infants, neonatal intensive care, analgesia, sucrose analgesia, ultrasound-guided catheterization, analgosedation, skin-to-skin care, family integrated care, pain assessment scales, central venous catheters