Abstract: Seventy-four studies enrolling 7049 infants were included. Results from only a few studies could be combined in meta-analyses and for most analyses the GRADE assessments indicated low- or moderate-quality evidence. There was high-quality evidence for the beneficial effect of sucrose (24%) with non-nutritive sucking (pacifier dipped in sucrose) or 0.5 mL of sucrose orally in preterm and term infants: Premature Infant Pain Profile (PIPP) 30 s after heel lance WMD -1.70 (95% CI -2.13 to -1.26; I2 = 0% (no heterogeneity); 3 studies, n = 278); PIPP 60 s after heel lance WMD -2.14 (95% CI -3.34 to -0.94; I2 = 0% (no heterogeneity; 2 studies, n = 164). There was high-quality evidence for the use of 2 mL 24% sucrose prior to venipuncture: PIPP during venipuncture WMD -2.79 (95% CI -3.76 to -1.83; I2 = 0% (no heterogeneity; 2 groups in 1 study, n = 213); and intramuscular injections: PIPP during intramuscular injection WMD -1.05 (95% CI -1.98 to -0.12; I2 = 0% (2 groups in 1 study, n = 232). Evidence from studies that could not be included in RevMan-analyses supported these findings. Reported adverse effects were minor and similar in the sucrose and control groups. Sucrose is not effective in reducing pain from circumcision. The effectiveness of sucrose for reducing pain/stress from other interventions such as arterial puncture, subcutaneous injection, insertion of nasogastric or orogastric tubes, bladder catherization, eye examinations and echocardiography examinations are inconclusive. Most trials indicated some benefit of sucrose use but that the evidence for other painful procedures is of lower quality as it is based on few studies of small sample sizes. The effects of sucrose on long-term neurodevelopmental outcomes are unknown. Sucrose is effective for reducing procedural pain from single events such as heel lance, venipuncture and intramuscular injection in both preterm and term infants. No serious side effects or harms have been documented with this intervention. We could not identify an optimal dose due to inconsistency in effective sucrose dosage among studies. Further investigation of repeated administration of sucrose in neonates is needed. There is some moderate-quality evidence that sucrose in combination with other non-pharmacological interventions such as non-nutritive sucking is more effective than sucrose alone, but more research of this and sucrose in combination with pharmacological interventions is needed. Sucrose use in extremely preterm, unstable, ventilated (or a combination of these) neonates needs to be addressed. Additional research is needed to determine the minimally effective dose of sucrose during a single painful procedure and the effect of repeated sucrose administration on immediate (pain intensity) and long-term (neurodevelopmental) outcomes.

Plain-language summary: We searched the medical literature widely up to February 2016 for studies that investigated the pain-relieving effect of sucrose for minor medical procedures in newborn full-term and premature babies. We included randomised controlled trials only, as these provide the most reliable medical evidence. We identified 74 studies that reported on a total of more than 7000 infants in this Cochrane Review. Thirty-eight studies included full-term babies only, 31 included premature babies only, and five included both full-term and premature babies. Heel lance was the painful procedure in 38 studies, and venipuncture in nine; the remaining studies investigated a wide variety of other minor painful procedures. The studies used a variety of delivery methods for the sucrose solution (oral syringe, dropper or sucrose-dipped pacifier), as well as a range of concentrations and volumes of dose. Sucrose treatment was compared with giving the babies a similar volume of water, a pacifier, routine care, breastfeeding, 'facilitated tucking' (holding the infant in a flexed position with arms close to the body and hands placed to promote sucking), laser acupuncture, swaddling, warmth, anaesthetic cream for the skin (EMLA), or a combination of these. The studies used a range of pain assessment scales to measure their results. We did not identify any studies that received funding from the industry. There was high-quality evidence that sucrose reduces different measures of newborn pain during heel lance, venipuncture and intramuscular injection. However, sucrose does not provide effective pain relief during circumcision. There is conflicting evidence for whether sucrose reduces pain for other minor painful procedures and further research is needed to investigate these more thoroughly. Twenty-nine studies reported on adverse events (harms of the sucrose and other treatments) and found that the number of minor adverse events (e.g. choking or gagging) was very low, and was similar in the different groups (so not attributable to the sucrose treatment). No major adverse events were reported. Although sucrose has been widely studied as a pain reliever for newborn babies, most studies have included few babies and have used many different measures of pain to assess its effectiveness. We identified high-quality evidence that sucrose reduces pain for heel lance, venipuncture and intramuscular injection. The quality of evidence was low or moderate in favour for the use of sucrose for other painful procedures.