A sugar solution placed in the mouth before a needle insertion likely curbs newborns’ pain, according to a new Cochrane review. The finding — combined with a 2023 Cochrane review and others — suggests that the longstanding practice now has enough evidence to be standardized across hospitals and used as a “gold standard” in clinical trials, the researchers said.

It also adds to growing research on the effects of nonpharmacologic pain interventions for infants — and hints at lingering gaps in our understanding of how babies process pain. 

“The brain of a neonate is not just a small adult brain — it’s substantially different,” said Lorenzo Fabrizi, PhD, chair of developmental systems neuroscience at University College London, London, England, who was not involved in the analysis.

Researchers developed a 10-point pain intensity scale based on a composite of several validated infant pain assessment tools measuring behaviors (crying and limb movement) and physiologic signs (increased heart rate and reduced oxygen saturation).

The sugar solution — a mixture of sucrose (table sugar) and water — reduced pain scores by 2.1 points compared with no intervention and by 3.5 points when combined with a pacifier compared with a pacifier alone. (The minimal clinically important difference in pain scores was 1.3 points.) Sucrose probably reduced pain compared with breastfeeding but made little to no difference compared with skin-to-skin contact, according to the analysis, which included 29 randomized controlled trials involving 2767 newborns.

“We don’t need studies that include no intervention or placebo or water group anymore,” said lead author Mariana Bueno, RN, PhD, assistant professor at the Lawrence Bloomberg Faculty of Nursing at the University of Toronto, Toronto, Ontario, Canada.

Despite the compelling evidence, a deeper question remains.

The Mysterious Developing Brain

Because infants can’t self-report — the clinical “gold standard” for assessing pain — there will always be limits to what we can infer about their internal experience. Fabrizi encourages caution in assuming that a lower behavioral pain score translates to lower pain.

“Sucrose reduces behavioral reactivity and physiologic reactivity to tissue damage, but we cannot say with certainty that pain is less,” Fabrizi said.

The parts of the brain that encode pain intensity and modulate behavioral reaction may not be the same. Sucrose may act more as a distraction that reduces behavioral response — much like an adult whose friend makes them smile while they are crying. “Your behavior may change,” Fabrizi said. “However, we do not know that the pain is actually gone.”

Interpreting infants’ pain is further complicated by the fact that their neural networks are still a work in progress. Fabrizi’s research on early nervous system development highlights the complexity of the process.

Pain has three major components in the brain, he said. Examining brain MRI databases, Fabrizi found that the sensory network (location and intensity) develops first and is hyperconnected compared with adults. The affective network (emotional/unpleasantness) follows, while the cognitive network (understanding the experience was bad and should be avoided) develops last and is not mature by term birth.

Clinical Implications

As research clarifies how infants process pain, the new analysis can guide their clinical care. Sucrose should only be used during painful procedures, such as immunizations in a primary care setting, but not for general fussiness.

“Sucrose should be administered as any other medication,” Bueno said. “We need clear reasoning, we need local protocols, and we need clinicians to follow guidelines.”

Long-term research on sucrose use is needed to determine its effects on brain development, Bueno said, and future research should also compare interventions — like sucrose to skin-to-skin care to breastfeeding, for instance. Parental involvement is also “being more and more studied,” Bueno said.

The trend is moving toward multimodal comfort, combining sucrose and pacifiers with skin-to-skin contact, facilitated tucking, and parental presence. A 2025 randomized controlled trial in Sweden found that a combination of skin-to-skin contact, breastfeeding, and parents’ singing may relieve infants’ pain while providing stress relief to parents.

“Usually we tell parents, ‘Oh, you don’t want to see your baby receiving a needle. You don’t want to see your baby distressed, so it would be better for you to step out,’” Bueno said. “But no, the opposite is true. We want the parents with their babies, comforting their babies.”