2026

Background Information

Children born preterm often experience difficulties in a range of cognitive skills, typically assessed by an examiner. These include general cognitive abilities and particular areas such as language, attention and executive functions. There is a need for efficient, scalable assessments that are relevant to everyday behaviours. For example, parental questionnaires are increasingly used, but it is unclear how well they can detect early cognitive difficulties in preterm children. Cognitive skills are also often correlated, such that people who perform well in one area usually perform well in another area. However, it is unknown if parental ratings of different skills correlate similarly.

Research Question

We used parental questionnaires to assess the language, attention and executive functions of 2-year-olds (96 preterm children and 87 term-born children). We explored associations between these skills and gestational age at birth, and also studied whether an underlying factor of shared ‘general ability’ links them.

Findings

Parents of preterm toddlers report reduced language abilities but similar attention and executive functions compared to term-born children. We found that these three skills are correlated with an underlying general ability that links them based on parents’ ratings.

Conclusions

Our findings show how parental ratings might be used to identify differences in preterm children’s abilities in many different areas, highlighting that they are particularly sensitive to differences in language. Future studies should compare parental reports with examiner-administered assessments to understand how both types of assessments relate to one another in early life.

Background information

Children born preterm often experience difficulties with cognitive skills, that is, how they think, learn and solve problems. However, even children born at the same stage of pregnancy can be affected in different ways. This means we need more precise methods to identify, early in life, which children may be at higher risk of cognitive difficulties.

Scientists have developed biological markers called EpiScores. These are based on epigenetics, which refers to small changes how a person’s DNA is used by the body without changing the DNA code itself. These changes can be influenced by biological factors, life experiences and the environment.

Protein EpiScores reflect specific proteins in the body. In the Theirworld Edinburgh Birth Cohort, we calculated protein EpiScores using saliva samples collected from babies around the time they were due to be born. Protein EpiScores can also be developed using blood samples, but saliva provides a non-invasive alternative. In previous work, we found that 43 saliva-based protein EpiScores were linked to preterm birth.

In this study, we combined information from these neonatal saliva-based protein EpiScores with results from children’s cognitive assessments at follow-up appointments.

Research question

We tested whether these 43 protein EpiScores, calculated from neonatal saliva samples, were associated with cognitive performance at ages 2 and 5 years in children born preterm and at term.

Findings

We found that several neonatal protein EpiScores were associated with cognitive performance at 2 or 5 years of age. Many of the EpiScores which showed meaningful links were related to proteins involved in infection and inflammation, as well as the development of the brain, blood vessels and other body systems. Some of these associations remained statistically significant even after taking into account the inflammatory conditions that are more common in infants born preterm.

Conclusion

Many protein EpiScores developed using neonatal saliva were linked to preschool cognitive performance. This study is the first to investigate a wide range of protein EpiScores in newborns and compare them with later developmental outcomes. These findings suggest that saliva-based neonatal EpiScores may be worth studying further as possible early markers of later cognitive ability, especially in preterm children who may be at risk of difficulties.