2021

What was found?

We found that parents of children who were born preterm want to receive information about the potential consequences of prematurity for development and learning when their child is still a baby. However, not all parents want this so flexibility should be offered to individual families. Parents feel that it is important to highlight the potential for positive progress and the benefits of early intervention and support when discussing challenges that their child might face. Parents feel that health visitors and educational professionals are not well informed about the consequences of prematurity for development and learning.

What we did?

Parents of children born preterm from around the UK were asked to complete a survey about their attitudes and preferences around research and communication about potential long-term outcomes of preterm birth.

What are the implications?

Opportunities for conversations between parents and doctors should be offered early on and in a flexible way. Doctors should work with parents to offer flexibility in the timing and format of delivery of information about long-term outcomes. These findings are important as they help doctors to make decisions about when and how to communicate with parents. They indicate how the quality and breadth of support parents and children can access could be improved through training for key professionals including health visitors, early years educators, and teachers.

Preterm birth may lead to language deficits that persist into school age and are associated with a range of negative sequelae across the life span. We aimed to build a model that predicts language outcomes at 2 years corrected gestational age for children born preterm. We analysed data from 89 preterm neonates who were recruited as part of Theirworld Edinburgh Birth Cohort and who underwent diffusion MRI of the brain at term-equivalent age and language assessment at 2 years corrected gestational age using the Bayley Scales of Infant and Toddler Development, 3^rd Edition. Using various machine learning techniques, we developed a model which accurately identifies preterm infants who have a high risk to develop language deficits in early childhood (accuracy: 91%, sensitivity: 86%, specificity: 96%). Specifically, we found that language delay is associated with features derived from diffusion MRI, male sex, multiple birth, an incomplete or no antenatal corticosteroid treatment, and type of feeding. This model has the potential to enable clinicians identify infants who are at risk of language delay, thus facilitating targeted early interventions and support services, which could improve the quality of life for children born preterm.

Infection or inflammation around the time of birth is associated with an increased risk of problems with learning, thinking and behaviour in children who are born too soon. Premature babies may benefit from therapies to reduce inflammation but the immune system responses in early life are not well understood. By combining information from placenta and blood from 177 infants, we show that the immune system response is significantly altered by preterm birth and remains altered for several days in infants who are exposed to inflammation in the womb before delivery.

These findings suggest that therapies to reduce inflammation and restore healthy brain development may be effective in the days after preterm birth and focus research attention on the discovery of potential immune system therapeutic targets.

This study explored whether early social attention differences seen following preterm birth are linked to later social cognitive development. At 5 years, children born preterm demonstrated equivalent social interaction abilities to term-born children, unrelated to their social attentional profile in infancy. The role of infant social attention in the preterm phenotype remains uncertain.

Preterm birth is associated with reduced social attention in infancy. Are these early social attention differences linked to later interactive ability? This study draws on a well‐characterized preterm cohort in whom we have previously demonstrated a reduced attentional preference for social information in infancy, using eye‐tracking. States of engagement during parent–child play at 60 months were coded for 36 preterm‐ and 31 term‐born children. We also repeated the eye‐tracking assessment of social attention previously performed in infancy and evaluated neurodevelopment via the Mullen Scales of Early Learning. Children born preterm or at term spent similar percentages of time in different engagement states. Infant and child social attentional profiles did not relate to the complexity of engagement. Preterm infants’ language impairments correlated with time spent in conversational joint engagement. Children born preterm showed complex social interaction abilities unrelated to their profile of social attention in infancy.

Social cognitive abilities are affected by preterm birth, but pathways to, and risk factors for this outcome are not well mapped. We examined direct assessment tasks including objective coding of parent-child play to chart social development in infancy and pre-school years. A systematic search and data-extraction procedure yielded seventy-nine studies (4930 preterm and 2109 term children, aged birth – five years), for inclusion. We detected a pattern of reduced social attention in the first 12 months of life with evidence of reduced performance in social cognitive tasks later in the preschool years. However, we did not identify a consistent, distinctive preterm social phenotype in early life. Instead, the interactive behaviour of preterm infants reflects factors from outside the social cognitive domain, such as attention, language, and socioeconomic status. By combining data across samples and measures we revealed the role of domain-general skills, which may in future prove fruitful intervention targets.

Birth weight, an indicator of fetal growth, is associated with cognitive outcomes in early life (which are predictive of cognitive ability in later life) and risk of metabolic and cardiovascular disease across the life course. Brain health in older age, indexed by MRI features, is associated with cognitive performance, but little is known about how variation in normal birth weight impacts on brain structure in later life. In a community dwelling cohort of participants in their early seventies we tested the hypothesis that birth weight is associated with the following MRI features: total brain (TB), grey matter (GM) and normal appearing white matter (NAWM) volumes; whiter matter hyperintensity (WMH) volume; a general factor of fractional anisotropy (gFA) and peak width skeletonised mean diffusivity (PSMD) across the white matter skeleton. We also investigated the associations of birth weight with cortical surface area, volume and thickness. Birth weight was positively associated with TB, GM and NAWM volumes in later life (β ≥ 0.194), and with regional cortical surface area but not gFA, PSMD, WMH volume, or cortical volume or thickness. These positive relationships appear to be explained by larger intracranial volume, rather than by age-related tissue atrophy, and are independent of body height and weight in adulthood. This suggests that larger birth weight is linked to more brain tissue reserve in older life, rather than age-related brain structural features, such as tissue atrophy or WMH volume.

Adult hair glucocorticoid concentrations reflect months of hypothalamic-pituitary-adrenal axis activity. However, little is known about the determinants of neonatal hair glucocorticoids. We tested associations between perinatal exposures and neonatal hair glucocorticoids. Cortisol and cortisone were measured by LC-MS/MS in paired maternal and infant hair samples collected within 10 days of birth (n = 49 term, n = 47 preterm), with neonatal samples collected at 6-weeks in n = 54 preterm infants. We demonstrate cortisol accumulation in hair increases with fetal maturity, with hair cortisol being higher in term than preterm born infants after delivery (median 401 vs 106 pg/mg; p < 0.001). In term born infants, neonatal hair cortisol is positively associated with maternal hair cortisol concentration (β = 0.240, p = 0.045) and negatively associated with birthweight z-score (β = -0.340, p = 0.006). Additionally, being born without maternal labour is associated with lower hair cortisol concentrations (β = -0.489, p < 0.001) and a lower ratio of cortisol to cortisone (β = -0.484, p = 0.001). In preterm infants, histological chorioamnionitis is associated with a higher cortisol to cortisone ratio in hair (β = 0.459, p = 0.001). In samples collected 6 weeks after preterm birth, hair cortisol concentration is associated with cortisol hair concentrations measured after birth (β = 0.523, p < 0.001), chorioamnionitis (β = 0.250, p = 0.049) and postnatal exposures including intravenous hydrocortisone therapy (β = 0.343, p < 0.007) and neonatal sepsis (β = 0.290, p = 0.017). In summary, neonatal hair cortisol is associated with birth gestation, maternal hair cortisol concentration and fetal growth. Additionally, exposures at delivery are important determinants of hair cortisol, and should be considered in the design of future research investigating how neonatal hair cortisol relates to prenatal exposures or fetal development.

What was found? Previous research shows that attention problems are common in preterm infants, children, and adults, but it is still not clear whether some attention skills are more likely to be affected than others.

What we did? We looked at the results from previous studies to find out what kind of attention problems are associated with prematurity and how common these are in babies, children and adults who were born early. We also looked at the different ways these studies measured attention. What are the implications? These findings highlight that attention outcomes following preterm birth are variable, and that we still can’t say for sure whether some kinds of attention are more likely to be affected by preterm birth compared to others. Researchers need to work hard to design studies that can answer these questions and to address challenges with how attention is measured, especially in young infants.