Sammallahti, Sara
(Helsingin yliopisto, 2018)
Background: Preterm birth (before 37 weeks of gestation) is a major cause of infant mortality and morbidity worldwide, and preventing its burden is a health care priority. Even in adulthood, individuals who were born preterm perform, on average, worse on tests of cognitive functioning than term-born peers do, and may have more mental health problems.
Early growth failure is common among preterm individuals, and some studies have suggested that those preterm individuals who grow poorly in infancy have more neurodevelopmental problems later on in childhood. It is unclear whether these associations persist into adulthood and whether they extend beyond the smallest and most immature of preterm infants, to the majority of preterm infants who are born late preterm (at 34-36 completed weeks of gestation). It also remains unknown whether early postnatal growth patterns predict mental health outcomes - some partly conflicting evidence suggests that intrauterine growth restriction at least associates with mental health problems.
The mechanisms explaining the associations between growth and neurodevelopment are also unclear. Early growth reflects a number of intertwined early-life environmental factors and individual characteristics, and while altering neonatal nutrition can affect growth, it is not known whether changes in nutrition can improve long-term neurodevelopmental outcomes. It has even been suggested that faster growth and higher nutritional intakes during the early postnatal period can present a trade-off between improved neurodevelopment and increased cardiovascular risk.
Methods: The 157 participants of the Helsinki Study of Very Low Birth Weight Adults (HeSVA, birth weight <1500g) and the 108 participants of the Arvo Ylppö Longitudinal Study (AYLS, gestational age 34-36 completed weeks) examined in this thesis were born in Finland between 1978 and 1986. They were invited to adult follow-up visits between 2004 and 2012. Among these young adults, I examined whether growth in weight, length, and head circumference between different early growth periods (between preterm birth, term age, and 12 months of corrected age in HeSVA, and between late preterm birth, 5 and 20 months of corrected age, and 56 months of age in AYLS) was associated with performance in neuropsychological tests, with self-rated symptoms of depression, attention deficit hyperactivity disorder, and other mental health problems, or with diagnosis of mental disorder based on a psychiatric interview in adulthood. In the AYLS cohort, the participants also reported final grade point average and special education in comprehensive school. I further examined whether daily intakes of energy in total, of energy from human milk, and of carbohydrates, protein, and fats during the initial hospitalization, which were relatively low compared to modern recommendations, predicted adult cognitive functioning (HeSVA).
As growth variables, I used standardised residual change scores from linear regression models where weight, length, and head circumference z scores were regressed on corresponding measures at previous time points, creating uncorrelated residuals that reflect growth conditional on previous history. These growth variables were then used as independent variables in linear and logistic regression models to predict the outcomes, while taking into account several potential confounders including child and parental background characteristics and neonatal morbidity.
Results: Faster growth during the first months of life was associated with better adult cognitive functioning in both cohorts. The size and direction of the effects were similar: for each SD faster growth in weight, head circumference, and length between birth and term age, the HeSVA participants had 0.23-0.41 SD higher general intelligence quotient, executive functioning component, and visual memory scores. For each SD faster weight gain and head growth from birth to 5 months, and head growth from 5 to 20 months, the AYLS participants had 0.19-0.41 SD higher general intelligence quotient and executive functioning component scores and grade point average. Those who grew faster also had lower odds of having received special education at school. Growth after these time periods did not predict cognitive functioning or school outcomes. In contrast, there were no consistent associations between early growth and adult mental health in either cohort. Even when taking into account several important neonatal complications and illnesses, the associations between early growth and adult cognitive functioning could not be wholly explained. Neonatal morbidity however seemed to largely account for the associations between higher energy intake between the first six weeks of life and better cognitive functioning among the HeSVA participants.
Conclusions: Faster growth during the first weeks and months of life after preterm birth is associated with better cognitive functioning, and these associations persist into adulthood. The mechanisms explaining these associations are largely unclear, but seem outcome-specific. Early intakes of nutrition may reflect or possibly even mediate the effects of neonatal morbidity on neurodevelopment, however the neonatal morbidities commonly associated with preterm birth do not wholly account for the associations between early growth and long-term neurodevelopment.
Keywords: premature birth; infant, very low birth weight; gestational age; birth weight; cognition; intelligence; executive functioning; memory; mental health; depression; attention deficit disorder with hyperactivity; substance-related disorders; anxiety disorders; education; growth; weight gain; body height; cephalometry; energy intake; milk, human; infant; adult; risk factors; follow-up studies; longitudinal studies; developmental origins of health and disease