Background
As neonatal medicine has been improving for the last decades, more very low birth weight (VLBW; birth weight ≤1500 g) infants survive. The preterm brain is especially vulnerable to injury and developmental disturbances [
1], increasing the risk of later neurodevelopmental problems [
2,
3]. This may have an impact on mental health and health-related quality of life (HRQoL); however, studies on long-term effects of VLBW into adulthood are sparse and yield mixed findings.
Children and adolescents born preterm with VLBW are reported to have more mental health problems than full-term controls, with an increased occurrence of attention deficits, internalizing symptoms and social problems in particular [
2,
4]. There is an important transitional phase from adolescence to adulthood involving increasing demands on independency, education and adult roles [
5], which may stress the underlying neuroimpairments in VLBW individuals. Indeed, preterm birth is shown to have an adverse effect on educational attainment, income and establishment of a family [
6], and mental health problems tend to persist or even increase into young adulthood [
7‐
9].
The concept of HRQoL refers to the impact of health conditions on a person’s total well-being, including psychological, social, and physical aspects [
10]. Measuring HRQoL gives valuable insight into the person’s perception of his or her own health status, complementing more objectively collected data, and should therefore be addressed when assessing long-term consequences of VLBW. Although self-reports of HRQoL in VLBW children and adolescents seem to be similar to their normal birth weight peers, parent-reports are typically lower [
11]. Some studies of VLBW young adults have revealed lower HRQoL based on societal standards [
12] and lower scores on HRQoL domains of mental health [
13] and physical functioning [
14,
15]. Other studies report similar HRQoL [
14,
16,
17] and well-being [
18] for VLBW young adults compared with controls. Longitudinal studies on changes of HRQoL in VLBW populations are sparse, but receive growing attention [
11,
19].
Developmental disturbances in the preterm brain are global and likely to affect both mental health and other areas of neurodevelopment, such as motor problems. Poorer fine and gross motor skills are prevalent in childhood, adolescence and young adulthood in VLBW individuals [
3,
20]. Both among adults with normal birth weight and <1000 g, self-reported childhood coordination problems have been associated with elevated levels of inattention and symptoms of anxiety and depression [
21]. Lower quality of life has been reported among adults with developmental coordination disorder [
22]. However, no previous studies have investigated associations of mental health and HRQoL with motor skills in VLBW young adults. As motor skills are often assessed in childhood, and we have previously reported stability of motor problems from early childhood to young adulthood [
20,
23], it may be possible to identify children at risk for later mental health problems and low HRQoL.
In this study, we aimed to investigate the effects of VLBW on mental health and HRQoL in young adults at 23 years of age, including changes from 20 to 23 years and whether mental health and HRQoL were associated with motor skills. We hypothesized that VLBW young adults at age 23 would have more mental health problems and lower HRQoL compared with controls. Due to increased demands following the transition to adulthood, we predicted a decrease in mental health and HRQoL from 20 to 23 years in the VLBW group. Based on previous findings, we hypothesized that more mental health problems and lower physical HRQoL would be associated with poorer motor skills at age 23.
Discussion
In this study, VLBW young adults reported more mental health problems and lower HRQoL compared with controls at 23 years of age. In the VLBW group, mental health and HRQoL decreased from 20 to 23 years. Furthermore, in this group, more internalizing and total mental health problems as well as lower physical and mental HRQoL were associated with poorer performance on motor tests at 23 years, especially lower motor speed. When we excluded VLBW participants with CP and/or low IQest, several group differences were no longer significant, but for the ASR, mean values and longitudinal changes were essentially the same, whereas associations with motor skills became weaker.
Strengths of this study are the longitudinal and multidisciplinary design and the use of reliable and valid methods [
29,
31,
32]. However, sample size was limited, especially when we excluded participants with CP and/or low IQ
est, resulting in reduced power in our analyses. Results and especially non-significant group differences should therefore be carefully interpreted, and one should focus more on means and standard deviations than
p-values. Furthermore, our limited sample size did not give the possibility to study sub groups. Loss to follow-up may result in selection bias. The reason why 18 (33 %) of the invited VLBW young adults at 23 years did not want to participate and one did not fill out the questionnaires is not known. Our participants did not differ from non-participants on perinatal data or previous examinations of motor skills [
20], mental health or HRQoL. The only difference in clinical characteristics between participants and non-participants was lower parental SES for VLBW non-participants. Low parental SES is associated with more mental health problems in childhood and adolescence [
42], thus our results are more likely to be an underestimation than an overestimation of problems.
Self-report questionnaires like the ASR and SF-36 give participants the opportunity to describe their own perspective of their lives. However, self-reports are prone to social desirability bias, and cognitive function may influence the ability of self-perception and understanding questionnaires. We therefore performed analyses also when excluding VLBW participants with CP and/or low IQ
est. In this VLBW cohort at 20 years, we found more symptoms of psychiatric disorders with diagnostic assessment by a psychiatrist than self-reported mental health problems on the ASR [
43], and poorer executive functions on neuropsychiatric testing than on self-reports [
44], which might indicate that the VLBW individuals underreported or had adjusted to their problems. Even though objective evaluations add valuable insights; how the young adults rate their own health, and especially their HRQoL, might be more important to them.
Our findings of more mental health problems in VLBW young adults, with emphasis on internalizing and attention problems are consistent with the literature [
2,
9,
13,
45‐
47]. In our study, the VLBW young adults also had a tendency of reporting more anxious/depressed problems and social problems than the control group, supporting the suggested “Preterm behavioural phenotype” characterized by anxiety, inattention and social difficulties [
4]. The VLBW young adults did not seem to be more depressed than controls according to BDI, in line with the findings of Räikkönen et al. [
48]. However, Westrupp et al. [
49] found that VLBW young adults in their late twenties were five times more likely to be diagnosed with depression. We speculate that depression may become more prevalent when our VLBW participants grow older. We also found that VLBW young adults reported less substance use with regard to alcohol, consistent with other studies [
15,
50,
51], where some also describe less risk-taking behaviour [
15,
18,
46]. These findings are in accordance with the personality type reported among young adults born with VLBW or very preterm (<33 weeks’ gestation), including less sensation seeking, extraversion and openness to experience, and higher conscientiousness, neuroticism and shyness [
52,
53]. Even though increased parental monitoring and protectiveness cannot be excluded [
47], Harrison [
54] suggests that VLBW children and young adults have cognitive and behavioural deficits that isolate them from both their peers and their peers’ risk-taking behaviour, and that the isolation and withdrawal are caused by a lack of social and intellectual resilience. Cognitive function has been found to modify the risk of mental health problems of VLBW young adults in some studies [
45]. In our study, group differences in mental health problems were no longer significant when we excluded VLBW participants with CP and/or low IQ
est, however scores were essentially the same. It is of concern that the VLBW young adults scored significantly higher for critical items of clinically relevant psychiatric symptoms, also when we excluded participants with CP and/or low IQ
est. We have previously reported a trend towards an increase of mental health problems from 14 to 20 years of age in this cohort [
7], and the further increase from 20 to 23 years found in the current study is worrying and needs to be confirmed by other studies.
Findings on HRQoL in VLBW populations are conflicting. In contrast to our findings, the systematic reviews of Zwicker and Harris [
11] and Allen et al. [
9] concluded in four studies [
12,
15,
18,
55] that VLBW young adults around age 20 have similar HRQoL to controls. However, poorer physical functioning [
15] and lower objective quality of life [
12] were reported. More recent studies from Switzerland [
14] and New Zealand [
16] also reported similar HRQoL to controls according to the SF-36 among young adults born with birth weight <1250 g or with VLBW at age 23. A Norwegian study by Båtsvik et al. [
8] found lower scores for the SF-36 domains of bodily pain, vitality, social functioning, role-emotional and mental health among young adults born before week 28 or with a birth weight ≤1000 g compared with term-born controls at age 24. When they excluded participants with disabilities, group differences were significant for social functioning, role-emotional and mental health. When we excluded VLBW participants with CP and/or low IQ
est in our study, group differences on SF-36 were reduced and no longer significant, but mean scores where still lower for all domains in the VLBW group compared with the control group. Cooke [
15] found poorer physical functioning on SF-36 in VLBW young adults able to attend mainstream schools, and Dinesen and Greisen [
12] reported lower objective quality of life based on societal standards for VLBW individuals without disabilities at 18 years. Hence, both preterm born young adults with and without disabilities might be at risk for lower HRQoL than controls.
We speculate that the lower HRQoL among VLBW young adults found in our study could be partly due to challenges related to the transition to young adulthood. The underlying neuroimpairments of VLBW individuals may become more evident with these challenges, such as moving away from home, starting to study or work, finding a partner and living more independent and social lives [
5]. In Norway, only 29 % of 20 to 24-year-olds live with their parents, in contrast to 83 % in Switzerland (Additional file
1), and parent-support might to some extent explain the discrepancy from the Swiss study [
14]. In New Zealand, the proportion of 20 to 24-year-olds living with their parents was 32 % in 2006 (Additional file
2), similar to that in Norway. However, Darlow et al. [
16] only used the component summaries of the SF-36 relative to 18 to 24-year norms, and their control group was recruited at 23 years among peers to the VLBW group. Our control group was followed from birth, and may therefore be more representative of the general population. The lower HRQoL found among extremely preterm young adults by Båtsvik et al. [
8] supports our findings and might be more comparable as it is a Norwegian study. However, they studied young adults born before week 28 or with a birth weight ≤1000 g, a group that may be more vulnerable than VLBW individuals.
The increase in mental health problems found in our study may also have an impact on the reduction of HRQoL from 20 to 23 years in the VLBW group. In children and adolescents, HRQoL may decrease with time if mental health problems increase [
56], and in VLBW young adults, internalizing problems are found to be strongly correlated to low HRQoL [
57]. Longitudinal studies of HRQoL in VLBW populations are sparse and show few changes from adolescence to young adulthood. In one study, HRQoL from 14 to 19 years were stable in the VLBW group, however clinically important changes in psychological attributes of HRQoL were reported [
57]. Van Lunenburg et al. [
58] did not find any changes in HRQoL among VLBW young adults from 19 to 28 years of age. This may indicate that the lower HRQoL we found at age 23 may stabilize and improve over the next years. However, the methods and cultural settings in these studies are not directly comparable. Both the VLBW and control group in our study reported a reduction in general health from 20 to 23 years, which might be a general change during this life period. People’s evaluations of their general health are found to be dynamic and changing within a two-year period for half the adult population [
59]. More studies are needed to understand the changes in HRQoL in preterm populations with time.
We have previously reported that VLBW young adults had poorer motor skills than controls at 23 years [
20]. The current study shows that internalizing and total mental health problems as well as lower physical and mental HRQoL were associated with poorer motor skills, especially motor speed, also when we excluded VLBW participants with CP and/or low IQ
est. Studies of adults with developmental coordination disorder showed that they reported more symptoms of anxiety and depression [
60] and lower quality of life than peers [
22]. Both among adults with normal birth weight and <1000 g, self-reported childhood coordination problems were associated with elevated levels of inattention and symptoms of anxiety and depression [
21]. Our study confirms and extends the existing knowledge by using clinically assessed motor skills in young adulthood to establish the associations of mental health and HRQoL with motor skills in VLBW young adults.
There is reason to believe that the motor and mental health problems in preterm populations share a common cause. The preterm brain is susceptible to a cascade of adverse events, often referred to as the ‘Encephalopathy of prematurity’ [
1], likely to affect both motor skills and mental health. The altered brain development continues into young adulthood [
61,
62], and we have previously reported changes in brain white matter that were associated with cognitive, motor and mental health impairments among VLBW adolescents [
63]. Poor executive functioning with difficulties holding information in mind and switching between mental sets is related to behavioural functioning [
2], and might also partly explain the social difficulties of VLBW individuals. There is emerging evidence that stressful prenatal and neonatal factors, such as preterm birth, may imprint a pattern of physiological activity in the developing brain, known as “foetal programming” [
64]. The immune system and the hypothalamus-pituitary-adrenal stress-regulating system are found to be especially vulnerable to long-term alteration in children born preterm [
65]. We therefore speculate that an altered stress-response might contribute to more mental health problems among the VLBW young adults.
Clinical implications
This study adds to the knowledge of mental health and HRQoL in VLBW young adults. In HRQoL studies, a difference or change of 0.5SD is suggested to reflect a clinical important difference [
66], and the finding of more mental health problems and lower HRQoL is therefore likely to impact the daily life of these young adults. The reduction of mental health and HRQoL in the transition to adulthood emphasizes the importance of long-term follow-up and performing longitudinal analyses. Awareness of the association of mental health and HRQoL with motor skills may be important as motor problems are easily identified in early childhood. This makes selection for early intervention possible. There is reason to be observant of and encourage research on problems that might become more visible as the VLBW young adults enter independent living and encounter the demands of adulthood.
Authors’ contributions
IMH prepared data for analyses, performed the statistical analyses and drafted the manuscript; KMTS prepared data for analyses and helped drafting the manuscript; AO participated in the design and coordination of the study and helped drafting the manuscript; SL supervised the statistical analyses; MSI helped interpreting results and drafting the manuscript; JS helped interpreting results and drafting the manuscript; AMB conceived of the study and participated in the design of the study; KAIE participated in the design and coordination of the study and helped performing the statistical analyses and drafting the manuscript. All authors read and approved the final manuscript.