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Premature Birth And Adult Risk Of Pain and Fatigue

Premature Birth And Adult Risk Of Pain and Fatigue

The Study

The researchers aimed to investigate the associations between mental health, pain, and tiredness in adults born very preterm (VP; <32 weeks) or with very low birth weight (VLBW; <1500 g) and at term, as well as whether physical activity influenced these associations. Adults born preterm were found to have an increased risk of mental health problems and other neurodevelopmental conditions.


Preterm birth is linked with an increased risk of adverse health outcomes in adulthood, encompassing mental health, neurodevelopmental, and physical conditions. Studies reveal that adults born very preterm (VP; <32 weeks of gestation) or with very low birthweight (VLBW; <1500 g) exhibit a distinct mental health profile. This profile is characterized by a higher prevalence of internalizing issues, such as anxious and depressive symptoms, inattention, and avoidant personality problems. Conversely, they tend to have fewer externalizing problems, including rule-breaking, intrusive, and antisocial personality problems when compared to their term-born peers. However, research on how these mental health problems correlate with other health outcomes in adults born VP is limited.

In the general population, mental health problems, pain, fatigue, and tiredness are common conditions, and there’s evidence suggesting a bidirectional relationship between mental health disorders and pain, as well as fatigue. Preterm birth may elevate the risk of experiencing pain later in life, possibly due to early painful and stressful experiences altering pain modulation systems. Although children and adolescents born VP may encounter more sleep issues than their term-born peers, fatigue or tiredness hasn’t been extensively studied in preterm populations. On the other hand, adults born VP report similar or lower vitality compared to their term-born counterparts, but the connection between mental health and tiredness or vitality within adults born VP/VLBW remains unexplored.

Physical activity has been associated with improved mental health and well-being among adolescents, irrespective of their gestational age. In the general population, being physically active is linked to reduced reports of pain and improved sleep. Thus, the extent of physical activity engagement might impact the association between mental health issues and reported pain or tiredness. Interestingly, adults born with VLBW tend to exercise less frequently than adults born at term. Consequently, the potential reciprocal influence between mental health, pain, tiredness, and physical activity in adults born VP/VLBW is intricate and largely uncharted. Each of these factors holds the potential to be a target for intervention, promoting overall health.

In this study, the researchers aimed to investigate the associations between mental health and pain or tiredness in adults born VP/VLBW, comparing them with adults born at term. Additionally, they sought to determine whether these associations were influenced by levels of physical activity.


This study was conducted within the framework of the EU Horizon 2020 Research on European Children and Adults Born Preterm (RECAP Preterm) Consortium, as documented on the RECAP website. In addition, we conducted a comprehensive search for available cohorts within the Adults Born Preterm International Collaboration and drew from the meta-analysis conducted by Pyhäla and colleagues in 2017.

Six prospective cohort studies, each containing data on mental health, pain, and tiredness in adulthood, were identified for inclusion in the research. 

These studies are the Arvo Ylppö Longitudinal Study (AYLS) in Finland, the Bavarian Longitudinal Study (BLS) in Germany, the EPICure Study in the United Kingdom and Ireland, the Preterm Birth and Early Life Programming of Adult Health and Disease Study (ESTER) in Finland, the Helsinki Study of Very Low Birth Weight Adults (HeSVA) in Finland, and the Norwegian University of Science and Technology Low Birth Weight in a Lifetime Perspective study (NTNU Low Birth Weight Life) in Norway. 

Data from all six birth cohort studies were securely encrypted and transferred to NTNU. Each of these studies had obtained country-specific ethical approval, and participants had provided written informed consent, all in accordance with the Declaration of Helsinki.


Irrespective of the original cohort study designs, the preterm group in the cohorts was defined as those born very preterm (VP, <32 weeks of gestation) and/or with very low birth weight (VLBW, <1500 g), while the term comparison group consisted of term-born individuals (≥37 weeks of gestation). In the case of the EPICure study, the preterm group included individuals born before week 26. 

All participants with available data on mental health, pain, and tiredness were included in the study, totaling 1,739 participants, of which 617 were born VP/VLBW and 1,122 were born at term. The participation rates varied from 33.1% to 74.6% across the different cohorts. It’s noteworthy that VP/VLBW non-participants tended to have lower birth weight and gestational age, while a higher proportion of both VP/VLBW and term-born non-participants exhibited lower parental education levels and neurosensory impairments.

The background characteristics encompassed personal data related to demographics and perinatal factors. This included details like birth weight, gestational age, gender, parental education, age at the mental health evaluation, and any neurosensory impairments assessed during childhood, which comprised conditions like visual, hearing, cognitive impairments, and non-ambulatory cerebral palsy. Parental education was standardized using the International Standard Classification of Education, categorized into low (levels 0-2), medium (3-5), and high (6-8) levels.


Results revealed that parental education was lower in the VP/VLBW group compared to the term-born group. Descriptive statistics for ASR (Adult Self-Report), pain, tiredness, and physical activity were reported for the entire sample and across various cohorts. Linear regression analysis demonstrated that an increase in internalizing, externalizing, and total problems scores corresponded to more pain and tiredness in both groups. 

Notably, the VP/VLBW group generally exhibited higher beta values for internalizing problems and tiredness compared to the term-born group. However, there were no significant differences between the groups in the associations between mental health and pain or tiredness, as indicated by the absence of significant interaction effects. Importantly, adjusting for parental education didn’t alter the results. When physical activity was considered as a covariate, the findings remained consistent, suggesting that physical activity didn’t affect the relationships between mental health issues and pain or tiredness in either the VP/VLBW or term-born comparison group.


In summary, the research findings point to a clear connection between mental health issues and the experience of pain and fatigue in adults, regardless of whether they were born very preterm (VP) or at full term. It’s worth noting that engaging in physical activity does not appear to diminish these associations. To delve deeper into this issue, future investigations should aim to uncover additional potential mechanisms that contribute to the heightened vulnerability of mental health problems among individuals born prematurely.

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