Courbette O, Girard-Bock C, Cloutier A, Luu TM, Nuyt AM, Faure C. Prematurity is a risk factor of disorders of gut-brain interaction in adults: A case-control study. World J Clin Pediatr 2025; 14(3): 103590 [DOI: 10.5409/wjcp.v14.i3.103590]
Corresponding Author of This Article
Olivier Courbette, MD, Department of Pediatric Gastroenterology, Sainte-Justine University Hospital Center, 3175 Chemin de la Côte Ste Catherine, Montreal H3T1C5, Quebec, Canada. olivier.courbette@gmail.com
Research Domain of This Article
Pediatrics
Article-Type of This Article
Case Control Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Olivier Courbette, Christophe Faure, Department of Pediatric Gastroenterology, Sainte-Justine University Hospital Center, Montreal H3T1C5, Quebec, Canada
Camille Girard-Bock, Anik Cloutier, Thuy Mai Luu, Anne Monique Nuyt, Department of Pediatrics, Sainte-Justine University Hospital Research Center, Montreal H3T1C5, Quebec, Canada
Author contributions: Courbette O performed the statistical analysis; Courbette O and Faure C contributed to the concept and design of the study and draft the article; Courbette O, Girard-Bock C, Cloutier A, Luu TM, Nuyt AM and Faure C contributed to the acquisition and analysis of the data; all authors have read and approve the final manuscript.
Supported by Sainte-Justine University Hospital Research Center excellence grant in 2020-2021.
Institutional review board statement: The study was reviewed and approved by the Sainte-Justine University Hospital Institutional Review Board (Approval No. 2019-1949).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at olivier.courbette@hpu.lenval.com on request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Olivier Courbette, MD, Department of Pediatric Gastroenterology, Sainte-Justine University Hospital Center, 3175 Chemin de la Côte Ste Catherine, Montreal H3T1C5, Quebec, Canada. olivier.courbette@gmail.com
Received: November 25, 2024 Revised: March 22, 2025 Accepted: April 15, 2025 Published online: September 9, 2025 Processing time: 204 Days and 10.6 Hours
Abstract
BACKGROUND
Disorders of gut-brain interaction (DGBI) are defined as a variable combination of chronic or recurrent gastrointestinal symptoms. Early-life stressors have been implicated as possible contributing factors.
AIM
To determine if prematurity and neonatal factors influence the development of DGBI in adults.
METHODS
A case-control study was carried out at a tertiary referral center from July 2019 to July 2021. Cases (adults born with extremely premature < 29 weeks of gestation) were recruited from the Health of Adults Born Preterm Investigation cohort. Control subjects were recruited from the general population. All participants completed the Rome IV diagnostic questionnaire online. Cases completed anxiety and depression questionnaires (Patient-Reported Outcomes Measurement Information System-29 items, Generalized Anxiety Disorder-7 items, Patient Health Questionnaire-9 items). Neonatal data and sociodemographic status were collected.
RESULTS
A total of 79 cases and 124 controls were enrolled in the study. The group of adults born preterm exhibited a significantly higher prevalence of functional bowel disorders (P = 0.01) and a trend suggesting a higher prevalence of functional gastroduodenal disorders (P = 0.06). Among women born prematurely, the prevalence of functional gastroduodenal disorders, functional bowel disorders, and functional constipation was significantly higher compared to the female control group (P = 0.02 for all). The identified risk factors are categorized as directly linked to prematurity (e.g., chorioamnionitis), indirectly related to prematurity (e.g., anxiety, depression, and social skills as consequences of prematurity), or independent of prematurity (e.g., female sex).
CONCLUSION
This is the first case-control study reporting the prevalence of DGBI in a cohort of well-characterized adults born prematurely. We confirm that prematurity is a risk factor for developing a DGBI.
Core Tip: In this study, using the Rome IV questionnaire, we assessed the prevalence of different disorders of gut-brain interaction (DGBI) in two populations: (1) Full-term; and (2) Preterm adults. Subsequently, we compared the results between these two populations and analyzed the risk factors for DGBI in the population of adults born prematurely using regression analysis. The group of adults born prematurely has a higher frequency of functional bowel problems. Functional constipation and functional gastroduodenal problems are substantially more common in prematurely born women than in controls. Ultimately, we confirm that extreme prematurity is a risk factor for developing a DGBI.
Citation: Courbette O, Girard-Bock C, Cloutier A, Luu TM, Nuyt AM, Faure C. Prematurity is a risk factor of disorders of gut-brain interaction in adults: A case-control study. World J Clin Pediatr 2025; 14(3): 103590
Disorders of gut-brain interaction (DGBI) (previously termed functional gastrointestinal disorders) are characterized by a set of chronic or recurring digestive symptoms, which lack any identifiable structural or biochemical cause[1]. These disorders are known to negatively impact life quality and are linked to higher healthcare utilization and associated costs[2,3]. It is estimated that up to 40% of the adult population may experience these conditions[4,5].
A variety of factors, including biological, genetic, psychological, and social influences, have been implicated in the development of these disorders[1]. Early-life stress, whether physical or emotional[6], has been recognized as a potential contributing factor[7–11]. Animal studies suggest that the neonatal period is particularly vulnerable to various stressors, such as maternal separation and colon irritation, both of which may lead to increased gut sensitivity and the later onset of gut-brain disorders[12,13]. Human studies have corroborated these findings, indicating that frequent medical procedures like gastric suctioning and surgical interventions during infancy might play a role in the development of these conditions[7,9].
Premature infants are often subjected to multiple medical procedures and the stress of maternal separation in neonatal intensive care units (NICUs)[14,15]. Such early experiences can have both immediate and long-term effects on various aspects of development, including behavior, physiological functioning, and overall well-being[15–17]. The challenges associated with prematurity may therefore act as an early trigger for these disorders later in life. However, research examining the relationship between premature birth and the onset of these disorders during infancy[18], childhood, adolescence[19], and adulthood[8,20] has produced mixed results.
This study sought to examine whether being born prematurely and the associated neonatal factors have an impact on the development of gut-brain interaction disorders in adulthood. The primary goal was to assess the prevalence of these conditions in adults born extremely preterm [before 29 weeks of gestation (WG)], comparing them with full-term adults. Additionally, the study aimed to identify the sociodemographic, psychosocial, and neonatal factors linked to the development of these disorders in individuals born preterm.
MATERIALS AND METHODS
Design
A case-control study was carried out in a tertiary referral center from July 2019 to July 2021. Cases and controls were recruited in the same geographic area (Quebec, Canada) and during the same study period.
Selection of cases
The cases were recruited from the Health of Adults Born Preterm Investigation (HAPI) cohort, described in detail in previous studies[21,22]. The subjects are adults aged 18 years to 31 years born with severe or extremely severe prematurity (inferior 29 weeks of estimated gestational age) from 1987 to 2000 in the province of Quebec (Canada). All HAPI cohort participants were included. We excluded patients with cognitive or intellectual disabilities who could not complete the questionnaire and patients with chronic or acute (last 4 weeks) digestive condition.
Selection of controls
Control subjects were recruited from an online panel of participants (LEGER Opinion, LEO) in the general adult population of Quebec (Canada). LEGER Opinion selected a sample with an age and sex distribution that corresponds to the general adult population of Quebec. Two controls were recruited for each case. We excluded patients with cognitive or intellectual disabilities who could not complete the questionnaire. In a second time, we excluded adults born premature (< 37 weeks of gestational age) and patients with a chronic or acute (last 4 weeks) digestive condition.
Questionnaires
All participants were invited to complete the Rome IV diagnostic questionnaire[23] which assesses gastrointestinal symptoms and allows the diagnosis of DGBI according to the Rome IV criteria. A link to an online survey was sent to all the participants. Subjects first completed consent and then proceeded to complete the study survey right away.
Several methods were employed to ensure the good quality of the data collected: (1) To avoid self-selection bias, the survey was only described as a health survey to prospective subjects, without any mention of gastrointestinal symptoms or disorders; (2) The survey was a secure, closed survey only accessible to the registered survey panel members specifically invited to participate; (3) Three multiple-choice attention test questions were built into the survey. Subjects who failed to respond appropriately to either question were terminated from the survey without completion; and (4) Three Rome IV diagnostic questions were repeated later in the survey to assess symptom reporting consistency. Data from subjects who failed to report comparable symptom frequency on two or more of these three repeated questions were eliminated from the analysis dataset.
The adults born preterm were also asked to complete the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 items V2.0 questionnaire (quality of life)[24,25]. This scale is validated in French in the adult population. PROMIS-29 is a generic patient-reported outcome measure, which includes four items from each of the seven PROMIS domains (physical function, depression, anxiety, fatigue, sleep disturbance, ability to participate in social roles and activities, pain interference) and a single item on pain intensity. A total raw score is computed for each domain from 4 to 20. The higher the score, the better is the function/ability or the worst is the symptom. Assessment of anxiety and depression was also carried out using the Generalized Anxiety Disorder-7 items (GAD-7)[26,27] and Patient Health Questionnaire-9 items (PHQ-9)[28,29] questionnaires available and validated in French.
Because pain experienced in the neonatal period is known to induce changes in the pain pathways that persist beyond infancy, we assessed the presence of pain related DGBI. A pain-related DGBI was defined as at least one pain-associated diagnostic according to the Rome IV criteria which includes: (1) Functional chest pain; (2) Functional heartburn; (3) Reflux hypersensitivity; (4) Epigastric pain syndrome; (5) Irritable bowel syndrome (IBS); (6) Abdominal pain subclass of unspecified functional bowel disorder; (7) Centrally mediated abdominal pain syndrome; (8) Biliary pain; (9) Levator ani syndrome; (10) Unspecified functional anorectal pain; and (11) Proctalgia fugax[23].
Other data collected in the adults born preterm group
Data from the neonatal medical charts were collected, including gestational age, antenatal corticosteroid therapy, C-section delivery, chorioamnionitis, birth weight, duration of mechanical ventilation, duration of total parenteral nutrition, oxygen therapy at 36 weeks of gestational age, duration of neonatal hospitalization, sepsis event, necrotizing enterocolitis, chorioamnionitis, postnatal corticosteroid therapy, intraventricular hemorrhage, and surgery in the neonatal period. The number of painful procedures of pain indexes throughout hospital stay could not be collected.
Age, sex, lifestyle (alcohol, tobacco, drugs), probiotic medication, Attention-Deficit Hyperactivity Disorder, antidepressants medication, and socio-professional category of the participant and their parents were also collected.
Ethics
This study was approved by the Ethic Review Board from Sainte-Justine University Hospital (No. 2019-1949). All participants provided written informed consent.
Statistical analysis
Continuous variables were expressed as mean ± SD or median (interquartile), as appropriate, while categorical variables were expressed as number/percentage (%). Comparisons between continuous variables were performed with the Mann-Whitney test, one-way analysis of variance, or Kruskal-Wallis test, whereas categorical variables were compared with the χ2 test or Fisher's exact test, as appropriate. The odds ratios (OR), estimations of the relative risk when frequency of the event is low, were calculated when appropriate. Due to the sex difference in the prevalence of DGBI, the groups were compared according to sex[1,30].
The association between DGBI and neonatal or lifestyle factors was assessed by univariate regression analysis. OR values were estimated. Subsequently, for each outcome, a multivariate regression model was created. The variables assessed as significant in the univariate regression analysis were entered as independent variables in multivariate logistic regression analysis. The OR and 95%CI values were estimated. The best model has been selected using the Akaike criteria. A P value less than 0.05 was considered statistically significant (α = 0.05). Missing data were removed.
Sample size calculation was conducted based on the estimation of the enrollment of 70 cases (HAPI cohort) and on the assumption that the prevalence of DGBI in premature subjects would be at least 20% higher compared to controls. Based on these estimates, with a nondirectional alpha value of 0.05 and a power of 0.80, 141 controls would be required to detect this level of difference, using G Power 3.1. The data were analyzed using R statistical software package (http://www.R-project.org/).
RESULTS
Study population
The study enrolled 79 adults born prematurely and 124 adults born at term. The flowcharts illustrating participant selection are shown in Figure 1. Among the preterm group, 30% were male (n = 24), with a median age of 27 years (range: 24–29 years). In the full-term group, 48% were male (n = 60), with a median age of 33 years (range: 27–50 years). A statistically significant difference in the sex distribution was observed between the groups (P = 0.02). Detailed demographic characteristics of the preterm-born cohort are presented in Tables 1 and 2.
Levels of education: High school or less; College and University
13; 30 and 34 (MD = 2)
17; 38 and 43
Employment or student status
70
89
Parents
Mother’s DGBI diagnostic
3 (MD = 21)
4
Father’s DGBI diagnostic
4 (MD = 19)
5
Income levels (Canadian dollars), the highest: ≤ 19999$; 20000–39999$; 40000–59999$ and ≥ 60000$
2; 4; 8 and 25 (MD = 40)
3; 5; 10 and 32
Levels of education, the highest: Secondary or less; Upper secondary; Post-secondary non tertiary; and University
2; 11; 17 and 40 (MD = 9)
3; 14; 22 and 51
Prevalence of DGBIs and group comparison
Using the Rome IV diagnostic criteria, 57% of preterm-born participants and 50% of full-term participants reported at least one DGBI (P = 0.41). The preterm cohort exhibited a significantly higher prevalence of functional bowel disorders (P = 0.01), with a tendency for increased prevalence of functional gastroduodenal disorders (P = 0.06). No notable differences were found between the groups for esophageal, central nervous system-related gastrointestinal pain, gallbladder, sphincter of Oddi, or anorectal disorders (Table 3).
Table 3 Prevalence of disorders of gut-brain interaction.
Population results
Cases (n)
Percentage (%)
Controls (n)
Percentage (%)
P value
Number
79
124
Sex
F: 55/M: 24
70/30
F: 64/M: 60
52/48
0.02
Sex ratio (M/F)
0.4
0.9
Age (year)
27 (24; 29)
33 (27; 50)
< 0.001
Age range
18-32
20-76
% (18-32 years old)
79
100
59
48
A: Esophageal disorders
5
6
12
10
0.56
B: Gastroduodenal disorders
23
29
21
17
0.06
B1a: Postprandial distress syndrome
10
13
8
7
0.21
B1b: Epigastric pain syndrome
6
8
6
5
0.61
C: Bowel disorders
40
51
40
32
0.01
C1: Irritable bowel syndrome
12
15
11
9
0.25
C2: Functional constipation
20
25
10
8
0.002
C3: Functional diarrhea
7
9
7
6
0.55
D: Centrally mediated disorders of gastrointestinal pain
Given the variation in DGBI prevalence between genders, a comparison by sex was made (Table 4). Among females born preterm, there was a significantly higher prevalence of functional gastroduodenal disorders (P = 0.02), functional bowel disorders (P = 0.02), and functional constipation (P = 0.02) compared to the full-term control group. No significant differences were observed for males between the two groups.
Table 4 Prevalence of disorders of gut-brain interaction according to sex, n (%).
Cases
Controls
P value
Sex
M
F
M
F
M
F
Number
24
55
60
64
Age
27 (24; 30)
27 (24; 29)
41 (29; 55)
29 (25; 44)
< 0.001
< 0.001
Range
18-32
21-32
22-75
20-75
A: Esophageal disorders
0
5 (9%)
4 (7%)
8 (13%)
0.47
0.76
B: Gastroduodenal disorders
3 (13%)
20 (36%)
11 (18%)
10 (16%)
0.75
0.02
B1a: Postprandial distress syndrome
3 (13%)
7 (13%)
5 (8%)
3 (5%)
0.86
0.21
B1b: Epigastric pain Syndrome
0
6 (11%)
2 (3%)
4 (6%)
0.91
0.56
C: Bowel disorders
5 (21%)
35 (64%)
14 (23%)
26 (41%)
1
0.02
C1: Irritable bowel syndrome
1
11
1
10
1
0.7
C2: Functional constipation
4
16
3
7
0.19
0.02
C3: Functional diarrhea
0
7
2
5
0.9
0.56
D: Centrally mediated disorders of gastrointestinal pain
Risk factors for DGBI: In the univariate model, factors significantly associated with the presence of at least one DGBI included female sex, higher pain intensity, increased pain interference, mild to severe depression, and elevated fatigue scores. No correlation was found between attention-deficit/hyperactivity disorder and DGBI occurrence. In the multivariate model, moderate-to-severe depression remained a significant predictor for having a DGBI (OR = 8.98; 95%CI: 2.01–64.9; P = 0.01) (Table 5).
Table 5 Risk factors with odds ratios and P value for several diagnoses of disorders of gut-brain interaction in adults born preterm.
Risk factors for functional gastroduodenal disorders: In the univariate analysis, a higher fatigue score, pain intensity, pain interference, moderate-to-severe depression, and antidepressant use were significantly associated with functional gastroduodenal disorders. In contrast, better physical function and higher social role participation scores were linked to a reduced risk. The multivariate analysis revealed that an increased ability to engage in social roles and activities had a protective effect against developing functional gastroduodenal disorders (OR = 0.74; 95%CI: 0.55–0.97; P = 0.04).
Risk Factors for functional bowel disorders, IBS, functional constipation, and abdominal pain-related DGBI: Functional bowel disorders in the univariate model were linked to higher pain intensity, female sex, pain interference, and moderate-to-severe depression. In the multivariate model, male sex emerged as a protective factor (OR = 0.3; 95%CI: 0.07–0.85; P = 0.03), while moderate-to-severe depression significantly increased the risk (OR = 6.8; 95%CI: 1.25–55.1; P = 0.04).
IBS was associated with chorioamnionitis, sleep disorders, elevated anxiety, pain interference, and pain intensity in the univariate model. In the multivariate analysis, both chorioamnionitis (OR = 14.9; 95%CI: 1.23–273.8; P = 0.04) and increased pain intensity (OR = 1.81; 95%CI: 1.14–3.15; P = 0.02) remained significant.
Functional constipation was linked to increased anxiety in the univariate model, which remained significant in the multivariate model (OR = 4.9; 95%CI: 1.05–24.7; P = 0.04).
Abdominal pain-related DGBI were associated with longer hospital stays, chorioamnionitis, anxiety, depression, pain intensity, and reduced social role participation in the univariate model. In the multivariate analysis, pain intensity remained a significant predictor (OR = 2.2; 95%CI: 1.18–5.3; P = 0.04).
No significant associations were found in the multivariate analysis for postprandial distress syndrome or unspecified functional bowel disorders (Supplementary Table 1).
DISCUSSION
In this study, we explored how common DGBI are in adults born extremely preterm, compared to those born at full term. Using the Rome IV criteria, we found that functional bowel disorders were more frequent among the preterm-born group. Among women, those born preterm were particularly affected, showing a significantly higher rate of functional gastroduodenal disorders and constipation than their full-term counterparts. We also identified several factors linked to an increased risk of developing DGBI in this population.
The prevalence of having at least one DGBI in the control group (50%) was similar to the prevalence (47.7%) reported in the Quebec population in the recent pan-Canadian study[5]. In this study, the most common diagnoses were functional constipation and functional dyspepsia post-prandial distress syndrome was the most common subtype of functional dyspepsia like in our control group.
The relationship between prematurity and the development of DGBI has been the subject of conflicting findings. Studies have shown that infantile colic and regurgitation during the first year of life are more common in preterm infants compared to those born full-term[18]. In pediatric and adolescent populations, a recent study highlighted a strong correlation between being born at 28 weeks to 32 WG and an increased likelihood of developing functional gastrointestinal disorders[19].
In adults, Koloski et al[20] found no link between functional dyspepsia or IBS and prematurity; however, their study relied on self-reported prematurity without specifying gestational age. Conversely, Carbajal et al[31], in a large-scale study, reported that preterm birth was associated with a lower prevalence of IBS. However, in their study, prematurity was defined broadly as any birth before 37 WG, without specifically focusing on those born extremely preterm[8]. In contrast, our research examines a carefully selected and homogeneous group of adults born before 29 WG, providing clearer evidence of the role of prematurity in the development of DGBI later in life.
Preterm neonates frequently undergo invasive medical procedures during their time in the NICU[31]. Those born extremely preterm are particularly susceptible to pain exposure during a critical phase of rapid brain development[32]. Nociceptive systems begin functioning between 24 weeks and 28 WG as thalamocortical connections form[33]; however, endogenous pain modulation, regulated by the brainstem, does not fully develop until closer to term-equivalent age[34]. Painful stimuli during the earliest stages of gestation may influence neurological maturation and nociceptive circuits, potentially fostering visceral hypersensitivity and increasing vulnerability to DGBI in later life[35].
Additionally, early adverse experiences have been repeatedly associated with disruptions in both the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system function[36,37]. These systems play a crucial role in regulating psychological and behavioral responses, particularly in adapting to environmental challenges and threats[37,38]. Moreover, impairments in the regulation of these systems have been linked to detrimental psychological and physiological outcomes in response to stressful experiences[38,39].
In our study, the prevalence of depression (47%) and anxiety (37%) among adults born preterm was higher than that of the general Canadian population[40], aligning with previous findings[41]. Both anxiety and depression are known risk factors for DGBI in adults[42]. This suggests that prematurity, by increasing the likelihood of developing anxiety and depression in adulthood, may contribute indirectly to the onset of DGBI.
Our study reveals that chorioamnionitis is linked to a higher risk of developing DGBI. This condition may contribute to DGBI by disrupting the balance of gut microbiota[43] or impairing intestinal barrier function[44]. Nevertheless, because all preterm infants in our case population received initial antibiotic treatment at birth, we were unable to determine a direct link between the development of DGBI and neonatal antibiotic exposure, as reported in previous studies[18].
The association between prematurity and functional constipation has been previously observed in childhood, particularly in cases involving necrotizing enterocolitis[45,46]. In our adult cohort, we found that preterm-born women had a higher prevalence of functional constipation, which was strongly associated with moderate to severe anxiety. However, no direct correlation with necrotizing enterocolitis was identified, possibly due to its low incidence (3%), leading to a possible type II error.
Our results support the notion that being male reduces the likelihood of developing DGBI[6,30]. Moreover, we highlight additional factors that appear to confer protection, including greater participation in social roles and activities and higher physical function. Poor physical functioning has been previously linked to increased severity of functional bowel disorders[6].
Our study has several notable strengths. First, it is based on data from the HAPI cohort, a well-defined and homogeneous group of individuals born extremely preterm who have been prospectively followed into adulthood. Their frequent participation in clinical studies allowed us to achieve a high response rate with accurate data collection. The control group was recruited from the province of Quebec (Canada), ensuring population homogeneity in terms of social and cultural background. Furthermore, our control group’s data align with findings from a recent pan-Canadian study on the epidemiology of DGBI in the Quebec population[5]. Second, the use of an anonymous online survey provided reliable prevalence estimates. Since all questions were mandatory, we obtained comprehensive and accurate responses. Additional quality control measures, such as repeated questions to assess response consistency and attention-check questions, further strengthened data reliability. Lastly, automatic data entry into the study database minimized the risk of manual input errors, ensuring data accuracy.
We recognize that there were significant differences in age and sex distribution between the case and control groups. Due to potential loss of statistical power, we did not stratify the comparison by decade. However, the analysis of the female subgroups (Table 4) highlights significant differences, with preterm-born women showing a higher prevalence of functional gastroduodenal disorders (P = 0.02), functional bowel disorders (P = 0.02), and functional constipation (P = 0.02) compared to controls.
One potential limitation of this study is the sociocultural nature of the HAPI cohort, as most participants and their parents had a high level of education, preventing an analysis of the impact of socioeconomic factors. Additionally, since our study focused on a homogeneous population of adults born before 29 WG, the findings cannot be generalized to all individuals born preterm. A further limitation lies in the exclusive use of the Rome IV questionnaire for assessing participants, in the absence of clinical confirmation of functional gastrointestinal disorders. Additionally, medical records for the control group were not available. Nevertheless, we consider that our rigorous exclusion criteria, together with the implementation of a checklist for potential organic causes of gastrointestinal symptoms, minimize the likelihood of diagnostic errors. Lastly, we were unable to collect data on potential adverse childhood experiences that may have occurred throughout early life, which could have influenced the development of DGBI.
The mechanisms by which prematurity influences the development of DGBI and pain perception later in life remain unclear. In humans, an abnormal HPA axis response has been observed in adults with IBS who have a history of childhood trauma[47]. Possible contributing mechanisms include epigenetic alterations[48] that interfere with corticotropin-releasing factor production[49], resulting in compromised intestinal barrier function[50] and changes in nerve growth factor expression[51]. Furthermore, disruptions in the gut microbiota during the neonatal phase may modulate the long-term reactivity of the HPA axis to stress[52,53], thereby promoting the onset of DGBI.
In clinical practice, several strategies could be implemented: (1) Optimization of the management of painful procedures; and (2) Better measurement of cumulative pain in neonatology. Furthermore, post-painful exposure management measures could be implemented in early childhood such as cognitive and behavioral therapies that have been proven helpful in the management of epigenetic dysregulation. Finally, early systematic screening of DGBI in childhood and adolescence could be implemented in premature born children. To prevent escalation of the symptoms and their continuation into adulthood, management could be proposed focused on combined approaches, including mind-targeted interventions (hypnotherapy and cognitive behavioural therapy)[54], and diet (probiotics). This strategy could have positive impacts on the symptoms and overall quality of life[55].
CONCLUSION
To our knowledge, this is the first investigation to assess the prevalence of DGBI in a thoroughly characterized population of adults born preterm. The results provide further evidence that being born extremely preterm (before 29 WG) significantly increases the likelihood of developing a DGBI later in life. The identified risk factors can be categorized as those directly related to prematurity (chorioamnionitis), those potentially arising as a consequence of prematurity (anxiety, depression, and social functioning), and those unrelated to prematurity (female sex).
Footnotes
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Pediatrics
Country of origin: Canada
Peer-review report’s classification
Scientific Quality: Grade A, Grade C
Novelty: Grade A, Grade B
Creativity or Innovation: Grade A, Grade C
Scientific Significance: Grade A, Grade C
P-Reviewer: Machado NC S-Editor: Luo ML L-Editor: A P-Editor: Yu HG
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