Prematurity is a risk factor of disorders of gut-brain interaction in adults: A case-control study

Table 1 General characteristics of the adults born preterm (Health of Adults Born Preterm Investigation cohort)

Characteristics of adults born prematurely		n (interquartile)	Percentage (%)
Social demographics	Men/women median age (years)	24/55, 27 (24; 29)	30/70
Neonatal factors	Gestational age (WG): 24; 25; 26; 27; 28 and 29	4; 16; 10; 20; 22 and 7	5; 20; 13; 25; 28 and 9
	Median birthweight (grams)	920 (768; 1116)
	Antenatal steroids	34 (MD = 9)	43
	Median duration of mechanical ventilation (days)	26 (4; 44) (MD = 10)
	Oxygen support at 36 WG	24 (MD = 9)	30
	Median total parenteral nutrition (days)	29 (16; 41) (MD = 13)
	Median hospitalization length (days)	78 (66; 106) (MD = 7)
	Sepsis event	13 (MD = 8)	17
	Necrotizing enterocolitis	2 (MD = 8)	3
	C-section	38 (MD = 8)	48
	Chorioamniotitis	8 (MD = 23)	10
	Post natal steroids	19 (MD = 11)	24
	Intraventricular Hemorrage	19 (MD = 8)	24
	Surgery	14 (MD = 18)	18
	Small for gestational age (ultrasound)	39 (MD = 17)	49
Patient-Reported Outcomes Measurement Information System-29 items questionnaire	Median physical function score	20 (19; 20)
	Median anxiety score	8 (5; 11)
	Median depression score	6 (4; 10)
	Median fatigue score	9 (7; 11)
	Median sleep disturbance score	10 (8; 12)
	Median ability to participate in social roles and activities score	18 (14; 20)
	Median pain interference score	4 (4; 5)
	Median pain intensity	1 (0; 3)
Patient Health Questionnaire-9 items-D score (depression)	Absent	40	51
	Mild	23	29
	Moderate to severe	14	18
Generalized Anxiety Disorder-7 items-D (anxiety)	Minimal	50	63
	Mild	18	23
	Moderate to severe	9	12

MD: Missing data; WG: Weeks of gestation.

Table 2 Lifestyle characteristics of the adults born preterm

Lifestyle characteristics		n	Percentage (%)
Participants	Probiotic use	8	10
	attention-deficit/hyperactivity disorder treatment	9 (MD = 2)	11
	Antidepressants use,	12 (MD = 5)	15
	Alcool consumption	62 (MD = 7)	83
	Drug consumption	13 (MD = 2)	17
	Tobacco use	8 (MD = 7)	10
	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

DGBI: Disorders of gut-brain interaction; MD: Missing data.

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	0	0	0	0	Not applicable
E: Gallbladder and sphincter of Oddi disorders	0	0	1	1	1
F: Anorectal disorders	3	4	12	10	0.2
At least one DGBI	45	57	62	50	0.41
At least 1 pain-related DGBI1	15	19	24	19	1

¹Pain-related disorders of gut-brain interaction; are defined as functional chest pain, functional heartburn, reflux hypersensitivity, epigastric pain syndrome, irritable bowel syndrome, abdominal pain subclass of unspecified functional bowel disorder, centrally mediated abdominal pain syndrome, biliary pain, levator ani syndrome, unspecified functional anorectal pain and proctalgia fugax.

DGBI: Disorders of gut-brain interaction; F: Female; M: Male.

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	0	0	0	0	N/A	N/A
E: Gallbladder and sphincter of Oddi disorders	0	0	0	1 (2%)	N/A	1
F: Anorectal disorders	0	3 (6%)	3 (5%)	9 (14%)	0.64	0.21
At least 1 pain-related DGBI1	1 (4%)	14 (26%)	7 (12%)	17 (27%)	0.52	1

¹Pain related disorders of gut-brain interaction are defined as functional chest pain, functional heartburn, reflux hypersensitivity, epigastric pain syndrome, irritable bowel syndrome, abdominal pain subclass of unspecified functional bowel disorder, centrally mediated abdominal pain syndrome, biliary pain, levator ani syndrome, unspecified functional anorectal pain and proctalgia fugax.

DGBI: Disorders of gut-brain interaction; F: Female; M: Male; N/A: Not applicable.

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	Odds ratios (95%CI)	P value
At least one DGBI
Male sex2	0.32 (0.11-0.84)	0.02
Fatigue score1,2	1.2 (1.02-1.34)	0.03
Pain interference score1,2	1.4 (1.07-2.02)	0.04
Pain intensity1,2	1.5 (1.15-1.95)	0.01
Mild depression (PHQ-9)2	3.4 (1.19-10.72)	0.03
Moderate to severe depression (PHQ-9)2	9 (2.1-63)	0.01
Moderate to severe depression (PHQ-9)3	8.98 (2.01-64.90)	0.01
At least one functional gastroduodenal disorder
Physical function score1,2	0.8 (0.64-0.94)	0.01
Fatigue score1,2	1.17 (1.01-1.34)	0.04
Ability to participate in social roles and activities score1,2	0.7 (0.5-0.8)	0.01
Pain interference score1,2	1.4 (1.12-1.73)	0.01
Pain intensity1,2	1.3 (1.04-1.69)	0.02
Moderate to severe anxiety (GAD-7)2	5.9 (1.18-29.18)	0.03
Antidepressant2	7.1 (1.84-28.69)	0.01
Ability to participate in social roles and activities score1,3	0.74 (0.55-0.97)	0.04
At least one functional bowel disorder
Male sex2	0.2 (0.08-0.64)	0.01
Pain interference score1,2	1.3 (1.05-1.79)	0.04
Pain intensity1,2	1.5 (1.17-1.98)	0.01
Moderate to severe depression (PHQ-9)2	10 (2.32-70.21)	0.01
Male gender3	0.3 (0.071-0.85)	0.03
Moderate to severe depression (PHQ-9)3	6.8 (1.25-55.12)	0.04
Irritable bowel syndrome
Chorioamniotis2	18.3 (3.37-123.46)	0.01
Anxiety score1,2	1.2 (1.05-1.46)	0.02
Sleep disorder score1,2	1.2 (1.02-1.43)	0.03
Pain interference score1,2	1.3 (1.09-1.62)	0.01
Pain intensity1,2	1.7 (1.29-2.35)	0.01
Moderate to severe anxiety (GAD7)2	11.3 (2.31-61.42)	0.01
Chorioamniotis3	14.94 (1.23-273.79)	0.04
Pain intensity1,3	1.81 (1.14-3.15)	0.02
Functional constipation
Moderate to severe anxiety (GAD7)2	5 (1.13-23.72)	0.03
Moderate to severe anxiety (GAD7)3	4.9 (1.05-24.66)	0.04
At least one pain related DGBI
Duration of mechanical ventilation (days)2	0.96 (0.92-0.99)	0.02
Hospitalization duration (days)2	0.97 (0.94-0.99)	0.02
Chorioamniotis2	18 (2.70-166.31)	0.01
Anxiety score1,2	1.22 (1.06-1.44)	0.01
Depression score1,2	1.17 (1.03-1.35)	0.02
Fatigue score1,2	1.2 (1.05-1.40)	0.01
Ability to participate in social roles and activities score1,2	0.81 (0.67-0.95)	0.01
Pain interference score1,2	1.5 (1.20-2.01)	0.01
Pain intensity1,2	1.8 (1.36-2.46)	0.01
Moderate to severe depression (PHQ-9)2	14.3 (2.74-110.58)	0.01
Moderate to severe anxiety (GAD-7)2	14.7 (3.08-86.35)	0.01
Antidepressant2	3.9 (0.10-14.99)	0.04
Pain intensity1,3	2.15 (1.18-5.3)	0.04

¹As evaluated through the Patient-Reported Outcomes Measurement Information System-29 items questionnaire.

²Univariate analysis.

³Multivariate analysis.

DGBI: Disorders of gut-brain interaction; GAD-7: Generalized Anxiety Disorder-7 items; PHQ-9: Patient Health Questionnaire-9 items.