GRADE evidence profiles geïncludeerde studies

Voor meer details verwijzen we naar de in 2014 gepubliceerde internationale richtlijn: “Evaluation and treatment of functional constipation in infants and children: evidence-based recommendations from ESPGHAN and NASPGHAN.” ⁴⁵

Prebiotics

Omneo vs Standard formula

Question: Should Nutrilon Omneo vs Standard formula: Nutrilon 1 be used for Constipation?^1,2
Settings: 38 children, 3–20 wk of age,receiving at least 2 bottles of milkbased formula per day, recruited from tertiary pediatric gastroenterology department in the Netherlands
Bibliography: Bongers ME, de Lorijn F, Reitsma JB, Groeneweg M, Taminiau JA, Benninga MA. The clinical effect of a new infant formula in term infants with constipation: a double-blind, randomized cross-over trial. Nutr J. 2007 11;6:8.

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Nutrilon Omneo

Standard formula: Nutrilon 1

Relative
(95% CI)

Absolute

Defecation frequency (change) (follow-up 3 weeks³; measured with: Bowel diary; range of scores: 0-10; Better indicated by lower values)

randomised trials

serious⁴

no serious inconsistency

serious⁵

serious⁶

none

MD 0.7 higher (0.8 lower to 2.3 higher)

⊕⊝⊝⊝
VERY LOW

IMPORTANT⁷

Painful defecation (follow-up 3 weeks³; assessed with: Bowel diary)

randomised trials

serious⁴

no serious inconsistency

serious⁵

serious⁶

none

7/20
(35%)

5/15
(33.3%)

RR 1 (0.4 to 2.7)

0 fewer per 1000 (from 200 fewer to 567 more)

⊕⊝⊝⊝
VERY LOW

CRITICAL⁷

¹ Containing a high concentration of sn-2 palmitic acid, a mixture of prebiotic oligosaccharides and partially hydrolyzed whey protein
² Constipation defined by at least one of the following symptoms: 1) defecation frequency < 3/week; 2) painful defecation; 3) abdominal or rectal palpable mass
³ Studies concerning a chronic condition should consider long-term outcomes
⁴ Adequate randomisation and blinding, however, the study was designed originally as a crossover trial but, because of the high rate of loss to follow-up monitoring (37% after 6 weeks), the results of the first treatment period only were analyzed. So, high loss to follow-up and failure to adhere to the intention to treat principle
⁵ The question being addressed by the guideline panel is different from the available evidence regarding the population: young infants who have to suffer only from 1 symptom: 1) defecation frequency < 3/week; 2) painful defecation; 3) abdominal or rectal palpable mass
⁶ Small sample size
⁷ Mean score of the 6 working group members

Probiotics

Lactobacillus GG and lactulose vs Placebo and lactulose

Question: Should Lactobacillus GG and lactulose vs Placebo and lactulose be used for functional constipation?^1,2,3
Settings: 84 children, 2–16 y of age, recruited from pediatric gastroenterology department in Poland
Bibliography: Banaszkiewicz A, Szajewska H. Ineffectiveness of Lactobacillus GG as an adjunct to lactulose for the treatment of constipation in children: a double-blind, placebo-controlled randomized trial. J Pediatr 2005; 146(3):364-369.

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Lactobacillus GG and lactulose

Placebo and lactulose

Relative
(95% CI)

Absolute

Treatment success, defined as at least 3 bowel movements per week with no fecal soiling⁴ (follow-up 12 weeks; assessed with: Bowel diary)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious⁵

none

31/43
(72.1%)

28/41
(68.3%)

RR 1.06 (0.8 to 1.4)

41 more per 1000 (from 137 fewer to 273 more)

⊕⊕⊕⊝
MODERATE

IMPORTANT⁶

Defecation frequency (change) (follow-up 12 weeks; measured with: Bowel diary; range of scores: 0-10; Better indicated by lower values)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious⁵

none

MD 0.70 lower (1.68 lower to 0.28 higher)

⊕⊕⊕⊝
MODERATE

IMPORTANT⁶

Fecal incontinence frequency (change) (follow-up 12 weeks; measured with: Bowel diary; range of scores: 0-10; Better indicated by lower values)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious⁶

none

MD 0.30 higher (0.99 lower to 1.59 higher)

⊕⊕⊕⊝

MODERATE

CRITICAL⁶

Straining on defecation (change) (follow-up 12 weeks; measured with: Bowel diary; Better indicated by lower values)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious⁵

none

MD 0.70 lower (1.33 to 0.07 lower)

⊕⊕⊕⊝

MODERATE

CRITICAL⁶

¹ Lactobacillus GG 10⁹ colonyforming units twice per day and 70% lactulose, 1 mL/kg per day
² 70% lactulose, 1 mL/kg per day
³ Defined as <3 spontaneous bowel movements per week for at least 12 weeks
⁴ At 12 weeks
⁵ Small sample size
⁶ Mean score of the 6 working group members

Bifidobacterium lactis DN-173 010 vs Placebo

Question: Should Bifidobacterium lactis DN-173 010 vs Placebo be used for Functional constipation?¹
Settings: 159 children, aged 3 to 16, were enrolled in 3 academic hospitals (Netherlands and Poland) and 12 Dutch nonacademic hospitals.
Bibliography: Tabbers MM, Chmielewska A, Roseboom MG, Crastes N, Perrin C, Reitsma JB, Norbruis O, Szajewska H, Benninga MA. Fermented milk containing Bifidobacterium lactis DN-173 010 in childhood constipation: a randomized, double-blind, controlled trial. Pediatrics. 2011;127(6):e1392-9.

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Bifidobacterium lactis DN-173 010

Placebo

Relative
(95% CI)

Absolute

Change in defecation frequency (follow-up 3 weeks²; measured with: Bowel diary; range of scores: 0-10; Better indicated by lower values)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious³

none

risk difference 0.3 higher (1.45 lower to 0.51 higher)

⊕⊕⊕⊝
MODERATE

IMPORTANT⁴

Rate of success: 3 or more bowel movements per week and <1 fecal incontinence episode in 2 weeks over the last 2 weeks of product consumption (follow-up 3 weeks²; assessed with: Bowel diary)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious³

none

27/71
(38%)

17/72
(23.6%)

RR 1.61 (0.97 to 2.86)

144 more per 1000 (from 7 fewer to 439 more)

⊕⊕⊕⊝
MODERATE

IMPORTANT⁴

Rate of responders: subjects who report a stool frequency 3 or more during the last week of product consumption. (follow-up 3 weeks²; assessed with: Bowel diary)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious³

none

51/71
(71.8%)

46/72
(63.9%)

RR 1.12 (0.9 to 1.41)

77 more per 1000 (from 64 fewer to 262 more)

⊕⊕⊕⊝
MODERATE

IMPORTANT⁴

Fecal incontinence episodes (y/n) (follow-up 3 weeks; assessed with: Bowel diary)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious³

none

26/71
(36.6%)

35/72
(48.6%)

OR 1.48 (0.83 to 2.64)⁷

97 more per 1000 (from 46 fewer to 228 more)

⊕⊕⊕⊝
MODERATE

CRITICAL⁴

Pain during defecation (y/n) (follow-up 3 weeks²; assessed with: Bowel diary)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious³

none

35/71
(49.3%)⁶

30/72
(41.7%)⁶

OR 0.67 (0.36 to 1.15)⁷

93 fewer per 1000 (from 212 fewer to 34 more)

⊕⊕⊕⊝
MODERATE

CRITICAL⁴

Abdominal pain (y/n) (follow-up 3 weeks; assessed with: Bowel diary)

randomised trials

no serious risk of bias

no serious inconsistency

no serious indirectness

serious³

none

41/71
(57.7%)

39/72
(54.2%)

OR 0.97 (0.56 to 1.69)⁵

8 fewer per 1000 (from 143 fewer to 125 more)

⊕⊕⊕⊝
MODERATE

IMPORTANT⁴

¹ ROME III criteria, but all should have a defecation frequency of < 3 times per week and 1 or more of the following criteria: fecal incontinence > 1 episode per week, a large amount of stools that clog the toilet, painful defecation, withholding behavior, or abdominal or rectal fecal impaction on physical examination. Intervention: 2 pots of 125 g per day of the fermented milk containing Blactis DN-173 010 at least 4,25 10⁹ colony-forming units, yogurt starter cultures (Lactobacillus delbrueckii ssp. Bulgaricus and Streptococcus thermophilus) and Lactococcus cremoris. Control: 2 pots of 125 g per day of a milk-based, nonfermented dairy product without probiotics

² Studies concerning a chronic condition should consider long-term outcomes
³ Small sample size
⁴ Mean score of the 6 working group members
⁵ OR reported by authors: In case of a binary outcome, a generalized estimating equation logistic regression was made to take the correlated structure of the data into account
⁶ By estimation, absolute numbers not reported

Lactobacillus casei rhamnosus vs Magnesiumoxide

Question: Should Lactobacillus casei rhamnosus vs Magnesium oxide be used in Functional constipation?^1,2,3
Settings: 45 children, 0–10 y of age, recruited from general pediatric practice in Taiwan
Bibliography: Bu LN, Chang MH, Ni YH, et al. Lactobacillus casei rhamnosus Lcr35 in children with chronic constipation. Pediatr Int 2007;49:485–490.

Quality assessment

No of patients

Effect

Quality

Importance

No of studies

Design

Risk of bias

Inconsistency

Indirectness

Imprecision

Other considerations

Lactobacillus casei rhamnosus

Magnesium oxide

Relative
(95% CI)

Absolute

Treatment success defined as 3 or more spontaneous defecations per week with no episodes of fecal soiling by the fourth week (follow-up 4 weeks; assessed with: Bowel diary)

randomised trials

serious

no serious inconsistency

no serious indirectness

serious

none

14/18
(77.8%)⁴

13/18
(72.2%)⁴

RR 1.08 (0.74 to 1.57)

58 more per 1000 (from 188 fewer to 412 more)

⊕⊕⊝⊝
LOW

IMPORTANT⁵

¹ 8 x10⁸ colonyforming units per day
² 50 mg/kg per day
³ <3 bowel movements per wk for > 2 mo and 1 of the at least 1 of the following symptoms: anal fissures with bleeding; fecal soiling; or passage of large and hard stool
⁴ By estimation, absolute numbers not given
⁵ Mean score of the 6 working group members