The effect of lactulose in the treatment of chronic functional constipation in children

JOURNAL OF MEDICAL RESEARCH

THE EFFECT OF LACTULOSE IN THE TREATMENT OF
CHRONIC FUNCTIONAL CONSTIPATION IN CHILDREN
Do Thi Minh Phuong, Nguyen Thi Viet Ha
Department of Pediatrics, Hanoi Medical University
Constipation is a common gastrointestinal problem in children. The aim of the present study was to
evaluate the beneficial effects of lactulose in the management of functional constipation in children. An
open clinical trial was conducted in 140 children aged 1 – 5 years at the National Children Hospital, Hanoi,
Vietnam with a diagnosis of functional constipation. The reslult suggest that frequency and consistency
of defecation, as well as clinical symptoms were improved significantly when using lactulose with 2 ml/
kg/day. The mean weekly stool frequency improved from 1.9 ± 0.8 times to 4.9 ± 1.8 times after 1 month
and to 5.9 ± 1.4 times after 3 months of treatment (p < 0.01). The rate of effective treatment (the weekly
stool frequency ≥ 3 times and fecal incontinence ≤ 1 time every two weeks) was 68% after 1 month and
increased to 72.8% after 2 and 3 months of treatment. In addition to using laxatives, fiber and fluid intake
per day > 80% standard recommendation improve the effect in the treatment. In conclusion, lactulose
is a safe, effective and well-tolerated long-term treatment for constipation. Regular supplement of fiber
and fluid in children with constipation is important to improve the effect in the treatment of constipation.

Keywords: chronic functional constipation, lactulose, children, Rome III

I. INTRODUCTION
Constipation is one of the mast common
constipation digestive complaints in children, and has recently grown into a disproportionate public health problem. A recent
systematic review of pediatric patents of
the sample reported constipation in 0.7% to
29.6% of the sample [1]. Functional constipation was recognized as a separate clinical
entity by combining features of functional
Corresponding author: Do Thi Minh Phuong, Department of Pediatrics, Hanoi Medical University
Email:
Received: 13 August 2017

Accepted: 16 November 2017

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fecal retention and functional constipation.
The North American Society for Pediatric
Gastroenterology, Hepatology and Nutrition
define constipation as a delay or difficulty in
defecation, present for 2 or more week [2].
The occurrence of chronic functional constipation in children can lead to significant abdominal pain, anal fissure, loss of appetite,
faecal incontinence and social isolation.
The aim of constipation management is
to produce soft, painless stools and to prevent the re-accumulation of feces, which
can be achieved through dietary modification, behavioral interventions, fecal disimpaction and the use of laxatives, or a combination thereof [6]. Lactulose is considered
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JOURNAL OF MEDICAL RESEARCH
to be safe and recommended for all ages in
the management of constipation by NASPGHAN and ESPGHAN [3]. Many studies
have demonstrated that lactulose improved
frequency and consistency of defecation
and clinical symptoms [4; 5; 7; 8]. To our
knowledge, however, no large studies evaluat the effect of lactulose in childhood constipation have been published in Vietnam.
The primary objective of the present study
was to evaluate the beneficial effects of lactulose in the treatment of chronic functional
constipation in children.

II. MATERIALS AND METHODS
1. Subjects

140 children aged 1 - 5 years recruited
from the sample consisted of the National
Children Hospital, Hanoi, Vietnam with a diagnosis of functional constipation
Study design
The treatment trial was performed in Hanoi, Vietnam from 1/10/2013 to 31/11/2014.
The Rome III guideline was used to diagnose patients with chronic functional constipation [9]. According to the guideline, in
the absence of organic pathology, patients
must meet two or more of the following criteria: 1) Two or fewer defecations in the toilet per week. 2) At least one episode of fecal
incontinence per week after the acquisition
of toileting skills. 3) History of retentive posturing or excessive volitional stool retention.
4) History of painful or hard bowel movements. 5) Presence of a large fecal mass in
the rectum. 6) The history of large diameter
stools which may obstruct the toilet. Infants
up to 4 years have to fulfill ≥ 2 of the crite-

62

ria for at least 1 month, whereas those > 4
years need to fulfill ≥ 2 of the criteria for at
least 2 months and have insufficient criteria
for irritable bowel syndrome. A total of 140
children from ages 1 - 5 years old presenting with constipation based on a modification of the Rome III criteria were eligible for
the trial.
Evaluation of treatment outcome
All patients were examined, advised to
change dietary, adherence to daily toilet
training, used lactulose with 2 ml/kg/day. If
patients have diarrhea, the dose of lactulose
will decrease 1 ml/kg/day. After 1 week of
treatment, patients still defecate hard stool

< 3 times per week, lactulose will increase
3 ml//kg/day. Parents received fiber chart
of common foods; the Bristol stool chart;
and a stool diary to record the frequency of
daily bowel movements, fecal soiling, stool
consistency, as well as any symptoms they
considered important. The children were
evaluated clinically at study entry and at 4,
8 and 12 weeks after enrollment. Treatment
responses were assessed by evaluation of
the daily stool diary. Treatment compliance
was assessed by direct interview with the
patient, checking the diary cards (on which
the number of daily capsules taken was
recorded), and counting the capsules returned by the patient at each visit.
Statistical analysis
Statistical analysis was performed using the computer software SPSS 16.0. Student’s t test was used to compare means
of continuous variables approximating a
normal distribution. The x² test or Fisher’s
exact test was used, as appropriate, to
compare percentages. A p-value < 0.05 was
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considered statistically significant.

III. RESULTS

2. Ethics

Baseline characteristics of study
groups
From 1/10/2013 to 31/11/2014, 140 children presenting with constipation were enrolled in the study.

This study was approved by the Science Council of Hanoi Medical University.
A written informed consent was signed by
children’s parents/ caretakers before participating in the present study.

Table 1. Baseline characteristics
Age (months)

35,9 ± 17,4

Gender

Boys (%)

51.8

Girls (%)

43.2

Disease duration (months)

11 ± 9.7

Mean weekly stool frequency

1,9 ± 0,8

Stool consistency (%)

Type 1

77.9

Type 2

22.2

Patients with painful bowel movements (%)

80.7

Patients with anal fissure (%)

54.3

Patients with a fecal mass in the rectum (%)

66,4

The beneficial effects of lactulose with 2 ml/kg/day in the treatment of chronic functional constipationin children.
Figure 1 shows the mean stool frequency increased from 1.9 ± 0.8 stools/ week at baseline to 4.9 ± 1.8 at weeks 4 and 5.9 ± 1.4 at the end of the study (p < 0.01).

Fingure 1. Change in the weekly stool frequency

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JOURNAL OF MEDICAL RESEARCH
The successful treatment rate (defined as weekly stool frequency ≥ 3 times and fecal incontinence ≤ 1 time every 2 weeks) was 68% after 4 weeks and increased to 72.8% after 8
and 12 weeks of treatment.
Table 2. Change in stool consistency during treatment
Stool consistency (%)

Type 1

Type 2

Type 3

Type 4

Baseline

78.6

21.4

0

0

4 weeks

0

9.7

49.5

40.8

8 weeks

0

2.9

30.1

67

12 weeks

0

0

14.6

85.4

p-value
< 0.01

< 0.01

Stool consistency : Type 1 – Separate hard lumps, like nuts; Type 2 – Sausage – shaped,
but lumpy; Type 3 – Like a sausage but with cracks on its surface; Type 4 – Like a sausage
or snake, smooth and soft.
The percentage of patients used 2ml of lactulose/ kg/ day after 4 weeks of treatment was
87.4%. This rate decreased to 80.6% (after 8 weeks) and 75.5% after 12 weeks (Table 2).
Table 3. Change in dose of lactulose from baseline to after 12 weeks
At 4 weeks

At 8 weeks

At 12 weeks

Dose

n

%

n

%

n

%

1 ml/kg/day

11

10.7

14

13.6

17

16.5

2 ml/kg/day

90

87.4

83

80.6

78

75.7

3 ml/kg/day

2

1.9

6

5.8

7

6.8

Time

Amount of water and fiber/ day affect to treatment

Table 3 shows a difference in the mean weekly stool frequency between fiber intake
per day > 80% and ≤ 80% standard recommended after 4 weeks, 8 weeks and 12 weeks of
treatment with p value.Children with fiber intake per day ≤ 80% standard recommendation
had increased risk for hard stools (type 2 - 3) compared to > 80% group at 4 weeks and 8
weeks (p < 0.05).
Table 4: Amount of fiber/day affect to mean weekly stool frequency
Time
At 4 weeks

64

Amount of fiber

n (%)

X ± SD

≤ 80%

49 (47.6)

4.4 ± 1.8

> 80%

54 (52.4)

5.2 ± 1.8

p value
0.03

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At 8 weeks
At 12 weeks

≤ 80%

35 (34)

4.7 ± 1.7

> 80%

68 (66)

5.5 ± 1.5

≤ 80%

11 (10.7)

5.5 ± 1.9

> 80%

92 (89.3)

6 ± 1.3

0.02
0.30

IV. DISCUSSION
Based on recommendations from NASPGHAN and ESPGHAN, we chose a daily
intake of mean dose of lactulose (2 ml/kg/
day) in this study. The results showed that
the frequency and consistency of defecation and other clinical symptoms as painful
bowel movements, anal fissure, fecal incontinence, blood in stool improved significantly (p < 0.05).
In this study, we used different doses of
lactulose to evaluate the effects of lactulose
in the treatment of functional constipation.

The effective dose of lactulose was changeable based on factors such as diet, adherence to treatment, duration of constipation
and any previous used medications. Banaszkiewicz’ trial used lactulose with 1 ml/
kg/day, which showed that the mean weekly
stool frequency improved, as did our study
[4]. According to Sadeghzadeh's study, the
frequency of defecation per week increased
from 0.8 ± 0.8 to 1.5 ± 0.98 times (in the
lactulose group) and from 1.7 ± 0.8 to 2.1
± 0.7 times (in the lactulose plus protease
group) after 4 weeks of treatment [5]. The
improvement of frequency of defecation in
this study was slower than our results.
In one study conducted by Wang, 111
patients over 8 years of age received lactulose with 15 ml/kg, the median stool frequency following 1 week of treatment inJMR 111 E2 (2) - 2018

creased to from 2 to 5 times per week, and
following 2 weeks of treatment increased
to 6 times per week. Prior to treatment, the
stool consistencies of all enrolled patients
ranged from type 1 to 3 on the Bristol Stool
Scale. Lactulose treatment also improved
the stool consistency to 3.64 ± 1.33 following 1 week of treatment and 3.63 ± 1.33 following 2 weeks [7].
In our study, almost 70% of children with
constipation were successfully treated after
4 weeks of treatment. This rate increased
up to 72.8% after 8 weeks. The lactulose
dose of 2 ml/kg/day is appropriate for children with constipation. After 4 weeks of
treatment, almost all patients maintained
the dose of 2 ml/kg/day; only 10.7% of
them reduced the dose (1 ml/kg/day) due

to diarrhea, and a few had to be increased
due to unresponsive treatment (1.9%). The
success rate in our study was higher than
Voskuijl’s study after 8 weeks of treatment
(29%). In Voskuijl’s study, the mean lactulose dose associated with improvement
were 11.52 (4.56) g/day (1.9 sachets) and
13.86 (6.66) g/day (2.3 sachets) at 4 and
8 weeks. The optimal dose of lactulose in
clinically successful patients < 6 years and
≥ 6 years was 0.96 (0.45) g/kg/day and 0.45
(0.27) g/kg/day, respectively [8]. According
to Wang, the effective rate of treatment was
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39.64% after 1 week and increased 41.44%
after 2 weeks of treatment [7].
Limited water and fiber intake per day
as risk factors for constipation have been
shown in many studies. The results of our
study showed that fiber intake per day ≤
80% standard recommendation affected the
effect of lactulose in improving the frequency and consistency of defecation and clinical
symptoms. Dietary fiber is good for treating
constipation, but the role of additional fiber
in improving the effect of constipation treatment is not yet approved. In Kokke, and
Loening-Baucke's clinical trials, there was
no significant improvement in bowel movements after fiber therapy compared with
placebo and traditional treatments such as

lactulose (Duphalac) [10; 11].
The strength of our study lies in the large
sample size for a pediatric trial, a compliance rate of 73,6%, and a follow-up. A
weakness of the study was the difficulty of
conducting a randomized double-blind trial
over a wide weight range, as would be unethical having control groups allowing more
optimal dosing.

V. CONCLUSION
Lactulose is a safe, effective and well-tolerated long-term treatment for constipation.
Regular supplement of fiber and fluid over
80%, according to standard recommendation for constipated children is important to
improve the effect in the treatment of constipation.

Acknowledgments
We would like to thank the doctors and
staff at the Gastrointestinal department at
66

the National Children Hospital in Hanoi,
Vietnam for their assistance. We also wish
to thank all children and their parents who
participated in the study for their precious
collaborative spirit.

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