The effect of a mixture of probiotics on constipation symptoms in pregnant women

Constipation is a common symptom during pregnancy. Up to 40% of women will
suffer from constipation symptoms at some stage during their pregnancy. Already
in early pregnancy defecation symptoms are reported, most of them already
present at 12 weeks gestation. Constipation is one of the most common
gastrointestinal conditions affecting 12-27% of the general population.
Pregnant women may experience constipation for the first time during pregnancy
or find their constipation symptoms worsening, if constipated prior to
pregnancy, during pregnancy. Apart from the discomfort of constipation
symptoms, it has also the potential to cause permanent damage. There is
evidence that straining to defecate can damage the pudendal nerve and impair
the supportive function of the pelvic floor musculature. Constipation is also
an important factor in developing uterovaginal prolapse.

To date, no trials have been performed to show the effect of a mixture of
probiotics on constipation symptoms in pregnant women. One adult study showed
an increase in defecation frequency in those receiving two strains of
probiotics. One paediatric pilot study showed that a mixture of probiotics
containing lactobacilli and bifidobacteria augments the defecation frequency in
those presenting with less than 3 bowel movements per week.

In collaboration with Winclove Bio Industries a new combination of probiotics
is developed for treatment of constipation. In a pilot study performed in
constipated children using the same combination of probiotics has shown
positive effects on gastro-intestinal symptoms such as abdominal pain without
side effects. Further studies need to be done to elucidate the role of a
mixture of probiotics in treating constipated pregnant women. This is of
importance as patients on general in daily practice seem to prefer probiotics
over medication, certainly during pregnancy. In concordance with the guidelines
for treatment of constipation during pregnancy, set up by a group of experts in
2003, non-pharmalogical measures are the first step in treatment. Probiotics
are candidates as a non-pharmalogical modification in treating constipation
during pregnancy.

Hypotheses
1) The use of a combination of probiotic strains results in a significant
increase in defecation frequency in pregnant women with constipation.

2) The use of a combination of probiotic strains results in less episodes of
difficult defecation, as described in the Rome III criteria in pregnant women
with constipation.

Prior to the study enrolment, pregnant women record defecation frequency,
consistency of stools, pain during defecation and the frequency of episodes of
faecal incontinence in a validated bowel diary for one week. At intake a
general medical history and physical examination will be performed. Subjects
fulfilling the Rome III criteria for constipation will be offered to
participate in the study.

Before study medication is given, all subjects will receive one enema (Klyx 120
ml (Sodium dioctylsulfosuccinate) once daily for three days to clear any faecal
remains. Study probiotics contain the following 6 probiotic strains:
- Bifidobacterium bifidum
- Bifidobacterium infantis
- Bifidobacterium longum
- Lactobacillus casei
- Lactobacillus plantarum
- Lactobacillus rhamnosus

The study protocol will last 6 weeks. All subjects receive 1dd 4 gram (4x109
CFU) of the probiotic strains for 4 weeks. The probiotics will be given with a
glass of water. If a subject does not defecate for three days during these 4
weeks, a stimulant laxative (bisacodyl 5-10 mg) will be prescribed on the
fourth day. During the treatment phase defecation frequency, consistency of
stools, pain during defecation and the frequency of episodes of faecal
incontinence and possible adverse effects such as abdominal pain, bloating,
flatulence, nausea, diarrhoea and bad taste will be recorded in a validated
defecation diary.

After 4 weeks the study medication is stopped and a follow-up visit is
scheduled at 6 weeks. Also during these 2 weeks defecation frequency,
consistency of stools, pain during defecation and the frequency of episodes of
faecal incontinence and possible adverse effects such as abdominal pain,
bloating, flatulence, nausea, diarrhoea and bad taste will be recorded in a
validated defecation diary.

Clinical evaluation and assessment of diaries will be carried out at enrolment
and at 2, 4 and 6 weeks.

Study probiotics contain the following 6 probiotic strains:
- Bifidobacterium bifidum
- Bifidobacterium infantis
- Bifidobacterium longum
- Lactobacillus casei
- Lactobacillus plantarum
- Lactobacillus rhamnosus

The study protocol will last 6 weeks. All subjects receive 1dd 4 gram (4x109
CFU) of the probiotic strains for 4 weeks. The probiotics will be given with a
glass of water.

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