TY - BOOK
T1 - The Effect of Probiotics on Diarrhea in Children with Severe Acute Malnutrition
T2 - an Intervention Study in Uganda
AU - Grenov, Benedikte
N1 - CURIS 2016 NEXS 387
PY - 2016
Y1 - 2016
N2 - The study was conducted as a randomized, double-blind, placebo-controlled study at
Mwanamugimu Nutrition Unit, Mulago Hospital, Kampala, Uganda, between March 2014 and
October 2015. The study enrolled 400 children between 6 and 59 months of age with SAM. The
children either received one daily dose of probiotics consisting of 10 billion colony-forming units of
two probiotic strains BB-12 and LGG (ratio 1:1) or placebo. Probiotics or placebo was administered
during hospitalization and during a subsequent 8-12 week outpatient treatment period. The primary
outcome was number of days with diarrhea during hospitalization. Secondary outcomes included
number of days with diarrhea during outpatient treatment, diarrhea incidence, diarrhea severity
according to the Vesikari scale, fever, vomit, pneumonia, weight gain and nutritional recovery. All
outcomes were analyzed separately for in- and outpatient treatment.
A stool diary was developed collecting data on stool frequency and consistency. The diary was
filled by caregivers and used to calculate diarrhea outcomes. The validity, reliability and sensitivity
of the diary were assessed.
Data from the intervention study were used to identify predictors of days with diarrhea and
dehydration during hospitalization. In addition the association between days with diarrhea as well as
dehydration and mortality during hospitalization were assessed.
Results
The study children had a mean age of 17.0 months, 58% were boys, 66% had edematous
malnutrition and 14% were HIV-seropositive. There was no effect of probiotics on days with
diarrhea during inpatient treatment (adjusted difference +0.2 days [95% CI -0.8; 1.2], p=0.69).
However a reduction in days with diarrhea was found in the probiotic group during outpatient
treatment (adjusted difference -2.2 days [95% CI -3.5; -0.3], p=0.025). There was no difference
between the probiotic and placebo groups with regard to diarrhea incidence and severity, vomiting,
fever, pneumonia, weight gain or nutritional recovery. Fortysix patients died, with 26 patients from
the probiotic group and 20 patients from the placebo group (p=0.38).
Caregivers understood the content of the stool diary (stool frequency and consistency), and after
three days of training, they were able to fill the diary with high reliability. The diary had a high
sensitivity to measure changes in stool frequency and consistency. Stool frequency and especially
stool consistency correlated strongly with dehydration assessed by medical doctors (p=0.0018 for
increasing stool frequency and p<0.0001 for increasing stool consistency).
Out of 592 diarrhea episodes reported during hospitalization, 355 were categorized as hospitalacquired
and 237 as admission diarrhea episodes. Young age and HIV predicted days with diarrhea
and dehydration during hospitalization. Both days with diarrhea and dehydration were strongly
associated with increased mortality during hospitalization. The mortality risk increased 1.4 times
(95% CI: 1.2; 1.6) per day of diarrhea and 2.3 times (95% CI: 1.6; 3.6) per point on the dehydration
scale.
Conclusion
LGG and BB-12 did not reduce the number of days with diarrhea during inpatient treatment of
children with SAM. However, they reduced days with diarrhea during the subsequent outpatient
treatment by 2.2 days corresponding to a reduction of 26%. Probiotics may therefore have a role in
community-based treatment of children with uncomplicated SAM or in follow-up of children
discharged from inpatient treatment of SAM with medical complications, but more studies are
needed to investigate this.
The stool diary was shown to have high validity, good reliability and high sensitivity. It may be
useful in other diarrhea studies among young children in low-income countries.
Diarrhea and dehydration were both strongly associated with increased mortality during
hospitalization of children with SAM. Improved management of diarrhea and prevention of
hospital-acquired diarrhea therefore seems to be important to reduce mortality in this vulnerable
patient group.
AB - The study was conducted as a randomized, double-blind, placebo-controlled study at
Mwanamugimu Nutrition Unit, Mulago Hospital, Kampala, Uganda, between March 2014 and
October 2015. The study enrolled 400 children between 6 and 59 months of age with SAM. The
children either received one daily dose of probiotics consisting of 10 billion colony-forming units of
two probiotic strains BB-12 and LGG (ratio 1:1) or placebo. Probiotics or placebo was administered
during hospitalization and during a subsequent 8-12 week outpatient treatment period. The primary
outcome was number of days with diarrhea during hospitalization. Secondary outcomes included
number of days with diarrhea during outpatient treatment, diarrhea incidence, diarrhea severity
according to the Vesikari scale, fever, vomit, pneumonia, weight gain and nutritional recovery. All
outcomes were analyzed separately for in- and outpatient treatment.
A stool diary was developed collecting data on stool frequency and consistency. The diary was
filled by caregivers and used to calculate diarrhea outcomes. The validity, reliability and sensitivity
of the diary were assessed.
Data from the intervention study were used to identify predictors of days with diarrhea and
dehydration during hospitalization. In addition the association between days with diarrhea as well as
dehydration and mortality during hospitalization were assessed.
Results
The study children had a mean age of 17.0 months, 58% were boys, 66% had edematous
malnutrition and 14% were HIV-seropositive. There was no effect of probiotics on days with
diarrhea during inpatient treatment (adjusted difference +0.2 days [95% CI -0.8; 1.2], p=0.69).
However a reduction in days with diarrhea was found in the probiotic group during outpatient
treatment (adjusted difference -2.2 days [95% CI -3.5; -0.3], p=0.025). There was no difference
between the probiotic and placebo groups with regard to diarrhea incidence and severity, vomiting,
fever, pneumonia, weight gain or nutritional recovery. Fortysix patients died, with 26 patients from
the probiotic group and 20 patients from the placebo group (p=0.38).
Caregivers understood the content of the stool diary (stool frequency and consistency), and after
three days of training, they were able to fill the diary with high reliability. The diary had a high
sensitivity to measure changes in stool frequency and consistency. Stool frequency and especially
stool consistency correlated strongly with dehydration assessed by medical doctors (p=0.0018 for
increasing stool frequency and p<0.0001 for increasing stool consistency).
Out of 592 diarrhea episodes reported during hospitalization, 355 were categorized as hospitalacquired
and 237 as admission diarrhea episodes. Young age and HIV predicted days with diarrhea
and dehydration during hospitalization. Both days with diarrhea and dehydration were strongly
associated with increased mortality during hospitalization. The mortality risk increased 1.4 times
(95% CI: 1.2; 1.6) per day of diarrhea and 2.3 times (95% CI: 1.6; 3.6) per point on the dehydration
scale.
Conclusion
LGG and BB-12 did not reduce the number of days with diarrhea during inpatient treatment of
children with SAM. However, they reduced days with diarrhea during the subsequent outpatient
treatment by 2.2 days corresponding to a reduction of 26%. Probiotics may therefore have a role in
community-based treatment of children with uncomplicated SAM or in follow-up of children
discharged from inpatient treatment of SAM with medical complications, but more studies are
needed to investigate this.
The stool diary was shown to have high validity, good reliability and high sensitivity. It may be
useful in other diarrhea studies among young children in low-income countries.
Diarrhea and dehydration were both strongly associated with increased mortality during
hospitalization of children with SAM. Improved management of diarrhea and prevention of
hospital-acquired diarrhea therefore seems to be important to reduce mortality in this vulnerable
patient group.
UR - https://rex.kb.dk/primo-explore/fulldisplay?docid=KGL01010309798&context=L&vid=NUI&search_scope=KGL&isFrbr=true&tab=default_tab&lang=da_DK
M3 - Ph.D. thesis
SN - 978-87-93476-68-4
BT - The Effect of Probiotics on Diarrhea in Children with Severe Acute Malnutrition
PB - Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen
CY - Copenhagen
ER -
