Of the 594 children randomised, 571 started the study, receiving either milk containing Lactobacillus GG (n=282) or control milk (n=289) (figure ). Fifty eight children did not complete the follow up period.
Progress of participants during seven month study
Table details characteristics of the children before treatment. The block randomisation resulted in a similar distribution of children in the age groups under 3 years and 3 years and over: 51 (18%) and 231 (82%) in the Lactobacillus group and 55 (19%) and 234 (81%) in the control group. Detailed analysis of age distribution, however, showed that there were differences between the groups. Also, there were more children in the control group who had had five or more respiratory infections during the preceding 12 months. Age and preceding infections both have an effect on the incidence of infections and as they were strongly correlated we adjusted only for age in comparisons of treatment.
Characteristics before treatment of children allocated to probiotic milk (Lactobacillus GG) and control groups. Figures are means (ranges) or numbers (percentage) of children
Intention to treat analysis
Symptoms of illness as reported by parents—There were no significant differences between the groups in the number of days with respiratory and gastrointestinal symptoms (table ). However, in the Lactobacillus group there were fewer days of absence because of illness—a Lactobacillus:control ratio of 0.85 (95% confidence interval 0.73 to 0.98)—and thus a reduction of 15%. The time without respiratory symptoms was significantly longer in the Lactobacillus group compared with the control group (5 (4.1 to 5.9) v 4 (3.5 to 4.6) weeks, P=0.03, fig ). Time without diarrhoea was not significantly different (25 (24 to 26) v 24 (23 to 25) weeks, respectively, P=0.20, fig ).
Table 2 Details of symptoms, absence, and symptom score during seven month treatment period. Unadjusted and age adjusted results based on intention to treat population, with children who completed intervention. Figures are geometric means (95% confidence (more ...)
Proportion of children without infection during seven month study (respiratory symptoms and diarrhoea)
Upper and lower respiratory tract infections diagnosed by doctor—The number of children with respiratory infections (otitis media, sinusitis, bronchitis, and pneumonia) was significantly lower in the Lactobacillus group (relative reduction 17%, table ). There were also fewer children in the Lactobacillus group who were prescribed antibiotics for respiratory infections (relative reduction 19%, table ).
Table 3 Number (percentage) of children having at least one respiratory tract infection, as diagnosed by doctor, or at least one course of antibiotics prescribed by doctor. Unadjusted and age adjusted results based on intention to treat population with children (more ...)
Age adjusted results—Adjustment for age reduced the difference between the groups in the number of days of absence (table ). After age adjustment the odds ratio for the Lactobacillus group was 0.89 (0.77 to 1.02). The time without respiratory symptoms was not significantly different between the groups (data not shown), but for the Lactobacillus group the estimated odds ratio was 0.86 (0.70 to 1.06, P=0.16), indicating reduced risk. Time without diarrhoea was also not significantly different between the groups, but the odds ratio for the Lactobacillus group was 0.87 (0.64 to 1.28, P=0.36). The numbers of children with respiratory tract infections diagnosed by a doctor and being given antibiotic treatments for these were not significantly different between the groups (table ). However, the age adjusted odds ratios for the Lactobacillus group were 0.75 (0.52 to 1.09, P=0.13) for all respiratory infections and 0.72 (0.50 to 1.03, P=0.08) for antibiotic treatment for respiratory infection.
After age adjustment there was a negative but non-significant correlation between the amount of milk consumed and the total number of days of illness (r=−0.12; P=0.07) and days with respiratory symptoms (r=−0.11; P=0.09). The negative correlation between the amount of Lactobacillus milk consumed and days with gastrointestinal symptoms was significant (r=−0.17; P=0.007).
Mean daily milk consumption was 260 ml in both groups (range 110-520 ml in the Lactobacillus and 100-600 ml in the control group). This quantity of milk contained 1-2x108 cfu of Lactobacillus GG. Compliance was also measured by the faecal recovery of Lactobacillus. Initially 12% of children in the Lactobacillus group and 4% in the control group carried Lactobacillus GG-type bacteria (P=0.29). Recovery figures were 97% v 9% (P<0.0001), respectively, in the middle of the study and 91% v 15% (P<0.0001) at the end. The median faecal Lactobacillus GG count in the Lactobacillus group was 5-8x104 cfu/g.
The responses to the questionnaire at the end of the study were similar in both groups. Neither Lactobacillus nor the control milk affected stool frequency or consistency. There was no difference between the groups in abdominal pain or allergic symptoms and no apparent side effects.