Kaisu Juntunen-Backman

Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double-blind placebo-controlled trial

Background:  Probiotic bacteria are suggested to reduce symptoms of the atopic eczema/dermatitis syndrome (AEDS) in food‐allergic infants. We aimed to investigate whether probiotic bacteria have any beneficial effect on AEDS.

Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort.

BACKGROUND Less microbial exposure in early childhood is associated with more allergic disease later. Allergic children have a different fecal microflora, with less lactobacilli and bifidobacteria. Beneficial effects regarding the development of allergy have been suggested to come through probiotic supplementation. OBJECTIVE We sought to study the effect of probiotic and prebiotic supplementation in preventing allergies. METHODS In a double-blinded, placebo-controlled study we randomized 1223 mothers with infants at high risk for allergy to receive a probiotic mixture (2 lactobacilli, bifidobacteria, and propionibacteria) or placebo during the last month of pregnancy and their infants to receive it from birth until age 6 months. Infants also received a prebiotic galacto-oligosaccharide or placebo. At 5 years, we evaluated the cumulative incidence of allergic diseases (eczema, food allergy, allergic rhinitis, and asthma) and IgE sensitization. RESULTS Of the 1018 intent-to-treat infants, 891 (88%) attended the 5-year visit. Frequencies of allergic and IgE-associated allergic disease and sensitization in the probiotic and placebo groups were similar: 52.6% versus 54.9% and 29.5% versus 26.6%, respectively, and 41.3% in both. No significant difference appeared in frequencies of eczema (39.3% vs 43.3%), atopic eczema (24.0% vs 25.1%), allergic rhinitis (20.7% vs 19.1%), or asthma (13.0% vs 14.1%) between groups. However, less IgE-associated allergic disease occurred in cesarean-delivered children receiving probiotics (24.3% vs 40.5%; odds ratio, 0.47; 95% CI, 0.23% to 0.96%; P = .035). CONCLUSIONS No allergy-preventive effect that extended to age 5 years was achieved with perinatal supplementation of probiotic bacteria to high-risk mothers and children. It conferred protection only to cesarean-delivered children.

Supplementary feeding in maternity hospitals and the risk of cow’s milk allergy: A prospective study of 6209 infants ☆ ☆☆ ★

BACKGROUND Early feeding with cows milk (CM) may increase the risk of cows milk allergy (CMA). OBJECTIVE We sought to examine prospectively whether supplementary feeding of CM at the maternity hospital would increase the risk when compared with feeding with pasteurized human milk or hydrolyzed formula. METHODS We studied 6209 unselected healthy, full-term infants, of whom 5385 (87%) required supplementary milk while in the hospital. The infants were randomly assigned to receive CM formula (1789 infants), pasteurized human milk (1859 infants), or whey hydrolysate formula (1737 infants). The comparison group (824 infants) was composed of infants who were exclusively breast-fed. The infants were followed for 18 to 34 months for symptoms suggestive of CMA. The primary endpoint was a challenge-proven adverse reaction to CM after a successful CM elimination diet. RESULTS The cumulative incidence of CMA in the infants fed CM was 2.4% compared with 1.7% in the pasteurized human milk group (odds ratio [OR], 0.70; 95% confidence interval [CI], 0. 44-1.12) and 1.5% in the whey hydrolysate group (OR, 0.61; 95% CI, 0. 38-1.00). In the comparison group, CMA developed in 2.1% of the infants. Among the infants who required supplementary feeding at hospital, both exposure to CM while in the hospital (OR, 1.54; 95% CI, 1.04-2.30; P =.03) and obvious parental atopy (OR, 2.32; 95% CI, 1.53-3.52; P <.001) increased the risk of CMA. CONCLUSIONS Our data indicate that feeding of CM at maternity hospitals increases the risk of CMA when compared with feeding of other supplements, but exclusive breast-feeding does not eliminate the risk.

Long-Term Safety and Impact on Infection Rates of Postnatal Probiotic and Prebiotic (Synbiotic) Treatment: Randomized, Double-Blind, Placebo-Controlled Trial

OBJECTIVE. Live probiotic bacteria and dietary prebiotic oligosaccharides (together termed synbiotics) increasingly are being used in infancy, but evidence of long-term safety is lacking. In a randomized, placebo-controlled, double-blind trial, we studied the safety and long-term effects of feeding synbiotics to newborn infants. METHODS. Between November 2000 and March 2003, pregnant mothers carrying infants at high risk for allergy were randomly assigned to receive a mixture of 4 probiotic species (Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve Bb99, and Propionibacterium freudenreichii ssp shermanii) or a placebo for 4 weeks before delivery. Their infants received the same probiotics with 0.8 g of galactooligosaccharides, or a placebo, daily for 6 months after birth. Safety data were obtained from clinical examinations and interviews at follow-up visits at ages 3, 6, and 24 months and from questionnaires at ages 3, 6, 12, and 24 months. Growth data were collected at each time point. RESULTS. Of the 1018 eligible infants, 925 completed the 2-year follow-up assessment. Infants in both groups grew normally. We observed no difference in neonatal morbidity, feeding-related behaviors (such as infantile colic), or serious adverse events between the study groups. During the 6-month intervention, antibiotics were prescribed less often in the synbiotic group than in the placebo group (23% vs 28%). Throughout the follow-up period, respiratory infections occurred less frequently in the synbiotic group (geometric mean: 3.7 vs 4.2 infections). CONCLUSION. Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections during the first 2 years of life.

Probiotic effects on faecal inflammatory markers and on faecal IgA in food allergic atopic eczema/dermatitis syndrome infants.

Probiotic bacteria are proposed to alleviate intestinal inflammation in infants with atopic eczema/dermatitis syndrome (AEDS) and food allergy. In such infants we investigated effects of probiotic bacteria on faecal IgA, and on the intestinal inflammation markers tumour necrosis factor‐α (TNF‐α), α1‐antitrypsin (AT), and eosinophil cationic protein (ECP). A total of 230 infants with AEDS and suspected cows milk allergy (CMA) received in a randomized double‐blinded manner, concomitant with elimination diet, Lactobacillus GG (LGG), a mixture of four probiotic strains (MIX), or placebo for 4 wk. Four weeks after treatment, CMA was diagnosed with a double‐blind placebo‐controlled milk challenge. Faecal samples of 102 infants, randomly chosen for analysis, were collected before treatment, after 4‐wk treatment, and on the first day of milk challenge. After treatment, IgA levels tended to be higher in probiotic groups than in the placebo group (LGG vs. placebo, p = 0.064; MIX vs. placebo, p = 0.064), and AT decreased in the LGG group, but not in other treatment groups. After challenge in IgE‐associated CMA infants, faecal IgA was higher for LGG than for placebo (p = 0.014), and TNF‐α was lower for LGG than for placebo, but non‐significantly (p = 0.111). In conclusion, 4‐wk treatment with LGG may alleviate intestinal inflammation in infants with AEDS and CMA.

Effects of inhaled budesonide on serum markers of bone metabolism in children with asthma

The effects of inhaled glucocorticoids on serum markers of bone formation were evaluated in asthmatic children. Serum total alkaline phosphatase (AP), bone alkaline phosphatase (BAP), osteocalcin, and the novel marker of bone formation, carboxypropeptide of type I procollagen (PICP), were measured. In the cross-sectional part, long-term glucocorticoid users were compared with sodium cromoglycate (SCG) users. In the boys (n = 16), but not in the girls (n = 11), PICP was significantly lower in the glucocorticoid users than in the SCG users. PICP correlated positively with BAP (n = 54; groups combined, r = 0.29, p < 0.05). In the longitudinal part, the effects of inhaled budesonide or SCG, both used for the first time, were evaluated before and after 1 and 5 months of treatment. The budesonide dose was 800 micrograms/m2/day for 1 month and thereafter half of that. The SCG dose was 30 mg/day throughout the study. Only during budesonide use did osteocalcin and PICP decrease, the median osteocalcin by 8% at 1 month (p < 0.05) and by 6% at 5 months (n = 15), and PICP by 5% at 1 month (p < 0.05) and by 28% at 5 months (n = 7, p < 0.01). AP and BAP did not change significantly. Decreased PICP suggests decreased bone formation rate. PICP might be clinically useful as a marker of early adverse effects of glucocorticoids on bone.

β-lactoglobulin secretion in human milk varies widely after cow's milk ingestion in mothers of infants with cow's milk allergy

Abstract Background: Cows milk proteins secreted in human milk may cause cows milk allergy (CMA) even during exclusive breast-feeding. We studied β-lactoglobulin levels in human milk of mothers of infants with CMA. We also studied intestinal absorption of macromolecules in the same mothers to see whether it is related to the secretion of β-lactoglobulin in human milk. Methods: CMA was verified with oral challenge in 46 of 55 infants assessed. β-Lactoglobulin levels were assessed in human milk from 53 of 55 mothers of the infants before (basal sample) and 1 and 2 hours after an oral cows milk load, which was given after a 24-hour milk-free diet. β-Lactoglobulin was determined by an ELISA with a detection limit of 0.002 μg/L. The 6-hour urine recovery of a high-molecular-weight polyethylene glycol (PEG) 3000 was assessed afer an oral load of PEG in 45 of 55 mothers. Results: β-Lactoglobulin was found in the 1- or 2-hour samples in 75% of the mothers. β-Lactoglobulin levels were increased in the 1- or 2-hour samples as compared with the basal levels in about half of the mothers. The respective levels were decreased in one third of the mothers whose basal β-lactoglobulin levels were higher than in the others. β-Lactoglobulin was found in none of the three human milk samples in 15% of the mothers. After an oral load of a high-molecular-weight PEG 3000, the 6-hour urine recovery of PEG was similar in the mothers of the infants with CMA and the mothers of infants without CMA. Neither was the urinary recovery of PEG related to the β-lactoglobulin levels in human milk. Conclusions: The results support the view that β-lactoglobulin in human milk may contribute to, but does not alone explain, the development of CMA in breast-fed infants.

The patch test, skin prick test, and serum milk-specific IgE as diagnostic tools in cow's milk allergy in infants.

We evaluated the value of the patch test, skin prick test, and milk‐specific IgE by CAP RAST in 301 infants with suspected hypersensitivity to cows milk. The patch test was carried out with milk powder, and the skin prick test with cows milk‐based formula. Hypersensitivity to cows milk was determined with double‐blind, placebo‐controlled challenge. An immediate reaction to cows milk challenge was observed in 100 infants (33%), a delayed reaction in 76 (25%), and a negative result in 125 (42%). Skin prick test wheals were significantly greater in infants with immediate reactions than in infants with delayed or negative reactions. Milk‐specific IgE was correlated with the skin prick test (r=0.78, P<0.001, n=268) but did not contribute to further discrimination of immediate reactions from delayed or negative reactions compared to skin prick test alone. In our study population, the skin prick test (diameter ≥3 mm) showed a specificity and sensitivity of 91% and 69%; the results for milk‐specific IgE (≥0.7 kU/l) were 88% and 58%, respectively. The patch test did not distinguish subjects with immediate or delayed reactions from those with negative reactions.

Daily versus as-needed inhaled corticosteroid for mild persistent asthma (The Helsinki early intervention childhood asthma study)

Objective: To compare the effect of inhaled budesonide given daily or as-needed on mild persistent childhood asthma. Patients, design and interventions: 176 children aged 5–10 years with newly detected asthma were randomly assigned to three treatment groups: (1) continuous budesonide (400 μg twice daily for 1 month, 200 μg twice daily for months 2–6, 100 μg twice daily for months 7–18); (2) budesonide, identical treatment to group 1 during months 1–6, then budesonide for exacerbations as needed for months 7–18; and (3) disodium cromoglycate (DSCG) 10 mg three times daily for months 1–18. Exacerbations were treated with budesonide 400 μg twice daily for 2 weeks. Main outcome measures: Lung function, the number of exacerbations and growth. Results: Compared with DSCG the initial regular budesonide treatment resulted in a significantly improved lung function, fewer exacerbations and a small but significant decline in growth velocity. After 18 months, however, the lung function improvements did not differ between the groups. During months 7–18, patients receiving continuous budesonide treatment had significantly fewer exacerbations (mean 0.97), compared with 1.69 in group 2 and 1.58 in group 3. The number of asthma-free days did not differ between regular and intermittent budesonide treatment. Growth velocity was normalised during continuous low-dose budesonide and budesonide therapy given as needed. The latter was associated with catch-up growth. Conclusions: Regular use of budesonide afforded better asthma control but had a more systemic effect than did use of budesonide as needed. The dose of ICS could be reduced as soon as asthma is controlled. Some children do not seem to need continuous ICS treatment.

Inhaled corticosteroids during and after respiratory syncytial virus-bronchiolitis may decrease subsequent asthma.

Respiratory syncytial virus (RSV) bronchiolitis in infancy can lead to bronchial hyper‐reactivity or recurrent obstructive bronchitis. The aim of the present study was to determine whether the type of treatment has an influence on respiratory status after RSV bronchiolitis. The study involved 117 infants (mean age 2.6 months), who needed hospital treatment because of RSV bronchiolitis. The patients were divided randomly into three groups. All received the same symptomatic treatment. Group I children received symptomatic treatment only, group II children were treated for 7 days with inhaled budesonide, 500 µg three times per day, administered via a nebulizer. Group III children received nebulized budesonide, 500 µg twice per day for two months. Follow‐up consisted of out‐patient check‐ups 2 and 6 months after the infection, and telephone contact two years after the infection. Statistically significant differences were seen between the groups. In group I 37% of the children had asthma, in group II 18%, and in group III 12%. According to the present study it seems that inhaled corticosteroid treatment during and after the acute phase of infant RSV bronchiolitis may have a beneficial effect on subsequent bronchial wheezing tendency.