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

Long-Term Safety and Impact on Infection Rates of Postnatal Probiotic and
Prebiotic (Synbiotic) Treatment: Randomized, Double-Blind, Placebo-Controlled
Trial
Kaarina Kukkonen, Erkki Savilahti, Tari Haahtela, Kaisu Juntunen-Backman, Riitta
Korpela, Tuija Poussa, Tuula Tuure and Mikael Kuitunen
Pediatrics 2008;122;8
DOI: 10.1542/peds.2007-1192

The online version of this article, along with updated information and services, is
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ARTICLE

Long-Term Safety and Impact on Infection Rates of
Postnatal Probiotic and Prebiotic (Synbiotic)
Treatment: Randomized, Double-Blind,
Placebo-Controlled Trial
Kaarina Kukkonen, MDa, Erkki Savilahti, MD, PhDb, Tari Haahtela, MD, PhDa, Kaisu Juntunen-Backman, MD, PhDa, Riitta Korpela, PhDc,
Tuija Poussa, MScd, Tuula Tuure, PhDe, Mikael Kuitunen, MD, PhDa
aDepartment of Pediatrics, Skin and Allergy Hospital, bDepartment of Pediatrics, Hospital for Children and Adolescents, and cDepartment of Pharmacology, Institute of
Biomedicine, University of Helsinki, Helsinki, Finland; dSTAT Consulting, Tampere, Finland; eValio Research and Development, Helsinki, Finland

Financial Disclosure: Salaries Dr Kukkonen received and grants Dr Kuitunen received from the Clinical Research Institute of Helsinki University Central Hospital were funded by Valio. Drs Korpela and Tuure were
employed by Valio Research Centre. Ms Poussa received consulting fees from Valio.

What’s Known on This Subject

What This Study Adds

Probiotics and prebiotics are known to modulate immune responses. The accumulating
evidence of their health-promoting effects has led to increased consumption in infancy.
However, long-term follow-up and safety data for administration to newborn infants are
lacking.

This study documents safety and provides long-term follow-up data on probiotics and
prebiotics administered to newborn infants. The study suggests that feeding probiotics
and prebiotics to allergy-prone infants may increase their resistance to respiratory
infections.

ABSTRACT
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.

www.pediatrics.org/cgi/doi/10.1542/
peds.2007-1192
doi:10.1542/peds.2007-1192

METHODS. Between November 2000 and March 2003, pregnant mothers carrying in-

fants 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).

This trial has been registered at www.
clinicaltrials.gov (identifier NCT00298337).
Key Words
probiotic, prebiotic, synbiotic, safety,
growth, respiratory infections, antibiotics
Abbreviations
GOS— galactooligosaccharide
OR— odds ratio
CI— confidence interval
Accepted for publication Nov 6, 2007
Address correspondence to Kaarina Kukkonen,
MD, Helsinki University Central Hospital, Skin
and Allergy Hospital, Meilahdentie 2, PO Box
160, 00029 HUCH Helsinki, Finland. E-mail:
kaarina.kukkonen@hus.fi

PEDIATRICS (ISSN Numbers: Print, 0031-4005;
Online, 1098-4275). Copyright © 2008 by the
American Academy of Pediatrics

CONCLUSION. Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections

during the first 2 years of life. Pediatrics 2008;122:8–12

P

ROBIOTICS ARE LIVE microbes that, when ingested, may modulate systemic immune responses.1 Their biological
effects are strain specific, and prerequisites to their effects are viability and the ability to colonize.2 Prebiotics are
indigestible nutrients, such as galactooligosaccharides (GOSs) in human breast milk, that stimulate the growth and
metabolic activity of beneficial bacteria in the gut flora but also may produce a direct immunologic effect.3,4
Long-term use of these immunomodulatory agents among infants has been beneficial in autoimmune and allergic
disorders, such as inflammatory bowel diseases5 and atopic eczema.6 Their use is also associated with increased
resistance to acute enteric and respiratory infections.7,8 With the accumulating evidence of the benefits they produce,
probiotics and prebiotics are added to dairy products, which results in long-term consumption9 among pregnant
mothers and young infants.

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KUKKONEN et al

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Gut microbiota affect nutrient uptake and thereby
host energy metabolism.10 In view of that, probiotics
may have an impact on weight gain and growth.

Probiotics and prebiotics are regulated mostly within the
context of food, not drugs. Although they are generally
considered safe,11 reporting on the long-term safety of bacterial strains proven to colonize and to induce a clinical
effect is warranted. In this placebo-controlled study, we
document safety and provide long-term follow-up data.
The synbiotics consisted of 4 probiotic strains and prebiotic
GOSs. They were given in a double-blinded manner to
pregnant mothers and to their allergy-prone infants from
birth to the age of 6 months.12
METHODS
A detailed description of the study design appears elsewhere.12 In brief, we enrolled 1223 pregnant mothers
carrying infants at high risk for allergy in an allergyprevention trial in Helsinki, Finland, between November
2000 and March 2003. Mothers took capsules containing
a mixture of Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve Bb99, and Propionibacterium freudenreichii ssp shermanii JS (8 –9 ϫ 109 colony-forming units
in each capsule) or a placebo twice daily for 4 weeks
before delivery. For 6 months after birth, the infants
received daily 1 opened capsule of the same probiotics
and 0.8 g of GOSs (of bovine origin) in liquid form or
placebo (microcrystalline cellulose plus sugar syrup).
Parents received illustrated instructions to mix the probiotic powder with liquid (water, breast milk, or formula) in a teaspoon and to feed it to the infants with the
spoon. Exclusion criteria included birth at Ͻ37 weeks of
gestation, being a B twin, and having a major malformation. Mothers provided their written informed consent, and the ethics committee at the local hospital approved the study protocol.
The study pediatrician, blinded to group allocation,
examined the infants and interviewed the parents at
ages 3, 6, and 24 months. At 3, 6, 12, and 24 months, the
parents completed questionnaires covering 0 to 3, 3 to 6,
6 to 12, and 12 to 24 months, respectively. We inquired
about neonatal morbidity, feeding-related behaviors,
nutrition, the environment, and numbers of infections,
antibiotics, and other diseases. The questionnaires were

delivered by mail except for the 3- to 6-month questionnaire, which was given in person at the 3-month visit.
The questionnaires were returned during the study visits
(at 3, 6, and 24 months) or by mail (at 12 months). The
parents were advised to contact the study pediatrician in
the event of adverse reactions. The infants’ anthropometric measures were obtained from primary health
care charts. Growth measurements were converted to
SD scores with Pediator software (Tilator Ltd, Sakyl
¨ a,
¨
Finland), by using data for Finnish children as reference
data.13
All analyses used an intention-to-treat approach. The
sample size calculations are presented elsewhere.12 Anthropometric measures were analyzed by using the t test
for independent samples. The ␹2 test was used to compare categorized or dichotomized conditions between
the groups. The results are given as odds ratios (ORs)

TABLE 1 Baseline Demographic and Clinical Characteristics of the
Infants in the Intention-to-Treat Synbiotic and Placebo
Groups

Male gender, %
Birth weight, mean Ϯ SD, g
Birth length, mean Ϯ SD, cm
Vaginal delivery, %
Maternal smoking, %
Daily exposure to tobacco smoke, %
Partially breastfed for Ն6 mo, %
Total duration of breastfeeding, mean Ϯ SD, mo
Attending day care before 2 y of age, %
Firstborn child in the family, %a

Maternal allergy, %
Both parents allergic, %

Synbiotic
(n ϭ 506)

Placebo
(n ϭ 512)

50
3595 Ϯ 483
50.5 Ϯ 2.0
83
16
32
71
8.6 Ϯ 5.4
50
58
81
38

49
3593 Ϯ 484
50.6 Ϯ 1.9
83
13
29
68
8.2 Ϯ 5.0

51
52
81
38

a P Ͻ .05 between the intention-to-treat groups, but no difference occurred between the study
groups included in this safety analysis (at follow-up times of Ն3 months). No significant differences in other baseline variables were observed.

with 95% confidence intervals (CIs). The numbers of
infections and antibiotic courses were skewed to the
right and were logarithmically transformed. The t test for
independent samples was then used for group comparisons, and the results are presented as synbiotic/placebo
ratios with 95% CIs. The data were analyzed with SPSS
14.0 (SPSS, Chicago, IL).
RESULTS
Study Groups
Of the 1223 randomly assigned mothers, 156 refused to
participate, and 49 of their infants (plus 14 B twins)
were ineligible. Of these, 8 infants in the synbiotic group
and 7 in the placebo group were born prematurely to
mothers who had started the intervention. The baseline
characteristics of the 1018 intention-to-treat infants
were comparable between the study groups (Table 1). A
total of 939 infants (synbiotic, n ϭ 468; placebo, n ϭ
471) completed the 6-month follow-up evaluation, and
925 (synbiotic, n ϭ 461; placebo, n ϭ 464) completed
the 2-year follow-up evaluation.
Neonatal Morbidity
We observed no significant differences in parent-reported neonatal morbidity of any cause for infants in the
synbiotic group, compared with those in the placebo

group (Table 2).
Infantile Colic and Defecation
Infantile colic, defined as crying Ն4 hours per day for Ն3
days per week,14 occurred in 4% and similar but lessfrequent crying (once or twice per week) occurred in
10% of each group. Defecating Ն3 times per day was less
frequent in the synbiotic group (18% vs 29%; P Ͻ .001).
Tolerance and Adverse Events
Feeding-related behaviors (vomiting, constipation, excessive crying, and abdominal discomfort) occurred simPEDIATRICS Volume 122, Number 1, July 2008

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TABLE 2 Neonatal Morbidity and Reasons for Discontinuation of
the 6-Month Intervention in the Study Groups
No. of Infants

Neonatal morbidity
Jaundice
Hypoglycemia
Infection
Oxygen supplementation
Other (meconium plug obstruction, patent
ductus arteriosus, or neonatal hepatitis)
Reasons for discontinuing the intervention
Abdominal discomfort
Vomiting
Crying
Difficulty in swallowing the product

Noncompliance
Reasons for hospitalization at 0–2 y
Respiratory infection
Septic infection
Seizures
Malignancy
Other

Synbiotic
(n ϭ 506)

Placebo
(n ϭ 512)

11
14
11
11
2

6
11
24
18
2

26
4
2
2

22

28
7
1
2
16

8
6
4
1
6

15
6
2
1
13

ilarly in the study groups (data shown elsewhere).12
Symptoms that caused discontinuation of the intervention are presented in Table 2. One of the 6 infants with
difficulties swallowing the powder experienced a choking event associated with ingestion of the powder but
recovered completely. Any other reason for hospitalization after discharge from the maternity hospital to 2
years of age (Table 2) was likely unrelated to the intervention.
Growth
The anthropometric measures at the ages of 6 months
and 2 years, showing similar normal growth in the 2
groups, are presented in Table 3.
Infections and Antibiotics

During the intervention (0 – 6 months), we observed no
significant difference between the synbiotic and placebo
groups in the occurrence (at least once) of respiratory
infections (66% vs 68%), middle ear infections (15% vs
19%), or gastroenteritis (13% vs 14%). However, fewer
infants received antibiotics in the synbiotic group than in
the placebo group (23% vs 28%; OR: 0.74; 95% CI:
0.55–1.00; P ϭ .049).
After the intervention, during the follow-up period
(6 –24 months), respiratory infections occurred less frequently in the synbiotic group (93%) than in the placebo group (97%; OR: 0.49; 95% CI: 0.27– 0.92; P ϭ
.023). The total number of respiratory infections was
significantly lower in the synbiotic group (geometric
mean: 3.7 vs 4.2 infections; ratio: 0.87; 95% CI: 0.79 –
0.97; P ϭ .009). In these respective groups, middle ear
infections occurred in 72% vs 76% (ratio: 0.83; 95% CI:
0.62–1.11; P ϭ .204). The total number of middle ear
infections tended to be lower in the synbiotic group
10

KUKKONEN et al

TABLE 3 Anthropometric Measurements at 6 and 24 Months of Age
for Infants Who Received Synbiotics or Placebo During the
First 6 Months of Life

Age, mean Ϯ SD, d
Length, mean Ϯ SD, cm
Length SD scores, mean Ϯ SD
Weight, mean Ϯ SD, kg
Head circumference, mean Ϯ

SD, cm

Visit

Synbiotic Group
(n ϭ 446)a

Placebo Group
(n ϭ 456)b

6 mo
24 mo
6 mo
24 mo
6 mo
24 mo
6 mo
24 mo
6 mo
24 mo

183 Ϯ 10
736 Ϯ 17
68.4 Ϯ 2.4
88.4 Ϯ 3.2
0.00 Ϯ 0.97
0.28 Ϯ 1.01
8.16 Ϯ 0.98
12.8 Ϯ 1.5
43.9 Ϯ 1.3

49.4 Ϯ 1.5

184 Ϯ 11
735 Ϯ 20
68.4 Ϯ 2.4
88.6 Ϯ 3.1
Ϫ0.04 Ϯ 0.98
0.34 Ϯ 0.96
8.09 Ϯ 0.95
12.8 Ϯ 1.4
43.9 Ϯ 1.3
49.5 Ϯ 1.7

Growth measurements were converted to SD scores by using data on Finnish children as
reference data.13
a Growth data were available for 442 infants at the age of 24 months.
b Growth data were available for 449 infants at the age of 24 months.

(geometric mean: 1.7 vs 1.9 infections; ratio: 0.89; 95%
CI: 0.78 –1.01; P ϭ .068). Gastroenteritis was equally
common in the synbiotic and placebo groups (74% vs
71%; geometric mean: 1.3 vs 1.2 episodes; ratio: 1.02;
95% CI: 0.92–1.12; P ϭ .736). During the follow-up
period (6 –24 months), most infants received antibiotics,
with no significant difference between the synbiotic
group (80%) and the placebo group (83%); the geometric mean number of antibiotic courses was 2.2 vs 2.4
(ratio: 0.92; 95% CI: 0.81–1.05; P ϭ .206).
DISCUSSION
We showed that treatment of mothers with probiotics
during late pregnancy and treatment of their healthy,

allergy-prone infants with synbiotics for 6 months after
birth were safe. Infants in both treatment groups grew
normally, and no difference in morbidity related to synbiotics occurred. In fact, the synbiotics seemed to improve the infants’ resistance to respiratory infections;
during their first 6 months of life, they were prescribed
antibiotics less frequently than were infants receiving
placebo and, thereafter to the age of 2 years, they experienced fewer respiratory infections.
This is the largest randomized, clinical trial on probiotics and prebiotics given to pregnant mothers and their
newborn infants. Probiotics and prebiotics have generally been well tolerated, but we documented the safety
of their prenatal use with respect to neonatal morbidity.
Our trial with baseline-comparable treatment groups,
good adherence to the treatment, and successful probiotic bacterial colonization was initiated when the use of
probiotics and prebiotics in infant foods was still uncommon.12
Vaginal flora is crucial to the initial colonization of the
newborn gut after normal delivery,15 and treating pregnant mothers with probiotics promotes newborn colonization with the same bacteria.16 Perinatal exposure may
be vital to the probiotic effect, because postnatal administration of Lactobacillus acidophilus showed no preventive
effect on atopy.17 In addition, the diversity of gut micro-

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biota is important for maturation of the immune system.18 Among these infants, total counts of bifidobacteria
and lactobacilli were significantly higher in the active
group, which indicates the effectiveness of our intervention.12
Some parents encountered problems in administering
the powder to their newborn infants. Although parents
had received illustrated instructions to mix the powder
with liquid, the powder caused a choking event in one
infant. Therefore, if the preparation is administered as a
powder, parents should receive personal instruction to
mix the powder with adequate quantities of breast milk

or formula. The GOS syrup alone was easily administered and had no such disadvantage.
We chose structured questionnaires and interviews
rather than diaries, to enhance compliance during the
long follow-up period. This limited the detailed information available on the duration and severity of infectious
diseases but allowed us to compare incidences of infections.
We observed no benefit of the synbiotics in feedingrelated behaviors. During our intervention, the majority
of infants (70%) were breastfed. Breast milk contains
large quantities of GOSs (0.8 g/100 mL), which is noteworthy when our results are compared with the benefits
of GOSs for bottle-fed infants.19,20 More than simethicone, Lactobacillus reuteri has ameliorated infantile colic
in breastfed infants.21 We observed no such effect, however. The overall incidence of infantile colic (4%) was
lower than that in the aforementioned trials20,21 and less
than the 9% incidence of infantile colic in a communitybased trial.22 Parents of colicky infants in our study received counseling from our trained nurses and thus
might have felt more confident in handling such symptoms.
Gut microbiota contribute to the host’s energy metabolism.10 Probiotic bacteria may enhance the uptake of
nutrients and thereby increase nutritional status (ie, improve growth and iron status).23 In Estonia, bottle-fed
infants who received L rhamnosus GG-enriched formula
for 6 months grew better than did those who received
regular formula.24 In the United States, growth was similar in 3- to 24-month-old infants who received Bifidobacterium lactis and Streptococcus thermophilus or a placebo.11 Consistently, the normal growth observed in
both our study groups did not support improved growth
with probiotics in otherwise well-nourished infants.
The occurrence of fewer respiratory infections with
our synbiotics is in line with the results of a large randomized trial in which L rhamnosus GG improved resistance to respiratory infections in infants attending day
care.8 In an Israeli multicenter trial, L reuteri and B lactis
provided no protection against respiratory infections
among children in day care, but the use of L reuteri was
associated with fewer prescribed antibiotics.25 In contrast, newborn Australian infants who received L acidophilus postnatally for 6 months received no protection
from atopy or respiratory infections but were more likely
to be given antibiotics.17 The lower frequency of antibiotic use among infants in day care who received formula
containing S thermophilus plus B lactis11 agrees with the

results of our study, indicating fewer antibiotic courses
throughout the intervention. We infer that feeding synbiotics promotes maturation of the immune system,
which results in 13% risk reduction for respiratory infections from 6 to 24 months of age.
Our synbiotics failed to prevent episodes of diarrhea,
which were rare (14%) during the intervention. In the
Finnish study among children in day care, L rhamnosus
GG in milk failed to reduce the already low incidence of
gastroenteritis.8
Our cohort consisted of infants who were genetically
at risk for atopy. Some researchers have proposed that
immune maturation in atopic infants is delayed,26 because they exhibit weaker antibody responses to vaccines27 and their resistance to respiratory infections is
compromised.28 Our results support the idea that probiotics and prebiotics may enhance immune maturation
and protect infants against respiratory pathogens.1
CONCLUSIONS
This study indicates that the use of live probiotic bacteria
and prebiotic nutrients, even when administered to
newborn infants over the long term, carries no risks.
Feeding probiotic bacteria to urban westernized infants
genetically prone to atopy may increase their resistance
to infection. Additional in vivo studies are warranted to
identify the immunologic mechanisms that produce
these benefits.
ACKNOWLEDGMENTS
This study was supported by the Helsinki University
Central Hospital Research Funds and Valio (Helsinki,
Finland).
REFERENCES
1. Cross ML. Microbes versus microbes: immune signals generated by probiotic lactobacilli and their role in protection against
microbial pathogens. FEMS Immunol Med Microbiol. 2002;34(4):
245–253

2. Viljanen M, Savilahti E, Haahtela T, et al. Probiotics in the
treatment of atopic eczema/dermatitis syndrome in infants: a
double-blind placebo-controlled trial. Allergy. 2005;60(4):
494 –500
3. Boehm G, Stahl B. Oligosaccharides from milk. J Nutr. 2007;
137(3 suppl 2):847S– 849S
4. Schley PD, Field CJ. The immune-enhancing effects of dietary
fibres and prebiotics. Br J Nutr. 2002;87(suppl 2):S221–S230
5. Schultz M, Sartor RB. Probiotics and inflammatory bowel diseases. Am J Gastroenterol. 2000;95(1 suppl):S19 –S21
6. Boyle RJ, Tang ML. The role of probiotics in the management
of allergic disease. Clin Exp Allergy. 2006;36(5):568 –576
7. Szajewska H, Mrukowicz JZ. Probiotics in the treatment and
prevention of acute infectious diarrhea in infants and children:
a systematic review of published randomized, double-blind,
placebo-controlled trials. J Pediatr Gastroenterol Nutr. 2001;
33(suppl 2):S17–S25
8. Hatakka K, Savilahti E, Po¨nka¨ A, et al. Effect of long term
consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial. BMJ. 2001;
322(7298):1327
9. Salminen MK, Tynkkynen S, Rautelin H, et al. Lactobacillus
bacteremia during a rapid increase in probiotic use of Lactoba-

PEDIATRICS Volume 122, Number 1, July 2008

Downloaded from pediatrics.aappublications.org at Viet Nam:AAP Sponsored on March 2, 2013

11


10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

cillus rhamnosus GG in Finland. Clin Infect Dis. 2002;35(10):
1155–1160
Kelly D, Conway S, Aminov R. Commensal gut bacteria: mechanisms of immune modulation. Trends Immunol. 2005;26(6):
326 –333
Saavedra JM, Abi-Hanna A, Moore N, Yolken RH. Long-term
consumption of infant formulas containing live probiotic
bacteria: tolerance and safety. Am J Clin Nutr. 2004;79(2):
261–267
Kukkonen K, Savilahti E, Haahtela T, et al. Probiotics and
prebiotic galacto-oligosaccharides in the prevention of allergic
diseases: a randomized, double-blind, placebo-controlled trial.

J Allergy Clin Immunol. 2007;119(1):192–198
Sorva R, Tolppanen EM, Perheentupa J. Variation of growth in
length and weight of children, part I: years 1 and 2. Acta
Paediatr Scand. 1990;79(5):490 – 497
Hyman PE, Milla PJ, Benninga MA, Davidson GP, Fleisher DF,
Taminiau J. Childhood functional gastrointestinal disorders:
neonate/toddler. Gastroenterology. 2006;130(5):1519 –1526
Penders J, Thijs C, Vink C, et al. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics.
2006;118(2):511–521
Schultz M, Gottl C, Young RJ, Iwen P, Vanderhoof JA. Administration of oral probiotic bacteria to pregnant women causes
temporary infantile colonization. J Pediatr Gastroenterol Nutr.
2004;38(3):293–297
Taylor AL, Dunstan JA, Prescott SL. Probiotic supplementation
for the first 6 months of life fails to reduce the risk of atopic
dermatitis and increases the risk of allergen sensitization in
high-risk children: a randomized controlled trial. J Allergy Clin
Immunol. 2007;119(1):184 –191
Ba¨ckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI.
Host-bacterial mutualism in the human intestine. Science. 2005;
307(5717):1915–1920
Ziegler E, Vanderhoof JA, Petschow B, et al. Term infants fed
formula supplemented with selected blends of prebiotics grow

20.

21.

22.

23.

24.

25.

26.

27.

28.

normally and have soft stools similar to those reported for
breast-fed infants. J Pediatr Gastroenterol Nutr. 2007;44(3):
359 –364
Moro G, Arslanoglu S, Stahl B, Jelinek J, Wahn U, Boehm G.
A mixture of prebiotic oligosaccharides reduces the incidence
of atopic dermatitis during the first six months of age. Arch Dis
Child. 2006;91(10):814 – 819
Savino F, Pelle E, Palumeri E, Oggero R, Miniero R. Lactobacillus reuteri (American Type Culture Collection strain 55730)
versus simethicone in the treatment of infantile colic: a prospective randomized study. Pediatrics. 2007;119(1). Available
at: www.pediatrics.org/cgi/content/full/119/1/e124
Canivet C, Jakobsson I, Hagander B. Colicky infants according
to maternal reports in telephone interviews and diaries: a large
Scandinavian study. J Dev Behav Pediatr. 2002;23(1):1– 8
Branca F, Rossi L. The role of fermented milk in complementary feeding of young children: lessons from transition countries. Eur J Clin Nutr. 2002;56(suppl 4):S16 –S20
Vendt N, Grunberg H, Tuure T, et al. Growth during the first 6
months of life in infants using formula enriched with Lactobacillus rhamnosus GG: double-blind, randomized trial. J Hum Nutr
Diet. 2006;19(1):51–58
Weizman Z, Asli G, Alsheikh A. Effect of a probiotic infant
formula on infections in child care centers: comparison of two

probiotic agents. Pediatrics. 2005;115(1):5–9
Jung T, Lack G, Schauer U, et al. Decreased frequency of
interferon-␥- and interleukin-2-producing cells in patients
with atopic diseases measured at the single cell level. J Allergy
Clin Immunol. 1995;96(4):515–527
Prescott SL, Sly PD, Holt PG. Raised serum IgE associated with
reduced responsiveness to DPT vaccination during infancy.
Lancet. 1998;351(9114):1489
Paunio M, Peltola H, Virtanen M, Leinikki P, Ma¨kela¨ A, Heinonen OP. Acute infections, infection pressure, and atopy. Clin
Exp Allergy. 2006;36(5):634 – 639

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personal satisfaction and unconditional love, she’d rake in a nifty sum of
nearly $117,000 a year. That’s according to a pre-Mother’s Day study released
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compensation. The eighth annual survey calculated a mom’s market value by
studying pay levels for 10 job titles with duties that a typical mom performs,
ranging from housekeeper and day care center teacher to van driver, psychologist and chief executive officer. One stay-at-home mom said the sixfigure salary sounds a little low.”
Burlington Free Press. May 9, 2008
Noted by JFL, MD

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Long-Term Safety and Impact on Infection Rates of Postnatal Probiotic and

Prebiotic (Synbiotic) Treatment: Randomized, Double-Blind, Placebo-Controlled
Trial
Kaarina Kukkonen, Erkki Savilahti, Tari Haahtela, Kaisu Juntunen-Backman, Riitta
Korpela, Tuija Poussa, Tuula Tuure and Mikael Kuitunen
Pediatrics 2008;122;8
DOI: 10.1542/peds.2007-1192
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
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