Scientific References
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Effect of probiotic supplementation in the first 6 months of life on specific antibody responses to infant Hepatitis B vaccination
Shu ESoha Dave Qi Rong Onga Irvin Gereza Xiaoe Zhangb Pavithra Chollateb Lynette Pei-Chi Sheka Bee Wah Leea Marion Awa
Department of Paediatrics, Yong Loo Lin School of Medicine, National University Health
System, 5 Lower Kent Ridge Road, Singapore 119074, Singapore
Singapore Clinical Research Institute Pte Ltd., Singapore
Probiotics have been shown to enhance specific immune responses to vaccines. We aim to assess the effect of probiotic supplementation on specific IgG antibody responses to Hepatitis B (HepB) vaccination in infants. Compared to controls, probiotic supplementation improved HepB surface antibody responses in subjects receiving monovalent doses of HepB vaccine at 0, 1 month and a DTPa–HepB combination vaccine at 6 months [placebo (n=28): 187.97 (180.70–195.24), probiotic (n = 29): 345.70 (339.41–351.99) mIU/ml] (p = 0.069), but not those who received 3 monovalent doses [placebo (n = 68): 302.34 (296.31–308.37), probiotic (n = 77): 302.06 (296.31–307.81) mIU/ml] (p = 0.996). Probiotics may enhance specific antibody responses in infants receiving certain Hepatitis B vaccine schedules.
Keywords
Probiotics Hepatitis B V accination

Vertical transmission of Malaria in a public maternity of Luanda, Angola (The transmission of malaria from a pregnant woman to the fetus)
Introduction: Malaria is a serious public health problem in Angola. In areas of high prevalence and endemic presence of malaria, the pregnant women are the main group of adults at risk. This has its adverse health consequences and may lead to spontaneous abortion, neonatal death, low birth weight, premature births and delayed cognitive development. Although the passage of plasmodium through the placenta remains a controversy, the occurrence of congenital malaria has been increasingly documented. In Angola, the prevalence of mother-fetus transmission of the disease is unknown. Therefore, it became necessary to investigate the congenital malaria occurrence, besides the already known characteristic occurrence of malaria in the pregnant women and newborn babies in the country.
Methods: This was conducted as a hospital based study, in one of the maternities of Luanda, capital of the country. The study sample consist of pregnant women and their respective live newborn babies weighting ≥ 500g, between June and August 2007. The following maternal information were collected (age, origin, level of education, marital status, gestational age, number of pregnancies), prenatal (prenatal care, number of consultations, prophylaxis for malaria). For the new born (anemia, jaundice, prematurity, fever and blood transfusion) were also collected using a standardized questionnaire. Blood samples from pregnant women’s placenta and umbilical cord were collected during admission and during the delivery for a parasitological examination. The registration and analysis of the data were conducted using the program Epi-Info (6.04d). The frequency of malaria was described and the magnitude of the association between the parasitemia in newborn babies and the characteristics both of the pregnant women and of the newborn babies were estimated by Odds ratio calculation, with intervals of 95% and value of p (≤ 5%).
Results: 500 pregnant women and their 507 newborn babies were observed, however four women pregnant with twins and one born dead were excluded from the study. Among the rest, 22 (4,4%) were positive for malaria (Plasmodium falciparum), parasitemia was detected in 100% of the samples of respective placentas, umbilical cords and new born babies.
Pregnant women who did not go through the prenatal care had five times more probability to transmit malaria to the foetus (p=0,018). Not taking the anti-malaria prophylaxis, represents three times more risk of malaria to the foetus, in relation to women who were treated. (p=0,021). In relation to the characteristics of both the delivery and newborn baby and the occurrence of maternal-fetal transmission, was not statistically significant in relation to any of the investigated variables.
Conclusion: The confirmation of the existence of malaria´s congenital vertical transmission in Luanda makes it imperative and importance to conduct an early laboratorial diagnosis in infants whose mothers present a positive result for malaria, as well as, the enhancement of the diagnostic program and treatment in the network of public health, especially in the pre-natal services.
RESEARCHER:
DR. ELISA PEDRO GASPAR
Graduation: Medical Doctor
Specialty: Pediatrician
Sub Specialty: Neonatology
Master: Maternal and child health & International Public Health
PhD: Doctor of Medicine

Meta-analysis: the effects of Lactobacillus rhamnosus GG supplementation for the prevention of healthcare-associated diarrhoea in children
Background:
In children, healthcare-associated diarrhoea, in particular, due to rotavirus, may prolong the hospital stay and increase medical costs, prompting interest in effective, low-cost, preventive strategies.
Aim :
To review systematically data on the efficacy of administering Lactobacillus rhamnosus GG (LGG) for the prevention of healthcare-associated diarrhoea.
Methods:
MEDLINE, Cochrane Library, trial registries and proceedings of major meetings were systematically searched for randomised controlled trials (RCTs) performed in children aged 1 month to 18 years that compared administration of LGG with placebo or no intervention. Two reviewers assessed studies for inclusion and risk of bias and extracted the data. Outcome measures included the incidences of healthcare-associated diarrhoea and rotavirus gastroenteritis. If appropriate, meta-analyses were carried out using the fixed effects model.
Results:
Three RCTs involving 1092 children were included. Compared with pla-cebo, LGG administration for the duration of hospital stay was associated with significantly lower rates of diarrhoea (two RCTs, n = 823, relative risk, RR 0.37, 95% confidence interval, CI 0.23–0.59) and symptomatic rotavirus gastroenteritis (three RCTs, n = 1043, RR 0.49, 95% CI 0.28–0.86). There was no significant difference between the LGG and the control groups in the incidence of asymptomatic rotavirus infection, duration of hospitalisa- tion or duration of diarrhoea. LGG was well tolerated, and no harms were reported in any of the trials. Aliment Pharmacol Ther 1 EMBASE, Health Source: Edition, the Nursing ⁄ Academic
Conclusion:
In hospitalised children, the administration of Lactobacillus rhamnosus GG compared with placebo has the potential to reduce the overall incidence of healthcare-associated diarrhoea, including rotavirus gastroenteritis.

Efficacy of Lactobacillus GG in prevention of nosocomial diarrhea in infants
Objective: Nosocomial diarrhea is a major problem in pediatric hospitals worldwide. We evaluated the efficacy of orally administered Lactobacillus GG (LGG) in the prevention of this disease in young children.
Study design: Eighty-one children aged 1 to 36 months who were hospital- ized for reasons other than diarrhea were enrolled in a double-blind trial and randomly assigned at admission to receive LGG (n = 45) at a dose of 6 × 109 colony-forming units or a comparable placebo (n = 36) twice daily orally for the duration of their hospital stay.
Results: LGG reduced the risk of nosocomial diarrhea (≥3 loose or watery stools/24 h) in comparison with placebo (6.7% vs 33.3%; relative risk: 0.2; [95% CI: 0.06–0.6]; number needed to treat: 4 [95% CI: 2–10]). The preva- lence of rotavirus infection was similar in LGG and placebo groups (20% vs 27.8%, respectively; relative risk: 0.72; 95% CI: 0.33–1.56). However, the use of LGG compared with placebo significantly reduced the risk of ro- tavirus gastroenteritis (1/45 [2.2%] vs 6/36 [16.7%], respectively; relative risk: 0.13; 95% CI: 0.02–0.79; number needed to treat: 7; 95% CI: 3–40).
Conclusions: Prophylactic use of LGG significantly reduced the risk of nosocomial diarrhea in infants, particularly nosocomial rotavirus gastroen- teritis. (J Pediatr 2001;138:361-5)
Download File: Efficacy of Lactobacillus GG in prevention of nosocomial diarrhea in infants

Prophylactic Use of a Probiotic in the Prevention of Colic, Regurgitation, and Functional Constipation
IMPORTANCE Infantile colic, gastroesophageal reflux, and constipation are the most common functional gastrointestinal disorders that lead to referral to a pediatrician during the first 6 months of life and are often responsible for hospitalization, feeding changes, use of drugs, parental anxiety, and loss of parental working days with relevant social consequences.
OBJECTIVE ToinvestigatewhetheroralsupplementationwithLactobacillusreuteriDSM 17938 during the first 3 months of life can reduce the onset of colic, gastroesophageal reflux, and constipation in term newborns and thereby reduce the socioeconomic impact of these conditions.
DESIGN Aprospective,multicenter,double-masked,placebo-controlledrandomizedclinical trial was performed on term newborns (age <1 week) born at 9 different neonatal units in Italy between September 1, 2010, and October 30, 2012.
SETTING Parentswereaskedtorecordinastructureddiarythenumberofepisodesof regurgitation, duration of inconsolable crying (minutes per day), number of evacuations per day, number of visits to pediatricians, feeding changes, hospitalizations, visits to a pediatric emergency department for a perceived health emergency, pharmacologic interventions, and loss of parental working days.
PARTICIPANTS Intotal,589infantswererandomlyallocatedtoreceiveLreuteriDSM17938or placebo daily for 90 days.
INTERVENTIONS Prophylacticuseofprobiotic.
MAINOUTCOMESANDMEASURES Reductionofdailycryingtime,regurgitation,and constipation during the first 3 months of life. Cost-benefit analysis of the probiotic supplementation.
RESULTS At3monthsofage,themeandurationofcryingtime(38vs71minutes;P<.01),the mean number of regurgitations per day (2.9 vs 4.6; P < .01), and the mean number of evacuations per day (4.2 vs 3.6; P < .01) for the L reuteri DSM 17938 and placebo groups, respectively, were significantly different. The use of L reuteri DSM 17938 resulted in an estimated mean savings per patient of €88 (US $118.71) for the family and an additional €104 (US $140.30) for the community.
CONCLUSIONSANDRELEVANCE ProphylacticuseofLreuteriDSM17938duringthefirst3 months of life reduced the onset of functional gastrointestinal disorders and reduced private and public costs for the management of this condition.
Download File: Prophylactic Use of a Probiotic in the Prevention of Colic, Regurgitation, and Functional Constipation

Occurrence of Lactobacillus reuteri in human breast milk
Human breast milk is considered to be of primary importance for the optimal health, growth and development of the infant (1). Aside from its nutritional value, it also contains several bioactive factors that may enhance the infant’s defences (1,2) and protect it against colonizing pathogens (3,4). It has been suggested that commensal and potential probiotic bacterial components present in breast milk may also be involved in the development of the infant’s gastrointestinal mucosal tissues and its acquisition of a healthy gut microbiota (2,5). Mother’s milk is a consistent source of microorgan- isms for the neonatal gut during several weeks after birth, and it is only after the introduction of solid food that the gut microbiota becomes more diverse and begins to resemble that of adults (5). The bacterial species generally found in healthy human breast milk belong to the genera Staphylococcus, Streptococcus, Lactobacillus, Micrococcus, Enterococcus and Bifidobacterium (4, 6). Some of these genera originate from the surface of the nipple and the surrounding skin and may be adapted to survival in the milk ducts in the breast (1,5).
Lactobacilli make up an important part of the healthy human intestinal microbiota and are thought to be involved in the control and maintenance of the microbiota (7). L. reuteri is an indigenous colonizer of the gastrointestinal (GI) tract of humans and animals (7,8). L. reuteri has been demonstrated to have probiotic properties (7, 12) and has previously been found in breast milk of Finnish women (8,13). Growing evidence that lactobacilli colonization at a very early age may protect the infant from develop- ing atopic allergy (14) points to a possible role for a natural supply of lactobacilli in the breast milk as a beneficial factor for the suckling infant.
Little information is available in the literature concerning the presence of lactobacilli, including L. reuteri, in human breast milk. The present study was undertaken to investigate (i) the occurrence of L. reuteri in human breast milk, and (ii) the possible links between the presence of L. reuteri and the mothers’ geographic areas of residence.

Lower protein in infant formula is associated with lower weight up to age 2 y: a randomized clinical trial1–4
Background: Protein intake during infancy was associated with rapid early weight gain and later obesity in observational studies. Objective: The objective was to test the hypothesis that higher protein intake in infancy leads to more rapid length and weight gain in the first 2 y of life.
Design: In a multicenter European study, 1138 healthy, formula-fed infants were randomly assigned to receive cow milk–based infant and follow-on formula with lower (1.77 and 2.2 g protein/100 kcal) or higher (2.9 and 4.4 g protein/100 kcal) protein contents for the first year. For comparison, 619 exclusively breastfed children were also followed. Weight, length, weight-for-length, and BMI were determined at inclusion and at 3, 6, 12, and 24 mo of age. The pri- mary endpoints were length and weight at 24 mo of age, expressed as length and weight-for-length z scores based on World Health Organization growth standards 2006.
Results: Six hundred thirty-six children in the lower (n 1⁄4 313) and higher (n 1⁄4 323) protein formula groups and 298 children in the breastfed group were followed until 24 mo. Length was not different between randomized groups at any time. At 24 mo, the weight-for- length z score of infants in the lower protein formula group was 0.20 (0.06, 0.34) lower than that of the higher protein group and did not differ from that of the breastfed reference group.
Conclusions: A higher protein content of infant formula is associ- ated with higher weight in the first 2 y of life but has no effect on length. Lower protein intake in infancy might diminish the later risk of overweight and obesity. This trial was registered at clinicaltrials.gov as NCT00338689.
Download File: Lower protein in infant formula is associated with lower weight up to age 2 y: a randomized clinical trial1–4

Effects of Bifidobacterium supplementation on intestinal microbiota composition and the immune response in healthy infants
Background: Intestinal microbiotas are thought to be the most important source of maturational stimuli to the development of the immune system. However, few studies have focused on the development of T helper (Th) 1 immune response and antibody response to vaccinations in healthy infants, especially in a large cohort. Through this randomized, double-blind control trial, we investigated the effects of Bifidobacterium longum BB536 (BB536) supplementation on intestinal microbiota composition and the immune response in term infants.
Methods: In total, 300 healthy newborns were recruited, randomized and fed formula either supplemented with BB536 or with no supplementation. Stool samples were analyzed at months 2, 4 and 11. The representative cytokine for Th1 [interferon-γ (IFN-γ)] and Th2 [interleukin-4 (IL-4)] secretion cells were measured using enzyme-linked immunospot assay at 4 and 7 months of age. The antibody response to vaccines was measured at months 7 and 11.
Results: A total of 264 infants completed the study. The amount of bifidobacteria and the bifidobacteria/ Enterobacteriaceae ratio (B/E) were significantly higher in the BB536 supplementation group at months 2 and 4. The number of IFN-γ secretion cells and the ratio of IFN-γ/IL-4 secretion cells were increased in the BB536 supplementation group at 7 months. Moreover, the higher value of B/E in the early stages seems to be related to the increased Th1 response. No difference was observed between groups in the antibody response after vaccination.
Conclusions: BB536 has positive effects on establishing a healthy intestinal microbiota early in life, and it also plays an important role in improving the Th1 immune response.
World J Pediatr 2016;12(2):177-182
Key words: intestinal microbiota; probiotics supplementation
Download File: Effects of Bifidobacterium supplementation on intestinal microbiota composition and the immune response in healthy infants

Effect of protein intake and weight gain velocity on body fat mass at 6 months of age: The EU Childhood Obesity Programme
INTRODUCTION: Higher protein intake during the first year of life is associated with increased weight gain velocity and body mass index (BMI). However, the relationship of protein intake and weight gain velocity with body composition is unclear. OBJECTIVE: To assess if the increases in weight gain velocity and BMI induced by protein intake early in life are related to an increase in fat or fat-free mass.
MATERIALS AND METHODS: In all, 41 infants randomized at birth to a higher or lower protein content formula (HP 1⁄4 17 and LP 1⁄4 24, respectively) and 25 breastfed infants were included. Anthropometric measures were assessed at baseline, 6, 12 and 24 months, and fat-free mass (FFM) and fat mass (FM) were assessed by isotope dilution at 6 months.
RESULTS: Weight gain velocity (g per month) during the first 6 months of life was significantly higher among HP infants
(807.8 (±93.8) vs 724.2 (±110.0) (P 1⁄4 0.015)). Weight gain velocity strongly correlated with FM z-score (r 1⁄4 0.564, Po0.001) but showed no association with FFM z-scores. FFM showed no association with BMI. Nevertheless, FM strongly correlated with BMI at 6, 12 and 24 months (r 1⁄4 0.475, Po0.001; r 1⁄4 0.332, P 1⁄4 0.007 and r 1⁄4 0.247, P 1⁄4 0.051, respectively). FFM and FM z-scores did not differ significantly between HP and LP infants (0.32±1.75 vs 0.31±1.17 and 0.54±2.81 vs 0.02±1.65, respectively). CONCLUSION: Our findings support the hypothesis that higher protein intakes early in life are associated with faster weight gain and in turn to higher adiposity. This mechanism could be a determinant factor for later obesity risk.
International Journal of Obesity (2012) 36, 548-553; doi:10.1038/ijo.2011.276; published online 7 February 2012
Keywords: body composition; isotope dilution; doubly labelled water; infant nutrition; metabolic programming; fat mass
Download File: Effect of protein intake and weigt gain velocity on body fat mass at 6 month of age