Effects of Infant Formula With Human Milk Oligosaccharides on Growth and Morbidity: A Randomized Multicenter Trial.

OBJECTIVES: The aim of the study was to evaluate the effects of infant formula supplemented with 2 human milk oligosaccharides (HMOs) on infant growth, tolerance, and morbidity. METHODS: Healthy infants, 0 to 14 days old, were randomized to an intact-protein, cow's milk-based infant formula (control, n = 87) or the same formula with 1.0 g/L 2'fucosyllactose (2'FL) and 0.5 g/L lacto-N-neotetraose (LNnT) (test, n = 88) from enrollment to 6 months; all infants received standard follow-up formula without HMOs from 6 to 12 months. Primary endpoint was weight gain through 4 months. Secondary endpoints included additional anthropometric measures, gastrointestinal tolerance, behavioral patterns, and morbidity through age 12 months. RESULTS: Weight gain was similar in both groups (mean difference [95% confidence interval] test vs control: -0.30 [-1.94, 1.34] g/day; lower bound of 95% confidence interval was above noninferiority margin [-3 g/day]). Digestive symptoms and behavioral patterns were similar between groups; exceptions included softer stool (P = 0.021) and fewer nighttime wake-ups (P = 0.036) in the test group at 2 months. Infants receiving test (vs control) had significantly fewer parental reports (P = 0.004-0.047) of bronchitis through 4 (2.3% vs 12.6%), 6 (6.8% vs 21.8%), and 12 months (10.2% vs 27.6%); lower respiratory tract infection (adverse event cluster) through 12 months (19.3% vs 34.5%); antipyretics use through 4 months (15.9% vs 29.9%); and antibiotics use through 6 (34.1% vs 49.4%) and 12 months (42.0% vs 60.9%). CONCLUSIONS: Infant formula with 2'FL and LNnT is safe, well-tolerated, and supports age-appropriate growth. Secondary outcome findings showing associations between consuming HMO-supplemented formula and lower parent-reported morbidity (particularly bronchitis) and medication use (antipyretics and antibiotics) warrant confirmation in future studies.

Growth and safety evaluation of infant formulae containing oligosaccharides derived from bovine milk: a randomized, double-blind, noninferiority trial.

BACKGROUND: A limited number of nondigestible oligosaccharides are available for use in infant formula. This study evaluated growth and safety in infants fed formula supplemented with a mixture of bovine milk-derived oligosaccharides (BMOS). This mixture, which was generated from whey permeate, contains galactooligosaccharides and other oligosaccharides from bovine milk, such as 3'- and 6'-sialyllactose. We hypothesized that growth in infants fed BMOS-supplemented formula would be noninferior to that in infants fed standard formula. METHODS: Healthy term infants ≤14 days old were randomly assigned to standard formula (control; n = 84); standard formula with BMOS (IF-BMOS; n = 99); or standard formula with BMOS and probiotics (Bifidobacterium longum, Lactobacillus rhamnosus) (IF-BMOS + Pro; n = 98). A breastfed reference group was also enrolled (n = 30). The primary outcome was mean weight gain/day from enrollment to age 4 months (noninferiority margin: -3.0 g/day). RESULTS: 189 (67.3%) formula-fed infants were included in the primary analysis. Mean differences in weight gain between the control and IF-BMOS and IF-BMOS + Pro groups were <1 g/day, with 97.5% confidence intervals above -3.0 g/day, indicating noninferior weight gain in the BMOS formula groups. Compared with control, infants in the BMOS groups had more frequent (p < 0.0001) and less hard (p = 0.0003) stools. No significant differences were observed between the control and BMOS groups in caregivers' reports of flatulence, vomiting, spitting up, crying, fussing, and colic. When based on clinical evaluation by the investigator, the incidence of colic was higher (p = 0.01) in IF-BMOS than in control; the incidence of investigator-diagnosed colic was not significantly different in control and IF-BMOS + Pro (p = 0.15). Stool bifidobacteria and lactobacilli counts were higher with IF-BMOS + Pro compared with control (p < 0.05), whereas Clostridia counts were lower (p < 0.05) in both BMOS groups compared with control. CONCLUSIONS: Infant formula containing BMOS either with or without probiotics provides adequate nutrition for normal growth in healthy term infants. Further studies are needed to fully explore the digestive tolerance of BMOS formula. TRIAL REGISTRATION: ClinicalTrials.gov NCT01886898 . Registered 24 June 2013.

Epidemiology of Toxoplasma and CMV serology and of GBS colonization in pregnancy and neonatal outcome in a Sicilian population.

BACKGROUND: Aim of our study is to analyze the immunological status in pregnancy for two main TORCH agents, Toxoplasma and Cytomegalovirus (CMV), and the results of group B streptococcus (GBS) screening, assessing the risk for congenital infection in a population from Palermo, Italy. METHODS: We retrospectively analyzed the medical records of all inborn live newborns who were born in our division during 2012, gathering information about the mother, the pregnancy and neonatal hospitalization at birth. Whenever data were available, we categorized the serologic status of the mothers for Toxoplasma and CMV. We also considered the results of rectal and vaginal swabs for GBS. We compared the results in Italian and immigrant mothers. The neonatal outcome was evaluated in all cases at risk. RESULTS: Prevalence of anti-Toxo IgG antibodies was 17.97%, and was significantly higher in immigrant women (30% vs 16.4% in Italian women; p = 0.0008). Prevalence of anti-CMV IgG antibodies was 65.87%. Again, it was significantly higher in immigrant women (91.4% vs 62.5%, p = 3.31e-08). We compared those data with a previous study performed in our hospital in 2005-2006, and found that the prevalence of anti-Toxoplasma and anti-CMV antibodies in our population has remained stable, both in the immigrant and in the local population. Seroconversion rates and neonatal infections were rare: no seroconversions were observed for Toxoplasma, 4 seroconversions for CMV. One neonatal Toxoplasma infection and two neonatal CMV infections were documented. In some cases with dubious patterns or probable persistence of IgM, we performed additional tests and follow-up. Vaginal and rectal swabs were positive for GBS in 7.98% of cases, with no significant difference between the Italian and the immigrant population. No GBS neonatal sepsis was documented. CONCLUSIONS: The prevalence of Toxoplasma IgG antibodies in pregnant women was low in our population, if compared with European countries and with other parts of Italy, and is significantly higher in immigrant women. The prevalence of CMV IgG antibodies was intermediate if compared to other countries, and it was higher in immigrant women. GBS positivity was low, and comparable in Italian and immigrant mothers. Neonatal infection was rare for all these agents.

Clinical evaluation of a new starter formula for infants containing live Bifidobacterium longum BL999 and prebiotics.

OBJECTIVES: The larger number of bifidobacteria in the intestine of breast-fed infants has been associated with their better health compared with formula-fed infants. We assessed the safety and tolerability of an experimental formula containing 2 x 10(7) colony-forming units of Bifidobacterium longum BL999 and 4 g/L of a prebiotic mixture containing 90% galacto-oligosaccharides and 10% fructo-oligosaccharides. METHODS: A 7-mo prospective, randomized, reference-controlled, double-blinded trial was performed in infants who were not breast fed after the 14th day of birth. One hundred thirty-eight infants were enrolled and assigned to receive the control or experimental formula until they were 112 d old. Mean weight gain (primary outcome) and recumbent length, head circumference, tolerability (gastrointestinal symptoms), and overall morbidity (secondary outcomes) were measured at 14, 28, 56, 84, and 112 d of age. RESULTS: Equivalence in mean weight gain between the two groups was shown. The treatment difference in the intention-to-treat and per-protocol populations were within the predefined equivalence boundaries of +/-3.9 g/d. No statistically significant difference in recumbent length, head circumference, or incidence of adverse events was found between the two groups. Infants in the experimental group had fewer incidences of constipation and had stool characteristics that suggest that the experimental formula was tolerated well. Furthermore, these infants showed a trend toward fewer respiratory tract infections. CONCLUSIONS: The starter formula containing BL999 and galacto-oligosaccharides/fructo-oligosaccharides is safe and well-tolerated.

Pregnant women as a sentinel population to target and implement hepatitis B virus (HBV) vaccine coverage: a three-year survey in Palermo, Sicily.

Hepatitis B virus (HBV) vaccine coverage was assessed using serologic patterns of infection (HBsAg, anti HBc) and vaccine-induced immunity (isolated anti HBs) among 3318 pregnant women attending the Obstetrical Unit of the University Hospital in Palermo who were screened over 3 years (2001-2003). Three thousand and eight of them (90.6%) were born in Sicily, whereas 310 (9.4%) were immigrants from non-EU countries. The overall prevalence of HBsAg was 1.1%, and it was significantly higher among immigrant than indigenous women (4.2% versus 0.8%; OR 5.26; p < 0.0001). Serologic evidence of past HBV infection (anti HBc) also was significantly higher in immigrants than in Sicilian women (24.5% versus 5.2%, respectively). Women aged 17-21 in our study were in cohorts that had been targeted since 1991 for mandatory HBV vaccination at age 12. In this targeted age group, 74.2% of the Sicilian women had isolated anti HBs, compared to only 15.0% among immigrants. The results suggest the need to improve HBV immunization of Sicilian adolescents and especially to implement active surveillance and to launch an HBV immunization programme that targets immigrants to Sicily.