Effects of osteopontin-enriched formula on lymphocyte subsets in the first 6 months of life: a randomized controlled trial.

BackgroundHuman milk is rich in osteopontin (OPN), which has immunomodulatory functions.MethodsIn a randomized controlled trial, standard formula (SF) and the same formula with 65 mg of OPN/L (F65) or 130 mg of OPN/L (F130), representing ~50 and 100% of the OPN concentration in human milk, were compared. We examined frequencies and composition of peripheral blood immune cells by four-color immunoflow cytometry of formula-fed infants at ages 1, 4, and 6 months, and compared them with a breastfed (BF) reference group.ResultsThe F130 group had increased T-cell proportions compared with the SF (P=0.036, average effect size 0.51) and F65 groups (P=0.008, average effect size 0.65). Compared with the BF group, the monocyte proportions were increased in the F65 (P=0.001, average effect size 0.59) and F130 (P=0.006, average effect size 0.50) groups, but were comparable among the formula groups.ConclusionOPN in an infant formula at a concentration close to that of human milk increased the proportion of circulating T cells compared with both SF and formula with added OPN at ~50% of the concentration in human milk. This suggests that OPN may favorably influence immune ontogeny in infancy and that the effects appear to be dose-dependent.

Growth, Nutrition, and Cytokine Response of Breast-fed Infants and Infants Fed Formula With Added Bovine Osteopontin.

OBJECTIVES: Breast milk contains a high concentration of osteopontin (OPN), a protein having multiple functions. In contrast, infant formula is low in OPN. A randomized clinical trial was performed to evaluate effects of adding a highly enriched bovine OPN fraction to formula, and infants whose mothers had already decided not to breast-feed were recruited. They were fed regular formula (F0) or the same formula with bovine OPN at 65 (F65) or 130 (F130) mg/L (50% and 100% of human milk level, respectively) from 1 to 6 months of age and were compared with a reference group of breast-fed (BF) infants. METHODS: Morbidity was recorded daily and 3-day dietary records collected monthly. Anthropometry was assessed monthly, and blood samples were taken at 1, 4, and 6 months of age. Hematology and iron status, serum cytokines, plasma amino acids, and blood urea nitrogen were analyzed. RESULTS: Formulas were well tolerated and there were no significant differences in formula intake or growth among the formula-fed groups. The F130 group had significantly lower plasma threonine than the F0 and F65 groups, and significantly lower plasma branched-chain amino acids (BCAAs) than the F0 group and, thus, was closer to BF infants. Plasma TNF-α was higher in formula-fed infants than in BF infants. Among the formula-fed groups, the proinflammatory cytokine TNF-α was significantly lower in the F65 and F130 groups than in the F0 group, suggesting that OPN downregulates inflammatory cytokines and thus affects immune function. CONCLUSIONS: Addition of OPN to infant formula changes amino acid metabolism and cytokine responses of FF infants and makes them more similar to BF infants. The lower prevalence of pyrexia in the F130 infants than in F0 infants suggests that adding OPN may confer health benefits.

Longitudinal Development of Infant Complementary Diet Diversity in 3 International Cohorts.

OBJECTIVES: To evaluate international differences in the development of minimum dietary diversity (MDD) between 6 and 12 months of age. STUDY DESIGN: Breastfed infants (115, 100, and 109 in Shanghai, Cincinnati, and Mexico City, respectively) were enrolled near birth and dietary intake assessed weekly by 24-hour recall of food frequency. Diet diversity per month from age 6-12 months was assessed as at least 4 of 7 food groups provided on the previous day. RESULTS: Across all cohorts, dietary diversity increased from 6 (31%) to 12 (92%) months of age. Shanghai infants were significantly more likely to achieve MDD than the other cohorts at each month of age. Meat/seafood accounted for a higher proportion of infant feeds in Shanghai compared with the other cohorts, and eggs were only fed in Shanghai, and proportional intake of dairy, grains, and fruit were highest in Cincinnati. Only 28% of Cincinnati infants fed >50% human milk achieved MDD between 6 and 12 months. CONCLUSIONS: The proportion of infants between 6 and 12 months achieving MDD was significantly higher in Shanghai than in Mexico City or Cincinnati at all ages. Of particular concern was low dietary diversity among highly breastfed Cincinnati cohort infants, suggesting a need for greater education of breastfeeding mothers about the need to introduce a diverse complementary food diet.

Specific infant feeding practices do not consistently explain variation in anthropometry at age 1 year in urban United States, Mexico, and China cohorts.

Infant feeding practices generally influence infant growth, but it is unclear how introduction of specific foods affects growth across global populations. We studied 3 urban populations in the Global Exploration of Human Milk study to determine the association between infant feeding and anthropometry at 1 y of age. Three hundred sixty-five breastfeeding mother-infant pairs (120 US, 120 China, and 125 Mexico) were recruited soon after the infant's birth. Enrollment required agreement to breastfeed ≥75% for at least 3 mo. Weekly, 24-h, food frequency data were conducted on infants for 1 y and exclusive breastfeeding (EBF) duration and timing of specific complementary food introduction were calculated. Weight and length were measured at age 1 y and anthropometry Z-scores calculated using WHO standards. Cohorts in the 3 urban populations (Shanghai, China; Cincinnati, USA; and Mexico City, Mexico) differed by median EBF duration (5, 14, and 7 wk, respectively; P < 0.001), timing of introduction of meat/eggs/legumes (4.8, 9.3, and 7.0 mo, respectively; P < 0.0001), and other feeding practices. By age 1 y, infants in Shanghai were heavier and longer than Cincinnati and Mexico City infants (P < 0.001). Adjusting for nonfeeding covariates, the only feeding variable associated with anthropometry was EBF duration, which was modestly inversely associated with weight-for-age but not length-for-age or BMI Z-scores at 1 y. Although feeding variables differed by cohort, their impact on anthropometry differences was not consistent among cohorts. Overall, across these urban, international, breast-fed cohorts, differences in specific feeding practices did not explain the significant variation in anthropometry.

Glycolipid metabolic status of overweight/obese adolescents aged 9- to 15-year-old and the BMI-SDS/BMI cut-off value of predicting dyslipidemiain boys, Shanghai, China: a cross-sectional study.

BACKGROUND: The prevalence of adolescents' obesity and overweight has dramatically elevated in China. Obese children were likely to insulin resistance and dyslipidemia, which are risk factors of cardiovascular diseases. However there was no cut-off point of anthropometric values to predict the risk factors in Chinese adolescents. The present study was to investigate glycolipid metabolism status of adolescents in Shanghai and to explore the correlations between body mass index standard deviation score (BMI-SDS) and metabolic indices, determine the best cut-off value of BMI-SDS to predict dyslipidemia. METHODS: Fifteen schools in Shanghai's two districts were chosen by cluster sampling and primary screening was done in children aged 9-15 years old. After screening of bodyweight and height, overweight and obese adolescents and age-matched children with normal body weight were randomly recruited in the study. Anthropometric measurements, biochemical measurements of glycolipid profiles were done. SPSS19.0 was used to analyze the data. Receiver operating characteristic (ROC) curves were made and the best cut-off values of BMI-SDS to predict dyslipidemia were determined while the Youden indices were maximum. RESULTS: Five hundred and thirty-eight adolescents were enrolled in this research, among which 283 have normal bodyweight, 115 were overweight and 140 were obese. No significant differences of the ages among 3 groups were found. There were significant differences of WC-SDS (p<0.001), triacylglycerol (p<0.05), high and low density lipoprotein cholesterol (p<0.01), fasting insulin (p<0.01) and C-peptide (p<0.001) among 3 groups. Significant difference of fasting glucose was only found between normal weight and overweight group. Significant difference of total cholesterol was found between obese and normal weight group. There was no significant difference of glycated hemoglobin among 3 groups. The same tendency was found in boys but not in girls. Only HDL-C reduced and TG increased while BMI elevated in girls. The best cut-off value of BMI-SDS was 1.22 to predict dyslipidemia in boys. The BMI cut-off was 21.67 in boys. CONCLUSION: Overweight and obese youths had reduced insulin sensitivity and high prevalence of dyslipidemia.When BMI-SDS elevated up to 1.22 and BMI was higher than 21.67 in boys, dyslipidemia may happen.

Is lymphatic invasion of microrectal neuroendocrine tumors an incidental event?: A case report.

BACKGROUND: A rectal neuroendocrine tumor (rNET) is a malignant tumor originating from neuroendocrine cells. Currently, tumor size is the primary basis for assessing tumor risk. CASE SUMMARY: This article reports the case of a 46-year-old male patient who underwent a colonoscopy that found a 3 mm rectal polypoid bulge. The pathological examination of a sample collected with biopsy forceps revealed a neuroendocrine tumor. Further endoscopic submucosal dissection rescue therapy was used. The presence of lymphatic vessels indicated that the tumor had infiltrated the negative resection margin. The lesion was located in the distal rectum near the anal canal. Therefore, to ensure the patient's quality of life, follow-up observation was conducted after full communication with the patient. No tumor recurrence or distant metastasis has been found during the 13-mo follow-up after surgery. CONCLUSION: Despite the presence of lymphatic invasion and extremely small diameter rNETs in our case, this phenomenon may not imply a higher risk of distant lymph node and organ metastasis.

Validation of diagnostic strategies of autoimmune atrophic gastritis: A case report.

BACKGROUND: Autoimmune atrophic gastritis (AAG) is a type of chronic gastritis that mainly affects the gastric corpus. Due to the lack of standard diagnostic criteria and overlaps with the courses of Helicobacter pylori-related atrophic gastritis, reports on the diagnostic strategy of AAG at an early stage are limited. CASE SUMMARY: A 71-year-old woman with severe anemia was diagnosed with AAG. Endoscopic views and pathological findings showed the coexistence of normal mucosa in the gastric antrum and atrophic mucosa in the gastric fundus. Serological tests showed that anti-parietal cell antibodies and anti-intrinsic factor antibodies were both positive. Immunohistochemical results, which showed negative H+-K+ ATPase antibody staining and positive chromogranin A (CgA) staining, confirmed the mechanism of this disease. After vitamin B12 and folic acid supplementation, the patient recovered well. CONCLUSION: Successful diagnosis of AAG includes serological tests, endoscopic characteristics, and immunohistochemistry for H+-K+ ATPase and CgA antibodies.

Sun exposure and vitamin D supplementation in relation to vitamin D status of breastfeeding mothers and infants in the global exploration of human milk study.

Although vitamin D (vD) deficiency is common in breastfed infants and their mothers during pregnancy and lactation, a standardized global comparison is lacking. We studied the prevalence and risk factors for vD deficiency using a standardized protocol in a cohort of breastfeeding mother-infant pairs, enrolled in the Global Exploration of Human Milk Study, designed to examine longitudinally the effect of environment, diet and culture. Mothers planned to provide breast milk for at least three months post-partum and were enrolled at four weeks postpartum in Shanghai, China (n=112), Cincinnati, Ohio (n=119), and Mexico City, Mexico (n=113). Maternal serum 25(OH)D was measured by radioimmunoassay (<50 nmol/L was categorized as deficient). Serum 25(OH)D was measured in a subset of infants (35 Shanghai, 47 Cincinnati and 45 Mexico City) seen at 26 weeks of age during fall and winter seasons. Data collected prospectively included vD supplementation, season and sun index (sun exposure×body surface area exposed while outdoors). Differences and factors associated with vD deficiency were evaluated using appropriate statistical analysis. vD deficiency in order of magnitude was identified in 62%, 52% and 17% of Mexican, Shanghai and Cincinnati mothers, respectively (p<0.001). In regression analysis, vD supplementation (p<0.01), obesity (p=0.03), season (p=0.001) and sites (p<0.001) predicted maternal vD status. vD deficiency in order of magnitude was found in 62%, 28%, and 6% of Mexican, Cincinnati and Shanghai infants, respectively (p<0.001). Season (p=0.022), adding formula feeding (p<0.001) and a higher sun index (p=0.085) predicted higher infant vD status. vD deficiency appears to be a global problem in mothers and infants, though the prevalence in diverse populations may depend upon sun exposure behaviors and vD supplementation. Greater attention to maternal and infant vD status starting during pregnancy is warranted worldwide.

[Variation of maternal milk adiponectin and its correlation with infant growth].

OBJECTIVE: To investigate the variation of human breast milk adiponectin (APN) concentration during lactation, analyze the relationship of APN concentrations in human breast milk with APN in infant serum, determine the association between maternal milk APN and infant body proportionality in the first year of life, and the period of greatest human milk exposure. METHOD: Subjects included 73 mother-infant pairs from Shanghai International Peace Maternity & Child Health Hospital. Maternal milk was collected at 2, 4, 13, 26 weeks and infant serum was collected at 26 weeks. The concentration of APN in maternal milk and infant serum were measured with commercially available ELISAs (R&D Systems). Weight-for-age Z-scores (WAZ), length-for-age Z-scores (LAZ), weight-for-length Z-scores (WLZ) and body mass index Z-scores (zBMI) of infants up to 1 year of age were calculated using World Health Organization (WHO) standards. Then the variation of maternal milk APN was investigated, the correlation between maternal milk APN and infant serum APN was analyzed; multivariate regression analysis was used to analyze covariates correlated with infant body proportionality, meanwhile determined the association between maternal milk APN and infant anthropometrics. RESULT: The concentration of APN in maternal milk at 2, 4, 13, 26 weeks was respectively (14.62 µg/L, 5.93 - 140.40 µg/L), (7.32 µg/L, 2.04 - 29.35 µg/L), (6.84 µg/L, 2.72 - 15.65 µg/L) and (4.88 µg/L, 1.12 - 13.38 µg/L). Higher milk APN in postpartum 2 weeks was associated with lower infant WAZ at 13, 26 and 52 weeks (P < 0.05). Milk APN in postpartum 4 weeks was inversely related to infant WAZ, WLZ, zBMI at 13, 26 and 52 weeks (all P < 0.05). Meanwhile, milk APN in postpartum 13 weeks had significantly negative correlation with infant WAZ, WLZ, zBMI at 13, 26 and 52 weeks (P < 0.01). Milk APN in postpartum 26 weeks also was inversely associated with infant WAZ, WLZ and zBMI at 52 weeks (P < 0.05). After adjusting covariates like birth weight using multivariate regression analysis, milk APN level is the most important influence factor to infant WAZ, WLZ, zBMI at 13, 26 and 52 weeks. There was a positive correlation between maternal milk APN and infant serum APN at 13, 26 weeks. CONCLUSION: Milk APN concentration declines throughout lactation. Maternal milk APN may play a vital role in the growth and development of breastfed infants, particularly closely associated with infant weight. Infant serum APN clearly correlated with maternal milk APN.

[Establishing the norm of cognitive adaptive test/clinical linguistic and auditory milestone scale in the children from 4 to 36 months of age in Shanghai, China].

OBJECTIVE: To meet the need for instrument assessing the cognitive abilities of infants and young children as well as discriminating between global developmental delay and particular deficits in either language or problem-solving skills, we intended to introduce Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) into China. METHODS: CAT/CLAMS were administered to 1604 normative children aged 4-36 months (in 16 age groups, about 100 children per age group) in Shanghai during the period from December 2003 to June 2004. In the meantime, Gesell Developmental Diagnosis was applied for 100 of these children, respectively aged 4, 6, 12, 18 and 30 months (20 children per age group). Interclass correlation coefficients (ICC) were adopted to analyze data in terms of inter-rater reliability and re-test reliability of the scales of CAT/CLAMS. Cronbach alpha coefficients were calculated to assess the inter consistency of the scales. Pearson correlation coefficients(r) were adopted to analyze the concurrent validity of the scales. The normative percentile graphs of CAT/CLAMS in the children from 4 to 36 Months of age in Shanghai, China were adopted. RESULTS: Administrations of the CAT/CLAMS for each subject usually took 10-20 minutes. Individual scores (CLAMS, CAT, and CAT/CLAMS) increased with ages (Pearson correlation coefficients were 0.96, 0.98 and 0.98, respectively, P < 0.01 for all). ICCs (intraclass correlation coefficient) in terms of individual scores for the inter-rater reliability test and the re-test reliability test were respectively > or = 0.96 (P < 0.01) and > or = 0.95 (P < 0.01), all the Cronbach alpha coefficients were > or = 0.98; in 100 children of the 5 age groups, there was significantly positive correlation between CAT/CLAMS and Gesell Developmental Diagnosis in terms of language skill DQ and adaptive skill DQ, and Full Scale DQ (r = 0.517, 0.703, 0.613, respectively, P < 0.01 for all). Moreover, this significant positive correlation was observed in each of the 5 age groups (r = 0.455-0.827, P < 0.05). CONCLUSION: CAT/CLAMS is suitable for discriminating between global developmental delay and particular deficits in either language or problem-solving skills. It is a quick, reliable, and valid instrument, with refined and quantified results. It is a good tool for developmental surveillance and screening of infants and young children.