OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disease characterised by accumulation of large-droplet fat in hepatocytes with possible progression to inflammation and fibrosis. Breastfeeding has benefits for child health, both during infancy and later in life, reducing the risk of manifestations of the metabolic syndrome. Here we investigated the association between early type of feeding (breastfed versus formula-fed and duration of breastfeeding) and later NAFLD development.

STUDY DESIGN: We investigated 191 young Caucasian children (3-18 years old) with NAFLD consecutively enrolled between January 2003 and September 2007 in our centre. 48% of these children (n = 91) had been breastfed for a median (interquartile range) time of 8 (7) months.

RESULTS: After correction for age, waist circumference, gestational age and neonatal weight, the odds of non-alcoholic steatohepatitis (NASH) (OR 0.04, 95% CI 0.01 to 0.10) and fibrosis (OR 0.32, 95% CI 0.16 to 0.65) were lower in breastfed versus not breastfed infants. Moreover, the odds of NASH (OR 0.70, exact 95% CI 0.001 to 0.87) and fibrosis (OR 0.86, exact 95% CI 0.75 to 0.98) decreased for every month of breastfeeding.

CONCLUSIONS: This observational study suggests that earlier feeding habits might affect the clinical expression of NASH from 3 to 18 years later, with an apparent drug-like preventive effect of breastfeeding.

OBJECTIVE: Beneficial effects of breast milk on cognitive skills and behavior ratings have been demonstrated previously in term and very low birth weight infants. Extremely low birth weight infants are known to be at increased risk for developmental and behavior morbidities. The benefits of breast milk that is ingested in the NICU by extremely low birth weight infants on development and behavior have not been evaluated previously.

METHODS: Nutrition data including enteral and parenteral feeds were collected prospectively, and follow-up assessments of 1035 extremely low birth weight infants at 18 months' corrected age were completed at 15 sites that were participants in the National Institute of Child Health and Human Development Neonatal Research Network Glutamine Trial between October 14, 1999, and June 25, 2001. Total volume of breast milk feeds (mL/kg per day) during hospitalization was calculated. Neonatal characteristics and morbidities, interim history, and neurodevelopmental and growth outcomes at 18 to 22 months' corrected age were assessed.

RESULTS: There were 775 (74.9%) infants in the breast milk and 260 (25.1%) infants in the no breast milk group. Infants in the breast milk group were similar to those in the no breast milk group in every neonatal characteristic and morbidity, including number of days of hospitalization. Mean age of first day of breast milk for the breast milk infants was 9.3 +/- 9 days. Infants in the breast milk group began to ingest non-breast milk formula later (22.8 vs 7.3 days) compared with the non-breast milk group. Age at achieving full enteral feeds was similar between the breast milk and non-breast milk groups (29.0 +/- 18 vs 27.4 +/- 15). Energy intakes of 107.5 kg/day and 105.9 kg/day during the hospitalization did not differ between the breast milk and non-breast milk groups, respectively. At discharge, 30.6% of infants in the breast milk group still were receiving breast milk. Mothers in the breast milk group were significantly more likely to be white (42% vs 27%), be married (50% vs 30%), have a college degree (22% vs 6%), and have private health insurance (34% vs 18%) compared with the no breast milk group. Mothers who were black, had a low household income (or = 85, higher mean Bayley Psychomotor Development Index, and higher Bayley Behavior Rating Scale percentile scores for orientation/engagement, motor regulation, and total score. There were no differences in the rates of moderate to severe cerebral palsy or blindness or hearing impairment between the 2 study groups. There were no differences in the mean weight (10.4 kg vs 10.4 kg), length (80.5 cm vs 80.5 cm), or head circumference (46.8 cm vs 46.6 cm) for the breast milk and no breast milk groups, respectively, at 18 months. Multivariate analyses, adjusting for confounders, confirmed a significant independent association of breast milk on all 4 primary outcomes: the mean Bayley (Mental Development Index, Psychomotor Development Index, Behavior Rating Scale, and incidence of rehospitalization). For every 10-mL/kg per day increase in breast milk ingestion, the Mental Development Index increased by 0.53 points, the Psychomotor Development Index increased by 0.63 points, the Behavior Rating Scale percentile score increased by 0.82 points, and the likelihood of rehospitalization decreased by 6%. In an effort to identify a threshold effect of breast milk on Bayley Mental Development Index and Psychomotor Development Index scores and Behavior Rating Scale percentile scores, the mean volume of breast milk per kilogram per day during the hospitalization was calculated, and infants in the breast milk group were divided into quintiles of breast milk ingestion adjusted for confounders. Overall, the differences across the feeding quintiles of Mental Development Index and Psychomotor Development Index were significant. There was a 14.0% difference in Behavior Rating Scale scores between the lowest and highest quintiles. For the outcomes (Mental Development Index, Psychomotor Development Index, Behavior Rating Scale, and Rehospitalization<1 year), only the values for the>80th percentile quintile of breast milk feeding were significantly different from the no breast milk values. In our adjusted regression analyses, every 10 mL/kg per day breast milk contributed 0.53 points to the Bayley Mental Development Index; therefore, the impact of breast milk ingestion during the hospitalization for infants in the highest quintile (110 mL/kg per day) on the Bayley Mental Development Index would be 10 x 0.53, or 5.3 points.

CONCLUSIONS: An increase of 5 points potentially would optimize outcomes and decrease costs by decreasing the number of very low birth weight children who require special education services. The societal implications of a 5-point potential difference (one third of an SD) in IQ are substantial. The potential long-term benefit of receiving breast milk in the NICU for extremely low birth weight infants may be to optimize cognitive potential and reduce the need for early intervention and special education services.

AIM: To study the effect of breastfeeding (BF) on growth, lung function and number of infections during the first 3 years of life in children with cystic fibrosis (CF). MATERIAL AND METHODS: One hundred forty-six CF patients, 5-18 years old, were recruited at their annual care visit. Information about infant feeding, psychosocial and socioeconomic conditions and smoking exposure was obtained by interviews. Anthropometric parameters at 1 year of age and the number of infections and hospitalisations during the first 3 years of life were obtained from clinical charts. Anthropometrics and pulmonary function parameters were obtained at enrollment. RESULTS: In CF patients, particularly those with pancreatic insufficiency, the prevalence of BF was lower than the general Italian population. After multivariate analysis patients with prolonged BF showed higher values of CED expiratory volume in 1 sec (FEV-1) (p = 0.001) and a lower number of infections during the first 3 years of life (p = 0.098). CONCLUSION: Prolonged BF is beneficial in children with CF and may protect them against decline of pulmonary function. Particular attention should be paid to promote BF in infants with CF.

BACKGROUND:Bovine beta-casein is a cow's milk protein that targets both humoral and cellular immune responses in patients with Type 1 diabetes and, to a lesser degree, also in normal subjects. In this study we aimed to determine whether the avoidance of cow's milk consumption early in life could prevent the development of antibody response to bovine beta-casein despite the mother being exposed on a daily basis to cow's milk consumption.

MATERIALS AND METHODS:We measured the antibody response to bovine beta-casein using an ELISA method in 28 healthy infants under 4 months of age, of whom 16 were exclusively breast-fed and 12 were bottle-fed with cow's milk. In addition, beta-casein antibodies were measured in 37 prepubertal children with Type 1 diabetes and in 31 healthy children who were exposed to cow's milk or dairy products to see whether differences in antibody titers exist in this young age group. Antibodies binding to beta-casein were also evaluated by immunoblotting analysis.

RESULTS:Elevated levels of beta-casein antibodies were found in bottle-fed infants compared to breast-fed infants (p<0.0001). Antibody levels to bovine beta-casein were also significantly higher in children with Type 1 diabetes compared to age-matched controls (p=0.03). By western blot analysis we confirmed specific binding to bovine beta-casein in bottle-fed infants, in children with Type 1 diabetes and in controls exposed to cow's milk, but not in infants who were exclusively breast-fed.

CONCLUSIONS:The results of this study indicate that breastfeeding within the first 4 months of life prevents the generation of antibody response to bovine beta-casein despite the mothers' consumption of cow's milk during the breastfeeding period. These findings may have relevance for disease prevention.

Breast-feeding plays an important role for the development of the newborn. Non-breast fed premature born infants show a significantly higher risk of developing diseases like infantile diarrhoea and necrotizing enterocolitis. In this study, the content of neurotrophic factors and cytokines, which might influence the postnatal development of the enteric nervous system (ENS), was determined in human breast milk. Glial cell-line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF) as well as a panel of cytokines were analyzed using single factor or multiplex ELISA. In order to link their presence in milk with possible effects on the development of the ENS, rat myenteric neurons were cultured in protein extracts from breast milk. Neurite outgrowth, neuron survival and nestin expression in glial cells were measured. Growth factors and cytokines were found in all breast milk samples at varying concentrations. It could be demonstrated that protein extracts of breast milk increased the amount of surviving enteric neurones as well as neurite outgrowth. Additionally it was shown, that the number of nestin and S100-expressing glial cells increased significantly after incubating in breast milk protein extracts. The data suggest that milk-born proteins support the development of the enteric nervous system.

BACKGROUND: The protective effect of breast-feeding on the development of childhood asthma remains a matter of controversy. We conducted a systematic review of prospective studies that evaluated the association between exclusive breast-feeding during the first 3 months after birth and asthma. STUDY DESIGN: We searched the 1966-1999 MEDLINE database and reviewed reference lists of relevant articles to identify 12 prospective studies that met pre-stated inclusion criteria. Methodological aspects of the studies, duration and exclusivity of breast-feeding, and outcomes were assessed. Effect estimates were abstracted by the investigators, using a standardized approach. RESULTS: The summary odds ratio (OR) for the protective effect of breast-feeding was 0.70 (95% CI 0.60 to 0.81). The effect estimate was greater in studies of children with a family history of atopy (OR = 0.52) than in studies of a combined population (OR = 0.73). CONCLUSIONS: Exclusive breast-feeding during the first months after birth is associated with lower asthma rates during childhood. The effect, caused by immunomodulatory qualities of breast milk, avoidance of allergens, or a combination of these and other factors, strengthens the advantage of breast-feeding, especially if a family history of atopy is present.

Nontypeable Haemophilus influenzae (NTHi) causes acute otitis media (AOM) in infants. Breast-feeding protects against AOM and/or nasopharyngeal (NP) colonization; however, the mechanism of protection is incompletely understood. Children with AOM and healthy children were studied according to feeding status: breastfed,breast/formula fed, or formula fed. Cumulative episodes of AOM, ELISA titers of serum IgG antibodies to whole-cell NTHi and vaccine candidate outer membrane protein P6, bactericidal titers of serum and NP colonization by NTHi were assessed. A lower incidence of AOM was found in breast- versus formula-fed children. Levels of specific serum IgG antibody to NTHi and P6 were highest in breast-fed, intermediate in breast/formula fed, and lowest in formula-fed infants. Serum IgG antibody to P6 correlated with bactericidal activity against NTHi. Among children with AOM, the prevalence of NTHi in the NP was lower in breast- versus nonbreast-fed infants. We conclude that breast-feeding shows an association with higher levels of antibodies to NTHi and P6, suggesting that breast-feeding modulates the serum immune response to NTHi and P6. Higher serum IgG might facilitate protection against AOM and NP colonization in breast-fed children.

BACKGROUND: Celiac disease, or permanent gluten-sensitive enteropathy, is an immunologic disease strictly dependent on exposure to wheat gluten or related proteins in rye and barley.

OBJECTIVE: The aim of this study was to explore whether breast-feeding and the mode of introducing dietary gluten influence the risk of celiac disease in childhood.

DESIGN: A population-based incident case-referent study of Swedish children, 627 cases with celiac disease and 1254 referents, was conducted; 78% of the matched sets were included in the final analyses. A questionnaire was used to assess patterns of food introduction to infants. Models were built, based on current epidemiologic and immunologic knowledge of celiac disease, to study the potential influence of dietary patterns on disease risk and were evaluated by conditional logistic regression in multivariate analyses.

RESULTS: The risk of celiac disease was reduced in children aged <2 y if they were still being breast-fed when dietary gluten was introduced [adjusted odds ratio (OR): 0.59; 95% CI: 0.42, 0.83]. This effect was even more pronounced in infants who continued to be breast-fed after dietary gluten was introduced (OR: 0.36; 95% CI: 0.26, 0.51). The risk was greater when gluten was introduced in the diet in large amounts (OR: 1.5; 95% CI: 1.1, 2.1) than when introduced in small or medium amounts. In older children, these risk factors were of no or only minor importance.

CONCLUSIONS: The gradual introduction of gluten-containing foods into the diet of infants while they are still being breast-fed reduces the risk of celiac disease in early childhood and probably also during the subsequent childhood period.

OBJECTIVE: The objective of this study was to evaluate the effects of breastfeeding on the risk for fever after routine immunizations.

METHODS: A prospective cohort study was conducted at a pediatric vaccination center in Naples, Italy. The mothers of the infants scheduled to receive routine immunizations were instructed on how to measure and record infant temperature on the evening of the vaccination and for the subsequent 3 days. The information about the incidence of fever was obtained by telephone on the third day after vaccination. The relative risk for fever in relation to the type of breastfeeding was estimated in multivariate analyses that adjusted for vaccine dose, maternal education and smoking, and number of other children in the household.

RESULTS: A total of 460 infants were recruited, and information on the outcome was obtained for 450 (98%). Fever was reported for 30 (25%), 48 (31%), and 94 (53%) of the infants who were being exclusively breastfed, partially breastfed, or not breastfed at all, respectively (P<.01). The relative risk for fever among infants who were exclusively and partially breastfed was 0.46 (95% confidence interval: 0.33-0.66) and 0.58 (95% confidence interval: 0.44-0.77), respectively. The protection conferred by breastfeeding persisted even when considering the role of several potential confounders.

CONCLUSIONS: In this study, breastfeeding was associated with a decreased incidence of fever after immunizations.

Infants at higher risk of allergic diseases might be breastfed for longer periods compared with infants at lower risk in the hope that breastfeeding might reduce the risk of atopic disorders. Therefore, this intention could manifest as an apparent allergy-promoting effect of breastfeeding or reverse causation. To analyze the effect of breast feeding on the prevalence of allergic diseases at school age, a large questionnaire survey was administered to the parents of schoolchildren aged 7-15 yrs. 13,215 parents responded (response rate, 90.1%). Prevalence rates of allergic diseases were compared according to the type of feeding in infancy (either complete breastfeeding, mixed feeding or complete artificial feeding). In both univariate and multivariate analysis, compared with those with complete artificial feeding, those with mixed and complete breastfeeding showed a significantly lower prevalence of bronchial asthma (BA) (p = 0.01 and 0.003, respectively). On the other hand, in univariate analysis, the prevalence of atopic dermatitis (AD) and food allergy (FA) were significantly higher in those with complete breastfeeding (p = 0.04 and 0.01, respectively). There was a significantly higher proportion of complete breastfeeding among those with greater risk of allergic diseases (presence of family history, either eczema or wheeze within 6 months after birth, or FA in infancy). Therefore, our multivariate analysis included these risks as confounding factors, and we found that the promoting effects of breastfeeding on AD and FA disappeared. In conclusion, our data clearly showed the inhibitory effect of breastfeeding on the prevalence of BA at school age. The apparent promoting effect of breastfeeding on the prevalence of AD and FA is most likely because of reverse causation.

An attenuated severity of infections is among the well-documented benefits of breast-feeding. The degree to which this attenuated severity extends to the amelioration of anorexia is understood incompletely, and possible underlying mechanisms have received limited evaluation. This study was designed to test whether breast-feeding attenuates reductions in energy intake associated with a mild immunologic stimulus and to assess poststimulus relationships among putative reductions in energy intake and serum interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha and leptin concentrations. A quasi-experimental, hospital-based study was conducted in 23 healthy fully breast- (BF) and formula-fed (FF) infants who received the quadruple diphtheria, pertussis, tetanus and hemophilus influenza (DPTH) immunization as an immunologic challenge. Only FF infants had decreased energy intakes (12 +/- 2%, P = 0.001) after immunization. Leptin concentrations increased after immunization only in FF infants (30 +/- 7%, P = 0.03). Correlations between postimmunization increases in IL-beta and reductions in energy intake were of borderline significance (r = -0.56, P = 0.08). These findings support the view that breast-feeding protects against anorectic responses to mild immunologic stimuli. Increases in leptin are associated with reductions in energy consumption in the postimmunization period in FF infants and postimmunization changes in IL-1beta concentrations likely are related to reductions in energy intake in response to immunologic stimuli.

To assess whether breastfeeding protects against acute gastroenteritis (AGE) due to rotavirus (RV) infection compared to RV-negative AGE (RV-) in children age 0-12 months. Data from a community-based study of children with AGE from 30 pediatric practices in Germany, Switzerland, and Austria were evaluated. A case-control design was conducted with RV-positive AGE (RV+) cases and RV- AGE as controls. Odds ratios and 95% confidence intervals were estimated using log-linear regression models adjusting for child's age, family size, number of siblings, child care attendance, and nationality. A total of 1,256 stool samples were collected from infants with AGE; 315 (25%) were RV+ and 941 RV-. Being breastfed in the period of disease inception reduced the risk of AGE due to RV+ (OR, 0.53; 95% CI, 0.37-0.76). In infants 0-6 months of age, the protective effect was stronger (OR, 0.33; 95% CI, 0.19-0.55) than in 7-12-month-old children. Our study adds to the evidence of a protective concurrent effect of breastfeeding against rotavirus infection in infants, particularly in children 6 months and younger. Breastfeeding is important to diminish rotavirus-related gastroenteritis in infants before vaccination can be introduced.

BACKGROUND: Although Autistic Disorder is associated with several congenital conditions, the cause for most cases is unknown. The present study was undertaken to determine whether breastfeeding or the use of infant formula supplemented with docosahexaenoic acid and arachidonic acid is associated with Autistic Disorder. The hypothesis is that breastfeeding and use of infant formula supplemented with docosahexaenoic acid/arachidonic acid are protective for Autistic Disorder.

METHODS: This is a case-control study using data from the Autism Internet Research Survey, an online parental survey conducted from February to April 2005 with results for 861 children with Autistic Disorder and 123 control children. The analyses were performed using logistic regression.

RESULTS: Absence of breastfeeding when compared to breastfeeding for more than six months was significantly associated with an increase in the odds of having autistic disorder when all cases were considered (OR 2.48, 95% CI 1.42, 4.35) and after limiting cases to children with regression in development (OR 1.95, 95% CI 1.01, 3.78). Use of infant formula without docosahexaenoic acid and arachidonic acid supplementation versus exclusive breastfeeding was associated with a significant increase in the odds of autistic disorder when all cases were considered (OR 4.41, 95% CI 1.24, 15.7) and after limiting cases to children with regression in development (OR 12.96, 95% CI 1.27, 132).

CONCLUSION: The results of this preliminary study indicate that children who were not breastfed or were fed infant formula without docosahexaenoic acid/arachidonic acid supplementation were significantly more likely to have autistic disorder.

OBJECT: Previous studies have shown nutritional benefits of breastfeeding for a child's health, especially for protection against infection. Protective factors in human milk locally and systemically prevent infections in the gastrointestinal as well as upper and lower respiratory tracts. It remains unclear whether breastfeeding protects infants against ventriculoperitoneal (VP) shunt infection.

METHODS: A cohort study was conducted from December 2003 to December 2006 at Children's Hospital Medical Center in Tehran, Iran. A total of 127 infants with hydrocephalus who were treated using a VP shunt in the first 6 months of life were enrolled. Each infant's breastfeeding method was classified as either exclusively breastfed (EBF), combination feedings of breast milk and formula (CFBF), or exclusively formula-fed (EFF). Infants were followed up to determine the occurrence of shunt infection within 6 months after operation. Statistical analysis was performed using survival methods.

RESULTS: Infants ranged in age from 4 to 170 days at the time of shunt insertion (mean 69.6 days), and 57% were males. Regarding the breastfeeding categories, 57.5% were EBF, 25.2% were CFBF, and 17.3% were EFF. During the follow-up, shunt infection occurred in 16 patients, within 15 to 173 days after shunt surgery (median 49 days). The 6-month risk of shunt infection was 8.5% (95% confidence interval [CI] 4-18%) in the EBF group, 16.5% (95% CI 7-35%) in the CFBF group, and 26.0% (95% CI 12-52%) in the EFF group. There was no statistically significant difference between these 3 groups (p=0.11). The trend test showed a significant trend between the extent of breastfeeding and the risk of shunt infection (p=0.035), which persisted even after adjustment for potential confounding variables (hazard ratio=2.01, 95% CI 1.01-4). CONCLUSIONS: This study supports the protective effect of breastfeeding against shunt infection during the first 6 months of life and the presence of a dose-response relationship, such that the higher the proportion of an infant's feeding that comes from human milk, the lower the incidence of shunt infection. Encouraging mothers of infants with VP shunts to breastfeed exclusively in the first 6 months of life is recommended.

OBJECTIVE: To test whether breastfeeding's protection against anorectic responses to infection is mediated by n-3 fatty acids' attenuation of interleukin (IL)-1beta and tumor necrosis factor (TNF)alpha.

DESIGN: Experimental and observational studies.

SETTING: A hospital-based study was conducted. SUBJECTS: Five groups of infants were followed; three in the experimental and two in the observational study.

METHODS: Breast-fed- (BF-1), DHA-supplemented formula- (SFF-1), and non-DHA-supplemented formula-fed (FF-1) infants were studied before and after immunization against diphtheria, tetanus, pertussis and haemophilus influenzae type b. Pre- and post-immunization energy intakes (EI) and serum IL-1beta and TNFalpha were measured. The two other groups, breast-fed (BF-2) and formula-fed (FF-2) infants with pneumonia were followed throughout hospitalization. EI, IL-1beta and TNFalpha were measured at admission and discharge. Baseline erythrocyte fatty acid contents were determined.

RESULTS: Both cytokines increased following immunization in all feeding groups. Post-immunization reductions in EI of SFF-1 infants (-11.8+/-5%, CI(95)=-23.3, 1.4%, P=0.07) were intermediate to those observed in BF-1 (-5.2+/-4.2%, CI(95)=-15.2, 5.9%, P=0.27) and FF-1 infants (-18+/-4.4%, CI(95)=-29%, -5.4%, P=0.02). In the observational study, TNFalpha (17.2+/-8.3 vs 3.4+/-3.0 ng/l, P=0.001) and decreases in EI (-31+/-43 vs -15+/-31%, CI(95)=-34%, 0.001%, P=0.056) were greater in FF-2 than in BF-2 infants at admission. Breastfeeding duration was associated positively with docosahexaenoic acid (DHA) erythrocyte contents, and negatively with admission TNFalpha. Decreases in EIs were associated with IL-1beta and TNFalpha concentrations.

CONCLUSION: Reductions in EI following immunologic or infectious stimuli were associated with increases in IL-1beta and TNFalpha. Those reductions were attenuated by breastfeeding, and mediated in part by tissue DHA.

The mammary gland undergoes significant remodeling during pregnancy and lactation, which is fuelled by controlled mammary stem cell (MaSC) proliferation. The scarcity of human lactating breast tissue specimens and the low numbers and quiescent state of MaSCs in the resting breast have hindered understanding of both normal MaSC dynamics and the molecular determinants that drive their aberrant self-renewal in breast cancer. Here, we demonstrate that human breastmilk contains stem cells (hBSCs) with multilineage properties. Breastmilk cells from different donors displayed variable expression of pluripotency genes normally found in human embryonic stem cells (hESCs). These genes included the transcription factors (TFs) OCT4, SOX2, NANOG, known to constitute the core self-renewal circuitry of hESCs. When cultured in the presence of mouse embryonic feeder fibroblasts, a population of hBSCs exhibited an encapsulated ESC-like colony morphology and phenotype and could be passaged in secondary and tertiary clonogenic cultures. While self-renewal TFs were found silenced in the normal resting epithelium, they were dramatically upregulated in breastmilk cells cultured in 3D spheroid conditions. Furthermore, hBSCs differentiated in vitro into cell lineages from all three germ layers. These findings provide evidence that breastmilk represents a novel and noninvasive source of patient-specific stem cells with multilineage potential and establish a method for expansion of these cells in culture. They also highlight the potential of these cells to be used as novel models to understand adult stem cell plasticity and breast cancer, with potential use in bioengineering and tissue regeneration. STEM Cells2012;30:2164-2174.

Background:Premature infants fed formula are more likely to develop necrotizing enterocolitis (NEC) than those who are breastfed, but the mechanisms of intestinal necrosis in NEC and protection by breast milk are unknown. We hypothesized that after lipase digestion, formula, but not fresh breast milk, contains levels of unbound free fatty acids (FFAs) that are cytotoxic to intestinal cells.Methods:We digested multiple term and preterm infant formulas or human milk with pancreatic lipase, proteases (trypsin and chymotrypsin), lipase + proteases, or luminal fluid from a rat small intestine and tested FFA levels and cytotoxicity in vitro on intestinal epithelial cells, endothelial cells, and neutrophils.Results:Lipase digestion of formula, but not milk, caused significant death of neutrophils (ranging from 47 to 99% with formulas vs. 6% with milk) with similar results in endothelial and epithelial cells. FFAs were significantly elevated in digested formula vs. milk and death from formula was significantly decreased with lipase inhibitor pretreatment, or treatments to bind FFAs. Protease digestion significantly increased FFA binding capacity of formula and milk but only enough to decrease cytotoxicity from milk.Conclusion:FFA-induced cytotoxicity may contribute to the pathogenesis of NEC.

The effect of breastfeeding on the development of allergic rhinitis and other atopic conditions has been assessed in many studies but remains controversial. To elucidate this issue, a systematic review was conducted of prospective studies that evaluated the association between exclusive breastfeeding during the first 3 mo after birth and allergic rhinitis. The 1966-2000 MEDLINE databases were searched and the reference lists of relevant articles were reviewed according to predetermined inclusion criteria. The methodological aspects of each study, duration and exclusivity of breastfeeding, outcome measures, control for potential confounding variables and other factors were assessed, and estimates of the association between breastfeeding and allergic rhinitis were abstracted independently by the investigators using a standardized approach. Six prospective studies met the inclusion criteria. The summary odds ratio for the protective effect of breastfeeding was 0.74 (95% confidence interval 0.54-1.01). The effect estimate in studies of children with a family history of atopy was 0.87 (95% confidence interval 0.48-1.58). CONCLUSION: Exclusive breastfeeding during the first 3 mo after birth protects against allergic rhinitis in children, both with and without a family history of atopy. The protective association, although of borderline statistical significance, was substantial. Larger prospective studies with strict methodology and longer periods of follow-up are needed.

PURPOSE: To determine the influence of breastmilk consumption, as a dose response, in very low-birth-weight (VLBW) infants (<1,500 g) on neurodevelopmental outcomes at 6 and 12 months corrected age, and to determine the influence of selected sociodemographic and infant variables on neurodevelopmental outcomes.

SUBJECTS: VLBW infants (n = 148) who were fed mother's milk or formula by parental choice.

DESIGN: Prospective cohort with longitudinal follow-up at 6 and 12 months corrected age.

METHODS: Self-administered questionnaires given to mothers at study entry, before discharge, and at 3-, 6-, and 12-month follow-up visits. During hospitalization, mothers recorded the 24-hour volume of expressed milk once per week. At each follow-up visit, the volume of a single feeding was assessed by pre- and postbreastfeeding test weights of infants measured on an electronic scale accurate to 1.0 g. The amount of breastfeeding was also assessed by feeding records and mother's report.

MAIN OUTCOME MEASURES: The Bayley Scales of Infant Development (2nd Edition), the Mental Developmental Index (MDI), and the Psychomotor Developmental Index (PDI).

PRINCIPAL RESULTS: After controlling for specific sociodemographic and infant variables, this study of VLBW infants showed no statistically significant effect of predominantly breastfeeding compared with predominantly formula feeding on neurodevelopmental outcomes to 12 months corrected age. The most significant predictor of MDI scores at 6 and 12 months corrected age was birth weight, in which higher birth weights predicted higher MDI scores.

CONCLUSIONS: Despite the lack of statistically significant differences, the findings suggest a small but consistent advantage in developmental scores in infants who were fed their mother's milk compared with those who were predominantly formula fed. Supporting parents to breastfeed preterm infants may maximize the potential advantages of early nutrition in the neurodevelopmental outcome of VLBW infants.

BACKGROUND: Breastfeeding is undisputedly preferable to formula feeding for infant nutrition because of its nutritional, immunological and psychological benefits. However, studies on the association between breastfeeding and development of atopic dermatitis (AD) have shown inconsistent results. OBJECTIVES: To examine the association between exclusive breastfeeding for at least 3 months after birth and the development of AD in childhood. METHODS: An electronic literature search of MEDLINE (January 1966-May 2008) and EMBASE (1980-May 2008) was conducted. Prospective cohort studies that met the predetermined criteria were independently assessed by three reviewers. The pooled effect estimate was calculated by random effects model. Heterogeneity across the studies was investigated by meta-regression analysis. RESULTS: Twenty-one studies with 27 study populations were included for meta-analysis. The summary odds ratio (OR) for the effect of exclusive breastfeeding on the risk of AD was 0.89 (95% confidence interval, CI 0.76-1.04). Heterogeneity was found across the studies (chi(2) = 83.6, d.f. = 26; P<0.001). Breastfeeding was associated with a decreased risk of AD (OR 0.70; 95% CI 0.50-0.99) when analysis was restricted to the studies comparing breastfeeding with conventional formula feeding. The pooled OR for study populations with atopic heredity was 0.78 (95% CI 0.58-1.05). CONCLUSIONS: There is no strong evidence of a protective effect of exclusive breastfeeding for at least 3 months against AD, even among children with a positive family history.