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1.  Protection, Promotion, and Support and Global Trends in Breastfeeding123 
Advances in Nutrition  2013;4(2):213-219.
A number of case studies have shown that promotion of breastfeeding (BF) coincides with improved BF and exclusive BF (EBF) practices. We quantify the relationship between BF promotion and changes in BF practices by analyzing the relationship between implementation of the WHO/UNICEF Global Strategy for Infant and Young Child Feeding as measured by the World Breastfeeding Trends Initiative (WBTi) and trends in EBF and BF duration over the past 20 y in 22 countries in Africa, Asia, the Middle East, and Latin America. The median annual increase in EBF was 1.0%/y in countries in the upper 50th percentile of WBTi scores, indicating national policies and programs most consistent with WHO/UNICEF recommendations, whereas the median increase in EBF was only 0.2%/y in countries with the lowest WBTi scores (P = 0.01). The median annual increase in BF duration in all countries was <0.1%/ y. The annual increase in EBF was not associated with maternal demographic factors, such as urban residence, paid maternal employment, maternal education, or gross national income. Our results show that the association between BF protection, promotion, and support and improved EBF is measurable and strengthened by case studies possibly causal.
PMCID: PMC3649101  PMID: 23493537
2.  Randomized Controlled Trial of Docosahexaenoic Acid Supplementation in Midwestern U.S. Human Milk Donors 
Breastfeeding Medicine  2013;8(1):86-91.
Docosahexaenoic acid (DHA) is a long-chain polyunsaturated fatty acid important for neonatal neurodevelopment and immune homeostasis. Preterm infants fed donor milk from a Midwestern source receive only 20% of the intrauterine accretion of DHA. We tested the hypothesis that DHA supplementation of donor mothers would provide preterm infants with DHA intake equivalent to fetal accretion.
Subjects and Methods
After Institutional Review Board approval and informed consent, human milk donors to the Mother's Milk Bank of Ohio were randomized to receive 1 g of DHA (Martek® [now DSM Nutritional Lipids, Columbia, MD]) or placebo soy oil. Dietary intake data were collected and analyzed by a registered dietitian. Fatty acids were measured by gas chromatography/flame ionization detection. Statistical analysis used linear mixed models.
Twenty-one mothers were randomly assigned to either the DHA group (n=10) or the placebo group (n=11). Donor age was a median of 31 years in both groups with a mean lactational stage of 19 weeks. Dietary intake of DHA at baseline in both groups was a median of 23 mg/day (range, 0–194 mg), significantly (p<0.0001) less than the minimum recommended intake of 200 mg/day. The DHA content of milk increased in the DHA-supplemented group (p<0.05).
The women enrolled in this study had low dietary DHA intake. Supplementation with preformed DHA at 1 g/day resulted in increased DHA concentrations in the donor milk with no adverse outcomes. Infants fed donor milk from supplemented women receive dietary DHA levels that closely mimic normal intrauterine accretion during the third trimester.
PMCID: PMC3566653  PMID: 22568471
3.  Human Milk Composition: Nutrients and Bioactive Factors 
The composition of human milk is the biologic norm for infant nutrition. Human milk also contains many hundreds to thousands of distinct bioactive molecules that protect against infection and inflammation and contribute to immune maturation, organ development, and healthy microbial colonization. Some of these molecules, e.g., lactoferrin, are being investigated as novel therapeutic agents. A dynamic, bioactive fluid, human milk changes in composition from colostrum to late lactation, and varies within feeds, diurnally, and between mothers. Feeding infants with expressed human milk is increasing. Pasteurized donor milk is now commonly provided to high risk infants and most mothers in the U.S. express and freeze their milk at some point in lactation for future infant feedings. Many milk proteins are degraded by heat treatment and freeze-thaw cycles may not have the same bioactivity after undergoing these treatments. This article provides an overview of the composition of human milk, sources of its variation, and its clinical relevance.
PMCID: PMC3586783  PMID: 23178060
human milk composition; breastfeeding; infant nutrition; pasteurization; bioactive factors
4.  Heightened attention to supplementation is needed to improve the vitamin D status of breastfeeding mothers and infants when sunshine exposure is restricted 
Maternal & child nutrition  2012;10.1111/j.1740-8709.2012.00422.x.
Although exclusively breastfed infants are at increased risk of vitamin D (vit D) deficiency if vit D supplementation is lacking and sun exposure is limited, assessment of both risk factors in the first year of life is lacking. We evaluated contribution of vit D intake and sunlight exposure to vit D status in 120 healthy, breastfeeding mother-infant dyads, who were followed for 1 year. Vitamin D intake and skin sunlight exposure were evaluated using questionnaires. Serum 25(OH)D, PTH and ALP levels were determined postnatally in mothers at 4 weeks and in infants at 4, 26 and 52 weeks. Vitamin D supplementation was low (<20%) and sunlight exposure was common (93%) in study infants. At 4 weeks, 17% of mothers were vit D deficient (<50 nmol/L) and 49% were insufficient (50-<75 nmol/L), while 18% of infants were severely vit D deficient (<25 nmol/L) and 77% were deficient (<50 nmol/L). At 26 weeks, winter/spring birth season and shorter duration of months of exclusive breastfeeding were protective of vit D deficiency in infants. Vitamin D deficiency in infants decreased to 12% at 52 weeks with sunlight exposure. Serum PTH levels were significantly higher in severely vit D deficient than sufficient infants. Vitamin D deficiency was widespread in early postpartum breastfeeding mothers and infants and declined to 1 in 8 infants at 52 weeks due mostly to sunshine exposure. When sunlight exposure is limited or restricted intensified vit D supplementation of breastfeeding mothers and infants is needed to improve vit D status.
PMCID: PMC3461108  PMID: 22708508
Vitamin D deficiency; breastfeeding; sunlight exposure; infants; mothers
5.  Fatty acid composition in the mature milk of Bolivian forager-horticulturalists: controlled comparisons with a US sample 
Maternal & child nutrition  2012;8(3):10.1111/j.1740-8709.2012.00412.x.
Breast milk fatty acid (FA) composition varies greatly among individual women, including in percentages of the long-chain polyunsaturated FAs (LCPUFA) 20:4n-6 (arachidonic acid, AA) and 22:6n-3 (docosahexaenoic acid, DHA), which are important for infant neurological development. It has been suggested that owing to wide variation in milk LCPUFA and low DHA in Western diets, standards of milk FA composition should be derived from populations consuming traditional diets. We collected breast milk samples from Tsimane women at varying lactational stages (6–82 weeks). The Tsimane are an indigenous, natural fertility, subsistence-level population living in Amazonia Bolivia. Tsimane samples were matched by lactational stage to samples from a US milk bank, and analysed concurrently for FA composition by gas-liquid chromatography. We compared milk FA composition between Tsimane (n = 35) and US (n = 35) mothers, focusing on differences in LCPUFA percentages that may be due to population-typical dietary patterns. Per total FAs, the percentages of AA, DHA, total n-3 and total n-6 LCPUFA were significantly higher among Tsimane mothers. Mean percentages of 18:2n-6 (linoleic acid) and trans FAs were significantly higher among US mothers. Tsimane mothers’ higher milk n-3 and n-6 LCPUFA percentages may be due to their regular consumption of wild game and freshwater fish, as well as comparatively lower intakes of processed foods and oils that may interfere with LCPUFA synthesis.
PMCID: PMC3851016  PMID: 22624983
lactation; diet; docosahexaenoic acid; arachidonic acid; breast milk; infant and child nutrition
6.  Poly-LacNAc as an Age-Specific Ligand for Rotavirus P[11] in Neonates and Infants 
PLoS ONE  2013;8(11):e78113.
Rotavirus (RV) P[11] is an unique genotype that infects neonates. The mechanism of such age-specific host restriction remains unknown. In this study, we explored host mucosal glycans as a potential age-specific factor for attachment of P[11] RVs. Using in vitro binding assays, we demonstrated that VP8* of a P[11] RV (N155) could bind saliva of infants (60.3%, N = 151) but not of adults (0%, N = 48), with a significantly negative correlation between binding of VP8* and ages of infants (P<0.01). Recognition to the infant saliva did not correlate with the ABO, secretor and Lewis histo-blood group antigens (HBGAs) but with the binding of the lectin Lycopersicon esculentum (LEA) that is known to recognize the oligomers of N-acetyllactosamine (LacNAc), a precursor of human HBGAs. Direct evidence of LacNAc involvement in P[11] binding was obtained from specific binding of VP8* with homopolymers of LacNAc in variable lengths through a glycan array analysis of 611 glycans. These results were confirmed by strong binding of VP8* to the Lec2 cell line that expresses LacNAc oligomers but not to the Lec8 cell line lacking the LacNAc. In addition, N155 VP8* and authentic P[11] RVs (human 116E and bovine B223) hemagglutinated human red blood cells that are known to express poly-LacNAc. The potential role of poly-LacNAc in host attachment and infection of RVs has been obtained by abrogation of 116E replication by the PAA-conjugated poly-LacNAc, human milk, and LEA positive infant saliva. Overall, our results suggested that the poly-LacNAc could serve as an age-specific receptor for P[11] RVs and well explained the epidemiology that P[11] RVs mainly infect neonates and young children.
PMCID: PMC3823915  PMID: 24244290
7.  Strategic Global Approaches to Improve Breastfeeding Rates123 
Advances in Nutrition  2012;3(6):829-830.
PMCID: PMC3648710  PMID: 23153740
8.  RNA Sequencing of the Human Milk Fat Layer Transcriptome Reveals Distinct Gene Expression Profiles at Three Stages of Lactation 
PLoS ONE  2013;8(7):e67531.
Aware of the important benefits of human milk, most U.S. women initiate breastfeeding but difficulties with milk supply lead some to quit earlier than intended. Yet, the contribution of maternal physiology to lactation difficulties remains poorly understood. Human milk fat globules, by enveloping cell contents during their secretion into milk, are a rich source of mammary cell RNA. Here, we pair this non-invasive mRNA source with RNA-sequencing to probe the milk fat layer transcriptome during three stages of lactation: colostral, transitional, and mature milk production. The resulting transcriptomes paint an exquisite portrait of human lactation. The resulting transcriptional profiles cluster not by postpartum day, but by milk Na:K ratio, indicating that women sampled during similar postpartum time frames could be at markedly different stages of gene expression. Each stage of lactation is characterized by a dynamic range (105-fold) in transcript abundances not previously observed with microarray technology. We discovered that transcripts for isoferritins and cathepsins are strikingly abundant during colostrum production, highlighting the potential importance of these proteins for neonatal health. Two transcripts, encoding β-casein (CSN2) and α-lactalbumin (LALBA), make up 45% of the total pool of mRNA in mature lactation. Genes significantly expressed across all stages of lactation are associated with making, modifying, transporting, and packaging milk proteins. Stage-specific transcripts are associated with immune defense during the colostral stage, up-regulation of the machinery needed for milk protein synthesis during the transitional stage, and the production of lipids during mature lactation. We observed strong modulation of key genes involved in lactose synthesis and insulin signaling. In particular, protein tyrosine phosphatase, receptor type, F (PTPRF) may serve as a biomarker linking insulin resistance with insufficient milk supply. This study provides the methodology and reference data set to enable future targeted research on the physiological contributors of sub-optimal lactation in humans.
PMCID: PMC3702532  PMID: 23861770
9.  Early microbial and metabolomic signatures predict later onset of necrotizing enterocolitis in preterm infants 
Microbiome  2013;1:13.
Necrotizing enterocolitis (NEC) is a devastating intestinal disease that afflicts 10% of extremely preterm infants. The contribution of early intestinal colonization to NEC onset is not understood, and predictive biomarkers to guide prevention are lacking. We analyzed banked stool and urine samples collected prior to disease onset from infants <29 weeks gestational age, including 11 infants who developed NEC and 21 matched controls who survived free of NEC. Stool bacterial communities were profiled by 16S rRNA gene sequencing. Urinary metabolomic profiles were assessed by NMR.
During postnatal days 4 to 9, samples from infants who later developed NEC tended towards lower alpha diversity (Chao1 index, P = 0.086) and lacked Propionibacterium (P = 0.009) compared to controls. Furthermore, NEC was preceded by distinct forms of dysbiosis. During days 4 to 9, samples from four NEC cases were dominated by members of the Firmicutes (median relative abundance >99% versus <17% in the remaining NEC and controls, P < 0.001). During postnatal days 10 to 16, samples from the remaining NEC cases were dominated by Proteobacteria, specifically Enterobacteriaceae (median relative abundance >99% versus 38% in the other NEC cases and 84% in controls, P = 0.01). NEC preceded by Firmicutes dysbiosis occurred earlier (onset, days 7 to 21) than NEC preceded by Proteobacteria dysbiosis (onset, days 19 to 39). All NEC cases lacked Propionibacterium and were preceded by either Firmicutes (≥98% relative abundance, days 4 to 9) or Proteobacteria (≥90% relative abundance, days 10 to 16) dysbiosis, while only 25% of controls had this phenotype (predictive value 88%, P = 0.001). Analysis of days 4 to 9 urine samples found no metabolites associated with all NEC cases, but alanine was positively associated with NEC cases that were preceded by Firmicutes dysbiosis (P < 0.001) and histidine was inversely associated with NEC cases preceded by Proteobacteria dysbiosis (P = 0.013). A high urinary alanine:histidine ratio was associated with microbial characteristics (P < 0.001) and provided good prediction of overall NEC (predictive value 78%, P = 0.007).
Early dysbiosis is strongly involved in the pathobiology of NEC. These striking findings require validation in larger studies but indicate that early microbial and metabolomic signatures may provide highly predictive biomarkers of NEC.
PMCID: PMC3971624  PMID: 24450576
Microbiome; Premature infants; Necrotizing enterocolitis; Dysbiosis
10.  Human milk adiponectin impacts infant weight trajectory during the second year of life 
Serum adiponectin (APN) is associated with lower childhood obesity, and APN concentration in human milk is associated with slower growth during active breastfeeding. Here, we examine infant weight gain in the second year of life after exposure to high or low levels of mother’s milk APN.
Breastfeeding mother-infant pairs were recruited in Mexico City and followed for 2 years; 192 infants with ≥12 months’ follow-up were analyzed. Monthly milk samples were assayed for APN; mothers were classified as producing high or low levels of milk APN. Infant and maternal serum APN were assessed during year 1. Infant anthropometry was measured monthly (year 1) or bi-monthly (year 2), and WHO Z-scores calculated. Longitudinal adjusted models assessed weight-for-age (WEI) and weight-for-length (WFL) Z-score trajectories from 1 to 2 years.
Maternal serum APN modestly correlated with milk APN (r=0.37, p<0.0001) and infant serum APN (r=0.29, p=0.01). Infants exposed to high milk APN experienced increasing WEI and WFL Z-scores between age 1 and 2 years in contrast to low milk APN exposure (p for group*time=0.02 and 0.054, respectively), adjusting for growth in the first 6 months and other covariates. In contrast, infant serum APN in year 1 was not associated with rate of weight gain in year 2.
High human milk APN exposure was associated with accelerated weight trajectory during the second year of life suggesting its role in catch up growth after slower weight gain during the first year of life.
PMCID: PMC3299902  PMID: 22094897
adiponectin; human milk; breastfeeding; weight gain; infancy
11.  Prolonged Initial Empirical Antibiotic Treatment is Associated with Adverse Outcomes in Premature Infants 
The Journal of pediatrics  2011;159(5):720-725.
To investigate the outcomes following prolonged empirical antibiotic administration to premature infants in the first week of life, concluding subsequent late onset sepsis (LOS), necrotizing enterocolitis (NEC), and death.
Study design
Study infants were ≤32 weeks gestational age and ≤ 1500 grams birth weight who survived free of sepsis and NEC for 7 days. Multivariable logistic regression was conducted to determine independent relationships between prolonged initial empirical antibiotic therapy (≥ 5 days) and study outcomes controlling for birth weight, gestational age, race, prolonged premature rupture of membranes, days on high frequency ventilation in 7 days, and the amount of breast milk received in the first 14 days of life.
Of the 365 premature infants surviving 7 days free of sepsis or NEC, 36% received prolonged initial empirical antibiotics, which was independently associated with subsequent outcomes: LOS (odds ratio [OR] 2.45, 95% confidence interval [CI] 1.28–4.67) and the combination of LOS, NEC, or death (OR 2.66, 95% CI 1.12–6.3).
Prolonged administration of empirical antibiotics to premature infants with sterile cultures in the first week of life is associated with subsequent severe outcomes. Judicious restriction of antibiotic use should be investigated as a strategy to reduce severe outcomes for premature infants.
PMCID: PMC3193552  PMID: 21784435
prolonged antibiotic treatment; death; human milk; late-onset sepsis; necrotizing enterocolitis; premature infant
12.  Fucosyltransferase 2 non-secretor and low secretor status predicts severe outcomes in premature infants 
The Journal of pediatrics  2011;158(5):745-751.
To investigate secretor gene fucosyltransferase2 (FUT2) polymorphism and secretor phenotype in relation to outcomes of prematurity.
Study design
Study infants were ≤32 weeks gestational age. Secretor genotype was determined from salivary DNA. Secretor phenotype was measured by H antigen, the carbohydrate produced by secretor gene enzymes, in saliva samples collected on day 9±5. The optimal predictive cut-point in salivary H values was identified by Classification and Regression Tree analysis. Study outcomes were death, necrotizing enterocolitis (NEC, Bell’s stage II/III), and confirmed sepsis.
There were 410 study infants, 26 deaths, 30 cases of NEC, and 96 cases of sepsis. Analyzed by genotype, 13% of 95 non-secretors, 5% of 203 heterozygotes, and 2% of 96 infants who were secretor dominant died (p=0.01). Analyzed by phenotype, 15% of 135 infants with low secretor phenotype died, compared with 2% of 248 infants with high secretor phenotype (predictive value=76%, p<0.001). Low secretor phenotype was associated (P<.05) with NEC, and non-secretor genotype was associated (P=.05) with gram negative sepsis. Secretor status remained significant after controlling for multiple clinical factors.
Secretor genotype and phenotype may provide strong predictive biomarkers of adverse outcomes in premature infants.
PMCID: PMC3412418  PMID: 21256510
13.  Genetic Diversity and Histo-Blood Group Antigen Interactions of Rhesus Enteric Caliciviruses▿  
Journal of Virology  2010;84(17):8617-8625.
Recently, we reported the discovery and characterization of Tulane virus (TV), a novel rhesus calicivirus (CV) (T. Farkas, K. Sestak, C. Wei, and X. Jiang, J. Virol. 82:5408-5416, 2008). TV grows well in tissue culture, and it represents a new genus within Caliciviridae, with the proposed name of Recovirus. We also reported a high prevalence of CV antibodies in macaques of the Tulane National Primate Research Center (TNPRC) colony, including anti-norovirus (NoV), anti-sapovirus (SaV), and anti-TV (T. Farkas, J. Dufour, X. Jiang, and K. Sestak, J. Gen. Virol. 91:734-738, 2010). To broaden our knowledge about CV infections in captive nonhuman primates (NHP), 500 rhesus macaque stool samples collected from breeding colony TNPRC macaques were tested for CVs. Fifty-seven (11%) samples contained recovirus isolates. In addition, one NoV was detected. Phylogenetic analysis classified the recovirus isolates into two genogroups and at least four genetic types. The rhesus NoV isolate was closely related to GII human NoVs. TV-neutralizing antibodies were detected in 88% of serum samples obtained from primate caretakers. Binding and plaque reduction assays revealed the involvement of type A and B histo-blood group antigens (HBGA) in TV infection. Taken together, these findings indicate the zoonotic potential of primate CVs. The discovery of a genetically diverse and prevalent group of primate CVs and remarkable similarities between rhesus enteric CVs and human NoVs opens new possibilities for research involving in vitro and in vivo models of human NoV gastroenteritis.
PMCID: PMC2919043  PMID: 20554772
14.  Characteristics and potential functions of human milk adiponectin 
The Journal of pediatrics  2010;156(2 Suppl):S41-S46.
Adiponectin is a protein hormone produced by adipose tissue whose circulating levels are inversely related to adiposity and inflammation. Adiponectin circulates as oligomers, from the low molecular weight trimer to the high molecular weight octodecamer (18mer) Each oligomer has distinct biological activities, which include enhancement of insulin sensitivity and metabolic control, and suppression of inflammation. Adiponectin occurs in human milk at higher concentrations than leptin. The adiponectin in human milk is almost entirely of the high molecular weight form, the form with the highest activity in controlling many types of metabolic processes. Human adiponectin fed to infant mice is transported across the intestinal mucosa into the serum. An inverse relationship between adiponectin levels in milk and adiposity (weight-for-height) of the breastfed infant was observed, and could be due to modulation of infant metabolism by milk adiponectin, and may be related to the observed protection against obesity by breastfeeding. Human milk may be a medium whereby the hormonal milieu (in response to internal factors and the environment) of the mother can be used to communicate with the breastfed infant to modify infant metabolic processes. Transmission of information from mother to infant through milk may allow adaptation to fluctuating environmental conditions.
PMCID: PMC2875873  PMID: 20105665
infant development; body weight; BMI; adiposity
15.  Human Milk Adiponectin Is Associated with Infant Growth in Two Independent Cohorts 
Breastfeeding Medicine  2009;4(2):101-109.
Adiponectin, a circulating adipocyte protein, is associated with lower obesity. We have previously shown that adiponectin is present in human milk. This study determined whether higher milk adiponectin is associated with infant growth and investigated milk adiponectin's oligomeric form.
Design and Methods
This is a study of two parallel longitudinal cohorts of breastfed infants born between 1998 and 2005. Forty-five mother–infant pairs from Cincinnati, OH and 277 mother–infant pairs from Mexico City, Mexico were analyzed. All participants were healthy, term infants breastfed at least 1 month who completed 6 months of follow-up. Monthly milk samples (n = 1,379) up to 6 months were assayed for adiponectin by radioimmunoassay. Infant weight-for-age, length-for-age, and weight-for-length Z-scores up to 6 months of age were calculated using World Health Organization standards. Repeated-measures analysis was conducted. The structural form of human milk adiponectin was assessed by western blot.
In the population studies, initial milk adiponectin was 24.0 ± 8.6 μg/L and did not differ by cohort. Over the first 6 months, higher milk adiponectin was associated with lower infant weight-for-age Z-score (−0.20 ± 0.04, p < 0.0001) and weight-for-length Z-score (−0.29 ± 0.08, p = 0.0002) but not length-for-age Z-score, adjusted for covariates, with no difference by cohort. By western blot, human milk adiponectin was predominantly in the biologically active high-molecular-weight form.
Our data suggest milk adiponectin may play a role in the early growth and development of breastfed infants.
PMCID: PMC2779028  PMID: 19500050
16.  Response to Brody et al. 
Breastfeeding Medicine  2009;4(2):123.
PMCID: PMC2932547  PMID: 19500056
17.  Epidemiology of Necrotizing Enterocolitis Temporal Clustering in Two Neonatology Practices 
The Journal of pediatrics  2008;154(5):656-661.
To develop a statistical method for defining clusters of necrotizing enterocolitis (NEC) cases in the neonatal intensive care unit (NICU).
Study design
2782 infants, between 1996–2004, weighing 401–1500 grams at birth were included. NEC was defined as Bell stage II or III. Two statistical methods used to define “disease clusters” were: (1) modified scan test; (2) comparison of observed and expected incidence density rates (IDR) of NEC at each NICU.
The proportion of infants with NEC was similar between NICUs (7.1% vs. 7.7%; p=0.6) as was the expected IDR of NEC (1.39/1000 patient-days vs. 1.32/1000 patient-days, p=0.72). Twelve temporal clusters of NEC were identified in the NICUs combined, comprising 18% of 203 total NEC cases during the study period. No seasonal/secular trends were noted for NEC rates or identified clusters. Potential NEC clusters of ≥3 cases at either NICU had >75% chance of being a true NEC cluster.
No operational definition of NEC cluster exists. This study introduced methods to be employed for prospective surveillance and guide studies to investigate etiologic relevance. Utilizing the proposed methods, statistically significant clusters (potential outbreaks) of NEC within NICUs can be identified early, providing early opportunity to implement cluster investigation protocols.
PMCID: PMC2700364  PMID: 19111317
disease clusters; outbreaks; neonatal intensive care unit; very low birth weight infants
18.  Use of a body proportionality index for growth assessment of preterm infants 
The Journal of pediatrics  2008;154(4):486-491.
We evaluated the utility of weight-for-length (defined as gm/cm3, “ponderal index”) as a complementary measure of growth in infants in neonatal intensive care units (NICUs).
Study design
Secondary analysis of infants (n=1214) 26-29 weeks at birth, included in a registry database (1991-2003), who had growth data at birth and discharge. Weight-for-age and weight-for-length were categorized as small (<10th percentile), appropriate or large (>90th percentile).
Statistical agreement between the weight-for-age and weight-for-length measures was poor (kappa=0.02 at birth, 0.10 at discharge, Bowker test for symmetry p<0.0001). From birth to discharge, the percent of small-for-age infants increased from 12% to 21%, and the percent of small-for-length infants decreased from 10% to 4%; the percent of large-for-age infants remained similar (<1%), and the percent of large-for-length infants increased from 5% to 17%. At discharge, 92% of small-for-age infants were appropriate or large-for-length, and 19% of appropriate-for-age infants were large-for-length.
Weight-for-age and weight-for-length are complementary measures. Weight-for-length or other measure of body proportionality should be considered for inclusion in routine growth monitoring of infants in the NICU.
PMCID: PMC2745983  PMID: 19041096
Growth status; growth; weight-for-age; weight/length3; ponderal index; weight/length ratio; obesity; overweight; underweight; small-for-gestational age; nutrition
19.  Reporting Individual Test Results of Environmental Chemicals in Breastmilk: Potential for Premature Weaning 
Breastfeeding Medicine  2008;3(4):207-213.
Environmental chemicals are readily measured in human milk. Although it is imperative to conduct studies on frequency of detection and effects of exposures to environmental chemicals in human milk, the potential impact of reporting individual test results to lactating women is poorly understood. The purpose of this study was to determine if mothers want to know if chemicals are in their breastmilk and if knowing the results would alter their breastfeeding practices.
We surveyed 381 mothers who were participating in a longitudinal birth cohort about whether they wanted to receive individual test results for environmental chemicals in their milk and whether they would alter their breastfeeding patterns if they were told that their milk contained “low” or “high” levels of phthalates.
Among the women who breastfed, 68% said that they wanted to know if there were chemicals in their breastmilk. Of breastfeeding women, 78% and 93% of mothers reported that they would either discontinue breastfeeding sooner than intended or pump and discard their milk if they were told they had “low” or “high” levels of phthalates in their milk, respectively. African American women were significantly more likely than Caucasian women to report that they would immediately wean if told of phthalates in their milk.
Concern about environmental chemicals in breastmilk may lead to early termination of breastfeeding. Chemical manufacturers and researchers should recognize the potential implications of isolating and reporting environmental chemicals in breastmilk.
PMCID: PMC2678545  PMID: 19086823
20.  Breastfeeding Helps Explain Racial and Socioeconomic Status Disparities in Adolescent Adiposity 
Pediatrics  2008;121(3):e458-e465.
Studies suggest that breastfeeding is protective for later obesity; however, this association has not held among all racial and socioeconomic status groups. Racial and socioeconomic status differences in breastfeeding behavior have also been noted. In this study, we formally test whether breastfeeding mediates the relationship between race and socioeconomic status with adolescent adiposity.
Data were analyzed from 739 black and white 10- to 19-year-old adolescents who participated in a large, school-based study. Parents provided information on parental education, used to measure socioeconomic status, and whether the child was breastfed as an infant. BMI was used to measure adolescent adiposity and was analyzed as a continuous measure (BMI z score) using linear regression and categorically (BMI ≥85th and ≥95th percentile) using logistic regression.
Black adolescents and those without a college-educated parent were less likely to have been breastfed for >4 months. Race and parental education were each independent predictors of BMI z score and of having BMI ≥85th percentile or BMI ≥95th percentile. When added to the model, being breastfed for >4 months was also independently associated with lower BMI z score and lower odds of having BMI ≥85th percentile or BMI ≥95th percentile. Inclusion of being breastfed for >4 months resulted in a 25% decrease in racial and parental education differences in adolescent BMI z score, supporting partial mediation.
Having been breastfed for >4 months was associated with lower adolescent BMI z score and lower odds of having a BMI ≥85th percentile or BMI ≥95th percentile, independent of race or parental education. Furthermore, these analyses suggest that being breastfed for >4 months partially explains the relationship between social disadvantage and increased adiposity. Increasing breastfeeding duration could result in lower adolescent adiposity for all racial and socioeconomic status groups and potentially minimize socioeconomic disparities in adiposity.
PMCID: PMC2759095  PMID: 18310167
adolescent obesity; breastfeeding; epidemiology; racial differences; socioeconomic status
21.  Norovirus and Histo-Blood Group Antigens: Demonstration of a Wide Spectrum of Strain Specificities and Classification of Two Major Binding Groups among Multiple Binding Patterns 
Journal of Virology  2005;79(11):6714-6722.
Noroviruses, an important cause of acute gastroenteritis, have been found to recognize human histo-blood group antigens (HBGAs) as receptors. Four strain-specific binding patterns to HBGAs have been described in our previous report. In this study, we have extended the binding patterns to seven based on 14 noroviruses examined. The oligosaccharide-based assays revealed additional epitopes that were not detected by the saliva-based assays. The seven patterns have been classified into two groups according to their interactions with three major epitopes (A/B, H, and Lewis) of human HBGAs: the A/B-binding group and the Lewis-binding group. Strains in the A/B binding group recognize the A and/or B and H antigens, but not the Lewis antigens, while strains in the Lewis-binding group react only to the Lewis and/or H antigens. This classification also resulted in a model of the norovirus/HBGA interaction. Phylogenetic analyses showed that strains with identical or closely related binding patterns tend to be clustered, but strains in both binding group can be found in both genogroups I and II. Our results suggest that noroviruses have a wide spectrum of host range and that human HBGAs play an important role in norovirus evolution. The high polymorphism of the human HBGA system, the involvement of multiple epitopes, and the typical protein/carbohydrate interaction between norovirus VLPs and HBGAs provide an explanation for the virus-ligand binding diversities.
PMCID: PMC1112114  PMID: 15890909
22.  Human Milk Secretory Antibodies against Attaching and Effacing Escherichia coli Antigens 
Emerging Infectious Diseases  2003;9(5):545-551.
Secretory immunoglobulin A (sIgA) is a primary factor responsible for preventing attachment of enteropathogens to gut epithelium in breastfeeding infants. We compared the frequency of sIgA to major surface antigens of enterohemorrhagic Escherichia coli (EHEC) in milk of 123 women from the United States and Mexico to determine whether regional differences existed in the frequency of antibodies to these surface antigens. In both groups of women, milk commonly has sIgA against various EHEC lipopolysaccharides, EspA, EspB, intimin, and less frequently against Shiga toxin. The study suggests that persons living in the U.S. are exposed to attaching/effacing enteropathogens more frequently than is generally assumed. The low frequency of antibodies to Stx1 (in 12% of Mexican and in 22% of U.S. samples) suggests that the rare appearance of hemolytic uremic syndrome in adults is not due to neutralization of toxin at the gut level. Only anti-EspA is found in most milk samples from both populations of women. EspA may represent a useful target for an immunization strategy to prevent EHEC disease in humans.
PMCID: PMC2972756  PMID: 12737737
Shiga toxin; EHEC; Escherichia coli; human milk; colostrum; EspA; research
23.  Lactation and Neonatal Nutrition: Defining and Refining the Critical Questions 
This paper resulted from a conference entitled “Lactation and Milk: Defining and refining the critical questions” held at the University of Colorado School of Medicine from January 18–20, 2012. The mission of the conference was to identify unresolved questions and set future goals for research into human milk composition, mammary development and lactation. We first outline the unanswered questions regarding the composition of human milk (Section I) and the mechanisms by which milk components affect neonatal development, growth and health and recommend models for future research. Emerging questions about how milk components affect cognitive development and behavioral phenotype of the offspring are presented in Section II. In Section III we outline the important unanswered questions about regulation of mammary gland development, the heritability of defects, the effects of maternal nutrition, disease, metabolic status, and therapeutic drugs upon the subsequent lactation. Questions surrounding breastfeeding practice are also highlighted. In Section IV we describe the specific nutritional challenges faced by three different populations, namely preterm infants, infants born to obese mothers who may or may not have gestational diabetes, and infants born to undernourished mothers. The recognition that multidisciplinary training is critical to advancing the field led us to formulate specific training recommendations in Section V. Our recommendations for research emphasis are summarized in Section VI. In sum, we present a roadmap for multidisciplinary research into all aspects of human lactation, milk and its role in infant nutrition for the next decade and beyond.
PMCID: PMC3428522  PMID: 22752723
Lactation; Infant nutrition; Human milk; Breastfeeding; Mammary gland development; Human nutrition; Preterm birth; Obesity; Undernutrition; Lactational programming; Milk

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