Breast hypoplasia markers among women who report insufficient milk production: A retrospective online survey.

OBJECTIVES: To estimate the proportions of anatomical breast characteristics suggestive of breast hypoplasia among breastfeeding women self-reporting low milk supply. We also explored breast hypoplasia risk factors. DESIGN: Online survey conducted between October 2021 and January 2022. SETTING: Five low milk supply Facebook groups. PARTICIPANTS: 487 women reporting low milk supply with their first child born ≥ 37 weeks gestation within 5 years of participation in this study, and residing in the USA, Australia or the UK. We present data on the primary outcome ('breast type') for 399 women. Women were excluded if the dyad was separated for more than 24 hours during the hospital stay, or if the mother reported removing milk less than 6 times per day from each breast on most days before being aware of having insufficient milk production. PRIMARY AND SECONDARY OUTCOME MEASURES: The proportions of proposed breast hypoplasia markers including atypical breast type, widely spaced breasts, breast asymmetry, stretch marks on the breast and lack of pregnancy breast growth. We also estimated the odds of having breast hypoplasia markers in at-risk groups compared to reference groups, adjusting for covariates. RESULTS: Approximately 68% reported at least one atypical breast (270/399; 95% CI: 62.9%, 72.1%). Around 47% reported widely spaced breasts (212/449; 95% CI: 42.7%, 52.7%), 72% a lack of pregnancy breast growth (322/449; 95% CI: 68.3%, 77.4%), and 76% stretch marks on the breast (191/250; 95% CI: 70.7%, 81.3%). Multiple logistic regression analyses identified being overweight during pubertal years as a risk factor for atypical breast type and lack of pregnancy breast growth. CONCLUSIONS: Participants in low milk supply Facebook groups reported high rates of breast hypoplasia markers. Being overweight during adolescence was a risk factor for breast hypoplasia markers. These findings should be confirmed in well-conducted large cohort studies to determine the strongest combination of hypoplasia markers in predicting low supply.

Obesity and Prenatal Intention as Predictors of Meeting Breastfeeding Recommendations in an Urban Birth Cohort.

Background and Objectives: Few U.S. women meet the public health recommendations to exclusively breastfeed for 6 months and continue breastfeeding for at least 1-2 years. We compared prenatally collected demographic, health, and breastfeeding support/intention variables to examine how these factors intersect to predict meeting breastfeeding recommendations. Methods: PREVAIL, a CDC-funded birth cohort in Cincinnati, OH, was approved by the IRB at CDC, Cincinnati Children's Hospital, and the hospitals where enrollment (third trimester, 2017-2018) occurred. The prenatal questionnaire captured sociodemographics, pre-pregnancy weight and height, breastfeeding environment, and breastfeeding intention, while health factors were obtained from obstetrical records. Body mass index (BMI) (kg/m2) was categorized as healthy (18.5-24.9), overweight (25-29.9), obesity 1 (30-34.9), and obesity 2+ (≥35). Mothers self-reported date of exclusive and any breastfeeding cessation through quarterly postnatal questionnaires. Random forest was used for variable selection, cross-validated in multivariable logistic models. Results: Analysis included n = 237 mothers with BMI ≥18.5. Random forest identified BMI category, prenatal intention, and insurance type as the most important predictors of meeting breastfeeding recommendations. The resulting logistic models explained >40% of the variance with an area under the curve of ≥0.89 for both recommendations. More than 73% of the risk of not meeting breastfeeding recommendations was attributable to having an elevated BMI or lacking strong breastfeeding intention. Conclusions: In PREVAIL, maternal BMI and prenatal intention explained most risks of not meeting breastfeeding exclusivity and duration recommendations. Our findings suggest efforts to improve breastfeeding exclusivity and duration should focus on strengthening prenatal breastfeeding intention and identifying effective interventions for supporting breastfeeding among mothers with higher BMI.

Prenatal SARS-CoV-2 infection alters postpartum human milk-derived extracellular vesicles.

Human milk-derived extracellular vesicles (HMEVs) are crucial functional components in breast milk, contributing to infant health and development. Maternal conditions could affect HMEV cargos; however, the impact of SARS-CoV-2 infection on HMEVs remains unknown. This study evaluated the influence of SARS-CoV-2 infection during pregnancy on postpartum HMEV molecules. Milk samples (9 prenatal SARS-CoV-2 vs. 9 controls) were retrieved from the IMPRINT birth cohort. After defatting and casein micelle disaggregation, 1 mL milk was subjected to a sequential process of centrifugation, ultrafiltration, and qEV-size exclusion chromatography. Particle and protein characterizations were performed following the MISEV2018 guidelines. EV lysates were analyzed through proteomics and miRNA sequencing, while the intact EVs were biotinylated for surfaceomic analysis. Multi-Omics was employed to predict HMEV functions associated with prenatal SARS-CoV-2 infection. Demographic data between the prenatal SARS-CoV-2 and control groups were similar. The median duration from maternal SARS-CoV-2 test positivity to milk collection was 3 months (range: 1-6 months). Transmission electron microscopy showed the cup-shaped nanoparticles. Nanoparticle tracking analysis demonstrated particle diameters of <200 nm and yields of >1e11 particles from 1 mL milk. Western immunoblots detected ALIX, CD9 and HSP70, supporting the presence of HMEVs in the isolates. Thousands of HMEV cargos and hundreds of surface proteins were identified and compared. Multi-Omics predicted that mothers with prenatal SARS-CoV-2 infection produced HMEVs with enhanced functionalities involving metabolic reprogramming and mucosal tissue development, while mitigating inflammation and lower EV transmigration potential. Our findings suggest that SARS-CoV-2 infection during pregnancy boosts mucosal site-specific functions of HMEVs, potentially protecting infants against viral infections. Further prospective studies should be pursued to reevaluate the short- and long-term benefits of breastfeeding in the post-COVID era.

An equitable, community-engaged translational framework for science in human lactation and infant feeding-a report from "Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN)" Working Group 5.

Human milk is the ideal source of nutrition for most infants, but significant gaps remain in our understanding of human milk biology. As part of addressing these gaps, the Breastmilk Ecology: Genesis of Infant Nutrition (BEGIN) Project Working Groups 1-4 interrogated the state of knowledge regarding the infant-human milk-lactating parent triad. However, to optimize the impact of newly generated knowledge across all stages of human milk research, the need remained for a translational research framework specific to the field. Thus, with inspiration from the simplified environmental sciences framework of Kaufman and Curl, Working Group 5 of the BEGIN Project developed a translational framework for science in human lactation and infant feeding, which includes 5 nonlinear, interconnected translational stages, T1: Discovery; T2: Human health implications; T3: Clinical and public health implications; T4: Implementation; and T5: Impact. The framework is accompanied by 6 overarching principles: 1) Research spans the translational continuum in a nonlinear, nonhierarchical manner; 2) Projects engage interdisciplinary teams in continuous collaboration and cross talk; 3) Priorities and study designs incorporate a diverse range of contextual factors; 4) Research teams include community stakeholders from the outset through purposeful, ethical, and equitable engagement; 5) Research designs and conceptual models incorporate respectful care for the birthing parent and address implications for the lactating parent; 6) Research implications for real-world settings account for contextual factors surrounding the feeding of human milk, including exclusivity and mode of feeding. To demonstrate application of the presented translational research framework and its overarching principles, 6 case studies are included, each illustrating research gaps across all stages of the framework. Applying a translational framework approach to addressing gaps in the science of human milk feeding is an important step toward the aligned goals of optimizing infant feeding across diverse contexts as well as optimizing health for all.

Fatty Acid Transfer from Blood to Milk Is Disrupted in Mothers with Low Milk Production, Obesity, and Inflammation.

BACKGROUND: Obesity is associated with chronic inflammation and is a risk factor for insufficient milk production. Inflammation-mediated suppression of LPL could inhibit mammary uptake of long-chain fatty acids (LCFAs; >16 carbons). OBJECTIVES: In an ancillary case-control analysis, we investigated whether women with low milk production despite regular breast emptying have elevated inflammation and disrupted transfer of LCFAs from plasma into milk. METHODS: Data and specimens from a low milk supply study and an exclusively breastfeeding control group were analyzed, with milk production measured by 24-h test-weighing at 2-10 wk postpartum. Low milk supply groups were defined as very low (VL; <300 mL/d; n = 23) or moderate (MOD; ≥300 mL/d; n = 20) milk production, and compared with controls (≥699 mL/d; n = 18). Serum and milk fatty acids (weight% of total) were measured by GC, serum and milk TNF-α by ELISA, and serum high-sensitivity C-reactive protein (hsCRP) by clinical analyzer. Group differences were assessed by linear regression models, chi-square exact tests, and Kruskal-Wallis nonparametric tests. RESULTS: VL cases, as compared with MOD cases and controls, had higher prevalence of elevated serum hsCRP (>5 mg/L; 57%, 15%, and 22%, respectively; P = 0.004), detectable milk TNF-α (67%, 32%, and 33%, respectively; P = 0.04), and obesity (78%, 40%, and 22%, respectively; P = 0.003). VL cases had lower mean ± SD LCFAs in milk (60% ± 3%) than MOD cases (65% ± 4%) and controls (66% ± 5%) (P < 0.001). Milk and serum LCFAs were strongly correlated in controls (r = 0.82, P < 0.001), but not in the MOD (r = 0.25, P = 0.30) or VL (r = 0.20, P = 0.41) groups (Pint < 0.001). CONCLUSIONS: Mothers with very low milk production have significantly higher obesity and inflammatory biomarkers, lower LCFAs in milk, and disrupted association between plasma and milk LCFAs. These data support the hypothesis that inflammation disrupts normal mammary gland fatty acid uptake. Further research should address impacts of inflammation and obesity on mammary fatty acid uptake for milk production.

Measures of Maternal Metabolic Health as Predictors of Severely Low Milk Production.

Background: A comprehensive approach to breastfeeding support requires elucidation of how metabolic health influences milk production. Objective: We compared metabolic health indicators in women with severely low milk output versus those with moderate/normal milk output using a case-control study design, with nested and external control groups. Design: Cases and nested controls were derived from women screened for a low milk supply trial, with cases defined as severely low milk output (<300 mL/24 hours), and nested controls defined as moderate/normal milk output (>300 mL/24 hours). In addition, we included an external control group of exclusively breastfeeding women. All were enrolled at 2-10 weeks postdelivery of a healthy term infant. Milk output and breast emptying frequency were recorded through test-weigh. Metabolic health variables included all components of the metabolic syndrome, homeostatic model assessment of insulin resistance (HOMA-IR), and diagnosis of gestational diabetes mellitus (GDM). Results: Maximum milk output, mL/24 hours, ranged as follows: 30-281 in cases (n = 18), 372-801 in nested controls (n = 12), and 661-915 in external controls (n = 12). Mean breast emptying frequency in cases was not significantly different from nested or external controls. All metabolic syndrome components and HOMA-IR were significantly worse in cases as compared with both nested and external control groups (p < 0.05). There was no significant difference between the nested and external control groups for these variables. GDM prevalence was 39%, 0%, and 8%, across cases, nested control, and external control groups, respectively (chi-square p-value = 0.02). Conclusion: Results from this small case-control study identify class 2+ obesity and poor metabolic health as strong risk factors for severely low milk production. These findings should be further validated in larger prospective cohort studies designed to identify individuals at risk for metabolically driven low milk supply. In addition, clinical and qualitative research studies aimed at improving patient-centered approaches to the management of persistent low milk supply are needed.

DHA Supplementation Attenuates Inflammation-Associated Gene Expression in the Mammary Gland of Lactating Mothers Who Deliver Preterm.

BACKGROUND: In a randomized trial of DHA supplementation to lactating mothers who delivered preterm, there were significant increases in DHA status in the mother and her infant. OBJECTIVES: Our objective here was to characterize the mammary gland transcriptomes from the above study. We hypothesized that proinflammatory gene expression would be attenuated in the increased DHA group compared with the standard DHA group. METHODS: In the original trial, mothers delivering at <29 wk gestation at the University of Cincinnati Medical Center and intending to express their milk were randomly assigned to supplementation with 200 mg/d DHA (standard group: STD) or 1000 mg/d DHA (experimental group: EXP) within 7 d of delivery. Here, we conducted RNA-seq transcriptome analysis of n = 5 EXP and n = 4 STD extracellular mammary mRNA samples extracted from the fat layer of milk samples obtained 4 wk postenrollment. Transcripts were assessed for differential expression (false discovery rate adjusted P value <0.05) and clustering between EXP compared with STD groups. Ontological analysis of all differentially expressed genes (DEGs) was performed with Toppcluster. RESULTS: There were 409 DEGs. We observed 5 main groups of biological processes that were upregulated, including those associated with improved immune regulation and management of oxidative stress; and 3 main groups of biological processes that were downregulated, including 1 associated with immune dysregulation. For example, we observed upregulation of inflammation-inhibiting genes including NFKB inhibitor alpha (NFKBIA; fold-change (FC), adjusted P value: FC = 1.70, P = 0.007) and interleukin-18 binding protein (IL18BP: FC = 2.2, adjusted P = 0.02); and downregulation of proinflammatory genes including interleukin 7 receptor (IL7R: FC = -1.9, adjusted P = 0.02) and interleukin 1 receptor like 1 (IL1RL1: FC = -13.0, adjusted P = 0.02). CONCLUSIONS: Increased DHA supplementation during lactation can modulate the expression of inflammation-related genes within the mammary gland. This might translate to milk composition with a more optimal inflammasome profile. Future research with a larger clinical trial and greater interrogation of clinical outcomes is warranted.

Exploring the Breastfeeding Experiences of African American Mothers Through a Critical Race Theory Lens.

Background: Data from the Ohio Department of Health for Hamilton County reveal that the rate of breastfeeding steadily increased for non-Hispanic white babies from 72% initiation in 2006 to 79.8% initiation in 2018. Over the same time period, the rate of breastfeeding initiation increased from 52% to 65.7% for African American babies. Despite positive gains in breastfeeding for the African American community, significant disparities remain. Research Aim/Question(s): Our aim was to gain insight into the breastfeeding experiences of African American women and professionals working primarily with African American women to promote and support breastfeeding. Methods: In this study, a critical race theory approach was used to explore the lived experiences of African American women and health care providers who serve African American communities through the analysis of breakout conference sessions. Breakout sessions were semistructured, with questions developed in a strengths, weaknesses, opportunities, and threats analysis format aimed at obtaining information related to sociocultural factors impacting breastfeeding initiation and duration, with the goal of developing actionable community objectives to address breastfeeding disparities for African American women. Results: Three themes emerged stereotypes and microaggressions, representation, and provider support. Conclusion: Qualitative analysis of the conference proceedings reveals insights that can be developed into an action plan to address breastfeeding disparities in Hamilton County.

Predictors of the Provision of Mother's Milk Feedings in Newborns Admitted to the Neonatal Intensive Care Unit.

Background: Breast milk reduces morbidity and mortality in infants admitted to neonatal intensive care unit (NICU). Objectives: We determined predictors of procuring mother's own milk (MOM) among NICU-admitted newborn-mother dyads: (1) initiation of any milk expression; (2) initiation of milk expression within 6 hours of birth; (3) MOM as the first enteral feeding; (4) colostrum for oral care within 36 hours of birth if not yet orally fed; and (5) provision of MOM at 21 days of life or discharge, whichever occurred first. Methods: We performed a retrospective chart review of NICU-admitted newborn-mother dyads at an urban medical center from June 1, 2018-May 31, 2019. We excluded infants not directly admitted to the NICU, those never enterally fed, multiple gestations if not the first to be discharged, and infants discharged to a nonbiological caregiver. We used chi-square analysis to examine unadjusted associations between independent variables and MOM outcomes and then used logistic regression to determine the adjusted odds ratio and 95% confidence interval (AOR [95% CI]) for predictors of MOM outcomes. Results: There were 341 mother-infant dyads who met inclusion criteria and 71% of these mothers initiated milk expression. Smoking, multiparity, gestational diabetes, and Hepatitis C lowered the odds for at least one MOM outcome; whereas mothers who delivered at 28-32 weeks versus ≥33 weeks, and infants with birthweight <1,500 g versus 1,500-2,500 g had higher odds for at least one MOM outcome. Conclusion: Maternal/infant dyad characteristics may predict some, but not all NICU breastfeeding outcomes. This suggests that hospital practices may influence these outcomes and can inform future interventions.

Breastfeeding Disparities and Their Mediators in an Urban Birth Cohort of Black and White Mothers.

Background: Black mothers in the United States have shorter breastfeeding (BF) durations and less exclusive breastfeeding (EBF) than others. The factors underlying these disparities require investigation. Methods: Using longitudinal data from a CDC-sponsored birth cohort in Cincinnati, Ohio, we analyzed the factors mediating racial disparity in BF outcomes. Study mothers were enrolled in prenatal clinics associated with two large birth hospitals. Analysis was restricted to racial groups with sufficient numbers in the cohort, non-Hispanic Black (n = 92) and White (n = 113) mothers, followed to at least 6 months postpartum. Results: Black mothers were 25 times more likely to reside in socioeconomically deprived neighborhoods and 20 times more likely to have an annual household income <$50,000/year than White mothers (p < 0.001). The gap in EBF for 6 weeks was 45 percentage points by racial group (13%-Black mothers versus 58%-White mothers, p < 0.001); in any BF at 6 months was 37 percentage points (28%-Black mothers versus 65%-White mothers, p < 0.001); and in mothers meeting their own intention to BF at least 6 months was 51 percentage points (29%-Black mothers versus 80%-White mothers, p < 0.001). Racial disparity in EBF at 6 weeks was mediated in logistic regression models by inequities in socioeconomic position, maternal hypertension, and BF intention. Racial disparities in BF at 6 months or meeting 6-month BF intention were mediated by inequities in socioeconomic position, maternal obesity, and EBF at 6 weeks. Not all BF disparities could be explained by models used in these analyses. Conclusions: Efforts to lessen BF disparities should address the underlying structural inequities that disproportionately affect Black mothers and children, should incorporate maternal health, and focus on breastfeeding exclusivity and duration. Few Black mothers achieved EBF at 6 weeks, which contributed to disparity in BF duration. Greater attention to Black mother-infant pairs is a public health priority.

First-Day Use of the Newborn Weight Loss Tool to Predict Excess Weight Loss in Breastfeeding Newborns.

Background and Objectives: Exclusive breastfeeding is recommended for most newborns. However, exclusively breastfed newborns sometimes experience excess weight loss (EWL, loss ≥10% of birth weight) while lactation is being established. Our primary objective was to evaluate the sensitivity and specificity of the Newborn Weight Loss Tool (NEWT) in early identification of exclusively breastfed newborns who develop EWL; and secondarily, identify breastfeeding variables associated with an at-risk NEWT trajectory. Materials and Methods: We conducted a secondary analysis of prospective data from mother-infant dyads screened for inclusion in the U.S. site of the WHO Growth Reference Study. We excluded records if: NEWT-specific criteria not met, missing key data, or >60 mL formula consumed. We defined NEWT "test-positive" based on an in-hospital weight at about 24 hours falling within the NEWT trajectory consistent with eventual EWL. We defined cases as true EWL based on weight measured at home on day of life 4 (DoL4). Results: Of 280 original records, 60 were excluded (n = 27, NEWT-specific exclusion; n = 15, missing data; n = 18, >60 mL formula), resulting in 220 paired newborn weights measured in-hospital (17 ± 8 hours), and at DoL4 (84 ± 8 hours). NEWT status correctly identified 6/28 EWL cases (21% sensitivity [95% confidence interval, CI, 8-34%]), and 158/192 noncases (82% specificity [95% CI, 75-89%]). NEWT test-positive status was associated with greater weight loss, lower perceived breastfeeding support, and infant less often showing feeding cues on DoL4 (p < 0.05). Conclusion: Sensitivity in predicting EWL is low when applying NEWT at about 24 hours of life; however, early test-positive status is associated with indicators of breastfeeding difficulties on DoL4.

Validity of a 3-Hour Breast Milk Expression Protocol in Estimating Current Maternal Milk Production Capacity and Infant Breast Milk Intake in Exclusively Breastfeeding Dyads.

Objective: An efficient method for measuring maternal milk production is needed. Our objectives were to: (1) validate a milk production rate (MPR) protocol in exclusively breastfeeding mothers; (2) determine MPR change following 48 hours of increased breast emptying; (3) assess agreement between MPR and infant test-weighing; and (4) characterize MPR in early postpartum exclusively breastfeeding mothers. Materials and Methods:N = 23 mothers emptied both breasts hourly over 3 hours (h0, h1, h2, and h3). We estimated steady-state MPR as mean (h2 and h3). Subset A mothers (n = 5) also completed MPR measurements after 48 hours of increased breast emptying. Subset B mothers (n = 16) also test-weighed for 48 hours. We used paired t-test to examine within-participant change in hourly milk yield and MPR; and we used Bland-Altman analysis to compare 24-hour milk production (g/24 hours) measured using test-weight versus MPR. Results are reported as mean ± standard deviation or (±95% limits of agreement). Results: Mothers were 54 ± 14 days postpartum. Paired difference in h3-h2 hourly milk yield was not significantly different (p > 0.05, 3 ± 10 g/hour). In Subset A (n = 5), MPR declined from 50 ± 13 to 43 ± 16 g/hour (p = 0.003) following 48 hours of increased breast emptying. In Study B (n = 16), mean infant test-weighed intake (TW) was 717 ± 119 g/24 hours, and mean MPR was 1,085 ± 300 g/24 hours. Mean difference (MPR-test-weigh) and mean ratio (MPR/test-weigh) significantly increased as MPR increased (p < 0.05). For infants with adequate weight gain (>20 g/24 hours, n = 12), mean MPR = 48 ± 12 g/hour (range, 35-78 g/hour). Conclusion: MPR is a valid measure of current maternal milk production capacity, but is not accurate for evaluating infant intake in exclusively breastfeeding dyads.

NIH workshop on human milk composition: summary and visions.

Nationally representative data from mother-child dyads that capture human milk composition (HMC) and associated health outcomes are important for advancing the evidence to inform federal nutrition and related health programs, policies, and consumer information across the governments in the United States and Canada as well as in nongovernment sectors. In response to identified gaps in knowledge, the National Institute of Diabetes and Digestive and Kidney Diseases of the NIH sponsored the "Workshop on Human Milk Composition-Biological, Environmental, Nutritional, and Methodological Considerations" held 16-17 November 2017 in Bethesda, Maryland. Through presentations and discussions, the workshop aimed to 1) share knowledge on the scientific need for data on HMC; 2) explore the current understanding of factors affecting HMC; 3) identify methodological challenges in human milk (HM) collection, storage, and analysis; and 4) develop a vision for a research program to develop an HMC data repository and database. The 4 workshop sessions included 1) perspectives from both federal agencies and nonfederal academic experts, articulating scientific needs for data on HMC that could lead to new research findings and programmatic advances to support public health; 2) information about the factors that influence lactation and/or HMC; 3) considerations for data quality, including addressing sampling strategies and the complexities in standardizing collection, storage, and analyses of HM; and 4) insights on how existing research programs and databases can inform potential visions for HMC initiatives. The general consensus from the workshop is that the limited scope of HM research initiatives has led to a lack of robust estimates of the composition and volume of HM consumed and, consequently, missed opportunities to improve maternal and infant health.

Infant milk-feeding practices and childhood leukemia: a systematic review.

BACKGROUND: During the Pregnancy and Birth to 24 Months Project, the US Departments of Agriculture and Health and Human Services initiated a review of evidence on diet and health in these populations. OBJECTIVES: The aim of these systematic reviews was to examine the relation of 1) never versus ever feeding human milk, 2) shorter versus longer durations of any human milk feeding, 3) shorter versus longer durations of exclusive human milk feeding, and 4) feeding a lower versus higher intensity of human milk to mixed-fed infants with acute childhood leukemia, generally, and acute lymphoblastic leukemia, specifically. METHODS: The Nutrition Evidence Systematic Review team conducted systematic reviews with external experts. We searched CINAHL, Cochrane, Embase, and PubMed for articles published January 1980 to March 2016, dual-screened the results using predetermined criteria, extracted data from and assessed risk of bias for each included study, qualitatively synthesized the evidence, developed conclusion statements, and graded the strength of the evidence. RESULTS: We included 24 articles from case-control or retrospective studies. Limited evidence suggests that never feeding human milk versus 1) ever feeding human milk and 2) feeding human milk for durations ≥6 mo are associated with a slightly higher risk of acute childhood leukemia, whereas evidence comparing never feeding human milk with feeding human milk for durations <6 mo is mixed. Limited evidence suggests that, among infants fed human milk, a shorter versus longer duration of human milk feeding is associated with a slightly higher risk of acute childhood leukemia. None of the included articles examined exclusive human milk feeding or the intensity of human milk fed to mixed-fed infants. CONCLUSIONS: Feeding human milk for short durations or not at all may be associated with slightly higher acute childhood leukemia risk. The evidence could be strengthened with access to broadly generalizable prospective samples; therefore, we recommend linking surveillance systems that collect infant feeding and childhood cancer data.

Infant milk-feeding practices and cardiovascular disease outcomes in offspring: a systematic review.

BACKGROUND: During the Pregnancy and Birth to 24 Months Project, the US Departments of Agriculture and Health and Human Services initiated a review of evidence on diet and health in these populations. OBJECTIVES: The aim of these systematic reviews was to examine the relation of 1) never versus ever feeding human milk, 2) shorter versus longer durations of any human milk feeding, 3) shorter versus longer durations of exclusive human milk feeding, and 4) lower versus higher intensities of human milk fed to mixed-fed infants with intermediate and endpoint cardiovascular disease (CVD) outcomes in offspring. METHODS: The Nutrition Evidence Systematic Review team conducted systematic reviews with external experts. We searched CINAHL, Cochrane, Embase, and PubMed for articles published January 1980-March 2016, dual-screened the results using predetermined criteria, extracted data from and assessed the risk of bias for each included study, qualitatively synthesized the evidence, developed conclusion statements, and graded the strength of the evidence. RESULTS: The 4 systematic reviews included 13, 24, 6, and 0 articles, respectively. The evidence was insufficient to draw conclusions about endpoint CVD outcomes across all 4 systematic reviews. Limited evidence suggests that never versus ever being fed human milk is associated with higher blood pressure within a normal range at 6-7 y of age. Moderate evidence suggests there is no association between the duration of any human milk feeding and childhood blood pressure. Limited evidence suggests there is no association between the duration of exclusive human milk feeding and blood pressure or metabolic syndrome in childhood. Additional evidence about intermediate outcomes for the 4 systematic reviews was scant or inconclusive. CONCLUSIONS: There is insufficient evidence to draw conclusions about the relationships between infant milk-feeding practices and endpoint CVD outcomes; however, some evidence suggests that feeding less or no human milk is not associated with childhood hypertension.

Infant milk-feeding practices and food allergies, allergic rhinitis, atopic dermatitis, and asthma throughout the life span: a systematic review.

BACKGROUND: During the Pregnancy and Birth to 24 Months Project, the USDA and Department of Health and Human Services initiated a review of evidence on diet and health in these populations. OBJECTIVES: The aim of these systematic reviews was to examine the relation of 1) never versus ever feeding human milk, 2) shorter versus longer durations of any human milk feeding, 3) shorter versus longer durations of exclusive human milk feeding prior to infant formula introduction, 4) feeding a lower versus higher intensity of human milk to mixed-fed infants, and 5) feeding a higher intensity of human milk by bottle versus breast with food allergies, allergic rhinitis, atopic dermatitis, and asthma. METHODS: The Nutrition Evidence Systematic Review team conducted systematic reviews with external experts. We searched CINAHL, Cochrane, Embase, and PubMed for articles published between January 1980 and March 2016, dual-screened the results according to predetermined criteria, extracted data from and assessed the risk of bias for each included study, qualitatively synthesized the evidence, developed conclusion statements, and graded the strength of the evidence. RESULTS: The systematic reviews numbered 1-5 above included 44, 35, 1, 0, and 0 articles, respectively. Moderate, mostly observational, evidence suggests that 1) never versus ever being fed human milk is associated with higher risk of childhood asthma, and 2) among children and adolescents who were fed human milk as infants, shorter versus longer durations of any human milk feeding are associated with higher risk of asthma. Limited evidence does not suggest associations between 1) never versus ever being fed human milk and atopic dermatitis in childhood or 2) the duration of any human milk feeding and allergic rhinitis and atopic dermatitis in childhood. CONCLUSIONS: Moderate evidence suggests that feeding human milk for short durations or not at all is associated with higher childhood asthma risk. Evidence on food allergies, allergic rhinitis, and atopic dermatitis is limited.

Infant milk-feeding practices and diagnosed celiac disease and inflammatory bowel disease in offspring: a systematic review.

BACKGROUND: During the Pregnancy and Birth to 24 Months Project, the USDA and US Department of Health and Human Services initiated an evidence review on diet and health in these populations. OBJECTIVE: The aim of these systematic reviews was to examine the relationships of never versus ever feeding human milk, shorter versus longer durations of any and exclusive human milk feeding, and feeding a lower versus a higher intensity of human milk to mixed-fed infants with diagnosed celiac disease and inflammatory bowel disease (IBD). METHODS: The Nutrition Evidence Systematic Review team (formerly called the Nutrition Evidence Library) conducted systematic reviews with external experts. We searched CINAHL, Cochrane, Embase, and PubMed for articles published January, 1980 to March, 2016, dual-screened the results using predetermined criteria, extracted data from and assessed risk of bias for each included study, qualitatively synthesized the evidence, developed conclusion statements, and graded the strength of the evidence. RESULTS: We included 9 celiac disease and 17 IBD articles. Limited case-control evidence suggests never versus ever being fed human milk is associated with higher risk of celiac disease, but concerns about reverse causality precluded a conclusion about the relationship of shorter versus longer durations of any human milk feeding with celiac disease. Evidence examining never versus ever feeding human milk and IBD was inconclusive, and limited, but consistent, case-control evidence suggests that, among infants fed human milk, shorter versus longer durations of any human milk feeding are associated with higher risk of IBD. For both outcomes, evidence examining the duration of exclusive human milk feeding was scant and no articles examined the intensity of human milk fed to mixed-fed infants. CONCLUSION: Limited case-control evidence suggests that feeding human milk for short durations or not at all associates with higher risk of diagnosed IBD and celiac disease, respectively. The small number of studies and concern about reverse causality and recall bias prevent stronger conclusions.

Infant milk-feeding practices and diabetes outcomes in offspring: a systematic review.

BACKGROUND: During the Pregnancy and Birth to 24 Months Project, the US Departments of Agriculture and Health and Human Services initiated a review of evidence on diet and health in these populations. OBJECTIVES: The aim of these systematic reviews was to examine the relation of 1) never versus ever feeding human milk, 2) shorter versus longer durations of any human milk feeding, 3) shorter versus longer durations of exclusive human milk feeding, and 4) feeding a lower versus higher intensity of human milk to mixed-fed infants with type 1 and type 2 diabetes in offspring. METHODS: The Nutrition Evidence Systematic Review team conducted systematic reviews with external experts. We searched CINAHL, Cochrane, Embase, and PubMed for articles published January 1980-March 2016, dual-screened the results according to predetermined criteria, extracted data from and assessed the risk of bias for each included study, qualitatively synthesized the evidence, developed conclusion statements, and graded the strength of the evidence. RESULTS: The 4 systematic reviews included 21, 37, 18, and 1 articles, respectively. Observational evidence suggests that never versus ever feeding human milk (limited evidence) and shorter versus longer durations of any (moderate evidence) and exclusive (limited evidence) human milk feeding are associated with higher type 1 diabetes risk. Insufficient evidence examined type 2 diabetes. Limited evidence suggests that the durations of any and exclusive human milk feeding are not associated with intermediate outcomes (e.g., fasting glucose, insulin resistance) during childhood. CONCLUSIONS: Limited to moderate evidence suggests that feeding less or no human milk is associated with higher risk of type 1 diabetes in offspring. Limited evidence suggests no associations between the durations of any and exclusive human milk feeding and intermediate diabetes outcomes in children. Additional research is needed on infant milk-feeding practices and type 2 diabetes and intermediate outcomes in US populations, which may have distinct metabolic risk.