https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(15)01024-7.pdf

Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect

In this Review, I present evidence supporting a multifactorial causation of childhood acute lymphoblastic leukaemia (ALL), a major subtype of paediatric cancer. ALL evolves in two discrete steps. First, in utero initiation by fusion gene formation or hyperdiploidy generates a covert, pre-leukaemic clone. Second, in a small fraction of these cases, the postnatal acquisition of secondary genetic changes (primarily V(D)J recombination-activating protein (RAG) and activation-induced cytidine deaminase (AID)-driven copy number alterations in the case of ETS translocation variant 6 (ETV6)–runt-related transcription factor 1 (RUNX1)+ ALL) drives conversion to overt leukaemia. Epidemiological and modelling studies endorse a dual role for common infections. Microbial exposures earlier in life are protective but, in their absence, later infections trigger the critical secondary mutations. Risk is further modified by inherited genetics, chance and, probably, diet. Childhood ALL can be viewed as a paradoxical consequence of progress in modern societies, where behavioural changes have restrained early microbial exposure. This engenders an evolutionary mismatch between historical adaptations of the immune system and contemporary lifestyles. Childhood ALL may be a preventable cancer.

/pdf/a-causal-mechanism-for-childhood-acute-lymphoblastic-22sefjym14.pdf

A causal mechanism for childhood acute lymphoblastic leukaemia.

The aim of this study was to quantify the excess cases of pediatric and maternal disease, death, and costs attributable to suboptimal breastfeeding rates in the United States. Using the current literature on the associations between breastfeeding and health outcomes for nine pediatric and five maternal diseases, we created Monte Carlo simulations modeling a hypothetical cohort of U.S. women followed from age 15 to age 70 years and their children from birth to age 20 years. We examined disease outcomes using (a) 2012 breastfeeding rates and (b) assuming that 90% of infants were breastfed according to medical recommendations. We measured annual excess cases, deaths, and associated costs, in 2014 dollars, using a 2% discount rate. Annual excess deaths attributable to suboptimal breastfeeding total 3,340 (95% confidence interval [1,886 to 4,785]), 78% of which are maternal due to myocardial infarction (n = 986), breast cancer (n = 838), and diabetes (n = 473). Excess pediatric deaths total 721, mostly due to Sudden Infant Death Syndrome (n = 492) and necrotizing enterocolitis (n = 190). Medical costs total $3.0 billion, 79% of which are maternal. Costs of premature death total $14.2 billion. The number of women needed to breastfeed as medically recommended to prevent an infant gastrointestinal infection is 0.8; acute otitis media, 3; hospitalization for lower respiratory tract infection, 95; maternal hypertension, 55; diabetes, 162; and myocardial infarction, 235. For every 597 women who optimally breastfeed, one maternal or child death is prevented. Policies to increase optimal breastfeeding could result in substantial public health gains. Breastfeeding has a larger impact on women's health than previously appreciated.

/pdf/suboptimal-breastfeeding-in-the-united-states-maternal-and-xq68dy72mj.pdf

Suboptimal breastfeeding in the United States: Maternal and pediatric health outcomes and costs.

BACKGROUND

To our knowledge, no publication providing overarching guidance on the conduct of systematic reviews of observational studies of etiology exists.

METHODS AND FINDINGS

Conducting Systematic Reviews and Meta-Analyses of Observational Studies of Etiology (COSMOS-E) provides guidance on all steps in systematic reviews of observational studies of etiology, from shaping the research question, defining exposure and outcomes, to assessing the risk of bias and statistical analysis. The writing group included researchers experienced in meta-analyses and observational studies of etiology. Standard peer-review was performed. While the structure of systematic reviews of observational studies on etiology may be similar to that for systematic reviews of randomised controlled trials, there are specific tasks within each component that differ. Examples include assessment for confounding, selection bias, and information bias. In systematic reviews of observational studies of etiology, combining studies in meta-analysis may lead to more precise estimates, but such greater precision does not automatically remedy potential bias. Thorough exploration of sources of heterogeneity is key when assessing the validity of estimates and causality.

CONCLUSION

As many reviews of observational studies on etiology are being performed, this document may provide researchers with guidance on how to conduct and analyse such reviews.

/pdf/cosmos-e-guidance-on-conducting-systematic-reviews-and-meta-1j1ds2pql6.pdf

COSMOS-E: Guidance on conducting systematic reviews and meta-analyses of observational studies of etiology.

Breastfeeding and human milk are the normative standards for infant feeding and nutrition. The short- and long-term medical and neurodevelopmental advantages of breastfeeding make breastfeeding, or the provision of human milk, a public health imperative. The American Academy of Pediatrics (AAP) recommends exclusive breastfeeding for approximately 6 months after birth. Furthermore, the AAP supports continued breastfeeding, along with appropriate complementary foods introduced at about 6 months, as long as mutually desired by mother and child for 2 years or beyond. These recommendations are consistent with those of the World Health Organization (WHO). Medical contraindications to breastfeeding are rare. The AAP recommends that birth hospitals or centers implement maternity care practices shown to improve breastfeeding initiation, duration, and exclusivity. The Centers for Disease Control and Prevention (CDC) and The Joint Commission monitor breastfeeding practices in US hospitals. Pediatricians play a critical role in hospitals, their practices, and communities as advocates of breastfeeding and, thus, need to be trained about the benefits of breastfeeding for mothers and children and in managing breastfeeding.

Policy Statement: Breastfeeding and the Use of Human Milk.

Importance Childhood cancer is a leading cause of mortality among children and adolescents in the developed world and the incidence increases by 0.9% each year. Leukemia accounts for about 30% of all childhood cancer but its etiology is still mostly unknown. Objective To conduct a meta-analysis of available scientific evidence on the association between breastfeeding and childhood leukemia. Data Sources A thorough search for articles published between January 1960 and December 2014 researching the association between breastfeeding and childhood leukemia was conducted on PubMed, the Cochrane Library, and Scopus (performed in July and December 2014), supplemented by manual searches of reference lists. Study Selection To be included in the meta-analyses, studies had to be case control; include breastfeeding as a measured exposure and leukemia as a measured outcome; include data on breastfeeding duration in months; and be published in a peer-reviewed journal with full text available in English. Data Extraction and Synthesis The search identified 24 relevant studies, 17 of which met all inclusion criteria. No publication bias or significant heterogeneity among these 17 studies were detected. The quality of each study that met the inclusion criteria was assessed using the Newcastle-Ottawa Scale. Multiple meta-analyses were conducted using the random effect model on raw data in the StatsDirect statistical program. Main Outcomes and Measures No or short duration of breastfeeding and the incidence of childhood leukemia. Results The meta-analysis of all 17 studies indicated that compared with no or shorter breastfeeding, any breastfeeding for 6 months or longer was associated with a 20% lower risk for childhood leukemia (odds ratio, 0.80; 95% CI, 0.72-0.90). A separate meta-analysis of 15 studies indicated that ever breastfed compared with never breastfed was associated with a 9% lower risk for childhood leukemia (odds ratio, 0.91; 95% CI, 0.80-1.04), although the definition of never breastfed differed between studies. All meta-analyses of subgroups of the 17 studies showed similar associations. Based on current meta-analyses results, 14% to 20% of all childhood leukemia cases may be prevented by breastfeeding for 6 months or more. Conclusions and Relevance Breastfeeding is a highly accessible, low-cost public health measure. This meta-analysis that included studies not featured in previous meta-analyses on the subject indicates that promoting breastfeeding for 6 months or more may help lower childhood leukemia incidence, in addition to its other health benefits for children and mothers.

https://jamanetwork.com/journals/jamapediatrics/articlepdf/2299705/poi150033.pdf

Breastfeeding and Childhood Leukemia Incidence: A Meta-analysis and Systematic Review

Childhood cancer incidence increases and although rare, it is a leading cause of mortality. Leukemia and lymphoma comprise 40% of all cancers in children but little is known of their etiology. In this study, we examined the associations of breastfeeding and other early life exposures with childhood leukemia and lymphoma. A population-based case–control study carried out in 2011–2013 comprised mothers of 190 incidents (2005–2013) of leukemia/lymphoma cases aged 1–19 yr at diagnosis and 384 population-based controls. Interviews based on a computerized structured questionnaire were conducted with the mothers. Multivariate logistic regression models adjusted for potential confounders assessed the association between breastfeeding patterns and childhood leukemia/lymphoma. Ever breastfeeding category was associated with a 64% decreased risk for childhood leukemia/lymphoma lsqb;odds ratio (OR) = 0.36, 95% confidence interval (CI): 0.22, 0.60lrqb; and similar trends, with a dose–response effect, were obse...

Efrat L. Amitay

Papers

Breastfeeding and Childhood Leukemia Incidence: A Meta-analysis and Systematic Review

Breastfeeding, Other Early Life Exposures and Childhood Leukemia and Lymphoma

Breastfeeding and Childhood Leukemia Incidence—Reply

Errors and Misleading Data in Table