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Breast milk and cognitive development--the role of confounders: a systematic review.

ABSTRACT: The association between breastfeeding and child cognitive development is conflicted by studies reporting positive and null effects. This relationship may be confounded by factors associated with breastfeeding, specifically maternal socioeconomic class and IQ.Systematic review of the literature.Any prospective or retrospective study, in any language, evaluating the association between breastfeeding and cognitive development using a validated method in healthy term infants, children or adults, was included.Extracted data included the study design, target population and sample size, breastfeeding exposure, cognitive development assessment tool used and participants' age, summary of the results prior to, and following, adjustment for confounders, and all confounders adjusted for. Study quality was assessed as well.84 studies met our inclusion criteria (34 rated as high quality, 26 moderate and 24 low quality). Critical assessment of accepted studies revealed the following associations: 21 null, 28 positive, 18 null after adjusting for confounders and 17 positive-diminished after adjusting for confounders. Directionality of effect did not correlate with study quality; however, studies showing a decreased effect after multivariate analysis were of superior quality compared with other study groupings (14/17 high quality, 82%). Further, studies that showed null or diminished effect after multivariate analysis corrected for significantly more confounders (7.7±3.4) as compared with those that found no change following adjustment (5.6±4.5, p=0.04). The majority of included studies were carried out during childhood (75%) and set in high-income countries (85.5%).Much of the reported effect of breastfeeding on child neurodevelopment is due to confounding. It is unlikely that additional work will change the current synthesis. Future studies should attempt to rigorously control for all important confounders. Alternatively, study designs using sibling cohorts discordant for breastfeeding may yield more robust conclusions.

SUBMITTER: Walfisch A

PROVIDER: S-EPMC3753522 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Breast milk and cognitive development--the role of confounders: a systematic review.

Walfisch Asnat A Sermer Corey C Cressman Alex A Koren Gideon G

BMJ open 20130823 8

<h4>Objectives</h4>The association between breastfeeding and child cognitive development is conflicted by studies reporting positive and null effects. This relationship may be confounded by factors associated with breastfeeding, specifically maternal socioeconomic class and IQ.<h4>Design</h4>Systematic review of the literature.<h4>Setting and participants</h4>Any prospective or retrospective study, in any language, evaluating the association between breastfeeding and cognitive development using ...[more]

PMID: 23975102

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Project description:BackgroundAs aging populations increase across the globe, research on lifestyle factors that prevent cognitive decline and dementia is urgently needed. Therefore, a systematic review was conducted to examine the effects of varying levels of milk intake alone or in combination with other dairy products on the outcomes of cognitive function and disorders in adults.MethodsA comprehensive search was conducted across 3 databases (PUBMED, CINAHL, and EMBASE) from their inception through October 2017. Prospective cohort studies and randomized controlled trials (RCTs) that enrolled adults were included. Studies with follow-up durations of less than 4 weeks and studies including schizophrenic patients were excluded. Two independent investigators conducted abstract and full-text screenings, data extractions, and risk-of-bias (ROB) assessments using validated tools. Studies were synthesized qualitatively using a strength of evidence (SoE) rating tool. A random-effects model for meta-analysis was conducted when at least 3 unique studies reported sufficient quantitative data for the same outcome.ResultsA total of 1 RCT and 7 cohort studies were included. One medium-quality small RCT (n = 38 participants) showed that only spatial working memory was marginally better in the high dairy diet group compared to the low dairy diet group. Two of the 7 cohort studies were rated as having a high ROB, and only 1 cohort study was rated as having a low ROB. There were large methodological and clinical heterogeneities, such as the methods used to assess milk or dairy intake and the characteristics of the study populations. It was impossible to conduct a dose-response meta-analysis because the studies utilized different categories of exposures (e.g., different frequencies of milk consumption or the amount of dairy intake). Thus, the overall SoE was rated as insufficient regarding the associations between milk intake and cognitive decline, dementia, and Alzheimer's disease outcomes. Our meta-analysis of 3 cohort studies showed no significant association between milk intake and cognitive decline outcome (pooled adjusted risk ratio = 1.21; 95% CI: 0.81, 1.82; for highest vs. lowest intake) with large statistical heterogeneity (I2 = 64.1%).ConclusionsThe existing evidence (mostly observational) is too poor to draw a firm conclusion regarding the effect of milk or dairy intake on the risk of cognitive decline or disorders in adults.

Project description:Micronutrients are fundamental for healthy brain development and deficiencies during early development can have a severe and lasting impact on cognitive outcomes. Evidence indicates that undernourished lactating individuals may produce breast milk containing lower concentrations of certain vitamins and minerals. Exclusively breastfed infants born to mothers deficient in micronutrients may therefore be at risk of micronutrient deficiencies, with potential implications for neurodevelopment. This systematic review aims to consider current knowledge on the effects of breast milk micronutrients on the developmental outcomes of infants. The databases Medline, Global Health, PsychInfo, Open Grey, and the Web of Science were searched for papers published before February 2021. Studies were included if they measured micronutrients in breast milk and their association with the neurodevelopmental outcomes of exclusively breastfed infants. Also, randomised control trials investigating neurocognitive outcomes following maternal supplementation during lactation were sought. From 5477 initial results, three observational studies were eligible for inclusion. These investigated associations between breast milk levels of vitamin B6, carotenoids, or selenium and infant development. Results presented suggest that pyroxidal, β-carotene, and lycopene are associated with infant neurodevelopmental outcomes. Limited eligible literature and heterogeneity between included papers prevented quantitative synthesis. Insufficient evidence was identified, precluding any conclusions on the relationship between breast milk micronutrients and infant developmental outcomes. Further, the evidence available was limited by a high risk of bias. This highlights the need for further research in this area to understand the long-term influence of micronutrients in breast milk, the role of other breast milk micronutrients in infant neurodevelopmental outcomes, and the impact of possible lactational interventions.

Project description:Breast milk is the primary source of nutrition and hydration for the newborn infant but also plays an important role in the child's first immune defense. Additionally, several breast milk factors have been implicated in immune-related health outcomes later in life, including immunoglobulins, cytokines, chemokines, growth factors and, more recently, non-coding RNA (ncRNA) species. In this systematic review, we provide a comprehensive summary of the current literature on endogenous ncRNAs found in human breast milk. Thirty (30) relevant studies were identified and, whilst the majority studies focused on microRNAs (miRNAs), there is evidence that breast milk contains high quantities of RNA which also include long-coding RNAs, circular RNAs, as well as other short RNAs and fragmented tRNA and rRNAs. Among studies investigating miRNAs, miR-148a-3p, miR-30a/d-5p, miR-22-3p, miR-146b-5p, miR-200a/c-3p, and the 5p end of the let-7 miRNAs were commonly reported among the top 10 miRNAs in the cell, lipid, and skim milk fractions of breast milk. Methodological difference and small sample sizes limit the possibility of conclusively identifying which maternal and infant characteristics affect the miRNA profile. The highly expressed miRNAs were generally reported to be similar across lactational stage, milk fraction, maternal and infant characteristics, or infant growth and health. All the same, individual studies identify potential differences in miRNA expression levels which should be confirmed by future studies. Stability, uptake, and physiological functions of miRNAs were also considered in several studies. Breast milk miRNAs are relatively resistant to a range of harsh conditions and uptake experiments suggest that extracellular vesicles containing miRNAs and circular RNAs can be taken up by intestinal epithelial cells. Although the evidence regarding the functional effect of breast milk miRNAs is limited, the predicted functions range from metabolic and biosynthetic processes to signaling pathways, cellular adhesion, communication, growth, and differentiation. Finally, this systematic review highlights some of the methodological challenges and knowledge gaps which can help direct future research in this field. In particular, it is important to further investigate the bioavailability of miRNAs in different milk fractions, and to characterize other ncRNAs which are largely unstudied.Systematic review registrationPROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=138989, identifier CRD42020138989.

Project description:It has been suggested that molecular pathological mechanisms responsible for periodontitis can be linked with biochemical alterations in neurodegenerative disorders. Hypothetically, chronic systemic inflammation as a response to periodontitis plays a role in the etiology of cognitive impairment. This study aimed to determine whether periodontitis (PDS) is a risk factor for age-related cognitive impairment (ACI) based on evidence of clinical studies. A comprehensive, structured systematic review of existing data adhering to the Preferred Reporting Items for Systematic Review and Meta Analyses (PRISMA) guidelines was carried out. Five electronic databases, PubMed, Embase, Scopus, Web of Science, and Cochrane, were searched for key terms published in peer-reviewed journals until January 2021. The Newcastle-Ottawa scale was used to assess the quality of studies and risk of bias. The primary and residual confounders were explored and evaluated. A meta-analysis synthesizing quantitative data was carried out using a random-effects model. Seventeen clinical studies were identified, including 14 cohort, one cross-sectional, and two case-control studies. Study samples ranged from 85 to 262,349 subjects, with follow-up between 2 and 32 years, and age above 45 years, except for two studies. The findings of studies suggesting the PDS-ACI relationship revealed substantial differences in design and methods. A noticeable variation related to the treatment of confounders was observed. Quality assessment unveiled a moderate quality of evidence and risk of bias. The subgroups meta-analysis and pooled sensitivity analysis of results from seven eligible studies demonstrated overall that the presence of PDS is associated with an increased risk of incidence of cognitive impairment (OR = 1.36, 95% CI 1.03-1.79), particularly dementia (OR = 1.39, 95% CI 1.02-1.88) and Alzheimer's disease (OR = 1.03 95% CI 0.98-1.07)). However, a considerable heterogeneity of synthesized data (I2 = 96%) and potential publication bias might affect obtained results. While there is a moderate statistical association between periodontitis and dementia, as well as Alzheimer's disease, the risk of bias in the evidence prevents conclusions being drawn about the role of periodontitis as a risk factor for age-related cognitive impairment.

Project description:BackgroundWorldwide, many guidelines recommend the use of expressed breast milk (EBM) and maternal expression of breast milk for the prevention and treatment of neonatal hypoglycemia. However, the impact of both practices on neonatal hypoglycemia is unclear. This study aims to determine the effectiveness of EBM and maternal expression of breast milk in preventing and treating neonatal hypoglycemia.MethodsWe registered our review in PROSPERO (CRD42022328072). We systematically reviewed five databases and four clinical trial registries to identify randomized controlled trials (RCT), non-randomized studies of intervention (NRSI), and cohort studies that compared infants who received EBM to infants who did not, and similar study designs that compared infants whose mothers expressed breast milk to infants whose mothers did not. Two independent reviewers carried out screening, data extraction, and quality assessment. The quality of included RCT, NRSI, and cohort studies were respectively assessed with the Cochrane Risk of Bias 2, Risk Of Bias In Non-randomised Studies-of Interventions, and the Newcastle-Ottawa Scale tools. Results from studies on EBM were synthesized separately from those on maternal expression of breast milk. Meta-analysis was undertaken using Revman 5.4. and fixed-effect models.ResultsNone of the ten included studies was specifically designed to determine the effect of EBM or maternal expression of breast milk on neonatal hypoglycemia. The effect of EBM on neonatal hypoglycemia was not estimable. There was no difference in the risk of hypoglycaemia among neonates whose mothers expressed breast milk compared to those whose mothers did not [RR (95%CI); one RCT: 0.92 (0.77, 1.10), high-certainty evidence; one cohort: 1.10 (0.74, 1.39), poor quality study].ConclusionsThere is insufficient evidence to determine the effectiveness of EBM for preventing or treating neonatal hypoglycemia. Limited data suggests maternal breast milk expression may not alter the risk of neonatal hypoglycemia. High-quality randomized controlled trials are needed to determine the effectiveness of EBM and maternal expression of breast milk for the prevention and treatment of neonatal hypoglycemia.

Project description:BackgroundMaternal Body Mass Index (BMI) is positively associated with infant obesity risk. Breast milk contains a number of hormones that may influence infant metabolism during the neonatal period; these may have additional downstream effects on infant appetite regulatory pathways, thereby influencing propensity towards obesity in later life.ObjectiveTo conduct a systematic review of studies examining the association between maternal BMI and the concentration of appetite-regulating hormones in breast milk.MethodPubmed was searched for studies reporting the association between maternal BMI and leptin, adiponectin, insulin, ghrelin, resistin, obestatin, Peptide YY and Glucagon-Like Peptide 1 in breast milk.ResultsTwenty six studies were identified and included in the systematic review. There was a high degree of variability between studies with regard to collection, preparation and analysis of breast milk samples. Eleven of fifteen studies reporting breast milk leptin found a positive association between maternal BMI and milk leptin concentration. Two of nine studies investigating adiponectin found an association between maternal BMI and breast milk adiponectin concentration; however significance was lost in one study following adjustment for time post-partum. No association was seen between maternal BMI and milk adiponectin in the other seven studies identified. Evidence for an association between other appetite regulating hormones and maternal BMI was either inconclusive, or lacking.ConclusionsA positive association between maternal BMI and breast milk leptin concentration is consistently found in most studies, despite variable methodology. Evidence for such an association with breast milk adiponectin concentration, however, is lacking with additional research needed for other hormones including insulin, ghrelin, resistin, obestatin, peptide YY and glucagon-like peptide-1. As most current studies have been conducted with small sample sizes, future studies should ensure adequate sample sizes and standardized methodology.

Dataset Information

Breast milk and cognitive development--the role of confounders: a systematic review.

Publications

Breast milk and cognitive development--the role of confounders: a systematic review.

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