Background: Exclusive breastfeeding (EB), feeding an infant solely breast milk, has been recommended worldwide due to its health benefits for infants and mothers. However, EB rates remain low, due to several socio-demographic, occupational, and cultural factors. Objectives: Our aim was to investigate the factors associated with EB amongst Arab mothers living in Israel, i.e., age, education, religiosity, employment status, and the number of children which impact breastfeeding practices. Methods: Data were collected through surveys from Arab mothers of different religious and geographical backgrounds. Results: The findings revealed that older maternal age, higher levels of religiosity, and an increased number of children were positively associated with EB. Employment reduced EB. Muslim mothers were more likely to combine breastfeeding with formula; Christian and Druze mothers showed higher EB rates. Geographical disparities were also noted. Conclusions: This study highlights the complex interplay of socio-demographic and cultural factors that impact breastfeeding practices amongst Arab mothers in Israel, with significant implications for policy development and maternal support programs. We underscore the importance of incorporating religious and cultural considerations into breastfeeding promotion strategies. Public health initiatives should target support for working mothers by advocating extended maternity leave and breastfeeding-friendly workplace policies. Furthermore, community-based interventions should engage family members in supporting breastfeeding mothers.

Probiotic supplementation has been actively investigated in preterm populations to reduce the risk of necrotizing enterocolitis (NEC) and late-onset sepsis. Despite this, few studies have focused on clinically relevant feeding tolerance and growth outcomes, and there is an alarming lack of evidence surrounding extremely preterm infants (defined as birth before 28 weeks gestational age), those most at risk of severe comorbidities. We aimed to investigate whether probiotics improve feeding tolerance, neonatal growth and neonatal morbidity among extremely preterm infants.

A literature search was conducted in Medline, Embase, Cochrane CENTRAL, Web of Science, and clinicaltrials.gov for ongoing trials. We included extremely preterm infants from randomized controlled trials and non-randomized trials with a concurrent control group. Two authors independently performed screening, data extraction and risk of bias assessment using the Risk of Bias 2 tool from Cochrane. The certainty of the evidence was assessed using GRADE.

Eleven RCTs and three non-randomized studies with a concurrent control group were included, analyzing a total of 14,888 extremely preterm infants. Meta-analyses revealed lower mean days to full enteral feeds (mean difference 1.1 days lower; 95% CI, 7.83 lower to 5.56 higher) and lower duration of parenteral nutrition (mean difference 2.4 days lower; 95% CI, 7.44 lower to 2.58 higher) in infants treated with probiotics; however, this was not statistically significant. There was a significant reduction in NEC (RR; 0.80, 95% CI; 0.68, 0.93) and all-cause mortality (RR; 0.56, 95% CI; 0.33, 0.93) in the probiotic group. All outcomes were graded at low or very low certainty of evidence.

The findings indicate a trend towards a potential beneficial effect of probiotic supplementation in reducing feeding intolerance and a notable reduction of risk of NEC and all-cause mortality in infants receiving probiotics. Future RCTs will focus on feeding intolerance, and growth outcomes are warranted.

Population aging is the most important social and medical demographic issue worldwide; therefore, healthy aging is important. The increasing prevalence of dementia and cognitive decline are major health concerns. Medium-chain triglycerides (MCTs) have been shown to improve cognitive decline. The present study investigated the effects and mechanisms of action of orally administered MCTs, including tricaprylin (TC8), tricaprin (TC10), and trilaurin (TC12), on cognitive function in mice fed a high-fat diet (HFD). The administration of TC8 and TC10 attenuated cognitive decline. A relationship has been reported between cognitive dysfunction and impaired glucose metabolism. The administration of TC8 and TC10 also reduced blood glucose levels in the glucose tolerance test. Cognitive improvements by MCTs are widely attributed to the ketogenic effect. In the present study, TC8 significantly increased blood ketone concentrations, whereas TC10 did not. On the other hand, TC10 increased the plasma concentration of glucagon-like peptide-1 (GLP-1), the hormone that promotes insulin secretion. The administration of the GLP-1 receptor antagonist, exendin(9-39), blocked the cognitive-enhancing effects of TC10. These results suggest that TC10 improved cognitive function via the GLP-1 receptor. The in vitro experiment indicated that 2-monocaprin (2-MC10), not TC10, stimulated the secretion of GLP-1 and decreased intracellular cAMP concentrations. In conclusion, we herein demonstrated that TC8 and TC10 attenuated cognitive decline through different mechanisms. This is the first study to suggest that TC10 attenuates cognitive decline via GLP-1.

Delivering adequate nutrition to preterm and sick neonates is critical for growth. Infants in the neonatal intensive care unit (NICU) require additional calories to supplement feedings for higher metabolic demands. Traditionally, clinicians enter free-text diet orders for a milk technician to formulate recipes, and dietitians manually calculate nutrition components to monitor growth. This daily process is complex and labor intensive with potential for error. Our goal was to develop an electronic health record (EHR)-integrated solution for entering feeding orders with automated nutrition calculations and mixing instructions. The EHR-integrated automated diet program (ADP) was created and implemented at a 52-bed level III academic NICU. The configuration of the parenteral nutrition orderable item within the EHR was adapted to generate personalized milk mixing recipes. Caloric, macronutrient, and micronutrient constituents were automatically calculated and displayed. To enhance administration safety, handwritten milk bottle patient labels were substituted with electronically generated and scannable patient labels. The program was further enhanced by calculating fortifier powder displacement factors to improve mixing precision. Order entry was optimized to allow for more complex mixing recipes and include a preference list of frequently ordered feeds. The EHR-ADP's safeguarded features allowed for catching multiple near-missed feeding administration errors. The NICU preterm neonate cohort had an average of 6-day decrease (P = 0.01) in the length of stay after implementation while maintaining the same weight gain velocity. The EHR-ADP may improve safety and efficiency; further improvements and wider utilization are needed to demonstrate the growth benefits of personalized nutrition.

The balance of omega-6/omega-3 (n-6/n-3) is crucial for proper brain function as they have opposite physiological roles.

To analyze the association between maternal serum ratios of n-6/n-3 in the first and third trimesters of pregnancy and the neurodevelopment of their children in the early days after birth in the population of Northern Spain's Mediterranean region.

Longitudinal study in which 336 mother-child pairs participated. Mother serum concentrations of long-chain polyunsaturated fatty acids (LCPUFAs), docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) were determined. Sociodemographic, clinical, lifestyle habits, and obstetrical variables were collected. The Bayley Scales of Infant and Toddler Development (BSID-III) was used to assess infant neurodevelopment. Multiple linear regression models adjusting for confounding factors were performed.

In the third trimester, a higher maternal n-6/n-3 ratio was negatively associated with infant motor development (β = -0.124, p = 0.023). Similarly, higher ARA/DHA ratios were negatively associated with total motor (β = -2.005, p = 0.002) and fine motor development (β = -0.389, p = 0.001). No significant associations were observed in the first trimester nor for the ARA/EPA ratio in the third trimester.

Our findings indicate that an elevated n-6/n-3 ratio and ARA/DHA ratio in the third trimester of pregnancy are associated with poorer motor development outcomes in infants. These results highlight the importance of optimizing maternal fatty acid balance during pregnancy to support fetal neurodevelopment, suggesting a need for further research to verify these associations and elucidate underlying mechanisms.

There is strong evidence proper nutrition is imperative for healthy infant neurodevelopment, providing the neural foundations for later cognition and behavior. Over the first years of life infants are supported by unique sources of nutrition (e.g., human milk, alternative milk sources). It is during this time that the brain undergoes its most drastic changes during postnatal development. Past research has examined associations between infant feeding and nutrition and morphological features of the brain, yet there remains a paucity of information on functional characteristics of neural activity during feeding. Within this article, we discuss how neuroimaging modalities can be optimized for researching the impacts of infant feeding and nutrition on brain function. We review past research utilizing EEG and fNIRS and describe our efforts to further develop neuroimaging approaches that allow for measurement of brain activity during active feeding with greater spatial resolution (e.g., fMRI and OPM-MEG). We also discuss current challenges, as well as the scientific and logistical limitations of each method. Once protocols have been optimized, these methods will provide the requisite insight into the underlying mechanisms of nutritional and feeding impacts on neurodevelopment, providing the missing piece in the field's efforts to understand this essential and ubiquitous part of early life.

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social and emotional development beginning prenatally and planned through early childhood. Many prenatal and early childhood exposures impact both later physical health and development. Moreover, early deficits in physical health, such as growth and vision, are associated with differences in brain development, language and cognitive functioning. For these reasons, the HBCD Study includes measures of early childhood physical health, many of which have clinical relevance, and are applicable for use as both predictors and outcomes. Study measures assess a broad range of physical health domains and include both objective measurement of child growth and health and subjective caregiver report of behaviors and attitudes about constructs known to influence growth and physical development. Lastly, we obtain caregiver report of the child's routine medical care as well as acute and chronic medical issues. We anticipate that these data will contextualize the impact of child physical growth and health on child brain development and function. In this report we present the rationale for each domain and an overview of the physical health measures included in the current HBCD Study protocol.

In the pediatric population, epilepsy is one of the most common neurological disorders that often results in cognitive dysfunction. It affects patients' life quality by limiting academic performance and self-esteem and increasing social rejection. There are several interventions for the neurohabilitation of cognitive impairment, including LEGO®-based therapy (LEGO® B-T), which promotes neuronal connectivity and cortical plasticity through the use of assembly sets and robotic programming. Therefore, the aim of this study was to analyze the effect of LEGO® B-T on cognitive processes in pediatric patients with epilepsy. Eligible patients were identified; in the treatment group, an initial evaluation was performed with the NEUROPSI and BANFE-2 neuropsychological tests. Then, the interventions were performed once a week, and a final test was performed. In the control group, after the initial evaluation, the final evaluation was performed. An overall improvement was observed in the LEGO® B-T patients, with a significant increase in BANFE-2 scores in the orbitomedial, anterior prefrontal, and dorsolateral areas. In addition, in the gain score analysis, the orbitomedial and memory scores were significantly different from the control group. LEGO® B-T neurohabilitation is a remarkable option for epilepsy patients, who are motivated when they observe improvements.

Processing speed is suboptimal among preterm-born children which is of concern as it is a foundational skill supporting higher-level cognitive functions. The study objective was to evaluate associations between early-life nutrition and processing speed in childhood.

Macronutrient and human milk (mother's own, donor) intakes from 137 children born preterm with very low birth weight enrolled in a nutrition feeding trial were included. Processing speed was evaluated at age 5 using the Wechsler Preschool and Primary Scale of Intelligence-fourth edition Processing Speed Index. Associations between early-life nutrition and processing speed were explored through linear regression.

Children had a mean (standard deviation [SD]) birth gestational age of 28.1 (2.5) weeks, weight of 1036 (260) g and 52% were male. The mean (SD) assessment age was 5.7 (0.2) years. Sex-dependent relationships were identified between first postnatal month protein, lipid and energy intakes and processing speed at 5 years. For females, lower protein (per 0.1 g/kg/d: -0.88, 95% confidence interval [CI]: -1.53, -0.23; p = 0.01) and energy (per 10 kcal/kg/d: -2.38, 95% CI: -4.70, -0.05; p = 0.03) intakes were related to higher processing speed scores. Mother's milk provision was positively associated (per 10% increase: 0.80, 95% CI: 0.22, 1.37; p = 0.01) and donor milk was negatively associated (per 10% increase: -1.15, 95% CI: -2.22, -0.08; p = 0.04) with processing speed scores; no sex differences were observed.

First postnatal month nutrition was related to processing speed at age 5 in children born preterm with very low birth weight. Early-life nutrition that supports processing speed may be leveraged to improve later cognitive outcomes for this vulnerable population.

Preterm born infants are at risk for brain injury and subsequent developmental delay. Treatment options are limited, but optimizing postnatal nutrition may improve brain- and neurodevelopment in these infants. In pre-clinical animal models, combined supplementation of docosahexaenoic acid (DHA), choline, and uridine-5-monophosphate (UMP) have shown to support neuronal membrane formation. In two randomized controlled pilot trials, supplementation with the investigational product was associated with clinically meaningful improvements in cognitive, attention, and language scores. The present study aims to assess the effect of a similar nutritional intervention on brain development and subsequent neurodevelopmental outcome in infants born very and extremely preterm.

This is a randomized, placebo-controlled, double-blinded, parallel-group, multi-center trial. A total of 130 infants, born at less than 30 weeks of gestation, will be randomized to receive a test or control product between term-equivalent age and 12 months corrected age (CA). The test product is a nutrient blend containing DHA, choline, and UMP amongst others. The control product contains only fractions of the active components. Both products are isocaloric powder supplements which can be added to milk and solid feeds. The primary outcome parameter is white matter integrity at three months CA, assessed using diffusion-tensor imaging (DTI) on MRI scanning. Secondary outcome parameters include volumetric brain development, cortical thickness, cortical folding, the metabolic and biochemical status of the brain, and product safety. Additionally, language, cognitive, motor, and behavioral development will be assessed at 12 and 24 months CA, using the Bayley Scales of Infant Development III and digital questionnaires (Dutch version of the Communicative Development Inventories (N-CDI), Ages and Stages Questionnaire 4 (ASQ-4), and Parent Report of Children's Abilities - Revised (PARCA-R)).

The investigated nutritional intervention is hypothesized to promote brain development and subsequent neurodevelopmental outcome in preterm born infants who have an inherent risk of developmental delay. Moreover, this innovative study may give rise to new treatment possibilities and improvements in routine clinical care.

WHO International Clinical Trials Registry: NL-OMON56181 (registration assigned October 28, 2021).

Coarse measures of socioeconomic status, such as parental income or parental education, have been linked to differences in white matter development. However, these measures do not provide insight into specific aspects of an individual's environment and how they relate to brain development. On the other hand, educational intervention studies have shown that changes in an individual's educational context can drive measurable changes in their white matter. These studies, however, rarely consider socioeconomic factors in their results. In the present study, we examined the unique relationship between educational opportunity and white matter development, when controlling other known socioeconomic factors. To explore this question, we leveraged the rich demographic and neuroimaging data available in the ABCD study, as well the unique data-crosswalk between ABCD and the Stanford Education Data Archive (SEDA). We find that educational opportunity is related to accelerated white matter development, even when accounting for other socioeconomic factors, and that this relationship is most pronounced in white matter tracts associated with academic skills. These results suggest that the school a child attends has a measurable relationship with brain development for years to come.

Raw, never stored or pasteurized mother's own milk (MOM) is not always available to feed preterm infants; however, storage and pasteurization of MOM diminishes some bioactive components. It can be difficult to feed raw MOM to preterm infants due to transportation and storage of small volumes that might be pumped away from the infant, and a concern that they might harbor bacteria. However, the higher availability of bioactive components in raw MOM may provide benefits to preterm infants compared to frozen or pasteurized MOM.

To systematically review and summarize the results of studies on feeding raw MOM versus frozen or pasteurized MOM to preterm infants born at less than 37 weeks of gestation.

Four databases were searched (Cochrane, Embase, Ovid MEDLINE, and Web of Science) for this systematic review. Of 542 studies identified, nine met inclusion criteria and were critically evaluated using the quality assessment tool for quantitative studies by the Effective Public Health Practice Project. Studies were organized using the Breastfeeding Challenges Facing Preterm Mother-Infant Dyads theoretical framework.

Included studies evaluated the outcomes of preterm infants fed raw versus pasteurized MOM (n = 7, 77.8%) or raw versus frozen MOM (n = 2, 22.2%). Researchers found that raw MOM did not increase infant infections and may have improved health and growth outcomes for study participants.

There is laboratory evidence supporting the safety and efficacy of the use of raw MOM for preterm infants. A raw MOM diet is recommended for preterm infants by professional organizations. Despite this, it may not be universally prioritized and could require purposeful implementation by each institution. Further research is needed to pursue the potential benefits of a raw MOM diet for preterm infants.

During the early weeks of life optimization of nutrition in extremely preterm infants presents a critical opportunity to attenuate the adverse neurological consequences of prematurity and potentially improve neurodevelopmental outcome. We hypothesized that the use of multicomponent lipid emulsion (MLE) in parenteral nutrition (PN) would be related to larger volume of the cerebellum on brain magnetic resonance at term of equivalent age (TEA) in extremely low birth weight (ELBW) infants.

We analyzed the brain magnetic resonance imaging (MRI) at TEA of a cohort of preterm infants with gestational age ≤28 weeks and/or birth weight <1,000 g randomly assigned in our previous trial to receive an MLE or soybean-based lipid emulsion (SLE). The primary outcome of the study was the cerebellar volume (CeV), valued on MRI acquired at TEA. Secondary outcomes included total brain volume (TBV), supratentorial volume, brainstem volume, and CeV corrected for TBV evaluated on MRI acquired at TEA.

MRIs at TEA of 34 infants were then analyzed: 17 in the MLE group and 17 in the SLE group. The postmenstrual age (PMA) at which MRIs were performed were comparable between the two study groups. The CeV as well as the PMA-corrected CeV were significantly higher in the MLE group than in the SLE group. No difference was found among the other brain volumes considered.

Our results suggest that the use of MLE in PN could promote CeV growth in ELBW infants, valued with MRI at TEA.

· Optimization of nutrition in extremely low birthweight infants.. · Use of multicomponent lipid emulsions in parenteral nutrition.. · Larger cerebellar volume with use of multicomponent lipid emulsion..

Extremely preterm infants, defined as those born before 28 weeks' gestational age, are a very vulnerable patient group at high risk for adverse outcomes, such as necrotizing enterocolitis and death. Necrotizing enterocolitis is an inflammatory gastrointestinal disease with high incidence in this cohort and has severe implications on morbidity and mortality. Previous randomized controlled trials have shown reduced incidence of necrotizing enterocolitis among older preterm infants following probiotic supplementation. However, these trials were underpowered for extremely preterm infants, rendering evidence for probiotic supplementation in this population insufficient to date.

The Probiotics in Extreme Prematurity in Scandinavia (PEPS) trial is a multicenter, double-blinded, placebo-controlled and registry-based randomized controlled trial conducted among extremely preterm infants (n = 1620) born at six tertiary neonatal units in Sweden and four units in Denmark. Enrolled infants will be allocated to receive either probiotic supplementation with ProPrems® (Bifidobacterium infantis, Bifidobacterium lactis, and Streptococcus thermophilus) diluted in 3 mL breastmilk or placebo (0.5 g maltodextrin powder) diluted in 3 mL breastmilk per day until gestational week 34. The primary composite outcome is incidence of necrotizing enterocolitis and/or mortality. Secondary outcomes include incidence of late-onset sepsis, length of hospitalization, use of antibiotics, feeding tolerance, growth, and body composition at age of full-term and 3 months corrected age after hospital discharge.

Current recommendations for probiotic supplementation in Sweden and Denmark do not include extremely preterm infants due to lack of evidence in this population. However, this young subgroup is notably the most at risk for experiencing adverse outcomes. This trial aims to investigate the effects of probiotic supplementation on necrotizing enterocolitis, death, and other relevant outcomes to provide sufficiently powered, high-quality evidence to inform probiotic supplementation guidelines in this population. The results could have implications for clinical practice both in Sweden and Denmark and worldwide.

( Clinicaltrials.gov ): NCT05604846.

The survival of preterm infants has steadily improved thanks to advances in perinatal and neonatal intensive clinical care. The focus is now on finding ways to improve morbidities, especially neurological outcomes. Although antenatal steroids and magnesium for preterm infants have become routine therapies, studies have mainly demonstrated short-term benefits for antenatal steroid therapy but limited evidence for impact on long-term neurodevelopmental outcomes. Further advances in neuroprotective and neurorestorative therapies, improved neuromonitoring modalities to optimize recruitment in trials, and improved biomarkers to assess the response to treatment are essential. Among the most promising agents, multipotential stem cells, immunomodulation, and anti-inflammatory therapies can improve neural outcomes in preclinical studies and are the subject of considerable ongoing research. In the meantime, bundles of care protecting and nurturing the brain in the neonatal intensive care unit and beyond should be widely implemented in an effort to limit injury and promote neuroplasticity. IMPACT: With improved survival of preterm infants due to improved antenatal and neonatal care, our focus must now be to improve long-term neurological and neurodevelopmental outcomes. This review details the multifactorial pathogenesis of preterm brain injury and neuroprotective strategies in use at present, including antenatal care, seizure management and non-pharmacological NICU care. We discuss treatment strategies that are being evaluated as potential interventions to improve the neurodevelopmental outcomes of infants born prematurely.

The transition from childhood to adolescence is characterized by enhanced neural plasticity and a consequent susceptibility to both beneficial and adverse aspects of one's milieu.

To understand the implications of the interplay between protective and risk-enhancing factors, we analyzed longitudinal data from the Adolescent Brain Cognitive Development (ABCD) Study (n = 834; 394 female). We probed the maturational correlates of positive lifestyle variables (friendships, parental warmth, school engagement, physical exercise, healthy nutrition) and genetic vulnerability to neuropsychiatric disorders (major depressive disorder, Alzheimer's disease, anxiety disorders, bipolar disorder, schizophrenia) and sought to further elucidate their implications for psychological well-being.

Genetic risk factors and lifestyle buffers showed divergent relationships with later attentional and interpersonal problems. These effects were mediated by distinguishable functional neurodevelopmental deviations spanning the limbic, default mode, visual, and control systems. More specifically, greater genetic vulnerability was associated with alterations in the normative maturation of areas rich in dopamine (D2), glutamate, and serotonin receptors and of areas with stronger expression of astrocytic and microglial genes, a molecular signature implicated in the brain disorders discussed here. Greater availability of lifestyle buffers predicted deviations in the normative functional development of higher density GABAergic (gamma-aminobutyric acidergic) receptor regions. The two profiles of neurodevelopmental alterations showed complementary roles in protection against psychopathology, which varied with environmental stress levels.

Our results underscore the importance of educational involvement and healthy nutrition in attenuating the neurodevelopmental sequelae of genetic risk factors. They also underscore the importance of characterizing early-life biomarkers associated with adult-onset pathologies.

Gut microbiota are associated with adverse neurodevelopmental outcomes in preterm infants; however, the precise causal relationship remains unclear. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to comprehensively study the relationship between gut microbiota and adverse neurodevelopmental outcomes in preterm infants and identify specific causal bacteria that may be associated with the occurrence and development of adverse neurodevelopmental outcomes in preterm infants. The genome-wide association analysis (GWAS) of the MiBioGen biogroup was used as the exposure data. The GWAS of six common adverse neurodevelopmental outcomes in premature infants from the FinnGen consortium R9 was used as the outcome data. Genetic variations, namely, single nucleotide polymorphisms (SNPs) below the locus-wide significance level (1 × 10-5) and genome-wide statistical significance threshold (5 × 10-8) were selected as instrumental variables (IVs). MR studies use inverse variance weighting (IVW) as the main method. To supplement this, we also applied three additional MR methods: MR-Egger, weighted median, and weighted mode. In addition, the Cochrane's Q test, MR-Egger intercept test, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out methods were used for sensitivity analysis. Our study shows a causal relationship between specific gut microbiota and neurodevelopmental outcomes in preterm infants. These findings provide new insights into the mechanism by which gut microbiota may mediate adverse neurodevelopmental outcomes in preterm infants.

This study aimed to explore the effects of breast milk feeding volume on the early behavioral neurodevelopment of extremely preterm infants (gestational age < 28 weeks).

The study was conducted from 1 January 2021 to 31 March 2023. A total of 187 preterm infants from a neonatal intensive care unit (NICU) in a Grade III Class A hospital in Zhejiang, China, were divided based on the proportion of breast milk in their total enteral nutrition: high proportion (≥ 80%, including exclusive breast milk feeding), medium proportion (20% ~ < 80%), and low proportion (< 20%). The study investigated motor performance and behavioral neurodevelopment at 37 weeks of corrected gestational age, as well as the total incidence of intracranial hemorrhage within the first four weeks postpartum.

The low breast milk feeding group had significantly lower scores in infant motor performance (31.34 ± 5.85) and elicited item scores (19.89 ± 5.55) compared to the medium and high groups (33.52 ± 4.33, 22.13 ± 4.22; and 35.86 ± 5.27, 23.91 ± 4.98), p < 0.05, respectively. Despite no significant difference in behavioral ability, the low proportion group exhibited lower passive muscle tension and primitive reflex scores than the medium and high proportion groups. The high proportion group showed higher active muscle tension scores. Ultrasound results revealed varying incidences of intracranial hemorrhage: 72.9% in low, 52.5% in medium, and 19.6% in the high proportion groups.

Medium to high levels of breast milk feeding contribute positively to motor and behavioral neurological development in extremely preterm infants and decrease the likelihood of ventricular hemorrhage. However, it does not have a significant effect on the development of behavioral abilities. Due to the limited sample size, the next step will be to expand the sample size and further investigate the extent of the impact on various aspects of the nervous system.

Understanding the interrelationship between the gut microbiota and host physiology, although still in its relative infancy, has taken important steps forward over the past decade. In the context of brain disorders including those characterized by neurodevelopmental and neurodegenerative changes there have been important advances. However, initially research involved correlational analyses, had limited translational scope, and lacked functional assessments. Thus, largescale longitudinal clinical investigations that assess causation and underlying mechanisms via in depth analysis methods are needed. In neurodegeneration research, strong causal evidence now links the gut microbiome to Alzheimer's (AD), and Parkinson's Disease (PD), as supported by human-to-animal transplantation studies. Longitudinal interventions are being conducted in AD, PD, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Neurodevelopmental research has also seen a boon in microbiome-related clinical research including in autism, Attention-deficit/hyperactivity disorder, and schizophrenia, which is confirming prior animal model work regarding the key time-windows in the gut microbiome important for infant cognition. While recent research advances represent important progress, fundamental knowledge gaps and obstacles remain. Knowing how and why the gut microbiome changes at the extremes of life will develop our mechanistic understanding and help build the evidence base as we strive toward counteracting microbial missteps with precision therapeutic interventions.

Premature infants, given their limited reserves, heightened energy requirements, and susceptibility to nutritional deficits, require specialized care.

To examine the complex interplay between nutrition and neurodevelopment in premature infants, underscoring the critical need for tailored nutritional approaches to support optimal brain growth and function.

PubMed and MeSH and keywords: preterm, early nutrition, macronutrients, micronutrients, human milk, human milk oligosaccharides, probiotics AND neurodevelopment or neurodevelopment outcomes. Recent articles were selected according to the authors' judgment of their relevance. Specific nutrients, including macro (amino acids, glucose, and lipids) and micronutrients, play an important role in promoting neurodevelopment. Early and aggressive nutrition has shown promise, as has recognizing glucose as the primary energy source for the developing brain. Long-chain polyunsaturated fatty acids, such as DHA, contribute to brain maturation, while the benefits of human milk, human milk oligosaccharides, and probiotics on neurodevelopment via the gut-brain axis are explored. This intricate interplay between the gut microbiota and the central nervous system highlights human milk oligosaccharides' role in early brain maturation.

Individualized nutritional approaches and comprehensive nutrient strategies are paramount to enhancing neurodevelopment in premature infants, underscoring human milk's potential as the gold standard of nutrition for preterm infants.

Growth in the neonatal period is critical for the neurodevelopment of the individual, both in low- and middle-income countries [...].

This study investigated the efficacy of kinesiology taping application in premature infants with dysphagia.

A total of 60 premature newborns (born ≤37weeks' gestational age who reached the age ≥34 weeks of postmenstrual age) with sucking and swallowing problems were randomly assigned to the kinesiology taping group [n=31; 18 males, 13 females; mean postmenstrual age 35.4 weeks (SD 0.9 weeks, range 34-38 weeks)] or control group without kinesiology taping application [n=29; 16 males, 13 females; mean postmenstrual age age 35.6 weeks (SD 1.4 weeks, range 34-40 weeks)].

Kinesiology taping group yielded significant improvement in the oral reflexes (p<0.001) and in the sucking functions including tongue movement, sucking power, number of sucks and sucking pause, maintenance of alertness, jaw movement, tongue cupping, and maintenance of rhythm (p<0.001, p=0.011, p=0.002, and p=0.001, respectively). There was a significant difference in favor of the taping group with respect to the number of neonates whose feeding improved (26 (84%) vs. 7 (24%), p<0.001).

The results of this study show that kinesiology taping can be applied as a safe and effective method to improve feeding functions in premature infants with sucking and swallowing difficulties.

Inequalities in preterm infant mortality exist between population subgroups within the United States.

To characterize trends in preterm infant mortality by maternal race and socioeconomic status to assess how inequalities in preterm mortality rates have changed over time.

This was a retrospective longitudinal descriptive study using the US National Center for Health Statistics birth infant/death data set for 12 256 303 preterm infant births over 26 years, between 1995 and 2020. Data were analyzed from December 2022 to March 2023.

Maternal characteristics including race, smoking status, educational attainment, antenatal care, and insurance status were used as reported on an infant's US birth certificate.

Preterm infant mortality rate was calculated for each year from 1995 to 2020 for all subgroups, with a trend regression coefficient calculated to describe the rate of change in preterm mortality.

The average US preterm infant mortality rate (IMR) decreased from 33.71 (95% CI, 33.71 to 34.04) per 1000 preterm births per year between 1995-1997, to 23.32 (95% CI, 23.05 to 23.58) between 2018-2020. Black non-Hispanic infants were more likely to die following preterm births than White non-Hispanic infants (IMR, 31.09; 95% CI, 30.44 to 31.74, vs 21.81; 95% CI, 21.43 to 22.18, in 2018-2020); however, once born, extremely prematurely Black and Hispanic infants had a narrow survival advantage (IMR rate ratio, 0.87; 95% CI, 0.84 to 0.91, in 2018-2020). The rate of decrease in preterm IMR was higher in Black infants (-0.015) than in White (-0.013) and Hispanic infants (-0.010); however, the relative risk of preterm IMR among Black infants compared with White infants remained the same between 1995-1997 vs 2018-2020 (relative risk, 1.40; 95% CI, 1.38 to 1.44, vs 1.43; 95% CI, 1.39 to 1.46). The rate of decrease in preterm IMR was higher in nonsmokers compared with smokers (-0.015 vs -0.010, respectively), in those with high levels of education compared with those with intermediate or low (-0.016 vs - 0.010 or -0.011, respectively), and in those who had received adequate antenatal care compared with those who did not (-0.014 vs -0.012 for intermediate and -0.013 for inadequate antenatal care). Over time, the relative risk of preterm mortality widened within each of these subgroups.

This study found that between 1995 and 2020, US preterm infant mortality improved among all categories of prematurity. Inequalities in preterm infant mortality based on maternal race and ethnicity have remained constant while socioeconomic disparities have widened over time.

Holoprosencephaly (HPE) is a congenital malformation with various degrees of incomplete separation of the cerebral hemispheres due to differentiation disorders of the forebrain. Although HPE with diabetes insipidus due to associated pituitary dysfunction has been reported, HPE with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) is very rare. Tolvaptan, a vasopressin V2 receptor antagonist, is effective in adults with SIADH. However, there is no report of its efficacy in infants with SIADH. The purpose of this report is to demonstrate that tolvaptan is effective for SIADH in infants and that administration of tolvaptan eliminates the need for restriction of water intake and sodium administration.

A 2414-g female infant was born at 38 wk by normal vaginal delivery. Facial anomalies and head magnetic resonance imaging indicated semilobar HPE. After birth, she had hyponatremia due to SIADH and was treated using water and sodium restriction. However, she developed an exaggerated response to the fluid restrictions, resulting in large fluctuations in serum sodium levels. Subsequent administration of tolvaptan improved the fluctuations in serum sodium levels without the need for adjustment of water or sodium administration. Serum sodium was maintained within the normal range after discontinuation of tolvaptan at 80 d of life. There were no side effects, such as hypernatremia or liver dysfunction, during the administration of tolvaptan.

This is the first report on the safety and efficacy of tolvaptan in an infant with SIADH associated with HPE.

To determine how neonatal growth velocity affects the association between birth weight and neurodevelopmental outcomes in infants born preterm.

This study is a secondary analysis of the Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia in Very Preterm Infants (MOBYDIck) randomized multicenter trial conducted in breastfed infants born at <29 weeks of gestation, whose mothers were supplemented with docosahexaenoic acid or placebo during the neonatal period. Neurodevelopmental outcomes were assessed at 18-22 months of corrected age using the Bayley-III cognitive and language composite scores. The role of neonatal growth velocity was assessed with causal mediation and linear regression models. Subgroup analyses were stratified by birth weight z-score categories (<25th, ≥25th-≤75th, and >75th percentiles).

Neurodevelopmental outcomes were available for 379 children (mean gestational age, 26.7 ± 1.5 weeks). Growth velocity partially mediated the relationships between birth weight and cognitive (β = -1.1; 95% CI, -2.2 to -0.02; P = .05) and language scores (β = -2.1; 95% CI, -3.3 to -0.8; P = .002). An increase by 1 g/kg/day in growth velocity was associated with an increase by 1.1 point in the cognitive score (95% CI, -0.03 to 2.1; P = .06) and 1.9 point in the language score (95% CI, 0.7 to 3.1; P = .001), after adjustment for birth weight z-score. For children with birth weight <25th percentile, a 1 g/kg/day increase in growth velocity was associated with an increase by 3.3 points in the cognitive score (95% CI, 0.5 to 6.0; P = .02) and 4.1 points in the language score (95% CI, 1.3 to 7.0; P = .004).

Postnatal growth velocity mediated the relationship between birth weight and neurodevelopmental performance, with larger effects for children with lower birth weight.

Clinicaltrials.gov identifier: NCT02371460.

Breast milk (BM) is a constantly changing fluid that represents the primary source of nutrition for newborns. It is widely recognized that breastfeeding provides benefits for both the child and the mother, including a lower risk of ovarian and breast cancer, type 2 diabetes mellitus, decreased blood pressure, and more. In infants, breastfeeding has been correlated with a lower risk of infectious diseases, obesity, lower blood pressure, and decreased incidence of respiratory infections, diabetes, and asthma. Various factors, such as the baby's sex, the health status of the mother and child, the mother's diet, and the mode of delivery, can affect the composition of breast milk. This review focuses on the biological impact of the nutrients in BM on the development and functionality of vital organs to promote the benefit of health.

Stunting affects 22% children globally, putting them at risk of adverse outcomes including delayed development. We investigated the effect of milk protein (MP) vs. soy and whey permeate (WP) vs. maltodextrin in large-quantity, lipid-based nutrient supplement (LNS), and LNS itself vs. no supplementation, on child development and head circumference among stunted children aged 1-5 years. We conducted a randomized, double-blind, community-based 2 × 2 factorial trial in Uganda (ISRCTN1309319). We randomized 600 children to one of four LNS formulations (~535 kcal/d), with or without MP (n = 299 vs. n = 301) or WP (n = 301 vs. n = 299), for 12 weeks or to no supplementation (n = 150). Child development was assessed using the Malawi Development Assessment Tool. Data were analyzed using linear mixed-effects models. Children had a median [interquartile range] age of 30 [23; 41] months and mean ± standard deviation height-for-age z-score of -3.02 ± 0.74. There were no interactions between MP and WP for any of the outcomes. There was no effect of either MP or WP on any developmental domain. Although LNS itself had no impact on development, it resulted in 0.07 (95%CI: 0.004; 0.14) cm higher head circumference. Neither dairy in LNS, nor LNS in itself, had an effect on development among already stunted children.

White matter (WM) injury is the most common type of brain injury in preterm infants and is associated with impaired neurodevelopmental outcome (NDO). Currently, there are no treatments for WM injury, but optimal nutrition during early preterm life may support WM development. The main aim of this scoping review was to assess the influence of early postnatal nutrition on WM development in preterm infants. Searches were performed in PubMed, EMBASE, and COCHRANE on September 2022. Inclusion criteria were assessment of preterm infants, nutritional intake before 1 month corrected age, and WM outcome. Methods were congruent with the PRISMA-ScR checklist. Thirty-two articles were included. Negative associations were found between longer parenteral feeding duration and WM development, although likely confounded by illness. Positive associations between macronutrient, energy, and human milk intake and WM development were common, especially when fed enterally. Results on fatty acid and glutamine supplementation remained inconclusive. Significant associations were most often detected at the microstructural level using diffusion magnetic resonance imaging. Optimizing postnatal nutrition can positively influence WM development and subsequent NDO in preterm infants, but more controlled intervention studies using quantitative neuroimaging are needed. IMPACT: White matter brain injury is common in preterm infants and associated with impaired neurodevelopmental outcome. Optimizing postnatal nutrition can positively influence white matter development and subsequent neurodevelopmental outcome in preterm infants. More studies are needed, using quantitative neuroimaging techniques and interventional designs controlling for confounders, to define optimal nutritional intakes in preterm infants.

Throughout infancy, the brain undergoes rapid changes in structure and function that are sensitive to environmental influences, such as diet. Breastfed (BF) infants score higher on cognitive tests throughout infancy and into adolescence than formula fed (FF) infants, and these differences in neurocognitive development are reflected in higher concentrations of white and grey matter as measured by MRI. To further explore the effect diet has on cognitive development, electroencephalography (EEG) is used as a direct measure of neuronal activity and to assess specific frequency bands associated with cognitive processes. Task-free baseline EEGs were collected from infants fed with human milk (BF), dairy-based formula (MF), or soy-based formula (SF) at 2, 3, 4, 5, and 6 months of age to explore differences in frequency bands in both sensor and source space. Significant global differences in sensor space were seen in beta and gamma bands between BF and SF groups at ages 2 and 6 months, and these differences were further observed through volumetric modeling in source space. We conclude that BF infants exhibit earlier brain maturation reflected in greater power spectral density in these frequency bands.

Preterm birth is associated with an increased risk for impaired body weight gain. While it is known that in prematurity several somatic and environmental factors (e.g., endocrine factors, nutrition) modulate short- and long-term body weight gain, the contribution of potentially impaired body weight control in the brain remains elusive. We hypothesized that the structure of hypothalamic nuclei involved in body weight control is altered after preterm birth, with these alterations being associated with aberrant body weight development into adulthood.

We assessed 101 very preterm (i.e., <32 weeks of gestational age) and/or very low birth weight (i.e., <1500g; VP/VLBW) and 110 full-term born (FT) adults of the population-based Bavarian Longitudinal Study with T1-weighted MRI, deep learning-based hypothalamus subunit segmentation, and multiple body weight assessments from birth into adulthood.

Volumes of the whole hypothalamus and hypothalamus subunits relevant for body weight control were reduced in VP/VLBW adults and associated with birth variables (i.e., gestational age and intensity of neonatal treatment), body weight (i.e., weight at birth and adulthood), and body weight trajectories (i.e., trajectory slopes and cluster/types such as long-term catch-up growth). Particularly, VP/VLBW subgroups, whose individuals showed catch-up growth and/or were small for gestational age, were mostly associated with volumes of distinct hypothalamus subunits such as lateral or infundibular/ventromedial hypothalamus.

Results demonstrate lower volumes of body weight control-related hypothalamus subunits after preterm birth that link with long-term body weight gain. Data suggest postnatal development of body weight -related hypothalamic nuclei in VP/VLBW individuals that corresponds with distinct body weight trajectories into adulthood.

The aim of this study was to determine the extent to which socioeconomic characteristics of the home and neighborhood are associated with racial inequalities in brain outcomes.

We performed a cross-sectional analysis of the baseline dataset (v.2.0.1) from the Adolescent Brain and Cognitive Development (ABCD) Study. Cognitive performance was assessed using the National Institutes of Health Toolbox (NIH-TB) cognitive battery. Standard socioeconomic indicators of the family and neighborhood were derived from census-related statistics. Cortical morphometric measures included MRI-derived thickness, area, and volume.

9638 children were included. Each NIH-TB cognitive measure was negatively associated with household and neighborhood socioeconomic characteristics. Differences in cognitive scores between Black or Hispanic children and other racial groups were mitigated by higher household income. Most children from lowest-income families or residents in impoverished neighborhoods were Black or Hispanic. These disparities were associated with racial differences in NIH-TB measures and mediated by smaller cortical brain volumes.

Neighborhood socioeconomic characteristics are associated with racial differences in preadolescent brain outcomes and mitigated by greater household income. Household income mediates racial differences more strongly than neighborhood-level socioeconomic indicators in brain outcomes. Highlighting these socioeconomic risks may direct focused policy-based interventions such as allocation of community resources to ensure equitable brain outcomes in children.

Neighborhood socioeconomic characteristics are associated with racial differences in preadolescent brain outcomes and mitigated by greater household income. Household income mediates racial differences more strongly than neighborhood-level socioeconomic indicators in brain outcomes. Highlighting these disparities related to socioeconomic risks may direct focused policy-based interventions such as allocation of community resources to ensure equitable brain outcomes in children.

The prevailing consensus from large epidemiological studies is that breastfeeding is associated with improved IQ and cognitive functioning in later childhood and adolescence. Current research is exploring the association between breastfeeding and early brain development in preterm infants.

To explore the differences in brain gray matter between breastmilk-fed and formula-fed preterm infants using structural and functional magnetic resonance imaging.

A convenience sample of breastmilk-fed preterm infants(n = 34) and formula-fed infants (n = 22) aged approximately 32 weeks. At near term-equivalent age, MR scanning was performed. Gray matter structural and functional differences between the two groups were assessed using MATLAB software for voxel-based morphometry (VBM) and amplitude of low-frequency fluctuation (ALFF) analysis.

Maternal and neonatal demographic characteristics showed no significant difference between the two groups. Breastmilk-fed infants had greater regional gray matter volume on MRI than formula-fed infants in multiple brain regions, including the bilateral frontal lobe (BA11, BA46), right temporal lobe (BA37), and left caudate nucleus, at a statistical threshold of p<0.01 (AlphaSim corrected) with a cluster size of >40 voxels. Compared with formula-fed infants, breastmilk-fed infants showed increased brain activation on fMRI in the right superior temporal gyrus (BA41).

Breastmilk-fed infants had greater regional gray matter development and increased regional gray matter function compared with formula-fed infants at near term-equivalent age, suggesting breastmilk feeding in the early period after birth may have some degree of influence on early brain development in preterm infants.

Lutein and zeaxanthin (L + Z) are carotenoids that accumulate in neural tissue and potentially confer benefits to cognition. Whereas cross-sectional studies have revealed positive associations between macular carotenoids (MC) and cognition, no studies have investigated whether L + Z supplementation impacts MC and cognition in childhood. Accordingly, the Integrated Childhood Ocular Nutrition Study aims to investigate the impact of L + Z supplementation over 9-months on academic abilities, attentional control, memory, and MC among preadolescent children. Children 8-10 years (N = 288) will enroll in a 9-month double-blind, placebo-controlled, randomized trial. The study is registered and approved as a clinical trial on the U.S. National Library of Medicine http://ClinicalTrials.gov registry (NCT05177679). Participants will be randomized into an active (10 mg lutein+2 mg zeaxanthin) or waitlist placebo-controlled group. Primary outcomes include hippocampal-dependent memory, attentional inhibition, and academic achievement using a spatial reconstruction task, an Eriksen flanker task, and the Kaufman Test of Academic and Educational Achievement 3rd edition, respectively. Secondary outcomes include event-related brain potentials of attentional resource allocation and information processing speed (i.e., P3/P300 amplitude and latency) recorded during the flanker task. Macular pigment optical density (MPOD) will be assessed using heterochromatic flicker photometry. Cognitive assessments will be completed prior to and after completion of the supplementation period. MPOD will be quantified prior to, at the mid-point of (4-5 months), and after (9 months) the supplementation period. It is hypothesized that L + Z supplementation will improve cognition and academic achievement. Further, benefits for cognition and achievement are anticipated to be mediated by increases in MC among treatment group participants.

Survival rates for extremely low-birth-weight (ELBW) infants are improving as neurodevelopmental impairment (NDI) rates stay stable, thereby increasing the overall number of infants with NDI. Although there are many determinants of NDI in this population, nutritional factors are of interest because they are readily modifiable in the clinical setting. Nurses can influence nutritional factors such as improving access to human milk feeding, using growth monitoring, establishing feeding policies, implementing oral care with colostrum, facilitating kangaroo care, and providing lactation education for the mother. All of these measures assist in leading to a decrease in NDI rates among ELBW infants.

The chemical composition of human milk has long-lasting effects on brain development. We examined the prognostic value of the human milk metabolome and exposome in children with the risk of neurodevelopmental delay (NDD).

This retrospective cohort study included 82 mother-infant pairs (40 male and 42 female infants). A total of 59 milk samples were from mothers with typically developing children and 23 samples were from mothers of children at risk. Milk samples were collected before 9 months of age (4.6 ± 2.5 months, mean ± SD). Neurocognitive development was assessed by maternal report at 14.2 ± 3.1 months using the Ages and Stages Questionnaires-2.

Metabolome and exposome profiling identified 453 metabolites and 61 environmental chemicals in milk. Machine learning tools identified changes in deoxysphingolipids, phospholipids, glycosphingolipids, plasmalogens, and acylcarnitines in the milk of mothers with children at risk for future delay. A predictive classifier had a diagnostic accuracy of 0.81 (95% CI: 0.66-0.96) for females and 0.79 (95% CI: 0.62-0.94) for males.

Once validated in larger studies, the chemical analysis of human milk might be added as an option in well-baby checks to help identify children at risk of NDD before the first symptoms appear.

Maternal milk for infants sampled before 9 months of age contained sex-specific differences in deoxysphingolipids, sphingomyelins, plasmalogens, phospholipids, and acylcarnitines that predicted the risk of neurodevelopmental delay at 14.2 months of age. Once validated, this early biosignature in human milk might be incorporated into well-baby checks and help to identify infants at risk so early interventions might be instituted before the first symptoms appear.

Background: Levels of fatty acid (FA) in breast milk (BM) may vary depending on the maternal diet. This study aimed to explore FA composition in BM of lactating women following dietary restrictions due to infant allergic conditions. Materials and Methods: Thai lactating mothers of term infants who were on exclusion diets were recruited. Mature BM was collected before and after a period (at least 2 weeks) of dietary restriction. FA in BM was analyzed by gas chromatography-mass spectrometry. Results: Fifty lactating women 33.7 ± 3.6 years of age were enrolled. Thirty-three percent of the lactating mothers restricted more than eight food items. Most common dietary restriction were cow's milk (88%) and eggs (74%). After the period of dietary exclusion, total polyunsaturated FA showed no significant change, while saturated FA (SFA) declined, and monounsaturated FA (MUFA) increased. A decrease in fat intake was associated with an increase in arachidonic acid (ARA) and docosahexaenoic acid (DHA) content in BM (r = -0.37, r = -0.36; p < 0.05). However, a rise in ARA, eicosapentaenoic acid (EPA), and DHA intake was associated with an increase in linoleic acid and EPA in BM, respectively (r = 0.38, r = 0.55 and r = 0.41; p < 0.05). Infant weight-for-age z-score did not significantly change after the period of maternal dietary exclusion. Conclusion: Maternal exclusion diet resulted in lower SFA and higher MUFA composition in BM. Further study should explore the long-term outcomes of maternal dietary restriction on infant and child health.

To determine whether maternal supplementation with high-dose docosahexaenoic acid (DHA) in breastfed, very preterm neonates improves neurodevelopmental outcomes at 18 to 22 months' corrected age (CA).

Planned follow-up of a randomized, double-blind, placebo-controlled, multicenter trial to compare neurodevelopmental outcomes in breastfed, preterm neonates born before 29 weeks' gestational age (GA). Lactating mothers were randomized to receive either DHA-rich algae oil or a placebo within 72 hours of delivery until 36 weeks' postmenstrual age. Neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development third edition (Bayley-III) at 18 to 22 months' CA. Planned subgroup analyses were conducted for GA (<27 vs ≥27 weeks' gestation) and sex.

Among the 528 children enrolled, 457 (86.6%) had outcomes available at 18 to 22 months' CA (DHA, N = 234, placebo, N = 223). The mean differences in Bayley-III between children in the DHA and placebo groups were -0.07 (95% confidence interval [CI] -3.23 to 3.10, P = .97) for cognitive score, 2.36 (95% CI -1.14 to 5.87, P = .19) for language score, and 1.10 (95% CI -2.01 to 4.20, P = .49) for motor score. The association between treatment and the Bayley-III language score was modified by GA at birth (interaction P = .07). Neonates born <27 weeks' gestation exposed to DHA performed better on the Bayley-III language score, compared with the placebo group (mean difference 5.06, 95% CI 0.08-10.03, P = .05). There was no interaction between treatment group and sex.

Maternal DHA supplementation did not improve neurodevelopmental outcomes at 18 to 22 months' CA in breastfed, preterm neonates, but subgroup analyses suggested a potential benefit for language in preterm neonates born before 27 weeks' GA.