Infant Brain Development Research Articles

NIDA starts new study, at infancy, complementary to ABCD

The National Institute on Drug Abuse (NIDA) has a new study underway, designed to look at how environmental exposures, especially to opioids and other drugs, affect infant and child brain development. The HEALthy Brain and Child Development (HBCD) Study recruits pregnant women to study their infants from birth. NIDA is conducting this study as part of the multi‐agency Helping to End Addiction Long‐term (HEAL) Initiative of the National Institutes of Health (see ADAW https://onlinelibrary.wiley.com/doi/10.1002/adaw.32345).

Social Determinants of Health, Infant Brain Development and Early Childhood Social-Emotional Development

Social Determinants of Health, Infant Brain Development and Early Childhood Social-Emotional Development

The Role of Maternal Secretor Status and Human Milk Oligosaccharides on Early Childhood Development: A Systematic Review and Meta-Analysis.

Background: Breast milk is the gold standard of infant nutrition, delivering nutrients and bioactive molecules as needed to support optimal infant growth and cognitive development. Increasing evidence links human milk oligosaccharides (HMOs) to these early childhood development milestones. Aims: To summarize and synthesize the evidence relating to HMOs and infant brain development, physical growth, and cognitive development. In addition, HMO concentrations in secretor and nonsecretor mothers were compared via a meta-analysis. Study Design: A systematic review and meta-analysis were carried out in accordance with the PRISMA statement. This review used three databases (PubMed, Scopus, and Web of Science) and was limited to English-language articles published between 2000 and June 30, 2023. Results: The initial searches yielded 245 articles, 27 of which were included in the systematic review and 12 in the meta-analysis. The meta-analysis revealed a substantial between-study heterogeneity, I2 = 97.3%. The pooled effect was 0.21 (95% CI: -0.41 to 0.83; p = 0.484), indicating that secretors had higher HMO concentrations, although this difference was not statistically significant. At one month of age, 2'FL, 3FL, and 3'SL play an important role in brain maturation and thus play a critical role in cognitive development. Secretors produce higher concentrations of 2'FL and 3'SL, explaining the benefits to infants of secretor mothers. Growth velocity was correlated to fucosylated and sialylated HMO concentrations, with lower concentrations linked to stunting. Conclusions: According to evidence from the systematically reviewed articles, HMOs are essential for a child's early development, but the extent to which they have an impact depends on maternal secretor status.

Effects of paternal arachidonic acid supplementation on offspring behavior and hypothalamus inflammation markers in the mouse.

Arachidonic acid (AA) is involved in inflammation and plays a role in growth and brain development in infants. We previously showed that exposure of mouse sires to AA for three consecutive generations induces a cumulative change in fatty acid (FA) involved in inflammation and an increase in body and liver weight in the offspring. Here, we tested the hypothesis that paternal AA exposure changes the progeny's behavioral response to a proinflammatory insult, and asked whether tissue-specific FA are associated with that response. Male BALB/c mice were supplemented daily with three doses of AA for 10 days and crossed to non-supplemented females (n = 3/dose). Two-month-old unsupplemented male and female offspring (n = 6/paternal AA dose) were exposed to Gram-negative bacteria-derived lipopolysaccharides (LPS) or saline control two hours prior to open field test (OFT) behavioral analysis and subsequent sacrifice. We probed for significant effects of paternal AA exposure on: OFT behaviors; individual FA content of blood, hypothalamus and hypothalamus-free brain; hypothalamic expression profile of genes related to inflammation (Tnfa, Il1b, Cox1, Cox2) and FA synthesis (Scd1, Elovl6). All parameters were affected by paternal AA supplementation in a sex-specific manner. Paternal AA primed the progeny for behavior associated with increased anxiety, with a marked sex dimorphism: high AA doses acted as surrogate of LPS in males, realigning a number of OFT behaviors that in females were differential between saline and LPS groups. Progeny hypothalamic Scd1, a FA metabolism enzyme with documented pro-inflammatory activity, showed a similar pattern of differential expression between saline and LPS groups at high paternal AA dose in females, that was blunted in males. Progeny FA generally were not affected by LPS, but displayed non-linear associations with paternal AA doses. In conclusion, we document that paternal exposure to AA exerts long-term behavioral and biochemical effects in the progeny in a sex-specific manner.

Intelligence Sparse Sensor Network for Automatic Early Evaluation of General Movements in Infants.

General movements (GMs) have been widely used for the early clinical evaluation of infant brain development, allowing immediate evaluation of potential development disorders and timely rehabilitation. The infants' general movements can be captured digitally, but the lack of quantitative assessment and well-trained clinical pediatricians presents an obstacle for many years to achieve wider deployment, especially in low-resource settings. There is a high potential to explore wearable sensors for movement analysis due to outstanding privacy, low cost, and easy-to-use features. This work presents a sparse sensor network with soft wireless IMU devices (SWDs) for automatic early evaluation of general movements in infants. The sparse network consisting of only five sensor nodes (SWDs) with robust mechanical properties and excellent biocompatibility continuously and stably captures full-body motion data. The proof-of-the-concept clinical testing with 23 infants showcases outstanding performance in recognizing neonatal activities, confirming the reliability of the system. Taken together with a tiny machine learning algorithm, the system can automatically identify risky infants based on the GMs, with an accuracy of up to 100% (99.9%). The wearable sparse sensor network with an artificial intelligence-based algorithm facilitates intelligent evaluation of infant brain development and early diagnosis of development disorders.

Microstate Analysis of Continuous Infant EEG: Tutorial and Reliability

Microstate analysis of resting-state EEG is a unique data-driven method for identifying patterns of scalp potential topographies, or microstates, that reflect stable but transient periods of synchronized neural activity evolving dynamically over time. During infancy – a critical period of rapid brain development and plasticity – microstate analysis offers a unique opportunity for characterizing the spatial and temporal dynamics of brain activity. However, whether measurements derived from this approach (e.g., temporal properties, transition probabilities, neural sources) show strong psychometric properties (i.e., reliability) during infancy is unknown and key information for advancing our understanding of how microstates are shaped by early life experiences and whether they relate to individual differences in infant abilities. A lack of methodological resources for performing microstate analysis of infant EEG has further hindered adoption of this cutting-edge approach by infant researchers. As a result, in the current study, we systematically addressed these knowledge gaps and report that most microstate-based measurements of brain organization and functioning except for transition probabilities were stable with four minutes of video-watching resting-state data and highly internally consistent with just one minute. In addition to these results, we provide a step-by-step tutorial, accompanying website, and open-access data for performing microstate analysis using a free, user-friendly software called Cartool. Taken together, the current study supports the reliability and feasibility of using EEG microstate analysis to study infant brain development and increases the accessibility of this approach for the field of developmental neuroscience.

Infant head and brain segmentation from magnetic resonance images using fusion-based deep learning strategies

Magnetic resonance (MR) imaging is widely used for assessing infant head and brain development and for diagnosing pathologies. The main goal of this work is the development of a segmentation framework to create patient-specific head and brain anatomical models from MR images for clinical evaluation. The proposed strategy consists of a fusion-based Deep Learning (DL) approach that combines the information of different image sequences within the MR acquisition protocol, including the axial T1w, sagittal T1w, and coronal T1w after contrast. These image sequences are used as input for different fusion encoder–decoder network architectures based on the well-established U-Net framework. Specifically, three different fusion strategies are proposed and evaluated, namely early, intermediate, and late fusion. In the early fusion approach, the images are integrated at the beginning of the encoder–decoder architecture. In the intermediate fusion strategy, each image sequence is processed by an independent encoder, and the resulting feature maps are then jointly processed by a single decoder. In the late fusion method, each image is individually processed by an encoder–decoder, and the resulting feature maps are then combined to generate the final segmentations. A clinical in-house dataset consisting of 19 MR scans was used and divided into training, validation, and testing sets, with 3 MR scans defined as a fixed validation set. For the remaining 16 MR scans, a cross-validation approach was adopted to assess the performance of the methods. The training and testing processes were carried out with a split ratio of 75% for the training set and 25% for the testing set. The results show that the early and intermediate fusion methodologies presented the better performance (Dice coefficient of 97.6 ± 1.5% and 97.3 ± 1.8% for the head and Dice of 94.5 ± 1.7% and 94.8 ± 1.8% for the brain, respectively), whereas the late fusion method generated slightly worst results (Dice of 95.5 ± 4.4% and 93.8 ± 3.1% for the head and brain, respectively). Nevertheless, the volumetric analysis showed that no statistically significant differences were found between the volumes of the models generated by all the segmentation strategies and the ground truths. Overall, the proposed frameworks demonstrate accurate segmentation results and prove to be feasible for anatomical model analysis in clinical practice.

Place of the Ketogenic Diet in Refractory Infantile Spasms

Introduction: The ketogenic diet is an alternative nutritional regimen for refractory epilepsies, including infantile spasms. The objective of our study is the primary and secondary evaluation at 12 months of the effectiveness and tolerance of the ketogenic diet on seizure frequency, EEG (electroencephalogram) patterns, and side effects. Patients and Methods: We evaluated the ketogenic diet as a second- or third-line treatment, following corticosteroid therapy and/or Vigabatrin. We assessed the effectiveness and tolerance of the ketogenic diet based on patients being seizure-free, experiencing a reduction in seizures of more than 50%, improvement in EEG background pattern (suppression of hypsarrhythmia), psychomotor development, side effects, and reduction in antiepileptic drugs during clinical, electrical, and neurocognitive follow-ups at 1, 3, and 12 months. Results: Thirty-eight children, twentytwo boys, and sixteen girls, with a gender ratio of 1.37, presenting with infantile spasms visualized directly clinically or through videos and electric evaluation, with or without hypsarrhythmia on EEG, all symptomatic: genetic etiologies (14, 36.9%), structural in 18 patients (47.3%), and metabolic in six patients (15.8%). At 3 months, the number of patients who were seizure-free with a normal EEG was 22 patients (57.9%), and those with a reduction in seizures of more than 50%, 15 patients (39.5%). At 12 months on the ketogenic diet, the number of patients who were seizure-free was 24 (63.2%), and those with a reduction in seizures of more than 50% 14 patients(36.8%). Good tolerance and efficiency of the diet were confirmed by treatment compliance, maintained high response rate, and a reduction in the number of antiepileptic drugs to 1.97. The children became more vigilant, attentive, and responsive to their parents. Conclusion: Implementing the ketogenic diet within a short period of time, less than a year, would yield even better results in terms of seizure frequency and behavior in a developing infant brain.

A FRET based ultrasensitive fluorescent aptasensor for 6′-sialyllactose detection

As a kind of human milk oligosaccharide, 6′-sialyllactose (6′-SL) plays an important role in promoting infant brain development and improving infant immunity. The content of 6′-SL in infant formula milk powder is thus one of the important nutritional indexes. Since the lacking of efficient and rapid detection methods for 6′-SL, it is of great significance to develop specific recognition elements and establish fast and sensitive detection methods for 6′-SL. Herein, using 6′-SL specific aptamer as the recognition element, catalytic hairpin assembly as the signal amplification technology and quantum dots as the signal label, a fluorescence biosensor based on fluorescence resonance energy transfer (FRET) was constructed for ultra-sensitive detection of 6′-SL. The detection limit of this FRET-based fluorescent biosensor is 0.3 nM, and it has some outstanding characteristics such as high signal-to-noise ratio, low time-consuming, simplicity and high efficiency in the actual sample detection. Therefore, it has broad application prospect in 6′-SL detection.

Lactoferrin intake from maternal milk during the neonatal hospitalization and early brain development among preterm infants.

Lactoferrin is an immuno-modulatory nutrient in human milk that may be neuroprotective. In 36 infants born <32 weeks' gestation, we sampled human milk at 14 and 28 days of chronologic age and measured lactoferrin by electrochemiluminescence multiplex immunoassay. Using 3T quantitative brain magnetic resonance imaging scans obtained at term equivalent, we estimated total and regional brain volumes. We compared outcomes between infants exposed to low (bottom tertile, range 0.06-0.13 mg/mL) vs. high (top tertile, range 0.22-0.35 mg/mL) lactoferrin using median regression in models adjusted for gestational age, birth weight z-score, sex, and postmenstrual age. Compared to infants exposed to low lactoferrin, infants exposed to high lactoferrin had 43.9 cc (95% CI: 7.6, 80.4) larger total brain volume, 48.3 cc (95% CI: 12.1, 84.6) larger cortical gray matter, and 3.8 cc (95% CI: 0.7, 7.0) larger deep gray matter volume at term equivalent age. Other regional brain volumes were not statistically different between groups. Higher lactoferrin exposure during the neonatal hospitalization was associated with larger total brain and gray matter volumes, suggesting that lactoferrin may have potential as a dietary supplement to enhance brain growth in the neonatal intensive care unit setting. This study suggests that lactoferrin, a whey protein found in human milk, may be beneficial for preterm infant brain development, and therefore has potential as a dietary supplement in the neonatal intensive care unit setting.

Oromotor rehabilitation on drooling and feeding activities in children with cerebral palsy: A case study

Abstract: Cerebral palsy (CP) is a neurological disorder that affects the brain and causes difficulties with muscle coordination, body movement, and balance. Children with CP frequently present with severe oral motor impairments. Children with CP suffer from a variety of motor disorders, which are frequently accompanied by sensory, cognitive, communication, perception, and behavioral disorders, as well as epilepsy, nutrition, dysphagia, and oral motor dysfunction. CP refers to a group of long-term movement and posture impairments that occur in the developing infant brain, limiting many activities such as independent walking, stair climbing, running, or walking on an uneven surface. The purpose of this case report is to describe the difficulty in oromotor functional activity experienced by a CP child. A 5-year-10-month-old baby presented with drooling and difficulty in feeding activities, which greatly affected her day-to-day activities. Her pediatric Ability for Basic Feeding and Swallowing in Children-10 (ABFS-C) was 6/15 and The Drooling Impact Scale (DIS) 72/100 total score improved to (DIS) 83/100 and (ABFS-C) 10/15.

High-resolution myelin-water fraction and quantitative relaxation mapping using 3D ViSTa-MR fingerprinting.

This study aims to develop a high-resolution whole-brain multi-parametric quantitative MRI approach for simultaneous mapping of myelin-water fraction (MWF), T1, T2, and proton-density (PD), all within a clinically feasible scan time. We developed 3D visualization of short transverse relaxation time component (ViSTa)-MRF, which combined ViSTa technique with MR fingerprinting (MRF), to achieve high-fidelity whole-brain MWF and T1/T2/PD mapping on a clinical 3T scanner. To achieve fast acquisition and memory-efficient reconstruction, the ViSTa-MRF sequence leverages an optimized 3D tiny-golden-angle-shuffling spiral-projection acquisition and joint spatial-temporal subspace reconstruction with optimized preconditioning algorithm. With the proposed ViSTa-MRF approach, high-fidelity direct MWF mapping was achieved without a need for multicompartment fitting that could introduce bias and/or noise from additional assumptions or priors. The in vivo results demonstrate the effectiveness of the proposed acquisition and reconstruction framework to provide fast multi-parametric mapping with high SNR and good quality. The in vivo results of 1 mm- and 0.66 mm-isotropic resolution datasets indicate that the MWF values measured by the proposed method are consistent with standard ViSTa results that are 30× slower with lower SNR. Furthermore, we applied the proposed method to enable 5-min whole-brain 1 mm-iso assessment of MWF and T1/T2/PD mappings for infant brain development and for post-mortem brain samples. In this work, we have developed a 3D ViSTa-MRF technique that enables the acquisition of whole-brain MWF, quantitative T1, T2, and PD maps at 1 and 0.66 mm isotropic resolution in 5 and 15 min, respectively. This advancement allows for quantitative investigations of myelination changes in the brain.

A Developmental Social Neuroscience Perspective on Infant Autism Interventions

Research on early biomarkers and behavioral precursors of autism has led to interventions initiated during the infant period that could potentially change the course of infant brain and behavioral development in autism. This article integrates neuroscience and clinical perspectives to explore how knowledge of infant brain and behavioral development can inform the design of infant autism interventions. Focusing on infants ≤12 months, we review studies on behavioral precursors of autism and their neural correlates and clinical trials evaluating the efficacy of infant autism interventions. We then consider how contemporary developmental social neuroscience theories of autism can shed light on the therapeutic strategies used in infant autism interventions and offer a new perspective that emphasizes improving child outcome and well-being by enhancing infant–environment fit. Finally, we offer recommendations for future research that incorporates brain-based measures to inform individualized approaches to intervention and discuss ethical issues raised by infant autism interventions. Readers are referred to Supplemental Table 1 for a glossary of terms used in this article.

Got (Optimal) Milk? Pooling Donations in Human Milk Banks with Machine Learning and Optimization

Problem definition: Human donor milk provides critical nutrition for millions of infants who are born preterm each year. Donor milk is collected, processed, and distributed by milk banks. The macronutrient content of donor milk is directly linked to infant brain development and can vary substantially across donations, which is why multiple donations are typically pooled together to create a final product. Approximately half of all milk banks in North America do not have the resources to measure the macronutrient content of donor milk, which means pooling is done heuristically. For these milk banks, an approach is needed to optimize pooling decisions. Methodology/results: We propose a data-driven framework combining machine learning and optimization to predict macronutrient content of donations and then optimally combine them in pools, respectively. In collaboration with our partner milk bank, we collect a data set of milk to train our predictive models. We rigorously simulate milk bank practices to fine-tune our optimization models and evaluate operational scenarios such as changes in donation habits during the COVID-19 pandemic. Finally, we conduct a year-long trial implementation, where we observe the current nurse-led pooling practices followed by our intervention. Pools created by our approach meet clinical macronutrient targets approximately 31% more often than the baseline, although taking 60% less recipe creation time. Managerial implications: This is the first paper in the broader blending literature that combines machine learning and optimization. We demonstrate that such pipelines are feasible to implement in a healthcare setting and can yield significant improvements over current practices. Our insights can guide practitioners in any application area seeking to implement machine learning and optimization-based decision support. History: This paper has been accepted as part of the 2023 Manufacturing &amp; Service Operations Management Practice-Based Research Competition. Supplemental Material: The e-companion is available at https://doi.org/10.1287/msom.2022.0455 .

Cerebral Hemodynamics in Infants with Sickle Cell Disease Indicate Presence of Early Hemodynamic Stress

Introduction: One of the most severe complications of sickle cell disease (SCD) is ischemic brain injury, caused by a combination of decreased oxygen transport delivery related to intravascular vaso-occlusion of sickle erythrocytes and/or cerebral vasculopathy. While newborn screening programs diagnose SCD shortly after birth, routine risk assessment for stroke typically starts with transcranial ultrasound doppler (TCD) at two years of age or later. Yet, little is known about how SCD affects cerebral hemodynamics during infancy, a crucial period for brain development. To address this gap, we used advanced quantitative near-infrared spectroscopy (qNIRS) to non-invasively monitor cerebral tissue hemoglobin concentration (HbT), oxygenation (SO 2), oxygen extraction fraction (cFTOE), blood flow (CBF), and oxygen metabolism (CMRO 2) in infants with SCD. Abnormal CBF and cFTOE indicate hemodynamic stress that may increase stroke risk. Our study aims to investigate the effects of SCD on cerebral oxygen transport in infancy and its associations with age and blood hemoglobin concentration (HgB). Methods: This is a subgroup analysis of a prospective, observational neuroimaging study of SCD at Boston Children's Hospital (NCT 04166526). Inclusion criteria of this subgroup are SCD patients age less than 24 months old at the time of enrollment who are not receiving chronic transfusions. Families read and signed informed consent before participating in research activities. Measurements were conducted with the patients' normally scheduled hematology appointments at Boston Children's Hospital. During each measurement session, bilateral frontal regions of the head were measured up to six times for 30 seconds each. qNIRS variables were compared with literature values obtained with the same optical technologies from a cohort of typically developed infants around 1 year old, equivalent to the median age in this study 1. Correlation analysis was used to analyze qNIRS variables with age and HgB from clinical lab tests. Results: To date, 8 (F/M: 4/4; HbSS/HbS/B +-thalassemia/HbSC: 6/1/1) patients were enrolled with a total of 16 measurements. The meanSD age at measurement was 11.5 5.23 months and the median (IQR) HgB was 9.4 (8.9-10) g/dL. Seven (44%) measurements were performed while patients were receiving treatment with hydroxyurea. There was no difference in HgB in the groups with and without hydroxyurea, though the treatment group was older (mean age: 15.4 vs 8.4 months, P=0.002). Group averages of qNIRS variables are summarized Table 1. Average cFTOE was 0.53 ± 0.07, significantly higher than the reference value of 0.32 (mean difference: 0.21, P&amp;lt;0.001), while the cohort's mean SO 2 of 45.78 ± 7.13% was significantly lower than the reference value of 68% (mean difference: -22.2, P&amp;lt;0.001). Furthermore, cFTOE inversely correlated with HgB (r= -0.63, P=0.04) while SO 2 increased with HgB (r= 0.63, P=0.04). HbT and cerebral blood volume (CBV) were also significantly lower than the reference values (mean difference of -24.8 μM and -0.75 ml/100g, P&amp;lt;0.001 and P&amp;lt;0.02, respectively) and positively correlated with age (r=0.51 and 0.57, P=0.04). CBF did not correlate with either age or HgB. Hemodynamic variables did not differ between groups with and without hydroxyurea, except for HbT and CBV likely secondary to the cohort age difference. Taken together, this suggests that CBF compensatory mechanisms were insufficient to prevent elevated oxygen extraction. Summary: These preliminary results suggest that inadequate oxygen transport to the brain secondary to SCD evokes a compensatory increase in cFTOE starting in early infancy. The progressive hemodynamic stress to brain health during the period of the brain's greatest growth and metabolic demand for oxygen is concerning because of the potential for injury as compensatory mechanisms become exhausted. Hydroxyurea did not reduce this stress, but may have prevented further declines. Recruitment is ongoing to increase the size of the cohort and to continue following patients' trajectories with age. We demonstrated the potential of qNIRS as biomarkers of cerebral hemodynamic compensation to determine when intervention is necessary and evaluate the effectiveness of a chosen intervention in individual patients. 1. Franceschini, M. A. et al. Assessment of infant brain development with frequency-domain near-infrared spectroscopy. Pediatr Res 61, 546-551, 2007.

Robust Unsupervised Super-Resolution of Infant MRI via Dual-Modal Deep Image Prior.

Magnetic resonance imaging (MRI) is commonly used for studying infant brain development. However, due to the lengthy image acquisition time and limited subject compliance, high-quality infant MRI can be challenging. Without imposing additional burden on image acquisition, image super-resolution (SR) can be used to enhance image quality post-acquisition. Most SR techniques are supervised and trained on multiple aligned low-resolution (LR) and high-resolution (HR) image pairs, which in practice are not usually available. Unlike supervised approaches, Deep Image Prior (DIP) can be employed for unsupervised single-image SR, utilizing solely the input LR image for de novo optimization to produce an HR image. However, determining when to stop early in DIP training is non-trivial and presents a challenge to fully automating the SR process. To address this issue, we constrain the low-frequency k-space of the SR image to be similar to that of the LR image. We further improve performance by designing a dual-modal framework that leverages shared anatomical information between T1-weighted and T2-weighted images. We evaluated our model, dual-modal DIP (dmDIP), on infant MRI data acquired from birth to one year of age, demonstrating that enhanced image quality can be obtained with substantially reduced sensitivity to early stopping.

Effects of pasteurization on osteopontin concentrations in human breastmilk.

Osteopontin (OPN) is an important breastmilk protein involved in infant intestinal, immunological, and brain development. However, little is known about how common milk pasteurization and storage techniques affect this important bioactive protein. Human milk osteopontin concentration was measured in single-donor fresh (n = 1) or frozen (n = 20) breastmilk, pooled Holder-pasteurized donor breastmilk (n = 11), and a shelf-stable (retort pasteurized) breastmilk product (n = 2) by ELISA. Single-donor breastmilk samples were subjected to pasteurization and/or freezing before measuring osteopontin concentrations. Holder pasteurization of breastmilk resulted in an ∼50% decrease in osteopontin concentration within single-donor samples. Breastmilk from mothers of preterm infants trended toward higher osteopontin concentration than mothers of term infants; however, samples from preterm mothers experienced greater osteopontin degradation upon pasteurization. A commercial breastmilk product that underwent retort pasteurization had lower osteopontin concentration than a Holder-pasteurized pooled breastmilk product. Finally, freezing breastmilk prior to Holder pasteurization resulted in less osteopontin degradation than Holder pasteurization prior to freezing. Commonly used breastmilk pasteurization and storage techniques, including freezing and Holder pasteurization, decrease the concentration of the bioactive protein osteopontin in human breastmilk. Holder pasteurization reduced osteopontin concentration by an average of 63%, while freezing resulted in an 8-12% decrease. Pasteurization of human breastmilk significantly decreases the concentration of the bioactive protein osteopontin. Use of both pasteurization and freezing techniques for breastmilk preservation results in greater loss of osteopontin. This study presents for the first time an analysis of osteopontin concentrations in single-donor pasteurized milk samples.

Impact of Maternal Fish Consumption on Serum Docosahexaenoic Acid (DHA) Levels in Breastfed Infants: A Cross-Sectional Study of a Randomized Clinical Trial in Japan.

Docosahexaenoic acid (DHA), an essential n-3 long-chain polyunsaturated fatty acid (LCPUFA) abundant in fish, is crucial for infant brain development. We investigated the associations between maternal dietary habits, infant feeding patterns, and serum levels of DHA and other LCPUFAs in infants aged 5-6 months in Japan, where fish consumption is high. This cross-sectional study used serum samples from 268 infants enrolled in a randomized clinical trial. The frequency of mothers' consumption of 38 food items and infant feeding patterns were prospectively surveyed. Cow's milk formula (CMF) supplemented with 15.9% linolenic acid, 1.6% α-linolenic acid, 0.40% DHA, and 0.27% arachidonic acid was used. Significant positive associations with infants' serum DHA levels were found for "Blue-back fish" (rho = 0.24; p = 0.0001) and "White fish" (rho = 0.25, p = 0.0001). The combined variable "Blue-White fish" was found to be significantly associated with higher serum DHA levels in infants (rho = 0.29, p < 0.0001). Predominantly breastfed infants had significantly higher serum DHA levels than those fed more CMF (rho = 0.32, p < 0.0001). After multivariate analysis, "Blue-White fish" and "Feeding patterns" remained significantly and independently associated with serum DHA levels. These findings suggest that frequent consumption of "Blue-back fish" and/or "White fish" by lactating mothers, along with prioritizing breastfeeding over DHA-supplemented CMF, might effectively increase infants' serum DHA levels.

16.3 A Multisite Study of Pandemic-Related Effects on Maternal Hardship and Infant Brain Development

16.3 A Multisite Study of Pandemic-Related Effects on Maternal Hardship and Infant Brain Development

Lipidomics insight on differences between human MFGM and dietary-derived lipids.

Milk fat globule membrane (MFGM) contains lipids, which are essential for promoting infant brain development and improving cognition. In this study, the lipid differences between human MFGM and four dietary lipid sources (cow MFGM, soybean, krill, and yolk) were compared using the UHPLC-Q-Exactive MS-based lipidomics techniques. A total of 45 lipid classes and 5048 lipid species were detected. The analysis of phospholipid classes revealed that the lipid composition of human MFGM and cow MFGM was more similar than the other dietary-derived lipids. Additionally, the human MFGM lipid species were compared with cow MFGM, soybean, krill, and yolk, and 401, 416, 494, and 444 significantly different lipids were identified, respectively. Through lipid metabolic pathway analysis, differential lipids were mainly involved in the glycerophospholipid metabolic pathway. Overall, these results will provide a rationale for the future addition of lipids to infant formula to more closely approximate human MFGM lipid profiles.