Early Life Development Research Articles

Profiles of 71 Human Milk Oligosaccharides and Novel Sub-Clusters of Type I Milk: Results from the Ulm SPATZ Health Study.

Although approximately 160 human milk oligosaccharides (HMOs) have been identified, current studies on HMO quantitation are limited to the 10-19 most abundant HMOs. We assessed the variations in the relative concentrations of 71 HMO structures over lactation in human milk samples by an advanced liquid chromatography-mass spectrometry approach. Samples were collected from 64 mothers at 6 weeks, 6 months, and 12 months of lactation in the Ulm SPATZ Health Study, a German birth cohort. In this longitudinal study, we fitted linear mixed-effect models to analyze changes in the log2-transformed and standardized HMO concentration over time. Based on the profile of 71 HMOs, we also fitted a group-based multi-trajectory (GBMT) model to cluster mothers secreting cluster type I milk, who account for the majority of lactating mothers. We found that 52 HMOs had a decreasing trend (regression coefficients ranging from -1.41 to -0.17) and 9 had an increasing trend (regression coefficients ranging from 0.25 to 0.64) during lactation, and the findings were statistically significant after multiple testing corrections. Using human milk samples of 49 mothers with type I milk, we further identified two novel sub-clusters with distinct longitudinal trajectories of concentrations of 71 HMOs during lactation: Type I-a (N = 20) and I-b (N = 29). These sub-clusters were not associated with maternal non-genetic characteristics. Our findings extend existing knowledge about the structural diversity of HMOs and their variations over lactation. These may pave the way to investigate the potential nutritional benefits of various HMOs on infant health and early life development in the future.

No Evidence of Early Developmental Delay in Juvenile-Onset Huntington's Disease Patients.

Previous studies suggest that early developmental delay is a common feature of Juvenile-Onset Huntington's disease (JOHD), with highest incidence in those with very high CAG repeats (> 80). However, all reports of developmental delay in JOHD are exclusively based on retrospective review of medical charts. Comprehensive assessment of birth history metrics may provide better insight into the question of early life development in JOHD. To explore the prevalence of prematurity, birth complications, low birth weight and developmental delay in patients with JOHD in comparison to control participants. Parents of patients with JOHD and gene-non-expanded (GNE) control participants from Kids-HD (n = 104) and Kids-JOHD (n = 34, 24% with CAG > 80) studies completed a comprehensive birth history questionnaire. Answers focused on prematurity, birth complications, and birth weight, and along with reports of early developmental milestones, were compared between groups. There were no statistically significant differences in prematurity, birth weights, birth complications, or motor and verbal developmental milestones between JOHD patients and GNE controls (all P values > 0.1). Furthermore, stratifying JOHD patients by CAG expansion (low vs. high) also showed no significant differences (GNE vs. low or GNE vs. high). These findings support the notion that JOHD does not manifest as developmental delay before motor symptom onset and highlight a new framework to understand the course and nature of the disease.

Analysis of early childhood intestinal microbial dynamics in a continuous-flow bioreactor

BackgroundThe human gut microbiota is inoculated at birth and undergoes a process of assembly and diversification during the first few years of life. Studies in mice and humans have revealed associations between the early-life gut microbiome and future susceptibility to immune and metabolic diseases. To resolve microbe and host contributing factors to early-life development and to disease states requires experimental platforms that support reproducible, longitudinal, and high-content analyses.ResultsHere, we deployed a continuous single-stage chemostat culture model of the human distal gut to study gut microbiota from 18- to 24-month-old children integrating both culture-dependent and -independent methods. Chemostat cultures recapitulated multiple aspects of the fecal microbial ecosystem enabling investigation of relationships between bacterial strains and metabolic function, as well as a resource from which we isolated and curated a diverse library of early life bacterial strains.ConclusionsWe report the reproducible, longitudinal dynamics of early-life bacterial communities cultured in an advanced model of the human gut providing an experimental approach and a characterized bacterial resource to support future investigations of the human gut microbiota in early childhood.

Maternal stress in the early postpartum period is associated with alterations in human milk microbiome composition

BackgroundMaternal stress is associated with negative early-life development and (mental)health outcomes. There is recent evidence that maternal stress in the postpartum period impacts the nutrient composition of human milk (HM). However, it is currently not known whether maternal stress is associated with changes in the HM microbiome during the critical early postpartum period. MethodsIn this prospective observational cohort study, lactating women were recruited into a high-stress (HS, n = 23) and control (CTL, n = 69) group. The HS group included mothers with infants hospitalized for at least two days. Maternal stress was assessed using validated questionnaires and cortisol concentrations in hair, saliva and HM. HM was collected at days 10 and 24 and its microbiome was analyzed using 16 s rRNA sequencing. HM bacterial composition was compared between study groups and their correlation with maternal stress levels, maternal characteristics and infant outcomes was determined. ResultsHM microbiome β-diversity differed significantly between study groups, with HS mothers displaying decreased abundance of Streptococcus, Gemella, and Veillonella, and increased levels of Staphylococcus, Corynebacterium and Acinetobacter compared to the control group. While the strongest correlation of β-diversity was with stress, HM microbiome β-diversity also correlated significantly with maternal education level and infant sex. No correlation between HM microbiome composition and HM cortisol concentrations was found. ConclusionsThis study demonstrates stress-associated alterations in the early HM microbiome that could potentially contribute to early gut colonization and subsequent (mental)health outcomes. Future research is needed to elucidate the physiological significance of these changes for infant development and health.

Impact of probiotic Bacillus sp. dietary supplementation on pancreatic and intestinal activities in seabream Sparus aurata.

The main objective of this study was to investigate the effects of commercial probiotic Bacillus sp. supplementation on seabream Sparus aurata larviculture under culture conditions. In this context, Bacillus was supplemented via rotifer feeding and water and its effects on pancreatic and intestinal enzyme activities as well as aquaculture parameters were evaluated during early life development. In the experimental group, as probiotic three Bacillus sp. spores were introduced via rotifer and larval culture tanks, while the larvae in control group did not feed any probiotic supplementation. At the end of the experiment on 40 days after hatching, the probiotic-supplemented group exhibited better growth performance and there were statistically differences in between groups of probiotic-treated and control regarding growth parameters (P<0.01), despite insignificant survival rate (P>0.05). In terms of enzymatic expressions, S. aurata larvae receiving probiotic supplementation through rotifers demonstrated noteworthy (P<0.05) enhancements in specific activities of pancreatic and intestinal enzymes, except for amylase (P>0.05), when compared to the control group. It is concluded that the administration of Bacillus sp. as probiotic bacteria through rotifer supplementation and water intake demonstrates significant positive impacts on both growth parameters and specific activities of main pancreatic and intestinal enzymes of seabream larvae.

Family Nurture Intervention and mother-preterm infant autonomic emotional connection in the neonatal intensive care unit: A review.

We review methods and outcomes of a novel parenting intervention, Family Nurture Intervention (FNI), that promotes early mother-infant autonomic co-regulation and emotional connection in the neonatal intensive care unit (NICU). FNI involves individualised mother-infant calming sessions combined with maternal emotional expression. Two parallel group randomised controlled trials have evaluated FNI. The first,recruited 150 preterm newborns (26-34 weeks GA) and their mothers, randomised into two groups: FNI (n = 78) and Standard Care (SC) only (n = 72). Dyadic, infant and maternal outcomes were assessed at discharge, 18-months and 4-5 years corrected age. The second,recruited 135 infants from two level 4 NICUs (FNI n = 66, SC n = 69) with similar outcomes assessed at discharge/term equivalent. Relative to SC, FNI infants showed improved development and relational health through 5 years. At term age, FNI infants had better autonomic regulation and more mature brain activity and cortical connectivity on EEG. FNI mothers also reported fewer anxiety and depression symptoms post-discharge. At 18-month, FNI infants obtained higher cognitive and language scores, and lower attention and social behaviour scores than SC infants. FNI improves the early life development and relational health of high-risk preterm infants. Further research is important to assess its efficacy in other high-risk populations and contexts.

The first and next 1000 days: a continuum for child development in early life

The first and next 1000 days: a continuum for child development in early life

The bidirectional interplay of obstructive sleep apnea and viral respiratory infections in children: A novel opportunity for primary prevention.

Obstructive sleep apnea (OSA) and viral respiratory infections are highly prevalent conditions in children and a major cause of respiratory morbidity in this age group. Severe viral respiratory infections are a known risk factor for pediatric OSA, which is primarily caused by hypertrophy of upper airway lymphoid tissues (adenoids and tonsils). This review examines recent progress in understanding early-life development of lymphoid tissues in the human upper airway, with a particular focus on how respiratory viruses may influence this process and contribute to OSA pathogenesis. It also explores the bidirectional relationship between OSA and severe viral infections, highlighting the need for ongoing monitoring and novel primary prevention strategies to address these interconnected conditions.

Early Caregiver Predictability Shapes Neural Indices of Statistical Learning Later in Infancy.

Caregivers play an outsized role in shaping early life experiences and development, but we often lack mechanistic insight into how exactly caregiver behavior scaffolds the neurodevelopment of specific learning processes. Here, we capitalized on the fact that caregivers differ in how predictable their behavior is to ask if infants' early environmental input shapes their brains' later ability to learn about predictable information. As part of an ongoing longitudinal study in South Africa, we recorded naturalistic, dyadic interactions between 103 (46 females and 57 males) infants and their primary caregivers at 3-6 months of age, from which we calculated the predictability of caregivers' behavior, following caregiver vocalization and overall. When the same infants were 6-12-months-old they participated in an auditory statistical learning task during EEG. We found evidence of learning-related change in infants' neural responses to predictable information during the statistical learning task. The magnitude of statistical learning-related change in infants' EEG responses was associated with the predictability of their caregiver's vocalizations several months earlier, such that infants with more predictable caregiver vocalization patterns showed more evidence of statistical learning later in the first year of life. These results suggest that early experiences with caregiver predictability influence learning, providing support for the hypothesis that the neurodevelopment of core learning and memory systems is closely tied to infants' experiences during key developmental windows.

Fetal weight growth trajectories and childhood development: A population-based cohort study

This study aimed to investigate whether fetal growth trajectories (FGTs) could predict early childhood development, indicate intrauterine metabolic changes, and explore potential optimal and suboptimal FGTs. FGTs were developed by using an unsupervised machine-learning approach. Children’s neurodevelopment, anthropometry, and respiratory outcomes in the first 6 years of life were assessed at different ages. In a subgroup of participants, we conducted a metabolomics analysis of cord blood to reveal the metabolic features of FGTs. We identified 6 FGTs: early decelerating, early decelerating with late catch-up growth, early accelerating, early accelerating with late medium growth, late decelerating, and late accelerating. The early accelerating with late medium growth pattern might be the optimal FGT due to its associations with better psychomotor development, mental development, intelligence quotient, and lung function and a lower risk of behaviour and respiratory problems. Compared with the optimal FGT, early decelerating and late decelerating FGTs were associated with poor neurodevelopment and lung function, while early accelerating FGT was associated with more severe autistic symptoms, poor lung function, and increased risks of overweight/obesity. Metabolic alterations were enriched in amino acid metabolism for early decelerating and late decelerating FGTs, whereas altered metabolites were enriched in lipid metabolism for early accelerating FGT. These findings suggest that FGTs are predictors of early life development and may indicate intrauterine adaptive metabolism. The discovery of optimal and suboptimal FGTs provides potential clues for the early identification and intervention of fetal origin dysplasia or disease, but further research on related mechanisms is still needed.

Korean Early Childhood Education and Care Panel Study: Data Utilization Strategies for Policy and Practice

The Korean Early Childhood Education and Care Panel Study (K-ECEC panel study), commencing in 2021, aimed to collect data related to early life growth and development. In particular, based on Bronfenbrenner’s ecological model, the study aims to collect intrinsic and extrinsic parental factors, educational and caregiving experiences in institutions, and environmental factors from the prenatal stage through infancy, toddlerhood, and early childhood. This is important for understanding child development with varied dimensional aspects. The K-ECEC panel study uses a stratified sampling strategy in order to recruit pregnant women based on regions and numbers of deliveries to individual hospitals. This resulted in the participation of 3,372 women, 95 of whom were from low-income families and 72 from multicultural families. The K-ECEC panel study is based on a household survey collecting information related to pregnancy, birth, and childrearing. The survey included an annual follow-up for individual households of newborns from 2022, and the second round of the survey was conducted in 2023. A total of 2,775 children participated in the first round of the survey, 1,423 of whom were boys. As there are few birth cohort studies considering policy-oriented aspects in Korea, the K-ECEC panel study is expected to provide data to understand childhood trajectories for growth and development. Furthermore, in terms of childcare and education, it is expected to be utilized to evaluate the policy effects of early life and parenting support.

Allergy in Young Adults Associates with Elevated Fractional Exhaled Nitric Oxide Levels and IgE-Verified Parental Allergy but Is Confounded by Self-Reported Symptoms

Introduction: Knowledge of IgE-verified allergy in young adults is limited as most studies are based on self-reported data. Allergic heredity is important in allergy development in early life, but less is known about the hereditary component later in life. The aim was to investigate IgE-verified and self-reported allergy and asthma at 20 years of age in association to parental allergy and environmental factors. Methods: In total, 281 individuals born into the cohort of well-characterized parents regarding allergic disease were followed to 20 years of age. The participants were categorized by parental allergy and examined regarding allergic diseases (IgE sensitization and allergic symptoms) at 2, 5, 10, and 20 years of age. FeNO was measured at 10 and 20 years. Results: In total, 45% of the study participants were allergic, with twice as many self-reported cases at age 20. Rhinitis was key to distinguishing confirmed allergy from self-reported. Having two allergic parents and increased FeNO were associated with an increased prevalence of allergic disease at 20 years. From a longitudinal perspective, rhinitis increased from childhood to young adulthood, in all heredity groups. Conclusion: In this longitudinal study, we have shown that two allergic parents as well as increased FeNO levels seem to be of importance for being allergic at 20 years old. Self-reported allergy was overreported – a result that should be considered in future survey-based reports on allergic diseases.

The mouse multi-organ proteome from infancy to adulthood

The early-life organ development and maturation shape the fundamental blueprint for later-life phenotype. However, a multi-organ proteome atlas from infancy to adulthood is currently not available. Herein, we present a comprehensive proteomic analysis of ten mouse organs (brain, heart, lung, liver, kidney, spleen, stomach, intestine, muscle and skin) at three crucial developmental stages (1-, 4- and 8-weeks after birth) acquired using data-independent acquisition mass spectrometry. We detect and quantify 11,533 protein groups across the ten organs and obtain 115 age-related differentially expressed protein groups that are co-expressed in all organs from infancy to adulthood. We find that spliceosome proteins prevalently play crucial regulatory roles in the early-life development of multiple organs, and detect organ-specific expression patterns and sexual dimorphism. This multi-organ proteome atlas provides a fundamental resource for understanding the molecular mechanisms underlying early-life organ development and maturation.

Early childhood inequalities: the rocky path from observation to action

Abstract The article on early childhood inequalities by Cattan and colleagues identifies a broad range of socio- and geo-demographic correlates of children’s cognitive and social–emotional development in early life through analyses of three UK population cohort studies. The findings suggest that early life inequalities are driven by a complex nexus of multiple, often inter-correlated factors that each have a small independent effect size. In this commentary, I discuss three key implications for research and practice that follow from the work of Cattan et al.: (1) the urgent need for a theoretical framework to identify and test the mechanisms that drive early life inequalities; (2) the persistent obstacles to ameliorating early childhood inequality; and (3) the immense value of population cohort studies for understanding socio-historical trends and developing evidence-based policies.

First success in captive breeding of the Tiger Cowrie, Cypraea tigris (Gastropoda: Cypraeidae), with notes on its early life development

ABSTRACT The larval development of cowries has remained underexplored due to challenges associated with restricted growth and high mortalities, and as a result, their larvae never achieve competency or metamorphosis. In this study, we conducted a series of experiments using Cypraea tigris larvae to optimise the culture protocols. Broadly, there were no apparent differences in larval survival rates among the seawater quality levels (0.2, 1 aged, 50 μm filtered seawater). In contrast, a microalgal diet solely of Tisochrysis lutea and a mixed diet of Rhodomonas salina + Chaetoceros mulleri had higher larval survival rates than two other mixed diets (i.e., T. lutea + Tetraselmis suecica and T. suecica + R. salina). The provision of 10 ppm of the antibiotic streptomycin sulphate also boosted larval survival by preventing ciliate infection and minimising bacterial growth. We subsequently improved culture protocols by applying new information from these experiments and report the first successful captive breeding of C. tigris through to settlement. The C. tigris larvae reared at 28°C attained competency as early as 40 days post-hatching and metamorphosed by 42 days upon transfer to a well-conditioned tank. Observations of C. tigris larvae and early-stage juvenile development were documented for the first time and are reported herein.

Early-Life Circumstances and Racial Disparities in Cognition Among Older Adults in the US

ImportanceGiven the critical role of neurocognitive development in early life, understanding the association between early-life circumstances and racial disparities in cognition has important implications.ObjectiveTo assess whether racial differences in early-life circumstances are collectively and individually associated with racial disparities in late-life cognition among older adults in the US.Design, Setting, and ParticipantsThis cross-sectional study used comprehensive life history data from the Health and Retirement Study, a nationally representative survey of US adults 50 years or older. Data analyses were performed from August 9, 2022, to January 20, 2024.Main Outcomes and MeasuresRacial differences in early-life circumstances and racial disparities in late-life cognition were investigated using a Blinder-Oaxaca decomposition regression model. Cognitive outcomes, including cognitive score and cognitive impairment, were evaluated using the Telephone Interview for Cognitive Status. Early-life educational experiences were primary explanatory variables; early-life cohort, regional, financial, health, trauma, family relationship factors, and educational attainment were additional explanatory variables; demographic and genetic factors were covariates.ResultsThe study sample comprised 9015 participants; 1634 non-Hispanic Black (hereafter, Black) individuals (18.1%) and 7381 non-Hispanic White (hereafter, White) individuals (81.9%). Among Black participants, the mean (SD) age was 69.2 (9.2) years and 1094 (67.0%) were women. Among White participants, the mean (SD) age was 73.2 (10.1) years and 4410 (59.7%) were women. Cognitive scores (scale, 0-27) were significantly lower among Black participants (13.5 [95% CI, 13.3-13.7] points) than among White participants (15.8 [95% CI, 15.7-15.9] points), while the prevalence of cognitive impairment (cognitive score <12) was significantly higher among Black participants (33.6 [95% CI, 31.3-35.9] percentage points [ppt]) than among White participants (16.4 [95% CI, 15.6-17.2] ppt). Substantial racial differences were observed in early-life circumstances. Overall, differences in early-life circumstances were associated with 61.5% of the racial disparities in cognitive score (1.4 [95% CI, 0.88-2.0] points), and 82.3% of the racial disparities in cognitive impairment (14.2 [95% CI, 8.8-19.5] ppt), respectively. In multivariable analyses, early-life educational experiences were associated with 35.2% of the disparities in cognitive score and 48.6% in cognitive impairment. Notably, school racial segregation (all segregated schooling before college) was associated with 28.8% to 39.7% of the racial disparities in cognition. These findings were consistent in a series of sensitivity analyses.Conclusions and RelevanceThe findings of this cross-sectional study suggest that less favorable early-life circumstances are associated with clinically meaningful racial disparities in late-life cognition. Policies that improve educational equity have the potential to reduce racial disparities in cognition in older ages. Clinicians may leverage early-life circumstances to promote the screening, prevention, and interventions of cognitive impairment more efficiently, thereby promoting health equity.

A vegetable fat-based diet delays psychomotor and cognitive development compared with maternal dairy fat intake in infant gray mouse lemurs

Dairy fat has a unique lipid profile; it is rich in short- and medium-chain saturated fatty acids that induce ketone production and has a balanced ω6/ω3 ratio that promotes cognitive development in early life. Moreover, the high consumption of vegetable oils in pregnant and lactating women raises concerns regarding the quality of lipids provided to offspring. Here, we investigate maternal dairy fat intake during gestation and lactation in a highly valuable primate model for infant nutritional studies, the gray mouse lemur (Microcebus murinus). Two experimental diets are provided to gestant mouse lemurs: a dairy fat-based (DF) or vegetable fat-based diet (VF). The psychomotor performance of neonates is tested during their first 30 days. Across all tasks, we observe more successful neonates born to mothers fed a DF diet. A greater rate of falls is observed in 8-day-old VF neonates, which is associated with delayed psychomotor development. Our findings suggest the potential benefits of lipids originating from a lactovegetarian diet compared with those originating from a vegan diet for the psychomotor development of neonates.

Early development of Acacia longifolia is more severely impacted by water and nutrient stress in invasive than native seedlings

Acacia longifolia (Andrews) Willd. is a legume native to southeast mainland Australia and Tasmania and has two described subspecies: A. l. subsp. longifolia and A. l. subsp. sophorae. The species has been introduced around the world and is considered invasive in several Mediterranean-type climate regions, including in South America, South Africa, and southern Europe. Previous studies comparing native and invasive populations of A. longifolia have focused on its reproductive ecology and population genetics, and little information exists on the species’ early life development and how abiotic factors influence it. Here, we performed a glasshouse experiment to compare the phenotypic responses of native and invasive (in Portugal) A. longifolia seedlings to different levels of water and nutrient availability. We found that seedlings of both subspecies responded similarly to different water and nutrient availability conditions in terms of biomass accumulation, root length, the number of phyllodes produced, phyllode water content, and root-to-shoot ratio. However, compared to native seedlings, invasive seedlings had limited capacity for stress responses. We found that invasive seedlings had lower drought tolerance than native seedlings, and thus the speed of invasion by A. longifolia into drier parts of Portugal may be hindered. Our results also hint of a possible role of seed “imprinting” in this species’ early growth responses, resulting in different resource allocation strategies such as favouring early growth and development over drought resistance in the invaded range. Further studies are required to better understand the species’ abiotic stress responses at the intraspecific level and their relation to its invasiveness.

Anthropogenic noise disrupts early-life development in a fish with paternal care

Anthropogenic noise is a global pollutant but its potential impacts on early life-stages in fishes are largely unknown. Here, using controlled laboratory experiments, we tested for impacts of continuous or intermittent exposure to low-frequency broadband noise on early life-stages of the common goby (Pomatoschistus microps), a marine fish with exclusive paternal care. Neither continuous nor intermittent noise exposure had an effect on filial cannibalism, showing that males were capable and willing to care for their broods. However, broods reared in continuous noise covered a smaller area and contained fewer eggs than control broods. Moreover, although developmental rate was the same in all treatments, larvae reared by males in continuous noise had, on average, a smaller yolk sac at hatching than those reared in the intermittent noise and control treatments, while larvae body length did not differ. Thus, it appears that the increased consumption of the yolk sac reserve was not utilised for increased growth. This suggests that exposure to noise in early life-stages affects fitness-related traits of surviving offspring, given the crucial importance of the yolk sac reserve during the early life of pelagic larvae. More broadly, our findings highlight the wide-ranging impacts of anthropogenic noise on aquatic wildlife living in an increasingly noisy world.

Brain volumes, behavioral inhibition, and anxiety disorders in children: results from the adolescent brain cognitive development study

BackgroundMagnetic resonance imaging (MRI) studies have identified brain changes associated with anxiety disorders (ADs), but the results remain mixed, particularly at a younger age. One key predictor of ADs is behavioral inhibition (BI), a childhood tendency for high avoidance of novel stimuli. This study aimed to evaluate the relationships between candidate brain regions, BI, and ADs among children using baseline data from the Adolescent Brain Cognitive Development (ABCD) study.MethodsWe analyzed global and regional brain volumes of 9,353 children (9–10 years old) in relation to BI and current ADs, using linear mixed models accounting for family clustering and important demographic and socioeconomic covariates. We further investigated whether and how past anxiety was related to brain volumes.ResultsAmong included participants, 249 (2.66%) had a current AD. Larger total white matter (Beta = -0.152; 95% CI [-0.281, -0.023]), thalamus (Beta = -0.168; 95% CI [-0.291, -0.044]), and smaller hippocampus volumes (Beta = 0.094; 95% CI [-0.008, 0.196]) were associated with lower BI scores. Amygdala volume was not related to BI. Larger total cortical (OR = 0.751; 95% CI [0.580;0.970]), amygdala (OR = 0.798; 95%CI [0.666;0.956]), and precentral gyrus (OR = 0.802; 95% CI [0.661;0.973]) volumes were associated with lower odds of currently having ADs. Children with past ADs had smaller total white matter and amygdala volumes.ConclusionsThe results show associations between brain volumes and both BI and ADs at an early age. Importantly, results suggest that ADs and BI have different neurobiological correlates and that earlier occurrences of ADs may influence brain structures related to BI and ADs, motivating research that can better delineate the similarities and divergence in the neurobiological underpinnings and building blocks of BI and ADs across their development in early life.