Infant Brain Development Research Articles

Protocol for the Emory University African American maternal stress and infant gut microbiome cohort study

BackgroundThe microbial population of the human gut (the gut microbiome) is an integral cog in the bidirectional communication axis that exists between the gastrointestinal tract and the central nervous system. African American infants disproportionately experience multiple, overlapping vulnerabilities such as preterm birth and formula rather than breast feeding that may disrupt the development of the infant microbiome. African American infants also are more likely to have mothers affected by chronic stress both pre- and post-natally. Perhaps relatedly, African American offspring are disproportionately affected by neurodevelopmental delays. Taken together, these findings suggest that one important mechanism that may link prenatal and postnatal stress and African American infant brain development is the composition of the infant microbiome.MethodsIn our ongoing longitudinal study, Maternal Stress and the Gut-Brain Axis in African American Infants (R01MD009746), we investigate associations between maternal prenatal and postnatal stress and the composition of the infant gut microbiome, in relation to cognitive and social-emotional development. We aim to recruit 300 African American mother-infant dyads, contingent on the mother’s previous participation in an associated prenatal cohort study: Biobehavioral Determinants of the Microbiome and Preterm Birth in Black Women (R01NR014800). Following enrollment, we assess infants at 1-week, and 3-, 6-, 12-and 18-months to collect: standardized assessments of infant neurocognitive and social-emotional development; questionnaire measures of infant feeding and health; observational data on maternal-infant interactions; maternal reports of postnatal stress; blood and saliva samples to evaluate maternal and infant psychoneuroimmunologic (PNI) function; and infant stool samples to characterize acquisition and trajectory of gut microbiome composition. Genetic variants of the major histocompatibility complex that may influence gut microbiome composition are also being evaluated.DiscussionThis rich data set will allow future consideration of risk and protective factors that influence neurodevelopment in African American infants who are exposed to varying levels of prenatal and early life stress. Evidence for a mechanistic role of the microbiome would provide a framework for future clinical evaluations of preventative interventions (e.g., probiotics, culturally-appropriate breastfeeding campaigns) that could potentially improve the health and development of African American children in infancy and across the lifespan.

Early vocal contact and music in the NICU: new insights into preventive interventions.

It is now clearly established that the environment and the sensory stimuli, particularly during the perinatal period, have an impact on infant's development. During the last trimester of gestation, activity-dependent plasticity shapes the fetal brain, and prematurity has been shown to alter the typical developmental trajectories. In this delicate period, preventive interventions aiming at modulating these developmental trajectories through activity-inducing interventions are currently underway to be tested. The purpose of this review paper is to describe the potentialities of early vocal contact and music on the preterm infant's brain development, and their potential beneficial effect on early development. Scientific evidence supports a behavioral orientation of the newborn to organized sounds, such as those of voice and music, and recent neuroimaging studies further confirm full cerebral processing of music as multisensory stimuli. However, the impact of long-term effects of music exposure and early vocal contact on preterm infants' long-term neurodevelopment needs be further investigated. To conclude, it is necessary to establish the neuroscientific bases of the early perception and the long-term effects of music and early vocal contact on the premature newborns' development. Scientific projects are currently on the way to fill this gap in knowledge.

NICU Diet, Physical Growth and Nutrient Accretion, and Preterm Infant Brain Development.

Half of very preterm infants experience neurodevelopmental impairments after NICU discharge. These adverse outcomes result in part from abnormal brain development and injury that occur during the NICU hospitalization. Although many factors influence infant brain development, nutritional determinants are of particular interest because they are highly modifiable within clinical care. Physical growth of preterm infants in the NICU continues to lag behind the reference fetus, suggesting reduced nutrient accretion during a critical period for brain development. Nutrient accretion is driven by intake of specific nutrients such as macro- and micronutrients as well as non-nutritional factors such as systemic inflammation. Most often, anthropometric indicators, such as weight, length, and head circumference, are used as proxies for nutrient accretion. A limitation of weight is that it does not differentiate the healthy growth of specific organs and tissues from excess fat accumulation. Body length provides information about skeletal growth, and linear growth stunting predicts neurodevelopmental impairment. Head circumference is only a crude proxy for brain size. More recently, application of new technologies such as air displacement plethysmography and magnetic resonance imaging has allowed the direct estimation of lean tissue accretion and brain growth in the NICU. These newer techniques can facilitate research to improve our understanding of the links among the NICU diet, inflammation, physical growth, and brain development. These new measures may also be relevant within clinical care to identify infants who may benefit from specific interventions to enhance nutrient accretion and brain development.

Thermal conditions during neonatal anoxia affect the endogenous level of brain-derived neurotrophic factor.

Anoxia during delivery is a complication that can disturb infant brain development leading to various types of neurological disorders. Our studies have shown that increased body temperature of newborn rats of both sexes intensifies the postanoxic oxidative stress and prevents triggering the endogenous adaptive response such as HIF-1α activation. Currently, brain-derived neurotrophic factor-BDNF is considered to be a modulator of neuronal plasticity. In the developing brain, mature BDNF and its precursor exhibit prosurvival action through the TrkB receptor and proapoptotic functions binding to p75NTR , respectively. The aim of our experiments was to check the effects of body temperature on the postanoxic level of BDNF and on the expression of its receptors as well as on the marker of apoptosis-caspase-3 in the rat brain. Two-day-old Wistar Han rats (male/female ratio, 1:1) were exposed to anoxia in 100% nitrogen atmosphere for 10min in different thermal conditions, which allowed them to regulate their rectal temperature at the following levels: normothermic-33°C; hyperthermic-37°C; and extremely hyperthermic-39°C. Thermal conditions during neonatal anoxia affected the level of proBDNF, BDNF as well as their receptors and caspase-3 in the forebrain. The increased BDNF protein level followed by decreased caspase-3 protein level was probably dependent on body temperature under anoxic conditions and was observed only in rats maintaining decreased body temperature. The positive effect of BDNF was not observed under hyperthermic conditions. Moreover, BDNF level changes correlated with body temperature probably affected the learning and spatial memory in juvenile rats.

Maternal and Infant Factors Associated with Human Milk Oligosaccharides Concentrations According to Secretor and Lewis Phenotypes.

Human milk oligosaccharides (HMOs) are multifunctional carbohydrates naturally present in human milk that act as prebiotics, prevent pathogen binding and infections, modulate the immune system and may support brain development in infants. HMOs composition is very individualized and differences in HMOs concentrations may affect the infant’s health. HMOs variability can be partially explained by the activity of Secretor (Se) and Lewis (Le) genes in the mother, but non-genetic maternal factors may also be involved. In this cross-sectional, observational study, 78 single human milk samples ranging from 17 to 76 days postpartum (median: 32 days, IQR: 25–46 days) were collected from breastfeeding Brazilian women, analyzed for 16 representative HMOs by liquid chromatography coupled to mass spectrometry and associations between maternal and infant factors with HMOs concentrations were investigated. HMOs concentrations presented a high variability even in women with the same SeLe phenotype and associations with maternal allergic disease, time postpartum and with infant’s weight, weight gain and sex. Overall, we present unprecedented data on HMOs concentrations from breastfeeding Brazilian women and novel associations of maternal allergic disease and infant’s sex with HMOs concentrations. Differences in HMOs composition attributed to maternal SeLe phenotype do not impact infant growth, but higher concentrations of specific HMOs may protect against excessive weight gain.

Bovine Milk Oligosaccharides with Sialyllactose Improves Cognition in Preterm Pigs.

Optimal nutrition is important after preterm birth to facilitate normal brain development. Human milk is rich in sialic acid and preterm infants may benefit from supplementing formula with sialyllactose to support neurodevelopment. Using pigs as models, we hypothesized that sialyllactose supplementation improves brain development after preterm birth. Pigs (of either sex) were delivered by cesarean section at 90% gestation and fed a milk diet supplemented with either an oligosaccharide-enriched whey with sialyllactose (n = 20) or lactose (n = 20) for 19 days. Cognitive performance was tested in a spatial T-maze. Brains were collected for ex vivo magnetic resonance imaging (MRI), gene expression, and sialic acid measurements. For reference, term piglets (n = 14) were artificially reared under identical conditions and compared with vaginally born piglets naturally reared by the sow (n = 12). A higher proportion of sialyllactose supplemented preterm pigs reached the T-maze learning criteria relative to control preterm pigs (p < 0.05), and approximated the cognition level of term reference pigs (p < 0.01). Furthermore, supplemented pigs had upregulated genes related to sialic acid metabolism, myelination, and ganglioside biosynthesis in hippocampus. Sialyllactose supplementation did not lead to higher levels of sialic acid in the hippocampus or change MRI endpoints. Contrary, these parameters were strongly influenced by postconceptional age and postnatal rearing conditions. In conclusion, oligosaccharide-enriched whey with sialyllactose improved spatial cognition, with effects on hippocampal genes related to sialic acid metabolism, myelination, and ganglioside biosynthesis in preterm pigs. Dietary sialic acid enrichment may improve brain development in infants.

Targeting Human Milk Fortification to Improve Preterm Infant Growth and Brain Development

Targeting Human Milk Fortification to Improve Preterm Infant Growth and Brain Development

Age-specific optimization of T1-weighted brain MRI throughout infancy

The infant brain undergoes drastic morphological and functional development during the first year of life. Three-dimensional T1-weighted Magnetic Resonance Imaging (3D T1w-MRI) is a major tool to characterize the brain anatomy, which however, manifests inherently low and rapidly changing contrast between white matter (WM) and gray matter (GM) in the infant brains (0-12 month-old). Despite the prior efforts made to maximize tissue contrast in the neonatal brains (≤1 months), optimization of imaging methods in the rest of the infancy (1–12 months) is not fully addressed, while brains in the latter period exhibit even more challenging contrast. Here, we performed a systematic investigation to improve the contrast between cortical GM and subcortical WM throughout the infancy. We first performed simultaneous T1 and proton density mapping in a normally developing infant cohort at 3T (n = 57). Based on the evolution of T1 relaxation times, we defined three age groups and simulated the relative tissue contrast between WM and GM in each group. Age-specific imaging strategies were proposed according to the Bloch simulation: inversion time (TI) around 800 ms for the 0-3 month-old group, dual TI at 500 ms and 700 ms for the 3-7 month-old group, and TI around 700 ms for 7-12 month-old group, using a centrically encoded 3D-MPRAGE sequence at 3T. Experimental results with varying TIs in each group confirmed improved contrast at the proposed optimal TIs, even in 3–7 month-old infants who had nearly isointense contrast. We further demonstrated the advantage of improved relative contrast in segmenting the neonatal brains using a multi-atlas segmentation method. The proposed age-specific optimization strategies can be easily adapted to routine clinical examinations, and the improved image contrast would facilitate quantitative analysis of the infant brain development.

Choline and DHA in Maternal and Infant Nutrition: Synergistic Implications in Brain and Eye Health.

The aim of this review is to highlight current insights into the roles of choline and docosahexaenoic acid (DHA) in maternal and infant nutrition, with special emphasis on dietary recommendations, gaps in dietary intake, and synergistic implications of both nutrients in infant brain and eye development. Adequate choline and DHA intakes are not being met by the vast majority of US adults, and even more so by women of child-bearing age. Choline and DHA play a significant role in infant brain and eye development, with inadequate intakes leading to visual and neurocognitive deficits. Emerging findings illustrate synergistic interactions between choline and DHA, indicating that insufficient intakes of one or both could have lifelong deleterious impacts on both maternal and infant health.

Maternal Omega-3 Nutrition, Placental Transfer and Fetal Brain Development in Gestational Diabetes and Preeclampsia.

Omega-3 fatty acids, particularly docosahexaenoic fatty acid (DHA), are widely recognized to impact fetal and infant neurodevelopment. The impact of DHA on brain development, and its inefficient synthesis from the essential alpha-linolenic acid (ALA), has led to recommended DHA intakes of 250–375 mg eicosapentaenoic acid + DHA/day for pregnant and lactating women by the Dietary Guidelines for Americans. Despite these recommendations, the intake of omega-3s in women of child-bearing age in the US remains very low. The low maternal status of DHA prior to pregnancy could impair fetal neurodevelopment. This review focuses on maternal omega-3 status in conditions of gestational diabetes mellitus (GDM) and preeclampsia, and the subsequent impact on placental transfer and cord blood concentration of omega-3s. Both GDM and preeclampsia are associated with altered maternal omega-3 status, altered placental omega-3 metabolism, reduced cord blood omega-3 levels and have an impact on neurodevelopment in the infant and on brain health later in life. These findings indicate lower DHA exposure of the developing baby may be driven by lower placental transfer in both conditions. Thus, determining approaches which facilitate increased delivery of DHA during pregnancy and early development might positively impact brain development in infants born to mothers with these diseases.

Evidence supporting nubility and reproductive value as the key to human female physical attractiveness

Abstract Selection should favor mating preferences that increase the chooser's reproductive success. Many previous studies have shown that the women men find most attractive in well-nourished populations have low body mass indices (BMIs) and small waist sizes combined with relatively large hips, resulting in low waist-hip ratios (WHRs). A frequently proposed explanation for these preferences is that such women may have enhanced health and fertility; but extensive evidence contradicts this health-and-fertility explanation. An alternative view is that men are attracted to signs of nubility and high reproductive value, i.e., by indicators of physical and sexual maturity in young women who have not been pregnant. Here we provide evidence in support of the view that a small waist size together with a low WHR and BMI is a strong and reliable sign of nubility. Using U.S. data from large national health surveys, we show that WHR, waist/thigh, waist/stature, and BMI are all lower in the age group (15-19) in which women reach physical and sexual maturity, after which all of these anthropometric measures increase. We also show that a smaller waist, in conjunction with relatively larger hips or thighs, is strongly associated with nulligravidity and with higher blood levels of docosahexaenoic acid (DHA), a fatty acid that is probably limiting for infant brain development. Thus, a woman with the small waist and relatively large hips that men find attractive is very likely to be nubile and nulliparous, with maximal bodily stores of key reproductive resources.

Iodine Nutrition in Weaning Infants in the United States.

As iodine is a requisite micronutrient for infant brain development, infants are at risk for iodine deficiency during the weaning period when their diet transitions from milk (breast-milk, infant formula, or follow-on formula) to solid food. Dietary iodine intake during this weaning period is likely minimal, as the iodine content of commercial baby food is not regulated, and the addition of salt to baby food is not recommended. This study reports the current status of iodine nutrition among weaning infants in the United States. Subjects (n = 60; 50% Caucasian, 30% black) were infants <12 months of age who were fed any combination of formula and/or baby food. Samples of all formula and food consumed in the previous 24 hours and a spot urine sample from each infant were obtained for the measurement of iodine. The estimated quantities of ingested formula and baby food were summed from a food diary recorded by the infants' parents. The mean age of the infants was 6.3 ± 3.5 months. The median urinary iodine concentration (UIC) was 117 μg/L (range 26.9-1302.8 μg/L). Estimated daily iodine intake obtained from the measured iodine content in infant formula/foods was 89 μg (range 0-288 μg). There was a positive correlation between the infants' UIC and the iodine content in the consumed foods (r = 0.4, p < 0.001). Although the median UIC of infants fed a combination of infant formula and baby food would meet the criteria for iodine sufficiency in a larger sample, those consuming the lowest quartile of iodine-containing nutritional sources had a median UIC <100 μg/L.

Higher Gestational Choline Levels in Maternal Infection Are Protective for Infant Brain Development

To assess whether maternal choline decreases effects of mothers' infectionson fetal brain circuit development and on expression of infant behavior at 1year of age. A cross-sectional study was conducted in a public hospital obstetrics and midwifery service, with prenatal assessments of maternal infection, C-reactive protein, and choline level and postnatal assessments of cerebral neuronal inhibition in 162 newborns. At 1year, 136 parents completed reports of their child's behavior. Maternal infection at 16weeks of gestation, experienced by 41% of mothers, raised mean maternal C-reactive protein (d'=0.47, P=.002) and decreased the development of cerebral inhibition of auditory response at 1month of age (d'=0.39, P<.001). Decreased newborn cerebral inhibition manifested as decreased behavioral self-regulation at 1year. Greater choline levels in mothers with infections were associated with improved newborn inhibition of auditory cerebral response, mitigating the effect of infection (β=-0.34 [95% CI, -5.35 to -0.14], P=.002). At 1year of age, children of mothers with infection and greater gestational choline levels had improved development of self-regulation, approaching the level of children of mothers without infection (β=0.29 [95% CI 0.05-0.54], P=.03). Greater maternal choline, recommended by the American Medical Association as a prenatal supplement, is associated with greater self-regulation among infants who experienced common maternal infections during gestation. Behavioral problems with diminished self-regulation often lead to referrals to pediatricians and might lead to later mental illness.

Comprehensive Preterm Breast Milk Metabotype Associated with Optimal Infant Early Growth Pattern.

Early nutrition impacts preterm infant early growth rate and brain development but can have long lasting effects as well. Although human milk is the gold standard for feeding new born full-term and preterm infants, little is known about the effects of its bioactive compounds on breastfed preterm infants’ growth outcomes. This study aims to determine whether breast milk metabolome, glycome, lipidome, and free-amino acids profiles analyzed by liquid chromatography-mass spectrometry had any impact on the early growth pattern of preterm infants. The study population consisted of the top tercile-Z score change in their weight between birth and hospital discharge (“faster grow”, n = 11) and lowest tercile (“slower grow”, n = 15) from a cohort of 138 premature infants (27–34 weeks gestation). This holistic approach combined with stringent clustering or classification statistical methods aims to discriminate groups of milks phenotype and identify specific metabolites associated with early growth of preterm infants. Their predictive reliability as biomarkers of infant growth was assessed using multiple linear regression and taking into account confounding clinical factors. Breast-milk associated with fast growth contained more branched-chain and insulino-trophic amino acid, lacto-N-fucopentaose, choline, and hydroxybutyrate, pointing to the critical role of energy utilization, protein synthesis, oxidative status, and gut epithelial cell maturity in prematurity.

Controlled release of microencapsulated docosahexaenoic acid (DHA) by spray–drying processing

The omega-3-fatty acid, docosahexaenoic acid (DHA) 22:6 n-3, is an important food component for the visual and brain development of infants. In this study two approaches have been explored for the encapsulation of DHA in the pH dependant polymer hydroxyl-propyl-methyl-cellulose-acetate-succinate (HPMCAS). In the first approach Direct Spray Drying (DSD) was implemented for the microencapsulation of DHA/HPMCAS organic solutions, whilst in the second approach solid lipid nanoparticle (SLN) dispersions of DHA, were first produced by high-pressure homogenization, prior to being spray dried in HPMCAS aqueous solutions. The DSD approach resulted in significantly higher quantities of DHA being encapsulated, at 2.09 g/100 g compared to 0.60 g/100 g in the spray-dried SLNs. The DHA stability increased with the direct spray-drying approach. Release studies of DHA in the direct sprayed dried samples revealed a lag time for 2 h in acidic media followed by rapid release in phosphate buffer (pH 6.8).

Review shows that thyroid hormone substitution could benefit transient hypothyroxinaemia of prematurity but treatment strategies need to be clarified.

Thyroid hormones are crucial for foetal and neonatal brain development. This paper provides an overview of the normal role of thyroid hormones in foetal brain development and the pathophysiology of transient hypothyroxinaemia of prematurity (THOP). It also discusses the diagnostic and therapeutic controversies around THOP and looks at directions for future research. We used the PubMed and Embase databases to identify papers published in English from 1969 to June 2018. This identified 20 papers about the impact of THOP on neurodevelopment and seven randomised controlled trials about therapeutic approaches from 1981-2016. THOP has been researched for more than three decades. The impact of temporarily low thyroxine levels, without any increase in pituitary-secreted thyroid-stimulating hormone at a critical timeframe in an infant's brain development, is still debated. Heterogeneity in THOP definitions, difficulties with thyroid hormone assessment, identifying patients at risk and a clear lack of sufficiently powered studies add to the current controversy. There are indications that thyroid hormone substitution might be useful in extremely low gestational age neonates with THOP. Some preterm infants could benefit from THOP treatment, but more studies are needed to clarify further treatment strategies, including the optimal timing of initiation and duration.

Deep Granular Feature-Label Distribution Learning for Neuroimaging-based Infant Age Prediction.

Neuroimaging-based infant age prediction is important for brain development analysis but often suffers insufficient data. To address this challenge, we introduce label distribution learning (LDL), a popular machine learning paradigm focusing on the small sample problem, for infant age prediction. As directly applying LDL yields dramatically increased number of day-to-day age labels and also extremely scarce data describing each label, we propose a new strategy, called granular label distribution (GLD). Particularly, by assembling the adjacent labels to granules and designing granular distributions, GLD makes each brain MRI contribute to not only its own age but also its neighboring ages at a granule scale, which effectively keeps the information augmentation superiority of LDL and reduces the number of labels. Furthermore, to extremely augment the information supplied by the small data, we propose a novel method named granular feature distribution (GFD). GFD leverages the variability of the brain images at the same age, thus significantly increasing the learning effectiveness. Moreover, deep neural network is exploited to approximate the GLD. These strategies constitute a new model: deep granular feature-label distribution learning (DGFLDL). By taking 8 types of cortical morphometric features from structural MRI as predictors, the proposed DGFLDL is validated on infant age prediction using 384 brain MRI scans from 35 to 848 days after birth. Our proposed method, approaching the mean absolute error as 36.1 days, significantly outperforms the baseline methods. Besides, the permutation importance analysis of features based on our method reveals important biomarkers of infant brain development.

Incorporating Recognition and Management of Perinatal Depression Into Pediatric Practice

Perinatal depression (PND) is the most common obstetric complication in the United States. Even when screening results are positive, mothers often do not receive further evaluation, and even when PND is diagnosed, mothers do not receive evidence-based treatments. Studies reveal that postpartum depression (PPD), a subset of PND, leads to increased costs of medical care, inappropriate medical treatment of the infant, discontinuation of breastfeeding, family dysfunction, and an increased risk of abuse and neglect. PPD, specifically, adversely affects this critical early period of infant brain development. PND is an example of an adverse childhood experience that has potential long-term adverse health complications for the mother, her partner, the infant, and the mother-infant dyad. However, PND can be treated effectively, and the stress on the infant can be buffered. Pediatric medical homes should coordinate care more effectively with prenatal providers for women with prenatally diagnosed maternal depression; establish a system to implement PPD screening at the 1-, 2-, 4-, and 6-month well-child visits; use community resources for the treatment and referral of the mother with depression; and provide support for the maternal-child (dyad) relationship, including breastfeeding support. State chapters of the American Academy of Pediatrics, working with state departments of public health, public and private payers, and maternal and child health programs, should advocate for payment and for increased training for PND screening and treatment. American Academy of Pediatrics recommends advocacy for workforce development for mental health professionals who care for young children and mother-infant dyads, and for promotion of evidence-based interventions focused on healthy attachment and parent-child relationships.

Bacterial Clearance Is Enhanced by α2,3- and α2,6-Sialyllactose via Receptor-Mediated Endocytosis and Phagocytosis.

Sialyllactose (SL) is a representative human milk oligosaccharide (HMO) of human breast milk. The roles of SL in infant brain development and immunity have been reported in previous studies. In this study, we identified the impact of SL on innate immunity. Our results showed that the administration of SL had significant efficacy on bacterial clearance in Pseudomonas aeruginosa K-infected mice. We also examined the role of SL in the human THP-1 macrophage-like cell line. SL effectively promoted receptor-mediated endocytosis and phagocytosis. Furthermore, SL accelerated the recruitment of Rac1 to the cell membrane, leading to the generation of reactive oxygen species for the elimination of phagocytosed bacteria. Our findings provide a new perspective on the role of SL in breast milk and suggest its application as a therapeutic agent to treat bacterial and viral infections.

Cesarean Delivery Impacts Infant Brain Development.

The cesarean delivery rate has increased globally in the past few decades. Neurodevelopmental outcomes associated with cesarean delivery are still unclear. This study investigated whether cesarean delivery has any effect on the brain development of offspring. A total of 306 healthy children were studied retrospectively. We included 3 cohorts: 2-week-old neonates (cohort 1, n = 32/11 for vaginal delivery/cesarean delivery) and 8-year-old children (cohort 2, n = 37/23 for vaginal delivery/cesarean delivery) studied at Arkansas Children's Hospital, and a longitudinal cohort of 3-month to 5-year-old children (cohort 3, n = 164/39 for vaginal delivery/cesarean delivery) studied independently at Brown University. Diffusion tensor imaging, myelin water fraction imaging, voxel-based morphometry, and/or resting-state fMRI data were analyzed to evaluate white matter integrity, myelination, gray matter volume, and/or functional connectivity, respectively. While not all MR imaging techniques were shared across the institutions/cohorts, post hoc analyses showed similar results of potential effects of cesarean delivery. The cesarean delivery group in cohort 1 showed significantly lower white matter development in widespread brain regions and significantly lower functional connectivity in the brain default mode network, controlled for a number of potential confounders. No group differences were found in cohort 2 in white matter integrity or gray matter volume. Cohort 3 had significantly different trajectories of white matter myelination between groups, with those born by cesarean delivery having reduced myelin in infancy but normalizing with age. Cesarean delivery may influence infant brain development. The impact may be transient because similar effects were not observed in older children. Further prospective and longitudinal studies may be needed to confirm these novel findings.