Brain Volumes In Infants Research Articles

Brain volume in infants with metopic synostosis: Less white matter volume with an accelerated growth pattern in early life.

Metopic synostosis patients are at risk for neurodevelopmental disorders despite a negligible risk of intracranial hypertension. To gain insight into the underlying pathophysiology of metopic synostosis and associated neurodevelopmental disorders, we aimed to investigate brain volumes of non-syndromic metopic synostosis patients using preoperative MRI brain scans. MRI brain scans were processed with HyperDenseNet to calculate total intracranial volume (TIV), total brain volume (TBV), total grey matter volume (TGMV), total white matter volume (TWMV) and total cerebrospinal fluid volume (TCBFV). We compared global brain volumes of patients with controls corrected for age and sex using linear regression. Lobe-specific grey matter volumes were assessed in secondary analyses. We included 45 metopic synostosis patients and 14 controls (median age at MRI 0.56 years [IQR 0.36] and 1.1 years [IQR 0.47], respectively). We found no significant differences in TIV, TBV, TGMV or TCBFV in patients compared to controls. TWMV was significantly smaller in patients (-62,233 mm3 [95% CI = -96,968; -27,498], Holm-corrected p = 0.004), and raw data show an accelerated growth pattern of white matter in metopic synostosis patients. Grey matter volume analyses per lobe indicated increased cingulate (1378 mm3 [95% CI = 402; 2355]) and temporal grey matter (4747 [95% CI = 178; 9317]) volumes in patients compared to controls. To conclude, we found smaller TWMV with an accelerated white matter growth pattern in metopic synostosis patients, similar to white matter growth patterns seen in autism. TIV, TBV, TGMV and TCBFV were comparable in patients and controls. Secondary analyses suggest larger cingulate and temporal lobe volumes. These findings suggest a generalized intrinsic brain anomaly in the pathophysiology of neurodevelopmental disorders associated with metopic synostosis.

Negative versus withdrawn maternal behavior: Differential associations with infant gray and white matter during the first 2 years of life.

Distinct neural effects of threat versus deprivation emerge by childhood, but little data are available in infancy. Withdrawn versus negative parenting may represent dimensionalized indices of early deprivation versus early threat, but no studies have assessed neural correlates of withdrawn versus negative parenting in infancy. The objective of this study was to separately assess the links of maternal withdrawal and maternal negative/inappropriate interaction with infant gray matter volume (GMV), white matter volume (WMV), amygdala, and hippocampal volume. Participants included 57 mother-infant dyads. Withdrawn and negative/inappropriate aspects of maternal behavior were coded from the Still-Face Paradigm at four months infant age. Between 4 and 24 months (M age = 12.28 months, SD = 5.99), during natural sleep, infants completed an MRI using a 3.0 T Siemens scanner. GMV, WMV, amygdala, and hippocampal volumes were extracted via automated segmentation. Diffusion weighted imaging volumetric data were also generated for major white matter tracts. Maternal withdrawal was associated with lower infant GMV. Negative/inappropriate interaction was associated with lower overall WMV. Age did not moderate these effects. Maternal withdrawal was further associated with reduced right hippocampal volume at older ages. Exploratory analyses of white matter tracts found that negative/inappropriate maternal behavior was specifically associated with reduced volume in the ventral language network. Results suggest that quality of day-to-day parenting is related to infant brain volumes during the first two years of life, with distinct aspects of interaction associated with distinct neural effects.

Effect of schizophrenia common variants on infant brain volumes: cross-sectional study in 207 term neonates in developing Human Connectome Project

Increasing lines of evidence suggest deviations from the normal early developmental trajectory could give rise to the onset of schizophrenia during adolescence and young adulthood, but few studies have investigated brain imaging changes associated with schizophrenia common variants in neonates. This study compared the brain volumes of both grey and white matter regions with schizophrenia polygenic risk scores (PRS) for 207 healthy term-born infants of European ancestry. Linear regression was used to estimate the relationship between PRS and brain volumes, with gestational age at birth, postmenstrual age at scan, ancestral principal components, sex and intracranial volumes as covariates. The schizophrenia PRS were negatively associated with the grey (β = −0.08, p = 4.2 × 10−3) and white (β = −0.13, p = 9.4 × 10−3) matter superior temporal gyrus volumes, white frontal lobe volume (β = −0.09, p = 1.5 × 10−3) and the total white matter volume (β = −0.062, p = 1.66 × 10−2). This result also remained robust when incorporating individuals of Asian ancestry. Explorative functional analysis of the schizophrenia risk variants associated with the right frontal lobe white matter volume found enrichment in neurodevelopmental pathways. This preliminary result suggests possible involvement of schizophrenia risk genes in early brain growth, and potential early life structural alterations long before the average age of onset of the disease.

Neonatal Intensive Care Unit Network Neurobehavioral Scale Profiles in Full-Term Infants: Associations with Maternal Adversity, Medical Risk, and Neonatal Outcomes

To examine healthy, full-term neonatal behavior using the Neonatal Intensive Care Unit Network Neurobehavioral Scale (NNNS) in relation to measures of maternal adversity, maternal medical risk, and infant brain volumes. This was a prospective, longitudinal, observational cohort study of pregnant mothers followed from the first trimester and their healthy, full-term infants. Infants underwent an NNNS assessment and high-quality magnetic resonance imaging 2-5weeks after birth. A latent profile analysis of NNNS scores categorized infants into neurobehavioral profiles. Univariate and multivariate analyses compared differences in maternal factors (social advantage, psychosocial stress, and medical risk) and neonatal characteristics between profiles. The latent profile analysis of NNNS summary scales of 296 infants generated 3 profiles: regulated (46.6%), hypotonic (16.6%), and fussy (36.8%). Infants with a hypotonic profile were more likely to be male (χ2=8.601; P=.014). Fussy infants had smaller head circumferences (F=3.871; P=.022) and smaller total brain (F=3.522; P=.031) and cerebral white matter (F=3.986; P=.020) volumes compared with infants with a hypotonic profile. There were no differences between profiles in prenatal maternal health, social advantage, or psychosocial stress. Three distinct neurobehavioral profiles were identified in healthy, full-term infants with hypotonic and fussy neurobehavioral features related to neonatal brain volumes and head circumference, but not prenatal exposure to socioeconomic or psychosocial adversity. Follow-up beyond the neonatal period will determine if identified profiles at birth are associated with subsequent clinical or developmental outcomes.

Maternal Childhood Maltreatment Is Associated With Lower Infant Gray Matter Volume and Amygdala Volume During the First Two Years of Life

BackgroundChildhood maltreatment affects approximately 25% of the world’s population. Importantly, the children of mothers who have been maltreated are at increased risk of behavioral problems. Thus, one important priority is to identify child neurobiological processes associated with maternal childhood maltreatment (MCM) that might contribute to such intergenerational transmission. This study assessed the impact of MCM on infant gray and white matter volumes and infant amygdala and hippocampal volumes during the first 2 years of life. MethodsFifty-seven mothers with 4-month-old infants were assessed for MCM, using both the brief Adverse Childhood Experiences screening questionnaire and the more detailed Maltreatment and Abuse Chronology of Exposure scale. A total of 58% had experienced childhood maltreatment. Between 4 and 24 months (age in months: mean = 12.28, SD = 5.99), under natural sleep, infants completed a magnetic resonance imaging scan using a 3T Siemens scanner. Total brain volume, gray matter volume, white matter volume, and amygdala and hippocampal volumes were extracted via automated segmentation. ResultsMCM on the Adverse Childhood Experiences and Maltreatment and Abuse Chronology of Exposure scales were associated with lower infant total brain volume and gray matter volume, with no moderation by infant age. However, infant age moderated the association between MCM and right amygdala volume, such that MCM was associated with lower volume at older ages. ConclusionsMCM is associated with alterations in infant brain volumes, calling for further identification of the prenatal and postnatal mechanisms contributing to such intergenerational transmission. Furthermore, the brief Adverse Childhood Experiences questionnaire predicted these alterations, suggesting the potential utility of early screening for infant risk.

Brain-derived neurotrophic factor Val66Met variant on brain volumes in infants.

The brain-derived neurotrophic factor (BDNF) has many important roles in neurogenesis and neuronal health. BDNF is also involved in learning and memory. Individuals with BDNF-Val66Met variant (Met +) are at higher risk for neuropsychiatric disorders and have smaller hippocampi and amgydalae compared to those without this variant (Met-). Whether these smaller brain volumes are already present at birth is unknown and were evaluated. 66 newborn infants were genotyped for BDNF-rs6265 and had brain MRI scans. The T1-weighted images were automatically parcellated for hippocampus and amygdala, as well as the intracranial volume (ICV), total brain volume, total gray and white matter, using a multi-atlas label fusion method implemented in the MRICloud ( https://braingps.anatomyworks.org ). The segmented brain volumes were normalized to the ICV for group comparisons. The two infant groups were not different in their demographics and birth characteristics. However, compared to Met- infants, the Met + infants had smaller hippocampi (p = 0.013), smaller amygdalae (p = 0.041), and less steep age-related declines in total brain volume and % white matter volume. The smaller relative hippocampal and amygdala volumes in Met + infants suggest that the Met + genotype affected prenatal developmental processes. In addition, the slower age-dependent declines in the relative total brain and white matter volumes of the Met + group in this cross-sectional dataset suggest the BDNF-Val66Met variant might have an ongoing negative influence on the postnatal developmental processes.

Decreased brain volumes in infants with prenatal opioid exposure

Background/Objective: Previous small studies have shown that prenatal opioid-exposed (POE) infants and older children display decreased cerebral, cerebellar, or subcortical brain volumes. However, these studies are plagued by suboptimal reference standards or were unable to correct for the influence of other environmental factors in older children. Therefore, our goal was to study differences in brain volume of POE infants when compared to a geographically matched population. We hypothesized that there will be a significant decrease in total brain volume of the POE infants in comparison to the non-opioid exposed control infants, including a reduction in the cerebellar volume. 
 
 Methods: This was an IRB approved prospective study of mothers and infants with POE and controls without POE. All recruited infants underwent MRI scans of the brain before they reached a corrected age of 2 months. The T1-weighted MRI images were analyzed by Infant FreeSurfer and segmented into ROIs. The segmentations were manually checked and edited. An ANOVA analysis was performed to compare the cerebellar and total brain volume datasets. We corrected for gender, corrected gestational age at MRI scan, and total brain volume where necessary. 
 
 Results: 42 infants were included in the study, 21 with POE and 21 control infants. There was a significant difference in the mean gestational age of POE infants (38.28±2.13) compared to control infants (39.42±0.72). On quantitative analysis, the POE group had a significantly reduced total brain and supratentorial volume in comparison to the controls. The cerebellar volume was also significantly smaller in POE, but this significance did not persist when the total brain volume was included in the model. 
 
 Conclusion: The supratentorial region is affected disproportionately more than the cerebellum in POE. Specific reductions in cortical, subcortical, and white matter volume need to be further investigated and their influence on developmental outcomes need to be studied.

Investigating altered brain development in infants with congenital heart disease using tensor-based morphometry

Magnetic resonance (MR) imaging studies have demonstrated reduced global and regional brain volumes in infants with congenital heart disease (CHD). This study aimed to provide a more detailed evaluation of altered structural brain development in newborn infants with CHD compared to healthy controls using tensor-based morphometry (TBM). We compared brain development in 64 infants with CHD to 192 age- and sex-matched healthy controls. T2-weighted MR images obtained prior to surgery were analysed to compare voxel-wise differences in structure across the whole brain between groups. Cerebral oxygen delivery (CDO2) was measured in infants with CHD (n = 49) using phase contrast MR imaging and the relationship between CDO2 and voxel-wise brain structure was assessed using TBM. After correcting for global scaling differences, clusters of significant volume reduction in infants with CHD were demonstrated bilaterally within the basal ganglia, thalami, corpus callosum, occipital, temporal, parietal and frontal lobes, and right hippocampus (p < 0.025 after family-wise error correction). Clusters of significant volume expansion in infants with CHD were identified in cerebrospinal fluid spaces (p < 0.025). After correcting for global brain size, there was no significant association between voxel-wise brain structure and CDO2. This study localizes abnormal brain development in infants with CHD, identifying areas of particular vulnerability.

Ventricular and total brain volumes in infants with congenital heart disease: a longitudinal study.

Quantitative MRI techniques help recognize delayed brain development in fetuses with congenital heart disease (CHD). Ventriculomegaly became an early marker of brain dysmaturity. Evaluate longitudinally the cerebral ventricular and total brain volumes (TBV) in infants with CHD compared to normal neonates: testing the fetal brain dysmaturity and following its progression post operatively. Fetal and post-operative MRIs were obtained on fetuses/neonates with CHD requiring invasive intervention within the first month after birth. Volumetric measurement was done with ITK-SNAP and analyzed post-hoc. Ten cases were evaluated with a significant decrease in ventricular volumes from the fetal to the post-operative neonatal timepoint (p = 0.0297). Infants with HLHS had a significant increase postoperatively in their TBV (p = 0.0396). TBV increased post operatively inversely mirrored by the decrement of the ventricular volumes. This could be explained by the establishment an increase of brain blood flow after surgery.

Nausea and Vomiting of Pregnancy and HG Risk Genes Associated With Blood Levels, Sleep, Stomach Pain, and Other Traits [23N

INTRODUCTION: Our genome-wide association study (GWAS) and replication study of nausea and vomiting of pregnancy (NVP) and Hyperemesis Gravidarum (HG) implicates the placenta and appetite hormone gene GDF15, its receptor GFRAL, PGR, and IGFBP7. The purpose of this study was to determine whether these genes and summary statistics overlap with other traits. METHODS: The GWAS catalog was searched for risk genes. The database and web interface platform, LD Hub, was used for genetic correlation analysis of summary statistics. RESULTS: Among 4220 GWASes, the HG risk locus GDF15 was associated with GDF15 protein levels, periodontitis, and lupus. GFRAL was associated with glomerular filtration rate, blood urea nitrogen levels, insomnia, body mass index, periodontal inflammation, blood protein levels, osteoporosis, and HIV-1 infection. IGFBP7 was associated with IGFBP7 protein levels, IgG glycosylation, diastolic blood pressure, brain volume in infants, heel bone mineral density, alcohol consumption, itch intensity from mosquitoes, and cotinine glucuronidation. PGR was associated with diastolic blood pressure, endometriosis/endometrial cancer, menstrual cycle length, lung adenocarcinoma, height, and adolescent idiopathic scoliosis. Among 855 pairs of traits, the leading findings showed variants increasing HG also increase stomach pain (P=.0004) and variants increasing NVP also increase sleeplessness/insomnia (P=1.37E-14). CONCLUSION: The finding that variants in GDF15 and IGFBP7 are associated with blood protein levels supports our study showing abnormal levels of GDF15 and IGFBP7 in women with HG. Overlap of the genes with other conditions provides biological insight. Associations with poor sleep and stomach pain may have implications for treatment strategies for NVP/HG.

Maternal Dietary Intake of Omega-3 Fatty Acids Correlates Positively with Regional Brain Volumes in 1-Month-Old Term Infants.

Maternal nutrition is an important factor for infant neurodevelopment. However, prior magnetic resonance imaging (MRI) studies on maternal nutrients and infant brain have focused mostly on preterm infants or on few specific nutrients and few specific brain regions. We present a first study in term-born infants, comprehensively correlating 73 maternal nutrients with infant brain morphometry at the regional (61 regions) and voxel (over 300 000 voxel) levels. Both maternal nutrition intake diaries and infant MRI were collected at 1month of life (0.9 ± 0.5months) for 92 term-born infants (among them, 54 infants were purely breastfed and 19 were breastfed most of the time). Intake of nutrients was assessed via standardized food frequency questionnaire. No nutrient was significantly correlated with any of the volumes of the 61 autosegmented brain regions. However, increased volumes within subregions of the frontal cortex and corpus callosum at the voxel level were positively correlated with maternal intake of omega-3 fatty acids, retinol (vitamin A) and vitamin B12, both with and without correction for postmenstrual age and sex (P < 0.05, q < 0.05 after false discovery rate correction). Omega-3 fatty acids remained significantly correlated with infant brain volumes after subsetting to the 54 infants who were exclusively breastfed, but retinol and vitamin B12 did not. This provides an impetus for future larger studies to better characterize the effect size of dietary variation and correlation with neurodevelopmental outcomes, which can lead to improved nutritional guidance during pregnancy and lactation.

Non-invasive estimation of brain-volume in infants

BackgroundNeurological development is determined by brain growth. Methods to measure total brain volume (TBV) in clinical settings are limited. MR-imaging represents the gold-standard. AimsThe present study tests the hypotheses that in infants without any brain pathology, TBV – as determined by MRI – can be accurately estimated by cranial volume (CrV), measured by 3D-laser scanning. In case of good correlation of CrV with TBV it was further tested, whether CrV can be also estimated by (I) head circumference (HC) or (II) by other technology than laser scanning. Study design & subjectsTo test the hypothesis, that TBV can be reliably estimated by CrV-measurement, data from routine MRI and 3D-laser-scanner measurements were analyzed in infants if no major structural brain anomaly was found in MR-imaging.To test whether CrV can be predicted by HC-measurements during infancy, data from routine follow-up visits were used from preterms born in a two year period. Preterms are invited for a routine follow-up visit (which includes laser scanning of the head) at an age of 3 months and, for further follow-ups at 6, 9 or 12 months.To compare accuracy of CrV measurement by other techniques, a puppet head was measured, using different 3D-measurement principles: (i) Structured light projection system, (ii) The non-invasive laser-shape-digitizer, and (iii) Structure-from-motion (SFM) technique. Outcome measuresTBV was compared with CrV using a Passing-Bablok-Regression. To determine how well HC predicts CrV, the coefficient of determinant (R2) was calculated for each age group. ResultsCrV and TBV of 25 infants (median age 19 month, body weight of 11 kg) showed a median bias of −86.7 mm3 with a slightly smaller TBV (median of 1034.1 mm3, IQR 875.9 … 1179.8 mm3) than CrV (median 1092.2, IQR 950.5 … 1258.4 mm3). CrV was poorly estimated by HC, with R2 between 0.79 and 0.87 at 3 and 9 month of age respectively. For the non-invasive laser-shape-digitizer and the SFM-technique the accuracy was good (radial coordinate differences ±0.3 vs. ±0.5 mm). ConclusionThe present study provides convincing evidence that CrV can be used to estimate TBV in routine care, whereas HC is a poor predictor of individual CrV.

Impact of Demographic and Obstetric Factors on Infant Brain Volumes: A Population Neuroscience Study

Impact of Demographic and Obstetric Factors on Infant Brain Volumes: A Population Neuroscience Study

Severe Congenital Heart Defects Are Associated with Global Reduction of Neonatal Brain Volumes

To determine neonatal global and regional brain volumes in infants with congenital heart disease (CHD) in comparison with healthy controls and to determine brain growth. Prospective cohort study in infants undergoing open-heart surgery for complex CHD. Global and regional volumetric measurements on preoperative cerebral magnetic resonance imaging were manually segmented in children without overt brain lesions. Preoperative brain volumetry of 19 patients demonstrates reduction in total and regional brain volumes, without any specific regional predilection compared with 19 healthy control infants (total brain volume reduction: 21%, regional brain volume reduction 8%-28%, all P < .001). Infants with CHD undergoing bypass surgery have smaller brain volumes prior to surgery without a specific regional predilection. This suggests a fetal origin of reduced brain growth.

Intracranial Volume and Whole Brain Volume in Infants with Unicoronal Craniosynostosis

Craniosynostosis has been hypothesized to result in alterations of the brain and cerebral blood flow due to reduced intracranial volume, potentially leading to cognitive deficits. In this study we test the hypothesis that intracranial volume and whole brain volume in infants with unilateral coronal synostosis differs from those in unaffected infants. Our study sample consists of magnetic resonance images acquired from 7- to 72-week-old infants with right unilateral coronal synostosis prior to surgery (n = 10) and age-matched unaffected infants (n = 10). We used Analyze 9.0 software to collect three cranial volume measurements. We used nonparametric tests to determine whether the three measures differ between the two groups. Correlations were calculated between age and the three volume measures in each group to determine whether the growth trajectory of the measurements differ between children with right unicoronal synostosis and unaffected infants. Our results show that the three volume measurements are not reduced in infants with right unicoronal synostosis relative to unaffected children. Correlation analyses between age and various volume measures show similar correlations in infants with right unicoronal synostosis compared with unaffected children. Our results show that the relationship between brain size and intracranial size in infants with right unicoronal synostosis is similar to that in unaffected children, suggesting that reduced intracranial volume is not responsible for alterations of the brain in craniosynostosis.