Intrauterine Brain Development Research Articles

Serum Activin A as Brain Injury Biomarker in the First Three Days of Life. A Prospective Case-Control Longitudinal Study in Human Premature Neonates.

Disruption of normal intrauterine brain development is a significant consequence of premature birth and may lead to serious complications, such as neonatal brain injury (NBI). This prospective case-control longitudinal study aimed at determining the levels and prognostic value of serum activin A during the first three days of life in human premature neonates which later developed NBI. It was conducted in a single tertiary hospital and eligible participants were live-born premature (<34 weeks) neonates. Each case (n = 29) developed NBI in the form of an intraventricular haemorrhage, or periventricular leukomalacia, and was matched according to birth weight and gestational age to one neonate with normal head ultrasound scans. Serum activin A levels in both groups showed a stable concentration during the first three days of life as no difference was observed within the two groups from the first to the third day. Neonates diagnosed with NBI had significantly higher activin A levels during the first two days of life compared to control neonates and its levels correlated to the severity of NBI during the second and third day of life. Although serum activin A on the second day was the best predictor for neonates at risk to develop NBI, the overall predictive value was marginally fair (area under the ROC-curve 69.2%). Activin A, in combination with other biomarkers, may provide the first clinically useful panel for the early detection of premature neonates at high risk of NBI.

Catenin Alpha 2 May Be a Biomarker or Potential Drug Target in Psychiatric Disorders with Perseverative Negative Thinking.

AlphaN-catenin gene CTNNA2 has been implicated in intrauterine brain development, as well as in several psychiatric disorders and cardiovascular diseases. Our present aim was to investigate CTNNA2 gene-wide associations of single-nucleotide polymorphisms (SNPs) with psychiatric and cardiovascular risk factors to test the potential mediating role of rumination, a perseverative negative thinking phenotype in these associations. Linear mixed regression models were run by FaST-LMM within a sample of 795 individuals from the Budakalasz Health Examination Survey. The psychiatric outcome variables were rumination and its subtypes, and ten Brief Symptom Inventory (BSI) scores including, e.g., obsessive-compulsive, depression, anxiety, hostility, phobic anxiety, and paranoid ideation. Cardiovascular outcome variables were BMI and the Framingham risk scores for cardiovascular disease, coronary heart disease, myocardial infarction, and stroke. We found nominally significant CTNNA2 associations for every phenotype. Rumination totally mediated the associations of CTNNA2 rs17019243 with eight out of ten BSI scores, but none with Framingham scores or BMI. Our results suggest that CTNNA2 genetics may serve as biomarkers, and increasing the expression or function of CTNNA2 protein may be a potential new therapeutic approach in psychiatric disorders with perseverative negative thinking including, e.g., depression. Generally, an antiruminative agent could be a transdiagnostic and preventive psychopharmacon.

Aberrant Claustrum Microstructure in Humans after Premature Birth.

Several observations suggest an impact of prematurity on the claustrum. First, the claustrum's development appears to depend on transient subplate neurons of intra-uterine brain development, which are affected by prematurity. Second, the claustrum is the most densely connected region of the mammalian forebrain relative to its volume; due to its effect on pre-oligodendrocytes, prematurity impacts white matter connections and thereby the development of sources and targets of such connections, potentially including the claustrum. Third, due to its high connection degree, the claustrum contributes to general cognitive functioning (e.g., selective attention and task switching/maintaining); general cognitive functioning, however, is at risk in prematurity. Thus, we hypothesized altered claustrum structure after premature birth, with these alterations being associated with impaired general cognitive performance in premature born persons. Using T1-weighted and diffusion-weighted magnetic resonance imaging in 70 very preterm/very low-birth-weight (VP/VLBW) born adults and 87 term-born adults, we found specifically increased mean diffusivity in the claustrum of VP/VLBW adults, associated both with low birth weight and at-trend with reduced IQ. This result demonstrates altered claustrum microstructure after premature birth. Data suggest aberrant claustrum development, which is potentially related with aberrant subplate neuron and forebrain connection development of prematurity.

Phasic and tonic alertness in preterm 5-year-old healthy children

ABSTRACT Preterm delivery may interrupt the intrauterine brain development and implies a risk factor for the developing brain. In the long term, most frequently particular forms of attention deficits are described which refer to the basic aspects of attention i.e., arousal or tonic alertness. As this reflects top-down processes, the current study focuses on bottom-up processed phasic alertness in preschool aged preterm children. Additionally, we made a division of response times into decision and movement time to quantify more exactly the contribution of cognitive and motor performance to reaction times. We investigated basic aspects of attention functioning and contrasted phasic and tonic alertness in 31 low-risk healthy preterm (28–36 weeks of gestation) and 22 term children of five to 6 years of age by using a self-designed computerized test. Preterm children exhibited delayed decision and reaction time in the tonic non-cued alertness condition but not in the phasic cued alertness condition compared to term children. Current results suggest that preterm birth, even when clinically relevant symptoms are absent, may have long-term consequences on basic aspects of attention functioning. Results further suggest that preterm children may profit from auditory cues to overcome these deviations, which yield evidence for a clear distinction between impaired top-down and intact bottom-up controlled processes. These findings might provide a promising groundwork for the development of therapeutical interventions and prevention strategies, whose use and impact to support preterm children should be addressed in further investigations.

Head Circumference of Babies at Birth in Nigeria.

Measuring head circumference (HC) of newborns is an important tool for evaluating intra-uterine brain development. HC reference charts currently in use in Nigeria are not representative of the local population. We thus present locally derived HC reference data for Nigerian infants at birth. We reviewed birth records of all infants at the Jos University Teaching Hospital (JUTH) over a 10 year period from January 2006. JUTH is a tertiary care center offering obstetric services to a large population of women in Jos and its environs. All births with gestational age between 28 and 42 weeks were included in the study. STATA version 14 was used to calculate gestational age associated HC percentile measurements. We included 18282 babies to generate the reference values. The mean HC value was 34.4 ± 2.1 cm (M = 34.6 ± 2.16 cm, F = 34.1 ± 2.02 cm, p < 0.001). Our HC reference values significantly differ from the USA and INTERGROWTH-21 charts currently in use in our country. Mean HC was higher in male infants compared with female infants. This difference was uniformly so across all gestational age groups. The use of our locally derived HC reference values could be more appropriate in defining normal head growth in Nigerian infant populations thereby improving newborn care.

Reduction of the event-related potential P3 in preterm born 5-year-old healthy children

ObjectivesAn abbreviated gestational period may interrupt intrauterine brain development and constitutes a serious risk factor. Many preterm children show some form of attention deficits in later life. However, there is ambiguity about the nature and extent of these attention deficits in the literature. Moreover, the majority of studies investigated attention functions in preterm children on a symptom based level or using neuropsychological tasks. In contrast, neurophysiological studies have been comparatively scarce which will be addressed in the current study. MethodsWe investigated attention functioning in 27 low risk preterm children and 20 term children of 5–6 years of age by using EEG recording in an attention driven task (oddball task). ResultsCompared with term children, preterm children showed no attention deficits on a symptom level, but failed to show an increased oddball P3. ConclusionCurrent results suggest subclinical attentional changes in preterm children on the electrophysiological level in contrast to normal performance in attentional behavioral tests. SignificanceOur results emphasize to have a closer look at preterm children early in preschool age even though clinically relevant symptoms seem to be absent.

Chapter 16 - Neurodevelopmental outcome of children with congenital heart disease

Congenital heart disease (CHD) constitutes the most common congenital malformation, with moderate or severe CHD occurring in around 6 in 1000 live births. Due to advances in medical care, survival rates have increased significantly. Thus, the majority of children with CHD survive until adolescence and adulthood. Children with CHD requiring cardiopulmonary bypass surgery are at risk for neurodevelopmental impairments in various domains, including mild impairments in cognitive and neuromotor functions, difficulties with social interaction, inattention, emotional symptoms, and impaired executive function. The prevalence for these impairments ranges from 20% to 60% depending on age and domain ("high prevalence-low severity"). Domains are often affected simultaneously, leading to school problems with the need for learning support and special interventions. The etiology of neurodevelopmental impairments is complex, consisting of a combination of delayed intrauterine brain development and newly occurring perioperative brain injuries. Mechanisms include altered intrauterine hemodynamic flow as well as neonatal hypoxia and reduced cerebral blood flow. The surgical procedure and postoperative phase add to this cascade of factors interfering with normal brain development. Early identification of children at high risk through structured follow-up programs is mandated to provide individually tailored early interventions and counseling to improve developmental health.

No Association between Polymorphisms of Vitamin D and Oxytocin Receptor Genes and Autistic Spectrum Disorder in a Sample of Turkish Children.

ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social skills and communication with repetitive behaviors. Etiology is still unclear although it is thought to develop with interaction of genes and environmental factors. Oxytocin has extensive effects on intrauterine brain development. Vitamin D, affects neural development and differentiation and contributes to the regulation of around 900 genes including oxytocin receptor gene. In the present study, the contribution of D vitamin receptor and oxytocin receptor gene polymorphisms in the development of ASD in Turkish community was investigated. To our knowledge, this is the first study examining these two associated genes together in the literature.MethodsEighty-five patients diagnosed with ASD according to DSM-5 who were referred to outpatient clinics of Child and Adolescent Psychiatry of Başkent University and Mersin University and 52 healthy, age and gender-matched controls were included in the present study. Vitamin D receptor gene rs731236 (Taq1), rs2228570 (Fok1), rs1544410 (Bsm1), rs7975232 (Apa1) polymorphisms and oxytocin receptor gene rs1042778 and rs2268493 polymorphisms were investigated using real time polymerase chain reaction method.ResultsNo significant difference between groups in terms of distribution of genotype and alleles in each of polymorphisms for these genes could be found.ConclusionKnowledge of genes and polymorphisms associated with the development of ASD may be beneficial for early diagnosis and future treatment. Further studies with larger populations are required to demonstrate molecular pathways which may play part in the development of ASD in Turkey.

ОСОБЕННОСТИ ТЕЧЕНИЯ РЕСПИРАТОРНОЙ МИКСТ-ВИРУСНОЙ ИНФЕКЦИИ У ЖЕНЩИН ВО ВТОРОМ ТРИМЕСТРЕ БЕРЕМЕННОСТИ ПРИ ВНУТРИУТРОБНОМ ИНФИЦИРОВАНИИ ИХ НОВОРОЖДЕННЫХ С ЦЕРЕБРАЛЬНОЙ ИШЕМИЕЙ

Clinical and serological features of the gestational process in 85 women with pregnancy, uncomplicated and complicated with parainfluenza-influenza infection in the second trimester of gestation, were studied. All examined women were divided into three groups. The first group (control) included 32 women with physiological course of pregnancy and their healthy full-term newborns. The second group included 32 patients with respiratory mixed-virus infection in the second trimester of gestation, and in their newborns there was diagnosed moderate cerebral ischemia and no signs of intrauterine infection. The third group included 21 women with respiratory mixed virus infection in the second trimester of pregnancy, which was the cause of antenatal infection in their full-term infants with cerebral ischemia of moderate severity. It was shown that the women of the third group compared with the second and first groups often complained of headache, photophobia, sweating and weakness, increase in body temperature to 37.6-38ºC, hoarseness of the voice, sore throat, as well as a prolonged course of acute nasopharyngitis and acute laryngitis. The above clinical features of acute respiratory viral infection in women in the second trimester of gestation may contribute to antenatal infection and may disrupt optimal conditions for intrauterine brain development in their babies.

Periconceptional maternal dairy-rich dietary pattern is associated with prenatal cerebellar growth.

BackgroundMaternal nutrition during pregnancy has been related to intrauterine brain development and neurodevelopmental disabilities in adult life. We aim to investigate associations between periconceptional maternal dietary patterns and prenatal cerebellar growth from the first trimester onwards.Materials and methods126 women with singleton non-malformed pregnancies were enrolled before 8 weeks of gestation in the Rotterdam periconceptional cohort between 2013 and 2015. Periconceptional maternal dietary patterns were extracted from food frequency questionnaires and associated with blood biomarkers and micronutrient intakes. Serial two-dimensional and three-dimensional ultrasound scans were performed at 9, 11, 22, 26 and 32 weeks of gestation for transcerebellar diameter (TCD) measurement. Linear mixed models were estimated to investigate associations between periconceptional maternal dietary patterns and longitudinal TCD measurements as a function of gestational age.ResultsWe performed a median of 4 scans per pregnancy, resulting in 570 total datasets. The success rate of TCD measurements was 87% (range 65–100%), depending on gestational age. The Mediterranean, Western, egg-rich and dairy-rich dietary patterns were extracted, explaining 37.2% of the overall variance of food intake in this population. The dairy-rich dietary pattern was positively associated with cerebellar growth trajectories (β = 0.02 (95% CI: 0.01; 0.03) √mm, p = 0.01). Maternal strong adherence to this dietary pattern increased TCD measurements by 0.8 standard deviation scores (SDs) compared to weak adherence, reflected in increased TCD estimates of 0.44 mm at 9 weeks (+6.8%), 0.88 mm at 22 weeks (+3.6%), and 1.17 mm at 32 weeks (+2.8%). No significant associations were detected for the Mediterranean, Western and egg-rich dietary patterns.ConclusionsThis study shows a positive association between periconceptional maternal adherence to a dairy-rich dietary pattern and human prenatal TCD measurements as a proxy of cerebellar growth. Next step is the investigation of the impact on neurodevelopmental outcomes in the offspring.

One More Reason Not to Smoke During Pregnancy

Many environmental factors affecting intrauterine brain development have been implicated in the pathogenesis of schizophrenia. In a prospective study

Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study

Thyroid hormone is involved in the regulation of early brain development. Since the fetal thyroid gland is not fully functional until week 18-20 of pregnancy, neuronal migration and other crucial early stages of intrauterine brain development largely depend on the supply of maternal thyroid hormone. Current clinical practice mostly focuses on preventing the negative consequences of low thyroid hormone concentrations, but data from animal studies have shown that both low and high concentrations of thyroid hormone have negative effects on offspring brain development. We aimed to investigate the association of maternal thyroid function with child intelligence quotient (IQ) and brain morphology. In this population-based prospective cohort study, embedded within the Generation R Study (Rotterdam, Netherlands), we investigated the association of maternal thyroid function with child IQ (assessed by non-verbal intelligence tests) and brain morphology (assessed on brain MRI scans). Eligible women were those living in the study area at their delivery date, which had to be between April 1, 2002, and Jan 1, 2006. For this study, women with available serum samples who presented in early pregnancy (<18 weeks) were included. Data for maternal thyroid-stimulating hormone, free thyroxine, thyroid peroxidase antibodies (at weeks 9-18 of pregnancy), and child IQ (assessed at a median of 6·0 years of age [95% range 5·6-7·9 years]) or brain MRI scans (done at a median of 8·0 years of age [6·2-10·0]) were obtained. Analyses were adjusted for potential confounders including concentrations of human chorionic gonadotropin and child thyroid-stimulating hormone and free thyroxine. Data for child IQ were available for 3839 mother-child pairs, and MRI scans were available from 646 children. Maternal free thyroxine concentrations showed an inverted U-shaped association with child IQ (p=0·0044), child grey matter volume (p=0·0062), and cortex volume (p=0·0011). For both low and high maternal free thyroxine concentrations, this association corresponded to a 1·4-3·8 points reduction in mean child IQ. Maternal thyroid-stimulating hormone was not associated with child IQ or brain morphology. All associations remained similar after the exclusion of women with overt hypothyroidism and overt hyperthyroidism, and after adjustment for concentrations of human chorionic gonadotropin, child thyroid-stimulating hormone and free thyroxine or thyroid peroxidase antibodies (continuous or positivity). Both low and high maternal free thyroxine concentrations during pregnancy were associated with lower child IQ and lower grey matter and cortex volume. The association between high maternal free thyroxine and low child IQ suggests that levothyroxine therapy during pregnancy, which is often initiated in women with subclinical hypothyroidism during pregnancy, might carry the potential risk of adverse child neurodevelopment outcomes when the aim of treatment is to achieve high-normal thyroid function test results. The Netherlands Organisation for Health Research and Development (ZonMw) and the European Community's Seventh Framework Programme.

ATTENTION FUNCTIONING IN CHILDREN WITH PRENATAL DRUG EXPOSURE.

Children born to drug abusers are exposed to teratogenic influences on intrauterine brain development and undergo postnatal withdrawal. We investigated the interplay of different domains and levels of attention functioning in 24 prenatally exposed and 25 nonexposed children who were 5 to 6 years old. Assessment included parent ratings and neuropsychological and electrophysiological methods. Exposed children had a higher prevalence of attention deficit hyperactivity symptoms, tended to have poorer performance in an attention test battery, and showed EEG alterations in P3 and N2c. Findings suggest long-term effects of prenatal drug exposure on specific domains and on different levels of attention functioning.

New Reference Curves for Head Circumference at Birth, by Gestational Age

The measurement of head circumference (HC) at birth reflects intrauterine brain development. HC charts currently used in Canada are either dated, mixed-gender, nonrepresentative of lower gestational ages (GAs), or reflective of other populations. To create both birth weight and HC curves, we combined weight and HC data from the Canadian Neonatal Network (CNN) database (admissions in NICUs across Canada) with McGill's Obstetrical Neonatal Database (MOND; all births at a tertiary hospital in Montreal, Canada). We included CNN data for GAs of 23 to 34 weeks (2003-2007) and MOND data for GAs of 35 to 41 weeks (1995-2006). Nonsingletons, congenital anomalies, and measurements greater than ±4 SD from the mean were excluded. Distributions of birth weight and HC at each GA were statistically (penalized spline regression) smoothed. Birth weight curves were compared with recent Canadian reference curves and HC curves with historical and/or frequently used curves. We included 39,896 births (3121 births at <30 weeks' GA) to generate the curves. Current weight curves were similar to Canadian reference charts for both genders. Weight and HC measurements in boys were higher than in girls. When classified according to recent international references, the proportion of CNN-MOND infants at ≥32 weeks' GA with HCs <10th percentile was significantly underestimated. When classified according to historical reference curves, a significant number of CNN-MOND infants of all GAs with HCs <10th and >90th percentiles were misclassified. We developed recent gender-specific reference curves for HC at birth for singletons at 23 to 41 completed weeks' GA, which included a large number of very premature infants, reflecting the current geotemporal Canadian population.

The Role of Fetal Neurology in the Progress of Perinatal Medicine

The prevalence of cerebral palsy has not decreased despite major improvements in clinical care in antenatal/ neonatal period as well as intrapartum period. In about 70% of cases, cerebral palsy results from events occurring before birth that can disrupt normal development of the brain. The antepartum risk factors should include fetal brain mal development and intrauterine brain injuries, which are unclassifiable into congenital brain anomalies and may exist inconspicuously during pregnancy and even after birth. Especially, neuronal migration disorder and acquired brain damage in utero should be responsible for postnatal neurological impairment. Imaging technologies including three dimensional ultrasound have been remarkably improved and contributed to prenatal evaluation of fetal Central Nervous System (CNS) development and assessment of CNS abnormalities in utero. In this article, objective and precise imaging diagnoses of fetal CNS including migration disorders and acquired brain damages. Furthermore, 3D bidirectional power Doppler angiography has depicted fine cerebral vessels of medullary veins which may relate with timing of insult as well as with postnatal neurological prognosis. It is promising to clarify the developmental mechanism of CNS damages with advanced ultrasound diagnostic techniques in the near future. Postnatal unexplained neurological deficits may strongly relate with intrauterine brain development therefore fetal neurology has great responsibility and an important role in perinatal medicine.

Effect of caesarean section on brain maturation

The rates of caesarean section (CS) are increasing worldwide. The short-term effects of CS in the newborn have been described and long-term reported risks of alterations of pathophysiology include altered microflora, increased risk of childhood asthma and childhood-onset type I diabetes mellitus. There has been emphasis on the respiratory morbidity related to the timing of elective CS. More recently, a population study demonstrated dose-dependent effect of each week of gestation on the need for special education. This highlights the importance of intrauterine brain development towards the end of pregnancy and hitherto largely unexplored possible effects on neurodevelopment if it is interrupted. The timing of CS is important not only because delivery before 39 weeks can increase respiratory morbidity, but also owing to the fact that ongoing intrauterine brain maturation could be significant for future neurodevelopment.

Schizophrenia and season of birth: relationship to geomagnetic storms

An excess pattern of winter and spring birth, of those later diagnosed as schizophrenic, has been clearly identified in most Northern Hemisphere samples with none or lesser variation in Equatorial or Southern Hemisphere samples. Pregnancy and birth complications, seasonal variations in light, weather, temperature, nutrition, toxins, body chemistry and gene expression have all been hypothesized as possible causes. In this study, the hypothesis was tested that seasonal variation in the geomagnetic field of the earth primarily as a result of geomagnetic storms (GMS) at crucial periods in intrauterine brain development, during months 2 to 7 of gestation could affect the later rate of development of schizophrenia. The biological plausibility of this hypothesis is also briefly reviewed. A sample of eight representative published studies of schizophrenic monthly birth variation were compared with averaged geomagnetic disturbance using two global indices (AA*) and (aa). Three samples showed a significant negative correlation to both geomagnetic indices, a further three a significant negative correlation to one of the geomagnetic indices, one showed no significant correlation to either index and one showed a significant positive correlation to one index. It is suggested that these findings are all consistent with the hypothesis and that geomagnetic disturbance or factors associated with this disturbance should be further investigated in birth seasonality studies.

Structural and Neurobehavioral Delay in Postnatal Brain Development of Preterm Infants1

Postnatal brain development of healthy prematurely born infants was assessed to study possible influence of premature birth and early extrauterine environment on structural, biochemical, and functional brain development. Myelination and differentiation of gray and white matter were studied by in vivo magnetic resonance (MR) imaging (MRI), changes in cerebral metabolism by 1HMR spectroscopy (MRS), and changes in early human neurobehavior by the assessment of preterm infant's behavior (APIB). The stage of intrauterine and extrauterine brain development in prematurely born infants at term was compared with the stage of mainly intrauterine brain development in a group of full-term infants. Eighteen preterm infants unremarkable with respect to neurologic and medical status were studied at approximately 2 wk of postnatal age [gestational age (GA) 1: 32.5 +/- 1.2 wk] and again at term (GA 2: 40.0 +/- 1.1 wk). For comparison a group of 13 full-term born infants (GA T: 40.6 +/- 2.1 wk) were studied by MR and six by APIB. When GA 2 to GA 1 was compared, significant maturational changes were found with MRI in gray and white matter and myelination, with 1H MRS in the concentration of N-acetylaspartate and with all scores of APIB. In preterm infants at term (GA 2) compared with full-term infants (GA T) significantly less gray and white matter differentiation and myelination was observed as well as significantly poorer performance in four neurobehavioral parameters (autonomic reactivity, motoric reactivity, state organization, attentional availability). We conclude that MRI and 1H MRS can be used to study postnatal brain development in preterm infants. Structural and biochemical maturation is accompanied by functional maturation as shown with the neurobehavior assessment. Preterm infants at term compared with full-term infants show a structural as well as a functional delay in brain development assessed at 40 wk of postconceptional age.

Use of monkey neonatal neurobehavioral test batteries in safety testing protocols

Developmental neurobehavioral test batteries are important in assessing potential reproductive and developmental toxicity of new chemicals and drugs. They provide a broad-based evaluation of a range of nervous system functions at a period of life when learning and adaptation are particularly critical. Nonhuman primates are an especially appropriate test species because of their similarities to humans in complexity of brain function and prolonged intrauterine brain development. Problems arise, however, in the analysis and interpretation of data bases generated when a relatively small number of animals are tested on a relatively large number of items. A 2-week neonatal test battery for rhesus monkey infants is described along with approaches to experimental design and statistical analyses that are helpful in providing sound and useful interpretation.

1117 INTRAUTERINE DIET FORTIFICATION AND OFFSPRING BRAIN DEVELOPMENT

Vegetable protein, providing 80% of protein requirements in Third World Countries, can be quantitatively adequate but qualitatively inadequate in protein content. Supplementation with limiting amino acids (AA's) is possible and might aid intrauterine offspring development. In the present experiments 21 Sprague Dawley rats were impregnated and groups of 7 begun on one of 3 diets: A) bread, B) bread + lysine and threonine, or C) lab chow. Weights of all offspring at birth were lower (p< .001) in group A (5.64 ± 0.52g) compared to groups B (6.39 ± 0.88g) or C (6.49 ± 0.34g). Two newborns from each of the 7 litters in each of the 3 groups were randomly selected for further brain studies. Total brain weights were lower for group A pups (.239 ± .019) compared to groups B (.279 ± .022, p<.05) or C (.258 ± .026, p<.001). Total DNA, representing total cell number, was higher in the cortices of AA supplemented (group B) offspring (.562 ± .019) compared to group A neonates (.537 ± .029, p<.01). DNA was also higher in the cerebellum-brain stem of group B animals (.169 ± .010) compared to group A animals (.158 ± .014, p<.05). There were no significant differences in DNA between the AA supplemented and the chow fed offspring. Total cortex protein was lower in group A animals compared to groups B (p<.001) or C (p<.02). These experiments demonstrate that amino acid fortification of a maternal vegetable protein diet results in improved intrauterine brain development.