Longer duration of gestation in term singletons is associated with better infant neurodevelopment

Background: Longer gestation at term and post-term age is associated with increased perinatal mortality. Nonetheless, recent neuroimaging studies indicated that longer gestation is also associated with better functioning of the child's brain. Aims: to assess whether longer gestation in term and post-term (in short: term) singletons is associated with better infant neurodevelopment. Study design: cross-sectional observational study. Subjects: Participants were all singleton term infants (n = 1563) aged 2–18 months of the IMP-SINDA project that collected normative data for the Infant Motor Profile (IMP) and Standardized Infant NeuroDevelopmental Assessment (SINDA). The group was representative of the Dutch population. Outcome measures: Total IMP score was the primary outcome. Secondary outcomes were atypical total IMP scores (scores &lt;15th percentile) and SINDA's neurological and developmental scores. Results: Duration of gestation had a quadratic relationship with IMP and SINDA developmental scores. IMP scores were lowest at a gestation of 38·5 weeks, SINDA developmental scores at 38·7 weeks. Next, both scores increased with increasing duration of gestation. Infants born at 41–42 weeks had significantly less often atypical IMP scores (adjusted OR [95 % CI]: 0·571 [0·341–0·957] and atypical SINDA developmental scores (adjusted OR: 0·366 [0·195–0·688]) than infants born at 39–40 weeks. Duration of gestation was not associated with SINDA's neurological score. Conclusions: In term singleton infants representative of the Dutch population longer gestation is associated with better infant neurodevelopment scores suggesting better neural network efficiency. Longer gestation in term infants is not associated with atypical neurological scores.</p

Longer Gestation Among Children Born Full Term Influences Cognitive and Motor Development

Children born preterm show persisting impairments in cognitive functioning, school achievement, and brain development. Most research has focused on implications of birth prior to 37 gestational weeks; however, the fetal central nervous system continues to make fundamental changes throughout gestation. Longer gestation is associated with reduced morbidity and mortality even among infants born during the period clinically defined as full term (37–41 gestational weeks). The implications of shortened gestation among term infants for neurodevelopment are poorly understood. The present study prospectively evaluates 232 mothers and their full term infants (50.4% male infants) at three time points across the first postnatal year. We evaluate the association between gestational length and cognitive and motor development. Infants included in the study were full term (born between 37 and 41 weeks gestation). The present study uses the combination of Last Menstrual Period (LMP) and early ultrasound for accurate gestational dating. Hierarchical Linear Regression analyses revealed that longer gestational length is associated with higher scores on the Bayley scales of mental and motor development at 3, 6 and 12 months of age after considering socio-demographic, pregnancy, and infant-level covariates. Findings were identical using revised categories of early, term, and late term proposed by the Working Group for Defining Term Pregnancy. Our findings indicate that longer gestation, even among term infants, benefits both cognitive and motor development

Deep and cortical gray matter volumetric of extremely low gestational age and full term newborn children at 9 to 11 years of age

PURPOSE: Extremely low gestation age newborns (ELGANs) are at high risk for developmental brain abnormalities. This study is to determine deep and superficial gray matter volumetric abnormalities of ELGAN children and full term children at 9 to 11 years of age. METHODS: High-resolution magnetic resonance imaging (MRI) scans were obtained from 160 ELGAN children (70 males and 90 females) and 30 full term children (15 males and 15 females) using a dual-echo turbo spin-echo (DE-TSE) pulse sequence at 3.0T (or 1.5T at only one site). The DICOM MR images were processed with quantitative MRI algorithms programmed in Mathcad. The brain deep gray matter (dGM) was manually segmented; dGM and cortical gray matter (cGM) volumes were quantified using semi-automated clustering segmentation algorithms. RESULTS: ELGAN children had smaller deep gray matter volume (41.86 ± 7.42 ml) than full term children (49.24 ± 10.91 ml). Deep gray matter volumes of ELGAN children showed similar distribution range (SD = 7.42 ml) with the full term children (SD = 10.91 ml). About 83% of the ELGAN children had smaller deep gray matter volumes compared to the average volume of full term children at the same ages. Male children had smaller deep gray matter volumes in ELGAN (42.77 ± 7.09 ml) than in full term (51.74 ± 9.76 ml), but female children had similar deep gray matter volumes in ELGAN (41.14 ± 7.62 ml) with full term (44.27 ± 7.56 ml). Additionally, smaller deep gray matter volumes were observed more often in males (90%) than in females (65%). Cortical gray matter volumes of ELGAN children distributed from 345.60 to 1177.50ml. Moreover, female ELGAN children had smaller cortical gray matter volumes (828.14 ± 147.61 ml) than males (883.13 ± 151.34 ml). Correlation analysis revealed a positive correlation between cerebral deep gray matter volumes and total gray matter volumes (total: r = 0.57, p<0.0001; male: r = 0.542, p < 0.0001; female: r = 0.587, p < 0.0001). CONCLUSION: Male ELGAN children had smaller brain deep gray matter volumes than full term children at ages of 9 to 11 years, but not females. Cortical gray matter volumes of female ELGAN were smaller than male ELGAN. Smaller deep gray matter volumes were associated with smaller total gray matter volumes in ELGAN children

Effects of gestational age at birth on perinatal structural brain development in healthy term-born babies

Infants born in early term (37-38 weeks gestation) experience slower neurodevelopment than those born at full term (40-41 weeks gestation). While this could be due to higher perinatal morbidity, gestational age at birth may also have a direct effect on the brain. Here we characterise brain volume and white matter correlates of gestational age at birth in healthy term-born neonates and their relationship to later neurodevelopmental outcome using T2 and diffusion weighted MRI acquired in the neonatal period from a cohort (n = 454) of healthy babies born at term age (>37 weeks gestation) and scanned between 1 and 41 days after birth. Images were analysed using tensor-based morphometry and tract-based spatial statistics. Neurodevelopment was assessed at age 18 months using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). Infants born earlier had higher relative ventricular volume and lower relative brain volume in the deep grey matter, cerebellum and brainstem. Earlier birth was also associated with lower fractional anisotropy, higher mean, axial, and radial diffusivity in major white matter tracts. Gestational age at birth was positively associated with all Bayley-III subscales at age 18 months. Regression models predicting outcome from gestational age at birth were significantly improved after adding neuroimaging features associated with gestational age at birth. This work adds to the body of evidence of the impact of early term birth and highlights the importance of considering the effect of gestational age at birth in future neuroimaging studies including term-born babies

Long-term functional outcomes and correlation with regional brain connectivity by MRI diffusion tractography metrics in a near-term rabbit model of intrauterine growth restriction

Background: Intrauterine growth restriction (IUGR) affects 5-10% of all newborns and is associated with increased risk of memory, attention and anxiety problems in late childhood and adolescence. The neurostructural correlates of long-term abnormal neurodevelopment associated with IUGR are unknown. Thus, the aim of this study was to provide a comprehensive description of the long-term functional and neurostructural correlates of abnormal neurodevelopment associated with IUGR in a near-term rabbit model (delivered at 30 days of gestation) and evaluate the development of quantitative imaging biomarkers of abnormal neurodevelopment based on diffusion magnetic resonance imaging (MRI) parameters and connectivity. Methodology: At +70 postnatal days, 10 cases and 11 controls were functionally evaluated with the Open Field Behavioral Test which evaluates anxiety and attention and the Object Recognition Task that evaluates short-term memory and attention. Subsequently, brains were collected, fixed and a high resolution MRI was performed. Differences in diffusion parameters were analyzed by means of voxel-based and connectivity analysis measuring the number of fibers reconstructed within anxiety, attention and short-term memory networks over the total fibers. Principal Findings: The results of the neurobehavioral and cognitive assessment showed a significant higher degree of anxiety, attention and memory problems in cases compared to controls in most of the variables explored. Voxel-based analysis (VBA) revealed significant differences between groups in multiple brain regions mainly in grey matter structures, whereas connectivity analysis demonstrated lower ratios of fibers within the networks in cases, reaching the statistical significance only in the left hemisphere for both networks. Finally, VBA and connectivity results were also correlated with functional outcome. Conclusions: The rabbit model used reproduced long-term functional impairments and their neurostructural correlates of abnormal neurodevelopment associated with IUGR. The description of the pattern of microstructural changes underlying functional defects may help to develop biomarkers based in diffusion MRI and connectivity analysis

Alterations in cortical thickness development in preterm-born individuals:Implications for high-order cognitive functions

AbstractVery preterm birth (gestational age <33weeks) is associated with alterations in cortical thickness and with neuropsychological/behavioural impairments. Here we studied cortical thickness in very preterm born individuals and controls in mid-adolescence (mean age 15years) and beginning of adulthood (mean age 20years), as well as longitudinal changes between the two time points. Using univariate approaches, we showed both increases and decreases in cortical thickness in very preterm born individuals compared to controls. Specifically (1) very preterm born adolescents displayed extensive areas of greater cortical thickness, especially in occipitotemporal and prefrontal cortices, differences which decreased substantially by early adulthood; (2) at both time points, very preterm-born participants showed smaller cortical thickness, especially in parahippocampal and insular regions. We then employed a multivariate approach (support vector machine) to study spatially discriminating features between the two groups, which achieved a mean accuracy of 86.5%. The spatially distributed regions in which cortical thickness best discriminated between the groups (top 5%) included temporal, occipitotemporal, parietal and prefrontal cortices. Within these spatially distributed regions (top 1%), longitudinal changes in cortical thickness in left temporal pole, right occipitotemporal gyrus and left superior parietal lobe were significantly associated with scores on language-based tests of executive function. These results describe alterations in cortical thickness development in preterm-born individuals in their second decade of life, with implications for high-order cognitive processing

Prenatal Maternal Psychological Distress and Fetal Developmental Trajectories: Associations with Infant Temperament

Associations between prenatal maternal psychological distress and offspring developmental outcomes are well documented, yet relatively little research has examined links between maternal distress and development in utero, prior to postpartum influences. Fetal heart rate (FHR) parameters are established indices of central and autonomic nervous system maturation and function which demonstrate continuity with postnatal outcomes. This prospective, longitudinal study of 149 maternal–fetal pairs evaluated associations between prenatal maternal distress, FHR parameters, and dimensions of infant temperament. Women reported their symptoms of psychological distress at five prenatal visits, and FHR monitoring was conducted at the last three visits. Maternal report of infant temperament was collected at 3 and 6 months of age. Exposure to elevated prenatal maternal psychological distress was associated with higher late-gestation resting mean FHR (FHRM) among female but not male fetuses. Higher late-gestation FHRM was associated with lower infant orienting/regulation and with higher infant negative affectivity, and these associations did not differ by infant sex. A path analysis identified higher FHRM as one pathway by which elevated prenatal maternal distress was associated with lower orienting/regulation among female infants. Findings suggest that, for females, elevated maternal distress alters fetal development, with implications for postnatal function. Results also support the notion that, for both sexes, individual differences in regulation emerge prenatally and are maintained into infancy. Collectively, these findings underscore the utility of direct assessment of development in utero when examining if prenatal experiences are carried forward into postnatal life

Disruption of rich club organisation in cerebral small vessel disease.

Cerebral small vessel disease (SVD) is an important cause of vascular cognitive impairment. Recent studies have demonstrated that structural connectivity of brain networks in SVD is disrupted. However, little is known about the extent and location of the reduced connectivity in SVD. Here they investigate the rich club organisation-a set of highly connected and interconnected regions-and investigate whether there is preferential rich club disruption in SVD. Diffusion tensor imaging (DTI) and cognitive assessment were performed in a discovery sample of SVD patients (n = 115) and healthy control subjects (n = 50). Results were replicated in an independent dataset (49 SVD with confluent WMH cases and 108 SVD controls) with SVD patients having a similar SVD phenotype to that of the discovery cases. Rich club organisation was examined in structural networks derived from DTI followed by deterministic tractography. Structural networks in SVD patients were less dense with lower network strength and efficiency. Reduced connectivity was found in SVD, which was preferentially located in the connectivity between the rich club nodes rather than in the feeder and peripheral connections, a finding confirmed in both datasets. In discovery dataset, lower rich club connectivity was associated with lower scores on psychomotor speed (β = 0.29, P < 0.001) and executive functions (β = 0.20, P = 0.009). These results suggest that SVD is characterized by abnormal connectivity between rich club hubs in SVD and provide evidence that abnormal rich club organisation might contribute to the development of cognitive impairment in SVD

Metabolic and cognitive effects after early prenatal dexamethasone treatment

Congenital adrenal hyperplasia (CAH), due to 21-hydroxylase deficiency (21OHD), is a disease with an inborn error of the adrenal steroid synthesis. This enzyme deficiency leads to cortisol shortage and androgen excess. If left untreated, CAH is potentially life-threatening especially in the neonatal period, but girls are also affected in the prenatal period with virilization caused by the surplus of adrenal androgen. Prenatal dexamethasone (DEX) treatment will minimize the androgen levels and reduce virilization. However, because the development of genitalia occurs in early gestation, the treatment must start in gestational week (GW) 6-8 to be efficient. Because of the recessive mode of inheritance and because genotyping of the fetus is not possible until GW 12, statistically, 7 of 8 fetuses will be treated unnecessarily during the first trimester of fetal life. This quandary emphasizes the importance of investigating the potential risks of DEX treatment. Glucocorticoid (GC) exposure during fetal development is known to negatively affect the child (e.g. cognition, behavior and metabolism and altered brain morphology). This thesis is part of a long-term study of children without CAH who were prenatally treated with DEX because of the potential risk of having CAH. Specifically, the thesis investigates the effects of DEX treatment on cognition (study I), behavior (study II), metabolism (study III) and blood pressure (study IV). Forty-two DEX-treated children and young adults without CAH (age range, 4-26 years) and 75 controls from the general population matched for age and sex were included in the studies. We identified a negative effect on cognition in DEX- treated girls but not in boys. Girls did worse on test assessing verbal IQ, non-verbal IQ and verbal working memory. There were no differences in behavioral problems, evaluated by parents and self-rated questionnaires in treated versus non-treated children. We found a lower HOMA-β in girls, but not in boys (another sex-dimorphic effect), suggesting a lower beta-cell function due to prenatal DEX exposure. In the younger age group (<16 years), fasting glucose levels were higher in the treated group in both sexes. In the older age group (≥16 years), total cholesterol and LDL cholesterol levels were higher in the exposed group in both sexes. When we assessed 24-hour ambulatory blood pressure, the only significant finding was higher pulse pressure in the younger age group during nighttime measurements. In conclusion, early prenatal DEX treatment seems to have a sex-dimorphic effect on cognition and glucose metabolism. It also affects blood lipids in both sexes. Owing to these findings, and other negative findings previously shown in this cohort, the safety of prenatal DEX treatment is questionable. New, and an earlier prenatal diagnosis is needed to avoid treating healthy fetuses and males with CAH