VPT Group Research Articles

Neurodevelopmental Outcomes and Neural Mechanisms Associated with Non-right Handedness in Children Born Very Preterm

Non-right handedness (NRH) is reportedly more common in very preterm (VPT; <32 weeks' gestation) children compared with term-born peers, but it is unclear whether neonatal brain injury or altered brain morphology and microstructure underpins NRH in this population. Given that NRH has been inconsistently reported to be associated with cognitive and motor difficulties, this study aimed to examine associations between handedness and neurodevelopmental outcomes in VPT 7-year-olds. Furthermore, the relationship between neonatal brain injury and integrity of motor tracts (corpus callosum and corticospinal tract) with handedness at age 7 years in VPT children was explored. One hundred seventy-five VPT and 69 term-born children completed neuropsychological and motor assessments and a measure of handedness at 7 years' corrected age. At term-equivalent age, brain injury on MRI was assessed and diffusion tensor measures were obtained for the corpus callosum and posterior limb of the internal capsule. There was little evidence of stronger NRH in the VPT group compared with term controls (regression coefficient [b] -1.95, 95% confidence interval [-5.67, 1.77]). Poorer academic and working memory outcomes were associated with stronger NRH in the VPT group. While there was little evidence that neonatal unilateral brain injury was associated with stronger NRH, increased area and fractional anisotropy of the corpus callosum splenium were predictive of stronger NRH in the VPT group. VPT birth may alter the relationship between handedness and academic outcomes, and neonatal corpus callosum integrity predicts hand preference in VPT children at school age. (JINS, 2015, 21, 610-621).

Preterm placental abruption: Tocolytic therapy regarded as a poor neonatal prognostic factor

Aim: To elucidate factors associated with a poor neonatal prognosis in preterm placental abruption. Methods: A multicenter retrospective study was conducted. A total of 247 cases with preterm placental abruption during 2009, derived from an electronic database constructed by the Japan Society of Obstetrics and Gynecology, were investigated as the subjects of this study, and were divided into three groups: very preterm (VPT, n=66) was delivered at 28 to 31 gestational weeks, preterm (n=56) was at 32 and 33 weeks, and late preterm (LPT, n=125) was at 34 to 36 weeks. Risk factors, clinical course, and neonatal/infantile outcomes were compared. Poor neonatal outcome was defined as stillbirth, or neonatal and infantile death, or cases with neurological disability at 2 years of age. Results: The number of subjects who received tocolytic therapy was significantly higher in the VPT group as compared with the LPT group. It was higher in the VPT group even after excluding the 57 stillbirths. Multiple logistic regression analysis revealed that poor prognostic factors were umbilical arterial pH (Δ=0.1) (0.17 [0.069-0.417], p<0.0001) and tocolytic therapy (28.5 [2.014-403.9], p<0.0132). Conclusion: Administration of tocolytic agents is a possible factor in a poor neonatal prognosis in preterm placental abruption. This finding may suggest that differential diagnosis could improve the prognosis.

Relation of perinatal risk and early parenting to executive control at the transition to school.

Executive control (EC) develops rapidly during the preschool years and is central to academic achievement and functional outcome. Although children with perinatal adversity are at known risk for EC impairments, little is known about the underlying nature of these impairments or the mechanisms that contribute to their development over time. Drawing on a cohort of 110 high-risk children born very preterm (VPT; < 33 weeks / < 1500 g) and 113 healthy full-term children, this study examined the implications of perinatal adversity and early parenting for children's EC as they transitioned to formal schooling. Parent supportive presence, intrusiveness, and parent-child synchrony were observed during a series of problem-solving tasks at ages 2 and 4 years. At age 6, children completed a comprehensive battery of EC tasks. Academic outcomes were assessed at age 9. The VPT group showed global EC impairments at age 6, although the unitary factor that best characterized the structure of EC was the same in both groups. High-risk dyads were characterized by more intrusive and less synchronous parent-child interactions in early childhood, which in turn predicted poorer child EC at age 6. EC partially mediated the relation of risk status to poorer academic achievement at age 9. Findings demonstrate the cumulative effects of perinatal adversity on children's EC in the crucial transition to schooling. They also highlight the importance of the parent-child relationship as a target for intervention efforts to help mitigate these effects.

Motor fMRI and cortical grey matter volume in adults born very preterm

The primary aim of this study was to investigate the functional neuroanatomy of motor planning, initiation and execution in a cohort of young adults (mean age 20 years) who were born very preterm (VPT; <33 weeks of gestation), as these individuals are at increased risk of experiencing neuromotor difficulties compared to controls. A cued motor task was presented to 20 right-handed VPT individuals and 20 controls within a functional magnetic resonance imaging (fMRI) paradigm. Whole-brain grey matter volume was also quantified and associations with functional data were examined. Despite comparable task performance, fMRI results showed that the VPT group displayed greater brain activation compared to controls in a region comprising the right cerebellum and the lingual, parahippocampal and middle temporal gyri. The VPT group also displayed decreased grey matter volume in the right superior frontal/premotor cortex and left middle temporal gyri. Grey matter volume in the premotor and middle temporal clusters was significantly negatively correlated with BOLD activation in the cerebellum. Overall, these data suggest that preterm birth is associated with functional neuronal differences that persist into adulthood, which are likely to reflect neural reorganisation following early brain injury.

Personality in Adults Who Were Born Very Preterm

AimTo investigate the personality in very preterm individuals (VPT; gestational age, GA, <32 weeks) at adult age in two cohorts born in 1974–76 and 1980–82, respectively, and to illuminate the effect of increased survival rates and the clinical implications of deviations in personality.MethodDemographic data were extracted for all individuals born in Denmark in 1974–76 and 1980–82. From each period one index-group each comprising 150 individuals with the lowest gestational age was selected. Thereafter two control groups born at term were matched by gender, age and residential area. Personality was assessed with the short version of NEO PI-R, and psychiatric diagnoses were obtained from the Danish Psychiatric Central Research Register.ResultsOf all the individuals born <32 weeks of gestation in 1980–82 67% were alive in 2006 vs. 43% of those born in 1974–76 (p<0.0001). A total of 433 individuals participated in the study, 76% of the VPT groups (n = 227, mean GA = 27.9) and 69% of the control groups (n = 206). There were no significant differences on personality scores between the two VPT groups. Compared to the control groups, the combined VPT groups scored higher on neuroticism (p = 0.005) and agreeableness (p = 0.012), but lower on extraversion (p = 0.002). Psychiatric disorder was strongly associated with higher scores on neuroticism and lower scores on extraversion.InterpretationImproved survival of VPT infants was not associated with increased deviances in the personality as adults. The personality traits in VPT individuals differ moderately from those of term born controls. High scores in neuroticism and low scores in extraversion were associated with increased risk psychiatric disorders. VPT adults also showed signs of positive adaptation in the form of an agreeable and confident attitude towards others.What this paper addsThe much improved survival rate in very preterm infants during the early years of active neonatology was not associated with increased risk of personality deviation. There are signs of positive adaptation in the form of increased agreeableness in young adults born very preterm.

White matter and cognition in adults who were born preterm.

Background and PurposeIndividuals born very preterm (before 33 weeks of gestation, VPT) are at risk of damage to developing white matter, which may affect later cognition and behaviour.MethodsWe used diffusion tensor MRI (DT-MRI) to assess white matter microstructure (fractional anisotropy; FA) in 80 VPT and 41 term-born individuals (mean age 19.1 years, range 17–22, and 18.5 years, range17–22 years, respectively). VPT individuals were part of a 1982–1984 birth cohort which had been followed up since birth; term individuals were recruited by local press advertisement. General intellectual function, executive function and memory were assessed.ResultsThe VPT group had reduced FA in four clusters, and increased FA in four clusters relative to the Term group, involving several association tracts of both hemispheres. Clusters of increased FA were associated with more severe neonatal brain injury in the VPT group. Clusters of reduced FA were associated with lower birth weight and perinatal hypoxia, and with reduced adult cognitive performance in the VPT group only.ConclusionsAlterations of white matter microstructure persist into adulthood in VPT individuals and are associated with cognitive function.

Reduction in postnatal cumulative nutritional deficit and improvement of growth in extremely preterm infants

To evaluate the influence of gestational age (GA) on cumulative nutritional deficit and postnatal growth in extremely preterm (EPT) infants after optimizing nutritional protocol as recently recommended. A prospective, nonrandomized, observational study in extremely preterm (EPT, <28 weeks) and very preterm (VPT, 28-30 weeks) infants. Eighty-four infants were included (BW: 978 ± 156 g, GA: 27.8 ± 1.3 weeks). Cumulative nutritional deficit increased during first week of life to -290 ± 84 and -285 ± 117 kcal/kg and -4.2 ± 3.1 and -4.8 ± 3.9 g/kg of protein in EPT and VPT groups, respectively. After 6 weeks, only cumulative energy deficit in EPT group remained significant (p < 0.05) even when 96% of theoretical energy intakes were provided. Weight z score decreased during first 3 days in average with initial weight loss, and then, the z score increased during the first 6 weeks of life in the majority (75%) of infants. Cumulative protein deficit during the first week of life was the major determinant of the postnatal growth during the first 6 weeks of life. Cumulative nutritional deficit may be drastically reduced in both EPT and VPT infants after optimizing nutritional policy during the first weeks of life, and the postnatal growth restriction could even be prevented.

Neural substrates of visual paired associates in young adults with a history of very preterm birth: Alterations in fronto-parieto-occipital networks and caudate nucleus

This study investigated neuronal activation during visuo-perceptual learning processing in adults who were born very preterm (VPT, <33 weeks' gestation). A visual paired associates task was administered during functional magnetic resonance imaging (fMRI) and neuronal activation was compared between 21 VPT-born adults of both sexes and 22 matched controls. The task consisted of 4 conditions (encoding, recognition, same/different discrimination condition (baseline) and a low-level baseline), each containing 8 stimuli pairs. There were no group differences in terms of correctly recognized visual pairs. However, during encoding, VPT-born individuals showed increased BOLD signal response compared to controls in left caudate nucleus, right cuneus (BA 18) and left superior parietal lobule (BA 7), and decreased signal in right inferior frontal gyrus (BA 46). During recognition, VPT-born adults showed increased BOLD signal response compared to controls in right cerebellum and in anterior cingulate gyrus (BA 32) bilaterally. The fMRI data were additionally analyzed controlling for structural differences in the hippocampus bilaterally, where the VPT group showed decreased probability of the absolute amount of grey matter compared to controls. Results of our study suggest that despite good task performance, VPT-born individuals activate different neural networks during mnemonic processing of visuo-perceptual material which may indicate neural compensation for the adult consequences of perinatal brain injury following very preterm birth, as well as maturational delays.

Malocclusion Traits and Orthodontic Treatment Needs in Prematurely Born Children

To evaluate if prematurely born children have higher prevalence of malocclusion traits and greater orthodontic treatment need than matched full-term born controls. Seventy-three preterm children were selected from the Medical Birth Register and divided into two subgroups according to their gestational age. One group consisted of 37 very preterm children (VPT), born in gestational week 29-32, and the other of 36 extremely preterm children (EPT), born before the 29th gestational week. The subjects were compared with a control group of 41 full-term children, who were matched for sex, age, and nationality. Data from clinical examinations, study casts, and panoramic radiographs were used to determine malocclusion traits. The dental health component of the index of orthodontic treatment need (IOTN) was used to rank the treatment need. Two or more malocclusion traits occurred significantly more often among EPT (83.3%) and VPT children (73.0%), compared with the full-term children (51.2%). Significantly higher prevalence of deep bites and was found in EPT and VPT groups compared with the full-term control group. Deep bite was the most common malocclusion trait in the EPT and VPT group. Higher orthodontic treatment need was found for the preterm children but no differences in prevalence of malocclusion traits and treatment need were found between VPT and EPT children. The clinician should be aware of the potential for a higher number of malocclusion traits and greater orthodontic treatment need in prematurely born children compared with full-term children.

Cerebellar growth and behavioural &amp; neuropsychological outcome in preterm adolescents

Adolescence is a time of social and cognitive development associated with changes in brain structure and function. These developmental changes may show an altered path in individuals born before 33 weeks' gestation (very preterm; VPT). The cerebellum is affected by VPT birth, but no studies have yet assessed the adolescent development of this structure, or whether developmental changes in cerebellar structure are associated with cognitive and behavioural outcome. We measured cerebellar volumes on structural magnetic resonance images in 65 adolescents who were born before 33 weeks' gestation (VPT) and 34 term-born adolescents (mean age VPT = 15.09, SD = 1.43/mean age term-born = 15.43, SD = 0.56) and again in adulthood (mean age VPT = 18.61, SD = 1.02/mean age term-born = 19.17, SD = 0.95). Participants also underwent neuropsychological tests; the Wechsler Abbreviated Scale of Intelligence and the Controlled Oral Word Association Test and completed the General Health Questionnaire-12. Repeated measures ANOVA showed a main effect of time-point (F = 4.59, df = 1, P = 0.035) and a time-point by group interaction (F = 8.03, df = 1, P = 0.006) on cerebellar growth. By adulthood, cerebellar volumes were 3.11% smaller in the preterm group than they had been in early adolescence (P = 0.000). Cerebellar volume did not change significantly in the control group (P = 0.612). There were significant negative correlations between change in cerebellar volume and GHQ-12 in the VPT group; total score (r = -0.324 P = 0.028) and several subscales; concentration (r = -0.378 P = 0.010), feeling useful (r = -0.311 P = 0.035), decision-making capability (r = -0.348 P = 0.018), overcoming difficulties (r = -0.331 P = 0.025), feeling confident (r = -0.309 P = 0.037) and feeling worthless (r = -0.329 P = 0.026). In the VPT group there were positive correlations between cerebellar volume and full-scale IQ (adolescence; r = 0.471, P = 0.002/adulthood; r = 0.309, P = 0.047), performance IQ (adolescence; r = 0.434, P = 0.004/adulthood; r = 0.345, P = 0.025) and verbal IQ (adolescence; r = 0.401, P = 0.008) which were not maintained after controlling for white matter volume. We have demonstrated a reduction in cerebellar volume between adolescence and young adulthood in VPT individuals, which is correlated with reduced self-reported wellbeing.

Growth of the Corpus Callosum in Adolescents Born Preterm

To examine the growth of the corpus callosum between adolescence and early adulthood in individuals who were born before 33 weeks' gestation (very preterm [VPT]) and its relation to neuropsychological function. A longitudinal cohort study of VPT individuals born between January 4, 1982, and December 29, 1984, and a term-born comparison group. A long-term follow-up study into perinatal predictors of outcome after preterm birth at University College Hospital, London. A total of 72 VPT and 34 term-born individuals were assessed in adolescence (aged 15 years) and in early adulthood (aged 19 years). Adult assessments took place between June 6, 2002, and October 23, 2004. Birth before 33 weeks' gestation. The cross-sectional area of 4 segments of the corpus callosum, measured on the midsagittal slice of high-resolution structural magnetic resonance images in adolescence and young adulthood. Total corpus callosum size increased in term and VPT groups, but growth was much greater in the VPT group (13.4% in the VPT group vs 3.3% in the term group). There were significant associations between adult performance IQ and growth of anterior (P = .001), midposterior (P = .009), and posterior (P = .009) segments in the VPT group. The corpus callosum grows dramatically in VPT adolescents, and this growth is associated with neuropsychological outcome. This may represent a delay of a normal maturational process in VPT individuals.

Cognitive maturation in preterm and term born adolescents

Background:Adolescence is a critical period of brain structural reorganisation and maturation of cognitive abilities. This relatively late developmental reorganisation may be altered in individuals who were born preterm.Methods:We carried out...

Neurological abnormalities in young adults born preterm

Objective: Individuals born before 33 weeks’ gestation (very preterm, VPT) have an increased likelihood of neurological abnormality, impaired cognitive function, and reduced academic performance in childhood. It is currently not...

Umbilical cord pH and base excess values in relation to neonatal morbidity for infants delivered preterm

Objective Our purpose was to determine the relationship/predictive value of umbilical cord pH and base excess (BE) values to adverse neonatal outcomes for preterm infants. Study design A tertiary center perinatal/neonatal database was used to obtain umbilical cord pH and BE values, adverse neonatal outcomes, and patient demographics for preterm (PT, 32-36 weeks gestational age) and very preterm (VPT, 25-32 weeks gestational age) singleton live-born infants delivered between November 1995 and March 2002. Results PT (n = 1807) and VPT (n = 603) groups demonstrated a significant inverse curvilinear relationship of umbilical cord pH and BE values to Apgar score <7 at 5 minutes, respiratory distress syndrome, assisted ventilation, and intraventricular hemorrhage/periventricular leukomalacia. Receiver operating characteristic area under the curve values ranged from 0.69 to 0.86 (PT) and 0.70 to 0.87 (VPT). There was little difference between umbilical vein, umbilical artery, pH, or BE in predictive value. Conclusion Umbilical cord pH and BE are related to subsequent adverse outcome events for infants delivered preterm. Worsening acidosis is associated with progressively greater increases in these outcomes with no discriminatory value within or between umbilical artery and umbilical vein pH and BE.

Characterization of genes required for protein sorting and vacuolar function in the yeast Saccharomyces cerevisiae.

To further our studies of protein sorting and biogenesis of the lysosome-like vacuole in yeast, we have isolated spontaneous mutations in 11 new VPL complementation groups, as well as additional alleles of the eight previously described VPL genes. These mutants were identified by selecting for cells that mislocalize vacuolar proteins to the cell surface. Morphological examination of the vpl mutants indicated that most contain vacuoles of normal appearance; however, some of the mutants generally lack a large vacuole, and instead accumulate smaller organelles. Of the 19 VPL complementation groups, 12 were found to be identical to 12 of 33 VPT complementation groups identified in a separate study. Moreover, the end1 mutant and all of the previously reported pep mutants, with the exception of pep4, were found to exhibit a profound vacuolar protein sorting defect, and complementation tests between the PEP, VPL VPT and END1 groups demonstrated that there are extensive overlaps between these groups. Collectively, mutants in these four collections define 49 complementation groups required to deliver or retain soluble vacuolar enzymes, including carboxypeptidase Y (CPY) and proteinase A. We have also isolated 462 new mutants that lack normal levels of vacuolar CPY activity. Among these latter mutants, only pep4 mutants were found to be specifically defective in vacuolar zymogen activation. We conclude that there is a large number of gene products required for sorting or retention of vacuolar proteins in yeast, and only a single gene, PEP4, that is essential for activation of CPY and other vacuolar zymogens.