Allin, M; Rooney, M; Griffiths, T; Cuddy, M; Wyatt, J; Rifkin, L; Murray, R
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 known whether neurological signs detected in VPT children persist into adulthood or become attenuated by maturation of the CNS. Method We assessed 153 VPT individuals and 71 term‐born controls at 17–18 years old, using a comprehensive neurological examination. This examination divides neurological signs into primary and integrative domains, the former representing the localising signs of classical neurology, and the latter representing signs requiring integration between different neural networks or systems. Integrative signs are sub‐divided into three groups: sensory integration, motor confusion, and sequencing. The VPT individuals have been followed up since birth, and neonatal information is available on them, along with the results of neurological assessment at 4 and 8 years of age and neuropsychological assessment at 18 years of age. Results The total neurology score and primary and integrative scores were significantly increased in VPT young adults compared to term‐born controls. Within the integrative domain, sensory integration and motor confusion scores were significantly increased in the VPT group, but sequencing was not significantly different between the VPT and term groups. Integrative neurological abnormalities at 18 were strongly associated with reduced IQ but primary abnormalities were not. Conclusions Neurological signs are increased in VPT adults compared to term‐born controls, and are strongly associated with reduced neuropsychological function. PMID:16543529
Daamen, Marcel; Bäuml, Josef G.; Scheef, Lukas; Meng, Chun; Jurcoane, Alina; Jaekel, Julia; Sorg, Christian; Busch, Barbara; Baumann, Nicole; Bartmann, Peter; Wolke, Dieter; Wohlschläger, Afra; Boecker, Henning
Very preterm birth is associated with an increased prevalence of attention problems and may especially impair executive attention, i.e., top-down control of attentional selection in situations where distracting information interferes with the processing of task-relevant stimuli. While there are initial findings linking structural brain alterations in preterm-born individuals with attention problems, the functional basis of these problems are not well understood. The present study used an fMRI adaptation of the Attentional Network Test to examine the neural correlates of executive attention in a large sample of N = 86 adults born very preterm and/or with very low birth weight (VP/VLBW), and N = 100 term-born controls. Executive attention was measured by comparing task behavior and brain activations associated with the processing of incongruent vs. congruent arrow flanker stimuli. Consistent with subtle impairments of executive attention, the VP/VLBW group showed lower accuracy and a tendency for increased response times during the processing of incongruent stimuli. Both groups showed similar activation patters, especially within expected fronto-cingulo-parietal areas, but no significant between-group differences. Our results argue for a maintained attention-relevant network organization in high-functioning preterm born adults in spite of subtle deficits in executive attention. Gestational age and neonatal treatment variables showed associations with task behavior, and brain activation in the dorsal ACC and lateral occipital areas, suggesting that the degree of prematurity (and related neonatal complications) has subtle modulatory influences on executive attention processing. PMID:26640769
Hovi, Petteri; Vohr, Betty; Ment, Laura R; Doyle, Lex W; McGarvey, Lorcan; Morrison, Katherine M; Evensen, Kari Anne I; van der Pal, Sylvia; Grunau, Ruth E; Brubakk, Ann-Mari; Andersson, Sture; Saigal, Saroj; Kajantie, Eero
Adults born preterm at very low birth weight (VLBW; <1500 g) have higher blood pressure than those born at term. It is not known whether all VLBW adults are at risk or whether higher blood pressure could be attributed to some of the specific conditions underlying or accompanying preterm birth. To identify possible risk or protective factors, we combined individual-level data from 9 cohorts that measured blood pressure in young adults born at VLBW or with a more stringent birth weight criterion. In the absence of major heterogeneity, we performed linear regression analysis in our pooled sample of 1571 adults born at VLBW and 777 controls. Adults born at VLBW had 3.4 mm Hg (95% confidence interval, 2.2-4.6) higher systolic and 2.1 mm Hg (95% confidence interval, 1.3-3.0) higher diastolic pressure, with adjustment for age, sex, and cohort. The difference in systolic pressure was present in men (1.8 mm Hg; 95% confidence interval, 0.1-3.5) but was stronger in women (4.7 mm Hg; 95% confidence interval, 3.2-6.3). Among the VLBW group, blood pressure was unrelated to gestational age, maternal smoking, multiple pregnancy, retinopathy of prematurity, or bronchopulmonary dysplasia. Blood pressure was higher than that of controls among VLBW adults unexposed to maternal preeclampsia. Among those exposed, it was even higher, especially if born appropriate for gestational age. In conclusion, although female sex and maternal preeclampsia are additional risk factors, the risk of higher blood pressure is not limited to any etiologic subgroup of VLBW adults, arguing for vigilance in early detection of high blood pressure in all these individuals.
Tseng, Chieh-En Jane; Froudist-Walsh, Seán; Brittain, Philip J; Karolis, Vyacheslav; Caldinelli, Chiara; Kroll, Jasmin; Counsell, Serena J; Williams, Steven C R; Murray, Robin M; Nosarti, Chiara
Very preterm (<32 weeks of gestation) birth is associated with structural brain alterations and memory impairments throughout childhood and adolescence. Here, we used functional MRI (fMRI) to study the neuroanatomy of recognition memory in 49 very preterm-born adults and 50 controls (mean age: 30 years) during completion of a task involving visual encoding and recognition of abstract pictures. T1-weighted and diffusion-weighted images were also collected. Bilateral hippocampal volumes were calculated and tractography of the fornix and cingulum was performed and assessed in terms of volume and hindrance modulated orientational anisotropy (HMOA). Online recognition memory task performance, assessed with A scores, was poorer in the very preterm compared with the control group. Analysis of fMRI data focused on differences in neural activity between the recognition and encoding trials. Very preterm born adults showed decreased activation in the right middle frontal gyrus and posterior cingulate cortex/precuneus and increased activation in the left inferior frontal gyrus and bilateral lateral occipital cortex (LOC) compared with controls. Hippocampi, fornix and cingulum volume was significantly smaller and fornix HMOA was lower in very preterm adults. Among all the structural and functional brain metrics that showed statistically significant group differences, LOC activation was the best predictor of online task performance (P = 0.020). In terms of association between brain function and structure, LOC activation was predicted by fornix HMOA in the preterm group only (P = 0.020). These results suggest that neuroanatomical alterations in very preterm born individuals may be underlying their poorer recognition memory performance. Hum Brain Mapp 38:644-655, 2017. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
Aanes, Synne; Bjuland, Knut Jørgen; Skranes, Jon; Løhaugen, Gro C C
The hippocampi are regarded as core structures for learning and memory functions, which is important for daily functioning and educational achievements. Previous studies have linked reduction in hippocampal volume to working memory problems in very low birth weight (VLBW; ≤ 1500 g) children and reduced general cognitive ability in VLBW adolescents. However, the relationship between memory function and hippocampal volume has not been described in VLBW subjects reaching adulthood. The aim of the study was to investigate memory function and hippocampal volume in VLBW young adults, both in relation to perinatal risk factors and compared to term born controls, and to look for structure-function relationships. Using Wechsler Memory Scale-III and MRI, we included 42 non-disabled VLBW and 61 control individuals at age 19-20 years, and related our findings to perinatal risk factors in the VLBW-group. The VLBW young adults achieved lower scores on several subtests of the Wechsler Memory Scale-III, resulting in lower results in the immediate memory indices (visual and auditory), the working memory index, and in the visual delayed and general memory delayed indices, but not in the auditory delayed and auditory recognition delayed indices. The VLBW group had smaller absolute and relative hippocampal volumes than the controls. In the VLBW group inferior memory function, especially for the working memory index, was related to smaller hippocampal volume, and both correlated with lower birth weight and more days in the neonatal intensive care unit (NICU). Our results may indicate a structural-functional relationship in the VLBW group due to aberrant hippocampal development and functioning after preterm birth.
Risnes, Kari R.; Pape, Kristine; Bjørngaard, Johan H.; Moster, Dag; Bracken, Michael B.; Romundstad, Pal R.
Background Close to one in ten individuals worldwide is born preterm, and it is important to understand patterns of long-term health and mortality in this group. This study assesses the relationship between gestational age at birth and early adult mortality both in a nationwide population and within sibships. The study adds to existing knowledge by addressing selected causes of death and by assessing the role of genetic and environmental factors shared by siblings. Methods Study population was all Norwegian men and women born from 1967 to 1997 followed using nation-wide registry linkage for mortality through 2011 when they were between 15 and 45 years of age. Analyses were performed within maternal sibships to reduce variation in unobserved genetic and environmental factors shared by siblings. Specific outcomes were all-cause mortality and mortality from cardiovascular diseases, cancer and external causes including accidents, suicides and drug abuse/overdoses. Results Compared with a sibling born in week 37–41, preterm siblings born before 34 weeks gestation had 50% increased mortality from all causes (adjusted Hazard Ratio (aHR) 1.54, 95% confidence interval (CI) 1.17, 2.03). The corresponding estimate for the entire population was 1.27 (95% CI 1.09, 1.47). The majority of deaths (65%) were from external causes and the corresponding risk estimates for these deaths were 1.52 (95% CI 1.08, 2.14) in the sibships and 1.20 (95% CI 1.01, 1.43) in the population. Conclusion Preterm birth before week 34 was associated with increased mortality between 15 and 45 years of age. The results suggest that increased premature adult mortality in this group is related to external causes of death and that the increased risks are unlikely to be explained by factors shared by siblings. PMID:27820819
Finke, Kathrin; Neitzel, Julia; Bäuml, Josef G; Redel, Petra; Müller, Hermann J; Meng, Chun; Jaekel, Julia; Daamen, Marcel; Scheef, Lukas; Busch, Barbara; Baumann, Nicole; Boecker, Henning; Bartmann, Peter; Habekost, Thomas; Wolke, Dieter; Wohlschläger, Afra; Sorg, Christian
Although pronounced and lasting deficits in selective attention have been observed for preterm born individuals it is unknown which specific attentional sub-mechanisms are affected and how they relate to brain networks. We used the computationally specified 'Theory of Visual Attention' together with whole- and partial-report paradigms to compare attentional sub-mechanisms of pre- (n=33) and full-term (n=32) born adults. Resting-state fMRI was used to evaluate both between-group differences and inter-individual variance in changed functional connectivity of intrinsic brain networks relevant for visual attention. In preterm born adults, we found specific impairments of visual short-term memory (vSTM) storage capacity while other sub-mechanisms such as processing speed or attentional weighting were unchanged. Furthermore, changed functional connectivity was found in unimodal visual and supramodal attention-related intrinsic networks. Among preterm born adults, the individual pattern of changed connectivity in occipital and parietal cortices was systematically associated with vSTM in such a way that the more distinct the connectivity differences, the better the preterm adults' storage capacity. These findings provide first evidence for selectively changed attentional sub-mechanisms in preterm born adults and their relation to altered intrinsic brain networks. In particular, data suggest that cortical changes in intrinsic functional connectivity may compensate adverse developmental consequences of prematurity on visual short-term storage capacity.
Pyhälä, Riikka; Pesonen, Anu-Katriina; Räikkönen, Katri; Järvenpää, Anna-Liisa; Andersson, Sture; Eriksson, Johan G.; Hovi, Petteri; Kajantie, Eero
Background Early life stress, such as painful and stressful procedures during neonatal intensive care after preterm birth, can permanently affect physiological, hormonal and neurobiological systems. This may contribute to altered programming of the hypothalamic-pituitary-adrenal axis (HPAA) and provoke changes in HPAA function with long-term health impacts. Previous studies suggest a lower HPAA response to stress in young adults born preterm compared with controls born at term. We assessed whether these differences in HPAA stress responsiveness are reflected in everyday life HPAA functioning, i.e. in diurnal salivary cortisol patterns, and reactivity to a low-dose dexamethasone suppression test (DST), in unimpaired young adults born preterm at very low birth weight (VLBW; <1500 g). Methods The participants were recruited from the Helsinki Study of Very Low Birth Weight Adults cohort study. At mean age 23.3 years (2.1 SD), 49 VLBW and 36 controls born at term participated in the study. For cortisol analyzes, saliva samples were collected on two consecutive days at 0, 15, 30 and 60 min after wake-up, at 12:00 h, 17:00 h and 22:00 h. After the last salivary sample of the first study day the participants were instructed to take a 0.5 mg dexamethasone tablet. Results With mixed-effects model no difference was seen in overall diurnal salivary cortisol between VLBW and control groups [13.9% (95% CI: -11.6, 47.0), P = 0.31]. Salivary cortisol increased similarly after awakening in both VLBW and control participants [mean difference -2.9% (29.2, 33.0), P = 0.85]. Also reactivity to the low-dose DST (awakening cortisol ratio day2/day1) was similar between VLBW and control groups [-1.1% (-53.5, 103.8), P = 0.97)]. Conclusions Diurnal cortisol patterns and reactivity to a low-dose DST in young adulthood were not associated with preterm birth. PMID:27618620
Chaminade, Thierry; Leutcher, Russia Ha-Vinh; Millet, Veronique; Deruelle, Christine
We investigated the consequences of premature birth on the functional neuroanatomy of the dorsal stream of visual processing. fMRI was recorded while sixteen healthy participants, 8 (two men) adults (19 years 6 months old, SD 10 months) born premature (mean gestational age 30 weeks), referred to as Premas, and 8 (two men) matched controls (20…
Menegaux, Aurore; Meng, Chun; Neitzel, Julia; Bäuml, Josef G; Müller, Hermann J; Bartmann, Peter; Wolke, Dieter; Wohlschläger, Afra M; Finke, Kathrin; Sorg, Christian
Preterm birth is associated with an increased risk for lasting changes in both the cortico-thalamic system and attention; however, the link between cortico-thalamic and attention changes is as yet little understood. In preterm newborns, cortico-cortical and cortico-thalamic structural connectivity are distinctively altered, with increased local clustering for cortico-cortical and decreased integrity for cortico-thalamic connectivity. In preterm-born adults, among the various attention functions, visual short-term memory (vSTM) capacity is selectively impaired. We hypothesized distinct associations between vSTM capacity and the structural integrity of cortico-thalamic and cortico-cortical connections, respectively, in preterm-born adults. A whole-report paradigm of briefly presented letter arrays based on the computationally formalized Theory of Visual Attention (TVA) was used to quantify parameter vSTM capacity in 26 preterm- and 21 full-term-born adults. Fractional anisotropy (FA) of posterior thalamic radiations and the splenium of the corpus callosum obtained by diffusion tensor imaging were analyzed by tract-based spatial statistics and used as proxies for cortico-thalamic and cortico-cortical structural connectivity. The relationship between vSTM capacity and cortico-thalamic and cortico-cortical connectivity, respectively, was significantly modified by prematurity. In full-term-born adults, the higher FA in the right posterior thalamic radiation the higher vSTM capacity; in preterm-born adults this FA-vSTM-relationship was inversed. In the splenium, higher FA was correlated with higher vSTM capacity in preterm-born adults, whereas no significant relationship was evident in full-term-born adults. These results indicate distinct associations between cortico-thalamic and cortico-cortical integrity and vSTM capacity in preterm-and full-term-born adults. Data suggest compensatory cortico-cortical fiber re-organization for attention deficits after preterm delivery.
Lohaugen, Gro C. C.; Gramstad, Arne; Evensen, Kari Anne I.; Martinussen, Marit; Lindqvist, Susanne; Indredavik, Marit; Vik, Torstein; Brubakk, Ann-Mari; Skranes, Jon
Aim: The aim of this study was to assess cognitive function at the age of 19 years in individuals of very low birthweight (VLBW; less than or equal to 1500g) and in term-born comparison individuals. Method: In this hospital-based follow-up study, 55 VLBW participants (30 males, 25 females; mean birthweight 1217g, SD 233g; mean gestational age…
Salvan, Piergiorgio; Froudist Walsh, Seán; Allin, Matthew P G; Walshe, Muriel; Murray, Robin M; Bhattacharyya, Sagnik; McGuire, Philip K; Williams, Steven C R; Nosarti, Chiara
Very preterm (VPT) birth is considered a risk factor not only for neurological impairment, but also for reduced function in several cognitive domains in childhood and later in life. Individuals who were born VPT are more likely to demonstrate learning and memory difficulties compared to term-born controls. These problems contribute to more VPT-born children repeating grades and underachieving in school. This, in turn, affects their prospects in adult life. Here we aimed to 1) study how the VPT-born adult brain functionally recruited specific areas during learning, i.e. encoding and recall across four repeated blocks of verbal stimuli, and to investigate how these patterns of activation differed from term-born subjects; and 2) probe the microstructural differences of white-matter tracts connecting these areas to other parts of the learning and memory network. To investigate these functional-structural relationships we analyzed functional and diffusion-weighted MRI. Functional-MRI and a verbal paired associate learning (VPAL) task were used to extract Blood Oxygenation Level Dependent (BOLD) activity in 21 VPT-born adults (<33 weeks of gestation) (mean age: 19.68 years ± 0.85; IQ: 99.86 ± 11.20) and 10 term-born controls (mean age: 19.87 years ± 2.04; IQ: 108.9 ± 13.18). Areas in which differences in functional activation were observed between groups were used as seed regions for tractography. Fractional anisotropy (FA) of the tract-skeleton was then compared between groups on a voxel-wise basis. Results of functional MRI analysis showed a significantly different pattern of activation between groups during encoding in right anterior cingulate-caudate body, and during retrieval in left thalamus, hippocampus and parts of left posterior parahippocampal gyrus. The number of correctly recalled word pairs did not statistically differ between individuals who were born VPT and controls. The VPT-born group was found to have reduced FA in tracts passing through the
Urgent action is needed to address preterm birth given that the first country-level estimates show that globally 15 million babies are born too soon and rates are increasing in most countries with reliable time trend data. As the first in a supplement entitled "Born Too Soon", this paper focuses on the global policy context. Preterm birth is critical for progress on Millennium Development Goal 4 (MDG) for child survival by 2015 and beyond, and gives added value to maternal health (MDG 5) investments also linking to non-communicable diseases. For preterm babies who survive, the additional burden of prematurity-related disability may affect families and health systems. Prematurity is an explicit priority in many high-income settings; however, more attention is needed especially in low- and middle-income countries where the invisibility of preterm birth as well as its myths and misconceptions have slowed action on prevention and care. Recent global attention to preterm birth hit a tipping point in 2012, with the May 2 publication of Born Too Soon: The Global Action Report on Preterm Birth and with the 2nd annual World Prematurity Day on November 17 which mobilised the actions of partners in many countries to address preterm birth and newborn health. Interventions to strengthen preterm birth prevention and care span the continuum of care for reproductive, maternal, newborn and child health. Both prevention of preterm birth and implementation of care of premature babies require more research, as well as more policy attention and programmatic investment. Declaration This article is part of a supplement jointly funded by Save the Children's Saving Newborn Lives programme through a grant from The Bill & Melinda Gates Foundation and March of Dimes Foundation and published in collaboration with the World Health Organization (WHO). The original article was published in PDF format in the WHO Report "Born Too Soon: the global action report on preterm birth (ISBN 978 92 4 150343
Basten, Maartje; Jaekel, Julia; Johnson, Samantha; Gilmore, Camilla; Wolke, Dieter
Each year, 15 million babies worldwide are born preterm. Preterm birth is associated with adverse neurodevelopmental outcomes across the life span. Recent registry-based studies suggest that preterm birth is associated with decreased wealth in adulthood, but the mediating mechanisms are unknown. This study investigated whether the relationship between preterm birth and low adult wealth is mediated by poor academic abilities and educational qualifications. Participants were members of two British population-based birth cohorts born in 1958 and 1970, respectively. Results showed that preterm birth was associated with decreased wealth at 42 years of age. This association was mediated by decreased intelligence, reading, and, in particular, mathematics attainment in middle childhood, as well as decreased educational qualifications in young adulthood. Findings were similar in both cohorts, which suggests that these mechanisms may be time invariant. Special educational support in childhood may prevent preterm children from becoming less wealthy as adults.
The survivors of the initial years of neonatal intensive care of preterm infants reached adulthood during the last decade. Reports of their adult outcomes examined have included neurodevelopmental, behavioral and health outcomes as well as social functioning and reproduction. Despite statistically significant differences between preterm young adults and controls in most outcomes studied, the majority of preterm survivors do well and live fairly normal lives. The two major predictors of adult outcomes are lower gestational age that reflect perinatal injury and family sociodemographic status which reflects both genetic and environmental effects.
Sripada, Kam; Løhaugen, Gro C; Eikenes, Live; Bjørlykke, Kjerstin M; Håberg, Asta K; Skranes, Jon; Rimol, Lars M
Individuals born preterm and at very low birth weight (birth weight ≤ 1500 g) are at an increased risk of perinatal brain injury and neurodevelopmental deficits over the long term. This study examined whether this clinical group has more problems with visual-motor integration, motor coordination, and visual perception compared to term-born controls, and related these findings to cortical surface area and thickness and white matter fractional anisotropy. Forty-seven preterm-born very low birth weight individuals and 56 term-born controls were examined at 18-22 years of age with a combined cognitive, morphometric MRI, and diffusion tensor imaging evaluation in Trondheim, Norway. Visual-motor skills were evaluated with the Beery-Buktenica Developmental Test of Visual-Motor Integration-V (VMI) copying test and its supplemental tests of motor coordination and visual perception. 3D T1-weighted MPRAGE images and diffusion tensor imaging were done at 1.5 T. Cortical reconstruction generated in FreeSurfer and voxelwise maps of fractional anisotropy calculated with Tract-Based Spatial Statistics were used to explore the relationship between MRI findings and cognitive results. Very low birth weight individuals had significantly lower scores on the copying and motor coordination tests compared with controls. In the very low birth weight group, VMI scores showed significant positive relationships with cortical surface area in widespread regions, with reductions of the superior temporal gyrus, insula, and medial occipital lobe in conjunction with the posterior ventral temporal lobe. Visual perception scores also showed positive relationships with cortical thickness in the very low birth weight group, primarily in the lateral occipito-temporo-parietal junction, the superior temporal gyrus, insula, and superior parietal regions. In the very low birth weight group, visual-motor performance correlated positively with fractional anisotropy especially in the corpus callosum
Boguszewski, Margaret Cristina da Silva; Cardoso-Demartini, Adriane de Andre
Approximately 15 million babies are born preterm across the world every year, with less than 37 completed weeks of gestation. Survival rates increased during the last decades with the improvement of neonatal care. With premature birth, babies are deprived of the intense intrauterine growth phase, and postnatal growth failure might occur. Some children born prematurely will remain short at later ages and adult life. The risk of short stature increases if the child is also born small for gestational age. In this review, the effects of being born preterm on childhood growth and adult height and the hormonal abnormalities possibly associated with growth restriction are discussed, followed by a review of current information on growth hormone treatment for those who remain with short stature during infancy and childhood.
Duerden, Emma G; Taylor, Margot J; Miller, Steven P
Infants born very preterm are high risk for acquired brain injury and disturbances in brain maturation. Although survival rates for preterm infants have increased in the last decades owing to improved neonatal intensive care, motor disabilities including cerebral palsy persist, and impairments in cognitive, language, social, and executive functions have not decreased. Evidence from neuroimaging studies exploring brain structure, function, and metabolism has indicated abnormalities in the brain development trajectory of very preterm-born infants that persist through to adulthood. In this chapter, we review neuroimaging approaches for the identification of brain injury in the preterm neonate. Advances in medical imaging and availability of specialized equipment necessary to scan infants have facilitated the feasibility of conducting longitudinal studies to provide greater understanding of early brain injury and atypical brain development and their effects on neurodevelopmental outcome. Improved understanding of the risk factors for acquired brain injury and associated factors that affect brain development in this population is setting the stage for improving the brain health of children born preterm.
Fallang, Bjørg; Hadders-Algra, Mijna
The present paper presents clinical and neurophysiological data of postural behavior in preterm children without CP. Clinical follow-up studies of preterm infants until toddler and school age have reported that low-risk preterm infants may have atypical postural behavior in terms of reduced amount of rotation during crawling, delayed dynamic balance, delayed onset of and a poor quality of early walking behavior. At school age, dysfunctions such as problems in standing on one leg and poor hopping are reported. Neurophysiological data of postural control at early age indicated the presence of a dysfunction in the capacity to modulate postural activity, and the postural activity has been characterized by temporal disorganization of EMG responses. Postural responses to goal-directed reaching in supine lying have been recorded and analyzed in terms of the total body center of pressure. In this study, preterm infants show less mobile postural behavior compared with full-term infants. In infancy, the less mobile postural behavior seemed to be adequate as it was related to better goal-directed reaching quality, but the results indicated that the relatively immobile postural behavior during reaching in early age was related to less favorable neuromotor behavior in school-age.
Poehlmann, Julie; Schwichtenberg, A. J. Miller; Shah, Prachi E.; Shlafer, Rebecca J.; Hahn, Emily; Maleck, Sarah
This prospective longitudinal study examined emerging effortful control skills at 24- and 36-months postterm in 172 children born preterm (less than 36 weeks gestation). Infant (neonatal health risks), family (sociodemographic risks), and maternal risk factors (depressive symptoms, anger expressions during play interactions) were assessed at six…
Lee, Clara S C; Pei, Jacqueline; Andrew, Gail; A Kerns, Kimberly; Rasmussen, Carmen
Researchers have reported benefits of working memory training in various populations, however, the training gains in preterm population is still inadequately studied. This study aimed to investigate the transfer and lasting effects of an online working memory training program on a group of preterm children aged between 4 and 6 years (mean gestational age = 28.3 weeks; mean birth weight = 1153 grams). Children were asked to perform the Cogmed JM at home for approximately 15 minutes a day, 5 days a week for 5 weeks. Their nontrained working memory and attention were assessed pre-training, post-training, and at 5-week follow-up. Parent ratings on children's executive functions were obtained at the three time points. Results revealed that significant improvements in verbal working memory was emerging in preterm children at 5-week follow-up, while significant gains in visuospatial working memory was found post-training and at 5-week follow-up in age-matched term-born children. These results indicated that working memory training has benefits on preterm children; however, the gains are different from those observed in term-born children. No significant differences in attention and parent-rated EF were found in either group across time. The possible explanations for the training benefits observed in preterm children were discussed.
Bann, Carla; Higgins, Rosemary; Vohr, Betty
BACKGROUND AND OBJECTIVES: Extremely preterm infants and infants born to adolescent mothers are at risk for adverse developmental. The objectives were to evaluate development and behavior outcomes of extremely low birth weight (ELBW) infants born to adolescent mothers <20 compared with adult mothers ≥20 years and to identify socioeconomic risk factors that affect outcomes. METHODS: Retrospective cohort analysis of 211 infants >27 weeks of adolescent mothers and 1723 infants of adult mothers at Neonatal Research Network centers from 2008 to 2011. Groups were compared and regression models were run to predict 18- to 22-month adverse outcomes. Primary outcomes were Bayley-III scores, neurodevelopmental impairment, and Brief Infant Toddler Social Emotional Assessment problem scores (BITSEA/P) ≥75th percentile. RESULTS: Adolescent mothers were more often single, Hispanic, less educated, and had public insurance. By 18 to 22 months, their children had significantly increased rates of having lived ≥3 places (21% vs 9%), state supervision (7% vs 3%), rehospitalization (56% vs 46%), and BITSEA/P ≥75th percentile (50% vs 32%) and nonsignificant Bayley-III language scores <85 (56% vs 49%, P = .07). In regression analysis, children of adolescent mothers were more likely to have BITSEA/P ≥75th percentile (relative risk 1.50, 95% confidence interval 1.08–2.07). Living ≥3 places and nonwhite race were predictors of adverse behavior. State supervision was an independent predictor of each Bayley-III composite <70 and neurodevelopmental impairment. CONCLUSIONS: ELBW infants of adolescent mothers experience high social and environmental risks that are associated with adverse behavior outcomes. These findings inform the need for comprehensive follow-up, coordinated care services, and behavior interventions for ELBW infants of adolescent mothers. PMID:25963007
White, Thomas P.; Symington, Iona; Castellanos, Nazareth P.; Brittain, Philip J.; Froudist Walsh, Seán; Nam, Kie-Woo; Sato, João R.; Allin, Matthew P.G.; Shergill, Sukhi S.; Murray, Robin M.; Williams, Steve C.R.; Nosarti, Chiara
Advances in neonatal medicine have resulted in a larger proportion of preterm-born individuals reaching adulthood. Their increased liability to psychiatric illness and impairments of cognition and behaviour intimate lasting cerebral consequences; however, the central physiological disturbances remain unclear. Of fundamental importance to efficient brain function is the coordination and contextually-relevant recruitment of neural networks. Large-scale distributed networks emerge perinatally and increase in hierarchical complexity through development. Preterm-born individuals exhibit systematic reductions in correlation strength within these networks during infancy. Here, we investigate resting-state functional connectivity in functional magnetic resonance imaging data from 29 very-preterm (VPT)-born adults and 23 term-born controls. Neurocognitive networks were identified with spatial independent component analysis conducted using the Infomax algorithm and employing Icasso procedures to enhance component robustness. Network spatial focus and spectral power were not generally significantly affected by preterm birth. By contrast, Granger-causality analysis of the time courses of network activity revealed widespread reductions in between-network connectivity in the preterm group, particularly along paths including salience-network features. The potential clinical relevance of these Granger-causal measurements was suggested by linear discriminant analysis of topological representations of connection strength, which classified individuals by group with a maximal accuracy of 86%. Functional connections from the striatal salience network to the posterior default mode network informed this classification most powerfully. In the VPT-born group it was additionally found that perinatal factors significantly moderated the relationship between executive function (which was reduced in the VPT-born as compared with the term-born group) and generalised partial directed coherence
Lundequist, Aiko; Böhm, Birgitta; Lagercrantz, Hugo; Forssberg, Hans; Smedler, Ann-Charlotte
Aim The aim of this study was to investigate long-term cognitive outcome in a cohort of 18-year-olds born preterm and previously assessed at the age of 5.5. Methods We tested 134 adolescents born preterm with a very low birthweight of <1500 g and 94 term-born controls with a comprehensive cognitive battery at 18 years of age. The cohort was subdivided into 73 extremely preterm, 42 very preterm and 19 moderately preterm infants with gestational ages of 23–27, 28–31 and 32–36 weeks, respectively. The moderately preterm group was dominated by adolescents born small for gestational age. Results Very preterm adolescents performed on a par with term-born controls. In contrast, extremely preterm adolescents displayed inferior results on all cognitive tests, more so if they had suffered neonatal complications. Moderately preterm adolescents scored lower than very preterm and full-term born adolescents, particularly on complex cognitive tasks. Conclusion Adolescents born at 28 weeks of gestation or later, with appropriate birthweight and no perinatal complications, functioned like term-born peers at 18 years of age. Extremely preterm birth per se posed a risk for long-term cognitive deficits, particularly executive deficits. Adolescents born moderately preterm but small for gestational age were at risk of general cognitive deficits. PMID:25394225
Lin, Yuan-Shan; Reilly, Marie; Mercer, Vicki S.
The purpose of this study was to examine, using a modified visual cliff apparatus, possible perceptual differences at crawling age between infants born preterm and infants born at term without documented visual or motor impairments. Sixteen infants born at term and 16 born preterm were encouraged to crawl to their caregivers on a modified visual…
Bowers, Katherine; Wink, Logan K.; Pottenger, Amy; McDougle, Christopher J.; Erickson, Craig
The objective of the study was to characterize the phenotype of males and females with autism spectrum disorder born preterm versus those born at term. Descriptive statistical analyses identified differences between male and female autism spectrum disorder subjects born preterm compared to term for several phenotypic characteristics and…
As part of a supplement entitled "Born Too Soon", this paper focuses on care of the preterm newborn. An estimated 15 million babies are born preterm, and the survival gap between those born in high and low income countries is widening, with one million deaths a year due to direct complications of preterm birth, and around one million more where preterm birth is a risk factor, especially amongst those who are also growth restricted. Most premature babies (>80%) are between 32 and 37 weeks of gestation, and many die needlessly for lack of simple care. We outline a series of packages of care that build on essential care for every newborn comprising support for immediate and exclusive breastfeeding, thermal care, and hygienic cord and skin care. For babies who do not breathe at birth, rapid neonatal resuscitation is crucial. Extra care for small babies, including Kangaroo Mother Care, and feeding support, can halve mortality in babies weighing <2000 g. Case management of newborns with signs of infection, safe oxygen management and supportive care for those with respiratory complications, and care for those with significant jaundice are all critical, and are especially dependent on competent nursing care. Neonatal intensive care units in high income settings are de-intensifying care, for example increasing use of continuous positive airway pressure (CPAP) and this makes comprehensive preterm care more transferable. For health systems in low and middle income settings with increasing facility births, district hospitals are the key frontier for improving obstetric and neonatal care, and some large scale programmes now include specific newborn care strategies. However there are still around 50 million births outside facilities, hence home visits for mothers and newborns, as well as women's groups are crucial for reaching these families, often the poorest. A fundamental challenge is improving programmatic tracking data for coverage and quality, and measuring disability
Keller-Margulis, Milena; Dempsey, Allison; Llorens, Ashlie
The developmental outcomes for children born preterm have been examined by many, with results unequivocally indicating that children born preterm tend to have poorer cognitive outcomes and more developmental difficulties. Less attention has been paid to academic outcomes. The purpose of this paper is to review the academic skills assessment of…
Odd, David Edward; Emond, Alan; Whitelaw, Andrew
Aim: To investigate whether infants born late preterm have poorer cognitive outcomes than term-born infants. Method: A cohort study based on the Avon Longitudinal Study of Parents and Children. Cognitive measures were assessed between the ages of 8 and 11 years. Exposure groups were defined as moderate/late preterm (32-36 weeks' gestation) or term…
Rythén, Marianne; Thilander, Birgit; Robertson, Agneta
It has been shown that children born extremely preterm (EPT) often suffer from medical complications and growth restrictions in early childhood. Catchup growth diminishes these effects but the children are known to have lower weight, height, and head circumference as school children. Effects on enamel development have been shown. How this affects the dento-alveolar outcome during adolescence is not known. Forty EPT children with a gestational age (GA) of less than 29 weeks, at 12-16 years of age, and matched healthy controls born at term, with a GA of 37-43 weeks, were examined. Data from the clinical examination, dental casts, and bitewing radiographs were collected and compared. Malocclusion was noted, and dento-alveolar length, width, palatal height, and mesio-distal tooth width were measured. Medical diagnoses, neurological, and neuropsychiatric disturbances were noted at the time of the survey. The two groups were compared with an epidemiological normal reference material. The results showed no differences between the controls and reference material. Angle Class II was the most frequent malocclusion associated with morbidity, neurological, and neuropsychiatric disturbances, followed by deep bite and overjet. Three or more malocclusions were almost twice as common among the EPT children compared with the controls. Significantly smaller incisors, canines, and first molars were found. In summary, the EPT children, during adolescence, had medical aberrations as well as dento-alveolar effects opposed to the healthy children born at term. Dentists should be aware of this and treatment plans should be made in due time.
McCoy, Thomasin E.; Conrad, Amy L.; Richman, Lynn C.; Nopoulos, Peg C.; Bell, Edward F.
The purpose of this study was to evaluate immediate auditory and visual memory processes in learning disability subtypes of 40 children born preterm. Three subgroups of children were examined: (a) primary language disability group (n = 13), (b) perceptual-motor disability group (n = 14), and (c) no learning disability diagnosis group without identified language or perceptual-motor learning disability (n = 13). Between-group comparisons indicate no significant differences in immediate auditory or visual memory performances between language and perceptual-motor learning disability groups. Within-group comparisons revealed that both learning disability groups performed significantly lower on a task of immediate memory when the mode of stimulus presentation and mode of response were visual. PMID:22375897
McCoy, Thomasin E; Conrad, Amy L; Richman, Lynn C; Nopoulos, Peg C; Bell, Edward F
The purpose of this study was to evaluate immediate auditory and visual memory processes in learning disability subtypes of 40 children born preterm. Three subgroups of children were examined: (a) primary language disability group (n = 13), (b) perceptual-motor disability group (n = 14), and (c) no learning disability diagnosis group without identified language or perceptual-motor learning disability (n = 13). Between-group comparisons indicate no significant differences in immediate auditory or visual memory performances between language and perceptual-motor learning disability groups. Within-group comparisons revealed that both learning disability groups performed significantly lower on a task of immediate memory when the mode of stimulus presentation and mode of response were visual.
Lin, Yuan-Shan; Reilly, Marie; Mercer, Vicki S
The purpose of this study was to examine, using a modified visual cliff apparatus, possible perceptual differences at crawling age between infants born preterm and infants born at term without documented visual or motor impairments. Sixteen infants born at term and 16 born preterm were encouraged to crawl to their caregivers on a modified visual cliff. Successful trials, crossing time, duration of visual attention, duration of tactile exploration, motor strategies, and avoidance behaviors were analyzed. A significant surface effect was found, with longer crossing times and longer durations of visual attention and tactile exploration in the condition with the visual appearance of a deep cliff. Although the two groups of infants did not differ on any of the timed measures, infants born at term demonstrated a larger number of motor strategies and avoidance behaviors by simple tally. This study indicates that infants born at term and those born preterm can perceive a visual cliff and adapt their responses accordingly.
Mürner-Lavanchy, I; Ritter, B C; Spencer-Smith, M M; Perrig, W J; Schroth, G; Steinlin, M; Everts, R
Working memory is crucial for meeting the challenges of daily life and performing academic tasks, such as reading or arithmetic. Very preterm born children are at risk of low working memory capacity. The aim of this study was to examine the visuospatial working memory network of school-aged preterm children and to determine the effect of age and performance on the neural working memory network. Working memory was assessed in 41 very preterm born children and 36 term born controls (aged 7-12 years) using functional magnetic resonance imaging (fMRI) and neuropsychological assessment. While preterm children and controls showed equal working memory performance, preterm children showed less involvement of the right middle frontal gyrus, but higher fMRI activation in superior frontal regions than controls. The younger and low-performing preterm children presented an atypical working memory network whereas the older high-performing preterm children recruited a working memory network similar to the controls. Results suggest that younger and low-performing preterm children show signs of less neural efficiency in frontal brain areas. With increasing age and performance, compensational mechanisms seem to occur, so that in preterm children, the typical visuospatial working memory network is established by the age of 12 years.
Counsell, Serena J.; Edwards, A. David; Chew, Andrew T. M.; Anjari, Mustafa; Dyet, Leigh E.; Srinivasan, Latha; Boardman, James P.; Allsop, Joanna M.; Hajnal, Joseph V.; Rutherford, Mary A.; Cowan, Frances M.
Survivors of preterm birth have a high incidence of neurodevelopmental impairment which is not explained by currently understood brain abnormalities. The aim of this study was to test the hypothesis that the neurodevelopmental abilities of 2-year-old children who were born preterm and who had no evidence of focal abnormality on conventional MR…
Simms, Victoria; Cragg, Lucy; Gilmore, Camilla; Marlow, Neil; Johnson, Samantha
Children born very preterm have poorer attainment in all school subjects, and a markedly greater reliance on special educational support than their term-born peers. In particular, difficulties with mathematics are especially common and account for the vast majority of learning difficulties in this population. In this paper, we review research relating to the causes of mathematics learning difficulties in typically developing children, and the impact of very preterm birth on attainment in mathematics. Research is needed to understand the specific nature and origins of mathematics difficulties in very preterm children to target the development of effective intervention strategies.
Schwichtenberg, A. J.; Anders, Thomas F.; Vollbrecht, Melissa; Poehlmann, Julie
Objective Following a transactional perspective, this longitudinal study assessed concurrent and time-lagged associations between infant daytime sleep behaviors and maternal play interactions within a sample of infants born preterm. Method Data were collected from 134 families recruited from 3 Wisconsin NICUs. Multiple methods were used to collect data at infant NICU discharge and when infants were 4, 9, and 24 months postterm, including parent-report infant sleep logs, family sociodemographic assets and a 15 minute video-taped play session. Results Within time points, infants who napped more had mothers who were rated as more positive and communicative or less negative during play interactions at 4, 9 and 24 months compared to infants who napped less. Time-lagged findings indicated that infants who took more naps experienced more optimal maternal interactive behaviors later in development than infants who took fewer naps. Additionally, mothers who expressed more negative affect at 4 months or 9 months predicted more infant daytime sleep later in development. Conclusion Previous studies document that nighttime parent-child interactions influence nighttime sleep. This study presents the natural extension that daytime sleep influences daytime interactions. The present study draws attention to the understudied area of daytime naps in young children and provides support for the longitudinal bi-directional processes between sleep and parenting interactions. PMID:20978444
Bora, Samudragupta; Pritchard, Verena E.; Chen, Zhe; Inder, Terrie E.; Woodward, Lianne J.
Background: Attention problems are among the most prevalent neurobehavioral morbidities affecting very preterm (VPT) born children. The first study aim was to document rates of persistent attention/hyperactivity problems from ages 4 to 9 years in a regional cohort of VPT born children. The second aim was to examine the extent to which persistent…
Northam, Gemma B.; Liegeois, Frederique; Tournier, Jacques-Donald; Croft, Louise J.; Johns, Paul N.; Chong, Wui K.; Wyatt, John S.; Baldeweg, Torsten
Although language difficulties are common in children born prematurely, robust neuroanatomical correlates of these impairments remain to be established. This study investigated whether the greater prevalence of language problems in preterm (versus term-born) children might reflect injury to major intra- or interhemispheric white matter pathways…
Zubiaurre-Elorza, Leire; Soria-Pastor, Sara; Junque, Carme; Sala-Llonch, Roser; Segarra, Dolors; Bargallo, Nuria; Macaya, Alfons
Aim To identify long-term effects of preterm birth and of periventricular leukomalacia (PVL) on cortical thickness (CTh). To study the relationship between CTh and cognitive-behavioral abnormalities. Methods We performed brain magnetic resonance imaging on 22 preterm children with PVL, 14 preterm children with no evidence of PVL and 22 full-term peers. T1-weighted images were analyzed with FreeSurfer software. All participants underwent cognitive and behavioral assessments by means of the Wechsler Intelligence Scales for Children-Fourth Edition (WISC-IV) and the Child Behavior Checklist (CBCL). Results We did not find global CTh differences between the groups. However, a thinner cortex was found in left postcentral, supramarginal, and caudal middle rostral gyri in preterm children with no evidence of PVL than in the full-term controls, while PVL preterm children showed thicker cortex in right pericalcarine and left rostral middle frontal areas than in preterm children with no evidence of PVL. In the PVL group, internalizing and externalizing scores correlated mainly with CTh in frontal areas. Attentional scores were found to be higher in PVL and correlated with CTh increments in right frontal areas. Interpretation The preterm group with no evidence of PVL, when compared with full-term children, showed evidence of a different pattern of regional thinning in the cortical gray matter. In turn, PVL preterm children exhibited atypical increases in CTh that may underlie their prevalent behavioral problems. PMID:22860067
King, Jennifer P; Gazmararian, Julie A; Shapiro-Mendoza, Carrie K
The purpose of this study was to identify disparities in neonatal, post-neonatal, and overall infant mortality rates among infants born late preterm (34-36 weeks gestation) and early term (37-38 weeks gestation) by race/ethnicity, maternal age, and plurality. In analyses of 2003-2005 data from US period linked birth/infant death datasets, we compared infant mortality rates by race/ethnicity, maternal age, and plurality among infants born late preterm or early term and also determined the leading causes of death among these infants. Among infants born late preterm, infants born to American Indian/Alaskan Native, non-Hispanic black, or teenage mothers had the highest infant mortality rates per 1,000 live births (14.85, 9.90, and 11.88 respectively). Among infants born early term, corresponding mortality rates were 5.69, 4.49, and 4.82, respectively. Among infants born late preterm, singletons had a higher infant mortality rate than twins (8.59 vs. 5.62), whereas among infants born early term, the rate was higher among twins (3.67 vs. 3.15). Congenital malformations and sudden infant death syndrome were the leading causes of death among both late preterm and early term infants. Infant mortality rates among infants born late preterm or early term varied substantially by maternal race/ethnicity, maternal age, and plurality. Information about these disparities may help in the development of clinical practice and prevention strategies targeting infants at highest risk.
Rimol, Lars M; Bjuland, Knut J; Løhaugen, Gro C C; Martinussen, Marit; Evensen, Kari Anne I; Indredavik, Marit S; Brubakk, Ann-Mari; Eikenes, Live; Håberg, Asta K; Skranes, Jon
While cross-sectional neuroimaging studies on cortical development predict reductions in cortical volume (surface area and thickness) during adolescence, this is the first study to undertake a longitudinal assessment of cortical surface area changes across the continuous cortical surface during this period. We studied the developmental dynamics of cortical surface area and thickness in adolescents and young adults (aged 15-20) born with very low birth weight (VLBW; <1500 g) as well as in term-born controls. Previous studies have demonstrated brain structural abnormalities in cortical morphology, as well as long-term motor, cognitive and behavioral impairments, in adolescents and young adults with VLBW, but the developmental dynamics throughout adolescence have not been fully explored. T1-weighted MRI scans from 51 VLBW (27 scanned twice) and 79 term-born adolescents (37 scanned twice) were used to reconstruct the cortical surface and produce longitudinal estimates of cortical surface area and cortical thickness. Linear mixed model analyses were performed, and the main effects of time and group, as well as time × group interaction effects, were investigated. In both groups, cortical surface area decreased up to 5% in some regions, and cortical thickness up to 8%, over the five-year period. The most affected regions were located on the lateral aspect of the hemispheres, in posterior temporal, parietal and to some extent frontal regions. There was no significant interaction between time and group for either morphometry variable. In conclusion, cortical thickness decreases from 15 to 20 years of age, in a similar fashion in the clinical and control groups. Moreover, we show for the first time that developmental trajectories of cortical surface area in preterm and term-born adolescents do not diverge during adolescence.
Rythén, Marianne; Niklasson, Aimon; Hellström, Ann; Hakeberg, Magnus; Robertson, Agneta
Children born extremely preterm often suffer from medical complications that have been shown to affect their oral health as toddlers and school children.The aim of this study was to investigate oral health and possible risk indicators for poor oral health in adolescents born extremely preterm compared with a control group and relate the findings to medical diagnoses at the clinical examination. Also in the same groups, compare the frequency of mineralization disturbances and its relation to postnatal morbidity and treatments. The medical records postnatally,was noted in 45 extremely preterm infants with a gestational age (GA) of <29 weeks, at 12 - 16 years of age and in age and gender matched fullterm controls with 37-43 weeks GA. A dental clinical examination was performed including a salivary examination. Medical diagnoses were noted at the time of the survey. Data from the patient dental records at 3, 6, and 9 years of age was compiled. The findings were related to gestational age, birth weight, neonatal and postnatal medical diagnoses treatments and medical diagnoses at the clinical examination. The result showed that the prevalence of plaque, gingivitis and the occurrence of Streptococcus mutans were higher among adolescents born extremely preterm compared to matched controls, and the saliva secretion was lower in the extremely preterm infants. The frequency of caries did not differ between the groups. Mineralization disturbances were more frequent in the primary dentition and more severe in the permanent dentition among the children born extremely preterm. No association between dental pathology, neonatal and postnatal morbidity and treatments was found. In conclusion, adolescents born extremely preterm have an increased number of risk indicators for a poorer oral outcome compared with the controls and more severe mineralization disturbances. These findings may imply an increased vulnerability for poorer oral health later in life.
Travis, Katherine E.; Ben-Shachar, Michal; Myall, Nathaniel J.; Feldman, Heidi M.
Diffusion properties of white matter tracts have been associated with individual differences in reading. Individuals born preterm are at risk of injury to white matter. In this study we compared the associations between diffusion properties of white matter and reading skills in children and adolescents born full term and preterm. 45 participants, aged 9–17 years, included 26 preterms (born < 36 weeks' gestation) and 19 full-terms. Tract fractional anisotropy (FA) profiles were generated for five bilateral white matter tracts previously associated with reading: anterior superior longitudinal fasciculus (aSLF), arcuate fasciculus (Arc), corticospinal tract (CST), uncinate fasciculus (UF) and inferior longitudinal fasciculus (ILF). Mean scores on reading for the two groups were in the normal range and were not statistically different. In both groups, FA was associated with measures of single word reading and comprehension in the aSLF, AF, CST, and UF. However, correlations were negative in the full term group and positive in the preterm group. These results demonstrate variations in the neurobiology of reading in children born full term and preterm despite comparable reading skills. Findings suggest that efficient information exchange required for strong reading abilities may be accomplished via a different balance of neurobiological mechanisms in different groups of readers. PMID:27158588
Yliherva, A; Olsén, P; Järvelin, M R
The linguistic skills of 8-year-old children born preterm (n = 42) with birthweight < 1750 grams from a 1-year birth cohort for 1985-86 in northern Finland were studied with three different language tests, namely the Illinois Test of Psycholinguistic Abilities (ITPA), the Token Test for Children (TTC) and the Morphological Test (MT) for Finnish children. Full-term control children (n = 42) with birthweight > or = 2500 grams from the same birth cohort were matched individually with their preterm pairs for age, sex, twinship, mother's education, place of residence, birth order and family type. The preterm children's language abilities were studied in relation to their neurological status and to the periventricular leukomalacia (PVL) findings of magnetic resonance imaging (MRI). The preterm children with minor neurodevelopmental dysfunctions (MND) scored worst and differed significantly from their matched controls in TTC. They also differed significantly from other preterm subgroups, namely healthy preterm and preterm children with cerebral palsy (CP), in verbal comprehension measured by TTC. PVL findings were not associated with performance in the language ability tests. A closer and regular follow-up of language development in the MND-disabled group among the low-birthweight preterm children is recommended.
Svedenkrans, Jenny; Kowalski, Jan; Norman, Mikael; Bohlin, Kajsa
Background Preterm birth is a risk factor for decreased exercise capacity and impaired cognitive functions in later life. The objective of this study was to disentangle the associations between preterm birth, physical fitness and cognitive performance in young adulthood. Methods This population-based cohort study included 218,802 young men born in Sweden 1973–1983. Data on birth characteristics was obtained from the Medical Birth Register and linked to exercise capacity assessed by ergometer cycling and cognitive tests performed at conscription for military service in 1993–2001. Cognitive performance was assessed using stanine (STAndard NINE) scores. The results were adjusted for socioeconomic factors. Results Exercise capacity was positively associated with cognitive performance across all gestational ages. The sub-group of men who were born extremely preterm (gestational age <28 weeks) and had low exercise capacity exhibited the lowest odds ratio (OR = 0.26, 95%CI:0.09–0.82) of having a cognitive function above the mean stanine score (2.9) for men born at term with normal birth weight. Men born extremely preterm with a high exercise capacity had similar or even higher ORs for cognitive function (OR = 0.59; 95% CI:0.35–0.99) than men born at term with low Wmax (OR = 0.57; 95% CI:0.55–0.59). Conclusions Physical fitness is associated with higher cognitive function at all gestational ages, also in young men born extremely preterm. Targeting early physical exercise may be a possible intervention to enhance cognitive performance and educational achievements in populations at risk, such as childhood and adult survivors of preterm birth. PMID:27548612
Dahan-Oliel, Noemi; Majnemer, Annette; Mazer, Barbara
Research on quality of life (QoL) of adolescents and young adults born preterm and those with congenital heart disease (CHD) was systematically reviewed, and factors associated with QoL were identified. Forty-five studies met the inclusion criteria for review. Although the majority of studies found that self-reported QoL of adolescents and young…
Purpose To compare the respiratory and neurological outcomes at two years of age of preterm children born before 33 weeks of gestation (WG) after early preterm premature rupture of membranes (EPPROM) between 14 and 24 WG with preterm children without EPPROM. Design and Patients This single-center case-control retrospective study was conducted at Rouen University Hospital between 1st January 2000 and 31st December 2010. All the cases with EPPROM born from 26WG to 32WG were included. Each newborn was matched by sex, gestational age (GA) and year of birth to two very preterm children, born without EPPROM. At two years of corrected age, motor and cognitive abilities were assessed by routine score based on the Amiel-Tison and Denver developmental scales. Results Ninety-four cases with EPPROM before 24WG have been included. The 31 children born from 26WG to 32WG were matched with 62 controls. The EPPROM group had poorer clinical evaluation at one year for motor (p = 0.003) and cognitive developmental scores (p = 0.016). Neuromotor rehabilitation was performed more often (p = 0.013). However, there was no difference at 2 years of age. Children born after EPPROM were hospitalized more often for bronchiolitis (p<0.001) during their first 2 years, which correlates with increased incidence of pneumothorax (p = 0.017), pulmonary hypoplasia (p = 0.004) and bronchopulmonary dysplasia (p = 0.005) during neonatal period. Conclusion At two years, despite an increase in severe bronchiolitis and the need for more neuromotor rehabilitation during the first month of the life after discharge, there was no difference in neurological outcomes in the very preterm children of the EPPROM group compared to those born at a similar GA without EPPROM. PMID:27829004
Cole, James H.; Filippetti, Maria Laura; Allin, Matthew P. G.; Walshe, Muriel; Nam, Kie Woo; Gutman, Boris A.; Murray, Robin M.; Rifkin, Larry; Thompson, Paul M.; Nosarti, Chiara
Background The hippocampus has been reported to be structurally and functionally altered as a sequel of very preterm birth (<33 weeks gestation), possibly due its vulnerability to hypoxic–ischemic damage in the neonatal period. We examined hippocampal volumes and subregional morphology in very preterm born individuals in mid- and late adolescence and their association with psychiatric outcome. Methods Structural brain magnetic resonance images were acquired at two time points (baseline and follow-up) from 65 ex-preterm adolescents (mean age = 15.5 and 19.6 years) and 36 term-born controls (mean age=15.0 and 19.0 years). Hippocampal volumes and subregional morphometric differences were measured from manual tracings and with three-dimensional shape analysis. Psychiatric outcome was assessed with the Rutter Parents’ Scale at baseline, the General Health Questionnaire at follow-up and the Peters Delusional Inventory at both time points. Results In contrast to previous studies we did not find significant difference in the cross-sectional or longitudinal hippocampal volumes between individuals born preterm and controls, despite preterm individual having significantly smaller whole brain volumes. Shape analysis at baseline revealed subregional deformations in 28% of total bilateral hippocampal surface, reflecting atrophy, in ex-preterm individuals compared to controls, and in 22% at follow-up. In ex-preterm individuals, longitudinal changes in hippocampal shape accounted for 11% of the total surface, while in controls they reached 20%. In the whole sample (both groups) larger right hippocampal volume and bilateral anterior surface deformations at baseline were associated with delusional ideation scores at follow-up. Conclusions This study suggests a dynamic association between cross-sectional hippocampal volumes, longitudinal changes and surface deformations and psychosis proneness. PMID:26091104
Hoon, Alexander H., Jr.; Faria, Andreia Vasconcellos
With advances in obstetric and perinatal management, the incidence of intraventricular hemorrhage in premature infants has declined, while periventricular leukomalacia remains a significant concern. It is now known that brain injury in children born preterm also involves neuronal-axonal disease in supratentorial and infratentorial structures. The…
Cserjesi, Renata; van Braeckel, Koenraad N. J. A.; Timmerman, Marieke; Butcher, Phillipa R.; Kerstjens, Jorien M.; Reijneveld, Sijmen A.; Bouma, Anke; Bos, Arend F.; Geuze, Reint H.
Aim: The aim of this study was to identify subgroups of children born moderately preterm (MPT) and term with distinctive levels and patterns of functioning, and the perinatal and demographic factors that predict subgroup membership. Method: A total of 378 children aged 7 years, 248 MPT (138 males, 110 females; gestational age 32-36 wks) and a…
Lynn, Lisa N.; Cuskelly, Monica; O'Callaghan, Michael J.; Gray, Peter H.
Survival rates are increasing for children born extremely preterm, yet despite the majority of these children having IQ scores within the average range, 50-70% of these children have later school difficulties. This paper reviews factors associated with academic difficulties in these children, emphasizing the contributions of executive functions…
Vinall, Jillian; Miller, Steven P; Chau, Vann; Brummelte, Susanne; Synnes, Anne R; Grunau, Ruth E
Procedural pain is associated with poorer neurodevelopment in infants born very preterm (≤ 32 weeks gestational age), however, the etiology is unclear. Animal studies have demonstrated that early environmental stress leads to slower postnatal growth; however, it is unknown whether neonatal pain-related stress affects postnatal growth in infants born very preterm. The aim of this study was to examine whether greater neonatal pain (number of skin-breaking procedures adjusted for medical confounders) is related to decreased postnatal growth (weight and head circumference [HC] percentiles) early in life and at term-equivalent age in infants born very preterm. Participants were n=78 preterm infants born ≤ 32 weeks gestational age, followed prospectively since birth. Infants were weighed and HC measured at birth, early in life (median: 32 weeks [interquartile range 30.7-33.6]) and at term-equivalent age (40 weeks [interquartile range 38.6-42.6]). Weight and HC percentiles were computed from sex-specific British Columbia population-based data. Greater neonatal pain predicted lower body weight (Wald χ(2)=7.36, P=0.01) and HC (Wald χ(2)=4.36, P=0.04) percentiles at 32 weeks postconceptional age, after adjusting for birth weight percentile and postnatal risk factors of illness severity, duration of mechanical ventilation, infection, and morphine and corticosteroid exposure. However, later neonatal infection predicted lower weight percentile at term (Wald χ(2)=5.09, P=0.02). Infants born very preterm undergo repetitive procedural pain during a period of physiological immaturity that appears to impact postnatal growth, and may activate a downstream cascade of stress signaling that affects later growth in the neonatal intensive care unit.
Taylor, Nicole M.; Jakobson, Lorna S.
The term "representational momentum" (RM) refers to the idea that our memory representations for moving objects incorporate information about movement--a fact that can lead us to make errors when judging an object's location (the RM effect). In this study, we explored the RM effect in a sample of children born very prematurely and a sample born at…
implemented in conjunction with antenatal care models that promote women's empowerment as a strategy for reducing preterm delivery. The global community needs to support more discovery research on normal and abnormal pregnancies to facilitate the development of preventive interventions for universal application. As new evidence is generated, resources need to be allocated to its translation into new and better screening and diagnostic tools, and other interventions aimed at saving maternal and newborn lives that can be brought to scale in all countries. Declaration This article is part of a supplement jointly funded by Save the Children's Saving Newborn Lives programme through a grant from The Bill & Melinda Gates Foundation and March of Dimes Foundation and published in collaboration with the Partnership for Maternal, Newborn and Child Health and the World Health Organization (WHO). The original article was published in PDF format in the WHO Report "Born Too Soon: the global action report on preterm birth" (ISBN 978 92 4 150343 30), which involved collaboration from more than 50 organizations. The article has been reformatted for journal publication and has undergone peer review according to Reproductive Health's standard process for supplements and may feature some variations in content when compared to the original report. This co-publication makes the article available to the community in a full-text format. PMID:24625215
Kwon, Soo Hyun; Scheinost, Dustin; Vohr, Betty; Lacadie, Cheryl; Schneider, Karen; Dai, Feng; Sze, Gordon; Constable, R Todd; Ment, Laura R
Sophisticated neuroimaging strategies demonstrate alterations in functional connectivity at school age, adolescence, and young adulthood in individuals born preterm. Recent data suggest these alterations are present in the postnatal period prior to term-equivalent age in neonates born preterm. Likewise, functional organization increases across development, but the influence of preterm birth on this fundamental infrastructure is immediate and unchanging. This article briefly reviews the current methods of measuring functional connectivity throughout development in those born preterm, and the association of functional connectivity with language disorders. Taken together, these data suggest that the effects of preterm birth on the functional organization of language in the developing brain are both proximate and long-lasting.
Brumberg, H L; Shah, S I
Poverty is associated with adverse long-term cognitive outcomes in children. Poverty is also linked with preterm delivery which, in turn, is associated with adverse cognitive outcomes. However, the extent of the effect of poverty on preterm delivery, as well as proposed mechanisms by which they occur, have not been well described. Further, the impact of poverty on preterm school readiness has not been reviewed. As the childhood poverty level continues to increase in the U.S., we examine the evidence around physiological, neurological, cognitive and learning outcomes associated with prematurity in the context of poverty. We use the evidence gathered to suggest an Eco-Bio-Developmental model, emphasizing poverty as a toxic stress which predisposes preterm birth and which, via epigenetic forces, can continue into the next generation. Continued postnatal social disadvantage for these developmentally high-risk preterm infants is strongly linked with poor neurodevelopmental outcomes, decreased school readiness, and decreased educational attainment which can perpetuate the poverty cycle. We suggest social remedies aimed at decreasing the impact of poverty on mothers, fathers, and children which may be effective in reducing the burden of preterm birth.
Garg, Amanmeet; Grunau, Ruth E.; Popuri, Karteek; Miller, Steven; Bjornson, Bruce; Poskitt, Kenneth J.; Beg, Mirza Faisal
Many studies using T1 magnetic resonance imaging (MRI) data have found associations between changes in global metrics (e.g. volume) of brain structures and preterm birth. In this work, we use the surface displacement feature extracted from the deformations of the surface models of the third ventricle, fourth ventricle and brainstem to capture the variation in shape in these structures at 8 years of age that may be due to differences in the trajectory of brain development as a result of very preterm birth (24-32 weeks gestation). Understanding the spatial patterns of shape alterations in these structures in children who were born very preterm as compared to those who were born at full term may lead to better insights into mechanisms of differing brain development between these two groups. The T1 MRI data for the brain was acquired from children born full term (FT, n=14, 8 males) and preterm (PT, n=51, 22 males) at age 8-years. Accurate segmentation labels for these structures were obtained via a multi-template fusion based segmentation method. A high dimensional non-rigid registration algorithm was utilized to register the target segmentation labels to a set of segmentation labels defined on an average-template. The surface displacement data for the brainstem and the third ventricle were found to be significantly different (p < 0.05) between the PT and FT groups. Further, spatially localized clusters with inward and outward deformation were found to be associated with lower gestational age. The results from this study present a shape analysis method for pediatric MRI data and reveal shape changes that may be due to preterm birth.
Pyhälä, Riikka; Hovi, Petteri; Räikkönen, Katri; Van Lieshout, Ryan J.; Boyle, Michael H.; Saigal, Saroj; Morrison, Katherine M.; Kajantie, Eero; Schmidt, Louis A.
Background. Adults born extremely preterm appear to have more difficulty managing the stresses of early adulthood than their term-born peers. Objective. To examine the effects of being born at extremely low birth weight (ELBW; birth weight < 1000 g) versus at full term on cardiovascular responses to stress. Method. Cardiovascular responses were elicited during administration of a widely used laboratory stressor, the Trier Social Stress Test (TSST). Results. Term-born adults exhibited a larger decrease in total peripheral resistance and larger increase in cardiac output for TSST performance, reflecting greater resilience, than did ELBW adults. Furthermore, in ELBW participants but not controls, cardiovascular responses were correlated with anxiety, suggesting that their responses reflected feelings of stress. Conclusions. Skills-training and practice with relevant stressors may be necessary to increase the personal resources of ELBW participants for managing stress as they transition to adulthood. PMID:27335948
Ferrari, Alize J; Whittingham, Koa; Boyd, Roslyn; Sanders, Matthew; Colditz, Paul
Over 10% of preterm infants develop major disabilities, 50% develop behavioural problems and 40% need special education (Huddy et al., 2001; Webster, 2003). Prem Baby Triple P is a new variant of the Positive Parenting Program (Triple P) adapted specifically for parents of very preterm infants. The aim of this study is to assess the acceptability of Prem Baby Triple P to parents of infants born preterm and to test whether parental attributions and parental perception of infant health/developmental status are barriers to intervention acceptability. One hundred and twenty-three parents of preterm infants participated, 83 parents of very preterm infants and 40 parents of preterm infants. In addition, 32 parents of term infants participated as a comparison group. The acceptability of Prem Baby Triple P was moderately high and did not differ significantly across the three groups. Parental attributions were not found to be barriers to intervention acceptability and parental perceptions that their infant is less healthy/developmentally delayed facilitated Prem Baby Triple P acceptance in parents of infants born very preterm. This suggests that the planned Prem Baby Triple P content is acceptable to parents of infants born very preterm and sensitised to medical and developmental issues. These findings, as social validation data, will contribute towards the further development of Prem Baby Triple P and a future randomised controlled trial.
Nam, Kie Woo; Castellanos, Nazareth; Simmons, Andrew; Froudist-Walsh, Seán; Allin, Matthew P.; Walshe, Muriel; Murray, Robin M.; Evans, Alan; Muehlboeck, J-Sebastian; Nosarti, Chiara
Very preterm birth (gestational age < 33 weeks) 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 15 years) and beginning of adulthood (mean age 20 years), 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. PMID:25871628
Counsell, Serena J; Edwards, A David; Chew, Andrew T M; Anjari, Mustafa; Dyet, Leigh E; Srinivasan, Latha; Boardman, James P; Allsop, Joanna M; Hajnal, Joseph V; Rutherford, Mary A; Cowan, Frances M
Survivors of preterm birth have a high incidence of neurodevelopmental impairment which is not explained by currently understood brain abnormalities. The aim of this study was to test the hypothesis that the neurodevelopmental abilities of 2-year-old children who were born preterm and who had no evidence of focal abnormality on conventional MR imaging were consistently linearly related to specific local changes in white matter microstructure. We studied 33 children, born at a median (range) gestational age of 28(+5) (24(+4)-32(+1)) weeks. The children were recruited as infants from the Neonatal Intensive Care Unit at Queen Charlotte's and Hammersmith Hospital in the early neonatal period and imaged at a median corrected age of 25.5 (24-27) months. The children underwent diffusion tensor imaging to measure fractional anisotropy (FA) as a measure of tissue microstructure, and neurodevelopmental assessment using the Griffiths Mental Development Scales [giving an overall developmental quotient (DQ) and sub-quotients scores for motor, personal-social, hearing-language, eye-hand coordination and performance scales] at 2 years corrected age. Tract-based spatial statistics with linear regression analysis of voxel-wise cross-subject statistics were used to assess the relationship between FA and DQ/sub-quotient scores and results confirmed by reduced major axis regression of regions with significant correlations. We found that DQ was linearly related to FA values in parts of the corpus callosum; performance sub-scores to FA values in the corpus callosum and right cingulum; and eye-hand coordination sub-scores to FA values in the cingulum, fornix, anterior commissure, corpus callosum and right uncinate fasciculus. This study shows that specific neurodevelopmental impairments in infants born preterm are precisely related to microstructural abnormalities in particular regions of cerebral white matter which are consistent between individuals. FA may aid prognostication and
Feldman, Heidi M.; Lee, Eliana S.; Yeatman, Jason D.; Yeom, Kristen W.
Children born preterm are at risk for deficits in language and reading. They are also at risk for injury to the white matter of the brain. The goal of this study was to determine whether performance in language and reading skills would be associated with white matter properties in children born preterm and full-term. Children born before 36 weeks…
DeHaan, K; Fuhr, D; Hariharan, S; Kamstra, B; Hendson, L; Adatia, I; Majaesic, C; Lovering, A T; Thompson, R B; Nicholas, D; Thebaud, B; Stickland, M K
Background Extreme preterm birth confers risk of long-term impairments in lung function and exercise capacity. There are limited data on the factors contributing to exercise limitation following extreme preterm birth. This study examined respiratory mechanics and ventilatory response during exercise in a large cohort of children born extremely preterm (EP). Methods This cohort study included children 8–12 years of age who were born EP (≤28 weeks gestation) between 1997 and 2004 and treated in a large regionalised neonatal intensive care unit in western Canada. EP children were divided into no/mild bronchopulmonary dysplasia (BPD) (ie, supplementary oxygen or ventilation ceased before 36 weeks gestational age; n=53) and moderate/severe BPD (ie, continued supplementary oxygen or ventilation at 36 weeks gestational age; n=50). Age-matched control children (n=65) were born at full term. All children attempted lung function and cardiopulmonary exercise testing measurements. Results Compared with control children, EP children had lower airway flows and diffusion capacity but preserved total lung capacity. Children with moderate/severe BPD had evidence of gas trapping relative to other groups. The mean difference in exercise capacity (as measured by oxygen uptake (VO2)% predicted) in children with moderate/severe BPD was −18±5% and −14±5.0% below children with no/mild BPD and control children, respectively. Children with moderate/severe BPD demonstrated a potentiated ventilatory response and greater prevalence of expiratory flow limitation during exercise compared with other groups. Resting lung function did not correlate with exercise capacity. Conclusions Expiratory flow limitation and an exaggerated ventilatory response contribute to respiratory limitation to exercise in children born EP with moderate/severe BPD. PMID:27259338
Poehlmann, Julie; Burnson, Cynthia; Weymouth, Lindsay A
Through assessment of 173 preterm infants and their mothers at hospital discharge and at 9, 16, 24, 36, and 72 months, the study examined early parenting, attachment security, effortful control, and children's representations of family relationships in relation to subsequent externalizing behavior problems. Less intrusive early parenting predicted more secure attachment, better effortful control skills, and fewer early behavior problems, although it did not directly relate to the structural or content characteristics of children's represented family relationships. Children with higher effortful control scores at 24 months had more coherent family representations at 36 months. Moreover, children who exhibited less avoidance in their family representations at 36 months had fewer mother-reported externalizing behavior problems at 72 months. The study suggests that early parenting quality and avoidance in children's represented relationships are important for the development of externalizing behavior problems in children born preterm.
Poehlmann, Julie; Burnson, Cynthia; Weymouth, Lindsay A.
Through assessment of 173 preterm infants and their mothers at hospital discharge and at 9, 16, 24, 36, and 72 months, the study examined early parenting, attachment security, effortful control, and children’s representations of family relationships in relation to subsequent externalizing behavior problems. Less intrusive early parenting predicted more secure attachment, better effortful control skills, and fewer early behavior problems, although it did not directly relate to the structural or content characteristics of children’s represented family relationships. Children with higher effortful control scores at 24 months had more coherent family representations at 36 months. Moreover, children who exhibited less avoidance in their family representations at 36 months had fewer mother-reported externalizing behavior problems at 72 months. The study suggests that early parenting quality and avoidance in children’s represented relationships are important for the development of externalizing behavior problems in children born preterm. PMID:24580068
Northam, Gemma B.; Liégeois, Frédérique; Tournier, Jacques-Donald; Croft, Louise J.; Johns, Paul N.; Chong, Wui K.; Wyatt, John S.
Although language difficulties are common in children born prematurely, robust neuroanatomical correlates of these impairments remain to be established. This study investigated whether the greater prevalence of language problems in preterm (versus term-born) children might reflect injury to major intra- or interhemispheric white matter pathways connecting frontal and temporal language regions. To investigate this, we performed a comprehensive assessment of language and academic abilities in a group of adolescents born prematurely, some of whom had evidence of brain injury at birth (n = 50, mean age: 16 years, mean gestational age: 27 weeks) and compared them to a term-born control group (n = 30). Detailed structural magnetic resonance imaging and diffusion-tractography analyses of intrahemispheric and interhemispheric white matter bundles were performed. Analysis of intrahemispheric pathways included the arcuate fasciculus (dorsal language pathway) and uncinate fasciculus/extreme capsule (ventral language pathway). Analysis of interhemispheric pathways (in particular, connections between the temporal lobes) included the two major commissural bundles: the corpus callosum and anterior commissure. We found language impairment in 38% of adolescents born preterm. Language impairment was not related to abnormalities of the arcuate fasciculus (or its subsegments), but was associated with bilateral volume reductions in the ventral language pathway. However, the most significant volume reduction was detected in the posterior corpus callosum (splenium), which contains interhemispheric connections between the occipital, parietal and temporal lobes. Diffusion tractography showed that of the three groups of interhemispheric fibres within the splenium, only those connecting the temporal lobes were reduced. Crucially, we found that language impairment was only detectable if the anterior commissure (a second temporal lobe commissural pathway) was also small. Regression analyses
Böhm, Birgitta; Lundequist, Aiko; Smedler, Ann-Charlotte
Visual-motor development and executive functions were investigated with the Bender Test at age 5½ years in 175 children born preterm and 125 full-term controls, within the longitudinal Stockholm Neonatal Project. Assessment also included WPPSI-R and NEPSY neuropsychological battery for ages 4-7 (Korkman, 1990). Bender protocols were scored according to Brannigan & Decker (2003), Koppitz (1963) and a complementary neuropsychological scoring system (ABC), aimed at executive functions and developed for this study. Bender results by all three scoring systems were strongly related to overall cognitive level (Performance IQ), in both groups. The preterm group displayed inferior visual-motor skills compared to controls also when controlling for IQ. The largest group differences were found on the ABC scoring, which shared unique variance with NEPSY tests of executive function. Multiple regression analyses showed that hyperactive behavior and inattention increased the risk for visual-motor deficits in children born preterm, whereas no added risk was seen among hyperactive term children. Gender differences favoring girls were strongest within the preterm group, presumably reflecting the specific vulnerability of preterm boys. The results indicate that preterm children develop a different neurobehavioral organization from children born at term, and that the Bender test with a neuropsychological scoring is a useful tool in developmental screening around school start.
Allen, Marilee C.; Cristofalo, Elizabeth; Kim, Christina
Preterm birth is associated with greater difficulty with transitions from childhood to adolescence to adulthood. Adolescents and young adults born preterm have higher rates of cerebral palsy, intellectual disability, cognitive impairment, learning disability, executive dysfunction, attention deficit disorder, and social-emotional difficulties than…
Pitchford, Nicola; Johnson, Samantha; Scerif, Gaia; Marlow, Neil
Cognitive impairment often follows preterm birth but its early underlying nature is not well understood. We used a novel approach by investigating the development of colour cognition in 54 very preterm children born less than or equal to 30 weeks gestational age without severe neurosensory impairment and 37 age-matched term-born controls, aged 2-5…
Gerstein, Emily D; Poehlmann-Tynan, Julie
This prospective, longitudinal study examined the transactional relations among perceived maternal parenting stress, maternal insensitivity, and child behavior across toddlerhood through age 6 within families of a child born preterm. A sample of 173 mother-child dyads were followed from just before the infant was discharged from the neonatal intensive care unit to 6 years of age, with observational measurements of maternal insensitivity and child noncompliance (24 and 36 months), maternal self-reports of perceived parenting stress (24 months, 36 months, 6 years), and maternal reports of child externalizing behavior at 6 years. Results indicated that maternal insensitivity at 36 months significantly mediated the relation between parenting stress at 24 months and externalizing behaviors at 6 years. Parenting stress was also directly associated with child noncompliance at 36 months and with child externalizing behavior at 6 years. Neonatal risk was associated with increased maternal insensitivity at 24 months, but also decreased parenting stress at 24 months. No significant "child effects" from child behavior to either maternal insensitivity or parenting stress were found. Parenting stress appears to play a critical role for children born preterm, and it is associated with children's behavior both directly and through its influence on parenting. The role of neonatal risk needs continued investigation, as families traditionally considered to be at lower risk may still face significant challenges.
Leviton, Alan; Allred, Elizabeth N.; Kuban, Karl C. K.; O'Shea, T. Michael; Paneth, Nigel; Onderdonk, Andrew B.; Fichorova, Raina N.; Dammann, Olaf
Gestational genitourinary infections, which have been associated with neurodevelopmental impairments among infants born near term, have not been studied among very preterm infants. The mothers of 989 infants born before 28 weeks of gestation were interviewed about urine, bladder, or kidney infections (UTIs) and cervical or vaginal infections (CVIs) during pregnancy, as well as other exposures and characteristics, and their charts were reviewed for the Extremely Low Gestational Age Newborns (ELGAN) Study (2002–2004). At 2 years of age, these infants underwent a neurodevelopmental assessment. Generalized estimating equation logistic regression models of developmental adversities were used to adjust for potential confounders. Infants born to women who reported a UTI were less likely than were others to have a very low Mental Development Index (adjusted odds ratio = 0.5; 95% confidence interval: 0.3, 0.8), whereas infants born to women who reported a CVI were more likely than others to have a low Psychomotor Development Index (adjusted odds ratio = 1.7; 95% confidence interval: 1.04, 2.7). In this high-risk sample, maternal gestational CVI, but not UTI, was associated with a higher risk of impaired motor development at 2 years of age. The apparent protective effect of UTI might be spurious, reflect confounding due to untreated asymptomatic bacteriuria among women who were not given a diagnosis of UTI, or reflect preconditioning. PMID:26667255
Hovi, Petteri; Andersson, Sture; Järvenpää, Anna-Liisa; Eriksson, Johan G.; Strang-Karlsson, Sonja; Kajantie, Eero; Mäkitie, Outi
Background Very-low-birth-weight (VLBW, <1,500 g) infants have compromised bone mass accrual during childhood, but it is unclear whether this results in subnormal peak bone mass and increased risk of impaired skeletal health in adulthood. We hypothesized that VLBW is associated with reduced bone mineral density (BMD) in adulthood. Methods and Findings The Helsinki Study of Very Low Birth Weight Adults is a multidisciplinary cohort study representative of all VLBW births within the larger Helsinki area from 1978 to 1985. This study evaluated skeletal health in 144 such participants (all born preterm, mean gestational age 29.3 wk, birth weight 1,127 g, birth weight Z score 1.3), and in 139 comparison participants born at term, matched for sex, age, and birth hospital. BMD was measured by dual energy X-ray absorptiometry at age 18.5 to 27.1 y. Adults born with VLBW had, in comparison to participants born at term, a 0.51-unit (95% confidence interval [CI] 0.28–0.75) lower lumbar spine Z score and a 0.56-unit (95% CI 0.34–0.78) lower femoral neck Z score for areal BMD. These differences remained statistically significant after adjustment for the VLBW adults' shorter height and lower self-reported exercise intensity. Conclusions Young adults born with VLBW, when studied close to the age of peak bone mass, have significantly lower BMD than do their term-born peers. This suggests that compromised childhood bone mass accrual in preterm VLBW children translates into increased risk for osteoporosis in adulthood, warranting vigilance in osteoporosis prevention. Please see later in the article for the Editors' Summary PMID:19707270
Doesburg, Sam M; Ribary, Urs; Herdman, Anthony T; Miller, Steven P; Poskitt, Kenneth J; Moiseev, Alexander; Whitfield, Michael F; Synnes, Anne; Grunau, Ruth E
Children born very preterm, even when intelligence is broadly normal, often experience selective difficulties in executive function and visual-spatial processing. Development of structural cortical connectivity is known to be altered in this group, and functional magnetic resonance imaging (fMRI) evidence indicates that very preterm children recruit different patterns of functional connectivity between cortical regions during cognition. Synchronization of neural oscillations across brain areas has been proposed as a mechanism for dynamically assigning functional coupling to support perceptual and cognitive processing, but little is known about what role oscillatory synchronization may play in the altered neurocognitive development of very preterm children. To investigate this, we recorded magnetoencephalographic (MEG) activity while 7–8 year old children born very preterm and age matched full-term controls performed a visual short-term memory task. Very preterm children exhibited reduced long-range synchronization in the alpha-band during visual short-term memory retention, indicating that cortical alpha rhythms may play a critical role in altered patterns functional connectivity expressed by this population during cognitive and perceptual processing. Long-range alpha-band synchronization was also correlated with task performance and visual-perceptual ability within the very preterm group, indicating that altered alpha-oscillatory mechanisms mediating transient functional integration between cortical regions may be relevant to selective problems in neurocognitive development in this vulnerable population at school age. PMID:20974268
Brogårdh-Roth, Susanne; Matsson, Lars; Klingberg, Gunilla
Although preterm birth is associated with an increased risk of medical problems and impairments, there is limited knowledge of how this affects oral health. It was hypothesized that when 10-12 yr of age, children who were preterm at birth would present with a higher prevalence of molar-incisor hypomineralization (MIH), more dental plaque, and a higher degree of gingival inflammation than full-term control children. Eighty-two preterm children, born between 24 and 32 wk of gestation, and 82 control children, born between 37 and 43 wk of gestation, were clinically examined for developmental defects in enamel, MIH, dental plaque, and gingival health. In addition, behaviour management problems were evaluated. Information on any aetiological factors with a potential influence on MIH and oral health was collected via questionnaires. Molar-incisor hypomineralization was more common in preterm children than in controls (38% vs. 16%), as were enamel developmental defects (69.5% vs. 51%). Low gestational age and low birth weight increased the risk of MIH. Preterm children had more plaque, a higher degree of gingival inflammation, and more behaviour-management problems than controls. In conclusion, oral health problems were more common in preterm children than in control children.
jointly funded by Save the Children's Saving Newborn Lives programme through a grant from The Bill & Melinda Gates Foundation and March of Dimes Foundation and published in collaboration with the World Health Organization (WHO). The original article was published in PDF format in the WHO Report "Born Too Soon: the global action report on preterm birth (ISBN 978 92 4 150343 30). The article has been reformatted for journal publication and has undergone peer review according to Reproductive Health's standard process for supplements and may feature some variations in content when compared to the original report. This co-publication makes the article available to the community in a full-text format. PMID:24625189
Treyvaud, Karli; Inder, Terrie E.; Lee, Katherine J.; Northam, Elisabeth A.; Doyle, Lex W.; Anderson, Peter J.
Relationships between the home environment and early developmental outcomes were examined in 166 children born very preterm in one tertiary maternity hospital to explore whether a more optimal home environment could promote resilience. In particular, we explored whether this effect was apparent over and above social risk and children's biological…
Somhovd, Mikael J.; Hansen, Bo M.; Brok, Jesper; Esbjorn, Barbara H.; Greisen, Gorm
Aim: To determine if adolescents who are born very preterm (less than 32wks; of gestation) and/or with very low birthweight (VLBW; less than 1500g) have a higher risk of experiencing clinically significant anxiety problems. Method: We used a systematic review and meta-analysis. We searched the databases ISI Web of Knowledge, PubMed, PsycNET,…
Gouin, Marion; Nguyen, Sylvie; Savagner, Christophe; Troussier, Francoise; Gascouin, Géraldine; Rozé, Jean-Christophe; Flamant, Cyril
Preterm infants are at greater risk of bronchopulmonary dysplasia, which is associated with neurodevelopmental impairment. These infants are also more likely to develop severe bronchiolitis, which can contribute to neurodevelopmental impairment. The aim of this study was to determine whether severe bronchiolitis in very preterm infants (born before 33 weeks of gestation) was associated with an increased risk of neurodevelopmental impairment at 2 years of age. We analyzed a population-based cohort of infants (the Loire Infant Follow-up Team cohort) born between 1 January 2003 and 31 December 2009. Severe bronchiolitis was defined as hospitalization due to bronchiolitis during the first year of life. Neurodevelopmental outcome was assessed at 2 years of corrected age. A total of 2,405 infants were included in this analysis and categorized based on neonatal respiratory status: 1,308 (54.4 %) received no respiratory assistance, 864(35.9 %) received oxygen for <28 days, and 167 (6.9 %) had mild and 66 (2.7) moderate or severe bronchopulmonary dysplasia. At 2 years, 502 children displayed non-optimal neurodevelopmental outcome (20.9 %). Moderate or severe bronchopulmonary dysplasia was significantly associated with non-optimal neurodevelopmental outcome at 2 years (adjusted odds ratios (OR) = 2.3 [95 % confidence interval (CI): 1.3-3.9], p = 0.003). In the first year, 318 infants acquired severe bronchiolitis (13.2 %), which was not associated with non-optimal neurodevelopmental outcome (adjusted OR = 1.0 [95 % CI: 0.8-1.4]; p = 0.88). In conclusion, respiratory status in the neonatal period was significantly associated with non-optimal neurodevelopmental outcome at 2 years, while severe bronchiolitis was not.
Ritter, Barbara Catherine; Perrig, Walter; Steinlin, Maja; Everts, Regula
This study investigated whether children aged between 8 and 12 years born very preterm (VPT) and/or at very low birth weight (VLBW) performed lower than same-aged term-born controls in cognitive and behavioral aspects of three executive functions: inhibition, working memory, and shifting. Special attention was given to sex differences. Fifty-two VPT/VLBW children (26 girls, 50%) born in the cohort of 1998-2003 and 36 same-aged term-born children (18 girls, 50%) were recruited. As cognitive measures, children completed tasks of inhibition (Color-Word Interference Test, D-KEFS; Delis, Kaplan, & Kramer, 2001), working memory (digit span backwards, HAWIK-IV; Petermann & Petermann, 2008), and shifting (Trail Making Test, number-letter-switching, D-KEFS; Delis et al., 2001). As behavioral measures, mothers completed the Behavior Rating Inventory of Executive Function (BRIEF; Gioia, Isquith, Guy, & Kenworthy, 2000). Scales of interest were inhibit, working memory, and shift. Analyses of the cognitive aspects of executive functions revealed that VPT/VLBW children performed significantly lower than controls in the shifting task but not in the working memory and inhibition tasks. Analyses of behavioral aspects of executive functions revealed that VPT/VLBW children displayed more problems than the controls in working memory in everyday life but not in inhibition and shifting. No sex differences could be detected either in cognitive or behavioral aspects of executive functions. To conclude, cognitive and behavioral measures of executive functions were not congruent in VPT/VLBW children. In clinical practice, the combination of cognitive and behavioral instruments is required to disclose children's executive difficulties.
Micali, Nadia; Kothari, Radha; Nam, Kie Woo; Gioroukou, Elena; Walshe, Muriel; Allin, Matthew; Rifkin, Larry; Murray, Robin M; Nosarti, Chiara
This study investigates the prevalence of eating disorder (ED) psychopathology, neuropsychological function, structural brain correlates and risk mechanisms in a prospective cohort of very preterm (VPT) young adults. We assessed ED psychopathology and neuropsychological correlates in 143 cohort individuals born at <33 weeks of gestation. Structural brain correlates and risk factors at birth, in childhood and adolescence, were investigated using prospectively collected data throughout childhood/adolescence. VPT-born individuals had high levels of ED psychopathology at age 21 years. Executive function did not correlate with ED symptomatology. VPT adults presenting with ED psychopathology had smaller grey matter volume at age 14/15 years in the left posterior cerebellum and smaller white matter volume in the fusiform gyrus bilaterally, compared with VPT adults with no ED psychopathology. Caesarean delivery predicted engaging in compensatory behaviours, and severe eating difficulty at age 14 years predicted ED symptomatology in young adulthood. VPT individuals are at risk for ED symptomatology, with evidence of associated structural alterations in posterior brain regions. Further prospective studies are needed to clarify the pathways that lead from perinatal/obstetric complications to ED and relevant neurobiological mechanisms. © 2015 The Authors. European Eating Disorders Review published by John Wiley &Sons, Ltd.
Calling, Susanna; Palmér, Karolina; Jönsson, Lena; Sundquist, Jan; Winkleby, Marilyn; Sundquist, Kristina
Aim Preterm birth is associated with a number of physical and mental health issues. The aim of this study was to find out if there was also any association between individuals born preterm in Sweden between 1984 and 2006 and the risk of unintentional injuries during childhood, adolescence and young adulthood. Methods The study followed 2,297,134 individuals, including 5.9% born preterm, from 1985 to 2007 for unintentional injuries leading to hospitalisation or death (n=244,021). The males and females were divided into four age groups: 1–5 years, 6–12 years, 13–18 years and 19–23 years. Hazard ratios were calculated for falls, transport injuries and other injuries. Results After adjusting for a comprehensive set of covariates, some of the preterm subgroups demonstrated slightly increased risks of unintentional injuries, while others showed slightly decreased risks. However, most of the estimates were borderline or non-significant in both males and females. In addition, the absolute risk differences between individuals born preterm and full term were small. Conclusion Despite the association between preterm birth and a variety of physical and mental health consequences, this study shows that there is no consistent risk pattern between preterm birth and unintentional injuries in childhood, adolescence and young adulthood. PMID:23181809
Padilla, Nelly; Skiöld, Béatrice; Eklöf, Eva; Mårtensson, Gustaf; Vollmer, Brigitte; Ådén, Ulrika
Objective Magnetic resonance imaging (MRI) of the brain carried out during the neonatal period shows that 55–80% of extremely preterm infants display white matter diffuse excessive high signal intensity (DEHSI). Our aim was to study differences in developmental outcome at the age of 6.5 years in children born extremely preterm with and without DEHSI. Study Design This was a prospective cohort study of 83 children who were born in Stockholm, Sweden, between 2004 and 2007, born at gestational age of < 27 weeks + 0 days and who underwent an MRI scan of their brain at term equivalent age. The outcome measures at 6.5 years included testing 66 children with the modified Touwen neurology examination, the Movement Assessment Battery for Children 2, the Wechsler Intelligence Scale for Children—Fourth Edition, Beery Visual-motor Integration test—Sixth Edition, and the Strengths and Difficulties Questionnaire. Group-wise comparisons were done between children with and without DEHSI using Student t-test, Mann Whitney U test, Chi square test and regression analysis. Results DEHSI was detected in 39 (59%) of the 66 children who were assessed at 6.5 years. The presence of DEHSI was not associated with mild neurological dysfunction, scores on M-ABC assessment, cognition, visual-motor integration, or behavior at 6.5 years. Conclusion The presence of qualitatively defined DEHSI on neonatal MRI did not prove to be a useful predictor of long-term impairment in children born extremely preterm. PMID:26886451
Eeles, Abbey L; Olsen, Joy E; Walsh, Jennifer M; McInnes, Emma K; Molesworth, Charlotte M L; Cheong, Jeanie L Y; Doyle, Lex W; Spittle, Alicia J
Neurobehavioral assessments provide insight into the functional integrity of the developing brain and help guide early intervention for preterm (<37 weeks' gestation) infants. In the context of shorter hospital stays, clinicians often need to assess preterm infants prior to term equivalent age. Few neurobehavioral assessments used in the preterm period have established interrater reliability.
Valizadeh, Leila; Sanaeefar, Mahnaz; Hosseini, Mohammad Bager; Asgari Jafarabadi, Mohammad; Shamili, Aryan
Introduction: Although the survival rate of infants born preterm has increased, the prevalence of developmental problems and motor disorders among this population of infants remains the same. This study investigated the effect of physical activity programs in and out of water on motor performance and neuromuscular development of infants born preterm and had induced immobility by mechanical ventilation. Methods: This study was carried out in Al-Zahra hospital, Tabriz. 76 premature infants were randomly assigned into four groups. One group received daily passive range of motion to all extremities based on the Moyer-Mileur protocol. Hydrotherapy group received exercises for shoulders and pelvic area in water every other day. A combination group received physical activity programs in and out of water on alternating days. Infants in a containment group were held in a fetal position. Duration of study was two weeks ‘from 32 through 33 weeks post menstrual age (PMA). Motor outcomes were measured by the Test of Infant Motor Performance. Neuromuscular developmental was assessed by New Ballard scale and leg recoil and Ankle dorsiflexion items from Dubowitz scale. Data were analyzed using SPSS version 13. Results: TIMP and neuromuscular scores improved in all groups. Motor performance did not differ between groups at 34 weeks PMA. Postural tone of leg recoil was significantly higher in physical activity groups post intervention. Conclusion: Physical activities and containment didn’t have different effects on motor performance in infants born preterm. Leg recoil of neuromuscular development items was affected by physical activity programs. PMID:28299299
Bloch, Joan Rosen
Objective To examine spatial patterns of neighborhood contextual factors of stress with preterm birth (PTB) and nativity (foreign-born and U.S.-born) among Black mothers. Design Descriptive geographic-spatial research. Setting & Participants Births to Philadelphia residents during 2003–2005 in the context of Philadelphia residential neighborhoods (N = 350) were studied. Methods All data were aggregated to neighborhood levels (census tracts). Maps were created to assess geographic-spatial patterns. A geographic information system (GIS) database was created that imported geo-coded data on births, crime (assaults with guns and domestic abuse), poverty, race, and nativity (foreign-born vs. U.S.-born). Results Clear visual patterns of “bad” neighborhoods emerged and were significantly associated with higher prevalence of PTB for foreign-born Black and U.S.-born Black mothers (p < .0001). Conclusions This study demonstrated how GIS visually clarified important spatial patterns of adverse living conditions and PTB prevalence. Nurses can use GIS to better understand living environments of mothers and their families and to target interventions in geographical areas with the greatest service needs. Further research on individual and contextual factors is warranted to address the observed health disparities among the heterogeneous groups of foreign-born Black mothers. Despite limitations of aggregate data, it is clear that where mothers live matters. This has important implications for nursing practice and policy. PMID:22273411
Khanolkar, Amal R; Wedrén, Sara; Essén, Birgitta; Sparén, Pär; Koupil, Ilona
Ethnic minorities/immigrant groups tend to have increased risk for preterm birth. Less is known about this risk in diverse immigrant groups, couples of mixed ethnic-origin and in relation to duration of residence. Data from the Swedish Medical Birth Register on 1,028,303 mothers who gave birth to 1,766,026 singleton live born infants (1982-2002), was linked to the Education and Total Population Registers. Immigrant parents were identified by country of birth. Risk of early preterm, late preterm and postterm birth was analyzed using multinomial logistic regression. Polish, Yugoslavian, Iranian, South Asian, East Asian and Sub-Saharan African parents, Swedish mothers who had children with non-Swedish fathers, and parents from two different immigrant groups had higher risk of early preterm birth [adjusted relative risk (RR) (95% CI) 1.76 (1.24-2.50), 1.57 (1.31-1.87), 1.67 (1.30-2.14), 1.52 (1.07-2.16), 1.51 (1.08-2.10), 2.03 (1.32-3.12), 1.56 (1.45-1.67), and 1.55 (1.35-1.77) respectively] compared to Swedish-born parents. South Asian, Sub-Saharan African, and East Asian immigrants had a higher risk of late preterm birth compared to Swedish-born parents. North African and Middle Eastern, Somali, and Ethiopian/Eritrean groups had increased risk of postterm birth [adjusted RR 1.31 (1.16-1.47), 2.57 (2.31-2.86), 1.85 (1.67-2.04) respectively]. Adjustment for covariates did not substantially change associations. Immigrant mothers resident <3 years had higher risk for early preterm and postterm birth compared to residents >10 years [adjusted RR 1.46 (1.24-1.71) and 1.16 (1.11-1.23) respectively]. In addition to higher risk of preterm birth in select immigrant groups, some immigrant groups are also at higher risk of postterm birth. Shorter duration of residence is associated with higher risk of non-term deliveries.
Johnson, Samantha; Kochhar, Puja; Hennessy, Enid; Marlow, Neil; Wolke, Dieter; Hollis, Chris
Objective To investigate antecedents of Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms in children born extremely preterm (EP; <26 weeks gestation). Method The EPICure Study recruited all babies born EP in the UK and Ireland in March-December 1995. Neurodevelopmental outcomes were assessed at 2.5 (n=283; 90%), 6 (n=160; 78%) and 11 (n=219; 71%) years of age. Parents and teachers completed the Du Paul Rating Scale-IV to assess inattention and hyperactivity/impulsivity symptoms at 11 years. Regression analyses were used to explore the association of neonatal, neurodevelopmental and behavioral outcomes to 6 years with ADHD symptoms at 11 years. Results EP children had significantly more inattention (mean difference 1.2 SD; 95% CI 0.9, 1.5) and hyperactivity/impulsivity (0.5 SD; 0.2, 0.7) than controls, with a significantly greater effect size for inattention than hyperactivity/impulsivity. Significant independent predictors of inattention at 11 years included smaller head circumference, lower IQ and pervasive peer relationship problems at 6 years, and motor development at 2.5 years. In contrast, significant independent predictors of hyperactivity/impulsivity included lower IQ, pervasive conduct problems and ADHD symptoms at 6 years, externalizing problems at 2.5 years and non-white maternal ethnicity. Conclusions EP children are at increased risk for ADHD symptoms, predominantly inattention, for which the antecedents differ by symptom domain. Attention deficits following EP birth were associated with poor brain growth and neurological function. Cognitive and behavioral assessments in early and middle childhood to identify neurodevelopmental and peer relationship problems may be beneficial for identifying EP children at risk for inattention. PMID:27096570
Perumal, Nandita; Gaffey, Michelle F; Bassani, Diego G; Roth, Daniel E
In epidemiologic research, there is no standard approach for accounting for gestational age (GA) at birth when interpreting postnatal anthropometric data in analyses of cohorts that include children born preterm (CBP). A scoping review was conducted to describe analytical approaches to account for GA at birth when applying the WHO Growth Standards (WHO-GS) to anthropometric data in epidemiologic studies. We searched PubMed, Scopus, MEDLINE, Embase, and Web of Science for studies that applied WHO-GS, included CBP in the study population, had access to data within 1 mo of age, and were published between 2006 and 2015 in English. Of the 80 included studies that used the WHO-GS, 80% (64 of 80) included all children regardless of GA, whereas 20% (16 of 80) restricted analyses that used WHO-GS to term-born children. Among the 64 studies that included all children, 53 (83%) used chronological age and 11 (17%) used corrected age for CBP. Of the 53 studies that used chronological age, 12 (23%) excluded data that were likely contributed by CBP (e.g., very low birth weight or extremely low outlying z scores) and 19 (36%) adjusted for or stratified by GA at birth in regression analyses. In summary, researchers commonly apply WHO-GS to CBP, usually based on chronological age. Methodologic challenges of analyzing data from CBP in the application of WHO-GS were rarely explicitly addressed. Further efforts are required to establish acceptable approaches to account for heterogeneity in GA at birth in the analysis of post-term anthropometric data in epidemiologic research.
Background Early interventions (EI) are recognised for their potential risk-reduction capacity. Although developmental delay is common in children born very preterm reports continue to suggest poor uptake of EI services. This study examined the risk determinants of EI in Australian children born less than 32 weeks gestation during the first year of life. Methods As part of a multi-centre-randomised-trial, 195 children were prospectively studied during their first year of life and EI use, type of follow-up, perinatal, social and parental psychosocial risk factors were collected using questionnaires. Child neurodevelopmental disability-status was assessed at 12-months (cerebral palsy, blind, deaf, developmental quotient 1standard deviation (SD) below mean). The associations between EI and variables were examined using Pearson’s chi-squared test (χ2) and regression techniques. Results A total of 55% of children received EI, 51% attended post discharge neonatal intensive care unit (NICU) and the remainder attended exclusive primary health care. Risk factors included, 50% perinatal, 19% social and 34% psychosocial and at 12-months 23% were categorised as disabled. Low social risk and NICU follow-up attendance were significantly associated with EI use but only perinatal risk (OR 3.1, 95% CI 1.7, 5.6, p = <0.01) and disability (OR 2.2, 95% CI 1.1, 4.7, p = 0.04) independently predicted EI use. Conclusions It is reassuring that children with perinatal risk receive EI, opportunity remains to improve EI uptake in families with social and parental psychosocial risk during the first year of life. PMID:24304976
Pascoe, L; Scratch, SE; Burnett, AC; Thompson, DK; Lee, KJ; Doyle, LW; Cheong, JLY; Inder, TE; Anderson, PJ
Objective 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. Further, 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. Method One hundred and 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. Results There was little evidence of stronger NRH in the VPT group compared with term controls (regression coefficient [b] −1.95, 95% confidence interval [CI] −5.67 to 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. Conclusions 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. PMID:26328609
Reiss, Allan L; Kesler, Shelli R; Vohr, Betty; Duncan, Charles C; Katz, Karol H; Pajot, Sarah; Schneider, Karen C; Makuch, Robert W; Ment, Laura R
We investigate sex-associated effects of preterm birth on cerebral gray matter (GM) and white matter (WM) volumes. Preterm children (n=65) and 31 healthy, term control children had usable magnetic resonance imaging (MRI) data acquired at 8 years of age. Both GM and WM volumes were significantly reduced in the preterm group compared with controls. However, only males with preterm birth had significantly reduced WM compared with term males (P=.021), whereas WM volumes were equivalent in the female groups. Lower birth weight was associated with reduced WM in both boys and girls with preterm birth, whereas intraventricular hemorrhage (IVH) was associated with reduced GM in girls only. Positive correlations between GM and cognitive outcome were observed in girls with preterm birth but not boys. We conclude that preterm birth has a significant impact on brain development with increased risk for smaller GM and WM cerebral volumes. Males appear particularly vulnerable to adverse effects of preterm birth on WM development. However, girls with preterm birth show stronger correlations between neuro-anatomical variables and both neonatal risk factors and cognitive outcome, compared with boys. These findings indicate that the sex of the very preterm newborn influences the mechanisms by which the developing brain is affected.
Winchester, Suzy Barcelos; Sullivan, Mary C; Marks, Amy Kerivan; Doyle, Thomas; DePalma, Jennifer; McGrath, Margaret M
The effects of gradient levels of perinatal morbidity on school outcomes have been investigated at age 12 in four preterm groups, classified as healthy (no medical or neurological illness), medical morbidity, neurological morbidity, and small-for-gestational-age (SGA), and a full-term comparison group. Teachers report on academic competence, social skills, and problem behaviors. Data on school type, classroom setting, and school service use are gathered from school records. Preterm groups are found to be equivalent to full-term peers in social skills and problem behavior. Preterm groups with neurological and SGA morbidity have the lowest academic competence scores. Unexpectedly, preterm infants with medical morbidity have higher academic competence scores compared with the other preterm groups. School service use increases with greater perinatal morbidity and is contingent on multiple rather than single indicators of perinatal morbidity. Continued monitoring of preterm infants through early adolescence will ensure that appropriate school services and resources are available to maximize their school success.
Rogers, Lynette K; Velten, Markus
The "fetal origin of adult disease Hypothesis" originally described by Barker et al. identified the relationship between impaired in utero growth and adult cardiovascular disease risk and death. Since then, numerous clinical and experimental studies have confirmed that early developmental influences can lead to cardiovascular, pulmonary, metabolic, and psychological diseases during adulthood with and without alterations in birth weight. This so called "fetal programming" includes developmental disruption, immediate adaptation, or predictive adaptation and can lead to epigenetic changes affecting a specific organ or overall health. The intrauterine environment is dramatically impacted by the overall maternal health. Both premature birth or low birth weight can result from a variety of maternal conditions including undernutrition or dysnutrition, metabolic diseases, chronic maternal stresses induced by infections and inflammation, as well as hypercholesterolemia and smoking. Numerous animal studies have supported the importance of both maternal health and maternal environment on the long term outcomes of the offspring. With increasing rates of obesity and diabetes and survival of preterm infants born at early gestational ages, the need to elucidate mechanisms responsible for programming of adult cardiovascular disease is essential for the treatment of upcoming generations.
Barker, Lisa; Draper, Elizabeth S.; Abrams, Keith R.; Modi, Neena; Manktelow, Bradley N.
Modelling length of stay in neonatal care is vital to inform service planning and the counselling of parents. Preterm babies, at the highest risk of mortality, can have long stays in neonatal care and require high resource use. Previous work has incorporated babies that die into length of stay estimates, but this still overlooks the levels of care required during their stay. This work incorporates all babies, and the levels of care they require, into length of stay estimates. Data were obtained from the National Neonatal Research Database for singleton babies born at 24–31 weeks gestational age discharged from a neonatal unit in England from 2011 to 2014. A Cox multistate model, adjusted for gestational age, was used to consider a baby’s two competing outcomes: death or discharge from neonatal care, whilst also considering the different levels of care required: intensive care; high dependency care and special care. The probabilities of receiving each of the levels of care, or having died or been discharged from neonatal care are presented graphically overall and adjusted for gestational age. Stacked predicted probabilities produced for each week of gestational age provide a useful tool for clinicians when counselling parents about length of stay and for commissioners when considering allocation of resources. Multistate modelling provides a useful method for describing the entire neonatal care pathway, where rates of in-unit mortality can be high. For a healthcare service focussed on costs, it is important to consider all babies that contribute towards workload, and the levels of care they require. PMID:27764232
Eryigit Madzwamuse, Suna; Baumann, Nicole; Jaekel, Julia; Bartmann, Peter; Wolke, Dieter
Background: Children born very preterm (VP <32 weeks gestation) and/or with very low birth weight (VBLW <1500 g; subsequently VP/VLBW) have been previously reported to have more cognitive impairment and specific executive functioning problems than term children; however, it remains unclear whether these problems persist into adulthood. This…
Brumbaugh, Jane E.; Conrad, Amy L.; Lee, Jessica K.; DeVolder, Ian J.; Zimmerman, M. Bridget; Magnotta, Vincent A.; Axelson, Eric D.; Nopoulos, Peggy C.
Background Late preterm birth (34-36 weeks’ gestation) is a common occurrence with potential for altered brain development. Methods This observational cohort study compared children at age 6-13 years based on the presence or absence of the historical risk factor of late preterm birth. Children completed a battery of cognitive assessments and underwent magnetic resonance imaging of the brain. Results Late preterm children (n=52) demonstrated slower processing speed (p=0.035) and scored more poorly in visual-spatial perception (p=0.032) and memory (p=0.007) than full term children (n=74). Parents of late preterm children reported more behavioral difficulty (p=0.004). There were no group differences in cognitive ability or academic achievement. Imaging revealed similar intracranial volumes but less total tissue and more cerebrospinal fluid (p=0.004) for late preterm children compared to full term children. The tissue difference was driven by differences in the cerebrum (p=0.028) and distributed across cortical (p=0.051) and subcortical tissue (p=0.047). Late preterm children had a relatively smaller thalamus (p=0.012) than full term children. Only full term children demonstrated significant decreases in cortical tissue volume (p<0.001) and thickness (p<0.001) with age. Conclusion Late preterm birth may affect cognition, behavior, and brain structure well beyond infancy. PMID:27064239
HOON, ALEXANDER H; STASHINKO, ELAINE E; NAGAE, LIDIA M; LIN, DORIS DM; KELLER, JENNIFER; BASTIAN, AMY; CAMPBELL, MICHELLE L; LEVEY, ERIC; MORI, SUSUMU; JOHNSTON, MICHAEL V
AIM Cerebral palsy (CP) is frequently linked to white matter injury in children born preterm. Diffusion tensor imaging (DTI) is a powerful technique providing precise identification of white matter microstructure. We investigated the relationship between DTI-observed thalamocortical (posterior thalamic radiation) injury, motor (corticospinal tract) injury, and sensorimotor function. METHOD Twenty-eight children born preterm(16 males, 12 females; mean age 5y 10mo, SD 2y 6mo, range 16mo–13y; mean gestational age at birth 28wks, SD 2.7wks, range 23–34wks) were included in this case–control study. Twenty-one children had spastic diplegia, four had spastic quadriplegia, two had hemiplegia, and one had ataxic hypotonic CP; 15 of the participants walked independently. Normative comparison data were obtained from 35 healthy age-matched children born at term(19 males, 16 females; mean age 5y 9mo, SD 4y 4mo, range 15mo–15y). Two-dimensional DTI color maps were created to evaluate 26 central white matter tracts, which were graded by a neuroradiologist masked to clinical status. Quantitative measures of touch, proprioception, strength (dynamometer), and spasticity (modified Ashworth scale) were obtained from a subset of participants. RESULTS All 28 participants with CP had periventricular white-matter injury on magnetic resonance imaging. Using DTI color maps, there was more severe injury in the posterior thalamic radiation pathways than in the descending corticospinal tracts. Posterior thalamic radiation injury correlated with reduced contralateral touch threshold, proprioception, and motor severity, whereas corticospinal tract injury did not correlate with motor or sensory outcome measures. INTERPRETATION These findings extend previous research demonstrating that CP in preterm children reflects disruption of thalamocortical connections as well as descending corticospinal pathways. PMID:19416315
Collins, James W; Rankin, Kristin M; David, Richard J
A paucity of published data exists on the factors underlying the relatively poor birth outcome of non-Hispanic White women in the United States. To determine whether downward economic mobility is a risk factor for preterm birth (<37 weeks, PTB) among upper class-born White women. Stratified and multilevel logistic regression analyses were performed on an Illinois transgenerational dataset of non-Hispanic White infants (1989-1991) and their women (1956-1976) with appended US census income information. The study sample was restricted to singleton births of Chicago-born upper-class (defined by early-life residence in affluent neighborhoods) non-Hispanic White women. Upper class-born White women (n = 4,891) who did not experience downward economic mobility by the time of delivery had a PTB rate of 5.4 %. Those women who experienced slight (n = 5,112), moderate (n = 2,158), or extreme (n = 339) downward economic mobility had PTB rates of 6.5, 8.5, and 10.1 %, respectively; RR (95 % CI) = 1.2 (1.0-4.0), 1.6 (1.3-1.9), and 1.9 (1.3-2.6), respectively. Maternal downward economic mobility was also associated with an increased prevalence of biologic, medical, and behavioral risk factors. Interestingly, the relationship between moderate to extreme downward mobility and preterm birth was stronger among former low birth weight (<2500 g, LBW) than non-LBW women: 2.8 (1.4-5.8) versus 1.6 (1.3-1.9), respectively. In multilevel logistic regression models, the adjusted odds ratio of preterm birth for former LBW and non-LBW women who experienced any downward mobility (compared to those women with lifelong upper class status) equaled 2.4 (1.1-5.3) and 1.1 (1.0-1.1), respectively. Downward economic mobility is associated with an increased risk of preterm birth among upper class-born White urban women; this phenomenon is strongest among former low birth weight women.
Tsai, Hui-Ju; Surkan, Pamela J.; Yu, Stella M.; Caruso, Deanna; Hong, Xiumei; Bartell, Tami R.; Wahl, Anastacia D.; Sampankanpanich, Claire; Reily, Anne; Zuckerman, Barry S.; Wang, Xiaobin
Abstract Preterm birth (PTB, <37 weeks of gestation) is influenced by a wide range of environmental, genetic and psychosocial factors, and their interactions. However, the individual and joint effects of genetic factors and psychosocial stress on PTB have remained largely unexplored among U.S. born versus immigrant mothers. We studied 1121 African American women from the Boston Birth Cohort enrolled from 1998 to 2008. Regression-based analyses were performed to examine the individual and joint effects of genetic ancestry and stress (including lifetime stress [LS] and stress during pregnancy [PS]) on PTB and related traits among U.S. born and immigrant mothers. Significant associations between LS and PTB and related traits were found in the total study population and in immigrant mothers, including gestational age, birthweight, PTB, and spontaneous PTB; but no association was found in U.S. born mothers. Furthermore, significant joint associations of LS (or PS) and African ancestral proportion (AAP) on PTB were found in immigrant mothers, but not in U.S. born mothers. Although, overall, immigrant women had lower rates of PTB compared to U.S. born women, our study is one of the first to identify a subset of immigrant women could be at significantly increased risk of PTB and related outcomes if they have high AAP and are under high LS or PS. In light of the growing number of immigrant mothers in the U.S., our findings may have important clinical and public health implications. PMID:28151865
Sarwer, D B; Bartlett, S P; Whitaker, L A; Paige, K T; Pertschuk, M J; Wadden, T A
This study represents an initial investigation into the adult psychological functioning of individuals born with craniofacial disfigurement. A total of 24 men and women born with a craniofacial anomaly completed paper and pencil measures of body image dissatisfaction, self-esteem, quality of life, and experiences of discrimination. An age- and gender-matched control group of 24 non-facially disfigured adults also completed the measures. As expected, craniofacially disfigured adults reported greater dissatisfaction with their facial appearance than did the control group. Craniofacially disfigured adults also reported significantly lower levels of self-esteem and quality of life. Dissatisfaction with facial appearance, self-esteem, and quality of life were related to self-ratings of physical attractiveness. More than one-third of craniofacially disfigured adults (38 percent) reported experiences of discrimination in employment or social settings. Among disfigured adults, psychological functioning was not related to number of surgeries, although the degree of residual facial deformity was related to increased dissatisfaction with facial appearance and greater experiences of discrimination. Results suggest that adults who were born with craniofacial disfigurement, as compared with non-facially disfigured adults, experience greater dissatisfaction with facial appearance and lower self-esteem and quality of life; however, these experiences do not seem to be universal.
Scratch, Shannon E.; Doyle, Lex W.; Thompson, Deanne K.; Ahmadzai, Zohra M.; Greaves, Ronda F.; Inder, Terrie E.; Hunt, Rodney W.
Context and Objectives: Little is known regarding the influence of GH on brain development, especially in infants born very preterm (VP; <30 weeks' gestation). Preterm infants are thought to have higher levels of GH in the first days of life compared with full-term infants. VP infants experience cognitive difficulties in childhood and have a diffuse pattern of structural brain abnormalities. This study aimed to explore the relationship between postnatal GH concentrations following VP birth and its association with cognitive functioning and brain volumes at age 7 years. Methods: Eighty-three infants born VP had GH concentrations measured at eight time points postnatally, and 2- and 6-week area under the curve (AUC) summary measures were calculated. Followup at age 7 years included neuropsychological assessment and brain magnetic resonance imaging. Univariable and multivariable regression modeling were used where AUC for GH was the main predictor of neurodevelopmental outcome at age 7 years. Results: Univariable modeling revealed that higher GH levels (2-week AUC) were related to poorer performance on a verbal working memory (P = .04) and shifting attention task (P = .01). These relationships persisted on multivariable modeling and when the 6-week AUC was analyzed; working memory (P = .03), immediate spatial memory (P = .02), and delayed spatial memory (P = .03) deficits were found. Higher GH levels were also associated with larger amygdala volumes after adjustment for potential confounders (P = .002, 2-week AUC; P = .03, 6-week AUC). Conclusions: Higher postnatal GH levels may potentially contribute to the documented neurodevelopmental abnormalities seen in children born VP at school age. PMID:25974734
Freeman, Nancy K.; Corning, Lisa L.
Recommends universal precautions policies and procedures to minimize for children and adults in early childhood settings the risk of infection from exposure to blood-borne pathogens such as hepatitis B or HIV. Outlines symptoms of hepatitis B and HIV/AIDS. Discusses legal and ethical implications related to inclusion. Lists resources for teachers…
Roberts, Rachel M.; George, Wing Man; Cole, Carolyn; Marshall, Peter; Ellison, Vanessa; Fabel, Helen
This study examined the effect of age-correction on IQ scores among preterm school-aged children. Data from the Flinders Medical Centre Neonatal Unit Follow-up Program for 81 children aged five years and assessed with the WPPSI-III, and 177 children aged eight years and assessed with the WISC-IV, were analysed. Corrected IQ scores were…
Probabilistic maps of the white matter tracts with known associated functions on the neonatal brain atlas: Application to evaluate longitudinal developmental trajectories in term-born and preterm-born infants.
Akazawa, Kentaro; Chang, Linda; Yamakawa, Robyn; Hayama, Sara; Buchthal, Steven; Alicata, Daniel; Andres, Tamara; Castillo, Deborrah; Oishi, Kumiko; Skranes, Jon; Ernst, Thomas; Oishi, Kenichi
Diffusion tensor imaging (DTI) has been widely used to investigate the development of the neonatal and infant brain, and deviations related to various diseases or medical conditions like preterm birth. In this study, we created a probabilistic map of fiber pathways with known associated functions, on a published neonatal multimodal atlas. The pathways-of-interest include the superficial white matter (SWM) fibers just beneath the specific cytoarchitectonically defined cortical areas, which were difficult to evaluate with existing DTI analysis methods. The Jülich cytoarchitectonic atlas was applied to define cortical areas related to specific brain functions, and the Dynamic Programming (DP) method was applied to delineate the white matter pathways traversing through the SWM. Probabilistic maps were created for pathways related to motor, somatosensory, auditory, visual, and limbic functions, as well as major white matter tracts, such as the corpus callosum, the inferior fronto-occipital fasciculus, and the middle cerebellar peduncle, by delineating these structures in eleven healthy term-born neonates. In order to characterize maturation-related changes in diffusivity measures of these pathways, the probabilistic maps were then applied to DTIs of 49 healthy infants who were longitudinally scanned at three time-points, approximately five weeks apart. First, we investigated the normal developmental pattern based on 19 term-born infants. Next, we analyzed 30 preterm-born infants to identify developmental patterns related to preterm birth. Last, we investigated the difference in diffusion measures between these groups to evaluate the effects of preterm birth on the development of these functional pathways. Term-born and preterm-born infants both demonstrated a time-dependent decrease in diffusivity, indicating postnatal maturation in these pathways, with laterality seen in the corticospinal tract and the optic radiation. The comparison between term- and preterm-born
CRUVINEL, Vanessa Resende Nogueira; GRAVINA, Danuze Batista Lamas; AZEVEDO, Tatiana Degani Paes Leme; de REZENDE, Catharina Siqueira; BEZERRA, Ana Cristina Barreto; de TOLEDO, Orlando Ayrton
Objectives The aim of this study was to evaluate the prevalence of enamel defects and their risk factors on primary and permanent dentitions of prematurely born children and full-term born children born at Regional Hospital of Asa Sul, Brasília, DF, Brazil. Material and Methods Eighty 5-10-year-old children of both genders were examined, being 40 born prematurely (G1) and 40 born full term (G2). The demographic variables, medical history and oral health behaviors were retrieved using a questionnaire and data obtained from clinical examination were recorded. The teeth were examined and the presence of enamel defects was diagnosed according to the DDE Index and registered in odontograms. Subsequently, the defects were categorized in four groups according to one of the criteria proposed in 1992 by the FDI Commission on Oral Health, Research and Epidemiology. Kruskal-Wallis, Chi-square, Kappa, Mann-Whitney tests and logistic regression were used for statistical analysis. Results 75% of total sample had enamel defects. There was a major prevalence of hypoplasia of the enamel in G1 (p<0.001). There was a significant relationship between low weight and presence of the imperfections on the enamel in G1 on the primary dentition. The logistic regression model showed that the other risk factors such as monthly per capita family income, educational level, dietary and hygiene habits, fluoride exposure, trauma, and diseases were not associated with enamel defects and caries. Conclusions Pre-term labor can be a predisposing factor for the presence of the enamel hypoplasia in the primary dentition. PMID:22858696
Lee, Anne CC; Katz, Joanne; Blencowe, Hannah; Cousens, Simon; Kozuki, Naoko; Vogel, Joshua P; Adair, Linda; Baqui, Abdullah H; Bhutta, Zulfiqar A; Caulfield, Laura E; Christian, Parul; Clarke, Siân E; Ezzati, Majid; Fawzi, Wafaie; Gonzalez, Rogelio; Huybregts, Lieven; Kariuki, Simon; Kolsteren, Patrick; Lusingu, John; Marchant, Tanya; Merialdi, Mario; Mongkolchati, Aroonsri; Mullany, Luke C; Ndirangu, James; Newell, Marie-Louise; Nien, Jyh Kae; Osrin, David; Roberfroid, Dominique; Rosen, Heather E; Sania, Ayesha; Silveira, Mariangela F; Tielsch, James; Vaidya, Anjana; Willey, Barbara A; Lawn, Joy E; Black, Robert E
Summary Background National estimates for the numbers of babies born small for gestational age and the comorbidity with preterm birth are unavailable. We aimed to estimate the prevalence of term and preterm babies born small for gestational age (term-SGA and preterm-SGA), and the relation to low birthweight (<2500 g), in 138 countries of low and middle income in 2010. Methods Small for gestational age was defined as lower than the 10th centile for fetal growth from the 1991 US national reference population. Data from 22 birth cohort studies (14 low-income and middle-income countries) and from the WHO Global Survey on Maternal and Perinatal Health (23 countries) were used to model the prevalence of term-SGA births. Prevalence of preterm-SGA infants was calculated from meta-analyses. Findings In 2010, an estimated 32·4 million infants were born small for gestational age in low-income and middle-income countries (27% of livebirths), of whom 10·6 million infants were born at term and low birthweight. The prevalence of term-SGA babies ranged from 5·3% of livebirths in east Asia to 41·5% in south Asia, and the prevalence of preterm-SGA infants ranged from 1·2% in north Africa to 3·0% in southeast Asia. Of 18 million low-birthweight babies, 59% were term-SGA and 41% were preterm. Two-thirds of small-for-gestational-age infants were born in Asia (17·4 million in south Asia). Preterm-SGA babies totalled 2·8 million births in low-income and middle-income countries. Most small-for-gestational-age infants were born in India, Pakistan, Nigeria, and Bangladesh. Interpretation The burden of small-for-gestational-age births is very high in countries of low and middle income and is concentrated in south Asia. Implementation of effective interventions for babies born too small or too soon is an urgent priority to increase survival and reduce disability, stunting, and non-communicable diseases. Funding Bill & Melinda Gates Foundation by a grant to the US Fund for UNICEF to
Chu, Carlton; Lagercrantz, Hugo; Forssberg, Hans; Nagy, Zoltan
Preterm birth has been shown to induce an altered developmental trajectory of brain structure and function. With the aid support vector machine (SVM) classification methods we aimed to investigate whether MRI data, collected in adolescence, could be used to predict whether an individual had been born preterm or at term. To this end we collected T1-weighted anatomical MRI data from 143 individuals (69 controls, mean age 14.6y). The inclusion criteria for those born preterm were birth weight ≤ 1500g and gestational age < 37w. A linear SVM was trained on the grey matter segment of MR images in two different ways. First, all the individuals were used for training and classification was performed by the leave-one-out method, yielding 93% correct classification (sensitivity = 0.905, specificity = 0.942). Separately, a random half of the available data were used for training twice and each time the other, unseen, half of the data was classified, resulting 86% and 91% accurate classifications. Both gestational age (R = -0.24, p<0.04) and birth weight (R = -0.51, p < 0.001) correlated with the distance to decision boundary within the group of individuals born preterm. Statistically significant correlations were also found between IQ (R = -0.30, p < 0.001) and the distance to decision boundary. Those born small for gestational age did not form a separate subgroup in these analyses. The high rate of correct classification by the SVM motivates further investigation. The long-term goal is to automatically and non-invasively predict the outcome of preterm-born individuals on an individual basis using as early a scan as possible.
Kistner, A; Deschmann, E; Legnevall, L; Vanpee, M
Aim This study examined the relationship between hypothalamic-associated hormones and behavioural and eating disorders in children with low birthweight. Methods We included 100 children (mean age 9.7 years): 39 were born preterm at <32 gestational weeks, 28 were full-term, but small for gestational age, and 33 were full-term controls. Behavioural histories were analysed, together with fasting blood samples of leptin, insulin, insulin-like growth factor-1 (IGF-I), prolactin, glucagon and cortisol. Results Preterm children had lower prolactin (p = 0.01) and higher IGF-I than controls (p < 0.05, adjusted for confounders), despite being significantly shorter than the predicted target height (p < 0.001). More preterm children displayed behavioural disorders (38% versus 10%, p < 0.001) and eating disorders (26% versus 8%, p < 0.05) than full-term children. These disorders were associated with lower leptin (p < 0.01), insulin (p < 0.05) and IGF-I (p < 0.05), but correlations between these hormones and leptin were similar among the groups. Combined behavioural and eating disorders were only observed in preterm children, who were also the shortest in height. Conclusion Behavioural and eating disorders among preterm children were associated with low leptin, insulin and IGF-1. Low prolactin in all preterm children indicated an increased dopaminergic tonus, which might inhibit body weight incrementation. This raises speculation about IGF-I receptor insensitivity. PMID:25040495
Urben, Sébastien; Van Hanswijck De Jonge, Laurence; Barisnikov, Koviljka; Pizzo, Roxane; Monnier, Maryline; Lazeyras, François; Borradori Tolsa, Cristina; Hüppi, Petra S
Within preterm-born children, being born male and at a lower gestational age (GA) have both been associated with a heightened risk for developmental difficulties. However, in this population little is known about the combined effect and the influence of these risk factors on cortical structures and executive control. In the present study, 58 preterm-born children (GA ranging from 24.0 to 35.1 weeks) were administered the computerized Child Attention Network Task at 6 years of age. Brain magnetic resonance imaging was performed and analyzed using Voxel-Based Morphometry (VBM) in all children. At a behavioral level, boys born <28 weeks of GA had significantly less executive control than preterm-born girls <28 weeks (p = .001) and preterm-born boys ≥28 (p = .003). The reduced executive control in preterm-born boys <28 weeks gestation was related to lower cortical densities in the inferior frontal gyrus (IFG) and dorsolateral prefrontal cortex (DLPFC). The current study links the higher incidence of reduced executive control in preterm-born boys to a higher degree of prematurity (low GA) and identifies brain structural abnormalities in the prefrontal cortex related to these deficits. The implications of these results are discussed.
Linsell, Louise; Malouf, Reem; Morris, Joan; Kurinczuk, Jennifer J; Marlow, Neil
Aim There is a large literature reporting risk factor analyses for poor neurodevelopment in children born very preterm (VPT: ≤32wks) or very low birthweight (VLBW: ≤1250g), which to date has not been formally summarized. The aim of this paper was to identify prognostic factors for cerebral palsy (CP) and motor impairment in children born VPT/VLBW. Method A systematic review was conducted using Medline, Embase, and Pyscinfo databases to identify studies published between 1 January 1990 and 1 June 2014 reporting multivariable prediction models for poor neurodevelopment in VPT/VLBW children (registration number CRD42014006943). Twenty-eight studies for motor outcomes were identified. Results There was strong evidence that intraventricular haemorrhage and periventricular leukomalacia, and some evidence that the use of postnatal steroids and non-use of antenatal steroids, were prognostic factors for CP. Male sex and gestational age were of limited use as prognostic factors for CP in cohorts restricted to ≤32 weeks gestation; however, in children older than 5 years with no major disability, there was evidence that male sex was a predictive factor for motor impairment. Interpretation This review has identified factors which may be of prognostic value for CP and motor impairment in VPT/VLBW children and will help to form the basis of future prognostic research. PMID:26862030
Huang, June-Hui; Huang, Huei-Lin; Chen, Hsiu-Lin; Lin, Lung-Chang; Tseng, Hsing-I; Kao, Tsung-Jen
The objective of this study was to examine the impact of low birth weight and preterm birth on a toddler's inattention and development, including cognitive, language, motor, social-emotional and adaptive behaviors. A total of 105 toddlers enrolled for the study; they were divided into four groups: 40 full-term and normal birth weight (NBW, birth weight greater than 2500 g) toddlers, 24 moderate birth weight (MLBW, birth weight between 2499 and 1500 g) toddlers, 20 very to extremely low birth weight (V-ELBW, 12 between 1000 and 1499 g and 8 lower than 1000 g) toddlers, and 21 term toddlers who were recruited from a clinic of developmental delay as the developmental delay at risk (DDR) group. The Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III) and Disruptive Behavior Rating Scale-Toddler were used. The findings were as follows: (1) DDR group performed worst in BSID-III; (2) although there were no statistical differences among the NBW, MLBW, and V-ELBW groups in BSID-III, the lower the birth weight, the lower the average performance, especially in language, adaptive social behavior, and adaptive practical behavior; and (3) comparing the inattention score, the DDR group was the poorest, normal and V-ELBW groups were the best, and MLBW group was in the middle. In conclusion, low birth weight and preterm delivery affected children's inattention and development of language, adaptive social behavior, and adaptive practical behavior.
Marchman, Virginia A; Adams, Katherine A; Loi, Elizabeth C; Fernald, Anne; Feldman, Heidi M
As rates of prematurity continue to rise, identifying which preterm children are at increased risk for learning disabilities is a public health imperative. Identifying continuities between early and later skills in this vulnerable population can also illuminate fundamental neuropsychological processes that support learning in all children. At 18 months adjusted age, we used socioeconomic status (SES), medical variables, parent-reported vocabulary, scores on the Bayley Scales of Infant and Toddler Development (third edition) language composite, and children's lexical processing speed in the looking-while-listening (LWL) task as predictor variables in a sample of 30 preterm children. Receptive vocabulary as measured by the Peabody Picture Vocabulary Test (fourth edition) at 36 months was the outcome. Receptive vocabulary was correlated with SES, but uncorrelated with degree of prematurity or a composite of medical risk. Importantly, lexical processing speed was the strongest predictor of receptive vocabulary (r = -.81), accounting for 30% unique variance. Individual differences in lexical processing efficiency may be able to serve as a marker for information processing skills that are critical for language learning.
Lipman, Ellen L.; Georgiades, Katholiki; Boyle, Michael H.
Objective: Children of teen mothers exhibit adverse outcomes through adolescence. It is unclear whether these adverse outcomes extend to adulthood and apply to all of her children, or only those born when she was a teen. We examine the associations between young adult functioning and being born to a teen mother aged less than or equal to 20 years…
Gladstone, Melissa; Oliver, Clare; Van den Broek, Nynke
Background Premature birth is the leading cause of neonatal death and second leading in children under 5. Information on outcomes of preterm babies surviving the early neonatal period is sparse although it is considered a major determinant of immediate and long-term morbidity. Methods Systematic review of studies reporting outcomes for preterm babies in low and middle income settings was conducted using electronic databases, citation tracking, expert recommendations and “grey literature”. Reviewers screened titles, abstracts and articles. Data was extracted using inclusion and exclusion criteria, study site and facilities, assessment methods and outcomes of mortality, morbidity, growth and development. The Child Health Epidemiology Reference Group criteria (CHERG) were used to assess quality. Findings Of 197 eligible publications, few (10.7%) were high quality (CHERG). The majority (83.3%) report on the outcome of a sample of preterm babies at time of birth or admission. Only 16.0% studies report population-based data using standardised mortality definitions. In 50.5% of studies, gestational age assessment method was unclear. Only 15.8% followed-up infants for 2 years or more. Growth was reported using standardised definitions but recommended morbidity definitions were rarely used. The criteria for assessment of neurodevelopmental outcomes was variable with few standardised tools - Bayley II was used in approximately 33% of studies, few studies undertook sensory assessments. Conclusions To determine the relative contribution of preterm birth to the burden of disease in children and to inform the planning of healthcare interventions to address this burden, a renewed understanding of the assessment and documentation of outcomes for babies born preterm is needed. More studies assessing outcomes for preterm babies who survive the immediate newborn period are needed. More consistent use of data is vital with clear and aligned definitions of health outcomes in
Brown, Josephine V.; Bakeman, Roger; Sampers, Jackie S.; Korner, Anneliese F.; Constantinou, Janet C.; Anand, K. J. S.
In spite of numerous recent outcome studies of extremely low birth weight (ELBW) infants, no data exist on their development prior to term. In this study we traced and compared the neurobehavioral development of 251 ELBW (less than 1,000 g) and 240 low birth weight (LBW; 1,000 g-2,500 g) preterms born between 1995 and 2004 from 32 to 37 weeks…
Linsell, Louise; Malouf, Reem; Morris, Joan; Kurinczuk, Jennifer J.; Marlow, Neil
Importance Cognitive delay is the most common form of impairment among children born very preterm (VPT) at 32 weeks or less or with very low birth weight (VLBW) of 1250 g or less. It is important to identify factors that are robust predictors of long-term outcome because the ability to predict future prognosis will assist in health care and educational service planning and provision. Objective To identify prognostic factors for poor cognitive development in children born VPT or with VLBW. Evidence Review A systematic review was conducted using MEDLINE, EMBASE, and PyscINFO databases to identify studies published between January 1, 1990, and June 1, 2014, reporting multivariable prediction models for neurodevelopment in VPT or VLBW children. Thirty-one studies comprising 98 risk factor models for cognitive outcome were identified. Two independent reviewers extracted key information on study design, outcome definition, risk factor selection, model development, and reporting and conducted a risk-of-bias assessment. Findings There was evidence that male sex, nonwhite race/ethnicity, lower level of parental education, and lower birth weight were predictive of global cognitive impairment in children younger than 5 years. In older children, only the influence of parental education was sustained. Male sex was also predictive of language impairment in early infancy, but not in middle childhood. Gestational age was a poor predictor of cognitive outcome, probably because of a reduced discriminatory power in cohorts restricted to a narrow gestational age range. The prognostic value of neonatal brain injury was unclear; however, studies adopted mixed strategies for managing children with physical or neurosensory disability. Conclusions and Relevance The influence of perinatal risk factors on cognitive development of VPT or VLBW children appears to diminish over time as environmental factors become more important. It is difficult to isolate cognitive outcomes from motor and
Molloy, Carly S; Di Battista, Ashley M; Anderson, Vicki A; Burnett, Alice; Lee, Katherine J; Roberts, Gehan; Cheong, Jeanie Ly; Anderson, Peter J; Doyle, Lex W
Children born extremely preterm (EP, <28 weeks) and/or extremely low birth weight (ELBW, <1000 g) have more academic deficiencies than their term-born peers, which may be due to problems with visual processing. The aim of this study is to determine (1) if visual processing is related to poor academic outcomes in EP/ELBW adolescents, and (2) how much of the variance in academic achievement in EP/ELBW adolescents is explained by visual processing ability after controlling for perinatal risk factors and other known contributors to academic performance, particularly attention and working memory. A geographically determined cohort of 228 surviving EP/ELBW adolescents (mean age 17 years) was studied. The relationships between measures of visual processing (visual acuity, binocular stereopsis, eye convergence, and visual perception) and academic achievement were explored within the EP/ELBW group. Analyses were repeated controlling for perinatal and social risk, and measures of attention and working memory. It was found that visual acuity, convergence and visual perception are related to scores for academic achievement on univariable regression analyses. After controlling for potential confounds (perinatal and social risk, working memory and attention), visual acuity, convergence and visual perception remained associated with reading and math computation, but only convergence and visual perception are related to spelling. The additional variance explained by visual processing is up to 6.6% for reading, 2.7% for spelling, and 2.2% for math computation. None of the visual processing variables or visual motor integration are associated with handwriting on multivariable analysis. Working memory is generally a stronger predictor of reading, spelling, and math computation than visual processing. It was concluded that visual processing difficulties are significantly related to academic outcomes in EP/ELBW adolescents; therefore, specific attention should be paid to academic
Lin, Vania W.; Baccarelli, Andrea A.; Burris, Heather H.
Preterm birth is a major cause of infant morbidity and mortality and a potential risk factor for adult chronic disease. With over 15 million infants born preterm worldwide each year, preterm birth poses a global health concern. There is a possible association between air pollution and preterm birth, though studies have been inconsistent, likely due to variation in study design. How air pollution induces health effects is uncertain; however, studies have repeatedly demonstrated the effects of air pollution on epigenetic modifications. More recent evidence suggests that epigenetics may, in turn, be linked to preterm birth. Discovery of environmentally modifiable epigenetic processes connected to preterm birth may help to identify women at risk of preterm birth, and ultimately lead to development of new preterm birth prevention measures. PMID:26900485
Feldman, Heidi M; Lee, Eliana S; Yeatman, Jason D; Yeom, Kristen W
Children born preterm are at risk for deficits in language and reading. They are also at risk for injury to the white matter of the brain. The goal of this study was to determine whether performance in language and reading skills would be associated with white matter properties in children born preterm and full-term. Children born before 36 weeks gestation (n=23, mean±SD age 12.5±2.0 years, gestational age 28.7±2.5 weeks, birth weight 1184±431 g) and controls born after 37 weeks gestation (n=19, 13.1±2.1 years, 39.3±1.0 weeks, 3178±413 g) underwent a battery of language and reading tests. Diffusion tensor imaging (DTI) scans were processed using tract-based spatial statistics to generate a core white matter skeleton that was anatomically comparable across participants. Fractional anisotropy (FA) was the diffusion property used in analyses. In the full-term group, no regions of the whole FA-skeleton were associated with language and reading. In the preterm group, regions of the FA-skeleton were significantly associated with verbal IQ, linguistic processing speed, syntactic comprehension, and decoding. Combined, the regions formed a composite map of 22 clusters on 15 tracts in both hemispheres and in the ventral and dorsal streams. ROI analyses in the preterm group found that several of these regions also showed positive associations with receptive vocabulary, verbal memory, and reading comprehension. Some of the same regions showed weak negative correlations within the full-term group. Exploratory multiple regression in the preterm group found that specific white matter pathways were related to different aspects of language processing and reading, accounting for 27-44% of the variance. The findings suggest that higher performance in language and reading in a group of preterm but not full-term children is associated with higher fractional anisotropy of a bilateral and distributed white matter network.
Treyvaud, Karli; Inder, Terrie E; Lee, Katherine J; Northam, Elisabeth A; Doyle, Lex W; Anderson, Peter J
Relationships between the home environment and early developmental outcomes were examined in 166 children born very preterm in one tertiary maternity hospital to explore whether a more optimal home environment could promote resilience. In particular, we explored whether this effect was apparent over and above social risk and children's biological risk, as measured by cerebral white matter abnormality (WMA) evaluated using magnetic resonance imaging (MRI) at term-corrected age and length of hospital stay (LOS), and whether the effect of the home environment differed according to WMA. The home environment and social-emotional outcomes were assessed at 2years' corrected age using the Home Screening Questionnaire (HSQ) and the Infant-Toddler Social and Emotional Assessment (ITSEA). Children's cognitive and motor development was assessed using the Bayley Scales of Infant Development II. A more optimal home environment was associated with better cognitive and social-emotional development after adjusting for social risk, WMA, and LOS. Neonatal cerebral WMA moderated the relationship between the home environment and dysregulation problems only, such that the home environment had less effect on dysregulation for children with mild or moderate to severe WMA. The need to support parents to create an optimal home environment is discussed.
Jakubs, Katherine; Bonde, Sara; Iosif, Robert E; Ekdahl, Christine T; Kokaia, Zaal; Kokaia, Merab; Lindvall, Olle
Inflammation influences several steps of adult neurogenesis, but whether it regulates the functional integration of the new neurons is unknown. Here, we explored, using confocal microscopy and whole-cell patch-clamp recordings, whether a chronic inflammatory environment affects the morphological and electrophysiological properties of new dentate gyrus granule cells, labeled with a retroviral vector encoding green fluorescent protein. Rats were exposed to intrahippocampal injection of lipopolysaccharide, which gave rise to long-lasting microglia activation. Inflammation caused no changes in intrinsic membrane properties, location, dendritic arborization, or spine density and morphology of the new cells. Excitatory synaptic drive increased to the same extent in new and mature cells in the inflammatory environment, suggesting increased network activity in hippocampal neural circuitries of lipopolysaccharide-treated animals. In contrast, inhibitory synaptic drive was more enhanced by inflammation in the new cells. Also, larger clusters of the postsynaptic GABA(A) receptor scaffolding protein gephyrin were found on dendrites of new cells born in the inflammatory environment. We demonstrate for the first time that inflammation influences the functional integration of adult-born hippocampal neurons. Our data indicate a high degree of synaptic plasticity of the new neurons in the inflammatory environment, which enables them to respond to the increase in excitatory input with a compensatory upregulation of activity and efficacy at their afferent inhibitory synapses.
Doengi, Michael; Krupp, Alexander J; Körber, Nils; Stein, Valentin
The survival of adult-born dentate gyrus granule cells critically depends on their synaptic integration into the existing neuronal network. Excitatory inputs are thought to increase the survival rate of adult born neurons. Therefore, whether enhancing the stability of newly formed excitatory synapses by overexpressing the synaptic cell adhesion molecule SynCAM 1 improves the survival of adult-born neurons was tested. Here it is shown that overexpression of SynCAM 1 improves survival of adult-born neurons, but has no effect on the proliferation rate of precursor cells. As expected, overexpression of SynCAM 1 increased the synapse density in adult-born granule neurons. While adult-born granule neurons have very few functional synapses 15 days after birth, it was found that at this age adult-born neurons in SynCAM 1 overexpressing mice exhibited around three times more excitatory synapses, which were stronger than synapses of adult-born neurons of control littermates. In summary, the data indicated that additional SynCAM 1 accelerated synapse maturation, which improved the stability of newly formed synapses and in turn increased the likelihood of survival of adult-born neurons.
Wu, Dan; Chang, Linda; Akazawa, Kentaro; Oishi, Kumiko; Skranes, Jon; Ernst, Thomas; Oishi, Kenichi
Preterm birth adversely affects postnatal brain development. In order to investigate the critical gestational age at birth (GAB) that alters the developmental trajectory of gray and white matter structures in the brain, we investigated diffusion tensor and quantitative T2 mapping data in 43 term-born and 43 preterm-born infants. A novel multivariate linear model-the change point model, was applied to detect change points in fractional anisotropy, mean diffusivity, and T2 relaxation time. Change points captured the "critical" GAB value associated with a change in the linear relation between GAB and MRI measures. The analysis was performed in 126 regions across the whole brain using an atlas-based image quantification approach to investigate the spatial pattern of the critical GAB. Our results demonstrate that the critical GABs are region- and modality-specific, generally following a central-to-peripheral and bottom-to-top order of structural development. This study may offer unique insights into the postnatal neurological development associated with differential degrees of preterm birth.
Patrianakos-Hoobler, Athena I.; Msall, Michael E.; Huo, Dezheng; Marks, Jeremy D.; Plesha-Troyke, Susan; Schreiber, Michael D.
Aim: To determine whether neurodevelopmental outcomes at the age of 2 years accurately predict school readiness in children who survived respiratory distress syndrome after preterm birth. Method: Our cohort included 121 preterm infants who received surfactant and ventilation and were enrolled in a randomized controlled study of inhaled nitric…
Radic, Julia A E; Vincer, Michael; McNeely, P Daniel
OBJECT Intraventicular hemorrhage (IVH) is a common complication of preterm birth, and the prognosis of IVH is incompletely characterized. The objective of this study was to describe the outcomes of IVH in a population-based cohort with minimal selection bias. METHODS All very preterm (≥ 30 completed weeks) patients born in the province of Nova Scotia were included in a comprehensive database. This database was screened for infants born to residents of Nova Scotia from January 1, 1993, to December 31, 2010. Among very preterm infants successfully resuscitated at birth, the numbers of infants who died, were disabled, developed cerebral palsy, developed hydrocephalus, were blind, were deaf, or had cognitive/language scores assessed were analyzed by IVH grade. The relative risk of each outcome was calculated (relative to the risk for infants without IVH). RESULTS Grades 2, 3, and 4 IVH were significantly associated with an increased overall mortality, primarily in the neonatal period, and the risk increased with increasing grade of IVH. Grade 4 IVH was significantly associated with an increased risk of disability (RR 2.00, p < 0.001), and the disability appeared to be primarily due to cerebral palsy (RR 6.07, p < 0.001) and cognitive impairment (difference in mean MDI scores between Grade 4 IVH and no IVH: -19.7, p < 0.001). No infants with Grade 1 or 2 IVH developed hydrocephalus, and hydrocephalus and CSF shunting were not associated with poorer outcomes when controlling for IVH grade. CONCLUSIONS Grades 1 and 2 IVH have much better outcomes than Grades 3 or 4, including a 0% risk of hydrocephalus in the Grade 1 and 2 IVH cohort. Given the low risk of selection bias, the results of this study may be helpful in discussing prognosis with families of very preterm infants diagnosed with IVH.
Simões, Eric A. F.; Anderson, Evan J.; Wu, Xionghua; Ambrose, Christopher S.
Objective To estimate the incidence of respiratory syncytial virus (RSV) disease as a function of chronologic age and exposure to young children in US preterm infants. Methods In the RSV Respiratory Events among Preterm Infants Outcomes and Risk Tracking (REPORT) study, preterm infants born at 32–35 weeks gestational age (wGA) were enrolled from 188 US clinics and followed September-May of 2009–2010 or 2010–2011. Infants with medically-attended acute respiratory illness had nasal/pharyngeal swabs collected for viral testing. Results of RSV tests conducted during routine clinical care were also collected. Event rates during November-March were modeled as a function of chronologic age and birth month using Poisson regression and adjusting for other covariates. Rates were calculated overall and for infants with and without exposure to young siblings or daycare attendance. Of 3317 infants screened, 1646 were enrolled as a consecutive sample. Infants with chronic lung disease of prematurity, hemodynamically significant congenital heart disease, life expectancy <6 months, or receiving or being considered for RSV immunoprophylaxis were excluded. 84% of patients completed the study. Demographics of the enrolled cohort were generally similar to those of US infants born at 32–35 wGA; infants 32–34 wGA, Hispanic infants, and infants of less-educated mothers were under-represented. Results Among 1642 evaluable infants, outpatient RSV lower respiratory illness incidence was highest at older ages, whereas RSV hospitalization and intensive care unit (ICU) admission were highest at younger ages. In all instances, young child exposure was associated with higher RSV incidence. The highest RSV hospitalization and ICU rates occurred among February-born infants with young child exposure, at 19.0 (95% CI, 13.5–27.0) and 6.5 (95% CI, 5.6–7.6) per 100 infant-seasons, respectively. Conclusions Preterm infants have a substantially elevated risk of RSV disease. Young age and
Franklin, Jeremy A; Anderson, Evan J; Wu, Xionghua; Ambrose, Christopher S; Simões, Eric A F
Background. Database studies have identified that public health insurance status is associated with an increased risk of severe respiratory syncytial virus (RSV) disease in US infants. However, these studies did not adjust for the presence of other risk factors and did not evaluate the risk in preterm infants. Methods. In this study, we evaluate the independent association between public insurance and severe RSV disease outcomes adjusting for other risk factors. The prospective, observational RSV Respiratory Events among Preterm Infants Outcomes and Risk Tracking (REPORT) study was conducted over 2 consecutive RSV seasons at 188 US clinical sites that enrolled preterm infants born at 32-35 wGA who had not received RSV immunoprophylaxis with palivizumab. Adjusted incidence rates per 100 infant-seasons of the RSV-associated endpoints of outpatient lower respiratory tract infection (LRI), emergency department (ED) visits, RSV hospitalizations (RSVHs), and intensive care unit admissions during peak RSV season (November-March) were compared for infants with private and public insurance. Results. Of 1642 evaluable infants enrolled in the REPORT study, 50.1% had private insurance and 49.9% had public health insurance. Adjusted rates of RSV outpatient LRIs were similar; however, rates of ED visits (hazard ratio [HR], 2.04; 95% confidence interval [CI], 1.20-3.45) were higher for subjects with public insurance, with a similar but nonsignificant trend observed for hospitalization (HR, 1.61; 95% CI, .93-2.78). Conclusions. Socioeconomic status, as evaluated by public versus private healthcare insurance, is a significant independent risk factor for ED use in US preterm infants and may contribute to increased RSVHs in this population.
Westera, J. J.; Houtzager, B. A.; Overdiek, B.; van Wassenaer, A. G.
The aim of the present study was to evaluate whether the application of Dutch versus US test procedures and norms of the Bayley Scales of Infant Development-2nd edition (BSID-II) leads to different developmental outcomes. The BSID-II was administered to 376 preterm infants (191 males, 185 females; mean gestational age 30wks [SD 2.7], mean…
... 70% of preterm infants are born during the late-preterm time frame. 3 Preterm birth is the most common cause of infant death ... NICHD News and Spotlights Common tests for preterm birth not useful for ... in treating mildly low thyroid function in pregnancy, NIH Network study finds ...
Hayakawa, M; Okumura, A; Hayakawa, F; Watanabe, K; Ohshiro, M; Kato, Y; Takahashi, R; Tauchi, N
AIMS—To clarify the features of the background electroencephalographic (EEG) activities in clinically well preterm infants born at less than 27 weeks gestation and to outline their chronological changes with increasing postconceptional age (PCA). METHODS—EEGs of clinically well premature infants born at less than 27 weeks gestation were recorded during the early postnatal period. The infants were separated into three groups according to their PCA at the time of EEG recording (21-22 weeks PCA, 23-24 weeks PCA, and 25-26 weeks PCA). The mean and maximum duration of interburst intervals (IBIs), the mean duration of bursts, and the percentage of continuous and discontinuous patterns in each PCA group were evaluated. RESULTS—There were three infants at 21-22 weeks PCA, seven at 23-24 weeks PCA, and five at 25-26 weeks PCA. Eighteen EEG recordings were obtained. The mean and maximum IBI duration decreased with increasing PCA. The percentage of continuous patterns increased with increasing PCA. Conversely, the percentage of discontinuous patterns decreased with increasing PCA. CONCLUSIONS—In premature infants born at less than 27 weeks gestation, the characteristics of the background EEG activities were similar to those of older premature infants. These changes reflect the development of the central nervous system in this period. At less than 27 weeks gestational age, the characteristics of background EEG activities were found to be as follows: PMID:11320041
Pihko, Elina; Lönnberg, Piia; Lauronen, Leena; Wolford, Elina; Andersson, Sture; Lano, Aulikki; Metsäranta, Marjo; Nevalainen, Päivi
Children born extremely preterm (EPT) may have difficulties in response inhibition, but the neural basis of such problems is unknown. We recorded magnetoencephalography (MEG) during a somatosensory Go/NoGo task in 6-year-old children born EPT (n = 22) and in children born full term (FT; n = 21). The children received tactile stimuli randomly to their left little (target) and index (non-target) finger and were instructed to squeeze a soft toy with the opposite hand every time they felt a stimulus on the little finger. Behaviorally, the EPT children performed worse than the FT children, both in responding to the target finger stimulation and in refraining from responding to the non-target finger stimulation. In MEG, after the non-target finger stimulation (i.e., during the response inhibition), the sensorimotor alpha oscillation levels in the contralateral-to-squeeze hemisphere were elevated in the FT children when compared with a condition with corresponding stimulation but no task (instead the children were listening to a story and not attending to the fingers). This NoGo task effect was absent in the EPT children. Further, in the sensorimotor cortex contralateral to the tactile stimulation, the post-stimulus suppression was less pronounced in the EPT than FT children. We suggest that the missing NoGo task effect and lower suppression of sensorimotor oscillations are markers of deficient functioning of the sensorimotor networks in the EPT children. PMID:28111544
Denizet, Marie; Cotter, Laurent; Lledo, Pierre-Marie; Lazarini, Françoise
The olfactory bulb (OB) is a highly plastic structure that can change organizational networks depending on environmental inputs in adult mammals. Particularly, in rodents, adult neurogenesis underlies plastic changes in the OB circuitry by continuously adding new interneurons to the network. We addressed the question of whether microglia, the immune cells of the brain, were involved in pruning OB neurons. Using lentiviral labeling of neurons in neonatal or adult mice and confocal analysis, we showed that microglia engulfed parts of neonatal-born and adult-born neurons in the healthy OB. We demonstrated that OB deafferentation by Dichlobenil administration induced sensory deprivation. It also increased phagocytosis of adult-born, but not neonatal-born neurons, by activated microglia. Conversely, intranasal lipopolysaccharide administration induced activation of microglia but changed neither adult neurogenesis nor olfaction. Our data reveal that steady-state microglia eliminate adult-born neurons and their synapses in both healthy and sensory deprived OBs, thereby adapting neuronal connections to the sensory experience.
Hodapp, Albert F.; LaVoie, Joseph C.
Five- to seven-year-old second-born children from white, middle-class, intact families were the subjects for this study. Older siblings served as role model for each child, and the parent surrogate models were selected from a pool and trained to act as the child's real parent. The imitation task emphasized verbal, postural, and motor responses of…
Zhuo, Jia-Min; Tseng, Hua-an; Desai, Mitul; Bucklin, Mark E; Mohammed, Ali I; Robinson, Nick TM; Boyden, Edward S; Rangel, Lara M; Jasanoff, Alan P; Gritton, Howard J; Han, Xue
Adult neurogenesis supports performance in many hippocampal dependent tasks. Considering the small number of adult-born neurons generated at any given time, it is surprising that this sparse population of cells can substantially influence behavior. Recent studies have demonstrated that heightened excitability and plasticity may be critical for the contribution of young adult-born cells for certain tasks. What is not well understood is how these unique biophysical and synaptic properties may translate to networks that support behavioral function. Here we employed a location discrimination task in mice while using optogenetics to transiently silence adult-born neurons at different ages. We discovered that adult-born neurons promote location discrimination during early stages of development but only if they undergo maturation during task acquisition. Silencing of young adult-born neurons also produced changes extending to the contralateral hippocampus, detectable by both electrophysiology and fMRI measurements, suggesting young neurons may modulate location discrimination through influences on bilateral hippocampal networks. DOI: http://dx.doi.org/10.7554/eLife.22429.001 PMID:27914197
Sharafi, Mastaneh; Duffy, Valerie B; Miller, Robin J; Winchester, Suzy B; Huedo-Medina, Tania B; Sullivan, Mary C
Being born prematurely associates with greater cardiovascular disease (CVD) risk in adulthood. Less understood are the unique and joint associations of dietary patterns and behaviors to this elevated risk among adults who are born prematurely. We aimed to model the associations between term status, dietary and lifestyle behaviors with CVD risk factors while accounting for the longitudinal effects of family protection, and medical or environmental risks. In wave-VIII of a longitudinal study, 23-year olds born prematurely (PT-adults, n = 129) and full term (FT-adults, n = 38) survey-reported liking for foods/beverages and activities, constructed into indexes of dietary quality and sensation-seeking, dietary restraint and physical activity. Measured CVD risk factors included fasting serum lipids and glucose, blood pressure and adiposity. In bivariate relationships, PT-adults reported lower dietary quality (including less affinity for protein-rich foods and higher affinity for sweets), less liking for sensation-seeking foods/activities, and less restrained eating than did FT-adults. In comparison to nationally-representative values and the FT-adults, PT-adults showed greater level of CVD risk factors for blood pressure and serum lipids. In structural equation modeling, dietary quality completely mediated the association between term status and HDL-cholesterol (higher quality, lower HDL-cholesterol) yet joined term status to explain variability in systolic blood pressure (PT-adults with lowest dietary quality had highest blood pressures). Through lower dietary quality, being born prematurely was indirectly linked to higher cholesterol/HDL, higher LDL/HDL and elevated waist/hip ratios. The relationship between dietary quality and CVD risk was strongest for PT-adults who had developed greater cumulative medical risk. Protective environments failed to attenuate relationships between dietary quality and elevated CVD risk among PT-adults. In summary, less healthy dietary
Allred, Elizabeth N; Dammann, Olaf; Fichorova, Raina N; Hooper, Stephen R; Hunter, Scott J; Joseph, Robert M; Kuban, Karl; Leviton, Alan; O'Shea, Thomas Michael; Scott, Megan N
Although multiple sources link inflammation with attention difficulties, the only human study that evaluated the relationship between systemic inflammation and attention problems assessed attention at age 2 years. Parent and/or teacher completion of the Childhood Symptom Inventory-4 (CSI-4) provided information about characteristics that screen for attention deficit hyperactive disorder (ADHD) among 793 10-year-old children born before the 28th week of gestation who had an IQ ≥ 70. The concentrations of 27 proteins in blood spots obtained during the first postnatal month were measured. 151 children with ADHD behaviors were identified by parent report, while 128 children were identified by teacher report. Top-quartile concentrations of IL-6R, TNF-α, IL-8, VEGF, VEFG-R1, and VEGF-R2 on multiple days were associated with increased risk of ADHD symptoms as assessed by a teacher. Some of this increased risk was modulated by top-quartile concentrations of IL-6R, RANTES, EPO, NT-4, BDNF, bFGF, IGF-1, PIGF, Ang-1, and Ang-2. Systemic inflammation during the first postnatal month among children born extremely preterm appears to increase the risk of teacher-identified ADHD characteristics, and high concentrations of proteins with neurotrophic properties appear capable of modulating this increased risk.
Kirshenbaum, Greer S.; Lieberman, Sophie R.; Briner, Tamara J.; Leonardo, E. David; Dranovsky, Alex
Recent evidence implicates adult hippocampal neurogenesis in regulating behavioral and physiologic responses to stress. Hippocampal neurogenesis occurs across the lifespan, however the rate of cell birth is up to 300% higher in adolescent mice compared to adults. Adolescence is a sensitive period in development where emotional circuitry and stress reactivity undergo plasticity establishing life-long set points. Therefore neurogenesis occurring during adolescence may be particularly important for emotional behavior. However, little is known about the function of hippocampal neurons born during adolescence. In order to assess the contribution of neurons born in adolescence to the adult stress response and depression-related behavior, we transiently reduced cell proliferation either during adolescence, or during adulthood in GFAP-Tk mice. We found that the intervention in adolescence did not change adult baseline behavioral response in the forced swim test, sucrose preference test or social affiliation test, and did not change adult corticosterone responses to an acute stressor. However following chronic social defeat, adult mice with reduced adolescent neurogenesis showed a resilient phenotype. A similar transient reduction in adult neurogenesis did not affect depression-like behaviors or stress induced corticosterone. Our study demonstrates that hippocampal neurons born during adolescence, but not in adulthood are important to confer susceptibility to chronic social defeat. PMID:25221485
Wang, Liang; Chang, Xingya; She, Liang; Xu, Duo; Huang, Wei; Poo, Mu-ming
Dendrite development of newborn granule cells (GCs) in the dentate gyrus of adult hippocampus is critical for their incorporation into existing hippocampal circuits, but the cellular mechanisms regulating their dendrite development remains largely unclear. In this study, we examined the function of brain-derived neurotrophic factor (BDNF), which is expressed in adult-born GCs, in regulating their dendrite morphogenesis. Using retrovirus-mediated gene transfection, we found that deletion and overexpression of BDNF in adult-born GCs resulted in the reduction and elevation of dendrite growth, respectively. This effect was mainly due to the autocrine rather than paracrine action of BDNF, because deletion of BDNF only in the newborn GCs resulted in dendrite abnormality of these neurons to a similar extent as that observed in conditional knockout (cKO) mice with BDNF deleted in the entire forebrain. Furthermore, selective expression of BDNF in adult-born GCs in BDNF cKO mice fully restored normal dendrite development. The BDNF autocrine action was also required for the development of normal density of spines and normal percentage of spines containing the postsynaptic marker PSD-95, suggesting autocrine BDNF regulation of synaptogenesis. Furthermore, increased dendrite growth of adult-born GCs caused by voluntary exercise was abolished by BDNF deletion specifically in these neurons and elevated dendrite growth due to BDNF overexpression in these neurons was prevented by reducing neuronal activity with coexpression of inward rectifier potassium channels, consistent with activity-dependent autocrine BDNF secretion. Therefore, BDNF expressed in adult-born GCs plays a critical role in dendrite development by acting as an autocrine factor.
Lind, Annika; Korkman, Marit; Lehtonen, Liisa; Lapinleimu, Helena; Parkkola, Riitta; Matomaki, Jaakko; Haataja, Leena
Aim: The aim of this study was to assess the cognitive level and neuropsychological performance at 5 years of age in children with a very low birthweight (VLBW; birthweight less than 1501g) born in 2001 to 2003. Method: A regional cohort of 97 children with a VLBW (mean gestational age 28wks [SD 3wks]; mean birthweight 1054g [SD 259g]; 50 male; 47…
Aquilino, William S.
Explored living arrangements among children born to unmarried mothers and the impact of childhood living arrangements on the young adult's life course. Analyses showed that living arrangement patterns after birth to a single mother influenced the likelihood of high school completion, post secondary education, and other conditions. (RJM)
Lindblad, Ida; Billstedt, Eva; Gillberg, Christopher; Fernell, Elisabeth
A group of 10 young adults from a population-based series in Sweden, of originally 42 individuals, born to mothers with mild intellectual disability (ID), were interviewed with regard to their experiences during childhood, adolescence, and their current situation. The interview revealed that 6 of the 10 individuals had been removed from their…
Lindblad, Ida; Billstedt, Eva; Gillberg, Christopher; Fernell, Elisabeth
Background: Young adults, born to population-representative mothers with intellectual disability (ID), were targeted for psychosocial/life event follow-up. Methods: The whole group originally comprised 42 individuals but 3 had died and 1 had moved abroad. The remaining 38 were approached and 10 consented to participate in an interview study.…
Moreno, Melissa M; Bath, Kevin; Kuczewski, Nicola; Sacquet, Joëlle; Didier, Anne; Mandairon, Nathalie
We have previously shown that an experience-driven improvement in olfactory discrimination (perceptual learning) requires the addition of newborn neurons in the olfactory bulb (OB). Despite this advance, the mechanisms which govern the selective survival of newborn OB neurons following learning remain largely unknown. We propose that activity of the noradrenergic system is a critical mediator providing a top-down signal to control the selective survival of newly born cells and support perceptual learning. In adult mice, we used pharmacological means to manipulate the noradrenergic system and neurogenesis and to assess their individual and additive effects on behavioral performance on a perceptual learning task. We then looked at the effects of these manipulations on regional survival of adult-born cells in the OB. Finally, using confocal imaging and electrophysiology, we investigated potential mechanisms by which noradrenaline could directly influence the survival of adult-born cells. Consistent with our hypotheses, direct manipulation of noradrenergic transmission significantly effect on adult-born cell survival and perceptual learning. Specifically, learning required both the presence of adult-born cell and noradrenaline. Finally, we provide a mechanistic link between these effects by showing that adult-born neurons receive noradrenergic projections and are responsive to noradrenaline. Based upon these data we argue that noradrenergic transmission is a key mechanism selecting adult-born neurons during learning and demonstrate that top-down neuromodulation acts on adult-born neuron survival to modulate learning performance.
Steinhoff-Wagner, Julia; Schönhusen, Ulrike; Zitnan, Rudolf; Hudakova, Monika; Pfannkuche, Helga; Hammon, Harald M
Oral glucose supply is important for neonatal calves to stabilize postnatal plasma glucose concentration. The objective of this study was to investigate ontogenic development of small intestinal growth, lactase activity, and glucose transporter in calves (n = 7 per group) that were born either preterm (PT; delivered by section 9 d before term) or at term (T; spontaneous vaginal delivery) or spontaneously born and fed colostrum for 4 days (TC). Tissue samples from duodenum and proximal, mid, and distal jejunum were taken to measure villus size and crypt depth, protein concentration of mucosa and brush border membrane vesicles (BBMV), total DNA and RNA concentration of mucosa, mRNA expression and activity of lactase, and mRNA expression of sodium-dependent glucose co-transporter-1 (SGLT1) and facilitative glucose transporter 2 (GLUT2) in mucosal tissue. Additionally, protein expression of SGLT1 in BBMV and GLUT2 in crude mucosal membranes and immunochemical localization of GLUT2 in the enterocytes were determined. Villus height in distal jejunum was lower in TC than in T. Crypt depth in all segments was largest and the villus height/crypt depth ratio in jejunum was smallest in TC calves. Concentration of RNA was highest in duodenal mucosa of TC calves, but neither lactase mRNA and activity nor SGLT1 and GLUT2 mRNA and protein expression differed among groups. Localization of GLUT2 in the apical membrane was greater, whereas in the basolateral membrane was lower in TC than in T and PT calves. Our study indicates maturation processes after birth for mucosal growth and trafficking of GLUT2 from the basolateral to the apical membrane. Minor differences of mucosal growth, lactase activity, and intestinal glucose transporters were seen between PT and T calves, pointing at the importance of postnatal maturation and feeding for mucosal growth and GLUT2 trafficking.
Steinhoff-Wagner, Julia; Schönhusen, Ulrike; Zitnan, Rudolf; Hudakova, Monika; Pfannkuche, Helga; Hammon, Harald M.
Oral glucose supply is important for neonatal calves to stabilize postnatal plasma glucose concentration. The objective of this study was to investigate ontogenic development of small intestinal growth, lactase activity, and glucose transporter in calves (n = 7 per group) that were born either preterm (PT; delivered by section 9 d before term) or at term (T; spontaneous vaginal delivery) or spontaneously born and fed colostrum for 4 days (TC). Tissue samples from duodenum and proximal, mid, and distal jejunum were taken to measure villus size and crypt depth, protein concentration of mucosa and brush border membrane vesicles (BBMV), total DNA and RNA concentration of mucosa, mRNA expression and activity of lactase, and mRNA expression of sodium-dependent glucose co-transporter-1 (SGLT1) and facilitative glucose transporter 2 (GLUT2) in mucosal tissue. Additionally, protein expression of SGLT1 in BBMV and GLUT2 in crude mucosal membranes and immunochemical localization of GLUT2 in the enterocytes were determined. Villus height in distal jejunum was lower in TC than in T. Crypt depth in all segments was largest and the villus height/crypt depth ratio in jejunum was smallest in TC calves. Concentration of RNA was highest in duodenal mucosa of TC calves, but neither lactase mRNA and activity nor SGLT1 and GLUT2 mRNA and protein expression differed among groups. Localization of GLUT2 in the apical membrane was greater, whereas in the basolateral membrane was lower in TC than in T and PT calves. Our study indicates maturation processes after birth for mucosal growth and trafficking of GLUT2 from the basolateral to the apical membrane. Minor differences of mucosal growth, lactase activity, and intestinal glucose transporters were seen between PT and T calves, pointing at the importance of postnatal maturation and feeding for mucosal growth and GLUT2 trafficking. PMID:26011395
Delane, Louise; Campbell, Catherine; Bayliss, Donna M; Reid, Corinne; Stephens, Amelia; French, Noel; Anderson, Mike
Children born very preterm (VP, ≤ 32 weeks) exhibit poor performance on tasks of executive functioning. However, it is largely unknown whether this reflects the cumulative impact of non-executive deficits or a separable impairment in executive-level abilities. A dual-task paradigm was used in the current study to differentiate the executive processes involved in performing two simple attention tasks simultaneously. The executive-level contribution to performance was indexed by the within-subject cost incurred to single-task performance under dual-task conditions, termed dual-task cost. The participants included 77 VP children (mean age: 7.17 years) and 74 peer controls (mean age: 7.16 years) who completed Sky Search (selective attention), Score (sustained attention) and Sky Search DT (divided attention) from the Test of Everyday Attention for Children. The divided-attention task requires the simultaneous performance of the selective- and sustained-attention tasks. The VP group exhibited poorer performance on the selective- and divided-attention tasks, and showed a strong trend toward poorer performance on the sustained-attention task. However, there were no significant group differences in dual-task cost. These results suggest a cumulative impact of vulnerable lower-level cognitive processes on dual-tasking or divided attention in VP children, and fail to support the hypothesis that VP children show a separable impairment in executive-level abilities.
Samaddar, Sreyashi; Vazquez, Kizzy; Ponkia, Dipen; Toruno, Pedro; Sahbani, Karim; Begum, Sultana; Abouelela, Ahmed; Mekhael, Wagdy; Ahmed, Zaghloul
Direct current electrical fields have been shown to be a major factor in the regulation of cell proliferation, differentiation, migration, and survival, as well as in the maturation of dividing cells during development. During adulthood, spinal cord cells are continuously produced in both animals and humans, and they hold great potential for neural restoration following spinal cord injury. While the effects of direct current electrical fields on adult-born spinal cells cultured ex vivo have recently been reported, the effects of direct current electrical fields on adult-born spinal cells in vivo have not been characterized. Here, we provide convincing findings that a therapeutic form of transspinal direct current stimulation (tsDCS) affects the migration and proliferation of adult-born spinal cells in mice. Specifically, cathodal tsDCS attracted the adult-born spinal cells, while anodal tsDCS repulsed them. In addition, both tsDCS polarities caused a significant increase in cell number. Regarding the potential mechanisms involved, both cathodal and anodal tsDCS caused significant increases in expression of brain-derived neurotrophic factor, while expression of nerve growth factor increased and decreased, respectively. In the spinal cord, both anodal and cathodal tsDCS increased blood flow. Since blood flow and angiogenesis are associated with the proliferation of neural stem cells, increased blood flow may represent a major factor in the modulation of newly born spinal cells by tsDCS. Consequently, we propose that the method and novel findings presented in the current study have the potential to facilitate cellular, molecular, and/or bioengineering strategies to repair injured spinal cords.NEW & NOTEWORTHY Our results indicate that transspinal direct current stimulation (tsDCS) affects the migratory pattern and proliferation of adult newly born spinal cells, a cell population which has been implicated in learning and memory. In addition, our results suggest a
Malvaut, Sarah; Saghatelyan, Armen
The adult mammalian brain is remarkably plastic and constantly undergoes structurofunctional modifications in response to environmental stimuli. In many regions plasticity is manifested by modifications in the efficacy of existing synaptic connections or synapse formation and elimination. In a few regions, however, plasticity is brought by the addition of new neurons that integrate into established neuronal networks. This type of neuronal plasticity is particularly prominent in the olfactory bulb (OB) where thousands of neuronal progenitors are produced on a daily basis in the subventricular zone (SVZ) and migrate along the rostral migratory stream (RMS) towards the OB. In the OB, these neuronal precursors differentiate into local interneurons, mature, and functionally integrate into the bulbar network by establishing output synapses with principal neurons. Despite continuous progress, it is still not well understood how normal functioning of the OB is preserved in the constantly remodelling bulbar network and what role adult-born neurons play in odor behaviour. In this review we will discuss different levels of morphofunctional plasticity effected by adult-born neurons and their functional role in the adult OB and also highlight the possibility that different subpopulations of adult-born cells may fulfill distinct functions in the OB neuronal network and odor behaviour. PMID:26839709
Malvaut, Sarah; Saghatelyan, Armen
The adult mammalian brain is remarkably plastic and constantly undergoes structurofunctional modifications in response to environmental stimuli. In many regions plasticity is manifested by modifications in the efficacy of existing synaptic connections or synapse formation and elimination. In a few regions, however, plasticity is brought by the addition of new neurons that integrate into established neuronal networks. This type of neuronal plasticity is particularly prominent in the olfactory bulb (OB) where thousands of neuronal progenitors are produced on a daily basis in the subventricular zone (SVZ) and migrate along the rostral migratory stream (RMS) towards the OB. In the OB, these neuronal precursors differentiate into local interneurons, mature, and functionally integrate into the bulbar network by establishing output synapses with principal neurons. Despite continuous progress, it is still not well understood how normal functioning of the OB is preserved in the constantly remodelling bulbar network and what role adult-born neurons play in odor behaviour. In this review we will discuss different levels of morphofunctional plasticity effected by adult-born neurons and their functional role in the adult OB and also highlight the possibility that different subpopulations of adult-born cells may fulfill distinct functions in the OB neuronal network and odor behaviour.
Villasana, Laura E.; Kim, Kristine N.
Abstract Traumatic brain injury (TBI) increases hippocampal neurogenesis, which may contribute to cognitive recovery after injury. However, it is unknown whether TBI-induced adult-born neurons mature normally and functionally integrate into the hippocampal network. We assessed the generation, morphology, and synaptic integration of new hippocampal neurons after a controlled cortical impact (CCI) injury model of TBI. To label TBI-induced newborn neurons, we used 2-month-old POMC-EGFP mice, which transiently and specifically express EGFP in immature hippocampal neurons, and doublecortin-CreERT2 transgenic mice crossed with Rosa26-CAG-tdTomato reporter mice, to permanently pulse-label a cohort of adult-born hippocampal neurons. TBI increased the generation, outward migration, and dendritic complexity of neurons born during post-traumatic neurogenesis. Cells born after TBI had profound alterations in their dendritic structure, with increased dendritic branching proximal to the soma and widely splayed dendritic branches. These changes were apparent during early dendritic outgrowth and persisted as these cells matured. Whole-cell recordings from neurons generated during post-traumatic neurogenesis demonstrate that they are excitable and functionally integrate into the hippocampal circuit. However, despite their dramatic morphologic abnormalities, we found no differences in the rate of their electrophysiological maturation, or their overall degree of synaptic integration when compared to age-matched adult-born cells from sham mice. Our results suggest that cells born after TBI participate in information processing, and receive an apparently normal balance of excitatory and inhibitory inputs. However, TBI-induced changes in their anatomic localization and dendritic projection patterns could result in maladaptive network properties. PMID:26478908
Breton-Provencher, Vincent; Bakhshetyan, Karen; Hardy, Delphine; Bammann, Rodrigo Roberto; Cavarretta, Francesco; Snapyan, Marina; Côté, Daniel; Migliore, Michele; Saghatelyan, Armen
Adult-born neurons adjust olfactory bulb (OB) network functioning in response to changing environmental conditions by the formation, retraction and/or stabilization of new synaptic contacts. While some changes in the odour environment are rapid, the synaptogenesis of adult-born neurons occurs over a longer time scale. It remains unknown how the bulbar network functions when rapid and persistent changes in environmental conditions occur but when new synapses have not been formed. Here we reveal a new form of structural remodelling where mature spines of adult-born but not early-born neurons relocate in an activity-dependent manner. Principal cell activity induces directional growth of spine head filopodia (SHF) followed by spine relocation. Principal cell-derived glutamate and BDNF regulate SHF motility and directional spine relocation, respectively; and spines with SHF are selectively preserved following sensory deprivation. Our three-dimensional model suggests that spine relocation allows fast reorganization of OB network with functional consequences for odour information processing. PMID:27578235
Duan, Yuntao; Wang, Shih-Hsiu; Song, Juan; Mironova, Yevgeniya; Ming, Guo-li; Kolodkin, Alex L; Giger, Roman J
Human SEMAPHORIN 5A (SEMA5A) is an autism susceptibility gene; however, its function in brain development is unknown. In this study, we show that mouse Sema5A negatively regulates synaptogenesis in early, developmentally born, hippocampal dentate granule cells (GCs). Sema5A is strongly expressed by GCs and regulates dendritic spine density in a cell-autonomous manner. In the adult mouse brain, newly born Sema5A−/− GCs show an increase in dendritic spine density and increased AMPA-type synaptic responses. Sema5A signals through PlexinA2 co-expressed by GCs, and the PlexinA2-RasGAP activity is necessary to suppress spinogenesis. Like Sema5A−/− mutants, PlexinA2−/− mice show an increase in GC glutamatergic synapses, and we show that Sema5A and PlexinA2 genetically interact with respect to GC spine phenotypes. Sema5A−/− mice display deficits in social interaction, a hallmark of autism-spectrum-disorders. These experiments identify novel intra-dendritic Sema5A/PlexinA2 interactions that inhibit excitatory synapse formation in developmentally born and adult-born GCs, and they provide support for SEMA5A contributions to autism-spectrum-disorders. DOI: http://dx.doi.org/10.7554/eLife.04390.001 PMID:25313870
Linsell, Louise; Malouf, Reem; Johnson, Samantha; Morris, Joan; Kurinczuk, Jennifer J.; Marlow, Neil
Objective Risk factors associated with adverse behavioral outcomes in very preterm (VPT) or very low birth weight (VLBW) infants are poorly understood. The aim of this article is to identify prognostic factors for behavioral problems and psychiatric disorders in children born ≤32 weeks gestational age or with birth weight ≤1250 g. Method A systematic review was conducted using MEDLINE, Embase, and Pyscinfo databases to identify studies published between January 1, 1990 and June 1, 2014 reporting multivariable prediction models for behavioral problems or psychiatric disorders in VPT/VLBW children. Fifteen studies were identified and 2 independent reviewers extracted key information on study design, outcome definition, risk factor selection, model development, reporting, and conducted a risk of bias assessment. Results The 15 studies included reported risk factor analyses for the following domains: general behavioral problems (n = 8), any psychiatric disorder (n = 2), autism spectrum symptoms/disorders (n = 5), and attention deficit/hyperactivity disorder (n = 1). Findings were inconclusive because of the following: small number of studies in each domain, heterogeneity in outcome measures, lack of overlap in the risk factors examined, and differences in strategies for dealing with children with neurological impairments. Conclusion There is a lack of evidence concerning risk factors for behavior problems and psychiatric disorders among VPT/VLBW survivors. This review has identified the need for further research examining the etiology of disorders of psychological development in the VPT/VLBW population to refine risk prediction and identify targets for intervention. Large well-conducted studies that use standard diagnostic evaluations to assess psychiatric disorders throughout childhood and adolescence are required. PMID:26703327
Matta, Joane; Carette, Claire; Levy Marchal, Claire; Bertrand, Julien; Pétéra, Mélanie; Zins, Marie; Pujos-Guillot, Estelle; Comte, Blandine; Czernichow, Sébastien
Objectives Compare the dietary intake of young adults born small for gestational age (SGA) versus those born appropriate for gestational age (AGA). Design Cross-sectional analysis. Setting Data at the 8-year follow-up Haguenau cohort (France). Data from 229 AGA-born adults and 172 SGA-born adults with available dietary information are presented. Methods Dietary intake was based on a food questionnaire including 19 items. The χ2 test was run to compare intake between SGA-born and AGA-born individuals. An a priori score was calculated based on the adherence to recommendations from the French Nutrition and Health Program and included 8 components with the lowest value indicating a lower adherence to recommendations. The score was then divided into quartiles. Relative risks and 95% CIs, controlling for age and sex in multivariate analysis, were calculated in order to determine the risk of belonging to the first versus the second to the fourth quartiles in SGA-born and AGA-born individuals. Results Intakes of SGA-born adults indicated that they consumed more meat, sugar and less fish than AGA-born individuals (all p<0.05). Multivariate analyses with adjustment for age and sex showed that the relative risk of belonging to the first quartile versus the other three quartiles did not disclose any significant difference in SGA-born versus AGA-born participants: RR=0.92 (95% CI 0.65 to 1.30). Conclusions Aside from the differences found by univariate analyses, no significant differences were obtained in multivariate analyses. Findings suggest that parameters of fetal programming are more associated with the development of metabolic syndrome in adulthood rather than dietary patterns. PMID:27473954
Warkentien, Siri; Clark, Michael; Jacinto, Beth
Learning to read and write in the English language is a challenge faced by numerous foreign-born adults who arrive in the United States each year. Since 1970, the foreign-born population living in the United States has increased both in number and as a percentage share of the entire population (Census 2007; Schmidley 2001). This growth contributes…
Bogovic, Petra; Logar, Mateja; Avsic-Zupanc, Tatjana; Strle, Franc; Lotric-Furlan, Stanka
The aim of the present study was to quantify the severity of acute illness in patients with tick-borne encephalitis and to ascertain this approach by comparing it to standard clinical assessment. We designed scoring system for quantification of the severity of acute illness in patients with tick-borne encephalitis. Certain number of points was allotted to the presence, intensity, and duration of individual symptoms/signs. According to the obtained score the disease was classified as mild, moderate, and severe. Tick-borne encephalitis was assessed clinically as mild when only signs/symptoms of meningeal involvement were found, moderate in case of monofocal neurological signs and/or mild to moderate signs/symptoms of central nervous system dysfunction, and severe in patients with multifocal neurological signs and/or symptoms of severe dysfunction of central nervous system. By designed scoring system 282 adult patients, 146 males and 136 females, average aged 52.2 ± 15.5 years (range 15–82 years), with confirmed tick-borne encephalitis, were prospectively assessed. In 279/282 (98.9%) patients the severity according to clinical assessment matched with the score ranges for mild, moderate, and severe disease. The proposed approach enables precise and straightforward appraisal of the severity of acute illness and could be useful for comparison of findings within/between study groups. PMID:24895617
Bonzano, Sara; Bovetti, Serena; Gendusa, Claudio; Peretto, Paolo; De Marchis, Silvia
The olfactory bulb (OB) is a highly plastic brain region involved in the early processing of olfactory information. A remarkably feature of the OB circuits in rodents is the constitutive integration of new neurons that takes place during adulthood. Newborn cells in the adult OB are mostly inhibitory interneurons belonging to chemically, morphologically and functionally heterogeneous types. Although there is general agreement that adult neurogenesis in the OB plays a key role in sensory information processing and olfaction-related plasticity, the contribution of each interneuron subtype to such functions is far to be elucidated. Here, we focus on the dopaminergic (DA) interneurons: we highlight recent findings about their morphological features and then describe the molecular factors required for the specification/differentiation and maintenance of the DA phenotype in adult born neurons. We also discuss dynamic changes of the DA interneuron population related to age, environmental stimuli and lesions, and their possible functional implications. PMID:27199651
Mandyam, Chitra D; Koob, George F
Addiction is a chronic relapsing disorder associated with compulsive drug taking, drug seeking and a loss of control in limiting intake, reflected in three stages of a recurrent cycle: binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation ("craving"). This review discusses the role of adult-born neural and glial progenitors in drug seeking associated with the different stages of the addiction cycle. A review of the current literature suggests that the loss of newly born progenitors, particularly in hippocampal and cortical regions, plays a role in determining vulnerability to relapse in rodent models of drug addiction. The normalization of drug-impaired neurogenesis or gliogenesis may help reverse neuroplasticity during abstinence and, thus, may help reduce the vulnerability to relapse and aid recovery.
Khatun, Mohsina; Al Mamun, Abdullah; Scott, James; William, Gail M.; Clavarino, Alexandra; Najman, Jake M.
Teenage motherhood has been associated with a wide variety of negative offspring outcomes including poorer cognitive development. In the context of limitations of previous research, this paper assesses the contemporary relevance of this finding. In this study we investigate the long-term cognitive status (IQ) among 21 year adult offspring born to teenage parents using the Mater University Study of Pregnancy- a prospective birth cohort study, which recruited all pregnant mothers attending a large obstetrical hospital in Brisbane, Australia, from 1981 to 1983. The analyses were restricted to a sub-sample of 2643 mother-offspring pair. Offspring IQ was measured using the Peabody Picture Vocabulary Test at 21 year. Parental age was reported at first clinic visit. Offspring born to teenage mothers (<20 years) have -3.0 (95% Confidence Interval (CI): -4.3, -1.8) points lower IQ compared to children born to mothers ≥20 years and were more likely to have a low IQ (Odds Ratio (OR) 1.7; 95% CI: 1.3, 2.3). Adjustment for a range of confounding and mediating factors including parental socioeconomic status, maternal IQ, maternal smoking and binge drinking in pregnancy, birthweight, breastfeeding and parenting style attenuates the association, though the effect remains statistically significant (-1.4 IQ points; 95% CI: -2.8,-0.1). Similarly the risk of offspring having low IQ remained marginally significantly higher in those born to teenage mothers (OR 1.3; 95% CI: 1.0, 1.9). In contrast, teenage fatherhood is not associated with adult offspring IQ, when adjusted for maternal age. Although the reduction in IQ is quantitatively small, it is indicative of neurodevelopmental disadvantage experienced by the young adult offspring of teenage mothers. Our results suggest that public policy initiatives should be targeted not only at delaying childbearing in the population but also at supporting early life condition of children born to teenage mothers to minimize the risk for
Bergami, Matteo; Masserdotti, Giacomo; Temprana, Silvio G; Motori, Elisa; Eriksson, Therese M; Göbel, Jana; Yang, Sung Min; Conzelmann, Karl-Klaus; Schinder, Alejandro F; Götz, Magdalena; Berninger, Benedikt
Neurogenesis in the dentate gyrus (DG) of the adult hippocampus is a process regulated by experience. To understand whether experience also modifies the connectivity of new neurons, we systematically investigated changes in their innervation following environmental enrichment (EE). We found that EE exposure between 2-6 weeks following neuron birth, rather than merely increasing the number of new neurons, profoundly affected their pattern of monosynaptic inputs. Both local innervation by interneurons and to even greater degree long-distance innervation by cortical neurons were markedly enhanced. Furthermore, following EE, new neurons received inputs from CA3 and CA1 inhibitory neurons that were rarely observed under control conditions. While EE-induced changes in inhibitory innervation were largely transient, cortical innervation remained increased after returning animals to control conditions. Our findings demonstrate an unprecedented experience-dependent reorganization of connections impinging onto adult-born neurons, which is likely to have important impact on their contribution to hippocampal information processing.
Sánchez-González, Liliana; Rodriguez-Lainz, Alfonso; O'Halloran, Alissa; Rowhani-Rahbar, Ali; Liang, Jennifer L; Lu, Peng-Jun; Houck, Peter M; Verguet, Stephane; Williams, Walter W
Pertussis is a common vaccine-preventable disease (VPD) worldwide. Its reported incidence has increased steadily in the United States, where it is endemic. Tetanus is a rare but potentially fatal VPD. Foreign-born adults have lower tetanus-diphtheria-pertussis (Tdap) and tetanus-diphtheria (Td) vaccination coverage than do U.S.-born adults. We studied the association of migration-related, socio-demographic, and access-to-care factors with Tdap and Td vaccination among foreign-born adults living in the United States. The 2012 and 2013 National Health Interview Survey data for foreign-born respondents were analyzed. Multivariable logistic regression was conducted to calculate prevalence ratios and 95% confidence intervals, and to identify variables independently associated with Tdap and Td vaccination among foreign-born adults. Tdap and Td vaccination status was available for 9316 and 12,363 individuals, respectively. Overall vaccination coverage was 9.1% for Tdap and 49.8% for Td. Younger age, higher education, having private health insurance (vs. public insurance or uninsured), having visited a doctor in the previous year, and region of residence were independently associated with Tdap and Td vaccination. Among those reporting a doctor visit, two-thirds had not received Tdap. This study provides further evidence of the need to enhance access to health care and immunization services and reduce missed opportunities for Tdap and Td vaccination for foreign-born adults in the United States. These findings apply to all foreign-born, irrespective of their birthplace, citizenship, language and years of residence in the United States. Addressing vaccination disparities among the foreign-born will help achieve national vaccination goals and protect all communities in the United States.
Ding, Tianbing; McConaha, Melinda; Boyd, Kelli L; Osteen, Kevin G; Bruner-Tran, Kaylon L
We have previously described diminished uterine progesterone response and increased uterine sensitivity to inflammation in adult female mice with a history of developmental exposure to TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin). Since parturition in mammals is an inflammatory process mediated in part by a decline in progesterone action, toxicant-mediated disruption of progesterone receptor (PR) expression at the maternal-fetal interface would likely impact the timing of birth. Therefore, in the current study, we examined pregnancy outcomes in adult female mice with a similar in utero exposure to TCDD. We also examined the impact of in utero TCDD exposure of male mice on pregnancy outcomes in unexposed females since the placenta, a largely paternally derived organ, plays a major role in the timing of normal parturition via inflammatory signaling. Our studies indicate that developmental exposure of either parent to TCDD is associated with preterm birth in a subsequent adult pregnancy due to altered PR expression and placental inflammation.
Winkle, Cortney C.; Olsen, Reid H. J.; Kim, Hyojin; Moy, Sheryl S.
During hippocampal development, newly born neurons migrate to appropriate destinations, extend axons, and ramify dendritic arbors to establish functional circuitry. These developmental stages are recapitulated in the dentate gyrus of the adult hippocampus, where neurons are continuously generated and subsequently incorporate into existing, local circuitry. Here we demonstrate that the E3 ubiquitin ligase TRIM9 regulates these developmental stages in embryonic and adult-born mouse hippocampal neurons in vitro and in vivo. Embryonic hippocampal and adult-born dentate granule neurons lacking Trim9 exhibit several morphological defects, including excessive dendritic arborization. Although gross anatomy of the hippocampus was not detectably altered by Trim9 deletion, a significant number of Trim9−/− adult-born dentate neurons localized inappropriately. These morphological and localization defects of hippocampal neurons in Trim9−/− mice were associated with extreme deficits in spatial learning and memory, suggesting that TRIM9-directed neuronal morphogenesis may be involved in hippocampal-dependent behaviors. SIGNIFICANCE STATEMENT Appropriate generation and incorporation of adult-born neurons in the dentate gyrus are critical for spatial learning and memory and other hippocampal functions. Here we identify the brain-enriched E3 ubiquitin ligase TRIM9 as a novel regulator of embryonic and adult hippocampal neuron shape acquisition and hippocampal-dependent behaviors. Genetic deletion of Trim9 elevated dendritic arborization of hippocampal neurons in vitro and in vivo. Adult-born dentate granule cells lacking Trim9 similarly exhibited excessive dendritic arborization and mislocalization of cell bodies in vivo. These cellular defects were associated with severe deficits in spatial learning and memory. PMID:27147649
De La Rosa-Prieto, Carlos; De Moya-Pinilla, Miguel; Saiz-Sanchez, Daniel; Ubeda-banon, Isabel; Arzate, Dulce M.; Flores-Cuadrado, Alicia; Liberia, Teresa; Crespo, Carlos; Martinez-Marcos, Alino
New neurons are continually generated in the subependymal layer of the lateral ventricles and the subgranular zone of dentate gyrus during adulthood. In the subventricular zone, neuroblasts migrate a long distance to the olfactory bulb where they differentiate into granule or periglomerular interneurons. In the hippocampus, neuroblasts migrate a short distance from the subgranular zone to the granule cell layer of the dentate gyrus to become granule neurons. In addition to the short-distance inputs, bulbar interneurons receive long-distance centrifugal afferents from olfactory-recipient structures. Similarly, dentate granule cells receive differential inputs from the medial and lateral entorhinal cortices through the perforant pathway. Little is known concerning these new inputs on the adult-born cells. In this work, we have characterized afferent inputs to 21-day old newly-born neurons. Mice were intraperitoneally injected with bromodeoxyuridine. Two weeks later, rhodamine-labeled dextran-amine was injected into the anterior olfactory nucleus, olfactory tubercle, piriform cortex and lateral and medial entorhinal cortices. One week later, animals were perfused and immunofluorescences were carried out. The data show that projection neurons from the mentioned structures, establish putative synaptic contacts onto 21-day-old neurons in the olfactory bulb and dentate gyrus, in some cases even before they start to express specific subpopulation proteins. Long-distance afferents reach middle and outer one-third portions of the molecular layer of the dentate gyrus and granule and, interestingly, periglomerular layers of the olfactory bulb. In the olfactory bulb, these fibers appear to establish presumptive axo-somatic contacts onto newly-born granule and periglomerular cells. PMID:25698936
Adlaf, Elena W; Vaden, Ryan J; Niver, Anastasia J; Manuel, Allison F; Onyilo, Vincent C; Araujo, Matheus T; Dieni, Cristina V; Vo, Hai T; King, Gwendalyn D; Wadiche, Jacques I; Overstreet-Wadiche, Linda
Adult-born neurons are continually produced in the dentate gyrus but it is unclear whether synaptic integration of new neurons affects the pre-existing circuit. Here we investigated how manipulating neurogenesis in adult mice alters excitatory synaptic transmission to mature dentate neurons. Enhancing neurogenesis by conditional deletion of the pro-apoptotic gene Bax in stem cells reduced excitatory postsynaptic currents (EPSCs) and spine density in mature neurons, whereas genetic ablation of neurogenesis increased EPSCs in mature neurons. Unexpectedly, we found that Bax deletion in developing and mature dentate neurons increased EPSCs and prevented neurogenesis-induced synaptic suppression. Together these results show that neurogenesis modifies synaptic transmission to mature neurons in a manner consistent with a redistribution of pre-existing synapses to newly integrating neurons and that a non-apoptotic function of the Bax signaling pathway contributes to ongoing synaptic refinement within the dentate circuit. DOI: http://dx.doi.org/10.7554/eLife.19886.001 PMID:28135190
Schmidt, Louis A.; Miskovic, Vladimir; Boyle, Michael; Saigal, Saroj
The authors examined internalizing behavior problems at middle childhood, adolescence, and young adulthood and brain-based measures of stress vulnerability in 154 right-handed, nonimpaired young adults (M age = 23 years): 71 (30 males, 41 females) born at extremely low birth weight (ELBW; less than 1,000 g) and 83 (35 males, 48 females) controls…
Kirschen, Gregory W; Shen, Jia; Tian, Mu; Schroeder, Bryce; Wang, Jia; Man, Guoming; Wu, Song; Ge, Shaoyu
The continuous addition of new dentate granule cells, exquisitely regulated by brain activity, renders the hippocampus plastic. However, how neural circuits encode experiences to impact the addition of adult-born neurons remains unknown. Here, we used endoscopic Ca(2+) imaging to track the real-time activity of individual dentate granule cells in freely-behaving mice. For the first time, we found that active dentate granule cells responded to a novel experience by preferentially increasing their Ca(2+) event frequency. This elevated activity, which we found to be associated with object exploration, returned to baseline by one hour in the same environment, but could be dishabituated via introduction to a novel environment. To seamlessly transition between environments, we next established a freely-controllable virtual reality system for unrestrained mice. We again observed increased firing of active neurons in a virtual enriched environment. Interestingly, multiple novel virtual experiences accumulatively increased the number of newborn neurons when compared to a single experience. Finally, optogenetic silencing of existing dentate granule cells during novel environmental exploration perturbed experience-induced neuronal addition. Together, our study shows that the adult brain conveys novel, enriched experiences to increase the addition of adult-born hippocampal neurons by increasing the firing of active dentate granule cells.SIGNIFICANCE STATEMENTAdult brains are constantly reshaping themselves from synapses to circuits as we encounter novel experiences from moment to moment. Importantly, this reshaping includes the addition of newborn hippocampal neurons. However, it remains largely unknown how our circuits encode experience-induced brain activity to govern the addition of new hippocampal neurons. By coupling in vivo Ca(2+) imaging of dentate granule neurons with a novel unrestrained virtual reality system for rodents, we discovered that a new experience rapidly
Sherf, Yehonatan; Sheiner, Eyal; Vardi, Ilana Shoham; Sergienko, Ruslan; Klein, Jamie; Bilenko, Natalya
Objective This study aims to evaluate the role of a family history of preterm delivery on the risk of preterm delivery in the next generation. Study Design A retrospective population-based study was conducted. Perinatal information was gathered from 2,303 familial triads, composed of mothers (F1), daughters (F2), and children (F3). All births occurred in the same regional medical center between the years 1991 and 2013. Statistical analysis using logistic regression was performed to define the risk of F2 delivering a preterm baby (F3) if she was born preterm herself, and then to define the risk of F2 delivering preterm if her mother (F1) gave birth preterm during any of her birthing events. Results The risk for preterm delivery of the F2 parturient was 34% greater if their mother (F1) at any of her births had delivered preterm, controlling for parity, maternal age at delivery, and preeclampsia (adjusted odds ratio: 1.34, 95% confidence interval: -1.01 to 1.77; p = 0.042). Conclusion The family history of preterm delivery is an independent risk factor for preterm delivery. The family history includes the mother as well as one of the mother's sisters (F2 generation) being born preterm.
Corvaglia, Luigi; Gabrielli, Liliana; Chiereghin, Angela; Lazzarotto, Tiziana
Background. The neonatal immune system is not fully developed at birth; newborns have adequate lymphocytes counts but these cells lack function. Objective. To assess the activity of T-cells and the influence of the main perinatal factors in very preterm infants (birth weight < 1500 g). Design. Blood samples from 59 preterm infants (21/59 were dizygotic twins) were collected at birth and at 30 days of life to measure CD4+ T-cell activity using the ImmuKnow™ assay. Fifteen healthy adults were included as a control group. Results. CD4+ T-cell activity was lower in VLBW infants compared with adults (p < 0.001). Twins showed lower immune activity compared to singletons (p = 0.005). Infants born vaginally showed higher CD4+ T-cell activity compared to those born by C-section (p = 0.031); infants born after prolonged Premature Rupture of Membranes (pPROM) showed higher CD4+ T-cell activity at birth (p = 0.002) compared to infants born without pPROM. Low CD4+ T-cell activity at birth is associated with necrotizing enterocolitis (NEC) in the first week of life (p = 0.049). Conclusions. Preterm infants show a lack in CD4+ T-cell activity at birth. Perinatal factors such as intrauterine inflammation, mode of delivery, and zygosity can influence the adaptive immune activation capacity at birth and can contribute to exposing these infants to serious complications such as NEC. PMID:28070527
Baum, J D
This editorial addresses the question of how best to feed the low birth weight infant. A study by Atkinson et al. on the composition of preterm mothers' milk found the nitrogen concentration in preterm milk to be considerably higher than in term milk. Preterm milk may be uniquely suited to the growth requirements of preterm infants. With the exception of calcium and phosphorus, preterm milk fits the requirements for preterm infant growth. Because of the difficulties of sustaining lactation without the infant sucking at the breast, partly due to the mother's motivation in the face of all the difficulties of having a baby in a Special Care Baby Unit, and partly due to the associated socioeconomic disadvantages, it is not possible for all mothers who deliver preterm babies to sustain their lactation. The composition of preterm milk should be used as a guide for the preparation of a human milk formula built from human milk products from a milk bank. The development of a human milk formula must take into account variations in the absorption of nutrients in low birth weight infants which may be affected by the processing of the milk, and variations in fat absorption in preterm infants which occur even when they are fed their mothers' fresh unprocessed milk.
Naoi, Nozomi; Fuchino, Yutaka; Shibata, Minoru; Niwa, Fusako; Kawai, Masahiko; Konishi, Yukuo; Okanoya, Kazuo; Myowa-Yamakoshi, Masako
Preterm infants are at increased risk of language-related problems later in life; however, few studies have examined the effects of preterm birth on cerebral responses to speech at very early developmental stages. This study examined cerebral activation and functional connectivity in response to infant-directed speech (IDS) and adult-directed speech (ADS) in full-term neonates and preterm infants at term-equivalent age using 94-channel near-infrared spectroscopy. The results showed that compared with ADS, IDS increased activity in larger brain areas such as the bilateral frontotemporal, temporal, and temporoparietal regions, both in full-term and preterm infants. Preterm infants exhibited decreased activity in response to speech stimuli in the right temporal region compared with full-term infants, although the significance was low. Moreover, preterm infants exhibited increased interhemispheric connectivity compared with full-term controls, especially in the temporal and temporoparietal regions. These differences suggest that preterm infants may follow different developmental trajectories from those born at term owing to differences in intrauterine and extrauterine development.
Constable, R Todd; Vohr, Betty R; Scheinost, Dustin; Benjamin, Jennifer R; Fulbright, Robert K; Lacadie, Cheryl; Schneider, Karen C; Katz, Karol H; Zhang, Heping; Papademetris, Xenophon; Ment, Laura R
Preterm (PT) subjects are at risk for developmental delay, and task-based studies suggest that developmental disorders may be due to alterations in neural connectivity. Since emerging data imply the importance of right cerebellar function for language acquisition in typical development, we hypothesized that PT subjects would have alternate areas of cerebellar connectivity, and that these areas would be responsible for differences in cognitive outcomes between PT subjects and term controls at age 20 years. Nineteen PT and 19 term control young adults were prospectively studied using resting-state functional MRI (fMRI) to create voxel-based contrast maps reflecting the functional connectivity of each tissue element in the grey matter through analysis of the intrinsic connectivity contrast degree (ICC-d). Left cerebellar ICC-d differences between subjects identified a region of interest that was used for subsequent seed-based connectivity analyses. Subjects underwent standardized language testing, and correlations with cognitive outcomes were assessed. There were no differences in gender, hand preference, maternal education, age at study, or Peabody Picture Vocabulary Test (PPVT) scores. Functional connectivity (FcMRI) demonstrated increased tissue connectivity in the biventer, simple and quadrangular lobules of the L cerebellum (p<0.05) in PTs compared to term controls; seed-based analyses from these regions demonstrated alterations in connectivity from L cerebellum to both R and L inferior frontal gyri (IFG) in PTs compared to term controls. For PTs but not term controls, there were significant positive correlations between these connections and PPVT scores (R IFG: r=0.555, p=0.01; L IFG: r=0.454, p=0.05), as well as Verbal Comprehension Index (VCI) scores (R IFG: r=0.472, p=0.04). These data suggest the presence of a left cerebellar language circuit in PT subjects at young adulthood. These findings may represent either a delay in maturation or the engagement of
Scharfman, Helen E.; Bernstein, Hannah L.
The dentate gyrus (DG) is important to many aspects of hippocampal function, but there are many aspects of the DG that are incompletely understood. One example is the role of mossy cells (MCs), a major DG cell type that is glutamatergic and innervates the primary output cells of the DG, the granule cells (GCs). MCs innervate the GCs as well as local circuit neurons that make GABAergic synapses on GCs, so the net effect of MCs on GCs – and therefore the output of the DG – is unclear. Here we first review fundamental information about MCs and the current hypotheses for their role in the normal DG and in diseases that involve the DG. Then we review previously published data which suggest that MCs are a source of input to a subset of GCs that are born in adulthood (adult-born GCs). In addition, we discuss the evidence that adult-born GCs may support the normal inhibitory ‘gate’ functions of the DG, where the GCs are a filter or gate for information from the entorhinal cortical input to area CA3. The implications are then discussed in the context of seizures and temporal lobe epilepsy (TLE). In TLE, it has been suggested that the DG inhibitory gate is weak or broken and MC loss leads to insufficient activation of inhibitory neurons, causing hyperexcitability. That idea was called the “dormant basket cell hypothesis.” Recent data suggest that loss of normal adult-born GCs may also cause disinhibition, and seizure susceptibility. Therefore, we propose a reconsideration of the dormant basket cell hypothesis with an intervening adult-born GC between the MC and basket cell and call this hypothesis the “dormant immature granule cell hypothesis.” PMID:26347618
Poggioli, Michela; Minichilli, Fabrizio; Bononi, Tiziana; Meghi, Pasquina; Andre, Paolo; Crecchi, Alessandra; Rossi, Bruno; Carboncini, Maria Chiara; Ottolini, Alberto
Preterm children have an increased risk of neurodevelopmental impairments which include psychomotor and language retardation. The objectives of the present retrospective cohort study were to examine the effects of an individually adapted, home-based, and family-centred early developmental habilitation program on neurodevelopmental and behavioural outcomes of very preterm children compared with a standard follow-up at 2 years' corrected age. Enrolled infants were retrospectively assigned to the intervention group (61 subjects) or to the control group (62 subjects) depending on whether they had or had not carried out a home-based family-centred early developmental habilitation program focused on environmental enrichment, parent-guided environmental interaction, and infant development. Developmental outcome was assessed for both groups at 24 months' corrected age using the Bayley Scales of Infant Development 2nd Edition. Intervention significantly improved both cognitive and behavioural outcomes. In addition, males had significantly lower scores than females either before or after treatment. However, the treatment was effective in both genders to the same extent. In conclusion, a timely updated environment suitable to the infant's developmental needs could provide the best substrate where the parent-infant relationship can be practised with the ultimate goal of achieving further developmental steps. PMID:28090357
Poggioli, Michela; Minichilli, Fabrizio; Bononi, Tiziana; Meghi, Pasquina; Andre, Paolo; Crecchi, Alessandra; Rossi, Bruno; Carboncini, Maria Chiara; Ottolini, Alberto; Bonfiglio, Luca
Preterm children have an increased risk of neurodevelopmental impairments which include psychomotor and language retardation. The objectives of the present retrospective cohort study were to examine the effects of an individually adapted, home-based, and family-centred early developmental habilitation program on neurodevelopmental and behavioural outcomes of very preterm children compared with a standard follow-up at 2 years' corrected age. Enrolled infants were retrospectively assigned to the intervention group (61 subjects) or to the control group (62 subjects) depending on whether they had or had not carried out a home-based family-centred early developmental habilitation program focused on environmental enrichment, parent-guided environmental interaction, and infant development. Developmental outcome was assessed for both groups at 24 months' corrected age using the Bayley Scales of Infant Development 2nd Edition. Intervention significantly improved both cognitive and behavioural outcomes. In addition, males had significantly lower scores than females either before or after treatment. However, the treatment was effective in both genders to the same extent. In conclusion, a timely updated environment suitable to the infant's developmental needs could provide the best substrate where the parent-infant relationship can be practised with the ultimate goal of achieving further developmental steps.
de Jong, Femke; Monuteaux, Michael C; van Elburg, Ruurd M; Gillman, Matthew W; Belfort, Mandy B
Lower birth weight because of fetal growth restriction is associated with higher blood pressure later in life, but the extent to which preterm birth (<37 completed weeks' gestation) or very low birth weight (<1500 g) predicts higher blood pressure is less clear. We performed a systematic review of 27 observational studies that compared the resting or ambulatory systolic blood pressure or diagnosis of hypertension among children, adolescents, and adults born preterm or very low birth weight with those born at term. We performed a meta-analysis with the subset of 10 studies that reported the resting systolic blood pressure difference in millimeters of mercury with 95% CIs or SEs. We assessed methodologic quality with a modified Newcastle-Ottawa Scale. The 10 studies were composed of 1342 preterm or very low birth weight and 1738 term participants from 8 countries. The mean gestational age at birth of the preterm participants was 30.2 weeks (range: 28.8-34.1 weeks), birth weight was 1280 g (range: 1098-1958 g), and age at systolic blood pressure measurement was 17.8 years (range: 6.3-22.4 years). Former preterm or very low birth weight infants had higher systolic blood pressure than term infants (pooled estimate: 2.5 mm Hg [95% CI: 1.7-3.3 mm Hg]). For the 5 highest quality studies, the systolic blood pressure difference was slightly greater, at 3.8 mm Hg (95% CI: 2.6-5.0 mm Hg). We conclude that infants who are born preterm or very low birth weight have modestly higher systolic blood pressure later in life and may be at increased risk for developing hypertension and its sequelae.
Semberova, J; O'Donnell, S M; Franta, J; Miletin, J
The available evidence does not support the routine use of inhaled nitric oxide (iNO) in the care of premature infants. We present a case series of 22 preterm infants born after prolonged preterm premature rupture of membranes and oligohydramnios with respiratory failure. Oxygenation index decreased significantly after commencement of iNO.
It is widely known that educational attainment has considerable influence on the prevalence of disability among native-born non-Hispanic older adults in the US. However, few studies have examined whether educational attainment has a similar effect on disability among foreign-born Asian older adults. If it does not have a similar effect on these adults, why not, and is its effect influenced by the age at which they immigrated to the US? This study addresses these questions by using the 2006 American Community Survey Public Use Microdata Sample (ACS PUMS). Logistic regression analyses reveal that education has differential effects on the two racial groups. Education protects foreign-born Asians less than native-born non-Hispanic whites. In addition, Asian adults who immigrated earlier are less likely to experience disability. Interestingly, the interaction between age at immigration and educational attainment for foreign-born Asian older adults indicates that less educated Asians are more likely to benefit from early immigration. Heterogeneity within the Asian group is also examined. The findings suggest that educational attainment has differential effects not only on the two racial groups but also on the foreign-born Asian group depending on age at immigration.
... Scientific Name Preterm labor Preterm birth Preterm infant Late-preterm birth ... first-time pregnancies No benefit in treating mildly low thyroid function in pregnancy, NIH Network study finds ...
Relationship between artificially sweetened and sugar-sweetened cola beverage consumption during pregnancy and preterm delivery in a multi-ethnic cohort: analysis of the Born in Bradford cohort study.
Petherick, E S; Goran, M I; Wright, J
The aim of this study was to investigate the relationship between the intake of sugar-sweetened (SS) and artificially sweetened (AS) cola beverages during pregnancy and the risk of preterm delivery (PTD). At baseline (2007-2010), 8914 pregnant women were recruited to the Born in Bradford birth cohort study at 24-28 weeks of pregnancy. Women completed a questionnaire describing their health and lifestyle behaviours, including their consumption of AS and SS cola beverages reported as cups per day, which were then linked to maternity records. The relationship between SS and AS cola beverage consumption was examined using logistic regression analyses. No relationship was observed between daily AS cola beverage consumption and PTD. Women who drank four cups per day of SS cola beverages had higher odds of a PTD when compared with women who did not consume these beverages daily. We conclude that high daily consumption of SS cola beverages during pregnancy is associated with increases in the rate of PTD.
Sun, Gerald J.; Sailor, Kurt A.; Mahmood, Qasim A.; Chavali, Nikhil; Christian, Kimberly M.; Song, Hongjun
In the adult mammalian hippocampus, newborn dentate granule cells are continuously integrated into the existing circuitry and contribute to specific brain functions. Little is known about the axonal development of these newborn neurons in the adult brain due to technological challenges that have prohibited large-scale reconstruction of long, thin, and complex axonal processes within the mature nervous system. Here, using a new serial end-block imaging (SEBI) technique, we seamlessly reconstructed axonal and dendritic processes of intact individual retrovirus-labeled newborn granule cells at different developmental stages in the young adult mouse hippocampus. We found that adult-born dentate granule cells exhibit tortuous, yet highly stereotyped, axonal projections to CA3 hippocampal subregions. Primary axonal projections of cohorts of new neurons born around the same time organize into laminar patterns with staggered terminations that stack along the septo-temporal hippocampal axis. Analysis of individual newborn neuron development further defined an initial phase of rapid axonal and dendritic growth within 21 d after newborn neuron birth, followed by minimal growth of primary axonal and whole dendritic processes through the last time point examined at 77 d. Our results suggest that axonal development and targeting is a highly orchestrated, precise process in the adult brain. These findings demonstrate a striking regenerative capacity of the mature CNS to support long-distance growth and guidance of neuronal axons. Our SEBI approach can be broadly applied for analysis of intact, complex neuronal projections in limitless tissue volume. PMID:23843512
Sun, Gerald J; Sailor, Kurt A; Mahmood, Qasim A; Chavali, Nikhil; Christian, Kimberly M; Song, Hongjun; Ming, Guo-li
In the adult mammalian hippocampus, newborn dentate granule cells are continuously integrated into the existing circuitry and contribute to specific brain functions. Little is known about the axonal development of these newborn neurons in the adult brain due to technological challenges that have prohibited large-scale reconstruction of long, thin, and complex axonal processes within the mature nervous system. Here, using a new serial end-block imaging (SEBI) technique, we seamlessly reconstructed axonal and dendritic processes of intact individual retrovirus-labeled newborn granule cells at different developmental stages in the young adult mouse hippocampus. We found that adult-born dentate granule cells exhibit tortuous, yet highly stereotyped, axonal projections to CA3 hippocampal subregions. Primary axonal projections of cohorts of new neurons born around the same time organize into laminar patterns with staggered terminations that stack along the septo-temporal hippocampal axis. Analysis of individual newborn neuron development further defined an initial phase of rapid axonal and dendritic growth within 21 d after newborn neuron birth, followed by minimal growth of primary axonal and whole dendritic processes through the last time point examined at 77 d. Our results suggest that axonal development and targeting is a highly orchestrated, precise process in the adult brain. These findings demonstrate a striking regenerative capacity of the mature CNS to support long-distance growth and guidance of neuronal axons. Our SEBI approach can be broadly applied for analysis of intact, complex neuronal projections in limitless tissue volume.
Ganella, Eleni P; Burnett, Alice; Cheong, Jeanie; Thompson, Deanne; Roberts, Gehan; Wood, Stephen; Lee, Katherine; Duff, Julianne; Anderson, Peter J; Pantelis, Christos; Doyle, Lex W; Bartholomeusz, Cali
Extremely preterm (EP, <28 weeks) and/or extremely low birth weight (ELBW, <1000 g) infants are at high risk of aberrant neurodevelopment. Sulcogyral folding patterns of the orbitofrontal cortex (OFC) are determined during the third trimester, however little is known about OFC patterning in EP/ELBW cohorts, for whom this gestational period is disturbed. This study investigated whether the distribution of OFC pattern types and frequency of intermediate and/or posterior orbital sulci (IOS/POS) differed between EP/ELBW and control adolescents. This study also investigated whether OFC pattern type was associated with mental illness or executive function outcome in adolescence. Magnetic resonance images of 194 EP/ELBW and 147 full term (>37 completed weeks) and/or normal birth weight (> 2500 g) adolescents were acquired, from which the OFC pattern of each hemisphere was classified as Type I, II, or III. Compared with controls, more EP/ELBW adolescents possessed a Type II in the left hemisphere (P = 0.019). The EP/ELBW group had fewer IOS (P = 0.024) and more POS (P = 0.021) in the left hemisphere compared with controls. OFC pattern type was not associated with mental illness, however in terms of executive functioning, Type III in the left hemisphere was associated with better parent-reported metacognition scores overall (P = 0.008) and better self-reported behavioral regulation scores in the control group (P = 0.001) compared with Type I. We show, for the first time that EP/ELBW birth is associated with changes in orbitofrontal development, and that specific patterns of OFC folding are associated with executive function at age 18 years in both EP/ELBW and control subjects.
Maldonado-Molina, Mildred M.; Reingle, Jennifer M.; Jennings, Wesley G.; Prado, Guillermo
Objective To evaluate the risk factors associated with the initiation of driving under the influence (DUI) among Hispanics in a longitudinal and nationally-representative sample of adolescents and young adults. Specifically, this study tests the effect of demographic variables, individual-level risk factors, and eco-processes (e.g., peer drug use, parental involvement) during adolescence on DUI among Hispanic young adults. Methods Data were derived from 1,734 Hispanic adolescents surveyed for the National Longitudinal Study of Adolescent Health (Add Health). Survey logistic regression procedures were used to examine the effects of nativity status on DUI initiation, to evaluate the independent effect of each risk factor (demographic, individual-level, and eco-processes), and to identify whether and to what extent these factors are associated with the initiation of DUI. Results The overall prevalence of DUI initiation was 18.3%. Differences were observed in the rates of DUI initiation by nativity status: first-generation immigrants reported the lowest rates of DUI initiation (15.4%) when compared with second-generation US-born Hispanic youth (17.4%) and third-generation and beyond US-born Hispanic youth (21.5%). US-born Hispanic youth were also more likely to report higher frequency of alcohol use (t=3.46, p=.001) and marijuana use (t=2.34, p=.021) compared to immigrant adolescents. After adjusting for a number of risk factors, men (OR=2.86), marijuana users (OR=1.98), and those who reported feeling safe in their neighborhoods (OR=2.02) were at an increased risk DUI initiation. Conclusions Findings provide support for the “immigrant paradox”: immigrant youth reported lower rates of DUI initiation and other high-risk behaviors when compared with US-born Hispanic youth. PMID:21216535
Quadrato, Giorgia; Benevento, Marco; Alber, Stefanie; Jacob, Carolin; Floriddia, Elisa M; Nguyen, Tuan; Elnaggar, Mohamed Y; Pedroarena, Christine M; Molkentin, Jeffrey D; Di Giovanni, Simone
New neurons generated in the adult dentate gyrus are constantly integrated into the hippocampal circuitry and activated during encoding and recall of new memories. Despite identification of extracellular signals that regulate survival and integration of adult-born neurons such as neurotrophins and neurotransmitters, the nature of the intracellular modulators required to transduce those signals remains elusive. Here, we provide evidence of the expression and transcriptional activity of nuclear factor of activated T cell c4 (NFATc4) in hippocampal progenitor cells. We show that NFATc4 calcineurin-dependent activity is required selectively for survival of adult-born neurons in response to BDNF signaling. Indeed, cyclosporin A injection and stereotaxic delivery of the BDNF scavenger TrkB-Fc in the mouse dentate gyrus reduce the survival of hippocampal adult-born neurons in wild-type but not in NFATc4(-/-) mice and do not affect the net rate of neural precursor proliferation and their fate commitment. Furthermore, associated with the reduced survival of adult-born neurons, the absence of NFATc4 leads to selective defects in LTP and in the encoding of hippocampal-dependent spatial memories. Thus, our data demonstrate that NFATc4 is essential in the regulation of adult hippocampal neurogenesis and identify NFATc4 as a central player of BDNF-driven prosurvival signaling in hippocampal adult-born neurons.
Using new direct measures of numeracy and literacy skills among 85,875 adults in 17 Western countries, we find that foreign-born adults have lower mean skills than native-born adults of the same age (16 to 64) in all of the examined countries. The gaps are small, and vary substantially between countries. Multilevel models reveal that immigrant populations’ demographic and socioeconomic characteristics, employment, and language proficiency explain about half of the cross-national variance of numeracy and literacy skills gaps. Differences in origin countries’ average education level also account for variation in the size of the immigrant-native skills gap. The more protective labor markets in immigrant-receiving countries are, the less well immigrants are skilled in numeracy and literacy compared to natives. For those who migrate before their teens (the 1.5 generation), access to an education system that accommodates migrants’ special needs is crucial. The 1 and 1.5 generation have smaller numeracy and literacy skills gaps in more ethnically diverse societies. PMID:28301541
Sandoval, C Jimena; Martínez-Claros, Marisela; Bello-Medina, Paola C; Pérez, Oswaldo; Ramírez-Amaya, Víctor
Adult-born neurons in the dentate gyrus (DG) functionally integrate into the behaviorally relevant hippocampal networks, showing a specific Arc-expression response to spatial exploration when mature. However, it is not clear when, during the 4- to 6-week interval that is critical for survival and maturation of these neurons, this specific response develops. Therefore, we characterized Arc expression after spatial exploration or cage control conditions in adult-born neurons from rats that were injected with BrdU on one day and were sacrificed 1, 7, 15, 30, and 45 days post-BrdU injection (PBI). Triple immunostaining for NeuN, Arc, and BrdU was analyzed through the different DG layers. Arc protein expression in BrdU-positive cells was observed from day 1 to day 15 PBI but was not related to behavioral stimulation. The specific Arc-expression response to spatial exploration was observed from day 30 and 45 in about 5% of the BrdU-positive cell population. Most of the BrdU-positive neurons expressing Arc in response to spatial exploration (∼90%) were located in DG layer 1, and no Arc expression was observed in cells located in the subgranular zone (SGZ). Using the current data and that obtained previously, we propose a mathematical model suggesting that new neurons are unlikely to respond to exploration by expressing Arc after they are 301 days old, and also that in a 7-month-old rat the majority (60%) of the neurons that respond to exploration must have been born during adulthood; thus, suggesting that adult neurogenesis in the DG is highly relevant for spatial information processing.
Sandoval, C. Jimena; Pérez, Oswaldo; Ramírez-Amaya, Víctor
Adult-born neurons in the dentate gyrus (DG) functionally integrate into the behaviorally relevant hippocampal networks, showing a specific Arc-expression response to spatial exploration when mature. However, it is not clear when, during the 4- to 6-week interval that is critical for survival and maturation of these neurons, this specific response develops. Therefore, we characterized Arc expression after spatial exploration or cage control conditions in adult-born neurons from rats that were injected with BrdU on one day and were sacrificed 1, 7, 15, 30, and 45 days post-BrdU injection (PBI). Triple immunostaining for NeuN, Arc, and BrdU was analyzed through the different DG layers. Arc protein expression in BrdU-positive cells was observed from day 1 to day 15 PBI but was not related to behavioral stimulation. The specific Arc-expression response to spatial exploration was observed from day 30 and 45 in about 5% of the BrdU-positive cell population. Most of the BrdU-positive neurons expressing Arc in response to spatial exploration (∼90%) were located in DG layer 1, and no Arc expression was observed in cells located in the subgranular zone (SGZ). Using the current data and that obtained previously, we propose a mathematical model suggesting that new neurons are unlikely to respond to exploration by expressing Arc after they are 301 days old, and also that in a 7-month-old rat the majority (60%) of the neurons that respond to exploration must have been born during adulthood; thus, suggesting that adult neurogenesis in the DG is highly relevant for spatial information processing. PMID:21408012
Lempel, Augusto Abel; Coll, Lucia; Schinder, Alejandro F; Uchitel, Osvaldo Daniel; Piriz, Joaquin
Pregabalin (PGB) is extensively prescribed to treat neurological and neuropsychiatrical conditions such as neuropathic pain, anxiety disorders, and epilepsy. Although PGB is known to bind selectively to the α2δ subunit of voltage-gated calcium channels, there is little understanding about how it exerts its therapeutic effects. In this article, we analyzed the effects of an in vivo chronic treatment with PGB over the physiology of dentate gyrus granule cells (DGGCs) using ex vivo electrophysiological and morphological analysis in adult mice. We found that PGB decreases neuronal excitability of DGGCs. In addition, PGB accelerates maturation of adult-born DGGCs, an effect that would modify dentate gyrus plasticity. Together, these findings suggest that PGB reduces activity in the dentate gyrus and modulates overall network plasticity, which might contribute to its therapeutic effects. Cover Image for this issue: doi: 10.1111/jnc.13783.
Mehta, Neil K; Elo, Irma T; Engelman, Michal; Lauderdale, Diane S; Kestenbaum, Bert M
In recent decades, the geographic origins of America's foreign-born population have become increasingly diverse. The sending countries of the U.S. foreign-born vary substantially in levels of health and economic development, and immigrants have arrived with distinct distributions of socioeconomic status, visa type, year of immigration, and age at immigration. We use high-quality linked Social Security and Medicare records to estimate life tables for the older U.S. population over the full range of birth regions. In 2000-2009, the foreign-born had a 2.4-year advantage in life expectancy at age 65 relative to the U.S.-born, with Asian-born subgroups displaying exceptionally high longevity. Foreign-born individuals who migrated more recently had lower mortality compared with those who migrated earlier. Nonetheless, we also find remarkable similarities in life expectancy among many foreign-born subgroups that were born in very different geographic and socioeconomic contexts (e.g., Central America, western/eastern Europe, and Africa).
Nguyen, Duc Ninh; Jiang, Pingping; Frøkiær, Hanne; Heegaard, Peter M. H.; Thymann, Thomas; Sangild, Per T.
Preterm neonates are highly sensitive to systemic infections in early life but little is known about systemic immune development following preterm birth. We hypothesized that preterm neonates have immature systemic immunity with distinct developmental trajectory for the first several weeks of life, relative to those born at near-term or term. Using pigs as a model, we characterized blood leukocyte subsets, antimicrobial activities and TLR-mediated cytokine production during the first weeks after preterm birth. Relative to near-term and term pigs, newborn preterm pigs had low blood leukocyte counts, poor neutrophil phagocytic rate, and limited cytokine responses to TLR1/2/5/7/9 and NOD1/2 agonists. The preterm systemic responses remained immature during the first postnatal week, but thereafter showed increased blood leukocyte numbers, NK cell proportion, neutrophil phagocytic rate and TLR2-mediated IL-6 and TNF-α production. These immune parameters remained different between preterm and near-term pigs at 2–3 weeks, even when adjusted for post-conceptional age. Our data suggest that systemic immunity follows a distinct developmental trajectory following preterm birth that may be influenced by postnatal age, complications of prematurity and environmental factors. Consequently, the immediate postnatal period may represent a window of opportunity to improve innate immunity in preterm neonates by medical, antimicrobial or dietary interventions. PMID:27830761
Garrett, Lillian; Zhang, Jingzhong; Zimprich, Annemarie; Niedermeier, Kristina M.; Fuchs, Helmut; Gailus-Durner, Valerie; Hrabě de Angelis, Martin; Vogt Weisenhorn, Daniela; Wurst, Wolfgang; Hölter, Sabine M.
Adult neurogenesis occurs in the adult mammalian subventricular zone (SVZ) along the walls of the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus. While a burgeoning body of research implicates adult neurogenesis in olfactory bulb (OB)- and hippocampal-related behaviors, the precise function continues to elude. To further assess the behavioral importance of adult neurogenesis, we herein generated a novel inducible transgenic mouse model of adult neurogenesis reduction where mice with CreERT2 under doublecortin (DCX) promoter control were crossed with mice where diphtheria toxin A (DTA) was driven by the Rosa26 promoter. Activation of DTA, through the administration of tamoxifen (TAM), results in a specific reduction of DCX+ immature neurons in both the hippocampal dentate gyrus and OB. We show that the decrease of DCX+ cells causes impaired social discrimination ability in both young adult (from 3 months) and middle aged (from 10 months) mice. Furthermore, these animals showed an age-independent altered coping behavior in the Forced Swim Test without clear changes in anxiety-related behavior. Notably, these behavior changes were reversible on repopulating the neurogenic zones with DCX+ cells on cessation of the TAM treatment, demonstrating the specificity of this effect. Overall, these results support the notion that adult neurogenesis plays a role in social memory and in stress coping but not necessarily in anxiety-related behavior. PMID:26617501
Garrett, Lillian; Zhang, Jingzhong; Zimprich, Annemarie; Niedermeier, Kristina M; Fuchs, Helmut; Gailus-Durner, Valerie; Hrabě de Angelis, Martin; Vogt Weisenhorn, Daniela; Wurst, Wolfgang; Hölter, Sabine M
Adult neurogenesis occurs in the adult mammalian subventricular zone (SVZ) along the walls of the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus. While a burgeoning body of research implicates adult neurogenesis in olfactory bulb (OB)- and hippocampal-related behaviors, the precise function continues to elude. To further assess the behavioral importance of adult neurogenesis, we herein generated a novel inducible transgenic mouse model of adult neurogenesis reduction where mice with CreER(T2) under doublecortin (DCX) promoter control were crossed with mice where diphtheria toxin A (DTA) was driven by the Rosa26 promoter. Activation of DTA, through the administration of tamoxifen (TAM), results in a specific reduction of DCX+ immature neurons in both the hippocampal dentate gyrus and OB. We show that the decrease of DCX+ cells causes impaired social discrimination ability in both young adult (from 3 months) and middle aged (from 10 months) mice. Furthermore, these animals showed an age-independent altered coping behavior in the Forced Swim Test without clear changes in anxiety-related behavior. Notably, these behavior changes were reversible on repopulating the neurogenic zones with DCX+ cells on cessation of the TAM treatment, demonstrating the specificity of this effect. Overall, these results support the notion that adult neurogenesis plays a role in social memory and in stress coping but not necessarily in anxiety-related behavior.
Ding, Xue-Feng; Gao, Xiang; Ding, Xin-Chun; Fan, Ming; Chen, Jinhui
Deficits in the Notch pathway are involved in a number of neurologic diseases associated with mental retardation or/and dementia. The mechanisms by which Notch dysregulation are associated with mental retardation and dementia are poorly understood. We found that Notch1 is highly expressed in the adult-born immature neurons in the hippocampus of mice. Retrovirus mediated knockout of notch1 in single adult-born immature neurons decreases mTOR signaling and compromises their dendrite morphogenesis. In contrast, overexpression of Notch1 intracellular domain (NICD), to constitutively activate Notch signaling in single adult-born immature neurons, promotes mTOR signaling and increases their dendrite arborization. Using a unique genetic approach to conditionally and selectively knockout notch 1 in the postnatally born immature neurons in the hippocampus decreases mTOR signaling, compromises their dendrite morphogenesis, and impairs spatial learning and memory. Conditional overexpression of NICD in the postnatally born immature neurons in the hippocampus increases mTOR signaling and promotes dendrite arborization. These data indicate that Notch signaling plays a critical role in dendrite development of immature neurons in the postnatal brain, and dysregulation of Notch signaling in the postnatally born neurons disrupts their development and thus contributes to the cognitive deficits associated with neurological diseases. PMID:27173138
O'Reilly, Michelle; Vollmer, Brigitte; Vargha-Khadem, Faraneh; Neville, Brian; Connelly, Alan; Wyatt, John; Timms, Chris; De Haan, Michelle
Many studies report chronic deficits in visual processing in children born preterm. We investigated whether functional abnormalities in visual processing exist in children born preterm but without major neuromotor impairment (i.e. cerebral palsy). Twelve such children (less than 33 weeks gestation or birthweight less than 1000 g) without major…
Rogers, Cynthia E.; Lenze, Shannon N.; Luby, Joan L.
Objective: Preterm children are at greater risk for psychiatric disorders, including anxiety disorders and attention-deficit/hyperactivity disorder (ADHD), than their term-born peers. Prior research has focused primarily on children born at early gestational ages. Less is known about the rate of psychiatric disorders among late preterm or early…
Choi, Sunha; Kim, Giyeon; Lee, Sungkyu
Using the 2004-2007 Medical Expenditure Panel Survey data that are linked to county-level data from the Area Health Resources Files, this study examined whether the healthy immigrant effect applies to mental health of foreign-born older adults. Additionally, testing a protective ethnic density effect on older foreign-born individuals' mental health, this study examined how the percentage of foreign-born population in the county affected the relationship between older adults' immigration status (U.S.-nativity and length of residence in the U.S.) and their mental health status. The sample included 29,011 individuals (level-1) from 920 counties (level-2) across 50 states and D.C. Using the Mental Component Summary of the Short-Form 12, the Kessler Index (K-6), and the Patient Health Questionnaire (PHQ-2), U.S.-born individuals (n = 24,225), earlier immigrants (≥15 years in the U.S.; n = 3866), and recent immigrants (<15 years in the U.S.; n = 920) were compared. The results indicate that recent immigrants showed worse mental health on all three measures compared with U.S.-born individuals and on the K-6 and PHQ-2 compared with earlier immigrants. Higher county-level foreign-born densities were associated with worse mental health status of individuals. However, the significant interactions found in the full conditional multilevel models indicated that the high foreign-born density functioned as a risk factor for worse mental health only among recent immigrants but not among the U.S.-born. In conclusion, the results revealed the vulnerability of older recent immigrants, especially those living in the counties with high foreign-born densities.
Hjetland, Reidar; Henningsson, Anna J; Vainio, Kirsti; Dudman, Susanne G; Grude, Nils; Ulvestad, Elling
The aim of this study was to assess the seroprevalence of antibodies to tick-borne encephalitis virus (TBEV) and Anaplasma phagocytophilum in a healthy adult population from Sogn and Fjordane county in western Norway. Sera from 1, 213 blood donors were analysed for IgG-antibodies to TBEV, and a random subgroup of 301 donors for IgG to A. phagocytophilum. In the TBEV ELISA, five (0.4%) sera were positive. These were all interpreted as "false" positives, as four had received vaccines against flaviviruses, and the remaining was negative for neutralizing antibodies to TBEV. Antibodies to A. phagocytophilum were detected by indirect immunofluorescence in 49 (16.2%) subjects (titer range 80-1280). The results indicate that TBE currently is not endemic in this part of western Norway. However, there is serological evidence of the existence of human granulocytic anaplasmosis in the population.
Schmidt, Louis A.; Miskovic, Vladimir; Boyle, Michael; Saigal, Saroj
The authors examined internalizing behavior problems at middle childhood, adolescence, and young adulthood and brain-based measures of stress vulnerability in 154 right-handed, non-impaired young adults (M age = 23 years): 71 (30 males, 41 females) born at extremely low birth weight (ELBW; < 1000 grams), and 83 (35 males, 48 females) controls born at normal birth weight (NBW). Internalizing behavior problems increased from adolescence to young adulthood among ELBW individuals. ELBW adults exhibited greater relative right frontal electroencephalogram (EEG) activity at rest and more concurrent internalizing behavior problems than NBW controls. Being born at ELBW may have subtle influences on brain-behavior relations even in survivors without major impairments and evidence of these influences may not emerge until young adulthood. PMID:20331661
Martyn, C. N.; Gale, C. R.; Sayer, A. A.; Fall, C.
OBJECTIVES--To examine the relation between fetal growth and cognitive function in adult life. DESIGN--A follow up study of men and women whose birth weights and other measurements of body size had been recorded at birth. SETTING--Hertfordshire, Preston, and Sheffield. SUBJECTS--1576 men and women born in Hertfordshire, Sheffield, or Preston between 1920 and 1943. MAIN OUTCOME MEASURES--Intelligence quotient as measured by the AH4 test and amount of decline in cognitive function with age as estimated by the difference between score on the Mill Hill vocabulary test and score on the AH4 test. RESULTS--Score on the intelligence test was higher in people who had a large biparietal head diameter at birth, but it was not related to any other measure of body size or proportions. No association was found between decline in cognitive function and any measure of size or proportions at birth. CONCLUSION--Impaired fetal growth was not associated with poorer cognitive performance in adult life. Adaptations made by the fetus in response to conditions that retard its growth seem to be largely successful in maintaining brain development. PMID:8646096
Bonzano, Sara; Bovetti, Serena; Fasolo, Aldo; Peretto, Paolo; De Marchis, Silvia
The olfactory bulb (OB) is the first brain region involved in the processing of olfactory information. In adult mice, the OB is highly plastic, undergoing cellular/molecular dynamic changes that are modulated by sensory experience. Odour deprivation induces down-regulation of tyrosine hydroxylase (TH) expression in OB dopaminergic interneurons located in the glomerular layer (GL), resulting in decreased dopamine in the OB. Although the effect of sensory deprivation is well established, little is known about the influence of odour enrichment on dopaminergic cells. Here we report that prolonged odour enrichment on C57BL/6J strain mice selectively increases TH-immunopositive cells in the GL by nearly 20%. Following odour enrichment on TH-green fluorescent protein (GFP) transgenic mice, in which GFP identified both mature TH-positive cells and putative immature dopaminergic cells expressing TH mRNA but not TH protein, we found a similar 20% increase in GFP-expressing cells, with no changes in the ratio between TH-positive and TH-negative cells. These data suggest that enriched conditions induce an expansion in the whole dopaminergic lineage. Accordingly, by using 5-bromo-2-deoxyuridine injections to label adult-generated cells in the GL of TH-GFP mice, we found an increase in the percentage of 5-bromo-2-deoxyuridine-positive dopaminergic cells in enriched compared with control conditions, whereas no differences were found for calretinin- and calbindin-positive subtypes. Strikingly, the fraction of newborn cells among the dopaminergic population doubled in enriched conditions. On the whole, our results demonstrate that odour enrichment drives increased integration of adult-generated dopaminergic cells that could be critical to adapt the OB circuits to the environmental incoming information.
Choi, Sunha; Kim, Giyeon
Using the 2004–2007 Medical Expenditure Panel Survey data that are linked to county-level data from the Area Health Resources Files, this study examined whether the healthy immigrant effect applies to mental health of foreign-born older adults. Additionally, testing a protective ethnic density effect on older foreign-born individuals’ mental health, this study examined how the percentage of foreign-born population in the county affected the relationship between older adults’ immigration status (U.S.-nativity and length of residence in the U.S.) and their mental health status. The sample included 29,011 individuals (level-1) from 920 counties (level-2) across 50 states and D.C. Using the Mental Component Summary of the Short-Form 12, the Kessler Index (K-6), and the Patient Health Questionnaire (PHQ-2), U.S.-born individuals (n = 24,225), earlier immigrants (≥15 years in the U.S.; n = 3866), and recent immigrants (<15 years in the U.S.; n = 920) were compared. The results indicate that recent immigrants showed worse mental health on all three measures compared with U.S.-born individuals and on the K-6 and PHQ-2 compared with earlier immigrants. Higher county-level foreign-born densities were associated with worse mental health status of individuals. However, the significant interactions found in the full conditional multilevel models indicated that the high foreign-born density functioned as a risk factor for worse mental health only among recent immigrants but not among the U.S.-born. In conclusion, the results revealed the vulnerability of older recent immigrants, especially those living in the counties with high foreign-born densities. PMID:26910461
Waterhouse, Emily G; An, Juan Ji; Orefice, Lauren L; Baydyuk, Maryna; Liao, Guey-Ying; Zheng, Kang; Lu, Bai; Xu, Baoji
Brain-derived neurotrophic factor (BDNF) has been implicated in regulating adult neurogenesis in the subgranular zone (SGZ) of the dentate gyrus; however, the mechanism underlying this regulation remains unclear. In this study, we found that Bdnf mRNA localized to distal dendrites of dentate gyrus granule cells isolated from wild-type (WT) mice, but not from Bdnf(klox/klox) mice where the long 3' untranslated region (UTR) of Bdnf mRNA is truncated. KCl-induced membrane depolarization stimulated release of dendritic BDNF translated from long 3' UTR Bdnf mRNA in cultured hippocampal neurons, but not from short 3' UTR Bdnf mRNA. Bdnf(klox/klox) mice exhibited reduced expression of glutamic acid decarboxylase 65 (a GABA synthase), increased proliferation of progenitor cells, and impaired differentiation and maturation of newborn neurons in the SGZ. These deficits in adult neurogenesis were rescued with administration of phenobarbital, an enhancer of GABA(A) receptor activity. Furthermore, we observed similar neurogenesis deficits in mice where the receptor for BDNF, TrkB, was selectively abolished in parvalbumin (PV)-expressing GABAergic interneurons. Thus, our data suggest that locally synthesized BDNF in dendrites of granule cells promotes differentiation and maturation of progenitor cells in the SGZ by enhancing GABA release, at least in part, from PV-expressing GABAergic interneurons.
Moore, Tamanna; Johnson, Samantha; Hennessy, Enid; Marlow, Neil
Aim: The aim of this article was to report the prevalence of, and risk factors for, positive autism screens using the Modified Checklist for Autism in Toddlers (M-CHAT) in children born extremely preterm in England. Method: All children born at not more than 26 weeks' gestational age in England during 2006 were recruited to the EPICure-2 study. At…
... percent of infants born very preterm or at low birth weight. However, even babies born “late preterm” (34–36 weeksâ gestation) or at moderately low birth weight (1,500–2,499 grams) are more ...
Boyle, Jennifer D; Boyle, Elaine M
Until recently, infants born at moderate preterm (32-33 weeks) and late preterm (34-36 weeks) gestations have gone largely unstudied. Since their outcomes were thought to be similar to those of infants born at 37 weeks and above, they have historically been managed in much the same way as infants born at term. However, accumulating data indicate that risks of morbidity and mortality are significantly greater in this group than previously believed. Since moderate and late preterm infants account for around 6% of all births, very large numbers of babies are potentially affected. Although their problems may be less obvious than those of extremely preterm infants, the population impact of long-term health and neurodevelopmental problems in this group will be substantial. This review summarises the current available literature, highlights gaps in knowledge and discusses the implications of late preterm birth for both clinical practice and research in the perinatal period and beyond.
Corpeleijn, Willemijn E; Kouwenhoven, Stefanie M P; van Goudoever, Johannes B
The cause of growth restriction in preterm infants is multifactorial, but it has been estimated that about 50% of the variance in early postnatal growth can be attributed to nutrition. Very low birth weight (VLBW) infants who were born small-for-gestational age (SGA) seem to have the highest risk to become growth restricted. Possibly, the intrauterine growth-retarded preterm infant is metabolically different from its appropriately grown counterpart and therefore has different nutritional needs. Neonatal nutrition and the resulting postnatal growth are major determinants in the short- and long-term outcomes of preterm neonates. Although having favorable effects on neurodevelopmental outcome, rapid postnatal weight gain after a period of nutritional restriction is associated with the development of insulin resistance and metabolic syndrome in later life. It seems likely that minimization of postnatal growth failure will decrease the need for catch-up growth and thereby decrease the risk of developing cardiovascular risk factors. Monitoring postnatal growth with current growth charts is complicated. Most growth charts that are currently being used are a reflection of current (nutritional) practices and are not a prescription of how VLBW should grow under optimal conditions. In addition to body weight, other aspects of growth such as lean body mass and length gain should also be taken into account when assessing the quality of postnatal growth. Noninvasive measurements of infant body composition are useful tools in evaluating the success of different nutritional interventions. However, all currently available methods have substantial drawbacks. A relatively new and promising method is air displacement plethysmography. This method still needs to be validated in preterm neonates. In conclusion, neonatal nutrition is a major determinant in the short- and long-term outcomes of preterm neonates. Monitoring postnatal growth is complicated by the lack of prescriptive growth
Examining Associations between Self-Rated Health and Proficiency in Literacy and Numeracy among Immigrants and U.S.-Born Adults: Evidence from the Program for the International Assessment of Adult Competencies (PIAAC).
Prins, Esther; Monnat, Shannon
This paper uses data from the Program for the International Assessment of Adult Competencies (PIAAC) to analyze the relationship between self-reported health (SRH) and literacy and numeracy proficiency for immigrants compared to U.S.-born respondents and for Hispanic versus Asian immigrants. The research questions were: (1) Are literacy and numeracy scores associated with adults' SRH? (2) Are associations between SRH and literacy and numeracy proficiency moderated by immigrant status? (3) Among immigrants, are literacy and numeracy scores more strongly associated with SRH for Hispanics versus Asians? Immigrants had significantly lower literacy and numeracy scores, yet reported better health than U.S.-born respondents. Ordinal logistic regression analyses showed that literacy and numeracy were both positively related to SRH for immigrants and U.S.-born adults, and should therefore be viewed as part of the growing evidence that literacy is an independent and significant social determinant of health. Second, U.S.-born and immigrant adults accrued similarly positive health benefits from stronger literacy and numeracy skills. Third, although Hispanic immigrants were more disadvantaged than Asian immigrants on almost all socioeconomic characteristics and had significantly lower literacy and numeracy scores and worse SRH than Asian immigrants, both Hispanic and Asian immigrants experienced similar positive health returns from literacy and numeracy proficiency. These findings underscore the potential health benefits of providing adult basic education instruction, particularly for immigrants with the least formal schooling and fewest socioeconomic resources.
Bayless, Sarah; Pit-ten Cate, Ineke M.; Stevenson, Jim
Children born very prematurely are at risk of low average IQ and behaviour difficulties throughout childhood and adolescence. Associations among preterm birth, IQ and behaviour have been reported; however, the nature of the relationship among these outcomes is not fully understood. Some studies have proposed that the consequences of preterm birth,…
Allen, Carolyn M; Founds, Sandra A
Although the etiology of preterm birth is incompletely understood, phenotype classifications combined with recent technologies such as genome-wide association studies and next-generation sequencing could lead to discovering genotypes associated with preterm birth. Identifying genetic contributions will allow for genetic screening tests to predict or detect pregnancies with potential for preterm birth. In this article we discuss current knowledge regarding phenotype classifications, genotypes, and their associations with preterm birth.
Preterm birth affects about 10% of infants born in the United States. Massage therapy is being used in some neonatal intensive care units for its potential beneficial effects on preterm infants. This article reviews published randomized controlled trials on the effects of massage in preterm infants. Most studies evaluating the effect of massage in weight gain in premature infants suggest a positive effect on weight gain. Increase in vagal tone has been reported in infants who receive massage and has been suggested as a possible mechanism for improved weight gain. More studies are needed on the underlying mechanisms of the effects of massage therapy on weight gain in preterm infants. While some trials suggest improvements in developmental scores, decreased stress behavior, positive effects on immune system, improved pain tolerance and earlier discharge from the hospital, the number of such studies is small and further evidence is needed. Further studies, including randomized controlled trials, are needed on the effects of massage in preterm infants.
Head, Lauren M; Baralt, Melissa; Darcy Mahoney, Ashley E
Preterm birth is associated with long-term deficits in executive functioning and cognitive performance. Using the model of brain plasticity as a theoretical framework, it is possible that preterm infants' neurodevelopmental sequelae can be altered. Evidence suggests that bilingualism confers cognitive advantages on executive functioning, so it is possible that bilingualism may improve preterm infants' neurodevelopment. However, bilingualism has only been studied in term children. This review examined literature that compared the performance of preterm-born children to term children and bilingual children to monolingual children on executive function tasks. To address cognitive disparities in preterm-born children, studies investigating the effect of bilingualism on preterm infants' executive functioning is warranted.
Li, Jingang; McDonald, Courtney A.; Fahey, Michael C.; Jenkin, Graham; Miller, Suzanne L.
Major advances in neonatal care have led to significant improvements in survival rates for preterm infants, but this occurs at a cost, with a strong causal link between preterm birth and neurological deficits, including cerebral palsy (CP). Indeed, in high-income countries, up to 50% of children with CP were born preterm. The pathways that link preterm birth and brain injury are complex and multifactorial, but it is clear that preterm birth is strongly associated with damage to the white matter of the developing brain. Nearly 90% of preterm infants who later develop spastic CP have evidence of periventricular white matter injury. There are currently no treatments targeted at protecting the immature preterm brain. Umbilical cord blood (UCB) contains a diverse mix of stem and progenitor cells, and is a particularly promising source of cells for clinical applications, due to ethical and practical advantages over other potential therapeutic cell types. Recent studies have documented the potential benefits of UCB cells in reducing brain injury, particularly in rodent models of term neonatal hypoxia–ischemia. These studies indicate that UCB cells act via anti-inflammatory and immuno-modulatory effects, and release neurotrophic growth factors to support the damaged and surrounding brain tissue. The etiology of brain injury in preterm-born infants is less well understood than in term infants, but likely results from episodes of hypoperfusion, hypoxia–ischemia, and/or inflammation over a developmental period of white matter vulnerability. This review will explore current knowledge about the neuroprotective actions of UCB cells and their potential to ameliorate preterm brain injury through neonatal cell administration. We will also discuss the characteristics of UCB-derived from preterm and term infants for use in clinical applications. PMID:25346720
Li, Xinjun; Sundquist, Jan; Sundquist, Kristina
To examine, nationwide, if there is an association between country of birth in mothers and preterm birth and to study whether any such association remains in second-generation immigrant women. In this follow-up study, a nationwide research database located at Lund University, Sweden, was used to identify all preterm born singletons in Sweden between January 1, 1982, and December 31, 2006. Incidence ratios were standardized with regard to maternal age at birth, marital status, geographical region, body height, and smoking history as well as period of birth, family income, and gender of the infant. Singletons of mothers born in Sweden were used as the reference group. There were 2,192,843 records for singletons over the study period, of whom 4.9 % were preterm births and 0.8 % were very preterm births. Increased risk of preterm birth was observed for mothers from Austria, Yugoslavia, Romania, Central Europe, and Asia. Increased risk of very preterm birth was observed for mothers from Eastern Europe, Central Europe, Africa, and Asia; these increased risk disappeared, however, in the second-generation female immigrants. Country of birth in mothers affected the risk of preterm birth; maternity care should pay special attention to women from certain population groups.
Tudehope, David I
Key principles underpinning feeding guidelines for preterm infants include support for developmental care, breastfeeding, milk expression, and creating feeding plans. Early trophic feeding with colostrum and transitional milk improves immune protection and promotes gut maturation. Studies of preterm infants demonstrate that feeding mother's milk (MM) decreases the incidence of infection and necrotizing enterocolitis and improves neurodevelopmental outcome but may decrease ponderal and linear growth. Standard practice in neonatal units is to promote mother's own milk as the feed of choice for all infants. However, it is not feasible or prudent to do so for all preterm infants. Mothers of preterm infants have lower rates of successful breastfeeding compared with those of term infants. MM can contain harmful bacterial or viral pathogens. Although preterm human milk (HM) contains higher concentrations of protein, sodium, zinc, and calcium than mature HM, it falls short of supplying adequate quantities of nutrients required by preterm infants. Therefore, HM supplemented with nutrients is recommended for all infants born before 32 weeks gestation and for certain infants born at 32-36 weeks of gestation. HM is the preferred feed, but preterm formula is an appropriate option when there is an inadequate supply of MM.
Johnson, Samantha; Wolke, Dieter; Hennessy, Enid; Marlow, Neil
This study assessed the impact of extremely preterm birth on academic attainment at 11 years of age, investigated neuropsychological antecedents of attainment in reading and mathematics, and examined early predictors of educational outcomes. Children born extremely preterm had significantly poorer academic attainment and a higher prevalence of learning difficulties than their term peers. General cognitive ability and specific deficits in visuospatial skills or phoneme deletion at 6 years were predictive of mathematics and reading attainment at 11 years in both extremely preterm and term children. Phonological processing, attention, and executive functions at 6 years were also associated with academic attainment in children born extremely preterm. Furthermore, social factors, neonatal factors (necrotizing enterocolitis, breech delivery, abnormal cerebral ultrasound, early breast milk provision), and developmental factors at 30 months (head circumference, cognitive development), were independent predictors of educational outcomes at 11 years. Neonatal complications combined with assessments of early cognitive function provide moderate prediction for educational outcomes in children born extremely preterm.
Petkovic, Maja; Chokron, Sylvie; Fagard, Jacqueline
The extent of and reasons for visuo-manual coordination deficits in moderate and late preterm born infants without neurological impairments are not well known. This paper presents a longitudinal study on the visuo-manual development of twelve preterm infants, born after 33-36 weeks of gestation without neurological complications, between the ages of 6 and 12 months. Visuo-manual integration and grasping were assessed using the Peabody Developmental Motor Scales, along with bimanual coordination and handedness tests. Visual function was examined once prior to the beginning of the study. Gross motor development was also evaluated every month. Preterm infants were compared to a control group of ten full-term infants according to corrected age. Compared to full-terms, the visual perception of preterm infants was close to normal, with only a measure of visual fixation lower than in full-terms. In contrast, preterm infants had delayed development of visuo-manual integration, grasping, bimanual coordination, and handedness even when compared using corrected age. Tonicity and gestational age at birth were the main variables associated to the delays. These results are discussed in terms of the possible factors underlying such delays. They need to be confirmed on a larger sample of preterm born children, and to be correlated with later development. This would allow developing markers of future neuropsychological impairments during childhood.
Gravett, M G
Although major advances have been made in both obstetric care of the high-risk patient and in neonatal care, prematurity and its consequences remain the major contributor to perinatal mortality. The identification of maternal or obstetric risk factors associated with preterm delivery has enhanced our ability to provide special obstetric care to gravidas at increased risk. The selective management of patients at increased risk for preterm delivery may ultimately reduce the incidence of preterm births. Maternal genital infections are also associated with preterm delivery. Further research is needed to explore the pathogenesis of preterm delivery associated with genital infections, since infections may represent a potentially preventable cause of prematurity.
Brown, Josephine V.; Bakeman, Roger; Coles, Claire D.; Sexson, William R.; Demi, Alice S.
Examined effects of prenatal drug exposure on infants born preterm and full-term to African American mothers. Found more extreme fetal growth deficits in later-born infants, and more extreme irritability increases in earlier-born infants. Gestation length did not moderate cardiorespiratory reactivity effects. Exposure effects occurred for…
Ota, Erika; Ganchimeg, Togoobaatar; Morisaki, Naho; Vogel, Joshua P.; Pileggi, Cynthia; Ortiz-Panozo, Eduardo; Souza, João P.; Mori, Rintaro
Background Small for gestational age (SGA) is not only a major indicator of perinatal mortality and morbidity, but also the morbidity risks in later in life. We aim to estimate the association between the birth of SGA infants and the risk factors and adverse perinatal outcomes among twenty-nine countries in Africa, Latin America, the Middle East and Asia in 359 health facilities in 2010–11. Methods We analysed facility-based, cross-sectional data from the WHO Multi-country Survey on Maternal and Newborn Health. We constructed multilevel logistic regression models with random effects for facilities and countries to estimate the risk factors for SGA infants using country-specific birthweight reference standards in preterm and term delivery, and SGA’s association with adverse perinatal outcomes. We compared the risks and adverse perinatal outcomes with appropriate for gestational age (AGA) infants categorized by preterm and term delivery. Results A total of 295,829 singleton infants delivered were analysed. The overall prevalence of SGA was highest in Cambodia (18.8%), Nepal (17.9%), the Occupied Palestinian Territory (16.1%), and Japan (16.0%), while the lowest was observed in Afghanistan (4.8%), Uganda (6.6%) and Thailand (9.7%). The risk of preterm SGA infants was significantly higher among nulliparous mothers and mothers with chronic hypertension and preeclampsia/eclampsia (aOR: 2.89; 95% CI: 2.55–3.28) compared with AGA infants. Higher risks of term SGA were observed among sociodemographic factors and women with preeclampsia/eclampsia, anaemia and other medical conditions. Multiparity (> = 3) (AOR: 0.88; 95% CI: 0.83–0.92) was a protective factor for term SGA. The risk of perinatal mortality was significantly higher in preterm SGA deliveries in low to high HDI countries. Conclusion Preterm SGA is associated with medical conditions related to preeclampsia, but not with sociodemographic status. Term SGA is associated with sociodemographic status and
Myers, Eliza; Ment, Laura R
Preterm birth has been defined as one of the major public health problems of this decade, preterm neonates being at high risk for neurodevelopmental disabilities. As preterm survival rates increase, the next great imperative for perinatal medicine is to understand and prevent the serious adverse neurodevelopmental outcomes of preterm birth. The challenge for neonatologists and neurologists alike is identifying early markers of outcome in the prematurely born. This article reviews current trends in prevalence, mortality, and morbidity, and the present status of outcome data for cognitive and neurosensory neurodevelopmental dysfunctions in preterm infants. New neuroimaging modalities and analysis tools are contributing to the understanding of neurologic sequelae of preterm birth by providing microstructural evidence of injury sustained by the preterm brain.
Bart, O.; Shayevits, S.; Gabis, L. V.; Morag, I.
The aim of the study was to prospectively assess the differences in participation and sensory modulation between late preterm infants (LPI) and term babies, and to predict it by LPI characteristics. The study population includes 124 late preterm infants at gestational age between 34 and 35 6/7 weeks who were born at the same medical center. The…
Spittle, Alicia J.; Cheong, Jeanie; Doyle, Lex W.; Roberts, Gehan; Lee, Katherine J.; Lim, Jeremy; Hunt, Rod W.; Inder, Terrie E.; Anderson, Peter J.
Aim: Children born very preterm are at risk for impaired motor performance ranging from cerebral palsy (CP) to milder abnormalities, such as developmental coordination disorder. White matter abnormalities (WMA) at term have been associated with CP in very preterm children; however, little is known about the impact of WMA on the range of motor…
Deng, Wei; Gage, Fred H.
The neurogenesis hypothesis of depression is based on the correlation between the rate of adult hippocampal neurogenesis and the affective status of rodents. However, studies investigating the role of neurogenesis in the causation of mood regulation have reported inconsistent results. Here, we explored whether the affective state can be affected differentially by adult-born neurons with distinctive physiological characteristics at different maturation stages. We revealed that reducing the immature newborn neuron population had no effect on anxiety- or depression-like behaviors in an array of tests; however, it enhanced hyponeophagia in a novelty suppressed feeding test, but only when the novel environment was drastically different from the home cage. We further demonstrated that reducing the immature newborn neuron population led to delayed habituation to a novel environment and impaired contextual learning. Hence, rather than being directly involved in mood regulation, our studies raise the possibility that adult neurogenesis may influence hyponeophagia through its role in mnemonic processing. PMID:25798094
MacDorman, Marian F; Callaghan, William M; Mathews, T J; Hoyert, Donna L; Kochanek, Kenneth D
Trends in preterm-related causes of death were examined by maternal race and ethnicity. A grouping of preterm-related causes of infant death was created by identifying causes that were a direct cause or consequence of preterm birth. Cause-of-death categories were considered to be preterm-related when 75 percent or more of total infant deaths attributed to that cause were deaths of infants born preterm, and the cause was considered to be a direct consequence of preterm birth based on a clinical evaluation and review of the literature. In 2004, 36.5 percent of all infant deaths in the United States were preterm-related, up from 35.4 percent in 1999. The preterm-related infant mortality rate for non-Hispanic black mothers was 3.5 times higher and the rate for Puerto Rican mothers was 75 percent higher than for non-Hispanic white mothers. The preterm-related infant mortality rate for non-Hispanic black mothers was higher than the total infant mortality rate for non-Hispanic white, Mexican, and Asian or Pacific Islander mothers. The leveling off of the U.S. infant mortality decline since 2000 has been attributed in part to an increase in preterm and low-birthweight births. Continued tracking of preterm-related causes of infant death will improve our understanding of trends in infant mortality in the United States.
Oostrom, Kim J.; Lafeber, Harrie N.; Jansma, Elise P.; Oosterlaan, Jaap
Background Neurodevelopmental sequelae in preterm born children are generally considered to result from cerebral white matter damage and noxious effects of environmental factors in the neonatal intensive care unit (NICU). Cerebral white matter damage is associated with sensory processing problems in terms of registration, integration and modulation. However, research into sensory processing problems and, in particular, sensory modulation problems, is scarce in preterm children. Aim This review aims to integrate available evidence on sensory modulation problems in preterm infants and children (<37 weeks of gestation) and their association with neurocognitive and behavioral problems. Method Relevant studies were extracted from PubMed, EMBASE.com and PsycINFO following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Selection criteria included assessment of sensory modulation in preterm born children (<37 weeks of gestation) or with prematurity as a risk factor. Results Eighteen studies were included. Results of this review support the presence of sensory modulation problems in preterm children. Although prematurity may distort various aspects of sensory modulation, the nature and severity of sensory modulation problems differ widely between studies. Conclusions Sensory modulation problems may play a key role in understanding neurocognitive and behavioral sequelae in preterm children. Some support is found for a dose-response relationship between both white matter brain injury and length of NICU stay and sensory modulation problems. PMID:28182680
Scheinost, Dustin; Kwon, Soo Hyun; Lacadie, Cheryl; Sze, Gordon; Sinha, Rajita; Constable, R Todd; Ment, Laura R
Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders. We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used. When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p < 0.05). Similarly, when compared to extremely preterm neonates without exposure to prenatal stress, extremely preterm neonates with exposure to prenatal stress show significantly less connectivity between the left amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p < 0.05). Exploratory analysis of the combined cohorts suggests additive effects of prenatal stress on alterations in amygdala connectivity associated with preterm birth. Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these
Lagercrantz, H; Edwards, D; Henderson-Smart, D; Hertzberg, T; Jeffery, H
Some autonomic nervous reflexes often tested in adult medicine have been studied in 21 preterm infants (25-37 gestational weeks). The aim was to develop such tests for preterm infants and see if there were any differences in babies with recurrent apnea and bradycardia and babies who had been exposed to sympathicolytic drugs before birth. To test sympathetic nervous activity the peripheral vascular resistance was measured before and during 45 degrees of head-up tilting. To test parasympathetic nervous activity the degree of bradycardia was measured in response to cold face test (application of an ice-cube on the fore-head) and laryngeal stimulation with saline. Finally the heart rate changes after a sudden noise (85 dB) were studied as an indicator of both sympathetic and vagal activity. The peripheral resistance was found to be relatively low in these preterm infants, particularly in some infants tested at the postnatal age of about two months. Heart rate and mean blood pressure did not change during tilting, while the peripheral resistance increased significantly mainly due to lowered limb blood flow. The median decrease of the heart rate during the cold face test was 20.0% and during laryngeal receptor stimulation 23.7%. The sudden noise usually caused a biphasic heart rate response. An autonomic nervous reflex score was calculated and found to be negative (parasympathetic) in infants with recurrent prolonged apnea and bradycardia and positive in infants with clinical signs of increased sympathetic nervous activity.
Hira-Friesen, Parvinder Kaur; Haan, Michael; Krahn, Harvey
This paper examines trades-related and university educational attainment (by age 25) of immigrant and Canadian-born Alberta youth while controlling for gender, family socio-economic status, high school grades, and parental encouragement regarding higher education. Data from the longitudinal Alberta School-Work Transitions Study (1996-2003) reveal…
Patel, Chirag J; Yang, Ting; Hu, Zhongkai; Wen, Qiaojun; Sung, Joyce; El-Sayed, Yasser Y; Cohen, Harvey; Gould, Jeffrey; Stevenson, David K; Shaw, Gary M; Ling, Xuefeng Bruce; Butte, Atul J
Identification of maternal environmental factors influencing preterm birth risks is important to understand the reasons for the increase in prematurity since 1990. Here, we utilized a health survey, the US National Health and Nutrition Examination Survey (NHANES) to search for personal environmental factors associated with preterm birth. 201 urine and blood markers of environmental factors, such as allergens, pollutants, and nutrients were assayed in mothers (range of N: 49-724) who answered questions about any children born preterm (delivery <37 weeks). We screened each of the 201 factors for association with any child born preterm adjusting by age, race/ethnicity, education, and household income. We attempted to verify the top finding, urinary bisphenol A, in an independent study of pregnant women attending Lucile Packard Children's Hospital. We conclude that the association between maternal urinary levels of bisphenol A and preterm birth should be evaluated in a larger epidemiological investigation.
Lubsen, Julia; Vohr, Betty; Myers, Eliza; Hampson, Michelle; Lacadie, Cheryl; Schneider, Karen C; Katz, Karol H; Constable, R Todd; Ment, Laura R
Prematurely born children are at increased risk for cognitive deficits, but the neurobiological basis of these findings remains poorly understood. Because variations in neural circuitry may influence performance on cognitive tasks, recent investigations have explored the impact of preterm birth on connectivity in the developing brain. Diffusion tensor imaging studies demonstrate widespread alterations in fractional anisotropy, a measure of axonal integrity and microstructural connectivity, throughout the developing preterm brain. Functional connectivity studies report that preterm neonates, children and adolescents exhibit alterations in both resting state and task-based connectivity when compared with term control subjects. Taken together, these data suggest that neurodevelopmental impairment following preterm birth may represent a disease of neural connectivity.
Lahat, Ayelet; Van Lieshout, Ryan J; Saigal, Saroj; Boyle, Michael H; Schmidt, Louis A
Although infants born at extremely low birth weight (ELBW; birth weight < 1000 g) are at increased risk for developing later psychopathology, the mechanisms contributing to this association are largely unknown. In the present study, we examined a putative cognitive link to psychopathology in a cohort of ELBW survivors. These individuals were followed up prospectively at age 8 and again at ages 22-26. At 8 years, participants completed measures of fluid and general intelligence. As young adults, a subset of ELBW survivors free of major neurosensory impairments provided self-reports of personality characteristics related to psychopathology. Data from 66 participants indicated that, as predicted, the association between ELBW and externalizing behaviors was moderated by fluid intelligence. Specifically, ELBW individuals with poor fluid intelligence who were born small for gestational age (birth weight < 10th percentile for gestational age) showed the highest level of externalizing behaviors. These findings provide support for a cumulative risk model and suggest that fluid intelligence might be a cognitive mechanism contributing to the development of psychopathology among nonimpaired individuals who were born at ELBW and small for gestational age.
Conway, Francine; Magai, Carol; Jones, Samuel; Fiori, Katherine; Gillespie, Michael
This study explores dynamic changes in network size and composition by examining patterns of older adults' social network change over time, that is: types of movements; the reason for the loss of network members; and the relation of movement and composition in concert. This study is a 6-year follow up of changes in the social networks of U.S.-Born Caucasian, African-American, and Caribbean older adults. One hundred and twenty-four community-dwelling older adults were interviewed during 2 data collection points over a 6-year period. Differences between Wave 1 and Wave 2 data were examined using paired sample t-tests confirmed with post-hoc tests and multivariate analyses. Results regarding types of movement showed that network changes were attributed to attrition--the "loss" of network members and a novel movement--the "addition" of network members not heretofore discussed. The results show an interaction between kinship status, ethnicity, and time--the attrition of non-kin members was underscored by ethnic differences. The type of network change was specific for type of network affiliation, such that children were more likely to be added to the networks of the young-old and kin were more likely to be lost in networks of the old-old. Older adults engage in social network interactions marked by compensatory processes beyond loss of network members such as social promotion and demotion. These social network processes are of emotional and functional significance for the older adult.
Mangin, Kathryn S.; Horwood, L. J.; Woodward, Lianne J.
Cognitive impairment is common among children born very preterm (VPT), yet little is known about how this risk changes over time. To examine this issue, a regional cohort of 110 VPT (= 32 weeks gestation) and 113 full-term (FT) born children was prospectively assessed at ages 4, 6, 9, and 12 years using the Wechsler Preschool and Primary Scale of…
... Medical risk factors for preterm labor and premature birth Getting late or no prenatal care . Prenatal care is medical ... your everyday life for preterm labor and premature birth Smoking , drinking ... having little education, low income, being unemployed or having little support from ...
Background Globally, about 15 million neonates are born preterm and about 85% of global preterm birth occurs in Asia and Africa regions. We aimed to estimate the incidence and risk factors for preterm birth in a rural Bangladeshi cohort. Methods Between June 2007 and September 2009, community health workers prospectively collected data from 32,126 mother-live-born baby pairs on household socio-demographic status, pregnancy history, antenatal care seeking and newborn gestational age determined by recall of date of last menstrual period. Results Among all live births, 22.3% were delivered prior to 37 weeks of gestation (i.e. preterm); of which 12.3% were born at 35–36 weeks of gestation (late preterm), 7.1% were born at 32–34 weeks (moderate preterm), and 2.9% were born at 28–31 weeks of gestation (very preterm). Overall, the majority of preterm births (55.1%) were late preterm. Risk of preterm birth was lower among women with primary or higher level of education (RR: 0.92; 95% CI: 0.88, 0.97), women who sought antenatal care at least once during the index pregnancy (RR: 0.86; 95% CI: 0.83, 0.90), and women who had completed all birth preparedness steps (RR: 0.32; 95% CI: 0.30, 0.34). In contrast, risk of preterm birth was higher among women with a history of child death (RR: 1.05; 95% CI: 1.01, 1.10), who had mid-upper arm circumference (MUAC) ≤250 mm, indicative of under nutrition (for women having MUAC <214 mm the risk was higher; RR: 1.26; 95% CI: 1.17, 1.35), who reported an antenatal complication (RR: 1.32; 95% CI: 1.14, 1.53), and who received iron-folic acid supplementation for 2–6 months during the index pregnancy (RR: 1.33; 95% CI: 1.24, 1.44). Conclusions In resource poor settings with high burden of preterm birth, alike Bangladesh, preterm birth risk could be reduced by close monitoring and/or frequent follow-up of women with history of child death and antenatal complications, by encouraging women to seek antenatal care from qualified
Makrydimas, George; Sotiriadis, Alexandros
About 13% of twins are born before 34 weeks and 7% before 32 weeks. The prediction of preterm birth in twins is based on the same tests as in singleton pregnancies. In twin pregnancies, the cut-off for short cervix at the second trimester scan is less than 25 mm (compared with 15 mm in singletons); length less than 20 mm is associated with 42% risk for birth before 32 weeks and cervical length less than 25 mm is associated with 28% risk for birth before 28 weeks. The measurement of cervical length in pregnancies with symptoms of preterm labour may have limited accuracy in predicting preterm birth. In asymptomatic women, a positive fetal fibronectin test seems to be associated with 35% risk for birth before 32 weeks and 40% risk for birth less than 34 weeks, whereas a negative test decreases the risk to 6% and 17%, respectively. The differences in the predictive value of tests between twins and singletons reflect the diverse pathophysiology of preterm birth between the two groups.
Beauchamp, Miriam H.; Thompson, Deanne K.; Howard, Kelly; Doyle, Lex W.; Egan, Gary F.; Inder, Terrie E.; Anderson, Peter J.
Children born preterm exhibit working memory deficits. These deficits may be associated with structural brain changes observed in the neonatal period. In this study, the relationship between neonatal regional brain volumes and working memory deficits at age 2 years were investigated, with a particular interest in the dorsolateral prefrontal…
Fazzi, Elisa; Bova, Stefania; Giovenzana, Alessia; Signorini, Sabrina; Uggetti, Carla; Bianchi, Paolo
Aim: Cognitive visual dysfunctions (CVDs) reflect an impairment of the capacity to process visual information. The question of whether CVDs might be classifiable according to the nature and distribution of the underlying brain damage is an intriguing one in child neuropsychology. Method: We studied 22 children born preterm (12 males, 10 females;…
Aarnoudse-Moens, Cornelieke S. H.; Smidts, Diana P.; Oosterlaan, Jaap; Duivenvoorden, Hugo J.; Weisglas-Kuperus, Nynke
We examined whether very preterm ([less than or equal to] 30 weeks gestation) children at early school age have impairments in executive function (EF) independent of IQ and processing speed, and whether demographic and neonatal risk factors were associated with EF impairments. A consecutive sample of 50 children (27 boys and 23 girls) born very…
Bonnet, S; de la Fuente, J; Nicollet, P; Liu, X; Madani, N; Blanchard, B; Maingourd, C; Alongi, A; Torina, A; Fernández de Mera, I G; Vicente, J; George, J-C; Vayssier-Taussat, M; Joncour, G
The importance of Dermacentor spp. in the transmission of tick-borne pathogens is not well recognized in Europe. To investigate the role of Dermacentor spp. in the transmission of tick-borne pathogens, questing ticks were collected in 9 sites from southern to northwestern France (Camargue Delta to Eastern Brittany) where Dermacentor spp. exist and tick-borne diseases had occurred previously. Three tick species were collected during the spring and autumn of 2009. Collected ticks (both males and females) included D. marginatus (n=377), D. reticulatus (n=74), and I. ricinus (n=45). All ticks were analyzed by PCR or reverse line blot for the presence of pathogens' DNA. Pathogens analyzed were based on veterinarian reports and included Anaplasma phagocytophilum, Coxiella burnetii, Anaplasma marginale, Borrelia burgdorferi, Bartonella spp., Babesia spp., Theileria spp., and Francisella sp. Francisella tularensis was not detected in any of the analyzed ticks. In D. marginatus, infection prevalence for A. phagocytophilum (3%) was similar to that found in I. ricinus in Europe. Other pathogens present in D. marginatus included A. marginale (0.5%), Bartonella spp. (9%), C. burnetii (12%), F. philomiragia (1.3%), and Theileria annulata/Babesia bovis (0.3%), which were detected for the first time in France. Pathogens detected in D. reticulatus included A. marginale (1%), Bartonella spp. (12%), C. burnetii (16%), Borrelia spp. (1.5%), and F. philomiragia (19%). Pathogens detected in I. ricinus included A. phagocytophilum (41%), Bartonella spp. (9%), C. burnetii (18%), A. marginale (1%), Borrelia spp. (4.5%), and Babesia sp. (7%). This study represents the first epidemiological approach to characterize tick-borne pathogens infecting Dermacentor spp. in France and that may be transmitted by ticks from this genus. Further experiments using experimental infections and transmission may be now conducted to analyze vector competency of Dermacentor spp. for these pathogens and to
Bucci, Maria Pia; Wiener-Vacher, Sylvette; Trousson, Clémence; Baud, Olivier; Biran, Valerie
Purpose We compared postural stability and subjective visual vertical performance in a group of very preterm-born children aged 3-4 years and in a group of age-matched full-term children. Materials and Methods A platform (from TechnoConcept) was used to measure postural control in children. Perception of subjective visual vertical was also recorded with posture while the child had to adjust the vertical in the dark or with visual perturbation. Two other conditions (control conditions) were also recorded while the child was on the platform: for a fixation of the vertical bar, and in eyes closed condition. Results Postural performance was poor in preterm-born children compared to that of age-matched full-term children: the surface area, the length in medio-lateral direction and the mean speed of the center of pressure (CoP) were significantly larger in the preterm-born children group (p < 0.04, p < 0.01, and p < 0.04, respectively). Dual task in both groups of children significantly affected postural control. The subjective visual vertical (SVV) values were more variable and less precise in preterm-born children. Discussion-Conclusions We suggest that poor postural control as well as perception of verticality observed in preterm-born children could be due to immaturity of the cortical processes involved in the motor control and in the treatment of perception and orientation of verticality. PMID:25790327
Cohen, Dale J.; White, Sheida; Cohen, Steffaney B.
This study analyzed the current state of the gender literacy gap and the change in the gender literacy gap between 1992 and 2003, using the 1992 National Adult Literacy Survey (NALS) and the 2003 National Assessment of Adult Literacy (NAAL). The results revealed that although there were significant gender literacy gaps in 1992, virtually all…
Petkovic, Maja; Rat-Fischer, Lauriane; Fagard, Jacqueline
Preterm born children without neurological impairments have been shown to present some visual-manual coordination deficits, more or less depending on their tonicity and the degree of prematurity. In this paper, we compare the development of tool use in 15–23-month-old preterm infants born after 33–36 weeks of gestation without neurological complications with that of full-term infants according to corrected age. Understanding the affordance of a tool is an important cognitive milestone in early sensorimotor period. Using a tool to bring within reach an out-of-reach object, for instance, has been shown to develop during the 2nd year in full-term infants. Here we presented preterm infants with an attractive toy out of reach and with a rake-like tool within reach in five conditions of spatial relationships between the toy and the tool. Like full-terms, preterm infants used the tool with success in conditions of spatial contiguity around 15–17 months. In conditions of a spatial gap between tool and toy, i.e., the only conditions which shows without ambiguity that the infant understands the affordance of the tool, preterm infants as a group showed no delay for tool use: the frequency of spontaneous successes started to increase after 18 months, and demonstration became effective after that age. However, further analyses showed that only the preterm infants without hypotonia and born after 36 weeks of pregnancy developed tool use without delay. Hypotonic preterm infants were still largely unsuccessful in the conditions of spatial gap, even at the end of the study. The degree of prematurity also influenced the performance at tool use. These results, following the observation of a delay in the development of bimanual coordination and of handedness in the same infants at 10–12 months in a previous study, show that low risk preterm infants can still be impaired for the development of new manual skills beyond the 1st year. Thus, hypotonic preterm infants and infants
Petkovic, Maja; Rat-Fischer, Lauriane; Fagard, Jacqueline
Preterm born children without neurological impairments have been shown to present some visual-manual coordination deficits, more or less depending on their tonicity and the degree of prematurity. In this paper, we compare the development of tool use in 15-23-month-old preterm infants born after 33-36 weeks of gestation without neurological complications with that of full-term infants according to corrected age. Understanding the affordance of a tool is an important cognitive milestone in early sensorimotor period. Using a tool to bring within reach an out-of-reach object, for instance, has been shown to develop during the 2nd year in full-term infants. Here we presented preterm infants with an attractive toy out of reach and with a rake-like tool within reach in five conditions of spatial relationships between the toy and the tool. Like full-terms, preterm infants used the tool with success in conditions of spatial contiguity around 15-17 months. In conditions of a spatial gap between tool and toy, i.e., the only conditions which shows without ambiguity that the infant understands the affordance of the tool, preterm infants as a group showed no delay for tool use: the frequency of spontaneous successes started to increase after 18 months, and demonstration became effective after that age. However, further analyses showed that only the preterm infants without hypotonia and born after 36 weeks of pregnancy developed tool use without delay. Hypotonic preterm infants were still largely unsuccessful in the conditions of spatial gap, even at the end of the study. The degree of prematurity also influenced the performance at tool use. These results, following the observation of a delay in the development of bimanual coordination and of handedness in the same infants at 10-12 months in a previous study, show that low risk preterm infants can still be impaired for the development of new manual skills beyond the 1st year. Thus, hypotonic preterm infants and infants born
Domínguez Rubio, Ana P; Sordelli, Micaela S; Salazar, Ana I; Aisemberg, Julieta; Bariani, María V; Cella, Maximiliano; Rosenstein, Ruth E; Franchi, Ana M
Preterm delivery is the leading cause of neonatal mortality and contributes to delayed physical and cognitive development in children. At present, there is no efficient therapy to prevent preterm labor. A large body of evidence suggests that intra-amniotic infections may be a significant and potentially preventable cause of preterm birth. This work assessed the effect of melatonin in a murine model of inflammation-associated preterm delivery which mimics central features of preterm infection in humans. For this purpose, preterm labor was induced in BALB/c mice by intraperitoneal injections of bacterial lipopolysaccharide (LPS) at 10.00 hr (10 μg LPS) and 13.00 hr (20 μg LPS) on day 15 of pregnancy. On day 14 of pregnancy, a pellet of melatonin (25 mg) had been subcutaneously implanted into a group of animals. In the absence of melatonin, a 100% incidence of preterm birth was observed in LPS-treated animals, and the fetuses showed widespread damage. By comparison, treatment with melatonin prevented preterm birth in 50% of the cases, and all pups from melatonin-treated females were born alive and their body weight did not differ from control animals. Melatonin significantly prevented the LPS-induced rises in uterine prostaglandin (PG) E2 , PGF2α, and cyclooxygenase-2 protein levels. In addition, melatonin prevented the LPS-induced increase in uterine nitric oxide (NO) production, inducible NO synthase protein, and tumor necrosis factor-alpha (TNFα) levels. Collectively, our results suggest that melatonin could be a new therapeutic tool to prevent preterm labor and to increase offspring survival.
Hodel, Amanda S.; Brumbaugh, Jane E.; Morris, Alyssa R.; Thomas, Kathleen M.
Interest in monitoring long-term neurodevelopmental outcomes of children born moderate-to-late preterm (32-36 weeks gestation) is increasing. Moderate-to-late preterm birth has a negative impact on academic achievement, which may relate to differential development of executive function (EF). Prior studies reporting deficits in EF in preterm…
Poehlmann, Julie; Schwichtenberg, A. J. Miller; Bolt, Daniel M.; Hane, Amanda; Burnson, Cynthia; Winters, Jill
This longitudinal study examined predictors of rates of growth in dyadic interaction quality in children born preterm who did not experience significant neurological findings during neonatal intensive care unit (NICU) hospitalization. Multiple methods were used to collect data from 120 preterm infants (48% girls, 52% boys) and their mothers.…
Butcher, Phillipa R.; van Braeckel, Koen; Bouma, Anke; Einspieler, Christa; Stremmelaar, Elisabeth F.; Bos, Arend F.
Background: The quality of very preterm infants' spontaneous movements at 11 to 16 weeks post-term age is a powerful predictor of their later neurological status. This study investigated whether early spontaneous movements also have predictive value for the intellectual and behavioural problems that children born very preterm often experience.…
Dall'Oglio, Anna M.; Rossiello, Barbara; Coletti, Maria F.; Bultrini, Massimiliano; De Marchis, Chiara; Rava, Lucilla; Caselli, Cristina; Paris, Silvana; Cuttini, Marina
Aim: The aim of this study was to determine neuropsychological performance (possibly predictive of academic difficulties) and its relationship with cognitive development and maternal education in healthy preterm children of preschool age and age-matched comparison children born at term. Method : A total of 35 infants who were born at less than 33…
Scott, Fiona E.; Mechelli, Andrea; Allin, Matthew P.; Walshe, Muriel; Rifkin, Larry; Murray, Robin M.; Nosarti, Chiara
Individuals born very preterm (VPT) are at risk of neurodevelopmental damage and of adverse educational outcomes in childhood and adolescence. The present study used voxel-based morphometry to investigate the association between grey matter and white matter volume and measures of language and executive functioning in VPT born adolescents and…
Bilguvar, Kaya; DiLuna, Michael L; Bizzarro, Matthew J; Bayri, Yasar; Schneider, Karen C; Lifton, Richard P; Gunel, Murat; Ment, Laura R
Intraventricular hemorrhage is a common complication of preterm infants. Mutations in the type IV procollagen gene, COL4A1, are associated with cerebral small vessel disease with hemorrhage in adults and fetuses. We report a rare variant in COL4A1 associated with intraventricular hemorrhage in dizygotic preterm twins. These results expand the spectrum of diseases attributable to mutations in type IV procollagens.
Schappin, Renske; Wijnroks, Lex; Uniken Venema, Monica M. A. T.; Jongmans, Marian J.
Background With improved medical outcome in preterm infants, the psychosocial situation of their families is receiving increasing attention. For parents, the birth of a preterm infant is generally regarded as a stressful experience, and therefore many interventions are based on reducing parental stress. Nevertheless, it remains unclear whether parents of children born preterm experience more stress than parents of term-born children, which would justify these interventions. This meta-analysis provides a comprehensive account of parental stress in parents of preterm infants, from birth of the infant through to their adolescence. Mean levels of stress in specific domains of family functioning were investigated, and stress levels in parents of preterm and term infants, and fathers and mothers of preterm infants, were compared. Furthermore, we investigated moderators of parental stress. Methods and Findings A random-effects meta-analysis was conducted including 38 studies describing 3025 parents of preterm (<37 wk) and low birth weight (<2500 g) infants. Parental stress was measured with two parent-reported questionnaires, the Parenting Stress Index and the Parental Stressor Scale: Neonatal Intensive Care Unit. The results indicate that parents of preterm-born children experience only slightly more stress than parents of term-born children, with small effect sizes. Furthermore, mothers have slightly more stress than fathers, but these effect sizes are also small. Parents report more stress for infants with lower gestational ages and lower birth weights. There is a strong effect for infant birth year, with decreasing parental stress from the 1980s onward, probably due to increased quality of care for preterm infants. Conclusions Based on our findings we argue that prematurity can best be regarded as one of the possible complications of birth, and not as a source of stress in itself. PMID:23405105
Dunietz, Galit Levi; Holzman, Claudia; McKane, Patricia; Li, Chenxi; Boulet, Sheree L.; Todem, David; Kissin, Dmitry M.; Copeland, Glenn; Bernson, Dana; Sappenfield, William M.; Diamond, Michael P.
Objective To investigate the risk of preterm birth among liveborn singletons to primiparas who conceived with assisted reproductive technology (ART) using four mutually exclusive categories of infertility (female infertility only, male infertility only, female and male infertility, and unexplained infertility) and to examine preterm birth risk along the gestational age continuum. Design Retrospective cohort study. Setting Not applicable. Patient(s) Singletons born to primiparas who conceived with or without ART. Intervention(s) None. Main Outcome Measure(s) Preterm (<37 weeks’ gestation) and preterm/early term birth <39 weeks’ gestation). Result(s) For the male infertility only, female infertility only, combined male and female infertility, and unexplained infertility groups, ART-conceived singletons were significantly more likely than non-ART singletons to be born preterm: adjusted odds ratio (aOR) 1.24 (95% CI, 1.13, 1.37), aOR 1.60 (95% CI, 1.50, 1.70), aOR 1.49 (95% CI, 1.35, 1.64), and aOR 1.26 (1.12, 1.43) respectively. Among infants whose mothers were diagnosed with infertility, the odds of preterm birth were highest between 28–30 weeks [female infertility only, aOR 1.95 (95% CI, 1.59, 2.39); male and female infertility: 2.21 (95% CI, 1.62, 3.00)] compared with infants in the general population. Within the ART population, singletons of couples with female infertility only were more likely to be born preterm than singletons born to couples with other infertility diagnoses. Conclusion(s) Among singleton births to primiparas, those conceived with ART had an increased risk for preterm birth, even when only the male partner had been diagnosed with infertility. The risk of preterm birth for ART-conceived infants whose mothers were diagnosed with infertility included the earliest deliveries. PMID:25707336
Each year, more than 1 in 10 of the world’s babies are born preterm, resulting in 15 million babies born too soon. World Prematurity Day, November 17, is a global effort to raise awareness about prematurity. This past year, there has been increased awareness of the problem, through new data and evidence, global partnership and country champions. Actions to improve care would save hundreds of thousands of babies born too soon from death and disability. Accelerated prevention requires urgent research breakthroughs. PMID:23148557
... in both full-term and preterm babies. The hepatitis B vaccine deserves special mention. In most circumstances, the AAP recommends the hepatitis B vaccine at birth or before the baby is discharged ...
Knight, Anna K.; Smith, Alicia K.
A biomarker is a biological measure predictive of a normal or pathogenic process or response. Biomarkers are often useful for making clinical decisions and determining treatment course. One area where such biomarkers would be particularly useful is in identifying women at risk for preterm delivery and related pregnancy complications. Neonates born preterm have significant morbidity and mortality, both in the perinatal period and throughout the life course, and identifying women at risk of delivering preterm may allow for targeted interventions to prevent or delay preterm birth (PTB). In addition to identifying those at increased risk for preterm birth, biomarkers may be able to distinguish neonates at particular risk for future complications due to modifiable environmental factors, such as maternal smoking or alcohol use during pregnancy. Currently, there are no such biomarkers available, though candidate gene and epigenome-wide association studies have identified DNA methylation differences associated with PTB, its risk factors and its long-term outcomes. Further biomarker development is crucial to reducing the health burden associated with adverse intrauterine conditions and preterm birth, and the results of recent DNA methylation studies may advance that goal. PMID:27089367
Burris, Heather H; Baccarelli, Andrea A; Wright, Robert O; Wright, Rosalind J
Preterm birth remains a leading cause of infant mortality and morbidity. Despite decades of research, marked racial and socioeconomic disparities in preterm birth persist. In the US, more than 16% of African American infants are born before 37 weeks of gestation compared to less than 11% of white infants. While income and education differences predict a portion of these racial disparities, income and education are proxies of the underlying causes rather than the true cause. How these differences lead to the pathophysiology remains unknown. Beyond tobacco smoke exposure, most preterm birth investigators overlook environment exposures that often correlate with poverty. Environmental exposures to industrial contaminants track along both socioeconomic and racial/ethnic lines due to cultural variation in personal product use, diet and residential geographical separation. Emerging evidence suggests that environmental exposure to metals and plasticizers contribute to preterm birth and epigenetic modifications. The extent to which disparities in preterm birth result from interactions between the social and physical environments that produce epigenetic modifications remains unclear. In this review, we highlight studies that report associations between environmental exposures and preterm birth as well as perinatal epigenetic sensitivity to environmental contaminants and socioeconomic stressors. PMID:26460521
Vargas González, Alejandro; Canales Muñoz, José Luis; Torres Gómez, Luis Guillermo; Barba Bustos, Ana María
One of the principal challenges of obstetrics is to reduce the percentage of perinatal mortality. Preterm birth is considered the main cause of neonatal morbidity and mortality. Preterm birth by medical indication, is a condition rarely documented in medical literature, but it requires analysis to determine the effect in perinatal health. In a third care hospital setting, a prospective study was performed on 154 pregnant women that delivered preterm babies between 25 and 36 weeks of gestation. The Relative Risk (RR) was obtained to compare the association between the medical indication of the preterm birth, the use of fetal pulmonary maturants, type of delivery, the health status of the newborn at birth and hospital discharge. The main causes of preterm birth by medical indication were: premature rupture of membranes, preeclampsia, intrauterine growth retardation and fetal distress. Neonatal mortality was 13%. The rate of cesarean section was higher than expected. Despite the various types of delivery, there were no significant differences between mortality, length of hospital stay or hospital complications. The probability of death to preterm born was explained to gestational age and was not modified for medical decision to interrupt pregnancy.
Hamama-Raz, Yaira; Rosenfeld, Sarah; Buchbinder, Eli
This article is based on a qualitative study examining the experiences of parents that lost a son during military service in Israel and consequently choose to give birth to another child. Seven couples and 3 mothers were interviewed for the study, and their interviews were analyzed using a phenomenological-hermeneutic approach. Three main themes were extracted from parents' descriptions of their experiences: (a) "From the place where pain and sadness was sown, a new smile was grown," relating to transforming the experience of loss into a new meaning for life; (b) "No to a child memorial," focusing on parents' awareness of the burden placed on the child who was born; and (c) "Different parenting," dealing with participant's parenting following their loss. The study's findings are discussed in the context of literature dealing with reconstructing meaning through coping and bereavement.
Tusor, Nora; Arichi, Tomoki; Counsell, Serena J; Edwards, A David
Infants who are born preterm have a high incidence of neurocognitive and neurobehavioral abnormalities, which may be associated with impaired brain development. Advanced magnetic resonance imaging (MRI) approaches, such as diffusion MRI (d-MRI) and functional MRI (fMRI), provide objective and reproducible measures of brain development. Indices derived from d-MRI can be used to provide quantitative measures of preterm brain injury. Although fMRI of the neonatal brain is currently a research tool, future studies combining d-MRI and fMRI have the potential to assess the structural and functional properties of the developing brain and its response to injury.
Paul, Rachel A; Smyser, Christopher D; Rogers, Cynthia E; English, Ian; Wallendorf, Michael; Alexopoulos, Dimitrios; Meyer, Erin J; Van Essen, David C; Neil, Jeffrey J; Inder, Terrie E
Allometry has been used to demonstrate a power–law scaling relationship in the brain of premature born infants. Forty-nine preterm infants underwent neonatal MRI scans and neurodevelopmental testing at age 2. Measures of cortical surface area and total cerebral volume demonstrated a power–law scaling relationship (α = 1.27). No associations were identified between these measures and investigated clinical variables. Term equivalent cortical surface area and total cerebral volume measures and scaling exponents were not related to outcome. These findings confirm a previously reported allometric scaling relationship in the preterm brain, and suggest that scaling is not a sensitive indicator of aberrant cortical maturation. PMID:25540808
Victor, S; Dickinson, H; Turner, M A
The aim of this study was to generate reference ranges for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in preterm infants by describing the observed plasma concentration of these enzymes in babies born between 22 and 36 weeks' gestation. A service evaluation was conducted in babies admitted to two large neonatal intensive care units in the UK. 7006 blood samples from 1860 infants admitted to the two units between 2004 and 2008 were included. Extremely premature infants had high plasma enzyme activities when compared to babies at a later corrected gestational age. This may be due to more severe illness immediately after birth.
de Oliveira, Victor Hugo; Quintana-Domeque, Climent
We study the relationship between environmental conditions at birth (GDP per capita and infant mortality rate) and adult stature using cohort-state level data in Brazil for the period 1950-1980. We find that GDP per capita, whose annual percentage growth rate was 4.8% during this period, not infant mortality rate, is a robust correlate of population stature in Brazil. Our results are robust to a battery of robustness checks. Using a useful bracketing property of the (state) fixed effects and lagged dependent variables (heights) estimators, we find that an increase in GDP per capita of the magnitude corresponding to that period is associated with 43-68% of the increase in adult height occurring in the same time span. Income, not disease, appears to be the main correlate of Brazilian population heights in the second half of the 20th Century.
Thomason, Moriah E; Scheinost, Dustin; Manning, Janessa H; Grove, Lauren E; Hect, Jasmine; Marshall, Narcis; Hernandez-Andrade, Edgar; Berman, Susan; Pappas, Athina; Yeo, Lami; Hassan, Sonia S; Constable, R Todd; Ment, Laura R; Romero, Roberto
It has been suggested that neurological problems more frequent in those born preterm are expressed prior to birth, but owing to technical limitations, this has been difficult to test in humans. We applied novel fetal resting-state functional MRI to measure brain function in 32 human fetuses in utero and found that systems-level neural functional connectivity was diminished in fetuses that would subsequently be born preterm. Neural connectivity was reduced in a left-hemisphere pre-language region, and the degree to which connectivity of this left language region extended to right-hemisphere homologs was positively associated with the time elapsed between fMRI assessment and delivery. These results provide the first evidence that altered functional connectivity in the preterm brain is identifiable before birth. They suggest that neurodevelopmental disorders associated with preterm birth may result from neurological insults that begin in utero.
Thomason, Moriah E.; Scheinost, Dustin; Manning, Janessa H.; Grove, Lauren E.; Hect, Jasmine; Marshall, Narcis; Hernandez-Andrade, Edgar; Berman, Susan; Pappas, Athina; Yeo, Lami; Hassan, Sonia S.; Constable, R. Todd; Ment, Laura R.; Romero, Roberto
It has been suggested that neurological problems more frequent in those born preterm are expressed prior to birth, but owing to technical limitations, this has been difficult to test in humans. We applied novel fetal resting-state functional MRI to measure brain function in 32 human fetuses in utero and found that systems-level neural functional connectivity was diminished in fetuses that would subsequently be born preterm. Neural connectivity was reduced in a left-hemisphere pre-language region, and the degree to which connectivity of this left language region extended to right-hemisphere homologs was positively associated with the time elapsed between fMRI assessment and delivery. These results provide the first evidence that altered functional connectivity in the preterm brain is identifiable before birth. They suggest that neurodevelopmental disorders associated with preterm birth may result from neurological insults that begin in utero. PMID:28067865
Tannenholz, Lindsay; Hen, René; Kheirbek, Mazen A.
Ablation of adult neurogenesis in mice has revealed that young adult-born granule cells (abGCs) are required for some of the behavioral responses to antidepressants (ADs), yet the mechanism by which abGCs contribute to AD action remains unknown. During their maturation process, these immature neurons exhibit unique properties that could underlie their ability to influence behavioral output. In particular, abGCs in the DG exhibit a period of heightened plasticity 4–6 weeks after birth that is mediated by GluN2B-expressing NMDA receptors. The functional contribution of this critical window to AD responsiveness is unclear. Here, we determined the behavioral and neurogenic responses to the AD fluoxetine (FLX) in mice lacking GluN2B-containing NMDA receptors in abGCs. We found that these mice exhibited an attenuated response to FLX in a neurogenesis-dependent behavioral assay of FLX action, while neurogenesis-independent behaviors were unaffected by GluN2B deletion. In addition, deletion of GluN2B attenuated FLX-induced increases in dendritic complexity of abGCs suggesting that the blunted behavioral efficacy of FLX may be caused by impaired differentiation of young abGCs. PMID:27303260
Gondwe, Austrida; Munthali, Alister; Ashorn, Per; Ashorn, Ulla
Objectives Malawi is estimated to have one of the highest preterm birth rates in the world. However, care of preterm infants at facility level in Malawi has not been explored. We aimed to explore the views of health stakeholders about the care of preterm infants in health facilities and the existence of any policy protocol documents guiding the delivery of care to these infants. Methods We conducted 16 in-depth interviews with health stakeholders (11 service providers and 5 policy makers) using an interview guide and asked for any existing policy protocol documents guiding care for preterm infants in the health facilities in Malawi. The collected documents were reviewed and all the interviews were digitally recorded, transcribed and translated. All data were analysed using content analysis approach. Results We identified four policy protocol documents and out of these, one had detailed information explaining the care of preterm infants. Policy makers reported that policy protocol documents to guide care for preterm infants were available in the health facilities but majority (63.6 %) of the service providers lacked knowledge about the existence of these documents. Health stakeholders reported several challenges in caring for preterm infants including lack of trained staff in preterm infant care, antibiotics, space, supervision and poor referral system. Conclusions Our study highlights that improving health care service provider knowledge of preterm infant care is an integral part in preterm child birth. Our findings suggests that policy makers and health decision makers should retain those trained in preterm new born care in the health facility's preterm unit.
Thomaz, C. E.; Boardman, J. P.; Counsell, S.; Hill, D. L. G.; Hajnal, J. V.; Edwards, A. D.; Rutherford, M. A.; Gillies, D. F.; Rueckert, D.
Pre-term birth is strongly associated with subsequent neuropsychiatric impairment. To identify structural differences in preterm infants we have examined a dataset of magnetic resonance (MR) images containing 88 preterm infants and 19 term born controls. We have analyzed these images by combining image registration, deformation based morphometry (DBM), multivariate statistics, and effect size maps (ESM). The methodology described has been performed directly on the MR intensity images rather than on segmented versions of the images. The results indicate that the approach described makes clear the statistical differences between the control and preterm samples, showing a leave-one-out classification accuracy of 94.74% and 95.45% respectively. In addition, finding the most discriminant direction between the groups and using DBM features and ESM we are able to identify not only what are the changes between preterm and term groups but also how relatively relevant they are in terms of volume expansion and contraction.
Rogers, Elizabeth E; Hintz, Susan R
Infants born at extreme preterm gestation are at risk for both death and disability. Although rates of survival have improved for this population, and some evidence suggests a trend toward decreased neuromotor impairment over the past decades, a significant improvement in overall early neurodevelopmental outcome has not yet been realized. This review will examine the rates and types of neurodevelopmental impairment seen after extremely preterm birth, including neurosensory, motor, cognitive, and behavioral outcomes. We focus on early outcomes in the first 18-36 months of life, as the majority of large neonatal studies examining neurodevelopmental outcomes stop at this age. However, this early age is clearly just a first glimpse into lifetime outcomes; the neurodevelopmental effects of extreme prematurity may last through school age, adolescence, and beyond. Importantly, prematurity appears to be an independent risk factor for adverse development, but this population demonstrates considerable variability in the types and severity of impairments. Understanding both the nature and prevalence of neurodevelopmental impairment among extremely preterm infants is important because it can lead to targeted interventions that in turn may lead to improved outcomes.
Smith, Jacqueline; Alcock, Gary; Usher, Kim
The maintenance of a constant body temperature is important to all humans but even more so for newborn babies (neonates), especially those born pre-term. Because accurate measurement of body temperature is an important component of thermoregulation management in the neonate, a review of the literature was undertaken to determine the most appropriate method and site of temperature measurement in both the preterm and term neonate. The available evidence indicates that the axilla remains the most common place for temperature measurement.
Cabral, Thais Invenção; Pereira da Silva, Louise Gracelli; Tudella, Eloisa; Simões Martinez, Cláudia Maria
Infants born preterm and/or with low birth weight may present a clinical condition of organic instability and usually face a long period of hospitalization in the Neonatal Intensive Care Units, being exposed to biopsychosocial risk factors to their development due to decreased spontaneous movement and excessive sensory stimuli. This study assumes that there are relationships between the integration of sensory information of preterm infants, motor development and their subsequent effects.
Buhimschi, Catalin S; Rosenberg, Victor A; Dulay, Antonette T; Thung, Stephen; Sfakianaki, Anna K; Bahtiyar, Mert-Ozan; Buhimschi, Irina A
Premature birth before 37 weeks of gestation is a significant public health problem. Each year, 4.5 million premature infants are born worldwide. Despite extensive research and a variety of interventions, the rate of preterm birth has steadily increased over the past 20 years and reached a high of 12.8% in 2006. The etiology of most preterm births remains elusive and is likely multifactorial, with many pathophysiological pathways involved, such as excessive stretching, oxidative stress, decidual hemorrhage, and infection. Genomics and proteomics have emerged to provide a better comprehension of the pathophysiological conditions leading to preterm birth, thereby providing a perspective for improving neonatal outcome.
de Freitas, Brunnella Alcantara Chagas; Lima, Luciana Moreira; Carlos, Carla Fernanda Lisboa Valente; Priore, Silvia Eloiza; Franceschini, Sylvia do Carmo Castro
Abstract Objective: Identify and analyze variables associated with shorter duration of breastfeeding in preterm infants. Methods: Retrospective cohort of premature infants followed up at secondary referral service in the period of 2010-2015. Inclusion: first appointment in the first month of corrected age and have undergone three or more consultations. Exclusion: diseases that impaired oral feeding. Outcome: duration of breastfeeding. A total of 103 preterm infants were evaluated, accounting for 28.8% of the preterm infants born in the municipality in that period, with a power of study of 80%. Descriptive analysis, t-test, chi-square test, Kaplan-Meier curves and Cox regression were used. p-values <0.05 were considered significant. Results: The median duration of breastfeeding among preterm infants was 5.0 months. The risk of breastfeeding discontinuation among preterm infants with gestational age <32 weeks was 2.6-fold higher than for those born at 32 weeks or more and the risk of breastfeeding interruption in preterm infants who were receiving breastfeeding supplementation in the first outpatient visit was 3-fold higher when compared to those who were exclusively breastfed in the first consultation. Conclusions: The median duration of breastfeeding in preterm infants was below the recommended one and discontinuation was associated with gestational <32 weeks and the fact that the infant was no longer receiving exclusive breastfeeding in the first outpatient visit. When these two variables were associated, their negative effect on the median duration of breastfeeding was potentiated. PMID:26614258
Dhobale, Madhavi V; Pisal, Hemlata R; Mehendale, Savita S; Joshi, Sadhana R
Neurotrophic factors such as brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are involved in development of the placenta and fetal brain. A series of human and animal studies in our department have shown that micronutrients (folic acid, vitamin B12) and omega 3 fatty acids like DHA are all interlinked in the one carbon cycle. Any alterations in one carbon components will lead to changes in methylation patterns that further affect the gene expression at critical periods of development resulting in complications during pregnancy. This may further contribute to risk for neurodevelopmental disorders in children born preterm. Therefore this study for the first time examines the mRNA levels from preterm and term placentae. A total number of 38 women delivering preterm (<37 weeks gestation) and 37 women delivering at term (=>37 weeks gestation) were recruited. The mRNA levels of BDNF and NGF were analyzed by real time quantitative polymerase chain reaction. Our results indicate that BDNF and NGF mRNA levels were lower in preterm group as compared to term group. There was a positive association of placental BDNF and NGF mRNA levels with cord plasma BDNF and NGF levels. The differential expression of BDNF and NGF gene in preterm placentae may also alter the vascular development in preterm deliveries. Our data suggests that the reduced mRNA levels of BDNF and NGF may possibly be a result of altered epigenetic mechanisms and may have an implication for altered fetal programming in children born preterm.
Baron, Ida Sue; Kerns, Kimberly A; Müller, Ulrich; Ahronovich, Margot D; Litman, Fern R
Executive function (EF) refers to fundamental capacities that underlie more complex cognition and have ecological relevance across the individual's lifespan. However, emerging executive functions have rarely been studied in young preterm children (age 3) whose critical final stages of fetal development are interrupted by their early birth. We administered four novel touch-screen computerized measures of working memory and inhibition to 369 participants born between 2004 and 2006 (52 Extremely Low Birth Weight [ELBW]; 196 late preterm; 121 term-born). ELBW performed worse than term-born on simple and complex working memory and inhibition tasks and had the highest percentage of incomplete performance on a continuous performance test. The latter finding indicates developmental immaturity and the ELBW group's most at-risk preterm status. Additionally, late-preterm participants performed worse compared with term-born on measures of complex working memory but did not differ from those term-born on response inhibition measures. These results are consistent with a recent literature that identifies often subtle but detectable neurocognitive deficits in late-preterm children. Our results support the development and standardization of computerized touch-screen measures to assess EF subcomponent abilities during the formative preschool period. Such measures may be useful to monitor the developmental trajectory of critical executive function abilities in preterm children, and their use is necessary for timely recognition of deficit and application of appropriate interventional strategies.
Kadam, Sandeep; Pandit, Anand; Patole, Sanjay
Introduction Early home discharge of preterm infants is a priority in developing countries due to bed shortage and poor socio-economic status. There is wide variation in home discharge policies for preterm infants. Limited data exists on optimal timing for discharging such infants. In view of the socio-economic and medico-legal importance of the issue, we aimed to study the outcomes of our ex-preterm infants discharged home ‘early’, to guide our clinical practice. Aim To study the rates of re-admissions/mortality within 4 weeks after discharge in preterm (born <34 weeks) infants. Materials and Methods This was an analysis of retrospectively collected data on all ex-preterm infants (gestation <34 weeks at birth) discharged home from our Neonatal Intensive Care Unit (NICU) during the study period. Infants enrolled were stratified based on their gestation age: Group I (n=54): 26-29 weeks, Group II (n=181): 30-34 weeks. Data on demographic characteristics, hospital course and outcomes were analysed for infants meeting inclusion criteria. Re-admission and/or mortality within 4 weeks after discharge were studied. Results The mean±(SD) duration of stay was 42±19 vs. 19±14 days in group I vs. II infants. Five (2.7%) infants were re-admitted within the first four weeks after discharge in group II; none in group I. Conclusion Early home discharge for preterm infants born <34 weeks was feasible and safe in our set-up. Large prospective studies are required to confirm these benefits. PMID:28208967
Temprana, Silvio G; Mongiat, Lucas A; Yang, Sung M; Trinchero, Mariela F; Alvarez, Diego D; Kropff, Emilio; Giacomini, Damiana; Beltramone, Natalia; Lanuza, Guillermo M; Schinder, Alejandro F
Developing granule cells (GCs) of the adult dentate gyrus undergo a critical period of enhanced activity and synaptic plasticity before becoming mature. The impact of developing GCs on the activity of preexisting dentate circuits remains unknown. Here we combine optogenetics, acute slice electrophysiology, and in vivo chemogenetics to activate GCs at different stages of maturation to study the recruitment of local target networks. We show that immature (4-week-old) GCs can efficiently drive distal CA3 targets but poorly activate proximal interneurons responsible for feedback inhibition (FBI). As new GCs transition toward maturity, they reliably recruit GABAergic feedback loops that restrict spiking of neighbor GCs, a mechanism that would promote sparse coding. Such inhibitory loop impinges only weakly in new cohorts of young GCs. A computational model reveals that the delayed coupling of new GCs to FBI could be crucial to achieve a fine-grain representation of novel inputs in the dentate gyrus.
Temprana, Silvio G.; Mongiat, Lucas A.; Yang, Sung M.; Trinchero, Mariela F.; Alvarez, Diego D.; Kropff, Emilio; Giacomini, Damiana; Beltramone, Natalia; Lanuza, Guillermo M.; Schinder, Alejandro F.
SUMMARY Developing granule cells (GCs) of the adult dentate gyrus undergo a critical period of enhanced activity and synaptic plasticity before becoming mature. The impact of developing GCs on the activity of preexisting dentate circuits remains unknown. Here we combine optogenetics, acute slice electrophysiology, and in vivo chemogenetics to activate GCs at different stages of maturation to study the recruitment of local target networks. We show that immature (four-week-old) GCs can efficiently drive distal CA3 targets, but poorly activate proximal interneurons responsible for feedback inhibition (FBI). As new GCs transition towards maturity, they reliably recruit GABAergic feedback loops that restrict spiking of neighbor GCs, a mechanism that would promote sparse coding. Such inhibitory loop impinges only weakly in new cohorts of young GCs. A computational model reveals that the delayed coupling of new GCs to FBI could be crucial to achieve a fine-grain representation of novel inputs in the dentate gyrus. PMID:25533485
Cohen, S E; Beckwith, L
Naturalistic home observations of 54 preterm infants and their caregivers were made when the infants were 1, 3 and 8 months of age. Differences were found in the kinds of everyday transactions which occur with preterm infants raised with and without siblings. At 1 month of age the care of firstborn and later-born infants was similar in most ways. At 3 months and 8 months firstborn infants clearly received more responsive care and more stimulation from their mothers than later-born infants. Furthermore, the firstborn infant received more social transactions from anybody. Firstborn preterm infants obtained higher Gesell developmental scores than later-born infants, replicating results reported with infant test performance of full-term infants.
Background Social factors affect the risk of very preterm birth and may affect subsequent outcomes in those born preterm. We assessed the influence of neighbourhood socio-economic characteristics on the risk and outcomes of singleton very preterm birth (<32 weeks of gestation) in two European regions with different health systems. Methods Live births (n=1118) from a population-based cohort of very preterm infants in 2003 in Trent (UK) and Ile-de-France (France) regions were geocoded to their neighbourhood census tracts. Odds ratios for very preterm singleton birth by neighbourhood characteristics (unemployment rate, proportion manual workers, proportion with high school education only, non home ownership) were computed using infants enumerated in the census as a control population. The impact of neighbourhood variables was further assessed by pregnancy and delivery characteristics and short term infant outcomes. Results Risk of very preterm singleton birth was higher in more deprived neighbourhoods in both regions (OR between 2.5 and 1.5 in the most versus least deprived quartiles). No consistent associations were found between neighbourhood deprivation and maternal characteristics or health outcomes for very preterm births, although infants in more deprived neighbourhoods were less likely to be breastfed at discharge. Conclusions Neighbourhood deprivation had a strong consistent impact on the risk of singleton very preterm birth in two European regions, but did not appear to be associated with maternal characteristics or infant outcomes. Differences in breastfeeding at discharge suggest that socio-economic factors may affect long term outcomes. PMID:23617598
Head, Lauren M
Preterm birth is associated with long-term deficits in executive functioning and cognitive performance. As advances in neonatal care enable more preterm infants to survive, development of strategies to address high rates of neurodevelopmental disabilities and poor academic achievement in preterm infants are crucial. Evidence suggests that infants' brains are plastic in nature and, therefore, can be shaped by the environment. Kangaroo care has become popularized as a means of modifying the stress of the NICU environment. However, few studies have examined whether kangaroo care affects neurodevelopmental outcomes in preterm infants. This review examined available literature that investigated the effect of kangaroo care on cognition in preterm infants. Current evidence suggests that short-term benefits of kangaroo care are associated with improved neurodevelopment. However, few studies have examined the long-term impact of kangaroo care on cognitive outcomes in preterm infants. To address neurological disparities in children born preterm, research using kangaroo care as a strategy to improve neurodevelopment in preterm infants is warranted.
Geldof, C. J. A.; van Wassenaer, A. G.; de Kieviet, J. F.; Kok, J. H.; Oosterlaan, J.
A range of neurobehavioral impairments, including impaired visual perception and visual-motor integration, are found in very preterm born children, but reported findings show great variability. We aimed to aggregate the existing literature using meta-analysis, in order to provide robust estimates of the effect of very preterm birth on visual…
Lobo, Michele A.; Galloway, James C.
Infants born preterm have increased risk for learning disabilities yet we lack assessments to successfully detect these disabilities in early life. We followed 23 full-term and 29 preterm infants from birth through 24 months to assess for differences in and stability of learning abilities across time. Measures included the Bayley-III cognitive…
Gagneur, Arnaud; Pinquier, Didier; Quach, Caroline
Vaccinations of premature infants are often delayed despite being at an increased risk of contracting vaccine preventable diseases. This article reviews the current knowledge on the immune response to widely used vaccines, on the protection derived from routine immunization and on vaccine safety and tolerability in a population of preterm infants. Available data evaluating the immune response of preterm infants support early immunization without correction for gestational age. For a number of antigens, the antibody response to initial doses of vaccines may be lower than that of term infants, but protective concentrations are often achieved and memory successfully induced. Vaccines are immunogenic, safe and well tolerated in preterm infants. Preterm infants should be vaccinated using the same schedules as those usually recommended for full-term infants, with the exception of the hepatitis B vaccine, where additional doses should be administered in infants receiving the first dose during the first days of life if they weighed less than 2000 g because of a documented reduced immune response. PMID:26291883
Ranger, Manon; Grunau, Ruth E
SUMMARY Infants born preterm (<37 weeks of gestation) are particularly vulnerable to procedural stress and pain exposure during neonatal intensive care, at a time of rapid and complex brain development. Concerns regarding effects of neonatal pain on brain development have long been expressed. However, empirical evidence of adverse associations is relatively recent. Thus, many questions remain to be answered. This review discusses the short- and long-term effects of pain-related stress and associated treatments on brain maturation and neurodevelopmental outcomes in children born preterm. The current state of the evidence is presented and future research directions are proposed. PMID:24641344
Rundell, Kristen; Panchal, Bethany
In the United States, preterm delivery is the leading cause of neonatal morbidity and is the most common reason for hospitalization during pregnancy. The rate of preterm delivery (before 37 weeks' gestation) has been declining since 2007. Clinical diagnosis of preterm labor is made if there are regular contractions and concomitant cervical change. Less than 10% of women with a clinical diagnosis of preterm labor will deliver within seven days of initial presentation. Women with a history of spontaneous preterm delivery are 1.5 to two times more likely to have a subsequent preterm delivery. Antenatal progesterone is associated with a significant decrease in subsequent preterm delivery in certain pregnant women. Current recommendations are to prescribe vaginal progesterone in women with a shortened cervix and no history of preterm delivery, and to use progesterone supplementation regardless of cervical length in women with a history of spontaneous preterm delivery. Cervical cerclage has been used to help correct structural defects or cervical weakening in high-risk women with a shortened cervix. A course of corticosteroids is the only antenatal intervention that has been shown to improve postdelivery neonatal outcomes, including a reduction in neonatal mortality, intracranial hemorrhage, necrotizing enterocolitis, and neonatal infection. Tocolytics, especially prostaglandin inhibitors and calcium channel blockers, may allow time for the administration of antenatal corticosteroids and transfer to a tertiary care facility if necessary. When used in specific at-risk populations, magnesium sulfate provides neuroprotection and decreases the incidence of cerebral palsy in preterm infants.
Lawn, Joy E; Kinney, Mary V; Belizan, José M; Mason, Elizabeth Mary; McDougall, Lori; Larson, Jim; Lackritz, Eve; Friberg, Ingrid K; Howson, Christopher P
Preterm birth complication is the leading cause of neonatal death resulting in over one million deaths each year of the 15 million babies born preterm. To accelerate change, we provide an overview of the comprehensive strategy required, the tools available for context-specifi c health system implementation now, and the priorities for research and innovation. There is an urgent need for action on a dual track: (1) through strategic research to advance the prevention of preterm birth and (2) improved implementation and innovation for care of the premature neonate. We highlight evidence-based interventions along the continuum of care, noting gaps in coverage, quality, equity and implications for integration and scale up. Improved metrics are critical for both burden and tracking programmatic change. Linked to the United Nation’s Every Women Every Child strategy, a target was set for 50% reduction in preterm deaths by 2025. Three analyses informed this target: historical change in high income countries, recent progress in best performing countries, and modelling of mortality reduction with high coverage of existing interventions. If universal coverage of selected interventions were to be achieved, then 84% or more than 921,000 preterm neonatal deaths could be prevented annually, with antenatal corticosteroids and Kangaroo Mother Care having the highest impact. Everyone has a role to play in reaching this target including government leaders, professionals, private sector, and of course families who are aff ected the most and whose voices have been critical for change in many of the countries with the most progress.
Ment, Laura R.; Kesler, Shelli; Vohr, Betty; Katz, Karol H.; Baumgartner, Heidi; Schneider, Karen C.; Delancy, Susan; Silbereis, John; Duncan, Charles C.; Constable, R. Todd; Makuch, Robert W.; Reiss, Allan L.
OBJECTIVE Although preterm very low birth weight infants have a high prevalence of neuroanatomical abnormalities when evaluated at term-equivalent age, patterns of brain growth in prematurely born infants during school age and adolescence remain largely unknown. Our goal was to test the hypothesis that preterm birth results in long-term dynamic changes in the developing brain. METHODS We performed serial volumetric MRI studies at ages 8 and 12 years in 55 preterm infants born weighing 600 to 1250 g and 20 term control children who participated in the follow-up component of a prospective, randomized, placebo-controlled intraventricular hemorrhage prevention study. RESULTS Total brain volumes increased 2% to 3% between the ages of 8 and 12 years for both preterm and term children. These changes involved reductions in cerebral gray matter while white matter increased. Between 8 and 12 years of age, preterm subjects experienced a 2% decrease in left cerebral gray matter compared with a 10% reduction in left cerebral gray for term controls. For right cerebral gray matter, preterm children experienced a 3% decrease in volume between years 8 and 12, compared with 9% for term controls (group-by-time). In contrast, preterm subjects had a 10% increase in cerebral white matter volumes bilaterally between ages 8 and 12 years, compared with >26% increases for both hemispheres for term controls. Significant differences in regional volume changes between study groups were found in bilateral temporal gray and in parietal white matter. CONCLUSIONS Preterm birth continues to perturb the trajectory of cerebral development during late childhood and early adolescence with preterm children, showing both lower gray matter reduction and less white matter gain over time compared with term control subjects. PMID:19171615
Rao, Raghavendra; Georgieff, Michael K.
SYNOPSIS Preterm infants are at risk for both iron deficiency and iron overload. The role of iron in multiple organ functions suggests that iron supplementation is essential for the preterm infant. Conversely, the potential for iron overload and the poorly developed anti-oxidant measures in the preterm infant argues against indiscriminate iron supplementation in this population. The purpose of this article is to review the predisposing factors and consequences of iron deficiency and iron overload in the preterm infant, the current recommendation for iron supplementation and its appropriateness, and describe potential management strategies that strike a balance between iron deficiency and iron toxicity. PMID:19161863
Brown, Colin J; Miller, Steven P; Booth, Brian G; Andrews, Shawn; Chau, Vann; Poskitt, Kenneth J; Hamarneh, Ghassan
Preterm infants develop differently than those born at term and are at higher risk of brain pathology. Thus, an understanding of their development is of particular importance. Diffusion tensor imaging (DTI) of preterm infants offers a window into brain development at a very early age, an age at which that development is not yet fully understood. Recent works have used DTI to analyze structural connectome of the brain scans using network analysis. These studies have shown that, even from infancy, the brain exhibits small-world properties. Here we examine a cohort of 47 normal preterm neonates (i.e., without brain injury and with normal neurodevelopment at 18 months of age) scanned between 27 and 45 weeks post-menstrual age to further the understanding of how the structural connectome develops. We use full-brain tractography to find white matter tracts between the 90 cortical and sub-cortical regions defined in the University of North Carolina Chapel Hill neonatal atlas. We then analyze the resulting connectomes and explore the differences between weighting edges by tract count versus fractional anisotropy. We observe that the brain networks in preterm infants, much like infants born at term, show high efficiency and clustering measures across a range of network scales. Further, the development of many individual region-pair connections, particularly in the frontal and occipital lobes, is significantly correlated with age. Finally, we observe that the preterm infant connectome remains highly efficient yet becomes more clustered across this age range, leading to a significant increase in its small-world structure.
Fewtrell, Mary S
Preterm infants are at risk of metabolic bone disease (MBD) because of an inadequate mineral intake. Although infants with MBD are frequently asymptomatic during the neonatal period, we previously reported that MBD predicted reduced linear growth in infancy and midchildhood. Nevertheless, some studies suggest that preterm infants undergo catch-up growth in bone mineralization during infancy. To examine the hypothesis that early nutrition programs affect later bone health and peak bone mass, we studied 20-y-old subjects who were born preterm and who were randomly assigned to a diet during the neonatal period; the diets used varied markedly in nutrient and mineral content, and phosphate supplements were not provided. Despite large variations in early nutrient and mineral intakes (and the occurrence of MBD) during the neonatal period, the randomly assigned diets did not influence peak bone mass or turnover. However, the proportion of (unsupplemented) human milk in the neonatal diet was significantly positively associated with later whole-body bone size and mineral content. Compared with population reference data, preterm subjects were significantly shorter and had lower lumbar spine bone mineral density; the deficits were greatest in those born small for gestational age (ie, a birth weight <1250 g). The lack of effect of the randomly assigned diets on peak bone mass suggests that the observed deficits in height and lumbar spine bone mass may not be related to suboptimal early nutrient or mineral intake. The higher whole-body bone mass associated with human milk intake, despite its very low nutrient content, may instead reflect nonnutritive factors in breast milk. These findings are relevant to discussions on the mineral requirements of preterm infants.
Pecks, Ulrich; Mohaupt, Markus G; Hütten, Matthias C; Maass, Nicolai; Rath, Werner; Escher, Geneviève
Fetal serum cholesterol and lipoprotein concentrations differ between preterm and term born neonates. An imbalance of the flow of cholesterol from the sites of synthesis or efflux from cells of peripheral organs to the liver, the reverse cholesterol transport (RCT), is linked to atherosclerosis and cardiovascular disease (CVD). Preterm delivery is a risk factor for the development of CVD. Thus, we hypothesized that RCT is affected by a diminished cholesterol acceptor capacity in preterm as compared to term fetuses. Cholesterol efflux assays were performed in RAW264.7, HepG2, and HUVEC cell lines. In the presence and absence of ABC transporter overexpression by TO-901317, umbilical cord sera of preterm and term born neonates (n = 28 in both groups) were added. Lipid components including high density lipoprotein (HDL), low density lipoprotein (LDL), apolipoprotein A1, and apolipoprotein E were measured and related to fractional cholesterol efflux values. We found overall, fractional cholesterol efflux to remain constant between the study groups, and over gestational ages at delivery, respectively. However, correlation analysis revealed cholesterol efflux values to be predominantly related to HDL concentration at term, while in preterm neonates, cholesterol efflux was mainly associated with LDL In conclusion cholesterol acceptor capacity during fetal development is kept in a steady state with different mechanisms and lipid fractions involved at distinct stages during the second half of fetal development. However, RCT mechanisms in preterm neonates seem not to be involved in the development of CVD later in life suggesting rather changes in the lipoprotein pattern causative.
Hagmann-von Arx, Priska; Manicolo, Olivia; Perkinson-Gloor, Nadine; Weber, Peter; Grob, Alexander; Lemola, Sakari
Objective The control of gait requires executive and attentional functions. As preterm children show executive and attentional deficits compared to full-term children, performing concurrent tasks that impose additional cognitive load may lead to poorer walking performance in preterm compared to full-term children. Knowledge regarding gait in preterm children after early childhood is scarce. We examined straight walking and if it is more affected in very preterm than in full-term children in dual-task paradigms. Study design Twenty preterm children with very low birth-weight (≤ 1500 g), 24 preterm children with birth-weight > 1500 g, and 44 full-term children, born between 2001 and 2006, were investigated. Gait was assessed using an electronic walkway system (GAITRite) while walking without a concurrent task (single-task) and while performing one concurrent (dual-task) or two concurrent (triple-task) tasks. Spatio-temporal gait parameters (gait velocity, cadence, stride length, single support time, double support time), normalized gait parameters (normalized velocity, normalized cadence, normalized stride length) and gait variability parameters (stride velocity variability, stride length variability) were analyzed. Results In dual- and triple-task conditions children showed decreased gait velocity, cadence, stride length, as well as increased single support time, double support time and gait variability compared to single-task walking. Further, results showed systematic decreases in stride velocity variability from preterm children with very low birth weight (≤ 1500 g) to preterm children with birth weight > 1500 g to full-term children. There were no significant interactions between walking conditions and prematurity status. Conclusions Dual and triple tasking affects gait of preterm and full-term children, confirming previous results that walking requires executive and attentional functions. Birth-weight dependent systematic changes in stride velocity
Scheinost, Dustin; Lacadie, Cheryl; Vohr, Betty R; Schneider, Karen C; Papademetris, Xenophon; Constable, R Todd; Ment, Laura R
Individuals born prematurely are at risk for developmental delay, and converging data suggest alterations in neural networks in the developing preterm brain. Nevertheless, those critical period processes such as cerebral lateralization that underlie these findings remain largely unexplored. To test the hypothesis that preterm birth alters the fundamental program of corticogenesis in the developing brain, we interrogated cerebral lateralization at rest in very prematurely born participants and term controls at young adulthood. Employing a novel, voxel-based measure of functional connectivity, these data demonstrate for the first time that cerebral lateralization of functional connectivity in right hemisphere language homologs is altered for very preterm participants. Very preterm participants with no evidence for severe brain injury exhibited a significant decrease in right hemisphere lateralization in the right parietal and temporal lobes in this data driven analysis. Further, for the very preterm participants, but not the term participants, these fundamental alterations in the cerebral lateralization for language significantly correlate with language scores. These findings provide evidence that cerebral asymmetry is both plastic and experiential, and suggest the need for further study of underlying environmental factors responsible for these changes.
Liu, Shiliang; Basso, Olga; Kramer, Michael S
The sequelae of preterm births may differ, depending on whether birth follows an acute event or a chronic condition. In a population-based cohort study of 2,711,645 Canadian hospital deliveries from 2003 to 2012, 3,059 women experienced unintentional injury during pregnancy. We assessed the impact of the acute event on pregnancy outcome and on neonatal complications, such as nontraumatic intracranial hemorrhage, respiratory distress syndrome, intubation, and death. We adjusted for maternal age, parity, pregnancy conditions, and (for neonates) gestational age in logistic regression analyses. Injury was significantly associated with fetal mortality and early preterm delivery. For preterm infants born to injured women during the hospitalization for injury versus those born to noninjured women, the adjusted odds ratios were 2.25 (95% confidence interval (CI): 1.23, 4.17) for neonatal death, 2.44 (95% CI: 1.76, 3.37) for respiratory distress, 2.20 (95% CI: 1.26, 3.84) for nontraumatic intracranial hemorrhage, and 2.17 (95% CI: 1.60, 2.96) for intubation, despite more favorable fetal growth in those born to noninjured women (adjusted birth-weight-for-gestational-age z score: 0.154 vs. 0.024, P = 0.041; small-for-gestational-age rate: 4.5% vs. 9.5%, P = 0.001). Our findings suggest that adaptation to the suboptimal intrauterine environment underlying chronic causes of preterm birth may protect preterm infants from adverse sequelae.
Kerstjens, Jorien M.; de Winter, Andrea F.; Bocca-TJeertes, Inger F.; Bos, Arend F.; Reijneveld, Sijmen A.
Aim: The aim of the study was to assess the influence of decreasing gestational age on the risk of developmental delay in various domains at age 4 years among children born at a wide range of gestational ages. Method: In a community-based cohort, the parents of 1439 preterm-born children (24 0/7 to 35 6/7wks) and 544 term-born children (38 0/7 to…
Magalhães, Lívia de Castro; Catarina, Patrícia Wendling; Barbosa, Vanêssa Maziero; Mancini, Marisa Cota; Paixão, Maria Lúcia
The objective of this study was to compare the perceptualmotor performance in school age children who were born preterm and full term. Two groups of children, ages 5 to 7, participated in this study. Group I had 35 children, from low-income families, born up to the 34 week of gestation and/or weight bellow 1500 g. Group II had 35 full-term children, matched by age, gender and socioeconomic status to the children in Group I. Children were tested on the Bender gestalt, the motor accuracy test and on balance and postural responses measures. The preterm group obtained significantly lower scores in the majority of the tests. These besides reinforcing the importance of the follow-up of preterm children up to school age, also indicate the need to stimulate the fine motor and postural control Devment, even among preterm children who do not show evidence of neurological impairment.
Thayath, Muhamad Nishad; Singh, Shikha; Sinha, Anju
ABSTRACT Preterm and low birthweight children comprise approximately 6% of all live births. It is now a well-known fact that premature children experience many oral complications associated with their preterm births. Prematurely born infants have a short prenatal development period and they are prone to many serious medical problems during the neonatal period, which may affect the development of oral tissues. Adverse perinatal factors, premature birth and exceptional early adaptation to extra-uterine life and functional activity may influence dental occlusal development and symmetry in the jaws. Thus, the goal of the present paper is to elucidate further the effect of preterm birth on the development of the dentition. How to cite this article: Zaidi I, Thayath MN, Singh S, Sinha A. Preterm Birth: A Primary Etiological Factor for Delayed Oral Growth and Development. Int J Clin Pediatr Dent 2015;8(3): 215-219. PMID:26628856
Rose, Susan A; Feldman, Judith F; Jankowski, Jeffery J; Van Rossem, Ronan
Although it is well established that preterms as a group do poorly relative to their full-term peers on tests of global cognitive functioning, the basis for this relative deficiency is less understood. The present paper examines preterm deficits in core cognitive abilities and determines their role in mediating preterm/full-term differences in IQ. The performance of 11-year-old children born preterm (birth weight <1750g) and their full-term controls were compared on a large battery of 15 tasks, covering four basic cognitive domains -- memory, attention, speed of processing and representational competence. The validity of these four domains was established using latent variables and confirmatory factor analysis (CFA). Preterms showed pervasive deficits within and across domains. Additionally, preterm deficits in IQ were completely mediated by these four cognitive domains in a structural equation model involving a cascade from elementary abilities (attention and speed), to more complex abilities (memory and representational competence), to IQ. The similarity of findings to those obtained with this cohort in infancy and toddlerhood suggest that preterm deficits persist - across time, across task, and from the non-verbal to the verbal period.
Eifinger, Frank; Fries, Jochen; Bald, Rainer; Körber, Friederike; Kribs, Angela; Roth, Bernhard
We firstly report on a dystrophic preterm infant with segmental arterial mediolysis (SAM) found in arteries of placental, umbilical and cerebral tissues. These arterial lesions of unknown etiology developing in the elderly are characterized by segmental lysis of the abdominal splanchnic arteries followed by aneurysms and acute bleeding. Typically, the lesions occur in a skip pattern. We could find a small number of SAM in the spleen but much more in placental and umbilical tissues. Rarely, a vascular elastosis and splitting of individual vessels in the spleen and lung could be detected. The histological findings are similar to that of adult patients.
McConaha, Melinda E; Ding, Tianbing; Lucas, John A; Arosh, Joe A; Osteen, Kevin G; Bruner-Tran, Kaylon L
We have recently reported that adult male C57BL/6 mice exposed in utero to the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) confer an increased risk of preterm birth (PTB) to unexposed females. Risk of PTB was coincident with decreased placental progesterone receptor (Pgr) mRNA expression and increased toll-like receptor 4 (Tlr4) mRNA expression, suggesting that toxicant exposure induced a heightened inflammatory response at the maternal-fetal interface. Since omega-3 fatty acids exhibit anti-inflammatory activity, in this study, we provided TCDD-exposed males a fish oil-enriched diet prior to mating. Although PTB was common in control females mated to TCDD-exposed males on the standard diet, fish oil supplementation of TCDD-exposed males eliminated PTB in unexposed partners. We also determined the influence of preconception, paternal fish oil supplementation on the placental inflammatory response in late pregnancy (E18.5) by examining the expression of Pgr and Tlr4 mRNA as well as the expression of 15-hydroxyprostaglandin dehydrogenase (PGDH). PGDH catabolizes the inflammatory PGE2 to an inactive form; thus, reduced expression of this enzyme would promote tissue inflammation. Compared with control pregnancies, examination of E18.5 placentas arising from TCDD-exposed males on the standard diet revealed a significant increase in Tlr4 mRNA expression corresponding to a reduction in Pgr mRNA and PGDH protein expression. In contrast, fish oil supplementation of toxicant-exposed males led to normalization of placental expression of both Pgr and Tlr4 mRNA and a marked increase in PGDH expression. These studies suggest that a paternal preconception diet that includes omega-3 fatty acids prevents the toxicant-associated increase in the placental inflammatory response at late gestation, preventing PTB.
Elke, Griesmaier; Vera, Neubauer; Maria, Gnigler; Michaela, Höck; Ursula, Kiechl-Kohlendorfer
The aim of the study was to investigate the frequency of and the predictors for rehospitalization in preterm infants into early childhood, focusing on gender differences. All preterm infants born at <32 weeks of gestation in North Tyrol between January 2003 and December 2005 were enrolled in this survey. About one fifth of all children were readmitted, showing an inverse downward trend with increasing age. The most common reason for readmission in the third (36.5%) and fourth (42.9%) years of life was respiratory infection, but changed to miscellaneous surgeries in the fifth (52.1%). Male sex showed significantly higher readmission rates and more miscellaneous surgeries. Additionally, male sex and chronic lung disease were risk conditions for rehospitalization in the multivariate analysis. Readmission rates and respiratory infections in preterm-born children showed an inverse downward trend with increasing age. In early childhood, gender difference still plays a role with regard to rehospitalization. PMID:27335903
Background Children born at low gestational ages face a range of risks and number of neonates surviving very preterm birth is increasing. We present the objectives and methods of a French national cohort of very and moderately preterm children, the EPIPAGE 2 study. It aims to examine short- and long-term outcomes of very preterm children and their determinants. Methods/Design Eligible participants for this prospective population-based study include all infants live born or stillborn and all terminations of pregnancy between 22 and 31 completed weeks of gestation in all the maternity units in 25 French regions. In addition, a sample of moderate preterm births, i.e. births and late terminations at 32–34 weeks, was included in the same regions. In all, 7804 babies (stillbirths and live births) and terminations of pregnancy out of 8400 eligible births in France in 2011 that were either very (22–31 weeks) or moderately preterm (32–34 weeks) were included. Data on pregnancy, delivery, and neonatal events were extracted from the obstetric and neonatal records. The follow-up will collect information at corrected ages of one and 2 years and at 5, 8, and 12 years of age. Of the 4467 children discharged alive from the hospital and eligible for follow-up, 155 (4%) families refused further follow-up and 22 died before one-year of age. Finally, 4290 were included in the follow-up. Eight additional projects investigating specific hypotheses among subsamples of the cohort by collecting specific data in addition to the core cohort data are being conducted to investigate 1) diagnosis of histologic chorioamnionitis, 2) early biomarkers of child health, 3) attitudes of care for extremely preterm infants, 4) painful procedures in neonatal intensive care units, 5) neonatal MRI cerebral abnormalities and their relation to executive functions, 6) associations between early gut colonization and early and late onset diseases, 7) impact of neonatal nutrition on child development
Bos, Arend F.; Roze, Elise
Aim: To determine the distribution of cognitive and motor scores in preterm children, and to establish the influence of brain lesions and decreasing gestational age thereon. Method: One hundred and six very preterm children (63 males, 43 females; gestational age 24.0-31.6wk; birthweight 480-2275g) were assessed for cognition and motor outcome at 6…
Duncan, S D; Devlin, L A
Baclofen is a gamma-aminobutyric acid agonist used primarily as a muscle relaxant to treat spasticity in children and adults. Withdrawal of oral baclofen is known to cause a withdrawal syndrome in adults. Only one previous case describes a withdrawal syndrome in a term infant, manifested by seizures, associated with the use of oral baclofen in the mother. This case describes a withdrawal syndrome and the unique use of baclofen for withdrawal in a preterm infant.
The use of music as part of a stress reduction therapy has been applied both to premature infants and their parents in the Neonatal Reanimation Service. This aim of music therapy amounts to an attempt to help the premature infant regaining its physical and neurological balance, so important to its psychological and physical development, mainly by masking the sometimes excessive noise present in the intensive care unit and/or in the incubator. Studies have demonstrated the positive impact of music therapy on oxygen saturation, heartbeat, and on the general level of relaxation experienced by premature infants. In this project, the palliative technique used was that of live singing, directly to the infant, accompanied by a pentatonic harp. The aim was to improve the state of health, both physical and psychological, of a group of premature infants, whose gestation period varied between 23 and 36 weeks. The technique used was to apply what amounts to a protective cocoon of sounds to a premature infant in the neonatal unit, which measurably reduced the level of stress as indicated by the babies' increasingly relaxed demeanour and induced a measurable increase on the level of oxygen saturation and a reduction of heart rate.
Ball, G.; Aljabar, P.; Arichi, T.; Tusor, N.; Cox, D.; Merchant, N.; Nongena, P.; Hajnal, J.V.; Edwards, A.D.; Counsell, S.J.
Brain development is adversely affected by preterm birth. Magnetic resonance image analysis has revealed a complex fusion of structural alterations across all tissue compartments that are apparent by term-equivalent age, persistent into adolescence and adulthood, and associated with wide-ranging neurodevelopment disorders. Although functional MRI has revealed the relatively advanced organisational state of the neonatal brain, the full extent and nature of functional disruptions following preterm birth remain unclear. In this study, we apply machine-learning methods to compare whole-brain functional connectivity in preterm infants at term-equivalent age and healthy term-born neonates in order to test the hypothesis that preterm birth results in specific alterations to functional connectivity by term-equivalent age. Functional connectivity networks were estimated in 105 preterm infants and 26 term controls using group-independent component analysis and a graphical lasso model. A random forest–based feature selection method was used to identify discriminative edges within each network and a nonlinear support vector machine was used to classify subjects based on functional connectivity alone. We achieved 80% cross-validated classification accuracy informed by a small set of discriminative edges. These edges connected a number of functional nodes in subcortical and cortical grey matter, and most were stronger in term neonates compared to those born preterm. Half of the discriminative edges connected one or more nodes within the basal ganglia. These results demonstrate that functional connectivity in the preterm brain is significantly altered by term-equivalent age, confirming previous reports of altered connectivity between subcortical structures and higher-level association cortex following preterm birth. PMID:26341027
Ball, G; Aljabar, P; Arichi, T; Tusor, N; Cox, D; Merchant, N; Nongena, P; Hajnal, J V; Edwards, A D; Counsell, S J
Brain development is adversely affected by preterm birth. Magnetic resonance image analysis has revealed a complex fusion of structural alterations across all tissue compartments that are apparent by term-equivalent age, persistent into adolescence and adulthood, and associated with wide-ranging neurodevelopment disorders. Although functional MRI has revealed the relatively advanced organisational state of the neonatal brain, the full extent and nature of functional disruptions following preterm birth remain unclear. In this study, we apply machine-learning methods to compare whole-brain functional connectivity in preterm infants at term-equivalent age and healthy term-born neonates in order to test the hypothesis that preterm birth results in specific alterations to functional connectivity by term-equivalent age. Functional connectivity networks were estimated in 105 preterm infants and 26 term controls using group-independent component analysis and a graphical lasso model. A random forest-based feature selection method was used to identify discriminative edges within each network and a nonlinear support vector machine was used to classify subjects based on functional connectivity alone. We achieved 80% cross-validated classification accuracy informed by a small set of discriminative edges. These edges connected a number of functional nodes in subcortical and cortical grey matter, and most were stronger in term neonates compared to those born preterm. Half of the discriminative edges connected one or more nodes within the basal ganglia. These results demonstrate that functional connectivity in the preterm brain is significantly altered by term-equivalent age, confirming previous reports of altered connectivity between subcortical structures and higher-level association cortex following preterm birth.
Gopagondanahalli, Krishna Revanna; Li, Jingang; Fahey, Michael C.; Hunt, Rod W.; Jenkin, Graham; Miller, Suzanne L.; Malhotra, Atul
Hypoxic–ischemic encephalopathy (HIE) is a recognizable and defined clinical syndrome in term infants that results from a severe or prolonged hypoxic–ischemic episode before or during birth. However, in the preterm infant, defining hypoxic–ischemic injury (HII), its clinical course, monitoring, and outcomes remains complex. Few studies examine preterm HIE, and these are heterogeneous, with variable inclusion criteria and outcomes reported. We examine the available evidence that implies that the incidence of hypoxic–ischemic insult in preterm infants is probably higher than recognized and follows a more complex clinical course, with higher rates of adverse neurological outcomes, compared to term infants. This review aims to elucidate the causes and consequences of preterm hypoxia–ischemia, the subsequent clinical encephalopathy syndrome, diagnostic tools, and outcomes. Finally, we suggest a uniform definition for preterm HIE that may help in identifying infants most at risk of adverse outcomes and amenable to neuroprotective therapies. PMID:27812521
Bischoff, Adrianne R; Tomlinson, Christopher; Belik, Jaques
It is widely accepted that sodium is an essential nutritional electrolyte and its deficiency is associated with neurological sequelae and poor growth. The provision of an adequate sodium intake to preterm neonates is hampered by the technical difficulty in clinically assessing total body sodium content. As addressed in this review, there is a lack of consensus on the definition of hyponatremia early in life, but there is no evidence that it should deviate from the widely accepted normative data for adult subjects. A low urinary sodium content is accepted by many as reflecting total body sodium deficiency, yet spot urinary sodium measurements are of questionable clinical value. The hormonal regulation of sodium homeostasis is here reviewed and the mechanism accounting for sodium deficiency-induced growth impairment in preterm infants addressed. Lastly, we provide evidence-based gestational and postnatal age-dependent recommendations for the provision of adequate sodium intake to preterm neonates.
Dean, Justin M; Bennet, Laura; Back, Stephen A; McClendon, Evelyn; Riddle, Art; Gunn, Alistair Jan
Children surviving premature birth have a high risk of cognitive and learning disabilities and attention deficit. In turn, adverse outcomes are associated with persistent reductions in cerebral growth on magnetic resonance imaging (MRI). It is striking that modern care has been associated with a dramatic reduction in the risk of cystic white matter damage, but modest improvements in terms of neurodevelopmental impairment. This review will explore the hypothesis that the disability is primarily associated with impaired neural connectivity rather than cell death alone. Very preterm infants exhibit reduced thalamocortical connectivity and cortical neuroplasticity compared with term-born controls. In preterm fetal sheep, moderate cerebral ischemia with no neuronal loss, but significant diffuse failure of maturation of cortical pyramidal neurons, was associated with impaired dendritic growth and synapse formation, consistent with altered connectivity. These changes were associated with delayed decline in cortical fractional anisotropy (FA) on MRI. Supporting these preclinical findings, preterm human survivors showed similar enduring impairment of microstructural development of the cerebral cortex defined by FA, consistent with delayed formation of neuronal processes. These findings offer the promise that better understanding of impairment of neural connectivity may allow us to promote normal development and growth of the cortex after preterm birth.
Bosworth, Rain G.; Dobkins, Karen R.
In order to investigate the contributions of visual experience vs. preprogrammed mechanisms on visual development, the current study compared contrast sensitivity in preterm vs. fullterm infants. If development is tied to time since conception, preterm infants should match the developmental trajectories of fullterm infants when plotted in postterm age. By contrast, if development is influenced by visual experience, preterm and fullterm infants should match when plotted in postnatal age. Luminance (light/dark) and chromatic (red/green) contrast sensitivities (CS) were measured in 25 preterm (born, on average, 6.6 weeks early) and 77 fullterm infants, between 1 and 6 months postterm. In the first few months, luminance CS was found to be predicted by postterm age, suggesting that preprogrammed development is sufficient to account for luminance CS. By contrast, chromatic CS exceeded that predicted by postterm age, which suggests that time since birth confers a benefit on chromatic CS. The preterms’ 6.6 weeks of additional time since birth is roughly equivalent to 3.7 weeks of development in chromatic CS. In sum, these results suggest that chromatic CS is more influenced by early postnatal visual experience than luminance CS, which may have implications for development of parvocellular and magnocellular pathways. PMID:20055548
Johnson, Samantha; Hollis, Chris; Kochhar, Puja; Hennessy, Enid; Wolke, Dieter; Marlow, Neil
Objective: To investigate the prevalence and risk factors for psychiatric disorders in extremely preterm children. Method: All babies born less than 26 weeks gestation in the United Kingdom and Ireland from March through December 1995 were recruited to the EPICure Study. Of 307 survivors at 11 years of age, 219 (71%) were assessed alongside 153…
Treyvaud, Karli; Ure, Alexandra; Doyle, Lex W.; Lee, Katherine J.; Rogers, Cynthia E.; Kidokoro, Hiroyuki; Inder, Terrie E.; Anderson, Peter J.
Background: Uncertainty remains about the rate of specific psychiatric disorders and associated predictive factors for very preterm (VPT) children. The aims of this study were to document rates of psychiatric disorders in VPT children aged 7 years compared with term born children, and to examine potential predictive factors for psychiatric…
Samara, Muthanna; Johnson, Samantha; Lamberts, Koen; Marlow, Neil; Wolke, Dieter
Aim: The aim of this study was to investigate the prevalence of eating problems and their association with neurological and behavioural disabilities and growth among children born extremely preterm (EPC) at age 6 years. Method: A standard questionnaire about eating was completed by parents of 223 children (125 males [56.1%], 98 females [43.9%])…
Taylor, H. Gerry; Espy, Kimberly Andrews; Anderson, Peter J.
Children with very low birth weight (VLBW, less than 1500 g) or very preterm birth (VPTB, less than 32 weeks gestational age or GA) have more mathematics disabilities or deficiencies (MD) and higher rates of mathematics learning disabilities (MLD) than normal birth weight term-born children (NBW, greater than 2500 g and greater than 36 weeks GA).…
The establishment of micronutrient requirements for infants remains a challenge. For healthy full-term infants, breast milk is an appropriate standard for virtually all nutrients. In contrast, guidelines for infants who are not healthy, and infants who are born preterm, are much more tenuous....
Kwon, Soo Hyun; Scheinost, Dustin; Lacadie, Cheryl; Sze, Gordon; Schneider, Karen C; Dai, Feng; Constable, R Todd; Ment, Laura R
Preterm birth results in alterations in neural connectivity, but the impact of prematurity on the functional organization of the developing brain has yet to be explored. To test the hypothesis that preterm birth alters cortical organization during the late second and third trimesters of gestation, we interrogated cerebral lateralization at rest in 26 very preterm subjects (birth weight 500-1500g) with no evidence of brain injury and 25 healthy term control subjects at term equivalent age. Employing an unbiased voxel-based measure of functional connectivity, these data demonstrated that cerebral lateralization is impaired in the prematurely-born. At term equivalent age, preterm neonates showed significantly less lateralization in regions subserving both receptive and expressive language, left Brodmann (BA) areas insula-BA22-BA21 and L BA45-BA47 (p<0.05 corrected for multiple comparisons for both). Exploratory region of interest analyses demonstrated significantly less inter-hemispheric connectivity from L BA22 to R BA22 in preterm infants compared to term controls (p<0.005) and from R BA22 to its homolog (p<0.005). L BA22, Wernicke's area, was more strongly connected to R BA39, foreshadowing neural networks for language in preterm subjects at school age, adolescence and young adulthood. For these very preterm neonates born at less than 30weeks' PMA, the degree of prematurity had no influence on lateralization in these differential regions.
Ullman, Henrik; Spencer-Smith, Megan; Thompson, Deanne K; Doyle, Lex W; Inder, Terrie E; Anderson, Peter J; Klingberg, Torkel
School-age children born preterm are particularly at risk for low mathematical achievement, associated with reduced working memory and number skills. Early identification of preterm children at risk for future impairments using brain markers might assist in referral for early intervention. This study aimed to examine the use of neonatal magnetic resonance imaging measures derived from automated methods (Jacobian maps from deformation-based morphometry; fractional anisotropy maps from diffusion tensor images) to predict skills important for mathematical achievement (working memory, early mathematical skills) at 5 and 7 years in a cohort of preterm children using both univariable (general linear model) and multivariable models (support vector regression). Participants were preterm children born <30 weeks' gestational age and healthy control children born ≥37 weeks' gestational age at the Royal Women's Hospital in Melbourne, Australia between July 2001 and December 2003 and recruited into a prospective longitudinal cohort study. At term-equivalent age ( ±2 weeks) 224 preterm and 46 control infants were recruited for magnetic resonance imaging. Working memory and early mathematics skills were assessed at 5 years (n = 195 preterm; n = 40 controls) and 7 years (n = 197 preterm; n = 43 controls). In the preterm group, results identified localized regions around the insula and putamen in the neonatal Jacobian map that were positively associated with early mathematics at 5 and 7 years (both P < 0.05), even after covarying for important perinatal clinical factors using general linear model but not support vector regression. The neonatal Jacobian map showed the same trend for association with working memory at 7 years (models ranging from P = 0.07 to P = 0.05). Neonatal fractional anisotropy was positively associated with working memory and early mathematics at 5 years (both P < 0.001) even after covarying for clinical factors using support vector regression but not
Arpi, Elena; Ferrari, Fabrizio
The behaviour problems of children born preterm at school age are well known, but there have been few studies on the behaviour problems of preterm-born infants during infancy and at preschool age. Fourteen cohort studies published in PubMed and PsycINFO between 2000 and 2012 were reviewed with a focus on the type, occurrence, comorbidity, stability, prediction, perinatal, social, and relational risk factors for behaviour problems of preterm-born children in infancy (0-2y) and at preschool age (3-5y). The relational risk factor was considered in an additional four papers. Very-preterm, very-low-birthweight, and moderately-preterm children, in both age groups, show more behaviour problems than term-born comparison children even after perinatal and social risk factors and cognitive performance have been controlled for. Poor social/interactive skills, poor behavioural and emotional self-regulation, emotional difficulties, and reduced attention are the most common behaviour problems. Behaviour problems in infancy are predictive of later behaviour problems and they should be included in follow-up programmes.
Sullivan, Mary C.; Hawes, Katheleen
This was a prospective longitudinal study of two cohorts comprised of one full term and three premature infant groups born 10 years apart. Birth cohort, perinatal morbidity, and birth weight effects were investigated at age 4. Cohort 1 (1985–1989) had longer gestation, higher birth weight, and better Apgar scores than Cohort 2 (1996–1999), which had more intraventricular hemorrhage and bronchopulmonary dysplasia. Cohort and perinatal morbidity group, but not birth weight, predicted motor scores. Preterm Cohort 2 children had better oral motor, fine motor, and total motor scores, but lower visual motor integration scores than Cohort 1. Motor problems continue to affect preterm children at age 4, in particular those who experience perinatal morbidity, despite a decade of neonatal intensive care advancements. PMID:18022834
Dunn, Michael S; Reilly, Maureen Charlotte
Newly born preterm infants often require respiratory support. Various approaches have been taken to provide this support, including elective intubation and ventilation, prophylactic surfactant and continuous positive airway pressure (CPAP). Elective intubation and ventilation allow the clinician to take control of the baby's airway and reduce the support as tolerated. Surfactant can be administered prophylactically to prevent lung injury and respiratory complications. Many neonatologists, however, advocate a less aggressive approach to the provision of support, which includes the application of early nasal CPAP with intubation and ventilation only if necessary. Avoiding intubation may be effective in minimising ventilator-induced lung injury, but withholding surfactant may be detrimental to the infant. In this paper, we examine the advantages and disadvantages of the different approaches that can be taken in providing respiratory support to preterm neonates shortly after birth and examine some strategies that integrate them.
Weinman, Maxine L.; Smith, Peggy B.
In a group of 154 U.S.-born and 127 Mexico-born Hispanic teens delivering at a county hospital in Houston, only 50 returned for their scheduled postpartum visit. Returning teens across groups were more likely to have no prenatal care, have a preterm or expired infant, report no educational plan, and have a support system. (KS)
Zeitlin, Jennifer; Combier, Evelyne; Levaillant, Marc; Lasbeur, Linda; Pilkington, Hugo; Charreire, Helene; Rivera, Lucile
Neighbourhood-level deprivation is associated with preterm birth; preterm birth rates are also higher for some, but not all migrant groups. We studied the impact of neighbourhood characteristics (a deprivation score and the proportion of foreign-born residents) on singleton preterm birth in the French district of Seine-Saint-Denis for women born in France, North Africa, sub-Saharan Africa and other countries. Multilevel logistic regression models were adjusted for maternal demographic and health care characteristics. For women born in France, the preterm birth rate rose with neighbourhood deprivation quintile (3.8% in the first to 5.7% in the fifth, adjusted odds ratio: 1.40 [95% confidence interval 1.14, 1.72]) and with increasing proportions of foreign-born residents. Preterm birth rates were not higher in more deprived neighbourhoods for women born outside of France and were lower in neighbourhoods with more foreign-born residents; in multilevel models, the inverse association with deprivation remained significant for women from sub-Saharan Africa. Area-based deprivation measures should be used with caution in populations with large numbers of migrants. These results raise questions about the health benefits of clustering for migrant communities as well as the negative consequences of acculturation.
Einspieler, Christa; Bos, Arend F.; Libertus, Melissa E.; Marschik, Peter B.
Apart from motor and behavioral dysfunctions, deficits in cognitive skills are among the well-documented sequelae of preterm birth. However, early identification of infants at risk for poor cognition is still a challenge, as no clear association between pathological findings based on neuroimaging scans and cognitive functions have been detected as yet. The Prechtl General Movement Assessment (GMA) has shown its merits for the evaluation of the integrity of the young nervous system. It is a reliable tool for identifying infants at risk for neuromotor deficits. Recent studies on preterm infants demonstrate that abnormal general movements (GMs) also reflect impairments of brain areas involved in cognitive development. The aim of this systematic review was to discuss studies that included (i) the Prechtl GMA applied in preterm infants, and (ii) cognitive outcome measures in six data bases. Seven studies met the inclusion criteria and yielded the following results: (a) children born preterm with consistently abnormal GMs up to 8 weeks after term had lower intelligence quotients at school age than children with an early normalization of GMs; (b) from 3 to 5 months after term, several qualitative, and quantitative aspects of the concurrent motor repertoire, including postural patterns, were predictive of intelligence at 7–10 years of age. These findings in 428 individuals born preterm suggest that normal GMs along with a normal motor repertoire during the first months after term are markers for normal cognitive development until at least age 10. PMID:27047429
Teeters, Angelique; Ammerman, Robert T.
BACKGROUND AND OBJECTIVES: Home visiting is 1 strategy to improve child health and parenting. Since implementation of home visiting trials 2 decades ago, US preterm births (<37 weeks) have risen by 20%. The objective of this study was to review evidence regarding home visiting and outcomes of preterm infants METHODS: Searches of Medline, Cumulative Index to Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, Cochrane Controlled Trial Register, PsycINFO, and Embase were conducted. Criteria for inclusion were (1) cohort or controlled trial designs; (2) home-based, preventive services for infants at medical or social risk; and (3) outcomes reported for infants born preterm or low birth weight (<2500 g). Data from eligible reports were abstracted by 2 reviewers. Random effects meta-analysis was used to synthesize data for developmental and parent interaction measures. RESULTS: Seventeen studies (15 controlled trials, 2 cohort studies) were reviewed. Five outcome domains were identified: infant development, parent-infant interaction, morbidity, abuse/neglect, and growth/nutrition. Six studies (n = 336) demonstrated a pooled standardized mean difference of 0.79 (95% confidence interval 0.57 to 1.02) in Home Observation for Measurement of the Environment Inventory scores at 1 year in the home-visited groups versus control. Evidence for other outcomes was limited. Methodological limitations were common. CONCLUSIONS: Reviewed studies suggest that home visiting for preterm infants promotes improved parent-infant interaction. Further study of interventions targeting preterm infants within existing programs may strengthen the impact and cost benefits of home visiting in at-risk populations. PMID:23940238
McPherson, Christopher; Haslam, Matthew; Pineda, Roberta; Rogers, Cynthia; Neil, Jeffrey J.; Inder, Terrie E.
Background Fentanyl is commonly utilized in preterm infants. Relatively little is known regarding the neurodevelopmental outcomes of preterm infants exposed to fentanyl. Objective To investigate the association between cumulative fentanyl dose and brain injury and diameters in a cohort of preterm infants Methods Data on demographics, perinatal course, and neonatal course, including total fentanyl exposure prior to term equivalent age, were retrospectively evaluated for 103 infants born at ≤ 30 weeks gestational age who underwent magnetic resonance imaging at term equivalent age (mean gestational age 26.9 ± 1.8 weeks). Magnetic resonance images were evaluated for brain injury and regional brain diameters. Developmental testing was conducted at term equivalent and 2 years of age. Results Seventy-eight infants (76%) received fentanyl (median cumulative dose 3 μg/kg, interquartile range 1 – 441 μg/kg). Cumulative fentanyl dose in the first week of life correlated with the incidence of cerebellar hemorrhage after correction for covariates (OR 2.1, 95% confidence interval 1.1 – 4.1). Cumulative fentanyl dose before term equivalent age correlated with reductions in transverse cerebellar diameter after correction for covariates including the presence of cerebellar hemorrhage (r = 0.461, p = 0.002). No correlation was detected between cumulative fentanyl dose and development at 2 years of age. Conclusions Higher cumulative fentanyl dose in preterm infants correlated with a higher incidence of cerebellar injury and lower cerebellar diameter at term equivalent age. Our findings must be taken with caution, but emphasize the need for future prospective trials examining the risks and benefits of commonly utilized analgesic agents in preterm infants. PMID:26369570
Leonard, Stephanie A.; Crespi, Catherine M.; Gee, Denise C.; Zhu, Yuda; Whaley, Shannon E.
The aim of this study was to assess potential prepregnancy risk factors for preterm birth in a low-income, Hispanic population in Southern California. Additionally, the study assessed whether the prevalence of preterm birth and any associations between risk factors and preterm birth differed between U.S.- and foreign-born mothers. The study sample included 1,174 mothers participating in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) within 1 year postpartum, including an augment sample of mothers who delivered preterm. Maternal sociodemographic traits, prepregnancy health-related characteristics and behaviors, and birth outcomes were collected by telephone survey. Odds ratios for associations between risk factors and preterm birth were estimated by logistic regression with sampling weights. Effect measure modification of any association by maternal nativity was also assessed using interaction terms. After adjustment for confounding, significant prepregnancy risk factors for preterm birth included maternal age ≥35 y (OR = 2.00; 95% CI: 1.04, 3.84) compared to age 18–24 y, and experience of a financially stressful life event among U.S.-born, but not foreign-born, women (OR = 2.61; 95% CI: 1.43, 4.77). The weighted prevalence of preterm birth was 15.1% and did not significantly differ by maternal nativity (P = 0.19). Further investigation with large, prospective studies is needed to better understand the risk factors for and disparities in preterm birth among the growing Hispanic population in the U.S. so that women who are at risk prepregnancy can be identified and provided risk-specific services. PMID:25994418
Variation in Adult Plant Phenotypes and Partitioning among Seed and Stem-Borne Roots across Brachypodium distachyon Accessions to Exploit in Breeding Cereals for Well-Watered and Drought Environments.
Chochois, Vincent; Vogel, John P; Rebetzke, Gregory J; Watt, Michelle
Seedling roots enable plant establishment. Their small phenotypes are measured routinely. Adult root systems are relevant to yield and efficiency, but phenotyping is challenging. Root length exceeds the volume of most pots. Field studies measure partial adult root systems through coring or use seedling roots as adult surrogates. Here, we phenotyped 79 diverse lines of the small grass model Brachypodium distachyon to adults in 50-cm-long tubes of soil with irrigation; a subset of 16 lines was droughted. Variation was large (total biomass, ×8; total root length [TRL], ×10; and root mass ratio, ×6), repeatable, and attributable to genetic factors (heritabilities ranged from approximately 50% for root growth to 82% for partitioning phenotypes). Lines were dissected into seed-borne tissues (stem and primary seminal axile roots) and stem-borne tissues (tillers and coleoptile and leaf node axile roots) plus branch roots. All lines developed one seminal root that varied, with branch roots, from 31% to 90% of TRL in the well-watered condition. With drought, 100% of TRL was seminal, regardless of line because nodal roots were almost always inhibited in drying topsoil. Irrigation stimulated nodal roots depending on genotype. Shoot size and tillers correlated positively with roots with irrigation, but partitioning depended on genotype and was plastic with drought. Adult root systems of B. distachyon have genetic variation to exploit to increase cereal yields through genes associated with partitioning among roots and their responsiveness to irrigation. Whole-plant phenotypes could enhance gain for droughted environments because root and shoot traits are coselected.
Variation in Adult Plant Phenotypes and Partitioning among Seed and Stem-Borne Roots across Brachypodium distachyon Accessions to Exploit in Breeding Cereals for Well-Watered and Drought Environments1[OPEN
Seedling roots enable plant establishment. Their small phenotypes are measured routinely. Adult root systems are relevant to yield and efficiency, but phenotyping is challenging. Root length exceeds the volume of most pots. Field studies measure partial adult root systems through coring or use seedling roots as adult surrogates. Here, we phenotyped 79 diverse lines of the small grass model Brachypodium distachyon to adults in 50-cm-long tubes of soil with irrigation; a subset of 16 lines was droughted. Variation was large (total biomass, ×8; total root length [TRL], ×10; and root mass ratio, ×6), repeatable, and attributable to genetic factors (heritabilities ranged from approximately 50% for root growth to 82% for partitioning phenotypes). Lines were dissected into seed-borne tissues (stem and primary seminal axile roots) and stem-borne tissues (tillers and coleoptile and leaf node axile roots) plus branch roots. All lines developed one seminal root that varied, with branch roots, from 31% to 90% of TRL in the well-watered condition. With drought, 100% of TRL was seminal, regardless of line because nodal roots were almost always inhibited in drying topsoil. Irrigation stimulated nodal roots depending on genotype. Shoot size and tillers correlated positively with roots with irrigation, but partitioning depended on genotype and was plastic with drought. Adult root systems of B. distachyon have genetic variation to exploit to increase cereal yields through genes associated with partitioning among roots and their responsiveness to irrigation. Whole-plant phenotypes could enhance gain for droughted environments because root and shoot traits are coselected. PMID:25975834
... with serious health problems. Some health problems, like cerebral palsy , can last a lifetime. Other problems, such as ... This medication may help reduce the risk of cerebral palsy that is associated with early preterm birth. What ...
Ceschin, Rafael; Wisnowski, Jessica L.; Paquette, Lisa B.; Nelson, Marvin D.; Blüml, Stefan; Panigrahy, Ashok
Thalamic structural co-variation with cortical regions has been demonstrated in preterm infants, but its relationship to cortical function and severity of non-cystic white matter injury (non-cystic WMI) is unclear. The relationship between thalamic morphology and both cortical network synchronization and cortical structural connectivity has not been established. We tested the hypothesis that in preterm neonates, thalamic volume would correlate with primary cortical visual function and microstructural integrity of cortico-cortical visual association pathways. A total of 80 term-equivalent preterm and 44 term-born infants underwent high-resolution structural imaging coupled with visual functional magnetic resonance imaging or diffusion tensor imaging. There was a strong correlation between thalamic volume and primary visual cortical activation in preterms with non-cystic WMI (r = 0.81, p-value = 0.001). Thalamic volume also correlated strongly with interhemispheric cortico-cortical connectivity (splenium) in preterm neonates with a relatively higher severity of non-cystic WMI (p-value < 0.001). In contrast, there was lower correlation between thalamic volume and intrahemispheric cortico-cortical connectivity, including the inferior longitudinal fasciculus and inferior frontal orbital fasciculus. This study shows distinct temporal overlap in the disruption of thalamo-cortical and interhemispheric cortico-cortical connectivity in preterm infants suggesting developmental synergy between thalamic morphology and the emergence of cortical networks in the last trimester. PMID:26106571
Namachivayam, Kopperuncholan; Coffing, Hayley P; Sankaranarayanan, Nehru Viji; Jin, Yingzi; MohanKumar, Krishnan; Frost, Brandy L; Blanco, Cynthia L; Patel, Aloka L; Meier, Paula P; Garzon, Steven A; Desai, Umesh R; Maheshwari, Akhil
Human milk contains biologically important amounts of transforming growth factor-β2 isoform (TGF-β2), which is presumed to protect against inflammatory gut mucosal injury in the neonate. In preclinical models, enterally administered TGF-β2 can protect against experimental necrotizing enterocolitis, an inflammatory bowel necrosis of premature infants. In this study, we investigated whether TGF-β bioactivity in human preterm milk could be enhanced for therapeutic purposes by adding recombinant TGF-β2 (rTGF-β2) to milk prior to feeding. Milk-borne TGF-β bioactivity was measured by established luciferase reporter assays. Molecular interactions of TGF-β2 were investigated by nondenaturing gel electrophoresis and immunoblots, computational molecular modeling, and affinity capillary electrophoresis. Addition of rTGF-β2 (20-40 nM) to human preterm milk samples failed to increase TGF-β bioactivity in milk. Milk-borne TGF-β2 was bound to chondroitin sulfate (CS) containing proteoglycan(s) such as biglycan, which are expressed in high concentrations in milk. Chondroitinase treatment of milk increased the bioactivity of both endogenous and rTGF-β2, and consequently, enhanced the ability of preterm milk to suppress LPS-induced NF-κB activation in macrophages. These findings provide a mechanism for the normally low bioavailability of milk-borne TGF-β2 and identify chondroitinase digestion of milk as a potential therapeutic strategy to enhance the anti-inflammatory effects of preterm milk.
Swaggart, Kayleigh A.; Pavlicev, Mihaela; Muglia, Louis J.
The molecular mechanisms controlling human birth timing at term, or resulting in preterm birth, have been the focus of considerable investigation, but limited insights have been gained over the past 50 years. In part, these processes have remained elusive because of divergence in reproductive strategies and physiology shown by model organisms, making extrapolation to humans uncertain. Here, we summarize the evolution of progesterone signaling and variation in pregnancy maintenance and termination. We use this comparative physiology to support the hypothesis that selective pressure on genomic loci involved in the timing of parturition have shaped human birth timing, and that these loci can be identified with comparative genomic strategies. Previous limitations imposed by divergence of mechanisms provide an important new opportunity to elucidate fundamental pathways of parturition control through increasing availability of sequenced genomes and associated reproductive physiology characteristics across diverse organisms. PMID:25646385
Swaggart, Kayleigh A; Pavlicev, Mihaela; Muglia, Louis J
The molecular mechanisms controlling human birth timing at term, or resulting in preterm birth, have been the focus of considerable investigation, but limited insights have been gained over the past 50 years. In part, these processes have remained elusive because of divergence in reproductive strategies and physiology shown by model organisms, making extrapolation to humans uncertain. Here, we summarize the evolution of progesterone signaling and variation in pregnancy maintenance and termination. We use this comparative physiology to support the hypothesis that selective pressure on genomic loci involved in the timing of parturition have shaped human birth timing, and that these loci can be identified with comparative genomic strategies. Previous limitations imposed by divergence of mechanisms provide an important new opportunity to elucidate fundamental pathways of parturition control through increasing availability of sequenced genomes and associated reproductive physiology characteristics across diverse organisms.
Moro, M A; Sanna, R; Cambosu, F; Soro, G; Dessole, S; Montella, A; Capobianco, G
The authors report a preterm neonate with dysmorphic traits and cleft palate who was born preterm because of precipitous delivery and died soon after birth notwithstanding neonatal intensive care unit (NICU) support. The cytogenetic analysis on fibroblasts from post-mortem skin biopsy demonstrated a Pallister-Killian syndrome (PKS). PKS is a cytogenetically syndrome characterized by a tissue limited mosaic distribution of one isochromosome 12p (tetrasomy 12p). Clinical manifestations of PKS are variable, and some symptoms may overlap with other malformative syndromes, thus the correct diagnosis mainly depends on the demonstration of the specific cytogenetic abnormality.
Li, Qing; Keith, Louis G; Kirby, Russell S
This paper examines nativity differences in adverse perinatal outcomes of Chinese-American mothers. Singleton live births to US-resident Chinese women (150,620 foreign-born, 15,040 US-born) and a random sample of 150,620 non-Hispanic White mothers were selected from 1995 to 2000 national linked birth/infant death certificate files. Associations between maternal nativity status and adverse perinatal outcomes were assessed using multivariable logistic regressions. Compared to US-born Chinese mothers, foreign-born Chinese mothers were less likely to be unmarried, teen mothers, have a non-Hispanic White or other race partner, be rural residents, and more likely to be less educated, or utilize prenatal care inadequately. Controlling for these factors, foreign-born Chinese-American mothers had significantly lower risks for low birth weight, preterm birth, and small-for-gestational age, whereas risks for infant mortality, neonatal mortality, and post-neonatal mortality did not differ significantly from those of infants of US-born Chinese mothers. Chinese Americans exhibited clear nativity differentials for adverse birth outcomes.
Grunau, Ruth E; Cepeda, Ivan L; Chau, Cecil M Y; Brummelte, Susanne; Weinberg, Joanne; Lavoie, Pascal M; Ladd, Mihoko; Hirschfeld, Aaron F; Russell, Evan; Koren, Gideon; Van Uum, Stan; Brant, Rollin; Turvey, Stuart E
Neonatal pain-related stress is associated with elevated salivary cortisol levels to age 18 months in children born very preterm, compared to full-term, suggesting early programming effects. Importantly, interactions between immune/inflammatory and neuroendocrine systems may underlie programming effects. We examined whether cortisol changes persist to school age, and if common genetic variants in the promoter region of the NFKBIA gene involved in regulation of immune and inflammatory responses, modify the association between early experience and later life stress as indexed by hair cortisol levels, which provide an integrated index of endogenous HPA axis activity. Cortisol was assayed in hair samples from 128 children (83 born preterm ≤ 32 weeks gestation and 45 born full-term) without major sensory, motor or cognitive impairments at age 7 years. We found that hair cortisol levels were lower in preterm compared to term-born children. Downregulation of the HPA axis in preterm children without major impairment, seen years after neonatal stress terminated, suggests persistent alteration of stress system programming. Importantly, the etiology was gender-specific such that in preterm boys but not girls, specifically those with the minor allele for NFKBIA rs2233409, lower hair cortisol was associated with greater neonatal pain (number of skin-breaking procedures from birth to term), independent of medical confounders. Moreover, the minor allele (CT or TT) of NFKBIA rs2233409 was associated with higher secretion of inflammatory cytokines, supporting the hypothesis that neonatal pain-related stress may act as a proinflammatory stimulus that induces long-term immune cell activation. These findings are the first evidence that a long-term association between early pain-related stress and cortisol may be mediated by a genetic variants that regulate the activity of NF-κB, suggesting possible involvement of stress/inflammatory mechanisms in HPA programming in boys born very
Preterm birth complication is the leading cause of neonatal death resulting in over one million deaths each year of the 15 million babies born preterm. To accelerate change, we provide an overview of the comprehensive strategy required, the tools available for context-specific health system implementation now, and the priorities for research and innovation. There is an urgent need for action on a dual track: (1) through strategic research to advance the prevention of preterm birth and (2) improved implementation and innovation for care of the premature neonate. We highlight evidence-based interventions along the continuum of care, noting gaps in coverage, quality, equity and implications for integration and scale up. Improved metrics are critical for both burden and tracking programmatic change. Linked to the United Nation's Every Women Every Child strategy, a target was set for 50% reduction in preterm deaths by 2025. Three analyses informed this target: historical change in high income countries, recent progress in best performing countries, and modelling of mortality reduction with high coverage of existing interventions. If universal coverage of selected interventions were to be achieved, then 84% or more than 921,000 preterm neonatal deaths could be prevented annually, with antenatal corticosteroids and Kangaroo Mother Care having the highest impact. Everyone has a role to play in reaching this target including government leaders, professionals, private sector, and of course families who are affected the most and whose voices have been critical for change in many of the countries with the most progress. Declaration This article is part of a supplement jointly funded by Save the Children's Saving Newborn Lives programme through a grant from The Bill & Melinda Gates Foundation and March of Dimes Foundation and published in collaboration with the Partnership for Maternal, Newborn and Child Health and the World Health Organization (WHO). The original article was
Scheinost, Dustin; Kwon, Soo Hyun; Shen, Xilin; Lacadie, Cheryl; Schneider, Karen C; Dai, Feng; Ment, Laura R; Constable, R Todd
Alterations in neural networks are associated with the cognitive difficulties of the prematurely born. Using functional magnetic resonance imaging, we analyzed functional connectivity for preterm (PT) and term neonates at term equivalent age. Specifically, we constructed whole-brain networks and examined rich club (RC) organization, a common construct among complex systems where important (or "rich") nodes connect preferentially to other important nodes. Both PT and term neonates showed RC organization with PT neonates exhibiting significantly reduced connections between these RC nodes. Additionally, PT neonates showed evidence of weaker functional segregation. Our results suggest that PT birth is associated with fundamental changes of functional organization in the developing brain.
Strobel, Natalie A; Peter, Sue; McAuley, Kimberley E; McAullay, Daniel R; Marriott, Rhonda; Edmond, Karen M
Objectives Our primary objective was to determine the incidence of hospital admission and emergency department presentation in Indigenous and non-Indigenous preterm infants aged postdischarge from birth admission to 11 months in Western Australia. Secondary objectives were to assess incidence in the poorest infants from remote areas and to determine the primary causes of hospital usage in preterm infants. Design Prospective population-based linked data set. Setting and participants All preterm babies born in Western Australia during 2010 and 2011. Main outcome measures All-cause hospitalisations and emergency department presentations. Results There were 6.9% (4211/61 254) preterm infants, 13.1% (433/3311) Indigenous preterm infants and 6.5% (3778/57 943) non-Indigenous preterm infants born in Western Australia. Indigenous preterm infants had a higher incidence of hospital admission (adjusted incident rate ratio (aIRR) 1.24, 95% CI 1.08 to 1.42) and emergency department presentation (aIRR 1.71, 95% CI 1.44 to 2.02) compared with non-Indigenous preterm infants. The most disadvantaged preterm infants (7.8/1000 person days) had a greater incidence of emergency presentation compared with the most advantaged infants (3.1/1000 person days) (aIRR 1.61, 95% CI 1.30 to 2.00). The most remote preterm infants (7.8/1000 person days) had a greater incidence of emergency presentation compared with the least remote preterm infants (3.0/1000 person days; aIRR 1.82, 95% CI 1.49 to 2.22). Conclusions In Western Australia, preterm infants have high hospital usage in their first year of life. Infants living in disadvantaged areas, remote area infants and Indigenous infants are at increased risk. Our data highlight the need for improved postdischarge care for preterm infants. PMID:28100563
Yip, Tiffany; Gee, Gilbert C.; Takeuchi, David T.
The association between racial and ethnic discrimination and psychological distress was examined among 2,047 Asians (18 to 75 years of age) in the National Latino and Asian American Study, the first-ever nationally representative study of mental health among Asians living in the United States. Stratifying the sample by age in years (i.e., 18 to 30, 31 to 40, 41 to 50, 51 to 75) and nativity status (i.e., immigrant vs. U.S.-born), ethnic identity was tested as either a protective or exacerbating factor. Analyses showed that ethnic identity buffered the association between discrimination and mental health for U.S.-born individuals 41 to 50 years of age. For U.S.-born individuals 31 to 40 years of age and 51 to 75 years of age, ethnic identity exacerbated the negative effects of discrimination on mental health. The importance of age and immigrant status for the association between ethnic identity, discrimination, and well-being among Asians in the United States is discussed. PMID:18473644
Sivertsen, Åse; Ariansen, Anja Maria Steinsland; Filip, Charles; Vindenes, Halvard A.; Feragen, Kristin B.; Moster, Dag; Lie, Rolv Terje; Haaland, Øystein A.
Background It has been reported that people born with orofacial clefts do worse in life than their peers regarding a range of social markers, such as academic achievement and reproduction. We have compared otherwise healthy individuals with and without clefts, to investigate if these differences are due to the cleft or other background factors. Materials and Methods In a retrospective national cohort study, based on compulsory registers with data collected prospectively, we included everybody born in Norway between 1967 and 1992 (1490279 individuals, 2584 with clefts). This cohort was followed until the year 2010, when the youngest individuals were 18 years old. In order to ensure that the individuals were not affected by unknown syndromes or diseases, we excluded all individuals with any chronic medical condition, or who had other birth defects than clefts, hydroceles and dislocated hips. Individuals with oral clefts who were included in the study are said to have isolated clefts. Results Isolated cleft patients are similar to the general population regarding education, income and social class. Isolated cleft patients have lower fertility than the background population, but considering only married couples this difference in fertility disappeared. Conclusions An oral cleft did not appear to affect future socioeconomic status or chances of becoming a parent for children born in Norway. An exception was males with cleft lip and palate, but differences were small. PMID:27631472
van den Heuvel, Martijn P; Kersbergen, Karina J; de Reus, Marcel A; Keunen, Kristin; Kahn, René S; Groenendaal, Floris; de Vries, Linda S; Benders, Manon J N L
The human connectome is the result of an elaborate developmental trajectory. Acquiring diffusion-weighted imaging and resting-state fMRI, we studied connectome formation during the preterm phase of macroscopic connectome genesis. In total, 27 neonates were scanned at week 30 and/or week 40 gestational age (GA). Examining the architecture of the neonatal anatomical brain network revealed a clear presence of a small-world modular organization before term birth. Analysis of neonatal functional connectivity (FC) showed the early formation of resting-state networks, suggesting that functional networks are present in the preterm brain, albeit being in an immature state. Moreover, structural and FC patterns of the neonatal brain network showed strong overlap with connectome architecture of the adult brain (85 and 81%, respectively). Analysis of brain development between week 30 and week 40 GA revealed clear developmental effects in neonatal connectome architecture, including a significant increase in white matter microstructure (P < 0.01), small-world topology (P < 0.01) and interhemispheric FC (P < 0.01). Computational analysis further showed that developmental changes involved an increase in integration capacity of the connectivity network as a whole. Taken together, we conclude that hallmark organizational structures of the human connectome are present before term birth and subject to early development.
Savini, Sara; Correani, Alessio; Pupillo, Daniele; D'Ascenzo, Rita; Biagetti, Chiara; Pompilio, Adriana; Simonato, Manuela; Verlato, Giovanna; Cogo, Paola; Taus, Marina; Nicolai, Albano; Carnielli, Virgilio Paolo
Several studies reported the association between total plasma phytosterol concentrations and the parenteral nutrition-associated cholestasis (PNAC). To date, no data are available on phytosterol esterification in animals and in humans during parenteral nutrition (PN). We measured free and esterified sterols (cholesterol, campesterol, stigmasterol, and sitosterol) plasma concentrations during PN in 16 preterm infants (500-1249 g of birth weight; Preterm-PN), in 11 term infants (Term-PN) and in 12 adults (Adult-PN). Gas chromatography-mass spectrometry was used for measurements. Plasma concentrations of free cholesterol (Free-CHO), free phytosterols (Free-PHY) and esterified phytosterols (Ester-PHY) were not different among the three PN groups. Esterified cholesterol (Ester-CHO) was statistically lower in Preterm-PN than Adult-PN. Preterm-PN had significantly higher Free-CHO/Ester-CHO and Free-PHY/Ester-PHY ratios than Adult-PN (Free-CHO/Ester-CHO: 1.1 ± 0.7 vs. 0.6 ± 0.2; Free-PHY/Ester-PHY: 4.1 ± 2.6 vs. 1.3 ± 0.8; *P < 0.05). Free-CHO/Ester-CHO and Free-PHY/Ester-PHY ratios of Term-PN (Free-CHO/Ester-CHO: 1.1 ± 0.4; Free-PHY/Ester-PHY: 2.9 ± 1.7) were not different from either Preterm-PN or from Adult-PN. Plasma Free-CHO/Ester-CHO and Free-PHY/Ester-PHY were unchanged after 24 h on fat-free PN both in Preterm-PN and in Adult-PN. Free-PHY/Ester-PHY did not correlate with phytosterol intake in Preterm-PN. Free-PHY/Ester-PHY of Preterm-PN was positively correlated with the Free-CHO/Ester-CHO and negatively correlated with gestational age and birth weight. In conclusion, PHY were esterified to a lesser extent than CHO in all study groups; the esterification was markedly decreased in Preterm-PN compared to Adult-PN. The clinical consequences of these findings warrant further investigations.
Carmichael, Suzan L.; Cullen, Mark R.; Mayo, Jonathan A.; Gould, Jeffrey B.; Loftus, Pooja; Stevenson, David K.; Wise, Paul H.; Shaw, Gary M.
Objective This study examined the ability of social, demographic, environmental and health-related factors to explain geographic variability in preterm delivery among black and white women in the US and whether these factors explain black-white disparities in preterm delivery. Methods We examined county-level prevalence of preterm delivery (20–31 or 32–36 weeks gestation) among singletons born 1998–2002. We conducted multivariable linear regression analysis to estimate the association of selected variables with preterm delivery separately for each preterm/race-ethnicity group. Results The prevalence of preterm delivery varied two- to three-fold across U.S. counties, and the distributions were strikingly distinct for blacks and whites. Among births to blacks, regression models explained 46% of the variability in county-level risk of delivery at 20–31 weeks and 55% for delivery at 32–36 weeks (based on R-squared values). Respective percentages for whites were 67% and 71%. Models included socio-environmental/demographic and health-related variables and explained similar amounts of variability overall. Conclusions Much of the geographic variability in preterm delivery in the US can be explained by socioeconomic, demographic and health-related characteristics of the population, but less so for blacks than whites. PMID:24740117
Riese, Marilyn L.
Irritability levels and activity reactivity to aversive tactile stimuli were compared for 144 full-term neonates and 191 preterm infants. Irritability ratings increased across the five trials both during and post stimulation for full-term females and males and for preterm females, but not for preterm males. Activity ratings decreased across trials…
Ramenghi, Luca A
Late preterm infants (born between 34+0 and 36+6 weeks gestation) account for the recent striking increase in premature birth and they carry a higher vulnerability to suffer brain insults compared to term infants. These babies can develop any kind of known brain lesions including those affecting the most premature babies (i.e.an intraventricular haemorrhage) and lesions affecting more typically term babies like asphyxia and stroke. In other words there is not a specific brain lesion characterizing this gestational age group, and there is not a specific maturational landmark although "subplate neurons" are suppose to ultimate their connectivity in this period and the cortical volume is significantly increasing. In addition we should not forget the possibility that "late preterm babies" may present neurological clinical impairments in the absence of recognized morphological brain lesions even with the use of highly sophisticated MR imaging techniques. For these reasons a wider use of more sophisticated neuro radiological studies is not sufficient to better understand why some studies highlight that the risk of developmental delay or disability can reach 36% higher among late preterm infants compared with term infants. We believe we should improve also our skills to identify even those very subtle clinical signs of impairment deserving further investigations although we often admit these babies in the normal post natal nurseries where clinical observation cannot be so appropriate.
Iwata, Sachiko; Katayama, Reiji; Kinoshita, Masahiro; Saikusa, Mamoru; Araki, Yuko; Takashima, Sachio; Abe, Toshi; Iwata, Osuke
Regional brain sizes of very-preterm infants at term-equivalent age differ from those of term-born peers, which have been linked with later cognitive impairments. However, dependence of regional brain volume loss on gestational age has not been studied in detail. To investigate the spatial pattern of brain growth in neonates without destructive brain lesions, head MRI of 189 neonates with a wide range of gestational age (24–42 weeks gestation) was assessed using simple metrics measurements. Dependence of MRI findings on gestational age at birth (Agebirth) and the corrected age at MRI scan (AgeMRI) were assessed. The head circumference was positively correlated with AgeMRI, but not Agebirth. The bi-parietal width, deep grey matter area and the trans-cerebellar diameter were positively correlated with both Agebirth and AgeMRI. The callosal thickness (positive), atrial width of lateral ventricle (negative) and the inter-hemispheric distance (negative) were exclusively correlated with Agebirth. The callosal thickness and cerebral/cerebellar transverse diameters showed predominant dependence on Agebirth over AgeMRI, suggesting that brain growth after preterm-birth was considerably restricted or even became negligible compared with that in utero. Such growth restriction after preterm birth may extensively affect relatively more matured infants, considering the linear relationships observed between brain sizes and Agebirth. PMID:27658730
Sprague, Ann; Stewart, Paula; Niday, Patricia; Nimrod, Carl; Walker, Robin
OBJECTIVE: To evaluate how well physicians and other prenatal care providers educate women about early recognition of and appropriate response to the signs and symptoms of preterm labour (PTL). To assess use of antenatal steroids for babies born at less than 34 weeks' gestation. DESIGN: Before-after study using a population-based approach. SETTING: Health care providers' offices, hospitals, and prenatal classes in Ottawa, Ont. PARTICIPANTS: Prenatal care providers, women in hospital after giving birth, prenatal class participants. INTERVENTIONS: Prenatal care providers received information and educational materials on PTL and preterm birth (PTB). They passed this information on to pregnant women at their 18- to 20-week prenatal visits. Teachers of prenatal classes gave the same information in early-series classes. Clinical practice guidelines were developed, and hospital staff received education on appropriate response to PTL. MAIN OUTCOME MEASURES: Use of educational materials and steroid treatment. RESULTS: Statistically significant increases were seen in the numbers of care providers who had educational material about PTL and PTB, who reported giving the educational material to all women, and who reported discussing signs and symptoms of PTL and PTB with all women; women who reported that their care providers talked with them about PTL and PTB, and women delivering preterm (< 34 weeks) babies who received steroids. CONCLUSION: Providing knowledge and standardized educational materials to health care providers can help improve preventive practice for PTL and educate women about PTL. PMID:12046368
Beckwith, L; Sigman, M; Cohen, S E; Parmelee, A H
Data on vocal output of 51 preterm infants and 16 term infants were obtained during naturalistic home observations at 1, 3, and 8 months; during the administration of a preference-for-novelty paradigm in the laboratory at 8 months; and by the administration of the Gesell Developmental Schedules at 9 months. Preterm and term infant groups were found to show both similarities and differences: both groups vocalized a similar amount in the preference-for-novelty situation; both groups earned similar scores on the language subtest of the Gesell; both groups increased the percentage of awake time they spent in nondistress vocalization from 1 to 8 months. Term infants showed an earlier increase than did preterm infants: term infants significantly increased during the 1-3 month period, whereas preterm infants only increased significantly during the 3-8 month period. The developmental differences suggest a link between vocal output and perinatal conditions in that caregiver behavior was not found to be different among groups. Within the preterm groups, some relationships were found between vocal output and later test performance: infants who vocalized more during mutual gazing with the mother earned significantly higher scores on the language subtest of the Gesell.
Elisabeth, Ralser; Elke, Griesmaier; Vera, Neubauer; Maria, Gnigler; Michaela, Höck; Ursula, Kiechl-Kohlendorfer
The aim of the study was to investigate the frequency of and the predictors for rehospitalization in preterm infants into early childhood, focusing on gender differences. All preterm infants born at <32 weeks of gestation in North Tyrol between January 2003 and December 2005 were enrolled in this survey. About one fifth of all children were readmitted, showing an inverse downward trend with increasing age. The most common reason for readmission in the third (36.5%) and fourth (42.9%) years of life was respiratory infection, but changed to miscellaneous surgeries in the fifth (52.1%). Male sex showed significantly higher readmission rates and more miscellaneous surgeries. Additionally, male sex and chronic lung disease were risk conditions for rehospitalization in the multivariate analysis. Readmission rates and respiratory infections in preterm-born children showed an inverse downward trend with increasing age. In early childhood, gender difference still plays a role with regard to rehospitalization.
Brummelte, Susanne; Chau, Cecil M Y; Cepeda, Ivan L; Degenhardt, Amanda; Weinberg, Joanne; Synnes, Anne R; Grunau, Ruth E
Early life stress can alter hypothalamic pituitary adrenal (HPA) axis function. Differences in cortisol levels have been found in preterm infants exposed to substantial procedural stress during neonatal intensive care, compared to infants born full-term, but only a few studies investigated whether altered programming of the HPA axis persists past toddler age. Further, there is a dearth of knowledge of what may contribute to these changes in cortisol. This prospective cohort study examined the cortisol profiles in response to the stress of cognitive assessment, as well as the diurnal rhythm of cortisol, in children (n=129) born at varying levels of prematurity (24-32 weeks gestation) and at full-term (38-41 weeks gestation), at age 7 years. Further, we investigated the relationships among cortisol levels and neonatal procedural pain-related stress (controlling for multiple medical confounders), concurrent maternal factors (parenting stress, depressive and anxiety symptoms) and children's behavioral problems. For each aim we investigate acute cortisol response profiles to a cognitive challenge as well as diurnal cortisol patterns at home. We hypothesized that children born very preterm will differ in their pattern of cortisol secretion from children born full-term, possibly depended on concurrent child and maternal factors, and that exposure to neonatal pain-related stress would be associated with altered cortisol secretion in children born very preterm, possibly in a sex-dependent way. Saliva samples were collected from 7-year old children three times during a laboratory visit for assessment of cognitive and executive functions (pretest, mid-test, end-study day acute stress profile) and at four times over two consecutive non-school days at home (i.e. morning, mid-morning, afternoon and bedtime-diurnal rhythm profile). We found that cortisol profiles were similar in preterm and full-term children, albeit preterms had slightly higher cortisol at bedtime compared to
Abitbol, Carolyn L; DeFreitas, Marissa J; Strauss, José
This educational review will highlight the historical and contemporary references that establish a basic understanding of measurements of kidney function in the neonate and its relevance for the life of an individual. Importantly, the differential renal function of preterm infants relative to term infants has become paramount with the increased viability of preterm infants and the realization that kidney function is associated with gestational age. Moreover, neonatal kidney function is primarily associated with absolute renal mass and hemodynamic stability. Neonatal kidney function and its early developmental progression predict lifelong cardiovascular and renal disease risks. Validation of estimation equations of kidney function in this population has provided important reference data for other investigations and a clinical basis for prospective and longitudinal follow-up. Future research should be directed towards a better understanding of surrogate markers of kidney function from infancy through adulthood. Pediatric nephrologists should be aware of the developmental aspects of kidney function including the importance of the congenital nephron endowment and the preservation of kidney function throughout a lifetime. • Nephrogenesis occurs in utero in concert with other organ systems by branching morphogenesis, including the lungs, pancreas, and vascular tree, with over 60 % of nephrons being formed during the last trimester. • Infants born preterm before 36 weeks' gestation are in active nephrogenesis and are at increased risk of having a decreased nephron endowment from prenatal and postnatal genetic and epigenetic hazards that will impact the patient for a lifetime. • Post-natal adaptation of kidney function is directly proportional to the number of perfused nephrons, estimated by total kidney volume (TKV), mean arterial pressure (MAP), and gestational age. • Accurate measurement of glomerular filtration rate (GFR) in infants is problematic due to the
Ment, Laura R; Hirtz, Deborah; Hüppi, Petra S
The neurodevelopmental disabilities of those who were born prematurely have been well described, yet the underlying alterations in brain development that lead to these changes remain poorly understood. Processes that are vulnerable to injury in the developing brain include maturation of oligodendrocyte precursors and genetically programmed changes in cortical connectivity; recent data have indicated that diffuse injury of the white matter accompanied by neuronal and axonal disruption is common in prematurely born infants. Recent advances in MRI include diffusion tensor imaging and sophisticated image analysis tools, such as functional connectivity, voxel-based morphometry, and mathematical morphology-based cortical folding strategies. These advanced techniques have shown that white matter structure is dependent on gestational age and have started to provide important information about the dynamic interactions between development, injury, and functional recovery in the preterm brain. Identification of early biomarkers for outcome could enable physicians and scientists to develop targeted pharmacological and behavioural therapies to restore functional connectivity.
Rothman, Adam L.; Sevilla, Monica B.; Mangalesh, Shwetha; Gustafson, Kathryn E.; Edwards, Laura; Cotten, C. Michael; Shimony, Joshua S.; Pizoli, Carolyn E.; El-Dairi, Mays A.; Freedman, Sharon F.; Toth, Cynthia A.
Purpose To assess retinal nerve fiber layer (RNFL) thickness at term-equivalent age in very preterm (<32 weeks gestational age) versus term-born infant cohorts, and compare very preterm infant RNFL thickness with brain anatomy and neurodevelopment. Design Cohort study. Methods RNFL was semi-automatically segmented (one eye per infant) in 57 very preterm and 50 term infants with adequate images from bedside portable, handheld spectral domain optical coherence tomography (Bioptigen, Inc., Research Triangle Park, NC) imaging at 37-42 weeks postmenstrual age. Mean RNFL thickness was calculated for the papillomacular bundle (−15° to + 15°) and temporal quadrant (−45° to +45°) relative to the fovea-optic nerve axis. Brain magnetic resonance imaging (MRI) scans clinically obtained in 26 very preterm infants were scored for global structural abnormalities by an expert masked to data except for age. Cognitive, language, and motor skills were assessed with Bayley Scales of Infant and Toddler Development-III (Pearson, San Antonio, TX) in 33 of the very preterm infants at 18-24 months corrected age. Results RNFL was thinner for very preterm versus term infants at the papillomacular bundle ([mean ± standard deviation] 61 ± 17 versus 72 ± 13 μm, p<0.001) and temporal quadrant (72 ± 21 versus 82 ± 16 μm, p=0.005). In very preterm infants, thinner papillomacular bundle RNFL correlated with higher global brain MRI lesion burden index (R2=0.35, p=0.001) and lower cognitive (R2=0.18, p=0.01) and motor (R2=0.17, p=0.02) scores. Relationships were similar for temporal quadrant. Conclusions Thinner RNFL in very preterm infants relative to term-born infants may relate to brain structure and neurodevelopment. PMID:26386157
Hodel, Amanda S; Brumbaugh, Jane E; Morris, Alyssa R; Thomas, Kathleen M
Interest in monitoring long-term neurodevelopmental outcomes of children born moderate-to-late preterm (32-36 weeks gestation) is increasing. Moderate-to-late preterm birth has a negative impact on academic achievement, which may relate to differential development of executive function (EF). Prior studies reporting deficits in EF in preterm children have almost exclusively assessed EF in affectively neutral contexts in high-risk preterm children (< 32 weeks gestation). Disrupted function in motivational or emotionally charged contexts (hot EF) following preterm birth remains uninvestigated, despite evidence that preterm children show differential development of neural circuitry subserving hot EF, including reduced orbitofrontal cortex volume. The present study is the first to examine whether low-risk, healthy children born moderate-to-late preterm exhibit impairments in the development of hot EF. Preterm children at age 4.5 years were less likely to choose larger, delayed rewards across all levels of reward magnitude on a delay discounting task using tangible rewards, but performed more similarly to their full-term peers on a delay aversion task involving abstract rewards and on measures of cool EF. The relationship between gestational age at birth and selection of delayed rewards extended across the entire gestational age range of the sample (32-42 weeks), and remained significant after controlling for intelligence and processing speed. Results imply that there is not a finite cut-off point at which children are spared from potential long-term neurodevelopmental effects of PT birth. Further investigation of reward processing and hot EF in individuals with a history of PT birth is warranted given the susceptibility of prefrontal cortex development to early environmental variations.
van der Pal, Sylvia M.; Maguire, Celeste M.; Bruil, Jeanet; le Cessie, Saskia; van Zwieten, Paul; Veen, Sylvia; Wit, Jan M.; Walther, Frans J.
This study explored the effects of basic developmental care on the behaviour of very pre-term infants and parental stress at 1 and 2 years of corrected age. A randomized controlled trial was done to compare basic Developmental Care (standardized nests and incubator covers) and controls (standard care). Parents of infants born less than 32 weeks of…
de Kieviet, Jorrit F.; Zoetebier, Lydia; van Elburg, Ruurd M.; Vermeulen, R. Jeroen; Oosterlaan, Jaap
Aim: The aim of this article was to clarify the impact and consequences of very preterm birth (born less than 32wks of gestation) and/or very low birthweight ([VLBW], weighing less than 1500g) on brain volume development throughout childhood and adolescence. Method: The computerized databases PubMed, Web of Knowledge, and EMBASE were searched for…
Smith, M. Cecil; Smith, Thomas J.
Data from the 2003 National Assessment of Adult Literacy were examined to determine if non-native-born adults in the US differ from their native-born counterparts in (1) participation in work-related training or education, and (2) perceptions that specific skills limit their job opportunities. Results indicated that non-native-born persons were…
Been, Jasper V.; Lugtenberg, Marlies J.; Smets, Eline; van Schayck, Constant P.; Kramer, Boris W.; Mommers, Monique; Sheikh, Aziz
Background Accumulating evidence implicates early life factors in the aetiology of non-communicable diseases, including asthma/wheezing disorders. We undertook a systematic review investigating risks of asthma/wheezing disorders in children born preterm, including the increasing numbers who, as a result of advances in neonatal care, now survive very preterm birth. Methods and Findings Two reviewers independently searched seven online databases for contemporaneous (1 January 1995–23 September 2013) epidemiological studies investigating the association between preterm birth and asthma/wheezing disorders. Additional studies were identified through reference and citation searches, and contacting international experts. Quality appraisal was undertaken using the Effective Public Health Practice Project instrument. We pooled unadjusted and adjusted effect estimates using random-effects meta-analysis, investigated “dose–response” associations, and undertook subgroup, sensitivity, and meta-regression analyses to assess the robustness of associations. We identified 42 eligible studies from six continents. Twelve were excluded for population overlap, leaving 30 unique studies involving 1,543,639 children. Preterm birth was associated with an increased risk of wheezing disorders in unadjusted (13.7% versus 8.3%; odds ratio [OR] 1.71, 95% CI 1.57–1.87; 26 studies including 1,500,916 children) and adjusted analyses (OR 1.46, 95% CI 1.29–1.65; 17 studies including 874,710 children). The risk was particularly high among children born very preterm (<32 wk gestation; unadjusted: OR 3.00, 95% CI 2.61–3.44; adjusted: OR 2.81, 95% CI 2.55–3.12). Findings were most pronounced for studies with low risk of bias and were consistent across sensitivity analyses. The estimated population-attributable risk of preterm birth for childhood wheezing disorders was ≥3.1%. Key limitations related to the paucity of data from low- and middle-income countries, and risk of residual
Fritzen, Charissa M.; Huang, Junjun; Westby, Kathleen; Freye, James D.; Dunlap, Brett; Yabsley, Michael J.; Schardein, Mike; Dunn, John R.; Jones, Timothy F.; Moncayo, Abelardo C.
Rocky Mountain spotted fever, Lyme disease, and ehrlichiosis are tick-borne diseases that are reported annually in Kentucky. We conducted a survey to describe infection prevalence of tick-borne pathogens in Amblyomma americanum and Dermacentor variabilis ticks collected in Kentucky. During 2007–2008, we collected 287 ticks (179 D. variabilis and 108 A. americanum) from canine, feral hog, horse, raccoon, white-tailed deer, and human hosts in six counties in Kentucky. Ticks were screened for Rickettsia spp., Borrelia spp., and Ehrlichia spp. by using polymerase chain reaction. Forty-one (14.3%) ticks (31 A. americanum and 10 D. variabilis) were polymerase chain reaction–positive for a Rickettsia spp. Fourteen (4.9%) ticks (6 A. americanum and 8 D. variabilis) were positive for E. chaffeensis, and 4 A. americanum (1.4%) were positive for E. ewingii. One (0.4%) A. americanum was positive for Borrelia lonestari. Although Rocky Mountain spotted fever is diagnosed in Kentucky, no R. rickettsii was found in ticks in this study. PMID:21976578
Fritzen, Charissa M; Huang, Junjun; Westby, Kathleen; Freye, James D; Dunlap, Brett; Yabsley, Michael J; Schardein, Mike; Dunn, John R; Jones, Timothy F; Moncayo, Abelardo C
Rocky Mountain spotted fever, Lyme disease, and ehrlichiosis are tick-borne diseases that are reported annually in Kentucky. We conducted a survey to describe infection prevalence of tick-borne pathogens in Amblyomma americanum and Dermacentor variabilis ticks collected in Kentucky. During 2007-2008, we collected 287 ticks (179 D. variabilis and 108 A. americanum) from canine, feral hog, horse, raccoon, white-tailed deer, and human hosts in six counties in Kentucky. Ticks were screened for Rickettsia spp., Borrelia spp., and Ehrlichia spp. by using polymerase chain reaction. Forty-one (14.3%) ticks (31 A. americanum and 10 D. variabilis) were polymerase chain reaction-positive for a Rickettsia spp. Fourteen (4.9%) ticks (6 A. americanum and 8 D. variabilis) were positive for E. chaffeensis, and 4 A. americanum (1.4%) were positive for E. ewingii. One (0.4%) A. americanum was positive for Borrelia lonestari. Although Rocky Mountain spotted fever is diagnosed in Kentucky, no R. rickettsii was found in ticks in this study.
Ramel, Sara E; Georgieff, Michael K
The brain is the most highly metabolic organ in the preterm neonate and consumes the greatest amount of nutrient resources for its function and growth. As preterm infants survive at greater rates, neurodevelopment has become the primary morbidity outcome of interest. While many factors influence neurodevelopmental outcomes in preterm infants, nutrition is of particular importance because the healthcare team has a great deal of control over its provision. Studies over the past 30 years have emphasized the negative neurodevelopmental consequences of poor nutrition and growth in the preterm infant. While all nutrients are important for brain development, certain ones including glucose, protein, fats (including long-chain polyunsaturated fatty acids), iron, zinc, copper, iodine, folate and choline have particularly large roles in the preterm infant. They affect major brain processes such as neurogenesis, neuronal differentiation, myelination and synaptogenesis, all of which are proceeding at a rapid pace between 22 and 42 weeks' post-conception. At the macronutrient level, weight gain, linear growth (independent of weight gain) and head circumference growth are markers of nutritional status. Each has been associated with long-term neurodevelopment. The relationship of micronutrients to neurodevelopment in preterm infants is understudied in spite of the large effect these nutrients have in other young populations. Nutrients do not function alone to stimulate brain development, but rather in concert with growth factors, which in turn are dependent on adequate nutrient status (e.g. protein, zinc) as well as on physiologic status. Non-nutritional factors such as infection, corticosteroids, and inflammation alter how nutrients are accreted and distributed, and also suppress growth factor synthesis. Thus, nutritional strategies to optimize brain growth and development include assessment of status at birth, aggressive provision of nutrients that are critical in this time
Marston, Louise; Peacock, Janet L.; Calvert, Sandra A.; Greenough, Anne; Marlow, Neil
Language development is often slower in preterm children compared with their term peers. We investigated factors associated with vocabulary acquisition at 2 years in a cohort of children born at 28 weeks' gestation or less. For children entered into the United Kingdom Oscillation Study, language development was evaluated by using the…
Ben-Shachar, Michal; Feldman, Heidi M.
Premature birth is highly prevalent and associated with neurodevelopmental delays and disorders. Adverse outcomes, particularly in children born before 32 weeks of gestation, have been attributed in large part to white matter injuries, often found in periventricular regions using conventional imaging. To date, tractography studies of white matter pathways in children and adolescents born preterm have evaluated only a limited number of tracts simultaneously. The current study compares diffusion properties along 18 major cerebral white matter pathways in children and adolescents born preterm (n = 27) and full term (n = 19), using diffusion magnetic resonance imaging and tractography. We found that compared to the full term group, the preterm group had significantly decreased FA in segments of the bilateral uncinate fasciculus and anterior segments of the right inferior fronto-occipital fasciculus. Additionally, the preterm group had significantly increased FA in segments of the right and left anterior thalamic radiations, posterior segments of the right inferior fronto-occipital fasciculus, and the right and left inferior longitudinal fasciculus. Increased FA in the preterm group was generally associated with decreased radial diffusivity. These findings indicate that prematurity-related white matter differences in later childhood and adolescence do not affect all tracts in the periventricular zone and can involve both decreased and increased FA. Differences in the patterns of radial diffusivity and axial diffusivity suggest that the tissue properties underlying group FA differences may vary within and across white matter tracts. Distinctive diffusion properties may relate to variations in the timing of injury in the neonatal period, extent of white matter dysmaturity and/or compensatory processes in childhood. PMID:26560745
Caravale, B; Tozzi, C; Albino, G; Vicari, S
Background: Major neurological handicaps and neuropsychological disturbances are more common in ex-preterm children than their counterparts born at term. Objective: To establish in a prospective study whether a characteristic neuropsychological profile exists in ex-preterm children who do not exhibit neurodevelopmental deficits on routine clinical examination. Methods: Thirty intellectually normal children born preterm (30–34 weeks gestation) without major neurological disabilities and a control group of term children matched for age, sex, and parental educational and occupational status were assessed at 3–4 years of age to obtain a complete neuropsychological profile. Intellectual ability, language comprehension and expression, perceptual and visual motor function, working memory, and attention and behavioural problems were investigated. Results: Even in the absence of major neurological signs, children born preterm achieved lower mean scores than controls on the Stanford-Binet intelligence scale (110.8 v 121, p<0.001), visual perception test (33.8 v 42.7, p<0.001), visual motor integration test (42.6 v 47.4, p = 0.049), memory for location test (8.4 v 9.5, p = 0.007), sustained attention test (41.6 v 51.5, p = 0.009), and the picture vocabulary test (33.3 v 44.7, p = 0.021). Conclusions: Neuropsychological abnormalities can be detected early in childhood in apparently normal ex-preterm children and are consistent with a growing body of evidence that prematurity may be associated with long term neuropsychological morbidity in childhood and adolescence. PMID:15956096
Kesler, Shelli R; Vohr, Betty; Schneider, Karen C; Katz, Karol H; Makuch, Robert W; Reiss, Allan L; Ment, Laura R
Preterm birth often results in significant learning disability, and previous magnetic resonance imaging (MRI) studies of preterm children have demonstrated reduction in overall cortical tissue with particular vulnerability in the temporal lobe. We measured cortical gyrification in 73 preterm and 33 term control children at 8 years of age and correlated these findings with tests of language ability to determine the associations among preterm birth, neurodevelopment and functional outcome. Preterm children demonstrated significantly increased bilateral temporal lobe gyrification index compared to term controls. Left temporal gyrification index was significantly negatively correlated with left temporal lobe gray matter volume as well as reading recognition scores in the preterm group. Cortical development in the temporal lobe appears to be differentially vulnerable to preterm birth.
Sifringer, Marco; van de Looij, Yohan; Herz, Josephine; Sizonenko, Stéphane V.; Kempe, Karina; Palasz, Joanna; Hadamitzky, Martin; Fandrey, Joachim
Cerebral white and grey matter injury is the leading cause of an adverse neurodevelopmental outcome in prematurely born infants. High oxygen concentrations have been shown to contribute to the pathogenesis of neonatal brain damage. Here, we focused on motor-cognitive outcome up to the adolescent and adult age in an experimental model of preterm brain injury. In search of the putative mechanisms of action we evaluated oligodendrocyte degeneration, myelination, and modulation of synaptic plasticity-related molecules. A single dose of erythropoietin (20,000 IU/kg) at the onset of hyperoxia (24 hours, 80% oxygen) in 6-day-old Wistar rats improved long-lasting neurocognitive development up to the adolescent and adult stage. Analysis of white matter structures revealed a reduction of acute oligodendrocyte degeneration. However, erythropoietin did not influence hypomyelination occurring a few days after injury or long-term microstructural white matter abnormalities detected in adult animals. Erythropoietin administration reverted hyperoxia-induced reduction of neuronal plasticity-related mRNA expression up to four months after injury. Thus, our findings highlight the importance of erythropoietin as a neuroregenerative treatment option in neonatal brain injury, leading to improved memory function in adolescent and adult rats which may be linked to increased neuronal network connectivity. PMID:27493706
Brady, Paul; Jimenez, Julio; Nagatomo, Taro; Deprest, Jan; Toelen, Jaan
The neonatal management of preterm born infants often results in damage to the developing lung and subsequent morbidity, referred to as bronchopulmonary dysplasia (BPD). Animal models may help in understanding the molecular processes involved in this condition and define therapeutic targets. Our goal was to identify molecular pathways using the earlier described preterm rabbit model of hyperoxia induced lung-injury. Transcriptome analysis by mRNA-sequencing was performed on lungs from preterm rabbit pups born at day 28 of gestation (term: 31 days) and kept in hyperoxia (95% O2) for 7 days. Controls were preterm pups kept in normoxia. Transcriptomic data were analyzed using Array Studio and Ingenuity Pathway Analysis (IPA), in order to identify the central molecules responsible for the observed transcriptional changes. We detected 2217 significantly dysregulated transcripts following hyperoxia, of which 90% could be identified. Major pathophysiological dysregulations were found in inflammation, lung development, vascular development and reactive oxygen species (ROS) metabolism. To conclude, amongst the many dysregulated transcripts, major changes were found in the inflammatory, oxidative stress and lung developmental pathways. This information may be used for the generation of new treatment hypotheses for hyperoxia-induced lung injury and BPD. PMID:26317699
Souza, Renato T.; Cecatti, Jose G.; Passini, Renato; Tedesco, Ricardo P.; Lajos, Giuliane J.; Nomura, Marcelo L.; Rehder, Patricia M.; Dias, Tabata Z.; Haddad, Samira M.; Pacagnella, Rodolfo C.; Costa, Maria L.
Background About 15 million children are born under 37 weeks of gestation worldwide. Prematurity is the leading cause of neonatal deaths and short/long term morbidities, entailing consequences not only for the individual, but also their family, health agencies, facilities and all community. The provider-initiated preterm birth is currently one of the most important obstetric conditions related to preterm births, particularly in middle and high income countries, thus decreasing the need for therapeutic preterm birth is essential to reduce global prematurity. Therefore detailed knowledge on the factors associated with provider-initiated preterm birth is essential for the efforts to reduce preterm birth rates and its consequences. In this current analysis we aimed to assess the proportion of provider-initiated (pi-PTB) among preterm births in Brazil and identify associated factors. Methods and Findings This is an analysis of a multicenter cross-sectional study with a nested case-control component called Brazilian Multicenter Study on Preterm Birth (EMIP). EMIP was conducted in 20 referral obstetric hospitals located in the three most populated of the five Brazilian regions. We analysed data of women with pi-PTB, defined as childbirth occurring at less than 37 weeks, medically indicated for maternal/fetal compromise or both; and women with term birth, childbirth at or after 37 weeks. Maternal, sociodemographic, obstetric, prenatal care, delivery, and postnatal characteristics were assessed as possible factors associated with pi-PTB, compared to term births. The overall prevalence of preterm births was 12.3%. Of these, approximately one-third of cases were initiated by the provider. Hypertensive disorders, placental abruption, and diabetes were the main maternal conditions leading to pi-PTB. Caesarean section was the most common mode of delivery. Chronic hypertension (OR 7.47; 95%CI 4.02–13.88), preeclampsia/eclampsia/HELLP syndrome (OR 15.35; 6.57–35.88), multiple
Ulrich, Craig; Quilici, David R.; Schlauch, Karen A.
Molecular mechanisms involved in uterine quiescence during gestation and those responsible for induction of labor at term are incompletely known. More than 10% of babies born worldwide are premature and 1,000,000 die annually. Preterm labor results in preterm delivery in 50% of cases in the United States explaining 75% of fetal morbidity and mortality. There is no Food and Drug Administration-approved treatment to prevent preterm delivery. Nitric oxide-mediated relaxation of human uterine smooth muscle is independent of global elevation of cGMP following activation of soluble guanylyl cyclase. S-nitrosation is a likely mechanism to explain cGMP-independent relaxation to nitric oxide and may reveal S-nitrosated proteins as new therapeutic targets for the treatment of preterm labor. Employing S-nitrosoglutathione as an nitric oxide donor, we identified 110 proteins that are S-nitrosated in 1 or more states of human pregnancy. Using area under the curve of extracted ion chromatograms as well as normalized spectral counts to quantify relative expression levels for 62 of these proteins, we show that 26 proteins demonstrate statistically significant S-nitrosation differences in myometrium from spontaneously laboring preterm patients compared with nonlaboring patients. We identified proteins that were up-S-nitrosated as well as proteins that were down-S-nitrosated in preterm laboring tissues. Identification and relative quantification of the S-nitrosoproteome provide a fingerprint of proteins that can form the basis of hypothesis-directed efforts to understand the regulation of uterine contraction-relaxation and the development of new treatment for preterm labor. PMID:23948706
Proietti, Elena; Riedel, Thomas; Fuchs, Oliver; Pramana, Isabelle; Singer, Florian; Schmidt, Anne; Kuehni, Claudia; Latzin, Philipp; Frey, Urs
Compared with term-born infants, preterm infants have increased respiratory morbidity in the first year of life. We investigated whether lung function tests performed near term predict subsequent respiratory morbidity during the first year of life and compared this to standard clinical parameters in preterms. The prospective birth cohort included randomly selected preterm infants with and without bronchopulmonary dysplasia. Lung function (tidal breathing and multiple-breath washout) was measured at 44 weeks post-menstrual age during natural sleep. We assessed respiratory morbidity (wheeze, hospitalisation, inhalation and home oxygen therapy) after 1 year using a standardised questionnaire. We first assessed the association between lung function and subsequent respiratory morbidity. Secondly, we compared the predictive power of standard clinical predictors with and without lung function data. In 166 preterm infants, tidal volume, time to peak tidal expiratory flow/expiratory time ratio and respiratory rate were significantly associated with subsequent wheeze. In comparison with standard clinical predictors, lung function did not improve the prediction of later respiratory morbidity in an individual child. Although associated with later wheeze, noninvasive infant lung function shows large physiological variability and does not add to clinically relevant risk prediction for subsequent respiratory morbidity in an individual preterm.
Particulate matter (PM) has been variably associated with preterm birth (PTB) (gestation <37 weeks), but the role played by specific chemical components of PM has been little studied. We examined the association between ambient PM <2.5 micrometers in aerodynamic diameter (PM2.S) ...
Olson, David M.; Severson, Emily M.; Verstraeten, Barbara S. E.; Ng, Jane W. Y.; McCreary, J. Keiko; Metz, Gerlinde A. S.
Preterm birth is a universal health problem that is one of the largest unmet medical needs contributing to the global burden of disease. Adding to its complexity is that there are no means to predict who is at risk when pregnancy begins or when women will actually deliver. Until these problems are addressed, there will be no interventions to reduce the risk because those who should be treated will not be known. Considerable evidence now exists that chronic life, generational or accumulated stress is a risk factor for preterm delivery in animal models and in women. This wear and tear on the body and mind is called allostatic load. This review explores the evidence that chronic stress contributes to preterm birth and other adverse pregnancy outcomes in animal and human studies. It explores how allostatic load can be used to, firstly, model stress and preterm birth in animal models and, secondly, how it can be used to develop a predictive model to assess relative risk among women in early pregnancy. Once care providers know who is in the highest risk group, interventions can be developed and applied to mitigate their risk. PMID:26694355
Conway, Francine; Magai, Carol; Jones, Samuel; Fiori, Katherine; Gillespie, Michael
This study explores dynamic changes in network size and composition by examining patterns of older adults' social network change over time, that is: types of movements; the reason for the loss of network members; and the relation of movement and composition in concert. This study is a 6-year follow up of changes in the social networks of U.S.-Born…
Thompson, Deanne K; Wood, Stephen J; Doyle, Lex W; Warfield, Simon K; Egan, Gary F; Inder, Terrie E
Hippocampi are asymmetrical in children and adults, where the right hippocampus is larger. To date, no literature has confirmed that hippocampal asymmetry is evident at birth. Furthermore, gender differences have been observed in normal hippocampal asymmetry, but this has not been examined in neonates. Stress, injury, and lower IQ have been associated with alterations to hippocampal asymmetry. These same factors often accompany preterm birth. Therefore, prematurity is possibly associated with altered hippocampal asymmetry. There were three aims of this study: First, we assessed whether hippocampi were asymmetrical at birth, second whether there was a gender effect on hippocampal asymmetry, and third whether the stress of preterm birth altered hippocampal asymmetry. This study utilized volumetric magnetic resonance imaging to compare left and right hippocampal volumes in 32 full-term and 184 preterm infants at term. Full-term infants demonstrated rightward hippocampal asymmetry, as did preterm infants. In the case of preterm infants, hippocampal asymmetry was proportional to total hemispheric asymmetry. This study is the first to demonstrate that the normal pattern of hippocampal asymmetry is present this early in development. We did not find gender differences in hippocampal asymmetry at term. Preterm infants tended to have less asymmetrical hippocampi than full-term infants, a difference which became significant after correcting for hemispheric brain tissue volumes. This study may suggest that hippocampal asymmetry develops in utero and is maintained into adulthood in infants with a normal neurological course.
Westrupp, Elizabeth M.; Mensah, Fiona K.; Giallo, Rebecca; Cooklin, Amanda; Nicholson, Jan M.
Objectives: The majority of children born preterm, with low birth weight, or small for gestational age are born with low-to-moderate risk (LTM), yet most research focuses on the high-risk group. Little is known about whether children with LTM perinatal risk are at greater risk for mental health problems, or what the role of early maternal…
Rougé, Carole; Butel, Marie-José; Piloquet, Hugues; Ferraris, Laurent; Legrand, Arnaud; Vodovar, Michel; Voyer, Marcel; de la Cochetière, Marie-France; Darmaun, Dominique; Rozé, Jean-Christophe
Background Fecal calprotectin has been proposed as a non-invasive marker of intestinal inflammation in inflammatory bowel disease in adults and children. Fecal calprotectin levels have been reported to be much higher in both healthy full-term and preterm infants than in children and adults. Objective To determine the time course of fecal calprotectin (f-calprotectin) excretion in preterm infants from birth until hospital discharge and to identify factors influencing f-calprotectin levels in the first weeks of life, including bacterial establishment in the gut. Methodology F-calprotectin was determined using an ELISA assay in 147 samples obtained prospectively from 47 preterm infants (gestational age, and birth-weight interquartiles 27–29 weeks, and 880–1320 g, respectively) at birth, and at 2-week intervals until hospital discharge. Principal Findings Although median f-calprotectin excretion was 138 µg/g, a wide range of inter- and intra-individual variation in f-calprotectin values (from day 3 to day 78) was observed (86% and 67%, respectively). In multivariate regression analysis, f-calprotectin correlated negatively with ante and per natal antibiotic treatment (p = 0.001), and correlated positively with the volume of enteral feeding (mL/kg/d) (p = 0.009), the need to interrupt enteral feeding (p = 0.001), and prominent gastrointestinal colonization by Clostridium sp (p = 0.019) and Staphylococcus sp (p = 0.047). Conclusion During the first weeks of life, the high f-calprotectin values observed in preterm infants could be linked to the gut bacterial establishment. PMID:20552029
Jonsson, Maria; van Doorn, Jan; van den Berg, Johannes
Difficulties with feeding and eating are more common among pre-term infants compared with full-term infants. The primary objective of this study was to describe parents' perceptions of developmental eating patterns and occurrence of eating difficulties in a group of pre-term infants, compared with a control group. A parent questionnaire was administered for a study group (27 pre-term infants born between 28-33 weeks gestation) and a control group (29 full-term infants born between 38-41 weeks gestation). Parents of the pre-term children reported significantly more problems with early feeding, but only half of them reported that their infants received intervention to aid their feeding development during neonatal care. At 3 years of age the pre-term children weighed significantly less than the full-term children, but their parents were more satisfied with their eating habits and portion sizes than the control group parents. This finding may reflect differing parenting experiences between the two groups rather than an actual difference in eating skills. It suggests that parents of pre- term infants would benefit from practical guidance in supporting their premature infants in developing eating skills. Future studies using objective measures are recommended to verify the findings reported here.
Wirbelauer, Johannes; Thomas, Wolfgang; Rieger, Lorenz; Speer, Christian P
It is unclear if very immature preterm infants who are born small for gestational age (SGA) have similar leukocyte counts as infants who are born appropriate for gestational age (AGA). Our study included 49 preterm infants with a gestational age ≤32 weeks and without exposure to chorioamnionitis and funisitis. Blood cells were counted in the first 2 hours of life. Eighteen SGA preterm infants were compared with 31 AGA preterm infants. Gestational age, sex, rate of caesarean section, and prenatal administration of corticosteroids did not differ between the groups. Median birth weight was 583 g in the SGA group versus 1100 g in the AGA group. Infants in the SGA group had significantly lower counts of leukocytes, total neutrophils, immature neutrophils, lymphocytes, and monocytes. These findings were not affected by maternal preeclampsia. No significant difference for nucleated red blood cell counts was found. Prenatal growth retardation is an independent factor for lower counts of different leukocytes in very immature preterm infants. It is not clear if these low leukocyte counts are associated with a higher risk of neonatal infections or if lower numbers of inflammatory cells protect the lung and brain of very immature SGA infants by reducing inflammatory events postnatally.
Henderson, Jane; Carson, Claire; Redshaw, Maggie
Background Approximately 15 million babies were born preterm worldwide in 2010 and in England in 2014 there were 52 249 preterm births. Preterm babies are at increased risk of poor outcomes and this can put enormous strain on the family. Objective This study aimed to test the hypothesis that giving birth preterm affects maternal health, mood and well-being, and alters women's feelings and perceptions about their baby. Methods Data collected in a population-based survey of maternity care in England in 2014 were used. Women were randomly selected and asked about their pregnancy, birth and postnatal experience when their babies were about 3 months of age. Descriptive statistics were produced, and logistic regression used to estimate ORs, adjusted for key confounders. Main outcome measures—Women's self-reported postnatal health, Edinburgh Postnatal Depression Scale, women's perceptions of their baby. Results 4578 women returned completed questionnaires. Of these, 42 (0.9%) had babies born before 32 weeks' gestation and 243 (5.5%) at 32–36 weeks. Comparing the three gestational age groups, no statistically significant differences in rates of depressive symptoms measured on the Edinburgh Postnatal Depression Scale were found. However, using a health problems checklist, anxiety, fatigue and flash-backs were more common in mothers of preterm babies. Overall, mothers of preterm babies had less early contact with their baby, more postnatal health problems, substantially less positive feelings towards their baby and made less use of the support options available. Conclusions Women with preterm births are at increased risk of ill-health and negative feelings about their baby in the early months after birth. They make less use of postnatal services and support than other women and this may be an area where the use of specialist services would be appropriate. PMID:27855105
Majhi, P; Bagga, R; Kalra, J; Sharma, M
In a prospective, randomised trial, 100 pregnant women with >/= one prior spontaneous pre-term birth were randomised into two groups. Group 1 women received 100 mg natural micronised progesterone intravaginally once daily from 20-24 weeks' gestation until 36 weeks. Group 2 women did not receive progesterone. Both groups were regularly supervised until delivery. Pre-term birth (<37 and <34 weeks) and other maternal, neonatal outcomes were primary and secondary outcomes, respectively. Chi-square test and Fisher exact test were used to compare categorical variables. Independent sample t-test and one-way ANOVA were used to compare continuous variables and multiple comparisons, respectively. Pre-term births <37 weeks were significantly lower in Group 1 (12% vs 38%, p = 0.002), but pre-term births <34 weeks were similar. The mean birth weight of neonates born to women in Group 1 was significantly higher (2800 vs 2,500 g, p = 0.023). We concluded intravaginal administration of 100 mg of natural micronised progesterone significantly reduced the incidence of pre-term birth <37 weeks in women with > or = one prior pre-term birth. Future research is warranted to assess the long-term safety and efficacy of progesterone.
Franco, Kátia Maria Dmytraczenko; Line, Sérgio Roberto Peres; de Moura-Ribeiro, Maria Valeriana Leme
This study investigated possible prenatal and neonatal variables that may influence the prevalence of tooth enamel hypoplasia in preterm and low birth weight children (LBW) and a matched control group of term children with normal birth weight (NBW). The study sample consisted of 61 children born preterm and with LBW examined at 18-34 months of age. The control group was formed by 61 infants born full term and with NBW examined at 31-35 months of age. All children were born at the Center of Integrated Attention of Women's Health (CAISM-UNICAMP). FDI criteria were followed for dental examination. Medical data was collected retrospectively from hospital records. Among preterms, 57.4% had some type of developmental defects of enamel (DDE), 52.5 % had opacities and 21.3 % presented hypoplasia. Among full-term children, 24.6% presented DDE, 24.6% had opacities and 3.3% had hypoplasia. LBW preterm infants presented a higher prevalence of hypoplasia than NBW controls. The deciduous teeth most affected by hypoplasia were maxillary incisors. There was no significant association with prenatal variables; among neonatal variables there was a significant association with respiratory distress syndrome and neurological examination at discharge with an altered result. PMID:19089191
Romero, Roberto; Dey, Sudhansu K; Fisher, Susan J
Preterm birth is associated with 5 to 18% of pregnancies and is a leading cause of infant morbidity and mortality. Spontaneous preterm labor, a syndrome caused by multiple pathologic processes, leads to 70% of preterm births. The prevention and the treatment of preterm labor have been long-standing challenges. We summarize the current understanding of the mechanisms of disease implicated in this condition and review advances relevant to intra-amniotic infection, decidual senescence, and breakdown of maternal-fetal tolerance. The success of progestogen treatment to prevent preterm birth in a subset of patients at risk is a cause for optimism. Solving the mystery of preterm labor, which compromises the health of future generations, is a formidable scientific challenge worthy of investment.
This report refers to preterm birth in Ancient Greece based on mythological, historical and archeological data. The two antique goddesses, patronesses of labor and birth, Artemis and Eileithyia, cared for full-term, as well as preterm infants, among them for the mythological preterms Dionysos and Eurystheus. The former was rapidly transported by Hermes and received special care by the nymphs Hyades in a mountain cave with "incubator" properties. Historical data are related to the nine months duration of a normal pregnancy, to the definition of "Elitomina" (preterms), the lower limit of viability, the causes for preterm birth, the existence of small for gestational age infants and relevant causes, the physical examination of neonates and postpartum care. Lastly, excavations in Athens and Astypalaia discovered burials - in wells or pots - of preterm infants with gestational age 24-37 weeks.
Hamson, D K; Wainwright, S R; Taylor, J R; Jones, B A; Watson, N V; Galea, L A M
Gonadal steroids are potent regulators of adult neurogenesis. We previously reported that androgens, such as testosterone (T) and dihydrotestosterone (DHT), but not estradiol, increased the survival of new neurons in the dentate gyrus of the male rat. These results suggest androgens regulate hippocampal neurogenesis via the androgen receptor (AR). To test this supposition, we examined the role of ARs in hippocampal neurogenesis using 2 different approaches. In experiment 1, we examined neurogenesis in male rats insensitive to androgens due to a naturally occurring mutation in the gene encoding the AR (termed testicular feminization mutation) compared with wild-type males. In experiment 2, we injected the AR antagonist, flutamide, into castrated male rats and compared neurogenesis levels in the dentate gyrus of DHT and oil-treated controls. In experiment 1, chronic T increased hippocampal neurogenesis in wild-type males but not in androgen-insensitive testicular feminization mutation males. In experiment 2, DHT increased hippocampal neurogenesis via cell survival, an effect that was blocked by concurrent treatment with flutamide. DHT, however, did not affect cell proliferation. Interestingly, cells expressing doublecortin, a marker of immature neurons, did not colabel with ARs in the dentate gyrus, but ARs were robustly expressed in other regions of the hippocampus. Together these studies provide complementary evidence that androgens regulate adult neurogenesis in the hippocampus via the AR but at a site other than the dentate gyrus. Understanding where in the brain androgens act to increase the survival of new neurons in the adult brain may have implications for neurodegenerative disorders.
Wyatt, Laura C; Trinh-Shevrin, Chau; Islam, Nadia S; Kwon, Simona C
Although the New York City Chinese population aged ≥ 65 years increased by 50% between 2000 and 2010, the health needs of this population are poorly understood. Approximately 3,001 Chinese individuals from high-density Asian American New York City areas were included in the REACH U.S. Risk Factor Survey; 805 (26.8%) were aged ≥ 65 years and foreign-born. Four health-related quality of life and three behavioral risk factor outcome variables were examined. Descriptive statistics were conducted by gender, and logistic regression models assessed sociodemographic and health factors associated with each outcome. Few women were current smokers (1.3% vs. 14.8% of men), 19% of respondents ate fruits and vegetables more than or equal to five times daily, and one-third of individuals received sufficient weekly physical activity. Days of poor health were similar to the national population aged ≥ 65 years, while self-reported fair or poor health was much greater among our Chinese sample; over 60% of respondents rated their health as fair or poor. Lower education and lower obesity were significantly associated with cigarette smoking among men, and older age was significantly associated with insufficient physical activity overall. Female gender was significantly associated with all poor health days; older age was significantly associated with poor days of physical health, and lower income was significantly associated with poor days of physical health and fair or poor self-reported health. This study provides important health-related information on a rapidly growing older population and highlights future research areas to inform culturally appropriate health promotion and disease prevention strategies and policies within community-based settings.
Gürakan, Berkan; Kayiran, Petek; Oztürk, Nilüfer; Kayiran, Sinan Mahir; Dindar, Aygün
While new pharmacological approaches have been demonstrated to effectively manage PH in adults, few reports have addressed PH treatment in neonates and infants. This case report describes the successful management of severe PH secondary to bronchopulmonary dysplasia, respiratory syncytial virus infection, and hypoxia in a preterm 4-month-old with the long-term use of orally administered sildenafil and inhaled iloprost.
Jering, Karola; Aschner, Michael; Beller, Amy; Hamm, Ellyn L.; Langdon, Margaret; Maitre, Nathalie L.
Perinatal mercury exposure has neurodevelopmental consequences, which may be worse in preterm infants. In our cohort (N=60), maternal and infant prenatal exposures were low, but infant levels increased during hospitalization and correlated only with duration of parenteral nutrition. A non-negligible exposure resulted from the nutrition preparation on equipment shared with adult preparations. PMID:25812777
Nagel, Christina; Aurich, Jörg; Trenk, Lisa; Ille, Natascha; Drillich, Marc; Pohl, Werner; Aurich, Christine
This study tested the hypothesis of gestational age affecting fetal cardiac activity and the stress response at birth. Heart rate (HR), heart rate variability variables, SD of the beat-to-beat interval and root mean square of successive beat-to-beat differences, and postnatal salivary cortisol concentration were studied in calves born at term (Term, n = 7, gestation length 286.3 ± 2.1 days) or after induction of parturition (Preterm, n = 7, gestation length 279.6 ± 0.2 days). Observation periods covered the last month of gestation (phase A), the last hours before birth including the first stage of labor (phase B), and the neonatal period (phase C). Fetal HR decreased in phase A (P < 0.001) and did not differ between groups. During phase B, HR increased (P < 0.05) and was higher in Preterm than in Term calves in phases B (P < 0.05) and C (P < 0.01). In Term calves, heart rate variability increased from Day 6 until birth (P < 0.05). At birth, SD of the beat-to-beat interval was higher in Term than in Preterm calves (P < 0.01). On Day 1 after birth (phase C), HR accelerations were more frequent in Term than Preterm calves (P < 0.01), whereas decelerations were more frequent in Preterm calves (P < 0.05). Cortisol concentration increased postnatally (P < 0.001) and was correlated with gestation length (r ≥ 0.68, P < 0.01). Because of a certain degree of immaturity, the ability to cope with the stress of birth may be impaired in calves born 1 week before term.
DeVincenzo, John P; Ambrose, Christopher S; Makari, Doris; Weiner, Leonard B
In July 2014, the Committee on Infectious Diseases (COID) updated their guidance on the use of palivizumab, recommending against use in preterm infants 29 to 35 weeks' gestational age (wGA). A primary data source cited to support this significant change was the low respiratory syncytial virus (RSV) hospitalization rate observed in the subpopulation of preterm (<37 wGA) infants evaluated from 2000 to 2005 through the New Vaccine Surveillance Network (NVSN). Here we critically appraise the preterm infant data from the NVSN in the context of data regarding the use of palivizumab in this same time period. Data from the NVSN, an analysis of Florida Medicaid data, and a national survey of US in-hospital palivizumab administration demonstrated that during 2001 to 2007, palivizumab was administered to 59% to 83% of preterm infants born at <32 wGA and 21% to 27% of all preterm infants (<37 wGA). When the NVSN data regarding incidence of RSV hospitalization in preterm infant subgroups were evaluated as a function of chronologic age, preterm infants <32 wGA showed a paradoxical increase in RSV hospitalization with older age, with the highest risk of RSV hospitalization occurring at 18 to 23 months of age. This pattern is most consistent with a reduction in RSV hospitalizations in <32 wGA infants in the first 12 to 18 months of life due to high palivizumab use at these young ages. The NVSN data were not designed to and cannot accurately describe RSV disease burden in preterm infants given the small size of the analyzed subpopulation and the high use of palivizumab during the study period.
Nguyen, Duc Ninh; Fuglsang, Eva; Jiang, Pingping; Birck, Malene M; Pan, Xiaoyu; Kamal, Shamrulazhar B S; Pors, Susanne E; Gammelgaard, Pernille L; Nielsen, Dennis S; Thymann, Thomas; Levy, Ofer; Frøkiær, Hanne; Sangild, Per T
Immature immunity may predispose preterm neonates to infections and necrotizing enterocolitis (NEC). Intravenous antibiotics are frequently given to prevent and treat sepsis, while oral antibiotics are seldom used. We hypothesized that oral antibiotics promote maturation of systemic immunity and delay gut bacterial colonization and thereby protect preterm neonates against both NEC and bacteremia in the immediate postnatal period. Preterm pigs were given formula and administered saline (CON) or broad-spectrum antibiotics orally (ORA) or systemically (SYS) for 5 d after birth. Temporal changes in blood parameters and bacterial composition in the intestine, blood and immune organs were analyzed. Newborn preterm pigs had few blood neutrophils and a high frequency of progenitor cells. Neutrophils gradually matured after preterm birth with increasing CD14 and decreasing CD172a expressions. Preterm neutrophil and monocyte TLR2 expression and TLR2-mediated blood cytokine responses were low relative to adults. ORA pigs showed enhanced blood neutrophil maturation with reduced cell size and CD172a expression. Only ORA pigs, but not SYS pigs, were protected from a high density of gut Gram-positive bacteria, high gut permeability, Gram-positive bacteremia and NEC. Neonatal oral antibiotics may benefit mucosal and systemic immunity via delayed gut colonization and enhanced blood neutrophil maturation just after preterm birth.
Husk, Jesse S; Keim, Sarah A
Among infants born at term, breastfeeding is associated with increased dietary variety in childhood. Preterm birth can limit early feeding options while simultaneously increasing risk for negative health outcomes that could benefit from dietary-based preventative measures. We assessed whether breastfeeding is associated with increased dietary variety at 1-3 years amongst children born preterm. We analyzed baseline data from two clinical trials investigating cognitive development after fatty-acid supplementation for 10-39 month-old children born before 35 weeks gestation (n = 189). At baseline, mothers reported breastfeeding history and completed a 161-item food-frequency questionnaire for their child. Dietary variety was assessed via 3 measures: (1) proportion items consumed at least once per month, (2) servings of a given item consumed relative to total monthly food servings, (3) daily probability of consuming a given item. Overall, 88% of children were ever breastfed (median duration = 89 days, range = 0-539), and 48% of children were ever exclusively breastfed (median duration = 59 days, range = 3-240). Exclusive breastfeeding duration was associated with dietary variety increases of 0.9% (95% CI = 0.1-1.7) for vegetables, 1.6% (95% CI = 0.2-3.0) for meat/fish, and 1.3% (95% CI = 0.2-2.4) for grain/starch, for each additional month of exclusive breastfeeding after adjustment for key confounders. Correspondingly, the variety of sweets consumed decreased by 1.2% (CI: -2.1, -0.3) per month of any breastfeeding after adjustment. These results are consistent with those in children born at term, and if causal, could provide additional support for exclusive breastfeeding to improve diet and health in children born preterm.
Flacking, Renée; Hellström-Westas, Lena
Objective There are indications that the prevalence of exclusively breastfed preterm infants is decreasing in Sweden. The objective was to investigate trends in exclusive breast feeding at discharge from Swedish neonatal units and associated factors in preterm infants. Design, setting and participants This is a register study with data from the Swedish Neonatal Quality Register. Data from 29 445 preterm infants (gestational age (GA) <37 weeks) who were born during the period 2004–2013 were retrieved. Data included maternal, perinatal and neonatal characteristics. Data were analysed for the whole population as well as for 3 GA groups. Results From 2004 to 2013, the prevalence of exclusive breast feeding decreased, in extremely preterm (GA 22–27 weeks) from 55% to 16%, in very preterm (GA 28–31 weeks) from 41% to 34% and in moderately preterm infants (GA 32–36 weeks) from 64% to 49%. The decline was statistically significant (p<0.001) in all 3 GA groups. This decline remained significant when adjustments were made for factors negatively associated with exclusive breast feeding and which became more prevalent during the study period, that is, small for GA (all groups) and maternal mental illness (very preterm and moderately preterm infants). Conclusions In the past 10 years, Sweden has experienced a lower rate of exclusive breast feeding in preterm infants, especially in extremely preterm infants. The factors analysed in this study explain only a small proportion of this decline. The decline in exclusive breast feeding at discharge from neonatal units raises concern and present challenges to the units to support and promote breast feeding. PMID:27965252
Reynolds, Eric W; Vice, Frank L; Bosma, James F; Gewolb, Ira H
The objective of this study was to develop a method to use digital signal processing (DSP) technology to describe quantitatively and statistically swallow-associated sounds in preterm infants and to use this method to analyze changes as infants mature. Twelve recordings of accelerometric and physiological data on bottle-feeding preterm infants between 32 and 39 weeks' postmenstrual age (PMA) were analyzed. Cervical auscultation was performed using an accelerometer attached over the larynx. Acoustic data were recorded and graphically displayed using DSP software. Initial discrete sounds (IDSs) were identified and used to construct an average waveform from which a 'variance index' (VI) was calculated for each infant. The shape of the IDS waveforms became progressively more uniform with advancing PMA, as indicated by a significant inverse correlation between VI and PMA (r=0.739; p=0.006). DSP technology facilitated the development of a new method to quantitatively analyze feeding in preterm infants. This method provides an elegant tool to track maturation of infant feeding and assessing feeding readiness. This technique makes the interpretation of cervical auscultation data less subjective by replacing the verbal description of the sounds of feeding with quantitative numeric values. It is anticipated that this method can be automated to facilitate further the analysis of cervical accelerometry data.
Aarnoudse-Moens, Cornelieke Sandrine Hanan; Weisglas-Kuperus, Nynke; Duivenvoorden, Hugo Joseph; van Goudoever, Johannes Bernard; Oosterlaan, Jaap
Objective of this study was to examine the impact of executive function (EF) on mathematical and attention problems in very preterm (gestational age ≤ 30 weeks) children. Participants were 200 very preterm (mean age 8.2 ± 2.5 years) and 230 term children (mean age 8.3 ± 2.3 years) without severe disabilities, born between 1996 and 2004. EFs assessed included verbal fluency, verbal working memory, visuospatial span, planning, and impulse control. Mathematics was assessed with the Dutch Pupil Monitoring System and parents and teachers rated attention problems using standardized behavior questionnaires. The impact of EF was calculated over and above processing speed indices and IQ. Interactions with group (very preterm versus term birth status) were examined. Analyses were conducted separately for two subsamples: children in preschool and children in primary school. Very preterm children performed poorer on tests for mathematics and had more parent and teacher rated attention problems than term controls (ß(s)>.11, P(s)<.01). IQ contributed unique variance to mathematics in preschool and in primary school (ß(s)>.16, P(s)<.007). A significant interaction of group with IQ (ß = -. 24, P = .02) showed that IQ contributed unique variance to attention problems as rated by teachers, but that effects were stronger for very preterm than for term infants. Over and above IQ, EF contributed unique variance to mathematics in primary school (ß = .13, P<.001), to parent rated inattention in preschool and in primary school (ß(s)>-.16, P(s)<.04), and to teacher rated inattention in primary school (ß = -.19; ß = .19, P(s)<.009). In conclusion, impaired EF is, over and above impaired IQ, an important predictor for poor mathematics and attention problems following very preterm birth.
Caughey, Aaron B.; Zupancic, John A. F.; Greenberg, James M.; Garfield, Susan S.; Thung, Stephen F.; Iams, Jay D.
Objective The objective of this study was to evaluate the potential impact to the U.S. health care system by adopting a novel test that identifies women at risk for spontaneous preterm birth. Methods A decision-analytic model was developed to assess clinical and cost outcomes over a 1-year period. The use of a prognostic test to predict spontaneous preterm birth in a hypothetical population of women reflective of the U.S. population (predictive arm) was compared with the current baseline rate of spontaneous preterm birth and associated infant morbidity and mortality (baseline care arm). Results In a population of 3,528,593 births, our model predicts a 23.5% reduction in infant mortality (8,300 vs. 6,343 deaths) with use of the novel test. The rate of acute conditions at birth decreased from 11.2 to 8.1%; similarly, the rate of developmental disabilities decreased from 13.2 to 11.5%. The rate of spontaneous preterm birth decreased from 9.8 to 9.1%, a reduction of 23,430 preterm births. Direct medical costs savings was $511.7M (− 2.1%) in the first year of life. Discussion The use of a prognostic test for reducing spontaneous preterm birth is a dominant strategy that could reduce costs and improve outcomes. More research is needed once such a test is available to determine if these results are borne out upon real-world use. PMID:27917307
Giarraputo, James; DeLoach, Jordan; Padbury, James; Uzun, Alper; Marsit, Carmen; Hawes, Katheleen; Lester, Barry
Background: Although there are no accepted “normal” levels of circulating cortisol in preterm infants, critically ill preterm infants show lower cortisol levels than healthy preterm infants. The regulation of cortisol reactivity by epigenetic changes in glucocorticoid receptor gene (NR3C1) expression has been demonstrated. This study aims to examine the relationship between medical morbidities in preterm infants and DNA methylation of NR3C1. Methods: Pyrosequencing was used to determine DNA methylation in CpG sites 1-4 of promoter region 1F of NR3C1. Cluster analysis placed 67 preterm infants born <1,500 g into groups based on medical morbidities. The DNA methylation pattern was compared across groups. Results: Cluster analysis identified a high medical risk cluster and a low medical risk cluster. A Mann-Whitney U-test showed lower methylation at CpG1 for infants in the high-risk group (M = 0.336, SE = 0.084) than infants in the low-risk group (M = 0.617, SE = 0.109, P = 0.032). The false discovery rate was low (q = 0.025). Cohen's D effect size was moderate (0.525). Conclusion: Decreased DNA methylation of CpG1 of NR3C1 in high-risk infants may allow for increased binding of transcription factors involved in the stress response, repair and regulation of NR3C1. This may ensure healthy growth in high-risk preterm infants over increasing cortisol levels. PMID:27653086
Buddington, R K; Sangild, P T; Hance, B; Huang, E Y; Black, D D
Despite clinical research and medical advances, care of the preterm infant remains a clinical challenge, with the immature gastrointestinal (GI) system limiting the types and amounts of nutrients that can be provided enterally to meet energy and nutrient requirements. Progress in understanding the relationship between dietary inputs and the developing GI system after preterm birth has been limited by ethical constraints of using preterm infants as experimental subjects and a lack of relevant animal models. We review development of the GI system of the pig during gestation, the similarities shared with human fetuses, and the responses to dietary stimuli. The GI systems of pigs and humans develop early in gestation, with growth and maturation accelerating during the final weeks prior to birth. As a consequence, deficits in GI digestive capacities are directly related to how early in gestation an infant or pig is delivered, thereby complicating attempts to provide adequate enteral nutrients for growth and development. Pigs differ from humans by being born with low activities of the brush border membrane carbohydrases necessary for hydrolysis of nonlactose carbohydrates. Fetuses of both species have impaired lipid digestion coinciding with lipid malabsorption after preterm birth. Protease activity, although present, may not be adequate and may limit growth potential. Undigested enteral inputs are available to the resident bacteria and the production of metabolites can influence health and nutrition. The preterm pig represents a relevant and translational animal model for understanding GI development and for identifying diet and regulatory factors that stimulate GI growth and maturation after preterm birth and thereby accelerate the transition from parenteral nutrition to full enteral nutrition.
Geldof, C J A; van Wassenaer, A G; de Kieviet, J F; Kok, J H; Oosterlaan, J
A range of neurobehavioral impairments, including impaired visual perception and visual-motor integration, are found in very preterm born children, but reported findings show great variability. We aimed to aggregate the existing literature using meta-analysis, in order to provide robust estimates of the effect of very preterm birth on visual perceptive and visual-motor integration abilities. Very preterm born children showed deficits in visual-spatial abilities (medium to large effect sizes) but not in visual closure perception. Tests reporting broad visual perceptive indices showed inconclusive results. In addition, impaired visual-motor integration was found (medium effect size), particularly in boys compared to girls. The observed visual-spatial and visual-motor integration deficits may arise from affected occipital-parietal-frontal neural circuitries.
Neu, Madalynn; Robinson, JoAnn; Schmiege, Sarah J.
Purpose The purpose of this randomized, controlled trial was to determine if nurse supported kangaroo holding of healthy preterm infants in the first eight weeks of the infant's life facilitates early behavioral organization and development. Methods We randomized 87 infants born between 32 to 35 weeks gestation and their mothers to one of three holding groups: kangaroo (skin-to-skin between mother's breasts), blanket (held in mother's arms), or control (no holding restrictions). Nurse supported groups (kangaroo and blanket) received 8 weekly visits from a registered nurse who encouraged holding and provided education about infant development. The control group received brief social visits. Mothers recorded time held in a daily diary. The Assessment of Preterm Infant Behavior was administered when infants were 40 to 44 weeks postconceptional age. Results Total holding time averaged four to five hours per day and did not differ among groups. Mothers held kangaroo style an average of 59 minutes per day in the kangaroo group, and 5 and 9 minutes per day in the blanket and control groups respectively (p <.001). Infants in the kangaroo and blanket groups had more optimal scores than the control group in Robust Crying (p = .015) indicating that they could arouse to vigorous crying and calm. Scores, except for Attention and State Regulation, were at least as high as those of full term infants. Clinical Implications When kangaroo holding is compared to blanket holding, both methods may provide equal early behavioral organization and developmental benefit to the infant. PMID:23625100
Greenslade, Sarah; Miller, Jacqueline; Tonkin, Emma; Marshall, Peter; Collins, Carmel T.
Aim: To determine how accurately the daily prescribed feed volume (mL/day) estimates the actual intake of breastfeeding preterm infants and to characterise the volume taken during a breastfeed at differing gestational and postmenstrual ages. Methods: A cross sectional study was conducted on preterm infants born <37 weeks gestation from two Australian neonatal units. To determine the volume taken in a 24-h period infants were weighed before and after each breastfeed. This volume was added to the charted intake to determine the total intake and then compared to the prescribed feed volume. Bland Altman analyses were used to assess the level of agreement between the two methods. Results: Fifty six infants were studied on 206 breastfeeding occasions. There was a small bias (27 mLs/day) but large 95% limits of agreement (–76 to 130 mL/day). The volume taken during a single breastfeed ranged from 0 to 101 mL (median 23 mL, IQR 9 to 31 mL) and was greater in more mature infants. Conclusions: Using the prescribed feed volume to estimate total intake has limited clinical utility for the individual infant, however the relatively small bias means that it may be useful within a population or for comparison between groups in which population means are compared. There was a large variation in volume taken during a breastfeed across all gestational and postmenstrual ages. PMID:26006120
Hirtz, Deborah G.; Weiner, Steven J.; Bulas, Dorothy; DiPietro, Michael; Seibert, Joanna; Rouse, Dwight J.; Mercer, Brian M.; Varner, Michael W.; Reddy, Uma M.; Iams, Jay D.; Wapner, Ronald J.; Sorokin, Yoram; Thorp, John M.; Ramin, Susan M.; Malone, Fergal D.; Carpenter, Marshall W.; O’Sullivan, Mary J.; Peaceman, Alan M.; Hankins, Gary D. V.; Dudley, Donald; Caritis, Steve N.
Objective To evaluate the relationship of maternal antenatal magnesium sulfate (MgSO4) with neonatal cranial ultrasound abnormalities and cerebral palsy (CP). Study design In a randomized trial of MgSO4 or placebo in women at high risk of preterm delivery, up to three cranial ultrasound were obtained in the neonatal period. Images were reviewed by at least two pediatric radiologists masked to treatment and other clinical conditions. Diagnoses were predefined for intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), intracerebral echolucency or echodensity, and ventriculomegaly. CP was diagnosed at two years by standardized neurological examination. Results Intraventricular hemorrhage, PVL, intracerebral echolucency or echodensity, and ventriculomegaly were all strongly associated with an increased risk of CP. MgSO4 administration did not affect the risk of cranial ultrasound abnormality observed at 35 weeks post-menstrual age or later. However, for the 82% of infants born at <32 weeks gestation, MgSO4 was associated with a reduction in risk of echolucency or echodensity. The reduction in risk for echolucency explained 21% of the effect of MgSO4 on CP (p=0.04), and for echodensity explained 20% of the effect (p=0.02). Conclusions MgSO4 given prior to preterm delivery was associated with decreased risk of developing echodensities and echolucencies at <32 weeks gestation. However, this effect can only partially explain the effect of MgSO4 on CP at two years of age. PMID:26254839
Ball, Gareth; Srinivasan, Latha; Aljabar, Paul; Counsell, Serena J; Durighel, Giuliana; Hajnal, Joseph V; Rutherford, Mary A; Edwards, A David
Cortical maturation was studied in 65 infants between 27 and 46 wk postconception using structural and diffusion magnetic resonance imaging. Alterations in neural structure and complexity were inferred from changes in mean diffusivity and fractional anisotropy, analyzed by sampling regions of interest and also by a unique whole-cortex mapping approach. Mean diffusivity was higher in gyri than sulci and in frontal compared with occipital lobes, decreasing consistently throughout the study period. Fractional anisotropy declined until 38 wk, with initial values and rates of change higher in gyri, frontal and temporal poles, and parietal cortex; and lower in sulcal, perirolandic, and medial occipital cortex. Neuroanatomical studies and experimental diffusion-anatomic correlations strongly suggested the interpretation that cellular and synaptic complexity and density increased steadily throughout the period, whereas elongation and branching of dendrites orthogonal to cortical columns was later and faster in higher-order association cortex, proceeding rapidly before becoming undetectable after 38 wk. The rate of microstructural maturation correlated locally with cortical growth, and predicted higher neurodevelopmental test scores at 2 y of age. Cortical microstructural development was reduced in a dose-dependent fashion by longer premature exposure to the extrauterine environment, and preterm infants at term-corrected age possessed less mature cortex than term-born infants. The results are compatible with predictions of the tension theory of cortical growth and show that rapidly developing cortical microstructure is vulnerable to the effects of premature birth, suggesting a mechanism for the adverse effects of preterm delivery on cognitive function.
Urquia, Marcelo Luis; Frank, John William; Moineddin, Rahim; Glazier, Richard Henry
Immigrants' health is jointly influenced by their pre- and post-migration exposures, but how these two influences operate with increasing duration of residence has not been well-researched. We aimed to examine how the influence of maternal country of birth and neighborhood deprivation effects, if any, change over time since migration and how neighborhood effects among immigrants compare with those observed in the Canadian-born population. Birth data from Ontario hospital records (2002-2007) were linked with an official Canadian immigration database (1985-2000). The outcome measure was preterm birth. Neighborhoods were ranked according to a neighborhood deprivation index developed for Canadian urban areas and collapsed into tertiles of approximately equal size. Time since immigration was measured from the date of arrival to Canada to the date of delivery, ranging from 1 to 22 years. We used cross-classified random effect models to simultaneously account for the membership of births (N = 83,233) to urban neighborhoods (N = 1,801) and maternal countries of birth (N = 168). There were no differences in preterm birth between neighborhood deprivation tertiles among immigrants with less than 15 years of residence. Among immigrants with 15 years of stay or more, the adjusted absolute risk difference (ARD%, 95% confidence interval) between high-deprived (tertile 3) and low-deprived (tertile 1) neighborhoods was 1.86 (0.68, 2.98), while the ARD% observed among the Canadian-born (N = 314,237) was 1.34 (1.11, 1.57). Time since migration modifies the neighborhood deprivation gradient in preterm birth among immigrants living in Ontario cities. Immigrants reached the level of inequalities in preterm birth observed at the neighborhood level among the Canadian-born after 14 years of stay, but neighborhoods did not influence preterm birth among more recent immigrants, for whom the maternal country of birth was more predictive of preterm birth.
Chabert, René; Guitton, Matthieu J; Amram, Daniel; Uziel, Alain; Pujol, Rémy; Lallemant, Jean-Gabriel; Puel, Jean-Luc
The present study was designed to investigate the early maturation of the brainstem regulation of the cochlear function in preterm neonates. Evoked otoacoustic emissions (EOAE) and their regulation via the medial olivocochlear efferent (MOC) reflex were investigated in a large population of preterm neonates and compared with full-term neonates and young babies from birth to 4 y and school-aged children. In 28-wk preterm neonates, EOAE were seen in the mid-frequency range. These responses extended both to the low (down to 1025 Hz) and high (up to 6152 Hz) frequency ranges at 38 wk of gestational age and remained stable up to 4 mo. At this stage, the amplitude of EOAE overlapped adult values. EOAE amplitudes then decreased to reach adult values at 3 y of age. Maturation of MOC efferents innervating the outer hair cells was investigated by studying the suppressive effect of contralateral sound on the EOAE amplitudes (MOC reflex). The first MOC responses were recorded in preterm neonates of 32-33 wk of gestational age, reaching adult-like values at 37 wk of gestational age. The maximum effect of MOC efferent activation occurred between 2000 and 4000 Hz. These results suggest that, in humans, MOC efferents mature in utero. Thus, testing the MOC reflex may have a clinical relevance to detect an abnormal development of the auditory pathways, particularly of a brainstem circuitry not explored through conventional testing.
Yang, Hong; Einspieler, Christa; Shi, Wei; Marschik, Peter B.; Wang, Yi; Cao, Yun; Li, Hui; Liao, Yuan-Gui; Shao, Xiao-Mei
Background A deviant motor behaviour at age 3 to 5 months is predictive of cerebral palsy (CP). Particular features of the early motor repertoire even proved predictive of the degree of functional limitations as classified on the Gross Motor Function Classification System (GMFCS) in children with CP, born preterm. Aims We aimed to determine whether an association between the early motor repertoire and the GMFCS also holds true for children born at term. Study design Longitudinal study. Subjects 79 infants (60 boys and 19 girls; 47 infants born at term; video recorded for the assessment of movements and posture at age 9 to 20 weeks postterm age) who developed CP. Outcome measures The GMFCS was applied at age 2 to 5 years. Results Motor optimality at age 3 to 5 months showed a significant correlation with functional mobility and activity limitation as classified on the GMFCS at age 2 to 5 years in both children born at term (Spearman rho = − 0.66, p < 0.001) and born preterm (rho = − 0.37, p < 0.05). Infants born preterm were more likely to show normal movement patterns than infants born at term. A normal posture and an abnormal, jerky (yet not monotonous) movement character resulted in better levels of function and mobility. With the exception of one, none of the infants showed fidgety movements. A cramped-synchronised movement character, repetitive opening and closing of the mouth, and abnormal finger postures characterised children who would show a poor self-mobility later. Conclusions Assessing the quality of motor performance at 9 to 20 weeks postterm age (irrespective of the gestational age) improves our ability to predict later functional limitations in children with CP. PMID:22795821
Medoff-Cooper, Barbara; Rankin, Kristin; Li, Zhuoying; Liu, Li; White-Traut, Rosemary
Objective The aim of this RCT was to evaluate sucking organization in premature infants following a preterm infant multi-sensory intervention, the Auditory, Tactile, Visual, and Vestibular (ATVV). Study Design A convenience sample of 183 healthy premature infants born 29 - 34 weeks post-menstrual age (PMA) enrolled. Sucking organization was measured at baseline, then weekly assessments, during the infant's hospital stay. Results A quadratic trend was observed for number of sucks, sucks per burst, and maturity index, with the intervention group increasing significantly faster by day 7 (Model estimates for group*day: β = 13.69, p < 0.01; β = 1.16, p < 0.01; and β = 0.12, p < 0.05, respectively). Sucking pressure increased linearly over time, with significant between-group differences at day 14 (β = 45.66, p < 0.01). Conclusion ATVV infants exhibited improved sucking organization during hospitalization, suggestive that ATVV intervention improves oral feeding. PMID:25822519
Garcia, Kessey M. B.; Davidson, Josy; Goulart, Ana L.; dos Santos, Amelia M. N.
OBJECTIVE: To compare thoracic musculoskeletal static alterations in adolescents born prematurely with those born at term and investigate neonatal and post-neonatal variables associated with thoracic alterations. METHOD: This is a cross-sectional study with 57 adolescents aged 10-15 years born prematurely and 57 adolescents born at term paired by gender and age. Photographs of the head and thorax in the front, back, and right side views were studied using a computer program. The two groups were compared in regards to: elevation of clavicles, elevation of shoulders, protrusion of the head, and anteroposterior and mediolateral thoracic length. Factor associated with thoracic disorders were evaluated by linear regression analysis. RESULTS: The Preterm group had mean gestational age of 32.0±2.8 weeks and the birth weight was 1462±338 and 3342±430 g for the Preterm and Term adolescents, respectively. Preterm adolescents had higher elevation of the left shoulder (22.7±5.4o vs. 20.6±5.3o;sim, p=0.038) and the right shoulder (22.2±4.4o vs. 18.5±5.7o; p<0.001). Smaller protrusion of the head (27.8±6.1o vs. 32.4±7.9o; p=0.008), mediolateral thoracic length (22.9±2.3 cm vs. 25.1±3.1 cm; p<0.001) and anteroposterior thoracic length (19.7±2.2 cm vs. 21.1±3.4 cm; p<0.001) were found in preterm adolescents. By multiple regression analysis, factors associated with higher shoulder elevation were birth weight <1500 g (p<0.001) and mechanical ventilation during neonatal period >5 days (p=0.009). CONCLUSION: Adolescents born prematurely presented greater thoracic musculoskeletal static alterations compared to those born at term. Factors associated with these alterations were: very low birth weight and longer duration of mechanical ventilation in the neonatal unit. PMID:25651130
Stewart, Amanda; Graham, Ernest
Preterm birth is the leading cause of neonatal mortality and a major public health concern. Risk factors for preterm birth include a history of preterm birth, short cervix, infection, short interpregnancy interval, smoking, and African-American race. The use of progesterone therapy to treat mothers at risk for preterm delivery is becoming more…
Saleh, Mohammad I; Nalbant, Demet; Widness, John A; Veng-Pedersen, Peter
A population pharmacokinetics/pharmacodynamic (PK/PD) model was developed to describe changes in erythropoiesis as a function of plasma erythropoietin (EPO) concentration over the first 30 days of life in preterm infants who developed severe anemia requiring red blood cell (RBC) transfusion. Several covariates were tested as possible factors influencing the responsiveness to EPO. Discarded blood samples in 27 ventilated preterm infants born at 24-29 wk of gestation were used to construct plasma EPO, hemoglobin (Hb), and RBC concentration-time profiles. The amount of Hb removed for laboratory testing and that transfused throughout the study period were recorded. A population PK/PD model accounting for the dynamic Hb changes experienced by these infants was simultaneously fitted to plasma EPO, Hb, and RBC concentrations. A covariate analysis suggested that the erythropoietic efficacy of EPO is increased for preterm infants at later gestational ages. The PD analysis showed a sevenfold difference in maximum Hb production rate dependent on gestational age and indicated that preterm infants, when stimulated by EPO, have the capacity to produce additional Hb that may result in a decrease in RBC transfusions. The present model has utility in clinical trial simulations investigating the treatment potential of erythropoietic stimulating agents in the treatment of anemia of prematurity.
Schneider, Nora; Garcia-Rodenas, Clara L.
Adequate nutrition is important for neurodevelopmental outcomes in preterm-born infants. In this review, we aim to summarize the current knowledge on nutritional interventions initiated during the hospital stay targeting brain and cognitive development benefits in preterm human infants. Studies can broadly be split in general dietary intervention studies and studies investigating specific nutrients or nutritional supplements. In general, mother’s breast milk was reported to be better for preterm infants’ neurodevelopment compared to infant formula. The differences in methodologies make it difficult to conclude any effects of interventions with individual nutrients. Only protein and iron level studies showed some consistent findings regarding optimal doses; however, confirmatory studies are needed. This review does not support some widely accepted associations, such as that between long-chain polyunsaturated fatty acid supplementation and visual development. Clear nutritional recommendations cannot be made based on this review. However, the type of infant nutrition (i.e., breast milk versus formula or donor milk), the timing of the nutritional intervention, and the dose of the nutrient/supplement have been found to be relevant factors in determining the success of nutritional intervention studies in preterm infants. PMID:28241501
Feder, Katya P; Majnemer, Annette; Bourbonnais, Daniel; Platt, Robert; Blayney, Marc; Synnes, Anne
Preterm infants are at high risk for developmental impairments at school age. However, the impact of these impairments on important life skills, such as handwriting, is unknown. Forty-eight first-grade children (27 males, 21 females; mean age 6y 7mo, SD 3.9mo; range 6y 1mo to 7y 3mo) born preterm (birthweight < 1250g; gestational age < 34wks), without major physical or cognitive disabilities, were matched to 69 healthy, term control children (32 males, 37 females; mean age 6y 10mo, SD 3.6mo; range 6y 3mo to 7y 4mo) by sex and school class. All children were assessed using the Evaluation Tool of Children's Handwriting-Manuscript and several sensorimotor measures. Preterm children demonstrated significantly lower legibility and slower speed scores (p < 0.01) compared with control children for most of the handwriting tasks. Factors associated with legibility were visual perception and eye-hand coordination (r < 0.50; p < 0.05) and sex (r < 0.12; p = 0.01). In-hand manipulation and finger identification (r < 0.43; p < 0.01) were significantly correlated with slow handwriting speeds. Behaviour difficulties associated with hyperactivity and poor attention (Connors Abbreviated Symptoms Questionnaire) had a confounding influence on both legibility and speed. These findings may help guide early identification efforts and medical/therapeutic interventions for preterm children.
Treyvaud, Karli; Doyle, Lex W.; Lee, Katherine J.; Ure, Alexandra; Inder, Terrie E.; Hunt, Rod W.; Anderson, Peter J.
Parenting influences child development, but it is unclear whether early parenting behavior can influence school-age outcomes in very preterm (VPT) children, and/or if certain groups of VPT children may be more affected by early parenting behavior. These research questions were examined. Participants were 147 children born <30 weeks' gestation…
Drewett, Robert; Blair, Peter; Emmett, Pauline; Emond, Alan
Aims: To examine the relationship between failure to thrive in preterm and term infants and postnatal depression in their mothers. Method: In a whole population birth cohort of 12,391 infants (excluding those born after term or with major congenital abnormalities) failure to thrive over the first nine months was identified using a conditional…
Henderson‐Smart, D J; Hutchinson, J L; Donoghue, D A; Evans, N J; Simpson, J M; Wright, I
Objective To identify prenatal risk factors for chronic lung disease (CLD) at 36 weeks postmenstrual age in very preterm infants. Population Data were collected prospectively as part of the ongoing audit of the Australian and New Zealand Neonatal Network (ANZNN) of all infants born at less than 32 weeks gestation admitted to all tertiary neonatal intensive care units in Australia and New Zealand. Methods Prenatal factors up to 1 minute of age were examined in the subset of infants born at gestational ages 22–31 weeks during 1998–2001, and who survived to 36 weeks postmenstrual age (n = 11 453). Factors that were significantly associated with CLD at 36 weeks were entered into a multivariate logistic regression model. Results After adjustment, low gestational age was the dominant risk factor, with an approximate doubling of the odds with each week of decreasing gestational age from 31 to less than 25 weeks (trend p<0.0001). Birth weight for gestational age also had a dose‐response effect: the lower the birth weight for gestational age, the greater the risk, with infants below the third centile having 5.67 times greater odds of CLD than those between the 25th and 75th centile (trend p<0.0001). There was also a significantly increased risk for male infants (odds ratio 1.51 (95% confidence interval 1.36 to 1.68), p<0.0001). Conclusions These population based data show that the prenatal factors low gestational age, low birth weight for gestational age, and male sex significantly predict the development of chronic respiratory insufficiency in very preterm infants and may assist clinical decision about delivery. PMID:16131530
Luque-Fernandez, Miguel Angel; Ananth, Cande V.; Sanchez, Sixto E.; Qiu, Chun-fang; Hernandez-Diaz, Sonia; Valdimarsdottir, Unnur; Gelaye, Bizu; Williams, Michelle A.
Purpose Data regarding circadian rhythm in the onset of spontaneous preterm premature rupture of membranes (PROM) and placental abruption (PA) cases are conflicting. We modeled the time of onset of preterm PROM and PA cases and examined if the circadian profiles varied based on the gestational age at delivery. Methods We used parametric and nonparametric methods, including trigonometric regression in the framework of generalized linear models, to test the presence of circadian rhythms in the time of onset of preterm PROM and PA cases, among 395 women who delivered a singleton between 2009 and 2010 in Lima, Peru. Results We found a diurnal circadian pattern, with a morning peak at 07h:32’ (95%CI:05h:46’ – 09h:18’) among moderate preterm PROM cases (P-value<0.001), and some evidence of a diurnal circadian periodicity among PA cases in term infants (P-value=0.067). However, we did not find evidence of circadian rhythms in the time of onset of extremely or very preterm PROM (P-value=0.259) and preterm PA (P-value=0.224). Conclusions The circadian rhythms of the time of onset of preterm PROM and PA cases varied based on gestational weeks at delivery. While circadian rhythms were presented among moderate preterm PROM and term PA cases, there was no evidence of circadian rhythms among preterm PA and very or extremely preterm PROM cases, underlying other mechanisms associated with the time of onset. PMID:25453346
Chang, Hannah H.; Larson, Jim; Blencowe, Hannah; Spong, Catherine Y.; Howson, Christopher P.; Cairns-Smith, Sarah; Lackritz, Eve M.; Lee, Shoo K.; Mason, Elizabeth; Serazin, Andrew C.; Walani, Salimah; Simpson, Joe Leigh; Lawn, Joy E.
Summary Background Each year,1.1 million babies die from prematurity, andmany survivors are disabled. Worldwide, 15 million babies are preterm(<37 weeks’ gestation),withtwo decades of increasing ratesinalmost all countries with reliable data. Improved care of babies has reduced mortality in high-income countries, although effective interventions have yet to be scaled-up in most low-income countries. A 50% reduction goal for preterm-specific mortality by 2025 has been set in the “Born Too Soon” report. However, for preterm birth prevention,understanding of drivers and potential impact of preventive interventions is limited. We examine trends and estimate the potential reduction in preterm birthsforvery high human development index (VHHDI) countries if current evidence-based interventions were widely implemented. This analysis is to inform a “Born Too Soon” rate reduction target. Methods Countries were assessed for inclusion based on availability and quality ofpreterm prevalence data (2000-2010), and trend analyses with projections undertaken. We analysed drivers of rate increases in the USA, 1998-2004. For 39 VHHDI countrieswith >10,000 births, country-by-country analyses were performed based on target population, incremental coverage increase,and intervention efficacy. Cost savings were estimated based on reported costs for preterm care in the USAadjusted usingWorld Bank purchasing power parity. Findings From 2010, even if all VHHDI countries achieved annual preterm birth rate reductions of the best performers, (Sweden and Netherlands), 2000-2010 or 2005-2010(Lithuania, Estonia)), rates would experience a relative reduction of<5% by 2015 on average across the 39 countries.Our analysis of preterm birth rise 1998-2004 in USA suggests half the change is unexplained, but important drivers includeinductions/cesareandelivery and ART.For all 39 VHHDI countries, five interventionsmodeling at high coveragepredicted 5%preterm birth rate relative reduction from 9
Segura-Cervantes, Enrique; Mancilla-Ramírez, Javier; González-Canudas, Jorge; Alba, Erika; Santillán-Ballesteros, René; Morales-Barquet, Deneb; Sandoval-Plata, Gabriela
The response of the adaptive immune system is usually less intense in premature neonates than term neonates. The primary objective of this study was to determine whether immunological parameters vary between preterm (PT) neonates (≥32 weeks of gestational age) and very preterm (VPT) neonates (<32 weeks of gestational age). A cross-sectional study was designed to prospectively follow PT and VPT neonates at risk of developing sepsis. Plasma concentrations of IFN-γ, TNF-α, IL-6, IL-4, and IL-10 were detected using flow cytometry. C-reactive protein (C-RP) and the complex SC5b-9 were detected in the plasma using commercial kits. A total of 83 patients were included. The laboratory results and clinical histories showed that 26 patients had sepsis; 14 were VPT, and 12 were PT. The levels of C-RP, SC5b-9 (innate immune response mediators), and IL-10 or IL-4 (anti-inflammatory cytokines) were elevated during sepsis in both groups. IFN-γ, TNF-α, and IL-6 (proinflammatory cytokines) were differentially elevated only in PT neonates. The VPT neonates with sepsis presented increases in C-RP, SC5b-9, and anti-inflammatory cytokines but not in proinflammatory cytokines, whereas PT neonates showed increases in all studied mediators of inflammation. PMID:27293317
Imdad, Aamer; Bhutta, Zulfiqar A
Globally, about 20 million infants are born with low birth weight (LBW; <2500 g). Of all LBW infants, approximately 95% are born in developing countries. The greatest incidence of LBW occurs in South-Central Asia; the second greatest is in Africa. The two main reasons for LBW are preterm birth (<37 weeks) and intrauterine growth restriction (IUGR), which are risk factors for increased morbidity and mortality in newborn infants. Maternal nutrition status is one of the most important risk factors for LBW/IUGR. Providing balanced protein energy and multiple micronutrient supplements to pregnant women will reduce incidence of IUGR. Calcium supplementation during pregnancy will reduce the incidence of pre-eclampsia and preterm birth in developing countries. Exclusive breastfeeding is protective for a mother and her infant and has been shown to reduce morbidity and mortality in infancy. Kangaroo mother care for preterm infants will reduce severe morbidity and mortality as well. Community-based intervention packages are among the most effective methods of reducing morbidity and mortality in mothers and children. Future research should focus on improving triage of preterm and IUGR infants. Exclusive breastfeeding should be promoted, and appropriate alternative food supplements should be provided when breastfeeding is not possible.
Cahill-Rowley, Katelyn; Rose, Jessica
Children born preterm with very-low birth-weight (VLBW) have increased risk of motor impairment. Early identification of impairment guides treatment to improve long-term function. Temporal-spatial gait parameters are an easily-recorded assessment of gross motor function. The objective of this study was to characterize preterm toddlers' gait and its relationship with neurodevelopment. Velocity, cycle time, step width, step length and time asymmetry, %stance, %single-limb support, and %double-limb support were calculated for 81 VLBW preterm and 43 typically-developing (TD) toddlers. Neurodevelopment was assessed with Bayley Scales of Infant Development-3rd Edition (BSID-III) motor composite and gross motor scores. Mean step width (p=.009) was wider in preterm compared to TD toddlers. Preterm toddlers with <85 BSID-III motor composite scores, indicating mild-to-moderate delay, had significantly increased step width, step length asymmetry, and step time compared to TD toddlers. Step time was also significantly longer for lower-scoring compared to higher-scoring (≥85 BSID-III motor composite scores) preterm toddlers, suggesting that step time may be particularly sensitive to gradations of motor performance. Velocity, cycle time, step length asymmetry, %stance, step length, and step time significantly correlated with BSID-III gross motor scores, suggesting that these parameters may be revealing of gross motor function. The differences in gait between lower-scoring preterm toddlers and TD toddlers, together with the correlations between gait and BSID-III motor scores, suggest that temporal-spatial gait parameters may be useful in building a clinically-relevant, easily-conducted assessment of toddler gross motor development.
Namachivayam, Kopperuncholan; Blanco, Cynthia L; Frost, Brandy L; Reeves, Aaron A; Jagadeeswaran, Ramasamy; MohanKumar, Krishnan; Safarulla, Azif; Mandal, Partha; Garzon, Steven A; Raj, J Usha; Maheshwari, Akhil
Human milk contains substantial amounts of transforming growth factor (TGF)-β, particularly the isoform TGF-β2. We previously showed in preclinical models that enterally administered TGF-β2 can protect against necrotizing enterocolitis (NEC), an inflammatory bowel necrosis of premature infants. In this study we hypothesized that premature infants remain at higher risk of NEC than full-term infants, even when they receive their own mother's milk, because preterm human milk contains less bioactive TGF-β than full-term milk. Our objective was to compare TGF-β bioactivity in preterm vs. full-term milk and identify factors that activate milk-borne TGF-β. Mothers who delivered between 23 0/7 and 31 6/7 wk or at ≥37 wk of gestation provided milk samples at serial time points. TGF-β bioactivity and NF-κB signaling were measured using specific reporter cells and in murine intestinal tissue explants. TGF-β1, TGF-β2, TGF-β3, and various TGF-β activators were measured by real-time PCR, enzyme immunoassays, or established enzymatic activity assays. Preterm human milk showed minimal TGF-β bioactivity in the native state but contained a large pool of latent TGF-β. TGF-β2 was the predominant isoform of TGF-β in preterm milk. Using a combination of several in vitro and ex vivo models, we show that neuraminidase is a key regulator of TGF-β bioactivity in human milk. Finally, we show that addition of bacterial neuraminidase to preterm human milk increased TGF-β bioactivity. Preterm milk contains large quantities of TGF-β, but most of it is in an inactive state. Addition of neuraminidase can increase TGF-β bioactivity in preterm milk and enhance its anti-inflammatory effects.
This review is a summary of the most important clinical findings and implications of tick-borne encephalitis (TBE) in children. It is based on a Pubmed search with the terms "tick-borne encephalitis", "children", "infection", "meningitis", "meningoencephalitis", and "outcome". TBE in children shares several features with their adult counterpart but has overall a better prognosis. Nevertheless, TBE is associated with substantial morbidity and mortality in a small group of children and seems to cause cognitive dysfunctions, which needs to be studied in further detail.
Pirozzolo, Jason J; LeMay, Donald C
Blood-borne infections are transmitted by way of direct blood contact from one individual to another from injured skin or a mucous membrane. Blood-borne infections can also be transmitted through blood doping and drug abuse and through sexual contact. Risk factors for hepatitis B virus (HBV) HBV infection include travel to regions with endemic hepatitis. Prevention of blood-borne pathogens in the student-athlete should focus on traditional transmission routes and off-the-field behavior because experts believe that field transmission of blood-borne pathogens is minimal. Worldwide, HBV, hepatitis C virus (HCV), and HIV are the most common pathogens encountered. This article focuses on HBV and HCV as being the most prevalent in athletics.
Conrad, Amy L.; Richman, Lynn; Lindgren, Scott; Nopoulos, Peg; Bell, Edward F.
Objective Preterm infants are frequently transfused with red blood cells based on standardized guidelines or clinical concern that anemia taxes infants’ physiological compensatory mechanisms and thereby threatens their health and well-being. The impact of various transfusion guidelines on long-term neurocognitive outcome is not known. The purpose of this study is to evaluate long-term neurocognitive outcome on children born prematurely and treated at birth with different transfusion guidelines. Methods Neurocognitive outcomes were examined at school age for 56 preterm infants randomly assigned to a liberal (n = 33) or restrictive (n = 23) transfusion strategy. Tests of intelligence, achievement, language, visual-spatial/motor, and memory skills were administered. Between-group differences were assessed. Results Those in the liberal transfusion group performed more poorly than those in the restrictive group on measures of associative verbal fluency, visual memory, and reading. Conclusions Findings highlight possible long-term neurodevelopmental consequences of maintaining higher hematocrit levels. PMID:21360360
Late preterm birth (defined as birth between 34 0/7 to 36 6/7 weeks gestation) and early-term birth (defined as birth between 37 0/7 to 38 6/7 weeks gestation) have become the topic of much recent literature and discussion as the morbidity associated with delivery at these gestational ages becomes evident. Although infants delivered during this time period remain at relatively low risk for complications, the rate of morbidities in this group, particularly as it relates to respiratory function, is increased several-fold when they are compared to infants delivered at 39 weeks. The following article reviews the morbidities and mortality associated with both late preterm and early-term birth, as well available data on long-term outcomes of neonates born at these gestational ages.
Ghotra, Satvinder; Jangaard, Krista; Pambrun, Chantale; Fernandez, Conrad Vincent
Methemoglobinaemia is a rare cause of cyanosis in newborns. Congenital methemoglobinaemias due to M haemoglobin or deficiency of cytochrome b5 reductase are even rarer. We present a case of congenital methemoglobinaemia presenting at birth in a preterm infant. A baby boy born at 29 weeks and 3 days of gestation had persistent central cyanosis immediately after delivery, not attributable to a respiratory or cardiac pathology. Laboratory methemoglobin levels were not diagnostic. Cytochrome b5 reductase levels were normal and a newborn screen was unable to pick up any abnormal variants of fetal haemoglobin. Genetic testing showed a γ globin gene mutation resulting in the M haemoglobin, called Hb F-M-Fort Ripley. The baby had no apparent cyanosis at a corrected gestational age of 42 weeks. Although rare, congenital methaemoglobin aemia should be considered in the differential in a preterm with central cyanosis and investigated with genetic testing for γ globin chain mutations if other laboratory tests are non-conclusive.
Boyd, Heather A; Poulsen, Gry; Wohlfahrt, Jan; Murray, Jeffrey C; Feenstra, Bjarke; Melbye, Mads
Preterm delivery (PTD) is a complex trait with a significant familial component. However, no specific inheritance patterns have been established. The authors examined the contribution of PTDs in both the woman's family and her partner's family to her risk of PTD. The authors linked birth information from Danish national registers with pedigree information from the Danish Family Relations Database for 1,107,124 live singleton deliveries occurring from 1978 to 2004. Risk ratios were estimated comparing women with and without various PTD histories. Women with previous PTDs were at greatly increased risk of recurrent PTD (risk ratio = 5.6, 95% confidence interval: 5.5, 5.8); however, their PTD risk was unaffected by a partner's history of preterm children with other women. PTDs to a woman's mother, full sisters, or maternal half-sisters also increased her PTD risk (risk ratio = 1.6, 95% confidence interval: 1.5, 1.6), whereas PTDs in her paternal half-sisters, the female partners of her male relatives, or members of her partner's family did not affect her PTD risk. Inheritance patterns were similar for all gestational ages from very early through late PTD. The substantial portion of PTD risk explained by effects passed through the female line suggests a role for either imprinting or mitochondrial inheritance.
Williamson, K. E.; Jakobson, L. S.; Saunders, D. R.; Troje, N. F.
Biological motion perception can be assessed using a variety of tasks. In the present study, 8- to 11-year-old children born prematurely at very low birth weight (<1500 g) and matched, full-term controls completed tasks that required the extraction of local motion cues, the ability to perceptually group these cues to extract information about body structure, and the ability to carry out higher order processes required for action recognition and person identification. Preterm children exhibited difficulties in all 4 aspects of biological motion perception. However, intercorrelations between test scores were weak in both full-term and preterm children—a finding that supports the view that these processes are relatively independent. Preterm children also displayed more autistic-like traits than full-term peers. In preterm (but not full-term) children, these traits were negatively correlated with performance in the task requiring structure-from-motion processing, r(30) = −.36, p < .05), but positively correlated with the ability to extract identity, r(30) = .45, p < .05). These findings extend previous reports of vulnerability in systems involved in processing dynamic cues in preterm children and suggest that a core deficit in social perception/cognition may contribute to the development of the social and behavioral difficulties even in members of this population who are functioning within the normal range intellectually. The results could inform the development of screening, diagnostic, and intervention tools. PMID:25103588
Williamson, K E; Jakobson, L S; Saunders, D R; Troje, N F
Biological motion perception can be assessed using a variety of tasks. In the present study, 8- to 11-year-old children born prematurely at very low birth weight (<1500 g) and matched, full-term controls completed tasks that required the extraction of local motion cues, the ability to perceptually group these cues to extract information about body structure, and the ability to carry out higher order processes required for action recognition and person identification. Preterm children exhibited difficulties in all 4 aspects of biological motion perception. However, intercorrelations between test scores were weak in both full-term and preterm children--a finding that supports the view that these processes are relatively independent. Preterm children also displayed more autistic-like traits than full-term peers. In preterm (but not full-term) children, these traits were negatively correlated with performance in the task requiring structure-from-motion processing, r(30) = -.36, p < .05), but positively correlated with the ability to extract identity, r(30) = .45, p < .05). These findings extend previous reports of vulnerability in systems involved in processing dynamic cues in preterm children and suggest that a core deficit in social perception/cognition may contribute to the development of the social and behavioral difficulties even in members of this population who are functioning within the normal range intellectually. The results could inform the development of screening, diagnostic, and intervention tools.
Ment, Laura R; Constable, R Todd
Functional MRI (fMRI) might provide important insights into emerging data that suggest that recovery from injury can occur in the brains of children born prematurely. Strategies employing auditory stimulation demonstrate blood-oxygen-level-dependent (BOLD) activation in preterm infants as young as 33 weeks' gestational age, and reliable BOLD signal in response to visual stimulation occurs at term-equivalent age. Strategies based on fMRI are particularly suited to the study of language and memory, and emerging data are likely to provide insights into perplexing reports that have demonstrated improving cognitive scores but persistent volumetric and microstructural changes in frontotemporal language systems in the prematurely born. Even when sex, gestational age and early medical and environmental interventions are taken into account, fMRI data from several investigators suggest the engagement of alternative neural networks for language and memory in the developing preterm brain.
Survival of preterm infants, which increased dramatically during the years after the introduction of neonatal intensive care, reached a plateau in the mid- to late 1990s. Neonatal morbidity, which increased initially, has decreased since 2000 and resulted in a decrease in the rates of cerebral palsy. Follow-up of preterm infants to early childhood and school age reveals higher rates of asthma, cerebral palsy, subnormal cognitive function, poorer academic achievement, and behavioral problems. Although many of the problems persist into adulthood, preterm survivors regard their overall health and quality of life similar to that of normal birth weight controls.
Burchell, A; McGeechan, A; Hume, R
BACKGROUND—Hepatic glucose-6-phosphatase activity is low at birth, and in term infants rises rapidly to adult levels. In contrast, in most preterm infants, it remains low postnatally making them vulnerable to repeated hypoglycaemic episodes, resultant cerebral damage, or risk of sudden and unexpected death. AIMS—To investigate the clinical features of preterm infants with low glucose-6-phosphatase enzyme activity to determine the influencing factors. METHODS—Clinical data from 36 preterm infants were correlated by stepwise multiple regression analysis with Vmax of hepatic glucose-6-phosphatase as the dependent variable. RESULTS—The most significant correlation was with the administration of insulin (units/kg/h postnatal life) with lesser effects of respiratory distress syndrome and dopamine administration. The Vmax changes reflected changes in the level of expression of the glucose-6-phosphatase protein. CONCLUSION—In a variety of animal models, hepatic glucose-6-phosphatase levels have been shown to decrease in response to insulin, which also decreases transcription of the glucose-6-phosphatase gene. The association of insulin administration with high levels of hepatic glucose-6-phosphatase activity and protein expression was therefore most unexpected. Results from model systems, or adults, must be extrapolated to the metabolism of preterm infants with caution. PMID:10794792
Kovar, I; Mayne, P; Barltrop, D
Both rickets and raised plasma alkaline phosphatase activity are common in the preterm infant. Measurement of plasma alkaline phosphatase activity is valuable in screening for active disease and in diagnosis, but normal reference data are not available for preterm babies. In 30 consecutive preterm infants (birthweight 1580 +/- 410 g, gestational age 31 +/- 2.5 weeks) serial measurements of plasma alkaline phosphatase activity, plasma levels of calcium and inorganic phosphorus, and the pattern of alkaline phosphatase isoenzymes were made. Four patterns of changes in plasma alkaline phosphatase activity with time were seen. 4 of the 30 infants were shown to have rickets; these children and 14 of the 26 non-rachitic infants showed an increasing/peak/decreasing pattern with increasing age, but levels were much higher in the rachitic infants. The activity in all 30 was raised above the adult and childhood reference ranges at some point in time. The data suggest that an activity of five times the upper limit of the normal adult reference range is acceptable in the preterm infant but an activity higher than this may suggest rickets.
Mamopoulos, Apostolos; Petousis, Stamatios; Tsimpanakos, John; Masouridou, Sophia; Kountourelli, Kelly; Margioula-Siarkou, Chrysoula; Papouli, Maria; Rousso, David
Background Neonates born between 24 + 0 and 27 + 6 gestational weeks, widely known as extremely preterm neonates, present a category characterized by increased neonatal mortality and morbidity. Main objective of the present study is to analyze the effect of various epidemiological and pregnancy-related parameters on unfavorable neonatal mortality and morbidity outcomes. Methods A retrospective study was performed enrolling cases delivered during 2003 - 2008 in our department. Cases of neonatal death as well as pathological Apgar score (≤ 4 in the first and ≤ 7 in the fifth minute of life), need for emergency resuscitation, respiratory disease syndrome (RDS), neonatal asphyxia, intraventricular hemorrhage (IVH) and neonatal death were recorded for neonates of our analysis. A multivariate regression model was used to correlate these outcomes with gestational week at delivery, maternal age, parity, kind of gestation (singleton or multiple), intrauterine growth restriction (IUGR), birth weight (BW), preterm premature rupture of membranes (PPROM), mode of delivery (vaginal delivery or cesarean section) and antenatal use of corticosteroids. Results Out of 5,070 pregnancies delivered, 57 extremely preterm neonates were born (1.1%). Mean BW was 780.35 ± 176.0, RDS was observed in 93.0% (n = 53), resuscitation was needed in 54.4% (n = 31) while overall mortality rate was 52.6% (n = 30). BW was independently associated with neonatal death (P = 0.004), pathological Apgar score in the first (P = 0.05) and fifth minute of life (P = 0.04) as well as neonatal sepsis (P = 0.05). Conclusion BW at delivery is independently affecting neonatal mortality and morbidity parameters in extremely preterm neonates. PMID:26015815
Vergnes, Jean-Noel; Kaminski, Monique; Lelong, Nathalie; Musset, Anne-Marie; Sixou, Michel; Nabet, Cathy
OBJECTIVE. The aim of this study was to analyse the association between maternal dental caries and pre-term birth (PTB), with a particular focus on the infection-suspected causes of pre-term births. MATERIALS AND METHODS. A secondary analysis was performed on data from the EPIPAP study, a French multi-centre case-control study. Cases were 1107 women giving birth to a singleton live-born infant before 37 weeks of gestation and controls were 1094 women delivering at 37 weeks or more. A sub-group of cases was defined as women with spontaneous labour and/or pre-term premature rupture of membranes (PPROM, n = 620). A full-mouth dental examination was performed after delivery. The main factor of interest was the presence of decay on at least one tooth. RESULTS. Crude associations between presence of tooth decay and PTB or spontaneous PTB/PPROM were significant (OR = 1.21 [1.01-1.45] and OR = 1.25 [1.01-1.55], respectively). After adjustment for two sets of potential confounders (four pre-term birth risk factors and four social characteristics), for periodontitis status and for inter-examiner variability, tooth decay was not significantly associated with either PTB or spontaneous PTB/PPROM (aOR = 1.10 [0.91-1.32] and aOR = 1.14 [0.91-1.42], respectively). CONCLUSIONS. This study failed to demonstrate a significant association between tooth decay and pre-term birth. However, future well-designed studies are needed to further assess the link between dental caries and adverse pregnancy outcomes.
Baraldi, Eugenio; Giordano, Giuseppe; Stocchero, Matteo; Moschino, Laura; Zaramella, Patrizia; Tran, Maria Rosa; Carraro, Silvia; Romero, Roberto; Gervasi, Maria Teresa
Objective Bronchopulmonary dysplasia (BPD) is a serious complication associated with preterm birth. A growing body of evidence suggests a role for prenatal factors in its pathogenesis. Metabolomics allows simultaneous characterization of low molecular weight compounds and may provide a picture of such a complex condition. The aim of this study was to evaluate whether an unbiased metabolomic analysis of amniotic fluid (AF) can be used to investigate the risk of spontaneous preterm delivery (PTD) and BPD development in the offspring. Study design We conducted an exploratory study on 32 infants born from mothers who had undergone an amniocentesis between 21 and 28 gestational weeks because of spontaneous preterm labor with intact membranes. The AF samples underwent untargeted metabolomic analysis using mass spectrometry combined with ultra-performance liquid chromatography. The data obtained were analyzed using multivariate and univariate statistical data analysis tools. Results Orthogonally Constrained Projection to Latent Structures-Discriminant Analysis (oCPLS2-DA) excluded effects on data modelling of crucial clinical variables. oCPLS2-DA was able to find unique differences in select metabolites between term (n = 11) and preterm (n = 13) deliveries (negative ionization data set: R2 = 0.47, mean AUC ROC in prediction = 0.65; positive ionization data set: R2 = 0.47, mean AUC ROC in prediction = 0.70), and between PTD followed by the development of BPD (n = 10), and PTD without BPD (n = 11) (negative data set: R2 = 0.48, mean AUC ROC in prediction = 0.73; positive data set: R2 = 0.55, mean AUC ROC in prediction = 0.71). Conclusions This study suggests that amniotic fluid metabolic profiling may be promising for identifying spontaneous preterm birth and fetuses at risk for developing BPD. These findings support the hypothesis that some prenatal metabolic dysregulations may play a key role in the pathogenesis of PTD and the development of BPD. PMID:27755564
Young, Julia M; Powell, Tamara L; Morgan, Benjamin R; Card, Dallas; Lee, Wayne; Smith, Mary Lou; Sled, John G; Taylor, Margot J
We evaluated whether the volume and growth rate of critical brain structures measured by MRI in the first weeks of life following very preterm (<32/40 weeks) birth could predict subsequent neurodevelopmental outcomes at 4 years of age. A significant proportion of children born very prematurely have cognitive deficits, but these problems are often only detected at early school age. Structural T2-weighted magnetic resonance images were acquired in 96 very preterm neonates scanned within 2 weeks of birth and 70 of these at term-equivalent age. An automated 3D image analysis procedure was used to measure the volume of selected brain structures across all scans and time points. At 4 years of age, 53 children returned for neuropsychological assessments evaluating IQ, language and visual motor integration. Associations with maternal education and perinatal measures were also explored. Multiple regression analyses revealed that growth of the caudate and globus pallidus between preterm birth and term-equivalent age predicted visual motor integration scores after controlling for sex and gestational age. Further associations were found between caudate and putamen growth with IQ and language scores. Analyses at either preterm or term-equivalent age only found associations between normalized deep grey matter growth and visual motor integration scores at term-equivalent age. Maternal education levels were associated with measures of IQ and language, but not visual motor integration. Thalamic growth was additionally linked with perinatal measures and presence of white matter lesions. These results highlight deep grey matter growth rates as promising biomarkers of long-term outcomes following very preterm birth, and contribute to our understanding of the brain-behaviour relations in these children.
Patra, Kousiki; Greene, Michelle M; Patel, Aloka L; Meier, Paula
Objective To evaluate the relative impact of maternal education level (MEL) on cognitive, language, and motor outcomes at 20 months' corrected age (CA) in preterm infants. Study Design A total of 177 preterm infants born between 2008 and 2010 were tested at 20 months' CA using the Bayley Scales of Infant and Toddler Development-III. Multiple regression analyses were done to determine the relative impact of MEL on cognitive, language, and motor scores. Results Infants born to mothers with high school MEL were 3.74 times more likely to have a subnormal motor index, while those born to mothers with some college and graduate school MEL had reduced odds (0.36 and 0.12, respectively) of having subnormal language index at 20 months. In linear regression, MEL was the strongest predictor of cognitive, language, and motor scores, and graduate school MEL was associated with increases in cognitive, motor, and language scores of 8.49, 8.23, and 15.74 points, respectively. Conclusions MEL is the most significant predictor of cognitive, language, and motor outcome at 20 months' CA in preterm infants. Further research is needed to evaluate if targeted interventions that focus on early childhood learning and parenting practices can ameliorate the impact of low MEL.
Posod, Anna; Odri Komazec, Irena; Kager, Katrin; Pupp Peglow, Ulrike; Griesmaier, Elke; Schermer, Elisabeth; Würtinger, Philipp; Baumgartner, Daniela
Cardiovascular disease is the leading cause of death worldwide. Evidence points towards an unfavorable cardiovascular risk profile of former preterm infants in adolescence and adulthood. The aim of this study was to determine whether cardiovascular risk predictors are detectable in former very preterm infants at a preschool age. Five- to seven-year-old children born at <32 weeks’ gestational age were included in the study. Same-aged children born at term served as controls. Basic data of study participants were collected by means of follow-up databases and standardized questionnaires. At study visit, anthropometric data, blood pressure readings and aortic intima-media thickness were assessed. Blood samples were obtained after an overnight fast. In comparison to children born at term, former preterm infants had higher systolic and diastolic blood pressure readings (odds ratio [95% confidence interval] per 1-SD higher blood pressure level 3.2 [2.0–5.0], p<0.001 and 1.6 [1.1–1.2], p = 0.008), fasting glucose levels (OR [95% CI] 5.2 [2.7–10.1], p<0.001), homeostasis model assessment index (OR [95% CI] 1.6 [1.0–2.6], p = 0.036), and cholesterol levels (OR [95% CI] 2.1 [1.3–3.4], p = 0.002). Systolic prehypertension (23.7% vs. 2.2%; OR [95% CI] 13.8 [3.1–60.9], p = 0.001), elevated glucose levels (28.6% vs. 5.9%; OR [95% CI] 6.4 [1.4–28.8], p = 0.016), and hypercholesterolemia (77.4% vs. 52.9%; OR [95% CI] 3.0 [1.3–7.1], p = 0.010) were significantly more prevalent in the preterm group. As former very preterm infants display an unfavorable cardiovascular risk profile already at a preschool age, implementation of routine cardiovascular follow-up programs might be warranted. PMID:27959909
Hudic, Igor; Schindler, Adolf E; Szekeres-Bartho, Julia; Stray-Pedersen, Babill
Progestin supplementation appears to be a promising approach to both preventing initiation of pre-term labor and treating it once it is already established. Successful pregnancy depends on maternal tolerance of the fetal "semi-allograft". A protein called progesterone-induced blocking factor (PIBF), by inducing a Th2 dominant cytokine production mediates the immunological effects of progesterone. Over time, various attempts have been made to clarify the question, whether progestogens can contribute positively to either prevention or treatment of pre-term labor and birth. Dydrogesterone treatment of women at risk of pre-term delivery results in increased PIBF production and IL-10 concentrations, and lower concentrations of IFNγ and could be effective for prevention or treatment of pre-term labor. Further randomized studies are needed.
Rode, Line; Tabor, Ann
The incidence of twin gestation has increased markedly over the past decades, mostly because of increased use of assisted reproductive technologies. Twin pregnancies are at increased risk of preterm delivery (i.e. birth before 37 weeks of gestation). Multiple gestations therefore account for 2-3% of all pregnancies but constitute at least 10% of cases of preterm delivery. Complications from preterm birth are not limited to the neonatal period, such as in retinopathy of prematurity, intraventricular haemorrhage, necrotising enterocolitis, respiratory disorder and sepsis; they can also constitute sequelae such as abnormal neurophysiological development in early childhood and underachievement in school. Several treatment modalities have been proposed in singleton high-risk pregnancies. The mechanism of initiating labour may, however, be different in singleton and twin gestations. Therefore, it is mandatory to evaluate the proposed treatments in randomised trials of multiple gestations. In this chapter, we describe the results of trials to prevent preterm delivery in twin pregnancies.
... https://medlineplus.gov/news/fullstory_163401.html Certain Bacteria May Affect Preterm Birth Risk Bad 'bugs' tied ... Feb. 3, 2017 (HealthDay News) -- Certain types of bacteria in a pregnant woman's cervix and vagina can ...
Background. Neighborhood-level deprivation has long been associated with adverse outcomes, including preterm birth (PTB), as observed in the authors' previous work using a composite deprivation index. Area disadvantage is multifaceted comprising income, employment, education and...
Previous research with vital records finds income incongruity associated with adverse birth outcomes. We examined the effects of negative income incongruity (reporting lower household income than the census tract median household income) on preterm birth (PTB <37 weeks completed ...
Wehby, George L; Pawluk, Mariela; Nyarko, Kwame A; López-Camelo, Jorge S
Little is understood about racial/ethnic disparities in infant health in South America. We quantified the extent to which the disparity in preterm birth (PTB; <37 gestational weeks) rate between infants of Native only ancestry and those of European only ancestry in Argentina and Ecuador are explained by household socio-economic, demographic, healthcare use, and geographic location indicators. The samples included 5199 infants born between 2000 and 2011 from Argentina and 1579 infants born between 2001 and 2011 from Ecuador. An Oaxaca-Blinder type decomposition model adapted to binary outcomes was estimated to explain the disparity in PTB risk across groups of variables and specific variables. Maternal use of prenatal care services significantly explained the PTB disparity, by nearly 57% and 30% in Argentina and Ecuador, respectively. Household socio-economic status explained an additional 26% of the PTB disparity in Argentina. Differences in maternal use of prenatal care may partly explain ethnic disparities in PTB in Argentina and Ecuador. Improving access to prenatal care may reduce ethnic disparities in PTB risk in these countries.
Blüml, Stefan; Wisnowski, Jessica L; Nelson, Marvin D; Paquette, Lisa; Panigrahy, Ashok
Significant physiological switches occur at birth such as the transition from fetal parallel blood flow to a two-circuit serial system with increased arterial oxygenation of blood delivered to all organs including the brain. In addition, the extra-uterine environment exposes premature infants to a host of stimuli. These events could conceivably alter the trajectory of brain development in premature infants. We used in vivo magnetic resonance spectroscopy to measure absolute brain metabolite concentrations in term and premature-born infants without evidence of brain injury at equivalent post-conceptional age. Prematurity altered the developmental time courses of N-acetyl-aspartate, a marker for axonal and neuronal development, creatine, an energy metabolite, and choline, a membrane metabolite, in parietal white matter. Specifically, at term-equivalency, metabolic maturation in preterm infants preceded development in term infants, but then progressed at a slower pace and trajectories merged at ≈340-370 post-conceptional days. In parieto/occipital grey matter similar trends were noticed but statistical significance was not reached. The timing of white matter development and synchronization of white matter and grey matter maturation in premature-born infants is disturbed. This may contribute to the greater risk of long-term neurological problems of premature infants and to their higher risk for white matter injury.
The fundamental principle underlying nutritional support is that intake meets needs thereby ensuring the best outcome, which, in the case of the preterm infant, is optimal growth and development. Achieving this goal is problematic. Most, if not all, very-low-birth-weight infants (VLBWI) are undernourished and under-grown when they are first discharged from the hospital. This has important implications for the nutritional care of preterm, particularly the breast-fed, VLBWI after hospital discharge.
Language development in infants born very preterm is often compromised. Poor language skills have been described in preschoolers and differences between preterms and full terms, relative to early vocabulary size and morphosyntactical complexity, have also been identified. However, very few data are available concerning early speech perception abilities and their predictive value for later language outcomes. An overview of the results obtained in a prospective study exploring the link between early speech perception abilities and lexical development in the second year of life in a population of very preterm infants (≤32 gestation weeks) is presented. Specifically, behavioral measures relative to (a) native-language recognition and discrimination from a rhythmically distant and a rhythmically close nonfamiliar languages, and (b) monosyllabic word-form segmentation, were obtained and compared to data from full-term infants. Expressive vocabulary at two test ages (12 and 18 months, corrected age for gestation) was measured using the MacArthur Communicative Development Inventory. Behavioral results indicated that differences between preterm and control groups were present, but only evident when task demands were high in terms of language processing, selective attention to relevant information and memory load. When responses could be based on acquired knowledge from accumulated linguistic experience, between-group differences were no longer observed. Critically, while preterm infants responded satisfactorily to the native-language recognition and discrimination tasks, they clearly differed from full-term infants in the more challenging activity of extracting and retaining word-form units from fluent speech, a fundamental ability for starting to building a lexicon. Correlations between results from the language discrimination tasks and expressive vocabulary measures could not be systematically established. However, attention time to novel words in the word segmentation
Behrendt, D; Dembinski, J; Heep, A; Bartmann, P
Objective: To assess serum concentrations of lipopolysaccharide binding protein (LBP) in preterm infants with neonatal bacterial infection (NBI). Methods: Blood samples were analysed of 57 preterm (28+1 to 36+6, median 33+2 weeks gestation) and 17 term infants admitted to the neonatal intensive care unit within the first 72 hours of life with suspicion of NBI. Samples were obtained at first suspicion of sepsis and after 12 and 24 hours. Diagnosis of NBI was confirmed by raised concentrations of C reactive protein and/or interleukin 6. The influence of gestational age and labour was analysed. Results: Maximum LBP concentrations in infants with NBI were greatly increased compared with infants without NBI (13.0–46.0 µg/ml (median 20.0 µg/ml) v 0.6–17.4 µg/ml (median 4.2 µg/ml)). LBP concentrations in infected infants were not yet significantly raised when NBI was first suspected. The LBP concentrations of preterm infants were comparable to those of term infants. Regression analysis revealed no significant effect of labour or gestational age on LBP. Conclusions: Raised LBP concentrations indicate NBI in preterm and term infants. Preterm infants of > 28 weeks gestation seem to be capable of producing LBP as efficiently as term infants. Neonatal LBP concentrations are not influenced by labour. LBP may be a useful diagnostic marker of NBI in preterm infants. PMID:15499153
Birle, Alexandra; Nebe, C. Thomas; Hill, Sandra; Hartmann, Karin; Poeschl, Johannes; Koch, Lutz
Bacterial infections, even without any perinatal risk factors, are common in newborns, especially in preterm neonates. The aim of this study was to evaluate possible impairment of neutrophil chemotaxis in term and preterm neonates compared with adults as well as neonates with different modes of delivery and anaesthesia. We analysed the expression of the adhesion molecule L-Selectin as well as shape change, spontaneous and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced transmigration of neutrophils in a flow cytometric assay of chemotaxis after spontaneous delivery with Cesarian Section (CS) under spinal anaesthesia (mepivacaine, sufentanil), epidural anaesthesia (ropivacaine or bupivacaine, sufentanil) or general anaesthesia (ketamine, thiopental, succinylcholine). Chemokinesis was higher (p=0.008) in cord blood neutrophils than in the adult ones, whereas those could be more stimulated by fMLP (p=0.02). After vaginal delivery neutrophils showed a higher spontaneous and fMLP-stimulated chemotactic response compared to neonates after CS without labor. Comparing different types of anaesthesia for CS, spinal anaesthesia resulted in less impairment on chemotaxis than general anaesthesia or epidural anaesthesia. The new flow cytometric assay of neutrophil chemotaxis is an appropriate and objective method to analyse functional differences even in very small volumes of blood, essential in neonatology. Term neonates do not show reduced chemotaxis compared to adults. Preterm neonates present with reduced chemotaxis and chemokinesis, confirming the well known deficits in their neutrophil function. The side effects of maternal drugs on the neonatal immune system have to be considered especially when the immune response is already impaired, as in preterm infants. PMID:25867529
Birle, Alexandra; Nebe, C Thomas; Hill, Sandra; Hartmann, Karin; Poeschl, Johannes; Koch, Lutz
Bacterial infections, even without any perinatal risk factors, are common in newborns, especially in preterm neonates. The aim of this study was to evaluate possible impairment of neutrophil chemotaxis in term and preterm neonates compared with adults as well as neonates with different modes of delivery and anaesthesia. We analysed the expression of the adhesion molecule L-Selectin as well as shape change, spontaneous and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced transmigration of neutrophils in a flow cytometric assay of chemotaxis after spontaneous delivery with Cesarian Section (CS) under spinal anaesthesia (mepivacaine, sufentanil), epidural anaesthesia (ropivacaine or bupivacaine, sufentanil) or general anaesthesia (ketamine, thiopental, succinylcholine). Chemokinesis was higher (p=0.008) in cord blood neutrophils than in the adult ones, whereas those could be more stimulated by fMLP (p=0.02). After vaginal delivery neutrophils showed a higher spontaneous and fMLP-stimulated chemotactic response compared to neonates after CS without labor. Comparing different types of anaesthesia for CS, spinal anaesthesia resulted in less impairment on chemotaxis than general anaesthesia or epidural anaesthesia. The new flow cytometric assay of neutrophil chemotaxis is an appropriate and objective method to analyse functional differences even in very small volumes of blood, essential in neonatology. Term neonates do not show reduced chemotaxis compared to adults. Preterm neonates present with reduced chemotaxis and chemokinesis, confirming the well known deficits in their neutrophil function. The side effects of maternal drugs on the neonatal immune system have to be considered especially when the immune response is already impaired, as in preterm infants.
An assessment battery, measuring multiple aspects of language, was administered to 29 children between 4 and 5 years of age who had been born prematurely. The children, who weighed less than 2,500 grams at birth after less than 37 weeks of gestation, were recruited from a cohort of children originally admitted to the neonatal intensive care unit…
Hay, William W; Hendrickson, Kendra C
Whereas human milk is the recommended diet for all infants, preterm formulas are indicated for enteral feeding of preterm very low birth weight infants when sufficient maternal breast milk and donor human milk are not available. Feeding with preterm formulas helps to ensure consistent delivery of nutrients. The balance of risks and benefits of feeding preterm formulas versus supplemented maternal and donor breast milk for preterm infants, however, is uncertain. Numerous studies and extensive practice have shown improved growth with preterm formulas, but there is concern for increased risks of necrotizing enterocolitis, possibly from cow milk antigen in the formulas or from different gut microbiomes, increased duration of total parenteral nutrition, and increased rates of sepsis in infants receiving preterm formulas. Furthermore, whereas preterm formulas improve neurodevelopmental outcomes compared to term formulas and unfortified donor milk, they do not produce neurodevelopmental outcomes better than fortified human milk, again indicating that maternal milk has unique properties that formulas need to mimic as closely as possible.
Lubin, Philip M.
We report on modeling of a balloon borne mission to survey the 1-5 micron region with sensitivity close to the zodiacal light limits in portions of this band. Such a survey is compelling for numerous science programs and is complimentary to the upcoming Euclid, WFIRST and other orbital missions. Balloons borne missions offer much lower cost access and rapid technological implementation but with much less exposure time and increased backgrounds. For some science missions the complimentary nature of these is extremely useful. .
Passini, Renato; Cecatti, Jose G.; Lajos, Giuliane J.; Tedesco, Ricardo P.; Nomura, Marcelo L.; Dias, Tabata Z.; Haddad, Samira M.; Rehder, Patricia M.; Pacagnella, Rodolfo C.; Costa, Maria L.; Sousa, Maria H.
Background Preterm birth rate is increasing and is currently a worldwide concern. The purpose of this study was to estimate the prevalence of preterm birth in a sample of health facilities in Brazil and to identify the main risk factors associated with spontaneous preterm births. Methods and Findings This was a multicentre cross sectional study on preterm births in 20 referral obstetric hospitals with a case-control component to identify factors associated with spontaneous preterm birth. Surveillance was implemented at all centres to identify preterm births. For eligible consenting women, data were collected through a post-delivery questionnaire completed with information from all mother-newborn medical records until death or discharge or at a maximum of 60 days post-delivery, whichever came first. The risk of spontaneous preterm birth was estimated with OR and 95%CI for several predictors. A non-conditional logistic regression analysis was then performed to identify independently associated factors. The overall prevalence of preterm birth was 12.3%. Among them, 64.6% were spontaneous and 35.4% therapeutic. In the case-control component, 2,682 spontaneous preterm births were compared to a sample of 1,146 term births. Multivariate analyses identified the following as risk factors for spontaneous preterm birth among women with at least one previous birth: a previous preterm birth (ORadj = 3.19, 2.30–4.43), multiple pregnancy (ORadj = 29.06, 8.43–100.2), cervical insufficiency (ORadj = 2.93, 1.07–8.05), foetal malformation (ORadj = 2.63, 1.43–4.85), polyhydramnios (ORadj = 2.30, 1.17–4.54), vaginal bleeding (ORadj = 2.16, 1.50–3.11), and previous abortion (ORadj = 1.39, 1.08–1.78). High BMI (ORadj = 0.94, 0.91–0.97) and weight gain during gestation (ORadj = 0.92, 0.89–0.95) were found to be protective factors. Conclusions The preterm birth rate in these health facilities in Brazil is high and spontaneous preterm
Hobson, C.; Dubillot, D.; Lardy, H.; Sirinelli, D.; Saliba, E.; Lopez, E.
We report a case of a preterm neonate born at 26 weeks' of gestation diagnosed with unilateral diaphragmatic paralysis. This paralysis was a consequence of a phrenic nerve injury due to extravasation of hyperosmolar parenteral nutrition fluid in the upper thorax. Chest X-rays and ultrasonography confirmed the diagnosis. The neonate was treated with prolonged respiratory support and did not require surgical treatment. This report describes a case of hemidiaphragmatic paralysis as a complication of central venous catheter insertion. In neonates, spontaneous recovery of diaphragmatic paralysis is possible. This study concludes that recovery of extravasation injury-induced phrenic nerve palsy in the context of conservative management is possible.
Van der Kaay, D C M; Horsch, S; Duvekot, J J
Both transverse lie and preterm premature rupture of membranes (PPROM) are associated with neonatal morbidity and mortality. We present a neonate born at 29 weeks gestation with severe birth trauma after PPROM and transverse lie. The patient had extensive swelling and areas of desquamated and necrotic skin of the right lower limb. Neonatal compartment syndrome (NCS) was suspected. Perfusion of the limb improved after decompressing subcutaneous incisions. A fetus in transverse lie may be mechanically damaged in the case of PPROM, especially at an early gestational age. Early recognition is of great interest in the management and prognosis of NCS.
Tully, Kristin P.; Holditch-Davis, Diane; Brandon, Debra
Objective To compare maternal report of planned and practiced home sleep locations of infants born late preterm (34 0/7 to 36 6/7 gestational weeks) with those infants born term (≥ 37 0/7 gestational weeks) over the first postpartum month. Methods Open-ended semi-structured maternal interviews were conducted in a U.S. hospital following birth and by phone at one month postpartum during 2010–2012. Participants were 56 mother-infant dyads: 26 late preterm and 30 term. Results Most women planned to room share at home with their infants and reported doing so for some or all of the first postpartum month. More women reported bed sharing during the first postpartum month than had planned to do so in both the late preterm and term groups. The primary reason for unplanned bed sharing was to soothe nighttime infant fussiness. Those participants who avoided bed sharing at home commonly discussed their fear for infant safety. A few parents reported their infants were sleeping propped on pillows and co-sleeping on a recliner. Some women in both the late preterm and term groups reported lack of opportunity to obtain a bassinet prior to childbirth. Conclusions The discrepancy between plans for infant sleep location at home and maternally reported practices were similar in late preterm and term groups. Close maternal proximity to their infants at night was derived from the need to assess infant well-being, caring for infants, and women’s preferences. Bed sharing concerns related to infant safety and the establishment of an undesirable habit, and alternative arrangements included shared recliner sleep. PMID:25626714
Tully, Kristin P; Holditch-Davis, Diane; Brandon, Debra
To compare maternal report of planned and practiced home sleep locations of infants born late preterm (34 0/7 to 36 6/7 gestational weeks) with those infants born term (≥37 0/7 gestational weeks) over the first postpartum month. Open-ended semi-structured maternal interviews were conducted in a US hospital following birth and by phone at 1 month postpartum during 2010-2012. Participants were 56 mother-infant dyads: 26 late preterm and 30 term. Most women planned to room share at home with their infants and reported doing so for some or all of the first postpartum month. More women reported bed sharing during the first postpartum month than had planned to do so in both the late preterm and term groups. The primary reason for unplanned bed sharing was to soothe nighttime infant fussiness. Those participants who avoided bed sharing at home commonly discussed their fear for infant safety. A few parents reported their infants were sleeping propped on pillows and co-sleeping on a recliner. Some women in both the late preterm and term groups reported lack of opportunity to obtain a bassinet prior to childbirth. The discrepancy between plans for infant sleep location at home and maternally reported practices were similar in late preterm and term groups. Close maternal proximity to their infants at night was derived from the need to assess infant well-being, caring for infants, and women's preferences. Bed sharing concerns related to infant safety and the establishment of an undesirable habit, and alternative arrangements included shared recliner sleep.
Jansson-Verkasalo, Eira; Ceponiene, Rita; Valkama, Marita; Vainionpää, Leena; Laitakari, Kyösti; Alku, Paavo; Suominen, Kalervo; Näätänen, Risto
Very low birth weight (VLBW, <1500 g) preterm birth has been associated with anatomic abnormalities in brain development and cognitive and language disorders. We examined object naming ability, and an electrophysiologic index of auditory sensory discrimination of speech sounds (the mismatch negativity, MMN) in 4-year-old VLBW prematurely born children. We found that half of the VLBW children were inferior to their controls in the object naming ability. Also the MMN amplitudes were smaller in the preterm group as compared with the controls. Further, the MMN amplitude varied as a function of children's performance on object naming, such that the weaker object-naming performance of the preterm group was paralleled by the diminished MMN amplitudes. Therefore, difficulties in auditory discrimination seem to be implicated in language difficulties encountered in VLBW prematurely born children.
Preface; 1. What does astronomy tell us?; 2. what is a star?; 3. Our galaxy; 4. Where are starts born?; 5. How to recognise the youngest stars; 6. Nature's womb; 7. How and why clouds collapse; 8. Towards a more sedate life; 9. High-mass stars and triggering mechanisms; 10. Planets; 11. Epilogue; Index.
Work, Telford H.
More than 150 arthropod-borne viruses are now recognized, and over 50 of these are known to produce human infections and disease. Among these viruses are those of the tick-borne Russian spring-summer complex, which is etiologically involved in a wide variety of human diseases of varying severity. The eight antigenically different members of this complex so far known are Russian spring-summer encephalitis, louping-ill, Central European encephalitis, Omsk haemorrhagic fever, Kyasanur Forest disease, Langat, Negishi and Powassan viruses. In his review of the problems posed by these viruses and of research on them, the author points out that, while this complex is distributed around the globe in the temperate zone of the northern hemisphere, the only serious tick-borne virus disease known in the tropics is Kyasanur Forest disease. It is probable, however, that there are other, unrecognized tick-borne viruses in the tropical areas of Asia, Africa and America of importance to human health, and that these will be brought to light as virological studies of diseases of now obscure etiology are pursued. PMID:14043753
Maitre, Nathalie L; Williams, John V
Premature birth (<37 weeks gestation) occurs in ~11% of all births in the US. These infants are at risk of chronic lung disease and respiratory conditions, including bronchopulmonary dysplasia. Respiratory viruses are important causes of acute respiratory illness (ARI) in preterm infants, leading to rehospitalization, increased health care burden, and long-term morbidity. Human metapneumovirus (HMPV) is a paramyxovirus discovered in 2001 that is related to respiratory syncytial virus. Epidemiologic studies show that HMPV is a leading cause of ARI in children and adults worldwide. Prematurity is a major risk factor for severe HMPV disease, requiring hospitalization. Moreover, limited data suggest that HMPV infection during infancy is associated with asthma and recurrent wheezing, which are common long-term pulmonary complication of prematurity. HMPV causes nosocomial outbreaks of ARI in hospitals and long-term care facilities, although there are few studies of the prevalence of HMPV in neonatal intensive care unit populations. HMPV is a common and important virus in premature infants, and caregivers for preterm infants should consider this virus in patients with acute respiratory symptoms. PMID:27891060
Liang, Juan; Mao, Meng; Dai, Li; Li, Xiaohong; Miao, Lei; Li, Qi; He, Chunhua; Li, Mingrong; Wang, He; Zhu, Jun; Wang, Yanping
Almost all (99%) neonatal deaths occur in developing countries, where the progress in reducing neonatal mortality rates (NMR) has been small; the Millennium Development Goal for child survival cannot be met if this situation continues. China is among the 10 countries that have the largest numbers of neonatal deaths. In order to provide effective interventions to reduce the national NMR for government policy makers, we analyse the trends, causes and characteristics of the neonatal deaths of preterm babies in different regions of China during the period 2003-2008. The data for this retrospective study were retrieved from the population-based Maternal and Child Health Surveillance System of China. The Cochran-Armitage trend test was used to analyse the trend of NMRs due to immaturity. The national NMR due to immaturity has decreased by 38.7% in 6 years. However, the proportion of preterm births among the causes of neonatal death has increased significantly from 33.6% in 2003 to 40.9% in 2008. The relative risk of neonatal death among preterm babies has shown significant regional disparity. In 2008, the adjusted relative risk was 1.30 [95% confidence interval (CI) 0.95, 1.78] in the inland regions and 2.37 [95% CI 1.56, 3.60] in the remote regions, both compared with the coastal regions. The proportion of neonatal deaths with a gestational age <32 weeks or a birthweight <1500 g was highest among the coastal regions. Most neonatal deaths of preterm babies in remote areas were born at home and were not treated before death. Our study suggests that preterm birth is the leading cause of neonatal death in China and neonatal mortality due to immaturity displayed regional differences. The Chinese government should implement major effective strategies for reducing the mortality of preterm infants to further decrease the total NMR. Priority interventions should be region-specific, depending on the availability of economic and health care resources.
Chapman, A K; Aucott, S W; Milstone, A M
Chlorhexidine gluconate (CHG) is a widely used topical antiseptic that is recommended by the Centers for Disease Control and Prevention for skin cleansing before central venous catheter insertion in adults and children. Because of limited safety data, CHG is not recommended for use in children <2 months of age. CHG is, however, frequently used in Neonatal Intensive Care Units across the United States. Here, we will review the safety of CHG use in preterm infants.
Hay, William W Jr
The goal of nutrition of the preterm infant is to meet the growth rate of the healthy fetus of the same gestational age and to produce the same body composition of the healthy fetus in terms of organ growth, tissue components, and cell number and structure. Nutritional quantity and quality are fundamental for normal growth and development of preterm infants, including neurodevelopmental outcomes. Failure to provide the necessary amounts of all of the essential nutrients has produced not only growth failure, but also increased morbidity and less than optimal neurodevelopment. Growth velocities during the NICU hospitalization period for preterm infants exert a significant effect on neurodevelopmental and anthropometric outcomes. Despite the obvious need for optimal nutrition, growth failure is almost universal among preterm infants. There is every reason, therefore, to optimize nutrition of the preterm infant, in terms of total energy and protein, but also in terms of individual components such as amino acids, specific carbohydrates and lipids, and even oxygen. This review presents scientific rationale for nutrient requirements and practical guidelines and approaches to intravenous and enteral feeding for preterm infants. Intravenous feeding, including amino acids, should be started right after birth at rates that are appropriate for the gestational age of the infant. Enteral feeding should be started as soon as possible after birth, using mother's colostrum and milk as first choices. Enteral feeding should begin with trophic amounts and advanced as rapidly as tolerated, decreasing IV nutrition accordingly, while maintaining nutrient intakes at recommended rates. Feeding protocols are valuable for improving nutrition and related outcomes. Further research is needed to determine the optimal nutrition and rate of growth in preterm infants that will achieve optimal neurocognitive benefits while minimizing the longer-term risk of chronic diseases.
Alexander, M; Garbus, H; Smith, A L; Rosenkrantz, T S; Fitch, R H
Hypoxia-ischemia (HI) occurs when blood and/or oxygen delivery to the brain is compromised. HI injuries can occur in infants born prematurely (<37 weeks gestational age) or at very low birth weight (<1500 g), as well as in term infants with birth complications. In both preterm and term HI populations, brain injury is associated with subsequent behavioral deficits. Neonatal HI injury can be modeled in rodents (e.g., the Rice-Vannucci method, via cautery of right carotid followed by hypoxia). When this injury is induced early in life (between postnatal day (P)1-5), neuropathologies typical of human preterm HI are modeled. When injury is induced later (P7-12), neuropathologies typical of those seen in HI term infants are modeled. The current study sought to characterize the similarities/differences between outcomes following early (P3) and late (P7) HI injury in rats. Male rats with HI injury on P3 or P7, as well as sham controls, were tested on a variety of behavioral tasks in both juvenile and adult periods. Results showed that P7 HI rats displayed deficits on motor learning, rapid auditory processing (RAP), and other learning/memory tasks, as well as a reduction in volume in various neuroanatomical structures. P3 HI animals showed only transient deficits on RAP tasks in the juvenile period (but not in adulthood), yet robust deficits on a visual attention task in adulthood. P3 HI animals did not show any significant reductions in brain volume that we could detect. These data suggest that: (1) behavioral deficits following neonatal HI are task-specific depending on timing of injury; (2) P3 HI rats showed transient deficits on RAP tasks; (3) the more pervasive behavioral deficits seen following P7 HI injury were associated with substantial global tissue loss; and (4) persistent deficits in attention in P3 HI subjects might be linked to neural connectivity disturbances rather than a global loss of brain volume, given that no such pathology was found. These combined
Mathew, Supriya; Mathur, Deepika; Chang, Anne B; McDonald, Elizabeth; Singh, Gurme