Preterm Subjects Research Articles

Pulmonary Gas Exchange and Exercise Capacity in Adults Born Preterm.

Preterm birth, and its often-required medical interventions, can result in respiratory and gas exchange deficits into childhood. However, the long-term sequelae into adulthood are not well understood. To determine exercise capacity and pulmonary gas exchange efficiency during exercise in adult survivors of preterm birth. Preterm (n = 14), very low birth weight (<1,500 g) adults (20-23 yr) and term-born, age-matched control subjects (n = 16) performed incremental exercise on a cycle ergometer to volitional exhaustion while breathing one of two oxygen concentrations: normoxia (fraction of inspired oxygen, 0.21) or hypoxia (fraction of inspired oxygen, 0.12). Ventilation, mixed expired gases, arterial blood gases, power output, and oxygen consumption were measured during rest and exercise. We calculated the alveolar-to-arterial oxygen difference to determine pulmonary gas exchange efficiency. Preterm subjects had lower power output at volitional exhaustion than did control subjects in normoxia (150 ± 10 vs. 180 ± 10 W; P = 0.01), despite similar normoxic oxygen consumption. However, during hypoxic exercise, there was no difference in power output at volitional exhaustion between the two groups (116 ± 10 vs. 135 ± 10 W; P = 0.11). Preterm subjects also exhibited a more acidotic, acid-base balance throughout exercise compared with control subjects. In contrast to other studies, adults born preterm, as a group developed a wider alveolar-to-arterial oxygen difference and lower PaO2 than did control subjects during normoxic but not hypoxic exercise. This study demonstrates that pulmonary gas exchange efficiency is lower in some adult survivors of preterm birth during exercise compared with control subjects. The gas exchange inefficiency, when present, is accompanied by low arterial blood oxygen tension. Preterm subjects also exhibit reduced power output. Overall, our findings suggest potential long-term consequences of extreme preterm birth and very low birth weight on cardiopulmonary function.

Gut hormones of preterm infants with abdominal symptoms and hypothyroxinemia.

The pathogenesis of abdominal symptoms in premature infants with hypothyroxinemia is not understood; therefore, we investigated changes in gut hormones before and after levothyroxine sodium (T4-Na) supplementation in preterm infants with abdominal symptoms and hypothyroxinemia. In eight preterm study subjects and 14 gestational age-matched controls, fasting serum concentration of leptin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), pancreatic polypeptide, insulin, amylin and ghrelin was measured using a bead array system. Serum GLP-1, GIP and PYY in the subjects before T4-Na supplementation were lower than in controls at age 2 weeks. After improvement of abdominal symptoms and free thyroxine, serum levels of the three gut hormones in the subjects were increased and were not different from those in the control patients. In preterm infants with abdominal symptoms, serum GLP-1, GIP and PYY might be related to thyroid function.

Longitudinal measurement of the developing grey matter in preterm subjects using multi-modal MRI

Preterm birth is a major public health concern, with the severity and occurrence of adverse outcome increasing with earlier delivery. Being born preterm disrupts a time of rapid brain development: in addition to volumetric growth, the cortex folds, myelination is occurring and there are changes on the cellular level. These neurological events have been imaged non-invasively using diffusion-weighted (DW) MRI. In this population, there has been a focus on examining diffusion in the white matter, but the grey matter is also critically important for neurological health. We acquired multi-shell high-resolution diffusion data on 12 infants born at ≤28weeks of gestational age at two time-points: once when stable after birth, and again at term-equivalent age. We used the Neurite Orientation Dispersion and Density Imaging model (NODDI) (Zhang et al., 2012) to analyse the changes in the cerebral cortex and the thalamus, both grey matter regions. We showed region-dependent changes in NODDI parameters over the preterm period, highlighting underlying changes specific to the microstructure. This work is the first time that NODDI parameters have been evaluated in both the cortical and the thalamic grey matter as a function of age in preterm infants, offering a unique insight into neuro-development in this at-risk population.

Temporal summation in children with a history of retinopathy of prematurity.

To assess temporal summation in children with a history of retinopathy of prematurity (ROP) by determining the critical duration (tCRIT) for complete temporal summation under rod-mediated conditions. From prior ERG studies, it is known that the kinetics of activation of phototransduction are prolonged in the ROP rod photoreceptor. Dark-adapted thresholds for detecting 10° diameter stimuli with durations from 10 to 640 ms were measured. A two-alternative, spatial, forced-choice psychophysical procedure was used. The tCRIT for complete summation was estimated in former preterm subjects with a history of severe ROP (n = 7), mild ROP (n = 23), and no ROP (n = 15). The subjects ranged in age from 10.4 to 17.6 (median 15.6) years. Age-similar term-born control subjects (n = 5) were also tested. Critical duration was significantly longer in subjects with a history of ROP than in subjects who never had ROP or who were born at term. Mean tCRIT in the mild ROP group [127.5 (SD = 19.9) ms] and severe group [147.6 (SD = 18.9) ms] did not differ significantly, but both were significantly longer than in former preterms who never had ROP [101.1 (SD = 16.5) ms] and in term-born controls [101.0 (SD = 19.5) ms]. In ROP subjects, tCRIT is significantly prolonged. This is likely due to abnormal kinetics in the rod outer segment.

Adaptive mechanisms of developing brain: Cerebral lateralization in the prematurely-born

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.

Effect of preterm birth on exercise capacity: A systematic review and meta‐analysis

Survivors of preterm-birth have increased prevalence of respiratory, cardiovascular, and neurological diseases in later life however, the overall impact of prematurity on cardiorespiratory exercise capacity is unclear. We, therefore, systematically reviewed the literature on cardiorespiratory exercise capacity in survivors of preterm birth. Relevant studies up to March 2013 were searched using eight electronic health databases. Studies reporting exercise capacity in participants born preterm (<37 weeks) were included. The main outcome of interest was oxygen uptake (V˙O2max⁡) at maximal exercise. Data were categorized into four groups: (i) preterm-born subjects including those with or without bronchopulmonary dysplasia (BPD) but excluding study groups biased towards BPD; (ii) preterm-born subjects (BPD excluded); (iii) preterm-born subjects who had BPD28 (defined as oxygen dependency at 28 days of life) in infancy; (iv) preterm born subjects with BPD36 (oxygen dependency at 36 weeks post menstrual age) in infancy. From 9,341 abstracts, 22 included publications reported V˙O2max⁡ in ml/kg/min from 685 preterm and 680 term-born subjects. Overall 20 studies reported results for preterm-born subjects including BPD; 14 studies for the preterm group excluding BPD; 10 studies for the BPD28 group; and 8 studies for BPD36 group. The mean differences (95% CI) for the four groups were -2.20 (-3.70, -0.70) ml/kg/min; -2.26 (-4.44, -0.07 ml/kg/min; -3.04 (-5.48, -0.61) ml/kg/min, and -3.05 (-5.93, -0.18) ml/kg/min, respectively. Despite marked deficits in spirometry, preterm-born children have a marginally decreased V˙O2max⁡, which is unlikely to be of great clinical significance. Pediatr Pulmonol. 2015; 50:293-301. © 2014 Wiley Periodicals, Inc.

PS-100 Blood Pressure And Aortic Distensibility As Early Markers Of An Increased Cardiovascular Risk In Preschool Children Born Preterm – Preliminary Data

Background and aims Numerous studies have shown that young adults born preterm have an increased risk of cardiovascular diseases. The aim of this study was to investigate which markers of an increased cardiovascular risk are already present at preschool age in children born preterm. Methods In preschool children born preterm (gestational age less than 32 weeks) and healthy control subjects born at term, blood pressure was determined oscillometrically. Elastic properties of the ascending and descending aorta were calculated using computerised wall contour analysis out of transthoracic M-mode echocardiographic tracings. Results 119 children were examined at 5 to 7 years of age (45 born preterm and 74 children born at term). Preschool children born preterm had significantly higher systolic blood pressure in comparison to preschool children born at term (p Conclusions Children born preterm already have higher systolic blood pressure and decreased distensibility of the descending aorta in comparison to children born at term at preschool age. Preliminary data of this study underline the importance of a continuous and systematical follow-up of children born preterm. Further studies are needed to investigate the clinical relevance of these findings and to find possible preventive measures to lower cardiovascular risk of this population.

O-110 Effect Of Preterm Birth On Adulthood Lung Function: Finnish Birth Registry And Clinical Follow-up Study

<h3>Background</h3> Preterm birth and maternal gestational disorders may adversely impact the pulmonary health of offspring. <h3>Aims</h3> To examine whether exposure to common conditions during fetal-life (preterm birth, gestational hypertension, gestational diabetes) predicts poorer lung function in young adults. <h3>Methods</h3> The ESTER study is a case-control cohort study of individuals born in Northern Finland 1985–89. Study design has two parts: 1) preterm birth included 139 early preterm (&lt;34 weeks) and 239 late preterm (34- &lt;37 weeks) birth subjects; 2) maternal pregnancy disorder included 154 subjects exposed to maternal gestational diabetes (GDM), 136 to pre-eclampsia (PE) and 179 to gestational hypertension (GH). Control group sizes varied. At mean age of 23.5y (±1.7), participants underwent a detailed clinical study including spirometric measurement of FVC, FEV1 and FEV/FVC%, as % from predicted. <h3>Results</h3> Participants born preterm had similar FVC but poorer airflow than term-born. This difference was seen among early and late preterm births (Table1), although for the late preterm, significant only in preliminary models. Lung function in individuals exposed to PE was lower, but this difference disappeared by adjusting for gestational length. Maternal GH or GDM were unrelated to lung function (Table 2). <h3>Conclusion</h3> Shorter gestation and fetal-life conditions are likely to have long-lasting impacts on lung function: preterm-born individuals are likely to experience increased airway obstruction. Even late preterm birth (majority of preterm births), can increase the risk of poor pulmonary outcome. Preeclampsia may have similar effects, adding to the fetal origins of poor pulmonary health. This could be counterbalanced by physical excercise.

Editorial (Thematic Issue: Cardiovascular Drug Therapy in Paediatric Age: From Metabolomics to Clinical Practice)

In adult patients, cardiovascular drugs are widely administered in the treatment of numerous diseases. The indications and doses are strictly codified by international Guidelines, which are periodically updated by the American and European Societies of Cardiology. In paediatric patients, however, the situation is substantially different. The lack of large interventional studies on the use of these compounds has led to a greater uncertainty, with a less extensive administration and more limited indications. Furthermore, some important differences in therapeutic approach for the same diseases are present between the U.S. and Europe. The purpose of this Special Issue is to review the pharmacological treatment of certain heart diseases, such as heart failure, and arterial blood pressure, which can result in both adult and pediatric patients [1, 2]. Differences and similarities have been highlighted. Regarding the differences in medical treatment for the same disease in the U.S. and Europe, it has been emphasized that the regulation of drugs is largely determined not only by scientific considerations, but also by other concerns - legal, cultural - which vary in different parts of the world. Such discrepancies are found even in the informational documents provided by pharmaceutical companies (different in USA and Europe for the same drug) and drug agencies (different between FDA and equivalent agencies in Europe). In this issue of Current Medicinal Chemistry, a specific paper is dedicated to the pharmacological treatment of the patency of ductus arteriosus in neonates, which is still a controversial issue. In fact, notwithstanding ibuprofen appears to be lesser dangerous for newborns than indomethacin, with a similar efficacy in closing the ductus; in a number of countries the latter is still administered to all preterm subjects as a prophylactic tool [3]. An unusual case report is the interesting starting point to perform an extensive literature review about the new indications of beta blockers [4]. In this respect, beta blockers, most specifically propranolol, have serendipitously been shown to induce involution of infantile hemangiomas. Mechanisms of action, target doses, formulation, contraindications and cardiovascular monitoring for beta blockers have been analyzed as well. It has recently been demonstrated that preterm birth is negatively associated with an early onset of cardiovascular diseases. Cardiovascular mortality is higher among former preterm adults than those born at term. This condition is referred to as cardiovascular perinatal programming. Metabolomics, a new and promising technique which allows the systematic study of the complete set of metabolites in a biological sample, has been recently applied to the identification of a possible future cardiovascular system involvement in subjects born preterm. Based on these premises, the purpose of the last review was to analyse the relationship between impaired growth during intrauterine life and adult cardiovascular disease risk and death [5].

Impaired central arterial elasticity in young adults born with intrauterine growth restriction.

Intrauterine growth retardation and prematurity at birth constitute risk factors for future cardiovascular adverse events. Some previous reports have highlighted that subjects born preterm may develop peripheral arterial dysfunction. However, central (aortic) arterial distensibility has not yet been fully investigated in these subjects. Sixty subjects were enrolled: thirty were high grade ex-preterm subjects (10 males [M] and 20 females [F], aged 17-28, mean 20.1±2.5 years). They were compared with 30 healthy, age-matched subjects born at term (C, 10 M and 20 F). Central aortic elasticity was assessed non-invasively by calculating two indexes derived from echocardiographic and blood pressure measures: aortic root distensibility and aortic stiffness index. Aortic distensibility was significantly lower (P<0.0001), and aortic stiffness index was significantly higher (P<0.0001) in former preterm individuals than in controls. The above stated indexes were correlated with birth weight (r=0.78, P<0.0001 and r=-0.41, P=0.02, respectively), as well as with gestational age (r=0.54, P=0.002 and r=-0.37, P=0.04, respectively). When excluding the influence of body mass index, intrauterine growth restriction - expressed as birth weight - remains the only determinant of impaired central arterial elasticity. Since aortic distensibility usually impairs in time, former preterm subjects appear to have a "vascular age" older than their healthy born at term peers. This finding may have important implications for cardiovascular morbidity in later life.

Augmented pulmonary artery pressure response during exercise in adults born extremely preterm, but not in those with bronchopulmonary dysplasia (1089.4)

Advances in perinatal care in the post surfactant era have increased survivability of infants born extremely preterm (&lt;32 weeks gestation), yet long‐term cardiopulmonary consequences of prematurity in adulthood remain largely unexplored. We studied adults who developed new bronchopulmonary dysplasia (BPD, 22.7 yrs), preterm subjects who did not develop BPD (PRE, 21.1 yrs), and fullterm controls (CONT, 22.7 yrs) at rest and during cycle ergometer exercise in the forward leaning aerobar position. Subjects exercised for 3 min at 25%, 50% and 75% of their maximum workload attained at VO2max from a separate visit. We measured metabolic rate, and pulmonary artery systolic pressure (PASP) with ultrasonography, at rest and during exercise. There were no differences in PASP between the groups at rest. At 50% and 75% VO2max, PASP was higher in PRE subjects than in BPD and CONT subjects, which were not significantly different from each other at any exercise intensity. The slope of the PASP to VO2 relationship was significantly greater in PRE subjects compared to BPD and CONT. These data suggest PRE subjects have a reduced ability for the pulmonary vasculature to accommodate increases in cardiac output during exercise compared to CONT and BPD subjects. Further research is needed to determine if this augmented pressure response during exercise may predispose PRE subjects to developing pulmonary arterial hypertension.Grant Funding Source: Supported by: AHA Scientist Development Grant

Cerebrovascular and ischemic heart disease in young adults born preterm: a population-based Swedish cohort study

Preterm birth is associated with overall cardiovascular mortality in young adulthood, but which specific conditions that underlie this association is unknown. We studied mortality and morbidity from cerebrovascular and ischemic heart disease in individuals born preterm. In a nationwide Swedish study, we included 1,306,943 individuals without congenital malformations born between 1983 and 1995, followed from 15 years of age to December 31st, 2010. Of these, 73,489 (5.6 %) were born preterm (<37 weeks of gestation). Cox proportional hazards regression analysis was used to calculate hazard ratios (HR) with 95 % confidence intervals (CI), after adjusting for maternal characteristics and birth weight for gestational age. Of 955 incident cases of cerebrovascular disease, 58 (6.1 %) occurred in preterm born subjects. The corresponding numbers of ischemic heart disease cases were 180 and 13 (7.2 %), respectively. Birth before 32 weeks was associated with a nearly twofold increased risk of cerebrovascular disease; adjusted HR, (95 % CI) = 1.89 (1.01-3.54) compared to term born individuals, whereas individuals born at 32-36 weeks were not at increased risk. Preterm birth was not associated with later ischemic heart disease; no cases of ischemic heart disease were recorded among those born before 32 weeks and the HR (95 % CI) for those born at 32-36 weeks of gestation was 1.45 (0.81-2.57), compared to term-born individuals. Birth before 32 weeks is associated with increased risk of cerebrovascular disease in young adulthood. Our data suggest that cardiovascular health promotion in follow-up programs after very preterm birth may be beneficial.

Inter-reflux and bolus clearance times in non-pathologic pediatric patients: data support computational models

Previous contributions suggested that gastroesophageal reflux can be modeled in terms of a Poisson process. This study aims to provide empirical data to validate this statement in pediatric patients so that computational models can be broadly used as an alternative for research. A retrospective review of 63 pediatric patients who underwent 24-hour impedance-pH monitoring to discard gastroesophageal reflux disease was conducted in this study. Patients were grouped by age as preterm (21), infants (21), and children (21). All the tracings were analyzed by a trained physician who identified the reflux entry and the bolus clearance time of each episode. The time between reflux episodes was tested against three probability distributions (gamma, exponential and inverse Gaussian) whereas the bolus clearance time was tested against a normal probability distribution. Parameters were estimated using the maximum likelihood method. The Kolmogorov-Smirnov test and the Kullback-Leibler divergence were computed to evaluate the goodness of fit. One-way analysis of variance was applied to compare results along the three groups. Exponential fitting for inter-reflux time was successful in 90.48% of children older than 1 year. The overall reflux rate was 57.58 reflux episodes per day whereas the mean bolus clearance time ranged between 10.87 in preterm subjects and 12.05 in children, showing a good Gaussian fitting. The time between reflux episodes can be modeled in terms of a Poisson process in non tube-fed patients, whereas the bolus clearance time follows a normal distribution in all cases.

Oxidatively modified LDL particles in the human placenta in early and late onset intrauterine growth restriction

IntroductionReduced serum LDL concentrations have been observed in pregnancies complicated by intrauterine growth restriction (IUGR) as compared to healthy pregnant women. Since increased oxidative stress has been suggested to play a major role in IUGR we now hypothesized that the lower LDL concentrations are accompanied by an accumulation of oxidized LDLs in the placenta. MethodsFifteen placentas of near term and preterm born IUGR, and a gestational age matched control group (CTRL n = 15) were analyzed. Placental minimal modified LDL and fully oxidized LDL particles were measured by ELISA, and by immunohistochemistry, and were related to maternal and fetal serum lipid profiles. ResultsWe found fully oxidized LDL but not minimal modified LDL being increased in the preterm subgroup of IUGR (n = 10) as compared to preterm CTRL (n = 10; p < 0.05). An increased staining intensity of trophoblasts in preterm IUGR subjects as compared to preterm CTRL has been confirmed by immunohistochemistry (p < 0.05). No difference could be found between the term groups (n = 5 each). Correlation analysis revealed an inverse relationship of maternal LDL (ρ = −0.49, p = 0.03) and fetal HDL cholesterol (ρ = −0.46, p = 0.04) with placental fully oxidized LDL particle concentration within preterms. DiscussionIUGR is a heterogeneous entity. Different pathomechanisms seem to underlie the disease in preterm and term subjects with oxidation of LDL within the placenta possibly taking place in preterm IUGRs. ConclusionsWe conclude that the reduced maternal LDL cholesterol concentration in IUGR pregnancies is attributed to increased accumulation of oxidized LDL particles within the placenta at least in early onset IUGR.

Abstract 185: Transient Neonatal High Oxygen Exposure Leads to Cardiac Dysfunction and Renin Angiotensin System Activation in Rats

Preterm infants are exposed to high oxygen (O2) pressure (relative to intrauterine levels) leading to systemic oxidative stress and impaired vascular development; as children and adults, preterm born subjects have higher blood pressure. In rats, high O2 exposure induces vascular dysfunction, in part mediated by the renin angiotensin system (RAS). However, impact of neonatal high O2 exposure on heart development and whether RAS activation prevails in the heart is unknown. We aimed to assess early heart alterations and activation of RAS after neonatal high O2 exposure. METHODS AND RESULTS: Sprague-Dawley pups were kept with their mother in 80% O2 (O2, n=8) or room air (Ctrl, n=8) from days 3-10 of life. Hearts were extracted at day 3 (pre O2-exposure, P3), day 5 (during, P5), 10 (after, P10) and 4 wks to assess myocardium hypertrophy (HE), fibrosis (Masson’s trichrome) and RAS components gene expressions by RT-PCR. Echocardiography was performed at 4 weeks to assess heart function. RAS components mRNA expression in O2 vs Ctrls shows up-regulation of AT1a and ACE2 genes at P5 (AT1a: 152±28 vs 58±16/ACE2: 140±20 vs 77±6% of P3) and P10 (AT1a: 374±35 vs 250±30 /ACE2: 326±70 vs 208±18% of P3) relative to values at P3. With age, AT1b and AT2 expressions decrease in Ctrls, whereas are maintained in O2-exposed rats to values similar to P3 (Ctrl vs O2, P5: AT1b: 18±5 vs 71±12/AT2: 48±20 vs 120±16; P10: AT1b: 33±9 vs 105±26/AT2: 27±8 vs 77±7% of P3). At P10, cardiomyocyte surface area is increased in O2 vs Ctrls (4.9±0.2 vs 2.9±0.1 μm2). At 4 wks, O2 group show increased fibrosis (49±4 vs 29±2 % pixels), left ventricular (LV) cavity diameter (3.6±0.2 vs 3.0±0.1 mm) and systolic dysfunction by decreased fraction of shortening (39±2 vs 47±2 %). AT1b gene expression (2.6±1.7 vs 0.3±0.2) is increased and AT2 receptor (7.5±0.9 vs 6.0±0.6) is decreased in O2 group vs Ctrl. CONCLUSION: Neonatal O2 exposure activates RAS in hearts. AT1 receptor is up-regulated at all ages studied in O2-exposed rat hearts while AT2 is up-regulated at P5 and P10. At 4 wks, AT1/AT2 imbalance prevails in O2 group hearts along with LV dysfunction and enhanced fibrosis and hypertrophy. RAS activation by neonatal O2-exposure might significantly impact in heart development and programming of cardiac dysfunction in rats.

Pune low birth weight study — Birth to adulthood — Cognitive development

To assess the cognitive development of non-handicapped low birth weight (LBW) infants at 18 years. Prospective cohort study. Infants born between 1987 - 1989 with birth weight less than 2000 g and discharged from a neonatal special care unit were followed up till the age of 18 years. The intelligence quotient (IQ) was determined by Ravens progressive matrices. Assessment of adjustment and aptitude was done. The cohort of 161 LBW infants was divided into three groups according to their gestation - preterm SGA (n=61), full term SGA (n=30) and preterm AGA (n=70). 71 full term AGA infants served as controls. The IQ of the study group (Percentile 39.3) was significantly lower than that of controls (Percentile 54.9) (P=0.002). Preterm SGA subjects had the lowest IQ (Percentile 35.5), though just within normal limits. Males from the study group had significantly lower IQ than male controls (P=0.03). The IQ of PTSGA subjects of college educated mothers (P=0.004) and belonging to higher socio-economic class (P=0.04) was significantly higher. On the differential aptitude test, PTSGA subjects were poor in speed and mechanical reasoning. The 18 year IQ could be best predicted by IQ at 6 and 12 years. Preterm SGA children have the lowest IQ at 18 years, males have lower IQ. Maternal education and socio-economic status have great impact on cognitive development. Good prediction of the 18 year IQ can be done by the 6 and 12 year IQ.

Cerebral Magnetic Resonance Imaging Findings in Children Born Extremely Preterm, Very Preterm, and at Term

The aim of this study was to compare findings on cerebral MRI scans of infants born extremely preterm (i.e., gestation < 28 weeks, very preterm; gestation 28-31 weeks) and at term. MRI scans obtained in a cohort of 29 extremely preterm children at 11 years, 51 very preterm young adults at 19 years, and respective term-born controls were scored according to presence and degree of MRI pathology. MRI pathology was found in 76% of the extremely preterm children vs 31% of their controls (odds ratio 4.3; 95% confidence interval, 1.5-137.5) and in 55% of the very preterm group vs 19% of their controls (odds ratio 5.2; 95% confidence interval, 2.5-10.9). The distribution of moderate and severe pathology did not differ among the groups. The extremely preterm, very preterm, and term subjects shared the same morphological pathology, revealing no specific preterm MRI pattern, but both premature cohorts had higher frequencies. Differences were mainly limited to mild pathology. Whether MRI lesions were more common in the extremely preterm than in the very preterm group is uncertain as the difference in frequency was similar in the two control groups, suggesting a lack of objective criteria for differentiating mild pathology from normality or that MRI scans normally differ at 11 and 19 years of age.

Neonatal Physiological and Behavioral Stress During Neurological Assessment

Physiological and behavioral effects of evaluative handling procedures were studied in 72 newborn infants: 36 preterm (30-35 weeks of gestation) and 36 full-term neonates (39-41 weeks of gestation). While the neurological assessment was physiologically and behaviorally destabilizing to both age groups, preterm subjects had higher heart rate (P < .001), greater increase in blood pressure (P < .01); decreased peripheral oxygenation inferred from mottled skin color (P < .001); and higher frequencies of finger splay (P < .001), arm salute (P < .01), hiccoughs (P < .001), and yawns (P < .001) than full-term subjects. Both groups demonstrated greater stress during the neuromotor phase of testing. Neonatal care professionals must scrutinize the diagnostic benefit, reliability, safety, and timing of neurological assessment given expected physiological and behavioral changes in stable preterm neonates.

195 Regional Changes of Cortical Thickness at 6 Years of Age in Preterm Born Children

BackgroundThe growing incidence of prematurely born children and the improvement of survival rates have been associated with highly problematic long term neurodevelopmental outcomes. Brain structural alterations associated with these mainly...

Pain Tolerance and Pain Perception in Adolescents Born Extremely Preterm

Neonatal pain experiences have been associated with altered processing and perception of pain in later life, but findings tend to vary among studies. We have compared experimental pain tolerance and subjective health complaints in a population-based cohort of adolescents born extremely preterm to that of matched term controls. Subjects performed a standardized cold pressor task (hand in ice water) and completed validated questionnaires regarding current subjective health complaints, including pain issues. Thirty-one (89%) of 35 eligible preterm subjects (mean gestational age 26.8 weeks) and 28 (80%) term controls participated in this follow-up study at mean age 17.8 years. Ten (32%) subjects born preterm versus 17 (61%) born at term reached the ceiling time of 180 seconds immersion time in the ice water, a hazard ratio for early withdrawal of 2.05 (95% confidence interval, 1.72 to 2.44), with males explaining most of the difference. For subjects born preterm, the risk of early withdrawal decreased significantly with more days of mechanical ventilation, more pain events, and more doses of morphine during the newborn period. Subjective pain ratings during the cold pressor task as well as health-related complaints and pain issues reported in the questionnaires were similar in the preterm and term groups. PerspectiveDespite reduced tolerance to experimental pain, subjects born preterm scored their pain experiences similarly to those of term controls. Surprisingly, preterm subjects exposed to most painful and invasive neonatal experiences and also to most doses of morphine had a pain response at follow-up most closely resembling that of the control group.