Term-born Adolescents Research Articles

Preterm birth and the risk of multimorbidity in adolescence: a multiregister-based cohort study

Multimorbidity affects people of all ages, but the risk factors of multimorbidity in adolescence are unclear. The aim of this study was to examine preterm birth (<37 weeks) as a shared risk factor for multiple health outcomes and the role of gestational age (degree of prematurity) in the development of increasingly complex multimorbidity (two, three, or four health outcomes) in adolescence (age 10-18 years). We used population-wide data from Finland (1 187 610 adolescents born 1987-2006) and Norway (555 431 adolescents born 1998-2007). Gestational age at birth was ascertained from medical birth registers and categorised as 23-27 weeks (extremely preterm), 28-31 weeks (very preterm), 32-33 weeks (moderately preterm), 34-36 weeks (late preterm), 37-38 weeks (early term), 39-41 weeks (term, reference category) and 42-44 weeks (post-term). Children who died or emigrated before their 10th birthday, and those with missing or implausible data on gestational age, birthweight, or covariates, were excluded. Health outcomes at age 10-18 years were ascertained from specialised health care and mortality registers. We calculated hazard ratios (HRs) and population attributable fractions (PAFs) with 95% CIs for multiple health outcomes during adolescence. Individuals were followed up from age 10 to 18 years (mean follow-up: 6 years, SD: 3 years). Preterm birth was associated with increased risks of 20 hospital-treated malignant, cardiovascular, endocrinological, neuropsychiatric, respiratory, genitourinary, and congenital health outcomes, after correcting for multiple testing and ignoring small effects (HR <1·2). Confounder-adjusted HRs comparing preterm with term-born adolescents were 2·29 (95% CI 2·19-2·39) for two health outcomes (PAF 9·0%; 8·3-9·6), and 4·22 (3·66-4·87) for four health outcomes (PAF 22·7%; 19·4-25·8) in the Finnish data. Results in the Norwegian data showed a similar pattern. We observed a consistent dose-response relationship between an earlier gestational age and elevated risks of increasingly complex multimorbidity in both datasets. Preterm birth is associated with increased risks of diverse multimorbidity patterns at age 10-18 years. Adolescents with a preterm-born background could benefit from diagnostic vigilance directed at multimorbidity and a multidisciplinary approach to health care. European Union Horizon 2020, Academy of Finland, Foundation for Pediatric Research, Sigrid Jusélius Foundation, Signe and Ane Gyllenberg Foundation.

No long-term effects of antenatal synthetic glucocorticoid exposure on epigenetic regulation of stress-related genes

Antenatal synthetic glucocorticoid (sGC) treatment is a potent modifier of the hypothalamic-pituitary-adrenal (HPA) axis. In this context, epigenetic modifications are discussed as potential regulators explaining how prenatal exposure to GCs might translate into persistent changes of HPA axis “functioning”. The purpose of this study was to investigate whether DNA methylation and gene expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4) may mediate the persistent effects of sGC on cortisol stress reactivity that have been previously observed. In addition, hair cortisol concentrations (hairC) were investigated as a valid biomarker of long-term HPA axis activity. This cross-sectional study comprised 108 term-born children and adolescents, including individuals with antenatal GC treatment and controls. From whole blood, DNA methylation was analyzed by targeted deep bisulfite sequencing. Relative mRNA expression was determined by RT-qPCR experiments and qBase analysis. Acute stress reactivity was assessed by the Trier Social Stress Test (TSST) measuring salivary cortisol by ELISA and hairC concentrations were determined from hair samples by liquid chromatography coupled with tandem mass spectrometry. First, no differences in DNA methylation and mRNA expression levels of the stress-associated genes between individuals treated with antenatal sGC compared to controls were found. Second, DNA methylation and mRNA expression levels were neither associated with cortisol stress reactivity nor with hairC. These findings do not corroborate the belief that DNA methylation and mRNA expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4) play a key mediating role of the persistent effects of sGC on HPA axis functioning.

Etiology of persistent mathematics difficulties from childhood to adolescence following very preterm birth

ABSTRACT Children born very preterm (VP; <32 weeks’ gestation) have poorer mathematics achievement than term-born peers. This study aimed to determine whether VP children’s mathematics difficulties persist from primary to secondary school and to explore the nature of mathematics difficulties in adolescence. For this study, 127 VP and 95 term-born adolescents were assessed at age 11–15 years. Mathematics achievement was assessed using the Wechsler Individual Achievement Test-II. Specific mathematics skills and general cognitive skills were assessed using standardized and experimental tests. VP adolescents had poorer mathematics achievement than term-born adolescents (−10.95 points; 95% CI −16.18, −5.73) and poorer number fact knowledge, understanding of arithmetic concepts, written arithmetic, counting, reading and writing large numbers, and algebra. Between-group differences in mathematics skills were no longer significant when working memory and visuospatial skills were controlled for (p’s >0.05), with the exception of writing large numbers and conceptual understanding of arithmetic. In a previous study, 83 of the VP adolescents and 49 of the term-born adolescents were assessed at age 8–10 years using measures of the same skills. Amongst these, the between-group difference in mathematics achievement remained stable over time. This study extends findings of a persistent deficit in mathematics achievement among VP children over the primary and secondary school years, and provides evidence of a deficit in factual, procedural and conceptual mathematics skills and in higher order mathematical operations among VP adolescents. We provide further evidence that VP children’s mathematics difficulties are driven by deficits in domain-general rather than domain-specific cognitive skills.

Physical Activity, Mental Health, and Well-Being in Very Pre-Term and Term Born Adolescents: An Individual Participant Data Meta-Analysis of Two Accelerometry Studies.

This study examined whether physical activity is associated with better mental health and well-being among very preterm (≤32 weeks) and term born (≥37 weeks) adolescents alike or whether the associations are stronger in either of the groups. Physical activity was measured with accelerometry in children born very preterm and at term in two cohorts, the Basel Study of Preterm Children (BSPC; 40 adolescents born ≤32 weeks of gestation and 59 term born controls aged 12.3 years) and the Millennium Cohort Study (MCS; 45 adolescents born ≤32 weeks of gestation and 3137 term born controls aged 14.2 years on average). In both cohorts, emotional and behavioral problems were mother-reported using the Strengths and Difficulties Questionnaire. Subjective well-being was self-reported using the Kidscreen-52 Questionnaire in the BSPC and single items in the MCS. Hierarchical regressions with ‘preterm status × physical activity’-interaction effects were subjected to individual participant data (IPD) meta-analysis. IPD meta-analysis showed that higher levels of physical activity were associated with lower levels of peer problems, and higher levels of psychological well-being, better self-perception/body image, and school related well-being. Overall, the effect-sizes were small and the associations did not differ significantly between very preterm and term born adolescents. Future research may examine the mechanisms behind effects of physical activity on mental health and wellbeing in adolescence as well as which type of physical activity might be most beneficial for term and preterm born children.

Social functioning questionnaires of adolescents born preterm show average profiles and attenuated sex differences.

Prematurity has been shown to affect social competence in children and adults. Our aim was to evaluate profiles of self-reported social behaviours and loneliness in preterm- and term-born adolescents. Preterm (≤1500g and, or, <32 gestational weeks)- and term-born infants were recruited in Turku University Hospital from 2001 to 2006. The Multisource Assessment of Children's Social Competence Scale and the Peer Network and Dyadic Loneliness Scale were completed at the age of 11. Profiles of social competence and loneliness were labelled as low, average or high. A total of 172 preterm-born and 134 term-born adolescents returned the questionnaires. Most frequently, preterm adolescents reported a profile of average social competence and average levels of loneliness. Preterm-born boys reported a profile of low social functioning less often (preterm-born 36% vs. term-born 54%), and preterm-born girls reported a profile of high social functioning less frequently (preterm-born 26% vs. term-born 37%) than same-sex controls. Sex differences in social functioning profiles were smaller in preterm than term-born adolescents. The majority of young adolescents born preterm reported a high or average social functioning profile irrespective of sex. Prematurity seems to level out differences between the sexes.

Comparison of Blood Pressure and Kidney Markers between Adolescent Former Preterm Infants and Term Controls.

Background: Preterm infants are at an increased risk of developing hypertension and chronic kidney disease later in life. No recommendations exist for blood pressure (BP) and renal follow up for these patients. Aim: To compare BP and serum and urinary kidney markers between preterm-born adolescents and term-born controls. Methods: BP measurements in 51 preterm-born (≤32 weeks gestational age) and 82 term-born adolescents at the age of 10–15 years were conducted. Stepwise regression analysis explored the association between BP and participant characteristics. Kidney markers measured in the serum and urine were creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and uromodulin. Kidney markers measured in the serum were cystatin C, beta-2 microglobulin, and beta trace protein. Results: Systolic BP was significantly higher in preterm boys compared with term boys, but not in girls, and low birth weight was associated with higher BP in boys. In the preterm group, maternal hypertension/preeclampsia and adolescent height were associated with higher systolic BP. Serum creatinine and NGAL were significantly higher in the preterm group. Conclusions: Our study confirms an inverse sex-dependant relationship between birth weight and BP at adolescent age. The higher serum creatinine and NGAL in the preterm group may indicate that premature birth affects kidney function in the long term.

Blunted cardiac output response to exercise in adolescents born preterm.

Premature birth is associated with lasting effects, including lower exercise capacity and pulmonary function, and is acknowledged as a risk factor for cardiovascular disease. The aim was to evaluate factors affecting exercise capacity in adolescents born preterm, including the cardiovascular and pulmonary responses to exercise, activity level and strength. 21 preterm-born and 20 term-born adolescents (age 12-14years) underwent strength and maximal exercise testing with thoracic bioimpedance monitoring. Baseline variables were compared between groups and ANCOVA was used to compare heart rate, cardiac output (Q) and stroke volume (SV) during exercise between groups while adjusting for body surface area. Preterm-borns had lower maximal aerobic capacity than term-borns (2.0 ± 0.5 vs. 2.5 ± 0.5 L/min, p = 0.01) and lower maximal power (124 ± 26 vs. 153 ± 33 watts, p < 0.01), despite similar physical activity scores. Pulmonary function and muscular strength did not differ significantly. Although baseline Q and SV did not differ between groups, preterm adolescents had significantly lower cardiac index (Qi) at 50, 75 and 100% of maximal time to exhaustion, driven by SV volume index (SVi, 50% max time: 53.0 ± 9.0 vs. 61.6 ± 11.4; 75%: 51.7 ± 8.4 vs. 64.3 ± 11.1; 100%: 51.2 ± 9.3 vs. 64.3 ± 11.5ml/m2, all p < 0.01), with similar heart rates. Otherwise healthy and physically active adolescents born very preterm exhibit lower exercise capacity than term-born adolescents. Despite similar baseline cardiovascular values, preterm-born adolescents demonstrate significantly reduced Qi and SVi during incremental and maximal exercise.

Impairments in error processing and their association with ADHD symptoms in individuals born preterm.

Preterm birth is associated with heightened risk for attention-deficit/hyperactivity disorder (ADHD)-like symptoms and neurocognitive impairments, including impairments in performance monitoring. Here, we investigate the cognitive and neurophysiological processes from a performance-monitoring task in preterm-born adolescents and examine whether these processes in preterm-born adolescents reflect identical neurophysiological impairments to those observed in term-born adolescents with ADHD. We compared 186 preterm-born individuals to 69 term-born individuals with ADHD and 135 term-born controls on cognitive-performance measures and event-related potentials (ERPs) of conflict monitoring (N2) and error processing (ERN, Pe) from a flanker task. Preterm-born adolescents demonstrated reduced N2, ERN and Pe amplitudes, compared to controls, and similar ERN and Pe impairments to term-born adolescents with ADHD. While ADHD symptoms correlated with ERN amplitude at FCz among the preterm-born, ERN amplitude at Fz, N2 and Pe amplitude were not associated with ADHD symptoms. Preterm-born individuals show impairments on neurophysiological indices of conflict monitoring (N2) and error processing (ERN and Pe). Early neurophysiological error processing may be a marker underlying the processes linked to the increased risk for ADHD among preterm-born individuals. Error detection processes are malleable and potential targets for non-pharmacological interventions. Preterm-born individuals are likely to benefit from early interventions.

Abstract P306: Preterm Birth is Associated with Increased Blood Pressure and Increased Urinary Angiotensinogen in Young Adults

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality and hypertension (HTN) is a major risk factor for CVD. Preterm birth is an emerging risk factor for both CVD and HTN, but the underlying mechanisms are poorly described. The renin-angiotensin system (RAS) plays a key role in HTN and CVD, and adolescents born preterm have higher blood pressure (BP) with a shift in the balance of the classical and alternative pathways of the RAS exhibited as increased angiotensin II and reduced angiotensin-(1-7) as compared to term-born adolescents. Although numerous factors influence the expression of angiotensins, the precursor protein angiotensinogen in the kidney is implicated in the development of HTN and CVD and may contribute to higher angiotensin II. As the status of renal angiotensinogen in individuals born preterm is unknown, we hypothesized that urinary angiotensinogen is increased in young adults born preterm as compared to their term-born peers. Methods: We compared urinary excretion of angiotensinogen corrected for urine creatinine and systolic and diastolic BP in 142 young adults (mean age 19.9 years) born preterm with very low birth weight (&lt;1500 g) to 32 young adults born term using Wilcoxon Rank-Sum test and t-test. We used generalized linear models to compare the ln(x) urinary angiotensinogen between the preterm and term groups adjusted for the potentially confounding factors race, maternal hypertensive pregnancy, and maternal smoking during pregnancy. Results: Compared to term, subjects born preterm had higher median urinary angiotensinogen (0.02 μg/g, IQR 0.01 to 0.04 vs. 0.01 μg/g, IQR 0.004 to 0.01, p &lt; 0.001) and higher mean systolic BP (111 mmHg, SD 11 vs. 106 mmHg, SD 10, p = 0.03). On crude and adjusted analyses urinary angiotensinogen was associated positively with preterm birth (crude β : 0.82, 95% CI 0.47 to 1.16; adjusted β : 0.79, 95% CI 0.39 to 1.18). Discussion: In addition to higher BP, young adults born preterm demonstrated increased urinary angiotensinogen as compared to their term-born peers. Preterm birth may induce programming of the renal RAS leading to higher angiotensinogen and a higher angiotensin-to-angiotensin-(1-7) ratio, potentially contributing to the increased risk of HTN in individuals born preterm.

Long-term impacts of prenatal synthetic glucocorticoids exposure on functional brain correlates of cognitive monitoring in adolescence

The fetus is highly responsive to the level of glucocorticoids in the gestational environment. Perturbing glucocorticoids during fetal development could yield long-term consequences. Extending prior research about effects of prenatally exposed synthetic glucocorticoids (sGC) on brain structural development during childhood, we investigated functional brain correlates of cognitive conflict monitoring in term-born adolescents, who were prenatally exposed to sGC. Relative to the comparison group, behavioral response consistency (indexed by lower reaction time variability) and a brain correlate of conflict monitoring (the N2 event-related potential) were reduced in the sGC exposed group. Relatedly, source localization analyses showed that activations in the fronto-parietal network, most notably in the cingulate cortex and precuneus, were also attenuated in these adolescents. These regions are known to subserve conflict detection and response inhibition as well as top-down regulation of stress responses. Moreover, source activation in the anterior cingulate cortex correlated negatively with reaction time variability, whereas activation in the precuneus correlated positively with salivary cortisol reactivity to social stress in the sGC exposed group. Taken together, findings of this study indicate that prenatal exposure to sGC yields lasting impacts on the development of fronto-parietal brain functions during adolescence, affecting multiple facets of adaptive cognitive and behavioral control.

Blood Pressure and Stroke Volume Response to Exercise in Adolescent Children Born Very Preterm

IntroductionMultiple studies have shown that adolescents born preterm have exercise intolerance. The etiology of the intolerance remains controversial. It has been demonstrated that infants and young adults born preterm have higher blood pressure (BP) than term‐borns of the same age. Very little is known about the effects of premature birth on cardiovascular function in adolescent children. The purpose of this study was to investigate BP and stroke volume responses to exercise in children. We hypothesized that adolescent children born prematurely would have an augmented BP response with a lower stroke volume response to exercise compared to children born at term.MethodsSubjects were adolescent children born in 2003 and 2004. Preterm subjects were born &lt;33 weeks gestation, and term‐born subjects were born &gt;38 weeks gestation. 21 adolescent children born premature and 20 term‐born controls completed the study. Measurements of systolic BP (SBP) and diastolic BP (DBP) were recorded at rest and during supine submaximal exercise (70% of predetermined maximal wattage). BP data was obtained using a brachial artery cuff every 2 minutes during a 10 minute rest period, and during a 10 minute submaximal exercise period. Rest and exercise mean arterial BP (MABP), SBP and DBP were averaged for every subject. A 3T cardiac MRI was used to determine left ventricular stroke volume using aortic blood flow from a 2D flow cine sequence during rest and exercise using Segment post‐processing software. Stroke volume was calculated the average of aortic flow waveforms from one cardiac cycle. Unpaired t‐tests were used to compare results between controls and preterms.ResultsChildren born preterm had higher SBP (114.8±5.7 mmHg vs. 109.7±4.7 mmHg respectively: p = 0.006), DBP (65.8±4.7 mmHg vs. 60.0±5.3 mmHg respectively: p = 0.001) and MABP (82.2±3.7 mmHg vs. 76.6 ±4.0 mmHg respectively: p &lt; 0.001) compared to term born children at rest. Contrary to our hypothesis, there was no difference in BP response to exercise. There was no difference in SV at rest between preterm and term‐born adolescents (73.0±22.7 vs. 81.6±9.6 ml respectively: p = 0.30). SV during exercise was significantly lower in preterms than controls (66.3±9.0 vs. 99.1±15.6 ml respectively: p = 0.02), resulting in a blunted SV response to exercise in preterms compared to controls (ΔSV; 2.4±1.8 vs. 17.5±6.6 ml respectively: p = 0.02).DiscussionWe found that adolescent children born preterm have higher BP at rest than term‐born controls, with no significant difference during exercise. Elevated BP, while not considered hypertensive, was in the upper limits of what is considered normal for this age group. While we did not find a difference in SV between preterm and term‐born controls at rest, we found that there was a blunted SV response to exercise in preterms. The inability to augment SV appropriately to exercise is indicative of cardiovascular or autonomic dysfunction. In combination, the higher BP and blunted SV response to exercise suggests a need for further cardiovascular investigations in this population.Support or Funding InformationNIH‐NHLBI R01–HL115061This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Autonomic function and blood pressure in adolescents born preterm

IntroductionPreterm birth affects 10% of births in the United States. The nervous and cardiovascular systems undergo significant development in the third trimester. The autonomic nervous system (ANS) plays a significant role in regulating heart rate and blood pressure. Parasympathetic nervous activity (PNA) increases throughout the third trimester, and preterm birth is known to result in lower PNA during infancy. Preterm birth is known to put young adults at greater risk of cardiac autonomic dysfunction, hypertension and cardiac hypertrophy. However, little is known about the onset of these cardiovascular abnormalities. Autonomic dysfunction and high blood pressure are associated with increased risk of cardiovascular disease. The purpose of our research is to investigate the long term effects of preterm birth on autonomic function and blood pressure at rest in adolescents born preterm and age‐matched term‐born controls. We hypothesize that preterms will have lower autonomic function, as determined by heart rate variability at rest, and elevated blood pressure compared to term‐born adolescents.Methods21 children born preterm (birthweight &lt;1500 g, gestational age &lt;32 weeks) and 20 children born full term (gestational age &gt;38 weeks) were studied. Heart rate variability measurements were obtained during a 15 minute supine resting period using a 3‐lead ECG. The standard deviation of R‐R interval (SDRR) and the root mean squared of successive differences (RMSSD) were calculated using PowerLab software. Blood pressures were obtained every 2 minutes during a 10 minute supine rest period using a brachial artery cuff, and the mean arterial blood pressure (MABP), systolic blood pressure (SBP), diastolic blood pressure (DBP) were determined. The relationship between MABP and RMSSD was determined using a linear regression. Results between groups were compared using Mann‐Whitney tests.ResultsPreterms had significantly lower birthweights than the controls (1097 ± 274 v 3497 ± 366 g, respectively, p&lt;0.001) and had lower gestational age (27.86 ± 2.10 v 39.74 ± 0.87 weeks, respectively, p&lt;0.001). Preterms had significantly higher MABP (82.2 ± 3.7 v 76.4 ± 4.0 mmHg, respectively, p&lt;0.001), DBP (65.8 ± 4.7 v 59.6 ± 5.1 mmHg, p=&lt;0.001), and SBP than controls (114.8 ± 5.7 v 109.9 ± 4.8 mmHg, p=.009). Preterms had lower HRV, SDRR (69.1 ± 33.8 v 110.1 ± 33.0 ms, p=.008), and RMSSD (58.8 ± 38.2 v 101.5 ± 36.2 ms, p=.012). There was a negative relationship between RMSSD and MABP (r2=0.324, p=0.007).DiscussionOur results demonstrate that adolescents born prematurely have lower HRV and higher resting blood pressure. Both autonomic dysfunction and elevated blood pressure are known to be correlated with increased risk of cardiovascular disease. Furthermore, we found a negative relationship between HRV and blood pressure in our population. Our results suggest that preterm individuals have higher sympathetic activity, and the inverse relationship between HRV and BP suggests that higher sympathetic vascular tone due to autonomic dysfunction leads to elevated BP. The individuals in our study were free of known cardiovascular or respiratory disease, and both groups were very active. Our results suggest that otherwise healthy preterm adolescents are potentially at increased risk of developing cardiovascular disease and further study is warranted.Support or Funding InformationNIH‐NHLBI R01–HL115061This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Altered EEG spectral power during rest and cognitive performance: a comparison of preterm-born adolescents to adolescents with ADHD

Preterm birth has been associated with an increased risk for ADHD-like behavioural symptoms and cognitive impairments. However, direct comparisons across ADHD and preterm-born samples on neurophysiological measures are limited. The aim of this analysis was to test whether quantitative EEG (QEEG) measures identify differences or similarities in preterm-born adolescents, compared to term-born adolescents with and without ADHD, during resting-state and cognitive task conditions. We directly compared QEEG activity between 186 preterm-born adolescents, 69 term-born adolescents with ADHD and 135 term-born control adolescents during an eyes-open resting-state condition (EO), which previously discriminated between the adolescents with ADHD and controls, and during a cued continuous performance task (CPT-OX). Absolute delta power was the only frequency range to demonstrate a significant group-by-condition interaction. The preterm group, like the ADHD group, displayed significantly higher delta power during EO, compared to the control group. In line with these findings, parent-rated ADHD symptoms in the preterm group were significantly correlated with delta power during rest. While the preterm and control groups did not differ with regard to absolute delta power during CPT-OX, the ADHD group showed significantly higher absolute delta power compared to both groups. Our results provide evidence for overlapping excess in the absolute delta range in preterm-born adolescents and term-born adolescents with ADHD during rest. During CPT-OX, preterm-born adolescents resembled controls. Increased delta power during rest may be a potential general marker of brain trauma, pathology or neurotransmitter disturbances.

Prevalence of Gum Disease in Preterm and Term Adolescents

Aim: Assess and compare the prevalence of gum disease in preterm and term-born adolescents. Materials and Methods: A cross section study was conducted involving adolescents between the ages of 10 and 19. One group of 120 preterm-born adolescents and a g roup of 149 term-born adolescents (control). Physicians conducted physical exams in these groups to measure pubertal stages, dividing the patients into 3 subgroups according to Tanner’s stages. The dental exam was conducted by four specialist dentist examiners. The community periodontal index of treatment need and measurements of plaque index were conducted. Results: Comparing the preterm-born adolescents to the termborn ones, it was verified that the term group presented a higher prevalence of gum disease than the preterm group and the difference was statistically significant (p < 0.01). There was no statistically significant difference in the prevalence of gum disease when comparing the preterm-born adolescents with weight at birth < 1500 to the ones weighing ≥ 1500 grams. The preterm-born adolescent group did not present significant difference in the prevalence of gum disease in relation to Tanner’s subgroups; however, when both groups were assessed together, it was verified that females, after the growth spurt, present a 3.7 times higher risk of gum disease. Conclusion: The ranges of weight upon birth, low weight and very low weight did not impact the prevalence of gum disease in premature adolescents. Growth spurt increases the risk of developing periodontal disease in the female gender. Girls, after the spurt, tend to have more gum disease than girls before the spurt.

Growth attainment in German children born preterm, and cardiovascular risk factors in adolescence. Analysis of the population representative KiGGS data.

To compare the growth attainment of preterm children and their cardiovascular risk factors at adolescence with the values measured in term children in Germany. About 17,641 children aged 0 to <18 years were studied between 2003 and 2006 in the population representative German KiGGS survey ("German Health Interview and Examination Survey for Children and Adolescents") using questionnaires, physical examinations, standardized anthropometric and blood pressure measurements, and blood sample analyses. Analysis of covariance (ANCOVA) was employed for the analyses of anthropometric parameters. About 11.8% of the 16,737 children with complete and valid data had been born preterm. After adjustment for covariates the estimated z-scores over the total age range were larger in term compared to preterm children for length/height (P<0.001; estimated difference B=0.277, 95% CI 0.191-0.362), head circumference (P<0.001; B=0.238, 95% CI 0.144-0.333), BMI (P=0.001; B=0.160, 95% CI 0.069-0.252), and skinfold thickness (P=0.220; B=0.058, 95% CI -0.035 to 0.151). The onset of pubertal development was slightly (but not significantly) earlier in term compared to preterm children. At 14 to <18 years, anthropometric and biochemical indicators of cardiovascular diseases were not worse in preterm compared to term children. Preterm-born German adolescents remained significantly shorter, lighter, and had a smaller head circumference than term-born adolescents, but the risk indicators for cardiovascular diseases were not higher.

Association of Preterm Birth With Attention-Deficit/Hyperactivity Disorder–Like and Wider-Ranging Neurophysiological Impairments of Attention and Inhibition

ObjectivePreterm birth has been associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD)–like symptoms and cognitive impairments similar to those seen in ADHD, including attention and inhibitory control difficulties. Yet data on direct comparisons across ADHD and preterm birth on cognitive-neurophysiological measures are limited.MethodWe directly compared 186 preterm-born adolescents to 69 term-born adolescents with ADHD and 135 term-born controls on cognitive-performance and event-related potential measures associated with attentional and inhibitory processing from a cued continuous performance test (CPT-OX), which we have previously shown to discriminate between the adolescents with ADHD and controls. We aimed to elucidate whether the ADHD-like symptoms and cognitive impairments in preterm-born individuals reflect identical cognitive-neurophysiological impairments in term-born individuals with ADHD.ResultsGo-P3 amplitude was reduced, reflecting impaired executive response control, in preterm-born adolescents compared to both controls and adolescents with ADHD. Moreover, in preterm-born adolescents, as in term-born adolescents with ADHD, contingent negative variation amplitude was attenuated, reflecting impairments in response preparation compared to controls. Although the ADHD group showed significantly increased NoGo-P3 amplitude at FCz compared to preterm group, at Cz preterm-born adolescents demonstrated significantly decreased NoGo-P3 amplitude compared to the control group, similar to term-born adolescents with ADHD.ConclusionThese findings indicate impairments in response preparation, executive response control, and response inhibition in preterm-born adolescents. Although the response preparation and response inhibition impairments found in preterm-born adolescents overlap with those found in term-born adolescents with ADHD, the preterm group also shows unique impairments, suggesting more wide-ranging impairments in the preterm group compared to the ADHD group.

Estado nutricional de adolescentes pertenecientes a una cohorte de niños nacidos prematuros

IntroductionCatch-up growth in preterm-born children occurs in the first months of life, but in some cases, growth recovery takes place in adolescence. The objective of this study was to study the growth and development of preterm-born adolescents from a cohort of preterm infants born between 1995 and 1996, who resided in the cities of Chillán and San Carlos in the Biobío Region, Chile. The results were then compared with term-born adolescents. Subjects and methodA sample of 91 children from the cohort was studied and compared with 91 term-born adolescents matched for gender, age, and attendance at the same educational institution. The nutritional status was assessed by BMI-for-age, height-for-age, body composition by skinfold, cardiovascular risk due to blood pressure, and waist circumference. ResultsThere was 23.0% and 24.1% overweight and obesity in preterm-born and term-born adolescents, respectively, with 25.5% of preterm-born and small for gestational age adolescents vs. 14.5% of those born adequate for gestational age were overweight. Lower height was observed in 16.5% and 5.5% of the preterm-born and term-born adolescents, respectively, and with a higher proportion of girls (P<.04). Preterm-born adolescents had a more fat mass than the controls, particularly in the suprailiac skinfold. No significant differences were found in blood pressure and waist circumference. ConclusionsThe results indicate that there is a group of preterm-born children who do not recover height during adolescence, especially girls.

Cortical trajectories during adolescence in preterm born teenagers with very low birthweight

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.

Cognitive Abilities in Preterm and Term-Born Adolescents

To investigate the influence of a range of prenatal and postnatal factors on cognitive development in preterm and term-born adolescents. Woodcock-Johnson III Tests of Cognitive Abilities were used to assess general intellectual ability and 6 broad cognitive abilities in 145 young adolescents aged approximately 12.5years and born 25-41weeks gestational age (GA). To study potential links between neurophysiologic and cognitive outcomes, corticomotor excitability was measured using transcranial magnetic stimulation and surface electromyography. The influence of various prenatal and postnatal factors on cognitive development was investigated using relative importance regression modeling. Adolescents with greater GA tended to have better cognitive abilities (particularly general intellectual ability, working memory, and cognitive efficiency) and higher corticomotor excitability. Corticomotor excitability explained a higher proportion of the variance in cognitive outcome than GA. But the strongest predictors of cognitive outcome were combinations of prenatal and postnatal factors, particularly degree of social disadvantage at the time of birth, birthweight percentile, and height at assessment. In otherwise neurologically healthy adolescents, GA accounts for little interindividual variability in cognitive abilities. The association between corticomotor excitability and cognitive performance suggests that reduced connectivity, potentially associated with brain microstructural abnormalities, may contribute to cognitive deficits in preterm children. It remains to be determined if the effects of low GA on cognitive outcomes attenuate over childhood in favor of a concomitant increase in the relative importance of heritability, or alternatively, if cognitive development is more heavily influenced by the quality of the postnatal environment.

Physiological Evidence Consistent with Reduced Neuroplasticity in Human Adolescents Born Preterm

Preterm-born children commonly experience motor, cognitive, and learning difficulties that may be accompanied by altered brain microstructure, connectivity, and neurochemistry. However, the mechanisms linking the altered neurophysiology with the behavioral outcomes are unknown. Here we provide the first physiological evidence that human adolescents born preterm at or before 37 weeks of completed gestation have a significantly reduced capacity for cortical neuroplasticity, the key overall mechanism underlying learning and memory. We examined motor cortex neuroplasticity in three groups of adolescents who were born after gestations of ≤32 completed weeks (early preterm), 33-37 weeks (late preterm), and 38-41 weeks (term) using a noninvasive transcranial magnetic brain stimulation technique to induce long-term depression (LTD)-like neuroplasticity. Compared with term-born adolescents, both early and late preterm adolescents had reduced LTD-like neuroplasticity in response to brain stimulation that was also associated with low salivary cortisol levels. We also compared neuroplasticity in term-born adolescents with that in term-born young adults, finding that the motor cortex retains a relatively enhanced neuroplastic capacity in adolescence. These findings provide a possible mechanistic link between the altered brain physiology of preterm birth and the subsequent associated behavioral deficits, particularly in learning and memory. They also suggest that altered hypothalamic-pituitary-adrenal axis function due to preterm birth may be a significant modulator of this altered neuroplasticity. This latter finding may offer options in the development of possible therapeutic interventions.