Children born prematurely exhibit a broad range of neuroanatomical abnormalities. The aim of this study was to investigate the long-term effects of very preterm birth on brain volume (cortical and subcortical), cortical thickness and surface area. The participants were 25 children born very preterm (<32 weeks gestational age) without significant post-natal medical sequelae and 32 term-born children between 7 and 10 years of age. Neuroanatomical measures were derived from an automated pipeline. The results suggest a pattern of decreased brain volume, surface area and cortical thickness for children born preterm and the relation between subcortical gray volume and total brain volume differed between groups. The cortex was significantly thinner for children born preterm than term-born children in focal regions of the parietal and temporal lobes. Therefore, even without significant postnatal medical sequelae, very preterm children still exhibit structural differences that persist into middle childhood.

This dissertation examined the relationship between maternal stressful life events and urogenital infection in preterm birth. A systematic literature review revealed ambivalent findings concerning the relationship between maternal stress and infection during pregnancy; the effects of this relationship on pregnancy outcome were not examined in the reviewed studies. The current study employed a biobehavioral model consisting of maternal stressful life events (illness among family members, divorced, moved, became homeless, partner lost job, mom lost job, argued with partner more than usual, partner did not want the child, inability to pay bills, got in a physical fight, partner went to jail, close friend/relative had a bad problem with drinking or drug use, and close friend/relative died) and urogenital infection (genital warts, herpes, chlamydia, gonorrhea, pelvic inflammatory disease, syphilis, Group B streptococcus, bacterial vaginosis, trichomoniasis, yeast infection, urinary tract infection, and other infection) to examine the relationship between these variables in preterm birth. Data from 1,647 respondents of the 2005 Florida Pregnancy Risk Assessment Monitoring System survey were analyzed using descriptive statistics, chi-square and student t- tests, analysis of variance, and structural equation modeling (SEM). Of the respondents, 42% were White, 37.8% had preterm deliveries, and the mean age was 27.1 years. White mothers who became homeless (p = 0.021) or had a partner in jail (p = 0.041) during the 12 months prior to delivery had more preterm deliveries as compared to full-term deliveries. Other non-White mothers who had an ill family member (p = 0.010) had fewer preterm deliveries. In general, mothers diagnosed with Group B streptococcus during pregnancy (p = 0.031) had fewer preterm deliveries. Black mothers diagnosed with herpes (p = 0.006) had fewer preterm deliveries. SEM revealed a significant relationship between maternal stress and infection, in general (p < 0.001), and among White (p < 0.001), Black (p < 0.001), and Hispanic (p < 0.001) mothers. The interaction between these variables was not significant, in general, or among racial/ethnic groups. Results of this study indicate that culturally tailored prevention programs designed to help women cope with multiple risk factors may prove beneficial in reducing preterm birth rates.

Maintaining adequate and stable blood oxygen level is important for preterm babies to avoid the risk of brain, lung and retinal injury such as retinopathy of prematurity (ROP). However, wide disparities in policies and practices of oxygenation in preterm babies exist among neonatal care providers as it is still unclear which best method of monitoring and what features of oxygen measurements are important to clinician’s interpretations for assessing preterm babies at risk of developing severe ROP or unstable health condition. This thesis consists of two projects: NZ-ROP that examines multiple factors of severe ROP including summary statistics (mean, standard deviation (SD), coefficient of variation (CV) and desaturation) for oxygen saturation (OS) features in very extreme preterm babies, and NZ-LP that investigates the efficacy of some of these statistics for health monitoring of late preterm babies. The OS data in NZ-ROP were recorded using modified oximeters that have offsets and inherent software artefact, both of which mask the actual saturation for certain OS ranges and may complicate the choice of methods in the analyses. Therefore, novel algorithms involving linear and quadratic interpolations are developed, implemented on the New Zealand data, and validated using the data of a UK preterm baby, as recorded from offsets and non-offsets oximeters. For all data sets, the algorithms produced saturation distributions that were very close to those obtained from the non-offset oximeter. The algorithms perform within the recommended standards of commercial oximeters currently used in the clinical practice. ROP is a multifactorial disease, with oxygenation fluctuations as one of the key contributors. The all-subsets logistic regression, robust and generalised additive statistical modelling, along with a model averaging approach, are applied in NZ-ROP to determine the relationship of variability and level of OS with severe ROP, and the extent of contribution of various clinical predictors to the severity of this eye disease. Desaturation, as a measure of OS variability, has the strongest association with severe ROP among all OS statistics, in particular, the risk of severe ROP is almost three times higher in babies that exhibit greater occurrences of desaturation episodes. Additionally, this study identifies longer periods of ventilation support, frequent desaturation events, extreme prematurity and low birth weight as the most important factors that substantially exacerbate the severity of ROP, and therefore signify babies’ underlying condition of being severely ill. Persistent cardiorespiratory instabilities prior to hospital discharge may expose preterm babies to a greater risk of neuro-developmental impairments. In NZ-LP, the statistical summaries of mean, SD and CV are computed from the OS measurements of healthy stable and unstable babies, and the performance of these statistics in detecting the unstable babies is evaluated using an extremeness index for outlying data and a hierarchical clustering technique. With SD and CV, the clinically unstable babies were very well separated from the group of stable babies, wherein, the separation was even more apparent with the use of CV. These suggest that measures of variability could be better than saturation level for highlighting babies’ underlying instability due to immature physiological systems, but the combination of variability and level through the CV are believed to be even better. Identification and summarisation of useful OS features quantitatively hold great promise for improved monitoring of oxygenation instability and diagnosis of severe ROP for preterm babies.

Children born very preterm (VPT) are known to be at high risk of under-achievement in mathematics. However the nature of these difficulties is poorly understood. In this study, a regionally representative cohort of 102 children born VPT and a comparison group of 108 children born full term (FT) during 1998-2000 were followed from birth to nine years. At age nine, children were tested using the Woodcock-Johnson III maths fluency subtest, and teacher reports of mathematical achievement and curriculum-based (numeracy project) achievement data were collected. The data was analysed using group comparisons and multiple regression. Parent and teacher ratings of executive function at age six were included as predictors. Findings indicated that children born VPT had elevated rates of mathematical difficulties across all measures including the standardised and curriculum-based measures, and teacher ratings. They also had higher rates of mathematical learning disability. With the exception of curriculum-based measures, these results remained significant even after controlling for socioeconomic status and severe neurodevelopmental impairment. Children born VPT showed particular difficulty using operational strategies, rather than with factual knowledge, and this effect was most marked for addition and multiplication. As well as difficulties in mathematics, children born VPT also showed more difficulty than children born FT in almost all areas of executive function. Difficulties with working memory at age six were significantly associated with poor performance in aspects of curriculum-based measures at age nine.

A preterm birth is associated with increased risk for neurocognitive deficits, but there is a need to further investigate brain/behavior relations among younger school age children born preterm. The main purpose of this study was to investigate relations between brain volumes and neuropsychological functioning, with an additional aim of examining side preference, among 18 school age children, nine born extremely/very preterm and nine born at-term. Brain volumes were examined using 3T MRI, neuropsychological functioning by WISC-IV and side preference through laterality observations. The children born preterm had, in general lower total brain volume, gray matter and WISC-IV score. Contrary to previous findings no difference was found regarding white matter volumes. Stronger right hand preference was associated to higher perceptual reasoning ability among both preterm and at-term born children, but the associations between right hand preference and brain volumes differed between the groups. The results in this study support previous findings showing long-term neurocognitive effects of a preterm birth.

The central nervous system (CNS) develops in a temporally and spatially organised manner. Any adverse events happening during the critical periods of early brain formation may lead to arrest in the process or injury to specific developed structures. Infants born at less than 30 weeks of gestation and those with intra-partum asphyxia are at risk of motor delay. The cause of this delay may be related to injuries in the brain such as the motor cortex, basal ganglia and cerebellum, all of which are essential in controlling movements. According to the dynamical systems theory of motor development, other than the CNS, body systems within the infant such as the musculoskeletal system, and external to the infant such as environmental enrichment and supportive child-rearing practice also have a decisive role in motor development in infants. / Paediatric physiotherapists have been involved in the management of these infants since birth. A number of well-established assessment tools are used to assess these infants’ motor functions. Most of these tools typically do not describe the movement patterns of infants but emphasise the achievement of age-specific motor milestones. The Alberta Infant Motor Scale (AIMS) is one of the few tools that acknowledge the importance of movement quality. / The overall aim of the present research was to examine the impact of adverse events in early infancy, including birth prior to 30 weeks of gestation and intra-partum asphyxia, on motor development of infants during the first two years of (corrected) age. One hundred and twenty infants were recruited, including 58 preterm infants, 10 infants with post-asphyxia neonatal encephalopathy (NE) and 52 term born infants as the control group. All the infants were assessed using the AIMS at 4, 8, 12 and 18 months of (corrected) age. / The preterm group scored significantly lower on various sub-scores of the AIMS at all age levels than the control group. Uneven progression in the sit subscale from 4 to 8 months corrected age (CA) was found in the preterm infants, possibly due to a dominant extensor strength, inadequate tonus and postural control in the trunk. At 12 and 18 months CA, limited variations in movements were evident in some preterm infants in the crawling, sitting and standing positions. The ten infants with post-asphyxia NE showed scattered motor development, related mostly to the severity of their NE. The moderate NE group had the most varied motor outcomes ranging from normal to suspected mild cerebral palsy. / The AIMS was shown to be a valid assessment tool in the preterm population although limitations in its use were found at 4 months CA and when the infants walked or were close to independent ambulation. The present results show that motor performance of typically and non-typically developing infants should be investigated longitudinally as variations are the characteristic of early development. The dynamical systems theory provides a more satisfactory explanation of the motoric differences in infants in this study. All these findings have great implications for the clinical management of these at risk infants.

While previous studies have found that a preterm (PT) birth leads to a higher risk for numerous adverse outcomes, including neurodevelopmental and behavioural problems, few, if any, have investigated the consistency of conceivable behavioural problems over time. The aim of this study was to investigate the existence and the stability of behavioural problems from four to eight years of age in a group of 18 children born PT without diagnosed neurological or developmental morbidity, in comparison to a group of 19 children born full term (FT). Additionally, the effects of gestational age (GA) as well as possible associations between behavioural problems and cognitive ability were investigated. Also, differences related to parents’ level of education were observed. Behavioural problems were evaluated with Child Behavior Checklist (CBCL) and cognitive ability was assessed at eight years of age by using Wechsler Intelligence Scale for Children (WISC-IV). Results showed significant differences between the groups regarding cognitive ability where children born PT had lower scores. Contrary to most previous findings, no evident differences between the two groups regarding amount of behavioural problems were found. Children born PT increased in amount of anxiety problems from four to eight years of age, while children born FT decreased, and a lower GA was related to increasing oppositional defiant problems. Generally, the mothers of children born PT had a lower level of education than those of the FT group. Thus, interpretations with caution due to the relatively small number of participants, these initial findings reveal the need for further prospective follow-up studies on the relationship between birth status and the change of behaviour problems in relation to both inter- and intra-effectors over time. / Tidigare forskning har visat att en för tidig födsel leder till en ökad risk för ett antal ofördelaktiga utfall, inklusive neuroutvecklingsrelaterade svårigheter och beteendeproblem. Få studier, om några, har undersökt stabiliteten av potentiella beteendeproblem över tid. Syftet med denna studie var att undersöka förekomst och stabilitet av beteendeproblematik mellan fyra till åtta års ålder i en grupp bestående av 18 barn födda för tidigt, utan neurologiska eller utvecklingsrelaterade störningar, jämfört med 19 barn födda fullgångna. Vidare undersöktes effekten av gestationsålder samt möjliga associationer mellan beteendeproblem och kognitiv förmåga. Skillnader i föräldrarnas utbildningsnivå mellan grupperna undersöktes också. Beteendeproblem skattades med Child Behavior Checklist (CBCL) och kognitiv förmåga bedömdes vid åtta års ålder med hjälp av Wechsler Intelligence Scale for Children (WISC-IV). Resultaten visade signifikanta skillnader mellan grupperna gällande kognitiv förmåga, där barn födda för tidigt hade lägre poäng. I motsats till vad flera tidigare studier funnit så visade vår studie inga signifikanta skillnader mellan grupperna gällande omfattning av beteendeproblem. Barn födda för tidigt uppvisade en ökning av ångestproblem från fyra till åtta års ålder medan barn fullgånget födda uppvisade en minskning, och lägre gestationsålder korrelerade med ökade trotsproblem. Generellt sett så hade mödrar till barn födda förtidigt en lägre utbildningsnivå än de i den fullgångna gruppen. Med försiktiga tolkningar på grund av det relativt låga antalet deltagare visar resultaten ett behov av vidare uppföljningsstudier av sambanden mellan födelsestatus och förändringen av beteendeproblem i relation till både inter- och intra-påverkande faktorer. / The relation between sensory-motor, behaviour functioning and brain development in preterm born children

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Antepartum suicidal behaviors are a leading cause of maternal injury and death. Previous research has not investigated associations between antepartum suicidal ideation and perinatal complications. Our study objective was to evaluate the relationship of antepartum suicidal ideation with low infant birthweight, small for gestational age, and preterm birth. A cohort study was conducted among 1,108 women receiving prenatal care in Peru. Suicidal ideation was measured using the Patient Health Questionnaire-9 during pregnancy. Birth outcomes were extracted from medical records. Linear regressions and multivariable logistic regressions were used to estimate were used to investigate associations between suicidal ideation and pregnancy outcomes. The prevalence of suicidal ideation was 8.7%, preterm delivery was 5.7%, low birthweight was 4.4%, and small for gestational age was 3.4%. In an adjusted model, infant birthweight was 94.2 grams lower for mothers with antepartum suicidal ideation (95% CI: −183.0, −5.5, p = 0.037) compared with those without suicidal ideation. After adjusting for confounders including depression, participants with suicidal ideation had a nearly four-fold increased odds of delivering a small for gestational age infant (OR: 3.73; 95% CI: 1.59–8.74). These findings suggest suicidal ideation during pregnancy is associated with adverse perinatal outcomes, especially low infant birthweight. / Revisión por pares

This thesis uses a multi-disciplinary approach to study cognitive-neurophysiological processes underlying attention-deficit/hyperactivity disorder (ADHD), and the underlying risk pathways from preterm birth to ADHD. In the first part of the thesis we use a measure of peripheral arousal (skin conductance) to better understand arousal dysregulation in ADHD and how it relates to cognitive performance. We show, using a large ADHD and control sibling sample, that ADHD is associated with peripheral hypo-arousal, and that a familial aetiology underlies the relationship between hypo-arousal and fluctuating reaction times, and between hypoarousal and ADHD. Our findings further suggest that peripheral hypo-arousal is an enduring deficit in ADHD, as it is observed in both ADHD remitters and ADHD persisters in our followup investigation. The second part of the thesis focuses on preterm birth as a risk factor for ADHD: we compare data we obtain from a new sample of preterm-born adolescents and their siblings to data from ADHD and control sibling pairs. First, we find that preterm-born individuals show several of the same cognitive-neurophysiological impairments as individuals with ADHD, but they also show further, additional impairments. Second, our results indicate that cognitive-neurophysiological impairments in the preterm group differentiate into those that are in line with a causal effect of preterm birth, and those that are not. Third, our findings further suggest that the association between ADHD symptoms and specific cognitive impairments is largely due to familial influences among term-born individuals, but largely due to non-shared effects (including preterm birth as an environmental insult) among pretermborn individuals. Overall, by using a combination of cognitive, neurophysiological, developmental and sibling-comparison designs, our findings provide new insight into arousal dysregulation in individuals with ADHD, and inform on cognitive-neurophysiological and aetiological processes that may underlie the association between preterm birth and ADHD.

Made available in DSpace on 2014-06-11T19:33:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2001Bitstream added on 2014-06-13T19:23:23Z : No. of bitstreams: 1 rugolojunior_a_dr_botfm.pdf: 1524515 bytes, checksum: b2ec74b5e5edffce6e56137de1331d01 (MD5) / A incidência de displasia broncopulmonar (DBP) é alta em prematuros de muito baixo peso. Dentre os vários fatores implicados em sua patogênese tem-se destacado a deficiência de vitamina A como um importante fator contributivo. O presente estudo teve como objetivo determinar a condição de vitamina A em prematuros de muito baixo peso e avaliar a relação entre os níveis plasmáticos de retinol e a DBP. Após a obtenção do consentimento materno, foram coletadas amostras de sangue materno, do cordão umbilical e do recém-nascido com 3, 14 e 28 dias de vida, para as dosagens do retinol plasmático, que foram efetuadas por cromatografia líquida de alta resolução (HPLC). Foram estudados 34 recém-nascidos com peso de nascimento médio de 1156 g (± 248 g) e idade gestacional mediana de 30 semanas, os quais foram divididos em dois grupos: Sem DBP (n = 24) e Com DBP (n = 10). Nestes grupos analisou-se as características demográficas maternas e dos recém-nascidos, as condições de nascimento, a evolução clínica no período neonatal, os níveis plasmáticos de retinol e a oferta de vitamina A por via enteral e parenteral. Os resultados das variáveis clínicas foram analisados pelos testes t de Student e Mann-Whitney e comparados entre e dentro dos grupos pelo teste de associação de Goodman. Para a análise dos dados da vitamina A utilizou-se os testes de Wilcoxon (para 2 grupos e 2 momentos) e Freedman (para 2 grupos e 4 momentos). A correlação entre as variáveis foi feita pelo coeficiente de correlação de Pearson. O nível de significância foi de 5%. As características maternas e as condições... / The incidence of bronchopulmonary dysplasia (BPD) is high in preterm very low birthweight infants. Multiple factors have been implicated in its pathogenesis, and the deficiency of vitamin A has been described as an important contributing cause. Several studies have shown that premature infants have low vitamin A status at birth and this has been associated with increased risk of developing chronic lung disease, however many trails showed inconsistent effects of vitamin A supplementation on prevention of bronchopulmonary dysplasia. The purpose of this study was to determine vitamin A status in the very low birthweight infants and to evaluate the relationship between plasma retinol levels and BPD. After parental informed consent, the maternal and cord blood samples were obtained at delivery, and peripheral blood of the infants were drawn at day 3, 14 and 28 of life. Plasma retinol content was determined by high performance liquid chromatography. Thirty four infants (1156 g ± 248 mean birthweight and 30weeks median gestation age) were enrolled, and assigned to 2 groups as follows: BPD (n=10), No-BPD (n=24). The maternal and neonatal demographic data, birth condition... (Complete abstract, click electronic access below)