Objetivo: medir a pressão intra-ocular (PIO) em pré-termos de muito baixo peso (PMBP) e correlacionar com a idade pós-concepção (IPC). Métodos: Estudo longitudinal incluindo 50 pré-termos. Local: Hospital de Clínicas de Porto Alegre. Período: entre novembro de 2008 e junho de 2010. Pacientes: PMBP definido como idade nascimento ≤ 1.500 g e idade gestacional ≤ 32 semanas. Intervenção: medidas semanais da PIO. Principais desfechos: variação da PIO de acordo com a idade pós-concepção (IPC definida como a idade gestacional ao nascimento mais a idade no momento do exame) nas semanas seguintes ao nascimento pré-termo. Análise estatística: modelos de efeitos mistos foram utilizados para determinar a variação da PIO em relação a IPC. Foram calculados as médias e os percentis 10 e 90 (P10 e P90) para os valores da PIO. Resultados: Cinqüenta PMBP com idade gestacional média de 29,7 ± 1,6 semanas e peso de nascimento de 1.127,7 ± 222,7 gramas foram avaliados. Não houve diferença significativa entre a PIO do olho direito e do olho esquerdo (p=0.177). A média da PIO em toda a coorte, considerando ambos os olhos, foi de 14,9 ± 4,5 mmHg, sendo que 13,5% das medidas isoladas da PIO foram superiores a 20 mmHg. A PIO reduziu em média 0,29 mmHg para cada aumento de uma semana da IPC (p=0.047 IC95%: -0,58 a -0,0035). A PIO média (P10-P90) reduziu de 16,3 mmHg (10,52-22,16) com 26,3 semanas de IPC para 13,1 mmHg (7,28-18,92) com 37,6 semanas de IPC. Conclusões: A PIO média em PMBP foi 14,9 ± 4,5 mmHg e apresentou correlação negativa em relação a idade pós-concepção. / Purpose: To measure intraocular pressure (IOP) in very low birth weight preterm infants and correlate it with the postconceptional age (PCA). Methods: Longitudinal study including 50 premature infants. Setting: Hospital de Clinicas de Porto Alegre, Brazil. Patients: Very low birth weight premature infants (defined as birth weight ≤1,500 g and gestational age ≤32 weeks). Intervention: Weekly measurements of the IOP. Main outcomes: The variation of IOP according to the postconceptional age (PCA defined as the gestational age at birth plus the age in weeks at the time of examination) in the weeks following preterm birth. Statistics: Mixed-effects models were used for the statistical analysis to determine IOP variation according to PCA. Means, 10th and 90th percentiles were calculated for IOP values. Results: Fifty preterm infants with a mean gestational age of 29.7 ± 1.6 weeks and mean birth weight of 1,127.7 ± 222.7 grams were evaluated. Mean IOP in the whole cohort considering both eyes was 14.9 ± 4.5 mmHg, and 13.5% of the IOP measurement values were greater than 20 mmHg. The analysis revealed a mean IOP reduction of 0.29 mmHg for each increase of PCA (p=0.047; 95% CI, -0.58 to -0.0035). Mean IOP (P10- P90) decreased from 16.3 mmHg (10.52-22.16) at 26.3 weeks PCA to 13.1 mmHg (7.28- 18.92) at 37.6 weeks PCA. Conclusions: Mean IOP in very low birth weight preterm infants was 14.9 ± 4.5 mmHg and was negatively correlated with PCA.

Objetivo: Determinar a influência da presença de cafeína no sangue de cordão umbilical na ocorrência de apneia. Métodos: Estudo de coorte prospectivo de recém-nascidos pretermos com peso de nascimento menor de 2.000 g. Os critérios de exclusão foram: mães que receberam opióides , ventilação mecânica durante os primeiros 4 dias de vida, malformação congênita cerebral e cardíaca maiores, asfixia perinatal, hemorragia peri-intraventricular severa, exsanguíneotransfusão antes do quarto dia de vida e uso de metilxantina antes da extubação. Os recém-nascidos foram divididos em: com e sem cafeína detectável no sangue de cordão umbilical e acompanhados nos primeiros quatro dias de vida para a ocorrência de apneia. Resultados: 87 com e 40 sem cafeína detectável no sangue de cordão umbilical foram estudados. A mediana da concentração de cafeína dos 87 pacientes com cafeína detectável no sangue de cordão umbilical foi 2,3 µg/ml (0,2-9,4 µg/ml). Não houve associação entre a ocorrência de apneia e a presença de cafeína no sangue de cordão umbilical. Recém-nascidos com cafeína detectável no cordão umbilical tiveram apnéia mais tarde (66.3 horas) do que aqueles com níveis indetectáveis (54.2 horas). Conclusão: a detecção de níveis de cafeína no sangue de cordão umbilical não diminuiu a ocorrência de apneia da prematuridade. Nós sugerimos que novos estudos com a administração de altas doses de cafeína para mães antes do parto prematuro, como estratégia para prevenir a apneia da prematuridade, devam ser realizados. / Objective: To determine the influence of presence of caffeine in umbilical cord blood on apnea occurrence. Methods: A prospective cohort study with preterm newborns with birth weight less than 2,000 g was undertaken. Exclusion criteria were: mothers that received opioids, mechanical ventilation during the first 4 days of life, cerebral and major cardiac malformations, perinatal asphyxia, severe periintraventricular hemorrhage, exchange transfusion before the fourth day of life, and those that received methylxantine prior to extubation. Neonates were divided in: with detectable and undetectable caffeine in umbilical cord blood. Newborns were followed for the first 4 days for occurrence of apnea spells. Results: 87 with and 40 without detectable caffeine in umbilical cord blood were studied. The median caffeine concentration of the 87 patients with detectable caffeine in umbilical blood was 2.3 µg/ml (0.2-9.4 µg/ml). There was no association between occurrence of apnea spells and presence of caffeine in umbilical cord blood. Neonates with detectable caffeine in umbilical blood had apnea later (66.3 ± 4.14 hours) than those with undetectable levels (54.2 ± 6.26 hours). Conclusion: The detected levels of caffeine in umbilical cord blood did not decrease the occurrence of apnea of prematurity. We suggest that further studies on administration of high dose of caffeine to mothers prior to a preterm delivery as a preventive measure for apnea of prematurity deserve to be conducted.

Crianças com histórico de prematuridade e muito baixo peso apresentam alto risco para alterações do desenvolvimento cognitivo e, consequentemente, desenvolvimento de linguagem. O objetivo da presente tese é descrever o desempenho de bebês pré-termo muito baixo peso, quanto ao desenvolvimento cognitivo e de linguagem expressiva, durante o período sensório-motor e início do pré-operatório, e comparar com o desenvolvimento de bebês de termo, seguindo os pressupostos teóricos da Epistemologia Genética. Doze bebês pré-termo muito baixo peso e 20 bebês nascidos de termo foram submetidos, pela pesquisadora, a sessões de observações mensais da cognição e linguagem expressiva, de acordo com o Protocolo de Observação do Desenvolvimento Cognitivo e de Linguagem Expressiva, a partir do momento que ingressaram no Ambulatório de Seguimento de Alto Risco até os 18 meses de idade corrigida e/ou Ambulatório de Puericultura, ou creche, até os 18 meses de idade cronológica. Todas as sessões foram filmadas em videoteipe e os dados analisados segundo protocolo específico. Para melhor discussão dos dados, a pesquisa foi dividida em dois estudos. O objetivo do Estudo I foi a proposição e aplicabilidade de protocolo para observação do desenvolvimento cognitivo e de linguagem expressiva, referente ao período sensório-motor e início do pré-operatório, que pudesse ser utilizado como instrumento de análise objetiva das realizações observadas em crianças. O Protocolo é constituído por quatro quadros contendo os indicadores do desenvolvimento cognitivo e de linguagem expressiva em seus estágios iniciais, bem como a pontuação correspondente às realizações apresentadas pela criança. Trata-se de proposta de sistematização da observação de dados longitudinais referentes às áreas do desenvolvimento mencionadas, permitindo a localização e o acompanhamento da criança em seu processo de construção do conhecimento e de linguagem expressiva durante os estágios iniciais. O objetivo do Estudo II foi analisar quantitativa e qualitativamente o desempenho quanto ao desenvolvimento cognitivo e de linguagem expressiva de bebês pré-termo muito baixo peso por meio da aplicação do Protocolo de Observação do Desempenho Cognitivo e de Linguagem Expressiva, durante o período sensório-motor e início do préoperatório e comparar com o de bebês de termo. Os resultados revelaram atraso significativo dessas áreas do desenvolvimento dos bebês pré-termo muito baixo peso em relação aos bebês de termo, sendo a defasagem mais facilmente observável a partir do 6o mês, mantendo-se durante todo o período sensório-motor e início do pré-operatório. A partir dos resultados deste estudo, reforça-se a importância do monitoramento fonoaudiológico de bebês de alto risco. / Infants born preterm and very low birth weight are at great risk for deficits on cognitive development and consequently on language acquisition. The aim of the present study is to describe the performance of very low birth weight preterm infants regarding expressive language and cognitive development during sensorimotor and beginning of preoperational period and to compare it with that of term infants, according to the Genetic Epistemology theoretical principles. Twelve very low birth weight preterm infants and 20 term infants underwent monthly evaluations in which cognition and expressive language were observed according to the Protocol for Expressive Language and Cognition Development Observation. The observation sessions were carried out from their ingress at the Outpatient Clinic for High-Risk Neonates until 18 months of corrected age and/or from their ingress at the Pediatric Outpatient Clinic, or at the Day Care Center, until 18 months of chronological age. All sessions were videotaped and data were analyzed according to a specific protocol. In order to better discuss the results, this research was divided into two studies. The aim of Study I was to propose and analyze the applicability of a protocol for expressive language and cognitive development observation during the sensorimotor and the beginning of preoperational period, that could be used as a tool for objective analysis of the achievements observed during infant\'s development. The Protocol comprises four charts containing the indicators of cognitive and expressive language development in their early stages, as well as a score corresponding to the child\'s achievements. It constitutes a proposition for systematization of longitudinal data observation concerning the developmental areas mentioned, allowing the child\'s placement and making it possible to follow the child\'s construction process of knowledge and language during early developmental stages. Study II had the aim to analyze, qualitatively and quantitatively, the performance of very low birth weight preterm infants on expressive language and cognitive development during sensorimotor and preoperational period using the Protocol for Expressive Language and Cognitive Development Observation, and to compare their performance to that presented by term infants. The results revealed a significant delay for very low birth weight preterm infants on both expressive language and cognitive development when compared to term infants. The gap found between groups was more evident after their 6th month, persisting through the sensorimotor period and continuing into the beginning of preoperational period. The results of this study reinforce the importance of speech-language monitoring for high risk infants.

Submitted by Rosangela Silva (rosangela.silva3@unioeste.br) on 2018-05-24T19:14:51Z No. of bitstreams: 2 Julio Cezar dos Santos.pdf: 1442616 bytes, checksum: dc9859e73b5e29a7f64edb68bb2c545e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2018-05-24T19:14:51Z (GMT). No. of bitstreams: 2 Julio Cezar dos Santos.pdf: 1442616 bytes, checksum: dc9859e73b5e29a7f64edb68bb2c545e (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-03-09 / Fundação Araucária de Apoio ao Desenvolvimento Científico e Tecnológico do Estado do Paraná (FA) / Little is known about chronic exposure to pyrethroids; however, contact with this type of substance is common and has often been found in breast milk and urine, in addition to environmental detections that have sometimes been related to diverse biological changes. The present study aims to evaluate the possible disruptive actions of deltamethrin in low doses on the thyroid, a hyposal function in the development in transgenerations of rats. For this, 6 non-consanguine adult, Wistar albino rats were used, provided by the Central Vivarium of the State University of the West of Paraná (UNIOESTE). All the experimental procedures were followed the protocol evaluated and approved by the Committee of Ethics in the Use of Animals of the State University of the West of Paraná (CEUA / UNIOESTE). The treatment group received a daily intraperitoneal injection of deltamethrin at the concentration of 0.01 mg.kg-1 of body weight between the 8th and 14th day of pregnancy, the control group received canola oil. Next generations (F1 and F2) did not receive treatment and were evaluated for growth and development, by birth weight, Lee index and weight at euthanasia. After euthanasia, the pituitary gland was isolated and weighted. A positive correlation was observed between weight variation throughout pregnancy and the number of pups born. There was no difference between the treatment and control groups in the birth weight of first generation rats (F1). The birth weight of the 2nd generation (F2) rats from the treated rats was lower in comparison with the weight of those from the control rats. When assessing weight, Lee's index and pituitary weight at euthanasia, there were no statistical differences between control and treatment. Females had larger pituitary glands when compared to males. We concluded that deltamethrin interferes with the birth weight of rats and this interference follows a transgenerational pattern of clinical implication. / Pouco se sabe sobre a exposição crônica a piretroides, apesar disso, o contato com esse tipo de substância é comum e frequentemente têm-se verificado sua presença no leite materno e urina, além das detecções ambientais que por algumas vezes foram relacionadas com alterações biológicas diversificadas. O presente estudo visa avaliar as possíveis ações disruptoras da deltametrina em baixas doses sobre a tireoide, função hiposária no desenvolvimento em transgerações de ratos. Para isso, foram utilizados seis ratos adultos não consanguíneos, albinos, da linhagem Wistar, fornecidos pelo Biotério Central da Universidade Estadual do Oeste do Paraná (UNIOESTE). Todos os procedimentos experimentais seguiram em concordância com protocolo avaliado e aprovado pelo Comitê de Ética no Uso de Animais da Universidade Estadual do Oeste do Paraná (CEUA/UNIOESTE). O grupo Tratamento recebeu uma injeção intraperitoneal diária de deltametrina na concentração de 0,01 mg.kg-1 de peso corpóreo, entre o 8º e 14º dia de prenhez; o grupo Controle recebeu óleo de canola. As gerações seguintes (F1 e F2) não receberam tratamento e foram avaliadas quanto ao crescimento e desenvolvimento, através do peso ao nascer, índice de Lee e peso na eutanásia. Após a eutanásia, a glândula hipófise foi isolada e pesada. Foi observada uma correlação positiva entre variação de peso - ao longo da prenhez - e o número de filhotes nascidos. Não houve diferença entre os grupos Tratamento e Controle, no peso do nascimento dos ratos da primeira geração (F1). O peso de nascimento dos ratos da 2ª geração (F2), oriundos das ratas tratadas, foi menor, comparado ao peso daqueles oriundos de ratas controle. Ao avaliar o peso, o índice de Lee e o peso da hipófise na eutanásia, não houve diferenças estatísticas entre controle e tratamento. As fêmeas apresentaram hipófises maiores, se comparadas aos machos. Concluímos que a deltametrina interfere no peso de nascimento dos ratos e esta interferência obedece a um padrão transgeracional de implicação clínica.

Magister Scientiae - MSc / This secondary analysis aimed to develop dietary scores to assess the dietary intake of pregnant women in the West Coast/ Winelands region and determine the association with LBW. Further to determine the association between the dietary scores and maternal socioeconomic and socio-demographic characteristics and maternal smoking and/or alcohol consumption during pregnancy. / South Africa

Philosophiae Doctor - PhD / Background:The Project reported on in this thesis took place between 2003 and 2006 and focused on the problem of high rates of low birth weight in the West Coast /Winelands area of the Western Cape Province, South Africa. A 32 page woman’s health handbook (WHH) was developed and field-tested using a participatory action research approach. The purpose of the WHH was to provide a health promotion tool that would increase the likelihood of satisfactory birth outcomes in future by: improving the continuity of care for women, especially in pregnancy; improving the interaction between health service providers and women during health consultations; and enabling women to improve their broader health literacy.Methods:The Project used both qualitative and quantitative methods and was carried out in three phases following steps in strategic communication development: situational and audience analysis; strategic design and development; and,field testing. The process involved three levels of stakeholders, or audiences: primary (women working on farms); secondary (local health service providers); tertiary (regional and provincial health department officials).Phase I began with a situational analysis of the two research sites in 2003 - Vredendal and Stellenbosch areas. Data was collected through key informant interviews, secondary data and general observations. The information on the two sub-districts was summarised. In order to understand the lifestyle and contextual issues facing the primary audience focus group discussions and key informant interviews with all three levels of the audience were carried out in 2004. The analysis utilised an inductive approach to generate themes that integrated the information from all sources and a framework for understanding substance use was developed. Ideas for the format and contents of the WHH were collected utilising the same methods and were summarised into categories.Phase II utilised the findings of Phase I to develop the first version of the WHH. This was pre-tested with all levels of the audience in individual interviews or focus groups to assess its accessibility, contents and appropriateness. The findings were used to prepare the second version of the WHH for Phase III.In Phase III the second version of the WHH was tested by recruiting a cohort of 103 participants who were utilising the antenatal clinic services in the two sites in 2005. A pre- and post-intervention questionnaire was used to collect qualitative and quantitative data to characterise the participants and, assess if the WHH that was given to them to keep had influenced their health knowledge and substance use behaviour. Analysis included simple frequencies, and a comparison of key outcome measures from the pre- and post-intervention questionnaires. Secondary level audience representatives were also interviewed, and content analysis carried out to identify theirperceptions of the WHH and any potential barriers to its future use in the clinics. A final version of the WHH was developed and 10 000 copies made available through a resource centre. The dissemination of a batch of the final version was followed up in 2006.Results:The first phase identified the extent to which environmental and health-related behaviour contributed to low birth weight, as well as, other negative consequences in the lives of the primary audience. Important factors noted included the resource poor and stressful environment in which farm-based women live and work, and the high rates of women smoking cigarettes and drinking alcohol in general, and through pregnancy.A first version of the WHH was developed and pre-tested in the second phase by applying principles of designing health education materials for audiences with mid to low literacy levels. Results from this stage led to the development of the second version of the WHH.Although the evaluation of the second version of the WHH did not show any significant change in the health knowledge of the participants on the pre- and post-test analysis, there was a reduction in the use of alcohol, and very positive feedback on utilisation issues from all audiences. There was widespread dissemination of the final version of the WHH, however, neither the provincial nor the regional health authorities had incorporated it into their annual health promotion plan or budget.Conclusion:The participatory action research approach in the development of the WHH ensured that the form and contents was appropriate for most of the primary audience and that the secondary and tertiary audiences were supportive of its potential to positively women’s health in the region in the future. The main factors that limited the impact of the WHH include the need for the health service providers to consistently practice interactive health consultations using the WHH, and the need for the reproduction and dissemination of the WHH to be led by the provincial health department.It is recommended that brief training of health service workers is required in order to ensure that the final version of the WHH is utilised to its full potential and, that the provincial and regional health authorities devise a reproduction and dissemination plan to ensure that all women using the public health services receive their own copy of the WHH.

Les prévalences de FPN, de prématurité et de RCIU dans notre population d’étude étaient de 9,1%, 10,3% et 25,3% respectivement. La majorité des enfants nés avec un FPN (75%) avaient un RCIU. Concernant la prématurité, seul le sexe de l’enfant était associé à un risque plus faible. A l’inverse, les garçons étaient plus à risque de RCIU. Les mères primipares et celles ayant un faible statut anthropométrique avaient une plus grande probabilité de donner naissance à des enfants en FPN et ceci s’exprimait principalement par le mécanisme RCIU. La même analyse sur le poids de naissance en quantitatif a donné des résultats similaires et a montré en plus un effet négatif indépendant de la petite taille de la mère (<155cm). Nous n’avons pas retrouvé d’effet de l’infection placentaire palustre ni de l’anémie maternelle. Les enfants nés avec un FPN, ceux ayant vécu un RCIU et ceux issus de mère en déficit nutritionnel présentaient un retard de croissance linéaire. Nous avons aussi mis en évidence que le FPN et le faible statut anthropométrique de la mère avaient un lien significatif avec la maigreur. La morbidité palustre n’était pas associée à l’évolution staturo-pondérale. Les bonnes pratiques alimentaires, objectivées par un bon score IYCF s’accompagnaient d’une corpulence correcte, alors qu’elles étaient associées de manière paradoxale à un retard de croissance linéaire. Le déficit nutritionnel maternel (faible statut anthropométrique ou petite taille) est impliqué dans la survenue du FPN mais est également responsable par un effet propre d’une mauvaise croissance staturo-pondérale. Nos résultats confirment bien l’existence d’un cycle intergénérationnel de la malnutrition. / The prevalence of low birth weight, preterm birth and IUGR in our study population were 9.1%, 10.3% and 25.3% respectively. The majority of children born with LBW (75%) had IUGR. Concerning prematurity, only the sex of the child was associated with a lower risk. Conversely, boys were more at risk of IUGR. Primiparous and those with low anthropometric status were more likely to give birth to children with LBW and this was expressed mainly by IUGR mechanism. The same analysis on birth weight as continuous variable gave similar results and showed in addition, an independent negative effect of maternal short stature (<155cm). We did not find an effect of placental malaria infection or maternal anemia. Children born with LBW, IUGR and those from mother with nutritional deficiency showed a linear growth retardation. We also demonstrated that LBW and low anthropometric status of the mother were significantly correlated with leanness. Malaria morbidity was not associated with growth. Good feeding practices objectified by a good IYCF score, were accompanied by a proper corpulence, while they were paradoxically associated with a linear growth delay. Maternal nutritional deficiency (low anthropometric status or short stature) is involved in the occurrence of LBW but also impacted negatively children’s growth through an independent effect. Our results confirm the existence of an intergenerational cycle of malnutrition.

Maternal depression during pregnancy can have a negative impact on the developing child. Numerous studies have focused on postpartum depression and the influences on infant outcomes; however, there are limited data on pregnancy-related depression. The problem addressed in this study was the inadequacy and insufficiency of depression screening during the pregnancy period and access to quality-related health services for women. The purpose of this quantitative retrospective study was to test social cognitive theory on low birth weight and prenatal care adherence to pregnancy-related depression in women residing in Colorado. This research measured an association between pregnancy-related depression and both low birth weight prevalence and prenatal care adherence. Secondary analysis of archived data included data from Colorado vital statistics and the 2016 Colorado Pregnancy Risk Assessment Monitoring System. Data were analyzed using Chi-square analysis and multiple logistic regression. The findings showed that pregnancy-related depression was statistically significant of very low birth weight. I reported a summary of findings on p. 68. Biopsychosocial variables were significant to pregnancy-related depression. Pregnancy-related depression was significant in prenatal and postpartum depression. The implications of these findings for social change include the potential to support improved depression screening strategies during pregnancy that may contribute to transformation within the community by promoting more efficient and accessible healthcare for women.

The aim of the diploma thesis is to evaluate the specifics of mental development of children of preschool and school age with very low to extremely low birth weight. The theoretical part is focused on prenatal and perinatal factors, the most common health problems and specifics of psychological development. Low birth weight, especially in the category of very low and extremely low birth weights poses a significant risk factor in somatic and mental development of these children. There is an increasing tendency in children with low birth weight to show the impact of immaturity in the areas of neurocognitive and psychosocial maturation. The aim of the empirical part is to evaluate the cognitive and socio-emotional development of children with very low to extreme low birth weight in two age groups (preschool and school age). The primary target group are children with perinatal stress, which are monitored and maintained therapeutically in the Center of complex care for children with perinatal stress at the Clinic of Pediatrics and Adolescent Medicine, General University Hospital and 1st Faculty of Medicine at Charles University. This thesis is dealt with within the project NF-CZ11-OV-1-009-2015 "New methods in the aftercare of children with perinatal stress in the Center of complex care for children...

Long-term outcome of extremely preterm neonates depends on many endogenous and exogenous factors. Long-term follow-up of extremely preterm neonates during childhood and analyses of IGF1 gene polymorphisms may help to better understand the problems connected with delayed postnatal growth and the progression of cardiovascular diseases and diabetes mellitus type 2 in adulthood. The aim was the long-term follow-up of anthropometric parameters in children born at 22−25th and 26−27th week of gestation and to study the association between postnatal growth of extremely preterm children, children small for gestational age (SGA) and children born at term with appropriate birth weight/length (AGA) and IGF1 gene polymorphisms: (CA)10-24 repetitive polymorphism in promoter, microsatellite marker D12S318 and 185 bp in 3'UTR, (CT)n polymorphism (CA)n polymorphism 216 bp in the intron 2. Methods. 242 infants born at 22-27+6 weeks were enrolled. Anthropometric parameters were measured at the ages of 2 and 5 years in 72 children born at 22-25+6 week (group I) and 85 children born at 26-27+6 week (group II). Polymorphisms of IGF1 were analysed in 51 extremely preterm, 208 AGA and 59 SGA children using fragment analyses. The data of postnatal growth data in AGA children were obtained at 18 months, in SGA and extremely...