<p><strong>Background:</strong> Postnatal growth of preterm infants does not match recommended intrauterine growth, due to the initial weight loss that accompanies healthy body composition rearrangements after birth. Thus, optimal postnatal growth for preterm infants is currently unknown.</p> <p><strong>Objectives: </strong>(1)<strong> </strong>Collect longitudinal postnatal growth data of 30–36 week GA preterm infants with unimpaired postnatal adaptation; (2) Develop regressions that predict the growth trajectory such an infant will adjust to by days of life 7/14/21; (3) Extrapolate and validate the regressions downwards to 25 weeks.</p> <p><strong>Methods:</strong> Infants of 30–36 week GA, born/admitted to 1/5 participating centres between 2008–2012, who met pre-specified criteria for unimpaired postnatal adaptation and who had at minimum 14 days of data were included. Day-specific anthropometric data from birth to discharge were abstracted retrospectively. Z-score regressions for days 7/14/21 were developed. Regressions were then extrapolated to 25 weeks and validated using an independent study population.</p> <p><strong>Results:</strong> Of 6203 infants, 665 met the screening criteria. By day 14, infants adjusted to stable growth trajectories that were 84±13% of the recommended weight-for-age. Using the following predictors: GA, z-score at birth and hospital-centre, regressions accurately predicted z-scores at days 7, 14 (n=665; R²=0.939, 0.889) and 21 (n=333; R²=0.841). Validation using 25-29 week GA infants (n=173) suggested models were also accurate within this age-range.</p> <p><strong>Conclusion: </strong>These results provide robust estimates of a hypothesis of healthy postnatal growth for preterm infants. Future steps include assessing long-term outcomes in a randomized control trial and assessing the quality of growth using body composition analyses.</p> / Master of Science in Medical Sciences (MSMS)

Colony-Stimulating Factor (CSF-1) is required for the proliferation, differentiation and survival of cells of the mononuclear phagocyte lineage. Mice with a mutation in their CSF-1 gene demonstrate abnormal development in many organ systems and severe growth retardation. These defects can be corrected by administration of rh- CSF-1, and when similarly administered to wild-type mice, can increase organ and body weight, thus highlighting the importance of CSF-1 in postnatal growth. CSF-1 is known to be elevated in the circulation in the immediate postnatal period of both mice and humans. It remains to be seen whether CSF-1 deficiency underlies important clinical issues such as low birth weight, and whether there are any functionally important variations in expression or biology of CSF-1, or the alternative CSF-1R ligand IL-34 that contributes to variation in somatic growth between individuals. This thesis aimed to use the pig as a model for human innate immunity and disease based upon recent publications that highlighted the similarities in their immune systems. To investigate the effects of CSF-1 on postnatal growth the first aim was to characterise the CSF-1R system in pigs and produce reagents. Biologically active porcine CSF-1 and IL-34 were produced along with expression of full length functional porcine CSF-1R and production of anti-CSF-1R antibodies. A bioassay was developed and optimised to assess the biological activity of these proteins. The cross-species reactivity of a range of species CSF-1 and IL-34 proteins was investigated in-vitro using the bioassay and cell culture systems. Recombinant CSF-1 is known to have a short half-life. Since conjugation of proteins to the Fc region of immunoglobulins has been used extensively to improve circulating half-life; a porcine Fc CSF-1 fusion protein was generated by commercial partners, Pfizer Animal Health. The conjugated and un-conjugated CSF-1 proteins had identical activity in cell line and primary cell assays in-vitro. The in-vivo activity of porcine Fc CSF-1 was tested initially in the Csf1r-EGFP+ mouse reporter line and C57BL/6 mice. The Fc CSF-1 protein was more active than the native protein in promoting increased monocyte and tissue macrophage numbers, increasing body weight and inducing hepatosplenomegaly. Hepatic growth was associated with extensive macrophage infiltration and hepatocyte proliferation, identified by gene expression profiling as well as immunohistochemistry. Fc CSF-1 was then tested in neonatal pigs. They were found to have an immature immune system that develops with age. No postnatal surge of CSF-1 was detected. Fc CSF-1 administration increased blood monocyte and neutrophil numbers confirming that CSF-1 is not saturating at this time. Nevertheless, no influence on postnatal growth rate was identified. This is discussed in terms of the differences in placental architecture in the pig compared to human and mouse. This thesis demonstrates the effectiveness of porcine Fc CSF-1 in both mice and porcine and highlights the important role that CSF-1 and macrophages play in liver homeostasis. Fc CSF-1 is identified as candidate therapeutic agent in humans and companion animals for tissue regeneration, and a tool for the study of the role of macrophages in physiology and pathology.

Background: Given that 43-97% of preterm infants face postnatal growth restriction by hospital discharge, monitoring of growth is challenging but critical for clinical management of preterm infants. Currently, serial anthropometric measurements of weight and height are used to monitor growth but lack sensitivity. Thus, by the time significant deviations in growth trajectory are identified, an infant has already reached sub-optimal growth. A biomarker that is predictive of sub-optimal growth can serve as a preventative tool in clinical decision making. Blood urea nitrogen (BUN) may be one such potential metabolic biomarker, as it has been used as a measure of protein adequacy and thus, may additionally indicate quality of growth. While protein intake has a well-established correlation with growth, it is currently unknown if BUN is correlated with postnatal growth and if it can be used as a biomarker for growth. Objectives: 1) to examine the relationship between BUN and macronutrient intake factors such as protein intake, protein-to-energy (P:E) ratios, and carbohydrate to non-protein energy (CHO:NPE %) to better understand BUN response; 2) to examine the potential of using BUN as a predictive metabolic biomarker of growth status in a multiple linear regression. We hypothesize that BUN will positively correlate with protein intake, P:E and negatively with CHO:NPE ratio. It will also be positively correlated with growth parameters: growth velocity, length gain, head circumference gain and fat free mass. Methods: Very low birth weight preterm infants (n=101) born ≤30 weeks of gestation at McMaster Children’s Hospital’s level III NICU were included. BUN was assessed at three time points: baseline (SDay1), study day 14 (SDay14) and study day 21 (SDay21). Intake of protein and energy were collected for the 24-hour period prior to the BUN measure, their averages computed over SDay14 and SDay21 and included as confounding predictor variables. Other confounding variables such as maternal characteristics and baseline study group characteristics were also considered. Growth velocity, length gain and head circumference gain at SDay14 and SDay21, and body composition (FFM%, FFMI) between 36-40 weeks were examined as dependent growth variables. After an initial univariate analysis of baseline and maternal confounders, multiple linear regression models were then developed in a block design as follows: for the analysis of BUN vs macronutrient factors- block 1: 24-hour macronutrient intake factors + relevant baseline and/or maternal confounders; block 2: average macronutrient factors; for the analysis of BUN vs growth- block 3: BUN. Results: In the analysis of BUN and macronutrient intake, BUN was found to have a significant positive correlation with P:E ratio at all time points. Protein intake was positively correlated with BUN only at SDay1 and SDay21. CHO:NPE ratio did not correlated with BUN at any time point. The R2 for the multiple regression of BUN and macronutrient factor analysis at SDay1, SDay14 and SDay21 was 0.19, 0.42 and 0.44 respectively. In the analysis of BUN vs growth, SDay1 BUN had a significant negative correlation with SDay21 growth velocity (p=0.02). The addition of SDay1 BUN to the model of SDay21 growth velocity was significant (p<0.01 of F change statistic, R2= 0.17). SDay21 BUN also had a significant negative correlation with SDay21 growth velocity (p<0.01) and its addition was significant to the model (p<0.01 of F change statistic, R2 =0.22). BUN was not related to SDay 14 growth velocity, or to length gain, head circumference gain or any body composition estimates at any time point. Additionally, P:E was found to be significantly negatively correlated with growth. Conclusion: BUN is a statistically and clinically significant marker of nutritional adequacy, both of protein intake and energy in relation to protein intake. Addition of BUN adds to the explanation of variation in growth, and this is statistically significant, however, the additional variation explained may be too small to be clinically significant. Additionally, we observed that P:E ratio was significantly negatively correlated with growth. Thus, it may be more clinically pertinent to use high BUN values as a marker of inadequate energy to protein intake to prevent future sub-optimal growth. / Thesis / Master of Science (MSc)

Muitos fatores podem influenciar o desenvolvimento placentário e fetal na égua, dentre eles destaca-se a idade, a paridade e o porte materno. A produção de hormônios esteroides pela unidade feto-placentária também pode ser influenciada pela paridade e raça, porém não existem relatos prévios que relacionem os efeitos da idade da égua sobre a produção desses hormônios na gestação. Este trabalho conta com três objetivos principais: o primeiro investigou a influência do número de partos e da idade materna sobre a eficiência placentária e a biometria do potro ao nascimento, utilizando a análise estereológica da placenta a termo. O segundo determinou a influencia da biometria parental na macro e microscopia placentária e consequências para o desenvolvimento fetal e para o crescimento, comportamento e funções fisiológicas pós-natais. Por último foi avaliada a influência da idade e paridade materna, e da raça do potro sob a produção de estrógenos, progesterona e cortisol plasmáticos em éguas prenhes. Quarenta fêmeas gestantes foram categorizadas de acordo com a idade (Id1: 4 a 8 anos; Id2: 8 a 12 anos; Id3: &ge; 13 anos), a pluriparidade (Par1: nulíparas, Par 2: 1 a 3 partos; Par3: &ge; 4partos) e a raça do produto (MP: Mangalarga Paulista; BH: Brasileiro de Hipismo). As coletas de plasma foram realizadas semanalmente a partir do quinto mês de gestação até o termo, e a quantificação dos hormônios foi realizada pela técnica de Espectrometria de Massas. Os partos foram acompanhados a campo e dados do escore Apgar, comportamento e amostras sanguíneas para análise bioquímica dos potros foram coletados nas primeiras doze horas de vida. As membranas corioalantóides foram recolhidas após o delivramento, pesadas e fotografadas em escala. Foram coletados fragmentos correspondentes às regiões do corpo do útero, corno uterino gestante e corno uterino contralateral para análise estereológica. Parâmetros de crescimento dos neonatos foram comparados do nascimento até os dois anos de idade, assim como foram coletados dados da altura, peso e perímetro torácico materno e paterno. Não foram observadas diferenças significativas na quantificação de esteróides quando considerados os fatores número de partos e raça do produto para a categorização das fêmeas. As concentrações de estrógenos foram estatisticamente superiores no grupo Id2 em relação ao Id3, em alguns meses do período gestacional avaliado. Foi observado que a idade e a paridade materna influenciam o desenvolvimento dos microcotilédones e a densidade total de superfície dos vilos, bem como a vascularização e a composição tecidual das diferentes regiões da placenta, contribuindo de fato para uma maior área de contato materno-fetal e transferência de gases e nutrientes entre mãe e feto, culminando com o nascimento de potros mais altos, mais pesados e com maior circunferência torácica. O porte paterno, e principalmente o materno, influenciou o desenvolvimento das vilosidades fetais e a área de superfície de contato materno-fetal, com efeito positivo no desenvolvimento e no crescimento fetal, resultando no nascimento de potros com melhores respostas adaptativas e metabólicas. Também destaca-se que o período de vida intrauterino foi determinante para a taxa de crescimento pós-natal até os 24 meses de vida. / Many factors may influence placental and fetal development in the mare, like age, parity and maternal size. The production of steroid hormones by fetal-placental unit can also be influenced by parity and breed, but there are no previous reports relating the effects of the mares age on the production of these hormones during pregnancy. This paper has three main objectives: the first investigated the influence of maternal age and parity on placental efficiency and size of the foal at birth, using stereological analysis of the term placenta. The second determined the influence of parental size on macro and microscopy of the placenta and consequences for fetal development and growth, behavior and postnatal physiological functions. Finally, the influence of maternal age and parity was evaluated, and the breed´s foal in the production of plasmatic oestrogens, progesterone and cortisol in pregnant mares. Forty pregnant females were categorized according to age (Id1: 4-8 years; Id2: 8-12 years; Id3: &ge; 13 years), parity (Par1: nulliparous, Par2: 1 to 3 births; Par3: &ge; 4 births) and foal´s breed (MP: Mangalarga Paulista; BH: Brazilian Sporthorse). Plasma samples were collected weekly from the fifth month of pregnancy to term, and quantification of hormones was performed by Mass Spectrometry. Deliveries were accompanied and Apgar score, behavior and blood samples for biochemical analysis of the foals were collected within the first twelve hours of life. The chorioallantoic membranes were collected after delivery, weighed and photographed to scale. Tissue sections were collected from regions: uterine body, pregnant uterine horn and contralateral uterine horn to be analyzed stereologically. Neonate´s growth parameters were compared from birth up to two years old, as well as data on maternal and paternal height, weight, and thoracic perimeter were collected. No significant differences were observed in the quantification of steroids when considering maternal parity and foal´s breed for the mares groups. The concentrations of oestrogens were significantly higher in Id2 group when compared with Id3, in some months of the gestational period evaluated. It was observed that maternal age and parity influence the development of the microcotyledons and total villi surface density, as well as the vascularization and tissue composition of different regions of the placenta, contributing in fact to a larger area of fetomaternal contact and transfer of gases and nutrients between mother and fetus, culminating with foals that were taller, heavier and with larger thoracic circumference at birth. The paternal, and mainly maternal size, influenced the development of fetal villi and the area of fetomaternal contact surface with a positive effect on the development and fetal growth, resulting in the birth of foals with better metabolic and adaptive responses. It also highlights that the period of intrauterine life was decisive for the postnatal growth rate up to 24 months of life.

Σκοπός: Η μεταγεννητική αύξηση των παιδιών που εκτέθηκαν στον καπνό του τσιγάρου ενδομητρίως δεν είναι πλήρως κατανοητή. Σκοπός της παρούσας μελέτης είναι να ερευνήσει την αύξηση παιδιών των οποίων οι μητέρες κάπνιζαν στη διάρκεια της εγκυμοσύνης, κατά τα πρώτα έξι χρόνια της ζωής τους. Μέθοδοι: Το βάρος σώματος, το μήκος σώματος και η περίμετρος κεφαλής μετρήθηκαν στη γέννηση και κατόπιν ετησίως για έξι έτη σε 100 παιδιά των οποίων οι μητέρες κάπνιζαν (ομάδα μελέτης) και 100 παιδιά των οποίων οι μητέρες δεν κάπνιζαν (ομάδα ελέγχου). Αποτελέσματα: Το βάρος και η περίμετρος κεφαλής ήταν σημαντικά μικρότερα στα νεογνά των οποίων οι μητέρες κάπνιζαν >15 τσιγάρα την ημέρα, αλλά η διαφορά έχασε τη στατιστική σημαντικότητα στον τρίτο χρόνο της ζωής. Το μήκος ήταν σημαντικά μικρότερο στα νεογνά της ομάδας μελέτης στη γέννηση και ακολουθούσε αύξηση της διαφοράς από το φυσιολογικό έως το δεύτερο έτος, οπότε η μέση διαφορά των παιδιών που οι μητέρες τους κάπνιζαν >15 τσιγάρα την ημέρα από τα παιδιά της ομάδας ελέγχου ήταν -3,4 εκατοστά (p<0,0001). Στη συνέχεια, τα παιδιά των καπνιστριών μητέρων παρουσίασαν επιτάχυνση του ρυθμού αύξησης και η διαφορά από την ομάδα ελέγχου στα 3, 4, 5 και 6 χρόνια ζωής ήταν -2,5 (p<0,0001), -2,2 (p=0,005), -2,1 (p=0,013), και -1,9 εκατοστά (p=0,055), αντίστοιχα. Η καθυστερημένη αύξηση σχετιζόταν με το κάπνισμα αυτό καθ’εαυτό και δείχθηκε ότι η καθυστέρηση της αύξησης είναι ανεξάρτητη από πολλούς συμπαράγοντες. Επίσης, στη γέννηση υπήρχε σημαντική αρνητική συσχέτιση μεταξύ του αριθμού των τσιγάρων που καπνίζονταν ημερησίως και των παραμέτρων αύξησης που μελετήθηκαν. Η αρνητική συσχέτιση παρέμεινε σημαντική έως τον έκτο χρόνο ζωής μόνο για το ύψος. Συμπέρασμα: Το μήκος παρουσιάζει την πιο επίμονη καθυστέρηση της αύξησης από τις παραμέτρους που μελετήθηκαν, δηλαδή το βάρος σώματος και την περίμετρο κεφαλής, αλλά μετά το δεύτερο έτος της ζωής συμβαίνει επιτάχυνση της αύξησης, και έτσι η ενδομήτρια έκθεση στον καπνό του τσιγάρου φαίνεται να μην έχει μόνιμη επίδραση στην τελική αύξηση των παιδιών. / Objectives: Postnatal growth in children exposed in utero to tobacco smoke is not well understood. This study investigated growth during the first 6 years in children whose mothers smoked during pregnancy. Materials and Methods: Weight, length, and head circumference were measured annually for 6 years in 100 children in each group of smoking (study) and non smoking (control) mothers. Results: Weight and head circumference were significantly smaller in the neonates whose mothers smoked >15 cigarettes/day, but the difference disappeared by 3 years of life. Length was significantly smaller in the study neonates at birth, followed by increasing divergence from normality up to 2 years, when the mean difference of children whose mothers smoked >15 cigarettes/day from control children was -3.4 cm (p<0.0001). Subsequently, they manifested catch-up growth, and the difference from the controls at 3, 4, 5, and 6 years was -2.5 cm (p<0.0001), -2.2 cm (p=0.005), -2.1 cm (p=0.013), and -1.9 cm (p=0.055), respectively. Discussion: The delayed growth was related to smoking per se and appeared to be independent of several confounding factors. At birth, there was a significant negative correlation between the number of cigarettes smoked per day and the growth parameters studied; it remained significant up to the sixth year only for length. Conclusion: Length exhibits the most persistent growth delay of the parameters studied, but catch-up growth occurs after the second year of life, and thus, intrauterine exposure to tobacco smoke seems to have no permanent effect on children’s growth.

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...

Muitos fatores podem influenciar o desenvolvimento placentário e fetal na égua, dentre eles destaca-se a idade, a paridade e o porte materno. A produção de hormônios esteroides pela unidade feto-placentária também pode ser influenciada pela paridade e raça, porém não existem relatos prévios que relacionem os efeitos da idade da égua sobre a produção desses hormônios na gestação. Este trabalho conta com três objetivos principais: o primeiro investigou a influência do número de partos e da idade materna sobre a eficiência placentária e a biometria do potro ao nascimento, utilizando a análise estereológica da placenta a termo. O segundo determinou a influencia da biometria parental na macro e microscopia placentária e consequências para o desenvolvimento fetal e para o crescimento, comportamento e funções fisiológicas pós-natais. Por último foi avaliada a influência da idade e paridade materna, e da raça do potro sob a produção de estrógenos, progesterona e cortisol plasmáticos em éguas prenhes. Quarenta fêmeas gestantes foram categorizadas de acordo com a idade (Id1: 4 a 8 anos; Id2: 8 a 12 anos; Id3: &ge; 13 anos), a pluriparidade (Par1: nulíparas, Par 2: 1 a 3 partos; Par3: &ge; 4partos) e a raça do produto (MP: Mangalarga Paulista; BH: Brasileiro de Hipismo). As coletas de plasma foram realizadas semanalmente a partir do quinto mês de gestação até o termo, e a quantificação dos hormônios foi realizada pela técnica de Espectrometria de Massas. Os partos foram acompanhados a campo e dados do escore Apgar, comportamento e amostras sanguíneas para análise bioquímica dos potros foram coletados nas primeiras doze horas de vida. As membranas corioalantóides foram recolhidas após o delivramento, pesadas e fotografadas em escala. Foram coletados fragmentos correspondentes às regiões do corpo do útero, corno uterino gestante e corno uterino contralateral para análise estereológica. Parâmetros de crescimento dos neonatos foram comparados do nascimento até os dois anos de idade, assim como foram coletados dados da altura, peso e perímetro torácico materno e paterno. Não foram observadas diferenças significativas na quantificação de esteróides quando considerados os fatores número de partos e raça do produto para a categorização das fêmeas. As concentrações de estrógenos foram estatisticamente superiores no grupo Id2 em relação ao Id3, em alguns meses do período gestacional avaliado. Foi observado que a idade e a paridade materna influenciam o desenvolvimento dos microcotilédones e a densidade total de superfície dos vilos, bem como a vascularização e a composição tecidual das diferentes regiões da placenta, contribuindo de fato para uma maior área de contato materno-fetal e transferência de gases e nutrientes entre mãe e feto, culminando com o nascimento de potros mais altos, mais pesados e com maior circunferência torácica. O porte paterno, e principalmente o materno, influenciou o desenvolvimento das vilosidades fetais e a área de superfície de contato materno-fetal, com efeito positivo no desenvolvimento e no crescimento fetal, resultando no nascimento de potros com melhores respostas adaptativas e metabólicas. Também destaca-se que o período de vida intrauterino foi determinante para a taxa de crescimento pós-natal até os 24 meses de vida. / Many factors may influence placental and fetal development in the mare, like age, parity and maternal size. The production of steroid hormones by fetal-placental unit can also be influenced by parity and breed, but there are no previous reports relating the effects of the mares age on the production of these hormones during pregnancy. This paper has three main objectives: the first investigated the influence of maternal age and parity on placental efficiency and size of the foal at birth, using stereological analysis of the term placenta. The second determined the influence of parental size on macro and microscopy of the placenta and consequences for fetal development and growth, behavior and postnatal physiological functions. Finally, the influence of maternal age and parity was evaluated, and the breed´s foal in the production of plasmatic oestrogens, progesterone and cortisol in pregnant mares. Forty pregnant females were categorized according to age (Id1: 4-8 years; Id2: 8-12 years; Id3: &ge; 13 years), parity (Par1: nulliparous, Par2: 1 to 3 births; Par3: &ge; 4 births) and foal´s breed (MP: Mangalarga Paulista; BH: Brazilian Sporthorse). Plasma samples were collected weekly from the fifth month of pregnancy to term, and quantification of hormones was performed by Mass Spectrometry. Deliveries were accompanied and Apgar score, behavior and blood samples for biochemical analysis of the foals were collected within the first twelve hours of life. The chorioallantoic membranes were collected after delivery, weighed and photographed to scale. Tissue sections were collected from regions: uterine body, pregnant uterine horn and contralateral uterine horn to be analyzed stereologically. Neonate´s growth parameters were compared from birth up to two years old, as well as data on maternal and paternal height, weight, and thoracic perimeter were collected. No significant differences were observed in the quantification of steroids when considering maternal parity and foal´s breed for the mares groups. The concentrations of oestrogens were significantly higher in Id2 group when compared with Id3, in some months of the gestational period evaluated. It was observed that maternal age and parity influence the development of the microcotyledons and total villi surface density, as well as the vascularization and tissue composition of different regions of the placenta, contributing in fact to a larger area of fetomaternal contact and transfer of gases and nutrients between mother and fetus, culminating with foals that were taller, heavier and with larger thoracic circumference at birth. The paternal, and mainly maternal size, influenced the development of fetal villi and the area of fetomaternal contact surface with a positive effect on the development and fetal growth, resulting in the birth of foals with better metabolic and adaptive responses. It also highlights that the period of intrauterine life was decisive for the postnatal growth rate up to 24 months of life.

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...

Introdução: Não há curvas de crescimento satisfatórias para lactentes pré-termo de muito baixo peso (PTMBP) até dois anos de idade corrigida (IC), considerando todos os avanços na assistência neonatal ocorridos nas últimas duas décadas. Objetivo: Elaborar curvas de peso, comprimento e perímetro cefálico até dois anos de IC para uma coorte de lactentes PTMBP; comparar as curvas dos adequados (AIG) e dos pequenos para a idade gestacional (PIG). Método: Uma coorte de lactentes PTMBP admitidos na Unidade de Tratamento Intensivo Neonatal do nosso serviço até 24 horas após nascimento entre novembro/2003 até setembro/2005 foi estudada até dois anos de IC. Lactentes com malformações maiores, síndromes cromossômicas, infecções congênitas e aqueles com menos de três revisões nos primeiros dois anos ambulatório de seguimento foram excluídos. Peso, comprimento e perímetro cefálico foram aferidos rotineiramente até 2 anos de IC. O estudo foi aprovado pelo Comitê de Ética e Pesquisa da Instituição. Resultados: Peso, comprimento e perímetro cefálico foram obtidos de 117 recémnascidos PTMBP (51 AIG e 66 PIG) e foram elaboradas curvas de crescimento para lactentes AIG e PIG. As curvas de peso, comprimento e perímetro cefálico de lactentes AIG e PIG têm o mesmo formato (p=0,211; p=0,193; p=0,463, respectivamente). As médias do peso, comprimento e perímetro cefálico com 40 semanas, 12 meses e 24 meses de IC são significativamente superiores entre lactentes AIG (p<0,01, Mixed Effect Models). Conclusão: As curvas de crescimento obtidas através desse estudo longitudinal são adequadas para monitorização do crescimento pós-natal de pré-termos de muito baixo peso AIG e PIG até 2 anos de IC. / Background: There are no satisfactory growth charts for very low birth weight (VLBW) infants from hospital discharge up to two years corrected age that take in consideration all the changes that occurred in neonatal care in the last twenty years. Objectives: To obtain weight, length and head circumference growth charts up to 2 year corrected age (CA) for a cohort of VLBW infants and, also to compare appropriate (AGA) and small (SGA) for gestational age growth curves. Methods: A cohort of VLBW infants admitted to our NICU up to 24 hours after birth from November 2003 through September 2005, and discharged from hospital was studied up to 2 years CA. Infants with major malformations, chromosomal syndromes, congenital infections (STORCH group), and those that had less than 3 appointments in the follow up clinic in the first two years were excluded. Weight, length, and head circumference were measured monthly up to 2 years CA. Results: Mean weight. Length, and head circumference were obtained from 117 newborns (51 AGA and 66 SGA). Growth curves for AGA and SGA infants were obtained. The weight, length, and head circumference growth curves had the same shape for AGA and SGA infants (p=0.211; p=0.193; p=0.463, respectively). Mean weight, length and head circumference at 40 weeks, 12 months and 24 months CA were significantly higher in AGA than in SGA infants (p<0.01, Mixed effect models). Conclusion: Growth curves obtained in this longitudinal study are adequate for monitoring post-natal growth of AGA and SGA VLBW infants.

Introdução: Não há curvas de crescimento satisfatórias para lactentes pré-termo de muito baixo peso (PTMBP) até dois anos de idade corrigida (IC), considerando todos os avanços na assistência neonatal ocorridos nas últimas duas décadas. Objetivo: Elaborar curvas de peso, comprimento e perímetro cefálico até dois anos de IC para uma coorte de lactentes PTMBP; comparar as curvas dos adequados (AIG) e dos pequenos para a idade gestacional (PIG). Método: Uma coorte de lactentes PTMBP admitidos na Unidade de Tratamento Intensivo Neonatal do nosso serviço até 24 horas após nascimento entre novembro/2003 até setembro/2005 foi estudada até dois anos de IC. Lactentes com malformações maiores, síndromes cromossômicas, infecções congênitas e aqueles com menos de três revisões nos primeiros dois anos ambulatório de seguimento foram excluídos. Peso, comprimento e perímetro cefálico foram aferidos rotineiramente até 2 anos de IC. O estudo foi aprovado pelo Comitê de Ética e Pesquisa da Instituição. Resultados: Peso, comprimento e perímetro cefálico foram obtidos de 117 recémnascidos PTMBP (51 AIG e 66 PIG) e foram elaboradas curvas de crescimento para lactentes AIG e PIG. As curvas de peso, comprimento e perímetro cefálico de lactentes AIG e PIG têm o mesmo formato (p=0,211; p=0,193; p=0,463, respectivamente). As médias do peso, comprimento e perímetro cefálico com 40 semanas, 12 meses e 24 meses de IC são significativamente superiores entre lactentes AIG (p<0,01, Mixed Effect Models). Conclusão: As curvas de crescimento obtidas através desse estudo longitudinal são adequadas para monitorização do crescimento pós-natal de pré-termos de muito baixo peso AIG e PIG até 2 anos de IC. / Background: There are no satisfactory growth charts for very low birth weight (VLBW) infants from hospital discharge up to two years corrected age that take in consideration all the changes that occurred in neonatal care in the last twenty years. Objectives: To obtain weight, length and head circumference growth charts up to 2 year corrected age (CA) for a cohort of VLBW infants and, also to compare appropriate (AGA) and small (SGA) for gestational age growth curves. Methods: A cohort of VLBW infants admitted to our NICU up to 24 hours after birth from November 2003 through September 2005, and discharged from hospital was studied up to 2 years CA. Infants with major malformations, chromosomal syndromes, congenital infections (STORCH group), and those that had less than 3 appointments in the follow up clinic in the first two years were excluded. Weight, length, and head circumference were measured monthly up to 2 years CA. Results: Mean weight. Length, and head circumference were obtained from 117 newborns (51 AGA and 66 SGA). Growth curves for AGA and SGA infants were obtained. The weight, length, and head circumference growth curves had the same shape for AGA and SGA infants (p=0.211; p=0.193; p=0.463, respectively). Mean weight, length and head circumference at 40 weeks, 12 months and 24 months CA were significantly higher in AGA than in SGA infants (p<0.01, Mixed effect models). Conclusion: Growth curves obtained in this longitudinal study are adequate for monitoring post-natal growth of AGA and SGA VLBW infants.