Memoria para optar al Título Profesional de Médico Veterinario. / En la producción ovina, la obtención de mellizos es una estrategia clave para mejorar la productividad predial. Sin embargo, los corderos mellizos nacen con menor peso que las crías gestadas individualmente, lo cual está asociado a mayor mortalidad perinatal, y en consecuencia se podría afectar negativamente la rentabilidad del sistema productivo. El desarrollo intrauterino de las crías depende principalmente de su potencial genético y de la disponibilidad de nutrientes y oxígeno. La transferencia de nutrientes y gases entre los compartimentos materno-fetal responde al flujo sanguíneo útero-placentario y a la capacidad (suficiencia) placentaria, por lo que la subnutrición materna y la insuficiencia placentaria pueden perjudicar el desarrollo de las crías al comprometerse el influjo de nutrientes y/o oxígeno. Este estudio se realizó utilizando 64 ovejas de la raza Corriedale, categorizadas por gestación (única o mellicera). Las ovejas fueron sometidas a dos planos nutricionales desde el día 30 hasta el término de la gestación; uno cubre el ∼70% y otro el ∼100% de los requerimientos energético-proteicos de la oveja gestante. Además se evaluó el peso y la condición corporal de las ovejas cada 30 días. A los 100 y 140 días de gestación se realizaron cesáreas y se tomaron muestras sanguíneas desde la vena umbilical de cada feto, para evaluar variables asociadas a la oxigenación fetal (PO2, PCO2, saturación de hemoglobina con oxígeno, hematocrito y pH) y de la morfometría fetal (longitud cabeza-cola, perímetro toráxico, largo de mano y largo de pata). Adicionalmente, a los 140 días de gestación se evaluó el peso y la morfología placentaria. Los resultados se analizaron mediante análisis de varianza (ANOVA), donde los factores fijos fueron el número de fetos en gestación (único o mellizos) y el plano nutricional (~70 ó ~100% de los requerimientos establecidos por el National Research Council, NRC), seguido del test post-hoc de Duncan para detección de diferencias entre grupos. Se consideraron diferencias significativas cuando p≤0,05. A los 100 días de gestación, no se evidenciaron diferencias estadísticamente significativas en ninguna de las variables estudiadas. A los 140 días de gestación el peso de las ovejas alimentadas con dieta control (~100% NRC) fueron mayores que el de las ovejas alimentadas con dieta de restricción (~70% NRC). Las ovejas del grupo control gestación única (CU) presentaron la mayor condición corporal al compararse con los demás grupos. Las ovejas de gestación mellicera presentaron mayores valores de peso placentario total por oveja y mayor número de placentomas por oveja que las de gestación única. Las ovejas de gestación única presentaron mayores valores de peso placentario total por feto y mayor número de placentomas por feto que las de gestación mellicera. Los tipos de placentomas predominantes en todos los grupos fueron los de tipo A y B, presentándose en menor proporción los C y D. Las concentraciones de oxígeno fetal fueron mayores en el grupo dieta control gestación única (CU) en comparación con los demás grupos experimentales. Además, se evidenció una correlación positiva, moderada (r=0.459) y estadísticamente significativa (p=0.013) entre la PO2 de la vena umbilical y peso fetal a los 140 días de gestación. Los fetos gestados individualmente presentaron mayor peso que los obtenidos por gestación mellicera / In sheep production, obtaining twins is a key strategy to improve farm productivity. However, twin lambs are born lighter and smaller than singletons, which is associated with higher perinatal mortality, therefore the profitability of the productive system can be reduced. The intrauterine development of the offspring depends mainly on their genetic potential and the availability of nutrients and oxygen. The transfer of nutrients and gases between the maternal-fetal compartments responds to utero-placental blood flow and placental capacity (sufficiency), so that maternal undernourishment and placental insufficiency can adversely affect the development of the offspring by compromising the nutrient and/or oxygen influx. This study was conducted on 60 corriedale bred sheep, separated by pregnancy rank (singleton or twin bearing). The sheep in this study underwent two nutritional plans from day 30 until the end of gestation, one that covered ~70% and another ~ 100% of the energetic-protein requirements of the pregnant sheep. The weight and body condition score of the sheep were evaluated every 30 days. At 100 and 140 days of gestation, caesarean sections were performed. Blood samples were collected from the umbilical vein of each fetus to evaluate variables associated with fetal oxygenation (PO2, PCO2, hemoglobin saturation with oxygen, hematocrit and pH). Fetal morphometric parameters were also measured (crown-rump length, thoracic perimeter, arm and leg length). Additionally, at 140 days of gestation, an evaluation of placental weight and morphology was performed. The results were evaluated by analysis of variance (ANOVA), where the fixed factors were the number of fetuses in gestation (single or twins) and the nutritional level (~70 or ~100% of the requirements established by the NRC), followed by the post-hoc Duncan test. Significant differences were considered at p≤0.05. At 100 days of gestation, no differences were evident in any of the variables studied. At 140 days of gestation the weight of the ewes fed with the control diet (~100% NRC) was greater than that of the ewes fed with the restriction diet (~70% NRC). The ewes from the single gestation control group (SC) had the highest body condition score when compared with the other groups. Twin-bearing ewes had higher values of total placental weight per sheep and a greater number of placentomes per sheep than those of single-gestation ewes. The single-gestation ewes had higher values of total placental weight per fetus and more placentomes per fetus than twin-bearing ewes. The predominant type of placentome in all groups were A and B, with a lower proportion of C and D. Fetal oxygen concentrations were higher in the single gestation control group (SC) compared to the other experimental groups. In addition, there was a positive correlation (r = 0.459) and statistically significant (p = 0.013) between the PO2 obtained from the umbilical vein and fetal weight at 140 days of gestation. All singletons were heavier than the twins / Financiamiento: Proyecto Fondecyt 1160892.

Orientador: Ricardo Barini / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-12T18:24:38Z (GMT). No. of bitstreams: 1 Sarno_ManoelAlfredoCurvelo._D.pdf: 2031340 bytes, checksum: 3b2a7d30a8001e19edce044e6d8670ab (MD5) Previous issue date: 2009 / Resumo: Introdução: A presença de anticorpos antifosfolipídeos freqüentemente está associada a complicações obstétricas como aborto de repetição, óbito fetal, descolamento prematuro da placenta e pré-eclâmpsia grave e precoce. Objetivo: avaliar associação dos antecedentes mórbidos, da Dopplervelocimetria de artérias uterinas, dos anticorpos antifosfolipídeos (AAF) e resultados obstétricos/perinatais em um grupo de gestantes. Sujeitos e Métodos: foi conduzido um estudo de coorte e corte transversal, onde foram analisadas gestantes atendidas nos Ambulatórios de Pré-Natal da Unicamp que aceitaram participar do estudo. Foi aplicado um questionário sobre os antecedentes mórbidos, realização de dosagem dos AAF, realizada Dopplervelocimetria de artérias uterinas e analisada correlação com resultados obstétricos/perinatais. Resultado: foram avaliadas 385 gestantes com média de idade de 26,6 (±6,3) anos. A anticardiolipina (aCL) e o anti-ß2 glicoproteína I (anti-ß2-gpI) foram avaliados em 382 gestantes, dos quais 4,4% apresentaram o anti-ß2gpI IgM positivo, 4,7% IgG, 6,2% aCL IgG e 6,7% IgM. O anticoagulante lúpico (AL) foi avaliado em 137 gestantes com positividade em 2,3%. 33,4% das gestantes tinham, pelo menos, um antecedente obstétrico desfavorável (aborto recorrente, óbito fetal, pré-eclâmpsia, parto prematuro, filho anterior nascido com peso menor que 2.500g ou descolamento prematuro de placenta) e 2,6% tinham eventos trombóticos (infarto, acidente vascular cerebral, tromboembolismo pulmonar ou trombose venosa profunda). 16,5% tinham pelo menos um antecedente e um AAF positivo, contra 13,3% sem antecedente (p=0,44). 10% apresentavam antecedente trombótico e AAF positivo contra 14,4% sem história de evento trombótico e AAF negativo (p=0,88). As complicações obstétricas/perinatais foram avaliadas em 305 gestantes sendo que no grupo com antecedentes 31,7% evoluíram para alguma complicação obstétrica na gestação em curso contra 28,4% do grupo sem antecedente (p=0,59). Analisando o desfecho pré-eclâmpsia com pelo menos um antecedente, 7,7% x 4,5% (p=0,29), índice Apgar no 5º minuto menor ou igual a 7, 4,9% x 5,6% (p=0,57), peso abaixo de 2.500g, 15,5% x 12% (p=0,47). Quando separados os grupos com e sem antecedentes e comparados ao Doppler de artérias uterinas as mulheres que relataram peso inferior a 2.500g tiveram 4,0 [IC95: 1,16-13,7] vezes mais chance de apresentar índice de pulsatilidade acima do percentil 95 (IP>P95) e 4,68 [IC95: 1,37-15,9] quando apresentavam antecedente de elevação da pressão arterial antes das 34 semanas em gestação anterior. Não foram encontradas correlações dos outros antecedentes com o Doppler. Quando o IP>P95 houve um risco relativo (RR) de 2,77 [IC95: 1,87-4,11] para pelo menos uma complicação obstétrica/perinatal, 5,19 [IC95: 1,41-19,1] para Apgar do 5º minuto menor que 7 e 6,94 [IC95: 4,31-11,1] de peso abaixo de 2.500g. Quando associado IP>P95 e pelo menos um antecedente o RR para peso abaixo de 2.500g foi de 6,06 [IC95: 3,19-11,5] e 6,61 [IC95: 3,46-12,6] para parto antes das 37 semanas. Quando comparados os dois grupos não foi encontrada significância estatística no desfecho de pré-eclâmpsia com RR de 4.70 [IC95: 0,80-27,4]. Na avaliação do IP>P95 e AAF, 11,1% tinham o IP>P95 e pelo menos um AAF, contra 14,4% no grupo sem essas características, com Razão de Prevalência (RP)=0,77 [IC95: 0,11-4,96]. A RP para o grupo com IP>P95 e pelo menos um antecedente para a presença de pelo menos um AAF, foi de 1,75 [IC95: 0,31-9,75]. Conclusão: os antecedentes obstétricos desfavoráveis, assim como o Doppler de artérias uterinas não se correlacionaram com os AAF. O aumento da resistência ao Doppler nas artérias uterinas, isoladamente ou em associação aos antecedentes mórbidos, apresentou maior chance de complicações obstétricas/perinatais. Não foram encontradas diferenças estatísticas quando avaliado o Doppler associado com antecedentes e AAF / Abstract: The presence of antiphospholipid antibodies is often associated with obstetrical complications such as recurrent miscarriage, fetal death, placental abruption and severe early preeclampsia. Objective: To evaluate the association between a history of morbidity, uterine artery Doppler flow, serum antiphospholipid antibodies (APA) and perinatal/obstetric outcomes in a group of pregnant women. Subjects and methods: A cross-sectional cohort study evaluated pregnant women receiving care at Unicamp's prenatal clinic, who agreed to participate in the study. A questionnaire was applied to obtain data on the patient's history of morbidity, serum antiphospholipid antibodies were measured and a Doppler scan of the uterine arteries was performed. Results were correlated with obstetrical/perinatal outcome. Results: A total of 385 pregnant women with a mean age of 26.6 ± 6.3 years were evaluated. Anticardiolipin (aCL) and anti-ß2 glycoprotein I (anti-ß2-gpI) were evaluated in a group of 382 pregnant women, 4.4% of whom tested positive for anti-ß2-gpI IgM, 4.7% for IgG, 6.2% for ACL IgG and 6.7% for IgM. Lupus anticoagulant (LA) was evaluated in 137 pregnant women, 2.3% of whom tested positive. Overall, 33.4% of patients had a medical history that included recurrent miscarriage, fetal death, preeclampsia, prematurity, previous pregnancy resulting in an infant with birthweight of <2.500g or placental abruption. In addition, 2.6% had experienced a thrombotic event such as myocardial infarction, stroke, pulmonary thromboembolism or deep vein thrombosis. Overall, 16.5% of patients had at least one of the above-mentioned conditions and tested positive for APA compared to 13.3% of those with no medical history of any of these conditions (p=0.44). Ten percent of the women had experienced a thrombotic event and tested positive for APA while 14.4% had never had a thrombotic event and tested negative for APA (p=0.88). Obstetric and perinatal outcomes were analyzed in 305 women, and results showed that 31.7% of the women with a medical history of morbidities suffered at least one obstetrical complication in the current pregnancy compared to 28.4% in the group of women who had no medical history of morbidity (p=0.59). When each outcome was correlated with a history of at least one medical condition, preeclampsia was found in 7.7% of cases versus 4.5% in the group with no medical history (p=0.29), 5th minute Apgar score = 7 in 4.9% compared to 5.6% (p=0.57) and birthweight <2.500g in 15.5% compared to 12% (p=0.47). When the groups of women with and without a medical history of complication were analyzed separately and correlated with uterine artery Doppler, the women who reported having had an infant with a birthweight <2.500 grams were four times more likely (95%CI: 1.16-13.7) to have a pulsatility index (PI) above the 95th percentile and 4.68 times more likely (95%CI: 1.37-15.9) if they had a history of increased blood pressure prior to 34 weeks in their previous pregnancy. No significant correlations were found between other medical conditions and PI above the 95th percentile. When the PI was above the 95th percentile, there was a relative risk (RR) of 2.77 (95%CI: 1.87-4.11) of developing at least one obstetrical/perinatal complication, a RR of 5.19 (95%CI: 1.41-19.1) of 5th minute Apgar score being = 7 and a RR of 6.94 (95%CI: 4.31-11.1) of birthweight <2.500 grams. When PI above the 95th percentile was associated with at least one prior complication, the RR for birthweight <2.500 grams was 6.06 (95%CI: 3.19 - 11.5) and 6.61 (95%CI: 3.46 - 12.6) for delivery prior to 37 weeks. When the two groups were compared, no statistically significant correlation was found with respect to eclampsia (RR 4.70; 95%CI: 0.80 - 27.4). In the evaluation of PI above the 95th percentile and APA, 11.1% of patients had PI above the 95th percentile and at least one APA compared to 14.4% in the group without these characteristics (prevalence ratio [PR] 0.77; 95%CI: 0.11-4.96). The PR for the group with PI above the 95th percentile and at least one previous medical condition was 1.75 (95%CI: 0.31-9.75). Conclusion: Neither history of morbidity nor uterine artery Doppler was found to be associated with antiphospholipid antibodies. A significant correlation was found between increased uterine artery Doppler resistance, both when analyzed alone or in association with medical history, and obstetric/perinatal complications. No statistically significant differences were found between uterine artery Doppler associated with medical history and antiphospholipid antibodies / Doutorado / Tocoginecologia / Doutor em Tocoginecologia