Introdução: O Diabetes mellitus tipo 1 (DM1) cursa com produção ausente ou irrisória de insulina e é a forma responsável pelos casos mais graves de distúrbios glicêmicos. O DM1 exerce forte influência sobre o crescimento fetal. Enquanto a hiperglicemia estimula o crescimento fetal devido à hiperinsulinemia, nas pacientes com vasculopatias a placentação inadequada pode levar o feto à restrição. Objetivos: identificar alterações de crescimento fetal e avaliá-las quanto a sua associação com o controle glicêmico materno e de marcadores laboratoriais de função renal. Métodos: foram avaliadas, de forma prospectiva em coorte observacional, 60 gestantes com DM1 que iniciaram o pré-natal no primeiro trimestre. A associação entre a classificação de peso ao nascimento com as seguintes variáveis foi analisada: média glicêmica, frequência de hipo e hiperglicemia, frequência de hipo e hiperglicemia grave, hemoglobina glicada, frutosamina, ácido úrico, creatinina e proteinúria de 24 horas. A predição do crescimento fetal também foi estudada. Resultados: Desvios do crescimento fetal em pacientes com DM1 ocorreram em 41% dos casos (n=25). Observou-se que 10% das gestações resultaram em PIG (n=6) e 31%, em GIG (n=19). Níveis aumentados de média glicêmica (p =0,006), baixa frequência de hipoglicemias (p = 0,027) e alta frequência de hiperglicemias (p = 0,014) se associaram a GIG no terceiro trimestre. Em todos os trimestres, valores séricos mais elevados de ácido úrico, creatinina e proteinúria de 24hs, se associaram de maneira significativa, ao grupo PIG. Foi construído um modelo, com taxa de acerto de 80.3%, para a predição de crescimento fetal com os valores de terceiro trimestre da média glicêmica e da creatinina. Conclusões: Foram identificadas variáveis relacionadas ao controle glicêmico materno e à marcadores laboratoriais de função renal que se associaram a alterações no crescimento fetal. Usando algumas dessas variáveis foi possível construir um modelo para predição do crescimento fetal com boa acurácia / Introduction. Diabetes mellitus type 1 (DM1) is described as absent or negligible production of insulin and it is responsible for the most severe cases of glycemic disorders. DM1 has a strong influence on fetal growth. In pregnant women the hyperglycemia stimulates fetal growth, and the vasculopathy influences the placentation process, which may lead to growth restriction. Objective. To identify fetal growth disorders and their association with maternal glycemic control and laboratory markers of renal function. Methods. Sixty pregnant women with DM1 were prospectively followed from the first trimester in an observational cohort. The association between birthweight classification with the following parameter were investigated: glycemic mean, frequency of hypo and hyperglycemia, frequency of severe hyper and hypoglycemia, glycated hemoglobin, fructosamine, uric acid, creatinine and proteinuria of 24 hours. The prediction of fetal growth was also investigated. Results. Abnormal fetal growth was observed in 41% (n= 25). Large for gestational age (LGA) was observed in 31.7% (n=19) and small for gestational age (SGA) in 10% (n= 6). High values of glycemic mean (p = 0.006), low frequency of hypoglycemia (p = 0.027) and high frequency of hyperglycemia (p = 0.014) were significantly associated with LGA fetal growth in the third trimester. In all trimesters, the SGA fetal growth was significantly associated with higher serum values of uric acid, creatinine and proteinuria of 24 hours. The prediction model for fetal growth, using values of glycemic mean and creatinine, was significant in the third trimester with an accuracy of 80.3%. Conclusions. The maternal glycemic control and the laboratory markers of renal function associated with the fetal growth disorders in pregnancies with DM1 were identified. Using these parameters it was possible to predict with a good accuracy the fetal growth in DM1

Introdução: O Diabetes mellitus tipo 1 (DM1) cursa com produção ausente ou irrisória de insulina e é a forma responsável pelos casos mais graves de distúrbios glicêmicos. O DM1 exerce forte influência sobre o crescimento fetal. Enquanto a hiperglicemia estimula o crescimento fetal devido à hiperinsulinemia, nas pacientes com vasculopatias a placentação inadequada pode levar o feto à restrição. Objetivos: identificar alterações de crescimento fetal e avaliá-las quanto a sua associação com o controle glicêmico materno e de marcadores laboratoriais de função renal. Métodos: foram avaliadas, de forma prospectiva em coorte observacional, 60 gestantes com DM1 que iniciaram o pré-natal no primeiro trimestre. A associação entre a classificação de peso ao nascimento com as seguintes variáveis foi analisada: média glicêmica, frequência de hipo e hiperglicemia, frequência de hipo e hiperglicemia grave, hemoglobina glicada, frutosamina, ácido úrico, creatinina e proteinúria de 24 horas. A predição do crescimento fetal também foi estudada. Resultados: Desvios do crescimento fetal em pacientes com DM1 ocorreram em 41% dos casos (n=25). Observou-se que 10% das gestações resultaram em PIG (n=6) e 31%, em GIG (n=19). Níveis aumentados de média glicêmica (p =0,006), baixa frequência de hipoglicemias (p = 0,027) e alta frequência de hiperglicemias (p = 0,014) se associaram a GIG no terceiro trimestre. Em todos os trimestres, valores séricos mais elevados de ácido úrico, creatinina e proteinúria de 24hs, se associaram de maneira significativa, ao grupo PIG. Foi construído um modelo, com taxa de acerto de 80.3%, para a predição de crescimento fetal com os valores de terceiro trimestre da média glicêmica e da creatinina. Conclusões: Foram identificadas variáveis relacionadas ao controle glicêmico materno e à marcadores laboratoriais de função renal que se associaram a alterações no crescimento fetal. Usando algumas dessas variáveis foi possível construir um modelo para predição do crescimento fetal com boa acurácia / Introduction. Diabetes mellitus type 1 (DM1) is described as absent or negligible production of insulin and it is responsible for the most severe cases of glycemic disorders. DM1 has a strong influence on fetal growth. In pregnant women the hyperglycemia stimulates fetal growth, and the vasculopathy influences the placentation process, which may lead to growth restriction. Objective. To identify fetal growth disorders and their association with maternal glycemic control and laboratory markers of renal function. Methods. Sixty pregnant women with DM1 were prospectively followed from the first trimester in an observational cohort. The association between birthweight classification with the following parameter were investigated: glycemic mean, frequency of hypo and hyperglycemia, frequency of severe hyper and hypoglycemia, glycated hemoglobin, fructosamine, uric acid, creatinine and proteinuria of 24 hours. The prediction of fetal growth was also investigated. Results. Abnormal fetal growth was observed in 41% (n= 25). Large for gestational age (LGA) was observed in 31.7% (n=19) and small for gestational age (SGA) in 10% (n= 6). High values of glycemic mean (p = 0.006), low frequency of hypoglycemia (p = 0.027) and high frequency of hyperglycemia (p = 0.014) were significantly associated with LGA fetal growth in the third trimester. In all trimesters, the SGA fetal growth was significantly associated with higher serum values of uric acid, creatinine and proteinuria of 24 hours. The prediction model for fetal growth, using values of glycemic mean and creatinine, was significant in the third trimester with an accuracy of 80.3%. Conclusions. The maternal glycemic control and the laboratory markers of renal function associated with the fetal growth disorders in pregnancies with DM1 were identified. Using these parameters it was possible to predict with a good accuracy the fetal growth in DM1

This study has determined the cellular site of adenosine deaminase (ADA) expression in the mouse during development from Days 5 through 13 (day vaginal plug was found = Day 0) of gestation. Developmental expression of ADA progressed in two overlapping phases defined genetically (maternal vs. embryonal) and according to region (decidual vs. placental). In the first phase, ADA enzyme activity increased almost 200-fold in the antimesometrial region (decidua capsularis + giant trophoblast cells) from Days 6 through 9 of gestation but remained low in the mesometrial region. Immunohistochemical staining revealed a major localization of ADA to the secondary decidua. In the second phase, ADA activity increased several-fold in the placenta (labyrinth + basal zones) from Days 9 through 13 of gestation but remained low in the embryo proper. Immunohistochemical staining revealed a major localization of ADA to secondary giant cells, spongiotrophoblast, and labyrinthine trophoblast. Regression of decidua capsularis and growth of the spongiotrophoblast population accounted for an antimesometrial to placental shift in both ADA enzyme activity and a 40-kDa immunoreactive protein band. To verify a shift from maternal to fetal expression, studies were performed with two strains of mice (ICR, Eday) homozygous for a different ADA isozyme (ADA-A, ADA-B). Blastocysts homozygous for Adab were transferred to the uterus of pseudopregnant female recipients homozygous for Adaa. The isozymic pattern in chimeric embryo-decidual units analyzed at Days 7, 9, 11, and 13 revealed a predominance of maternal-encoded enzyme at Days 7 through 11 of gestation and a shift to fetal-encoded enzyme by Day 13. Thus, maternal expression of ADA in the antimesometrial decidua may play a role during establishment of the embryo in the uterine environment, whereas fetal expression of ADA in the trophoblast might be important to placentation.