La reproduction est un pilier majeur de la productivité des fermes laitières. Dans ce contexte, il est pertinent d’identifier à l’avance les animaux à risque d’avoir des performances en reproduction sous-optimales, surtout si un traitement efficace est disponible pour améliorer ces performances. Les endométrites clinique et subclinique sont des conditions définies selon leur impact sur les performances en reproduction subséquentes et donc, des outils très intéressants de surveillance de la santé utérine. Le premier objectif de cette étude était de déterminer simultanément des seuils diagnostiques pour les endométrites clinique (diagnostiquée par le Metricheck) et subclinique (diagnostiquée par la cytologie endométriale ou par l’estérase leucocytaire) selon leur impact sur les performances en reproduction à la première saillie. L’écoulement vaginal purulent a été identifié comme seuil pour l’endométrite clinique, alors que les seuils identifiés pour l’endométrite subclinique ont été un pourcentage de polymorphonucléaires de 6% à la cytologie et une « forte quantité de leucocytes » à l’estérase leucocytaire. Le second objectif de l’étude était d’évaluer l’effet d’un traitement intra-utérin de céphapirine sur les performances à la première saillie des animaux sains et atteints d’endométrite. Aucun effet du traitement n’a été observé chez les vaches saines ou atteintes d’endométrite clinique, alors qu’une tendance à l’amélioration des performances a été associée au traitement chez celles atteintes d’endométrite subclinique. L’anovulation post-partum prolongée pourrait altérer l’efficacité du traitement de céphapirine, surtout chez les vaches atteintes d’endométrite clinique. / Reproduction is a major concern in the dairy industry. In this context, it is relevant to have an early identification of cows at risk of altered subsequent reproductive performance, especially if a treatment is available and effective to improve this performance. Clinical and subclinical endometritis are defined based on their impact on reproductive performance and are interesting tools for reproductive tract health surveillance. The first objective of this research project was to determine simultaneously diagnostic criteria for clinical (diagnosed by Metricheck) and subclinical (diagnosed by endometrial cytology or leukocyte esterase testing) endometritis based on their impact on reproductive performance at first service. Clinical endometritis was defined as presence of purulent vaginal discharge whereas subclinical endometritis was defined as presence of ≥ 6% of polymorphonuclear cells using endometrial cytology or the presence of “large amount of leukocytes” using leukocyte esterase testing. The second objective of this research project was to determine the effect of an intrauterine infusion of cephapirin on the reproductive performance at first service in cows with clinical endometritis, subclinical endometritis, and in cows unaffected by endometritis. Cephapirin treatment had no effect on first service pregnancy risk in unaffected cows or in cows affected by clinical endometritis. However, there was a tendency of a positive effect of the treatment in cows affected by subclinical endometritis. Presence of prolonged postpartum anovulation in cows may reduce the efficacy of the cephapirin treatment, especially in cows affected by clinical endometritis.

La reproduction est un pilier majeur de la productivité des fermes laitières. Dans ce contexte, il est pertinent d’identifier à l’avance les animaux à risque d’avoir des performances en reproduction sous-optimales, surtout si un traitement efficace est disponible pour améliorer ces performances. Les endométrites clinique et subclinique sont des conditions définies selon leur impact sur les performances en reproduction subséquentes et donc, des outils très intéressants de surveillance de la santé utérine. Le premier objectif de cette étude était de déterminer simultanément des seuils diagnostiques pour les endométrites clinique (diagnostiquée par le Metricheck) et subclinique (diagnostiquée par la cytologie endométriale ou par l’estérase leucocytaire) selon leur impact sur les performances en reproduction à la première saillie. L’écoulement vaginal purulent a été identifié comme seuil pour l’endométrite clinique, alors que les seuils identifiés pour l’endométrite subclinique ont été un pourcentage de polymorphonucléaires de 6% à la cytologie et une « forte quantité de leucocytes » à l’estérase leucocytaire. Le second objectif de l’étude était d’évaluer l’effet d’un traitement intra-utérin de céphapirine sur les performances à la première saillie des animaux sains et atteints d’endométrite. Aucun effet du traitement n’a été observé chez les vaches saines ou atteintes d’endométrite clinique, alors qu’une tendance à l’amélioration des performances a été associée au traitement chez celles atteintes d’endométrite subclinique. L’anovulation post-partum prolongée pourrait altérer l’efficacité du traitement de céphapirine, surtout chez les vaches atteintes d’endométrite clinique. / Reproduction is a major concern in the dairy industry. In this context, it is relevant to have an early identification of cows at risk of altered subsequent reproductive performance, especially if a treatment is available and effective to improve this performance. Clinical and subclinical endometritis are defined based on their impact on reproductive performance and are interesting tools for reproductive tract health surveillance. The first objective of this research project was to determine simultaneously diagnostic criteria for clinical (diagnosed by Metricheck) and subclinical (diagnosed by endometrial cytology or leukocyte esterase testing) endometritis based on their impact on reproductive performance at first service. Clinical endometritis was defined as presence of purulent vaginal discharge whereas subclinical endometritis was defined as presence of ≥ 6% of polymorphonuclear cells using endometrial cytology or the presence of “large amount of leukocytes” using leukocyte esterase testing. The second objective of this research project was to determine the effect of an intrauterine infusion of cephapirin on the reproductive performance at first service in cows with clinical endometritis, subclinical endometritis, and in cows unaffected by endometritis. Cephapirin treatment had no effect on first service pregnancy risk in unaffected cows or in cows affected by clinical endometritis. However, there was a tendency of a positive effect of the treatment in cows affected by subclinical endometritis. Presence of prolonged postpartum anovulation in cows may reduce the efficacy of the cephapirin treatment, especially in cows affected by clinical endometritis.

Increasing evidence implicates the presence of bacteria in intrauterine tissues as an important risk factor for spontaneous preterm labor. Epigenetic alterations of innate immunity genes may increase the mother’s sensitivity to subclinical levels of bacteria. This study examined the presence of TET2, TLR-2, and TLR-9 in intrauterine tissue, and evaluated whether epigenetic alterations of these genes, as well as IL-8, changed their expression in human decidual tissue and a macrophage cell culture. Immunohistochemicalstaining was used to detect the presence of these proteins in intrauterine tissue. Gene expression changes were evaluated in stimulated monocytes and macrophages. Fluorescence immunohistochemistry was used to track translocation of TET2 in stimulated monocytes and macrophages. Secreted IL-8 concentration was detected with ELISA. Decidual expression of TET2, TLR-2, and TLR-9 increased in the order TNL < TL < sPTL < iPTL. This study found that TET2, TLR-2, TLR-9, and IL-8 are regulated by epigenetic mechanisms. This study was the first to report activation of TET2 involves its translocation from the cytosol to the nucleus in macrophages.

This study aimed at identifying the socio-demographic and service related factors influencing intra uterine contraceptive device (IUD) utilization among family planning clients in Addis Ababa. With a quantitative, cross sectional descriptive design approach, data was collected using structured questionnaires administered by healthcare supervisors. A total of 366 family planning clients and 35 family planning service providers were interviewed. The findings indicated that the level of education, occupation, parity and fertility plan have significant (p<0.05) association with utilization of IUD. Healthcare service provider’s knowledge and skills for provision of intra uterine contraceptive device services were low. Community members lack awareness and knowledge of the benefit and side effects of the device. Therefore, community members need education to promote adherence and effective use of IUD. Similarly, healthcare service providers need skill training and education to ensure quality provision of IUD service / Health Studies / M.A. (Public Health)

Les pathologies vasculaires placentaires sont fréquentes et graves. La forme maternelle prédominante est la pré-éclampsie et la forme fœtale le retard de croissance intra-utérin. Les questions posées autour de ce sujet concernent tout d'abord la prédiction de la survenue de ces pathologies suffisamment tôt afin de permettre une surveillance rapprochée, une administration de corticoïdes et une prise en charge dans une maternité de niveau adaptée. La prévention de la survenue et de la récidive ainsi que le traitement de ces pathologies la phase constituée sont aussi des problématiques encore non résolues. Notre objectif était de travailler sur ces différentes questions pa l'intermédiaire de trois études : l'étude ANGIOPRED), l'étude VOLUPLA et l'étude GROWTH. Les résultats de ces travaux et une revue d la littérature mettent en évidence une perturbation des facteurs de l'hémostase et des facteurs angiogéniques dans la pré-éclampsie et dans le retard de croissance. L'association des facteurs maternels, échographiques, angiogéniques et sériques constitue un modèle prédictif efficace principalement du fait d'une excellente valeur prédictive négative. Le volume placentaire est corrélé au taux de D- Dimères et est intéressant pour la prédiction des pathologies vasculaires placentaires. De nouveaux travaux devront poursuivre l'étude d la prédiction, de la prévention et du traitement des pathologies liées au placenta. Le traitement est notamment l'objet de l'étude Growth qui vise à évaluer l'efficacité de l'énoxaparine dans le traitement du retard de croissance vasculaire constitué. / Placenta-mediated adverse pregnancy outcomes are frequent and severe pathologies whose predominant maternal form is preeclampsia and fetal form, intrauterine growth retardation. The questions asked about this subject concern first of all the prediction of the occurrence of its pathologies in a sufficiently early way to allow for close monitoring, administration of corticosteroids, and management in an appropriate level of maternity. The prevention of the occurrence and recurrence and the treatment of its pathologies in the constituted phase are also unresolved problems. Our objective was therefore to work on its various questions through three studies: the ANGIOPREI study, the VOLUPLA study and the GROWTH study. The results of his work and of the literature show that the factors of haemostasis anc angiogenic factors are disturbed in preeclampsia and in growth retardation. The association of maternal, ultrasound, angiogenic and serum factors constitutes a predictive model that is effective mainly by an excellent negative predictive value. The placental volume is correlated with the D-dimer level and is interesting for placenta-mediated adverse pregnancy outcomes prediction. New studies will have to continue the exploration of the prediction, prevention and treatment of this pathologies related to the placenta. The treatment is notably the object of the study Growth which aims to evaluate the effectiveness of the Enoxaparin for the treatment of constituted vascular growt retardation.

OBJETIVO: O objetivo deste estudo foi avaliar fatores clínicos, laboratoriais, dopplervelocimétricos e hematimétricos preditivos da velocidade de hemólise entre a primeira e a segunda transfusões intrauterinas em gestantes aloimunizadas. MÉTODOS: Este estudo retrospectivo compreendeu gestações únicas, com fetos não hidrópicos, submetidos à primeira e à segunda transfusões intrauterinas pela técnica intravascular direta simples, acompanhadas no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Foram coletados os seguintes dados das gestantes: idade materna, antecedente obstétrico, antecedente obstétrico relacionado à aloimunização (classificado em grave, moderado, leve e nenhum), tipos e títulos dos anticorpos antieritrocitários e dados da transfusão intrauterina (TIU) (idade gestacional da TIU, valores da concentração da hemoglobina antes e depois da primeira e antes da segunda TIU, medida da velocidade sistólica máxima da artéria cerebral média antes da primeira e da segunda TIUs, volume de sangue infundido, concentração de hemoglobina do sangue transfundido, intervalo de tempo entre as transfusões e o tipo de punção uterina transplacentária ou não). Foram calculados a razão entre a quantidade de hemoglobina endógena em relação à quantidade total de hemoglobina após a primeira transfusão, a expansão de volume e taxa de hemólise. RESULTADOS: Quarenta e uma gestantes foram incluídas e apresentaram na primeira TIU, idade gestacional média de 26,1 ± 4,6 semanas, média de volume de sangue infundido de 44,4 ± 23,5 ml e média de expansão de volume de 51,3 ± 14,5%. A média do intervalo entre as transfusões foi de 15,7±6,5 dias. A média da taxa de hemólise foi de -0,40 ± 0,25 g/dl/d entre a primeira e a segunda transfusões e não houve diferença estatisticamente significante da taxa de hemólise nos distintos grupos de antecedente obstétrico relacionado à aloimunização (p = 0,21). Não houve diferença significante entre a média da hemólise e o tipo de punção intrauterina (p = 0,387). A análise multivariada anterógrada demonstrou correlação significativa da taxa de hemólise com a concentração de hemoglobina depois da 1ª TIU (r = 0,60, p<0,001), o intervalo de tempo entre as transfusões (r = 0,64, p<0,001) e a Vmáx ACM antes da segunda TIU (r = 0,56, p<0,001). A equação encontrada que melhor representa a taxa de hemólise foi: 0,31517 + 0,03463 x Intervalo 0,314038 x Vmáx ACM pré 2 0,068719 x Hb DP pós 1 (r2 = 0,58). CONCLUSÃO: A taxa de hemólise fetal entre a primeira e a segunda transfusões intrauterinas em gestantes aloimunizadas pode ser predita pela combinação da concentração de hemoglobina após a primeira TIU, do intervalo de tempo entre as transfusões e medida da Vmáx ACM antes da segunda TIU / OBJECTIVE: To evaluate clinical and laboratory factors, dopplervelocimetric and hematimetric values in the prediction of fetal hemolysis between first and second intrauterine transfusion in alloimmunized pregnant women. METHODS: This retrospective study involved singleton pregnancies with non hydropic fetus, that underwent to first and second intrauterine transfusions (IUT) by simple direct intravascular technique, accompanied at Hospital das Clínicas da Faculdade de Medicina de São Paulo. The following data were collected: maternal age, obstetric history, previus history of alloimmunization (classified in severe, moderate, mild and none), antibodies type and titre and data from the IUT (gestational age, hemoglobin levels before and after first IUT and before second IUT, middle cerebral artery peak systolic velocity before first and second IUT, transfused blood volume, transfused blood hemoglobin concentration, time interval between transfusions and type of intrauterine puncture). The ratio between amount of endogenous hemoglobin and total amount of hemoglobin after IUT, volume expansion and hemolysis rate were calculated. RESULTS: Forty-one pregnant women were included and presented at first IUT, mean gestational age of 26.1 ± 4.6 weeks, mean of transfused blood volume of 44.4 ± 23.5ml and mean expansion volume of 51.3 ± 14.5%. The mean interval between the transfusions was 15.7±6.5 days. The mean hemolysis rate was 0.40 ± 0.25 g/dl/d between the first and second transfusions and there was not significant difference between the distinct groups of previous history of alloimmunization (p = 0.21). There was not significant difference between mean hemolysis rate and the type of intrauterine punction (p = 0.387). Stepwise multiple regression analysis demonstrated that hemolysis correlated significantly with hemoglobin levels after the first transfusion (r = 0.60, p<0,001), the interval of time between transfusions (r = 0.64, p<0,001) and middle cerebral artery peak systolic velocity before the second transfusion (r = 0.56, p<0.001). The best-fit equation for hemolysis rate was: 0.31517 + 0.03463 x Interval 0.314038 x MCA PSV pre 2 0.068719 x Hb zeta pos1 (r2 = 0.58). CONCLUSION: Fetal hemolysis rate between first and second transfusions in alloimmune disease can be predicted by a combination of hemoglobin levels after the first transfusion, interval between both procedures and middle cerebral artery peak systolic velocity before the second transfusion

As gestações gemelares monocoriônicas e diamnióticas (MCDA) apresentam maior risco de restrição de crescimento fetal (RCF) e complicações perinatais. O objetivo deste estudo foi avaliar a morbidade e mortalidade perinatal em gestações gemelares MCDA: na presença de RCF e dopplervelocimetria de artéria umbilical normal e anormal; nos diferentes padrões de dopplervelocimetria de artéria umbilical (doppler normal, índice de pulsatilidade aumentado, fluxo diastólico intermitente de artéria umbilical, diástole zero e diástole reversa) e na presença de RCF seletiva e não seletiva. Estudo retrospectivo, com levantamento dos casos no período entre 2004 e 2011, no Setor de Gestações Múltiplas da Clínica Obstétrica do HCFMUSP. Desta forma, foram inseridas 48 gestações gemelares, com 60 fetos abaixo do percentil 10 de uma curva específica para gêmeos. Casos que apresentaram malformações fetais (n=36) ou síndrome da transfusão fetofetal (n=43) não foram incluídos no estudo. O grupo com RCF e dopplervelocimetria anormal apresentou menor média de idade gestacional no parto (33,39 versus 35,48, p <0,001), menor média de peso ao nascimento (1137,12 gramas versus 1675,77 gramas, p < 0,001), maior frequência de internação em Unidade de terapia intensiva (UTI) neonatal (69,23% versus 19,23%, p = 0,0003), maior frequência de doença respiratória (73,08 versus 34,62, p = 0,005) e maior frequência de óbito intrauterino e neonatal (p = 0,025). Na avaliação dos diferentes padrões de dopplervelocimetria da artéria umbilical (normal, índice de pulsatilidade aumentado, fluxo diastólico intermitente, diástole zero e diástole reversa), os grupos diferiram em relação à média da idade gestacional no parto (35,48; 34,22; 33,33; 33,15 e 32,45 semanas, p < 0,001), frequência de internação em UTI neonatal (19,23; 50,00; 50,00; 85,71 e 100,00%, p < 0,001) e desfecho com alta hospitalar (96,15; 100,00; 83,33; 71,43 e 25,00%, p < 0,001). O grupo com diástole reversa apresentou os piores resultados perinatais. Na avaliação da RCF seletiva, não foi observada diferença significativa em relação à idade gestacional no parto (33,4 versus 33,4, p = 0,953), mas houve maior necessidade de intubação orotraqueal (62,5% versus 32,3%, p = 0,001) e ventilação mecânica (75,0% versus 41,2%, p = 0,0006) em relação ao grupo de RCF não seletiva. No grupo RCF seletiva houve maior número de casos de dopplervelocimetria de artéria umbilical com índice de pulsatilidade aumentada, fluxo intermitente, diástole zero e reversa (p = 0,005). Como conclusão o estudo demonstrou maior morbidade e mortalidade perinatal no grupo com dopplervelocimetria anormal com diferença significativa em relação aos padrões distintos de dopplervelocimetria e piores resultados na presença de diástole reversa. O grupo de RCF seletiva apresentou maior frequência de anormalidades na dopplervelocimetria de artéria umbilical e morbidade neonatal em relação ao grupo com RCF não seletiva / Monochorionic diamniotic (MCDA) twin pregnancies have and increased risk for intrauterine growth restriction (IUGR) and perinatal complications. The aim of this study is to evaluate perinatal morbidity and mortality in MCDA twin pregnancies: in the presence of IUGR with normal and abnormal umbilical artery dopplervelocimetry; in different umbilical artery flow patterns (normal dopplervelocimetry, increased pulsatility index, intermittent flow pattern, absent end diastolic flow and reversed end diastolic flow) and in the presence of selective and non-selective IUGR. This was a retrospective study in the Multiple Pregnancy Unit at the Obstetric Clinic of HCFMUSP, between 2004 and 2011. The study included 48 twin pregnancies, where 60 fetuses weighted less than the 10th percentile according to twins charts. Cases with fetal malformation (n=36) or twin to twin transfusion syndrome (n=43) were not included in the study. The group with IUGR and abnormal umbilical artery Doppler presented lower mean gestational age at delivery (33.39 versus 35.48, p <0.001), lower mean birthweight (1137.12 g versus 1675.77 g, p < 0.001), higher need of neonatal intensive care unit (NICU, 69.23% versus 19.23%, p = 0.0003), higher frequency of respiratory disease (73.08 versus 34.62, p = 0.005) and higher incidence of intrauterine and neonatal death (p = 0.025). In the different umbilical artery flow patterns (normal dopplervelocimetry, increased pulsatility index, intermittent flow pattern, absent end diastolic flow and reversed end diastolic flow) the group differ in relation to gestational age at delivery (35.48; 34.22; 33.33; 33.15 and 32.45 weeks; p < 0.001), need of NICU (19.23; 50.00; 50.00; 85.71 and 100,00%; p < 0.001) and alive at hospital discharge (96.15; 100,00; 83.33; 71.43 and 25,00%; p < 0.001). The group with reversed and diastolic flow presented the worse perinatal outcome. In the selective and non-selective IUGR groups, no difference was observed in relation to gestational age at delivery (33.4 versus 33.4 weeks, p = 0.953), however there was higher need for orotracheal intubation (62.5% versus 32.3%, p = 0.001) and mechanical ventilation (75.0% versus 41.2%, p = 0.0006) in the selective IUGR group. Abnormal umbilical artery Doppler such as increased pulsatility index, intermittent blood flow, absent and reversed flow were more frequent in the selective IUGR group (p = 0.005). As conclusion, the study demonstrated higher perinatal morbidity and mortality in the IUGR group with abnormal umbilical artery Doppler with significant difference in relation to Doppler patterns and the worse outcome was related to reversed diastolic flow pattern. The selective IUGR group presents higher frequency of abnormal umbilical artery dopplervelocimetry and neonatal morbidity compared to non- selective IUGR group

OBJETIVO: O objetivo deste estudo foi avaliar fatores clínicos, laboratoriais, dopplervelocimétricos e hematimétricos preditivos da velocidade de hemólise entre a primeira e a segunda transfusões intrauterinas em gestantes aloimunizadas. MÉTODOS: Este estudo retrospectivo compreendeu gestações únicas, com fetos não hidrópicos, submetidos à primeira e à segunda transfusões intrauterinas pela técnica intravascular direta simples, acompanhadas no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Foram coletados os seguintes dados das gestantes: idade materna, antecedente obstétrico, antecedente obstétrico relacionado à aloimunização (classificado em grave, moderado, leve e nenhum), tipos e títulos dos anticorpos antieritrocitários e dados da transfusão intrauterina (TIU) (idade gestacional da TIU, valores da concentração da hemoglobina antes e depois da primeira e antes da segunda TIU, medida da velocidade sistólica máxima da artéria cerebral média antes da primeira e da segunda TIUs, volume de sangue infundido, concentração de hemoglobina do sangue transfundido, intervalo de tempo entre as transfusões e o tipo de punção uterina transplacentária ou não). Foram calculados a razão entre a quantidade de hemoglobina endógena em relação à quantidade total de hemoglobina após a primeira transfusão, a expansão de volume e taxa de hemólise. RESULTADOS: Quarenta e uma gestantes foram incluídas e apresentaram na primeira TIU, idade gestacional média de 26,1 ± 4,6 semanas, média de volume de sangue infundido de 44,4 ± 23,5 ml e média de expansão de volume de 51,3 ± 14,5%. A média do intervalo entre as transfusões foi de 15,7±6,5 dias. A média da taxa de hemólise foi de -0,40 ± 0,25 g/dl/d entre a primeira e a segunda transfusões e não houve diferença estatisticamente significante da taxa de hemólise nos distintos grupos de antecedente obstétrico relacionado à aloimunização (p = 0,21). Não houve diferença significante entre a média da hemólise e o tipo de punção intrauterina (p = 0,387). A análise multivariada anterógrada demonstrou correlação significativa da taxa de hemólise com a concentração de hemoglobina depois da 1ª TIU (r = 0,60, p<0,001), o intervalo de tempo entre as transfusões (r = 0,64, p<0,001) e a Vmáx ACM antes da segunda TIU (r = 0,56, p<0,001). A equação encontrada que melhor representa a taxa de hemólise foi: 0,31517 + 0,03463 x Intervalo 0,314038 x Vmáx ACM pré 2 0,068719 x Hb DP pós 1 (r2 = 0,58). CONCLUSÃO: A taxa de hemólise fetal entre a primeira e a segunda transfusões intrauterinas em gestantes aloimunizadas pode ser predita pela combinação da concentração de hemoglobina após a primeira TIU, do intervalo de tempo entre as transfusões e medida da Vmáx ACM antes da segunda TIU / OBJECTIVE: To evaluate clinical and laboratory factors, dopplervelocimetric and hematimetric values in the prediction of fetal hemolysis between first and second intrauterine transfusion in alloimmunized pregnant women. METHODS: This retrospective study involved singleton pregnancies with non hydropic fetus, that underwent to first and second intrauterine transfusions (IUT) by simple direct intravascular technique, accompanied at Hospital das Clínicas da Faculdade de Medicina de São Paulo. The following data were collected: maternal age, obstetric history, previus history of alloimmunization (classified in severe, moderate, mild and none), antibodies type and titre and data from the IUT (gestational age, hemoglobin levels before and after first IUT and before second IUT, middle cerebral artery peak systolic velocity before first and second IUT, transfused blood volume, transfused blood hemoglobin concentration, time interval between transfusions and type of intrauterine puncture). The ratio between amount of endogenous hemoglobin and total amount of hemoglobin after IUT, volume expansion and hemolysis rate were calculated. RESULTS: Forty-one pregnant women were included and presented at first IUT, mean gestational age of 26.1 ± 4.6 weeks, mean of transfused blood volume of 44.4 ± 23.5ml and mean expansion volume of 51.3 ± 14.5%. The mean interval between the transfusions was 15.7±6.5 days. The mean hemolysis rate was 0.40 ± 0.25 g/dl/d between the first and second transfusions and there was not significant difference between the distinct groups of previous history of alloimmunization (p = 0.21). There was not significant difference between mean hemolysis rate and the type of intrauterine punction (p = 0.387). Stepwise multiple regression analysis demonstrated that hemolysis correlated significantly with hemoglobin levels after the first transfusion (r = 0.60, p<0,001), the interval of time between transfusions (r = 0.64, p<0,001) and middle cerebral artery peak systolic velocity before the second transfusion (r = 0.56, p<0.001). The best-fit equation for hemolysis rate was: 0.31517 + 0.03463 x Interval 0.314038 x MCA PSV pre 2 0.068719 x Hb zeta pos1 (r2 = 0.58). CONCLUSION: Fetal hemolysis rate between first and second transfusions in alloimmune disease can be predicted by a combination of hemoglobin levels after the first transfusion, interval between both procedures and middle cerebral artery peak systolic velocity before the second transfusion

As gestações gemelares monocoriônicas e diamnióticas (MCDA) apresentam maior risco de restrição de crescimento fetal (RCF) e complicações perinatais. O objetivo deste estudo foi avaliar a morbidade e mortalidade perinatal em gestações gemelares MCDA: na presença de RCF e dopplervelocimetria de artéria umbilical normal e anormal; nos diferentes padrões de dopplervelocimetria de artéria umbilical (doppler normal, índice de pulsatilidade aumentado, fluxo diastólico intermitente de artéria umbilical, diástole zero e diástole reversa) e na presença de RCF seletiva e não seletiva. Estudo retrospectivo, com levantamento dos casos no período entre 2004 e 2011, no Setor de Gestações Múltiplas da Clínica Obstétrica do HCFMUSP. Desta forma, foram inseridas 48 gestações gemelares, com 60 fetos abaixo do percentil 10 de uma curva específica para gêmeos. Casos que apresentaram malformações fetais (n=36) ou síndrome da transfusão fetofetal (n=43) não foram incluídos no estudo. O grupo com RCF e dopplervelocimetria anormal apresentou menor média de idade gestacional no parto (33,39 versus 35,48, p <0,001), menor média de peso ao nascimento (1137,12 gramas versus 1675,77 gramas, p < 0,001), maior frequência de internação em Unidade de terapia intensiva (UTI) neonatal (69,23% versus 19,23%, p = 0,0003), maior frequência de doença respiratória (73,08 versus 34,62, p = 0,005) e maior frequência de óbito intrauterino e neonatal (p = 0,025). Na avaliação dos diferentes padrões de dopplervelocimetria da artéria umbilical (normal, índice de pulsatilidade aumentado, fluxo diastólico intermitente, diástole zero e diástole reversa), os grupos diferiram em relação à média da idade gestacional no parto (35,48; 34,22; 33,33; 33,15 e 32,45 semanas, p < 0,001), frequência de internação em UTI neonatal (19,23; 50,00; 50,00; 85,71 e 100,00%, p < 0,001) e desfecho com alta hospitalar (96,15; 100,00; 83,33; 71,43 e 25,00%, p < 0,001). O grupo com diástole reversa apresentou os piores resultados perinatais. Na avaliação da RCF seletiva, não foi observada diferença significativa em relação à idade gestacional no parto (33,4 versus 33,4, p = 0,953), mas houve maior necessidade de intubação orotraqueal (62,5% versus 32,3%, p = 0,001) e ventilação mecânica (75,0% versus 41,2%, p = 0,0006) em relação ao grupo de RCF não seletiva. No grupo RCF seletiva houve maior número de casos de dopplervelocimetria de artéria umbilical com índice de pulsatilidade aumentada, fluxo intermitente, diástole zero e reversa (p = 0,005). Como conclusão o estudo demonstrou maior morbidade e mortalidade perinatal no grupo com dopplervelocimetria anormal com diferença significativa em relação aos padrões distintos de dopplervelocimetria e piores resultados na presença de diástole reversa. O grupo de RCF seletiva apresentou maior frequência de anormalidades na dopplervelocimetria de artéria umbilical e morbidade neonatal em relação ao grupo com RCF não seletiva / Monochorionic diamniotic (MCDA) twin pregnancies have and increased risk for intrauterine growth restriction (IUGR) and perinatal complications. The aim of this study is to evaluate perinatal morbidity and mortality in MCDA twin pregnancies: in the presence of IUGR with normal and abnormal umbilical artery dopplervelocimetry; in different umbilical artery flow patterns (normal dopplervelocimetry, increased pulsatility index, intermittent flow pattern, absent end diastolic flow and reversed end diastolic flow) and in the presence of selective and non-selective IUGR. This was a retrospective study in the Multiple Pregnancy Unit at the Obstetric Clinic of HCFMUSP, between 2004 and 2011. The study included 48 twin pregnancies, where 60 fetuses weighted less than the 10th percentile according to twins charts. Cases with fetal malformation (n=36) or twin to twin transfusion syndrome (n=43) were not included in the study. The group with IUGR and abnormal umbilical artery Doppler presented lower mean gestational age at delivery (33.39 versus 35.48, p <0.001), lower mean birthweight (1137.12 g versus 1675.77 g, p < 0.001), higher need of neonatal intensive care unit (NICU, 69.23% versus 19.23%, p = 0.0003), higher frequency of respiratory disease (73.08 versus 34.62, p = 0.005) and higher incidence of intrauterine and neonatal death (p = 0.025). In the different umbilical artery flow patterns (normal dopplervelocimetry, increased pulsatility index, intermittent flow pattern, absent end diastolic flow and reversed end diastolic flow) the group differ in relation to gestational age at delivery (35.48; 34.22; 33.33; 33.15 and 32.45 weeks; p < 0.001), need of NICU (19.23; 50.00; 50.00; 85.71 and 100,00%; p < 0.001) and alive at hospital discharge (96.15; 100,00; 83.33; 71.43 and 25,00%; p < 0.001). The group with reversed and diastolic flow presented the worse perinatal outcome. In the selective and non-selective IUGR groups, no difference was observed in relation to gestational age at delivery (33.4 versus 33.4 weeks, p = 0.953), however there was higher need for orotracheal intubation (62.5% versus 32.3%, p = 0.001) and mechanical ventilation (75.0% versus 41.2%, p = 0.0006) in the selective IUGR group. Abnormal umbilical artery Doppler such as increased pulsatility index, intermittent blood flow, absent and reversed flow were more frequent in the selective IUGR group (p = 0.005). As conclusion, the study demonstrated higher perinatal morbidity and mortality in the IUGR group with abnormal umbilical artery Doppler with significant difference in relation to Doppler patterns and the worse outcome was related to reversed diastolic flow pattern. The selective IUGR group presents higher frequency of abnormal umbilical artery dopplervelocimetry and neonatal morbidity compared to non- selective IUGR group

L’insuffisance placentaire par défaut de vascularisation est une pathologie fréquente de la grossesse, de diagnostic difficile, avec des complications potentiellement graves (retard de croissance intra utérin, prééclampsie). L’objectif de ce travail de Thèse a été de développer l’IRM fonctionnelle multiparamétrique pour l’exploration du placenta à 4.7 T chez la rate gestante. Matériel et méthode : L’IRM de diffusion (SE- EPI DWI) avec analyse IVIM et l’IRM dynamique avec injection de gadolinium (DCE) et haute résolution temporelle (< 1s) ont été développées puis étudiées sur un modèle murin contrôlé d’hypoperfusion placentaire par ligature du pédicule vasculaire utérin gauche au 17ème jour de gestation. Les paramètres obtenus sur les placentas hypoperfusés de la corne gauche ligaturée étaient comparés à ceux des placentas normaux de la corne droite. L’effet de l’hyperoxygénation maternelle était étudié en diffusion. Résultats : Ont été étudiés 73 placentas, dont 23 pathologiques (n= 10 rates) en diffusion et 53 placentas, dont 11 pathologiques (n=12 rates) en DCE. Les paramètres significativement diminués du côté hypoperfusé étaient le coefficient apparent de diffusion (ADC), la fraction de perfusion (f) en diffusion et le flux sanguin maternel (F) en DCE. Sous hyperoxygénation maternelle, l’ADC et le coefficient de diffusion (D) augmentaient et f diminuait. Les paramètres obtenus en diffusion et en DCE n’étaient pas nettement corrélés entre eux. Conclusion : Un outil d’IRM fonctionnelle placentaire multiparamétrique a été développé à 4.7 T chez la rate gestante. La DWI comme la DCE apparaissent complémentaires pour le diagnostic d’hypoperfusion placentaire. / Placental insufficiency caused by deficient vascularization is common during pregnancy, difficult to diagnose and can lead to severe materno-fetal complications (intrauterine growth restriction, preeclampsia). The aim of this work was to develop multi-parametric functional magnetic resonance imaging (MRI) to assess the placenta at 4.7 T on a murine model. Materials and methods : Diffusion-weighted imaging (SE-EPI-DWI) with the intravoxel incoherent motion (IVIM) analysis and dynamic contrast enhanced MRI (DCE) with a high-time resolution (<1 s) were developed and evaluated on a controlled rat model of reduced placental perfusion, achieved by ligation of the left uterine vascular pedicle on the 17th embryonic day. Parameters from the placentas in the left ligated horn were compared to those from the normal placentas in the non ligated horn. The effect of maternal hyperoxygenation on placental microvascularization was studied with DWI.Results: For DWI, 73 placentas were examined, 23 from the ligated side (n=10 rats). For DCE, 53 placentas were analysed, 11 from the ligated side (n=12 rats). In the uterine horn with reduced perfusion, the apparent diffusion coefficient (ADC), the perfusion fraction (f) obtained with DWI and the placental blood flow (F) obtained with DCE were significantly decreased. Under maternal hyperoxygenation, ADC and the diffusion coefficient (D) increased whereas f decreased. DWI and DCE parameters were not significantly correlated with each other. Conclusion: Multi-parametric MRI has been developed for murine placental analysis at 4.7T. DWI and DCE are complementary tools for the diagnosis of reduced placental perfusion.