Thesis (D.P.H.)--University of Oklahoma. / Bibliography: leaves 71-75.

Currently there is no test to accurately predict stillbirth. It is proposed that better identification of placental disease in utero may aid stillbirth prediction and prevention. Pregnancies complicated by reduced fetal movement (RFM) have increased risk of stillbirth. We hypothesised that RFM is a symptom of placental dysfunction associated with adverse pregnancy outcome (APO) and that this placental abnormality can be detected antenatally and used to identify fetuses at highest-risk of APO. We tested this hypothesis by: 1) comparison of ex vivo placental structure and function between APO RFM pregnancies and their normal outcome RFM counterparts, 2) comparison of in utero estimates of placental size, vascularity, vascular and endocrine functions obtained from placental ultrasound, Doppler waveform analysis and maternal circulating placentally-derived hormone concentrations, to their ex vivo correlates and 3) examination of the predictive potential of placental biomarkers at the time of RFM.Ex vivo placentas from APO RFM pregnancies, compared to normal outcome RFM counterparts, were smaller (diameter, area, weight and volume, p<0.0001), less vascular (vessel number and density, p≤0.002), with arteries that were less responsive to sodium nitroprusside (p<0.05), and with aberrant endocrine function (reduced tissue content and/or release of human chorionic gonadotrophin (hCG), human placental lactogen (hPL) and soluble fms-like Tyrosine Kinase-1 (sFlt-1), p<0.03). Placental volume (PV) ex vivo correlated with sonographic estimated PV (p<0.004), hPL, hCG and placental growth factor (PlGF) concentrations in the maternal circulation (p<0.03). Ex vivo villous vessel number and density correlated with Doppler impedance at the umbilical artery free-loop (UAD-F, p=0.02) and intraplacental arteries (p<0.0001) respectively, whilst UAD-F impedance correlated with arterial thromboxane sensitivity (p<0.04). Examination of placental structure and function at the time of presentation with RFM identified 15 independently-predictive biomarkers. Three potential predictive models, incorporating measures of placental size (PlGF), endocrine function (sFlt-1), arterial thromboxane sensitivity and villous vascularity (UAD-F), were proposed. Using these models, sensitivity for APO was improved from 8.9% with baseline care (assessment of fetal size and gestation) to up to 37.5% at a fixed specificity of 99% (p<0.05). This series of studies shows that antenatal placental examination is possible and improves identification of pregnancies at highest risk of stillbirth in a high-risk population by up to 29%. Therefore such tests merit further development to prospectively assess their ability to predict and prevent stillbirth itself.

Introdução: A gestação após transplante de órgãos tem se tornado cada vez mais comum, especialmente após avanços das técnicas em relação ao transplante e novos imunossupressores adotados na terapêutica. Objetivo: Avaliar os resultados maternos e perinatais das pacientes gestantes submetidas a transplante renal prévio. Método: No período de 1995 a 2007, foram avaliados restrospectivamente todos os casos de pacientes submetidas a transplante renal, que tiveram parto na Clínica Obstétrica do HCFMUSP. Resultados: Foram selecionadas 31 gestações em 22 pacientes. A idade média foi de 29 anos (18-39). Em 52% dos casos (16 casos) a gestação ocorreu 5 anos após o transplante. Em 21 pacientes (68%) o esquema imunossupressor utilizado foi composto por ciclosporina, azatioprina e prednisona. A incidência de abortamentos foi de 22% (7 casos). A hipertensão esteve presente em 21 casos (87,5%), seguida de anemia 17 (70,83%) e prematuridade 15 (71%). A função renal no início do pré-natal teve o seguinte comportamento: uréia no início 45±7,1 mg/dl (28-105) e no parto 68±27,6 (35-128); creatinina no início do pré-natal 1,28±0,55 mg/dl (0,9-3,6) e no parto 2,06±1,16 mg/dl (1,12-6,4); ácido úrico no início 6,1±1,5 mg/dl (3,5-9,2) e no parto 8,54±2,79 mg/dl (2-14) e a proteinúria de 24 horas no início 0,19±0,09 g/vol.24h (0,03-0,31) e no parto 1,34±0,96 g/vol.24h (0,11-3,65). A via de parto: oito (33%) partos por via vaginal e 16 (66%) foram cesarianas. A idade gestacional média ao nascimento foi de 34,8±2,29 semanas (28-38) e o peso ao nascimento foi 2366,5±261,6g (1100-4650). As complicações neonatais foram: icterícia 15 (71,5%); desconforto respiratório 10 (47,6%); hipoglicemia 5 (23,8%); anemia 4 (19%), intubação orotraqueal 3 (14,3%), utilização NPP 3 (14,3%), hipocalcemia 3 (14,3); pneumonia 2 (9,5%); hemorragia intracraniana 1 (4,8%) e sepse 1 (4,8). Ocorreram 3 óbitos fetais. Conclusão: a taxa de sobrevida neonatal no estudo de foi de 88%, a hipertensão foi a intercorrência materna mais freqüente, a utilização da terapêutica imunossupressora utilizada não levou a malformação fetal e a morbidade neonatal esteve associada a complicações inerentes da prematuridade 15 casos (71%). / Introduction: The pregnancy after organ transplant has become very common, especially after the technical advance related to new immunosuppressive therapy on the transplant. Objective: Analysis of the maternal and pregnancy outcomes of the patients that has renal transplant. Method: During the period between 1995 and 2007, it was analyzed retrospectively all the patient submitted on renal transplant, and also has had delivery in the Hospital das Clínicas of the University of São Paulo Medical School. Results: We have obtained a total of 31 pregnancies in 22 patients. The average age was 29 years of age (18- 39). In 52 % of the cases (16 cases) the pregnancy occurred 5 years after the transplant. In 21 patients (68%) the immunosuppressive treatment used was based on ciclosporine, azatioprine and prednisone. The incidence of abortion was 22% (7 cases), that was excluded. The hypertension was present in 21 cases (87,5%), followed by anemia 17 (70,83%) and prematurity 15 (71%). In the beginning of the pre-natal the renal function presented the following: serum urea in the beginning of prenatal care was 45±7,1 mg/dl (28-105)and the time of delivery was 68±27,6 (35-128); serum creatinine in the beginning was 1,28±0,55 mg/dl (0,9-3,6) and the time of delivery was 2,06±1,16 mg/dl (1,12- 6,4);serum uric acid in the beginning of prenatal care was 6,1±1,5 mg/dl (3,5-9,2) and the time of delivery was 8,54±2,79 mg/dl (2-14). The proteinuria 24 hours at the beginning of prenatal care was 0,19±0,09 g/vol.24h (0,03-0,31) and the time of delivery was 1,34±0,96 g/vol.24h (0,11-3,65). Cesarean section was performed in 16 (66%) cases, vaginal delivery in 8 (33%). The mean gestational age at delivery was 34,8±2,29 weeks (range: 28-38) and the mean birthweight at delivery was 2366,5±261,6g (range 1100-4650). The neonatal complications were observed during the study: ictericia 15 (71,5%); respiratory distress 10 (47,6%); hipoglicemia 5 (23,8%); anemia 4 (19%), orotracheal intubation 3 (14,3%), use of NPP 3 (14,3%), hipocalcemie 3 (14,3); pneumonie 2 (9,5%); intracranial hemorrhage 1 (4,8%) e sepses 1 (4,8). Occurred 3 fetal deaths. Conclusion: in the study the statistics of neonatal success was 88%, the most frequent maternal complication was the hypertension. The immunosuppressive therapy utilized didn\'t cause fetal malformation and the neonatal morbid was associated with prematurity complications itself in 15 cases (71%).

Introdução: A gestação após transplante de órgãos tem se tornado cada vez mais comum, especialmente após avanços das técnicas em relação ao transplante e novos imunossupressores adotados na terapêutica. Objetivo: Avaliar os resultados maternos e perinatais das pacientes gestantes submetidas a transplante renal prévio. Método: No período de 1995 a 2007, foram avaliados restrospectivamente todos os casos de pacientes submetidas a transplante renal, que tiveram parto na Clínica Obstétrica do HCFMUSP. Resultados: Foram selecionadas 31 gestações em 22 pacientes. A idade média foi de 29 anos (18-39). Em 52% dos casos (16 casos) a gestação ocorreu 5 anos após o transplante. Em 21 pacientes (68%) o esquema imunossupressor utilizado foi composto por ciclosporina, azatioprina e prednisona. A incidência de abortamentos foi de 22% (7 casos). A hipertensão esteve presente em 21 casos (87,5%), seguida de anemia 17 (70,83%) e prematuridade 15 (71%). A função renal no início do pré-natal teve o seguinte comportamento: uréia no início 45±7,1 mg/dl (28-105) e no parto 68±27,6 (35-128); creatinina no início do pré-natal 1,28±0,55 mg/dl (0,9-3,6) e no parto 2,06±1,16 mg/dl (1,12-6,4); ácido úrico no início 6,1±1,5 mg/dl (3,5-9,2) e no parto 8,54±2,79 mg/dl (2-14) e a proteinúria de 24 horas no início 0,19±0,09 g/vol.24h (0,03-0,31) e no parto 1,34±0,96 g/vol.24h (0,11-3,65). A via de parto: oito (33%) partos por via vaginal e 16 (66%) foram cesarianas. A idade gestacional média ao nascimento foi de 34,8±2,29 semanas (28-38) e o peso ao nascimento foi 2366,5±261,6g (1100-4650). As complicações neonatais foram: icterícia 15 (71,5%); desconforto respiratório 10 (47,6%); hipoglicemia 5 (23,8%); anemia 4 (19%), intubação orotraqueal 3 (14,3%), utilização NPP 3 (14,3%), hipocalcemia 3 (14,3); pneumonia 2 (9,5%); hemorragia intracraniana 1 (4,8%) e sepse 1 (4,8). Ocorreram 3 óbitos fetais. Conclusão: a taxa de sobrevida neonatal no estudo de foi de 88%, a hipertensão foi a intercorrência materna mais freqüente, a utilização da terapêutica imunossupressora utilizada não levou a malformação fetal e a morbidade neonatal esteve associada a complicações inerentes da prematuridade 15 casos (71%). / Introduction: The pregnancy after organ transplant has become very common, especially after the technical advance related to new immunosuppressive therapy on the transplant. Objective: Analysis of the maternal and pregnancy outcomes of the patients that has renal transplant. Method: During the period between 1995 and 2007, it was analyzed retrospectively all the patient submitted on renal transplant, and also has had delivery in the Hospital das Clínicas of the University of São Paulo Medical School. Results: We have obtained a total of 31 pregnancies in 22 patients. The average age was 29 years of age (18- 39). In 52 % of the cases (16 cases) the pregnancy occurred 5 years after the transplant. In 21 patients (68%) the immunosuppressive treatment used was based on ciclosporine, azatioprine and prednisone. The incidence of abortion was 22% (7 cases), that was excluded. The hypertension was present in 21 cases (87,5%), followed by anemia 17 (70,83%) and prematurity 15 (71%). In the beginning of the pre-natal the renal function presented the following: serum urea in the beginning of prenatal care was 45±7,1 mg/dl (28-105)and the time of delivery was 68±27,6 (35-128); serum creatinine in the beginning was 1,28±0,55 mg/dl (0,9-3,6) and the time of delivery was 2,06±1,16 mg/dl (1,12- 6,4);serum uric acid in the beginning of prenatal care was 6,1±1,5 mg/dl (3,5-9,2) and the time of delivery was 8,54±2,79 mg/dl (2-14). The proteinuria 24 hours at the beginning of prenatal care was 0,19±0,09 g/vol.24h (0,03-0,31) and the time of delivery was 1,34±0,96 g/vol.24h (0,11-3,65). Cesarean section was performed in 16 (66%) cases, vaginal delivery in 8 (33%). The mean gestational age at delivery was 34,8±2,29 weeks (range: 28-38) and the mean birthweight at delivery was 2366,5±261,6g (range 1100-4650). The neonatal complications were observed during the study: ictericia 15 (71,5%); respiratory distress 10 (47,6%); hipoglicemia 5 (23,8%); anemia 4 (19%), orotracheal intubation 3 (14,3%), use of NPP 3 (14,3%), hipocalcemie 3 (14,3); pneumonie 2 (9,5%); intracranial hemorrhage 1 (4,8%) e sepses 1 (4,8). Occurred 3 fetal deaths. Conclusion: in the study the statistics of neonatal success was 88%, the most frequent maternal complication was the hypertension. The immunosuppressive therapy utilized didn\'t cause fetal malformation and the neonatal morbid was associated with prematurity complications itself in 15 cases (71%).

<p>Antenatal care has been associated with improved maternal and perinatal outcomes but there is no agreement on the most effective model in terms of content as well as the number and timing of visits. A cluster randomised controlled trial was conducted in a rural area of Zimbabwe to assess a 5-visit goal-oriented antenatal care model against standard care. In the same population was also determined the sensitivity of factors used for risk screening to predict pregnancy complications and the effectiveness of the referral system in managing women with identified risk markers or pregnancy complications. </p><p>Pregnancy records of 10 572 out of total 13 517 recruited women were available for analysis. The new model did not change the number of visits but resulted in better use of health care. The classical risk screening system had low predictive value and identified too large a risk group for referral. Nulliparous women had an increased risk for pregnancy complications whereas women with previous uncomplicated pregnancies were at low risk of complications even with high parity. Multiparous women with previous complications had an increased risk of complications but better utilisation of health care services for delivery reduced adverse perinatal outcomes. There was a functional referral system in Gutu and women complied with referral indications but efficiency of the system was reduced by failure of care providers to comply with referral recommendations. </p><p>Antenatal care can be improved in a rural setting through a focussed programme and the unpredictability of many pregnancy complications limits the value of antenatal risk screening. Until universal access to essential obstetric care facilities is attained in low resource settings, a critical re-examination of risk factors could avoid overburdening the referral system.</p>

Antenatal care has been associated with improved maternal and perinatal outcomes but there is no agreement on the most effective model in terms of content as well as the number and timing of visits. A cluster randomised controlled trial was conducted in a rural area of Zimbabwe to assess a 5-visit goal-oriented antenatal care model against standard care. In the same population was also determined the sensitivity of factors used for risk screening to predict pregnancy complications and the effectiveness of the referral system in managing women with identified risk markers or pregnancy complications. Pregnancy records of 10 572 out of total 13 517 recruited women were available for analysis. The new model did not change the number of visits but resulted in better use of health care. The classical risk screening system had low predictive value and identified too large a risk group for referral. Nulliparous women had an increased risk for pregnancy complications whereas women with previous uncomplicated pregnancies were at low risk of complications even with high parity. Multiparous women with previous complications had an increased risk of complications but better utilisation of health care services for delivery reduced adverse perinatal outcomes. There was a functional referral system in Gutu and women complied with referral indications but efficiency of the system was reduced by failure of care providers to comply with referral recommendations. Antenatal care can be improved in a rural setting through a focussed programme and the unpredictability of many pregnancy complications limits the value of antenatal risk screening. Until universal access to essential obstetric care facilities is attained in low resource settings, a critical re-examination of risk factors could avoid overburdening the referral system.

Thesis (M.S.)--University of Michigan, 1996.

Thesis (M.S.)--University of Michigan, 1996.

O objetivo do estudo foi avaliar os aspectos clínicos epidemiológicos, as principais complicações maternas e os resultados perinatais nas gestações gemelares. Foi realizado estudo retrospectivo com análise de gestações gemelares, com idade gestacional maior que 20 semanas e parto no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de janeiro de 2003 a dezembro de 2006. Das 303 gestações gemelares, 289 apresentavam dados completos. A incidência de gestação gemelar foi de 3,3% e 96,2% naturalmente concebidas. Em relação à corionicidade, 60,5% eram dicoriônicas (DC), 30,8% monocoriônicas diamnióticas (MCDA), 6,6% monocoriônicas monoamnióticas (MCMA) e em 2,1% dos casos a corionicidade não foi determinada. A idade materna média foi de 29,1 anos e 39,4% eram nulíparas. Cerca de 30% das pacientes apresentavam patologia clínica prévia e as mais prevalentes foram: hipertensão arterial crônica (12,5%), cardiopatias (4,8%) e pneumopatias (4,5%). Complicações gestacionais foram observadas em 85,1% dos casos, sendo as principais: parto prematuro (65,7%), doença hipertensiva específica da gestação (15,6%) e rotura prematura de membranas (13,5%). Ocorreram 395 internações e tempo médio de internação de 6,1 dias. Dessas, 45,8% foram para resolução da gestação por trabalho de parto ou por indicação materno-fetal. A idade gestacional média no parto foi de 34,6 semanas, significativamente menor nas gestações monocoriônicas (MC) do que nas DC (33,5 versus 35,4 semanas, p< 0,001). A via de parto mais freqüente foi à cesárea (84,8%). Dos 578 produtos conceptuais, três eram acárdicos (0,5%), 35 natimortos (6,0%) e 540 nativivos (93,5%). A proporção de óbitos durante a internação no berçário foi de 11,5%, sendo 2,8 vezes maior nas gestações MC em relação às DC. As complicações neonatais mais freqüentes foram: prematuridade (65,7%), baixo peso ao nascer (71,8), restrição do crescimento fetal (18,7%) e as malformações (13,6%). Todos esses parâmetros apresentaram resultado significativamente piores para os recém-nascidos das gestações MC em relação às DC. No presente estudo, concluiu-se que, as gestações gemelares apresentam elevada incidência de complicações maternas, principalmente relacionadas ao parto prematuro, hipertensão arterial sistêmica e rotura prematura de membranas. O resultado perinatal adverso esteve relacionado à prematuridade, malformações e às complicações inerentes à monocorionicidade. A taxa de sobrevida nas gestações gemelares DC e MC sem malformações ou síndrome da transfusão feto-fetal é semelhante / The aims of this retrospective study were to describe clinical and epidemiological aspects of twin pregnancies delivered between January 2003 and December 2006 at the Hospital das Clínicas, São Paulo University Medical School. Maternal complications and perinatal outcome were also studied. Amongst 303 twin pregnancies delivered at a gestational age of more than 20 weeks, 289 cases had completed medical records. The incidence of twin deliveries was 3.3% and 96.2% were naturally conceived. 60.5% were dichorionic (DC), 30.8% monochorionic diamniotic (MCDA), 6.6% monochorionic monoamniotic (MCMA) and in 2.1% of cases, chorionicity was unknown. Mean maternal age was 29.1 years and 39.4% were nulliparous. About 30% of women had a prior clinical history and the most frequent conditions were: chronic hypertension (12.5%), cardiac disease (4.8%) and respiratory complications (4.5%). Pregnancy complications were observed in 85.1% of the cases, and the most common were preterm delivery (65.7%), pregnancy induced hypertension (15.6%) and premature rupture of membranes (13.5%). In this group, there were 395 hospital admissions (1.4 admissions per patient) and the average length of stay was 6.1 days (range 1 to 65 days). Of these, 45.8% were for pregnancy resolution due to labor or maternal-fetal complications. Mean gestational age at delivery was 34.6 weeks, being significantly lower in monochorionic compared to dichorionic twins (33.5 versus 35.4 weeks, p<0001). Cesarean section was the most common route of delivery (84.8%). Amongst the 578 fetuses/newborns, three were acardiac (0.5%), 35 were stillbirths (6.0%) and 540 were born alive (93.5%). Neonatal death occurred in 11.5%, and was 2.8 times higher in MC pregnancies compared to DC. The most common perinatal complications were preterm birth (65.7%), low birth weight (71.8%), fetal growth restriction (18.7%) and fetal malformations (13.6%). All these complications were significantly worse in MC compared to DC pregnancies. Twin pregnancies show high rates of maternal and perinatal complications, such as preterm birth, hypertension, premature rupture of membranes, fetal birth defects and complications inherent to monochorionicity

O presente estudo teve por objetivo investigar fatores preditores de óbito intra uterino e/ou parto prematuro abaixo de 32 semanas em gestações gemelares, em que um feto apresentava pelo menos uma malformação estrutural \"major\". Consistiu em levantamento retrospectivo (1999-2012), realizado no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, e compreendeu 51 gestações (dicoriônicas: 31, monocoriônicas diamnióticas: 15, monocoriônicas monoamnióticas: 4, e 1 caso com corionicidade não determinada). O diagnóstico da anomalia fetal foi realizado com idade gestacional média de 21,5±3,7 semanas, e todos os casos ingressaram no serviço até 26 semanas de gestação. Quanto ao órgão ou sistema acometido, as frequências observadas foram: 31,4%, cardíacas; 29,4%, parede; 21,5%, sistema nervoso central; 17,6%, coluna; 17,6%, derrames; 15,7%, tórax; 13,7%, trato genito-urinário; 3,9%, extremidades e partes moles; 1,9%, trato gastro-intestinaI e 1,9%, face. A predição dos desfechos foi investigada por meio de regressão logística \"stepwise\" incluindo as seguintes variáveis: idade materna, idade gestacional no momento do diagnóstico, corionicidade, sexo dos fetos, além do número e tipo de malformações encontradas. O nível de significância estatística foi definido como < 0,15. Óbito intrauterino do feto malformado (n=15, 29,4%) apresentou relação significativa com o número de anomalias fetais (p=0,02, OR= 2,54, IC95%= 1,14-5,62), presença de derrame (p=0,06, OR= 4,7, IC95%= 0,95-24) e gestação monocoriônica (p=0,11, OR= 2,8, IC95%= 0,78- 9,8). Óbito do cogemelar normal (n=4, 7,8%) se relacionou com a monocorionicidade (p=0,14, OR= 5,8, IC95%= 0,56-61). Parto abaixo de 32 semanas ocorreu em 14 (27,5%) gestações, e a presença de derrame cavitário foi a variável que se relacionou significativamente com esse desfecho (p= 0,04, OR = 5,5, IC95% = 1,07-28) / The aim of the present study was to investigate predictors of fetal death and premature delivery before 32 weeks in twin pregnancies with one fetus affected by a major structural malformation. It was a retrospective study (1999-2012), conducted at São Paulo University Medical School Hospital, involving 51 pregnancies (dichorionic: 31, monochorionic diamniotic: 15, monochorionic monoamniotic: 4, and 1 case in which chorionicity was not established). Fetal abnormality was diagnosed at a mean gestation of 21.5±3.7 weeks, and all cases were enrolled until 26 weeks. Cardiac abnormalities were observed in 31.4%, abdominal wall defects: 29.4%, central nervous system: 21.5%, spine: 17.6%, effusions: 17.6%, non-cardiac thoracic abnormalities: 15.7%, genital and urinary system: 13.7%, limbs and soft tissue: 3.9%, intestinal: 1.9% and facial defects: 1.9%. Prediction of abnormal outcome was examined with stepwise logistic regression analysis and independent variables included: maternal age, gestational age at diagnosis, chorionicity, fetal gender, number and type of fetal abnormality. Significance level was set at 0.15. Fetal death occurred in 15 (29.4%) abnormal fetuses and was significantly correlated with the number of fetal malformations (p=0.02, OR= 2.54, 95%CI= 1.14-5.62), presence of effusion (p=0.06, OR= 4.7, 95%CI= 0.95-24) and monochorionic pregnancies (p=0.11, OR= 2.8, 95%CI= 0.78-9.8). Normal co-twin fetal death occurred in 4 cases (7.8%) and was related to monochorionic pregnancies (p=0.14, OR= 5.8, 95%CI= 0.56-61). Delivery before 32 weeks was observed in 14 (27.5%) pregnancies and was related to presence of effusion (p= 0.04, OR= 5.5, 95%CI= 1.07-28)