OBJETIVO: Avaliar o comportamento alimentar de recém-nascidos (RN) pequenos (PIG) e grandes (GIG) para a idade gestacional através de questionário específico e comparar com RN adequados para a idade gestacional (AIG). METODOLOGIA: Estudo de coorte prospectivo, cuja primeira fase consistiu na realização de uma entrevista para coleta de dados da mãe da gestação e do parto, bem como de dados socioeconômicos, com mães que tiveram seus filhos a termo no Hospital de Clínicas de Porto Alegre. Na segunda fase do estudo foi aplicado o questionário Baby Eating Behaviour Questionnaire (BEBQ) através de contato por telefone, com 1 mês do nascimento. RESULTADOS: Foram avaliados 126 RN (43 AIG, 43 PIG e 40 GIG). As análises não demonstraram diferenças significativas nos principais dados demográficos e perinatais em relação aos diferentes grupos de estudo. No entanto, foi observada uma maior escolaridade em mães de RN PIG (p=0,004) e uma menor prevalência de aleitamento materno exclusivo até a alta hospitalar em RN GIG (p=0,002). A análise de variância não encontrou diferença significativa entre os grupos em relação aos domínios do BEBQ, mesmo quando corrigido por sexo do RN. CONCLUSÃO: O estudo demonstrou que alterações do comportamento alimentar ainda não estão presentes com 1 mês de vida, sugerindo que não são inatas, e sim desenvolvidas com o passar do tempo. O estudo tem como limitação as avaliações do crescimento baseadas em registros de terceiros. / OBJECTIVE: To evaluate feeding behavior of infants born small (SGA) and large (LGA) for gestational age using a questionnaire, and compare them with infants born adequate for gestational age (AGA). METHODS: Prospective cohort study was carried out in which the first phase consisted of an interview about gestation and delivery, as well as socioeconomic data, with mothers who had their babies born at term in the Hospital de Clínicas de Porto Alegre. In the second phase of the study, the Baby Eating Questionnaire (BEBQ) was applied through telephone interview 1 month of birth. RESULTS: 126 infants (43 AGA, 43 SGA and 40 LGA) with a mean gestational age of 39.4 weeks were assessed. The analyses did not show significant differences in the main demographic and perinatal data between the different study groups. However, a higher level of schooling was observed in mothers of SGA infants (p = 0.004) and a lower prevalence of exclusive breastfeeding in the LGA (p = 0.002). The analysis of variance found no significant difference between the groups in any of the BEBQ domains, even when corrected for the sex of the baby. CONCLUSION: This study demonstrated that changes in feeding behavior are not yet present at 1 month of age, suggesting that they are not innate, but developed over time. The study is limited to growth assessments based on third-party records.

Introdução: A gestação ectópica (GE) corresponde a 6% das mortes maternas no primeiro trimestre, seu diagnóstico está fundamentado em dois exames complementares: ultrassonografia transvaginal (USTV) e dosagem do β-hCG sérico. Contudo, um erro muito comum dos profissionais de saúde é apreciar somente o exame complementar, sem considerar o quadro clínico e os fatores de risco. Usando uma coorte teórica com mais de 800 pacientes com diferentes incidências de GE, Mol e col. propuseram dois modelos probabilísticos para seu diagnóstico: Modelo Fixo e Modelo Flexível. O Modelo Fixo propôs o uso de uma zona discriminatória para os valores de β-hCG sérico, ou seja, concentração acima de 1500 mIU/ml deve haver evidência de gravidez intra-uterina, caso contrário é considerado um caso de EP. Entretanto, entre os dois modelos o Modelo Flexível apresentou melhor desempenho para o diagnostico de GE. Para o diagnostico é necessário a análise dos resultados da USTV, valores de β-hCG sérico, sinais e sintomas, e fatores de risco que consistem em: GE prévia, história de cirurgia tubária, tabagismo, uso de dispositivo intrauterino (DIU), história de ≥ três abortos espontâneos, infertilidade feminina, história de doença inflamatória pélvica (DIP), história de infecções sexualmente transmissíveis (ISTs) e ter ≥ cinco parceiros sexuais Objetivo: Avaliar a incidência, os fatores de risco e a presença de sinais e sintomas das mulheres no primeiro trimestre gestacional, atendidas no Setor de Emergência Ginecológica do Hospital de Clínicas de Porto Alegre (HCPA).Método: Trata-se de um estudo de coorte prospectivo realizado no período de 14 de abril de 2011 a 31 de dezembro de 2013 com mulheres com <12 semanas de gestação atendidas no Setor de Emergência Ginecológica do HCPA.Resultados: Foram incluídos no estudo 845 mulheres. A taxa de GE confirmada nesta população foi de 8,5% (95%IC= 6.8 a 10.6). Os fatores de risco mais relevantes para GE foram GE prévia (RR=4; 95%IC= 2.4 a 6.5) e história de cirurgia tubária (RR=2.8; 95%IC= 1.5 a 5.2). Pacientes assintomáticas e sem fator de risco têm uma chance de 5% de ter uma GE. Uma mulher grávida com dor e sangramento presentes e com fator de risco tem 52% mais chances de ter uma GE. Conclusão: A incidência diagnóstica confirmada de GE foi de 8,5% (95%IC= 6.8 a 10.6). Entre os fatores de risco para GE, os que apresentaram maior risco relativo foram, respectivamente, GE prévia e história de cirurgia tubária. Os sinais e sintomas mais relevantes para o diagnóstico de GE foram dor mais sangramento, que estão fortemente, relacionadas ao diagnóstico de GE. / Background: Ectopic Pregnancy (EP) corresponds to 6% of maternal deaths in the first trimester. Its diagnosis is based on two complementary tests: transvaginal ultrasonography (TVUS) and serum β-HCG. However, very common mistake of health professionals is to appreciate only the complementary examination, without considering the clinical picture and the risk factors. Using a theoretical cohort with more than 800 patients with different incidences of EP, Mol et al. proposed two probabilistic models for diagnosis of EP: Fixed Model and Flexible Model. The Fixed Model proposed the use of a discriminatory zone for the values serum β-hCG, i.e., concentration above 1500 mIU/ml there should be evidence of intrauterine pregnancy, otherwise it is considered a case of EP. However, between the models the Flexible Model presented a better performance for diagnosis of EP. This form, it important to analyse of USTV results, serum β-hCG values, signs and symptoms, and risk factors consisting of: previous EP, history of tubal surgery, smoking, use of intrauterine devices (IUD), three or more miscarriage, female infertility, history of Pelvic Inflammatory Disease (PID), history of Sexually Transmitted Infections (STIs) and more than five sexual partners. These risk factors, however, present variations in different populations Study Design: In this prospective cohort, women between 14 and 49 year old, with a confirmed first trimester pregnancy (gestational age <12 weeks), attend in emergency room setting of HCPA between April 14th, 2011 and December 31st, 2013. Results: A total of 845 women were included in the study. The rate of confirmed EP in this population was 8.5% (n=72; 95% CI, 6.8 to 10.6). The most relevant risk factors for EP were previous EP (RR=4; 95% CI, 2.4 to 6.5) and history of tubal surgery (RR=2.8; 95% CI,1.5 to 5.2). Asymptomatic patients without a risk factor have 5% chance of having an EP. A pregnant woman present with pain and bleeding and if she has a risk factor, the chances of having an EP increase to 52%. Conclusion: A confirmed diagnosis incidence of ectopic pregnancy was 8.5% (95% CI, 6.8 to 10.6). Among the risk factors for EP, those presenting the highest relative risk were, respectively, history of EP and previous tubal surgery. The most relevant signs and symptoms for diagnosis of EP were pain plus bleeding, which are strongly related to the diagnosis of EP.

L’insuffisance placentaire est une pathologie grave avec un diagnostic souvent trop tardif empêchant la mise en place de thérapeutiques efficaces. Le but de ce travail de Thèse est de développer chez la rate gestante et de transposer à l’Homme des outils d’IRM fonctionnelle (IRMf) placentaire qui permettrait une quantification de la perfusion placentaire en pratique clinique.Matériels et méthodes : Trois études en IRMf font partie de cette Thèse.Les deux premières ont été réalisées sur un modèle murin. Une séquence dynamique avec injection d’un agent de contraste (DCE) a été développée avec une particule de fer de type SPIO dans un modèle chirurgical d’hypoperfusion placentaire chronique, avec mesure de la perfusion placentaire f en ml/min/100ml et de la fraction volumique (Vb) en %. Une autre technique d’IRMf a été développée avec l’Arterial Spin Labeling (ASL) permettant d’estimer la perfusion placentaire en ml/min/100g sans injection de produit de contraste exogène. La dernière étude était une recherche translationnelle. Elle a consisté au développement de séquences de DCE avec injection de chélate de gadolinium, pour obtenir la perfusion f en ml/min/100ml et la fraction volumique en %. Nous avons également étudié, au décours de cette étude, la pharmacocinétique materno-fœtale du chélate de gadolinium.Résultats : Chez l’animal en DCE avec SPIO, notre étude nous a permis de montrer qu'il était possible d'utiliser l’effet T1 des SPIO pour caractériser la microcirculation placentaire par f=159,4 ml/min/100ml (+/- 54,6) et Vb =39,2% (+/- 11,9) pour 31 placentas « normaux ». En cas de RCIU, f diminue significativement pour les 23 placentas étudiés (f= 108,1 ml/min/100ml +/- 41, p=0,004), alors que la fraction volumique placentaire n'est pas modifiée (Vb=42,8% +/- 16,7, p=0,24). L’ASL nous a permis d’estimer la perfusion placentaire pour 47 placentas en condition physiologique, avec une perfusion estimée à 146,8 ml/min/100g (+/- 70,1).Chez l’Homme, 14 placentas ont été étudiés avec une perfusion placentaire globale estimée à 183 ml/min/100ml (+/-144) et nous avons également mis en évidence deux types de cinétique de rehaussement placentaire (précoce et intense et plus tardif et moins intense). La pharmacocinétique nous a permis d'étudier quantitativement le passage du chélate de gadolinium chez le fœtus. Ce passage est faible: par rapport à la concentration initiale du Dotarem®, la concentration sanguine fœtale correspond à 18,1x10-6 %, la concentration dans le liquide amniotique à 242,8 x10-6 % et 0,3 % de la dose initiale de Dotarem® est présente dans le placenta environ 70 heures après l’injection.Conclusion : Ce travail illustre la variété des techniques d'IRM fonctionnelle disponibles pour l'étude du placenta. La perfusion placentaire peut être quantifiée en DCE avec un agent particulaire à base de fer (SPIO) ou sans injection de produit de contraste en ASL chez le rat. L’étude de la perfusion placentaire chez l'Homme est possible en DCE avec les chélates de gadolinium.Mots clés : IRM, DCE, chélates de Gadolinium, ASL, perfusion placentaire, grossesse, placenta, retard de croissance intra-utérin. / Placental insufficiency is a serious medical condition with a diagnosis made usually too late to prevent introduction of effective therapies. The aim of this thesis is to develop, in pregnant rats and translate to humans, functional MRI (fMRI) tools allowing quantification of placental perfusion in clinical practice.Materials and Methods: Three studies using fMRI are part of this thesis. The first two were performed on a murine model. A dynamic sequence with injection of a contrast agent (DCE) has been developed with an iron oxide particle (SPIO) in a surgical model of chronic placental hypoperfusion with placental perfusion measurement (f) in ml / min / 100 ml and placental fractionnal volume (Vb) in %. Another technique of fMRI was developed with Arterial Spin Labeling (ASL) to estimate placental perfusion in ml / min / 100g without injection of contrast media.The latest study was a translational research. It consisted in the development of a dynamic sequence with injection of gadolinium chelate, in order to obtain perfusion (f) in ml / min / 100 ml and placental fractionnal volume (Vb) in %. We also studied maternal and fetal pharmacokinetics of gadolinium chelate.Results: In animals with SPIO DCE, our study allowed us to show that it is possible to use the T1 effect of SPIO to characterize the placental microcirculation by f = 159.4 ml / min / 100ml (+ / - 54.6) and Vb = 39.2% (11.9 +/-) for 31 « normal » placentas. In case of IUGR, f decreases significantly for the 23 examined placentas (f = 108.1 ml / min / 100ml +/- 41, p = 0.004), whereas the volume fraction placenta is not modified (Vb = 42 +/- 16.7 8 %, p = 0.24). ASL has allowed us to estimate placental perfusion for 47 placentas under physiological conditions, with an estimated perfusion of 146.8 ml / min / 100 g (70.1 +/-).In humans, 14 placentas were studied with an estimated perfusion of 183 ml / min / 100ml (+/- 144) and we also identified two types of placental kinetic enhancement (early and intense and later and less intense). Pharmacokinetics have allowed us to study quantitatively the transfer of gadolinium chelate in the fetus. This transfer is low compared to the initial concentration of Dotarem® : fetal blood concentration is 18.1x10-6%, concentration in amniotic fluid is 242.8 x10-6 % and 0.3% of the Dotarem® initial dose is present in the placenta approximately 70 hours after injection.Conclusion: This study illustrates the variety of functional MRI techniques available for placental study. Placental perfusion can be quantified by DCE with an iron oxide particle (SPIO) or without injection of contrast in ASL, in a rat model. The study of placental perfusion in humans is also possible in DCE with gadolinium chelates.

INTRODUÇÃO: A associação entre restrição do crescimento fetal (RCF) e alterações renais envolvem questões como a relação entre a redução da vascularização renal nesses fetos e a hemodinâmica fetal durante a gestação que, até o momento, não estão suficientemente exploradas. Considerando que a causa primária da redução nefrônica nesses fetos seria o hipofluxo renal causado pela redistribuição da hemodinâmica fetal frente a estímulos hipoxêmicos, seria de esperar que a gravidade do acometimento fetal levasse a menor vascularização renal em fetos com RCF. OBJETIVOS: Este estudo objetivou avaliar fetos com restrição de crescimento fetal e, assim, (1) descrever o índice de pulsatilidade das artérias renais, o volume renal e os índices de vascularização renal, bem como (2) verificar correlações entre os achados dopplervelocimétricos das artérias umbilicais, da artéria cerebral média e do ducto venoso e o índice de pulsatilidade das artérias renais, o volume renal e os índices de vascularização renal (IV, IF, IVF) e entre o índice de pulsatilidade das artérias renais, o volume renal, os índices de vascularização e o índice de líquido amniótico. MÉTODOS: Oitenta e um fetos com RCF foram avaliados por Power Doppler tridimensional, no sentido de se determinarem dados relativos ao índice de pulsatilidade das artérias renais, o volume renal, os índices de vascularização renal, os índices de pulsatilidade das artérias umbilicais, da artéria cerebral média e do ducto venoso, e o índice de líquido amniótico. Os valores identificados foram submetidos a análises estatísticas com o intuito de se determinarem eventuais correlações entre os parâmetros renais avaliados. RESULTADOS: O índice de pulsatilidade das artérias renais variou entre 1,50 e 3,44, com mediana de 2,39 + 0,41; o volume renal variou de 1,90 a 18,90, com mediana de 8,54 + 3,43; o IV renal variou de 0,05 a 7,75, com mediana de 1,57 + 1,58; o IF variou de 19,04 a 40,0, com mediana de 28,29 + 5,06; e o IVF variou de 0,03 a 5,18, com mediana de 0,96 + 1,3. Não houve correlação entre o índice de pulsatilidade das artérias renais e o índice de pulsatilidade das artérias umbilicais, da artéria cerebral média e do ducto venoso; tampouco foi observada correlação entre o volume renal e o índice de pulsatilidade das artérias umbilicais, da artéria cerebral média e do ducto venoso. O IV renal e o IVF renal foram negativamente correlacionados com o índice de pulsatilidade do ducto venoso, e positivamente correlacionados com o índice de líquido amniótico. Não houve correlação entre os índices de vascularização e os achados dopplervelocimétricos das artérias umbilicais e da artéria cerebral média, nem entre o índice de pulsatilidade das artérias renais, do volume renal e do IF renal com o ILA. CONCLUSÕES: O índice de pulsatilidade do ducto venoso se mostrou melhor preditor de alterações nos índices de vascularização renal, indicando que essas alterações se tornam mais evidentes em fetos com RCF com maior comprometimento hemodinâmico / INTRODUCTION: The association between intrauterine growth restriction (IUGR) and renal alterations refers to issues such as the relation between reduced renal vascularization in these fetuses and the fetal hemodynamics during pregnancy, which were not sufficiently investigated so far. Considering that the primary cause of nefrons reduction in these fetuses would be the renal hypoflow caused by the redistribution of the fetal hemodynamics resulting from hypoxic stimuli, it would be expected that the severety of the fetal impairment could result in worse renal vascularization in IUGR fetuses. OBJECTIVES: This study aimed at evaluating IUGR fetuses in order to (1) describe the pulsatility index of renal arteries, the renal volume and the renal vascularization indexes, as well as (2) verify correlations of the doppler findings in the umbilical arteries, middle cerebral artery, and venous duct with the pulsatility index of the renal arteries, the renal volume, and the renal vascularization indexes (VI, FI, VFI), and of the pulsatility index of the renal arteries, the renal volume, and the renal vascularization indexes with the amniotic liquid index. METHODS: 81 fetuses with IUGR were assessed with tridimentional power doppler in order to determine data regarding the pulsatility index of the renal arteries, the renal volume, the renal vascularization indexes, the pulsatility indexes of umbilical arteries, middle cerebral artery and venous duct, and the amniotic liquid index. Data were undertaken to statistical analysis for establishing eventual correlations among such assessed parameters. RESULTS: Pulsatility index of renal arteries ranged from 1.50 to 3.44 (median of 2.39 + 0.41); renal volume ranged from 1.90 to 18.90 (median of 8.54 + 3.43); renal VI ranged from 0.05 to 7.75 (median of 1.57 + 1.58); renal FI ranged from 19.04 to 40.0 (median of 28.29 + 5.06); and renal VFI ranged from 0.03 to 5.18 (median of 0.96 + 1.3. There was no correlation between the pulsatility index of renal arteries and the pulsatility indexes of the umbilical arteries, middle cerebral artery, and venous duct; correlations were not observed as well between the renal volume and the pulsatility indexes of the umbilical arteries, middle cerebral artery, and venous duct. Renal VI and VFI correlated negatively with the pulsatility index of the venous duct, and positively with the amniotic liquid index. There was no correlation betweem renal vascularization indexes and doppler findings in umbilical arteries and in middle cerebral artery, neither between pulsatility index of renal arteries, renal volume and renal FI and the amniotic liquid index. CONCLUSION: The pulsatility index of the venous duct was better predictive of alterations in renal vascularization index, suggesting that such alterations are more evident in IUGR fetuses with more severe hemodynamic impairments

LEITE, F. Influência da restrição de crescimento intra-uterino na idade da menarca: estudo da coorte de nascidos vivos de Ribeirão Preto de 1978/9. 2008. 85 p. Dissertação (Mestrado) apresentada à Faculdade de Medicina de Ribeirão Preto/USP. A idade da menarca é um marco da puberdade e, quando antecipada, parece estar associada a um maior risco de desenvolvimento de câncer de mama, síndrome metabólica e obesidade. É possível que alterações no ambiente intrauterino, como a restrição de crescimento do feto, levem a interferências no sistema hipotálamo-hipófise-gonadal resultando em alterações na idade da menarca. Em vista da controvérsia dos fatores que influenciam na idade da menarca, este estudo testou a hipótese da associação entre restrição de crescimento intra-uterino (baixo peso ao nascer, pequeno para idade gestacional, restrição intra-uterina de Kramer) e antecipação da idade da menarca. Em uma sub-amostra foi testada a possível interação entre a restrição de crescimento intra-uterino e o índice de massa corpórea. Para esse estudo foram utilizadas informações coletadas nos seguimentos de 1987/9 e 2004/5 de 1056 meninas nascidas em Ribeirão Preto, provenientes do estudo de coorte dos nascidos vivos em Ribeirão Preto de 1978/9. Menarca antecipada foi definida como primeiro sangramento vaginal ocorrido antes dos 12 anos de idade. Análise univariada foi seguida de análise bivariada e multivariada por meio de modelo generalizado empregando distribuição de Poisson para estimativa de riscos relativos e erro padrão por meio de método robusto. Os fatores de confusão controlados foram idade, escolaridade e situação conjugal da mãe, número de irmãos, comprimento ao nascer, prematuridade e índice de massa corpórea (apenas para a subamostra). Em média, a menarca ocorreu aos 12,3 anos (DP=1,5). A ocorrência de menarca antecipada foi de 27,7% (n= 293) para a coorte inteira e de 29,1% (n= 172) na sub-amostra. Foi encontrada associação negativa entre restrição de crescimento intra-uterino, seja representado por baixo peso ao nascer (Risco Relativo, RR= 0,47; Intervalo de Confiança de 95%, IC95%: 0,26-0,84), pequeno para idade gestacional (RR = 0,57;IC95%:0,37-0,89) ou restrição de Kramer (RR= 0,65; IC95%:0,47-0,92), com a antecipação da idade da menarca. Os resultados foram semelhantes na análise da sub-amostra, porém sem significância estatística. Quando o índice de massa corpórea foi considerado na análise da sub-amostra, não houve modificação dos resultados. Desta forma, este estudo demonstrou associação negativa entre restrição de crescimento intra-uterino e antecipação da idade da menarca, ou seja, a restrição de crescimento foi fator de proteção da menarca antecipada. / LEITE, F. Influence of intrauterine growth restriction on the age of menarche: the cohort study of live births of Ribeirao Preto in 1978/9. 2008. 85 p. Dissertation (Master) submitted to the Faculty of Medicine of Ribeirao Preto/USP. This study tested the hypothesis of association between intrauterine growth restriction and early age of menarche. For this study, follow-up data (n = 1056) from the population based livebirth cohort study of Ribeirao Preto of 19789 were analyzed. Early menarche was defined as having the first menstrual event before 12 years-old and intrauterine growth restriction was defined by three measurements: low birthweight (< 2500grs), small for gestational age (< 10% Williams growth curve) and fetal growth ratio (< 0.85 mean weight for gestational age). Relative risks were estimated by generalized estimation equations (Poisson distribution) with robust method for estimation of standard errors. Analyzes were adjusted for maternal age, education and marital status, number of siblings, birth length and preterm. Body mass index was tested as intervenient or interaction factor in a subsample of the cohort examined at 9 yrs-old. The mean age of menarche was 12.3 years (Standard Deviation = 1.5). Early menarche was observed for 27.7% for the entire cohort and 29.1% for the sub-sample. Negative association was observed between intrauterine growth restriction and early menarche. The adjusted relative risks and respective confidence intervals (95% CI) for low birth weight, small for gestational age and fetal growth ratio were respectively: 0.47 (95% CI: 0.26-0.84), 0.57 (95% CI: 0,37-0,89), and 0.65 (95%CI: 0,47-0, 92). No evidence that body mass index was an intermediate or interaction factor was observed. Thus, this study showed a negative association between intrauterine growth restriction and anticipation of age of menarche.

INTRODUÇÃO: Exposição a fatores ambientais e estresse durante o período intrauterino estão associados com alterações da trajetória do neurodesenvolvimento de forma sexo-dependente. Mecanismos epigenéticos estão envolvidos a esta associação. OBJETIVOS: Analisar de acordo com a exposição ao estresse na gestação o impacto do sexo e de alterações de metilação do DNA no sangue de cordão umbilical nas medidas antropométricas do neonato. MÉTODOS: Foram recrutadas 94 gestantes e aplicados questionários de medidas exposição ao estresse e fatores de risco durante a gravidez. A coleta de sangue do cordão umbilical seguiu protocolo padronizado. Para analisar o estresse foi utilizada análise de componentes principais (ACP) dos fatores de exposição avaliados: status socioeconômico, educação, ganho de peso, índice de massa corporal pré-gravídico, presença de doença psiquiátrica, estresse psicossocial durante a gravidez. Após o ACP fizemos análise de agrupamento por K-means. As análises de metilação foram realizadas utilizando Illumina Infinium Human Methylation450 (450K) BeadChip. Os dados foram analisados pelos pacotes Minfi e ChAMP (Chip Analysis Methylation Pipeline). A partir das posições diferencialmente metiladas (PDMs) foi feito análise de enriquecimento de processos biológicos com a ferramenta WebGestalt. Para avaliar impacto do sexo e alterações de metilação no desfecho antropométrico do neonato usamos modelos de análise linear de regressão múltipla. RESULTADOS: A coorte final para a avaliação do estresse foi composta por 89 pares mãe/recém-nascidos, sendo 50 meninas e 39 meninos. A ACP mostrou que os primeiros 3 componentes explicaram 60% da variabilidade da amostra. Sendo o primeiro componente (CP1) estresse psíquico, o segundo CP estresse social e o CP3 exposição a tóxicos. O biplot dos primeiros dois componentes sugeriu a separação das mães em dois grupos, confirmados pela análise de agrupamentos. Usando o ponto de corte de p-valor < 0,01 e deltabeta-valor>5%, encontramos 110 posições PDMs entre os grupos e restringindo este valor para p-valor < 0,01 e delta beta valor > 10% encontramos 13 PDMs. Usando apenas as crianças adequadas para idade gestacional fizemos análise de metilação diferencial entre os sexos. Foram encontradas 426 PDMs. Nenhuma das 13 PDMs encontradas entre os dois grupos pertenciam ao conjunto das PDMs entre sexos. No modelo de regressão linear multivariada controlando para sexo da criança e idade da mãe não encontramos nenhuma PDM associada aos desfechos antropométricos do neonato. Na análise estratificada por grupos os sítios cg24702040 (MAP3K21), cg21550016 (PAX8) foram estatisticamente significantes para perímetro abdominal e cg18706028 (CCKBR) e cg21550016 (PAX8) foram estatisticamente significantes para índice do perímetro cefálico para a idade. Este estudo sugere que o estresse materno independente do sexo pode afetar o crescimento fetal, mediado por respostas epigenéticas em genes relacionados à resposta ao estresse, regulação negativa da via de sinalização do receptor do fator de crescimento epidérmico, biogênese da sinapse e processo apoptótico / BACKGROUND: Exposure to environmental factors and stress during the intrauterine period are associated with changes in the neurodevelopmental trajectory in a sex-dependent manner. Epigenetic mechanisms are involved in this association. OBJECTIVES: Analyze according to exposure to stress during pregnancy the impact of sex and DNA methylation alterations on umbilical cord blood in the anthropometric measurements of the neonate METHODS: A total of 94 pregnant women were recruited and questionnaires were used to measure stress exposure and risk factors during pregnancy. Umbilical cord blood collection followed a standardized protocol. In order to analyze the stress, the principal components analysis (PCA) of the exposure factors evaluated were: socioeconomic status, education, weight gain, pre-gravid body mass index, presence of psychiatric illness, and psychosocial stress during pregnancy. After the PCA we did group analysis by k-means. Methylation analyzes were performed using Illumina Infinium Human Methylation 450 (450K) BeadChip. The data were analyzed by the Minfi and ChAMP (Chip Analysis Methylation Pipeline) packages. From the differentially methylated positions (DMPs) was made analysis of enrichment of biological processes with the tool WebGestalt. To evaluate gender impact and methylation alterations in the neonatal anthropometric outcome we used multiple regression linear analysis models. RESULTS: The final cohort for the evaluation of stress was composed of 89 mother/newborn pairs, being 50 girls and 39 boys. The PCA showed that the first 3 components accounted for 60% of the variability of the sample. Being the first component (PC1) psychic stress, the second PC social stress and PC3 exposure to toxic. The biplot of the first two components suggested the separation of the mothers into two groups, confirmed by cluster analysis. Using the cutoff point of p-value < 0.01 and delta beta-value > 5%, we found 110 DMPs between the groups and restricting this value to p-value < 0.01 and delta beta-value > 10 % we found 13 DMPs. Using only children suitable for gestational age we did differential methylation analysis between genders. There were 426 DMPs found. None of the 13 DMPs found between the two groups belonged to the pool of DMPs between the sexes. In the multivariate linear regression model controlling for child sex and age of the mother we did not find any DMP associated with the anthropometric outcomes of the neonate. In group-stratified analysis the cg24702040 (MAP3K21), cg21550016 (PAX8) sites were statistically significant for abdominal perimeter and cg18706028 (CCKBR) and cg21550016 (PAX8) were statistically significant for head cephalic circumference for age. This study suggests that maternal stress independent of sex can affect fetal growth, mediated by epigenetic responses in genes related to stress response, negative regulation of the epidermal growth factor receptor signaling pathway, biogenesis of the synapse and apoptotic process

<p>The objectives of this case-control study, investigating 51 in-patient women with acute pelvic inflammatory disease (PID) and 50 healthy women attending for routine gynecological check-up, were to investigate the background and reproductive history of women, who are considered at low risk of sexually transmitted infection presenting with PID, to examine whether intrauterine device (IUD) use <i>per se</i> and long use affects the microbiology and clinical course of the disease, to identify risk factors for PID and to examine whether IUD use is an independent risk factor for PID.</p><p>The most striking difference regarding the background and reproductive history between women with PID and healthy women over age 25 were related to socio-demographic factors and not to common risk factors for PID.</p><p>There was little difference between healthy women and women with current PID with regard to single microbes. The finding of combinations of several anaerobic or aerobic/anaerobic microbes appeared to be associated with PID, particularly in women over 35. The pathogenesis of non-sexually transmitted PID appears to be associated with a synergistic effect between several pathogens, possibly facilitated by the presence of an IUD.</p><p>IUD use <i>per se</i> was associated with an increased risk of PID in women 35 and older. There was an association between IUD use and complicated PID in women over 35, which was possibly influenced by long-term IUD use. Age over 35 and IUD use, independently of each other, were associated with an increased risk of failed conservative treatment, necessitating surgery in patients with PID.</p><p>An observational study showed that Latvian obstetrician-gynecologists participate actively in contraceptive counseling and are very experienced with regard to IUD use. Physicians’ attitudes and perceptions towards IUD are generally positive and their clinical considerations are in good agreement with that of doctors in other countries. Antibiotics are widely used around IUD insertion by doctors, possibly driven by a liberal attitude towards IUD use in women with a potential risk of STI. The study could identify some possible gaps in the theoretical knowledge about the IUD and other methods.</p>

A case-control study was performed to evaluate the Swedish population-based symphysis fundus (SF) reference curves. The study included 242 small for gestational age (SGA) neonates (169 term and 73 preterm infants) as cases and 296 non-SGA infants as controls. Two Swedish SF curves were evaluated. In term pregnancies they showed a sensitivity of 32 % and 51 % and a specificity of 90 % and 83 %, respectively, at a cut-off level of &lt; - 2 SD from the mean according to the SF reference curve. The sensitivity for SGA was higher in preterm pregnancies (49 % and 58 %, respectively) and the first alarm below – 2 SD was noted before 32 weeks in 37 % and 43 % of the preterm pregnancies, respectively. (Study I) A study of self-administered SF measurements was designed to achieve more regular and frequent SF measurements. Thirty-three women with singleton, ultrasound dated pregnancies performed SF measurements on average 14 weeks from gestational week 20 to 25 until delivery. Self-administered SF measurements were higher and had higher variance than midwives’ measurements. Four consecutive SF measurements on each occasion can compensate for higher variance. Reliable self-administered SF measurements can be obtained. (Study II) Self-administered SF measurements from 191 women were used to construct absolute and relative SF growth references. The influence of fetal sex, maternal obesity and parity was assessed in regression models. The lnSF growth was statistically influenced by maternal obesity, and a borderline significance was recorded for fetal sex and parity. Statistical analysis and graphical displays show no evidence that the relative lnSF growth should be dependent on these variables. (Study III) To improve detection of infants with intrauterine growth restriction (IUGR) rather than SGA a new statistical model (the SR method) was used. The SR method was evaluated with SF measurements from 1122 pregnant women. The sensitivity for neonatal morbidity and SGA was low, between 6 and 36 % for SGA (&lt; -2SD). Neonates classified as SGA (&lt; -2SD and &lt; 10th percentile) had increased morbidity compared with the total study group. Neonates suspected to be SGA before delivery by the population-based SF measurement method had lower morbidity than those not suspected. The SR method was found not to improve detection of fetuses with increased morbidity or SGA neonates in this study. Better screening methods to detect IUGR and SGA prior to delivery are needed. (Study IV)

The objectives of this case-control study, investigating 51 in-patient women with acute pelvic inflammatory disease (PID) and 50 healthy women attending for routine gynecological check-up, were to investigate the background and reproductive history of women, who are considered at low risk of sexually transmitted infection presenting with PID, to examine whether intrauterine device (IUD) use per se and long use affects the microbiology and clinical course of the disease, to identify risk factors for PID and to examine whether IUD use is an independent risk factor for PID. The most striking difference regarding the background and reproductive history between women with PID and healthy women over age 25 were related to socio-demographic factors and not to common risk factors for PID. There was little difference between healthy women and women with current PID with regard to single microbes. The finding of combinations of several anaerobic or aerobic/anaerobic microbes appeared to be associated with PID, particularly in women over 35. The pathogenesis of non-sexually transmitted PID appears to be associated with a synergistic effect between several pathogens, possibly facilitated by the presence of an IUD. IUD use per se was associated with an increased risk of PID in women 35 and older. There was an association between IUD use and complicated PID in women over 35, which was possibly influenced by long-term IUD use. Age over 35 and IUD use, independently of each other, were associated with an increased risk of failed conservative treatment, necessitating surgery in patients with PID. An observational study showed that Latvian obstetrician-gynecologists participate actively in contraceptive counseling and are very experienced with regard to IUD use. Physicians’ attitudes and perceptions towards IUD are generally positive and their clinical considerations are in good agreement with that of doctors in other countries. Antibiotics are widely used around IUD insertion by doctors, possibly driven by a liberal attitude towards IUD use in women with a potential risk of STI. The study could identify some possible gaps in the theoretical knowledge about the IUD and other methods.

The geometry of an organ’s vascular system determines the blood flow distribution to tissues for exchange of gas and nutrients by determining its vascular resistance. The importance of vascular geometry is evident in the placenta, where insufficient fetoplacental vascularity elevates vascular resistance thereby impairing perfusion, leading to one of the most common and severe pregnancy complications, intrauterine growth restriction (IUGR). The mouse is becoming a widely used model for human placental development due to the increasing availability of mouse models thought to have a placental defect. Vascular geometry can now be imaged and quantified using micro-computed tomography (micro-CT) and results used to estimate resistance to blood flow. This thesis first describes the implementation of contrast agent perfusion and micro-CT imaging of the mouse fetoplacental vasculature throughout late gestation. Application of a vascular segmentation technique is then described and evaluated for quantification of the arterial fetoplacental tree. Normal fetoplacental vascular development in late gestation is described for two common mouse strains, CD1 and C57Bl6 (B6). In B6 placentas, both late gestational capillary growth and thinning of the interhaemal membrane were blunted relative to CD1. Analysis of CD1 and B6 tree geometry revealed a constant number of arterial segments throughout late gestation in both strains but expansion of arterial diameters in B6 only, resulting in decreased B6 arterial resistance and shear stress in late gestation. Strain dependence shows the importance of genetics in fetoplacental vascular development. Quantification of the arterial tree in a mouse model of maternal pre-pregnancy exposure to chemicals commonly found in cigarettes revealed an increase in vascular tortuousity and a reduced number of arteriole sized vessels. This led to an increase in vascular resistance and a predicted decrease in blood flow, which could contribute to the observed reduction in fetal weights. In future studies, the methods described herein can be used in phenotyping numerous mouse models which currently are suspected to have a placental vascular defect.