Apesar de sua importância clínica e epidemiológica, a fisiopatologia da préeclâmpsia ainda não foi completamente compreendida. Sabe-se que a doença constitui-se de uma fase pré-clínica e um estágio clínico. Durante a última década muito esforço tem se concentrado na identificação precoce da doença, ainda em sua fase pré-clínica. A literatura científica tem demonstrado claramente um desequilíbrio na regulação da angiogênese das gestantes com pré-eclâmpsia, marcado por níveis elevados do fator antiangiogênico soluble fms-like tyrosine kinase-1 (sFlt-1) e níveis diminuídos do fator pró-angiogênico placental growth fator (PlGF). Embora um número crescente de estudos em populações de alto risco tenha avaliado o papel desses biomarcadores no diagnóstico de pré-eclâmpsia, dados sobre sua utilização para a predição de pré-eclâmpsia superajuntada, cujo diagnóstico pode ser particularmente difícil, permanecem relativamente escassos e controversos. Com o presente estudo pretendemos avaliar o desempenho de medidas seriadas dos níveis maternos circulantes dos fatores sFlt-1 e PlGF, bem como da razão sFlt-1/PlGF, para predição de pré-eclâmpsia superajuntada e compará-lo ao seu desempenho na predição de pré-eclâmpsia em sua forma \"pura\", não superajuntada. Para este propósito, estudamos uma coorte prospectiva composta de dois braços, um de gestantes com hipertensão arterial crônica e outro de gestantes normotensas, e avaliamos os níveis séricos de sFlt-1 e de PlGF e a razão sFlt-1/PlGF nas idades gestacionais de 20, 26, 32 e 36 semanas, tendo como desfecho principal o diagnóstico de pré-eclâmpsia. Um total de 97 gestantes foram acompanhadas, 37 normotensas e 60 com hipertensão arterial crônica. Entre elas, 4 (10,8%) desenvolveram pré-eclâmpsia e 14 (23,3%) desenvolveram pré-eclâmpsia superajuntada. Para predição de pré-eclâmpsia, a análise ROC (Receiver Operating Characteristics) apresentou área sob a curva (AUC - area under curve) de 0,83 (IC 95% = 0,68-0,99, P = 0,035) para dosagem de PlGF com 20 semanas e AUC = 0,92 (IC 95% = 0,81 - 1,00, P = 0,007) para a razão sFlt-1/PlGF com 26 semanas de gestação. A variação percentual dos níveis de PlGF entre 26 e 32 semanas de gestação apresentou AUC = 0,96 (IC de 95% = 0,89-1,00, P = 0,003). Para a predição de pré-eclâmpsia superajuntada, a razão sFlt-1/PIGF na idade gestacional de 32 semanas apresentou AUC = 0,69 (IC de 95% = 0,53-0,85, P = 0,039). Entre 20 e 26 semanas de gestação, a variação percentual do PIGF e da razão sFlt-1/PlGF apresentaram, respectivamente, AUC = 0,74 (IC de 95% = 0,58-0,90, P = 0,018) e AUC = 0,71 (IC 95% = 0,52-0,91, P = 0,034). Por nossos resultados podemos concluir que, embora os níveis de PlGF e a razão sFlt-1/ PlGF tenham apresentado bons desempenhos na predição de pré-eclâmpsia, é preciso ter cuidado ao usá-los para a predição de pré-eclâmpsia superajuntada. Nessas gestantes, a dosagem dos fatores angiogênicos apresenta capacidade de predição menor e mais tardia. Avaliações seriadas dos fatores podem melhorar o desempenho dos testes para predição de pré-eclâmpsia superajuntada em idades gestacionais mais precoces / Despite being a major public health problem, the pathophysiology of preeclampsia is incompletely understood. Preeclampsia progression comprises a pre-clinical stage and a clinical stage. During the last decade much work has focused on identifying the pre-clinical stage of preeclampsia. Many researchers have clearly demonstrated an anti-angiogenic imbalance that is marked by higher levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and lower levels of placental growth factor (PlGF) in the subjects who develop preeclampsia compared with those who do not. Although a growing number of studies in the high-risk population have shown the role of these biomarkers in diagnosing preeclampsia, superimposed preeclampsia, which can be a challenging diagnosis, remains partially understudied and the literature regarding this subject continues to be relatively scarce as well as controversial. By this study, we aimed to evaluate the performance of serial measurements of maternal circulating sFlt-1 and PlGF levels for the prediction of superimposed preeclampsia in chronic hypertensive subjects and to compare it to the prediction of preeclampsia in normotensive control subjects. For this purpose, we evaluated a two-armed prospective cohort of women with normotensive and chronic hypertensive pregnancies and assessed the serum levels of sFlt-1 and PlGF and the sFlt-1/PlGF ratio at gestational ages of 20, 26, 32 and 36 weeks, having preeclampsia as the primary outcome to be predicted. A total of 97 women were followed-up, 37 in the normotensive group and 60 in the chronic hypertensive group. Among them, 4 (10.8%) women developed preeclampsia and 14 (23.3%) developed superimposed preeclampsia. For predicting preeclampsia, PlGF at 20 gestational weeks presented an AUC=0.83 (CI 95% = 0.68 - 0.99, P=0.035) and the sFlt-1/PlGF ratio at 26 gestational weeks presented an AUC=0.92 (CI95% = 0.81 - 1.00, P=0.007). The percent change of the PlGF levels between 26 and 32 gestational weeks presented an AUC=0.96 (CI 95% = 0.89 - 1.00, P=0.003). For predicting superimposed preeclampsia, the sFlt-1/PlGF ratio at 32 gestational weeks presented an AUC=0.69 (CI 95% = 0.53 - 0.85, P=0.039). Between 20 and 26 gestational weeks, the percent change of PlGF and the sFlt-1/PlGF ratio presented, respectively, an AUC=0.74 (CI 95% = 0.58 - 0.90, P=0.018) and an AUC=0.71 (CI 95% = 0.52 - 0.91, P=0.034). By our results, we concluded that, although the PlGF level and the sFlt-1/PlGF ratio present good performances in the prediction of preeclampsia, caution is required when using them for the prediction of superimposed preeclampsia. Sequential assessments slightly improve the test performances for predicting superimposed preeclampsia at earlier gestational ages

Orientador: Mary Angela Parpinelli / Dissertação (mestrado) - Universidade Estadual de Campinas. Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-15T15:30:35Z (GMT). No. of bitstreams: 1 Lotufo_FatimaAparecidaHenrique_M.pdf: 1366983 bytes, checksum: f3a2fcc82a35cb99043657d9ceecf225 (MD5) Previous issue date: 2010 / Resumo: Objetivos: aplicar os critérios diagnósticos de near miss, definidos pela Organização Mundial da Saúde (OMS) a uma população de mulheres no ciclo grávido-puerperal internada em unidade de terapia intensiva geral (UTI), identificar os determinantes primários da morbidade materna grave (MMG), os indicadores do cuidado obstétrico e os resultados maternos e perinatais. Método: estudo de corte transversal incluindo 158 mulheres, no período de 2004 a 2007. Os casos foram classificados segundo desfecho da internação em: óbito, near miss materno (NMM) e condições potencialmente ameaçadoras da vida (CPAV) e os dados coletados dos prontuários. Foram aplicados testes de y2 com correção Yates, exato de Fisher, Odds Ratio (OR) com intervalo de confiança de 95% e regressão múltipla. Resultados: Dentre as 158 internações ocorreram 5 óbitos, 43 near miss e 110 casos CPAV. A razão de near miss foi de 4,4 casos por 1000 nascidos vivos (NV), a razão de near miss por óbito foi de 8,6 casos para 1 morte materna e o índice de mortalidade foi de 10,4%. As síndromes hipertensivas foram o principal determinante primário da internação em 67,7% (107/158 casos), mas as hemorragias foram a principal causa de near miss (17/43 near miss e dois óbitos), principalmente por atonia uterina e gravidez ectópica complicada, com índice de mortalidade por esta causa de 10,5%. Conclusões, a padronização dos critérios diagnósticos de near miss permitirá comparação uniforme dos indicadores entre distintos contextos. As síndromes hemorrágicas foram os principais determinantes primários para near miss e morte materna na instituição e sugerem a existência de demoras no cuidado obstétrico / Abstract: Objectives: to apply the new diagnostic criteria for maternal near miss, defined by the World Health Organization (WHO) to a population of women during pregnancy and postpartum period admitted to a general Intensive Care Unit (ICU); to identify the primary determinants of severe maternal morbidity (SMM), the indicators of obstetrical care and the maternal and perinatal outcomes. Method: a cross sectional study including 158 women between 2004 and 2007. The cases were classified according to the outcome of hospital admission in death, maternal near miss and potentially life threatening conditions (PLTC) and the data were collected from clinical records. Yates corrected y2 and Exact of Fisher tests, Odds Ratios (OR) with their 95% confidence intervals and multiple logistic regression analyses were used. Results: Among the 158 admissions, there were 5 deaths, 43 maternal near miss and 110 cases of PLTC. The near miss ratio was 4.4 cases per 1000 live births (LB), the ratio between near miss and death was 8.6 cases per 1 maternal death and the general mortality index was 10.4%. Hypertensive syndromes were the main primary determinant of admission in 67.7% (107/158 cases), but hemorrhage was the main cause of maternal near miss (17/43 near miss and two deaths), mainly due to uterine atony and complicated ectopic pregnancy, with a mortality index by this cause of 10.5%. Conclusions: the standardization of diagnostic criteria for maternal near miss allowed quantifying SMM in a standard way, facilitating the comparison between different contexts. Hemorrhage was the main primary determinant for maternal near miss and death at the institution suggesting that delays could exist for appropriate obstetric care / Mestrado / Tocoginecologia / Mestre em Tocoginecologia

Contexte : La pré-éclampsie (PE) est une pathologie ischémique placentaire se manifestant par un syndrome materno-fœtal pendant la grossesse, et dont seul l’accouchement peut interrompre la progression. La PE peut survenir dans le post-partum et cette forme atypique de PE n’est pas expliquée par notre compréhension actuelle de la maladie. L’objectif de ce travail est de formuler des hypothèses physiopathologiques et de les explorer par l’étude des facteurs de risques, des potentiels facteurs déclencheur et de les corréler à l’étude de l’histopathologie des placentas. Méthode : Il s’agit d’une étude cas-témoins, comparant les caractéristiques démographiques et obstétricales des cas de PE du post-partum (n=50), à celles des cas de PE ante-partum précoce (n=100) et tardive (n=100), et à des grossesses normotensives (n=100). Pour l’étude de l’histopathologie placentaire, 30 placentas par groupe ont été étudiés. Les patientes ont été recrutées sur la base de registres de patientes avec troubles hypertensifs, tenus par les centres participants et sur la base des codes diagnostiques issus de la classification internationale des maladies (CIM). Résultats : Aucune différence statistiquement significative n’a été observée entre les groupes en terme d’âge, d’indice de masse corporelle, de primiparité, de recours aux techniques de procréation médicalement assistée et de décès néonataux. La PE du post-partum est associée à l’ethnie afro-caribéenne (OR 3.0, IC 95% 1.3-6.7 ; p <0.01), l’hypertension artérielle (HTA) pré-gestationnelle (OR 46.3, IC 95% 7.4-∞; p <0.01), la gémellité (OR 7.7, IC 95% 1.4-78.7) ; p<0.01), un état infectieux péri-partum (OR 6.5, IC 95% 1.8-29.7 ; p<0.01), la provocation du travail (OR 6.0, IC 95% 1.8-21.4 ; p <0.01), et des valeurs de tension artérielle (TA) avant la sortie de la maternité normales-hautes, tant pour la valeur systolique (OR 10.2, IC 95% 4.3-25.4 ; p<0.01) que pour la valeur diastolique (OR 30.2, IC 95% 8.3-168.3 ; p<0.01). Au niveau placentaire, 40% des placentas des cas de PE post-partum présentaient une déciduite aiguë (PE précoce: 5.7% (2), p<0.01; PE tardive: 16.7% (5), p=0.046; normotendues: 3.2% (1), p<0.01), 39.4% (13) démontraient une anomalie de la maturité villositaire (PE précoce: 77.2% (27), p<0.01; PE tardive: 26.7% (8), p=0.3; normotendues: 3.2% (1), p<0.01), 18.2% (6) montraient une vasculopathie déciduale (PE précoce: 34.3% (12), p=0.13; PE tardive: 10% (3), p=0.35; normotendues: 9.7% (3), p=0.33) et 9.1% (3) présentaient des signes d’ischémie et d’infarctus (PE précoce: 51.4% (18), p<0.01; PE tardive: 13.3% (4), p=0.6; normotendues: 16.1% (5), p=0.4). Conclusions : Les résultats de nos travaux suggèrent que les patientes présentant une PE dans le post-partum ont un profil de risque similaire à celui de la PE typique de l’ante partum, en particulier des PE tardives survenant au delà de 34 SA. La modification de la date de l’accouchement par l’intervention médicale et la provocation du travail pourrait agir comme facteur déclencheur de la PE dans le post-partum, de même qu’une infection aiguë. Les premiers signes de PE post-partum peuvent être détectés par la mesure de la TA avant la sortie de la maternité. Aucune différence significative n’a été observée au niveau placentaire, en terme de vasculopathie déciduale et de signes d’ischémie placentaire. Le taux de déciduite aiguë était plus important dans la PE du post-partum. Au total, la PE du post-partum semble être une pathologie maternelle, survenant dans un contexte d’état inflammatoire accru, possiblement déclenchée par une infection aiguë, où la maladie ischémique placentaire joue peu ou aucun rôle. / Background: Pre-eclampsia (PE) is an ischemic placental disease that is clinically expressed by a maternal-fetal syndrome. Only delivery can stop the progression of the disease. PE can occur after delivery and this atypical from of PE is not explained by our current understanding of the physiopathology. The objective of this work was to formulate physiopathological hypotheses for post-partum PE, to explore them by identifying the risk factors, potential triggers and to correlate them to a histological study of the placenta of women who would later present with post-partum pre-eclampsia. Methods: This is a case-control study, comparing the demographic and obstetrical characteristics of cases of post-partum PE (n=50) with cases of early-onset PE (n=100), late-onset PE (n=100) and normotensive pregnancies (n=100). For the pathological study, 30 placentas per group were included. Patients were identified on a registry of hypertensive disorders of pregnancy and through the codification of the International Classification of Diseases (ICD). Results: There was no difference in term of age, body mass index, primiparity, use of reproductive technology and neonatal death between groups. Post-partum PE was associated with Afro-Caribbean ethnicity (OR 3.0, CI 95% 1.3-6.7; p <0.01), pre-gestationnal hypertension (OR 46.3, CI 95% 7.4-∞; p <0.01), twin pregnancies (OR 7.7, CI 95% 1.4-78.7); p<0.01), peri-partum infectious diseases (OR 6.5, IC 95% 1.8-29.7; p<0.01), induction of labor (OR 6.0, IC 95% 1.8-21.4; p <0.01), and normal-high blood pressure value before discharge of the maternity ward, for the systolic value (OR 10.2, IC 95% 4.3-25.4; p<0.01) as well as for the diastolic value (OR 30.2, IC 95% 8.3-168.3 ; p<0.01). Forty percent of placenta of post-partum PE had acute deciduitis (early PE: 5.7% (2), p<0.01; late PE: 16.7% (5), p=0.046; normal: 3.2% (1), p<0.01), 39.4% (13) had abnormal maturation of the villi (early PE: 77.2%(27), p<0.01; late PE: 26.7%(8), p=0.3; normal: 3.2 %(1), p<0.01), 18.2% (6) had decidual arteriolopathy (early PE: 34.3% (12), p=0.13; late PE: 10% (3), p=0.35; normal: 9.7% (3), p=0.33) and 9.1% (3) had villous ischemia and infarction (early PE: 51.4% (18), p<0.01; late PE: 13.3% (4), p=0.6; normal: 16.1% (5), p=0.4). Conclusions: Our work suggests that patients presenting with post-partum PE have similar risk profile than the typical antepartum PE, in particular with late-onset PE (after 34 weeks of gestation). Modification of the delivery date by medical intervention and induction of labor, might act as a trigger, as well as an acute infection. First signs of post-partum PE can be detected through measurement of blood pressure before discharge of the maternity. There were no significant differences in the placentas in terms of decidual arteriolopathy and villi ischemic changes between post-partum PE, late onset PE and the controls. There was a higher level of acute deciduitis in the placenta of post-partum PE. Altogether, our results suggests that post-partum preeclampsia is more of a maternal disease, characterized by an increased inflammatory state, potentially triggered by infection, and in which placental ischemic disease has little or no role to play.

<p>We defined hypertension in pregnancy as a composite of gestational hypertension, preeclampsia and eclampsia. The etiology of hypertension in pregnancy remains controversial. The three chapters of this thesis explore the risk of hypertension in pregnancy from various kidney conditions. Chapter 1 introduces the reader to the thesis. Chapter 2 is a systematic review that studied the risk of developing hypertension in pregnant women with chronic kidney disease but not on dialysis. We found that women with chronic kidney disease had at least a twofold higher relative risk of developing hypertension during pregnancy compared with women having no chronic kidney disease. Chapter 3 is a retrospective study looking at the risk of developing gestational hypertension and preeclampsia in women who had symptomatic gastroenteritis after drinking water infected with <em>E. coli</em> O157:H7 during the Walkerton outbreak in May 2000. We conducted this study using linked datasets at the Institute of Evaluative Sciences (ICES) Toronto, Ontario. We observed that there was no increased risk of developing gestational hypertension or preeclampsia among the symptomatic women compared with women from the neighbouring towns who were asymptomatic or did not drink the water. Chapter 4 is a protocol of a prospective cohort study recruiting female kidney donors and healthy non-donors as the comparative group to study pregnancy outcomes in these individuals. This is a multicentre study involving 12 transplant centres throughout Canada. There are 59 participants in this study to date (Feb 28, 2013) of which seven have been pregnant so far. Data collection for this study is ongoing.</p> / Doctor of Philosophy (PhD)

Die Schwangerschaft ist ein komplexer Vorgang, bei dem es zu einer Interaktion zwischen dem mütterlichen Immunsystem und dem Fetus kommt. Der allogene Fetus kann als natürlich auftretendes Allotransplantat angesehen werden. Man nimmt daher an, dass die Toleranzmechanismen, die im Rahmen einer erfolgreichen Schwangerschaft auftreten, den Mechanismen zur Akzeptanz eines Transplantates ähnlich sind. HO-1 wurde als ein gewebe-schützendes und anti-apoptotisches Molekül beschrieben, welches eine wichtige Rolle bei der Akzeptanz von Transplantaten spielt. Verschiedene Studien konnten zeigen, dass HO-1 in der Plazenta verschiedener Spezies exprimiert wird und dass die Expression von HO-1 bei Schwangerschaftskomplikationen, wie dem spontanen Abort, vermindert ist. Dies lässt vermuten, dass HO im Laufe der Schwangerschaft eine Rolle spielt. In diesem Kontext sollte die vorliegende Arbeit das Verständnis über die Funktion von HO-1 bei den beiden Schwangerschaftskomplikationen spontaner Abort und Präeklampsie (Schwangerschaftshypertonie) erweitern. Mit Hilfe des Mausmodells für einen spontanen Abort, bei dem weibliche CBA/J Mäuse mit männlichen DAB/2J Mäusen verpaart werden, wurde der Einfluss der HO-1 Expression auf die Abortrate untersucht und mit BALB/c-verpaarten CBA/J Weibchen, welche eine normale Schwangerschaft aufweisen, verglichen. In Mäusen mit spontanem Abort zeigte sich eine Reduktion der HO-1 und HO-2 Expression. Die Induktion von HO-1 mittels Co-PP war in der Lage, die Abortrate zu senken, wohingegen eine Reduktion der HO-1 mittels Zn-PP die Abortrate erhöhte. Es zeigte sich, dass es neben der Induktion von HO-1 auch zu einer erhöhten Expression des anti-apoptotischen Moleküls Bag-1 kam. Im Mausmodell für Präeklampsie wurde ebenfalls die Expression von HO-1 und möglicher Interaktionspartner untersucht. Des Weiteren wurde der Einfluss einer erhöhten bzw. verminderten HO-1 Expression auf die Präeklampsie-ähnlichen Symptome in diesem Mausmodell analysiert. Im Laufe der Arbeit zeigte sich jedoch, dass HO-1 Veränderungen keinen Einfluss auf die Präeklampsie-ähnlichen Symptome hat. Die Daten dieser Arbeit lassen vermuten, dass eine erhöhte Expression von HO-1 zum Zeitpunkt der Implantation den Fetus vor einem spontanen Abort schützt und dass die protektive Funktion von HO-1 durch eine Interaktion mit anti-apoptotischen Molekülen wird. Bei der Präeklampsie hingegen scheint HO-1 keine bzw. nur eine untergeordnete Rolle zu spielen. / Pregnancy maintenance is a very complex phenomenon, involving interactions between the maternal immune system and the semiallogenic foetus, which does not lead to immune rejection but to tolerance. Thus it is thought that the tolerance mechanisms involved in a successful pregnancy are closely related to those allowing graft acceptances. Heme Oxygenases (HO) were described to be tissue-protective and to have anti-apoptotic properties. Up-regulation of HO, particularly of HO-1, allows tissue tolerance after transplantation. The presence of HO-1 had been reported in the placenta of different species during normally progressing pregnancies; in pregnancy complications like spontaneous abortion the levels of HO-1 were reduced. This led to the proposal that HO-1 may play a protective role. The aim of this work was to analyze the influence of HO-1 changes in the outcome of pregnancy, using two different murine models for pregnancy complications, namely of spontaneous abortion and pre-eclampsia. The influence of HO-1 expression on the abortion rate was analysed in DBA/2J-mated CBA/J females, which spontaneously show high abortion rates compared to BALB/c-mated CBA/J females, having fully normal pregnancy. The induction of HO-1 by Co-PP led to diminished abortion rates, while the blocking of HO-1 and HO-2 by Zn-PP boosted abortion. In mice with reduced abortion rates after HO-1 induction, up-regulated levels of the anti-apoptotic molecule Bag-1 could be observed. In mice showing signs for preeclampsia after transfer of Th1 activated cells, the expression of HO-1, Th1/Th2 and eNOS was analysed. Furthermore HO-1 was of up- or down-regulated by using Co-PP or Zn-PP respectively. HO-1 changes did not influence the outcome of the disease, as we could not observe a diminution in the blood pressure levels. In summary, the results of this study indicate that high levels of HO-1 during implantation are able to prevent foetal rejection and that the beneficial effects of the HO-1 induction are related to the up-regulation of tissue protective molecules as Bag-1. No relationship could be observed between HO-1 levels and preeclampsia outcome.

<p>UVOD: Hipertenzivna oboljenja u trudnoći predstavljaju heterogenu grupu bolesti koja se javljaju kod 3-8% trudnica op&scaron;te populacije. Najteže forme ovih oboljenja preeklampsija, eklampsija i HELLP sindrom su vodeći uzročnici morbiditeta i mortaliteta majke i ploda u odnosu na sve druge komplikacije u trudnoći. Etiopatogeneza ovih oboljenja je jo&scaron; uvek nedovoljno razja&scaron;njena ali se smatra da placenta ima ključnu ulogu u nastanku ovih komplikacija, odnosno da placentalna insuficijencija, koja nastaje kao posledica nedovoljne adaptacije decidualnih i intramiometrijalnih delova spiralnih arterija već u prvih nekoliko nedelja trudnoće, dovodi do redukcije utero-placentalne cirkulacije i lokalne placentalne hipoksije, &scaron;to se nepovoljno održava i na majku i na plod. U cilju razja&scaron;njenja patofiziolo&scaron;kih mehanizama nastanka hipertenzivnih oboljenja u trudnoći i pronalaska dovoljno senzitivnih makera koji bi pomogli u ranom predviđanju nastanka najtežih formi ovih oboljenja, do sada su ispitivani brojni proteini koji učestvuju u procesima stvaranja i razvoja placentalne vaskularne mreže kao &scaron;to su vaskularni endotelni faktor rasta (VEGF-A), placentalni faktor rasta (PlGF) i solubilni receptor fms-like tirozin kinaza receptor (sFlt-1). CILJ: Uporediti serumske koncentracije (sFlt-1, PlGF, VEGF-A, PAPP-a, free&szlig;hCG, glukoze, ukupnog holesterola, HDL holesterola, LDL holesterola, triglicerida, apo-AI, apoB, AST, ALT, GGT, kreatinina, ureje, mokraćne kiseline, hsCRP, Na, K, Cl, P, Mg i Ca između grupe trudnica sa preeklampsijom, hroničnom i gestacijskom hipertenzijom i kontrolne grupe trudnica u prvom trimestru trudnoće između 11 i 14. nedelje gestacije. Ispitati da li se vrednosti odabranih laboratorijskih parametara (sFlt-1, VEGF-A i PLGF) kod ispitivanih trudnica statistički značajno razlikuju u odnosu na gestacijsku nedelju u trenutku porođaja, težinu i dužinu i APGAR skor bodovanja novorođenčeta. Ispitati da li se vrednosti angiogenih proteina:sFlt-1, VEGF-A, PlGF značajno razlikuju kod ispitivanih trudnica u odnosu na broj prethodnih trudnoća i starosti trudnica. MATERIJAL I METODE: Istraživanje je sprovedeno kao prospektivno analitička studija u Kliničkom centru Vojvodine, u periodu od juna 2012. do februara 2015. godine. U istraživanje je uključeno ukupno 143 trudnice starosti od 18 &ndash; 43 godine. Sve trudnice uključene u istraživanje podeljene su na dve ispitivane i jednu kontrolnu grupu. Prvu ispitivanu grupu činilo je 43 trudnice koje su po definisanim kriterijuma razvile preeklampsiju u aktuelnoj trudnoći. Drugu ispitivanu grupu činilo je 46 trudnica kojima je dijagnostikovana ili potvrđena hronična ili gestacijska hipertenzija u aktuelnoj trudnoći. Kontrolnu grupu činilo je 54 zdravih trudnica sa verifikovanim fiziolo&scaron;kim ishodom trudnoće u terminu, bez maternalnih i fetalnih komplikacija. Prilikom regrutovanja trudnica (između 11+0 i 13+6 nedelja gestacije) za uče&scaron;će u istraživanju, uzeti su anamnestički podaci o faktorima rizika za pojavu hipertenzivnih oboljenja u trudnoći, i u okviru kliničkog i aku&scaron;erskog pregleda urađena su antropometrijska merenja, merenje krvnog pritiska, i specijalizovani ultrazvučni pregled ploda radi utvrđivanja gestacijske starosti ploda i određivanja rizika za pojavu hromozomskih anomalija ploda. Trudnicama je nakon uzimanja anamnestičkih podataka i kliničkog i aku&scaron;erskog pregleda i potpisanog pisanog pristanka pacijenta o dobrovoljnom učestvovanju u istraživanju izvađena krv radi određivanja odabranih laboratorijskih parametara. Serumske koncentracije sFlt1, VEGF-A i PIGF određivane su kvantitativnom ELISA tehnikom (R&amp;D Systems Europe Ltd. Abingdon, UK), dok su: glukoza, ukupni holesterol, HDL holesterol, LDL holesterol, trigliceridi, apo-AI I apoB, AST, ALT, GGT, kreatinin, ureja, mokraćna kiselina, hsCRP, Na, K, Cl, Mg, P, Ca određivani na automatizovanim analizatorskim sistemima. Sve trudnice su kategorisane u 2 ispitivane i kontrolnu grupu na osnovu pojave ili isključenja hipertenzivnih oboljenja u aktuelnoj trudnoći. Statistička obrada podataka urađena je u statističkom programu STATISTICA 12 (StatSoft Inc.,Tulsa, OK, USA). Podaci su predstavljeni tabelarno i grafički, nivo statističe značajnosti p, je tumačen statistički značajnim ukoliko su vrednosti p&lt;0,05. REZULTATI: Vrednosti serumskih koncentracija sFlt-1 se statistički značajno razlikuju u sve tri grupe ispitanica i značajno su vi&scaron;e u grupama sa hipertenzivnim oboljenjima u odnosu na zdravu grupu ispitanica, p&lt;0,001. Serumske koncentracije VEGF-A su značajno niže u grupi trudnica sa preeklampsijom u odnosu na zdrave trudnice kontrolne grupe (p&lt;0,001), dok se nivoi serumskih koncentracija PlGF statistički značajno razlikuju između sve tri grupe trudnica tako da su najniže vrednosti uočene u grupi sa preeklampsijom (p&lt;0,001) u odnosu na preostale dve grupe ispitanica. Nije uočeno postojanje statistički značajne razlike u nivoima PAPP-A, biohemijskih parametara (glukoze, AST, ALT, GGT kreatinina, ureje, mokraćne kiseline), lipidskih parametara (uk. holesterol, LDL, apo A-I, apo B), parametara inflamatornog (kompletna krvna slika, fibrinogen), hemostaznog (D-dimer, vWF-antigen) i elektrolitskog statusa (Na, K, Cl, P, Mg), p&gt;0,05. Nivoi free &szlig;hCG i HDL holesterola su značajno niže, dok su vrednosti hsCRP i triglicerida značajno vi&scaron;e u grupi trudnica sa preeklampsijom u odnosu na grupu bez hipertenzivnih poremećaja u trudnoći. Serumske koncentracije sFlt-1 preko 865 pg/ml imaju senzitivnost od 93% i specifičnost od 81,5% u predviđanju nastanka preeklampsije, dok serumske koncentracije PlGF ispod 60 pg/ml senzitivnost od 88,4% i specifičnost od 79,6% u predviđanju pojave preeklampsije. Serumske koncentracije sFlt-1, VEGF-A i PlGF ne pokazuju statistički značajnu razliku u odnosu na godine života trudnice i broja prethodnih trudnoća p&gt;0,05. Serumske koncentracije sFlt-1 i PlGF se značajno razlikuju u odnosu na telesnu težinu novorođenčeta, tako da su niže vrednosti oba proteina detektovane u grupi novorođenčadi sa porođajnom težinom ispod 1500 gr. u odnosu na telesnu masu između 2800-3300 gr, p&lt;0,001. Takođe su nađene niže vrednosti sFlt-1 i PlGF u grupi trudnica koje su se porodile pre 33. nedelje gestacije u odnosu na nedelju gestacije u trenutku porođaja preko 37 nedelje gestacije, p&lt;0,001. Serumske koncentracije sFlt-1 i PlGF se značajno razlikuju u odnosu na indeks telesne mase majke tako da su vi&scaron;e vrednosti sFlt-1 i niže vednosti PlGF nađene u grupi trudnica sa indeksom telesne mase ispod 25 u odnosu na grupu trudnica sa indeksom telesne mase preko 30 kg/m2, p&lt;0,001. Serumske koncentracije sFlt-1 u prvom trimestru trudnoće su značajno povezane sa parametrima inflamacije (hsCRP), vrednostima dijastolnog krvnog pritiska i nivoima free &szlig;hCG. Takođe se uočava značajna povezanost koncentracije PlGF sa indeksom telesne mase, vrednostima sistolnog krvnog pritiska i koncentracijom hsCRP u prvom trimestru trudnoće. ZAKLJUČAK: Nivoi antiangiogenog proteina sFlt-1 su vi&scaron;e u grupi trudnica sa preeklampsijom u odnosu na grupu sa hroničnom i gestacijskom hipertenzijom i grupu trudnica bez hipertenzivnih poremećaja trudnoći. Nivoi proangiogenog proteina VEGF-A su značajno niže u grupi trudnica sa preeklampsijom i hroničnom i gestacijskom hipertenzijom u odnosu na grupu trudnica bez hipertenzivnih poremećaja u trudnoći. Serumske koncentracije proangiogenog proteina PlGF su niže u grupi trudnica sa preeklampsijom u odnosu na grupu sa hroničnom i gestacijskom hipertenzijom i grupu trudnica bez hipertenzivnih poremećaja trudnoći. Serumske koncentracije placentalnog proteina free &szlig;hCG i HDL holesterola su značajno niže, dok su vrednosti hsCRP i triglicerida značajno vi&scaron;e u grupi trudnica sa preeklampsijom u odnosu na grupu bez hipertenzivnih poremećaja u trudnoći. Između trudnica sa hipertenzivnim poremećajima u trudnoći i zdravih trudnica nije uočeno postojanje značajne razlike u vrednostima placentalnog proteina PAPP-A, biohemijskih parametara (glukoze, AST, ALT, GGT kreatinina, ureje, mokraćne kiseline), lipidskih parametara (uk. holesterol, LDL, apo A-I, apo B), parametara inflamatornog (kompletna krvna slika, fibrinogen), hemostaznog (D-dimer, vWF-antigen) i elektrolitskog statusa (Na, K, Cl, P, Mg). Serumske koncentracije sFlt-1 i PlGF se značajno razlikuju u odnosu na gestacijsku starost na porođaju i telesnu masu novorođenčeta i niže su kod trudnica koje su se prevremeno porodile kao i kod novorođenčati sa manjom porođajnom težinom. Serumske koncentracije sFlt-1 se značajno razlikuju u odnosu telesnu dužinu i APGAR skor novorođenčeta, tako da su vi&scaron;e vrednosti sFlt-1 udružene sa većom telesnom dužinom novorođenčeta i boljim APGAR skorom. Serumske koncentracije sFlt-1, VEGF-A i PlGF se ne razlikuju značajno u odnosu na godine života trudnice i broja prethodnih trudnoća. Nivoi proteina angiogeneze sFlt-1 i PlGF predstavljaju dobre prediktore u predviđanju nastanka preeklampsije u prvom trimestru trudnoće.</p> / <p>INTRODUCTION: Hypertensive disorders in pregnancy are a heterogeneous group of diseases that occur in 3-8% of all pregnancies. The most difficult forms of these diseases: preeclampsia, eclampsia and HELLP syndrome are the leading causes of maternal and fetal morbidity and mortality in relation to all other pregnancy complications. Etiopathogenesis of these diseases is still insufficiently understood but it is thought that the placenta plays a key role in the development of these complications, and that placental insufficiency, which occurs as a result of insufficient adaptation of decidual intramiometrial and parts of the spiral arteries in the first few weeks of pregnancy, leading to a reduction of utero- placental circulation and local placental hypoxia, which adversely affects the mother and the fetus. In order to elucidate the pathophysiological mechanisms of hypertensive disorders in pregnancy and to find sufficiently sensitive makers for early prediction of the most severe forms of these diseases, so far have been investigated a number of proteins involved in the processes of creation and development of placental vascular network such as vascular endothelial growth factor (VEGF-A), placental growth factor (PlGF) and soluble fms-like receptor tyrosine kinase receptor (sFlt-1). OBJECTIVE: The aim of the study was to compare serum concentration of sFlt-1, PlGF, VEGF-A, PAPP-A, free&szlig;hCG, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, apo-AI, apo B, AST, ALT, GGT, creatinine, urea, uric acid, hsCRP, Na, K, Cl, P, Mg and Ca between the group of pregnant women with preeclampsia, chronic and gestational hypertension and the control group of pregnant women in the first trimester of pregnancy between 11 and 14 weeks gestation. Also the aim was to examine whether the value of selected laboratory parameters (sFlt-1, VEGF-A and PlGF) differ in relation to gestational week at the time of birth, weight, length and APGAR scoring system of newborns. The aim was to examine whether the value of angiogenic proteins: sFlt-1, VEGF-A and PlGF differ significantly in relation to the number of previous pregnancies and age of the pregnant woman. MATERIALS AND METHODS: The study was conducted as a prospective analytical study in the Clinical Center of Vojvodina, in the period from June 2012 to February 2015. The study included a total of 143 pregnant women aged 18 - 43 years. All pregnant women included in the study were divided into two study and one control group. The first study group consisted of 43 pregnant women who developed preeclampsia during the current pregnancy. The second study group consisted of 46 pregnant women who are newly diagnosed or confirmed chronic or gestational hypertension during the current pregnancy. The control group consisted of 54 healthy pregnant women with verified physiological outcome of pregnancy at term without maternal and fetal complications. Patients were included in the study between 11 + 0 and 13 + 6 weeks of gestation. All patients had data about risk factors for developing hypertensive disorders in pregnancy. After clinical and obstetric examination all patients underwent anthropometric measurements, measurement of blood pressure, and specialized ultrasound examination to determine precise gestational age of the fetus and to determine the risk for fetal chromosomal abnormalities. All patients signed a written consent of the patient&#39;s voluntary participation in the study. Serum levels of sFlt1, VEGF-A and PlGF were determined by quantitative ELISA (R &amp; D Systems Europe Ltd., Abingdon, UK), while glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, apo-AI, apo B, AST, ALT, GGT, creatinine, urea, uric acid, hsCRP, Na, K, Cl, P, Mg, Ca were determined on automated analyzer systems. All pregnant women were categorized into 2 study and a control group on the basis of presence of hypertensive disorders in the current pregnancy. Statistical analysis was performed in 12 statistical program STATISTICA (StatSoft Inc., Tulsa, OK, USA). The data are presented in tables and graphs, the level of significance p is interpreted statistically significant if the p value was less than &lt;0.05. RESULTS: Serum concentrations of sFlt-1 are statistically significantly different in all study groups and significantly higher in the groups with hypertensive disorders compared to healthy subjects p &lt;0.001. Serum levels of VEGF-A are significantly lower in the preeclampsia group compared to healthy control group (p &lt;0.001), while the levels of serum concentration of PlGF statistically significantly different between all groups so that the lowest values are observed in the preeclampsia group (p &lt;0.001) compared to the other two study groups. There is no statistically significant differences in the levels of PAPP-A, biochemical parameters (glucose, AST, ALT, GGT creatinine, urea, uric acid), lipid parameters (total cholesterol, LDL, apo AI, apo B), inflammatory parameters (complete blood count, fibrinogen), hemostatic (D-dimer, vWF-antigen) and electrolyte status (Na, K, Cl, P, Mg, Ca), p&gt; 0.05. Levels of free &szlig;hCG and HDL cholesterol levels are significantly lower, while the value of hsCRP and triglycerides significantly higher in the group of women with preeclampsia compared to the healthy control group. Serum concentrations of sFlt-1 over 865 pg/ml have a sensitivity of 93% and specificity of 81.5% in predicting preeclampsia, while serum PlGF concentration below 60 pg/ml, a sensitivity of 88.4% and a specificity of 79.6% in predicting preeclampsia. Serum concentrations of sFlt-1, VEGF-A and PlGF do not show a statistically significant difference compared to the age of pregnant women and the number of previous pregnancies p&gt; 0.05. Serum concentrations of sFlt-1 and PlGF are significantly different in relation to the weight of the newborn, so that the lower values of both proteins are in the group of infants with birth weight below 1500 gr. in relation to the body weight between 2800-3300 gr., p &lt;0.001. There is also lower concentrations of sFlt-1 and PlGF in a group with deliveries before 33 weeks of gestation compared to the deliveries after 37 week of gestation, p &lt;0.001. Serum concentrations of sFlt-1 and PlGF are significantly different in relation to the mother&#39;s body mass index so that the lower values of sFlt-1 and PlGF are in the group of women with a body mass index below 25 in relation to a group with a body mass index over 30 kg/m2, p &lt;0.001. Serum concentrations of sFlt-1 in the first trimester of pregnancy were significantly associated with the parameters of inflammation (hsCRP), diastolic blood pressure and levels of free &szlig;hCG. It is also observed a significant correlation between PlGF with a body mass index, systolic blood pressure and hsCRP concentration in the first trimester of pregnancy. CONCLUSION: The levels of anti-angiogenic protein sFlt-1 are higher in the group of pregnant women with preeclampsia than in the group with chronic and gestational hypertension and the control healthy group. Levels of proangiogenic VEGF-A protein are significantly lower in the preeclampsia group and group with gestational and chronic hypertension compared to the control group. Serum levels of proangiogenic PlGF protein are significantly lower in the preeclampsia group than in the group with chronic and gestational hypertension and the control group. Serum concentrations of placental protein free &szlig;hCG and HDL cholesterol are significantly lower, while the value of hsCRP and triglycerides significantly higher in the preeclampsia group compared to the control group. Among pregnant women with hypertensive disorders in pregnancy and healthy pregnant women there are no significant differences in the values of placental PAPP-A protein, biochemical parameters (glucose, AST, ALT, GGT creatinine, urea, uric acid), lipid parameters (total cholesterol, LDL, apo AI, apo B), inflammatory parameters (complete blood count, fibrinogen), hemostatic (D-dimer, vWF-antigen) and electrolyte status (Na, K, Cl, P, Mg, Ca). Serum concentrations of sFlt-1 and PlGF are significantly different in relation to gestational age at delivery and newborn body weight and are lower in group with preterm delivery and newborns with lower birth weight. Serum concentrations of sFlt-1 are significantly different compared to body length and Apgar score, so that the higher values of sFlt-1 are associated with better outcome of newborns (greater body length and better APGAR score). Serum concentrations of sFlt-1, VEGF-A and PlGF are not different significantly with respect to age of pregnancy and the number of previous pregnancies. The levels of sFlt-1 and PlGF represents helpful markers in prediction of preeclampsia in the first trimester of pregnancy.</p>

Muitas mulheres estão adiando a maternidade até a 4ª ou 5ª década de vida, um fenômeno mundial. O objetivo do estudo foi avaliar resultado da gestação em 281 mulheres com 40 anos ou mais, atendidas no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo entre Julho de 1998 e Julho de 2005. A incidência de diabetes gestacional e doença hipertensiva específica da gestação (DHEG) foi de 14,6% e 19,6%, respectivamente. Dezessete (6,0%) mulheres tiveram abortamento e 4 (1,4%) óbito fetal. Três recém-nascidos apresentavam síndrome de Down e 6 outras malformações (índice de detecção de 88,9%). Mulheres com DHEG tiveram maior risco para fetos com baixo peso. História prévia de hipertensão não foi fator de risco para DHEG. Gestantes com DHEG ou diabetes gestacional não apresentaram risco maior para parto pré-termo. Obesidade foi fator de risco para diabetes gestacional. Mulheres sem companheiro e nulíparas tiveram maior incidência de malformações e baixos índices de Apgar. Mulheres com idade materna muito avançada (maior ou igual a 45 anos) apresentaram incidência maior de óbito fetal e de índice de Apgar baixo. A assistência pré-natal específica possibilita a detecção das complicações maternas e a instituição precoce do tratamento / Many women are delaying childbearing until the fourth or fifth decade in life, and it has become a common and worldwide phenomenon. The aim of this study is to evaluate pregnancy outcome in women of 40 or older who were care at our institution. During the period from July 1998 to July 2005 a total of 281 women with advanced maternal age presenting at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo were studied. The incidence of gestational diabetes and preeclampsia was 14.6% e 19.2%, respectively. Seventeen women had miscarriage (6.0%) and four presented fetal death (1.4%). There were three infants with Down syndrome and six with other anomalies (detection rate of 88.9%). Women presenting preeclampsia were at higher risk for presenting low birthweight. Previous history of hypertension was not a risk factor for preeclampsia. Pregnant women with gestational diabetes or preeclampsia did not carry a higher risk for preterm delivery. Obesity was a significant prognostic factor for gestational diabetes. Nulliparous and single women had higher incidence of fetal anomalies and low Apgar score. Women with very advanced maternal age (>= 45 years old) had higher rate of fetal death and low Apgar score. Prenatal care devoted for women with advanced maternal age allows an early detection and treatment of adverse maternal-fetal outcomes.

Uterine NK (uNK) cells are a distinct subset of NK cells in the decidua of humans and rodents during pregnancy, which are essential for remodelling of the spiral arteries supplying the feto-placental unit. Similarly to peripheral NK cells, uNK cells express Natural Killer receptors (NKRs) that engage MHC class I molecules. Evidence from human genetic association studies suggests that, in the presence of allogeneic cognate paternal MHC class I ligands, inhibitory uterine NKRs are associated with disorders of pregnancy arising from impaired decidual vascular remodelling. Conversely, enhancement of human uNK cell activity through activating NKRs is associated with high birth weight. Evidence from mouse models corroborates that uNK cell activity is modulated by interactions between NKRs and MHC class I, but has largely focussed on the effect of paternal MHC. In this study, the contribution of maternal immunogenetic regulation of NK cell function to reproductive outcome was assessed independently of parental MHC disparity in mice. To evaluate the role of NKR genes in isolation, I used congenic B6.BALB-TC1 (TC1) mice that differ from C57BL/6 (B6) mice only within the region of chromosome six encoding NKRs that recognise MHC class I. Absence of a major inhibitory NKR for self-MHC, Ly49I, in TC1 mice causes a compensatory shift in the NKR repertoire expressed and preserves a majority subpopulation of educated NK cells. B6 and TC1 splenic and uterine NK cells are similarly functionally reactive and mature, and no significant differences could be detected in spiral arterial remodelling or fetal growth between these strains in MHC-syngeneic matings. This supports data from human immunogenetic studies showing that maternal uterine NKRs are not associated with differences in pregnancy outcome in the absence of novel paternal MHC class I ligands, and highlights the importance of maternal and paternal co-regulation of uNK cell activity during pregnancy. No mouse models of uNK cell activation are currently available with which to corroborate human immunogenetic associations between activating uterine NKRs and high birth weight. Male m157-transgenic (m157-Tg) mice, which ubiquitously express viral m157 glycoprotein ligands for the activating NKR Ly49H, were mated with B6 females. Exclusive expression of m157 glycoprotein by trophoblast improved placental efficiency, but did not enhance fetal growth. Some fertility clinics surmise that uNK cell activation initiates the pathogenesis of spontaneous abortion. It has been suggested that this may occur due to reduced expression by human uNK cells of miR-483-3p, which stimulates endogenous insulin-like growth factor (IGF)-1 production and uNK cell cytotoxicity in vitro. It is demonstrated here that neither miR-483-3p nor IGF-1 regulate murine NK cell development, maturation or function. No discernible reproductive phenotype is evident in miR-483 deficient females. It can be inferred that post-transcriptional control by miR-483 is not biologically relevant to murine NK cell function. Although m157-Tg mice may provide an interesting model to further study uNK cell-mediated placental adaptations, it remains important to identify a murine model of enhanced uNK cell function to corroborate human immunogenetic associations with high birth weight and to challenge the supposition that uNK cell activation is harmful to pregnancy.

Muitas mulheres estão adiando a maternidade até a 4ª ou 5ª década de vida, um fenômeno mundial. O objetivo do estudo foi avaliar resultado da gestação em 281 mulheres com 40 anos ou mais, atendidas no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo entre Julho de 1998 e Julho de 2005. A incidência de diabetes gestacional e doença hipertensiva específica da gestação (DHEG) foi de 14,6% e 19,6%, respectivamente. Dezessete (6,0%) mulheres tiveram abortamento e 4 (1,4%) óbito fetal. Três recém-nascidos apresentavam síndrome de Down e 6 outras malformações (índice de detecção de 88,9%). Mulheres com DHEG tiveram maior risco para fetos com baixo peso. História prévia de hipertensão não foi fator de risco para DHEG. Gestantes com DHEG ou diabetes gestacional não apresentaram risco maior para parto pré-termo. Obesidade foi fator de risco para diabetes gestacional. Mulheres sem companheiro e nulíparas tiveram maior incidência de malformações e baixos índices de Apgar. Mulheres com idade materna muito avançada (maior ou igual a 45 anos) apresentaram incidência maior de óbito fetal e de índice de Apgar baixo. A assistência pré-natal específica possibilita a detecção das complicações maternas e a instituição precoce do tratamento / Many women are delaying childbearing until the fourth or fifth decade in life, and it has become a common and worldwide phenomenon. The aim of this study is to evaluate pregnancy outcome in women of 40 or older who were care at our institution. During the period from July 1998 to July 2005 a total of 281 women with advanced maternal age presenting at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo were studied. The incidence of gestational diabetes and preeclampsia was 14.6% e 19.2%, respectively. Seventeen women had miscarriage (6.0%) and four presented fetal death (1.4%). There were three infants with Down syndrome and six with other anomalies (detection rate of 88.9%). Women presenting preeclampsia were at higher risk for presenting low birthweight. Previous history of hypertension was not a risk factor for preeclampsia. Pregnant women with gestational diabetes or preeclampsia did not carry a higher risk for preterm delivery. Obesity was a significant prognostic factor for gestational diabetes. Nulliparous and single women had higher incidence of fetal anomalies and low Apgar score. Women with very advanced maternal age (>= 45 years old) had higher rate of fetal death and low Apgar score. Prenatal care devoted for women with advanced maternal age allows an early detection and treatment of adverse maternal-fetal outcomes.

This dissertation examined risk factors for hypertensive disorders of pregnancy (HDP) — specifically whether neighborhood socioeconomic deprivation exacerbates individual socioeconomic disadvantage (deprivation amplification) to increase the likelihood of developing HDP. To select the optimal areal unit at which to investigate HDP, geographic proxies for neighborhoods were explored. A thematic review qualitatively examined nontraditional neighborhood boundaries identified through internet sources. Data from 2008–2012 Miami-Dade County, Florida birth records (n=121,421) and the U.S. Census Bureau were used for the remaining analyses. Ordinary least squares (OLS) and geographically weighted regression (GWR) analysis empirically compared the proportion of HDP prevalence explained by six areal units: census block groups, census tracts, ZIP code tabulation areas (ZCTAs), and three types of natural neighborhood — census units clustered based on an eight-item Neighborhood Deprivation Index. Multilevel logistic regression examined relationships between HDP, neighborhood deprivation, and individual-level factors. Odds ratios (OR) and adjusted odds ratios (aOR) were calculated. The thematic review found 22 potential alternatives to census boundaries developed through techniques such as crowd-sourcing and qualitative research. In the sensitivity analysis, census tracts aggregated at the scale of ZCTAs performed twice as well as any other model (GWR2 = 0.27) and were used as the Aim 3 unit of analysis. In the multilevel logistic regression, HDP was associated with moderate (aOR=1.13; CI: 1.05, 1.21) and high neighborhood deprivation (aOR=1.16; CI: 1.07, 1.26). Compared with mothers with private insurance, uninsured women (aOR=1.69; CI: 1.56, 1.84) and Medicaid recipients (aOR=1.12; CI: 1.05, 1.18) had higher HDP odds. Non-Hispanic Black women’s HDP odds were 1.58 times those of non-Hispanic White women. Cross-level interactions — between neighborhood deprivation and educational attainment and neighborhood deprivation and insurance status — did not reach statistical significance. Private sector neighborhood boundaries hold promise for developing new public health tools. Because they are relatively easy to generate from census data, natural neighborhoods may balance tradition and innovation. While no evidence of deprivation amplification was found, results suggested that individual-level and neighborhood deprivation are HDP risk factors. Interventions that target expectant mothers in deprived neighborhoods — particularly non-Hispanic Black and Hispanic women who lack health insurance — may help reduce HDP prevalence and disparities.