Introduction: Gestational diabetes (GDM) affects one in three pregnancies and women with GDM have a 10-fold higher risk of developing type-2 diabetes during their lifetime. Similarly, hypertensive disorders (HPD) of pregnancy affect up to one in seven pregnancies and have a 4-fold increase in the risk of hypertension and a 2-fold risk of cardiovascular diseases (CVD) over the lifetime. Primary care (PC) transitions are critical for the management of GDM and HDP to reduce the long-term risk of developing type-2 diabetes, hypertension, and CVD. Despite clinical guidelines recommending PC follow-up for continuous and sustainable care practice, only 50% of postpartum mothers transition to PC within 12 months. Few studies examine this issue and none in South Carolina. Therefore, our study uses Medicaid Claims data to examine the extent to which postpartum mothers with GDM and HDP transition to PC within 12 months of childbirth. Methods: We examined cross-sectional data of Medicaid women with a live birth in the years 2017 and 2018 in South Carolina. Women above the age of 20, receiving postpartum services within 12 months of delivery were included in the study. Primary care visits was the outcome variable of interest. Any women with at least one primary care visit (Family/General Practice Physician visit) claim in the 12 months following birth were considered as a primary care transition. GDM, HDP, and both (GDM &HDP) were the primary independent variables of interest. Results: In 14,273 postpartum mothers, the prevalence of GDM, HDP, and both (GDM & HDP) were found to be 10.02%, 15.05%, and 3.60% respectively. Among the women with GDM, 47.02% had visited PC compared to 35.02% of women without GDM (p<0.001). Similarly, 48.12% of women with HDP visited PC compared to 34.23% of women without HDP (p<0.001). In addition, 52.66% of women with both (GDM & HDP) visited PC compared to 35.72% of women without both (GDM & HDP) (p<0.001). After adjusting for maternal age, ethnicity, residence, and pay category, women with GDM were 1.43 times more likely to visit PC as compared to the women with no GDM (95% CI: 1.27–1.61). Similarly, the odds of visiting PC by women with HDP was 1.67 times higher as compared to women without HDP (95% CI: 1.51 – 1.84). Conclusion: In this study, postpartum mothers with GDM and HDP had higher odds of PC visits compared with those without GDM and without HDP respectively. This is positive. However, the overall percentage of women visiting PC with chronic disease was lower than 50%. To change health outcomes among women with chronic diseases like GDM and HDP, lifelong screening and disease management are needed. It is necessary to link postpartum mothers with PC to improve illness management and raise screening adherence. However, more barriers preventing under-resourced women from receiving PC should be analyzed and addressed.

Implantation requires complex molecular and cellular events involving coagulation, angiogenesis and immunological processes that need to be well regulated for a pregnancy to establish and progress normally.  The overall aim of this thesis was to study different models associated with atypical angiogenesis, impaired implantation and/or placentation, such as recurrent miscarriage (RM), oocyte donation (OD) and preeclampsia. Histidine-rich glycoprotein (HRG), a serum protein with angiogenic potential has been previously shown to have an impact on implantation and fertility.  In two retrospective case-control studies, women suffering from RM (Study I) and gestational hypertensive disorders (GHD) (Study IV) have been compared to healthy control women, regarding carriership of HRG genotypes (HRG A1042G and C633T SNP, respectively).  According to the findings of this thesis, heterozygous carriers of the HRG A1042G SNP suffer from RM more seldom than homozygous carriers (Study I).  Additionally, the presence of the HRG 633T allele was associated with increased odds of GHD (GHD IV).  Studies II and III comprised a national cohort of relatively young women with optimal health status conceiving singletons with donated oocytes versus autologous oocytes (spontaneously or via IVF).  We explored differences in various obstetric (Study II) and neonatal (Study III) outcomes from the Swedish Medical Birth Register.  Women conceiving with donated oocytes had a higher risk of GHD, induction of labor and cesarean section, as well as postpartum hemorrhage and retained placenta, when compared to autologously conceiving women.  OD infants had higher odds of prematurity and lower birthweight and length when born preterm, compared to neonates from autologous oocytes.  With regard to the indication of OD treatment, higher intervention but neverthelss favourable neonatal outcomes were observed in women with diminished ovarian reserve; the risk of GHD did not differ among OD recipients after adjustment. In conclusion, HRG genetic variation appears to contribute to placental dysfunction disorders.  HRG is potential biomarker that may contribute in the prediction of the individual susceptibility for RM and GHD.  Regarding OD in Sweden, the recipients-despite being of optimal age and health status- need careful preconceptional counselling and closer prenatal monitoring, mainly due to increased prevalence of hypertensive disorders and prematurity.

ARAUJO, F. M. Ocorrência Familial e Associação de Polimorfismos dos Genes H19 e IGF2 com as Síndromes Hipertensivas Gestacionais. 2007. 118f. Disertação (Mestrado) Faculdade de Medicina, Universidade de São Paulo, Ribeirão Preto, 2007. As síndromes hipertensivas gestacionais [Pré-eclâmpsia/eclâmpsia (PE/E), hipertensão gestacional (HG) e hipertensão arterial crônica (HAC)] estão entre as maiores causas de morte materna e fetal. A PE é a mais prevalente dessas síndromes e o papel dos fatores genéticos na sua etiologia é bem aceito, embora o padrão de herança seja ainda assunto para debate. Os genes H19 e IGF2 sofrem imprinting (marcação) genômico e estão envolvidos na formação placentária e no desenvolvimento fetal. O objetivo do presente trabalho foi a pesquisa de ocorrência familial e da associação com os polimorfismos H19/RsaI e do IGF2/ApaI das síndromes hipertensivas gestacionais e do peso do recém-nascido. Todas as pacientes do estudo foram atendidas no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo e o projeto foi aprovado pelo Comitê de Ética deste hospital e pela Comissão Nacional de Ética em Pesquisa. Para a condução do estudo familial foram selecionadas 226 mulheres (75 apresentavam PE, 49 com HG e 102 do grupo controle). Os dados foram analisados pelos Testes Exato de Fisher e do Qui-quadrado, resultando em uma maior freqüência estatisticamente significativa (p <0,05) de parentes de primeiro-grau com PE/E entre o grupo de PE/E comparado aos outros grupos. Não foi observada influência da cor da pele na distribuição entre os grupos de pacientes. Para a pesquisa de polimorfismos de comprimento de fragmento de restrição H19/RsaI (alelos A e B) e IGF2/ApaI (alelos A e G) através da reação em cadeia da polimerase , foi extraído DNA de sangue periférico de 236 pacientes (55 apresentavam PE, 40 com HG, 34 com HAC e 107 do grupo controle). Os resultados, analisados através dos Testes do Qui-quadrado e G, não mostraram associação estatisticamente significativa entre os polimorfismos e as síndromes hipertensivas gestacionais ou HAC. Houve uma maior freqüência do alelo G na população estudada. Foi observado que em torno de 80% das pacientes dos quatro grupos estudados apresentou pelo menos uma cópia do alelo B e uma do alelo G, concomitantemente. A associação do peso do recém-nascido com os polimorfismos foi analisada utilizando-se os Testes Kolmogorov-Smirnov (a P<0,05) e os Não-paramétricos de Kruskal-Wallis (a P<0,05), não tendo sido evidenciadas diferenças estatisticamente significativas. No grupo da PE houve uma diminuição estatisticamente significativa do peso dos recém-nascidos quando não havia correção para a idade gestacional. Embora não tenha sido evidenciada correlação entre os polimorfismos e os fenótipos estudados, trabalhos futuros com um número amostral maior serão importantes para auxiliar no entendimento do envolvimento de fatores epigenéticos nas síndromes hipertensivas gestacionais e fornecer indícios para a prevenção, o tratamento e o aconselhamento genético. / ARAUJO, F. M. Familial Occurrence and H19 and IGF2 Polymorphism Association with Gestational Hypertensive Disorders. 2007. 118p. Dissertation (Master\'s degree) - University of Medicine, University of São Paulo, Ribeirão Preto, 2007. Gestational hypertensive disorders [preeclampsia/eclampsia (PE/E), gestational hypertension (GH) and chronic hypertension (CH)] are among the largest causes of maternal and fetal death. PE is the more prevalent of those syndromes and the role of the genetic factors in its etiology is well accepted, although the pattern of inheritance is still subject for debate. The imprinted genes H19 and IGF2 are involved in the placental formation and in the fetal development. The objective of the present study was to verify the familial occurrence of these disorders and the H19/RsaI and IGF2/ApaI polymorphism association with gestational hypertensive disorders and the weight of the newborn. All patients of the study were referred to the Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, University of São Paulo, and the project was approved by the Hospital Ethic Committee and the National Commission of Ethics in Research. For the familial study, 226 women were selected (75 presented PE/E, 49 with GH and 102 from the control group). The data were analyzed by Exact of Fisher and Qui-square tests, and the frequency of families with at least one female first-degree relative (mothers and/or sisters) with PE/E was higher among the PE/E group compared to the other groups, and it was statistically significant (P<0.05). There was no statistically significant influence of the \"skin color\". Blood samples of 236 pregnant women (55 with PE/E, 40 with GH, 34 with CH and 107 from the control group) were obtained for DNA extraction, and PCR. Genotyping was carried out by enzymatic digestion with ApaI (IGF2) and RsaI (H19). The statistical analyses were performed by Qui-square and G tests. The genotypes were not significantly associated with the different groups. A higher frequency of the G allele (IGF2) was observed. Around 80% of the patients presented at least one copy of the allele B (H19) and G (IGF2), concomitantly. The association of the weight of the newborn with the polymorphisms was analyzed using the Kolmogorov-Smirnov (P <0.05) and the No-parametric Test of Kruskal-Wallis (P <0.05) tests, and statistically significant differences were not evidenced. In the group of the PE/E there was a statistically significant decrease of the weight of the newborn when the correction for the gestational age was not carried out. Although correlation has not been evidenced between the polymorphisms and the phenotypes, future studies with a higher number of patients and other imprinted genes will be important to elucidate the involvement of epigenetic factors for the prevention, treatment and genetic counseling of the gestational hypertensive disorders

ARAUJO, F. M. Ocorrência Familial e Associação de Polimorfismos dos Genes H19 e IGF2 com as Síndromes Hipertensivas Gestacionais. 2007. 118f. Disertação (Mestrado) Faculdade de Medicina, Universidade de São Paulo, Ribeirão Preto, 2007. As síndromes hipertensivas gestacionais [Pré-eclâmpsia/eclâmpsia (PE/E), hipertensão gestacional (HG) e hipertensão arterial crônica (HAC)] estão entre as maiores causas de morte materna e fetal. A PE é a mais prevalente dessas síndromes e o papel dos fatores genéticos na sua etiologia é bem aceito, embora o padrão de herança seja ainda assunto para debate. Os genes H19 e IGF2 sofrem imprinting (marcação) genômico e estão envolvidos na formação placentária e no desenvolvimento fetal. O objetivo do presente trabalho foi a pesquisa de ocorrência familial e da associação com os polimorfismos H19/RsaI e do IGF2/ApaI das síndromes hipertensivas gestacionais e do peso do recém-nascido. Todas as pacientes do estudo foram atendidas no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo e o projeto foi aprovado pelo Comitê de Ética deste hospital e pela Comissão Nacional de Ética em Pesquisa. Para a condução do estudo familial foram selecionadas 226 mulheres (75 apresentavam PE, 49 com HG e 102 do grupo controle). Os dados foram analisados pelos Testes Exato de Fisher e do Qui-quadrado, resultando em uma maior freqüência estatisticamente significativa (p <0,05) de parentes de primeiro-grau com PE/E entre o grupo de PE/E comparado aos outros grupos. Não foi observada influência da cor da pele na distribuição entre os grupos de pacientes. Para a pesquisa de polimorfismos de comprimento de fragmento de restrição H19/RsaI (alelos A e B) e IGF2/ApaI (alelos A e G) através da reação em cadeia da polimerase , foi extraído DNA de sangue periférico de 236 pacientes (55 apresentavam PE, 40 com HG, 34 com HAC e 107 do grupo controle). Os resultados, analisados através dos Testes do Qui-quadrado e G, não mostraram associação estatisticamente significativa entre os polimorfismos e as síndromes hipertensivas gestacionais ou HAC. Houve uma maior freqüência do alelo G na população estudada. Foi observado que em torno de 80% das pacientes dos quatro grupos estudados apresentou pelo menos uma cópia do alelo B e uma do alelo G, concomitantemente. A associação do peso do recém-nascido com os polimorfismos foi analisada utilizando-se os Testes Kolmogorov-Smirnov (a P<0,05) e os Não-paramétricos de Kruskal-Wallis (a P<0,05), não tendo sido evidenciadas diferenças estatisticamente significativas. No grupo da PE houve uma diminuição estatisticamente significativa do peso dos recém-nascidos quando não havia correção para a idade gestacional. Embora não tenha sido evidenciada correlação entre os polimorfismos e os fenótipos estudados, trabalhos futuros com um número amostral maior serão importantes para auxiliar no entendimento do envolvimento de fatores epigenéticos nas síndromes hipertensivas gestacionais e fornecer indícios para a prevenção, o tratamento e o aconselhamento genético. / ARAUJO, F. M. Familial Occurrence and H19 and IGF2 Polymorphism Association with Gestational Hypertensive Disorders. 2007. 118p. Dissertation (Master\'s degree) - University of Medicine, University of São Paulo, Ribeirão Preto, 2007. Gestational hypertensive disorders [preeclampsia/eclampsia (PE/E), gestational hypertension (GH) and chronic hypertension (CH)] are among the largest causes of maternal and fetal death. PE is the more prevalent of those syndromes and the role of the genetic factors in its etiology is well accepted, although the pattern of inheritance is still subject for debate. The imprinted genes H19 and IGF2 are involved in the placental formation and in the fetal development. The objective of the present study was to verify the familial occurrence of these disorders and the H19/RsaI and IGF2/ApaI polymorphism association with gestational hypertensive disorders and the weight of the newborn. All patients of the study were referred to the Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, University of São Paulo, and the project was approved by the Hospital Ethic Committee and the National Commission of Ethics in Research. For the familial study, 226 women were selected (75 presented PE/E, 49 with GH and 102 from the control group). The data were analyzed by Exact of Fisher and Qui-square tests, and the frequency of families with at least one female first-degree relative (mothers and/or sisters) with PE/E was higher among the PE/E group compared to the other groups, and it was statistically significant (P<0.05). There was no statistically significant influence of the \"skin color\". Blood samples of 236 pregnant women (55 with PE/E, 40 with GH, 34 with CH and 107 from the control group) were obtained for DNA extraction, and PCR. Genotyping was carried out by enzymatic digestion with ApaI (IGF2) and RsaI (H19). The statistical analyses were performed by Qui-square and G tests. The genotypes were not significantly associated with the different groups. A higher frequency of the G allele (IGF2) was observed. Around 80% of the patients presented at least one copy of the allele B (H19) and G (IGF2), concomitantly. The association of the weight of the newborn with the polymorphisms was analyzed using the Kolmogorov-Smirnov (P <0.05) and the No-parametric Test of Kruskal-Wallis (P <0.05) tests, and statistically significant differences were not evidenced. In the group of the PE/E there was a statistically significant decrease of the weight of the newborn when the correction for the gestational age was not carried out. Although correlation has not been evidenced between the polymorphisms and the phenotypes, future studies with a higher number of patients and other imprinted genes will be important to elucidate the involvement of epigenetic factors for the prevention, treatment and genetic counseling of the gestational hypertensive disorders

Präeklampsie ist weltweit eine der Hauptursachen perinataler Morbidität und Mortalität für Mutter und Kind. Es wird vermutet, dass unterschiedliche pathophysiologische Mechanismen je nach Zeitpunkt des Auftretens der Präeklampsie vorliegen. Eine Unterscheidung zwischen früher, mittlerer und später Präeklampsie scheint relevant für Screening, klinische Manifestation und Management der Erkrankung zu sein. Ziel dieser Studie ist es die drei Typen der Präeklampsie bezüglich Risikofaktoren, Entbindungsmodalität und maternaler und neonataler Morbiditäten und Mortalitäten zu charakterisieren und zusätzlich mit denen der Gestationshypertonie und chronischen Hypertonie zu vergleichen. In einem retrospektiven Studienaufbau wurden 1089 Einlingsschwangerschaften mit hypertensiver Schwangerschaftserkrankung, deren Entbindung in einem Zeitraum von 10 Jahren (2003-2012) erfolgte, analysiert. Die maternalen und neonatalen Charakteristika der verschiedenen Gruppen hypertensiver Schwangerschaftserkrankungen wurden miteinander verglichen. Es wurden deskriptive und analytische (Chi-quadrat-Test und U-Test) statistische Methoden verwendet. Es zeigten sich signifikant unterschiedliche maternale Komorbiditäten und Risikofaktoren in den untersuchten Gruppen hypertensiver Schwangerschaftserkrankungen. Für die Mehrzahl der untersuchten Parameter waren Fälle mit Präeklampsie häufiger durch Morbidität und Mortalität betroffen waren. Patientinnen mit früher Präeklampsie fielen durch einen signifikant höheren mittleren arteriellen Druck vor Entbindung, eine erhöhte Kaiserschnittrate, eine ausgeprägtere Proteinurie und eine häufigere Korrelation zu HELLP-Syndrom, Eklampsie und vorzeitige Plazentalösung auf. Die Häufigkeit pathologischer Doppleruntersuchungen in den Arteriae uterinae und der Arteria umbilicalis verhielt sich umgekehrt proportional zur Schwangerschaftswoche zum Zeitpunkt der Entbindung. Ein nachteiliges fetales Outcome bezogen auf die perinatale und neonatale Mortalität, Beatmung über einen längeren Zeitraum als 24 Stunden, RDS-Syndrom, fetale Wachstumsrestriktion und Verlegung auf eine neonatologische Intensivstation trat unter früher Präeklampsie häufiger als unter mittlerer und bei mittlerer häufiger als unter später Präeklampsie auf. Das neonatale Outcome von Feten unter der 33. SSW war nicht vom Ausmaß der mütterlichen hypertensiven Erkrankung abhängig. Die späte Präeklampsie viel durch günstigere Outcomes als die Gestationshypertonie und chronische Hypertonie auf. Die Ergebnisse der Studie unterstützen die These, dass unterschiedliche pathophysiologische Mechanismen Präeklampsie bedingen können und dass frühe, mittlere und späte Präeklampsie entweder verschiedene Erkrankungen sind, oder die Präeklampsie eine Erkrankung darstellt, die durch verschiedene Einflussfaktoren ein unterschiedlich starkes Ausmaß annimmt. Das Gestationsalter ist demnach das entscheidende Kriterium für die klinische Ausprägung. Die unterschiedlichen Risikoprofile der einzelnen Formen hypertensiver Schwangerschaftserkrankungen fordern ein angepasstes klinisches Management.:I. Inhaltsverzeichnis II. Abkürzungsverzeichnis 1 Einleitung 1 2 Grundlagen 3 2.1 Hypertensive Schwangerschaftserkrankungen 3 2.1.1 Begriffe und Definitionen 3 2.1.2 Chronische Hypertonie 4 2.1.3 Gestationshypertonie 5 2.1.4 Präeklampsie 5 2.1.4.1 Epidemiologie 5 2.1.4.2 Pathogenese 6 2.1.4.3 Prädisposition und Risikofaktoren 7 2.1.4.4 Maternale Morbidität und Mortalität 8 2.1.4.5 Screening 9 2.1.4.6 Prävention 10 2.1.4.7 Management 11 2.2 Aspekte des fetalen Outcomes 12 2.2.1 Frühgeburtlichkeit 13 2.2.2 Fetale Wachstumsrestriktion 14 2.2.3 Totgeburt, neonatale und perinatale Mortalität 15 2.2.4 Fetale Komplikationen 15 2.3 Dopplersonographie in der Schwangerschaft 18 2.3.1 Aa. uterinae 19 2.3.2 Arteria umbilicalis 20 2.3.3 Arteria cerebri media 20 2.3.4 Ductus venosus 20 3 Material und Methoden 22 3.1 Maternale Variablen 22 3.2 Fetale und neonatale Variablen 24 3.3 Statistische Auswertung 25 3.3.1 Deskriptive Statistik 25 3.3.2 Analytische Statistik 25 4 Ergebnisse 27 4.1 Demographische Daten 28 4.2 Maternale Risikofaktoren 28 4.2.1 Body-Mass-Index 30 4.2.2 Alter 30 4.2.3 Parität 31 4.2.4 Diabetes 31 4.2.5 Nikotinabusus 32 4.3 Maternale Vorerkrankungen und Komorbiditäten 32 4.3.1 Depression, Asthma und chronisch entzündliche Darmerkrankungen 32 4.3.2 Thrombembolische Ereignisse 32 4.3.3 Nierenerkrankungen 33 4.3.4 Chronische Hypertonie 33 4.4 Schwangerschaftsbezogene Risikofaktoren 33 4.4.1 Pulsatilitätsindex der Arteria uterina 33 4.4.2 Konzeption 35 4.5 Kindliches Geschlecht 35 4.6 Entbindung – Geburtsmodus und Indikation 35 4.7 Maternale Komplikationen 37 4.7.1 HELLP-Syndrom 38 4.7.2 Eklampsie 41 4.7.3 Schwere Präeklampsie 41 4.7.4 Proteinurie 41 4.8 Maternale Mortalität 42 4.9 Das fetale Outcome 43 4.9.1 Wachstumsrestriktion und small for gestational age 45 4.9.1.1 Distribution 45 4.9.1.2 Outcome 47 4.9.2 Frühgeborene vor der vollendeten 33. SSW 49 4.9.2.1 Maternale Aspekte 50 4.9.2.2 Doppleruntersuchungen und Lungenreifeinduktion 50 4.9.2.3 Geburtsparameter 51 4.9.2.4 Geburtsgewicht und intrauterine Wachstumsrestriktion 53 5 Diskussion 55 5.1 Analyse der maternalen Faktoren 55 5.1.1 Analyse der Risikofaktoren und anderer Anamneseparameter 55 5.1.2 Analyse des Geburtsmodus oder der -indikation 57 5.1.3 Analyse der Patientinnen mit chronischer Hypertonie 58 5.1.4 Analyse der Patientinnen mit Gestationshypertonie 59 5.1.5 Analyse der prädiktiven Aussagekraft der Dopplersonographie der Aa uterinae für die Entwicklung einer Präeklampsie 60 5.1.6 Analyse der Komplikationen der Präeklampsie 61 5.2 Analyse des fetalen Outcomes 63 5.2.1 Analyse des fetalen Outcomes unter Gestationshypertonie 63 5.2.2 Analyse des fetalen Outcomes unter chronischer Hypertonie 64 5.2.3 Analyse des fetalen Outcomes unter Präeklampsie 66 5.2.4 Fetale Wachstumsrestriktion und Präeklampsie 67 5.2.5 Subanalyse der Feten mit Geburt vor der 33. SSW 69 5.3 Limitierung und Einordnung der Ergebnisse 71 6 Zusammenfassung 74 7 Literaturverzeichnis 77 8 Anhang 95 8.1 Tabellenverzeichnis 95 8.2 Abbildungsverzeichnis 97 III. Danksagung

No description available.

Clinical observations of individual patients are the cornerstones for furthering our understanding of the human body, diseases, and therapeutics. Traditionally, clinical observations were communicated through publishing case reports and case series. The effort of identifying and investigating unusual clinical observations has always rested on the shoulders of busy clinicians. To date, there has been little effort dedicated to increasing the efficiency of identifying unique and uncommon patient observations that may lead to valuable discoveries. In this thesis, we propose and implement an augmented intelligence framework to identify potential novel clinical observations by combining machine analytics through outlier analysis with the judgment of subject-matter experts. Preeclampsia is a significant cause of maternal and perinatal mortality and morbidity, and advances in its management have been slow. Considering the complex etiological nature of preeclampsia, clinical observations are essential in advancing our understanding of the disease and therapeutic approaches. Thus, the objectives and studies in this thesis aim to answer the hypothesis that using outlier analysis in preeclampsia-related medical data would lead to identifying previously uninvestigated clinical cases with new clinical insight. This thesis combines three articles published or submitted for publication in peer-reviewed journals. The first article (published) is a systematic review examining the extent to which case reports and case series in preeclampsia have contributed new knowledge or discoveries. We report that under one-third of the identified case reports and case series presented new knowledge. In our second article (submitted for publication), we provide an overview of outlier analysis and introduce the framework of augmented intelligence using our proposed extreme misclassification contextual outlier analysis approach. Furthermore, we conduct a systematic review of obstetrics-related research that used outlier analysis to answer scientific questions. Our systematic review findings indicate that such use is in its infancy. In our third article (published), we implement the proposed augmented intelligence framework using two different outlier analysis methods on two independent datasets from separate studies in preeclampsia and hypertensive disorders of pregnancy. We identify several clinical observations as potential novelties, thus supporting the feasibility and applicability of outlier analysis to accelerate clinical discovery.

Objectif: Évaluer l'efficacité du dépistage de l’hypertension gestationnelle par les caractéristiques démographiques maternelles, les biomarqueurs sériques et le Doppler de l'artère utérine au premier et au deuxième trimestre de grossesse. Élaborer des modèles prédictifs de l’hypertension gestationnelle fondées sur ces paramètres. Methods: Il s'agit d'une étude prospective de cohorte incluant 598 femmes nullipares. Le Doppler utérin a été étudié par échographie transabdominale entre 11 +0 à 13 +6 semaines (1er trimestre) et entre 17 +0 à 21 +6 semaines (2e trimestre). Tous les échantillons de sérum pour la mesure de plusieurs biomarqueurs placentaires ont été recueillis au 1er trimestre. Les caractéristiques démographiques maternelles ont été enregistrées en même temps. Des courbes ROC et les valeurs prédictives ont été utilisés pour analyser la puissance prédictive des paramètres ci-dessus. Différentes combinaisons et leurs modèles de régression logistique ont été également analysés. Résultats: Parmi 598 femmes, on a observé 20 pré-éclampsies (3,3%), 7 pré-éclampsies précoces (1,2%), 52 cas d’hypertension gestationnelle (8,7%) , 10 cas d’hypertension gestationnelle avant 37 semaines (1,7%). L’index de pulsatilité des artères utérines au 2e trimestre est le meilleur prédicteur. En analyse de régression logistique multivariée, la meilleure valeur prédictive au 1er et au 2e trimestre a été obtenue pour la prévision de la pré-éclampsie précoce. Le dépistage combiné a montré des résultats nettement meilleurs comparés avec les paramètres maternels ou Doppler seuls. Conclusion: Comme seul marqueur, le Doppler utérin du deuxième trimestre a la meilleure prédictive pour l'hypertension, la naissance prématurée et la restriction de croissance. La combinaison des caractéristiques démographiques maternelles, des biomarqueurs sériques maternels et du Doppler utérin améliore l'efficacité du dépistage, en particulier pour la pré-éclampsie nécessitant un accouchement prématuré. / Objective: To evaluate the screening efficacy of maternal demographic characteristics, serum biomarkers and uterine artery Doppler (uaD) during the first and the second trimester for the hypertensive disorders of pregnancy. To elaborate prediction models of these diseases based on the combination of selected maternal demographic characteristics, maternal serum biomarkers and uaD indexes. Methods: This is a prospective pregnant cohort study of 598 singleton nulliparous consecutive women. UaD investigation was performed by transabdominal sonography between 11+0 and 13+6 weeks, and between 17+0 and 21+6 weeks. All the serum samples for measurement of several placental biomarkers were collected at the first trimester. Maternal demographic characteristics were recorded at the same time. Receiver operating characteristic curves and predictive values were used to analyze the predictive powers of the above parameters. Different combinations and their logistic regression predictive models were analyzed. Results: Among 598 women, 20 developed preeclampsia (3.3%), 7 developed early-onset preeclampsia (1.2%), 52 developed gestational hypertension (8.7%), 10 developed gestational hypertension with delivery before 37 weeks (1.7%). Second trimester uterine artery pulsatility index was the best predictor with statistical significance for all the outcomes. In the multivariable logistic regression analysis, the best predictive value in the first and second trimester was obtained for the prediction of early onset preeclampsia. The combined screening showed significantly better results compared to either maternal parameters or Doppler alone. Conclusion: As a single marker, second trimester Doppler has the highest predictive value for hypertensive disorders, preterm birth and SGA. Combination of the maternal demographic characteristics, maternal serum biomarker and uaD improves the screening efficacy, especially when this necessitates early delivery.

RÉSUMÉ Objectif: Évaluer l'efficacité du dépistage de l’hypertension gestationnelle par les caractéristiques démographiques maternelles, les biomarqueurs sériques et le Doppler de l'artère utérine au premier et au deuxième trimestre de grossesse. Élaborer des modèles prédictifs de l’hypertension gestationnelle fondées sur ces paramètres. Methods: Il s'agit d'une étude prospective de cohorte incluant 598 femmes nullipares. Le Doppler utérin a été étudié par échographie transabdominale entre 11 +0 à 13 +6 semaines (1er trimestre) et entre 17 +0 à 21 +6 semaines (2e trimestre). Tous les échantillons de sérum pour la mesure de plusieurs biomarqueurs placentaires ont été recueillis au 1er trimestre. Les caractéristiques démographiques maternelles ont été enregistrées en même temps. Des courbes ROC et les valeurs prédictives ont été utilisés pour analyser la puissance prédictive des paramètres ci-dessus. Différentes combinaisons et leurs modèles de régression logistique ont été également analysés. Résultats: Parmi 598 femmes, on a observé 20 pré-éclampsies (3,3%), 7 pré-éclampsies précoces (1,2%), 52 cas d’hypertension gestationnelle (8,7%) , 10 cas d’hypertension gestationnelle avant 37 semaines (1,7%). L’index de pulsatilité des artères utérines au 2e trimestre est le meilleur prédicteur. En analyse de régression logistique multivariée, la meilleure valeur prédictive au 1er et au 2e trimestre a été obtenue pour la prévision de la pré-éclampsie précoce. Le dépistage combiné a montré des résultats nettement meilleurs comparés avec les paramètres maternels ou Doppler seuls. Conclusion: Comme seul marqueur, le Doppler utérin du deuxième trimestre a la meilleure prédictive pour l'hypertension, la naissance prématurée et la restriction de croissance. La combinaison des caractéristiques démographiques maternelles, des biomarqueurs sériques maternels et du Doppler utérin améliore l'efficacité du dépistage, en particulier pour la pré-éclampsie nécessitant un accouchement prématuré. Mot clés: Hypertension gestationnelle, Doppler utérins, Biomarqueurs sériques maternels, Caractéristiques démographiques maternelles, Dépistage, Modèle prédictif Multivarié. / ABSTRACT Objective: To evaluate the screening efficacy of maternal demographic characteristics, serum biomarkers and uterine artery Doppler (uaD) during the first and the second trimester for the hypertensive disorders of pregnancy. To elaborate prediction models of these diseases based on the combination of selected maternal demographic characteristics, maternal serum biomarkers and uaD indexes. Methods: This is a prospective pregnant cohort study of 598 singleton nulliparous consecutive women. UaD investigation was performed by transabdominal sonography between 11+0 and 13+6 weeks, and between 17+0 and 21+6 weeks. All the serum samples for measurement of several placental biomarkers were collected at the first trimester. Maternal demographic characteristics were recorded at the same time. Receiver operating characteristic curves and predictive values were used to analyze the predictive powers of the above parameters. Different combinations and their logistic regression predictive models were analyzed. Results: Among 598 women, 20 developed preeclampsia (3.3%), 7 developed early-onset preeclampsia (1.2%), 52 developed gestational hypertension (8.7%), 10 developed gestational hypertension with delivery before 37 weeks (1.7%). Second trimester uterine artery pulsatility index was the best predictor with statistical significance for all the outcomes. In the multivariable logistic regression analysis, the best predictive value in the first and second trimester was obtained for the prediction of early onset preeclampsia. The combined screening showed significantly better results compared to either maternal parameters or Doppler alone. Conclusion: As a single marker, second trimester Doppler has the highest predictive value for hypertensive disorders, preterm birth and SGA. Combination of the maternal demographic characteristics, maternal serum biomarker and uaD improves the screening efficacy, especially when this necessitates early delivery. Key words: Hypertensive disorders of pregnancy, Doppler, Maternal serum biomarkers, Maternal demographic characteristics, Screening, Multivariable predictive model.