Abortion and severe pre-eclampsia/eclampsia remain the major causes of maternal mortality in Zimbabwe. Based on this problem, factors associated with maternal mortality due to abortion and severe pre-eclampsia/eclampsia were investigated to improve pregnancy outcomes. Cases and controls were selected from 4895 abortion and 318 severe preeclampsia/ eclampsia obstetric records to conduct a retrospective case-control study. Significant risk factors identified for reducing maternal mortality due to postabortion complications included the administration of oxytocic drugs and evacuations of the uterus whilst anaemia and sepsis apparently reduced these women's chances of survival. No significant factors could be identified which influenced maternal deaths among women suffering from severe pre-eclampsia/eclampsia. Magnesium sulphate was not routinely administered, as recommended internationally. In both groups, cases apparently received better reported quantitative care than controls. Recommendations based on this research report include improved midwifery education and in-service training, regular audits of patients' records and changed policies for managing these conditions more effectively in Zimbabwe. / Health Studies / D. Litt. et Phil. (Advanced Nursing Sciences)

<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.

Introdução: As síndromes hipertensivas na gestação (SHG) afetam grande parte das gestantes com uma proporção cada vez maior. É responsável por desfechos negativos importantes para mulheres e bebês, sendo a primeira causa de morte materna no Brasil. As fontes de dados para as SHG em estudos epidemiológicos são exames clínicos ou registros profissionais (cartão de pré-natal ou prontuário hospitalar). Entretanto essas fontes podem ser de difícil acesso para alguns estudos, fazendo necessário conhecer a validade para SHG autorreferida no Brasil. Os fatores tradicionalmente associados às SHG são primiparidade, multiparidade, diabetes, sobrepeso e obesidade, idades nos limites da vida reprodutiva, hipertensão crônica e histórico de SHG. Entretanto fatores socioeconômico-demográficos figuram ocasionalmente entre os fatores associados às SHG. Para orientar políticas públicas, é necessário estudar a ocorrência das SHG no Brasil e seus fatores associados com dados de abrangência nacional. Objetivos: Avaliar a validade da informação autorreferida para SHG, analisar os fatores associados às SHG no Brasil e examinar a invisibilização do efeito da interseccionalidade entre variáveis socioeconômico-demográficas. Método: Trata-se de um estudo transversal com análise secundária da pesquisa \"Nascer no Brasil: Inquérito Nacional sobre o Parto e Nascimento\", realizada em 2011-12. Foram entrevistadas 23.940 puérperas e coletadas informações de seus prontuários e cartões de pré-natal. Para estimar a validade da informação autorreferida sobre SHG foram estabelecidas sensibilidade, especificidade e coeficiente kappa, assumindo por padrão ouro os registros profissionais como padrão ouro, estratificando por variáveis socioeconômico-demográficas e obstétricas. Foi investigada a associação entre a SHG e variáveis socioeconômico-demográficas, estilo de vida, estado de saúde e obstétricas por meio de regressão logística. Resultados: A Ocorrência das SHG foi 11,14% segundo os registros profissionais e 15,87% quando autorreferida. A sensibilidade foi 75%, especificidade foi 90% e coeficiente kappa foi 0,545 (IC95% 0,525 - 0,566) valor considerado de força moderada. A validade da SHG autorreferida foi melhor entre as mulheres brancas, das regiões Sul e Sudeste, que utilizaram financiamento próprio pela assistência ao parto, estrato econômico Classe B ou A, que passaram por uma cesariana na última gestação e ensino médio completo ou mais. A validade foi pior entre mulheres com indicação de cesariana por SHG. Após regressão logística, idade da mãe (&#946;1 = 1,052 [IC95% 1,039-1,065]), IMC (&#946;1 = 1,162 [IC95% 1,148-1,176], histórico pessoal de hipertensão gestacional (OR = 4,041 [IC95% 3,345-4,883]), diabetes (OR = 1,615 [IC95% 1,354-1,926]) e gestação múltipla (OR =2,035 [IC95% 1,288-3,215]) permaneceram independentemente associadas às SHG. Ter tido 1 ou dois partos anteriores (OR = 0,386 [IC95% 0,33-0,452]) e multiparidade (OR = 0,336 [IC95% 0,26-0,434]) apresentaram efeito protetor quando comparadas às primíparas e fonte de pagamento privada (OR = 0,841 [IC95% 0,708-0,998]) e ensino superior completo (OR = 0,652 [IC95% 0,494-0,860]) diminuem a chance de desenvolver uma SHG. As variáveis socioeconômico-demográficas como raça/cor da pele, escolaridade, fonte de pagamento, escore socioeconômico e região de residência apresentam grande sobreposição. Conclusões: A validade da informação autorreferida é moderada, com importantes variações que denotam iniquidades na comunicação entre profissionais e usuárias. As variáveis socioeconômico-demográficas apresentam grande interação por sobreposição, perdendo a significância estatística. A interseccionalidade entre raça/cor da pele, escolaridade, fonte de pagamento, escore socioeconômico e região de residência produz um grupo de mulheres de maior vulnerabilidade. As iniquidades na atenção a gestação e parto revelam a necessidade de pesquisas, ações e políticas públicas que busquem alterar a situação de adversidade vivenciada pelas mulheres na maternidade. / Introduction: Hypertensive disorders of pregnancy (HDP) affect many pregnant women with an increasing proportion. It is responsible for significant negative outcomes for women and babies, and for most maternal deaths in Brazil. The data sources for HDP in epidemiological studies are clinical examinations or professional records (antenatal card or hospital medical records). However, these sources may be difficult to access for some studies, making necessary to know the validity for self-reported HDP in Brazil. The factors traditionally associated with SHG are primiparity, multiparity, diabetes, overweight and obesity, age at reproductive life limits, chronic hypertension and history of HDP. Socioeconomic-demographic factors occasionally appear among the factors associated with HDP. Therefore, it is necessary to know the occurrence of HDP in Brazil and its associated factors through a national study with recent information. Objectives: To evaluate the validity of the self-reported information for SHG, to analyze the occurrence and associated factors with HDP in Brazil and to reflect on the invisibility of the intersectionality effect among socioeconomic-demographic variables. Method: This is a cross-sectional study, a secondary analysis of the \"Birth in Brazil\" survey, conducted in 2011-12. 23,940 postpartum women were interviewed and information was collected from their medical records and antenatal cards. To estimate the validity of self-reported information on HDP, sensitivity, specificity and kappa coefficient was established, with professional records as gold standard, stratified by socioeconomic-demographic and obstetric variables. The association between SHG and socioeconomic-demographic variables, lifestyle, health status and obstetric variables were investigated through logistic regression. Results: The occurrence of HDP was 11.14% according to professional records and 15.87% when self-referenced. The sensitivity was 75%, specificity was 90% and kappa coefficient was 0.545 (95% CI 0.525 - 0.566) considered as moderate. The validity of self-reported SHG was better among white women from the South and Southeast regions, self-financing, Class B or A economic stratum, cesarean section and more education. Validity was worse among women with cesarean section indicated for HDP. After logistic regression, greater maternal age, higher BMI, personal history of gestational hypertension, diabetes, multiple gestation and primiparity remained independently associated with HDP. Women who payed for care and more educated had a decreased chance of developing a HDP. Socioeconomic-demographic variables present great overlap. Conclusions: The validity of self-reported information is moderate, with important variations that denote inequities in communication between professionals and women. The socioeconomic-demographic variables present great interaction by overlapping, losing the statistical significance. The intersectionality of these characteristics produces a group of women of greater vulnerability. Inequities in attention to pregnancy and childbirth reveal the need for research, actions and public policies that seek to change the situation of adversity experienced by women when they experience motherhood.

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.

名古屋大学博士学位論文 学位の種類 : 博士(医学)(論文) 学位授与年月日:平成4年7月20日 淺田義正氏の博士論文として提出された

Abortion and severe pre-eclampsia/eclampsia remain the major causes of maternal mortality in Zimbabwe. Based on this problem, factors associated with maternal mortality due to abortion and severe pre-eclampsia/eclampsia were investigated to improve pregnancy outcomes. Cases and controls were selected from 4895 abortion and 318 severe preeclampsia/ eclampsia obstetric records to conduct a retrospective case-control study. Significant risk factors identified for reducing maternal mortality due to postabortion complications included the administration of oxytocic drugs and evacuations of the uterus whilst anaemia and sepsis apparently reduced these women's chances of survival. No significant factors could be identified which influenced maternal deaths among women suffering from severe pre-eclampsia/eclampsia. Magnesium sulphate was not routinely administered, as recommended internationally. In both groups, cases apparently received better reported quantitative care than controls. Recommendations based on this research report include improved midwifery education and in-service training, regular audits of patients' records and changed policies for managing these conditions more effectively in Zimbabwe. / Health Studies / D. Litt. et Phil. (Advanced Nursing Sciences)

O objetivo do presente estudo foi avaliar a diferença de resultados maternos e neonatais em gestações complicadas por trombofilias hereditárias em pacientes com e sem tromboembolismo venoso. Apesar do aumento de evidências, na literatura, sobre a associação de trombofilias congênitas e resultados obstétricos adversos, há ainda dúvida se pacientes trombofílicas com tromboembolismo venoso apresentam resultados maternos e neonatais piores que as pacientes trombofílicas sem tromboembolismo venoso. O estudo analisou 66 gestantes com trombofilias hereditárias, de forma retrospectiva observacional e comparativa, das quais 33 apresentavam tromboembolismo venoso e 36 o não apresentavam. Os principais desfechos relacionados a resultados maternos e neonatais adversos foram: pré-eclâmpsia grave, descolamento prematuro de placenta, restrição de crescimento fetal, natimortalidade, prematuridade e complicações hemorrágicas maternas. As trombofilias congênitas incluídas no estudo foram o fator V de Leiden (FVL), mutação da protrombina G20210A, mutação C677T do gene da 5,10-metilenotetrahidrofolato redutase (MTHFR), deficiência de proteína S, deficiência de proteína C e deficiência de antitrombina. Ambos os grupos apresentaram características populacionais similares. A ocorrência de complicações maternas e fetais/neonatais foi similar nos dois grupos: pré-eclâmpsia grave (P=0,097), descolamento prematuro de placenta (P=0,478), restrição de crescimento fetal (P=0,868), natimortalidade (P=0,359), prematuridade (P=0,441) e complicações hemorrágicas maternas (P=0,478). Este estudo concluiu que a presença de tromboembolismo venoso em gestantes com trombofilia hereditária apresenta resultados maternos e neonatais semelhantes àquelas com trombofilias hereditárias sem tromboembolismo venoso. / The aim of this study was to evaluate differences in maternal and neonatal outcomes in pregnancies complicated by inherited thrombophilias between patients with and without venous thromboembolism. Despite increasing evidence in the literature indicating an association between inherited thrombophilias and adverse obstetric outcomes, doubts remain whether thrombophilic patients with venous thromboembolism present poorer maternal and neonatal outcomes than thrombophilic patients without venous thromboembolism. In this retrospective, observational and comparative study, 66 pregnant women with inherited thrombophilias, including 33 with venous thromboembolism and 36 without thromboembolism, were investigated. The main end-points analyzed were severe pre-eclampsia, placental abruption, fetal growth restriction, stillbirth, preterm delivery, and maternal hemorrhagic complications. The congenital thrombophilias included in this study were factor V Leiden (FVL), prothrombin G20210A mutation, C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, protein S deficiency, protein C deficiency, and antithrombin deficiency. The two groups were similar in terms of population characteristics. The frequency of maternal and fetal/neonatal complications was similar in the two groups: severe pre-eclampsia (P=0.097), placental abruption (P=0.478), fetal growth restriction (P=0.868), stillbirth (P=0.359), preterm delivery (P=0.441), and maternal hemorrhagic complications (P=0.478). This study concluded that venous thromboembolism in thrombophilic patients does not worsen maternal or neonatal outcomes when compared to thrombophilic patients without venous thromboembolism.