Science.gov

Sample records for early onset pre-eclampsia

  1. ASSESSMENT OF OXIDATIVE STRESS IN EARLY AND LATE ONSET PRE-ECLAMPSIA AMONG GHANAIAN WOMEN.

    PubMed

    Tetteh, P W; Adu-Bonsaffoh, K; Antwi-Boasiako, C; Antwi, D A; Gyan, B; Obed, S A

    2015-01-01

    Pre-eclampsia is a multisystem pregnancy-related disorder with multiple theories regarding its aetiology resulting in lack of reliable screening tests and well-established measures for primary prevention. However, oxidative stress is increasingly being implicated in the pathogenesi of pre-eclampsia although conflicting findings have been reported. To determine and compare the levels of oxidative stress in early and late onset pre-eclampsia by measuring urinary excretion of isoprostane and total antioxidant power (TAP) in a cohort of pre-eclamptic women at Korle Bu Teaching Hospital. This was a cross-sectional study conducted at Korle-Bu Teaching Hospital, Accra, Ghana involving pre-eclamptic women between the ages 18 and 45 years who gave written informed consent. Urinary isoprostane levels were determined using an enzyme-linked immunosorbent assay (ELISA) kit whereas the Total Anti-oxidant Power in urine samples was determined using Total Antioxidant Power Colorimetric Microplate Assay kit. The data obtained were analyzed using MEGASTAT statistical software package. We included 102 pre-eclamptic women comprising 68 (66.7%) and 34 (33.3%) with early-onset and late-onset pre-eclampsia respectively. There were no statistically significant differences between the mean maternal age, haematological indices, serum ALT, AST, ALT, albumin, urea, creatinine uric acid and total protein at the time of diagnosis. The mean gestational age at diagnosis of early and late onset pre-eclampsia were 31.65 ± 0.41 and 38.03 ± 0.21 respectively (p ˂ 0.001). Also, there were statistically significant differences between the diastolic blood pressure (BP), systolic BP and mean arterial pressure (MAP) at diagnosis of pre-eclampsia in the two categories. The mean urinary Isoprostane excretion was significantly higher in the early onset pre-eclamptic group (3.04 ± 0.34 ng/mg Cr) compared to that of the late onset pre-eclamptic group (2.36 ± 0.45 ng/mg Cr), (p=0.019). Urinary total

  2. Is Fetal Growth Restriction Associated with a More Severe Maternal Phenotype in the Setting of Early Onset Pre-Eclampsia? A Retrospective Study

    PubMed Central

    Weiler, Jane; Tong, Stephen; Palmer, Kirsten R.

    2011-01-01

    Background Both pre-eclampsia and fetal growth restriction are thought to result from abnormal placental implantation in early pregnancy. Consistent with this shared pathophysiology, it is not uncommon to see growth restriction further confound the course of pre-eclampsia and vice versa. It has been previously suggested that superimposed growth restriction is associated with a more severe pre-eclamptic phenotype, however this has not been a consistent finding. Therefore, we set out to determine whether the presence of fetal growth restriction among women with severe early-onset pre-eclampsia was associated with more severe maternal disease compared to those without a growth-restricted fetus. Methods and Findings We undertook a retrospective cohort study of women presenting to a tertiary hospital with severe early-onset pre-eclampsia (<34 weeks' gestation) between 2005–2009. We collected clinical data, including severity of pre-eclampsia, maternal and neonatal outcomes. Of 176 cases of severe pre-eclampsia, 39% (n = 68) were further complicated by fetal growth restriction. However, no significant difference was seen in relation to the severity of pre-eclampsia between those with or without a growth-restricted baby. The presence of concomitant growth restriction was however associated with a significantly increased risk of stillbirth (p = 0.003) and total perinatal mortality (p = 0.02). Conclusions The presence of fetal growth restriction among women with severe early-onset pre-eclampsia is not associated with increased severity of maternal disease. However the incidence of stillbirth and perinatal death is significantly increased in this sub-population. PMID:22046419

  3. Genome-wide hypermethylation coupled with promoter hypomethylation in the chorioamniotic membranes of early onset pre-eclampsia

    PubMed Central

    Ching, Travers; Song, Min-Ae; Tiirikainen, Maarit; Molnar, Janos; Berry, Marla; Towner, Dena; Garmire, Lana X.

    2014-01-01

    Pre-eclampsia is the leading cause of fetal and maternal morbidity and mortality. Early onset pre-eclampsia (EOPE) is a disorder that has severe maternal and fetal outcomes, whilst its etiology is poorly understood. We hypothesize that epigenetics plays an important role to mediate the development of EOPE and conducted a case–control study to compare the genome-wide methylome difference between chorioamniotic membranes from 30 EOPE and 17 full-term pregnancies using the Infinium Human Methylation 450 BeadChip arrays. Bioinformatics analysis tested differential methylation (DM) at CpG site level, gene level, and pathway and network level. A striking genome-wide hypermethylation pattern coupled with hypomethylation in promoters was observed. Out of 385 184 CpG sites, 9995 showed DM (2.6%). Of those DM sites, 91.9% showed hypermethylation (9186 of 9995). Over 900 genes had DM associated with promoters. Promoter-based DM analysis revealed that genes in canonical cancer-related pathways such as Rac, Ras, PI3K/Akt, NFκB and ErBB4 were enriched, and represented biological functional alterations that involve cell cycle, apoptosis, cancer signaling and inflammation. A group of genes previously found to be up-regulated in pre-eclampsia, including GRB2, ATF3, NFKB2, as well as genes in proteasome subunits (PSMA1, PMSE1, PSMD1 and PMSD8), harbored hypomethylated promoters. Contrarily, a cluster of microRNAs, including mir-519a1, mir-301a, mir-487a, mir-185, mir-329, mir-194, mir-376a1, mir-486 and mir-744 were all hypermethylated in their promoters in the EOPE samples. These findings collectively reveal new avenues of research regarding the vast epigenetic modifications in EOPE. PMID:24944161

  4. Early Onset Pre-Eclampsia Is Associated with Altered DNA Methylation of Cortisol-Signalling and Steroidogenic Genes in the Placenta

    PubMed Central

    Hogg, Kirsten; Blair, John D.; McFadden, Deborah E.; von Dadelszen, Peter; Robinson, Wendy P.

    2013-01-01

    Placental cortisol is inactivated in normotensive pregnancies, but is frequently present in pre-eclampsia associated placentae. Since glucocorticoids are strongly associated with the programming of long-term health, we assessed DNA methylation of genes involved in cortisol signalling and bioavailability, and hormonal signalling in the placenta of normotensive and hypertensive pregnancies. Candidate genes/CpG sites were selected through analysis of Illumina Infinium HumanMethylation450 BeadChip array data on control (n = 19) and early onset pre-eclampsia (EOPET; n = 19) placental samples. DNA methylation was further quantified by bisulfite pyrosequencing in a larger cohort of control (n = 111) cases, in addition to EOPET (n = 19), late onset pre-eclampsia (LOPET; n = 18) and normotensive intrauterine growth restriction (nIUGR; n = 13) cases. DNA methylation (percentage points) was increased at CpG sites within genes encoding the glucocorticoid receptor (NR3C1 exon 1D promoter; +8.46%; P<0.01) and corticotropin releasing hormone (CRH) binding protein (CRHBP intron 3; +9.14%; P<0.05), and decreased within CRH (5′ UTR; −4.30%; P = 0.11) in EOPET-associated placentae, but not in LOPET nor nIUGR cases, compared to controls. Differential DNA methylation was not observed among groups at the 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) gene promoter. Significant hypomethylation was observed in pre-eclampsia but not nIUGR placentae for steroidogenic genes, including CYP11A1 (exon1; EOPET; −9.66%; P<0.00001, and LOPET; −5.77%; P<0.001), 3β-hydroxy-delta-5-steroid dehydrogenase type 1 (HSD3B1 exon 2; EOPET; −12.49%; P<0.00001, and LOPET; −6.88%; P<0.001), TEA domain family member 3 (TEAD3 intron 1; EOPET; −12.56%; P<0.00001) and CYP19 (placental-specific exon 1.1 promoter; EOPET; −10.62%, P<0.0001). These data represent dysregulation of the placental epigenome in pre-eclampsia related to genes involved in maintaining the

  5. Development and validation of Prediction models for Risks of complications in Early-onset Pre-eclampsia (PREP): a prospective cohort study.

    PubMed

    Thangaratinam, Shakila; Allotey, John; Marlin, Nadine; Mol, Ben W; Von Dadelszen, Peter; Ganzevoort, Wessel; Akkermans, Joost; Ahmed, Asif; Daniels, Jane; Deeks, Jon; Ismail, Khaled; Barnard, Ann Marie; Dodds, Julie; Kerry, Sally; Moons, Carl; Riley, Richard D; Khan, Khalid S

    2017-04-01

    The prognosis of early-onset pre-eclampsia (before 34 weeks' gestation) is variable. Accurate prediction of complications is required to plan appropriate management in high-risk women. To develop and validate prediction models for outcomes in early-onset pre-eclampsia. Prospective cohort for model development, with validation in two external data sets. Model development: 53 obstetric units in the UK. Model transportability: PIERS (Pre-eclampsia Integrated Estimate of RiSk for mothers) and PETRA (Pre-Eclampsia TRial Amsterdam) studies. Pregnant women with early-onset pre-eclampsia. Nine hundred and forty-six women in the model development data set and 850 women (634 in PIERS, 216 in PETRA) in the transportability (external validation) data sets. The predictors were identified from systematic reviews of tests to predict complications in pre-eclampsia and were prioritised by Delphi survey. The primary outcome was the composite of adverse maternal outcomes established using Delphi surveys. The secondary outcome was the composite of fetal and neonatal complications. We developed two prediction models: a logistic regression model (PREP-L) to assess the overall risk of any maternal outcome until postnatal discharge and a survival analysis model (PREP-S) to obtain individual risk estimates at daily intervals from diagnosis until 34 weeks. Shrinkage was used to adjust for overoptimism of predictor effects. For internal validation (of the full models in the development data) and external validation (of the reduced models in the transportability data), we computed the ability of the models to discriminate between those with and without poor outcomes ( c -statistic), and the agreement between predicted and observed risk (calibration slope). The PREP-L model included maternal age, gestational age at diagnosis, medical history, systolic blood pressure, urine protein-to-creatinine ratio, platelet count, serum urea concentration, oxygen saturation, baseline treatment with

  6. Risk factors for and perinatal mortality of abruptio placentae in patients hospitalised for early onset severe pre-eclampsia - a case controlled study.

    PubMed

    Odendaal, H J; Hall, D R; Grové, D

    2000-07-01

    We set out to determine which patients admitted for expectant management of early onset severe pre-eclampsia develop abruptio placentae and to compare the perinatal mortality rate of patients who developed abruptio placentae with those who did not have this complication. This was a case controlled study, using gestational age at delivery to select a control group for 69 patients who developed abruptio placentae. The only significant difference on admission was the higher uric acid levels in patients who developed abruptio placentae. Mean admission to delivery intervals were 11.9 and 8.8 days for the control and abruption groups respectively (P = 0.0083). Fifty-eight per cent of the babies in the abruptio placentae group developed late decelerations, as determined by fetal heart rate monitoring compared with 32% in the control group. Lactate dehydrogenase levels before delivery were significantly higher in the abruption group, but it only became elevated shortly before delivery and in the minority of cases. There were two intrauterine and four neonatal deaths in the abruption group and two neonatal deaths in the control group. Late decelerations detected by frequent fetal heart rate monitoring in patients with early onset severe pre-eclampsia is the only early warning of abruptio placentae.

  7. Combined Screening for Early Detection of Pre-Eclampsia

    PubMed Central

    Park, Hee Jin; Shim, Sung Shin; Cha, Dong Hyun

    2015-01-01

    Although the precise pathophysiology of pre-eclampsia remains unknown, this condition continues to be a major cause of maternal and fetal mortality. Early prediction of pre-eclampsia would allow for timely initiation of preventive therapy. A combination of biophysical and biochemical markers are superior to other tests for early prediction of the development of pre-eclampsia. Apart from the use of parameters in first-trimester aneuploidy screening, cell-free fetal DNA quantification is emerging as a promising marker for prediction of pre-eclampsia. This article reviews the current research of the most important strategies for prediction of pre-eclampsia, including the use of maternal risk factors, mean maternal arterial pressure, ultrasound parameters, and biomarkers. PMID:26247944

  8. Maternal left ventricular hypertrophy and diastolic dysfunction and brain natriuretic peptide concentration in early- and late-onset pre-eclampsia.

    PubMed

    Borges, V T M; Zanati, S G; Peraçoli, M T S; Poiati, J R; Romão-Veiga, M; Peraçoli, J C; Thilaganathan, B

    2018-04-01

    Pre-eclampsia (PE) is associated with maternal cardiac remodeling and diastolic dysfunction. The aim of this study was to assess and compare maternal left ventricular structure and diastolic function and levels of brain natriuretic peptide (BNP) in women with early-onset (< 34 weeks' gestation) vs those with late-onset (≥ 34 weeks' gestation) PE. This was a prospective, cross-sectional, observational study of 30 women with early-onset PE, 32 with late-onset PE and 23 normotensive controls. Maternal cardiac structure and diastolic function were assessed by echocardiography and plasma levels of BNP were measured by enzyme immunoassay. Early- and late-onset PE were associated with increased left ventricular mass index and relative wall thickness compared with normotensive controls. In women with early-onset PE, the prevalence of concentric hypertrophy (40%) and diastolic dysfunction (23%) was also significantly higher (both P < 0.05) compared with women with late-onset PE (16% for both). Maternal serum BNP levels were significantly higher (P < 0.05) in women with early-onset PE and correlated with relative wall thickness and left ventricular mass index. Early-onset PE is associated with more severe cardiac impairment than is late-onset PE, as evidenced by an increased prevalence of concentric hypertrophy, diastolic dysfunction and higher levels of BNP. These findings suggest that early-onset PE causes greater myocardial damage, increasing the risk of both peripartum and postpartum cardiovascular morbidity. Although these cardiovascular effects are easily identified by echocardiographic parameters and measuring BNP, further studies are needed to assess their clinical utility. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

  9. [Effect of Low Molecular Weight Heparin Calcium Combined Compound Danshen Injection on Perinatal Outcomes of Nephrotic Syndrome Patients with Early Onset Severe Pre-eclampsia].

    PubMed

    Tong, Chong-xin; Xing, Xiao-fen; Qiao, Shu-hua; Liu, Lin; Shan, Ling

    2015-08-01

    To observe the effect of low molecular weight heparin calcium (LMWHC) combined Compound Danshen Injection (DI) on nephrotic syndrome patients with early onset severe preeclampsia. Totally 80 nephrotic syndrome patients with early onset severe pre-eclampsia were randomly assigned to four groups voluntarily, i.e., Group A (22 cases, treated by magnesium sulfate), B (19 cases, treated by magnesium sulfate plus LMWHC), C (21 cases, magnesium sulfate plus DI), D (18 cases, magnesium sulfate plus LMWHC and DI). Umbilical arterial S/D ratios, amniotic fluid index (AFI), prolonged gestational age, placenta weight, neonatal weight, and Apgar score were compared among the four groups. Compared with before treatment in the same group, umbilical arterial S/D ratios decreased in the four groups (P <0. 05). AFI decreased in Group A, while it increased in Group B, C, and D (P<0. 05). Compared with Group A at the same time point, umbilical arterial S/D ratios decreased, and AFI increased in Group B, C, and D (P <0. 01 , P <0. 05). Prolonged gestational age and neonatal weight were increased in Group B, C, and D (P <0. 01, P <0. 05). Placenta weight were increased in Group B and D (P <0. 05). Apgar scores at 1 and 5 min were improved in Group D (P <0. 05). Compared with Group B and C at the same time point, umbilical arterial S/D ratios decreased, and AFI increased in Group D (P<0. 05). Compared with Group B, prolonged gestational age and placenta weight were decreased in Group C, but prolonged gestational age and placenta weight were increased in Group D (P <0.05). Compared with Group C, prolonged gestational age, placenta weight, and neonatal weight were increased in Group D (P <0. 05). Treatment of nephrotic syndrome patients with early onset severe pre-eclampsia by LMWHC combined DI could prolong gestational ages, obviously improve prenatal outcomes, with better effect obtained than using any of them alone.

  10. Relationship between histopathological changes in post partum renal biopsies and renal function tests of African women with early onset pre-eclampsia.

    PubMed

    Khedun, S M; Naicker, T; Moodley, J

    2000-05-01

    To improve the diagnostic accuracy of concurrent renal disease in hypertension of pregnancy, biopsy evaluation is essential. In addition, establishing underlying renal disease is important for prognosis on future pregnancies. We therefore designed a study to determine the diagnostic yield of postpartum renal biopsy and the nature and frequency of complications associated with this procedure. Also, to determine relationships, if any, between renal function tests and ultrastructural and histopathological findings. Fifty renal biopsies were performed in the immediate postpartum period in black African women with early onset pre-eclampsia. Each biopsy specimen was placed in a separate container and coded so that sampling was unknown to the electron microscopist. Each biopsy specimen was divided into three parts, and processed and stained for light, fluorescent and transmission electron microscopy using conventional techniques. Renal tissue biopsies were adequate for diagnostic purposes in all cases. There were no complications in any of the 50 patients studied. Ultrastructural examination confirmed the light microscopy findings. In addition the ultrastructural findings showed intramembranous deposits, foot process fusion and mesangial deposits. In 16 patients with normal renal function tests; the biopsies evaluation from these patients showed ultrastructural changes. In the remaining 34 patients with abnormal renal function tests of varying severity; biopsy evaluation from these patients showed both ultrastructural and histopathological changes. Renal biopsy procedure is safe, and ultrastructural and histological findings obtained from postpartum renal biopsies are more informative than the routine renal function tests.

  11. Pre-eclampsia and first-onset postpartum psychiatric episodes: a Danish population-based cohort study

    PubMed Central

    Bergink, V.; Laursen, T. M.; Johannsen, B. M. W.; Kushner, S. A.; Meltzer-Brody, S.; Munk-Olsen, T.

    2016-01-01

    Background Recent evidence suggests that postpartum psychiatric episodes may share similar etiological mechanisms with immune-related disorders. Pre-eclampsia is one of the most prevalent immune-related disorders of pregnancy. Multiple clinical features are shared between pre-eclampsia and postpartum psychiatric disorders, most prominently a strong link to first pregnancies. Therefore, we aimed to study if pre-eclampsia is a risk factor for first-onset postpartum psychiatric episodes. Method We conducted a cohort study using the Danish population registry, with a total of 400 717 primiparous women with a singleton delivery between 1995 and 2011. First-lifetime childbirth was the main exposure variable and the outcome of interest was first-onset postpartum psychiatric episodes. The main outcome measures were monthly incidence rate ratios (IRRs), with the period 11–12 months after birth as the reference category. Adjustments were made for age, calendar period, reproductive history, and perinatal maternal health including somatic and obstetric co-morbidity. Results Primiparous women were at particularly high risk of first-onset psychiatric episodes during the first month postpartum [IRR 2.93, 95% confidence interval (CI) 2.53–3.40] and pre-eclampsia added to that risk (IRR 4.21, 95% CI 2.89–6.13). Having both pre-eclampsia and a somatic co-morbidity resulted in the highest risk of psychiatric episodes during the 3-month period after childbirth (IRR 4.81, 95% CI 2.72–8.50). Conclusions We confirmed an association between pre-eclampsia and postpartum psychiatric episodes. The possible explanations for this association, which are not mutually exclusive, include the psychological impact of a serious medical condition such as pre-eclampsia and the neurobiological impact of pre-eclampsia-related vascular pathology and inflammation. PMID:26243040

  12. A narrative synthesis of factors that affect women speaking up about early warning signs and symptoms of pre-eclampsia and responses of healthcare staff.

    PubMed

    Carter, Wendy; Bick, Debra; Mackintosh, Nicola; Sandall, Jane

    2017-02-13

    families can detect early onset, and is an issue which needs further exploration. There is very limited research exploring clinical staff response to women who raise concerns about their health when experiencing symptoms and signs of pre-eclampsia/eclampsia with further research needed if safety and quality of care are to be improved.

  13. Maternal bradycardia occurring prior to onset of HELLP syndrome in a woman with pre-eclampsia.

    PubMed

    Hosokawa, Ami; Umazume, Takeshi; Yamada, Takahiro; Minakami, Hisanori

    2017-05-13

    A 36-year-old nulliparous woman developed pre-eclampsia at gestational week (GW) 28 -6/7 Cardiac status was checked regularly. Heart rate of 93 beats per minute (bpm) with left atrial diameter (LAD) of 35 mm, left ventricular hypertrophy and inferior vena cava diameter (IVCD) of 8 mm at GW 32 -0/7 decreased to 48 bpm with an expanded IVCD to 25 mm, dilated left atrium (LAD to 39 mm), increased pulmonary arterial pressure, increased systemic vascular resistance (approximate 3000  dyn s/cm 5 ) and biphasic intrarenal venous flow pattern 3.5 hours prior to childbirth at GW 32 -3/7 Epigastralgia, tachycardia (160 bpm) and marked hypertension (201/111 mm Hg) occurring 2 hours after echocardiography necessitated caesarean section, with subsequent development of HELLP syndrome. Acute fluid shift from the splanchnic vasculature to central vasculature may have occurred causing HELLP syndrome as a result from vasospasm associated with sympathetic hyperactivity. The cause of bradycardia prior to tachycardia remains unclear. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Analysis of cardiovascular oscillations: A new approach to the early prediction of pre-eclampsia

    NASA Astrophysics Data System (ADS)

    Malberg, H.; Bauernschmitt, R.; Voss, A.; Walther, T.; Faber, R.; Stepan, H.; Wessel, N.

    2007-03-01

    Pre-eclampsia (PE) is a serious disorder with high morbidity and mortality occurring during pregnancy; 3%-5% of all pregnant women are affected. Early prediction is still insufficient in clinical practice. Although most pre-eclamptic patients show pathological uterine perfusion in the second trimester, this parameter has a positive predictive accuracy of only 30%, which makes it unsuitable for early, reliable prediction. The study is based on the hypothesis that alterations in cardiovascular regulatory behavior can be used to predict PE. Ninety-six pregnant women in whom Doppler investigation detected perfusion disorders of the uterine arteries were included in the study. Twenty-four of these pregnant women developed PE after the 30th week of gestation. During pregnancy, additional several noninvasive continuous blood pressure recordings were made over 30 min under resting conditions by means of a finger cuff. The time series extracted of systolic as well as diastolic beat-to-beat pressures and the heart rate were studied by variability and coupling analysis to find predictive factors preceding genesis of the disease. In the period between the 18th and 26th weeks of pregnancy, three special variability and baroreflex parameters were able to predict PE several weeks before clinical manifestation. Discriminant function analysis of these parameters was able to predict PE with a sensitivity and specificity of 87.5% and a positive predictive value of 70%. The combined clinical assessment of uterine perfusion and cardiovascular variability demonstrates the best current prediction several weeks before clinical manifestation of PE.

  15. Cardiac diastolic function after recovery from pre-eclampsia.

    PubMed

    Soma-Pillay, P; Louw, M C; Adeyemo, A O; Makin, J; Pattinson, R C

    Pre-eclampsia is associated with significant changes to the cardiovascular system during pregnancy. Eccentric and concentric remodelling of the left ventricle occurs, resulting in impaired contractility and diastolic dysfunction. It is unclear whether these structural and functional changes resolve completely after delivery. The objective of the study was to determine cardiac diastolic function at delivery and one year post-partum in women with severe pre-eclampsia, and to determine possible future cardiovascular risk. This was a descriptive study performed at Steve Biko Academic Hospital, a tertiary referral hospital in Pretoria, South Africa. Ninety-six women with severe preeclampsia and 45 normotensive women with uncomplicated pregnancies were recruited during the delivery admission. Seventy-four (77.1%) women in the pre-eclamptic group were classified as a maternal near miss. Transthoracic Doppler echocardiography was performed at delivery and one year post-partum. At one year post-partum, women with pre-eclampsia had a higher diastolic blood pressure (p = 0.001) and body mass index (p = 0.02) than women in the normotensive control group. Women with early onset pre-eclampsia requiring delivery prior to 34 weeks' gestation had an increased risk of diastolic dysfunction at one year post-partum (RR 3.41, 95% CI: 1.11-10.5, p = 0.04) and this was irrespective of whether the patient had chronic hypertension or not. Women who develop early-onset pre-eclampsia requiring delivery before 34 weeks are at a significant risk of developing cardiac diastolic dysfunction one year after delivery compared to normotensive women with a history of a low-risk pregnancy.

  16. Population-based trends in pregnancy hypertension and pre-eclampsia: an international comparative study

    PubMed Central

    Ford, Jane B; Algert, Charles S; Antonsen, Sussie; Chalmers, James; Cnattingius, Sven; Gokhale, Manjusha; Kotelchuck, Milton; Melve, Kari K; Langridge, Amanda; Morris, Carole; Morris, Jonathan M; Nassar, Natasha; Norman, Jane E; Norrie, John; Sørensen, Henrik Toft; Walker, Robin; Weir, Christopher J

    2011-01-01

    Objective The objective of this study was to compare international trends in pre-eclampsia rates and in overall pregnancy hypertension rates (including gestational hypertension, pre-eclampsia and eclampsia). Design Population data (from birth and/or hospital records) on all women giving birth were available from Australia (two states), Canada (Alberta), Denmark, Norway, Scotland, Sweden and the USA (Massachusetts) for a minimum of 6 years from 1997 to 2007. All countries used the 10th revision of the International Classification of Diseases, except Massachusetts which used the 9th revision. There were no major changes to the diagnostic criteria or methods of data collection in any country during the study period. Population characteristics as well as rates of pregnancy hypertension and pre-eclampsia were compared. Results Absolute rates varied across the populations as follows: pregnancy hypertension (3.6% to 9.1%), pre-eclampsia (1.4% to 4.0%) and early-onset pre-eclampsia (0.3% to 0.7%). Pregnancy hypertension and/or pre-eclampsia rates declined over time in most populations. This was unexpected given that factors associated with pregnancy hypertension such as pre-pregnancy obesity and maternal age are generally increasing. However, there was also a downward shift in gestational age with fewer pregnancies reaching 40 weeks. Conclusion The rate of pregnancy hypertension and pre-eclampsia decreased in northern Europe and Australia from 1997 to 2007, but increased in Massachusetts. The use of a different International Classification of Diseases coding version in Massachusetts may contribute to the difference in trend. Elective delivery prior to the due date is the most likely explanation for the decrease observed in Europe and Australia. Also, the use of interventions that reduce the risk of pregnancy hypertension and/or progression to pre-eclampsia (low-dose aspirin, calcium supplementation and early delivery for mild hypertension) may have contributed to the

  17. Impact of Road Traffic Pollution on Pre-eclampsia and Pregnancy-induced Hypertensive Disorders

    PubMed Central

    Halldorsson, Thorhallur I.; Olsen, Sjurdur F.; Hjortebjerg, Dorrit; Ketzel, Matthias; Grandström, Charlotta; Raaschou-Nielsen, Ole; Sørensen, Mette

    2017-01-01

    Background: Road traffic is a major source of air pollution and noise. Both exposures have been associated with hypertension in adults, but pregnant women have been less studied. Methods: We examined single and joint effects of ambient air pollution and road traffic noise on pre-eclampsia and pregnancy-induced hypertensive disorders among 72,745 singleton pregnancies (1997–2002) from the Danish National Birth Cohort with complete covariate data and residential address history from conception until live born birth. Nitrogen dioxide (NO2) and noise from road traffic (Lden) were modeled at all addresses. Outcome and covariate data were derived from registries, hospital records, and questionnaires. Results: A 10-µg/m3 increase in NO2 exposure during first trimester was associated with increased risk of pre-eclampsia (n = 1,880, adjusted odds ratio = 1.07 [95% confidence interval = 1.01, 1.14]) and pregnancy-induced hypertensive disorders (n = 2,430, adjusted odds ratio = 1.07 [1.01, 1.13]). A 10 dB higher road traffic noise was also associated with increased risk of pre-eclampsia (1.10 [1.02, 1.18]) and pregnancy-induced hypertensive disorders (1.08 [1.02, 1.15]). For both exposures, the associations were strongest for mild pre-eclampsia (n = 1,393) and early-onset pre-eclampsia (n = 671), whereas higher risk for severe pre-eclampsia (n = 487) was not evident. In mutually adjusted models, estimates for both exposures decreased and only the association between NO2 and mild pre-eclampsia remained. Conclusions: Road traffic may increase the risk of pre-eclampsia and hypertensive disorders in pregnancy through exposure to both ambient air pollution and noise, although associations with the two exposures were generally not found to be independent of one another. See video abstract, http://links.lww.com/EDE/B112. PMID:27648591

  18. The interrelationship of complement-activation fragments and angiogenesis-related factors in early pregnancy and their association with pre-eclampsia

    PubMed Central

    Lynch, AM; Murphy, JR; Gibbs, RS; Levine, RJ; Giclas, PC; Salmon, JE; Holers, VM

    2016-01-01

    Objective To determine the interrelationships during early pregnancy of complement-activation fragments Bb, C3a and sC5b-9, and angiogenesis-related factors placental growth factor (PiGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), and their associations with pre-eclampsia. Design Prospective cohort study. Setting Denver complement study (June 2005–June 2008). Population A total of 668 pregnant women with singleton gestations, recruited between 10 and 15 weeks of gestation. Methods Using univariable and multivariable logistic regression analysis, concentrations of complement-activation fragments and angiogenesis-related factors were compared between 10 and 15 weeks of gestation in women who subsequently did or did not develop pre-eclampsia. Interrelationships between these variables were tested using the non-parametric Spearman rank correlation coefficient. Main outcome measure Pre-eclampsia. The association of complement-activation fragments and angiogenesis-related factors with obesity was also examined. Results The mean (±SD) levels of complement Bb in early pregnancy among women who did and did not develop pre-eclampsia were 0.84 (±0.26) µg/ml and 0.69 (±0.2) µg/ml, respectively (P = 0.001). Concentrations of PiGF were significantly (P = 0.01) lower (31 ± 12 pg/ml) in early pregnancy in the pre-eclamptic group of women, as compared with the normotensive group (39 ± 32 pg/ml). The adjusted odds ratio (AOR) of Bb and PiGF were 2.1 (CI = 1.4–3.1, P < 0.0003) and 0.2 (CI = 0.07–0.7, P = 0.01), respectively. There was no significant difference in the levels of C3a, sC5b-9, sFlt-1 and sEng in early pregnancy among women who developed pre-eclampsia, compared with women who remained normotensive during pregnancy. Higher levels of Bb (P = 0.0001) and C3a (P = 0.03), and lower levels of sFlt-1 (P = 0.0002) and sEng (P = 0.0001) were found among women with obesity, compared with non-obese controls. No meaningful relationships

  19. Pre-eclampsia part 2: prediction, prevention and management

    PubMed Central

    Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Korzeniewski, Steven J.; Yeo, Lami; Romero, Roberto

    2018-01-01

    An antiangiogenic state might constitute a terminal pathway for the multiple aetiologies of pre-eclampsia, especially those resulting from placental abnormalities. The levels of angiogenic and antiangiogenic proteins in maternal blood change prior to a diagnosis of pre-eclampsia, correlate with disease severity and have prognostic value in identifying women who will develop maternal and/or perinatal complications. Potential interventions exist to ameliorate the imbalance of angiogenesis and, hence, might provide opportunities to improve maternal and/or perinatal outcomes in pre-eclampsia. Current strategies for managing pre-eclampsia consist of controlling hypertension, preventing seizures and timely delivery of the fetus. Prediction of pre-eclampsia in the first trimester is of great interest, as early administration of aspirin might reduce the risk of pre-eclampsia, albeit modestly. Combinations of biomarkers typically predict pre-eclampsia better than single biomarkers; however, the encouraging initial results of biomarker studies require external validation in other populations before they can be used to facilitate intervention in patients identified as at increased risk. Angiogenic and antiangiogenic factors might also be useful in triage of symptomatic patients with suspected pre-eclampsia, differentiating pre-eclampsia from exacerbations of pre-existing medical conditions and performing risk assessment in asymptomatic women. This Review article discusses the performance of predictive and prognostic biomarkers for pre-eclampsia, current strategies for preventing and managing the condition and its long-term consequences. PMID:25003612

  20. Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction

    PubMed Central

    2011-01-01

    Background It has been well documented that pre-eclampsia and unexplained fetal growth restriction (FGR) have a common etiological background, but little is known about their linkage at the molecular level. The aim of this study was to further investigate the mechanisms underlying pre-eclampsia and unexplained FGR. Methods We analyzed differentially expressed genes in placental tissue from severe pre-eclamptic pregnancies (n = 8) and normotensive pregnancies with or (n = 8) without FGR (n = 8) using a microarray method. Results A subset of the FGR samples showed a high correlation coefficient overall in the microarray data from the pre-eclampsia samples. Many genes that are known to be up-regulated in pre-eclampsia are also up-regulated in FGR, including the anti-angiogenic factors, FLT1 and ENG, believed to be associated with the onset of maternal symptoms of pre-eclampsia. A total of 62 genes were found to be differentially expressed in both disorders. However, gene set enrichment analysis for these differentially expressed genes further revealed higher expression of TP53-downstream genes in pre-eclampsia compared with FGR. TP53-downstream apoptosis-related genes, such as BCL6 and BAX, were found to be significantly more up-regulated in pre-eclampsia than in FGR, although the caspases are expressed at equivalent levels. Conclusions Our current data indicate a common pathophysiology for FGR and pre-eclampsia, leading to an up-regulation of placental anti-angiogenic factors. However, our findings also suggest that it may possibly be the excretion of these factors into the maternal circulation through the TP53-mediated early-stage apoptosis of trophoblasts that leads to the maternal symptoms of pre-eclampsia. PMID:21810232

  1. Maternal serum bisphenol A levels and risk of pre-eclampsia: a nested case-control study.

    PubMed

    Ye, Yunzhen; Zhou, Qiongjie; Feng, Liping; Wu, Jiangnan; Xiong, Yu; Li, Xiaotian

    2017-12-01

    Although recent studies have indicated the potential adverse effects of maternal bisphenol A (BPA) exposure on pregnancy such as increasing the risk of pre-eclampsia, epidemiological evidence is limited. We aimed to evaluate the relationship between maternal BPA exposure and the risk of pre-eclampsia. We conducted a nested case-control study among 173 women (74 cases of pre-eclampsia and 99 controls). BPA concentrations were measured using liquid chromatography-mass spectrometry in the maternal serum samples collected during 16-20 gestational weeks. Multivariate logistic models were used to examine the relationship between maternal serum BPA concentrations and the risk of pre-eclampsia. BPA was detectable (>0.1 µg/l) in 78.6% of the maternal serum samples at three levels: low (<2.24 µg/l), medium (2.24-4.44 µg/l), and high (>4.44 µg/l). BPA concentrations were significantly higher in the serum samples collected from the pre-eclampsia cases than those from controls (median: 3.40 vs. 1.50 µg/l, P < 0.01). With adjustment for maternal age, primiparous and BMI, the odds of developing pre-eclampsia were significantly elevated in subjects with high serum BPA levels compared with those with low levels (adjusted OR = 16.46, 95%CI = 5.42-49.85) regardless of subcategories of pre-eclampsia including severity and onset time. Among the pre-eclampsia subjects, the maternal serum concentration of BPA was not different between the early- and late-onset subjects (median: 3.09 vs. 3.50 µg/l, P = 0.57), but surprisingly higher in mild pre-eclampsia subjects compared with severe pre-eclampsia subjects (median: 5.20 vs. 1.80 µg/l, P < 0.01). These results demonstrated that maternal exposure to high level of BPA could be associated with an increased risk of pre-eclampsia. © The Author 2017. Published by Oxford University Press on behalf of the European Public Health Association.

  2. Maternal serum bisphenol A levels and risk of pre-eclampsia: a nested case–control study

    PubMed Central

    Ye, Yunzhen; Zhou, Qiongjie; Feng, Liping; Wu, Jiangnan; Xiong, Yu; Li, Xiaotian

    2017-01-01

    Abstract Background Although recent studies have indicated the potential adverse effects of maternal bisphenol A (BPA) exposure on pregnancy such as increasing the risk of pre-eclampsia, epidemiological evidence is limited. We aimed to evaluate the relationship between maternal BPA exposure and the risk of pre-eclampsia. Methods We conducted a nested case–control study among 173 women (74 cases of pre-eclampsia and 99 controls). BPA concentrations were measured using liquid chromatography-mass spectrometry in the maternal serum samples collected during 16–20 gestational weeks. Multivariate logistic models were used to examine the relationship between maternal serum BPA concentrations and the risk of pre-eclampsia. Results BPA was detectable (>0.1 µg/l) in 78.6% of the maternal serum samples at three levels: low (<2.24 µg/l), medium (2.24-4.44 µg/l), and high (>4.44 µg/l). BPA concentrations were significantly higher in the serum samples collected from the pre-eclampsia cases than those from controls (median: 3.40 vs. 1.50 µg/l, P < 0.01). With adjustment for maternal age, primiparous and BMI, the odds of developing pre-eclampsia were significantly elevated in subjects with high serum BPA levels compared with those with low levels (adjusted OR = 16.46, 95%CI = 5.42–49.85) regardless of subcategories of pre-eclampsia including severity and onset time. Among the pre-eclampsia subjects, the maternal serum concentration of BPA was not different between the early- and late-onset subjects (median: 3.09 vs. 3.50 µg/l, P = 0.57), but surprisingly higher in mild pre-eclampsia subjects compared with severe pre-eclampsia subjects (median: 5.20 vs. 1.80 µg/l, P < 0.01). Conclusions These results demonstrated that maternal exposure to high level of BPA could be associated with an increased risk of pre-eclampsia. PMID:29186464

  3. Pre-eclampsia and preterm birth in Reunion Island: a 13 years cohort-based study. Comparison with international data.

    PubMed

    Iacobelli, Silvia; Bonsante, Francesco; Robillard, Pierre-Yves

    2016-09-01

    To assess the prevalence of preterm birth in pre-eclamptic deliveries in Reunion Island, a tropical overseas French department (départements d'outre-mer, DOM) and to compare this prevalence with that of international literature. All singleton live-born deliveries referred to three maternity centers in Reunion Island over 13 years were eligible. Data for comparison were found through searches of MEDLINE, bibliographies of identified studies, proceedings of meetings on pre-eclampsia and contact with relevant researchers. Incidence of pre-eclampsia, proportion of preterm (<37(0/7) weeks gestation), late (34(0/7)-36(6/7) weeks) and early (<34(0/7) weeks) preterm birth in pre-eclamptic deliveries were analyzed. Pre-eclampsia occurred in 2.3% of 51 927 singleton live-born deliveries in Reunion Island. The prevalence of preterm birth among pre-eclamptic deliveries was 59.8% (28.6% late and 31.2% early preterm birth). Among identified reports, only one prospective study from Canada (1986-1995) described preterm and early preterm birth rates higher than Reunion Island. A cohort-based report from Guadeloupe, another tropical French DOM, showed a preterm birth prevalence of 60.9%, with 30.8% of early preterm birth. Predominance of early- or late-onset pre-eclampsia has huge geographical differences. Further investigations are required to address risk factors for preterm birth and early onset pre-eclampsia in French DOM.

  4. IFPA Senior Award Lecture: making sense of pre-eclampsia - two placental causes of preeclampsia?

    PubMed

    Redman, C W; Sargent, I L; Staff, A C

    2014-02-01

    Incomplete spiral artery remodelling is the first of two stages of pre-eclampsia, typically of early onset. The second stage comprises dysregulated uteroplacental perfusion and placental oxidative stress. Oxidatively stressed syncytiotrophoblast (STB) over-secretes proteins that perturb maternal angiogenic balance and are considered to be pre-eclampsia biomarkers. We propose that, in addition and more fundamentally, these STB-derived proteins are biomarkers of a cellular (STB) stress response, which typically involves up-regulation of some proteins and down-regulation of others (positive and negative stress proteins respectively). Soluble vascular growth factor receptor-1 (sVEGFR-1) and reduced growth factor (PlGF) then exemplify positive and negative STB stress response proteins in the maternal circulation. Uncomplicated term pregnancy is associated with increasing sVEGFR-1 and decreasing PlGF, which can be interpreted as evidence of increasing STB stress. STB pathology, at or after term (for example focal STB necrosis) demonstrates this stress, with or without pre-eclampsia. We review the evidence that when placental growth reaches its limits at term, terminal villi become over-crowded with diminished intervillous pore size impeding intervillous perfusion with increasing intervillous hypoxia and STB stress. This type of STB stress has no antecedent pathology, so the fetuses are well-grown, as typifies late onset pre-eclampsia, and prediction is less effective than for the early onset syndrome because STB stress is a late event. In summary, abnormal placental perfusion and STB stress contribute to the pathogenesis of early and late onset pre-eclampsia. But the former has an extrinsic cause - poor placentation, whereas the latter has an intrinsic cause, 'microvillous overcrowding', as placental growth reaches its functional limits. This model explains important features of late pre-eclampsia and raises questions of how antecedent medical risk factors such as

  5. Pre-eclampsia part 1: current understanding of its pathophysiology

    PubMed Central

    Chaiworapongsa, Tinnakorn; Chaemsaithong, Piya; Yeo, Lami; Romero, Roberto

    2018-01-01

    Pre-eclampsia is characterized by new-onset hypertension and proteinuria at ≥20 weeks of gestation. In the absence of proteinuria, hypertension together with evidence of systemic disease (such as thrombocytopenia or elevated levels of liver transaminases) is required for diagnosis. This multisystemic disorder targets several organs, including the kidneys, liver and brain, and is a leading cause of maternal and perinatal morbidity and mortality. Glomeruloendotheliosis is considered to be a characteristic lesion of pre-eclampsia, but can also occur in healthy pregnant women. The placenta has an essential role in development of this disorder. Pathogenetic mechanisms implicated in pre-eclampsia include defective deep placentation, oxidative and endoplasmic reticulum stress, autoantibodies to type-1 angiotensin II receptor, platelet and thrombin activation, intravascular inflammation, endothelial dysfunction and the presence of an antiangiogenic state, among which an imbalance of angiogenesis has emerged as one of the most important factors. However, this imbalance is not specific to pre-eclampsia, as it also occurs in intrauterine growth restriction, fetal death, spontaneous preterm labour and maternal floor infarction (massive perivillous fibrin deposition). The severity and timing of the angiogenic imbalance, together with maternal susceptibility, might determine the clinical presentation of pre-eclampsia. This Review discusses the diagnosis, classification, clinical manifestations and putative pathogenetic mechanisms of pre-eclampsia. PMID:25003615

  6. Elucidating the Pathogenesis of Pre-eclampsia Using In Vitro Models of Spiral Uterine Artery Remodelling.

    PubMed

    McNally, Ross; Alqudah, Abdelrahim; Obradovic, Danilo; McClements, Lana

    2017-10-23

    The aim of the study is to perform a critical assessment of in vitro models of pre-eclampsia using complementary human and cell line-based studies. Molecular mechanisms involved in spiral uterine artery (SUA) remodelling and trophoblast functionality will also be discussed. A number of proteins and microRNAs have been implicated as key in SUA remodelling, which could be explored as early biomarkers or therapeutic targets for prevention of pre-eclampsia. Various 2D and 3D in vitro models involving trophoblast cells, endothelial cells, immune cells and placental tissue were discussed to elucidate the pathogenesis of pre-eclampsia. Nevertheless, pre-eclampsia is a multifactorial disease, and the mechanisms involved in its pathogenesis are complex and still largely unknown. Further studies are required to provide better understanding of the key processes leading to inappropriate placental development which is the root cause of pre-eclampsia. This new knowledge could identify novel biomarkers and treatment strategies.

  7. An open-label randomized-controlled trial of low dose aspirin with an early screening test for pre-eclampsia and growth restriction (TEST): Trial protocol.

    PubMed

    Mone, Fionnuala; Mulcahy, Cecilia; McParland, Peter; Stanton, Alice; Culliton, Marie; Downey, Paul; McCormack, Dorothy; Tully, Elizabeth; Dicker, Patrick; Breathnach, Fionnuala; Malone, Fergal D; McAuliffe, Fionnuala M

    2016-07-01

    Pre-eclampsia remains a worldwide cause of maternal and perinatal morbidity and mortality. Low dose aspirin (LDA) can reduce the occurrence of pre-eclampsia in women with identifiable risk factors. Emerging screening tests can determine the maternal risk of developing placental disease, such as pre-eclampsia from the first trimester of pregnancy. The aim of this study is to determine if it is more beneficial in terms of efficacy and acceptability to routinely prescribe LDA to nulliparous low-risk women compared to test indicated LDA on the basis of a positive screening test for placental disease. We propose a three armed multi-center open-labeled randomized control trial of; (i) routine LDA, (ii) no aspirin, and (iii) LDA on the basis of a positive first trimester pre-eclampsia screening test. LDA (75mg once daily) shall be given from the first trimester until 36-week gestation. The primary outcome measures include; (i) the proportion of eligible women that agree to participate (acceptability), (ii) compliance with study protocol (acceptability and feasibility), (iii) the proportion of women in whom it is possible to obtain first trimester trans-abdominal uterine artery Doppler examination (feasibility) and (iv) the proportion of women with a completed screening test that are issued the screening result within one week of having the test performed (feasibility). This will be the first clinical trial to determine the efficacy and acceptability in low-risk women of taking routine LDA versus no aspirin versus LDA based on a positive first trimester screening test for the prevention of placental disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Pre-eclampsia Diagnosis and Treatment Options: A Review of Published Economic Assessments.

    PubMed

    Zakiyah, Neily; Postma, Maarten J; Baker, Philip N; van Asselt, Antoinette D I

    2015-10-01

    Pre-eclampsia is a pregnancy complication affecting both mother and fetus. Although there is no proven effective method to prevent pre-eclampsia, early identification of women at risk of pre-eclampsia could enhance appropriate application of antenatal care, management and treatment. Very little is known about the cost effectiveness of these and other tests for pre-eclampsia, mainly because there is no clear treatment path. The aim of this study was to provide a comprehensive overview of the existing evidence on the health economics of screening, diagnosis and treatment options in pre-eclampsia. We searched three electronic databases (PubMed, EMBASE and the Cochrane Library) for studies on screening, diagnosis, treatment or prevention of pre-eclampsia, published between 1994 and 2014. Only full papers written in English containing complete economic assessments in pre-eclampsia were included. From an initial total of 138 references, six papers fulfilled the inclusion criteria. Three studies were on the cost effectiveness of treatment of pre-eclampsia, two of which evaluated magnesium sulphate for prevention of seizures and the third evaluated the cost effectiveness of induction of labour versus expectant monitoring. The other three studies were aimed at screening and diagnosis, in combination with subsequent preventive measures. The two studies on magnesium sulphate were equivocal on the cost effectiveness in non-severe cases, and the other study suggested that induction of labour in term pre-eclampsia was more cost effective than expectant monitoring. The screening studies were quite diverse in their objectives as well as in their conclusions. One study concluded that screening is probably not worthwhile, while two other studies stated that in certain scenarios it may be cost effective to screen all pregnant women and prophylactically treat those who are found to be at high risk of developing pre-eclampsia. This study is the first to provide a comprehensive overview

  9. Pre-eclampsia: pathophysiology, diagnosis, and management

    PubMed Central

    Uzan, Jennifer; Carbonnel, Marie; Piconne, Olivier; Asmar, Roland; Ayoubi, Jean-Marc

    2011-01-01

    The incidence of pre-eclampsia ranges from 3% to 7% for nulliparas and 1% to 3% for multiparas. Pre-eclampsia is a major cause of maternal mortality and morbidity, preterm birth, perinatal death, and intrauterine growth restriction. Unfortunately, the pathophysiology of this multisystem disorder, characterized by abnormal vascular response to placentation, is still unclear. Despite great polymorphism of the disease, the criteria for pre-eclampsia have not changed over the past decade (systolic blood pressure >140 mmHg or diastolic blood pressure ≥90 mmHg and 24-hour proteinuria ≥0.3 g). Clinical features and laboratory abnormalities define and determine the severity of pre-eclampsia. Delivery is the only curative treatment for pre-eclampsia. Multidisciplinary management, involving an obstetrician, anesthetist, and pediatrician, is carried out with consideration of the maternal risks due to continued pregnancy and the fetal risks associated with induced preterm delivery. Screening women at high risk and preventing recurrences are key issues in the management of pre-eclampsia. PMID:21822394

  10. Management of pre-eclampsia: issues for anaesthetists.

    PubMed

    Dennis, A T

    2012-09-01

    Pre-eclampsia is a leading cause of maternal morbidity and mortality. Substandard care is often present and many deaths are preventable. The aim of this review is to summarise the key management issues for anaesthetists in the light of the current literature. A systematic literature search of electronic databases was undertaken including MEDLINE, EMBASE and the Cochrane Library using the key words obstetrics, pregnancy, pregnancy complications, maternal, pre-eclampsia, preeclampsia, cardiac function, haemodynamics, haemolysis, elevated liver enzymes, low platelets (HELLP), eclampsia, anaesthesia, anesthesia, neuraxial. Relevant Colleges and Societies websites were examined for pertinent guidelines. The disease is defined within the context of hypertensive diseases, and early recognition of pre-eclampsia and its complications, as well as multidisciplinary expert team management is highlighted. Accurate monitoring and recording of observations including the use of transthoracic echocardiography is discussed. The importance of the treatment of systolic blood pressure>180 mmHg and the use of intravenous antihypertensive medication as well as the use of parenteral magnesium sulphate for the treatment and prevention of eclampsia is emphasised . Restricted intravenous fluid therapy and avoidance of ergometrine is discussed. Neuraxial analgesia and anaesthesia, and general anaesthesia for birth is summarised as well as postpartum management including analgesia, thromboprophylaxis, management of acute pulmonary oedema and the use of pharmacological agents in the setting of breastfeeding. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

  11. [Pre-eclampsia prevention in 2018 in general population and in lupic women: At the dawn of a personalized medicine?

    PubMed

    de Moreuil, C; Fauchais, A-L; Merviel, P; Tremouilhac, C; Le Moigne, E; Pasquier, E; Pan-Petesch, B; Lacut, K

    2018-06-19

    Pre-eclampsia prevention represents a major public health issue, as this vasculo-placental disorder generates a great burden of foeto-maternal morbi-mortality. Aspirin has proved its efficacy in primary and secondary pre-eclampsia prevention, especially when it is given at 150mg per day bedtime before 15 weeks of gestation to high-risk women. In the English trial ASPRE, high-risk women were identified by an algorithm taking into account angiogenic biomarkers ascertained at the end of first trimester of pregnancy. This article focuses on physiopathological mechanisms and risk factors of pre-eclampsia and on the interest of early angiogenic biomarkers dosing during pregnancy, for the assessment of pre-eclampsia risk. Unlike Great Britain or Israel, cost-effectiveness of this algorithm in general population has not been assessed in France. Finally, systemic lupus erythematous is at high risk of vasculo-placental disorders. Although few studies of angiogenic biomarkers dosing during lupus pregnancies identified a correlation between high sFlt1 levels at the end of first trimester and subsequent onset of severe vasculo-placental disorders, with a very good negative predictive value of sFtl1. Angiogenic biomarkers ascertainment for screening of vasculo-placental disorders in pregnant women with systemic lupus erythematous could allow targeting at best women needing an aspirin treatment and a closer monitoring. Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.

  12. Human resource constraints and the prospect of task-sharing among community health workers for the detection of early signs of pre-eclampsia in Ogun State, Nigeria.

    PubMed

    Akeju, David O; Vidler, Marianne; Sotunsa, J O; Osiberu, M O; Orenuga, E O; Oladapo, Olufemi T; Adepoju, A A; Qureshi, Rahat; Sawchuck, Diane; Adetoro, Olalekan O; von Dadelszen, Peter; Dada, Olukayode A

    2016-09-30

    The dearth of health personnel in low income countries has attracted global attention. Ways as to how health care services can be delivered in a more efficient and effective way using available health personnel are being explored. Task-sharing expands the responsibilities of low-cadre health workers and allows them to share these responsibilities with highly qualified health care providers in an effort to best utilize available human resources. This is appropriate in a country like Nigeria where there is a shortage of qualified health professionals and a huge burden of maternal mortality resulting from obstetric complications like pre-eclampsia. This study examines the prospect for task-sharing among Community Health Extension Workers (CHEW) for the detection of early signs of pre-eclampsia, in Ogun State, Nigeria. This study is part of a larger community-based trial evaluating the acceptability of community treatment for severe pre-eclampsia in Ogun State, Nigeria. Data was collected between 2011 and 2012 using focus group discussions; seven with CHEWs (n = 71), three with male decision-makers (n = 35), six with community leaders (n = 68), and one with member of the Society of Obstetricians and Gynaecologists of Nigeria (n = 9). In addition, interviews were conducted with the heads of the local government administration (n = 4), directors of planning (n = 4), medical officers (n = 4), and Chief Nursing Officers (n = 4). Qualitative data were analysed using NVivo version 10.0 3 computer software. The non-availability of health personnel is a major challenge, and has resulted in a high proportion of facility-based care performed by CHEWs. As a result, CHEWs often take on roles that are designated for senior health workers. This role expansion has exposed CHEWs to the basics of obstetric care, and has resulted in informal task-sharing among the health workers. The knowledge and ability of CHEWs to perform basic clinical assessments

  13. Alteration in iron status in pre eclampsia.

    PubMed

    Basher, K; Deb, K

    2006-01-01

    The aim of the study is to compare and contrast serum iron status in pre eclamptic women with normal pregnant women which may help in the establishment of diagnosis of pre eclampsia before appearance of its clinical manifestation. A total of 82 women in the last half of pregnancy, between 17 to 40 years of age, who attended the model family planning clinic, out patient and in patient departments of Obstetrics and Gynecology unit of Mymensingh Medical College Hospital, Mymensingh were selected for this purpose before any treatment was given in present pregnancy. Out of them 32 pregnant women were taken as control because they did not show any evidence of complication during the time of selection and 50 pregnant women were randomly selected as cases on the basic of having pre eclampsia. Mean value of serum iron was significantly increased in the pre eclamptic women in comparison to controls whereas mean values of both total iron binding capacity (TIBC) and unsaturated iron binding capacity (UIBC) were significantly decreased in pre eclamptic women in contrast to controls. The results allude to the possible contribution of released iron free radicals from ischaemic placenta in pre eclampsia to its etiology. So, routine investigation of serum iron status of pregnant women as part of antenatal checkup may help in the establishment of diagnosis of pre eclampsia before appearance of its clinical manifestation.

  14. Pre-eclampsia and childhood asthma.

    PubMed

    Magnus, Maria C; Håberg, Siri E; Magnus, Per; Engeland, Anders; Nafstad, Per; Karlstad, Øystein; Nystad, Wenche

    2016-12-01

    Studies of pre-eclampsia and childhood asthma are conflicting, and none have performed a formal mediation analysis of preterm birth.We examined the association between pre-eclampsia and asthma at 7 years using national registries, including all births in Norway from 1999 to 2006 (n=406 907), and a subsample of children in the Norwegian Mother and Child Cohort Study (MoBa) (n=45 028) using log-linear regression. We performed a mediation analysis of preterm birth, and a sibling comparison to evaluate unobserved confounding.There was a positive association between pre-eclampsia and asthma in the registry study, with an adjusted relative risk of 1.31 (95% CI 1.22-1.41), but not in MoBa, which had an adjusted relative risk of 1.19 (95% CI 0.99-1.44). The odds ratios for the direct effect not mediated through preterm birth and the indirect effect in the registry linkage were 1.19 (95% CI 1.10-1.29) and 1.12 (95% CI 1.11-1.14), respectively. The sibling comparison indicated no association between pre-eclampsia and asthma (adjusted OR 1.07, 95% CI 0.87-1.33).In this large study, which used different datasets and analytic approaches, there was little evidence for an association between pre-eclampsia and childhood asthma. The association was weak and largely explained by pre-term birth and confounders shared by siblings. Copyright ©ERS 2016.

  15. Molecular association of pathogenetic contributors to pre-eclampsia (pre-eclampsia associome)

    PubMed Central

    2015-01-01

    Background Pre-eclampsia is the most common complication occurring during pregnancy. In the majority of cases, it is concurrent with other pathologies in a comorbid manner (frequent co-occurrences in patients), such as diabetes mellitus, gestational diabetes and obesity. Providing bronchial asthma, pulmonary tuberculosis, certain neurodegenerative diseases and cancers as examples, we have shown previously that pairs of inversely comorbid pathologies (rare co-occurrences in patients) are more closely related to each other at the molecular genetic level compared with randomly generated pairs of diseases. Data in the literature concerning the causes of pre-eclampsia are abundant. However, the key mechanisms triggering this disease that are initiated by other pathological processes are thus far unknown. The aim of this work was to analyse the characteristic features of genetic networks that describe interactions between comorbid diseases, using pre-eclampsia as a case in point. Results The use of ANDSystem, Pathway Studio and STRING computer tools based on text-mining and database-mining approaches allowed us to reconstruct associative networks, representing molecular genetic interactions between genes, associated concurrently with comorbid disease pairs, including pre-eclampsia, diabetes mellitus, gestational diabetes and obesity. It was found that these associative networks statistically differed in the number of genes and interactions between them from those built for randomly chosen pairs of diseases. The associative network connecting all four diseases was composed of 16 genes (PLAT, ADIPOQ, ADRB3, LEPR, HP, TGFB1, TNFA, INS, CRP, CSRP1, IGFBP1, MBL2, ACE, ESR1, SHBG, ADA). Such an analysis allowed us to reveal differential gene risk factors for these diseases, and to propose certain, most probable, theoretical mechanisms of pre-eclampsia development in pregnant women. The mechanisms may include the following pathways: [TGFB1 or TNFA]-[IL1B]-[pre-eclampsia]; [TNFA

  16. Pre-eclampsia and offspring cardiovascular health: mechanistic insights from experimental studies.

    PubMed

    Davis, Esther F; Newton, Laura; Lewandowski, Adam J; Lazdam, Merzaka; Kelly, Brenda A; Kyriakou, Theodosios; Leeson, Paul

    2012-07-01

    Pre-eclampsia is increasingly recognized as more than an isolated disease of pregnancy. Women who have had a pregnancy complicated by pre-eclampsia have a 4-fold increased risk of later cardiovascular disease. Intriguingly, the offspring of affected pregnancies also have an increased risk of higher blood pressure and almost double the risk of stroke in later life. Experimental approaches to identify the key features of pre-eclampsia responsible for this programming of offspring cardiovascular health, or the key biological pathways modified in the offspring, have the potential to highlight novel targets for early primary prevention strategies. As pre-eclampsia occurs in 2-5% of all pregnancies, the findings are relevant to the current healthcare of up to 3 million people in the U.K. and 15 million people in the U.S.A. In the present paper, we review the current literature that concerns potential mechanisms for adverse cardiovascular programming in offspring exposed to pre-eclampsia, considering two major areas of investigation: first, experimental models that mimic features of the in utero environment characteristic of pre-eclampsia, and secondly, how, in humans, offspring cardiovascular phenotype is altered after exposure to pre-eclampsia. We compare and contrast the findings from these two bodies of work to develop insights into the likely key pathways of relevance. The present review and analysis highlights the pivotal role of long-term changes in vascular function and identifies areas of growing interest, specifically, response to hypoxia, immune modification, epigenetics and the anti-angiogenic in utero milieu.

  17. Pre-eclampsia and offspring cardiovascular health: mechanistic insights from experimental studies

    PubMed Central

    Davis, Esther F.; Newton, Laura; Lewandowski, Adam J.; Lazdam, Merzaka; Kelly, Brenda A.; Kyriakou, Theodosios; Leeson, Paul

    2012-01-01

    Pre-eclampsia is increasingly recognized as more than an isolated disease of pregnancy. Women who have had a pregnancy complicated by pre-eclampsia have a 4-fold increased risk of later cardiovascular disease. Intriguingly, the offspring of affected pregnancies also have an increased risk of higher blood pressure and almost double the risk of stroke in later life. Experimental approaches to identify the key features of pre-eclampsia responsible for this programming of offspring cardiovascular health, or the key biological pathways modified in the offspring, have the potential to highlight novel targets for early primary prevention strategies. As pre-eclampsia occurs in 2–5% of all pregnancies, the findings are relevant to the current healthcare of up to 3 million people in the U.K. and 15 million people in the U.S.A. In the present paper, we review the current literature that concerns potential mechanisms for adverse cardiovascular programming in offspring exposed to pre-eclampsia, considering two major areas of investigation: first, experimental models that mimic features of the in utero environment characteristic of pre-eclampsia, and secondly, how, in humans, offspring cardiovascular phenotype is altered after exposure to pre-eclampsia. We compare and contrast the findings from these two bodies of work to develop insights into the likely key pathways of relevance. The present review and analysis highlights the pivotal role of long-term changes in vascular function and identifies areas of growing interest, specifically, response to hypoxia, immune modification, epigenetics and the anti-angiogenic in utero milieu. PMID:22455350

  18. Significantly higher number of fetal cells in the maternal circulation of women with pre-eclampsia.

    PubMed

    Jansen, M W; Korver-Hakkennes, K; van Leenen, D; Visser, W; in 't Veld, P A; de Groot, C J; Wladimiroff, J W

    2001-12-01

    Although the pathophysiology of pre-eclampsia is unknown, several studies have indicated that abnormal placentation early in pregnancy might play a key role. It has recently been suggested that this abnormal placentation may result in transfusion of fetal cells (feto-maternal transfusion) in women with pre-eclampsia. In the present study, fetal nucleated red blood cells were isolated from 20 women with pre-eclampsia and 20 controls using a very efficient magnetic activated cell sorting (MACS) protocol. The number of male cells was determined using two-color fluorescence in situ hybridization (FISH) for X and Y chromosomes. Significantly more XY cells could be detected in women with pre-eclampsia (0.61+/-1.2 XY cells/ml blood) compared to women with uncomplicated pregnancies (0.02+/-0.04 XY cells/ml blood) (Mann-Whitney U-test, p<0.001). These results suggest that fetal cell trafficking is enhanced in women with pre-eclampsia, and this finding may contribute to the understanding of the pathophysiology of the disease. Copyright 2001 John Wiley & Sons, Ltd.

  19. Diet and Pre-eclampsia: A Prospective Multicentre Case-Control Study in Ethiopia.

    PubMed

    Endeshaw, Mulualem; Abebe, Fantu; Bedimo, Melkamu; Asart, Anemaw

    2015-06-01

    against pre-eclampsia (AOR=0.51, 95% CI: 0.29, 0.91; AOR=0.46, 95% CI: 0.24, 0.90, respectively). In addition, compliance with folate intake during pregnancy has shown a significant independent effect on the prevention of pre-eclampsia in this study (AOR=0.16, 95% CI: 0.08, 0.29). Adequate vegetable and fruit consumption and compliance with folate intake during pregnancy are independent protective factors against pre-eclampsia. On the other hand, higher MUAC, anaemia and daily coffee intake during pregnancy are risk factors for the development of pre-eclampsia. Audience-specific education and promotion of the use of the protective factors identified in this study should be prioritized. The risk factors identified can be used for prediction and early diagnoses of pre-eclampsia allowing timely interventions to be performed to minimize deaths associated with severe pre-eclampsia/eclampsia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Serum Fatty Acid Binding Protein 4 (FABP4) Predicts Pre-eclampsia in Women With Type 1 Diabetes.

    PubMed

    Wotherspoon, Amy C; Young, Ian S; McCance, David R; Patterson, Chris C; Maresh, Michael J A; Pearson, Donald W M; Walker, James D; Holmes, Valerie A

    2016-10-01

    To examine the association between fatty acid binding protein 4 (FABP4) and pre-eclampsia risk in women with type 1 diabetes. Serum FABP4 was measured in 710 women from the Diabetes and Pre-eclampsia Intervention Trial (DAPIT) in early pregnancy and in the second trimester (median 14 and 26 weeks' gestation, respectively). FABP4 was significantly elevated in early pregnancy (geometric mean 15.8 ng/mL [interquartile range 11.6-21.4] vs. 12.7 ng/mL [interquartile range 9.6-17]; P < 0.001) and the second trimester (18.8 ng/mL [interquartile range 13.6-25.8] vs. 14.6 ng/mL [interquartile range 10.8-19.7]; P < 0.001) in women in whom pre-eclampsia later developed. Elevated second-trimester FABP4 level was independently associated with pre-eclampsia (odds ratio 2.87 [95% CI 1.24-6.68], P = 0.03). The addition of FABP4 to established risk factors significantly improved net reclassification improvement at both time points and integrated discrimination improvement in the second trimester. Increased second-trimester FABP4 independently predicted pre-eclampsia and significantly improved reclassification and discrimination. FABP4 shows potential as a novel biomarker for pre-eclampsia prediction in women with type 1 diabetes. © 2016 by the American Diabetes Association.

  1. Maternal and fetal plasma zinc in pre-eclampsia.

    PubMed

    Bassiouni, B A; Foda, A I; Rafei, A A

    1979-04-01

    Zinc is important for fetal growth and is involved in several important enzyme systems. Maternal and umbilical plasma zinc concentrations were determined in 52 parturient women with mild and severe pre-eclampsia, and were compared with those obtained from 20 women in labor whose pregnancies had progressed normally. A decrease in maternal as well as umbilical plasma zinc concentrations was observed in pre-eclamptic women, and this decrease was statistically significant in severe pre-eclampsia. The causes of these changes in plasma zinc concentrations in pre-eclampsia were discussed, and the possible adverse effects of zinc deficiency on the mother and fetus were mentioned. Low plasma zinc concentrations in pre-eclampsia may be a sign of zinc deficiency, implying possible risks to the mother and her fetus. It is recommended that maintenance of adequate dietary zinc nutrition during pregnancy, and particularly in pre-eclampsia, is important.

  2. Accuracy of angiogenic biomarkers at ⩽20weeks' gestation in predicting the risk of pre-eclampsia: A WHO multicentre study.

    PubMed

    Widmer, Mariana; Cuesta, Cristina; Khan, Khalid S; Conde-Agudelo, Agustin; Carroli, Guillermo; Fusey, Shalini; Karumanchi, S Ananth; Lapaire, Olav; Lumbiganon, Pisake; Sequeira, Evan; Zavaleta, Nelly; Frusca, Tiziana; Gülmezoglu, A Metin; Lindheimer, Marshall D

    2015-10-01

    To assess the accuracy of angiogenic biomarkers to predict pre-eclampsia. Prospective multicentre study. From 2006 to 2009, 5121 pregnant women with risk factors for pre-eclampsia (nulliparity, diabetes, previous pre-eclampsia, chronic hypertension) from Argentina, Colombia, Peru, India, Italy, Kenya, Switzerland and Thailand had their serum tested for sFlt-1, PlGF and sEng levels and their urine for PlGF levels at ⩽20, 23-27 and 32-35weeks' gestation (index tests, results blinded from carers). Women were monitored for signs of pre-eclampsia, diagnosed by systolic blood pressure ⩾140mmHg and/or diastolic blood pressure ⩾90mmHg, and proteinuria (protein/creatinine ratio ⩾0.3, protein ⩾1g/l, or one dipstick measurement ⩾2+) appearing after 20weeks' gestation. Early pre-eclampsia was defined when these signs appeared ⩽34weeks' gestation. Pre-eclampsia. Pre-eclampsia was diagnosed in 198 of 5121 women tested (3.9%) of whom 47 (0.9%) developed it early. The median maternal serum concentrations of index tests were significantly altered in women who subsequently developed pre-eclampsia than in those who did not. However, the area under receiver operating characteristics curve at ⩽20weeks' gestation were closer to 0.5 than to 1.0 for all biomarkers both for predicting any pre-eclampsia or at ⩽34weeks' gestation. The corresponding sensitivity, specificity and likelihood ratios were poor. Multivariable models combining sEng with clinical features slightly improved the prediction capability. Angiogenic biomarkers in first half of pregnancy do not perform well enough in predicting the later development of pre-eclampsia. Copyright © 2015. Published by Elsevier B.V.

  3. Tests for predicting complications of pre-eclampsia: A protocol for systematic reviews

    PubMed Central

    Thangaratinam, Shakila; Coomarasamy, Arri; Sharp, Steve; O'Mahony, Fidelma; O'Brien, Shaughn; Ismail, Khaled MK; Khan, Khalid S

    2008-01-01

    Background Pre-eclampsia is associated with several complications. Early prediction of complications and timely management is needed for clinical care of these patients to avert fetal and maternal mortality and morbidity. There is a need to identify best testing strategies in pre eclampsia to identify the women at increased risk of complications. We aim to determine the accuracy of various tests to predict complications of pre-eclampsia by systematic quantitative reviews. Method We performed extensive search in MEDLINE (1951–2004), EMBASE (1974–2004) and also will also include manual searches of bibliographies of primary and review articles. An initial search has revealed 19500 citations. Two reviewers will independently select studies and extract data on study characteristics, quality and accuracy. Accuracy data will be used to construct 2 × 2 tables. Data synthesis will involve assessment for heterogeneity and appropriately pooling of results to produce summary Receiver Operating Characteristics (ROC) curve and summary likelihood ratios. Discussion This review will generate predictive information and integrate that with therapeutic effectiveness to determine the absolute benefit and harm of available therapy in reducing complications in women with pre-eclampsia. PMID:18694494

  4. Post-partum recovery course in patients with gestational hypertension and pre-eclampsia.

    PubMed

    Mikami, Yukiko; Takagi, Kenjiro; Itaya, Yukiko; Ono, Yoshihisa; Matsumura, Hideyoshi; Takai, Yasushi; Seki, Hiroyuki

    2014-04-01

    We examined the post-partum recovery course in patients with pre-eclampsia (PE) and gestational hypertension (GH) and evaluated the associated factors. In a retrospective review of 145 patients with GH or PE who gave birth between 1 January 2008 and 30 October 2011 at our institution, there were 125 PE and 20 GH cases. Data collected included the gestational age at initial examination and delivery, delivery mode, time for normalization of blood pressure (BP), and time until resolution of proteinuria in PE patients. Comparisons were made between singleton and multiple pregnancies, onset (early, <32 weeks; late, ≥ 32 weeks) and fetal growth restriction in singleton pregnancies. The mean interval for normalization of BP was 41.8 ± 29.4 days (median, 31.5). The mean interval for resolution of proteinuria was 30.0 ± 39.6 days (median, 27.0). Ninety percent of patients required 77 and 60 days to recover from hypertension and proteinuria, respectively. The time for BP normalization was longer in the early-onset group. The time for resolution of proteinuria was not affected by any factor examined. A post-partum observation period of 12 weeks is acceptable for differentiating PE and GH from chronic hypertension or renal disease. GH severity did not affect the recovery period, but proteinuria severity did. Onset time was a factor influencing the recovery from PE and GH. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

  5. Is inflammation the cause of pre-eclampsia?

    PubMed Central

    Ramma, Wenda; Ahmed, Asif

    2011-01-01

    It has been proposed that either excessive inflammation or an imbalance in angiogenic factors cause pre-eclampsia. In the present review, the arguments for and against the role of inflammation and/or angiogenic imbalance as the cause of pre-eclampsia are discussed on the basis of the Bradford–Hill criteria for disease causation. Although both angiogenic imbalance and systemic inflammation are implicated in pre-eclampsia, the absence of temporality of inflammatory markers with pre-eclampsia challenges the concept that excessive inflammation is the cause of pre-eclampsia. In contrast, the elevation of anti-angiogenic factors that precede the clinical signs of pre-eclampsia fulfils the criterion of temporality. The second most important criterion is the dose–response relationship. Although such a relationship has not been proven between pro-inflammatory cytokines and pre-eclampsia, high levels of anti-angiogenic factors have been shown to correlate with increased incidence and disease severity, hence satisfying this condition. Finally, as the removal of circulating sFlt-1 (soluble Fms-like tyrosine kinase receptor-1) from pre-eclamptic patients significantly improves the clinical outcome, it fulfils the Hill's experiment principle, which states that removal of the cause by an appropriate experimental regimen should ameliorate the condition. In contrast, treatment with high doses of corticosteroid fails to improve maternal outcome in pre-eclampsia, despite suppressing inflammation. Inflammation may enhance the pathology induced by the imbalance in the angiogenic factors, but does not by itself cause pre-eclampsia. Development of therapies based on the angiogenic and cytoprotective mechanisms seems more promising. PMID:22103497

  6. Biomarkers of glomerular dysfunction in pre-eclampsia - A systematic review.

    PubMed

    Kerley, Robert N; McCarthy, Cathal

    2018-03-10

    Early detection of pre-eclampsia remains one of the major focuses of antenatal obstetric care. There is often a delay in the diagnosis, mainly due to the non-specific nature of the condition. Podocytes which play a pivotal role in glomerular function become injured in pre-eclampsia leading to subsequent proteinuria. Our aim was to review available studies to determine the clinical utility of biomarkers of podocyte injury in pre-eclampsia. We used QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria to perform a systematic review of the literature to determine the clinical utility of podocyte injury biomarkers in predicting pre-eclampsia. This study identified five potential renal biomarkers including podocytes, nephrin, synaptopodin, podocin and podocalyxin. The pooled sensitivity of all biomarkers was 0.78 (95% CI 0.74-0.82) with a specificity of 0.82 (95% CI 0.79-0.85). The area under the Summary of Receiver Operating Characteristics Curve (SROC) was 0.926 (SE 0.30). Urinary nephrin achieved the highest diagnostic values with a sensitivity of 0.81 (95% CI 0.72-0.88) and specificity of 0.84 (95% CI 0.79-0.84). Biomarkers of glomerular injury show promise as diagnostic aids in pre-eclampsia. A large-scale prospective cohort study is warranted before these biomarkers can be recommended for routine clinical care. Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

  7. Maternal rubella immunity status and pre-eclampsia.

    PubMed

    Lao, Terence T; Sahota, Daljit S; Law, Lai-Wa; Leung, Tak-Yeung

    2017-07-01

    To determine if maternal immune maladaptation associated with pre-eclampsia is reflected in the rubella immunity status. Incidence of pre-eclampsia was compared between rubella non-immune and immune gravidae carrying a singleton pregnancy beyond 24 weeks, taking into account maternal characteristics and reported risk factors for pre-eclampsia. The 9870 (10.4%) rubella non-immune gravidae among the 95 024 in the cohort exhibited no difference in incidence of underlying medical disorders, but they were slightly but significantly older, shorter, heavier, and had more pre-eclampsia (OR 1.24, 95% CI 1.05-1.47) despite having fewer nulliparas. Regression analysis confirmed an overall association between rubella non-immunity with pre-eclampsia (aOR 1.27, 95% CI 1.06-1.54), which was related to multiparas (aOR 1.42, 95% CI 1.05-1.91) and carrying a male fetus (aOR 1.37, 95% CI 1.06-1.78). The association between rubella non-immunity and pre-eclampsia reflects immune maladaptation in multiparas and toward a male fetus. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. ST2 and IL-33 in Pregnancy and Pre-Eclampsia

    PubMed Central

    Snider, James V.; Tannetta, Dionne S.; Child, Tim; Redman, Christopher W. G.; Sargent, Ian L.

    2011-01-01

    Normal pregnancy is associated with a mild systemic inflammatory response and an immune bias towards type 2 cytokine production, whereas pre-eclampsia is characterized by a more intense inflammatory response, associated with endothelial dysfunction and a type 1 cytokine dominance. Interleukin (IL)-33 is a newly described member of the IL-1 family, which binds its receptor ST2L to induce type 2 cytokines. A soluble variant of ST2 (sST2) acts as a decoy receptor to regulate the activity of IL-33. In this study circulating IL-33 and sST2 were measured in each trimester of normal pregnancy and in women with pre-eclampsia. While IL-33 did not change throughout normal pregnancy, or between non-pregnant, normal pregnant or pre-eclamptic women, sST2 was significantly altered. sST2 was increased in the third trimester of normal pregnancy (p<0.001) and was further increased in pre-eclampsia (p<0.001). This increase was seen prior to the onset of disease (p<0.01). Pre-eclampsia is a disease caused by placental derived factors, and we show that IL-33 and ST2 can be detected in lysates from both normal and pre-eclampsia placentas. ST2, but not IL-33, was identified on the syncytiotrophoblast layer, whereas IL-33 was expressed on perivascular tissue. In an in vitro placental perfusion model, sST2 was secreted by the placenta into the ‘maternal’ eluate, and placental explants treated with pro-inflammatory cytokines or subjected to hypoxia/reperfusion injury release more sST2, suggesting the origin of at least some of the increased amounts of circulating sST2 in pre-eclamptic women is the placenta. These results suggest that sST2 may play a significant role in pregnancies complicated by pre-eclampsia and increased sST2 could contribute to the type 1 bias seen in this disorder. PMID:21949719

  9. Biomarkers for the management of pre-eclampsia in pregnant women

    PubMed Central

    Petla, Lakshmi Tanuja; Chikkala, Rosy; Ratnakar, K.S.; Kodati, Vijayalakshmi; Sritharan, V.

    2013-01-01

    Pre-eclampsia (PE) is a pregnancy related disorder characterized by hypertension and proteinuria noticeable after 20 wk of gestation. It is a leading cause of maternal and foetal mortality and morbidity worldwide. The aetiology of the disease is unknown, but recent studies have revealed that this disorder appears to originate in placenta and is characterized by widespread maternal endothelial dysfunction. Till date, delivery of placenta is the only cure for the disease. So, there is a need for the identification of highly specific and sensitive biochemical markers that would allow early identification of patients at risk and thus help in providing proper prenatal care. Several promising biomarkers have been proposed, alone or in combination, that may help in predicting women who are likely to develop PE. Maternal serum concentrations of these biomarkers either increase or decrease in PE during gestation. This review focuses on the various biomarkers available and their utility in predicting pre-eclampsia. PMID:24056556

  10. Monocytes and Macrophages in Pregnancy and Pre-Eclampsia

    PubMed Central

    Faas, Marijke M.; Spaans, Floor; De Vos, Paul

    2014-01-01

    Preeclampsia is an important complication in pregnancy, characterized by hypertension and proteinuria in the second half of pregnancy. Generalized activation of the inflammatory response is thought to play a role in the pathogenesis of pre-eclampsia. Monocytes may play a central role in this inflammatory response. Monocytes are short lived cells that mature in the circulation and invade into tissues upon an inflammatory stimulus and develop into macrophages. Macrophages are abundantly present in the endometrium and play a role in implantation and placentation in normal pregnancy. In pre-eclampsia, these macrophages appear to be present in larger numbers and are also activated. In the present review, we focused on the role of monocytes and macrophages in the pathophysiology of pre-eclampsia. PMID:25071761

  11. The Efficiency of First-Trimester Uterine Artery Doppler, ADAM12, PAPP-A and Maternal Characteristics in the Prediction of Pre-Eclampsia

    PubMed Central

    GOETZINGER, Katherine R.; ZHONG, Yan; CAHILL, Alison G.; ODIBO, Linda; MACONES, George A.; ODIBO, Anthony O.

    2014-01-01

    Objective To estimate the efficiency of first-trimester uterine artery Doppler, A-disintegrin and metalloprotease 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A) and maternal characteristics in the prediction of pre-eclampsia. Methods This is a prospective cohort study of patients presenting for first-trimester aneuploidy screening between 11-14 weeks’ gestation. Maternal serum ADAM12 and PAPP-A levels were measured by immunoassay, and mean uterine artery Doppler pulsatility indices (PI) were calculated. Outcomes of interest included pre-eclampsia, early pre-eclampsia, defined as requiring delivery at <34 weeks’ gestation, and gestational hypertension. Logistic regression analysis was used to model the prediction of pre-eclampsia using ADAM12 multiples of the median (MoM), PAPP-A MoM, and uterine artery Doppler PI MoM, either individually or in combination. Sensitivity, specificity, and area under the receiver-operating characteristic curves (AUC) were used to compare the screening efficiency of the models using non-parametric U-statistics. Results Of 578 patients with complete outcome data, there were 54 (9.3%) cases of preeclampsia and 13 (2.2%) cases of early pre-eclampsia. Median ADAM12 levels were significantly lower in patients who developed pre-eclampsia compared to those who did not. (0.81 v. 1.01 MoMs; p<0.04) For a fixed false positive rate (FPR) of 10%, ADAM12, PAPP-A, and uterine artery Doppler in combination with maternal characteristics identified 50%, 48%, and 52% of patients who developed pre-eclampsia, respectively. Combining these first-trimester parameters did not improve the predictive efficiency of the models. Conclusion First-trimester ADAM12, PAPP-A, and uterine artery Doppler are not sufficiently predictive of pre-eclampsia. Combinations of these parameters do not further improve their screening efficiency. PMID:23980220

  12. Role of cytokines in development of pre-eclampsia associated with periodontal disease - Cohort Study.

    PubMed

    Kumar, Ashok; Begum, Nargis; Prasad, Sudha; Lamba, Arundeep K; Verma, Mahesh; Agarwal, Sarita; Sharma, Shashi

    2014-04-01

    The present study was designed to find any association of cytokines in women with periodontal disease and development of pre-eclampsia in North Indian population. A total of 504 consecutively registered primigravida with a single live pregnancy were recruited at 14-18 weeks of gestation from antenatal clinic of Maulana Azad Medical College & associated Lok Nayak Hospital and Maulana Azad Institute of Dental Sciences, New Delhi. One periodontist performed oral health examination of all patients at inclusion into study. Blood samples were collected to measure the level of cytokines IL-4, IL-10, TNF-α and IFN-γ. The profile of blood levels of cytokines from women with periodontal disease was observed. The log serum levels of TNF-α & IL-4 at 16-18 weeks of gestation were significantly higher in women with periodontal disease (4.13 ± 2.06; 0.47 ± 1.56 pg/ml respectively) than in women with healthy gums (2.16 ± 1.51; 0.02 ± 1.84 pg/ml respectively, p < 0.001). Periodontal disease is associated with log serum TNF-α levels at cut-off ≥14.43 pg/ml at sensitivity 71.2% and specificity 62% (OR = 4.04; 95%CI = 2.77-5.87). Woman with periodontal disease who later developed pre-eclampsia had lower levels of TNF-α (3.72 ± 1.33 pg/ml) than those with periodontal disease who did not develop pre-eclampsia (4.20 ± 2.15 pg/ml, p ≥ 0.05). Reduced TNF-α level secretion in the early second trimester in women with periodontal disease appears to be associated with the development of pre-eclampsia. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. A prospective study of maternal carboxyhaemoglobin and pre-eclampsia risk.

    PubMed

    Rudra, Carole B; Williams, Michelle A; Schiff, Melissa A; Koenig, Jane Q; Dills, Russell; Yu, Jianbo

    2010-01-01

    We aimed to measure the relationship between early-pregnancy maternal carboxyhaemoglobin and subsequent pre-eclampsia risk. A nested case-control analysis was conducted using data from a western Washington State cohort study (1996-2004). We measured maternal whole blood carboxyhaemoglobin in 128 women who developed pre-eclampsia and 419 normotensive controls (mean gestational age at blood draw, 14.8 weeks). After adjustment for confounders, high (>/=1%) vs. low (<0.7%) carboxyhaemoglobin odds ratios [OR] and 95% confidence intervals [CI] were 4.09 [1.30, 12.9] in multiparous women, 0.53 [0.23, 1.26] in primiparae and 1.11 [0.55, 2.25] in the overall study population (parity interaction P = 0.01). The influence of parity on the association was unexpected. The association between high carboxyhaemoglobin and pre-eclampsia risk in multiparae implicates hypoxia at the fetal-maternal interface as a pathogenic mechanism. These results also suggest that the aetiology of the disease may differ according to parity.

  14. Placental stress and pre-eclampsia: a revised view.

    PubMed

    Redman, C W G; Sargent, I L

    2009-03-01

    In pre-eclampsia, poor placentation causes both oxidative and endoplasmic reticulum stress of the placenta. It is believed placental hypoxia stimulates excessive production of soluble fms-like tyrosine kinase 1 (sFlt-1), which binds and deactivates circulating vascular endothelial growth factor (VEGF). When maternal endothelium is deprived of VEGF it becomes dysfunctional hence leading to the clinical syndrome of the mother. In this paper the previous claim that poor placentation may predispose more to placental oxidative stress than hypoxia is reiterated. We show why pre-eclampsia is not only an endothelial disease, but also a disorder of systemic inflammation. We question that hypoxia is the only or indeed the main stimulus to release of sFlt-1; and emphasise the role of inflammatory mechanisms. Hypoxia cannot be assumed simply because hypoxia-inducible transcription factors (HIF) are upregulated. Concurrent assessments of nuclear factor-kappaB (NF-kappaB), a transcription factor for inflammatory responses are desirable to obtain a more complete picture. We point out that the pre-eclampsia placenta is the source of bioactive circulating factors other than sFlt-1 in concentrations that are much higher than in normal pregnancy. These may also contribute to the final inflammatory syndrome. We propose a modified version of the two-stage model for pre-eclampsia.

  15. The definition of severe and early-onset preeclampsia. Statements from the International Society for the Study of Hypertension in Pregnancy (ISSHP).

    PubMed

    Tranquilli, Andrea L; Brown, Mark A; Zeeman, Gerda G; Dekker, Gustaaf; Sibai, Baha M

    2013-01-01

    There is discrepancy in the literature on the definitions of severe and early-onset pre-eclampsia. We aimed to determine those definitions for clinical purposes and to introduce them in the classification of the hypertensive disorders of pregnancy for publication purposes. We circulated a questionnaire to the International Committee of the International Society for the Study of Hypertension in Pregnancy focusing on the thresholds for defining severe preeclampsia and the gestation at which to define early-onset preeclampsia, and on the definition and inclusion of the HELLP syndrome or other clinical features in severe preeclampsia. The questions were closed, but all answers had space for more open detailed comments. There was a general agreement to define preeclampsia as severe if blood pressure was >160mmHg systolic or 110mmHg diastolic. There was scarce agreement on the amount of proteinuria to define severity. The HELLP syndrome was considered a feature to include in the severe classification. Most investigators considered early-onset preeclampsia as that occurring before 34weeks. A definition of pre-eclampsia is paramount for driving good clinical practice. Classifications on the other hand are useful to enable international comparisons of clinical data and outcomes. We used the results of this survey to update our previous classification for the purposes of providing clinical research definitions of severe and early onset pre-eclampsia that will hopefully be accepted in the international literature. Copyright © 2012 International Society for the Study of Hypertension in Pregnancy. All rights reserved.

  16. Candidate gene study of genetic thrombophilic polymorphisms in pre-eclampsia and recurrent pregnancy loss in Sinhalese women.

    PubMed

    Dissanayake, Vajira H W; Sirisena, Nirmala D; Weerasekera, Lakshini Y; Gammulla, Chumithri G; Seneviratne, Harshalal R; Jayasekara, Rohan W

    2012-09-01

    Genetic thrombophilias are known to contribute to adverse pregnancy outcomes. Studies in Western populations show that 5, 10-methylenetetrahydrofolate reductase (MTHFR) 677C>T and Factor V (F5) 1691G>A (Leiden) polymorphisms are commonly associated with pre-eclampsia and recurrent spontaneous pregnancy loss. The objective of this study was to investigate the association of MTHFR 677C>T (rs1801133); 1298A>C (rs1801131) and F5 1691G>A (rs6025); 4070A>G (rs1800595) polymorphisms with pre-eclampsia and recurrent pregnancy loss among Sinhalese women in Sri Lanka. Genotype and allele frequencies at each polymorphic site in the MTHFR and F5 genes and the haplotypes defined by them were determined in 175 Sinhalese women with pre-eclampsia, 171 normotensive controls, 200 Sinhalese women with two or more recurrent pregnancy losses and 200 controls with two or more living children and no pregnancy losses. Genotyping was done by polymerase chain reaction/restriction fragment length polymorphism. Odds ratios and χ(2) -testing were performed to compare genotype/haplotype frequencies at each polymorphic site for both cases and controls. The genotype frequencies at each polymorphic site in the MTHFR 677C>T; 1298A>C; F5 1691G>A and 4070A>G genes and the haplotypes defined by them were not significantly associated with either pre-eclampsia or recurrent pregnancy loss. There was no significant association of genetic thrombophilia with either early or late pregnancy losses. The MTHFR and F5 polymorphisms and the haplotypes defined by them were not significantly associated with either pre-eclampsia or recurrent pregnancy loss in this group of Sinhalese women. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  17. Biomarkers of oxidative stress in pre-eclampsia.

    PubMed

    Poston, Lucilla; Chappell, Lucy; Seed, Paul; Shennan, Andrew

    2011-01-01

    Pre-eclampsia is associated with oxidative stress, confirmed by measurement of biomarkers and relevant antioxidant enzymes in the placenta and maternal circulation. Studies in vitro have described the pathways by which placental ischaemia can lead to oxidative stress as well as endoplasmic reticulum stress, which is coupled to synthesis of reactive oxygen species. However, clinical trials of antioxidants vitamins C and E, with an associated increase of plasma vitamins C and E concentrations have shown no benefit in prevention of the disorder, which may infer lack of a mechanistic role. Before oxidative stress is dismissed as an irrelevant accompaniment to pre-eclampsia further studies of proven biomarkers of oxidative stress are required to determine whether vitamins C and E supplementation leads to evidence of reversal of oxidative processes and tissue damage. If not, alternative antioxidant strategies may be worthy of consideration. Copyright © 2010 Society of Egyptian Anesthesiologists. Published by Elsevier B.V. All rights reserved.

  18. The potential therapeutic effects of ergothioneine in pre-eclampsia.

    PubMed

    Kerley, Robert N; McCarthy, Cathal; Kell, Douglas B; Kenny, Louise C

    2018-03-01

    Ergothioneine (ERG), is a water-soluble amino acid that is derived entirely from dietary sources. It has received much attention as a therapeutic agent due to its anti-oxidant properties, and there are claims of preferential accumulation within high oxidative stress organs. Pre-eclampsia, a condition accompanied by increased oxidative stress, is one of the leading causes of maternal morbidity and mortality. Despite intense research efforts, its aetiologies remain somewhat unclear and there are still no effective treatment options. Clinical trials of the anti-oxidants vitamin C and vitamin E have proven largely ineffective with little improvement in clinical outcome or even a negative response. This could be explained in part by their inability to permeate the plasma and mitochondrial membranes and scavenge mitochondria-derived superoxide species, and for the former by the fact that it is actually a pro-oxidant in the presence of unliganded iron. ERG accumulates within tissues through the action of a specific organic cation transporter, SLC22A4 (previously referred to as OCTN1), which is possibly also expressed in mammalian mitochondria. Mitochondrial dysfunction has been implicated in a variety of vascular diseases including pre-eclampsia. This review discusses the use of ERG as a possibly mitochondrial-targeted anti-oxidant, focusing on its physical properties, potential mechanisms of action, safety profile and administration in relation to pregnancies complicated by pre-eclampsia. Copyright © 2017. Published by Elsevier Inc.

  19. Circulating vascular cell adhesion molecule-1 in pre-eclampsia, gestational hypertension, and normal pregnancy: evidence of selective dysregulation of vascular cell adhesion molecule-1 homeostasis in pre-eclampsia.

    PubMed

    Higgins, J R; Papayianni, A; Brady, H R; Darling, M R; Walshe, J J

    1998-08-01

    is not an early preclinical feature of pre-eclampsia, does not persist post partum, is not a feature of nonproteinuric gestational hypertension, and is not observed with other major leukocyte adhesion molecules. Induction of vascular cell adhesion molecule-1 expression in pre-eclampsia may contribute to leukocyte-mediated tissue injury in this condition or may reflect perturbation of other, previously unrecognized, functions of this molecule in pregnancy.

  20. Nursing care for women with pre-eclampsia and/or eclampsia: integrative review.

    PubMed

    Ferreira, Maria Beatriz Guimarães; Silveira, Caroline Freitas; Silva, Sueli Riul da; Souza, Delvane José de; Ruiz, Mariana Torreglosa

    2016-04-01

    To analyze the available evidence in the literature on nursing care for women with pre-eclampsia and/or eclampsia. Integrative review searching for primary studies in the databases PubMed, CINAHL, LILACS and SciELO. The sample size consisted of 17 primary studies published between January 2000 and December 2014, grouped into four categories: standardizing blood pressure measurement technique; training with simulation; instruments for standardization of care and quality of care The main nursing actions were: physical examination, early detection of signs of pre-eclampsia/eclampsia, monitoring of laboratory tests, fetal assessment, qualification and training of professionals. We identified the need for standardization of care from instruments, protocols and blood pressure measurement technique, early identification and treatment of hypertensive crisis through institutional protocols and review of cases and work processes. Women with pre-eclampsia and/or eclampsia require specific nursing care, which must be guided by care protocols based on scientific evidence. Analisar as evidências disponíveis na literatura sobre assistência de enfermagem às mulheres com pré-eclâmpsia e/ou eclâmpsia. Revisão integrativa cuja busca dos estudos primários foi realizada nas bases de dados PubMed, CINAHL, LILACS e SciELO. Amostra foi composta por 17 estudos primários, publicados entre janeiro de 2000 e dezembro de 2014, agrupados em quatro categorias: padronização da técnica de mensuração da pressão arterial; treinamentos com simulação; instrumentos para padronização da assistência e qualidade da assistência As principais ações de enfermagem foram: exame físico, identificação precoce de sinais de pré-eclâmpsia/eclâmpsia, acompanhamento de exames laboratoriais, avaliação fetal, capacitação e treinamento dos profissionais. Identificou-se a necessidade de padronização do atendimento a partir de instrumentos e protocolos e da técnica de aferição da

  1. Hypertensive choroidopathy in pre-eclampsia: two consecutive cases.

    PubMed

    Dewilde, Evelien; Huygens, Marc; Cools, Geertrui; Van Calster, Joachim

    2014-01-01

    Hypertensive retinopathy is well known, but choroidopathy is uncommon and associated with acute increases in blood pressure. Nonperfused areas of the choriocapillaris lead to changes of overlying retinal pigment epithelium (RPE), resulting in neurosensory or RPE detachments. The authors describe two patients with serous retinal detachments associated with acute arterial hypertension in pre-eclampsia and HELLP (hemolysis, elevated liver enzyme levels, and low platelet count) syndrome. Subretinal fluid was demonstrated on ultra-widefield fundus imaging and optical coherence tomography. Fluorescein angiography and indocyanine green angiography enabled imaging of the choroidal hypoperfusion. All signs and symptoms resolved after 1 and 3 months, respectively, with persistent macular pigmentary changes in both patients. Copyright 2014, SLACK Incorporated.

  2. Cardiovascular mortality after pre-eclampsia in one child mothers: prospective, population based cohort study.

    PubMed

    Skjaerven, Rolv; Wilcox, Allen J; Klungsøyr, Kari; Irgens, Lorentz M; Vikse, Bjørn Egil; Vatten, Lars J; Lie, Rolv Terje

    2012-11-27

    To assess the association of pre-eclampsia with later cardiovascular death in mothers according to their lifetime number of pregnancies, and particularly after only one child. Prospective, population based cohort study. Medical Birth Registry of Norway. We followed 836,147 Norwegian women with a first singleton birth between 1967 and 2002 for cardiovascular mortality through linkage to the national Cause of Death Registry. About 23,000 women died by 2009, of whom 3891 died from cardiovascular causes. Associations between pre-eclampsia and cardiovascular death were assessed by hazard ratios, estimated by Cox regression analyses. Hazard ratios were adjusted for maternal education (three categories), maternal age at first birth, and year of first birth The rate of cardiovascular mortality among women with preterm pre-eclampsia was 9.2% after having only one child, falling to 1.1% for those with two or more children. With term pre-eclampsia, the rates were 2.8% and 1.1%, respectively. Women with pre-eclampsia in their first pregnancy had higher rates of cardiovascular death than those who did not have the condition at first birth (adjusted hazard ratio 1.6 (95% confidence interval 1.4 to 2.0) after term pre-eclampsia; 3.7 (2.7 to 4.8) after preterm pre-eclampsia). Among women with only one lifetime pregnancy, the increase in risk of cardiovascular death was higher than for those with two or more children (3.4 (2.6 to 4.6) after term pre-eclampsia; 9.4 (6.5 to 13.7) after preterm pre-eclampsia). The risk of cardiovascular death was only moderately elevated among women with pre-eclamptic first pregnancies who went on to have additional children (1.5 (1.2 to 2.0) after term pre-eclampsia; 2.4 (1.5 to 3.9) after preterm pre-eclampsia). There was little evidence of additional risk after recurrent pre-eclampsia. All cause mortality for women with two or more lifetime births, who had pre-eclampsia in first pregnancy, was not elevated, even with preterm pre-eclampsia in first

  3. Advances in the pathophysiology of pre-eclampsia and related podocyte injury

    PubMed Central

    Craici, Iasmina M.; Wagner, Steven J.; Weissgerber, Tracey L.; Grande, Joseph P.; Garovic, Vesna D.

    2014-01-01

    Pre-eclampsia is a pregnancy-specific hypertensive disorder that may lead to serious maternal and fetal complications. It is a multisystem disease that is commonly, but not always, accompanied by proteinuria. Its cause(s) remain unknown, and delivery remains the only definitive treatment. It is increasingly recognized that many pathophysiological processes contribute to this syndrome, with different signaling pathways converging at the point of systemic endothelial dysfunction, hypertension, and proteinuria. Different animal models of pre-eclampsia have proven utility for specific aspects of pre-eclampsia research, and offer insights into pathophysiology and treatment possibilities. Therapeutic interventions that specifically target these pathways may optimize pre-eclampsia management and may improve fetal and maternal outcomes. In addition, recent findings regarding placental, endothelial, and podocyte pathophysiology in pre-eclampsia provide unique and exciting possibilities for improved diagnostic accuracy. Emerging evidence suggests that testing for urinary podocytes or their markers may facilitate the prediction and diagnosis of pre-eclampsia. In this review, we explore recent research regarding placental, endothelial, and podocyte pathophysiology. We further discuss new signaling and genetic pathways that may contribute to pre-eclampsia pathophysiology, emerging screening and diagnostic strategies, and potential targeted interventions. PMID:24573315

  4. Pre-eclampsia: contribution of maternal constitutional factors and the consequences for cardiovascular health.

    PubMed

    Barden, Anne

    2006-09-01

    1. Pre-eclampsia is a serious complication of pregnancy that is potentially life threatening for both the mother and baby. It encompasses a number of abnormalities that may be present in other clinical conditions. 2. A placenta is essential for the development of pre-eclampsia and can be important in the pathogenesis of pre-eclampsia. Normal pregnancy is associated with remodelling of the maternal spiral arteries, which deliver blood to the placental villous space. Remodelling involves invasion by placental cytotrophoblasts that cause the maternal spiral arteries to lose their smooth muscle and become capacitance vessels; this process, known as placentation, is complete by 20 weeks of pregnancy. Poor placentation is associated with small-for-gestational-age fetuses and some cases of pre-eclampsia. It is thought that poor placentation can result in a hypoxic placenta that releases 'toxic substances' into the maternal circulation, contributing to the maternal syndrome. A number of candidate 'toxic substances' have been proposed, but none is universally raised in pre-eclampsia. 3. Although the placenta is necessary for the development of pre-eclampsia, the extent to which placental abnormalities contribute to the condition varies. It is becoming apparent that maternal constitutional factors may also be important in this syndrome. Underlying hypertension, diabetes and obesity strongly predispose to pre-eclampsia. However, a continuum of risk may exist for blood pressure, bodyweight, glucose and lipids, which, in combination with each other and some degree of placental abnormalities, may lead to the development of pre-eclampsia. 4. The present review will focus on the maternal constitutional factors that define the metabolic syndrome and examine their contribution to pre-eclampsia and the long-term consequences for cardiovascular health.

  5. The role of genetics in pre-eclampsia and potential pharmacogenomic interventions

    PubMed Central

    Williams, Paula Juliet; Morgan, Linda

    2012-01-01

    The pregnancy-specific condition pre-eclampsia not only affects the health of mother and baby during pregnancy but also has long-term consequences, increasing the chances of cardiovascular disease in later life. It is accepted that pre-eclampsia has a placental origin, but the pathogenic mechanisms leading to the systemic endothelial dysfunction characteristic of the disorder remain to be determined. In this review we discuss some key factors regarded as important in the development of pre-eclampsia, including immune maladaptation, inadequate placentation, oxidative stress, and thrombosis. Genetic factors influence all of these proposed pathophysiological mechanisms. The inherited nature of pre-eclampsia has been known for many years, and extensive genetic studies have been undertaken in this area. Genetic research offers an attractive strategy for studying the pathogenesis of pre-eclampsia as it avoids the ethical and practical difficulties of conducting basic science research during the preclinical phase of pre-eclampsia when the underlying pathological changes occur. Although pharmacogenomic studies have not yet been conducted in pre-eclampsia, a number of studies investigating treatment for essential hypertension are of relevance to therapies used in pre-eclampsia. The pharmacogenomics of antiplatelet agents, alpha and beta blockers, calcium channel blockers, and magnesium sulfate are discussed in relation to the treatment and prevention of pre-eclampsia. Pharmacogenomics offers the prospect of individualized patient treatment, ensuring swift introduction of optimal treatment whilst minimizing the use of inappropriate or ineffective drugs, thereby reducing the risk of harmful effects to both mother and baby. PMID:23226061

  6. Interleukin-1 family cytokines and their regulatory proteins in normal pregnancy and pre-eclampsia

    PubMed Central

    Southcombe, J H; Redman, C W G; Sargent, I L; Granne, I

    2015-01-01

    Maternal systemic inflammation is a feature of pre-eclampsia, a condition in pregnancy characterized by hypertension and proteinuria. Pre-eclampsia is caused by the placenta; many placental factors contribute to the syndrome's progression, and proinflammatory cytokines have been identified previously as one such mediator. The interleukin (IL)-1 family of cytokines are key regulators of the inflammatory network, and two naturally occurring regulatory molecules for IL-1 family cytokines, IL-1RA and sST2, have been found previously to be elevated in maternal blood from women with pre-eclampsia. Here we investigate more recently identified IL-1 family cytokines and regulatory molecules, IL-1RAcP, IL-37, IL-18BP, IL-36α/β/γ/Ra and IL-38 in pre-eclampsia. Pregnant women have more circulating IL-18BP and IL-36Ra than non-pregnant women, and sIL-1RAcP is elevated from women with pre-eclampsia compared to normal pregnancies. The placenta expresses all the molecules, and IL-37 and IL-18BP are up-regulated significantly in pre-eclampsia placentas compared to those from normal pregnancies. Together, these changes contribute to the required inhibition of maternal systemic cytotoxic immunity in normal pregnancy; however, in pre-eclampsia the same profile is not seen. Interestingly, the increased circulating levels of sIL-1RAcP and increased placental IL-18BP and IL-37, the latter of which we show to be induced by hypoxic damage to the placenta, are all factors which are anti-inflammatory. While the placenta is often held responsible for the damage and clinical symptoms of pre-eclampsia by the research community, here we show that the pre-eclampsia placenta is also trying to prevent inflammatory damage to the mother. PMID:25693732

  7. Community health workers' knowledge and practice in relation to pre-eclampsia in Ogun State, Nigeria: an essential bridge to maternal survival.

    PubMed

    Sotunsa, J O; Vidler, M; Akeju, D O; Osiberu, M O; Orenuga, E O; Oladapo, O T; Qureshi, R; Sawchuck, D; Adetoro, O O; von Dadelszen, P; Dada, O A

    2016-09-30

    Pre-eclampsia is a leading cause of maternal and fetal morbidity and mortality worldwide. Early detection and treatment have been instrumental in reducing case fatality in high-income countries. To achieve this in a low-income country, like Nigeria, community health workers who man primary health centres must have adequate knowledge and skills to identify and provide emergency care for women with pre-eclampsia. This study aimed to determine community health workers' knowledge and practice in the identification and treatment of pre-eclampsia, as they are essential providers of maternal care services in Nigeria. This study was part of a multi-country evaluation of community treatment of pre-eclampsia. Qualitative data were obtained from four Local Government Areas of Ogun State, in south western Nigeria by focus group discussions (N = 15) and in-depth interviews (N = 19). Participants included a variety of community-based health care providers - traditional birth attendants, community health extension workers, nurses and midwives, chief nursing officers, medical officers - and health administrators. Data were transcribed and validated with field notes and analysed with NVivo 10.0. Community-based health care providers proved to be aware that pre-eclampsia was due to the development of hypertension and proteinuria in pregnant women. They had a good understanding of the features of the condition and were capable of identifying women at risk, initiating care, and referring women with this condition. However, some were not comfortable managing the condition because of the limitation in their 'Standing Order'; these guidelines do not explicitly authorize community health extension workers to treat pre-eclampsia in the community. Community-based health care providers were capable of identifying and initiating appropriate care for women with pre-eclampsia. These competencies combined with training and equipment availability could improve maternal health in the rural

  8. The effects of sildenafil citrate on uterine angiogenic status and serum inflammatory markers in an L-NAME rat model of pre-eclampsia.

    PubMed

    Soobryan, Nerolen; Murugesan, Saravanakumar; Phoswa, Wendy; Gathiram, Prem; Moodley, Jagidesa; Mackraj, Irene

    2017-01-15

    Pre-eclampsia (PE), a hypertensive disorder of pregnancy, is detrimental to both mother and foetus. There is currently no effective treatment, but we have shown that Sildenafil Citrate (SC) improve various foetal outcomes in N ω -nitro-L arginine methyl ester (L-NAME) rat model of PE. Therefore, we aimed to investigate the effects of SC on a uterine angiogenic status and serum inflammatory markers in an L-NAME rat model of PE. One hundred and twenty adult nulliparous pregnant female Sprague-Dawley rats were used for the study. These were divided into five equal groups; the pregnant control, early and late onset PE and respective SC treated animals. Hypertension was manifested by considerably increased systolic blood pressure and placental lipid peroxidative marker (thiobarbituric acid reactive substances) and also we assessed the activities of plasma nitric oxide level, serum inflammatory marker (TGF-β and IFN-γ) and uterine angiogenic status (VEGF and sFlt-1) at two stages of PE. The administration of SC decreased systolic blood pressure, placental lipid peroxidation product and altered uterine angiogenic status; increased plasma nitric oxide levels in an early and late onset L-NAME model of PE. In addition, histological findings of SC treated preeclamptic rat placenta support the biochemical findings of this study. Our findings revealed that SC enhanced plasma NO levels and uterine angiogenic status in an L-NAME model of PE at two gestational stages. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Relationship between air pollution and pre-eclampsia in pregnant women: a case-control study.

    PubMed

    Nahidi, F; Gholami, R; Rashidi, Y; Majd, H Alavi

    2014-01-09

    Pre-eclampsia is the main cause of maternal and fetal death and disability worldwide. Its incidence in the Islamic Republic of Iran is 5%-12%. Air pollution has been reported to be one of the causative factors, and this case-control study determined its effect on pre-eclampsia in 195 pregnant women (65 with pre-eclampsia and 130 without) admitted to hospitals in Tehran. Women were divided into high and low exposure groups according to the mean density of exposure to pollutants during pregnancy. There was no statistically significant relationship between exposure to air pollutants including CO, particulate matter, SO2, NO2 and O3 and pre-eclampsia. The combined effect was also not significant. Air pollution is one of the problems of modern society and its avoidance is almost impossible for pregnant women. This study should reduce concern about pregnant women living in polluted cities.

  10. Number of decidual natural killer cells & macrophages in pre-eclampsia

    PubMed Central

    Milosevic-Stevanovic, Jelena; Krstic, Miljan; Radovic-Janosevic, Dragana; Popovic, Jasmina; Tasic, Marija; Stojnev, Slavica

    2016-01-01

    Background & objectives: The process of human placentation is complex and still not well understood. This study was aimed to examine the relationship between clinical features of pre-eclampsia and degree of trophoblastic invasion after its immunohistochemical visualization in the context of possible alterations in the number of natural killer (NK) cells and macrophages in the decidua. Methods: This prospective study included a study group comprising 30 pregnant women with pre-eclampsia delivered by caesarean section and a control group comprising 20 healthy pregnant women also delivered by caesarean section. Samples of placental bed obtained during caesarean section were analyzed after immunohistochemical labelling CD56+ NK cells, CD68+ macrophages and cytokeratin 7 trophoblastic cells. Results: In pre-eclampsia, there was a significantly lower number of CD56+ NK cells in the decidua (P<0.001) and a higher number of CD68+ macrophages (P<0.001) compared to control group. In the subgroup of pre-eclampsia with intrauterine growth retardation (IUGR), a significantly greater number of NK cells (P<0.05) was recorded, as well as an increased number of macrophages, but not significantly compared to pre-eclampsia without IUGR. There was no significant difference in the distribution of these cells in the decidua in relation to the severity of pre-eclampsia. CD56+ NK cells were significantly less (P<0.05) and macrophages were more (P<0.05) in the group with poor trophoblastic invasion. Interpretation & conclusions: Alterations in the number of immune cells in relation to the degree of trophoblastic invasion indicated their role in aetiopathogenesis of pre-eclampsia, while the direct association between their number and severity of pre-eclampsia was not confirmed. PMID:28474619

  11. Clinical accuracy of inflationary oscillometry in pregnancy and pre-eclampsia: Omron-MIT Elite.

    PubMed

    Chung, Y; Brochut, M C; de Greeff, A; Shennan, A H

    2012-10-01

    To evaluate the accuracy of the Omron MIT Elite in pregnancy and pre-eclampsia according to the British Hypertension Society protocol (BHS). Prospective observational study. Antenatal clinics and wards at St. Thomas' Hospital (London, UK). Forty-five pregnant women including 15 with pre-eclampsia. Nine sequential same arm blood pressure (BP) measurements were taken from each woman by trained observers, alternating between mercury sphygmomanometry and the test device. Grading criteria of the BHS protocol (A/B grade=pass; C/D=fail). The Omron MIT Elite achieved a grade A/A in both pregnancy and pre-eclampsia. The mean difference (SD) between the mercury standard and the device in pregnancy was -1.1 (5.2)mmHg and 1.5 (4.8)mmHg for systolic and diastolic BP respectively compared to 0.2 (5.3)mmHg and 2.2 (5.5)mmHg in pre-eclampsia. The Omron MIT Elite can be recommended for use in pregnancy and pre-eclampsia according to the BHS protocol. To date, this is the most accurate automated BP device validated in pre-eclampsia. Copyright © 2012. Published by Elsevier B.V.

  12. Association between previous spontaneous abortion and pre-eclampsia during a subsequent pregnancy.

    PubMed

    Sepidarkish, Mahdi; Almasi-Hashiani, Amir; Maroufizadeh, Saman; Vesali, Samira; Pirjani, Reihaneh; Samani, Reza O

    2017-01-01

    To determine the impact of a history of spontaneous abortion on pre-eclampsia during a subsequent pregnancy. A cross-sectional study enrolled pregnant women admitted to obstetrics and gynecology wards at 103 hospitals in Tehran, Iran for delivery between July 6 and July 21, 2015. Consenting participants were interviewed by midwives; data were collected using a five-part questionnaire and patients' medical records were retrieved. Patient data were analyzed by multiple logistic regression to identify variables associated with increased odds of pre-eclampsia. In total, 5170 patients were interviewed and 252 had experienced pre-eclampsia. The number of previous spontaneous abortions was found to be associated with pre-eclampsia, and a higher number of previous spontaneous abortions was associated with increased odds of patients having experienced pre-eclampsia (adjusted odds ratio 1.28, 95% confidence interval 1.03-1.59; P=0.025). A history of spontaneous abortion was associated with increased odds of pre-eclampsia during a subsequent pregnancy. © 2016 International Federation of Gynecology and Obstetrics.

  13. Fractional excretion of urea in pre-eclampsia: a clinical observation.

    PubMed

    Zar, Tausif; Kohn, Orly F; Kaplan, Andre A

    2011-11-01

    Pre-eclampsia is one of the leading causes of maternal and fetal mortality and morbidity. It occurs in 7% of all the pregnancies and accounts for 80% of the cases of pregnancy-induced hypertension. Diagnosis of pre-eclampsia in patients with pre-existing chronic kidney disease, proteinuria, and hypertension is a dilemma. The fractional excretion of urea has been described as a marker for renal perfusion. Since pre-eclampsia is associated with a marked decline in renal perfusion, we explored the utility of the fractional excretion of urea as a marker for pre-eclampsia. Urine and serum chemistries were evaluated in 6 pregnant women with pre-eclampsia on their first visit, immediately prior to delivery, and postpartum. For each of these three measurements, the fractional excretion of urea was calculated and proteinuria was assessed by random urine protein-creatinine ratio or 24-hour urine protein studies. In patients diagnosed with pre-eclampsia, the fractional excretion of urea decreased substantially from higher values obtained during the 3rd trimester to values consistent with renal hypoperfusion (< 35%) just prior to delivery, and it rapidly normalized immediately after delivery. Alterations in fractional excretion of urea, which suggest a decreased renal perfusion, may be a useful tool in supporting the diagnosis of preeclampsia.

  14. Working hours and risk of gestational hypertension and pre-eclampsia.

    PubMed

    Chang, Pei-Jen; Chu, Li-Ching; Hsieh, Wu-Shiun; Chuang, Yi-Li; Lin, Shio-Jean; Chen, Pau-Chung

    2010-01-01

    The potential impact of employment on maternal health, particularly in relation to gestational hypertension and pre-eclampsia, has been subject to research. However, there is limited evidence on associations between shift work and long working hours on the incidence of these conditions. To evaluate potential associations between maternal shift work and long working hours during pregnancy and gestational hypertension or pre-eclampsia. Multistage stratified systematic sampling was used to recruit 24 200 post-partum women from the Taiwan national birth registration database in 2005. Subjects underwent home interview 6 months after their deliveries by structured questionnaire to obtain characteristics of maternal employment and potential confounders. Diagnosis of gestational hypertension and pre-eclampsia was obtained from the birth registration. There was no association between employment status and gestational hypertension or pre-eclampsia. Also, no significant association between gestational hypertension or pre-eclampsia and maternal shift work or long working hours during pregnancy was found in all or primiparous women. There was no convincing evidence that maternal shift work or long working hours had a higher risk of gestational hypertension or pre-eclampsia. However, further research is warranted to confirm these negative findings.

  15. Comparison of subfoveal choroidal thickness in healthy pregnancy and pre-eclampsia

    PubMed Central

    Kim, J W; Park, M H; Kim, Y J; Kim, Y T

    2016-01-01

    Purpose Pregnancy is a known predisposing factor for central serous chorioretinopathy (CSC). Choroidal thickness (CT) increases in patients with CSC. This study was designed to evaluate CT in pregnant women. Patients and methods This was a prospective study. Fourteen healthy pregnant women and seven patients with pre-eclampsia were included. Twenty-one normal subjects were also recruited. CT was measured using enhanced-depth imaging optical coherence tomography. Results The mean CT of normal subjects, healthy pregnant women and patients with pre-eclampsia were 264.95±21.03, 274.23±29.30 and 389.79±25.13 μm, respectively (normal subjects vs healthy gravidas: P>0.05; normal subjects vs pre-eclampsia: P<0.001; healthy gravidas vs pre-eclampsia: P<0.001). CT decreased from 381.05±22.96 μm to 335.17±9.97 μm 1 week after delivery in patients with pre-eclampsia. Conclusions Pregnancy itself did not increase CT, whereas pre-eclampsia did appear to result in increased CT. This suggests that additional unknown factors induce hyperpermeability in pregnant women. PMID:26541086

  16. Pre-Eclampsia and Eclampsia: An Update on the Pharmacological Treatment Applied in Portugal †

    PubMed Central

    Peres, Gonçalo Miguel; Mariana, Melissa

    2018-01-01

    Pre-eclampsia and eclampsia are two hypertensive disorders of pregnancy, considered major causes of maternal and perinatal death worldwide. Pre-eclampsia is a multisystemic disease characterized by the development of hypertension after 20 weeks of gestation, with the presence of proteinuria or, in its absence, of signs or symptoms indicative of target organ injury. Eclampsia represents the consequence of brain injuries caused by pre-eclampsia. The correct diagnosis and classification of the disease are essential, since the therapies for the mild and severe forms of pre-eclampsia are different. Thus, this review aims to describe the most advisable antepartum pharmacotherapy for pre-eclampsia and eclampsia applied in Portugal and based on several national and international available guidelines. Slow-release nifedipine is the most recommended drug for mild pre-eclampsia, and labetalol is the drug of choice for the severe form of the disease. Magnesium sulfate is used to prevent seizures caused by eclampsia. Corticosteroids are used for fetal lung maturation. Overall, the pharmacological prevention of these diseases is limited to low-dose aspirin, so it is important to establish the safest and most effective available treatment. PMID:29367581

  17. Contribution of genome-environment interaction to pre-eclampsia in a Havana Maternity Hospital.

    PubMed

    Lardoeyt, Roberto; Vargas, Gerardo; Lumpuy, Jairo; García, Ramón; Torres, Yuselis

    2013-07-01

    Pre-eclampsia is a major cause of morbidity and mortality during pregnancy worldwide and is among the leading causes of maternal mortality in Cuba. It is a complex, multifactoral disease, in which interaction of genetic and environmental factors should not be overlooked if the goal is proper risk assessment to support personalized preventive genetic counseling and more effective prenatal care to prevent pregnancy complications. Determine the contribution to pre-eclampsia of interaction between a predisposing genome and adverse environmental factors in pregnant women in a Havana maternity hospital. This was the exploratory phase of a hospital-based case-control study, using January 2007-December 2009 patient records from the Eusebio Hernández University Hospital, a provincial maternity hospital in Havana. Eighty pregnant women diagnosed with pre-eclampsia and 160 controls were studied. The main variables were age, parity, nutritional status (measured by BMI), alcohol use, tobacco use, and history of pre-eclampsia in relatives of the pregnant woman (proband) or of her partner. Pearson chi square and Fisher exact test were used to assess statistical significance of associations between variables and odds ratio as a measure of association strength. Familial aggregation was studied and a case-control design used to assess gene-environment interaction, using multiplicative and additive models. Among the environmental risk factors studied, alcohol showed the strongest effect on pre-eclampsia risk (OR 3.87, 95% CI 1.64-9.13). Familial pre-eclampsia clustering was observed; risk was increased for both first-degree (OR 2.43, 95% CI 1.62-3.73) and second-degree (OR 1.89, 95% CI 1.34-2.68) relatives as well as for husband's relatives (OR 2.32, 95% CI 1.40-3.86). There was evidence of interaction between alcohol consumption and family history. Familial aggregation of the disorder was demonstrated, the first Cuban epidemiological evidence of genetic and enviromental

  18. Association of biochemical markers with the severity of pre-eclampsia.

    PubMed

    Maged, Ahmed M; Aid, Gamal; Bassiouny, Nehal; Eldin, Doaa S; Dahab, Sherif; Ghamry, Nevein K

    2017-02-01

    To assess the association between pre-eclampsia severity and biochemical and ultrasonography markers. A retrospective study was undertaken of women with severe pre-eclampsia (group 1, n=90), mild pre-eclampsia (group 2, n=90), or a normal pregnancy (group 3, n=90) who attended a hospital in Egypt in October 2013-April 2015. Associations between pre-eclampsia and biochemical, cardiotocography, and ultrasonography markers were investigated. There were significant differences between the groups in C-reactive protein (331.44±112.38, 251.43±59.05, and 23.81±16.19 nmol/L; P≤0.05 for all), platelet count (113.40±36.72, 172.93±57.60, and 212.68±70.00×10 9 /L; P≤0.05 for group 1 comparisons), alanine transaminase (52.24±14.83, 38.34±13.12, and 23.11±6.92 U/L; P≤0.05 for group 1 comparisons), and serum uric acid (600.80±117.19, 481.83±118.97, and 243.89±53.54 μmol/L; P=0.050 for group 3 comparisons). Cardiotocography score was worse among women with severe pre-eclampsia than among those in the other two groups (P=0.039 for both comparisons). Biophysical profile score and umbilical artery resistance index differed by group (P≤0.05 for all). Middle cerebral artery resistance index was lower among women with severe pre-eclampsia (P≤0.05). The levels of C-reactive protein, blood urea nitrogen, serum uric acid, and alanine transaminase, and the platelet count were linked with the presence and severity of pre-eclampsia. © 2016 International Federation of Gynecology and Obstetrics.

  19. Cardiovascular risk factor assessment after pre-eclampsia in primary care

    PubMed Central

    2009-01-01

    Background Pre-eclampsia is associated with an increased risk of development of cardiovascular disease later in life. It is not known how general practitioners in the Netherlands care for these women after delivery with respect to cardiovascular risk factor management. Methods Review of medical records of 1196 women in four primary health care centres, who were registered from January 2000 until July 2007 with an International Classification of Primary Care (ICPC) code indicating pregnancy. Records were searched for indicators of pre-eclampsia. Of those who experienced pre-eclampsia and of a random sample of 150 women who did not, the following information on cardiovascular risk factor management after pregnancy was extracted from the records: frequency and timing of blood pressure, cholesterol and glucose measurements - and vascular diagnoses. Additionally the sensitivity and specificity of ICPC coding for pre-eclampsia were determined. Results 35 women experienced pre-eclampsia. Blood pressure was more often checked after pregnancy in these women than in controls (57.1% vs. 12.0%, p < 0.001). In 50% of the cases blood pressure was measured within 3 months after delivery with no further follow-up visit. A check for glucose and cholesterol levels was rare, and equally frequent in PE and control women. 20% of the previously normotensive women in the PE group had hypertension at one or more occasions after three months post partum versus none in the control group. The ICPC coding for pre-eclampsia showed a sensitivity of 51.4% and a specificity of 100.0%. Conclusion Despite the evidence of increased risk of future cardiovascular disease in women with a history of pre-eclampsia, follow-up of these women is insufficient and undeveloped in primary care in the Netherlands. PMID:19995418

  20. Protocol for the prospective validation study: 'Screening programme for pre-eclampsia' (SPREE).

    PubMed

    Tan, M Y; Koutoulas, L; Wright, D; Nicolaides, K H; Poon, L C Y

    2017-08-01

    Pre-eclampsia (PE), which affects about 2% of pregnancies, is a major cause of maternal and perinatal morbidity and mortality. Early detection of PE can improve pregnancy outcome by providing timely intervention and closer monitoring. The current guideline from the UK National Institute for Health and Care Excellence (NICE) recommends that, at the booking visit, women identified with one major risk factor or more than one moderate risk factor for PE should be advised to take low-dose aspirin daily from 12 weeks until delivery. However, performance of the current method of screening is poor and identifies only about 35% of PE. Extensive studies in the last decade have established that the best performance for early prediction of PE can be achieved by using a novel Bayes' theorem-based method that combines maternal characteristics and medical history together with measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) at 11-13 weeks' gestation. This forms the 'combined test', which could be simplified to the 'mini combined test' when only maternal factors, MAP and PAPP-A are taken into consideration. We present the protocol (version 3.1, 14 November 2016) for the 'Screening programme for pre-eclampsia' (SPREE) study, a prospective multicenter cohort study that will be carried out in seven National Health Service maternity hospitals in England. Eligible pregnant women attending their routine scan at 11-13 weeks' gestation will be invited to participate in this study. Maternal characteristics and history and measurements of MAP, UtA-PI, serum PAPP-A and PlGF will be recorded according to standardized protocols. The patient-specific risk for PE will be calculated and data on pregnancy outcomes collected. We hypothesize that the first-trimester mini combined test and combined test for PE screening, using the Bayes' theorem-based method, are likely to

  1. Mediators of the association between pre-eclampsia and cerebral palsy: population based cohort study

    PubMed Central

    Heimstad, Runa; Iversen, Ann-Charlotte; Austgulen, Rigmor; Lydersen, Stian; Andersen, Guro L; Irgens, Lorentz M; Vik, Torstein

    2013-01-01

    Objective To test the hypothesis that pre-eclampsia is a risk factor for cerebral palsy mediated through preterm birth and being born small for gestational age. Design Population based cohort study. Setting Clinical data from the Norwegian Cerebral Palsy Registry were linked with perinatal data prospectively recorded by the Medical Birth Registry of Norway. Participants All singleton babies who survived the neonatal period during 1996-2006 (849 children with cerebral palsy and 616 658 control children). Main outcome measures Cerebral palsy and cerebral palsy subtypes. Results Children exposed to pre-eclampsia had an excess risk of cerebral palsy (unadjusted odds ratio 2.5, 95% confidence interval 2.0 to 3.2) compared with unexposed children. Among children born at term (≥37 weeks), exposure to pre-eclampsia was not associated with an excess risk of cerebral palsy in babies not born small for gestational age (1.2, 0.7 to 2.0), whereas children exposed to pre-eclampsia and born small for gestational age had a significantly increased risk of cerebral palsy (3.2, 1.5 to 6.7). Non-small for gestational age babies born very preterm (<32 weeks) and exposed to pre-eclampsia had a reduced risk of cerebral palsy compared with unexposed children born at the same gestational age (0.5, 0.3 to 0.8), although the risk was not statistically significantly reduced among children exposed to pre-eclampsia and born small for gestational age (0.7, 0.4 to 1.3). Exposure to pre-eclampsia was not associated with a specific cerebral palsy subtype. Conclusions Exposure to pre-eclampsia was associated with an increased risk of cerebral palsy, and this association was mediated through the children being born preterm or small for gestational age, or both. Among children born at term, pre-eclampsia was a risk factor for cerebral palsy only when the children were small for gestational age. PMID:23838554

  2. Reliable pre-eclampsia pathways based on multiple independent microarray data sets.

    PubMed

    Kawasaki, Kaoru; Kondoh, Eiji; Chigusa, Yoshitsugu; Ujita, Mari; Murakami, Ryusuke; Mogami, Haruta; Brown, J B; Okuno, Yasushi; Konishi, Ikuo

    2015-02-01

    Pre-eclampsia is a multifactorial disorder characterized by heterogeneous clinical manifestations. Gene expression profiling of preeclamptic placenta have provided different and even opposite results, partly due to data compromised by various experimental artefacts. Here we aimed to identify reliable pre-eclampsia-specific pathways using multiple independent microarray data sets. Gene expression data of control and preeclamptic placentas were obtained from Gene Expression Omnibus. Single-sample gene-set enrichment analysis was performed to generate gene-set activation scores of 9707 pathways obtained from the Molecular Signatures Database. Candidate pathways were identified by t-test-based screening using data sets, GSE10588, GSE14722 and GSE25906. Additionally, recursive feature elimination was applied to arrive at a further reduced set of pathways. To assess the validity of the pre-eclampsia pathways, a statistically-validated protocol was executed using five data sets including two independent other validation data sets, GSE30186, GSE44711. Quantitative real-time PCR was performed for genes in a panel of potential pre-eclampsia pathways using placentas of 20 women with normal or severe preeclamptic singleton pregnancies (n = 10, respectively). A panel of ten pathways were found to discriminate women with pre-eclampsia from controls with high accuracy. Among these were pathways not previously associated with pre-eclampsia, such as the GABA receptor pathway, as well as pathways that have already been linked to pre-eclampsia, such as the glutathione and CDKN1C pathways. mRNA expression of GABRA3 (GABA receptor pathway), GCLC and GCLM (glutathione metabolic pathway), and CDKN1C was significantly reduced in the preeclamptic placentas. In conclusion, ten accurate and reliable pre-eclampsia pathways were identified based on multiple independent microarray data sets. A pathway-based classification may be a worthwhile approach to elucidate the pathogenesis of pre-eclampsia

  3. Relationship between Fas and Fas Ligand gene polymorphisms and pre-eclampsia.

    PubMed

    Masoumi, Elham; Tavakkol-Afshari, Jalil; Nikpoor, Amin Reza; Ghaffari-Nazari, Haniyeh; Tahaghoghi-Hajghorbani, Sahar; Jalali, Seyed Amir

    2016-10-01

    In normal pregnancy, the Th1 subtype, responsible for the production of inflammatory cytokines, is reduced, and the Th2 subtype is increased to prohibit inflammation. In pre-eclampsia, the Th1 cell population is increased; thus, subsequent inflammation and trophoblast destruction occur. Polymorphisms in the Fas and Fas Ligand (FasL) promoter regions can influence Fas and FasL expression and accused to increase of Th1 subtype. DNA samples from 153 pregnant women with pre-eclampsia and 140 controls were genotyped through polymerase chain reaction-restriction fragment length polymorphism. A Fisher's exact test was used to compare the distribution of individual polymorphisms. Fas-1377 AA, AG and GG genotypes were observed in 2.61%, 18.30% and 79.08% in the pre-eclampsia group opposed to 0%, 27.14% and 72.85% in the control group (P = 0.037), respectively. Fas-670 AA, AG and GG genotypes were observed in 37.9%, 41.8% and 20.3% of pre-eclampsia patients compared with 33.6%, 50.7% and 15.7% in healthy pregnant women (P = 0.291), respectively. No statically significant differences in the FasL-844 genotype were observed between the groups (P = 0.69). The Fas-1377G > A polymorphism is associated with a higher risk of pre-eclampsia. © 2016 Japan Society of Obstetrics and Gynecology.

  4. The genetics of pre-eclampsia and other hypertensive disorders of pregnancy

    PubMed Central

    Williams, Paula J.; Broughton Pipkin, Fiona

    2011-01-01

    Hypertension is the most frequent medical complication occurring during pregnancy. In this chapter, we aim to address the genetic contribution to these disorders, with specific focus on pre-eclampsia. The pathogenic mechanisms underlying pre-eclampsia remain to be elucidated; however, immune maladaptation, inadequate placental development and trophoblast invasion, placental ischaemia, oxidative stress and thrombosis are all thought to represent key factors in the development of disease. Furthermore, all of these components have genetic factors that may be involved in the pathogenic changes occurring. The familial nature of pre-eclampsia has been known for many years and, as such, extensive genetic research has been carried out in this area using strategies that include candidate gene studies and linkage analysis. Interactions between fetal and maternal genotypes, the effect of environmental factors, and epistasis will also be considered. PMID:21429808

  5. The effects of sildenafil citrate on urinary podocin and nephrin mRNA expression in an L-NAME model of pre-eclampsia.

    PubMed

    Baijnath, Sooraj; Murugesan, Saravanakumar; Mackraj, Irene; Gathiram, Prem; Moodley, Jagidesa

    2017-03-01

    We investigated the effects of sildenafil citrate (SC) on podocyturia in N ω -nitro-L-arginine methyl ester hydrochloride (L-NAME) model of pre-eclampsia (PE). One hundred and twenty Sprague-Dawley rats (SDR) were divided into five groups like pregnant control (PC), early-onset PE (EOPE), late-onset PE(LOPE), early and late-onset PE with SC-treated groups [EOPE (SC); LOPE (SC)]. PE was induced in SDR by oral administration of L-NAME in drinking water for 4-8 days for EOPE and 8-14 day for LOPE. The blood pressure, urine volume and total urine protein were increased in EOPE and LOPE groups when compared to PC, and all the above parameters decreased in EOPE (SC) and LOPE (SC) groups when compared to EOPE and LOPE groups, respectively. The EOPE and LOPE groups showed an increase in urinary nephrin mRNA and podocin mRNA levels compared to PC group. Increases in serum and renal soluble fms-like tyrosine kinase-1 (sFlt-1) expression levels and decreases in renal vascular endothelial growth factor (VEGF) expression and serum placenta growth factor (PlGF) levels were observed in EOPE and LOPE groups when compared to PC group. In addition, decreases in serum and renal sFlt-1 expression levels and increases in renal VEGF expression and serum PlGF levels were observed in EOPE (SC) and LOPE (SC) groups when compared to EOPE and LOPE groups, respectively. The light microscopy showed that the renal tissue of L-NAME-treated rats had extensive glomerular damage, tubular damage and infiltration by mononuclear cells when compared to PC group. Therefore, SC ameliorated podocyturia through its effects on the antiangiogenic/angiogenic status in this animal model.

  6. Angiogenic profile and smoking in the Finnish Genetics of Pre-Eclampsia Consortium (FINNPEC) cohort.

    PubMed

    Jääskeläinen, Tiina; Suomalainen-König, Sanna; Hämäläinen, Esa; Pulkki, Kari; Romppanen, Jarkko; Heinonen, Seppo; Laivuori, Hannele

    2017-11-01

    The biological mechanism by which smoking reduces the risk of pre-eclampsia (PE) is unresolved. We studied serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF) and their ratio, in addition to soluble endoglin (sEng) in early and late pregnancy to ascertain whether these factors are altered in women who smoke. First trimester serum samples were available from 217 women who later developed PE and 238 women who did not develop PE. Second/third trimester serum samples were available from 174 PE and 54 non-PE women. PE women who smoked during pregnancy had elevated first trimester concentrations of serum PlGF [geometric mean (95% CI): 39.8 (32.6-48.5) pg/ml, p = .001] and reduced sEng concentration [5.0 (4.6-5.6) ng/ml, p = .047] compared to PE non-smokers [30.0 (28.1-32.1) pg/ml and 6.1 (5.9-6.4) ng/ml, respectively]. Non-smoking women in the PE group had the highest sFlt-1/PlGF ratio in early and late pregnancy. The protective effect of smoking in reducing the risk of PE may be due to the early pregnancy change towards pro-angiogenic marker profile. Also, in late pregnancy, smoking exerted effect in sFlt-1/PlGF ratio in PE pregnancies, and may complicate its use as a prognostic and diagnostic marker. Key messages Smoking appears to have angiogenic effects in early pregnancy with reduced sEng concentrations and elevated PlGF concentrations in both normal and PE pregnancies. Throughout pregnancy, smoking exerted effect in PlGF concentration and sFlt-1/PlGF ratio in PE pregnancies, and thus may complicate its use as a prognostic and diagnostic marker.

  7. Validity of the diagnosis of pre-eclampsia in the Medical Birth Registry of Norway.

    PubMed

    Thomsen, Liv C V; Klungsøyr, Kari; Roten, Linda T; Tappert, Christian; Araya, Elisabeth; Baerheim, Gunhild; Tollaksen, Kjersti; Fenstad, Mona H; Macsali, Ferenc; Austgulen, Rigmor; Bjørge, Line

    2013-08-01

    Evaluating the validity of pre-eclampsia registration in the Medical Birth Registry of Norway (MBRN) according to both broader and restricted disease definitions. Retrospective nested cohort study. Multicenter study. In this study, two cohorts of women with pre-eclamptic pregnancies registered in the MBRN were selected. Study group 1 contained 966 pregnancies from 1967 to 2002. Concomitant participation in the Nord-Trøndelag Health Study 2 was required. Study group 2 comprised 1138 pregnancies recorded in 1967-2005, examined as a pre-eclampsia biobank was established. Diagnostic criteria vary. The broader criteria for pre-eclampsia, used by the MBRN, are one measurement of hypertension and proteinuria (Criterion A). Criteria used internationally today require two measurements of hypertension and proteinuria (Criterion B). The diagnostic validities in Study groups 1 and 2 were judged against medical records according to Criterion A and B, respectively. Positive predictive value (PPV) and trend analyses. The diagnosis was confirmed in 88.3% of pregnancies in Study group 1, and in 63.6% in Study group 2. PPV was high for Study group 1 throughout the period. For Study group 2, results improved significantly after 1986. This study ascertains high PPV of pre-eclampsia in the MBRN using broader traditional criteria, although the PPV decreases through assessment using restricted modern criteria. This illustrates how inclusion of direct measurements may improve registration of complex disorders defined by changing diagnostic criteria. © 2013 Nordic Federation of Societies of Obstetrics and Gynecology.

  8. Thrombophilic mutations in pre-eclampsia and pregnancy-induced hypertension.

    PubMed

    Omar, Siti Z; Qvist, Rajes; Khaing, Si L; Muniandy, Sekaran; Bhalla, Sunil

    2008-04-01

    The aim of the present study was to determine the existence or prevalence of thrombophilic markers such as Factor V Leiden, prothrombin G20210A, protein S, protein C, activated protein C and anti-thrombin in pre-eclampsia and pregnancy-induced hypertensive patients. Blood samples were collected from a total number of 124 women at the maternity unit, University of Malaya Medical Center. These included 49 patients with pre-eclampsia, 63 patients with pregnancy-induced hypertension and 12 normal pregnant women. DNA was extracted from the blood samples. Factor V Leiden (Taq I) and prothrombin G20210A (Hind III) genotyping was done on polymerase chain reaction-restriction fragment length polymorphism. Anti-thrombin activity and the concentrations of protein C, protein S and activated protein C were measured using the IL Coagulation System (Hemosil). Of the 124 subjects, one pre-eclampsia patient was homozygous for Factor V Leiden mutation but prothrombin G20210A mutation was not present in any of the subjects. The subject with Factor V Leiden mutation also had a low activated protein C resistance and a low protein S concentration. Factor V Leiden mutation is present in the Asian population and may very well serve as one of the genetic factors responsible for pre-eclampsia and other adverse pregnancy outcomes.

  9. GENETIC VARIANTS, IMMUNE FUNCTION AND RISK OF PRE-ECLAMPSIA AMONG AMERICAN INDIANS

    PubMed Central

    Best, Lyle G.; Nadeau, Melanie; Davis, Kylie; Lamb, Felicia; Bercier, Shellee; Anderson, Cindy M.

    2011-01-01

    Objective To determine the prevalence in an American Indian population of genetic variants with putative effects on immune function and determine if they are associated with pre-eclampsia. Methods In a study of 66 cases and 130 matched controls, six single nucleotide polymorphisms (SNP) with either previously demonstrated or postulated modulating effects on the immune system were genotyped. Allele frequencies and various genetic models were evaluated by conditional logistic regression in both univariate and multiply adjusted models. Results Although most genetic variants lacked evidence of association with pre-eclampsia, the minor allele of the CRP related, rs1205 SNP in a dominant model with adjustment for age at delivery, nulliparity and body mass index, exhibited an odds ratio of 0.259 (95% CI of 0.08 – 0.81, p=0.020) in relation to severe pre-eclampsia (48 cases). The allelic prevalence of this variant was 46.1% in this population. Conclusion Of the six SNPs related to immune function in this study, a functional variant in the 3'UTR of the CRP gene was shown to be associated with severe pre-eclampsia in an American Indian population. PMID:22004660

  10. Health care provider knowledge and routine management of pre-eclampsia in Pakistan.

    PubMed

    Sheikh, Sana; Qureshi, Rahat Najam; Khowaja, Asif Raza; Salam, Rehana; Vidler, Marianne; Sawchuck, Diane; von Dadelszen, Peter; Zaidi, Shujat; Bhutta, Zulfiqar

    2016-09-30

    Maternal mortality ratio is 276 per 100,000 live births in Pakistan. Eclampsia is responsible for one in every ten maternal deaths despite the fact that management of this disease is inexpensive and has been available for decades. Many studies have shown that health care providers in low and middle-income countries have limited training to manage patients with eclampsia. Hence, we aimed to explore the knowledge of different cadres of health care providers regarding aetiology, diagnosis and treatment of pre-eclampsia and eclampsia and current management practices. We conducted a mixed method study in the districts of Hyderabad and Matiari in Sindh province, Pakistan. Focus group discussions and interviews were conducted with community health care providers, which included Lady Health Workers and their supervisors; traditional birth attendants and facility care providers. In total seven focus groups and 26 interviews were conducted. NVivo 10 was used for analysis and emerging themes and sub-themes were drawn. All participants were providing care for pregnant women for more than a decade except one traditional birth attendant and two doctors. The most common cause of pre-eclampsia mentioned by community health care providers was stress of daily life: the burden of care giving, physical workload, short birth spacing and financial constraints. All health care provider groups except traditional birth attendants correctly identified the signs, symptoms, and complications of pre-eclampsia and eclampsia and were referring such women to tertiary health facilities. Only doctors were aware that magnesium sulphate is recommended for eclampsia management and prevention; however, they expressed fears regarding its use at first and secondary level health facilities. This study found several gaps in knowledge regarding aetiology, diagnosis and treatment of pre-eclampsia among health care providers in Sindh. Findings suggest that lesser knowledge regarding management of pre-eclampsia

  11. Community perceptions of pre-eclampsia and eclampsia in Ogun State, Nigeria: a qualitative study.

    PubMed

    Akeju, David O; Vidler, Marianne; Oladapo, Olufemi T; Sawchuck, Diane; Qureshi, Rahat; von Dadelszen, Peter; Adetoro, Olalekan O; Dada, Olukayode A

    2016-06-08

    Pre-eclampsia is a complication of pregnancy responsible for high rates of morbidity and mortality, particularly in sub-Saharan Africa. When undetected or poorly managed, it may progress to eclampsia which further worsens the prognosis. While most studies examining pre-eclampsia have used a bio-medical model, this study recognizes the role of the socio-cultural environment, in order to understand perceptions of pre-eclampsia within the community. The study was conducted in Ogun State, Nigeria in 2011-2012. Data were obtained through twenty-eight focus group discussions; seven with pregnant women (N = 80), eight with new mothers (N = 95), three with male decision-makers (N = 35), six with community leaders (N = 68), and three with traditional birth attendants (N = 36). Interviews were also conducted with the heads of the local traditional birth attendants (N = 4) and with community leaders (N = 5). Data were transcribed verbatim and analysed in NVivo 10 software. There was no terminology reportedly used for pre-eclampsia in the native language - Yoruba; however, hypertension has several terms independent of pregnancy status. Generally, 'gìrì âlábôyún' describes seizures specific to pregnancy. The cause of hypertension in pregnancy was thought to be due to depressive thoughts as a result of marital conflict and financial worries, while seizures in pregnancy were perceived to result from prolonged exposure to cold. There seemed to be no traditional treatment for hypertension. However for seizures the use of herbs, concoctions, incisions, and topical application of black soap were widespread. This study illustrates that knowledge of pre-eclampsia and eclampsia are limited amongst communities of Ogun State, Nigeria. Findings reveal that pre-eclampsia was perceived as a stress-induced condition, while eclampsia was perceived as a product of prolonged exposure to cold. Thus, heat-related local medicines and herbal concoctions were the

  12. Potential for task-sharing to Lady Health Workers for identification and emergency management of pre-eclampsia at community level in Pakistan.

    PubMed

    Salam, Rehana A; Qureshi, Rahat Najam; Sheikh, Sana; Khowaja, Asif Raza; Sawchuck, Diane; Vidler, Marianne; von Dadelszen, Peter; Zaidi, Shujaat; Bhutta, Zulfiqar

    2016-09-30

    An estimated 276 Pakistani women die for every 100,000 live births; with eclampsia accounting for about 10 % of these deaths. Community health workers contribute to the existing health system in Pakistan under the banner of the Lady Health Worker (LHW) Programme and are responsible to provide a comprehensive package of antenatal services. However, there is a need to increase focus on early identification and prompt diagnosis of pre-eclampsia in community settings, since women with mild pre-eclampsia often present without symptoms. This study aims to explore the potential for task-sharing to LHWs for the community-level management of pre-eclampsia and eclampsia in Pakistan. A qualitative exploratory study was undertaken February-July 2012 in two districts, Hyderabad and Matiari, in the southern province of Sindh, Pakistan. Altogether 33 focus group discussions (FGDs) were conducted and the LHW curriculum and training materials were also reviewed. The data was audio-recorded, then transcribed verbatim for thematic analysis using QSR NVivo-version10. Findings from the review of the LHW curriculum and training program describe that in the existing community delivery system, LHWs are responsible for identification of pregnant women, screening women for danger signs and referrals for antenatal care. They are the first point of contact for women in pregnancy and provide nutritional counselling along with distribution of iron and folic acid supplements. Findings from FGDs suggest that LHWs do not carry a blood pressure device or antihypertensive medications; they refer to the nearest public facility in the event of a pregnancy complication. Currently, they provide tetanus toxoid in pregnancy. The health advice provided by lady health workers is highly valued and accepted by pregnant women and their families. Many Supervisors of LHWs recognized the need for increased training regarding pre-eclampsia and eclampsia, with a focus on identifying women at high risk. The entire

  13. Disparities in pre-eclampsia and eclampsia among immigrant women giving birth in six industrialised countries

    PubMed Central

    Urquia, ML; Glazier, RH; Gagnon, AJ; Mortensen, LH; Nybo Andersen, A-M; Janevic, T; Guendelman, S; Thornton, D; Bolumar, F; Río Sánchez, I; Small, R; Davey, M-A; Hjern, A

    2014-01-01

    Objective To assess disparities in pre-eclampsia and eclampsia among immigrant women from various world regions giving birth in six industrialised countries. Design Cross-country comparative study of linked population-based databases. Setting Provincial or regional obstetric delivery data from Australia, Canada, Spain and the USA and national data from Denmark and Sweden. Population All immigrant and non-immigrant women delivering in the six industrialised countries within the most recent 10-year period available to each participating centre (1995–2010). Methods Data was collected using standardised definitions of the outcomes and maternal regions of birth. Pooled data were analysed with multilevel models. Within-country analyses used stratified logistic regression to obtain odds ratios (OR) with 95% confidence intervals (95% CI). Main outcome measures Pre-eclampsia, eclampsia and pre-eclampsia with prolonged hospitalisation (cases per 1000 deliveries). Results There were 9 028 802 deliveries (3 031 399 to immigrant women). Compared with immigrants from Western Europe, immigrants from Sub-Saharan Africa and Latin America & the Caribbean were at higher risk of pre-eclampsia (OR: 1.72; 95% CI: 1.63, 1.80 and 1.63; 95% CI: 1.57, 1.69) and eclampsia (OR: 2.12; 95% CI: 1.61, 2.79 and 1.55; 95% CI: 1.26, 1. 91), respectively, after adjustment for parity, maternal age and destination country. Compared with native-born women, European and East Asian immigrants were at lower risk in most industrialised countries. Spain exhibited the largest disparities and Australia the smallest. Conclusion Immigrant women from Sub-Saharan Africa and Latin America & the Caribbean require increased surveillance due to a consistently high risk of pre-eclampsia and eclampsia. PMID:24758368

  14. Disparities in pre-eclampsia and eclampsia among immigrant women giving birth in six industrialised countries.

    PubMed

    Urquia, M L; Glazier, R H; Gagnon, A J; Mortensen, L H; Nybo Andersen, A-M; Janevic, T; Guendelman, S; Thornton, D; Bolumar, F; Río Sánchez, I; Small, R; Davey, M-A; Hjern, A

    2014-11-01

    To assess disparities in pre-eclampsia and eclampsia among immigrant women from various world regions giving birth in six industrialised countries. Cross-country comparative study of linked population-based databases. Provincial or regional obstetric delivery data from Australia, Canada, Spain and the USA and national data from Denmark and Sweden. All immigrant and non-immigrant women delivering in the six industrialised countries within the most recent 10-year period available to each participating centre (1995-2010). Data was collected using standardised definitions of the outcomes and maternal regions of birth. Pooled data were analysed with multilevel models. Within-country analyses used stratified logistic regression to obtain odds ratios (OR) with 95% confidence intervals (95% CI). Pre-eclampsia, eclampsia and pre-eclampsia with prolonged hospitalisation (cases per 1000 deliveries). There were 9,028,802 deliveries (3,031,399 to immigrant women). Compared with immigrants from Western Europe, immigrants from Sub-Saharan Africa and Latin America & the Caribbean were at higher risk of pre-eclampsia (OR: 1.72; 95% CI: 1.63, 1.80 and 1.63; 95% CI: 1.57, 1.69) and eclampsia (OR: 2.12; 95% CI: 1.61, 2.79 and 1.55; 95% CI: 1.26, 1. 91), respectively, after adjustment for parity, maternal age and destination country. Compared with native-born women, European and East Asian immigrants were at lower risk in most industrialised countries. Spain exhibited the largest disparities and Australia the smallest. Immigrant women from Sub-Saharan Africa and Latin America & the Caribbean require increased surveillance due to a consistently high risk of pre-eclampsia and eclampsia. © 2014 The Authors. BJOG An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.

  15. Plasma endothelin-1 and big endothelin-1 levels in women with pre-eclampsia.

    PubMed

    Sudo, N; Kamoi, K; Ishibashi, M; Yamaji, T

    1993-08-01

    To examine a possible role for endothelin-1 (ET-1) and conversion of big ET-1 to ET-1 in the pathophysiology of pre-eclampsia, we measured plasma levels of ET-1 and big ET-1 in 16 women with pre-eclampsia in the third trimester and compared them with those in 11 age-matched normotensive pregnant women and in 10 age-matched pregnant women with chronic hypertension in the third trimester. The plasma concentrations of ET-1 and big ET-1 in the normotensive pregnant women were significantly lower than those in 16 non-pregnant women with a higher molar ratio of big ET-1 to ET-1 in the former group. The plasma concentrations of ET-1 and big ET-1 in the women with pre-eclampsia, on the other hand, were significantly higher than those in the normotensive pregnant women and the molar ratio of big ET-1 to ET-1 in the former group was less than that in the latter group. In sharp contrast, plasma ET-1 and big ET-1 levels in the pregnant women with chronic hypertension were not significantly different from those in the normotensive pregnant women. When examined after delivery, elevated plasma ET-1 and big ET-1 in the women with pre-eclampsia declined, with restoration of normal blood pressure, to the levels in the normotensive women after parturition. There were no significant differences of the levels of ET-1 and big ET-1 in umbilical venous plasma and simultaneously drawn maternal plasma at cesarean section between normotensive pregnant women and women with pre-eclampsia, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Unravelling the theories of pre-eclampsia: are the protective pathways the new paradigm?

    PubMed Central

    Ahmed, Asif; Ramma, Wenda

    2015-01-01

    Pre-eclampsia is a vascular disorder of pregnancy where anti-angiogenic factors, systemic inflammation and oxidative stress predominate, but none can claim to cause pre-eclampsia. This review provides an alternative to the ‘two-stage model’ of pre-eclampsia in which abnormal spiral arteries modification leads to placental hypoxia, oxidative stress and aberrant maternal systemic inflammation. Very high maternal soluble fms-like tyrosine kinase-1 (sFlt-1 also known as sVEGFR) and very low placenta growth factor (PlGF) are unique to pre-eclampsia; however, abnormal spiral arteries and excessive inflammation are also prevalent in other placental disorders. Metaphorically speaking, pregnancy can be viewed as a car with an accelerator and brakes, where inflammation, oxidative stress and an imbalance in the angiogenic milieu act as the ‘accelerator’. The ‘braking system’ includes the protective pathways of haem oxygenase 1 (also referred as Hmox1 or HO-1) and cystathionine-γ-lyase (also known as CSE or Cth), which generate carbon monoxide (CO) and hydrogen sulphide (H2S) respectively. The failure in these pathways (brakes) results in the pregnancy going out of control and the system crashing. Put simply, pre-eclampsia is an accelerator–brake defect disorder. CO and H2S hold great promise because of their unique ability to suppress the anti-angiogenic factors sFlt-1 and soluble endoglin as well as to promote PlGF and endothelial NOS activity. The key to finding a cure lies in the identification of cheap, safe and effective drugs that induce the braking system to keep the pregnancy vehicle on track past the finishing line. Linked Articles This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-6 PMID:25303561

  17. First and second trimester maternal serum inhibin A levels in twins with pre-eclampsia.

    PubMed

    Svirsky, Ran; Maymon, Ron; Melcer, Yaakov; Klog, Esther; Cuckle, Howard

    2016-11-01

    To investigate maternal serum inhibin as a marker of pre-eclampsia (PE) in twins. One hundred forty-three twins and 109 unaffected singleton pregnancies were recruited in the first trimester from the same institution. Blood samples were stored at recruitment and in the second trimester, retrospectively tested for inhibin and values expressed in multiples of the gestation-specific median (MoMs) in singletons, adjusted for maternal weight, as appropriate. The median inhibin level in unaffected twins was 2.04 MoM compared with 1.00 MoM in singletons (P < 0.0001, Wilcoxon Rank Sum Test, one-tailed). Excluding early fetal losses the median in 22 samples from 12 twins with PE was 2.65 MoM compared with 1.99 MoM in 201 samples from 120 unaffected twins (P < 0.02, Wilcoxon Rank Sum Test). This effect was restricted to second trimester samples with medians in cases and controls of 2.86 and 1.91 MoM respectively. Logistic regression of inhibin A together with established PE marker placental growth factor and placental associated plasma protein showed that in the second trimester, it improved screening performance although not reaching statistical significance (P = 0.08). Inhibin A is a potential second trimester marker of PE in twins. It may improve on existing twin screening protocols but more data are required. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

  18. Elevated circulating soluble thrombomodulin activity, tissue factor activity and circulating procoagulant phospholipids: new and useful markers for pre-eclampsia?

    PubMed

    Rousseau, Aurélie; Favier, Rémi; Van Dreden, Patrick

    2009-09-01

    One of the most frequently proposed mechanisms for pre-eclampsia refers to uteroplacental thrombosis. However, the contribution of classical thrombotic risk factors remains questionable. The aims of this study were to investigate the activities of thrombomodulin, tissue factor and procoagulant phospholipids to assess endothelial cell injury in pregnant women with pre-eclampsia and to compare them with other classical markers of vascular injury and thrombotic risk. Using three new functional assays we studied the plasma levels of these new markers in 35 healthy women, 30 healthy pregnant women, and 35 women with pre-eclampsia. We found that plasma levels of thrombomodulin activity, tissue factor activity and procoagulant phospholipids were significantly elevated in women with pre-eclampsia versus normal pregnant and non-pregnant women. It is thus suggested that elevated levels of these parameters in pre-eclampsia may reflect vascular endothelium damage, and may be a more valuable biomarker than antigen for the assessment of endothelial damage in pre-eclampsia. The high increased levels of procoagulant phospholipids and tissue factor activities in pre-eclampsia could suggest that the procoagulant potential may be implicated in this complication and makes these markers very promising for the understanding, follow-up and therapeutic handling of complicated pregnancy.

  19. Assessment of the diagnostic value of a urinary adipsin rapid strip test for pre-eclampsia: A prospective multicenter study.

    PubMed

    Peng, Bing; Zhang, Li; Yan, Jianying; Qi, Hongbo; Zhang, Weiyuan; Fan, Ling; Hu, Yayi; Lin, Li; Li, Xiaotian; Hu, Rong; Xie, Lan; Zhang, Jianping; Wu, Yanqiao; Li, Li; Zhou, Rong

    2017-01-01

    The purpose of the present study was to evaluate the clinical value of the rapid strip test of urinary adipsin for the quick diagnosis of pre-eclampsia. In a multicenter diagnostic test study, we studied the diagnostic accuracy of the rapid strip test of urinary adipsin in women presenting with pre-eclampsia. A total of 204 pre-eclampsia patients and 254 healthy pregnant women were recruited for this study, respectively. The rapid strip test of urinary adipsin was used to detect the adipsin in the urine of each patient. The diagnostic value of the rapid strip test of urinary adipsin for pre-eclampsia was demonstrated by its high sensitivity and specificity (95.10% and 97.64%, respectively). The diagnostic accuracy was 96.51%. The consistency analysis showed that the kappa value was 0.93 compared with the gold standard diagnosis of pre-eclampsia. The rapid strip test of urinary adipsin is a non-invasive test for the diagnosis of pre-eclampsia with high sensitivity and specificity. It could help the quick diagnosis of pre-eclampsia in clinical practice greatly. © 2016 Japan Society of Obstetrics and Gynecology.

  20. Exploring knowledge of pre-eclampsia and views on a potential screening test in women with type 1 diabetes.

    PubMed

    Wotherspoon, Amy C; Young, Ian S; McCance, David R; Holmes, Valerie A

    2017-07-01

    to explore knowledge of pre-eclampsia and opinions on potential screening tests for pre-eclampsia in women with type 1 diabetes. a qualitative study using semi-structured interviews of women planning a pregnancy, currently pregnant or post-partum with experience of pre-eclampsia. SETTING, PARTICIPANTS AND METHODS: eleven women with type 1 diabetes were recruited from a pre-pregnancy planning clinic or antenatal clinic. Semi-structured interviews were conducted with the women, asking a series of open-ended questions about their current knowledge of pre-eclampsia and their views on screening for pre-eclampsia. Data analysis was conducted using inductive thematic analysis. four main themes were identified: Information, sources of stress, awareness and acceptability of screening. Generally, women's knowledge of pre-eclampsia was limited. Most did not appear to be aware of their increased risk of developing the disease. Similarly, the majority of women were unaware as to why their blood pressure and urine were checked regularly. The introduction of a screening test for pre-eclampsia was favoured, with only a small number of women raising concerns related to the screening tests. health care professionals need to raise awareness of pre-eclampsia in this high risk group. The introduction of a screening test for pre-eclampsia appears to be acceptable in this population, however, further research is required to validate these findings and also to explore the views of women in other high risk groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Estimation of proteinuria as a predictor of complications of pre-eclampsia: a systematic review

    PubMed Central

    Thangaratinam, Shakila; Coomarasamy, Arri; O'Mahony, Fidelma; Sharp, Steve; Zamora, Javier; Khan, Khalid S; Ismail, Khaled MK

    2009-01-01

    Background Proteinuria is one of the essential criteria for the clinical diagnosis of pre-eclampsia. Increasing levels of proteinuria is considered to be associated with adverse maternal and fetal outcomes. We aim to determine the accuracy with which the amount of proteinuria predicts maternal and fetal complications in women with pre-eclampsia by systematic quantitative review of test accuracy studies. Methods We conducted electronic searches in MEDLINE (1951 to 2007), EMBASE (1980 to 2007), the Cochrane Library (2007) and the MEDION database to identify relevant articles and hand-search of selected specialist journals and reference lists of articles. There were no language restrictions for any of these searches. Two reviewers independently selected those articles in which the accuracy of proteinuria estimate was evaluated to predict maternal and fetal complications of pre-eclampsia. Data were extracted on study characteristics, quality and accuracy to construct 2 × 2 tables with maternal and fetal complications as reference standards. Results Sixteen primary articles with a total of 6749 women met the selection criteria with levels of proteinuria estimated by urine dipstick, 24-hour urine proteinuria or urine protein:creatinine ratio as a predictor of complications of pre-eclampsia. All 10 studies predicting maternal outcomes showed that proteinuria is a poor predictor of maternal complications in women with pre-eclampsia. Seventeen studies used laboratory analysis and eight studies bedside analysis to assess the accuracy of proteinuria in predicting fetal and neonatal complications. Summary likelihood ratios of positive and negative tests for the threshold level of 5 g/24 h were 2.0 (95% CI 1.5, 2.7) and 0.53 (95% CI 0.27, 1) for stillbirths, 1.5 (95% CI 0.94, 2.4) and 0.73 (95% CI 0.39, 1.4) for neonatal deaths and 1.5 (95% 1, 2) and 0.78 (95% 0.64, 0.95) for Neonatal Intensive Care Unit admission. Conclusion Measure of proteinuria is a poor predictor of

  2. Antenatal blood pressure for prediction of pre-eclampsia, preterm birth, and small for gestational age babies: development and validation in two general population cohorts

    PubMed Central

    Silverwood, Richard J; de Stavola, Bianca L; Inskip, Hazel; Cooper, Cyrus; Godfrey, Keith M; Crozier, Sarah; Fraser, Abigail; Nelson, Scott M; Lawlor, Debbie A; Tilling, Kate

    2015-01-01

    Study question Can routine antenatal blood pressure measurements between 20 and 36 weeks’ gestation contribute to the prediction of pre-eclampsia and its associated adverse outcomes? Methods This study used repeated antenatal measurements of blood pressure from 12 996 women in the Avon Longitudinal Study of Parents and Children (ALSPAC) to develop prediction models and validated these in 3005 women from the Southampton Women’s Survey (SWS). A model based on maternal early pregnancy characteristics only (BMI, height, age, parity, smoking, existing and previous gestational hypertension and diabetes, and ethnicity) plus initial mean arterial pressure was compared with a model additionally including current mean arterial pressure, a model including the deviation of current mean arterial pressure from a stratified normogram, and a model including both at different gestational ages from 20-36 weeks. Study answer and limitations The addition of blood pressure measurements from 28 weeks onwards improved prediction models compared with use of early pregnancy risk factors alone, but they contributed little to the prediction of preterm birth or small for gestational age. Though multiple imputation of missing data was used to increase the sample size and minimise selection bias, the validation sample might have been slightly underpowered as the number of cases of pre-eclampsia was just below the recommended 100. Several risk factors were self reported, potentially introducing measurement error, but this reflects how information would be obtained in clinical practice. What this study adds The addition of routinely collected blood pressure measurements from 28 weeks onwards improves predictive models for pre-eclampsia based on blood pressure in early pregnancy and other characteristics, facilitating a reduction in scheduled antenatal care. Funding, competing interests, data sharing UK Wellcome Trust, US National Institutes of Health, and UK Medical Research Council. Other

  3. Effect of Sildenafil on Pre-Eclampsia-Like Mouse Model Induced By L-Name.

    PubMed

    Motta, C; Grosso, C; Zanuzzi, C; Molinero, D; Picco, N; Bellingeri, R; Alustiza, F; Barbeito, C; Vivas, A; Romanini, M C

    2015-08-01

    N(omega)-nitro-L-arginine methyl ester (L-NAME) decreases the vasodilator effect of nitric oxide (NO) and induces pre-eclampsia in mouse. Sildenafil inhibits the degradation of nitric oxide and increases vasodilation. This study aimed to determine the effects of sildenafil citrate on angiogenesis and oxidative stress at the maternal foetal interface on pre-eclampsia-like mouse model induced by L-NAME. Twenty pregnant mice were divided into four groups: (i) vehicle control; (ii) L-NAME; (iii) sildenafil; (4) L-NAME+sildenafil. L-NAME was administered from day 7 of pregnancy and sildenafil from day 8 until day 16; animals were euthanized on day 17. Placental and foetal sizes and weights were measured; lipid peroxide levels and catalase activity in placental homogenates were determined, and placental vascular endothelia were identified by lectin-histochemistry using BSA-I lectin. Western blot analysis was used to determine VEGF expression in placental homogenates. No changes were seen in placental and foetal development in mice with normal pregnancies treated with sildenafil. Treatments with L-NAME reduced significantly the placental weight and average height and decreased the percentage of the endothelial surface. These alterations may be mediated by the reduction of NO levels in trophoblastic cells, due to the inhibitory effect of L-NAME on nitric oxide synthase (NOS) synthesis. This effect was offset by the treatment with sildenafil, with an increase in the percentage of the endothelial surface. In conclusion, our results indicate that treatment with sildenafil on pre-eclampsia mouse model can be used without adverse effects on the concept and its use in the treatment of pre-eclampsia is promising. © 2015 Blackwell Verlag GmbH.

  4. [Care plan for women with cesarean section and pre-eclampsia].

    PubMed

    Sabbagh-Sequera, Miriam; Loidi-García, Jose María; Romero-Vázquez, Gloria Maria

    2015-01-01

    Pregnancy pathologies in general, and pre-eclampsia in particular, are problems usually treated in post-anesthesia recovery and hospitalization units. Pre-eclampsia is the most frequent form of hypertension associated with pregnancy (50%). It affects from 7% to 10% of pregnant women. It is known as pregnancy and puerperium multisystem syndrome. It is due to a reduction of the systemic perfusion generated by the vasospasms and the activation of the coagulation systems. A clinical case is presented of the immediate post-surgery period of a patient, who has been operated on cesarean section after having been diagnosed with pre-eclampsia. A nursing care plan was prepared, based on Marjory Gordon functional patterns and guided by NANDA-NOC-NIC taxonomy, where 6 nursing diagnoses, which are the basis for the fulfillment of this nursing process, are identified: Risk of infection, excess fluid volume, risk of bleeding, insufficient knowledge about its pathological process, severe pain, and anxiety. The application of this care plan leads to an improvement in the patient care and in the work organization. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  5. The nitric oxide pathway and possible therapeutic options in pre-eclampsia.

    PubMed

    Johal, Tamanrit; Lees, Christoph C; Everett, Thomas R; Wilkinson, Ian B

    2014-08-01

    Pre-eclampsia is a serious multisystem disorder with diverse clinical manifestations. Although not causal, endothelial dysfunction and reduced nitric oxide bioavailability are likely to play an important role in the maternal and fetal pathophysiology of this condition. Lack of treatment modalities that can target the underlying pathophysiological changes and reverse the endothelial dysfunction frequently leads to iatrogenic preterm delivery of the fetus, causing neonatal morbidity and mortality, and the condition itself is associated with short- and longer term maternal morbidity and mortality. Drugs that target various components of the nitric oxide-soluble guanylyl cyclase pathway can help to increase NO bioavailability. The purpose of this review is to outline the current status of clinical research involving these therapeutic modalities in the context of pre-eclampsia, with the focus being on the following: nitric oxide donors, including organic nitrates and S-nitrosothiols; l-arginine, the endogenous precursor of NO; inhibitors of cyclic guanosine 3',5'-monophosphate breakdown, including sildenafil; and other novel inhibitors of NO donor metabolism. The advantages and limitations of each modality are outlined, and scope for development into established therapeutic options for pre-eclampsia is explored. © 2013 The British Pharmacological Society.

  6. The nitric oxide pathway and possible therapeutic options in pre-eclampsia

    PubMed Central

    Johal, Tamanrit; Lees, Christoph C; Everett, Thomas R; Wilkinson, Ian B

    2014-01-01

    Pre-eclampsia is a serious multisystem disorder with diverse clinical manifestations. Although not causal, endothelial dysfunction and reduced nitric oxide bioavailability are likely to play an important role in the maternal and fetal pathophysiology of this condition. Lack of treatment modalities that can target the underlying pathophysiological changes and reverse the endothelial dysfunction frequently leads to iatrogenic preterm delivery of the fetus, causing neonatal morbidity and mortality, and the condition itself is associated with short- and longer term maternal morbidity and mortality. Drugs that target various components of the nitric oxide–soluble guanylyl cyclase pathway can help to increase NO bioavailability. The purpose of this review is to outline the current status of clinical research involving these therapeutic modalities in the context of pre-eclampsia, with the focus being on the following: nitric oxide donors, including organic nitrates and S-nitrosothiols; l-arginine, the endogenous precursor of NO; inhibitors of cyclic guanosine 3′,5′-monophosphate breakdown, including sildenafil; and other novel inhibitors of NO donor metabolism. The advantages and limitations of each modality are outlined, and scope for development into established therapeutic options for pre-eclampsia is explored. PMID:24313856

  7. Maternal overweight and obesity and risk of pre-eclampsia in women with type 1 diabetes or type 2 diabetes.

    PubMed

    Persson, Martina; Cnattingius, Sven; Wikström, Anna-Karin; Johansson, Stefan

    2016-10-01

    Women with type 1 or type 2 diabetes are at increased risk of pre-eclampsia. Overweight and obesity are associated with an increased risk of pre-eclampsia in women without diabetes. The aim of the study was to investigate the impact of maternal overweight and obesity on the risk of pre-eclampsia in women with type 1 diabetes or type 2 diabetes. In a population-based cohort study including singleton births in Sweden, we estimated the risk of pre-eclampsia among women with type 1 diabetes (n = 7062) and type 2 diabetes (n = 886), and investigated whether maternal overweight (BMI 25-29.9 kg/m(2)) and obesity (BMI ≥30.0 kg/m(2)) modified the risk. Logistic regression analyses were used to estimate crude and adjusted ORs with 95% CIs, using women without diabetes as the reference group (n = 1,509,525). Compared with women without diabetes, the adjusted ORs for pre-eclampsia in women with type 1 and type 2 diabetes were 5.74 (95% CI 5.31, 6.20) and 2.11 (95% CI 1.65, 2.70), respectively. The corresponding risks of pre-eclampsia combined with preterm birth were even higher. Risks of pre-eclampsia increased with maternal overweight (BMI 25-29.9 kg/m(2)) and obesity (BMI ≥30.0 kg/m(2)), foremost in women without diabetes, to a lesser extent in women with type 1 diabetes but not in women with type 2 diabetes. Maternal overweight and obesity increased risks of pre-eclampsia in women with type 1 diabetes but not in women with type 2 diabetes. Even so, considering associations between maternal BMI and overall maternal and offspring risk, all women (with and without diabetes) should aim for a normal weight before pregnancy.

  8. A Prevention of Pre-eclampsia with the Use of Acetylsalicylic Acid and Low-molecular Weight Heparin - Molecular Mechanisms.

    PubMed

    Darmochwal-Kolarz, Dorota; Kolarz, Bogdan; Korzeniewski, Michal; Kimber-Trojnar, Zaneta; Patro-Malysza, Jolanta; Mierzynski, Radzisław; Przegalinska-Kałamucka, Monika; Oleszczuk, Jan

    Pre-eclampsia appears to be the main cause for the maternal and fetal morbidity and mortality. Pregnant women with pre-eclampsia are more likely to be threatened with conditions which potentially may be lethal, such as: disseminated intravascular coagulation, cerebral hemorrhage, liver and renal failure. Pregnancy complicated with pre-eclampsia is also associated with a greater risk for iatrogenic prematurity, intrauterine growth retardation, premature abruption of placenta, and even intrauterine fetal death. In the majority of cases the reasons for arterial hypertension among pregnant women remain obscure. For the past decades, there were many abortive attempts in the use of some microelements, vitamins or specific diets, such as polyunsaturated fatty acids, for the prophylaxis of pre-eclampsia. Recently, it has been shown that a prevention of pre-eclampsia with the use of a lowmolecular- weight heparins (LMWHs) and acetylsalicylic acid (ASA) could considerably reduce the frequency of preeclampsia. In this review, we present the studies concerning the applications of LMWHs and aspirin in the prophylaxis of pre-eclampsia and some important data about the mechanisms of anti-inflammatory actions of LMWHs and ASA.

  9. Pre-eclampsia, eclampsia and adverse maternal and perinatal outcomes: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health.

    PubMed

    Abalos, E; Cuesta, C; Carroli, G; Qureshi, Z; Widmer, M; Vogel, J P; Souza, J P

    2014-03-01

    To assess the incidence of hypertensive disorders of pregnancy and related severe complications, identify other associated factors and compare maternal and perinatal outcomes in women with and without these conditions. Secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health (WHOMCS) database. Cross-sectional study implemented at 357 health facilities conducting 1000 or more deliveries annually in 29 countries from Africa, Asia, Latin America and the Middle East. All women suffering from any hypertensive disorder during pregnancy, the intrapartum or early postpartum period in the participating hospitals during the study period. We calculated the proportion of the pre-specified outcomes in the study population and their distribution according to hypertensive disorders' severity. We estimated the association between them and maternal deaths, near-miss cases, and severe maternal complications using a multilevel logit model. Hypertensive disorders of pregnancy. Potentially life-threatening conditions among maternal near-miss cases, maternal deaths and cases without severe maternal outcomes. Overall, 8542 (2.73%) women suffered from hypertensive disorders. Incidences of pre-eclampsia, eclampsia and chronic hypertension were 2.16%, 0.28% and 0.29%, respectively. Maternal near-miss cases were eight times more frequent in women with pre-eclampsia, and increased to up to 60 times more frequent in women with eclampsia, when compared with women without these conditions. The analysis of this large database provides estimates of the global distribution of the incidence of hypertensive disorders of pregnancy. The information on the most frequent complications related to pre-eclampsia and eclampsia could be of interest to inform policies for health systems organisation. © 2014 RCOG The World Health Organization retains copyright and all other rights in the manuscript of this article as submitted for publication.

  10. Acute Maternal Infection and Risk of Pre-Eclampsia: A Population-Based Case-Control Study

    PubMed Central

    Minassian, Caroline; Thomas, Sara L.; Williams, David J.; Campbell, Oona; Smeeth, Liam

    2013-01-01

    Background Infection in pregnancy may be involved in the aetiology of pre-eclampsia. However, a clear association between acute maternal infection and pre-eclampsia has not been established. We assessed whether acute urinary tract infection, respiratory tract infection, and antibiotic drug prescriptions in pregnancy (a likely proxy for maternal infection) are associated with an increased risk of pre-eclampsia. Methods and Findings We used a matched nested case-control design and data from the UK General Practice Research Database to examine the association between maternal infection and pre-eclampsia. Primiparous women aged at least 13 years and registered with a participating practice between January 1987 and October 2007 were eligible for inclusion. We selected all cases of pre-eclampsia and a random sample of primiparous women without pre-eclampsia (controls). Cases (n = 1533) were individually matched with up to ten controls (n = 14236) on practice and year of delivery. We calculated odds ratios and 95% confidence intervals for pre-eclampsia comparing women exposed and unexposed to infection using multivariable conditional logistic regression. After adjusting for maternal age, pre-gestational hypertension, diabetes, renal disease and multifetal gestation, the odds of pre-eclampsia were increased in women prescribed antibiotic drugs (adjusted odds ratio 1.28;1.14–1.44) and in women with urinary tract infection (adjusted odds ratio 1.22;1.03–1.45). We found no association with maternal respiratory tract infection (adjusted odds ratio 0.91;0.72–1.16). Further adjustment for maternal smoking and pre-pregnancy body mass index made no difference to our findings. Conclusions Women who acquire a urinary infection during pregnancy, but not those who have a respiratory infection, are at an increased risk of pre-eclampsia. Maternal antibiotic prescriptions are also associated with an increased risk. Further research is required to elucidate the underlying

  11. Action on Pre-eclampsia: Crisis and recovery.

    PubMed

    Milne, Fiona

    2011-01-01

    This is a review of the antenatal guidelines developed under the auspices of the charity Action on Preeclampsia since 2001. They are evidence-based and cover the screening and diagnosis of preeclampsia. They include a risk assessment early in pregnancy, referral for specialist input, a two tier schedule of assessment based on risk, signs and symptoms, referral for step-up care and confirmation of diagnosis, including blood tests. They describe methods for improving reliability of proteinuria testing, and reducing errors in the measurement of blood pressure. Management flowcharts are provided. Copyright © 2010 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

  12. Epidural therapy for the treatment of severe pre-eclampsia in non labouring women.

    PubMed

    Ray, Amita; Ray, Sujoy

    2017-11-28

    Pre-eclampsia is a pregnancy-specific multi-organ disorder, which is characterised by hypertension and multisystem organ involvement and which has significant maternal and fetal morbidity and mortality. Failure of the placental vascular remodelling and reduced uteroplacental flow form the etiopathological basis of pre-eclampsia. There are several established therapies for pre-eclampsia including antihypertensives and anticonvulsants. Most of these therapies aim at controlling the blood pressure or preventing complications of elevated blood pressure, or both. Epidural therapy aims at blocking the vasomotor tone of the arteries, thereby increasing uteroplacental blood flow. This review was aimed at evaluating the available evidence about the possible benefits and risks of epidural therapy in the management of severe pre-eclampsia, to define the current evidence level of this therapy, and to determine what (if any) further evidence is required. To assess the effectiveness, safety and cost of the extended use of epidural therapy for treating severe pre-eclampsia in non-labouring women. This review aims to compare the use of extended epidural therapy with other methods, which include intravenous magnesium sulphate, anticonvulsants other than magnesium sulphate, with or without use of the antihypertensive drugs and adjuncts in the treatment of severe pre-eclampsia.This review only considered the use of epidural anaesthesia in the management of severe pre-eclampsia in the antepartum period and not as pain relief in labour. We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (13 July 2017) and reference lists of retrieved studies. Randomised controlled trials (RCTs) or quasi-RCTs comparing epidural therapy versus traditional therapy for pre-eclampsia in the form of antihypertensives, anticonvulsants, magnesium sulphate, low-dose dopamine, corticosteroids or a combination of

  13. Association between pre-eclampsia and locally derived traffic-related air pollution: a retrospective cohort study.

    PubMed

    Pereira, Gavin; Haggar, Fatima; Shand, Antonia W; Bower, Carol; Cook, Angus; Nassar, Natasha

    2013-02-01

    Pre-eclampsia is a common complication of pregnancy and is a major cause of fetal-maternal mortality and morbidity. Despite a number of plausible mechanisms by which air pollutants might contribute to this process, few studies have investigated the association between pre-eclampsia and traffic emissions, a major contributor to air pollution in urban areas. The authors investigated the association between traffic-related air pollution and risk of pre-eclampsia in a maternal population in the urban centre of Perth, Western Australia. The authors estimated maternal residential exposure to a marker for traffic-related air pollution (nitrogen dioxide, NO(2)) during pregnancy for 23 452 births using temporally adjusted land-use regression. Logistic regression was used to investigate associations with pre-eclampsia. Each IQR increase in levels of traffic-related air pollution in whole pregnancy and third trimester was associated with a 12% (1%-25%) and 30% (7%-58%) increased risk of pre-eclampsia, respectively. The largest effect sizes were observed for women aged younger than 20 years or 40 years or older, aboriginal women and women with pre-existing and gestational diabetes, for whom an IQR increase in traffic-related air pollution in whole pregnancy was associated with a 34% (5%-72%), 35% (0%-82%) and 53% (7%-219%) increase in risk of pre-eclampsia, respectively. Elevated exposure to traffic-related air pollution in pregnancy was associated with increased risk of pre-eclampsia. Effect sizes were highest for elevated exposures in third trimester and among younger and older women, aboriginal women and women with diabetes.

  14. Evaluation of biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes mellitus: A systematic review.

    PubMed

    Wotherspoon, Amy C; Young, Ian S; McCance, David R; Holmes, Valerie A

    2016-07-01

    Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. Women with type 1 diabetes are considered a high-risk group for developing pre-eclampsia. Much research has focused on biomarkers as a means of screening for pre-eclampsia in the general maternal population; however, there is a lack of evidence for women with type 1 diabetes. To undertake a systematic review to identify potential biomarkers for the prediction of pre-eclampsia in women with type 1 diabetes. We searched Medline, EMBASE, Maternity and Infant Care, Scopus, Web of Science and CINAHL SELECTION CRITERIA: Studies were included if they measured biomarkers in blood or urine of women who developed pre-eclampsia and had pre-gestational type 1 diabetes mellitus Data collection and analysis A narrative synthesis was adopted as a meta-analysis could not be performed, due to high study heterogeneity. A total of 72 records were screened, with 21 eligible studies being included in the review. A wide range of biomarkers was investigated and study size varied from 34 to 1258 participants. No single biomarker appeared to be effective in predicting pre-eclampsia; however, glycaemic control was associated with an increased risk while a combination of angiogenic and anti-angiogenic factors seemed to be potentially useful. Limited evidence suggests that combinations of biomarkers may be more effective in predicting pre-eclampsia than single biomarkers. Further research is needed to verify the predictive potential of biomarkers that have been measured in the general maternal population, as many studies exclude women with diabetes preceding pregnancy. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Reduced risk of pre-eclampsia with organic vegetable consumption: results from the prospective Norwegian Mother and Child Cohort Study.

    PubMed

    Torjusen, Hanne; Brantsæter, Anne Lise; Haugen, Margaretha; Alexander, Jan; Bakketeig, Leiv S; Lieblein, Geir; Stigum, Hein; Næs, Tormod; Swartz, Jackie; Holmboe-Ottesen, Gerd; Roos, Gun; Meltzer, Helle Margrete

    2014-09-10

    Little is known about the potential health effects of eating organic food either in the general population or during pregnancy. The aim of this study was to examine associations between organic food consumption during pregnancy and the risk of pre-eclampsia among nulliparous Norwegian women. Prospective cohort study. Norway, years 2002-2008. 28 192 pregnant women (nulliparous, answered food frequency questionnaire and general health questionnaire in mid-pregnancy and no missing information on height, body weight or gestational weight gain). Relative risk was estimated as ORs by performing binary logistic regression with pre-eclampsia as the outcome and organic food consumption as the exposure. The prevalence of pre-eclampsia in the study sample was 5.3% (n=1491). Women who reported to have eaten organic vegetables 'often' or 'mostly' (n=2493, 8.8%) had lower risk of pre-eclampsia than those who reported 'never/rarely' or 'sometimes' (crude OR=0.76, 95% CI 0.61 to 0.96; adjusted OR=0.79, 95% CI 0.62 to 0.99). The lower risk associated with high organic vegetable consumption was evident also when adjusting for overall dietary quality, assessed as scores on a healthy food pattern derived by principal component analysis. No associations with pre-eclampsia were found for high intake of organic fruit, cereals, eggs or milk, or a combined index reflecting organic consumption. These results show that choosing organically grown vegetables during pregnancy was associated with reduced risk of pre-eclampsia. Possible explanations for an association between pre-eclampsia and use of organic vegetables could be that organic vegetables may change the exposure to pesticides, secondary plant metabolites and/or influence the composition of the gut microbiota. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  16. Reduced risk of pre-eclampsia with organic vegetable consumption: results from the prospective Norwegian Mother and Child Cohort Study

    PubMed Central

    Torjusen, Hanne; Brantsæter, Anne Lise; Haugen, Margaretha; Alexander, Jan; Bakketeig, Leiv S; Lieblein, Geir; Stigum, Hein; Næs, Tormod; Swartz, Jackie; Holmboe-Ottesen, Gerd; Roos, Gun; Meltzer, Helle Margrete

    2014-01-01

    Objective Little is known about the potential health effects of eating organic food either in the general population or during pregnancy. The aim of this study was to examine associations between organic food consumption during pregnancy and the risk of pre-eclampsia among nulliparous Norwegian women. Design Prospective cohort study. Setting Norway, years 2002–2008. Participants 28 192 pregnant women (nulliparous, answered food frequency questionnaire and general health questionnaire in mid-pregnancy and no missing information on height, body weight or gestational weight gain). Main outcome measure Relative risk was estimated as ORs by performing binary logistic regression with pre-eclampsia as the outcome and organic food consumption as the exposure. Results The prevalence of pre-eclampsia in the study sample was 5.3% (n=1491). Women who reported to have eaten organic vegetables ‘often’ or ‘mostly’ (n=2493, 8.8%) had lower risk of pre-eclampsia than those who reported ‘never/rarely’ or ‘sometimes’ (crude OR=0.76, 95% CI 0.61 to 0.96; adjusted OR=0.79, 95% CI 0.62 to 0.99). The lower risk associated with high organic vegetable consumption was evident also when adjusting for overall dietary quality, assessed as scores on a healthy food pattern derived by principal component analysis. No associations with pre-eclampsia were found for high intake of organic fruit, cereals, eggs or milk, or a combined index reflecting organic consumption. Conclusions These results show that choosing organically grown vegetables during pregnancy was associated with reduced risk of pre-eclampsia. Possible explanations for an association between pre-eclampsia and use of organic vegetables could be that organic vegetables may change the exposure to pesticides, secondary plant metabolites and/or influence the composition of the gut microbiota. PMID:25208850

  17. Inadequate safety reporting in pre-eclampsia trials: a systematic evaluation.

    PubMed

    Duffy, Jmn; Hirsch, M; Pealing, L; Showell, M; Khan, K S; Ziebland, S; McManus, R J

    2018-06-01

    Randomised trials and their syntheses in meta-analyses offer a unique opportunity to assess the frequency and severity of adverse reactions. To assess safety reporting in pre-eclampsia trials. Systematic search using bibliographic databases, including Cochrane Central Register of Controlled Trials, Embase, and MEDLINE, from inception to August 2017. Randomised trials evaluating anticonvulsant or antihypertensive medication for pre-eclampsia. Descriptive statistics appraising the adequacy of adverse reaction and toxicity reporting. We included 60 randomised trials. Six trials (10%) were registered with the International Clinical Trials Registry Platform, two registry records referred to adverse reactions, stating 'safety and toleration' and 'possible side effects' would be collected. Twenty-six trials (43%) stated the frequency of withdrawals within each study arm, and five trials (8%) adequately reported these withdrawals. Adverse reactions were inconsistently reported across eligible trials: 24 (40%) reported no serious adverse reactions and 36 (60%) reported no mild adverse reactions. The methods of definition or measurement of adverse reactions were infrequently reported within published trial reports. Pre-eclampsia trials regularly omit critical information related to safety. Despite the paucity of reporting, randomised trials collect an enormous amount of safety data. Developing and implementing a minimum data set could help to improve safety reporting, permitting a more balanced assessment of interventions by considering the trade-off between the benefits and harms. National Institute for Health Research (DRF-2014-07-051), UK; Maternity Forum, Royal Society of Medicine, UK. Developing @coreoutcomes could help to improve safety reporting in #preeclampsia trials. @NIHR_DC. © 2017 Royal College of Obstetricians and Gynaecologists.

  18. Mass Spectrometry-Based Proteomics for Pre-Eclampsia and Preterm Birth

    PubMed Central

    Law, Kai P.; Han, Ting-Li; Tong, Chao; Baker, Philip N.

    2015-01-01

    Pregnancy-related complications such as pre-eclampsia and preterm birth now represent a notable burden of adverse health. Pre-eclampsia is a hypertensive disorder unique to pregnancy. It is an important cause of maternal death worldwide and a leading cause of fetal growth restriction and iatrogenic prematurity. Fifteen million infants are born preterm each year globally, but more than one million of those do not survive their first month of life. Currently there are no predictive tests available for diagnosis of these pregnancy-related complications and the biological mechanisms of the diseases have not been fully elucidated. Mass spectrometry-based proteomics have all the necessary attributes to provide the needed breakthrough in understanding the pathophysiology of complex human diseases thorough the discovery of biomarkers. The mass spectrometry methodologies employed in the studies for pregnancy-related complications are evaluated in this article. Top-down proteomic and peptidomic profiling by laser mass spectrometry, liquid chromatography or capillary electrophoresis coupled to mass spectrometry, and bottom-up quantitative proteomics and targeted proteomics by liquid chromatography mass spectrometry have been applied to elucidate protein biomarkers and biological mechanism of pregnancy-related complications. The proteomes of serum, urine, amniotic fluid, cervical-vaginal fluid, placental tissue, and cytotrophoblastic cells have all been investigated. Numerous biomarkers or biomarker candidates that could distinguish complicated pregnancies from healthy controls have been proposed. Nevertheless, questions as to the clinically utility and the capacity to elucidate the pathogenesis of the pre-eclampsia and preterm birth remain to be answered. PMID:26006232

  19. Community health worker knowledge and management of pre-eclampsia in rural Karnataka State, India.

    PubMed

    Ramadurg, Umesh; Vidler, Marianne; Charanthimath, Umesh; Katageri, Geetanjali; Bellad, Mrutyunjaya; Mallapur, Ashalata; Goudar, Shivaprasad; Bannale, Shashidhar; Karadiguddi, Chandrashekhar; Sawchuck, Diane; Qureshi, Rahat; von Dadelszen, Peter; Derman, Richard

    2016-09-30

    In India, the hypertensive disorders of pregnancy and postpartum haemorrhage are responsible for nearly 40 % of all maternal deaths. Most of these deaths occur in primary health settings which frequently lack essential equipment and medication, are understaffed, and have limited or no access to specialist care. Community health care workers are regarded as essential providers of basic maternity care; and the quality of care they provide is dependent on the level of knowledge and skills they possess. However, there is limited research regarding their ability to manage pregnancy complications. This study aims to describe the current state of knowledge regarding pre-eclampsia and eclampsia among community health care workers (auxiliary nurse midwives, accredited social health activists, staff nurses) in northern Karnataka, India. Furthermore, this study describes the treatment approaches used by various cadres of community health workers for these conditions. The findings of this study can help plan focussed training sessions to build upon their strengths and to address the identified gaps. Data were collected as part of a larger study aimed at assessing the feasibility of community-based treatment for pre-eclampsia. Eight focus group discussions were conducted in 2012-2013 in northern Karnataka State: four with staff nurses and auxiliary nurse midwives and four with accredited social health activists. In addition, twelve auxiliary nurse midwives and staff nurses completed questionnaires to explore their competence and self-efficacy in managing pre-eclampsia. Qualitative data were audio-recorded, transcribed verbatim and translated for thematic analysis using NVivo 10. Community health workers described their understanding of the origins of hypertension and seizures in pregnancy. Psychological explanations of hypertension were most commonly reported: stress, tension, and fear. The most common explanation for eclampsia was not receiving a tetanus vaccination. Despite

  20. [Sex-hormone binding globulin (SHBG) levels during pregnancy as predictors for pre-eclampsia and fetal growth restriction].

    PubMed

    Valdés R, Enrique; Lattes A, Karina; Muñoz S, Hernán; Cumsille, Miguel Angel

    2012-05-01

    Sex-Hormone Binding Globulin (SHBG) may be associated to Pre-eclampsia (PE) and Fetal Growth Restriction (RCIU). To determine if maternal serum SHBG concentrations during the first and second trimesters are predictive biomarkers of Pre-eclampsia and RCIU. Prospective cohort study carried out in the Fetal Medicine Unit, Universidad de Chile Clinical Hospital between January, 2005 and December, 2006. Blood samples were obtained from unselected pregnant women during routine 11-14 week and 22-25 week ultrasound examinations, conforming two different study groups. Posteriorly, serum SHBG concentrations were determined in women who developed Pre-eclampsia, RCIU and their respective controls. Fifty five patients were included in the 11-14 weeks group. Nine women that developed PE, 10 that developed RCIU and 36 controls were selected from this group. There were no significant differences in SHBG levels between patients with PE, RCIU or controls (324.7 (26.6), 336.8 (33.9) and 377.5 (24.3) nmol/L, respectively). Fifty four women were included in the 22-25 weeks group. Eight women who developed Pre-eclampsia, 15 who developed RCIU and 31 controls were selected. Again, there were no significant differences in SHBG levels between patients with PE, RCIU or controls (345.5 (151.1), 383.8 (143.4) and 345.5 nmol/l (151.1), respectively). Maternal SHBG serum levels did not predict subsequent development of Pre-eclampsia and RCIU.

  1. Cohort profile: the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC).

    PubMed

    Jääskeläinen, Tiina; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Kivinen, Katja; Pouta, Anneli; Laivuori, Hannele

    2016-11-10

    The Finnish Genetics of Pre-eclampsia Consortium (FINNPEC) Study was established to set up a nationwide clinical and DNA database on women with and without pre-eclampsia (PE), including their partners and infants, in order to identify genetic risk factors for PE. FINNPEC is a cross-sectional case-control cohort collected from 5 university hospitals in Finland during 2008-2011. A total of 1450 patients with PE and 1065 pregnant control women without PE (aged 18-47 years) were recruited. Altogether, there were 1377 full triads (625 PE and 752 control triads). The established cohort holds both clinical and genetic information of mother-infant-father triads representing a valuable resource for studying the pathogenesis of the disease. Furthermore, maternal biological samples (first and third trimester serum and placenta) will provide additional information for PE research. Until now, research has encompassed studies on candidate genes, Sanger and next-generation sequencing, and various studies on the placenta. FINNPEC has also participated in the InterPregGen study, which is the largest investigation on maternal and fetal genetic factors underlying PE until now. Ongoing studies focus on elucidating the role of immunogenetic and metabolic factors in PE. Data on morbidity and mortality will be collected from mothers and fathers through links to the nationwide health registers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  2. Pre-eclampsia in American Indians/Alaska Natives and Whites: The Significance of Body Mass Index.

    PubMed

    Zamora-Kapoor, Anna; Nelson, Lonnie A; Buchwald, Dedra S; Walker, Leslie R; Mueller, Beth A

    2016-11-01

    Introduction The prevalence of pre-eclampsia, a major cause of maternal morbidity, varies by race, being greater in African Americans, and lower in Asians and Hispanics than in White women. Little is known about its prevalence in American Indians/Alaska Natives (AI/ANs). We estimated pre-eclampsia risk in AI/ANs compared to Whites, with consideration of the potential effect of obesity, a major risk factor for pre-eclampsia, and a condition disproportionately affecting AI/AN women. Methods This retrospective cohort study of linked birth-hospital discharge data from Washington State (2003-2013) included all AI/AN women and a sample of White first-time mothers with singleton deliveries. Logistic regression was used to estimate odds ratio (OR) and 95 % confidence intervals (CI) for pre-eclampsia risk in AI/ANs compared to Whites, first controlling for several important risk factors, and subsequently with additional adjustment for pre-pregnancy body mass index (BMI). Results AI/ANs had an increased risk of pre-eclampsia compared to Whites after controlling for all covariates except BMI (OR 1.17, 95 % CI 1.06-1.29). After further adjustment for BMI, the racial disparity in pre-eclampsia risk was greatly attenuated (OR 1.05, 95 % CI 0.95-1.16). Discussion This population-based study suggests that any increased risk in AI/ANs relative to Whites may be at least partly due to differences in BMI.

  3. Pre-eclampsia in American Indians/Alaska Natives and Whites: The Significance of Body Mass Index

    PubMed Central

    Nelson, Lonnie A.; Buchwald, Dedra S.; Walker, Leslie R.; Mueller, Beth A.

    2016-01-01

    Introduction The prevalence of pre-eclampsia, a major cause of maternal morbidity, varies by race, being greater in African Americans, and lower in Asians and Hispanics than in White women. Little is known about its prevalence in American Indians/Alaska Natives (AI/ANs). We estimated pre-eclampsia risk in AI/ANs compared to Whites, with consideration of the potential effect of obesity, a major risk factor for pre-eclampsia, and a condition disproportionately affecting AI/AN women. Methods This retrospective cohort study of linked birth-hospital discharge data from Washington State (2003–2013) included all AI/AN women and a sample of White first-time mothers with singleton deliveries. Logistic regression was used to estimate odds ratio (OR) and 95 % confidence intervals (CI) for pre-eclampsia risk in AI/ANs compared to Whites, first controlling for several important risk factors, and subsequently with additional adjustment for pre-pregnancy body mass index (BMI). Results AI/ANs had an increased risk of pre-eclampsia compared to Whites after controlling for all covariates except BMI (OR 1.17, 95 % CI 1.06–1.29). After further adjustment for BMI, the racial disparity in pre-eclampsia risk was greatly attenuated (OR 1.05, 95 % CI 0.95–1.16). Discussion This population-based study suggests that any increased risk in AI/ANs relative to Whites may be at least partly due to differences in BMI. PMID:27461024

  4. The Prognostic Role of Angiotensin II Type 1 Receptor Autoantibody in Non-Gravid Hypertension and Pre-eclampsia

    PubMed Central

    Lei, Jinghui; Li, Yafeng; Zhang, Suli; Wu, Ye; Wang, Pengli; Liu, Huirong

    2016-01-01

    Abstract Angiotensin II type 1 receptor autoantibody (AT1-AA) is found in patients with non-gravid hypertension or pre-eclampsia, but the relationship is uncertain. The aim of the present study was to assess the association between AT1-AA and high blood pressure using meta-analysis, and to evaluate the prognosis value of AT1-AA for hypertensive diseases. Literature search from PubMed, Embase, and Cochrane databases were conducted using keywords “hypertension” or “pre-eclampsia,” “angiotensin II receptor type 1 autoantibody,” and its aliases from April 1999 to December 2015. Studies evaluating the association between AT1-AA and non-gravid hypertension or pre-eclampsia were included in this analysis. The quality of the eligible studies was assessed based on the Newcastle–Ottawa Scale with some modifications. Two researchers then independently reviewed all included studies and extracted all relevant data. Association between AT1-AA and hypertension was tested with pooled odds ratios (ORs) and 95% confidence intervals (CIs). Finally, we evaluated whether AT1-AA predicted the prognosis of hypertension by using a summary receiver-operating characteristic (ROC) curve and sensitivity analysis. Ten studies were finally included in this meta-analysis. AT1-AA showed more significant association with pre-eclampsia than that with non-gravid hypertension (pooled OR 32.84, 95% CI 17.19–62.74; and pooled OR 4.18, 95% CI 2.20–7.98, respectively). Heterogeneity among studies was also detected probably due to different hypertensive subtypes and AT1-AA measuring methods. Area under summary ROC curve (AUC) of pre-eclampsia was 0.92 (sensitivity 0.76; specificity 0.86). Area under the ROC curve of overall hypertensive diseases or non-gravid hypertension was lower than that of pre-eclampsia (0.86 and 0.72, respectively) with lower sensitivities (0.46 and 0.26, respectively). The major limitation of this analysis was the publication bias due to lack of unpublished data

  5. Levels of serum-circulating angiogenic factors within 1 week prior to delivery are closely related to conditions of pregnant women with pre-eclampsia, gestational hypertension, and/or fetal growth restriction.

    PubMed

    Nanjo, Sakiko; Minami, Sawako; Mizoguchi, Mika; Yamamoto, Madoka; Yahata, Tamaki; Toujima, Saori; Shiro, Michihisa; Kobayashi, Aya; Muragaki, Yasuteru; Ino, Kazuhiko

    2017-12-01

    We aimed to investigate maternal serum angiogenic marker profiles within 1 week prior to delivery in cases of gestational hypertension (GH), pre-eclampsia (PE), and/or fetal growth restriction (FGR) with different clinical conditions. We enrolled 165 women with singleton pregnancy. The participants were classified based on three characteristics: (i) proteinuria (GH and PE); (ii) FGR (PE with FGR [PE + FGR], PE alone, and FGR alone); and (iii) onset (early onset PE [EO PE] and late-onset PE [LO PE]). All sera were obtained within 1 week prior to delivery, and soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), and placental growth factor (PlGF) were measured with enzyme-linked immunosorbent assay. (i) In PE, a significantly increased sFlt-1, sEng, and sFlt-1 to PlGF ratio (sFlt-1/PlGF) and significantly decreased PlGF were observed compared with GH and Term control, whereas in GH, only sFlt-1/PlGF was significantly higher than Term control. (ii) In PE + FGR, similar changes were more markedly shown compared with PE alone. The FGR alone group exhibited similar tendencies as PE, although significant differences were found in PlGF and sEng levels. (iii) In EO PE, significant changes were observed in all factors compared with LO PE or Term control, while no significant change in PlGF levels was observed between LO PE and Term control. We demonstrated that the levels of circulating angiogenic factors just before delivery are correlated with the severity of hypertensive disorders of pregnancy and FGR. Profiling these specific markers may contribute to better understanding of the clinical conditions in individual patients and their pathogenesis. © 2017 Japan Society of Obstetrics and Gynecology.

  6. Comparison of serum trace element levels in patients with or without pre-eclampsia.

    PubMed

    Farzin, Leila; Sajadi, Fattaneh

    2012-10-01

    In developing countries, nutritional deficiency of essential trace elements is a common health problem, particularly among pregnant women because of increased requirements of various nutrients. Accordingly, this study was initiated to compare trace elements status in women with or without pre-eclampsia. In this study, serum trace elements including zinc (Zn), selenium (Se), copper (Cu), calcium (Ca) and magnesium (Mg) were determined by using atomic absorption spectrometry (AAS) in 60 patients and 60 healthy subjects. There was no significant difference in the values of Cu between two groups (P > 0.05). A significant difference in Zn, Se, Ca and Mg levels were observed between patients with pre-eclampsia and control group (P < 0.001, P<0.01, P<0.01 and P<0.001, respectively). Zn, Se, Ca and Mg levels were found to be 76.49 ± 17.62 μg/ dl, 8.82 ± 2.10 μg/ dl, 8.65 ± 2.14 mg/dl and 1.51 ± 0.34 mg/dl in Pre-eclamptic cases, and these values were found statistically lower compared to the controls (100.61 ± 20.12 μg/dl, 10.47 ± 2.78 μg/dl, 9.77 ± 3.02 mg/dl and 1.78 ± 0.27 mg/dl, respectively). While Cu levels were 118.28 ± 16.92 and 116.55 ± 15.23 μg/dl in the patients and the healthy subjects, respectively. In addition, no significant difference was found between two groups with respect to Hemoglobin Concentration (HbC) and Total White Blood Cell Count (TWBC) (P>0.05). Our findings indicate that the levels of Zn, Se, Ca and Mg are significantly altered in pregnant women with pre-eclampsia. This research shows that these deficiencies can not due to hemodilution.

  7. Comparison of serum trace element levels in patients with or without pre-eclampsia

    PubMed Central

    Farzin, Leila; Sajadi, Fattaneh

    2012-01-01

    Objective: In developing countries, nutritional deficiency of essential trace elements is a common health problem, particularly among pregnant women because of increased requirements of various nutrients. Accordingly, this study was initiated to compare trace elements status in women with or without pre-eclampsia. Materials and Methods: In this study, serum trace elements including zinc (Zn), selenium (Se), copper (Cu), calcium (Ca) and magnesium (Mg) were determined by using atomic absorption spectrometry (AAS) in 60 patients and 60 healthy subjects. Results: There was no significant difference in the values of Cu between two groups (P > 0.05). A significant difference in Zn, Se, Ca and Mg levels were observed between patients with pre-eclampsia and control group (P < 0.001, P<0.01, P<0.01 and P<0.001, respectively). Zn, Se, Ca and Mg levels were found to be 76.49 ± 17.62 μg/ dl, 8.82 ± 2.10 μg/ dl, 8.65 ± 2.14 mg/dl and 1.51 ± 0.34 mg/dl in Pre-eclamptic cases, and these values were found statistically lower compared to the controls (100.61 ± 20.12 μg/dl, 10.47 ± 2.78 μg/dl, 9.77 ± 3.02 mg/dl and 1.78 ± 0.27 mg/dl, respectively). While Cu levels were 118.28 ± 16.92 and 116.55 ± 15.23 μg/dl in the patients and the healthy subjects, respectively. In addition, no significant difference was found between two groups with respect to Hemoglobin Concentration (HbC) and Total White Blood Cell Count (TWBC) (P>0.05). Conclusion: Our findings indicate that the levels of Zn, Se, Ca and Mg are significantly altered in pregnant women with pre-eclampsia. This research shows that these deficiencies can not due to hemodilution. PMID:23825993

  8. A protocol for developing, disseminating, and implementing a core outcome set for pre-eclampsia.

    PubMed

    Duffy, James M N; van 't Hooft, Janneke; Gale, Chris; Brown, Mark; Grobman, William; Fitzpatrick, Ray; Karumanchi, S Ananth; Lucas, Nuala; Magee, Laura; Mol, Ben; Stark, Michael; Thangaratinam, Shakila; Wilson, Mathew; von Dadelszen, Peter; Williamson, Paula; Khan, Khalid S; Ziebland, Sue; McManus, Richard J

    2016-10-01

    Pre-eclampsia is a serious complication of pregnancy and contributes to maternal and offspring mortality and morbidity. Randomised controlled trials evaluating therapeutic interventions for pre-eclampsia have reported many different outcomes and outcome measures. Such variation contributes to an inability to compare, contrast, and combine individual studies, limiting the usefulness of research to inform clinical practice. The development and use of a core outcome set would help to address these issues ensuring outcomes important to all stakeholders, including patients, will be collected and reported in a standardised fashion. An international steering group including healthcare professionals, researchers, and patients, has been formed to guide the development of this core outcome set. Potential outcomes will be identified through a comprehensive literature review and semi-structured interviews with patients. Potential core outcomes will be entered into an international, multi-perspective online Delphi survey. All key stakeholders, including healthcare professionals, researchers, and patients will be invited to participate. The modified Delphi method encourages whole and stakeholder group convergence towards consensus 'core' outcomes. Once core outcomes have been agreed upon it is important to determine how they should be measured. The truth, discrimination, and feasibility assessment framework will assess the quality of potential outcome measures. High quality outcome measures will be associated with core outcomes. Mechanisms exist to disseminate and implement the resulting core outcome set within an international context. Embedding the core outcome set within future clinical trials, systematic reviews, and clinical practice guidelines could make a profound contribution to advancing the usefulness of research to inform clinical practice, enhance patient care, and improve maternal and offspring outcomes. The infrastructure created by developing a core outcome set

  9. Antihypertensive effects of inducible nitric oxide synthase inhibition in experimental pre-eclampsia.

    PubMed

    Amaral, Lorena M; Pinheiro, Lucas C; Guimaraes, Danielle A; Palei, Ana C T; Sertório, Jonas T; Portella, Rafael L; Tanus-Santos, Jose E

    2013-10-01

    Upregulation of inducible nitric oxide synthase (iNOS) has been reported in both experimental and clinical hypertension. However, although pro-inflammatory cytokines that up-regulate iNOS contribute to pre-eclampsia, no previous study has tested the hypothesis that a selective iNOS inhibitor (1400 W) could exert antihypertensive effects associated with decreased iNOS expression and nitrosative stress in pre-eclampsia. This study examined the effects of 1400 W in the reduced uteroplacental perfusion pressure (RUPP) placental ischaemia animal model and in normal pregnant rats. Sham-operated and RUPP rats were treated with daily vehicle or 1 mg/kg/day N-[3-(Aminomethyl) benzyl] acetamidine (1400 W) subcutaneously for 5 days. Plasma 8-isoprostane levels, aortic reactive oxygen species (ROS) levels and nicotinamide adenine dinucleotide phosphate (NADPH)-dependent ROS production were evaluated by ELISA, dihydroethidium fluorescence microscopy and lucigenin chemiluminescence respectively. Inducible nitric oxide synthase expression was assessed by western blotting analysis and aortic nitrotyrosine was evaluated by immunohistochemistry. Mean arterial blood pressure increased by ~30 mmHg in RUPP rats, and 1400 W attenuated this increase by ~50% (P < 0.05). While RUPP increased plasma 8-isoprostane levels, aortic ROS levels, and NADPH-dependent ROS production (P < 0.05), treatment with 1400 W blunted these alterations (P < 0.05). Moreover, while RUPP increased iNOS expression and aortic nitrotyrosine levels (P < 0.05), treatment with 1400 W blunted these alterations (P < 0.05). These results clearly implicate iNOS in the hypertension associated with RUPP. Our findings may suggest that iNOS inhibitors could be clinically useful in the therapy of pre-eclampsia, especially in particular groups of patients genetically more prone to express higher levels of iNOS. This issue deserves further confirmation. © 2013 The Authors. Journal of Cellular and Molecular

  10. Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes pre-eclampsia in Type 1 diabetes

    PubMed Central

    Yu, Y; Hanssen, KF; Kalyanaraman, V; Chirindel, A; Jenkins, AJ; Nankervis, AJ; Torjesen, PA; Scholz, H; Henriksen, T; Lorentzen, B; Garg, SK; Menard, MK; Hammad, SM; Scardo, JA; Stanley, JR; Wu, M; Basu, A; Aston, CE; Lyons, TJ

    2014-01-01

    Objective Increased advanced glycation end-products (AGEs) and their soluble receptors (sRAGE) have been implicated in the pathogenesis of pre-eclampsia (PE). However, this association has not been elucidated in pregnancies complicated by diabetes. We aimed to investigate the serum levels of these factors in pregnant women with Type 1 diabetes mellitus (T1DM), a condition associated with a four-fold increase in PE. Design Prospective study in women with T1DM at 12.2 ± 1.9, 21.6 ± 1.5 and 31.5 ± 1.7 weeks of gestation [mean ± standard deviation (SD); no overlap] before PE onset. Setting Antenatal clinics. Population Pregnant women with T1DM (n = 118; 26 developed PE) and healthy nondiabetic pregnant controls (n = 21). Methods Maternal serum levels of sRAGE (total circulating pool), Nε-(carboxymethyl)lysine (CML), hydroimidazolone (methylglyoxal-modified proteins) and total AGEs were measured by immunoassays. Main outcome measures Serum sRAGE and AGEs in pregnant women with T1DM who subsequently developed PE (DM PE+) versus those who remained normotensive (DM PE–). Results In DM PE+ versus DM PE–, sRAGE was significantly lower in the first and second trimesters, prior to the clinical manifestation of PE (P < 0.05). Further, reflecting the net sRAGE scavenger capacity, sRAGE : hydroimidazolone was significantly lower in the second trimester (P < 0.05) and sRAGE : AGE and sRAGE : CML tended to be lower in the first trimester (P < 0.1) in women with T1DM who subsequently developed PE versus those who did not. These conclusions persisted after adjusting for prandial status, glycated haemoglobin (HbA1c), duration of diabetes, parity and mean arterial pressure as covariates. Conclusions In the early stages of pregnancy, lower circulating sRAGE levels, and the ratio of sRAGE to AGEs, may be associated with the subsequent development of PE in women with T1DM. PMID:22900949

  11. A criteria-based audit of the management of severe pre-eclampsia in Kampala, Uganda.

    PubMed

    Weeks, A D; Alia, G; Ononge, S; Otolorin, E O; Mirembe, F M

    2005-12-01

    To improve the quality of clinical care for women with severe pre-eclampsia. A criteria-based audit was conducted in a large government hospital in Uganda. Management practices were evaluated against standards developed by an expert panel by retrospectively evaluating 43 case files. Results of the audit were presented, and recommendations developed and implemented. A re-audit was conducted 6 months later. The initial audit showed that most standards were rarely achieved. Reasons were discussed. Guidelines were produced, additional supplies were purchased following a fundraising effort, labor ward procedures were streamlined, and staffing was increased. In the re-audit there were significant improvements in diagnosis, monitoring, and treatment. Criteria-based audit can improve the quality of maternity care in countries with limited resources.

  12. A meta-analysis of eNOS and ACE gene polymorphisms and risk of pre-eclampsia in women.

    PubMed

    Shaik, A P; Sultana, A; Bammidi, V K; Sampathirao, K; Jamil, K

    2011-10-01

    A meta-analyses of endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) gene polymorphisms in pre-eclampsia was performed. We shortlisted 33 studies (17 for ACE; 16 for eNOS gene polymorphisms), of which 29 articles (16 for ACE and 15 for eNOS) were analysed. Overall, 1,620 cases with pre-eclampsia and 2,158 controls were analysed for intron 16 insertion-deletion polymorphism in ACE gene. A total of 1,610 subjects with pre-eclampsia and 2,875 controls were analysed for the Glu298Asp in eNOS gene. Overall, the random-effects odds ratio (OR) with Glu298Asp in eNOS gene was 0.958 (95% confidence intervals, CI 0.747-1.228, p > 0.05), and for the insertion-deletion/ACE polymorphism was 0.987 (95% CI 0.698-1.395, p > 0.05). Significant heterogeneity was observed in the studies that evaluated polymorphisms in ACE (Q value = 55.6; I(2) = 73; p value = 0.000); and eNOS (Q value = 37.2; I(2) = 62.4; p value = 0.001) polymorphisms. No significant risk of pre-eclampsia was observed in both eNOS and ACE genes with these polymorphisms.

  13. Ibuprofen versus acetaminophen as a post-partum analgesic for women with severe pre-eclampsia: randomized clinical study.

    PubMed

    Vigil-De Gracia, Paulino; Solis, Valentin; Ortega, Nelson

    2017-06-01

    To compare differences in blood pressure levels between patients with severe post-partum pre-eclampsia using ibuprofen or acetaminophen. A randomized controlled trial was made in women with severe pre-eclampsia or superimposed pre-eclampsia after vaginal birth. The patient was randomly selected to receive either 400 mg of ibuprofen every 8 h or 1 g of acetaminophen every 6 h during the post-partum. The primary variable was systolic hypertension ≥150 mmHg and/or diastolic hypertension ≥100 mmHg after the first 24 h post-partum. Secondary variables were the arterial blood pressure readings at 24, 48, 72, and 96 h post-partum and maternal complications. A total of 113 patients were studied: 56 in the acetaminophen group and 57 in the ibuprofen group. With regard to the primary outcome, more cases were significantly hypertensive in the ibuprofen group (36/57; 63.1%) than in the acetaminophen group (16/56; 28.6%). Severe hypertension (≥160/110 mmHg) was not significantly different between the groups, 14.5% (acetaminophen) and 24.5% (ibuprofen). The levels of arterial blood pressure show a hammock-shaped curve independent of the drug used, however, is more noticeable with ibuprofen. This study shows that ibuprofen significantly elevates blood pressure in women with severe pre-eclampsia during the post-partum period.

  14. Factors associated with persistent hypertension after puerperium among women with pre-eclampsia/eclampsia in Mulago hospital, Uganda.

    PubMed

    Ndayambagye, Emmanuel B; Nakalembe, Miriam; Kaye, Dan K

    2010-03-12

    Women with severe pre-eclampsia/eclampsia are at risk of developing chronic hypertension in future. Chronic hypertension may manifest initially as persistent hypertension at the end of the puerperium. The objective was to determine the incidence and maternal biochemical, hematological and socio-demographic risk factors for persistent hypertension in patients with pre-eclampsia/eclampsia. This was a prospective cohort study conducted from November 2008 to May 2009 at Mulago hospital labor ward and postnatal clinic. Participants were 200 women managed for pre-eclampsia/eclampsia and followed up to the end of the puerperium. Data was collected through using pre-coded interviewer-administered questionnaires, checking medical records and laboratory investigations. STATA (release 9) software was used for data analysis. At bivariate analysis, the relative risk of persistent hypertension was estimated at the 95% confidence level. Using multivariate logistic regression analysis, factors that were independently associated with persistent hypertension were evaluated. Fifty four (27.7%) out of the total 195 women had persistent hypertension after puerperium. Serum creatinine and the age of the patient were the only factors associated with persistence of hypertension after puerperium. Nearly every one in four mothers with pre-eclampsia/eclampsia are at risk of persistent hypertension after the puerperium. Serum creatinine, serum uric acid and participants' age were the only factors independently associated with persistence of hypertension after the puerperium.

  15. Distortion of maternal-fetal angiotensin II type 1 receptor allele transmission in pre-eclampsia.

    PubMed Central

    Morgan, L; Crawshaw, S; Baker, P N; Brookfield, J F; Broughton Pipkin, F; Kalsheker, N

    1998-01-01

    OBJECTIVE: To investigate the fetal angiotensin II type 1 receptor genotype in pre-eclampsia. DESIGN: Case-control study. POPULATION: Forty-one maternal-fetal pairs from pre-eclamptic pregnancies and 80 maternal-fetal pairs from normotensive pregnancies. METHODS: Maternal and fetal DNA was genotyped at three diallelic polymorphisms, at nucleotides 573, 1062, and 1166, in the coding exon of the angiotensin II type 1 receptor gene, and at a dinucleotide repeat polymorphism in its 3' flanking region. RESULTS: Allele and genotype frequencies at the four polymorphic regions investigated did not differ between pre-eclamptic and normotensive groups, in either fetal or maternal samples. Mothers heterozygous for the dinucleotide repeat allele designated A4 transmitted this allele to the fetus in 15 of 18 informative pre-eclamptic pregnancies and in eight of 26 normotensive pregnancies. This was greater than the expected probability in pre-eclamptic pregnancies (p=0.04) and less than expected in normotensive pregnancies (p<0.005). The 573T variant, which is in partial linkage disequilibrium with the A4 allele, showed a similar distortion of maternal-fetal transmission. CONCLUSION: Angiotensin II type 1 receptor gene expression in the fetus may contribute to the aetiology of pre-eclampsia. It is unclear whether susceptibility is conferred by the fetal genotype acting alone, or by allele sharing by mother and fetus. Possible mechanisms for the effect of the angiotensin II type 1 receptor gene are suggested by the association of the 573T variant with low levels of surface receptor expression on platelets. If receptor expression is similarly genetically determined in the placenta, responsiveness to angiotensin II may be affected, with the potential to influence placentation or placental prostaglandin secretion. PMID:9719367

  16. Mechanisms underlying the reduced endothelium-dependent relaxation in human omental resistance artery in pre-eclampsia

    PubMed Central

    Suzuki, Yoshikatsu; Kajikuri, Junko; Suzumori, Kaoru; Itoh, Takeo

    2000-01-01

    In pre-eclampsia, a functional change occurs in the role played by endothelium-derived nitric oxide (NO) in the regulation of smooth muscle contraction in resistance arteries. We investigated the underlying mechanism in human omental resistance arteries from normotensive pregnant and pre-eclamptic women in the presence of diclofenac (an inhibitor of cyclo-oxygenase).In endothelium-intact strips, the sensitivity to 9,11-epithio-11,12-methano-thromboxane A2 (STA2) was significantly higher in pre-eclampsia, and this was not modified by either NG-nitro-l-arginine (l-NNA, an inhibitor of NO synthase) or removal of the endothelium.Bradykinin and substance P each produced an endothelium-dependent relaxation of the STA2-induced contraction in both groups, although the relaxation was significantly smaller for pre-eclampsia. l-NNA markedly attenuated the endothelium-dependent relaxation in the normotensive pregnant group but not in the pre-eclamptic group.In the presence of l-NNA, the relaxation induced by sodium nitroprusside (SNP) on the STA2 contraction was significantly smaller for pre-eclamptic than for normotensive pregnant women.In endothelium-denuded strips, the relaxation induced by 8-para- chlorophenyl thio-guanosine-3′,5′-cyclic monophosphate (8-pCPT-cGMP) on the STA2 contraction was significantly less for pre-eclampsia.In β-escin-skinned strips from both groups of women, 8-pCPT-cGMP (1–10 μm) concentration-dependently attenuated the contraction induced by 0.5 μm Ca2+. However, its relaxing action was significantly weaker in pre-eclampsia.It is suggested that the weaker responsiveness to NO seen in strips from pre-eclamptic women may be partly due to a reduced smooth muscle responsiveness to cyclic GMP. PMID:10944179

  17. Haplotypes of heparin-binding epidermal-growth-factor-like growth factor gene are associated with pre-eclampsia.

    PubMed

    Harendra, Galhenagey Gayani; Jayasekara, Rohan W; Dissanayake, Vajira H W

    2012-01-01

    Heparin-binding epidermal-growth-factor-like growth factor (HBEGF) plays an important role in placentation, including impaired placentation, the primary defect seen in pre-eclampsia. We carried out a case-control disease-association study to examine the association of single nucleotide polymorphisms (SNP) in the HBEGF gene and haplotypes defined by them with pre-eclampsia in a Sinhalese population in Sri Lanka. A total of 175 women with pre-eclampsia and 171 matched normotensive controls were genotyped for six SNP selected in silico as having putative functional effects using mass array Sequenom iplex methodology and a newly designed polymerase chain reaction-restriction fragment length polymorphism assay. The individual SNP were not associated with pre-eclampsia. The haplotypes defined by them, however, showed both predisposing (rs13385T,rs2074613G,rs2237076G,rs2074611C,rs4150196A,rs1862176A; odds ratio,1.65; 95% confidence interval1.04-2.60; P=0.032) and protective (rs13385C,rs2074613G,rs2237076A,rs2074611C,rs4150196A,rs1862176A; odds ratio,0.20; 95% confidence interval, 0.04-0.89; P=0.034) effects. These results confirm that polymorphisms in the HGEGF gene are associated with pre-eclampsia. The haplotypes are likely to exert their effects through the numerous transcription regulation factors binding to the polymorphic sites, namely GATA-1, GATA-3, MZF-1 and AML-1a. © 2011 The Authors. Journal of Obstetrics and Gynaecology Research © 2011 Japan Society of Obstetrics and Gynecology.

  18. Association of Plasminogen Activator Inhibitor-Type 1 (-675 4G/5G) Polymorphism with Pre-Eclampsia: Systematic Review

    PubMed Central

    Morgan, Jessie A.; Bombell, Sarah; McGuire, William

    2013-01-01

    Background and Aims Excessive generation of plasminogen activator inhibitor-type 1 (PAI-1) is implicated in the pathogenesis of pre-eclampsia and related conditions. The PAI-1 (−675 4G/5G) promoter polymorphism (rs1799889) affects transcriptional activity and is a putative genetic risk factor for pre-eclampsia. The aim of this study was identify, appraise and synthesise the available evidence for the association of the PAI-1 (−675 4G/5G) polymorphism with pre-eclampsia. Methods Systematic review and random effects meta-analysis of genetic association studies. Results We found 12 eligible genetic association studies in which a total of 1511 women with pre-eclampsia, eclampsia or HELLP syndrome and 3492 controls participated. The studies were generally small (median number of cases 102, range 24 to 403) and underpowered to detect plausible association sizes. Meta-analysis of all of the studies detected statistically significant gene-disease associations in the recessive [pooled odds ratio 1.28 (95% confidence interval 1.09, 1.50); population attributable risk 7.7%] and dominant [pooled odds ratio 1.21 (95% confidence interval 1.01, 1.44); population attributable risk 13.7%] models. We did not find evidence of statistical heterogeneity, funnel plot asymmetry or small study bias. Conclusions These data suggest that the fibrinolytic pathway regulated by the PAI-1 gene may contribute to the pathogenesis of pre-eclampsia and related conditions. This association, if confirmed in larger genetic association studies, may inform research efforts to develop novel interventions or help to prioritise therapeutic targets that merit evaluation in randomised clinical trials. PMID:23457639

  19. Maternal serum placental growth factor at 12, 22, 32 and 36 weeks' gestation in screening for pre-eclampsia.

    PubMed

    Tsiakkas, A; Cazacu, R; Wright, A; Wright, D; Nicolaides, K H

    2016-04-01

    To examine the distribution of maternal serum placental growth factor (PlGF) at 12, 22, 32 and 36 weeks' gestation in singleton pregnancies which develop pre-eclampsia (PE) and examine the performance of this biomarker in screening for PE. Serum PlGF was measured in 40 212 cases at 11-13 weeks, in 10 282 cases at 19-24 weeks, in 10 400 at 30-34 weeks and 4043 at 35-37 weeks. Bayes' theorem was used to combine the a-priori risk from maternal characteristics and medical history with serum PlGF. The performance of screening for PE requiring delivery < 32, at 32 + 0 to 36 + 6 and ≥ 37 weeks' gestation was estimated. In pregnancies that developed PE, serum PlGF was decreased and the separation in multiples of the median (MoM) values from normal was greater with earlier, compared to later, gestational age at which delivery for PE became necessary. Additionally, the slope of the regression lines of PlGF MoM with gestational age at delivery in pregnancies that developed PE increased with advancing gestational age at screening. The detection rates (DRs), at a false-positive rate (FPR) of 10%, for PE delivering < 32 weeks were 79% and 97% with screening at 12 and 22 weeks, respectively. The DRs for PE delivering at 32 + 0 to 36 + 6 weeks were 57%, 65% and 90% with screening at 12, 22 and 32 weeks. The DRs for PE delivering ≥ 37 weeks were 40%, 37%, 54% and 64% with screening at 12, 22, 32 and 36 weeks, respectively. The performance of combined screening with maternal factors, medical history and PlGF is superior in screening for early, compared to late, PE and improves with advancing gestational age at screening. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  20. Are women with history of pre-eclampsia starting a new pregnancy in good nutritional status in South Africa and Zimbabwe?

    PubMed

    Cormick, Gabriela; Betrán, Ana Pilar; Harbron, Janetta; Dannemann Purnat, Tina; Parker, Catherine; Hall, David; Seuc, Armando H; Roberts, James M; Belizán, José M; Hofmeyr, G Justus

    2018-06-15

    Maternal nutritional status before and during pregnancy is an important contributor to pregnancy outcomes and early child health. The aim of this study was to describe the preconceptional nutritional status and dietary intake during pregnancy in high-risk women from South Africa and Zimbabwe. This is a prospective observational study, nested to the CAP trial. Anthropometric measurements before and during pregnancy and dietary intake using 24-h recall during pregnancy were assessed. The Intake Distribution Estimation software (PC-SIDE) was used to evaluate nutrient intake adequacy taking the Estimated Average Requirement (EAR) as a cut-off point. Three hundred twelve women who had pre-eclampsia in their last pregnancy and delivered in hospitals from South Africa and Zimbabwe were assessed. 73.7 and 60.2% women in South Africa and Zimbabwe, respectively started their pregnancy with BMI above normal (BMI ≥ 25) whereas the prevalence of underweight was virtually non-existent. The majority of women had inadequate intakes of micronutrients. Considering food and beverage intake only, none of the micronutrients measured achieved the estimated average requirement. Around 60% of pregnant women reported taking folic acid or iron supplements in South Africa, but almost none did so in Zimbabwe. We found a high prevalence of overweight and obesity and high micronutrient intake inadequacy in pregnant women who had the previous pregnancy complicated with pre-eclampsia. The obesity figures and micronutrient inadequacy are issues of concern that need to be addressed. Pregnant women have regular contacts with the health system; these opportunities could be used to improve diet and nutrition. PACTR201105000267371 . Registered 06 December 2010.

  1. Early-Onset Neonatal Sepsis

    PubMed Central

    Simonsen, Kari A.; Anderson-Berry, Ann L.; Delair, Shirley F.

    2014-01-01

    SUMMARY Early-onset sepsis remains a common and serious problem for neonates, especially preterm infants. Group B streptococcus (GBS) is the most common etiologic agent, while Escherichia coli is the most common cause of mortality. Current efforts toward maternal intrapartum antimicrobial prophylaxis have significantly reduced the rates of GBS disease but have been associated with increased rates of Gram-negative infections, especially among very-low-birth-weight infants. The diagnosis of neonatal sepsis is based on a combination of clinical presentation; the use of nonspecific markers, including C-reactive protein and procalcitonin (where available); blood cultures; and the use of molecular methods, including PCR. Cytokines, including interleukin 6 (IL-6), interleukin 8 (IL-8), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α), and cell surface antigens, including soluble intercellular adhesion molecule (sICAM) and CD64, are also being increasingly examined for use as nonspecific screening measures for neonatal sepsis. Viruses, in particular enteroviruses, parechoviruses, and herpes simplex virus (HSV), should be considered in the differential diagnosis. Empirical treatment should be based on local patterns of antimicrobial resistance but typically consists of the use of ampicillin and gentamicin, or ampicillin and cefotaxime if meningitis is suspected, until the etiologic agent has been identified. Current research is focused primarily on development of vaccines against GBS. PMID:24396135

  2. sFlt-1/PlGF ratio test for pre-eclampsia: an economic assessment for the UK.

    PubMed

    Vatish, M; Strunz-McKendry, T; Hund, M; Allegranza, D; Wolf, C; Smare, C

    2016-12-01

    To assess the economic impact of introducing into clinical practice in the UK the soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PlGF) ratio test for guiding the management of pre-eclampsia. We used an economic model estimating the incremental value of information, from a UK National Health Service payer's perspective, generated by the sFlt-1/PlGF ratio test, compared with current diagnostic procedures, in guiding the management of women with suspected pre-eclampsia. The economic model estimated costs associated with the diagnosis and management of pre-eclampsia in pregnant women between 24 + 0 and 36 + 6 weeks' gestation, managed in either a 'test' scenario in which the sFlt-1/PlGF test is used in addition to current diagnostic procedures, or a 'no-test' scenario in which clinical decisions are based on current diagnostic procedures alone. Test characteristics and resource use were derived from PROGNOSIS, a non-interventional study in women presenting with clinical suspicion of pre-eclampsia. The main outcome measure from the economic model was the cost per patient per episode of care, from first suspicion of pre-eclampsia to birth. Introduction of the sFlt-1/PlGF ratio test into clinical practice is expected to result in cost savings of £344 per patient compared with a no-test scenario. Savings are generated primarily through an improvement in diagnostic accuracy and subsequent reduction in unnecessary hospitalization. Introducing the sFlt-1/PlGF ratio test into clinical practice in the UK was shown to be cost-saving by reducing unnecessary hospitalization of women at low risk of developing pre-eclampsia. In addition, the test ensures that those women at higher risk are identified and managed appropriately. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. © 2016 The Authors. Ultrasound in Obstetrics & Gynecology

  3. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia.

    PubMed

    Duley, Lelia; Gülmezoglu, A Metin; Henderson-Smart, David J; Chou, Doris

    2010-11-10

    Eclampsia, the occurrence of a seizure (fit) in association with pre-eclampsia, is rare but potentially life-threatening. Magnesium sulphate is the drug of choice for treating eclampsia. This review assesses its use for preventing eclampsia. To assess the effects of magnesium sulphate, and other anticonvulsants, for prevention of eclampsia. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (4 June 2010), and the Cochrane Central Register of Controlled Trials Register (The Cochrane Library 2010, Issue 3). Randomised trials comparing anticonvulsants with placebo or no anticonvulsant, or comparisons of different drugs, for pre-eclampsia. Two authors assessed trial quality and extracted data independently. We included 15 trials. Six (11,444 women) compared magnesium sulphate with placebo or no anticonvulsant: magnesium sulphate more than a halved the risk of eclampsia (risk ratio (RR) 0.41, 95% confidence interval (CI) 0.29 to 0.58; number needed to treat for an additional beneficial outcome (NNTB) 100, 95% CI 50 to 100), with a non-significant reduction in maternal death (RR 0.54, 95% CI 0.26 to 1.10) but no clear difference in serious maternal morbidity (RR 1.08, 95% CI 0.89 to 1.32). It reduced the risk of placental abruption (RR 0.64, 95% CI 0.50 to 0.83; NNTB 100, 95% CI 50 to 1000), and increased caesarean section (RR 1.05, 95% CI 1.01 to 1.10). There was no clear difference in stillbirth or neonatal death (RR 1.04, 95% CI 0.93 to 1.15). Side effects, primarily flushing, were more common with magnesium sulphate (24% versus 5%; RR 5.26, 95% CI 4.59 to 6.03; number need to treat for an additional harmful outcome (NNTH) 6, 95% CI 5 to 6).Follow-up was reported by one trial comparing magnesium sulphate with placebo: for 3375 women there was no clear difference in death (RR 1.79, 95% CI 0.71 to 4.53) or morbidity potentially related to pre-eclampsia (RR 0.84, 95% CI 0.55 to 1.26) (median follow-up 26 months); for 3283 children exposed in utero

  4. Early- versus Late-Onset Dysthymia

    PubMed Central

    Sansone, Lori A.

    2009-01-01

    In the current Diagnostic and Statistical Manual of Mental Disorders, dysthymic disorder is categorized as either early-onset or late-onset, based upon the emergence of symptoms before or after the age of 21, respectively. Does this diagnostic distinction have any meaningful clinical implications? In this edition of The Interface, we present empirical studies that have, within a single study, compared individuals with early-versus late-onset dysthymia. In this review, we found that, compared to those with late-onset dysthymia, early-onset patients are more likely to harbor psychiatric comorbidity both on Axis I and II, exhibit less psychological resilience, and have more prominent family loadings for mood disorders. These findings suggest that this distinction is meaningful and that the early-onset subtype of dysthymia is more difficult to effectively treat. PMID:20049145

  5. Community perceptions of pre-eclampsia in rural Karnataka State, India: a qualitative study.

    PubMed

    Vidler, Marianne; Charantimath, Umesh; Katageri, Geetanjali; Ramadurg, Umesh; Karadiguddi, Chandrashekhar; Sawchuck, Diane; Qureshi, Rahat; Dharamsi, Shafik; von Dadelszen, Peter; Derman, Richard; Goudar, Shivaprasad; Mallapur, Ashalata; Bellad, Mrutyunjaya

    2016-06-08

    Maternal deaths have been attributed in large part to delays in recognition of illness, timely transport to facility, and timely treatment once there. As community perceptions of pregnancy and their complications are critical to averting maternal morbidity and mortality, this study sought to contribute to the literature and explore community-based understandings of pre-eclampsia and eclampsia. The study was conducted in rural Karnataka State, India, in 2012-2013. Fourteen focus groups were held with the following community stakeholders: three with community leaders (n = 27), two with male decision-makers (n = 19), three with female decision-makers (n = 41), and six with reproductive age women (n = 132). Focus groups were facilitated by local researchers with clinical and research expertise. Discussions were audio-recorded, transcribed verbatim and translated to English for thematic analysis using NVivo 10. Terminology exists in the local language (Kannada) to describe convulsions and hypertension, but there were no terms that are specific to pregnancy. Community participants perceived stress, tension and poor diet to be precipitants of hypertension in pregnancy. Seizures in pregnancy were thought to be brought on by anaemia, poor medical adherence, lack of tetanus toxoid immunization, and exposure in pregnancy to fire or water. Sweating, fatigue, dizziness-unsteadiness, swelling, and irritability were perceived to be signs of hypertension, which was recognized to have the potential to lead to eclampsia or death. Home remedies, such as providing the smell of onion, placing an iron object in the hands, or squeezing the fingers and toes, were all used regularly to treat seizures prior to accessing facility-based care although transport is not delayed. It is evident that 'pre-eclampsia' and 'eclampsia' are not well-known; instead hypertension and seizures are perceived as conditions that may occur during or outside pregnancy. Improving community

  6. Early- versus Late-Onset Systemic Sclerosis

    PubMed Central

    Alba, Marco A.; Velasco, César; Simeón, Carmen Pilar; Fonollosa, Vicent; Trapiella, Luis; Egurbide, María Victoria; Sáez, Luis; Castillo, María Jesús; Callejas, José Luis; Camps, María Teresa; Tolosa, Carles; Ríos, Juan José; Freire, Mayka; Vargas, José Antonio; Espinosa, Gerard

    2014-01-01

    Abstract Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤30 years (early onset), age between 31 and 59 years (standard onset), and age ≥60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients. PMID:24646463

  7. Analysis of the original causes of placental oxidative stress in normal pregnancy and pre-eclampsia: a hypothesis.

    PubMed

    Yang, Xiang; Guo, Lili; Li, Huaifang; Chen, Xinliang; Tong, Xiaowen

    2012-07-01

    Pre-eclampsia (PE) and eclampsia remain enigmatic despite intensive research. Growing evidence suggests that placental oxidative stress (OS) is involved in the etiopathogenesis of pre-eclampsia. Reduced perfusion as a result of abnormal placentation was proposed to be responsible for placental OS in PE. However, placental OS was also observed in normal pregnancy. The exact differences and correlation of placental OS in PE and normal pregnancy remain elusive. In this review, we attempted to link both normal pregnancy and PE on the causes of placental OS and proposed a hypothesis that placental OS in normal pregnancy, plus the exploration of other placental and/or maternal factors, could provide a novel explanation of that in PE. We concluded that pregnancy, placental abnormality and preexisting maternal constitutional conditions are three principle factors that could contribute to placental OS in PE. The specific causes in each clinical case could be heterogeneous, which requires individual analysis.

  8. The role of vitamin D in pre-eclampsia: a systematic review.

    PubMed

    Purswani, Juhi M; Gala, Pooja; Dwarkanath, Pratibha; Larkin, Heather M; Kurpad, Anura; Mehta, Saurabh

    2017-07-15

    The etiology of pre-eclampsia (PE) is not yet fully understood, though current literature indicates an upregulation of inflammatory mediators produced by the placenta as a potential causal mechanism. Vitamin D is known to have anti-inflammatory properties and there is evidence of an inverse relationship between dietary calcium intake and the incidence of PE. Evidence of the role of vitamin D status and supplementation in the etiology and prevention of PE is reviewed in this article along with identification of research gaps to inform future studies. We conducted a structured literature search using MEDLINE electronic databases to identify published studies until February 2015. These sources were retrieved, collected, indexed, and assessed for availability of pregnancy-related data on PE and vitamin D. Several case-control studies and cross-sectional studies have shown an association between vitamin D status and PE, although evidence has been inconsistent. Clinical trials to date have been unable to show an independent effect of vitamin D supplementation in preventing PE. The included clinical trials do not show an independent effect of vitamin D supplementation in preventing PE; however, issues with dose, timing, and duration of supplementation have not been completely addressed.

  9. Choroidal changes in pre-eclampsia during pregnancy and the postpartum period: comparison with healthy pregnancy.

    PubMed

    Duru, Necati; Ulusoy, Döndü Melek; Özköse, Ayşe; Ataş, Mustafa; Karatepe, Arzu Seyhan; Ataş, Fatma; Arifoğlu, Hasan Basri; Yılmaz, Uğur

    2016-01-01

    To investigate subfoveal choroidal thickness (SFCT) in patients with pre-eclampsia using enhanced depth imaging optical coherence tomography (EDI-OCT). A sample of 73 pregnant women was studied over 28 weeks of gestation. The sample was divided into two groups: one comprising pre-eclamptic pregnant women (n=32), and the other comprising healthy pregnant women (n=41). The SFCT was determined for all patients using EDI-OCT during pregnancy and at the third month of the postpartum period. The SFCTs in pre-eclamptic pregnant women were 351.97 ± 22.44 and 332.28 ± 20.32 µm during the pregnancy and postpartum periods (p<0.001), respectively, whereas these values in healthy pregnant women were 389.73 ± 49.64 and 329.78 ± 22.36 µm (p<0.001), respectively. During pregnancy SFCT in pre-eclamptic pregnant women was significantly thinner than that in healthy pregnant women (p<0.001). However, there was no statistically significant difference during the postpartum period (p=0.623). The results suggest that SFCT is significantly decreased in pre-eclamptic pregnant women than in healthy pregnant women, despite no statistically significant difference in SFCT existing between the groups during the postpartum period.

  10. Factor VIII levels and the risk of pre-eclampsia, HELLP syndrome, pregnancy related hypertension and severe intrauterine growth retardation.

    PubMed

    Witsenburg, C P J; Rosendaal, F R; Middeldorp, J M; Van der Meer, F J M; Scherjon, S A

    2005-01-01

    Recently, acquired as well as genetic prothrombotic factors are associated with thrombotic events. These factors have also been related to conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome and severe intrauterine growth restriction (IUGR). The aim of this study was to determine whether elevated factor VIII levels are associated with uteroplacental insufficiency, in particular pre-eclampsia, HELLP syndrome or pregnancy-induced hypertension and intrauterine growth retardation. Plasma samples of 75 women with a history of pregnancy complicated by pre-eclampsia, HELLP syndrome, pregnancy induced hypertension or intrauterine growth restriction were tested for factor VIII:C (FVIII:C) levels at a minimum of 10 weeks post-partum. Laboratory results were compared to factor VIII:C levels found in a healthy control group of 272 women. Mean factor VIII:C levels were similar at 123 IU/dl in both the patient group and the controls. In a logistic regression model, after adjusting for age and blood group, no effect of factor VIII:C levels on the risk of pregnancy complications was observed, with the exception of IUGR with (OR 2.9, CI 1.0-8.7) or without hypertension (OR 2.0, CI 0.7-6.4). If the elevated level of factor VIII would be the sole factor responsible for the increased risk observed, one would expect to find an effect of blood group on risk as well (blood group being an important determinant of FVIII:C). While no such effect could be shown a causal relationship between elevated levels of factor VIII and conditions of uteroplacental insufficiency such as pre-eclampsia, HELLP syndrome, pregnancy-induced hypertension and IUGR is not very likely.

  11. Genetic recapitulation of human pre-eclampsia risk during convergent evolution of reduced placental invasiveness in eutherian mammals

    PubMed Central

    Elliot, Michael G.; Crespi, Bernard J.

    2015-01-01

    The relationship between phenotypic variation arising through individual development and phenotypic variation arising through diversification of species has long been a central question in evolutionary biology. Among humans, reduced placental invasion into endometrial tissues is associated with diseases of pregnancy, especially pre-eclampsia, and reduced placental invasiveness has also evolved, convergently, in at least 10 lineages of eutherian mammals. We tested the hypothesis that a common genetic basis underlies both reduced placental invasion arising through a developmental process in human placental disease and reduced placental invasion found as a derived trait in the diversification of Euarchontoglires (rodents, lagomorphs, tree shrews, colugos and primates). Based on whole-genome analyses across 18 taxa, we identified 1254 genes as having evolved adaptively across all three lineages exhibiting independent evolutionary transitions towards reduced placental invasion. These genes showed strong evidence of enrichment for associations with pre-eclampsia, based on genetic-association studies, gene-expression analyses and gene ontology. We further used in silico prediction to identify a subset of 199 genes that are likely targets of natural selection during transitions in placental invasiveness and which are predicted to also underlie human placental disorders. Our results indicate that abnormal ontogenies can recapitulate major phylogenetic shifts in mammalian evolution, identify new candidate genes for involvement in pre-eclampsia, imply that study of species with less-invasive placentation will provide useful insights into the regulation of placental invasion and pre-eclampsia, and recommend a novel comparative functional-evolutionary approach to the study of genetically based human disease and mammalian diversification. PMID:25602073

  12. [The usefulness of routine laboratory tests in the evaluation of sudden threat of pregnant woman and fetus in pre-eclampsia].

    PubMed

    Malarewicz, Andrzej; Gruszka, Olga; Szymkiewicz, Jadwiga; Rogala, Jerzy

    2006-04-01

    The fact that the progress of pre-eclampsia is highly unpredictable is the reason to run necessary monitoring, among others, by means of laboratory tests. Their aim is to determine explicitly if the pregnancy can be continued and terminated naturally or should be terminated by pre-term induced delivery or Caesarean section. There is a wide range of laboratory investigations recommended in pregnancy complicated by pre-eclampsia. The results reported in the literature though are controversial and inexplicit. The purpose of the research was to verify routine lab tests results used in decision making for emergency termination of pregnancy as a result of increased threatening clinical symptoms and to evaluate their usefulness in decision making to start delivery. The investigation covered 152 women who were divided into three groups. One consisted of 62 pregnant women with light form of pre-eclampsia, the other of 24 pregnant women with severe form of pre-eclampsia. The control group consisted of 66 healthy pregnant women. All pregnant women with pre-eclampsia diagnosed delivered by Caesarean section. The decision to perform the operation was based on biophysical findings of the fetus. At the moment of decision-making, blood was drawn for laboratory testing of the following parameters: systemic blood, coagulation parameters, total protein and protein fractios, non-protein nitrogen blood components, glucose, electrolytes, indicating enzymes and excretory enzymes of protein metabolism, lipid fractions. Routine lab tests performed in pre-eclampsia do not indicate distinct abnormalities the moment fetus life threatening clinical symptoms occur that enforce the decision of immediate delivery, the exception are the indicating enzymes. Acute clinical symptoms that endanger fetus life in pre-eclampsia correlate with distinct activity of AspAT, AIAT and LDH. Laboratory tests are of no prognostic value in the prediction of sudden worsening of the fetus condition in pre-eclampsia.

  13. Genetics Home Reference: early-onset glaucoma

    MedlinePlus

    ... called a syndrome. If glaucoma appears before the age of 5 without other associated abnormalities, it is called primary congenital glaucoma. Other individuals experience early onset of primary open-angle glaucoma, the most ...

  14. Screening for pre-eclampsia in the first trimester: role of maternal hemodynamics and bioimpedance in non-obese patients.

    PubMed

    Gagliardi, G; Tiralongo, G M; LoPresti, D; Pisani, I; Farsetti, D; Vasapollo, B; Novelli, G P; Andreoli, A; Valensise, H

    2017-11-01

    To test if maternal hemodynamics and bioimpedance, assessed at the time of combined screening for PE, are able to identify in the first trimester of gestation normotensive non-obese patients at risk for pre-eclampsia (PE) and/or intrauterine growth restriction (IUGR). One hundred and fifty healthy nulliparous non-obese women (body mass index < 30 kg/m 2 ) in the first trimester of pregnancy underwent assessment by UltraSonic Cardiac Output Monitor (USCOM) to detect hemodynamic parameters, bioimpedance analysis to characterize body composition, and combined screening for PE (assessment of maternal history, biophysical and maternal biochemical markers). Patients were followed until term, noting the appearance of PE and/or IUGR. One hundred and thirty-eight patients had an uneventful pregnancy (controls), while 12 (8%) developed complications (cases). USCOM showed, in cases compared with controls, lower cardiac output (5.6 ± 0.3 vs 6.7 ± 1.1 L/min, P < 0.001), lower inotropy index (1.54 ± 0.38 vs 1.91 ± 0.32 W/m 2 , P < 0.001) and higher total vascular resistance (1279.8 ± 166.4 vs 1061.4 ± 179.5 dynes × s/cm 5 , P < 0.001). Bioimpedance analysis showed, in cases compared with controls, lower total body water (53.7 ± 3.3% vs 57.2 ± 5.6%, P = 0.037). Combined screening was positive for PE in 8% of the controls and in 50% of the cases (P < 0.001). After identification of cut-off values for USCOM and bioimpedance parameters, forward multivariate logistic regression analysis identified as independent predictors of complications in pregnancy the inotropy index (derived by USCOM), fat mass (derived from bioimpedance analysis) and combined screening. Combined screening for PE and assessment of bioimpedance and maternal hemodynamics can be used to identify early markers of impaired cardiovascular adaptation and body composition that may lead to complications in the third trimester of pregnancy. Copyright

  15. Assessment of angiogenesis modulators in pregnant women with pre-eclampsia: a case-control study.

    PubMed

    Mundim, Guilhermo Justino; Paschoini, Marina Carvalho; Araujo Júnior, Edward; Da Silva Costa, Fabricio; Rodrigues Júnior, Virmondes

    2016-02-01

    This study aimed to evaluate the serum concentration of factors associated with placental angiogenesis in pre-eclamptic and normotensive pregnant women. This was a prospective, cross-sectional, case-control study in which the pro-angiogenic factors PlGF, VEGF and IL-10, and the anti-angiogenic factors IL-6, IL-17 and TNF-α of 55 pregnant women (31 with pre-eclampsia-PE and 24 normotensive), with gestational age ≥20 weeks, were measured in maternal blood through the enzyme-linked immunosorbent assay (ELISA). The Mann-Whitney and Kruskal-Wallis tests were used for comparison between groups. Serum PIGF was reduced in the group of pregnant women with PE when compared with the normotensive women (493.2 ± 55.1 pg/mL vs. 4.4 ± 26.5 pg/mL; p < 0.001). There was no significant difference in PlGF levels in the pre-eclamptic pregnant women in relation to gestational age or proteinuria levels (p > 0.05). The serum levels of VEGF, IL-17, IL-10 and TNF-α were lower in the pregnant women with PE when compared with their normotensive peers, while the IL-6 levels were higher; however, this difference was not statistically significant (p > 0.05). Serum PlGF levels were reduced in the pregnant women with PE and were unrelated to disease severity. Serum levels of VEGF, IL-17, IL-10 and TNF-α were reduced in the pre-eclamptic pregnant women when compared with their normotensive peers, without statistically significant differences.

  16. Carboxyhemoglobin levels in umbilical cord blood of women with pre-eclampsia and intrauterine growth restriction.

    PubMed

    Yusuf, Kamran; Kamaluddeen, Majeeda; Wilson, R Douglas; Akierman, Albert

    2012-11-01

    Pre-eclampsia (PE) and intrauterine growth restriction (IUGR) are associated with abnormal placentation. Heme oxygenase (HO) and carbon monoxide (CO) are involved in normal placental development and function and vasomotor control in the placenta. The objective of our study was to measure CO levels, as assessed by carboxyhemoglobin (COHb) levels in the umbilical cord arterial blood of women with PE, normotensive IUGR (<10th percentile for birth weight), and normotensive pregnancies with appropriate-for-gestational age (AGA) infants. We prospectively analyzed COHb levels in the umbilical arterial blood of women with PE, normotensive IUGR, and normotensive AGA pregnancies. Exclusion criteria included cigarette smoke exposure, hemolytic disorders, a positive direct anti-globulin test, chronic hypertension, fever, and any significant medical illness. COHb levels were measured using the ABL 725 blood gas analyzer. There were 41 women in the normotensive AGA group, 42 in the PE group, and 36 in the normotensive IUGR group. Maternal age, mode of delivery, gravidity, parity, and gender of the infants were similar in the three groups. Gestational age and birth weight were significantly higher in the normotensive AGA group compared with the other two groups. COHb levels were significantly lower in the PE group compared with the normotensive AGA group (0.38±0.06% vs. 0.77±0.11%, P<0.05). COHb levels, although lower in the normotensive IUGR group compared with the normotensive AGA group, did not reach statistical significance. Our data suggests the HO-CO system may have a role in the pathogenesis of PE. We also, for the first time, provide information on umbilical arterial COHb levels in normotensive IUGR pregnancies.

  17. Cardiovascular function in women with recurrent miscarriage, pre-eclampsia and/or intrauterine growth restriction.

    PubMed

    Mahendru, Amita A; Everett, Thomas R; McEniery, Carmel M; Wilkinson, Ian B; Lees, Christoph C

    2013-03-01

    To investigate prepregnancy cardiovascular function and risk factors in women with previous pregnancy complications. Thirty-four women with previous normal pregnancy (controls), 26 with unexplained recurrent miscarriage (RM) and 14 with pre-eclampsia (PE) and/or intrauterine growth restriction (IUGR), planning to conceive were recruited. Brachial and central blood pressures (BP), cardiac output (CO), peripheral vascular resistance (PVR), aortic stiffness, blood biochemistry and platelet aggregation were assessed. Women with previous PE/IUGR had higher brachial diastolic BP (78 ± 9 vs 71 ± 7 mmHg; p = 0.03), central systolic BP (107 ± 10 vs 99 ± 8 mmHg; p = 0.03), mean arterial pressure (92 ± 10 vs 84 ± 8 mmHg; p = 0.01) and PVR (1499 ± 300 vs 1250 ± 220 dynes.s(-1) cm(-5); p = 0.005), than the controls. No differences were observed in either cardiovascular function or blood biochemistry in women with unexplained RM compared with the controls. Women with previous PE/IUGR though not with RM had a stronger family history of cardiovascular disease (CVD) than controls. Women with previous PE and/or IUGR had higher BP and PVR compared with controls, which may predispose them to CVD later in life. However, in the absence of underlying vascular pathology, women with unexplained RM did not have abnormal cardiovascular function. Prepregnancy period provides an opportunity to identify cardiovascular risks in relation to previous obstetric history.

  18. Serum FRAP Levels and Pre-eclampsia among Pregnant Women in a Rural Community of Northern India

    PubMed Central

    Gupta, Anant; Gupta, Sanjeev Kumar; Prakash, Shyam; Kalaivani, Mani; Pandav, Chandrakant S.; Rai, Sanjay Kumar; Misra, Puneet

    2016-01-01

    Introduction There is a balance between the oxidative and the anti-oxidative forces in human body. Some studies document decreased level of anti-oxidant in pre-eclampsia while other studies showed normal level of anti-oxidant in pre-eclampsia and the evidence is equivocal. Aim The aim of the present study was to assess enzymatic anti-oxidant activities in pre-eclamptic women and compare it with normotensive pregnant women with period of gestation between 28 to 36 weeks. Materials and Methods A community-based cross-sectional survey was conducted (from November 2012-December 2013) at the Ballabgarh Health and Demographic Surveillance System (HDSS) site which was managed by Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi, India. All registered pregnant women with period of gestation between 28 weeks – 36 weeks were eligible for inclusion in the study. All eligible pregnant women were contacted through home visit. A total of 217 pregnant women were enrolled out of which 209 blood samples were collected from pregnant women. About three ml of blood from antecubital vein was drawn without use of tourniquet, under aseptic conditions. It was later analysed for the serum anti-oxidative measures {Malanoaldehyde, Vitamin C, Ferric Reducing Ability of Plasma (FRAP) levels}. Data were entered on Epi-Info version 3.5.4. Data management and analysis was carried out in Stata 11. The means were compared using t-test and p-value stated. Categorical data was analysed using chi-square test. Logistic regression was used and adjusted p-value was stated. Results A total of 217 pregnant women were eligible for the study and all were enrolled. Out of the 217 blood samples collected, eight samples accidently got destroyed. A total of 28 out of remaining 209 pregnant women (13.4%) had pre-eclampsia. Mean age (SD) was 22.4 (2.3) years, mean height (SD) was 156.6 (6.9) cm, mean weight (SD) was 65.1 (9.7) kg in pre-eclampsia group. In pre-eclampsia group mean

  19. Identification of placental nutrient transporters associated with intrauterine growth restriction and pre-eclampsia.

    PubMed

    Huang, Xiao; Anderle, Pascale; Hostettler, Lu; Baumann, Marc U; Surbek, Daniel V; Ontsouka, Edgar C; Albrecht, Christiane

    2018-03-02

    Gestational disorders such as intrauterine growth restriction (IUGR) and pre-eclampsia (PE) are main causes of poor perinatal outcomes worldwide. Both diseases are related with impaired materno-fetal nutrient transfer, but the crucial transport mechanisms underlying IUGR and PE are not fully elucidated. In this study, we aimed to identify membrane transporters highly associated with transplacental nutrient deficiencies in IUGR/PE. In silico analyses on the identification of differentially expressed nutrient transporters were conducted using seven eligible microarray datasets (from Gene Expression Omnibus), encompassing control and IUGR/PE placental samples. Thereby 46 out of 434 genes were identified as potentially interesting targets. They are involved in the fetal provision with amino acids, carbohydrates, lipids, vitamins and microelements. Targets of interest were clustered into a substrate-specific interaction network by using Search Tool for the Retrieval of Interacting Genes. The subsequent wet-lab validation was performed using quantitative RT-PCR on placentas from clinically well-characterized IUGR/PE patients (IUGR, n = 8; PE, n = 5; PE+IUGR, n = 10) and controls (term, n = 13; preterm, n = 7), followed by 2D-hierarchical heatmap generation. Statistical evaluation using Kruskal-Wallis tests was then applied to detect significantly different expression patterns, while scatter plot analysis indicated which transporters were predominantly influenced by IUGR or PE, or equally affected by both diseases. Identified by both methods, three overlapping targets, SLC7A7, SLC38A5 (amino acid transporters), and ABCA1 (cholesterol transporter), were further investigated at the protein level by western blotting. Protein analyses in total placental tissue lysates and membrane fractions isolated from disease and control placentas indicated an altered functional activity of those three nutrient transporters in IUGR/PE. Combining bioinformatic analysis

  20. Prevention and management of severe pre-eclampsia/eclampsia in Afghanistan

    PubMed Central

    2013-01-01

    Background An evidence-based strategy exists to reduce maternal morbidity and mortality associated with severe pre-eclampsia/eclampsia (PE/E), but it may be difficult to implement in low-resource settings. This study examines whether facilities that provide emergency obstetric and newborn care (EmONC) in Afghanistan have the capacity to manage severe PE/E cases. Methods A further analysis was conducted of the 2009–10 Afghanistan EmONC Needs Assessment. Assessors observed equipment and supplies available, and services provided at 78 of the 127 facilities offering comprehensive EmONC services and interviewed 224 providers. The providers also completed a written case scenario on severe PE/E. Descriptive statistics were used to summarize facility and provider characteristics. Student t-test, one-way ANOVA, and chi-square tests were performed to determine whether there were significant differences between facility types, doctors and midwives, and trained and untrained providers. Results The median number of severe PE/E cases in the past year was just 5 (range 0–42) at comprehensive health centers (CHCs) and district hospitals, compared with 44 (range 0–130) at provincial hospitals and 108 (range 32–540) at regional and specialized hospitals (p < 0.001). Most facilities had the drugs and supplies needed to treat severe PE/E, including the preferred anticonvulsant, magnesium sulfate (MgSO4). One-third of the smallest facilities and half of larger facilities reported administering a second-line drug, diazepam, in some cases. In the case scenario, 96% of doctors and 89% of midwives recognized that MgSO4 should be used to manage severe PE/E, but 42% of doctors and 58% of midwives also thought diazepam had a role to play. Providers who were trained on the use of MgSO4 scored significantly higher than untrained providers on six of 20 items in the case scenario. Providers at larger facilities significantly outscored those at smaller facilities on five items. There

  1. Prevention and management of severe pre-eclampsia/eclampsia in Afghanistan.

    PubMed

    Kim, Young Mi; Ansari, Nasratullah; Kols, Adrienne; Tappis, Hannah; Currie, Sheena; Zainullah, Partamin; Bailey, Patricia; van Roosmalen, Jos; Stekelenburg, Jelle

    2013-10-12

    An evidence-based strategy exists to reduce maternal morbidity and mortality associated with severe pre-eclampsia/eclampsia (PE/E), but it may be difficult to implement in low-resource settings. This study examines whether facilities that provide emergency obstetric and newborn care (EmONC) in Afghanistan have the capacity to manage severe PE/E cases. A further analysis was conducted of the 2009-10 Afghanistan EmONC Needs Assessment. Assessors observed equipment and supplies available, and services provided at 78 of the 127 facilities offering comprehensive EmONC services and interviewed 224 providers. The providers also completed a written case scenario on severe PE/E. Descriptive statistics were used to summarize facility and provider characteristics. Student t-test, one-way ANOVA, and chi-square tests were performed to determine whether there were significant differences between facility types, doctors and midwives, and trained and untrained providers. The median number of severe PE/E cases in the past year was just 5 (range 0-42) at comprehensive health centers (CHCs) and district hospitals, compared with 44 (range 0-130) at provincial hospitals and 108 (range 32-540) at regional and specialized hospitals (p < 0.001). Most facilities had the drugs and supplies needed to treat severe PE/E, including the preferred anticonvulsant, magnesium sulfate (MgSO4). One-third of the smallest facilities and half of larger facilities reported administering a second-line drug, diazepam, in some cases. In the case scenario, 96% of doctors and 89% of midwives recognized that MgSO4 should be used to manage severe PE/E, but 42% of doctors and 58% of midwives also thought diazepam had a role to play. Providers who were trained on the use of MgSO4 scored significantly higher than untrained providers on six of 20 items in the case scenario. Providers at larger facilities significantly outscored those at smaller facilities on five items. There was a significant difference between

  2. Economic evaluation of Community Level Interventions for Pre-eclampsia (CLIP) in South Asian and African countries: a study protocol.

    PubMed

    Khowaja, Asif R; Mitton, Craig; Bryan, Stirling; Magee, Laura A; Bhutta, Zulfiqar A; von Dadelszen, Peter

    2015-05-26

    Globally, hypertensive disorders of pregnancy, particularly pre-eclampsia and eclampsia, are the leading cause of maternal and neonatal mortality, and impose substantial burdens on the families of pregnant women, their communities, and healthcare systems. The Community Level Interventions for Pre-eclampsia (CLIP) Trial evaluates a package of care applied at both community and primary health centres to reduce maternal and perinatal disabilities and deaths resulting from the failure to identify and manage pre-eclampsia at the community level. Economic evaluation of health interventions can play a pivotal role in priority setting and inform policy decisions for scale-up. At present, there is a paucity of published literature on the methodology of economic evaluation of large, multi-country, community-based interventions in the area of maternal and perinatal health. This study protocol describes the application of methodology for economic evaluation of the CLIP in South Asia and Africa. A mixed-design approach i.e. cost-effectiveness analysis (CEA) and qualitative thematic analysis will be used alongside the trial to prospectively evaluate the economic impact of CLIP from a societal perspective. Data on health resource utilization, costs, and pregnancy outcomes will be collected through structured questionnaires embedded into the pregnancy surveillance, cross-sectional survey and budgetary reviews. Qualitative data will be collected through focus groups (FGs) with pregnant women, household male-decision makers, care providers, and district level health decision makers. The incremental cost-effectiveness ratio will be calculated for healthcare system and societal perspectives, taking into account the country-specific model inputs (costs and outcome) from the CLIP Trial. Emerging themes from FGs will inform the design of the model, and help to interpret findings of the CEA. The World Health Organization (WHO) strongly recommends cost-effective interventions as a key

  3. Pre-eclampsia- an additional risk factor for cognitive impairment at school age after intrauterine growth restriction and very preterm birth.

    PubMed

    Morsing, E; Maršál, K

    2014-02-01

    To explore the possible influence of pre-eclampsia on cognitive outcome in children born very preterm after intrauterine growth restriction (IUGR) and abnormal umbilical artery blood flow. Cognitive function was evaluated at 5-8 years of age with Wechsler scales in 34 children born before 30 gestational weeks after IUGR (PT-IUGR) (11 children were exposed to maternal pre-eclampsia, 23 non-exposed) and in 34 children with no maternal pre-eclampsia and birth weight appropriate-for-gestational age (PT-AGA) matched for gestational age at birth, gender and age at examination. The subjects in the PT-IUGR group exposed to maternal pre-eclampsia had lower mean verbal IQ (VIQ) (mean ± SD 74 ± 16) and lower full scale IQ (FSIQ) (70 ± 19) in comparison with both the non-exposed PT-IUGR (VIQ 89 ± 15; p=0.013; FSIQ 83 ± 14, p=0.029), and, the PT-AGA group (VIQ 96 ± 15, p<0.001; FSIQ 90 ± 14, p=0.001). The differences remained significant after adjustment for known confounders. VIQ and FSIQ did not differ between the non-exposed IUGR and PT-AGA children. Fetal exposure to maternal pre-eclampsia seems to have an additional negative impact to that of IUGR on cognitive function in children born very preterm. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Transient diabetes insipidus in a post-partum woman with pre-eclampsia associated with residual placental vasopressinase activity.

    PubMed

    Rodrigo, Natassia; Hocking, Samantha

    2018-01-01

    This case illustrates the exceedingly rare phenomenon of transient diabetes insipidus, in association with pre-eclampsia, occurring in the post-partum period following an in vitro fertilisation pregnancy, in an otherwise well 48-year-old lady. Diabetes insipidus can manifest during pregnancy, induced by increased vasopressinase activity secreted by placental trophoblasts and usually manifests in the third trimester. This presentation elucidates not only the intricate balance between the physiology of pregnancy and hormonal homeostasis, but also the importance of post-partum care as the physiological changes of pregnancy still hold pathological potential in the weeks immediately following delivery. Diabetes insipidus (DI) is a rare complication of pregnancy occurring in 1 in 30 000 pregnancies.It is associated with excessive vasopressinase activity, secreted by placental trophoblasts, which increases the rate of degradation of anti-diuretic hormone.It is responsive to synthetic desmopressin 1-deanimo-8-d-arginine vasopressin as this form is not degraded by placental vasopressinase.Vasopressinase is proportional to placental weight, which is increased in pregnancies conceived with assisted reproductive techniques including in vitro fertilisation.Vasopressinase-induced DI is associated with pre-eclampsia.

  5. Endothelin type B (ETB) receptors: friend or foe in the pathogenesis of pre-eclampsia and future cardiovascular disease (CVD) risk?

    PubMed

    Mirabito Colafella, Katrina M

    2018-01-16

    In a recent issue of Clinical Science, Stanhewicz et al. investigated persistent microvascular dysfunction in women up to 16 months postpartum. The authors found sensitivity to the pressor effects of endothelin-1 (ET-1) was enhanced when compared with women who had a normotensive pregnancy. Importantly, the authors demonstrated that this effect was mediated via the endothelin type B (ET B ) receptors. Therefore, the present study highlights the possibility that alterations in the localization of the ET B receptor contributes to the pathogenesis of pre-eclampsia and future cardiovascular disease (CVD) risk. Currently, there is great interest in the role of the endothelin system in pre-eclampsia. Targetting the endothelin system, potentially by modulating upstream pathways to prevent ET B receptor dysfunction, may improve health outcomes for women and their offspring during pre-eclampsia and later life. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  6. The role of maternal serumbeta-HCG and PAPP-A levels at gestational weeks 10 to 14 in the prediction of pre-eclampsia

    PubMed Central

    Ozdamar, Ozkan; Gun, Ismet; Keskin, Ugur; Kocak, Necmettin; Mungen, Ercument

    2014-01-01

    Objective: We aimed to detect whether maternal serum free β-hCG and PAPP-A levels and NT measurements vary between normal pregnancies and those that subsequently develop pre-eclampsia and to evaluate the role of these screening serum analytes in the prediction of pre-eclampsia. Methods: Using a case-control study design, we identified all women who had been screened by double test within 11+0 and 13+6 weeks of gestation and who had developed pre-eclampsia during the subsequent pregnancy course, over a 6-year period between January 2006 and December 2012 at two tertiary referral hospital. All women who had undergone a double test during that time, without a diagnosis of pre-eclampsia and who had not had any adverse obstetric outcomes, were also identified, and three women among them were randomly selected as controls for each case. Maternal and neonatal data were abstracted from the medical records and PAPP-A, β-hCG, NT and CRL MoM values were compared between the two groups. Results: Although β-hCG values show no statistically significant difference (p=0.882), PAPP-A levels were significantly reduced in the pre-eclampsia group compared to the control group (p<0.001). NT and CRL values showed no significant difference between the two groups (p=0.674 and p=0.558, respectively). Conclusion: Measuring PAPP-A in the first trimester may be useful in the prediction of pre-eclampsia. PMID:24948981

  7. THE LINK BETWEEN EARLY ONSET DRINKING AND EARLY ONSET ALCOHOL-IMPAIRED DRIVING IN YOUNG MALES

    PubMed Central

    Zhang, Lening; Wieczorek, William F.; Welte, John W.

    2014-01-01

    Background Young drivers represent a disproportionate number of the individuals involved in alcohol-impaired driving. Although there is a known association between drinking and alcohol-impaired driving in young drivers, the link between early onset drinking and early onset alcohol-impaired driving has not been explored. Objectives The present study aimed to assess this link along with potentially confounding factors. Methods The assessment used a proportional hazards model with data collected from the Buffalo Longitudinal Study of Young Men, a population based sample of 625 males at ages of 16–19 years old. Results Controlling for the effects of potentially relevant confounds, the early onset of drinking was the most influential factor in predicting the early onset of alcohol-impaired driving. Race and the early onset of other forms of delinquency also played a significant role in the early onset of alcohol-impaired driving. Conclusion Preventing an early start of drinking among adolescents may be the most critical factor to address in preventing an early start of alcohol-impaired driving. PMID:24766089

  8. The link between early onset drinking and early onset alcohol-impaired driving in young males.

    PubMed

    Zhang, Lening; Wieczorek, William F; Welte, John W

    2014-05-01

    Young drivers represent a disproportionate number of the individuals involved in alcohol-impaired driving. Although there is a known association between drinking and alcohol-impaired driving in young drivers, the link between early onset drinking and early onset alcohol-impaired driving has not been explored. The present study aimed to assess this link along with potentially confounding factors. The assessment used a proportional hazards model with data collected from the Buffalo Longitudinal Study of Young Men, a population-based sample of 625 males at aged 16-19. Controlling for the effects of potentially relevant confounds, the early onset of drinking was the most influential factor in predicting the early onset of alcohol-impaired driving. Race and the early onset of other forms of delinquency also played a significant role in the early onset of alcohol-impaired driving. Preventing an early start of drinking among adolescents may be the most critical factor to address in preventing an early start of alcohol-impaired driving.

  9. Participant recruitment and retention in longitudinal preconception randomized trials: lessons learnt from the Calcium And Pre-eclampsia (CAP) trial.

    PubMed

    Lawrie, Theresa A; Betrán, Ana Pilar; Singata-Madliki, Mandisa; Ciganda, Alvaro; Hofmeyr, G Justus; Belizán, José M; Purnat, Tina Dannemann; Manyame, Sarah; Parker, Catherine; Cormick, Gabriela

    2017-10-26

    The preconception period has the potential to influence pregnancy outcomes and randomized controlled trials (RCTs) are needed to evaluate a variety of potentially beneficial preconception interventions. However, RCTs commencing before pregnancy have significant participant recruitment and retention challenges. The Calcium And Pre-eclampsia trial (CAP trial) is a World Health Organization multi-country RCT of calcium supplementation commenced before pregnancy to prevent recurrent pre-eclampsia in which non-pregnant participants are recruited and followed up until childbirth. This sub-study explores recruitment methods and preconception retention of participants of the CAP trial to inform future trials. Recruiters at the study sites in Argentina, South Africa and Zimbabwe completed post-recruitment phase questionnaires on recruitment methods used. Qualitative data from these questionnaires and quantitative data on pre-pregnancy trial visit attendance and pregnancy rates up to September 2016 are reported in this paper. RStudio (Version 0.99.903 https://www.rstudio.org ) statistical software was used for summary statistics. Between July 2011 and 8 September 2016, 1354 women with previous pre-eclampsia were recruited. Recruitment took 2 years longer than expected and was facilitated mainly through medical record/register and maternity ward/clinic-based strategies. Recruiters highlighted difficulties associated with inadequate medical records, redundant patient contact details, and follow-up of temporarily ineligible women as some of the challenges faced. Whilst the attendance rates at pre-pregnancy visits were high (78% or more), visits often occurred later than scheduled. Forty-five percent of participants became pregnant (614/1354), 33.5% (454/1354) within 1 year of randomization. In preconception trials, both retrospective and prospective methods are useful for recruiting eligible women with certain conditions. However, these are time-consuming in low

  10. Unusual early-onset Huntingtons disease.

    PubMed

    Vargas, Antonio P; Carod-Artal, Francisco J; Bomfim, Denise; Vázquez-Cabrera, Carolina; Dantas-Barbosa, Carmela

    2003-06-01

    Huntington's disease is an autosomal dominant progressive neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral disorders leading to functional disability. In contrast to patients with adult onset, in which chorea is the major motor abnormality, children often present with spasticity, rigidity, and significant intellectual decline associated with a more rapidly progressive course. An unusual early-onset Huntington's disease case of an 11-year-old boy with severe hypokinetic/rigid syndrome appearing at the age of 2.5 years is presented. Clinical diagnosis was confirmed by polymerase chain reaction study of the expanded IT-15 allele with a compatible size of 102 cytosine-adenosine-guanosine repeats L-Dopa mildly ameliorated rigidity, bradykinesia, and dystonia. We conclude that Huntington's disease should be included in the differential diagnoses of regressive syndromes of early childhood.

  11. An experimental study to evaluate the technological limitations in the understanding of the haemodynamic change in pre-eclampsia.

    PubMed

    Sengupta

    1998-08-01

    BACKGROUND: Conventional indices could not define the pathogenesis of pre-eclampsia and its predictability. It has also not been possible to record these indices from the local uteroplacental system where the pathology lies. OBJECTIVE: To investigate the limitations of the currently available blood pressure-flow measuring indices and techniques commonly used in pregnancy.METHOD: Blood pressure and velocity profiles were obtained under various pathophysiological conditions for pregnant and non-pregnant animals and human subjects. The data were analysed using both conventional and computer-based spectral methods. RESULTS: Continuous monitoring of blood pressure and velocity together with their spectral analysis appeared to be a useful sensitive indicator in pregnancy beyond the commonly available conventional analytical method. In high-resistance flow such as in hypertension and in pre-eclampsia, the power amplitude was relatively low at low frequency. Power amplitude remained high at low frequency in normal low-resistance state of pregnancy. CONCLUSION: The results suggest the need to develop a highly sensitive instrumentation whereby any minute variation in mean arterial pressure that is of clinical significance can be measured. Alternatively, analytical advancement, such as use of power spectrum analysers, might prove to be useful and sensitive. Variability of heart rate is an important determinant of the underlying pathophysiology in pregnancy. It is concluded that the heart rate of pre-eclamptics and hypertensives has to increase in order to maintain a constant organic blood flow whereas in normal pregnancy bloow flow can rise even without an incrase in heart rate. Future research should be directed towards blood flow mapping, power spectral analysis and image processing of the blood pressure-flow profile obtained from local and systemic compartments under different pathophysiological conditions of pregnancy.

  12. Effect of supplementation during pregnancy with L-arginine and antioxidant vitamins in medical food on pre-eclampsia in high risk population: randomised controlled trial

    PubMed Central

    Perichart-Perera, Otilia; Espino, Salvador; Avila-Vergara, Marco Antonio; Ibarra, Isabel; Ahued, Roberto; Godines, Myrna; Parry, Samuel; Macones, George; Strauss, Jerome F

    2011-01-01

    Objective To test the hypothesis that a relative deficiency in L-arginine, the substrate for synthesis of the vasodilatory gas nitric oxide, may be associated with the development of pre-eclampsia in a population at high risk. Design Randomised, blinded, placebo controlled clinical trial. Setting Tertiary public hospital in Mexico City. Participants Pregnant women with a history of a previous pregnancy complicated by pre-eclampsia, or pre-eclampsia in a first degree relative, and deemed to be at increased risk of recurrence of the disease were studied from week 14-32 of gestation and followed until delivery. Interventions Supplementation with a medical food—bars containing L-arginine plus antioxidant vitamins, antioxidant vitamins alone, or placebo—during pregnancy. Main outcome measure Development of pre-eclampsia/eclampsia. Results 222 women were allocated to the placebo group, 228 received L-arginine plus antioxidant vitamins, and 222 received antioxidant vitamins alone. Women had 4-8 prenatal visits while receiving the bars. The incidence of pre-eclampsia was reduced significantly (χ2=19.41; P<0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17 (95% confidence interval 0.12 to 0.21). Antioxidant vitamins alone showed an observed benefit, but this effect was not statistically significant compared with placebo (χ2=3.76; P=0.052; absolute risk reduction 0.07, 0.005 to 0.15). L-arginine plus antioxidant vitamins compared with antioxidant vitamins alone resulted in a significant effect (P=0.004; absolute risk reduction 0.09, 0.05 to 0.14). Conclusions Supplementation during pregnancy with a medical food containing L-arginine and antioxidant vitamins reduced the incidence of pre-eclampsia in a population at high risk of the condition. Antioxidant vitamins alone did not have a protective effect for prevention of pre-eclampsia. Supplementation with L-arginine plus antioxidant vitamins needs to be

  13. Salinity in drinking water and the risk of (pre)eclampsia and gestational hypertension in coastal Bangladesh: a case-control study.

    PubMed

    Khan, Aneire Ehmar; Scheelbeek, Pauline Franka Denise; Shilpi, Asma Begum; Chan, Queenie; Mojumder, Sontosh Kumar; Rahman, Atiq; Haines, Andy; Vineis, Paolo

    2014-01-01

    Hypertensive disorders in pregnancy are among the leading causes of maternal and perinatal death in low-income countries, but the aetiology remains unclear. We investigated the relationship between salinity in drinking water and the risk of (pre)eclampsia and gestational hypertension in a coastal community. A population-based case-control study was conducted in Dacope, Bangladesh among 202 pregnant women with (pre)eclampsia or gestational hypertension, enrolled from the community served by the Upazilla Health Complex, Dacope and 1,006 matched controls from the same area. Epidemiological and clinical data were obtained from all participants. Urinary sodium and sodium levels in drinking water were measured. Logistic regression was used to calculate odds ratios, and 95% confidence intervals. Drinking water sources had exceptionally high sodium levels (mean 516.6 mg/L, S.D 524.2). Women consuming tube-well (groundwater) were at a higher disease risk than rainwater users (p<0.001). Adjusted risks for (pre)eclampsia and gestational hypertension considered together increased in a dose-response manner for increasing sodium concentrations (300.01-600 mg/L, 600.1-900 mg/L, >900.01 mg/L, compared to <300 mg/L) in drinking water (ORs 3.30 [95% CI 2.00-5.51], 4.40 [2.70-7.25] and 5.48 [3.30-9.11] (p-trend<0.001). Significant associations were seen for both (pre)eclampsia and gestational hypertension separately. Salinity in drinking water is associated with increased risk of (pre)eclampsia and gestational hypertension in this population. Given that coastal populations in countries such as Bangladesh are confronted with high salinity exposure, which is predicted to further increase as a result of sea level rise and other environmental influences, it is imperative to develop and evaluate affordable approaches to providing water with low salt content.

  14. The Effect of High Dose Folic Acid throughout Pregnancy on Homocysteine (Hcy) Concentration and Pre-Eclampsia: A Randomized Clinical Trial

    PubMed Central

    Sayyah-Melli, Manizheh; Ghorbanihaghjo, Amir; Alizadeh, Mahasti; Kazemi-Shishvan, Maryamalsadat; Ghojazadeh, Morteza; Bidadi, Sanam

    2016-01-01

    Pre-eclampsia is a pregnancy-related multi-systemic hypertensive disorder and affects at least 5% of pregnancies. This randomized clinical trial aimed at assessing the effect of low doses and high doses of folic acid on homocysteine (Hcy) levels, blood pressure, urea, creatinine and neonatal outcome. A randomized clinical trial was done at Alzahra Teaching Hospital, Tabriz University of Medical Sciences from April 2008 to March 2013. Four-hundred and sixty nulliparous pregnant women were randomly assigned into two groups. Group 1 (n = 230) received 0.5 mg of folic acid and group 2 (n = 230) received 5 mg of folic acid per daily. They were followed until delivery. Blood pressure and laboratory changes, including plasma Hcy levels, were measured and compared between the groups. Homocysteine concentrations were significantly higher at the time of delivery in group 1 (13.17±3.89 μmol/l) than in group 2 (10.31±3.54, μmol/l) (p<0.001). No statistically significant differences were observed in systolic and diastolic blood pressure (p = 0.84 and 0.15, respectively). Birth weight was significantly higher in group 2 (p = 0.031) and early abortion was significantly higher in group 1 than group 2 (p = 0.001). This study has provided evidence that a high dosage of folic acid supplements throughout pregnancy reduces Hcy concentrations at the time of delivery. Trial Registration: Iranian Registry of Clinical Trials IRCT201402175283N9 PMID:27166794

  15. Vitamin D status is associated with uteroplacental dysfunction indicated by pre-eclampsia and small-for-gestational-age birth in a large prospective pregnancy cohort in Ireland with low vitamin D status.

    PubMed

    Kiely, Mairead E; Zhang, Joy Y; Kinsella, Michael; Khashan, Ali S; Kenny, Louise C

    2016-08-01

    Associations between vitamin D and pregnancy outcomes have been inconsistent. We described the distribution of 25-hydroxyvitamin D3 [25(OH)D3], 3-epi-25(OH)D3, and 25(OH)D2 in early pregnancy and investigated associations with pre-eclampsia and small-for-gestational-age (SGA) birth, which are indicative of uteroplacental dysfunction. The SCOPE (Screening for Pregnancy Endpoints) Ireland prospective pregnancy cohort study included 1768 well-characterized low-risk, nulliparous women resident at 52°N. Serum 25(OH)D3, 3-epi-25(OH)D3, and 25(OH)D2 were quantified at 15 wk of gestation with the use of a CDC-accredited liquid chromatography-tandem mass spectrometry method. The mean ± SD total 25(OH)D concentration was 56.7 ± 25.9 nmol/L, and 17% and 44% of women had 25(OH)D concentrations <30 and <50 nmol/L, respectively. The prevalence of pre-eclampsia was 3.8%, and 10.7% of infants were SGA. There was a lower risk of pre-eclampsia plus SGA combined (13.6%) at 25(OH)D concentrations >75 nmol/L (adjusted OR: 0.64; 95% CI: 0.43, 0.96). The main predictors of 25(OH)D were the use of vitamin D-containing supplements (adjusted mean difference: 20.1 nmol/L; 95% CI: 18.5, 22.7 nmol/L) and summer sampling (adjusted mean difference: 15.5 nmol/L; 95% CI: 13.4, 17.6 nmol/L). Non-Caucasian ethnicity (adjusted mean difference: -19.3 nmol/L; 95% CI: -25.4, -13.2 nmol/L) and smoking (adjusted mean difference: -7.0 nmol/L; 95% CI: -10.5, -3.6 nmol/L) were negative predictors of 25(OH)D. The mean ± SD concentration of 3-epi-25(OH)D3, which was detectable in 99.9% of samples, was 2.6 ± 1.6 nmol/L. Determinants of 3-epi-25(OH)D3 were 25(OH)D3 (adjusted mean difference: 0.052 nmol/L; 95% CI: 0.050, 0.053 nmol/L) and maternal age (adjusted mean difference: -0.018 nmol/L; 95% CI: -0.026, -0.009 nmol/L). The mean ± SD concentration of 25(OH)D2 was 3.1 ± 2.7 nmol/L, which was present in all samples. No adverse effects of 25(OH)D concentrations >125 nmol/L were observed. In the first

  16. Early-onset scoliosis: current treatment.

    PubMed

    Cunin, V

    2015-02-01

    Early-onset scoliosis, which appears before the age of 10, can be due to congenital vertebral anomalies, neuromuscular diseases, scoliosis-associated syndromes, or idiopathic causes. It can have serious consequences for lung development and significantly reduce the life expectancy compared to adolescent scoliosis. Extended posterior fusion must be avoided to prevent the crankshaft phenomenon, uneven growth of the trunk and especially restrictive lung disease. Conservative (non-surgical) treatment is used first. If this fails, fusionless surgery can be performed to delay the final fusion procedure until the patient is older. The gold standard delaying surgical treatment is the implantation of growing rods as described by Moe and colleagues in the mid-1980s. These rods, which are lengthened during short surgical procedures at regular intervals, curb the scoliosis progression until the patient reaches an age where fusion can be performed. Knowledge of this technique and its complications has led to several mechanical improvements being made, namely use of rods that can be distracted magnetically on an outpatient basis, without the need for anesthesia. Devices based on the same principle have been designed that preferentially attach to the ribs to specifically address chest wall and spine dysplasia. The second category of surgical devices consists of rods used to guide spinal growth that do not require repeated surgical procedures. The third type of fusionless surgical treatment involves slowing the growth of the scoliosis convexity to help reduce the Cobb angle. The indications are constantly changing. Improvements in surgical techniques and greater surgeon experience may help to reduce the number of complications and make this lengthy treatment acceptable to patients and their family. Long-term effects of surgery on the Cobb angle have not been compared to those involving conservative "delaying" treatments. Because the latter has fewer complications associated with

  17. Early-onset Alzheimer's Disease Phenotypes: Neuropsychology and Neural Networks

    ClinicalTrials.gov

    2017-05-11

    Alzheimer Disease, Early Onset; Alzheimer Disease; Alzheimer Disease, Late Onset; Dementia, Alzheimer Type; Logopenic Progressive Aphasia; Primary Progressive Aphasia; Visuospatial/Perceptual Abilities; Posterior Cortical Atrophy; Executive Dysfunction; Corticobasal Degeneration; Ideomotor Apraxia

  18. Synergistic effect of maternal obesity and periodontitis on preterm birth in women with pre-eclampsia: a prospective study.

    PubMed

    Lee, Hyo-Jin; Ha, Jung-Eun; Bae, Kwang-Hak

    2016-08-01

    The aim of this study was to investigate if pregnant women with both obesity and periodontitis are more likely to experience preterm birth (PTB) in women with pre-eclampsia (PE) than pregnant women with only obesity or only periodontitis. The study examined a total of 328 pregnant women at 21-24 weeks of gestation. Overweight and obesity was defined based on criteria proposed by the WHO Expert Consultation. Periodontal conditions were assessed by measuring periodontal clinical attachment loss. PTB was defined as delivery at <37 weeks, and PE was defined as blood pressure higher than 140/90 mmHg on two separate occasions with at least 1+ proteinuria on a random urine screen after the 20th week of pregnancy. After adjusting for other important cofactors, pregnant women with periodontitis were 5.56 times [95% confidence interval (CI) = 1.22-25.39] more likely to have PTB with PE than women without periodontitis. The association was much stronger (odds ratio = 15.94, 95% CI = 3.31-76.71) in women with both obesity and periodontitis. Our results of this study indicate that pregnant women with both pre-pregnancy obesity and periodontitis are significantly more likely to have PTB with PE than pregnant women with only periodontitis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Epigallocatechin gallate enhances treatment efficacy of oral nifedipine against pregnancy-induced severe pre-eclampsia: A double-blind, randomized and placebo-controlled clinical study.

    PubMed

    Shi, D-D; Guo, J-J; Zhou, L; Wang, N

    2018-02-01

    Oral nifedipine is commonly used to treat pre-eclampsia, one of the most severe complications during pregnancy, but its clinical efficacy is less than ideal. Epigallocatechin gallate (EGCG), a natural compound from green tea, could benefit cardiovascular health especially hypertension. We investigated the clinical efficacy of EGCG, when complemented with oral nifedipine, in treating pre-eclampsia. A total of 350 pregnant women with severe pre-eclampsia were recruited and randomized to receive oral nifedipine, together with placebo (NIF+placebo) or EGCG (NIF+EGCG). The primary treatment outcome was the time needed to control blood pressure and interval time before a new hypertensive crisis, whereas the secondary treatment outcome was the number of treatment doses to effectively control blood pressure, maternal adverse effects and neonatal complications. Comparing NIF+EGCG group to NIF+placebo group, the time needed to control blood pressure was significantly shorter (NIF+EGCG 31.2±16.7 minutes, NIF+placebo 45.3±21.9 minutes; 95% CI 9.7-18.5 minutes), whereas interval time before a new hypertensive crisis was significantly prolonged (NIF+EGCG 7.2±2.9 hours, NIF+placebo 4.1±3.7 hours; 95% CI 2.3-3.9 hours), and the number of treatment dosages needed to effectively control blood pressure was also lower. Between the two treatment groups, no differences in incidence rates of maternal adverse effects or neonatal complications were observed. EGCG is both safe and effective in enhancing treatment efficacy of oral nifedipine against pregnancy-induced severe pre-eclampsia, but formal validation is required prior to its recommendation for use outside of clinical trials. © 2017 John Wiley & Sons Ltd.

  20. Assessment of quality of care among in-patients with postpartum haemorrhage and severe pre-eclampsia at st. Francis hospital nsambya: a criteria-based audit.

    PubMed

    Lumala, Alfred; Sekweyama, Peter; Abaasa, Andrew; Lwanga, Humphrey; Byaruhanga, Romano

    2017-01-13

    The maternal mortality ratio of Uganda is still high and the leading causes of maternal mortality are postpartum haemorrhage (PPH), severe pre-eclampsia and eclampsia. Criteria-based audit (CBA) is a way of improving quality of care that has not been commonly used in low income countries. This study aimed at finding out the quality of care provided to patients with these conditions and to find out if the implementation of recommendations from the audit cycle resulted in improvement in quality of care. This study was a CBA following a time series study design. It was done in St. Francis Hospital Nsambya and it involved assessment of adherence to standards of care for PPH, severe pre-eclampsia and eclampsia. An initial audit was done for 3 consecutive months, then findings were presented to health workers and recommendations made; we implemented the recommendations in a subsequent month and this comprised three interventions namely continuing medical education (CME), drills and displaying guidelines; a re-audit was done in the proceeding 3 consecutive months and analysis compared adherence rates of the initial audit with those of the re-audit. Pearson Chi-Square test revealed that the adherence rates of 7 out of 10 standards of care for severe pre-eclampsia/eclampsia were statistically significantly higher in the re-audit than in the initial audit; also, the adherence rates of 3 out of 4 standards of care for PPH were statistically significantly higher in the re-audit than in the initial audit. The giving of feedback on quality of care and the implementation of recommendations made during the CBA including CME, drills and displaying guidelines was associated with improvements in the quality of care for patients with PPH, severe pre-eclampsia and eclampsia.

  1. An analysis of the meanings of pre-eclampsia for pregnant and postpartum women and health professionals in Rio Grande do Norte, Brazil.

    PubMed

    de Azevedo, Daniela Vasconcelos; de Araújo, Ana C P F; Clara Costa, Iris C

    2011-12-01

    To understand the meanings of pre-eclampsia for pregnant and postpartum women and health-care professionals. a word-association test and semi-structured interviews. A maternity hospital located in Natal, Rio Grande do Norte, Brazil that serves pregnant and postpartum women considered to be at high risk. 51 Pregnant women, 10 postpartum women and 87 health-care professionals completed a word-association test; 18 pregnant women, two postpartum women and 20 health-care professionals for the interviews. Thematic categories based on the word-association test and the interviews were created to help the data analysis. χ(2) test was used to compare the categories raised by both groups in the word-association test to determine the association between the frequencies of these categories. The meanings of pre-eclampsia to pregnant and postpartum women were fear, risk, care and lack of information. To the health-care professionals, the meanings were care, fear, risk, high blood pressure, oedema and proteinuria. The frequencies of the categories 'fear', 'care' and 'risk' were statistically different (χ(2) = 31.84, 14.5, 38.19, respectively; df = 2, p < 0.001) between the group of pregnant and postpartum women and the group of health-care professionals. For the first group, the most significant meanings were fear and risk, compared with care for the second group. The analysis of the interviews confirmed and deepened the results of the word-association test, and also demonstrated that the pregnant and postpartum women had no information about pre-eclampsia. There is a gap between how women and health professionals view their experiences of pre-eclampsia. A warm welcome to the health-care facility, with clear explanations about the disease and the procedures to be performed during the visits and hospitalisation would be important aspects for the physical and mental well-being of pregnant and postpartum women. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Genetic dissection of the pre-eclampsia susceptibility locus on chromosome 2q22 reveals shared novel risk factors for cardiovascular disease

    PubMed Central

    Johnson, Matthew P.; Brennecke, Shaun P.; East, Christine E.; Dyer, Thomas D.; Roten, Linda T.; Proffitt, J. Michael; Melton, Phillip E.; Fenstad, Mona H.; Aalto-Viljakainen, Tia; Mäkikallio, Kaarin; Heinonen, Seppo; Kajantie, Eero; Kere, Juha; Laivuori, Hannele; Austgulen, Rigmor; Blangero, John; Moses, Eric K.; Pouta, Anneli; Kivinen, Katja; Ekholm, Eeva; Hietala, Reija; Sainio, Susanna; Saisto, Terhi; Uotila, Jukka; Klemetti, Miira; Inkeri Lokki, Anna; Georgiadis, Leena; Huovari, Elina; Kortelainen, Eija; Leminen, Satu; Lähdesmäki, Aija; Mehtälä, Susanna; Salmen, Christina

    2013-01-01

    Pre-eclampsia is an idiopathic pregnancy disorder promoting morbidity and mortality to both mother and child. Delivery of the fetus is the only means to resolve severe symptoms. Women with pre-eclamptic pregnancies demonstrate increased risk for later life cardiovascular disease (CVD) and good evidence suggests these two syndromes share several risk factors and pathophysiological mechanisms. To elucidate the genetic architecture of pre-eclampsia we have dissected our chromosome 2q22 susceptibility locus in an extended Australian and New Zealand familial cohort. Positional candidate genes were prioritized for exon-centric sequencing using bioinformatics, SNPing, transcriptional profiling and QTL-walking. In total, we interrogated 1598 variants from 52 genes. Four independent SNP associations satisfied our gene-centric multiple testing correction criteria: a missense LCT SNP (rs2322659, P = 0.0027), a synonymous LRP1B SNP (rs35821928, P = 0.0001), an UTR-3 RND3 SNP (rs115015150, P = 0.0024) and a missense GCA SNP (rs17783344, P = 0.0020). We replicated the LCT SNP association (P = 0.02) and observed a borderline association for the GCA SNP (P = 0.07) in an independent Australian case–control population. The LRP1B and RND3 SNP associations were not replicated in this same Australian singleton cohort. Moreover, these four SNP associations could not be replicated in two additional case–control populations from Norway and Finland. These four SNPs, however, exhibit pleiotropic effects with several quantitative CVD-related traits. Our results underscore the genetic complexity of pre-eclampsia and present novel empirical evidence of possible shared genetic mechanisms underlying both pre-eclampsia and other CVD-related risk factors. PMID:23420841

  3. Placental Growth Factor (PlGF) in Women with Suspected Pre-Eclampsia Prior to 35 Weeks’ Gestation: A Budget Impact Analysis

    PubMed Central

    Duckworth, Suzy; Seed, Paul T.; Mackillop, Lucy; Shennan, Andrew H.; Hunter, Rachael

    2016-01-01

    Objective To model the resource implications of placental growth factor (PlGF) testing in women with suspected pre-eclampsia prior to 35 weeks’ gestation as part of a management algorithm, compared with current practice. Methods Data on resource use from 132 women with suspected pre-eclampsia prior to 35 weeks’ gestation, enrolled in a prospective observational cohort study evaluating PlGF measurement within antenatal assessment units within two UK consultant-led maternity units was extracted by case note review. A decision analytic model was developed using these data to establish the budget impact of managing women with suspected pre-eclampsia for two weeks from the date of PlGF testing, using a clinical management algorithm and reference cost tariffs. The main outcome measures of resource use (numbers of outpatient appointments, ultrasound investigations and hospital admissions) were correlated to final diagnosis and used to calculate comparative management regimes. Results The mean cost saving associated with the PlGF test (in the PlGF plus management arm) was £35,087 (95% CI -£33,181 to -£36,992) per 1,000 women. This equated to a saving of £582 (95% CI -552 to -£613) per woman tested. In 94% of iterations, PlGF testing was associated with cost saving compared to current practice. Conclusions This analysis suggests PlGF used as part of a clinical management algorithm in women presenting with suspected pre-eclampsia prior to 35 weeks’ gestation could provide cost savings by reducing unnecessary resource use. Introduction of PlGF testing could be used to direct appropriate resource allocation and overall would be cost saving. PMID:27741259

  4. Parallel decrease in arterial distensibility and in endothelium-dependent dilatation in young women with a history of pre-eclampsia.

    PubMed

    Pàez, Olga; Alfie, José; Gorosito, Marta; Puleio, Pablo; de Maria, Marcelo; Prieto, Noemì; Majul, Claudio

    2009-10-01

    Pre-eclampsia not only complicates 5 to 8% of pregnancies but also increases the risk of maternal cardiovascular disease and mortality later in life. We analyzed three different aspects of arterial function (pulse wave velocity, augmentation index, and flow-mediated dilatation), in 55 nonpregnant, normotensive women (18-33 years old) according to their gestational history: 15 nulliparous, 20 with a previous normotensive, and 20 formerly pre-eclamptic pregnancy. Former pre-eclamptic women showed a significantly higher augmentation index and pulse wave velocity (P < 0.001 and P < 0.05, respectively) and lower flow-mediated dilatation (p = 0.01) compared to control groups. In contrast, sublingual nitroglycerine elicited a comparable vasodilatory response in the three groups. The augmentation index correlated significantly with pulse wave velocity and flow-mediated dilatation (R = 0.28 and R = -0.32, respectively, P < 0.05 for both). No significant correlations were observed between augmentation index or flow-mediated dilatation with age, body mass index (BMI), brachial blood pressure, heart rate, or metabolic parameters (plasma cholesterol, glucose, insulin, or insulin resistance). Birth weight maintained a significantly inverse correlation with the augmentation index (R = -0.51, p < 0.002) but not with flow-mediated dilatation. Our findings revealed a parallel decrease in arterial distensibility and endothelium-dependent dilatation in women with a history of pre-eclampsia compared to nulliparous women and women with a previous normal pregnancy. A high augmentation index was the most consistent alteration associated with a history of pre-eclampsia. The study supports the current view that the generalized arterial dysfunction associated with pre-eclampsia persists subclinically after delivery.

  5. First trimester serum afamin concentrations are associated with the development of pre-eclampsia and gestational diabetes mellitus in pregnant women.

    PubMed

    Tramontana, Allessandra; Dieplinger, Benjamin; Stangl, Gerhard; Hafner, Erich; Dieplinger, Hans

    2018-01-01

    Aim of this study was to assess the prognostic capability of afamin to predict pregnancy complications. First-trimester screening was consecutively performed in 4948 pregnant women, of whom 474 women developed pregnancy complications [gestational hypertension (n=84), pre-eclampsia (n=30), intrauterine growth restriction (n=107), preterm birth (n=44), and gestational diabetes mellitus (n=209)]. To each woman with pregnancy complications an uncomplicated pregnancy was matched for body mass index. Afamin serum concentrations were measured in 948 pregnant women at the first-trimester screening. Median afamin concentrations were significantly higher in women developing pre-eclampsia or gestational diabetes mellitus when compared to women with uncomplicated pregnancies (76mg/L vs. 65mg/L, p=0.001 and 80mg/L vs. 69mg/L, p<0.001). There was no difference in median afamin values between all other pregnancy complications and their matched controls. Increased afamin (i.e. >65mg/L) was a strong and independent predictor for the development of pre-eclampsia (risk ratio, 24.58; 95%CI, 2.82-214.12; p=0.004) as well as gestational diabetes mellitus (risk ratio, 2.07; 95%CI, 1.33-3.22; p=0.001). In this large nested case-control study increased afamin concentrations were a strong and independent predictor for pre-eclampsia and gestational diabetes mellitus, suggesting a potential role of afamin as predictive marker for pregnancy-related metabolic disorders. Copyright © 2017. Published by Elsevier B.V.

  6. Elevated levels of hypoxia-inducible microRNA-210 in pre-eclampsia: new insights into molecular mechanisms for the disease

    PubMed Central

    Zhang, Yi; Fei, Mingyu; Xue, Geng; Zhou, Qi; Jia, Yin; Li, Li; Xin, Hong; Sun, Shuhan

    2012-01-01

    Abstract Pre-eclampsia is a leading cause of maternal and foetal morbidity and mortality worldwide. Insufficient uteroplacental oxygenation is believed to be responsible for the disease. However, what molecular events involve in hypoxic responses and how they affect placental development remain unclear. Recently, miRNAs have emerged as a new class of molecules in response to hypoxia. We show here that the expression of microRNA-210 (mir-210) is up-regulated in patients with pre-eclampsia, as well as in trophoblast cells cultured under hypoxic conditions. Ectopic expression of mir-210 inhibited the migration and invasion capability of trophoblast cells. Ephrin-A3 and Homeobox-A9, which related with cell migration and vascular remodelling, were then experimentally validated as the functional targets of mir-210 both in vivo and in vitro. Using luciferase reporter, chromatin immunoprecipitation (ChIP) and small interfering RNA (siRNA) experiments, we finally identified a new transcriptional mechanism that the overexpression of mir-210 under hypoxia was regulated by NF-κB transcriptional factor p50, apart from the well-known HIF 1α. Taken together, our study implicates an important role for mir-210 in the molecular mechanism of pre-eclampsia. PMID:21388517

  7. Association between decreased plasma levels of soluble human leukocyte antigen-G and severe pre-eclampsia.

    PubMed

    He, Yingdong; Chen, Shi; Huang, He; Chen, Qian

    2016-04-01

    The aim of this study was to investigate the levels of different isoforms of soluble human leukocyte antigen-G (sHLA-G) in maternal plasma during early and late pregnancy, and to investigate the expression of sHLA-G isoforms in women with early or late-onset severe preeclampsia. This prospective, nested, case-control study was performed in 24 early-onset severe preeclamptic, 34 late-onset severe preeclamptic, and 74 uncomplicated pregnant women. Plasma levels of sHLA-G1/5 were measured using ELISA. Plasma sHLA-G1 levels in women with late-onset severe preeclampsia were markedly lower compared with normal controls (median: 0 vs. 1.22 ng/mL) at the first trimester, and plasma sHLA-G1 levels in women with early-onset severe preeclampsia were markedly lower compared with normal controls at the second (median: 0 vs. 1.24 ng/mL) and third (median: 0 vs. 1.34 ng/mL) trimesters. There was no difference between the late-onset and early-onset groups at three trimesters. As for sHLA-G5, there was no difference in concentrations among the three groups at any time point. However, compared with controls, more women with early- or late-onset severe preeclampsia had undetectable sHLA-G5 levels in the first (71.4% and 76.2% vs. 14.1%), second (75.0% and 73.3% vs. 19.0%), and third (100.0% and 70.4% vs. 14.8%, respectively) trimester (all P<0.05). sHLA-G1 levels in the first (odds ratio [OR]=0.254, 95% confidence interval [CI]=0.109-0.591, P=0.010), second (OR=0.315, 95% CI=0.158-0.627, P=0.001), and third (OR=0.170, 95% CI=0.054-0.533, P=0.002) trimester was a risk factor for severe preeclampsia. Severe preeclampsia was associated with low/undetectable maternal plasma levels of sHLA-G. Low sHLA-G1 levels might be a risk marker for severe preeclampsia.

  8. Childhood adversity, early-onset depressive/anxiety disorders, and adult-onset asthma.

    PubMed

    Scott, Kate M; Von Korff, Michael; Alonso, Jordi; Angermeyer, Matthias C; Benjet, Corina; Bruffaerts, Ronny; de Girolamo, Giovanni; Haro, Josep Maria; Kessler, Ronald C; Kovess, Viviane; Ono, Yutaka; Ormel, Johan; Posada-Villa, José

    2008-11-01

    To investigate a) whether childhood adversity predicts adult-onset asthma; b) whether early-onset depressive/anxiety disorders predict adult-onset asthma; and c) whether childhood adversity and early-onset depressive/anxiety disorders predict adult-onset asthma independently of each other. Previous research has suggested, but not established, that childhood adversity may predict adult-onset asthma and, moreover, that the association between mental disorders and asthma may be a function of shared risk factors, such as childhood adversity. Ten cross-sectional population surveys of household-residing adults (>18 years, n = 18,303) assessed mental disorders with the Composite International Diagnostic Interview (CIDI 3.0) as part of the World Mental Health surveys. Assessment of a range of childhood family adversities was included. Asthma was ascertained by self-report of lifetime diagnosis and age of diagnosis. Survival analyses calculated hazard ratios (HRs) for risk of adult-onset (>age 20 years) asthma as a function of number and type of childhood adversities and early-onset (onset asthma with risk increasing with the number of adversities experienced (HRs = 1.49-1.71). Early-onset depressive and anxiety disorders also predicted adult-onset asthma (HRs = 1.67-2.11). Childhood adversities and early-onset depressive and anxiety disorders both predicted adult-onset asthma after mutual adjustment (HRs = 1.43-1.91). Childhood adversities and early-onset depressive/anxiety disorders independently predict adult-onset asthma, suggesting that the mental disorder-asthma relationship is not a function of a shared background of childhood adversity.

  9. Salinity in Drinking Water and the Risk of (Pre)Eclampsia and Gestational Hypertension in Coastal Bangladesh: A Case-Control Study

    PubMed Central

    Khan, Aneire Ehmar; Scheelbeek, Pauline Franka Denise; Shilpi, Asma Begum; Chan, Queenie; Mojumder, Sontosh Kumar; Rahman, Atiq; Haines, Andy; Vineis, Paolo

    2014-01-01

    Background Hypertensive disorders in pregnancy are among the leading causes of maternal and perinatal death in low-income countries, but the aetiology remains unclear. We investigated the relationship between salinity in drinking water and the risk of (pre)eclampsia and gestational hypertension in a coastal community. Methods A population-based case-control study was conducted in Dacope, Bangladesh among 202 pregnant women with (pre)eclampsia or gestational hypertension, enrolled from the community served by the Upazilla Health Complex, Dacope and 1,006 matched controls from the same area. Epidemiological and clinical data were obtained from all participants. Urinary sodium and sodium levels in drinking water were measured. Logistic regression was used to calculate odds ratios, and 95% confidence intervals. Findings Drinking water sources had exceptionally high sodium levels (mean 516.6 mg/L, S.D 524.2). Women consuming tube-well (groundwater) were at a higher disease risk than rainwater users (p<0.001). Adjusted risks for (pre)eclampsia and gestational hypertension considered together increased in a dose-response manner for increasing sodium concentrations (300.01–600 mg/L, 600.1–900 mg/L, >900.01 mg/L, compared to <300 mg/L) in drinking water (ORs 3.30 [95% CI 2.00–5.51], 4.40 [2.70–7.25] and 5.48 [3.30–9.11] (p-trend<0.001). Significant associations were seen for both (pre)eclampsia and gestational hypertension separately. Interpretation Salinity in drinking water is associated with increased risk of (pre)eclampsia and gestational hypertension in this population. Given that coastal populations in countries such as Bangladesh are confronted with high salinity exposure, which is predicted to further increase as a result of sea level rise and other environmental influences, it is imperative to develop and evaluate affordable approaches to providing water with low salt content. PMID:25268785

  10. PP043. Do women know what pre-eclampsia is? What is the level of knowledge of the disease in a small population connected to a social net?

    PubMed

    Mosca, C P; Sapata, J M; Sato, J L; Marin, E J; Sass, N

    2012-07-01

    Pre-eclampsia is responsible for a great number of maternal deaths in our country. Even in urban areas that, theoretically, has more access to information and more medical assistance possibilities, much more women have very severe cases that could be avoided. Many initiatives to reduce this problem include effective women participation in that item, making us to believe that actual information access would allow precocious detection of the problem, leading to reduction of the maternal and perinatal risks. To investigate a specific female population about how much they understand about the disease and its risks. Using the social net Facebook®, a survey was developed for online use, where direct questions related to pre-eclampsia were made. The questions involved information about age, times of pregnancy, knowledge about pre-eclampsia and their risks. It was considered an inclusion criterion the women who decided to participate in the survey spontaneously, and their identity was preserved. This form was sent to 1000 women, and 120 fully answered the questions and they were put under analysis. The studied group had average age between 22 and 35years. From the total, 107 (89.6%) had at least initiated high school, and the rest (11%) said that they had at least finished elementary school. From the analyzed data, it was found that 60 (50%) of the interviewed women, did not know anything about the subject. The rest said that they had some knowledge about the topic. From those, 14 (23%) had already heard about pre-eclampsia, but did not know what was it, 44 (73%) had a vaguely notion but did not know about the risks, and just 2 (4%) gave the entirely correct definition and knew about its implications. From all, 24 (20%) from the interviewed had at least once been pregnant, and 15 from those, had never heard about the pathology. Despite of the impact that pre-eclampsia represents on mother and baby's health, our results show that information in the studied group, is poor

  11. Risk factors of pre-eclampsia/eclampsia and its adverse outcomes in low- and middle-income countries: a WHO secondary analysis.

    PubMed

    Bilano, Ver Luanni; Ota, Erika; Ganchimeg, Togoobaatar; Mori, Rintaro; Souza, João Paulo

    2014-01-01

    Pre-eclampsia has an immense adverse impact on maternal and perinatal health especially in low- and middle-income settings. We aimed to estimate the associations between pre-eclampsia/eclampsia and its risk factors, and adverse maternal and perinatal outcomes. We performed a secondary analysis of the WHO Global Survey on Maternal and Perinatal Health. The survey was a multi-country, facility-based cross-sectional study. A global sample consisting of 24 countries from three regions and 373 health facilities was obtained via a stratified multi-stage cluster sampling design. Maternal and offspring data were extracted from records using standardized questionnaires. Multi-level logistic regression modelling was conducted with random effects at the individual, facility and country levels. Data for 276,388 mothers and their infants was analysed. The prevalence of pre-eclampsia/eclampsia in the study population was 10,754 (4%). At the individual level, sociodemographic characteristics of maternal age ≥30 years and low educational attainment were significantly associated with higher risk of pre-eclampsia/eclampsia. As for clinical and obstetric variables, high body mass index (BMI), nulliparity (AOR: 2.04; 95%CI 1.92-2.16), absence of antenatal care (AOR: 1.41; 95%CI 1.26-1.57), chronic hypertension (AOR: 7.75; 95%CI 6.77-8.87), gestational diabetes (AOR: 2.00; 95%CI 1.63-2.45), cardiac or renal disease (AOR: 2.38; 95%CI 1.86-3.05), pyelonephritis or urinary tract infection (AOR: 1.13; 95%CI 1.03-1.24) and severe anemia (AOR: 2.98; 95%CI 2.47-3.61) were found to be significant risk factors, while having >8 visits of antenatal care was protective (AOR: 0.90; 95%CI 0.83-0.98). Pre-eclampsia/eclampsia was found to be a significant risk factor for maternal death, perinatal death, preterm birth and low birthweight. Chronic hypertension, obesity and severe anemia were the highest risk factors of preeclampsia/eclampsia. Implementation of effective interventions prioritizing risk

  12. Angiogenic factors combined with clinical risk factors to predict preterm pre-eclampsia in nulliparous women: a predictive test accuracy study.

    PubMed

    Myers, J E; Kenny, L C; McCowan, L M E; Chan, E H Y; Dekker, G A; Poston, L; Simpson, N A B; North, R A

    2013-09-01

    To assess the performance of clinical risk factors, uterine artery Doppler and angiogenic markers to predict preterm pre-eclampsia in nulliparous women. Predictive test accuracy study. Prospective multicentre cohort study Screening for Pregnancy Endpoints (SCOPE). Low-risk nulliparous women with a singleton pregnancy were recruited. Clinical risk factor data were obtained and plasma placental growth factor (PlGF), soluble endoglin and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 14-16 weeks of gestation. Prediction models were developed using multivariable stepwise logistic regression. Preterm pre-eclampsia (delivered before 37(+0)  weeks of gestation). Of the 3529 women recruited, 187 (5.3%) developed pre-eclampsia of whom 47 (1.3%) delivered preterm. Controls (n = 188) were randomly selected from women without preterm pre-eclampsia and included women who developed other pregnancy complications. An area under a receiver operating characteristic curve (AUC) of 0.76 (95% CI 0.67-0.84) was observed using previously reported clinical risk variables. The AUC improved following the addition of PlGF measured at 14-16 weeks (0.84; 95% CI 0.77-0.91), but no further improvement was observed with the addition of uterine artery Doppler or the other angiogenic markers. A sensitivity of 45% (95% CI 0.31-0.59) (5% false-positive rate) and post-test probability of 11% (95% CI 9-13) were observed using clinical risk variables and PlGF measurement. Addition of plasma PlGF at 14-16 weeks of gestation to clinical risk assessment improved the identification of nulliparous women at increased risk of developing preterm pre-eclampsia, but the performance is not sufficient to warrant introduction as a clinical screening test. These findings are marker dependent, not assay dependent; additional markers are needed to achieve clinical utility. © 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.

  13. Risk Factors of Pre-Eclampsia/Eclampsia and Its Adverse Outcomes in Low- and Middle-Income Countries: A WHO Secondary Analysis

    PubMed Central

    Bilano, Ver Luanni; Ota, Erika; Ganchimeg, Togoobaatar; Mori, Rintaro; Souza, João Paulo

    2014-01-01

    Background Pre-eclampsia has an immense adverse impact on maternal and perinatal health especially in low- and middle-income settings. We aimed to estimate the associations between pre-eclampsia/eclampsia and its risk factors, and adverse maternal and perinatal outcomes. Methods We performed a secondary analysis of the WHO Global Survey on Maternal and Perinatal Health. The survey was a multi-country, facility-based cross-sectional study. A global sample consisting of 24 countries from three regions and 373 health facilities was obtained via a stratified multi-stage cluster sampling design. Maternal and offspring data were extracted from records using standardized questionnaires. Multi-level logistic regression modelling was conducted with random effects at the individual, facility and country levels. Results Data for 276,388 mothers and their infants was analysed. The prevalence of pre-eclampsia/eclampsia in the study population was 10,754 (4%). At the individual level, sociodemographic characteristics of maternal age ≥30 years and low educational attainment were significantly associated with higher risk of pre-eclampsia/eclampsia. As for clinical and obstetric variables, high body mass index (BMI), nulliparity (AOR: 2.04; 95%CI 1.92–2.16), absence of antenatal care (AOR: 1.41; 95%CI 1.26–1.57), chronic hypertension (AOR: 7.75; 95%CI 6.77–8.87), gestational diabetes (AOR: 2.00; 95%CI 1.63–2.45), cardiac or renal disease (AOR: 2.38; 95%CI 1.86–3.05), pyelonephritis or urinary tract infection (AOR: 1.13; 95%CI 1.03–1.24) and severe anemia (AOR: 2.98; 95%CI 2.47–3.61) were found to be significant risk factors, while having >8 visits of antenatal care was protective (AOR: 0.90; 95%CI 0.83–0.98). Pre-eclampsia/eclampsia was found to be a significant risk factor for maternal death, perinatal death, preterm birth and low birthweight. Conclusion Chronic hypertension, obesity and severe anemia were the highest risk factors of preeclampsia

  14. Women Born Preterm or with Inappropriate Weight for Gestational Age Are at Risk of Subsequent Gestational Diabetes and Pre-Eclampsia

    PubMed Central

    á Rogvi, Rasmus; Forman, Julie Lyng; Damm, Peter; Greisen, Gorm

    2012-01-01

    Introduction Low birthweight, which can be caused by inappropriate intrauterine growth or prematurity, is associated with development of gestational diabetes mellitus (GDM) as well as pre-eclampsia later in life, but the relative effects of prematurity and inappropriate intrauterine growth remain uncertain. Methods Through nation-wide registries we identified all Danish mothers in the years 1989–2007. Two separate cohorts consisting mothers born 1974–1977 (n = 84219) and 1978–1981 (n = 32376) were studied, due to different methods of registering birthweight and gestational age in the two periods. Data was linked with information on GDM, pre-eclampsia and education. Results In a multivariate logistic regression model the odds of developing GDM was increased by 5–7% for each week the mother was born before term (p = 0.018 for 1974–1977, p = 0.048 for 1978–1981), while the odds were increased by 13–17% for each standard deviation (SD) reduction in birthweight for gestational age for those who were small or normal for gestational age (p<0.0001 and p = 0.035) and increased by 118–122% for each SD increase above the normal range (p<0.0001 and p = 0.024). The odds of pre-eclampsia was increased by 3–5% for each week the mother was born before term (p = 0.064 and p = 0.04), while the odds were increased 11–12% for each SD reduction in birthweight for gestational age (p<0.0001 and p = 0.0002). Conclusion In this cohort of young Danish mothers, being born premature or with increasingly low birthweight for gestational age was associated with an increased risk of GDM and pre-eclampsia in adulthood, while increasingly high birthweight for gestational age was associated with an increased risk of GDM and a decreased risk of pre-eclampsia. Inappropriate weight for gestational age was a more important risk factor than prematurity. PMID:22479500

  15. [Early onset scoliosis. What are the options?].

    PubMed

    Farrington, D M; Tatay-Díaz, A

    2013-01-01

    The prognosis of children with progressive early onset scoliosis has improved considerably due to recent advances in surgical and non-surgical techniques and the understanding of the importance of preserving the thoracic space. Improvements in existing techniques and development of new methods have considerably improved the management of this condition. Derotational casting can be considered in children with documented progression of a <60° curve without previous surgical treatment. Both single and dual growing rods are effective, but the latter seem to offer better results. Hybrid constructs may be a better option in children who require a low-profile proximal anchor. The vertical expandable prosthetic titanium rib (VEPTR(®)) appears to be beneficial for patients with congenital scoliosis and fused ribs, and thoracic Insufficiency Syndrome. Children with medical comorbidities who may not tolerate repeated lengthenings should be considered for Shilla or Luque Trolley technique. Growth modulation using shape memory alloy staples or other tethers seem promising for mild curves, although more research is required to define their precise indications. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

  16. Specific Intellectual Deficits in Children with Early Onset Diabetes Mellitus.

    ERIC Educational Resources Information Center

    Rovet, Joanne F.; And Others

    1988-01-01

    Compares 27 children with early onset diabetes (EOD) with 24 children with late onset diabetes (LOD) and 30 sibling controls in performance on tests of intellectual functioning and school achievement. Results revealed that duration of illness, age of onset, and hypoglycemic convulsions significantly predicted spatial ability. (Author/RWB)

  17. Maternal serum soluble fms-like tyrosine kinase-1 at 12, 22, 32 and 36 weeks' gestation in screening for pre-eclampsia.

    PubMed

    Tsiakkas, A; Mendez, O; Wright, A; Wright, D; Nicolaides, K H

    2016-04-01

    To examine the distribution of maternal serum soluble fms-like tyrosine kinase-1 (sFlt-1) at 12, 22, 32 and 36 weeks' gestation in singleton pregnancies that develop pre-eclampsia (PE) and examine the performance of this biomarker in screening for PE. Serum sFlt-1 was measured in 7066 cases at 11-13 weeks, 8079 cases at 19-24 weeks, 8472 at 30-34 weeks and 4043 at 35-37 weeks. Bayes' theorem was used to combine the a-priori risk from maternal characteristics and medical history with serum levels of sFlt-1. The performance of screening for PE in women requiring delivery < 32, between 32 + 0 and 36 + 6 and ≥ 37 weeks' gestation was estimated. In pregnancies that developed PE, serum sFlt-1 was increased and the separation in multiples of the median (MoM) values from normal was greater with earlier, compared to later, gestational age at which delivery for PE became necessary. In pregnancies that developed PE, the slope of the regression lines of sFlt-1 MoM with gestational age at delivery increased with advancing gestational age at screening. Measurement of sFlt-1 at 11-13 weeks did not improve the prediction of PE achieved by maternal factors alone, sFlt-1 at 19-24 weeks improved the prediction of PE delivering < 37 weeks but not for PE delivering ≥ 37 weeks, sFlt-1 at 30-34 weeks improved the prediction of PE delivering < 37 and PE delivering ≥ 37 weeks and sFlt-1 at 35-37 weeks improved the prediction of PE delivering ≥ 37 weeks. The detection rates (DRs), at a false-positive rate (FPR) of 10%, of PE delivering < 32 weeks were 52% and 65% with screening at 12 and 22 weeks, respectively. The DRs for PE delivering between 32 + 0 and 36 + 6 weeks were 44%, 44% and 93% with screening at 12, 22 and 32 weeks. The DR for PE delivering ≥ 37 weeks were 37%, 37%, 52% and 69% with screening at 12, 22, 32 and 36 weeks, respectively. The performance of combined screening with maternal factors, medical history and serum sFlt-1 is superior for detection of early

  18. Maternal serum alpha-fetoprotein at 12, 22 and 32 weeks' gestation in screening for pre-eclampsia.

    PubMed

    Bredaki, F E; Matalliotakis, M; Wright, A; Wright, D; Nicolaides, K H

    2016-04-01

    To examine the distribution of maternal serum alpha-fetoprotein (AFP) at 12, 22 and 32 weeks' gestation in singleton pregnancies which develop pre-eclampsia (PE) and examine the performance of this biomarker in screening for PE. Serum AFP was measured in 17 071 cases at 11-13 weeks, in 8583 cases at 19-24 weeks and 8609 cases at 30-34 weeks' gestation. Bayes' theorem was used to combine the a-priori risk from maternal characteristics and medical history with AFP. The performance of screening for PE requiring delivery < 32, at 32 + 0 to 36 + 6, < 37 and ≥ 37 weeks' gestation was estimated. In pregnancies that developed PE, serum AFP multiples of the median (MoM) was increased at 11-13 and 19-24 weeks' gestation, but not at 30-34 weeks, and the values were inversely related to gestational age at delivery. Combined screening with maternal factors and serum AFP improved the prediction provided by maternal factors alone for PE delivering < 37 weeks, but not for PE delivering ≥ 37 weeks. The performance of screening for preterm PE was better at 19-24 weeks than at 11-13 weeks and the detection rate (DR) for a given false-positive rate (FPR) was higher for PE delivering < 32 weeks than for PE delivering at 32 + 0 to 36 + 6 weeks. The DRs, at 10% FPR, of combined screening at 11-13 weeks for PE delivering < 32 and at 32 + 0 to 36 + 6 weeks were 54% and 45%, respectively, and these improved to 72% and 53% with screening at 19-24 weeks. Measurement of serum AFP at 11-13 and 19-24 weeks' gestation improves the prediction of preterm PE provided by maternal factors alone. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  19. With adaptation, the WHO guidelines on calcium supplementation for prevention of pre-eclampsia are adopted by pregnant women.

    PubMed

    Omotayo, Moshood O; Martin, Stephanie L; Stoltzfus, Rebecca J; Ortolano, Stephanie E; Mwanga, Erick; Dickin, Katherine L

    2018-04-01

    The World Health Organization (WHO) recommends calcium supplementation for prevention of pre-eclampsia, but factors affecting adoption and acceptability of the recommendations among pregnant women have not been examined. We explored adoption of the WHO guidelines in Kenya, using the trials of improved practices. We recruited 38 pregnant women and assigned participants to three regimens representing potential trade-offs among daily dose, bioavailability, and acceptability. Participants were provided with supplements, requested to select preferred product type, counselled on how to take them, and interviewed 4 times over 6 weeks to assess their experiences. We tracked bottle opening with electronic monitors, as proxy for supplement consumption. We analysed interview transcripts thematically. All participants were willing to try the supplements. Average daily consumption ranged from 77 to 1,577 mg/d. Most participants (74%) chose the chewable product. Participants preferred its "sweet taste" and liked the ability to consume it without water. Women in the 2-dose regimen were least likely to switch; however, women assigned to the 3-dose regimen, or who switched to the 3-dose regimen, consumed the most calcium per day. Difficulties with the 4-dose regimen included afternoon doses when women were likely to forget and having to wait hours after supper for last dose. Use of an illustrated calendar, keeping supplements in conspicuous locations and requesting support from relatives were strategies that supported adherence. Pregnant women are likely to adopt Ca supplementation, with appropriate programmatic adaptations. Careful attention to product attributes, regimen complexity, and strategies for reassuring and reminding women are needed to adapt the WHO guidelines. © 2017 John Wiley & Sons Ltd.

  20. Fetal sex-specific differences in gestational age at delivery in pre-eclampsia: a meta-analysis

    PubMed Central

    Schalekamp-Timmermans, Sarah; Arends, Lidia R; Alsaker, Elin; Chappell, Lucy; Hansson, Stefan; Harsem, Nina K; Jälmby, Maya; Jeyabalan, Arundhathi; Laivuori, Hannele; Lawlor, Debbie A; Macdonald-Wallis, Corrie; Magnus, Per; Myers, Jenny; Olsen, Jørn; Poston, Lucilla; Redman, Christopher W; Staff, Anne C; Villa, Pia; Roberts, James M; Steegers, Eric A

    2017-01-01

    Abstract Background: Pre-eclampsia (PE) is a major pregnancy disorder complicating up to 8% of pregnancies. Increasing evidence indicates a sex-specific interplay between the mother, placenta and fetus. This may lead to different adaptive mechanisms during pregnancy. Methods: We performed an individual participant data meta-analysis to determine associations of fetal sex and PE, with specific focus on gestational age at delivery in PE. This was done on 219 575 independent live-born singleton pregnancies, with a gestational age at birth between 22.0 and 43.0 weeks of gestation, from 11 studies participating in a worldwide consortium of international research groups focusing on pregnancy. Results: Of the women, 9033 (4.1%) experienced PE in their pregnancy and 48.8% of the fetuses were female versus 51.2% male. No differences in the female/male distribution were observed with respect to term PE (delivered ≥ 37 weeks). Preterm PE (delivered < 37 weeks) was slightly more prevalent among pregnancies with a female fetus than in pregnancies with a male fetus [odds ratio (OR) 1.11, 95% confidence interval (CI) 1.02–1.21]. Very preterm PE (delivered < 34 weeks) was even more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus (OR 1.36, 95% CI 1.17–1.59). Conclusions: Sexual dimorphic differences in the occurrence of PE exist, with preterm PE being more prevalent among pregnancies with a female fetus as compared with pregnancies with a male fetus and with no differences with respect to term PE. PMID:27605586

  1. Evidence for a genetic etiology of early-onset delinquency.

    PubMed

    Taylor, J; Iacono, W G; McGue, M

    2000-11-01

    Age at onset of antisocial behavior discriminates persistent and transitory offenders. The authors proposed that early-onset delinquency has an underlying genetic influence that manifests in problems related to inhibition, whereas late-onset delinquency is more environmentally mediated. To test these notions, they selected 36 early starters, 86 late starters, and 25 nondelinquent controls from a large sample of 11-year-old twins and compared them on several measures related to inhibition and a peer group measure. As expected, early starters had more psychological, behavioral, and emotional problems related to inhibition than late starters and controls. A longitudinal analysis indicated an increase an antisocial behavior among peers of late starters shortly before their delinquency onset. Family history data and a twin analysis provided evidence of greater genetic influence on early-onset than late-onset delinquency.

  2. Nearwork in early-onset myopia.

    PubMed

    Saw, Seang-Mei; Chua, Wei-Han; Hong, Ching-Ye; Wu, Hui-Min; Chan, Wai-Ying; Chia, Kee-Seng; Stone, Richard A; Tan, Donald

    2002-02-01

    To determine the relationship of nearwork and myopia in young elementary school-age children in Singapore. A cross-sectional study of 1005 school children aged 7 to 9 years was conducted in two schools in Singapore. Cycloplegic autorefraction, keratometry, and biometry measurements were performed. In addition, the parents completed a detailed questionnaire on nearwork activity (books read per week, reading in hours per day and diopter hours [addition of three times reading, two times computer use, and two times video games use in hours per day]). Other risk factors, such as parental myopia, socioeconomic status, and light exposure history, were assessed. In addition to socioeconomic factors, several nearwork indices were associated with myopia in these young children. The multivariate adjusted odds ratio of higher myopia (at least -3.0 D) for children who read more than two books per week was 3.05 (95% confidence interval [CI], 1.80-5.18). However, the odds ratios of higher myopia for children who read more than 2 hours per day or with more than 8 diopter hours (1.50; 95% CI, 0.87-2.55 and 1.04; 95% CI, 0.61-1.78, respectively) were not significant, after controlling for several factors. Children aged 7 to 9 years with a greater current reading exposure were more likely to be myopic. This association of reading and myopia in a young age cohort was greater than the strength of the reading association generally found in older myopic subjects. Whether these results identify an association of early-onset myopia with nearwork activity or other potentially confounding factors is discussed.

  3. Genetics Home Reference: early-onset primary dystonia

    MedlinePlus

    ... such as seizures or a loss of intellectual function (dementia). Early-onset primary dystonia does not affect a person's intelligence. On ... of torsinA. The altered protein's effect on the function of nerve cells in the brain ... with early-onset primary dystonia do not have a loss of nerve ...

  4. [Assessment of prophylaxis and treatment of blood loss in patients with pre-eclampsia].

    PubMed

    Timokhova, S Iu; Golubtsov, V V; Zabolotskikh, I B

    2014-01-01

    To improve treatment results of women with massive obstetrical blood loss. Subjects and methods: 96 female patients with average and heavy degree preeclampsia worsened massive blood developing were involved into the investigation. The women were divided into two groups: main (n=55) (basic) - it's patients were treated with complex of offered wiays control (n=41) - it's patients were evaluated retrospectively. During the investigation the parameters of hemostasis system and periphery blood values were performed as dynamic evaluations, acidity-basic state and water-electrolyte balance parameters, medical history were monitored. As a result of the investigation it was found out that these offered actions complex application about reducing massive obstetric blood accelerates restoration of clinic, bio-chemical paramnleters during the early post-operating period The application of the offered methods has reduced both inltraoperative blood loss in women with preeclamsia and use of blood components and the time spent on the hemostasis system correction for all the women of the base group.

  5. Adverse Housing Conditions and Early-Onset Delinquency.

    PubMed

    Jackson, Dylan B; Newsome, Jamie; Lynch, Kellie R

    2017-09-01

    Housing constitutes an important health resource for children. Research has revealed that, when housing conditions are unfavorable, they can interfere with child health, academic performance, and cognition. Little to no research, however, has considered whether adverse housing conditions and early-onset delinquency are significantly associated with one another. This study explores the associations between structural and non-structural housing conditions and delinquent involvement during childhood. Data from the Fragile Families and Child Wellbeing Study (FFCWS) were employed in this study. Each adverse housing condition was significantly associated with early-onset delinquency. Even so, disarray and deterioration were only significantly linked to early delinquent involvement in the presence of health/safety hazards. The predicted probability of early-onset delinquency among children exposed to housing risks in the presence of health/safety hazards was nearly three times as large as the predicted probability of early-onset delinquency among children exposed only to disarray and/or deterioration, and nearly four times as large as the predicted probability of early-onset delinquency among children exposed to none of the adverse housing conditions. The findings suggest that minimizing housing-related health/safety hazards among at-risk subsets of the population may help to alleviate other important public health concerns-particularly early-onset delinquency. Addressing household health/safety hazards may represent a fruitful avenue for public health programs aimed at the prevention of early-onset delinquency. © Society for Community Research and Action 2017.

  6. Health System Barriers to Access and Use of Magnesium Sulfate for Women with Severe Pre-Eclampsia and Eclampsia in Pakistan: Evidence for Policy and Practice

    PubMed Central

    Bigdeli, Maryam; Zafar, Shamsa; Assad, Hafeez; Ghaffar, Adbul

    2013-01-01

    Severe pre-eclampsia and eclampsia are rare but serious complications of pregnancy that threaten the lives of mothers during childbirth. Evidence supports the use of magnesium sulfate (MgSO4) as the first line treatment option for severe pre-eclampsia and eclampsia. Eclampsia is the third major cause of maternal mortality in Pakistan. As in many other Low- and Middle-Income Countries (LMIC), it is suspected that MgSO4 is critically under-utilized in the country. There is however a lack of information on context-specific health system barriers that prevent optimal use of this life-saving medicine in Pakistan. Combining quantitative and qualitative methods, namely policy document review, key informant interviews, focus group discussions and direct observation at health facility, we explored context-specific health system barriers and enablers that affect access and use of MgSO4 for severe pre-eclampsia and eclampsia in Pakistan. Our study finds that while international recommendations on MgSO4 have been adequately translated in national policies in Pakistan, the gap remains in implementation of national policies into practice. Barriers to access to and effective use of MgSO4 occur at health facility level where the medicine was not available and health staff was reluctant to use it. Low price of the medicine and the small market related to its narrow indications acted as disincentives for effective marketing. Results of our survey were further discussed in a multi-stakeholder round-table meeting and an action plan for increasing access to this life-saving medicine was identified. PMID:23555626

  7. The feasibility of community level interventions for pre-eclampsia in South Asia and Sub-Saharan Africa: a mixed-methods design.

    PubMed

    Khowaja, Asif Raza; Qureshi, Rahat Najam; Sawchuck, Diane; Oladapo, Olufemi T; Adetoro, Olalekan O; Orenuga, Elizabeth A; Bellad, Mrutyunjaya; Mallapur, Ashalata; Charantimath, Umesh; Sevene, Esperança; Munguambe, Khátia; Boene, Helena Edith; Vidler, Marianne; Bhutta, Zulfiqar A; von Dadelszen, Peter

    2016-06-08

    Globally, pre-eclampsia and eclampsia are major contributors to maternal and perinatal mortality; of which the vast majority of deaths occur in less developed countries. In addition, a disproportionate number of morbidities and mortalities occur due to delayed access to health services. The Community Level Interventions for Pre-eclampsia (CLIP) Trial aims to task-shift to community health workers the identification and emergency management of pre-eclampsia and eclampsia to improve access and timely care. Literature revealed paucity of published feasibility assessments prior to initiating large-scale community-based interventions. Arguably, well-conducted feasibility studies can provide valuable information about the potential success of clinical trials prior to implementation. Failure to fully understand the study context risks the effective implementation of the intervention and limits the likelihood of post-trial scale-up. Therefore, it was imperative to conduct community-level feasibility assessments for a trial of this magnitude. A mixed methods design guided by normalization process theory was used for this study in Nigeria, Mozambique, Pakistan, and India to explore enabling and impeding factors for the CLIP Trial implementation. Qualitative data were collected through participant observation, document review, focus group discussion and in-depth interviews with diverse groups of community members, key informants at community level, healthcare providers, and policy makers. Quantitative data were collected through health facility assessments, self-administered community health worker surveys, and household demographic and health surveillance. Refer to CLIP Trial feasibility publications in the current and/or forthcoming supplement. Feasibility assessments for community level interventions, particularly those involving task-shifting across diverse regions, require an appropriate theoretical framework and careful selection of research methods. The use of

  8. The effect of pre-eclampsia-like syndrome induced by L-NAME on learning and memory and hippocampal glucocorticoid receptor expression: A rat model.

    PubMed

    Zhu, Hao; Zhu, Weimin; Hu, Rong; Wang, Huijun; Ma, Duan; Li, Xiaotian

    2017-02-01

    We aimed to study the impacts of pre-eclampsia on the cognitive and learning capabilities of adolescent rat offspring and to explore the possible underlying mechanisms at the molecular level. Pregnant rats were subcutaneously injected with saline solution (control) (n = 16) or NG-nitro-L-arginine methyl ester (L-NAME) (n = 16) from the 13th day of gestation until parturition. The brain tissues from fetal rats delivered by cesarean section were examined in both groups with hematoxylin and eosin (H&E) staining. Rats born vaginally in both groups were subjected to the Morris water maze test when 8-week-old and their hippocampi were analyzed for glucocorticoid receptor (GR) expression. A pre-eclampsia-like model was successfully built in pregnant rats by infusion of the NO synthase inhibitor L-NAME, including phenotypes as maternal hypertension and proteinuria, high stillbirth rate, and fetal growth retardation. Neuroepithelial cell proliferation was found in the hippocampus of fetal rats in the L-NAME group. Grown to 8-week-old, the L-NAME group showed significantly longer escape latency than the control group in the beginning as well as in the end of navigation trials. At the same time, the swimming distance achieved by the L-NAME group was significantly longer than that of the control group. Such differences in cognitive and learning capabilities between the two groups were not gender dependent. Besides, the 8-week-old rats in the L-NAME group had increased GR expression in the hippocampus than the control group. Pre-eclampsia would impair cognitive and learning capabilities in adolescent offspring, and the upregulated expression of hippocampal GR may be involved in the underlying mechanisms.

  9. Co-Occurring Problems of Early Onset Persistent, Childhood Limited, and Adolescent Onset Conduct Problem Youth

    ERIC Educational Resources Information Center

    Barker, Edward D.; Oliver, Bonamy R.; Maughan, Barbara

    2010-01-01

    Background: It is increasingly recognized that youth who follow early onset persistent (EOP), childhood limited (CL) and adolescent onset (AO) trajectories of conduct problems show somewhat varying patterns of risk (in childhood) and adjustment problems (in adolescence and adulthood). Little, however, is known about how other adjustment problems…

  10. Candidate-gene association study of mothers with pre-eclampsia, and their infants, analyzing 775 SNPs in 190 genes.

    PubMed

    Goddard, Katrina A B; Tromp, Gerard; Romero, Roberto; Olson, Jane M; Lu, Qing; Xu, Zhiying; Parimi, Neeta; Nien, Jyh Kae; Gomez, Ricardo; Behnke, Ernesto; Solari, Margarita; Espinoza, Jimmy; Santolaya, Joaquin; Chaiworapongsa, Tinnakorn; Lenk, Guy M; Volkenant, Kimberly; Anant, Madan Kumar; Salisbury, Benjamin A; Carr, Janet; Lee, Min Soeb; Vovis, Gerald F; Kuivaniemi, Helena

    2007-01-01

    Pre-eclampsia (PE) affects 5-7% of pregnancies in the US, and is a leading cause of maternal death and perinatal morbidity and mortality worldwide. To identify genes with a role in PE, we conducted a large-scale association study evaluating 775 SNPs in 190 candidate genes selected for a potential role in obstetrical complications. SNP discovery was performed by DNA sequencing, and genotyping was carried out in a high-throughput facility using the MassARRAY(TM) System. Women with PE (n = 394) and their offspring (n = 324) were compared with control women (n = 602) and their offspring (n = 631) from the same hospital-based population. Haplotypes were estimated for each gene using the EM algorithm, and empirical p values were obtained for a logistic regression-based score test, adjusted for significant covariates. An interaction model between maternal and offspring genotypes was also evaluated. The most significant findings for association with PE were COL1A1 (p = 0.0011) and IL1A (p = 0.0014) for the maternal genotype, and PLAUR (p = 0.0008) for the offspring genotype. Common candidate genes for PE, including MTHFR and NOS3, were not significantly associated with PE. For the interaction model, SNPs within IGF1 (p = 0.0035) and IL4R (p = 0.0036) gave the most significant results. This study is one of the most comprehensive genetic association studies of PE to date, including an evaluation of offspring genotypes that have rarely been considered in previous studies. Although we did not identify statistically significant evidence of association for any of the candidate loci evaluated here after adjusting for multiple testing using the false discovery rate, additional compelling evidence exists, including multiple SNPs with nominally significant p values in COL1A1 and the IL1A region, and previous reports of association for IL1A, to support continued interest in these genes as candidates for PE. Identification of the genetic regulators of PE may have broader implications

  11. Overlap of proteomics biomarkers between women with pre-eclampsia and PCOS: a systematic review and biomarker database integration

    PubMed Central

    Khan, Gulafshana Hafeez; Galazis, Nicolas; Docheva, Nikolina; Layfield, Robert; Atiomo, William

    2015-01-01

    STUDY QUESTION Do any proteomic biomarkers previously identified for pre-eclampsia (PE) overlap with those identified in women with polycystic ovary syndrome (PCOS). SUMMARY ANSWER Five previously identified proteomic biomarkers were found to be common in women with PE and PCOS when compared with controls. WHAT IS KNOWN ALREADY Various studies have indicated an association between PCOS and PE; however, the pathophysiological mechanisms supporting this association are not known. STUDY DESIGN, SIZE, DURATION A systematic review and update of our PCOS proteomic biomarker database was performed, along with a parallel review of PE biomarkers. The study included papers from 1980 to December 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS In all the studies analysed, there were a total of 1423 patients and controls. The number of proteomic biomarkers that were catalogued for PE was 192. MAIN RESULTS AND THE ROLE OF CHANCE Five proteomic biomarkers were shown to be differentially expressed in women with PE and PCOS when compared with controls: transferrin, fibrinogen α, β and γ chain variants, kininogen-1, annexin 2 and peroxiredoxin 2. In PE, the biomarkers were identified in serum, plasma and placenta and in PCOS, the biomarkers were identified in serum, follicular fluid, and ovarian and omental biopsies. LIMITATIONS, REASONS FOR CAUTION The techniques employed to detect proteomics have limited ability in identifying proteins that are of low abundance, some of which may have a diagnostic potential. The sample sizes and number of biomarkers identified from these studies do not exclude the risk of false positives, a limitation of all biomarker studies. The biomarkers common to PE and PCOS were identified from proteomic analyses of different tissues. WIDER IMPLICATIONS OF THE FINDINGS This data amalgamation of the proteomic studies in PE and in PCOS, for the first time, discovered a panel of five biomarkers for PE which are common to women with PCOS, including transferrin

  12. Characterisation of syncytiotrophoblast vesicles in normal pregnancy and pre-eclampsia: expression of Flt-1 and endoglin.

    PubMed

    Tannetta, Dionne S; Dragovic, Rebecca A; Gardiner, Chris; Redman, Christopher W; Sargent, Ian L

    2013-01-01

    The placental syncytiotrophoblast releases micro and nanovesicles (STBM), into the maternal circulation in normal pregnancy and in increased amounts in pre-eclampsia (PE), which have proinflammatory and antiangiogenic activity and are implicated in PE pathophysiology. Better characterisation of STBM is essential to understand their role in PE. STBM prepared by placental lobe dual perfusion (pSTBM) and mechanical disruption (mSTBM) were analysed by four colour flow cytometry (4CFC), nanoparticle tracking analysis (NTA) and Western blotting to determine vesicle size, purity and Flt-1 and endoglin (Eng) expression. Biological activity of STBM associated Flt-1 and endoglin was assessed by the ability of VEGF, PlGF and TGFβ to bind to mSTBM and inhibit mSTBM induced endothelial monolayer disruption. STBM content was consistently high (~87-95%) across the different preparations. However, surface antigen intensities differed, with significantly lower placental alkaline phosphatase (P<0.05) and Eng (P<0.05) expression on mSTBM, and Flt-1 (P<0.05) expression on pSTBM. For PE placenta derived preparations, pSTBM contained lower Eng positive STBM (P<0.05) and mSTBM Eng expression was increased (P<0.05). Western blotting revealed increased Flt-1/sFlt-1 (P<0.02) and decreased placental alkaline phosphatase (P = 0.0002) content of PE placenta pSTBM. Using NTA, perfused PE placentas released significantly larger MV (P<0.001). Finally, VEGF, PlGF and TGFβ bound to mSTBM at physiologically relevant concentrations and inhibited mSTBM induced endothelial disruption (P<0.05-P<0.001). This study has found differences in physical and antigenic characteristics of normal and PE placenta STBM preparations produced by placental perfusion or mechanical disruption. We have also demonstrated that large quantities of biologically active STBM associated endoglin and Flt-1/sFlt-1 could contribute to the increased circulating levels measured in PE patients and add to the perturbation of the

  13. A randomised controlled trial of consumption of dark chocolate in pregnancy to reduce pre-eclampsia: Difficulties in recruitment, allocation and adherence.

    PubMed

    Gnanendran, Subashini; Porrett, Jemma; Woods, Cindy; Buttrose, Maryke; Jukka, Clare; Hollins, Jane; Robson, Stephen; de Costa, Caroline

    2018-06-01

    In 2013-2014 we undertook a randomised controlled trial (RCT) to determine whether the daily ingestion of dark chocolate during pregnancy could reduce the incidence of pre-eclampsia in primigravidae. However, after two years we had not succeeded in recruiting more than 3.5% of the number of participants required to answer the research question, and the trial was halted. We also reviewed the literature on this topic and found it to be limited. We report here our findings and discuss the difficulties facing researchers in this area. © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  14. Operational Thought in Alzheimer's Disease Early Onset and SDAT.

    ERIC Educational Resources Information Center

    Emery, Olga B.; Breslau, Lawrence D.

    For more than a decade it has been convention to assume that senile dementia Alzheimer's type (SDAT) and Alzheimer's disease early onset represent a unitary disease process with only an onset difference. This assumption has been neither confirmed nor disconfirmed. To address this issue, a study was conducted which analyzed the dissolution of…

  15. Lost human capital from early-onset chronic depression.

    PubMed

    Berndt, E R; Koran, L M; Finkelstein, S N; Gelenberg, A J; Kornstein, S G; Miller, I M; Thase, M E; Trapp, G A; Keller, M B

    2000-06-01

    Chronic depression starts at an early age for many individuals and could affect their accumulation of "human capital" (i.e., education, higher amounts of which can broaden occupational choice and increase earnings potential). The authors examined the impact, by gender, of early- (before age 22) versus late-onset major depressive disorder on educational attainment. They also determined whether the efficacy and sustainability of antidepressant treatments and psychosocial outcomes vary by age at onset and quantified the impact of early- versus late-onset, as well as never-occurring, major depressive disorder on expected lifetime earnings. The authors used logistic and multivariate regression methods to analyze data from a three-phase, multicenter, double-blind, randomized trial that compared sertraline and imipramine treatment of 531 patients with chronic depression aged 30 years and older. These data were integrated with U.S. Census Bureau data on 1995 earnings by age, educational attainment, and gender. Early-onset major depressive disorder adversely affected the educational attainment of women but not of men. No significant difference in treatment responsiveness by age at onset was observed after 12 weeks of acute treatment or, for subjects rated as having responded, after 76 weeks of maintenance treatment. A randomly selected 21-year-old woman with early-onset major depressive disorder in 1995 could expect future annual earnings that were 12%-18% lower than those of a randomly selected 21-year-old woman whose onset of major depressive disorder occurred after age 21 or not at all. Early-onset major depressive disorder causes substantial human capital loss, particularly for women. Detection and effective treatment of early-onset major depressive disorder may have substantial economic benefits.

  16. Genetics of Severe Early Onset Epilepsies

    ClinicalTrials.gov

    2017-08-24

    Epilepsy; Epileptic Encephalopathy; Ohtahara Syndrome; Infantile Spasms; Dravet Syndrome; Malignant Migrating Partial Epilepsy of Infancy; Early Myoclonic Epileptic Encephalopathy; PCDH19-related Epilepsy and Related Conditions

  17. Early Onset Malignancies - Genomic Study of Cancer Disparities

    Cancer.gov

    The Early Onset Malignancies Initiative studies the genomic basis of six cancers that develop at an earlier age, occur in higher rates, and are typically more aggressive in certain minority populations.

  18. Whole Exome Analysis of Early Onset Alzheimer’s Disease

    DTIC Science & Technology

    2015-04-01

    autosomal recessive early-onset Parkinson’s disease and juvenile Parkinson disease , Parkin has been shown to promote intracellular Abeta1–42 clearance [15... Parkinsonism . Conclusions Mutations were found in 6/50 families. The presence of an APOE-4 allele may account for disease status in one affected non...AD_________________ Award Number: W81XWH-12-1-0013 TITLE: Whole Exome Analysis of Early Onset Alzheimer’s Disease PRINCIPAL INVESTIGATOR

  19. Blood-Based Biomarkers of Early-Onset Breast Cancer

    DTIC Science & Technology

    2015-10-01

    n=51). The women with early-onset breast cancer were disease and treatment free for at least 6 months at time of blood donation . Cases and controls...were age matched to age at blood donation . 2. KEYWORDS: biomarkers, early-onset breast cancer, expression profiling, risk-assessment, breast cancer...matched controls. This prospectively collected cohort consists of blood donated to blood banks ~15 years ago and subsequently linked to the California

  20. Obstetrical outcomes in patients with early onset gestational diabetes.

    PubMed

    Gupta, Simi; Dolin, Cara; Jadhav, Ashwin; Chervenak, Judith; Timor-Tritsch, Ilan; Monteagudo, Ana

    2016-01-01

    The objective of this study was to characterize patients with early onset gestational diabetes and compare outcomes to patients diagnosed with standard gestational diabetes and pregestational diabetes. This is a retrospective cohort study of patients diagnosed with gestational or pregestational diabetes. All patients received a glucose challenge test at their first prenatal visit to diagnose early onset gestational diabetes and were recommended to have postpartum glucose tolerance tests to detect undiagnosed type 2 diabetes. Outcomes were compared between patients with early onset gestational diabetes and both standard gestational diabetes and pregestational diabetes with p < 0.05 was used for significance. Four hundred and twenty-four patients met the inclusion criteria. Nine percent of the patients with early onset gestational diabetes were found to have undiagnosed type 2 diabetes based on postpartum testing and 91% to have resolution in the postpartum period. No patient with early onset gestational diabetes and resolution in the postpartum period had abnormal screening for renal or ophthalmologic disease, but 5% had abnormal fetal echocardiograms. These patients were more likely to require pharmacotherapy for glycemic control than patients with standard gestational diabetes and less likely than patients with pregestational diabetes (55% versus 39% versus 81%). Most patients diagnosed with early onset gestational diabetes do not have undiagnosed type 2 diabetes but do have unique characteristics and obstetrical outcomes.

  1. Decreased expression of Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2 may be involved in the development of pre-eclampsia.

    PubMed

    Li, Juan; Luo, Xin; Xiao, Xiaoqiu; Zhang, Xuemei; Qi, Hongbo; Liu, Xiru; Zhang, Hua; Gao, Li; Yang, Zhongmei

    2014-01-01

    Wiskott–Aldrich syndrome protein family verprolin-homologous protein 2 (WAVE2) is a protein that mediates actin cytoskeletal reorganization and lamellipodia protrusion formation, which are required for cell migration and invasion. The primary purpose of this study was to determine whether there is an association between reactive oxygen species (ROS) and WAVE2 in pre-eclampsia, and whether WAVE2 expression in trophoblast cells is vulnerable to oxidative stress. This study observed excessive generation of ROS and decreased expression of WAVE2 in pre-eclamptic placentas compared with normotensive controls. Moreover, there was a significant negative correlation between ROS and WAVE2 protein in pre-eclamptic placenta (P < 0.001). An in-vitro model of hypoxia–reoxygenation (H/R) was used to imitate oxidative stress in placental trophoblasts, and it was found that the expression of WAVE2 protein in trophoblasts was decreased after H/R treatment. Additionally, compared with normoxia, decreased cell proliferation, higher cell apoptosis and attenuated cell migration and invasion were detected in trophoblasts exposed to H/R. In conclusion, the findings strongly suggest that excessive oxidative stress can decrease WAVE2 expression in trophoblasts and that the decreased expression of WAVE2 in trophoblast cells may be involved in the development of pre-eclampsia. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  2. Disease evolution in late-onset and early-onset systemic lupus erythematosus.

    PubMed

    Aljohani, R; Gladman, D D; Su, J; Urowitz, M B

    2017-10-01

    Objective The objective of this study was to compare clinical features, disease activity, and outcome in late-onset versus early-onset systemic lupus erythematosus (SLE) over 5 years of follow up Method Patients with SLE since 1970 were followed prospectively according to standard protocol and tracked on a computerized database. Patients entering the cohort within one year of diagnosis constitute the inception cohort. Patients with late-onset (age at diagnosis ≥50) disease were identified and matched 1:2 based on gender and first clinic visit (±5) years with patients with early-onset disease (age at diagnosis 18-40 years). Results A total of 86 patients with late-onset disease (84.9% female, 81.4% Caucasian, mean age at SLE diagnosis ± SD 58.05 ± 7.30) and 169 patients with early-onset disease (86.4% female, 71% Caucasian, mean age at SLE diagnosis ± SD 27.80 ± 5.90) were identified. At enrollment, late-onset SLE patients had a lower total number of American College of Rheumatology (ACR) criteria, with less renal and neurologic manifestations. Mean SLE Disease Activity Index 2000 (SLEDAI-2K) scores were lower in late-onset SLE, especially renal features and anti-dsDNA positivity. Over 5 years, mean SLEDAI-2K scores decreased in both groups, while mean Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) scores increased more significantly in the late-onset group; they developed more cardiovascular, renal, and ocular damage, and had higher prevalence of cardiovascular risk factors. Conclusion Although the late-onset SLE group had a milder presentation and less active disease, with the evolution of disease, they developed more organ damage likely as a consequence of cardiovascular risk factors and aging.

  3. Genetic Risk Score Analysis in Early-Onset Bipolar Disorder

    PubMed Central

    Croarkin, Paul E.; Luby, Joan L.; Cercy, Kelly; Geske, Jennifer R.; Veldic, Marin; Simonson, Matthew; Joshi, Paramjit T.; Wagner, Karen Dineen; Walkup, John T.; Nassan, Malik M.; Cuellar-Barboza, Alfredo B.; Casuto, Leah; McElroy, Susan L.; Jensen, Peter S.; Frye, Mark A.; Biernacka, Joanna M.

    2018-01-01

    Objective In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder. Method Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003–2008. Mayo Clinic Bipolar Biobank samples were collected from 2009–2013. Genotyping and analyses for the present study took place from 2013–2014. The diagnosis of bipolar disorder was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with bipolar disorder, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly “odz, odd Oz/ten-m homolog 4 {Drosophila}, ODZ4”]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n=69), adult patients with bipolar disorder (n=732) including a subset with early-onset illness [n=192]), and healthy controls (n=776). GRS analyses were performed comparing early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. Results GRS analysis revealed associations of the risk score with early-onset bipolar disorder (P=.01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset bipolar disorder with a CACNA1C haplotype (global test, P=.01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset bipolar disorder (P=.017), which did not remain significant after correction for multiple comparisons. Conclusion These preliminary analyses suggest that previously identified bipolar disorder risk loci

  4. Genetic Risk Score Analysis in Early-Onset Bipolar Disorder.

    PubMed

    Croarkin, Paul E; Luby, Joan L; Cercy, Kelly; Geske, Jennifer R; Veldic, Marin; Simonson, Matthew; Joshi, Paramjit T; Wagner, Karen Dineen; Walkup, John T; Nassan, Malik M; Cuellar-Barboza, Alfredo B; Casuto, Leah; McElroy, Susan L; Jensen, Peter S; Frye, Mark A; Biernacka, Joanna M

    In this study, we performed a candidate genetic risk score (GRS) analysis of early-onset bipolar disorder (BD). Treatment of Early Age Mania (TEAM) study enrollment and sample collection took place from 2003 to 2008. Mayo Clinic Bipolar Biobank samples were collected from 2009 to 2013. Genotyping and analyses for the present study took place from 2013 to 2014. The diagnosis of BD was based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria. Eight single-nucleotide polymorphisms (SNPs), previously reported in genome-wide association studies to be associated with BD, were chosen for GRS analysis in early-onset bipolar disease. These SNPs map to 3 genes: CACNA1C (calcium channel, voltage-dependent, L type, alpha 1C subunit), ANK3 (ankyrin-3, node of Ranvier [ankyrin G]), and ODZ4 (teneurin transmembrane protein 4 [formerly "odz, odd Oz/10-m homolog 4 {Drosophila}, ODZ4"]). The 8 candidate SNPs were genotyped in patients from the TEAM study (n = 69); adult patients with BD (n = 732), including a subset with early-onset illness (n = 192); and healthy controls (n = 776). GRS analyses were performed to compare early-onset cases with controls. In addition, associations of early-onset BD with individual SNPs and haplotypes were explored. GRS analysis revealed associations of the risk score with early-onset BD (P = .01). Gene-level haplotype analysis comparing TEAM patients with controls suggested association of early-onset BD with a CACNA1C haplotype (global test, P = .01). At the level of individual SNPs, comparison of TEAM cases with healthy controls provided nominally significant evidence for association of SNP rs10848632 in CACNA1C with early-onset BD (P = .017), which did not remain significant after correction for multiple comparisons. These preliminary analyses suggest that previously identified BD risk loci, especially CACNA1C, have a role in early-onset BD, possibly with stronger effects than for late-onset BD.

  5. Hippocampal Morphology and Distinguishing Late-Onset From Early-Onset Elderly Depression

    PubMed Central

    Ballmaier, Martina; Narr, Katherine L.; Toga, Arthur W.; Elderkin-Thompson, Virginia; Thompson, Paul M.; Hamilton, Liberty; Haroon, Ebrahim; Pham, Daniel; Heinz, Andreas; Kumar, Anand

    2010-01-01

    Objective Despite evidence for hippocampal abnormalities in elderly depression, it is unknown whether these changes are regionally specific. This study used three-dimensional mapping techniques to identify regional hippocampal abnormalities in early- and late-onset depression. Neuropsychological correlates of hippocampal morphology were also investigated. Method With high-resolution magnetic resonance imaging, hippocampal morphology was compared among elderly patients with early- (N=24) and late-onset (N=22) depression and comparison subjects (N=34). Regional structural abnormalities were identified by comparing distances, measured from homologous hippocampal surface points to the central core of each individual’s hippocampal surface model, between groups. Results Hippocampal volumes differed between depressed patients and comparison subjects but not between patients with early- and late-onset depression. However, statistical mapping results showed that regional surface contractions were significantly pronounced in late-compared to early-onset depression in the anterior of the subiculum and lateral posterior of the CA1 subfield in the left hemisphere. Significant shape differences were observed bilaterally in anterior CA1–CA3 subfields and the subiculum in patients in relation to comparison subjects. These results were similar when each disease group was separately compared to comparison subjects. Hippocampal surface contractions significantly correlated with memory measures among late- but not early-onset depressed patients or comparison subjects. Conclusions More pronounced regional volume deficits and their associations with memory in late-onset depression may suggest that these patients are more likely to develop cognitive impairment over time than individuals with early-onset depression. Mapping regional hippocampal abnormalities and their cognitive correlates may help guide research in defining risk profiles and treatment strategies. PMID:17986679

  6. Chorioamnionitis and Culture-Confirmed, Early-Onset Neonatal Infections

    PubMed Central

    Hansen, Nellie I.; Schrag, Stephanie J.; Hale, Ellen; Van Meurs, Krisa; Sánchez, Pablo J.; Cantey, Joseph B.; Faix, Roger; Poindexter, Brenda; Goldberg, Ronald; Bizzarro, Matthew; Frantz, Ivan; Das, Abhik; Benitz, William E.; Shane, Andi L.; Higgins, Rosemary; Stoll, Barbara J.

    2016-01-01

    BACKGROUND: Current guidelines for prevention of neonatal group B streptococcal disease recommend diagnostic evaluations and empirical antibiotic therapy for well-appearing, chorioamnionitis-exposed newborns. Some clinicians question these recommendations, citing the decline in early-onset group B streptococcal disease rates since widespread intrapartum antibiotic prophylaxis implementation and potential antibiotic risks. We aimed to determine whether chorioamnionitis-exposed newborns with culture-confirmed, early-onset infections can be asymptomatic at birth. METHODS: Multicenter, prospective surveillance for early-onset neonatal infections was conducted during 2006–2009. Early-onset infection was defined as isolation of a pathogen from blood or cerebrospinal fluid collected ≤72 hours after birth. Maternal chorioamnionitis was defined by clinical diagnosis in the medical record or by histologic diagnosis by placental pathology. Hospital records of newborns with early-onset infections born to mothers with chorioamnionitis were reviewed retrospectively to determine symptom onset. RESULTS: Early-onset infections were diagnosed in 389 of 396 586 live births, including 232 (60%) chorioamnionitis-exposed newborns. Records for 229 were reviewed; 29 (13%) had no documented symptoms within 6 hours of birth, including 21 (9%) who remained asymptomatic at 72 hours. Intrapartum antibiotic prophylaxis exposure did not differ significantly between asymptomatic and symptomatic infants (76% vs 69%; P = .52). Assuming complete guideline implementation, we estimated that 60 to 1400 newborns would receive diagnostic evaluations and antibiotics for each infected asymptomatic newborn, depending on chorioamnionitis prevalence. CONCLUSIONS: Some infants born to mothers with chorioamnionitis may have no signs of sepsis at birth despite having culture-confirmed infections. Implementation of current clinical guidelines may result in early diagnosis, but large numbers of uninfected

  7. Early onset obsessive-compulsive disorder with and without tics.

    PubMed

    de Mathis, Maria Alice; Diniz, Juliana B; Shavitt, Roseli G; Torres, Albina R; Ferrão, Ygor A; Fossaluza, Victor; Pereira, Carlos; Miguel, Eurípedes; do Rosario, Maria Conceicão

    2009-07-01

    Research suggests that obsessive-compulsive disorder (OCD) is not a unitary entity, but rather a highly heterogeneous condition, with complex and variable clinical manifestations. The aims of this study were to compare clinical and demographic characteristics of OCD patients with early and late age of onset of obsessive-compulsive symptoms (OCS); and to compare the same features in early onset OCD with and without tics. The independent impact of age at onset and presence of tics on comorbidity patterns was investigated. Three hundred and thirty consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD were evaluated: 160 patients belonged to the "early onset" group (EOG): before 11 years of age, 75 patients had an "intermediate onset" (IOG), and 95 patients were from the "late onset" group (LOG): after 18 years of age. From the 160 EOG, 60 had comorbidity with tic disorders. The diagnostic instruments used were: the Yale-Brown Obsessive Compulsive Scale and the Dimensional Yale-Brown Obsessive Compulsive Scale (DY-BOCS), Yale Global Tics Severity Scale, and Structured Clinical Interview for DSM-IV Axis I Disorders-patient edition. Statistical tests used were: Mann-Whitney, full Bayesian significance test, and logistic regression. The EOG had a predominance of males, higher frequency of family history of OCS, higher mean scores on the "aggression/violence" and "miscellaneous" dimensions, and higher mean global DY-BOCS scores. Patients with EOG without tic disorders presented higher mean global DY-BOCS scores and higher mean scores in the "contamination/cleaning" dimension. The current results disentangle some of the clinical overlap between early onset OCD with and without tics.

  8. Acute presentation of gestational diabetes insipidus with pre-eclampsia complicated by cerebral vasoconstriction: a case report and review of the published work.

    PubMed

    Mor, Amir; Fuchs, Yael; Zafra, Kathleen; Haberman, Shoshana; Tal, Reshef

    2015-08-01

    Gestational diabetes insipidus (GDI) is a rare, self-limited complication of pregnancy. As it is related to excess placental vasopressinase enzyme activity, which is metabolized in the liver, GDI is more common in pregnancies complicated by conditions associated with liver dysfunction. We present a case of a 41-year-old woman at 38 weeks' gestation who presented with pre-eclampsia with severe features, including impaired liver function and renal insufficiency. Following cesarean section she was diagnosed with GDI, which was further complicated by cerebral vasoconstriction as demonstrated by magnetic resonance angiography. This case raises the possibility that cerebral vasoconstriction may be related to the cause of GDI. A high index of suspicion of GDI should be maintained in patients who present with typical signs and symptoms, especially in the setting of pregnancy complications associated with liver dysfunction. © 2015 The Authors. Journal of Obstetrics and Gynaecology Research © 2015 Japan Society of Obstetrics and Gynecology.

  9. Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks' gestation (HYPITAT): a multicentre, open-label randomised controlled trial.

    PubMed

    Koopmans, Corine M; Bijlenga, Denise; Groen, Henk; Vijgen, Sylvia M C; Aarnoudse, Jan G; Bekedam, Dick J; van den Berg, Paul P; de Boer, Karin; Burggraaff, Jan M; Bloemenkamp, Kitty W M; Drogtrop, Addy P; Franx, Arie; de Groot, Christianne J M; Huisjes, Anjoke J M; Kwee, Anneke; van Loon, Aren J; Lub, Annemiek; Papatsonis, Dimitri N M; van der Post, Joris A M; Roumen, Frans J M E; Scheepers, Hubertina C J; Willekes, Christine; Mol, Ben W J; van Pampus, Maria G

    2009-09-19

    Robust evidence to direct management of pregnant women with mild hypertensive disease at term is scarce. We investigated whether induction of labour in women with a singleton pregnancy complicated by gestational hypertension or mild pre-eclampsia reduces severe maternal morbidity. We undertook a multicentre, parallel, open-label randomised controlled trial in six academic and 32 non-academic hospitals in the Netherlands between October, 2005, and March, 2008. We enrolled patients with a singleton pregnancy at 36-41 weeks' gestation, and who had gestational hypertension or mild pre-eclampsia. Participants were randomly allocated in a 1:1 ratio by block randomisation with a web-based application system to receive either induction of labour or expectant monitoring. Masking of intervention allocation was not possible. The primary outcome was a composite measure of poor maternal outcome--maternal mortality, maternal morbidity (eclampsia, HELLP syndrome, pulmonary oedema, thromboembolic disease, and placental abruption), progression to severe hypertension or proteinuria, and major post-partum haemorrhage (>1000 mL blood loss). Analysis was by intention to treat and treatment effect is presented as relative risk. This study is registered, number ISRCTN08132825. 756 patients were allocated to receive induction of labour (n=377 patients) or expectant monitoring (n=379). 397 patients refused randomisation but authorised use of their medical records. Of women who were randomised, 117 (31%) allocated to induction of labour developed poor maternal outcome compared with 166 (44%) allocated to expectant monitoring (relative risk 0.71, 95% CI 0.59-0.86, p<0.0001). No cases of maternal or neonatal death or eclampsia were recorded. Induction of labour is associated with improved maternal outcome and should be advised for women with mild hypertensive disease beyond 37 weeks' gestation. ZonMw.

  10. Characterization of Early Partial Seizure Onset: Frequency, Complexity and Entropy

    PubMed Central

    Jouny, Christophe C.; Bergey, Gregory K.

    2011-01-01

    Objective A clear classification of partial seizures onset features is not yet established. Complexity and entropy have been very widely used to describe dynamical systems, but a systematic evaluation of these measures to characterize partial seizures has never been performed. Methods Eighteen different measures including power in frequency bands up to 300Hz, Gabor atom density (GAD), Higuchi fractal dimension (HFD), Lempel-Ziv complexity, Shannon entropy, sample entropy, and permutation entropy, were selected to test sensitivity to partial seizure onset. Intracranial recordings from forty-five patients with mesial temporal, neocortical temporal and neocortical extratemporal seizure foci were included (331 partial seizures). Results GAD, Lempel-Ziv complexity, HFD, high frequency activity, and sample entropy were the most reliable measures to assess early seizure onset. Conclusions Increases in complexity and occurrence of high-frequency components appear to be commonly associated with early stages of partial seizure evolution from all regions. The type of measure (frequency-based, complexity or entropy) does not predict the efficiency of the method to detect seizure onset. Significance Differences between measures such as GAD and HFD highlight the multimodal nature of partial seizure onsets. Improved methods for early seizure detection may be achieved from a better understanding of these underlying dynamics. PMID:21872526

  11. Early onset marfan syndrome: Atypical clinical presentation of two cases

    PubMed Central

    Ozyurt, A; Baykan, A; Argun, M; Pamukcu, O; Halis, H; Korkut, S; Yuksel, Z; Gunes, T; Narin, N

    2015-01-01

    Early onset Marfan Syndrome (eoMFS) is a rare, severe form of Marfan Syndrome (MFS). The disease has a poor prognosis and most patients present with resistance to heart failure treatment during the newborn period. This report presents two cases of eoMFS with similar clinical features diagnosed in the newborn period and who died at an early age due to the complications related to the involvement of the cardiovascular system. PMID:26929908

  12. OP007. PLGF in combination with other commonly utilised tests and other biomarkers for predicting need for delivery for pre-eclampsia within 14days in women presenting prior to 35weeks' gestation.

    PubMed

    Lucy, Chappell; Suzy, Duckworth; Melanie, Griffin; Paul, Seed; Christopher, Redman; Andrew, Shennan

    2013-04-01

    Current means of assessing women presenting with suspected pre-eclampsia using BP and proteinuria are of limited use in predicting need for imminent delivery. We undertook a prospective multicentre study to determine diagnostic accuracy of PlGF <5th centile (Triage assay) and other candidate biomarkers in women presenting with suspected pre-eclampsia at 20-35weeks' gestation, in determining need for delivery for pre-eclampsia within 14days. We calculated ROC curves for predictive potential and undertook principal factor analysis to determine additional predictive ability for biomarker combinations. In 287 women enrolled prior to 35weeks, ROC area (0.88, SE 0.03) for PlGF <5th centile for pre-eclampsia requiring delivery within 14days was greater than all other commonly utilised tests (systolic and diastolic BP, urate, ALT), either singly (range 0.58-0.68), or in combination (0.69) (p<0.001 for all comparisons), and was greater than that of all other biomarkers; addition of 2 other biomarker panels (either procalcitonin, nephrin and BNP; or cystatin and PAPP-A) increased ROC area to 0.90 but these biomarkers had limited predictive ability on their own. In women presenting prior to 35weeks' gestation with suspected pre-eclampsia, low PlGF has a greater ROC area than other commonly utilised tests. Additional biomarkers add only a small increment to the predictive value of a single PlGF measurement. Copyright © 2013. Published by Elsevier B.V.

  13. Different Alterations of Cerebral Regional Homogeneity in Early-Onset and Late-Onset Parkinson's Disease

    PubMed Central

    Sheng, Ke; Fang, Weidong; Zhu, Yingcheng; Shuai, Guangying; Zou, Dezhi; Su, Meilan; Han, Yu; Cheng, Oumei

    2016-01-01

    HIGHLIGHTS Eighteen EOPD, 21 LOPD and 37 age-matched normal control subjects participated in the resting state fMRI scans.Age at onset of PD modulates the distribution of cerebral regional homogeneity during resting state.Disproportionate putamen alterations are more prominent in PD patients with a younger age of onset. Objective: Early-onset Parkinson's disease (EOPD) is distinct from late-onset PD (LOPD) as it relates to the clinical profile and response to medication. The objective of current paper is to investigate whether characteristics of spontaneous brain activity in the resting state are associated with the age of disease onset. Methods: We assessed the correlation between neural activity and age-at-onset in a sample of 39 PD patients (18 EOPD and 21 LOPD) and 37 age-matched normal control subjects. Regional homogeneity (ReHo) approaches were employed using ANOVA with two factors: PD and age. Results: In the comparisons between LOPD and EOPD, EOPD revealed lower ReHo values in the right putamen and higher ReHo values in the left superior frontal gyrus. Compared with age-matched control subjects, EOPD exhibited lower ReHo values in the right putamen and higher ReHo values in the left inferior temporal gyrus; However, LOPD showed lower ReHo values in the right putamen and left insula. The ReHo values were negatively correlated with the UPDRS total scores in the right putamen in LOPD, but a correlation between the ReHo value and UPDRS score was not detected in EOPD. Conclusions: Our findings support the notion that age at onset is associated with the distribution of cerebral regional homogeneity in the resting state and suggest that disproportionate putamen alterations are more prominent in patients with a younger age of onset. PMID:27462265

  14. [Early-onset and late-onset male hypogonadotropic hypogonadism and osteoporosis].

    PubMed

    Okada, Hiroshi; Shin, Takeshi; Kobori, Yoshitomo

    2016-07-01

    Hypogonadism is classified into two major clinical entities, namely early-onset hypogonadism and late-onset hypogonadism. The former is characterized by the malfunction of hypothalamo-pituitary-gonadal(testicular)axis or by the primary hypofunction of testes(e.g. Klinefelter's syndrome). The latter is summarized as LOH syndrome which is attributed to the dropped level of bioavailable testosterone. In these diseases testosterone is the key molecule which may cause various symptoms relating not only to physical health but also to mental or psychologic health. In this review issues concerning bone health in these disease are described.

  15. Early-Onset Psychosis in Youth with Intellectual Disability

    ERIC Educational Resources Information Center

    Friedlander, R. I.; Donnelly, T.

    2004-01-01

    Accurate diagnosis of psychotic disorders may be very difficult in youth with intellectual disabilities. The authors reviewed the assessment, treatment and follow-up of 21 youths with ID referred because of early onset of psychotic symptoms. Just over one half of the patients had a diagnosis of schizophrenia or schizo-affective disorder. One third…

  16. Neurocognition in Early-Onset Schizophrenia and Schizoaffective Disorders

    ERIC Educational Resources Information Center

    Hooper, Stephen R.; Giuliano, Anthony J.; Youngstrom, Eric A.; Breiger, David; Sikich, Linmarie; Frazier, Jean A.; Findling, Robert L.; McClellan, Jon; Hamer, Robert M.; Vitiello, Benedetto; Lieberman, Jeffrey A.

    2010-01-01

    Objective: We examined the neuropsychological functioning of youth enrolled in the NIMH funded trial, Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). We compared the baseline neuropsychological functioning of youth with schizophrenia (SZ, n = 79) to those with schizoaffective disorder (SA, n = 40), and examined the relationship…

  17. Early Onset Bipolar Spectrum Disorder: Psychopharmacological, Psychological, and Educational Management

    ERIC Educational Resources Information Center

    McIntosh, David E.; Trotter, Jeffrey S.

    2006-01-01

    Although published research continues to advocate medication as the first line of treatment for early onset bipolar spectrum disorder (EOBSD; N. Lofthouse & M.A. Fristad, 2004), preliminary research demonstrating the utility of cognitive, cognitive-behavioral, and psychoeducational therapies is promising. It appears as if future treatment of EOBSD…

  18. Early-Onset Bipolar Spectrum Disorders: Diagnostic Issues

    ERIC Educational Resources Information Center

    Danner, Stephanie; Fristad, Mary A.; Arnold, L. Eugene; Youngstrom, Eric A.; Birmaher, Boris; Horwitz, Sarah M.; Demeter, Christine; Findling, Robert L.; Kowatch, Robert A.

    2009-01-01

    Since the mid 1990s, early-onset bipolar spectrum disorders (BPSDs) have received increased attention in both the popular press and scholarly press. Rates of diagnosis of BPSD in children and adolescents have increased in inpatient, outpatient, and primary care settings. BPSDs remain difficult to diagnose, particularly in youth. The current…

  19. Early onset marijuana use is associated with learning inefficiencies.

    PubMed

    Schuster, Randi Melissa; Hoeppner, Susanne S; Evins, A Eden; Gilman, Jodi M

    2016-05-01

    Verbal memory difficulties are the most widely reported and persistent cognitive deficit associated with early onset marijuana use. Yet, it is not known what memory stages are most impaired in those with early marijuana use. Forty-eight young adults, aged 18-25, who used marijuana at least once per week and 48 matched nonusing controls (CON) completed the California Verbal Learning Test, Second Edition (CVLT-II). Marijuana users were stratified by age of initial use: early onset users (EMJ), who started using marijuana at or before age 16 (n = 27), and late onset marijuana user group (LMJ), who started using marijuana after age 16 (n = 21). Outcome variables included trial immediate recall, total learning, clustering strategies (semantic clustering, serial clustering, ratio of semantic to serial clustering, and total number of strategies used), delayed recall, and percent retention. Learning improved with repetition, with no group effect on the learning slope. EMJ learned fewer words overall than LMJ or CON. There was no difference between LMJ and CON in total number of words learned. Reduced overall learning mediated the effect on reduced delayed recall among EMJ, but not CON or LMJ. Learning improved with greater use of semantic versus serial encoding, but this did not vary between groups. EMJ was not related to delayed recall after adjusting for encoding. Young adults reporting early onset marijuana use had learning weaknesses, which accounted for the association between early onset marijuana use and delayed recall. No amnestic effect of marijuana use was observed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  20. Intraspinal anomalies in early-onset idiopathic scoliosis.

    PubMed

    Pereira, E A C; Oxenham, M; Lam, K S

    2017-06-01

    In the United Kingdom, lower incidences of intraspinal abnormalities in patients with early onset idiopathic scoliosis have been observed than in studies in other countries. We aimed to determine the rates of these abnormalities in United Kingdom patients diagnosed with idiopathic scoliosis before the age of 11 years. This retrospective study of patients attending an urban scoliosis clinic identified 71 patients satisfying a criteria of: clinical diagnosis of idiopathic scoliosis; age of onset ten years and 11 months or less; MRI screening for intraspinal abnormalities. United Kingdom census data combined with patient referral data was used to calculate incidence. Mean age at diagnosis was six years with 39 right-sided and 32 left-sided curves. Four patients (5.6%) were found to have intraspinal abnormalities on MRI. These consisted of: two combined Arnold-Chiari type 1 malformations with syrinx; one syrinx with a low lying conus; and one isolated syrinx. Overall annual incidence of early onset idiopathic scoliosis was one out of 182 000 (0.0006%). This study reports the lowest rates to date of intraspinal anomalies in patients with early onset idiopathic scoliosis, adding to knowledge regarding current incidences of these abnormalities as well as any geographical variation in the nature of the disease. Cite this article: Bone Joint J 2017;99-B:829-33. ©2017 The British Editorial Society of Bone & Joint Surgery.

  1. Whole Exome Analysis of Early Onset Alzheimer’s Disease

    DTIC Science & Technology

    2016-04-01

    Early Onset Alzheimer’s Disease 5a. CONTRACT NUMBER W81XWH-12-1-0013 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) Margaret A. Pericak...relationship between SORL1, AD, and Parkinsonism . 16 Appendix V: ABCA7 Frameshift Deletion Associated with Alzheimer’s Disease in African Americans...onset Alzheimer disease identified using whole-exome sequencing G. W. Beecham1, B. W. Kunkle1, B. Vardarajan2, P. L. Whitehead1, S . Rolati1, E. R

  2. Atypical antipsychotics in the treatment of early-onset schizophrenia

    PubMed Central

    Hrdlicka, Michal; Dudova, Iva

    2015-01-01

    Atypical antipsychotics (AAPs) have been successfully used in early-onset schizophrenia (EOS). This review summarizes the randomized, double-blind, controlled studies of AAPs in EOS, including clozapine, risperidone, olanzapine, aripiprazole, paliperidone, quetiapine, and ziprasidone. No significant differences in efficacy between AAPs were found, with the exception of clozapine and ziprasidone. Clozapine demonstrated superior efficacy in treatment-resistant patients with EOS, whereas ziprasidone failed to demonstrate efficacy in the treatment of EOS. Our review also focuses on the onset of action and weight gain associated with AAPs. The data on onset of action of AAPs in pediatric psychiatry are scanty and inconsistent. Olanzapine appears to cause the most significant weight gain in patients with EOS, while ziprasidone and aripiprazole seem to cause the least. PMID:25897226

  3. Late onset dysthymic disorder and major depression differ from early onset dysthymic disorder and major depression in elderly outpatients.

    PubMed

    Devanand, D P; Adorno, Elizabeth; Cheng, Jocelyn; Burt, Tal; Pelton, G H Gregory H; Roose, S P Steven P; Sackeim, H A Harold A

    2004-03-01

    Age of onset may affect clinical features and prognosis in elderly patients with major depression (MDD), but there is a lack of such data in elderly patients with dysthymic disorder (DD) and systematic comparisons of late onset MDD and DD have not been conducted. In a Late Life Depression Clinic, patients > or = 60 years old who met DSM-III-R or DSM-IV criteria for MDD or DD were studied. The 24-item Hamilton Rating Scale for Depression (HRSD) and SCID-P were completed, family history was obtained, and medical illnesses were assessed. In the total sample (n=370; 211 MDD and 159 DD), compared to early onset patients, late onset (onset > or =60 years) patients had a higher rate of cardiovascular disease (chi(2)=4.12, df=1, P<0.05), lower rate of anxiety disorder (chi(2)=4.19, df=1, P<0.05), and a lower rate of family history of affective disorder (chi(2)=9.37, df=1, P<0.002). Late onset DD patients were more likely to have cardiovascular disease than early onset DD patients (chi(2)=5.63, df=1, P<0.02), but the rate of cardiovascular disease did not differ between late and early onset MDD patients (chi(2)=0.35, df=1, P<0.6). Late onset MDD patients were less likely to have a family history of affective disorder than early onset MDD patients (chi(2)=10.71, df=1, P<0.001). Prevalence of anxiety disorders did not differ between the early and late onset MDD patients (chi(2)=0.07, df=1, P<0.79), but was more common in the early onset DD compared to the late onset DD patients (17.98% versus 4.29%, chi(2)=6.98, df=1, P<0.01). Late onset DD did not differ from late onset MDD in the rates of cardiovascular disease, anxiety disorders, and family history of affective disorder. Excluding patients with double depression (n=32) did not alter the cardiovascular or family history findings, but the difference in anxiety disorders between early and late onset DD patients was no longer significant. Academic clinic sample results may not generalize to community populations. In the

  4. Early-onset dementias: diagnostic and etiological considerations

    PubMed Central

    2013-01-01

    This paper summarizes the body of literature about early-onset dementia (EOD) that led to recommendations from the Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. A broader differential diagnosis is required for EOD compared with late-onset dementia. Delays in diagnosis are common, and the social impact of EOD requires special care teams. The etiologies underlying EOD syndromes should take into account family history and comorbid diseases, such as cerebrovascular risk factors, that may influence the clinical presentation and age at onset. For example, although many EODs are more likely to have Mendelian genetic and/or metabolic causes, the presence of comorbidities may drive the individual at risk for late-onset dementia to manifest the symptoms at an earlier age, which contributes further to the observed heterogeneity and may confound diagnostic investigation. A personalized medicine approach to diagnosis should therefore be considered depending on the age at onset, clinical presentation, and comorbidities. Genetic counseling and testing as well as specialized biochemical screening are often required, especially in those under the age of 40 and in those with a family history of autosomal dominant or recessive disease. Novel treatments in the drug development pipeline for EOD, such as genetic forms of Alzheimer's disease, should target the specific pathogenic cascade implicated by the mutation or biochemical defect. PMID:24565469

  5. Early intervention for late-onset ornithine transcarbamylase deficiency.

    PubMed

    Fujisawa, Daisuke; Mitsubuchi, Hiroshi; Matsumoto, Shirou; Iwai, Masanori; Nakamura, Kimitoshi; Hoshide, Ryuji; Harada, Nawomi; Yoshino, Makoto; Endo, Fumio

    2015-01-01

    We report the case of a family with late-onset ornithine transcarbamylase deficiency (OTCD). Several family members had died from OTCD, and the c.221G>A, p.Lys221Lys mutation was detected at the 3' end of exon 6 of OTC in the X-chromosome of some members. We provided genetic counseling on pregnancy, delivery, and neonate management to a 4th-generation female carrier and decided on metabolic management of her child from birth. Two male patients were diagnosed with late-onset OTCD on the basis of blood amino acid and genetic analysis, and they received arginine supplementation from the asymptomatic, early neonatal period. These children grew and developed normally, without decompensation. Patients with late-onset OTCD can and should be diagnosed and treated in the early neonatal period, especially those from families already diagnosed with late-onset OTCD, and family members must be provided with genetic counseling. © 2015 Japan Pediatric Society.

  6. Early identification of 'acute-onset' chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Sung, Jia-Ying; Tani, Jowy; Park, Susanna B; Kiernan, Matthew C; Lin, Cindy Shin-Yi

    2014-08-01

    Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased

  7. [Treatment of early onset scoliosis : How far can we go?].

    PubMed

    Studer, D; Hasler, C C; Schulze, A

    2015-11-01

    Recently, inconsistent definitions of early onset scoliosis (EOS) and a wide variety of treatment options have been observed. To clearly define the term EOS, to depict non-operative and operative treatment options, and to present the limitations of the boundaries of these techniques. Review of the literature, including conference presentations and expert opinions, in addition to personal experiences. Early onset scoliosis (EOS) refers to spine deformity that is present before 10 years of age, regardless of etiology. All existing operative treatment options share a high risk of complications. Therefore, non-operative treatment should act as a time-buying approach to postpone surgery. Awareness of treatment options and their specific indications, in addition to respecting each patient's individual needs and feasibilities, are crucial for the optimal outcome.

  8. Genetic Determinism of Primary Early-Onset Osteoarthritis.

    PubMed

    Aury-Landas, Juliette; Marcelli, Christian; Leclercq, Sylvain; Boumédiene, Karim; Baugé, Catherine

    2016-01-01

    Osteoarthritis (OA) is the most common joint disease worldwide. A minority of cases correspond to familial presentation characterized by early-onset forms which are genetically heterogeneous. This review brings a new point of view on the molecular basis of OA by focusing on gene mutations causing early-onset OA (EO-OA). Recently, thanks to whole-exome sequencing, a gain-of-function mutation in the TNFRSF11B gene was identified in two distant family members with EO-OA, opening new therapeutic perspectives for OA. Indeed, unraveling the molecular basis of rare Mendelian OA forms will improve our understanding of molecular processes involved in OA pathogenesis and will contribute to better patient diagnosis, management, and therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Whole Exome Analysis of Early Onset Alzheimer’s Disease

    DTIC Science & Technology

    2013-04-01

    FTD), FTD with Parkinsonism , and early-onset Alzheimer Disease (EOAD)-like presentations. Using whole exome capture with subsequent sequencing, we...dementia. The MAPT R406W mutation is associated with EOAD-like symptoms and Parkinsonism without FTD, as well as distinct cognitive courses. KEY...OUTCOMES: Carney RM, Kohli MA, Kunkle BW, Naj AC, Gilbert JR, Züchner S, PERICAK-VANCE MA, Parkinsonism and distinct dementia patterns in a

  10. Early Onset Diabetes - Genetic And Hormonal Analysis In Pakistani Population.

    PubMed

    Wahid, Maryam; Kamran, Mohammad

    2016-01-01

    Mitochondrial DNA mutation and hormonal imbalance is involved in the pathogenesis of early onset diabetes but data is lacking in Pakistani population. The study was planned to delineate the clinical presentation of early onset diabetes with possible hormonal and genetic etiological factors and aascertain the possible etiological role of insulin and glucagon in these patients either on oral hypoglycaemic or subcutaneous insulin therapy. Retrospective, analytical case control study with conventional sampling technique carried at Centre for Research in Experimental and Applied Medicine (CREAM) affiliated with the department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi from Dec 2006 to July 2011. Study included the patients (20-35 years of age) with early onset diabetes on oral hypoglycemic (n=240), insulin therapy (n=280), and compared with non-diabetic healthy controls (n=150). A fragment surrounding tRNALeu (UUR) gene was amplified by AmpliTaq from mtDNA which was extracted from peripheral blood leucocytes. Then it was subjected to restriction endonucleases, ApaI for A3242G mutation and HaeIII for G3316A mutation detection. Plasma glucose, glycosylated Hb, osmolality, insulin and glucagon levels along with ABGs analysis was also done. Non diabetic controls comprised of 51% males and 49% females, diabetics on oral hypoglycemic 60% males and 40 % females and on insulin therapy 54% males and 46% females. Insulin dependent diabetics had statistically significant hyperglucagonemia, acidemia and bicarbonate deficit. MtDNA A3242G and G3316A mutations were not detected. relative hyperglucagonemia and acidemia in Insulin dependent diabetics was a potent threat leading to DKA. The absence of two mtDNA mutations in ND1 gene rules out the possibility of involvement of these mutations in early onset diabetes in Pakistani population.

  11. Graves' disease presenting as bi-ventricular heart failure with severe pulmonary hypertension and pre-eclampsia in pregnancy--a case report and review of the literature.

    PubMed

    Sabah, Khandker Mohammad Nurus; Chowdhury, Abdul Wadud; Islam, Mohammad Shahidul; Cader, Fathima Aaysha; Kawser, Shamima; Hosen, Md Imam; Saleh, Mohammed Abaye Deen; Alam, Md Shariful; Chowdhury, Mohammad Monjurul Kader; Tabassum, Humayara

    2014-11-18

    Graves' disease, a well-known cause of hyperthyroidism, is an autoimmune disease with multi-system involvement. More prevalent among young women, it appears as an uncommon cardiovascular complication during pregnancy, posing a diagnostic challenge, largely owing to difficulty in detecting the complication, as a result of a low index of suspicion of Graves' disease presenting during pregnancy. Globally, cardiovascular disease is an important factor for pregnancy-related morbidity and mortality. Here, we report a case of Graves' disease detected for the first time in pregnancy, in a patient presenting with bi- ventricular heart failure, severe pulmonary hypertension and pre- eclampsia. Emphasis is placed on the spectrum of clinical presentations of Graves' disease, and the importance of considering this thyroid disorder as a possible aetiological factor for such a presentation in pregnancy. A 30-year-old Bangladeshi-Bengali woman, in her 28th week of pregnancy presented with severe systemic hypertension, bi-ventricular heart failure and severe pulmonary hypertension with a moderately enlarged thyroid gland. She improved following the administration of high dose intravenous diuretics, and delivered a premature female baby of low birth weight per vaginally, twenty four hours later. Pre-eclampsia was diagnosed on the basis of hypertension first detected in the third trimester, 3+ oedema and mild proteinuria. Electrocardiography revealed sinus tachycardia with incomplete right bundle branch block and echocardiography showed severe pulmonary hypertension with an estimated pulmonary arterial systolic pressure of 73 mm Hg, septal and anterior wall hypokinesia with an ejection fraction of 51%, grade I mitral and tricuspid regurgitation. Thyroid function tests revealed a biochemically hyperthyroid state and positive anti- thyroid peroxidase antibodies was found. (99m)Technetium pertechnetate thyroid scans demonstrated diffuse toxic goiter as evidenced by an enlarged thyroid

  12. Age at onset of DSM-IV pathological gambling in a non-treatment sample: Early- versus later-onset.

    PubMed

    Black, Donald W; Shaw, Martha; Coryell, William; Crowe, Raymond; McCormick, Brett; Allen, Jeff

    2015-07-01

    Pathological gambling (PG) is a prevalent and impairing public health problem. In this study we assessed age at onset in men and women with PG and compared the demographic and clinical picture of early- vs. later-onset individuals. We also compared age at onset in PG subjects and their first-degree relatives with PG. Subjects with DSM-IV PG were recruited during the conduct of two non-treatment clinical studies. Subjects were evaluated with structured interviews and validated questionnaires. Early-onset was defined as PG starting prior to age 33years. Age at onset of PG in the 255 subjects ranged from 8 to 80years with a mean (SD) of 34.0 (15.3) years. Men had an earlier onset than women. 84% of all subjects with PG had developed the disorder by age 50years. Early-onset subjects were more likely to be male, to prefer action games, and to have substance use disorders, antisocial personality disorder, attention deficit/hyperactivity disorder, trait impulsiveness, and social anxiety disorder. Later-onset was more common in women and was associated with a preference for slots and a history of sexual abuse. Age at onset of PG is bimodal and differs for men and women. Early-onset PG and later-onset PG have important demographic and clinical differences. The implications of the findings are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Early Onset Marijuana Use Is Associated with Learning Inefficiencies

    PubMed Central

    Schuster, Randi Melissa; Hoeppner, Susanne S.; Evins, A. Eden; Gilman, Jodi M.

    2016-01-01

    Objective Verbal memory difficulties are the most widely reported and persistent cognitive deficit associated with early-onset marijuana use. Yet, it is not known what memory stages are most impaired in those with early marijuana use. Method Forty-eight young adults, aged 18–25, who used marijuana at least once per week and 48 matched non-using controls (CON) completed the California Verbal Learning Test, Second Edition (CVLT-II). Marijuana users were stratified by age of initial use: ‘early onset’ users (EMJ), who started using marijuana at or before age 16 (n = 27), and ‘late onset’ marijuana user group (LMJ), who started using marijuana after age 16 (n = 21). Outcome variables included trial immediate recall, total learning, clustering strategies (semantic clustering, serial clustering, ratio of semantic to serial clustering, and total number of strategies used), delayed recall, and percent retention. Results Learning improved with repetition, with no group effect on the learning slope. EMJ learned fewer words overall than LMJ or CON. There was no difference between LMJ and CON in total number of words learned. Reduced overall learning mediated the effect on reduced delayed recall among EMJ, but not CON or LMJ. Learning improved with greater use of semantic versus serial encoding, but this did not vary between groups. EMJ was not related to delayed recall after adjusting for encoding. Conclusions Young adults reporting early onset marijuana use had learning weaknesses, which accounted for the association between early onset marijuana use and delayed recall. No amnestic effect of marijuana use was observed. PMID:26986749

  14. Deferred and immediate imitation in regressive and early onset autism

    PubMed Central

    Rogers, Sally J.; Young, Gregory S.; Cook, Ian; Giolzetti, Angelo; Ozonoff, Sally

    2010-01-01

    Deferred imitation has long held a privileged position in early cognitive development, considered an early marker of representational thought with links to language development and symbolic processes. Children with autism have difficulties with several abilities generally thought to be related to deferred imitation: immediate imitation, language, and symbolic play. However, few studies have examined deferred imitation in early autism. The present study examined both deferred, spontaneous imitation and immediate, elicited imitation on a set of carefully matched tasks in 36 young children with autism: 16 with early onset autism, 20 with regressive autism and two contrast groups, younger typically developing children (n = 20) and age matched children with significant developmental delays (n = 21). Analyses of co-variance controlling for differences in verbal mental age revealed significant main effects for task, but no main effect of group and no interaction of task by group. Deferred imitation scores were lower than immediate imitation scores for all groups. Imitation performance was related to overall intellectual functioning for all groups, and there were moderate and significant relations between imitation in the immediate elicited condition and in the spontaneous deferred condition for all groups. Finally, there were no differences between onset subgroups in imitation scores, suggesting that the two share a similar phenotype involving both types of imitation. PMID:18221343

  15. Functional Connectivity of the Amygdala in Early Childhood Onset Depression

    PubMed Central

    Luking, Katherine R.; Repovs, Grega; Belden, Andy C.; Gaffrey, Michael S.; Botteron, Kelly N.; Luby, Joan L.; Barch, Deanna M.

    2011-01-01

    Objective Adult major depressive disorder (MDD) is associated with reduced cortico-limbic functional connectivity thought to indicate decreased top-down control of emotion. However, it is unclear whether such connectivity alterations are also present in early childhood onset MDD. Method Fifty-one children ages 7–11 years, prospectively studied since preschool age, completed resting state fMRI and were assigned to four groups: 1) C-MDD (N=13) personal history of early childhood onset MDD; 2) M-MDD (N=11) a maternal history of affective disorders; 3) CM-MDD (N=13) both maternal and early childhood onset MDD or 4) CON (N=14) without either a personal or maternal history. We used seed-based resting state functional connectivity (rsfcMRI) analysis in an independent sample of adults to identify networks showing both positive (e.g., limbic regions) and negative (e.g., dorsal frontal/parietal regions) connectivity with the amygdala. These regions were then used in ROI based analyses of our child sample. Results We found a significant interaction between maternal affective disorder history and the child's MDD history for both positive and negative rsfcMRI networks. Specifically, when copared to CON, we found reduced connectivity between the amygdala and the “Negative Network” in children with C-MDD, M-MDD and CM-MDD. Children with either C-MDD or a maternal history of MDD (but not CM-MDD) displayed reduced connectivity between the amygdala and the “Positive Network”. Conclusions Our finding of an attenuated relationship between the amygdala, a region affected in MDD and involved in emotion processing, and cognitive control regions is consistent with a hypothesis of altered regulation of emotional processing in C-MDD suggesting developmental continuity of this alteration into early childhood. PMID:21961777

  16. Effects of gestational hypertension and pre-eclampsia in mRNA expression of fibrinolysis genes in primary cultured human umbilical vein endothelial cells.

    PubMed

    Poblete-Naredo, Irais; Rodríguez-Yáñez, Yury; Corona-Núñez, Rogelio O; González-Monroy, Stuart; Salinas, Juan E; Albores, Arnulfo

    2018-05-17

    Hypertension disorders (HD) and pre-eclampsia (PRE) are leading causes of maternal deaths worldwide. PRE is associated with vascular endothelial dysfunction and with deregulation of the fibrinolysis pathway genes. Fibrinolysis is the fibrin clot hydrolysis process catalyzed by plasmin, a proteolytic enzyme formed from plasminogen. Plasminogen is cleaved by tissue-type (tPA) and urokinase-type (uPA) activators and inhibited by the plasminogen activator inhibitors type-1 (PAI-1) and type-2 (PAI-2). The whole process maintains blood hemostasis. This study aims to assess PAI-1, PAI-2, tPA and uPA mRNA expression in primary cultured human umbilical vein endothelial cells (HUVEC) isolated and cultured from healthy, HD and PRE women. Results show that PAI-1 and PAI-2 mRNA decreased in HD-HUVEC, whereas PAI-1 and uPA decreased in PRE-HUVEC cultures compared to control ones. Notably, the expression ratio between pro- and anti-fibrinolytic actors remained unchanged among the studied groups. It seems that newborn's hemostasis is maintained balanced probably by a compensatory mechanism that involves changes in the fibrinolysis gene expression profile. The real impact of these changes in mRNA expression is unknown, however, it is suggested that these changes could be associated with an increased predisposition to vascular disease development in the progeny. Copyright © 2018. Published by Elsevier Ltd.

  17. THE PREDICTIVE VALUE OF SERUM URIC ACID FOR THE OCCURRENCE, SEVERITY AND OUTCOMES OF PRE-ECLAMPSIA AMONG PARTURIENTS AT NNEWI, NIGERIA.

    PubMed

    Osakwe, Chukwudi Richmond; Ikpeze, Okechukwu C; Ezebialu, Ifeanyi Uzoma; Osakwe, Joy Oluchi; Mbadugha, Norah Nwadiogo

    2015-01-01

    To determine the predictive value of serum uric acid for preeclampsia, its severity and pregnancy outcome. This is a cohort study that was performed on normal pregnant women attending antenatal clinic at Nnamdi Azikiwe University Teaching Hospital Nnewi Nigeria. Serum uric acid was determined in 200 women attending antenatal clinic between the gestational ages of 14 and 26 weeks. The women were followed up at 2 weekly intervals until 36 weeks and weekly thereafter until delivery. Women who developed pre-eclampsia or eclampsia were identified. Pregnancy outcomes were determined as well as fetal and placental weights. The data was analised with SPSS version 16.0. The chi square was used for test of significance. The positive and negative predictive values were determined. A total of 200 normal pregnant women were recruited for the study. Nine of them were lost to follow up. Subsequently, 10.5% of the women developed preeclampsia. The positive and negative predictive values of serum uric acid for preeclampsia were 78.9% and 97.1%, respectively. Serum uric acid was found to be a useful predictor of the occurrence of preeclampsia and its severity.

  18. Using clinical symptoms to predict adverse maternal and perinatal outcomes in women with preeclampsia: data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study.

    PubMed

    Yen, Tin-Wing; Payne, Beth; Qu, Ziguang; Hutcheon, Jennifer A; Lee, Tang; Magee, Laura A; Walters, Barry N; von Dadelszen, Peter

    2011-08-01

    Preeclampsia is a leading cause of maternal morbidity. The clinical challenge lies in predicting which women with preeclampsia will suffer adverse outcomes and would benefit from treatment, while minimizing potentially harmful interventions. Our aim was to determine the ability of maternal symptoms (i.e., severe nausea or vomiting, headache, visual disturbance, right upper quadrant pain or epigastric pain, abdominal pain or vaginal bleeding, and chest pain or dyspnea) to predict adverse maternal or perinatal outcomes. We used data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study, a multicentre, prospective cohort study designed to investigate the maternal risks associated with preeclampsia. Relative risks and receiver operating characteristic (ROC) curves were assessed for each preeclampsia symptom and outcome pair. Of 2023 women who underwent assessment, 52% experienced at least one preeclampsia symptom, with 5.2% and 5.3% respectively experiencing an adverse maternal or perinatal outcome. No symptom and outcome pair, in either of the maternal or perinatal groups, achieved an area under the ROC curve value > 0.7, which would be necessary to demonstrate a discriminatory predictive value. Maternal symptoms of preeclampsia are not independently valid predictors of maternal adverse outcome. Caution should be used when making clinical decisions on the basis of symptoms alone in the preeclamptic patient.

  19. Intrauterine growth restriction and placental gene expression in severe preeclampsia, comparing early-onset and late-onset forms.

    PubMed

    Nevalainen, Jaana; Skarp, Sini; Savolainen, Eeva-Riitta; Ryynänen, Markku; Järvenpää, Jouko

    2017-10-26

    To evaluate placental gene expression in severe early- or late-onset preeclampsia with intrauterine growth restriction compared to controls. Chorionic villus sampling was conducted after cesarean section from the placentas of five women with early- or late-onset severe preeclampsia and five controls for each preeclampsia group. Microarray analysis was performed to identify gene expression differences between the groups. Pathway analysis showed over-representation of gene ontology (GO) biological process terms related to inflammatory and immune response pathways, platelet development, vascular development, female pregnancy and reproduction in early-onset preeclampsia. Pathways related to immunity, complement and coagulation cascade were overrepresented in the hypergeometric test for the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Ten genes (ABI3BP, C7, HLA-G, IL2RB, KRBOX1, LRRC15, METTL7B, MPP5, RFLNB and SLC20A) had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to early controls. There were 362 genes that had a ≥±1 fold expression difference in severe early-onset preeclampsia group compared to late-onset preeclampsia group including ABI3BP, C7, HLA-G and IL2RB. There are significant differences in placental gene expression between severe early- and late-onset preeclampsia when both are associated with intrauterine growth restriction. ABI3BP, C7, HLA-G and IL2RB might contribute to the development of early form of severe preeclampsia.

  20. Childhood Risk Factors for Early-Onset Drinking*

    PubMed Central

    Donovan, John E.; Molina, Brooke S. G.

    2011-01-01

    Objective: There is relatively little research on the childhood antecedent predictors of early-onset alcohol use. This study examined an array of psychosocial variables assessed at age 10 and reflecting Problem Behavior Theory as potential antecedent risk factors for the initiation of alcohol use at age 14 or younger. Method: A sample of 452 children (238 girls) ages 8 or 10 and their families was drawn from Allegheny County, PA, using targeted-age directory sampling and random-digit dialing procedures. Children and parents were interviewed using computer-assisted interviews. Logistic regression analyses were used to examine the age-10 univariate and multivariate predictors of the initiation of alcohol use by age 14 or younger. Results: Twenty-five percent of the sample reported having more than a sip or a taste of alcohol in their life by age 14. Sex, race, and age cohort did not relate to early drinking status. Children with two parents were less likely to initiate drinking early. Early initiation of drinking related significantly to an array of antecedent risk factors (personality, social environment, and behavioral) assessed at age 10 that reflect psychosocial proneness for problem behavior. In the multivariate model, the variables most predictive of early-onset drinking were having a single parent, sipping or tasting alcohol by age 10, having parents who also started drinking at an early age, and parental drinking frequency. Conclusions: Initiation of alcohol use by age 14 reflects childhood psychosocial proneness to engage in problem behavior as measured by Problem Behavior Theory and having a family environment conducive to alcohol use. PMID:21906502

  1. Comparison of early versus late onset familial Mediterranean fever.

    PubMed

    Yasar Bilge, Nazife Sule; Sari, Ismail; Solmaz, Dilek; Senel, Soner; Emmungil, Hakan; Kilic, Levent; Yilmaz Oner, Sibel; Yildiz, Fatih; Yilmaz, Sedat; Ersozlu Bozkirli, Duygu; Aydin Tufan, Muge; Yilmaz, Sema; Yazisiz, Veli; Pehlivan, Yavuz; Bes, Cemal; Yildirim Cetin, Gozde; Erten, Sukran; Gonullu, Emel; Sahin, Fezan; Akar, Servet; Aksu, Kenan; Kalyoncu, Umut; Direskeneli, Haner; Erken, Eren; Sayarlioglu, Mehmet; Cınar, Muhammed; Kasifoglu, Timucin

    2018-04-01

    Familial Mediterranean fever (FMF) is the most common autoinflammatory disease. One of the common characteristics of this disease is its young age predominance. Nearly 90% of patients experience disease flares during early adult age periods. Currently there are limited data for the comparison of early versus late onset FMF and therefore the primary aim of this study was to investigate these two subsets with regard to their certain demographic, clinical and genetic differences. Early (≤ 20 years, Group 1) and late (> 20 years, Group 2) onset FMF patients were identified from the national FMF registry that involves 2246 patients from 15 adult rheumatology clinics located in different geographical areas of Turkey. Of the 2246 patients, 1633 (72.7%) were aged ≤ 20 years old (Group 1) and the remaining 613 were older than 20 years (Group 2). Delay in diagnosis was longer in Group 1 and fever, peritonitis, pleuritis, erysipelas-like erythema (ELE), arthritis, family history of FMF and amyloidosis were more common in Group 1. On the other hand, sex distribution, rates of amyloidosis, vasculitis and kidney failure were not different between the groups. Among patients with available genotypes, homozygous and heterozygous M694V mutations were significantly higher and heterozygous E148Q mutation was significantly lower in Group 1 compared to Group 2. Patients with FMF whose symptoms start before 20 years of age seem to have severe symptoms and M694V mutation may be responsible for the early expression of the disease. © 2018 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  2. Premature adrenarche: novel lessons from early onset androgen excess.

    PubMed

    Idkowiak, Jan; Lavery, Gareth G; Dhir, Vivek; Barrett, Timothy G; Stewart, Paul M; Krone, Nils; Arlt, Wiebke

    2011-08-01

    Adrenarche reflects the maturation of the adrenal zona reticularis resulting in increased secretion of the adrenal androgen precursor DHEA and its sulphate ester DHEAS. Premature adrenarche (PA) is defined by increased levels of DHEA and DHEAS before the age of 8 years in girls and 9 years in boys and the concurrent presence of signs of androgen action including adult-type body odour, oily skin and hair and pubic hair growth. PA is distinct from precocious puberty, which manifests with the development of secondary sexual characteristics including testicular growth and breast development. Idiopathic PA (IPA) has long been considered an extreme of normal variation, but emerging evidence links IPA to an increased risk of developing the metabolic syndrome (MS) and thus ultimately cardiovascular morbidity. Areas of controversy include the question whether IPA in girls is associated with a higher rate of progression to the polycystic ovary syndrome (PCOS) and whether low birth weight increases the risk of developing IPA. The recent discoveries of two novel monogenic causes of early onset androgen excess, apparent cortisone reductase deficiency and apparent DHEA sulphotransferase deficiency, support the notion that PA may represent a forerunner condition for PCOS. Future research including carefully designed longitudinal studies is required to address the apparent link between early onset androgen excess and the development of insulin resistance and the MS.

  3. Alertness and cognitive control: Testing the early onset hypothesis.

    PubMed

    Schneider, Darryl W

    2018-05-01

    Previous research has revealed a peculiar interaction between alertness and cognitive control in selective-attention tasks: Congruency effects are larger on alert trials (on which an alerting cue is presented briefly in advance of the imperative stimulus) than on no-alert trials, despite shorter response times (RTs) on alert trials. One explanation for this finding is the early onset hypothesis, which is based on the assumptions that increased alertness shortens stimulus-encoding time and that cognitive control involves gradually focusing attention during a trial. The author tested the hypothesis in 3 experiments by manipulating alertness and stimulus quality (which were intended to shorten and lengthen stimulus-encoding time, respectively) in an arrow-based flanker task involving congruent and incongruent stimuli. Replicating past findings, the alerting manipulation led to shorter RTs but larger congruency effects on alert trials than on no-alert trials. The stimulus-quality manipulation led to longer RTs and larger congruency effects for degraded stimuli than for intact stimuli. These results provide mixed support for the early onset hypothesis, but the author discusses how data and theory might be reconciled if stimulus quality affects stimulus-encoding time and the rate of evidence accumulation in the decision process. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  4. Co-occurring problems of early onset persistent, childhood limited, and adolescent onset conduct problem youth.

    PubMed

    Barker, Edward D; Oliver, Bonamy R; Maughan, Barbara

    2010-11-01

    It is increasingly recognized that youth who follow early onset persistent (EOP), childhood limited (CL) and adolescent onset (AO) trajectories of conduct problems show somewhat varying patterns of risk (in childhood) and adjustment problems (in adolescence and adulthood). Little, however, is known about how other adjustment problems differentially co-develop with the EOP, CL and AO trajectories across the childhood and adolescent years. Using data from the Avon Longitudinal Study of Parents and Children, an epidemiological, longitudinal cohort of boys and girls, we estimated growth curves for parent-reported hyperactivity, emotional difficulties, peer relational problems, and prosocial behaviors conditional on trajectories of conduct problems (i.e., EOP, CL and AO) from ages 4 to 13 years. At ages 7-8 years, DSM-IV-based diagnoses of conduct disorder, oppositional-defiant disorder, attention deficit/hyperactivity disorder (ADHD), anxiety, depression were examined by conduct problems trajectory. Overall, the development of hyperactivity, emotional difficulties, peer relational problems, and prosocial behaviors mirrored the development of conduct problems, showing similar trajectories. Results indicated that the problems of EOP youth were persistent across domains, CL youth showed decreased behavior problems while increasing in prosocial behaviors, and AO youth increased in adjustment problems after 10 years of age. © 2010 The Authors. Journal of Child Psychology and Psychiatry © 2010 Association for Child and Adolescent Mental Health.

  5. STRIDER: Sildenafil Therapy In Dismal prognosis Early-onset intrauterine growth Restriction--a protocol for a systematic review with individual participant data and aggregate data meta-analysis and trial sequential analysis.

    PubMed

    Ganzevoort, Wessel; Alfirevic, Zarko; von Dadelszen, Peter; Kenny, Louise; Papageorghiou, Aris; van Wassenaer-Leemhuis, Aleid; Gluud, Christian; Mol, Ben Willem; Baker, Philip N

    2014-03-11

    In pregnancies complicated by early-onset extreme fetal growth restriction, there is a high risk of preterm birth and an overall dismal fetal prognosis. Sildenafil has been suggested to improve this prognosis. The first aim of this review is to assess whether sildenafil benefits or harms these babies. The second aim is to analyse if these effects are modified in a clinically meaningful way by factors related to the women or the trial protocol. The STRIDER (Sildenafil Therapy In Dismal prognosis Early-onset intrauterine growth Restriction) Individual Participant Data (IPD) Study Group will conduct a prospective IPD and aggregate data systematic review with meta-analysis and trial sequential analysis. The STRIDER IPD Study Group started trial planning and funding applications in 2012. Three trials will be launched in 2014, recruiting for three years. Further trials are planned to commence in 2015.The primary outcome for babies is being alive at term gestation without evidence of serious adverse neonatal outcome. The latter is defined as severe central nervous system injury (severe intraventricular haemorrhage (grade 3 and 4) or cystic periventricular leukomalacia, demonstrated by ultrasound and/or magnetic resonance imaging) or other severe morbidity (bronchopulmonary dysplasia, retinopathy of prematurity requiring treatment, or necrotising enterocolitis requiring surgery). The secondary outcomes are improved fetal growth velocity assessed by ultrasound abdominal circumference measurements, gestational age and birth weight (centile) at delivery, and age-adequate performance on the two-year Bayley scales of infant and toddler development-III (composite cognitive score and composite motor score). Subgroup and sensitivity analyses in the IPD meta-analysis include assessment of the influence of several patient characteristics: an abnormal or normal serum level of placental growth factor, absent/reversed umbilical arterial end diastolic flow at commencement of treatment

  6. Assessment of facility readiness and provider preparedness for dealing with postpartum haemorrhage and pre-eclampsia/eclampsia in public and private health facilities of northern Karnataka, India: a cross-sectional study.

    PubMed

    Jayanna, Krishnamurthy; Mony, Prem; B M, Ramesh; Thomas, Annamma; Gaikwad, Ajay; H L, Mohan; Blanchard, James F; Moses, Stephen; Avery, Lisa

    2014-09-04

    The maternal mortality ratio in India has been declining over the past decade, but remains unacceptably high at 212 per 100,000 live births. Postpartum haemorrhage (PPH) and pre- eclampsia/eclampsia contribute to 40% of all maternal deaths. We assessed facility readiness and provider preparedness to deal with these two maternal complications in public and private health facilities of northern Karnataka state, south India. We undertook a cross-sectional study of 131 primary health centres (PHCs) and 148 higher referral facilities (74 public and 74 private) in eight districts of the region. Facility infrastructure and providers' knowledge related to screening and management of complications were assessed using facility checklists and test cases, respectively. We also attempted an audit of case sheets to assess provider practice in the management of complications. Chi square tests were used for comparing proportions. 84.5% and 62.9% of all facilities had atleast one doctor and three nurses, respectively; only 13% of higher facilities had specialists. Magnesium sulphate, the drug of choice to control convulsions in eclampsia was available in 18% of PHCs, 48% of higher public facilities and 70% of private facilities. In response to the test case on eclampsia, 54.1% and 65.1% of providers would administer anti-hypertensives and magnesium sulphate, respectively; 24% would administer oxygen and only 18% would monitor for magnesium sulphate toxicity. For the test case on PPH, only 37.7% of the providers would assess for uterine tone, and 40% correctly defined early PPH. Specialists were better informed than the other cadres, and the differences were statistically significant. We experienced generally poor response rates for audits due to non-availability and non-maintenance of case sheets. Addressing gaps in facility readiness and provider competencies for emergency obstetric care, alongside improving coverage of institutional deliveries, is critical to improve maternal

  7. Nutritional status among women with pre-eclampsia and healthy pregnant and non-pregnant women in a Latin American country.

    PubMed

    Reyes, Laura; Garcia, Ronald; Ruiz, Silvia; Dehghan, Mahshid; López-Jaramillo, Patricio

    2012-03-01

    Pre-eclampsia (PE) is one of the leading causes of maternal and perinatal morbidity and mortality worldwide. It has been proposed that, among other risk factors, the nutritional status of women can lead to the endothelial dysfunction that characterizes this entity. The aim of the present study was to compare the nutritional status of women with PE with healthy pregnant and non-pregnant women. A multicenter case-control study was carried out. Between September 2006 and July 2009, 201 women with PE were compared with 201 pregnant, and 201 non-pregnant aged-matched women without cardiovascular or endocrine diseases. A clinical history and physical examination was performed. Fasting blood samples were drawn to measure serum glucose and lipid profile. The nutritional status of participants was assessed using a food frequency questionnaire. The average age of women was 26.6 ± 7.2 years. Compared to healthy pregnant controls, women with PE had a higher body mass index, higher fasting blood glucose levels, higher triglycerides, and lower high-density lipoprotein cholesterol levels. Women with PE had a higher intake of carbohydrates, energy intake and cereal compared to healthy pregnant and non-pregnant controls. A conditional logistic regression demonstrated that carbohydrate and sodium intake are associated with PE development. Diets of women with PE were characterized by higher energy and carbohydrate intake compared to normal pregnant and non-pregnant women. This suggests that higher carbohydrate and sodium intake increases the risk of PE among women in Colombia. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  8. Diagnostic accuracy of spot urine protein-to-creatinine ratio for proteinuria and its association with adverse pregnancy outcomes in Chinese pregnant patients with pre-eclampsia.

    PubMed

    Cheung, H C; Leung, K Y; Choi, C H

    2016-06-01

    International guidelines have endorsed spot urine protein-to-creatinine ratio of >30 mg protein/mmol creatinine as an alternative to a 24-hour urine sample to represent significant proteinuria. This study aimed to determine the accuracy of spot urine protein-to-creatinine ratio in predicting significant proteinuria and adverse pregnancy outcome. This case series was conducted in a regional obstetric unit in Hong Kong. A total of 120 Chinese pregnant patients with pre-eclampsia delivered at Queen Elizabeth Hospital from January 2011 to December 2013 were included. Relationship of spot urine protein-to-creatinine ratio and 24-hour proteinuria; accuracy of the ratio against 24-hour urine protein at different cut-offs; and relationship of such ratio and adverse pregnancy outcome were studied. Spot urine protein-to-creatinine ratio was correlated with 24-hour urine protein with Pearson correlation coefficient of 0.914 (P<0.0001) when the ratio was <200 mg/mmol. The optimal threshold of spot urine protein-to-creatinine ratio for diagnosing proteinuria in Chinese pregnant patients (33 mg/mmol) was similar to that stated in the international literature (30 mg/mmol). A cut-off of 20 mg/mmol provided a 100% sensitivity, and 52 mg/mmol provided a 100% specificity. There was no significant difference in spot urine protein-to-creatinine ratio between cases with and without adverse pregnancy outcome. Spot urine protein-to-creatinine ratio had a positive and significant correlation with 24-hour urine results in Chinese pre-eclamptic women when the ratio was <200 mg/mmol. Nonetheless, this ratio was not predictive of adverse pregnancy outcome.

  9. Analysis of Polymorphisms in Interleukin-10, Interleukin-6, and Interleukin-1 Receptor Antagonist in Mexican-Mestizo Women with Pre-eclampsia

    PubMed Central

    Valencia Villalvazo, Elith Yazmin; Canto-Cetina, Thelma; Romero Arauz, Juan Fernando; Coral-Vázquez, Ramón Mauricio; Canizales-Quinteros, Samuel; Coronel, Agustín; Carlos Falcón, Juan; Hernández Rivera, Jaime; Ibarra, Roberto; Polanco Reyes, Lucila

    2012-01-01

    Due to the fact that studies seeking associations of polymorphisms in regulatory regions of cytokine genes with pre-eclampsia (PE) have not always been consistent in different population analyses, the aim of this study was to investigate the possible association between rs1800896 of interleukin-10 (IL-10), rs1800795 of interleukin-6 (IL-6), and the variable number of tandem repeats (VNTR) in intron 2 of interleukin-1 receptor antagonist (IL-1Ra), as well as gene–gene interactions between these three polymorphisms with the presence of PE in Mexican-Mestizo women and one Amerindian population from México (Maya). A case–control study was performed where 411 pre-eclamptic cases and 613 controls were genotyped. For the rs1800896 of IL-10 and rs1800795 of IL-6, we used real-time polymerase chain reaction (PCR) allelic discrimination and for the VNTR of IL-1Ra, PCR. Allele frequency differences were assessed by Chi-squared test; logistic regression was used to test for associations; a gene–gene interaction was conducted. Genotypic and allelic distribution of the polymorphisms was similar in our population. The estimated of the gene–gene interaction between the polymorphisms did not differ significantly. However, we observed important differences in the distribution of the alleles and genotypes of the three polymorphisms analyzed between Mestiza-Mexicanas and Maya-Mestizo women. In conclusion, we did not find an association between polymorphisms in IL-10, IL-6, and IL-1Ra and PE in Mexican-Mestizo and Maya-Mestizo women. To our knowledge, this is the first time that these three polymorphisms were analyzed together with gene–gene interaction in women with PE. PMID:23013217

  10. TGFB1 Functional Gene Polymorphisms (C-509T and T869C) in the Maternal Susceptibility to Pre-eclampsia in South Indian Women.

    PubMed

    Deepthi, Goske; Chaithri, Ponnaluri Kamakshi; Latha, Prasanna; Rani, Vital Usha; Rahman, Police Fazul; Jahan, Parveen

    2015-10-01

    Pre-eclampsia (PE), a pregnancy-specific vascular disorder characterized by hypertension and proteinuria, is hypothesized to be the result of inadequate placental angiogenesis with attendant systemic inflammation. The pleiotropic cytokine, Transforming Growth Factor-β1 (TGF-β1), is considered to be a key candidate gene in the molecular pathogenesis of PE by virtue of its ability to not only regulate angiogenesis and apoptosis of target cells, but also by acting as a master controller of Th1/Th2 cytokine balance and production of the anti-inflammatory peripheral regulatory T cells (FOXP3+ Tregs). Based on this presumption, we screened a total of 469 pregnant women from South India that include 239 patients with PE and 230 healthy controls for the two functional polymorphisms of TGFB1 gene (C-509T and T869C). The genotype frequencies of these two polymorphisms differed significantly between the PE and control groups (P = 0.01 and P = 0.002, for the TGFB1 C-509T and T869C polymorphisms, respectively). Under the over-dominant model, the CT genotype of the TGFB1 C509T polymorphism showed a high protective effect (P = 3e-04), while the TT genotype of the same variant appeared to be the predisposing genotype (P = 0.003). The T-T and C-C haplotypes were found to be the risk haplotypes blocks towards PE (OR = 4.72; P = 0.031, OR = 5.39; P = 0.03), respectively. Strong linkage disequilibrium was seen between the two polymorphisms. Our investigations revealed a significant influence of TGFB1 C-509T and T869C polymorphisms on the PE risk in South Indian women. The study represents one of the first of its kind from the Indian subcontinent. © 2015 The Foundation for the Scandinavian Journal of Immunology.

  11. A clinical evaluation of placental growth factor in routine practice in high-risk women presenting with suspected pre-eclampsia and/or fetal growth restriction.

    PubMed

    Ormesher, L; Johnstone, E D; Shawkat, E; Dempsey, A; Chmiel, C; Ingram, E; Higgins, L E; Myers, J E

    2018-03-13

    To evaluate the use of plasma Placental Growth Factor (PlGF), recommended by the recent NICE guidance, in women with suspected pre-eclampsia (PE) and/or fetal growth restriction (FGR). Non-randomised prospective clinical evaluation study in high-risk antenatal clinics in a tertiary maternity unit. PlGF testing was performed in addition to routine clinical assessment in 260 women >20 weeks' gestation with chronic disease (hypertension, renal disease ± diabetes) with a change in maternal condition or in women with suspected FGR to determine the impact on clinical management. Results were revealed and standardised care pathways followed. Outcome of pregnancies with a low PlGF (<12 pg/ml and 13-100 pg/ml), impact on clinical service and the diagnostic accuracy of alternative PlGF cut-offs. 206/260 (79.2%) women had an adverse outcome (PE/birthweight < 10th centile/preterm birth). In our cohort, a low PlGF (<12 pg/ml) was associated with a shorter test-birth interval and universally (100% PPV) with an adverse pregnancy outcome, although 29/61 (47.5%) of women with PlGF < 12 pg/ml continued their pregnancy >14 days. The PlGF result altered clinical management (surveillance or timing of birth) in 196/260 (75.4%) cases. Alternative PlGF thresholds did not significantly improve diagnostic performance. Our evaluation confirms the value of PlGF as a diagnostic tool for placental dysfunction. However, low PlGF in isolation should not trigger iatrogenic delivery. Further research linking placental pathology, maternal disease and maternal PlGF levels is urgently needed before this test can be implemented in routine clinical practice. Copyright © 2018. Published by Elsevier B.V.

  12. Effect of Turkish classical music on prenatal anxiety and satisfaction: A randomized controlled trial in pregnant women with pre-eclampsia.

    PubMed

    Toker, Eylem; Kömürcü, Nuran

    2017-02-01

    The present study aimed to evaluate the effect of music therapy on anxiety and satisfaction in pregnant women with preeclampsia. A randomized controlled trial was performed on 70 pregnant women with pre-eclampsia hospitalized in the research and application hospital of Kahramanmaras Sütcü İmam University between December 2012 and February 2014. The subjects were allocated to experimental or control groups in a random manner (n=35 each). Pregnant women in the experimental group were subject to a 30min Turkish classical music therapy trial each day for a period of 7days (5days before and 2days after labor) whereas those in the control group received routine care and also were assigned to 30min of bed rest a day. The Personal Information Form, State-Trait Anxiety Inventory, and Newcastle Satisfaction with Nursing Scale were administered to participants. Data were analyzed using descriptive statistics, student t-test, and Mann-Whitney U test where appropriate. Outcome measures were anxiety scale scores, satisfaction scale scores, vital signs, fetal movement and fetal heart rate. The differences between anxiety scores were not statistically significant (p>0.05). On the other hand, Newcastle Satisfaction with Nursing Scale scores of the experiment group were higher than the control group (p<0.01). Finally, when considering fetal movement counts, a significant increase was determined in the experiment group, whereas Music Therapy had a minimalizing effect on fetal heart rate and a lowering effect on blood pressure (p<0.05). It may be suggested that nurses and midwives can utilize music therapy in the care and follow-up of pregnant women with preeclampsia in obstetrics units. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Neural abnormalities in early-onset and adolescence-onset conduct disorder.

    PubMed

    Passamonti, Luca; Fairchild, Graeme; Goodyer, Ian M; Hurford, Georgina; Hagan, Cindy C; Rowe, James B; Calder, Andrew J

    2010-07-01

    Conduct disorder (CD) is characterized by severe antisocial behavior that emerges in childhood (early-onset CD [EO-CD]) or adolescence (adolescence-onset CD [AO-CD]). Early-onset CD is proposed to have a neurodevelopmental basis, whereas AO-CD is thought to emerge owing to social mimicry of deviant peers. However, this developmental taxonomic theory is debated after reports of neuropsychological impairments in both CD subtypes. A critical, although unaddressed, issue is whether these subtypes present similar or distinct neurophysiological profiles. Hence, we investigated neurophysiological responses to emotional and neutral faces in regions associated with antisocial behavior (ie, the amygdala, ventromedial prefrontal cortex, insula, and orbitofrontal cortex) in individuals with EO-CD and AO-CD and in healthy control subjects. To investigate whether EO-CD and AO-CD subjects show neurophysiological abnormalities. Case-control study. Government research institute, university department. Seventy-five male adolescents and young adults aged 16 to 21 years, including 27 with EO-CD, 25 with AO-CD, and 23 healthy controls. Main Outcome Measure Neural activations measured by functional magnetic resonance imaging while participants viewed angry, sad, and neutral faces. Comparing angry vs neutral faces, participants with both CD subtypes displayed reduced responses in regions associated with antisocial behavior compared with controls; differences between the CD subtypes were not significant. Comparing each expression with fixation baseline revealed an abnormal (increased) amygdala response to neutral but not angry faces in both groups of CD relative to controls. For sad vs neutral faces, reduced amygdala activation was observed in EO-CD relative to AO-CD and control participants. Comparing each expression with fixation revealed hypoactive amygdala responses to sadness in individuals with EO-CD relative to AO-CD participants and controls. These findings were not accounted for

  14. Theory of Mind differences in older patients with early-onset and late-onset paranoid schizophrenia.

    PubMed

    Smeets-Janssen, M M J; Meesters, P D; Comijs, H C; Eikelenboom, P; Smit, J H; de Haan, L; Beekman, A T F; Stek, M L

    2013-11-01

    Theory of Mind (ToM) is considered an essential element of social cognition. In younger schizophrenia patients, ToM impairments have extensively been demonstrated. It is not clear whether similar impairments can be found in older schizophrenia patients and if these impairments differ between older patients with early-onset and late-onset schizophrenia. Theory of Mind abilities were assessed using the Hinting Task in 15 older patients (age 60 years and older) with early-onset paranoid schizophrenia, 15 older patients with late-onset paranoid schizophrenia and 30 healthy controls. ANCOVA was performed to test differences between groups. Analyses were adjusted for level of education. Effect sizes, partial eta squared (ε(2) ), were computed as an indication of the clinical relevance of the findings. Patients with early-onset schizophrenia scored significantly lower on the Hinting Task (mean 16.1; SD 4.3) compared with patients with late-onset schizophrenia (mean 18.6; SD 1.5) and with healthy controls (mean 19.0; SD 1.4). The effect size of this difference was large (ε(2)  = 0.2). These results suggest that ToM functioning may be a protective factor modulating the age at onset of psychosis. Further studies into the relationship between social cognition and onset age of psychosis are warranted. Copyright © 2013 John Wiley & Sons, Ltd.

  15. Comparing Characteristics of Early-Onset Injection Drug Users to Those With Late-Onset Injection in Kermanshah, Iran.

    PubMed

    Jorjoran Shushtari, Zahra; Noroozi, Alireza; Mirzazadeh, Ali; Ahounbar, Elahe; Hajbi, Ahmad; Najafi, Mohammad; Bazrafshan, Ali; Farhadi, Mohammad Hossin; Farhoudian, Ali; Higgs, Peter; Shahboulagh, Farahnaz Mohammadi; Waye, Katherine; Noroozi, Mehdi

    2017-05-12

    Characteristics and behaviors of early-onset injection drug users are under studied topics in Iran. This study aimed to identify and compare the demographic characteristics as well as the drug using behaviors of early-onset and late-onset injection drug users in Kermanshah, West Iran. In this cross-sectional study using snowball and convenience sampling, we recruited 450 people during the Fall of 2014 from two drop in centers in Kermanshah, Iran. We collected data through face-to-face interviews. Early-onset injection is defined as whether the person reported their first injection at 22 years of age or younger. Subsequently, late-onset injection is defined as 23 years of age or older. We compared the characteristics of the two groups through both univariate and multiple logistic analyses. Overall, 54% (CI 95%: 44.3%, 62.2%) were early injectors. After controlling for low socioeconomic status, initiation of drug use at a young age, multiple drug use and methamphetamine use were all significantly associated with a higher likelihood of early-onset injection. Additionally, early-onset injection was associated with recent syringe borrowing (OR = 2.6, p = 0.001), recent syringe lending (OR = 1.4, p = 0.01), recent cooker sharing (OR = 3.2, p = 0.01) and injecting two or more times a day (OR = 2.2, p = 0.04). Early-onset injectors were more likely to report a lower socioeconomic status, initiation of first drug use at a younger age, using methamphetamine alongside polydrug use, and engaging in higher risk taking behaviors like borrowing needles. With these associations, the study emphasizes the need for drug-prevention programs to focus on the transition to injection drug use at younger ages.

  16. Early Onset Recurrent Subtype of Adolescent Depression: Clinical and Psychosocial Correlates

    ERIC Educational Resources Information Center

    Hammen, Constance; Brennan, Patricia A.; Keenan-Miller, Danielle; Herr, Nathaniel R.

    2008-01-01

    Background: Evaluated trajectories of adolescent depression and their correlates in a longitudinal study of a community sample: early onset (by age 15) with major depression (MDE) recurrence between 15 and 20; early onset with no recurrence; later onset of major depression after age 15 with and without recurrence by 20; and never-depressed.…

  17. Early-onset schizophrenia: Symptoms and social class of origin.

    PubMed

    Gallagher, Bernard J; Jones, Brian J

    2017-09-01

    The genesis of schizophrenia is multifactorial, including biological and environmental risk factors. We tested for an interactive effect between early-onset schizophrenia (EOS) and social class of origins (socioeconomic status (SES)). Data were further analyzed for a possible connection to type of schizophrenic symptoms. Sampling/Methods: Data for the study are taken from the medical records of 642 patients from a large state hospital in the northeastern United States. Clinical assessments were divided into positive and negative symptomatology through application of the Scale for the Assessment of Negative Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS) and the Positive and Negative Syndrome Scale (PANSS). Detailed information about age of onset and SES of origin was obtained through Social Service Assessment interviews. We uncovered a significant impact of EOS among the poor that elevates risk for negative symptomatology. Poor SES alone does not increase the likelihood of EOS, but it magnifies the deleterious effect of EOS on negative symptoms. Future research on these variables may inform the relative contribution of each.

  18. Early and Real-Time Detection of Seasonal Influenza Onset

    PubMed Central

    Marques-Pita, Manuel

    2017-01-01

    Every year, influenza epidemics affect millions of people and place a strong burden on health care services. A timely knowledge of the onset of the epidemic could allow these services to prepare for the peak. We present a method that can reliably identify and signal the influenza outbreak. By combining official Influenza-Like Illness (ILI) incidence rates, searches for ILI-related terms on Google, and an on-call triage phone service, Saúde 24, we were able to identify the beginning of the flu season in 8 European countries, anticipating current official alerts by several weeks. This work shows that it is possible to detect and consistently anticipate the onset of the flu season, in real-time, regardless of the amplitude of the epidemic, with obvious advantages for health care authorities. We also show that the method is not limited to one country, specific region or language, and that it provides a simple and reliable signal that can be used in early detection of other seasonal diseases. PMID:28158192

  19. Early-Onset Vemurafenib-Induced DRESS Syndrome.

    PubMed

    Munch, Marion; Peuvrel, Lucie; Brocard, Anabelle; Saint Jean, Mélanie; Khammari, Amir; Dreno, Brigitte; Quereux, Gaelle

    2016-01-01

    Vemurafenib is a BRAF inhibitor indicated in metastatic or unresectable melanoma in patients with BRAF mutations. Vemurafenib is frequently toxic, but the toxicity is often not serious. The third case of vemurafenib-induced drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is reported herein. The case is unusual in that the onset was early, with symptoms emerging as of day 8 of treatment. Treatment of DRESS syndrome is not currently based on precise recommendations, but systemic corticosteroid therapy is effective in serious cases. Severe toxidermias under vemurafenib are exceptional; immediate discontinuation of treatment upon diagnosis is imperative. Switching from vemurafenib to dabrafenib then seems to constitute an interesting therapeutic alternative, since its efficacy is the same but with fewer cutaneous adverse reactions. This case highlights the importance of awareness of the risk of DRESS syndrome associated with vemurafenib and monitoring for warning signs from treatment initiation. © 2015 S. Karger AG, Basel.

  20. Escherichia coli early-onset sepsis: trends over two decades.

    PubMed

    Mendoza-Palomar, Natalia; Balasch-Carulla, Milena; González-Di Lauro, Sabina; Céspedes, Maria Concepció; Andreu, Antònia; Frick, Marie Antoinette; Linde, Maria Ángeles; Soler-Palacin, Pere

    2017-09-01

    Escherichia coli early-onset sepsis (EOS) is an important cause of mortality and morbidity in neonates, especially in preterm and very low birth weight (VLBW) newborns. The aim of our study was to evaluate potential changes in the clinical and microbiological characteristics of E. coli EOS in our setting. Epidemiological, clinical, and microbiological data from all neonates with proven E. coli EOS from January 1994 to December 2014 were retrospectively collected in a single tertiary care hospital in Barcelona (Spain). Seventy-eight E. coli EOS cases were analyzed. A slight increase in the incidence of E. coli EOS was observed during the study period. VLBW newborns remained the group with higher incidence (10.4 cases per 1000 live births) and mortality (35.3%). Systematic use of PCR increased E. coli EOS diagnosis, mainly in the term newborn group. There was an increase in resistant E. coli strains causing EOS, with especially high resistance to ampicillin and gentamicin (92.8 and 28.6%, respectively). Nonetheless, resistant strains were not associated with poorer clinical outcomes. There is an urgent need to reconsider the empirical therapy used in neonatal EOS, particularly in VLBW newborns. What is Known: • E. coli early-onset sepsis (EOS) and E. coli resistant strains have been described as overall stable but increasing in VLBW neonates (< 1.500 g) in previous studies. What is New: • Our study shows an increasing incidence of E. coli EOS in all age groups, overruling group B Streptoccocus for the last 10 years. E. coli resistant strains also increased equally in all age groups, with high resistance rates to our first line antibiotics (ampicillin and gentamicin). • Empiric antibiotic therapy of EOS, mainly in VLBW newborns, should be adapted to this new scenario.

  1. Early Identification of Autism: Early Characteristics, Onset of Symptoms, and Diagnostic Stability

    ERIC Educational Resources Information Center

    Webb, Sara Jane; Jones, Emily J. H.

    2009-01-01

    In the first year of life, infants who later go on to develop autistic spectrum disorders (ASD) may exhibit subtle disruptions in social interest and attention, communication, temperament, and head circumference growth that occur prior to the onset of clinical symptoms. These disruptions may reflect the early course of ASD development and may also…

  2. Spot protein-creatinine ratio and spot albumin-creatinine ratio in the assessment of pre-eclampsia: a diagnostic accuracy study with decision-analytic model-based economic evaluation and acceptability analysis.

    PubMed

    Waugh, Jason; Hooper, Richard; Lamb, Edmund; Robson, Stephen; Shennan, Andrew; Milne, Fiona; Price, Christopher; Thangaratinam, Shakila; Berdunov, Vladislav; Bingham, Jenn

    2017-10-01

    The National Institute for Health and Care Excellence (NICE) guidelines highlighted the need for 'large, high-quality prospective studies comparing the various methods of measuring proteinuria in women with new-onset hypertensive disorders during pregnancy'. The primary objective was to evaluate quantitative assessments of spot protein-creatinine ratio (SPCR) and spot albumin-creatinine ratio (SACR) in predicting severe pre-eclampsia (PE) compared with 24-hour urine protein measurement. The secondary objectives were to investigate interlaboratory assay variation, to evaluate SPCR and SACR thresholds in predicting adverse maternal and fetal outcomes and to assess the cost-effectiveness of these models. This was a prospective diagnostic accuracy cohort study, with decision-analytic modelling and a cost-effectiveness analysis. The setting was 36 obstetric units in England, UK. Pregnant women (aged ≥ 16 years), who were at > 20 weeks' gestation with confirmed gestational hypertension and trace or more proteinuria on an automated dipstick urinalysis. Women provided a spot urine sample for protein analysis (the recruitment sample) and were asked to collect a 24-hour urine sample, which was stored for secondary analysis. A further spot sample of urine was taken immediately before delivery. Outcome data were collected from hospital records. There were four index tests on a spot sample of urine: (1) SPCR test (conducted at the local laboratory); (2) SPCR test [conducted at the central laboratory using the benzethonium chloride (BZC) assay]; (3) SPCR test [conducted at the central laboratory using the pyrogallol red (PGR) assay]; and (4) SACR test (conducted at the central laboratory using an automated chemistry analyser). The comparator tests on 24-hour urine collection were a central test using the BZC assay and a central test using the PGR assay. The primary reference standard was the NICE definition of severe PE. Secondary reference standards were a clinician

  3. Patients with late-adult-onset ulcerative colitis have better outcomes than those with early onset disease.

    PubMed

    Ha, Christina Y; Newberry, Rodney D; Stone, Christian D; Ciorba, Matthew A

    2010-08-01

    The influence of age on the presentation, clinical course, and therapeutic response of patients with adult-onset ulcerative colitis (UC) is understudied. Given potential age-related differences in risk factors and immune function, we sought to determine if disease behavior or clinical outcomes differed between patients diagnosed with UC in later versus earlier stages of adulthood. We performed a retrospective cohort study of 295 patients with UC seen at a tertiary care center from 2001 to 2008. Adult subjects newly diagnosed with UC between the ages of 18 and 30 years were defined as early onset, those newly diagnosed at age 50 or older were defined as late onset. The 2 groups were analyzed for differences in medication use and clinical end points, including disease extent, severity at the time of diagnosis, and steroid-free clinical remission at 1 year after disease onset. Disease extent and symptom severity were similar between groups at the time of diagnosis. One year after diagnosis, more patients in the late-onset group achieved steroid-free clinical remission (64% vs 49%; P = .01). Among those who required systemic steroid therapy, more late-onset patients achieved steroid-free remission by 1 year (50% vs 32%; P = .01). Former smoking status was a more common risk factor in the late-onset cohort (P < .001), whereas more early onset patients had a positive family history (P = .008). Patients with early and late-adult-onset UC have similar initial clinical presentations, but differ in disease risk factors. Late-onset patients have better responses to therapy 1 year after diagnosis. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

  4. Genomic Analyses of Patients With Unexplained Early-Onset Scoliosis.

    PubMed

    Gao, Xiaochong; Gotway, Garrett; Rathjen, Karl; Johnston, Charles; Sparagana, Steven; Wise, Carol A

    2014-09-01

    To test for rare genetic mutations, a cohort of patients with unexplained early-onset scoliosis (EOS) was screened using high-density microarray genotyping. A cohort of patients with adolescent idiopathic scoliosis (AIS) was similarly screened and the results were compared. Patients with scoliosis in infancy or early childhood (EOS) are at high risk for progressive deformity and associated problems including respiratory compromise. Early-onset scoliosis is frequently associated with genetic disorders but many patients present with nonspecific clinical features and without an associated diagnosis. The authors hypothesized that EOS in these patients may be caused by rare genetic mutations detectable by next-generation genomic methods. The researchers identified 24 patients with unexplained EOS from pediatric orthopedic clinics. They genotyped them, along with 39 connecting family members, using the Illumina OmniExpress-12, version 1.0 beadchip. Resulting genotypes were analyzed for chromosomal changes, specifically copy number variation and absence of heterozygosity. They screened 482 adolescent idiopathic scoliosis (AIS) patients and 744 healthy controls, who were similarly genotyped with the same beadchip, for chromosomal changes identified in the EOS cohort. Copy number variation and absence of heterozygosity analyses revealed a genetic diagnosis of chromosome 15q24 microdeletion syndrome in 1 patient and maternal uniparental disomy of chromosome 14 in a second one. Prior genetic testing and clinical evaluations had been negative in both cases. A large novel chromosome 10 deletion was likely causal in a third EOS patient. These mutations identified in the EOS patients were absent in AIS patients and controls, and thus were not associated with AIS or found in asymptomatic individuals. These data underscore the usefulness of updated genetic evaluations including high-density microarray-based genotyping and other next-generation methods in patients with unexplained

  5. Early childhood predictors of early onset of smoking: a birth prospective study.

    PubMed

    Hayatbakhsh, Reza; Mamun, Abdullah A; Williams, Gail M; O'Callaghan, Michael J; Najman, Jake M

    2013-10-01

    Early onset of smoking is associated with subsequent abuse of other substances and development of negative health outcomes. This study aimed to examine early life predictors of onset of smoking in an Australian young cohort. Data were from the Mater Hospital and University of Queensland Study of Pregnancy (MUSP), a population-based prospective birth cohort study (1981-2012). The present study is based on a cohort of 3714 young adults who self-reported smoking status and age of onset of smoking at the 21-year follow-up. Of these, data were available for 3039 on early childhood factors collected between the baseline and 14-year follow-up of the study. Of 3714 young adults, 49.6% (49.9% males and 49.3% females) reported having ever smoked cigarettes. For those who had ever smoked, mean and median ages at first smoke were 15.5 and 16.0years, respectively. In multivariate Cox proportional hazard analysis mother's education, change in maternal marital status, maternal cigarette smoking and alcohol consumption, maternal depression and child externalizing when the child was 5years statistically significantly predicted early onset of smoking. The data suggest that individuals exposed to personal and environmental risk factors during the early stage of childhood are at increased risk of initiation to cigarette smoking at an earlier age. Identification of the pathways of association between these early life factors and initiation to cigarette smoking may help reduce risk of tobacco smoking in adolescents and its adverse consequences. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Rapid onset of efficacy of rasagiline in early Parkinson's disease.

    PubMed

    Zambito Marsala, Sandro; Vitaliani, Roberta; Volpe, Daniele; Capozzoli, Francesca; Baroni, Luciana; Belgrado, Enrico; Borsato, Carlo; Gioulis, Manuela; Marchini, Corrado; Antonini, Angelo

    2013-11-01

    Rasagiline is a monoamine oxidase type-B inhibitor used as monotherapy or in addition to levodopa in the treatment of Parkinson's disease (PD). This naturalistic single-blind study was aimed at evaluating the rapidity of onset effect of rasagiline on motor symptoms in a cohort of early relatively elderly PD patients. 102 outpatients (55 males, median age 71 years) have been selected: 26 were PD therapy-naive and 76 received rasagiline as add-on therapy. The third section of the Unified Parkinson's Disease Rating Scale (UPDRSIII) and the Hoehn-Yahr (HY) scale were assessed at baseline and after 1 and 4 weeks thereafter. The mean UPDRS III total score (-6.7 at week 1 and -8.9 at week 4) and single items, as well as mean HY score (-0.40 at week 1 and -0.67 at week 4), significantly decreased from baseline (p < 0.001). Improvements were significant in both therapy-naive and add-on therapy patients: the mean decreases from baseline to week 4 in UPDRSIII and HY score were -8.8 and -0.46, and -9.0 and -0.74, respectively, in the two subgroups. The mean decrease from baseline in UPDRSIII and HY score did not significantly differ in patients aged > or ≤71 years. Rasagiline had a rapid therapeutic effect from the first week of therapy, which further improved at 4 weeks. The rapid onset of action and the absence of a dose titration are important issues in the management of the PD patient.

  7. Incidence of early-onset dementia in Mar del Plata.

    PubMed

    Sanchez Abraham, M; Scharovsky, D; Romano, L M; Ayala, M; Aleman, A; Sottano, E; Etchepareborda, I; Colla Machado, C; García, M I; Gonorazky, S E

    2015-03-01

    Early-onset dementia (EOD) is defined as dementia with onset before the age of 65 years. EOD is increasingly recognised as an important clinical and social problem with devastating consequences for patients and caregivers. Determine the annual crude incidence rate and the specific incidence rates by sex and age in patients with EOD, and the standardised rate using the last national census of the population of Argentina (NCPA), from 2010. Hospital Privado de Comunidad, Mar del Plata, Argentina, attends a closed population and is the sole healthcare provider for 17 614 people. Using the database pertaining to the Geriatric Care department, we identified all patients diagnosed with EOD between 1 January, 2005 and 31 December, 2011. EOD was defined as dementia diagnosed in patients younger than 65. The study period yielded 14 patients diagnosed with EOD out of a total of 287 patients evaluated for memory concerns. The crude annual incidence of EOD was 11 per 100 000/year (CI 95%: 6.25-19.1): 17 per 100 000 (CI 95%: 7.2-33.1) in men and 8 per 100 000 (CI 95%: 3.4-17.2) in women. We observed a statistically significant increase when comparing incidence rates between patients aged 21 to <55 years and ≥ 55 to <65 years (3 vs 22 per 100 000, P=.0014). The rate adjusted by NCPA census data was 5.8 cases of EOD habitants/year. This study, conducted in a closed population, yielded an EOD incidence rate of 11 per 100 000 inhabitants/year. To the best of our knowledge, this is the first prospective epidemiological study in Argentina and in Latin America. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  8. Gaze holding deficits discriminate early from late onset cerebellar degeneration.

    PubMed

    Tarnutzer, Alexander A; Weber, K P; Schuknecht, B; Straumann, D; Marti, S; Bertolini, G

    2015-08-01

    The vestibulo-cerebellum calibrates the output of the inherently leaky brainstem neural velocity-to-position integrator to provide stable gaze holding. In healthy humans small-amplitude centrifugal nystagmus is present at extreme gaze-angles, with a non-linear relationship between eye-drift velocity and eye eccentricity. In cerebellar degeneration this calibration is impaired, resulting in pathological gaze-evoked nystagmus (GEN). For cerebellar dysfunction, increased eye drift may be present at any gaze angle (reflecting pure scaling of eye drift found in controls) or restricted to far-lateral gaze (reflecting changes in shape of the non-linear relationship) and resulting eyed-drift patterns could be related to specific disorders. We recorded horizontal eye positions in 21 patients with cerebellar neurodegeneration (gaze-angle = ±40°) and clinically confirmed GEN. Eye-drift velocity, linearity and symmetry of drift were determined. MR-images were assessed for cerebellar atrophy. In our patients, the relation between eye-drift velocity and gaze eccentricity was non-linear, yielding (compared to controls) significant GEN at gaze-eccentricities ≥20°. Pure scaling was most frequently observed (n = 10/18), followed by pure shape-changing (n = 4/18) and a mixed pattern (n = 4/18). Pure shape-changing patients were significantly (p = 0.001) younger at disease-onset compared to pure scaling patients. Atrophy centered around the superior/dorsal vermis, flocculus/paraflocculus and dentate nucleus and did not correlate with the specific drift behaviors observed. Eye drift in cerebellar degeneration varies in magnitude; however, it retains its non-linear properties. With different drift patterns being linked to age at disease-onset, we propose that the gaze-holding pattern (scaling vs. shape-changing) may discriminate early- from late-onset cerebellar degeneration. Whether this allows a distinction among specific cerebellar disorders remains to be determined.

  9. Retained placenta is associated with pre-eclampsia, stillbirth, giving birth to a small-for-gestational-age infant, and spontaneous preterm birth: a national register-based study.

    PubMed

    Endler, M; Saltvedt, S; Cnattingius, S; Stephansson, O; Wikström, A-K

    2014-11-01

    To evaluate whether defective placentation disorders, i.e. pre-eclampsia, stillbirth, small for gestational age (SGA), and spontaneous preterm birth, are associated with risk of retained placenta. Population-based cohort study. Sweden. Primiparous women in Sweden with singleton vaginal deliveries between 1997 and 2009 at 32-41 weeks of gestation (n = 386,607), without placental abruption or infants with congenital malformations. Risks were calculated as odds ratios (ORs) by unconditional logistic regression with 95% confidence intervals (95% CIs) after adjustments for maternal, delivery, and infant characteristics. Retained placenta, defined by the presence of both a diagnostic code (of retained placenta) and a procedure code (for the manual removal of the placenta). The overall rate of retained placenta was 2.17%. The risk of retained placenta was increased for women with pre-eclampsia (adjusted OR, aOR, 1.37, 95% CI 1.21-1.54), stillbirth (aOR 1.71, 95% CI 1.28-2.29), SGA birth (aOR 1.47, 95% CI 1.28-1.70), and spontaneous preterm birth (32-34 weeks of gestation, aOR 2.35, 95% CI 1.97-2.81; 35-36 weeks of gestation, aOR 1.55, 95% CI 1.37-1.75). The risk was further increased for women with preterm pre-eclampsia (aOR 1.69, 95% CI 1.25-2.28) and preterm SGA birth (aOR 2.19, 95% CI 1.42-3.38). There was no association between preterm stillbirth (aOR 1.10, 95% CI 0.63-1.92) and retained placenta, but the exposed group comprised only 15 cases. Defective placentation disorders are associated with an increased risk of retained placenta. Whether these relationships indicate a common pathophysiology remains to be investigated. © 2014 Royal College of Obstetricians and Gynaecologists.

  10. Correlations between serum assays of human chorionic gonadotrophin (hCG) and human placental lactogen (hPL) and pre-eclampsia or intrauterine growth restriction (IUGR) among nulliparas younger than 38 years.

    PubMed

    Merviel, P; Müller, F; Guibourdenche, J; Berkane, N; Gaudet, R; Bréart, G; Uzan, S

    2001-03-01

    To study the relation between serum human chorionic gonadotrophin (hCG) levels measured at 15-18 weeks and gestational disorders, assess their correlation with the artery uteroplacental Doppler (AUD) at 24 weeks among nulliparas, and assess the predictivity of the hCG/hPL (human placental lactogen) ratio for pre-eclampsia. Retrospective study of two groups of women younger than 38 years old: one with an elevated serum hCG level (2 MoM (multiples of the median) or more) and a normal fetal karyotype (group A), and the other with a lower hCG level (group B). Within each group, we studied the nulliparas separately (respectively groups AO and BO). We analyzed the double screening, elevated hCG levels with abnormal AUD, for the predicting of hypertensive disorders. Elevated hCG levels were significantly (p<0.05) more prevalent among women who developed gestational diabetes (groups A and AO) and among nulliparas with pregnancy-induced hypertension and pre-eclampsia (AO). Among nulliparas, the combination of the hCG assay and a subsequent Doppler increased the positive predictive value (PPV) of the assay from 19 to 75%, without reducing its negative predictive value (NPV) for gestational vascular disorders. The hCG/hPL ratio did not improve the predictivity of the hCG assay alone for pre-eclampsia. An hCG level of 2 MoM or more at 15-18 weeks identifies a group of women at risk of gestational vascular disorders; it therefore ought to lead to an AUD at 24 weeks. This double screening should be able to define a population of women at risk of developing a hypertensive disorder, who could thus benefit from a preventive treatment, as aspirin.

  11. Transforming growth factor beta-1 (TGF-β1) gene single nucleotide polymorphisms (SNPs) and susceptibility to pre-eclampsia in Iranian women: A case-control study.

    PubMed

    Khani, Masood; Amani, Davar; Taheripanah, Robabeh; Sanadgol, Nima; Feizollahzadeh, Sadegh; Rahmani, Zahra

    2015-10-01

    Pre-eclampsia (PE) is a disorder of pregnancy characterized by high blood pressure and proteinuria. Transforming growth factor beta-1 (TGF-β1) is an important replicated PE candidate gene, and few studies have evaluated the direct association of TGF-β polymorphisms and risk to PE. The aim of this study was to investigate the association between three SNPs of TGF-β1 and serum level of this cytokine in PE patients and controls. In this study the polymorphisms of the TGF-β1 gene at the coding region, and positions 29T→C (Leu 10 Pro), 74G→C (Arg 25 Pro) and 788C→T (Thr 263 Ile) were studied in 123 PE and 120 normal subjects using PCR-restriction fragment length polymorphism PCR-(RFLP) and amplification refractory mutation system (ARMS)-PCR methods. Moreover, serum TGF-β1 was determined by enzyme-linked immunosorbent assay (ELISA) technique. At positions 74G→C and 29T→C the genotypes and allele frequencies showed no significant differences between PE patients and normal controls (P=0.3 and P=0.5 respectively). While in the case of position 788C→T both genotypes and allele frequencies were significantly different between PE patients and controls (P=0.02). Haplotype analysis on three polymorphic sites showed no significant differences between PE and control individuals (P=0.8). TGC and CGC haplotypes were the most frequent in both studied groups. The mean serum TGF-β1 level was significantly higher (62.73ng/ml) in PE patients compared with pregnant (47.01ng/ml) and non-pregnant (40.68ng/ml) control groups (P=0.0001). The results of this study suggest that TGF-β1 gene 788C→T polymorphism is an important factor mediating the casual pathway of preeclampsia. Copyright © 2015 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

  12. Prediction of severe pre-eclampsia/HELLP syndrome by combination of sFlt-1, CT-pro-ET-1 and blood pressure: exploratory study.

    PubMed

    Lind Malte, A; Uldbjerg, N; Wright, D; Tørring, N

    2018-06-01

    To evaluate the performance of a combination of angiogenic and vasoactive biomarkers to predict the development of severe pre-eclampsia (PE)/HELLP syndrome in the third trimester. Included were 215 women referred in the third trimester to an obstetric outpatient clinic with suspected PE (mean gestational age, 35 + 4 weeks), and 94 with normal pregnancy attending a midwife clinic. Cases were categorized as having subclinical PE, essential hypertension, gestational hypertension, moderate PE, and severe PE/HELLP syndrome. Blood samples were analyzed by immunoassay and groups were compared with respect to potential clinical and biochemical biomarkers, with the primary outcome being development of severe PE/HELLP syndrome within 1 week and within 2 weeks of analysis. The most promising markers were also assessed in combination. In the patients presenting with mild to moderate symptoms of PE, the individual markers which performed best for the prediction of progression to severe PE/HELLP syndrome within 1 week and within 2 weeks of biomarker evaluation were C-terminal pro-endothelin-1 (CT-pro-ET-1) (area under the receiver-operating characteristics curve (AUC), 0.82 and 0.78, respectively), soluble fms-like tyrosine kinase-1 (sFlt-1) (AUC, 0.81 and 0.76), systolic blood pressure (AUC, 0.80 and 0.68) and midregional pro-atrial natriuretic peptide (AUC, 0.79 and 0.77). The combination of biomarkers with the best performance was CT-pro-ET-1, sFlt-1 and systolic blood pressure, achieving an AUC of 0.94 for prediction of development of severe PE/HELLP syndrome within 1 week and an AUC of 0.83 for prediction of their development within 2 weeks of biomarker evaluation. The performance of CT-pro-ET-1 for prediction of the development of PE/HELLP syndrome in the third trimester was promising, especially in combination with sFlt-1 and systolic blood pressure. This was an exploratory study and our findings should be confirmed in further studies. Copyright © 2017

  13. Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia between 34 and 37 weeks' gestation (HYPITAT-II): a multicentre, open-label randomised controlled trial.

    PubMed

    Langenveld, Josje; Broekhuijsen, Kim; van Baaren, Gert-Jan; van Pampus, Maria G; van Kaam, Anton H; Groen, Henk; Porath, Martina; Oudijk, Martijn A; Bloemenkamp, Kitty W; Groot, Christianne J de; van Beek, Erik; van Huizen, Marloes E; Oosterbaan, Herman P; Willekes, Christine; Wijnen-Duvekot, Ella J; Franssen, Maureen T M; Perquin, Denise A M; Sporken, Jan M J; Woiski, Mallory D; Bremer, Henk A; Papatsonis, Dimitri N M; Brons, Jozien T J; Kaplan, Mesruwe; Nij Bijvanck, Bas W A; Mol, Ben-Willen J

    2011-07-07

    Gestational hypertension (GH) and pre-eclampsia (PE) can result in severe complications such as eclampsia, placental abruption, syndrome of Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) and ultimately even neonatal or maternal death. We recently showed that in women with GH or mild PE at term induction of labour reduces both high risk situations for mothers as well as the caesarean section rate. In view of this knowledge, one can raise the question whether women with severe hypertension, pre-eclampsia or deterioration chronic hypertension between 34 and 37 weeks of gestation should be delivered or monitored expectantly. Induction of labour might prevent maternal complications. However, induction of labour in late pre-term pregnancy might increase neonatal morbidity and mortality compared with delivery at term. Pregnant women with severe gestational hypertension, mild pre-eclampsia or deteriorating chronic hypertension at a gestational age between 34+0 and 36+6 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant monitoring. In the expectant monitoring arm, women will be induced only when the maternal or fetal condition detoriates or at 37+0 weeks of gestation. The primary outcome measure is a composite endpoint of maternal mortality, severe maternal complications (eclampsia, HELLP syndrome, pulmonary oedema and thromboembolic disease) and progression to severe pre-eclampsia. Secondary outcomes measures are respiratory distress syndrome (RDS), neonatal morbidity and mortality, caesarean section and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be intention to treat. The power calculation is based on an expectant reduction of the maternal composite endpoint from 5% to 1% for an expected increase in neonatal RDS from 1% at 37 weeks to 10% at 34 weeks. This implies that 680 women have to be randomised. This trial will

  14. Neurocognition in early-onset schizophrenia and schizoaffective disorders.

    PubMed

    Hooper, Stephen R; Giuliano, Anthony J; Youngstrom, Eric A; Breiger, David; Sikich, Linmarie; Frazier, Jean A; Findling, Robert L; McClellan, Jon; Hamer, Robert M; Vitiello, Benedetto; Lieberman, Jeffrey A

    2010-01-01

    We examined the neuropsychological functioning of youth enrolled in the NIMH funded trial, Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). We compared the baseline neuropsychological functioning of youth with schizophrenia (SZ, n = 79) to those with schizoaffective disorder (SA, n = 40), and examined the relationship of different variables of illness severity and adaptive behavior to neuropsychological functioning. Participants ranged in age from 8 to 19 years. Diagnostic status was confirmed via structured interview over multiple time points. Domains of neuropsychological functioning included fine-motor, attention, working memory, problem-solving efficiency, inhibitory control, and social cognition. Other variables included intelligence (IQ), academic achievement skills, adaptive behavior, and different measures of illness severity. The two groups did not differ on IQ or on any of the neuropsychological domains. The SZ group performed significantly lower in spelling. A high proportion of individuals in both groups reflected significant intellectual and academic achievement skill deficits. Significant correlations were found between the neurocognitive domains and both illness severity and adaptive behavior variables. There were few differences between the SZ and SA groups on IQ, achievement, or neuropsychological functioning; however, both groups showed significantly high rates of deficits in IQ and basic academic skills. Correlations of the neurocognitive functions with illness severity and adaptive behavior were small to moderate in magnitude. These findings continue to implicate the importance of neurocognitive functioning as a key area of vulnerability in the study of youth with schizophrenia spectrum disorders.

  15. Sex-specific cognitive abnormalities in early-onset psychosis.

    PubMed

    Ruiz-Veguilla, Miguel; Moreno-Granados, Josefa; Salcedo-Marin, Maria D; Barrigon, Maria L; Blanco-Morales, Maria J; Igunza, Evelio; Cañabate, Anselmo; Garcia, Maria D; Guijarro, Teresa; Diaz-Atienza, Francisco; Ferrin, Maite

    2017-01-01

    Brain maturation differs depending on the area of the brain and sex. Girls show an earlier peak in maturation of the prefrontal cortex. Although differences between adult females and males with schizophrenia have been widely studied, there has been less research in girls and boys with psychosis. The purpose of this study was to examine differences in verbal and visual memory, verbal working memory, auditory attention, processing speed, and cognitive flexibility between boys and girls. We compared a group of 80 boys and girls with first-episode psychosis to a group of controls. We found interactions between group and sex in verbal working memory (p = 0.04) and auditory attention (p = 0.01). The female controls showed better working memory (p = 0.01) and auditory attention (p = 0.001) than males. However, we did not find any sex differences in working memory (p = 0.91) or auditory attention (p = 0.93) in the psychosis group. These results are consistent with the presence of sex-modulated cognitive profiles at first presentation of early-onset psychosis.

  16. Facial emotion identification in early-onset psychosis.

    PubMed

    Barkl, Sophie J; Lah, Suncica; Starling, Jean; Hainsworth, Cassandra; Harris, Anthony W F; Williams, Leanne M

    2014-12-01

    Facial emotion identification (FEI) deficits are common in patients with chronic schizophrenia and are strongly related to impaired functioning. The objectives of this study were to determine whether FEI deficits are present and emotion specific in people experiencing early-onset psychosis (EOP), and related to current clinical symptoms and functioning. Patients with EOP (n=34, mean age=14.11, 53% female) and healthy controls (HC, n=42, mean age 13.80, 51% female) completed a task of FEI that measured accuracy, error pattern and response time. Relative to HC, patients with EOP (i) had lower accuracy for identifying facial expressions of emotions, especially fear, anger and disgust, (ii) were more likely to misattribute other emotional expressions as fear or disgust, and (iii) were slower at accurately identifying all facial expressions. FEI accuracy was not related to clinical symptoms or current functioning. Deficits in FEI (especially for fear, anger and disgust) are evident in EOP. Our findings suggest that while emotion identification deficits may reflect a trait susceptibility marker, functional deficits may represent a sequelae of illness. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. Biallelic TBCD Mutations Cause Early-Onset Neurodegenerative Encephalopathy.

    PubMed

    Miyake, Noriko; Fukai, Ryoko; Ohba, Chihiro; Chihara, Takahiro; Miura, Masayuki; Shimizu, Hiroshi; Kakita, Akiyoshi; Imagawa, Eri; Shiina, Masaaki; Ogata, Kazuhiro; Okuno-Yuguchi, Jiu; Fueki, Noboru; Ogiso, Yoshifumi; Suzumura, Hiroshi; Watabe, Yoshiyuki; Imataka, George; Leong, Huey Yin; Fattal-Valevski, Aviva; Kramer, Uri; Miyatake, Satoko; Kato, Mitsuhiro; Okamoto, Nobuhiko; Sato, Yoshinori; Mitsuhashi, Satomi; Nishino, Ichizo; Kaneko, Naofumi; Nishiyama, Akira; Tamura, Tomohiko; Mizuguchi, Takeshi; Nakashima, Mitsuko; Tanaka, Fumiaki; Saitsu, Hirotomo; Matsumoto, Naomichi

    2016-10-06

    We describe four families with affected siblings showing unique clinical features: early-onset (before 1 year of age) progressive diffuse brain atrophy with regression, postnatal microcephaly, postnatal growth retardation, muscle weakness/atrophy, and respiratory failure. By whole-exome sequencing, we identified biallelic TBCD mutations in eight affected individuals from the four families. TBCD encodes TBCD (tubulin folding co-factor D), which is one of five tubulin-specific chaperones playing a pivotal role in microtubule assembly in all cells. A total of seven mutations were found: five missense mutations, one nonsense, and one splice site mutation resulting in a frameshift. In vitro cell experiments revealed the impaired binding between most mutant TBCD proteins and ARL2, TBCE, and β-tubulin. The in vivo experiments using olfactory projection neurons in Drosophila melanogaster indicated that the TBCD mutations caused loss of function. The wide range of clinical severity seen in this neurodegenerative encephalopathy may result from the residual function of mutant TBCD proteins. Furthermore, the autopsied brain from one deceased individual showed characteristic neurodegenerative findings: cactus and somatic sprout formations in the residual Purkinje cells in the cerebellum, which are also seen in some diseases associated with mitochondrial impairment. Defects of microtubule formation caused by TBCD mutations may underlie the pathomechanism of this neurodegenerative encephalopathy. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  18. Early-onset arthritis in retired National Football League players.

    PubMed

    Golightly, Yvonne M; Marshall, Stephen W; Callahan, Leigh F; Guskiewicz, Kevin

    2009-09-01

    Injury has been identified as a potential risk factor for osteoarthritis. However, no previous study has addressed playing-career injuries and subsequent osteoarthritis in a large sample of former athletes. The purpose of this study was to describe the prevalence and determinants of arthritis and osteoarthritis in retired professional football players. Self-reported arthritis prevalence and retrospectively-recalled injury history were examined in a cross-sectional survey of 2,538 retired football players. Football players reported a high incidence of injury from their professional playing days (52.8% reported knee injuries, 74.1% reported ligament/tendon injuries, and 14.2% reported anterior cruciate ligament tears). For those under 60 years, 40.6% of retired NFL players reported arthritis, compared with 11.7% of U.S. males (prevalence ratio = 3.5, 95% CI: 3.3 to 3.7). Within the retired NFL player cohort, osteoarthritis was more prevalent in those with a history of knee injury (prevalence ratio = 1.7, 95% CI: 1.5 to 1.9) and ligament/tendon injury (prevalence ratio = 1.6, 95% CI: 1.4 to 1.9). In males under the age of 60, arthritis is over 3 times more prevalent in retired NFL players than in the general U.S. population. This excess of early-onset arthritis may be due to the high incidence of injury in football.

  19. Early and Late Onset Side Effects of Photodynamic Therapy

    PubMed Central

    Borgia, Francesco; Giuffrida, Roberta; Caradonna, Emanuela; Guarneri, Fabrizio; Cannavò, Serafinella P.

    2018-01-01

    Photodynamic Therapy (PDT) is a non-invasive treatment successfully used for neoplastic, inflammatory and infectious skin diseases. One of its strengths is represented by the high safety profile, even in elderly and/or immuno-depressed subjects. PDT, however, may induce early and late onset side effects. Erythema, pain, burns, edema, itching, desquamation, and pustular formation, often in association with each other, are frequently observed in course of exposure to the light source and in the hours/days immediately after the therapy. In particular, pain is a clinically relevant short-term complication that also reduces long-term patient satisfaction. Rare complications are urticaria, contact dermatitis at the site of application of the photosensitizer, and erosive pustular dermatosis. Debated is the relationship between PDT and carcinogenesis: the eruptive appearance of squamous cell carcinoma (SCC) in previously treated areas has been correlated to a condition of local and/or systemic immunosuppression or to the selection of PDT-resistant SCC. Here we review the literature, with particular emphasis to the pathogenic hypotheses underlying these observations. PMID:29382133

  20. Psychosocial impact of early onset dementia among caregivers.

    PubMed

    Kimura, Nathália R S; Maffioletti, Virgínia L R; Santos, Raquel L; Baptista, Maria Alice Tourinho; Dourado, Marcia C N

    2015-01-01

    There is growing recognition of early onset dementia (EOD) as a significant clinical and social problem because of its effects on physical and mental health of people with dementia (PWD) and their caregivers. To analyze the psychosocial impact of EOD in family caregivers. The study design was qualitative. Nine EOD caregivers (7 women) were recruited at a service for Alzheimer's disease and assessed using semi-structured interviews. Interpretative phenomenological analysis was used to analyze caregivers' reports. Five themes emerged from the narratives: psychological and emotional impact; physical impact; financial and professional impact; social impact and need for support services. The majority of the caregivers of people with EOD perceived their emotional wellbeing as poor or extremely poor. Carers reported poor physical health, which tends to be longer-lasting than mental health problems. Two caregivers had to retire after the disclosure of the dementia diagnosis, and seven reduced their work loads because they had to look after PWD. Preserving the abilities of PWD is essential to maintain their self-esteem, dignity and sense of utility. For the caregivers, interventions and stimulating activities make PWD feel worthwhile and contribute to improving life. The caregivers of people with EOD assume the role of caregiver prematurely and need to balance this activity with other responsibilities. There is a need for more studies of EOD in order to improve understanding of the impact of this disease and to enable development of adequate services for PWD and their caregivers.

  1. Molecular genetics of early-onset Alzheimer's disease revisited.

    PubMed

    Cacace, Rita; Sleegers, Kristel; Van Broeckhoven, Christine

    2016-06-01

    As the discovery of the Alzheimer's disease (AD) genes, APP, PSEN1, and PSEN2, in families with autosomal dominant early-onset AD (EOAD), gene discovery in familial EOAD came more or less to a standstill. Only 5% of EOAD patients are carrying a pathogenic mutation in one of the AD genes or a apolipoprotein E (APOE) risk allele ε4, most of EOAD patients remain unexplained. Here, we aimed at summarizing the current knowledge of EOAD genetics and its role in ongoing approaches to understand the biology of AD and disease symptomatology as well as developing new therapeutics. Next, we explored the possible molecular mechanisms that might underlie the missing genetic etiology of EOAD and discussed how the use of massive parallel sequencing technologies triggered novel gene discoveries. To conclude, we commented on the relevance of reinvestigating EOAD patients as a means to explore potential new avenues for translational research and therapeutic discoveries. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Somatic mutations in early onset luminal breast cancer

    PubMed Central

    de Lyra, Eduardo Carneiro; Hirata Katayama, Maria Lucia; Maistro, Simone; de Vasconcellos Valle, Pedro Wilson Mompean; de Lima Pereira, Gláucia Fernanda; Rodrigues, Lívia Munhoz; de Menezes Pacheco Serio, Pedro Adolpho; de Gouvêa, Ana Carolina Ribeiro Chaves; Geyer, Felipe Correa; Basso, Ricardo Alves; Pasini, Fátima Solange; del Pilar Esteves Diz, Maria; Brentani, Maria Mitzi; Guedes Sampaio Góes, João Carlos; Chammas, Roger; Boutros, Paul C.; Koike Folgueira, Maria Aparecida Azevedo

    2018-01-01

    Breast cancer arising in very young patients may be biologically distinct; however, these tumors have been less well studied. We characterized a group of very young patients (≤ 35 years) for BRCA germline mutation and for somatic mutations in luminal (HER2 negative) breast cancer. Thirteen of 79 unselected very young patients were BRCA1/2 germline mutation carriers. Of the non-BRCA tumors, eight with luminal subtype (HER2 negative) were submitted for whole exome sequencing and integrated with 29 luminal samples from the COSMIC database or previous literature for analysis. We identified C to T single nucleotide variants (SNVs) as the most common base-change. A median of six candidate driver genes was mutated by SNVs in each sample and the most frequently mutated genes were PIK3CA, GATA3, TP53 and MAP2K4. Potential cancer drivers affected in the present non-BRCA tumors include GRHL2, PIK3AP1, CACNA1E, SEMA6D, SMURF2, RSBN1 and MTHFD2. Sixteen out of 37 luminal tumors (43%) harbored SNVs in DNA repair genes, such as ATR, BAP1, ERCC6, FANCD2, FANCL, MLH1, MUTYH, PALB2, POLD1, POLE, RAD9A, RAD51 and TP53, and 54% presented pathogenic mutations (frameshift or nonsense) in at least one gene involved in gene transcription. The differential biology of luminal early-age onset breast cancer needs a deeper genomic investigation. PMID:29854292

  3. Correlates and prevalence of hypogonadism in patients with early- and late-onset type 2 diabetes.

    PubMed

    Li, Y; Zhang, M; Liu, X; Cui, W; Rampersad, S; Li, F; Lin, Z; Yang, P; Li, H; Sheng, C; Cheng, X; Qu, S

    2017-07-01

    This study aims to compare the prevalence of hypogonadism between male patients with early-onset type 2 diabetes mellitus (T2DM) and late-onset type 2 diabetes. A total of 122 male patients with early-onset T2DM (diagnosis age ≤40 years) and 100 male patients with late-onset T2DM (diagnosis age >40 years) were recruited from our in-patient department between 1 January 2013 and 28 December 2015. Serum FSH, LH, testosterone, lipid profile, uric acid, HbA1c, and beta-cell function were determined in blood samples. The diagnosis of hypogonadism was based on the levels of LH, FSH, and total testosterone. The mean onset age was 29.86 ± 6.31 and 54.47 ± 9.97 years old in the early-onset group and late-onset group, respectively. Compared with late-onset T2DM, those with early-onset T2DM had a higher proportion of new-onset diabetes, were more likely to be obese, and had worse glycemic control, lipid control, and lower sex hormone-binding globulin (SHBG). The prevalence of hypogonadism was much higher in the early-onset group than in the late-onset group (48.0% vs. 26.7%, p < 0.05). The rate of secondary hypogonadism in the early-onset group and late-onset group were 44.3% and 25.0%, respectively (p < 0.05). Obesity, waist circumference, and SHBG were significantly associated with serum total testosterone level in all, early-onset, and late-onset T2DM. Both all and early-onset T2DM groups had positive correlations between total testosterone and fasting C-peptide, total cholesterol, triglycerides, and uric acid. Our results indicate that in a population of admission to a large urban hospital in China, the prevalence of hypogonadism was higher in the patients with early-onset T2DM than that of late-onset T2DM. This prevalence might be attributable to greater obesity, worse lipid control, and lower SHBG levels in those patients. © 2017 American Society of Andrology and European Academy of Andrology.

  4. Evidence for apolipoprotein E {epsilon}4 association in early-onset Alzheimer`s patients with late-onset relatives

    SciTech Connect

    Perez-Tur, J.; Delacourte, A.; Chartier-Harlin, M.C.

    1995-12-18

    Recently several reports have extended the apolipoprotein E (APOE) {epsilon}4 association found in late-onset Alzheimer`s disease (LOAD) patients to early-onset (EO) AD patients. We have studied this question in a large population of 119 EOAD patients (onset {<=}60 years) in which family history was carefully assessed and in 109 controls. We show that the APOE {epsilon}A allele frequency is increased only in the subset of patients who belong to families where LOAD secondary cases are present. Our sampling scheme permits us to demonstrate that, for an individual, bearing at least one {epsilon}4 allele increases both the risk of AD beforemore » age 60 and the probability of belonging to a family with late-onset affected subjects. Our results suggest that a subset of EOAD cases shares a common determinism with LOAD cases. 19 refs., 3 tabs.« less

  5. Complications of growth-sparing surgery in early onset scoliosis.

    PubMed

    Akbarnia, Behrooz A; Emans, John B

    2010-12-01

    Review of available literature, authors' opinion. To describe complications associated with growth-sparing surgical treatment of early onset scoliosis (EOS). EOS has many potential etiologies and is often associated with thoracic insufficiency syndrome. The growth of the spine, thorax, and lungs are interrelated, and severe EOS typically involves disturbance of the normal development of all 3. Severe EOS may be treated during growth with surgical techniques, intended to preserve growth while controlling deformity, the most common of which are spinal "growing rods" (GR) or "vertical expandable prosthetic titanium rib" (VEPTR). Although presently popular, there is minimal long-term data on the outcome of growth-sparing surgical techniques on EOS. Review. Potential adverse outcomes of GR or VEPTR treatment of EOS include failure to prevent progressive deformity or thoracic insufficiency syndrome, an unacceptably short or stiff spine or deformed thorax, increased family burden of care, and potentially negative psychological consequences from repeated surgical interventions. Neither technique reliably controls all deformity over the entirety of growth period. Infections are common to both GR and VEPTR. Rod breakage and spontaneous premature spinal fusion beneath rods are troublesome complications in GR, whereas drift of rib attachments and chest wall scarring are anticipated complications in VEPTR treatment. Indications for GR and VEPTR overlap, but thoracogenic scoliosis and severe upper thoracic kyphosis are best treated by VEPTR and GR, respectively. Surgeons planning treatment of EOS should anticipate the many complications common to growth-sparing surgery, share their knowledge with families, and use complications as one factor in the complex decision as to when and whether to initiate the repetitive surgeries associated with GR or VEPTR in the treatment of severe EOS.

  6. Deficits in Facial Expression Recognition in Male Adolescents with Early-Onset or Adolescence-Onset Conduct Disorder

    ERIC Educational Resources Information Center

    Fairchild, Graeme; Van Goozen, Stephanie H. M.; Calder, Andrew J.; Stollery, Sarah J.; Goodyer, Ian M.

    2009-01-01

    Background: We examined whether conduct disorder (CD) is associated with deficits in facial expression recognition and, if so, whether these deficits are specific to the early-onset form of CD, which emerges in childhood. The findings could potentially inform the developmental taxonomic theory of antisocial behaviour, which suggests that…

  7. Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Rationale, Design, and Methods

    ERIC Educational Resources Information Center

    McClellan, Jon; Sikich, Linmarie; Findling, Robert L.; Frazier, Jean A.; Vitiello, Benedetto; Hlastala, Stefanie A.; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E.; Ritz, Louise; Anderson, Robert; Hamer, Robert M.; Lieberman, Jeffrey A.

    2007-01-01

    Objective: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early…

  8. Social Status of Adolescents with an Early Onset of Externalizing Behavior: The SNARE Study

    ERIC Educational Resources Information Center

    Franken, Aart; Harakeh, Zeena; Veenstra, Rene; Vollebergh, Wilma; Dijkstra, Jan Kornelis

    2017-01-01

    This study investigated the social status (i.e., popularity, likeability, and friendships) of adolescents with an early onset of externalizing behavior (i.e., alcohol use, tobacco use, and antisocial behavior). Building on Moffitt's dual-taxonomy model, it was hypothesized that early onset adolescents were more popular, but not necessarily more…

  9. Verbal and Academic Skills in Children with Early-Onset Type 1 Diabetes

    ERIC Educational Resources Information Center

    Hannonen, Riitta; Komulainen, Jorma; Eklund, Kenneth; Tolvanen, Asko; Riikonen, Raili; Ahonen, Timo

    2010-01-01

    Aim: Basic verbal and academic skills can be adversely affected by early-onset diabetes, although these skills have been studied less than other cognitive functions. This study aimed to explore the mechanism of learning deficits in children with diabetes by assessing basic verbal and academic skills in children with early-onset diabetes and in…

  10. A randomized controlled clinical trial investigating the effect of calcium supplement plus low-dose aspirin on hs-CRP, oxidative stress and insulin resistance in pregnant women at risk for pre-eclampsia.

    PubMed

    Asemi, Z; Samimi, M; Heidarzadeh, Z; Khorrammian, H; Tabassi, Z

    2012-05-15

    Increased levels of pro-inflammatory factors, markers of oxidative stress and insulin resistance during pregnancy have been associated with the development of pre-eclampsia. There is some evidence to suggest that calcium supplement and aspirin can reduce the risk of the disorder. To our knowledge, no reports are available indicating the effects of consumed calcium supplement plus aspirin on high sensitivity C-reactive protein (hs-CRP), oxidative stress parameters and insulin resistance in pregnant women at risk for pre-eclampsia. This study was designed to investigate the effects of consumed calcium supplement plus low-dose aspirin on hs-CRP, oxidative stress parameters and insulin resistance among Iranian pregnant women at risk for pre-eclampsia. This randomized single-blind controlled clinical trial was carried out among 42 pregnant women at risk for pre-eclampsia, primigravida, aged 18-40 year old who were carrying singleton pregnancy at their third trimester. Subjects were randomly assigned to received either the placebo (n = 22) or calcium supplement plus low-dose aspirin (n = 20) for 9 weeks. Calcium supplement plus low-dose aspirin were containing 500 mg carbonate calcium plus 80 mg aspirin. Fasting blood samples were taken at baseline and after 9 weeks intervention to measure serum hs-CRP, oxidative stress parameters including plasma Total Antioxidant Capacity (TAC) and Total Glutathione (GSH), Fasting Plasma Glucose (FPG), serum insulin and HOMA-IR score. Consumption of calcium supplement plus low-dose aspirin resulted in a significant difference serum hs-CRP levels as compared to the placebo (102.87 vs. 3227.75 ng mL(-1), p = 0.01). Also, mean changes for plasma TAC (68.96 vs. -74.46 mmol L(-1), p = 0.04) and total GSH levels (304.33 vs. -39.33 micromol L(-1), p = 0.03) were significantly different between the two groups. No significant differences were found comparing calcium supplement plus low-dose aspirin and placebo in terms of their effects on FPG

  11. Diagnosis and prognosis of early-onset intrahepatic cholestasis of pregnancy: a prospective study.

    PubMed

    Lin, Jing; Gu, Wei; Hou, Yanyan

    2017-11-07

    To explore the gestational age of early-onset intrahepatic cholestasis (ICP) of pregnancy, and to analyze the relationship between the clinical biochemical indices and pregnancy outcomes in order to arrive at a reasonable diagnosis and administer appropriate treatment. This is a retrospective clinical study. We selected 47,260 pregnant women who received prenatal care and underwent childbirth at the International Peace Maternity and Child Health Hospital affiliated to Shanghai Jiao Tong University from January 2014 to December 2016 for participating in this study. Of these 47,260 women, 407 developed ICP. To calculate the gestational week cutoff between early- and late-onset ICP by the receiver-operating characteristic (ROC) curve and Youden's index. Two independent samples t tests and chi square test were used to compare the differences in biochemical indices and pregnancy outcomes between the two groups. We found that 34 weeks is the most appropriate cutoff gestational age for the diagnosis of early-onset ICP. Early-onset ICP is characterized by early onset, long disease duration and a higher incidence of preterm labor, fetal distress, and fetal low birth weight compared to late-onset ICP. Thirty-four weeks is the most appropriate cutoff gestational age for the diagnosis of early-onset ICP. And to reduce the adverse pregnancy outcomes in cases of early-onset ICP, we suggest prolonging gestation up to 37 weeks as far as possible before selecting iatrogenic birth.

  12. Early-onset obsessive-compulsive disorder and personality disorders in adulthood.

    PubMed

    Maina, Giuseppe; Albert, Umberto; Salvi, Virginio; Pessina, Enrico; Bogetto, Filippo

    2008-03-15

    Obsessive-compulsive disorder (OCD) often emerges in childhood or adolescence. The aim of the present study was to evaluate whether adult patients with prepuberal onset differ from subjects with later onset in terms of personality disorder comorbidity. The Structured Clinical Interview for DSM-IV Axis II Disorders was used to assess 148 patients with a principal diagnosis of OCD according to the Structured Clinical Interview for DSM-IV Axis I Disorders. The following two subgroups of subjects were selected according to the age at onset of symptomatology: patients with an early-onset (< or =10 years), and patients with a later onset (> or =17 years). Of the 148 patients screened for the present study, 33 (22.3%) had an early onset and 1369 (46.6%) had a later onset. With regard to personality disorders, early-onset patients showed more OC personality disorders (OCPD) than later onset patients. Our finding suggests that OCD in childhood increases the risk for developing OCPD in adulthood, or that early-onset OCD and OCPD share a common pathogenesis.

  13. Early onset prostate cancer has a significant genetic component.

    PubMed

    Lange, Ethan M; Salinas, Claudia A; Zuhlke, Kimberly A; Ray, Anna M; Wang, Yunfei; Lu, Yurong; Ho, Lindsey A; Luo, Jingchun; Cooney, Kathleen A

    2012-02-01

    Prostate cancer (PCa) affects more than 190,000 men each year with ∼10% of men diagnosed at ≤55 years, that is, early onset (EO) PCa. Based on historical findings for other cancers, EO PCa likely reflects a stronger underlying genetic etiology. We evaluated the association between EO PCa and previously identified single nucleotide polymorphisms (SNPs) in 754 Caucasian cases from the Michigan Prostate Cancer Genetics Project (mean 49.8 years at diagnosis), 2,713 Caucasian controls from Illumina's iControlDB database and 1,163 PCa cases diagnosed at >55 years from the Cancer Genetic Markers of Susceptibility Study (CGEMS). Significant associations existed for 13 of 14 SNPs (rs9364554 on 6q25, rs10486567 on 7p15, rs6465657 on 7q21, rs6983267 on 8q24, rs1447295 on 8q24, rs1571801 on 9q33, rs10993994 on 10q11, rs4962416 on 10q26, rs7931342 on 11q13, rs4430796 on 17q12, rs1859962 on 17q24.3, rs2735839 on 19q13, and rs5945619 on Xp11.22, but not rs2660753 on 3p12). EO PCa cases had a significantly greater cumulative number of risk alleles (mean 12.4) than iControlDB controls (mean 11.2; P = 2.1 × 10(-33)) or CGEMS cases (mean 11.9; P = 1.7 × 10(-5)). Notably, EO PCa cases had a higher frequency of the risk allele than CGEMS cases at 11 of 13 associated SNPs, with significant differences for five SNPs. EO PCa cases diagnosed at <50 (mean 12.8) also had significantly more risk alleles than those diagnosed at 50-55 years (mean 12.1; P = 0.0003). These results demonstrate the potential for identifying PCa-associated genetic variants by focusing on the subgroup of men diagnosed with EO disease. Copyright © 2011 Wiley Periodicals, Inc.

  14. Early Onset Prostate Cancer Has A Significant Genetic Component

    PubMed Central

    Lange, Ethan M.; Salinas, Claudia A.; Zuhlke, Kimberly A.; Ray, Anna M.; Wang, Yunfei; Lu, Yurong; Ho, Lindsey A.; Luo, Jingchun; Cooney, Kathleen A.

    2011-01-01

    BACKGROUND Prostate cancer (PCa) affects more than 190,000 men each year with ~10% of men diagnosed at ≤ 55 years, i.e., early onset (EO) PCa. Based on historical findings for other cancers, EO PCa likely reflects a stronger underlying genetic etiology. METHODS We evaluated the association between EO PCa and previously identified single nucleotide polymorphisms (SNPs) in 754 Caucasian cases from the Michigan Prostate Cancer Genetics Project (mean 49.8 years at diagnosis), 2,713 Caucasian controls from Illumina’s iControlDB database and 1,163 PCa cases diagnosed at >55 years from the Cancer Genetic Markers of Susceptibility Study (CGEMS). RESULTS Significant associations existed for 13 of 14 SNPs (rs9364554 on 6q25, rs10486567 on 7p15, rs6465657 on 7q21, rs6983267 on 8q24, rs1447295 on 8q24, rs1571801 on 9q33, rs10993994 on 10q11, rs4962416 on 10q26, rs7931342 on 11q13, rs4430796 on 17q12, rs1859962 on 17q24.3, rs2735839 on 19q13, and rs5945619 on Xp11.22, but not rs2660753 on 3p12). EO PCa cases had a significantly greater cumulative number of risk alleles (mean 12.4) than iControlDB controls (mean 11.2; p=2.1×10−33) or CGEMS cases (mean 11.9; p=1.7 × 10−5). Notably, EO PCa cases had a higher frequency of the risk allele than CGEMS cases at 11 of13 associated SNPs, with significant differences for five SNPs. EO PCa cases diagnosed at <50 (mean 12.8) also had significantly more risk alleles than those diagnosed at 50–55 years (mean 12.1; p = 0.0003). CONCLUSIONS These results demonstrate the potential for identifying PCa-associated genetic variants by focusing on the subgroup of men diagnosed with EO disease. PMID:21538423

  15. Early onset scoliosis with intraspinal anomalies: management with growing rod.

    PubMed

    Jayaswal, Arvind; Kandwal, Pankaj; Goswami, Ankur; Vijayaraghavan, G; Jariyal, Ashok; Upendra, B N; Gupta, Ankit

    2016-10-01

    To evaluate clinical and radiological outcomes of growing rod (GR) in the management of Early Onset Scoliosis (EOS) with intraspinal anomalies. The effect of repeated distractions following GR, in the presence of intraspinal anomalies has not been studied. During 2007-2012, 46 patients underwent fusionless surgery. Out of these 46 patients, 13 patients had one or more intraspinal anomalies. 11 patients had undergone prior neurosurgical procedure while 2 (filum terminale lipoma and syringomyelia) did not. A total of 88 procedures were conducted during the treatment period; 13 index surgeries, 74 distractions of GR and 1 unplanned surgery. The age at surgery was 6.8 ± 2.5 years (3.5-12 years). 11 patients had congenital scoliosis and 2 had idiopathic scoliosis. A total of 19 (41.30 %) intraspinal anomalies [Tethered Cord Syndrome (TCS) 08, Split Cord Malformation (SCM) 08, Syringomyelia 01, Meningomyelocele 01, Filum terminale Lipoma 01] were seen. The average lengthening procedures per patient were 5.7 (4-9) with distraction interval of 6.7 (6-7.25) months. Pre-operative Cobb angle was 78.50 ± 18.1 (54-114°) and improved to 53.10 ± 16.70 (36-84°) at final follow-up. A total of 15 complications related to implant (9), wound (2), anesthesia (2) and neurological (2) occurred in 7 patients. Among the two neurological complications, one patient sustained fall in the post-op period and reported to the emergency department with paraplegia and broken proximal screw. While other patient experienced MEP changes during index procedure. None of the patients had any neurological complications during repeated lengthening procedures. The most common cord anomalies associated with EOS in our study are TCS and SCM. Although presence of previous intraspinal anomaly does not seem to increase the incidence of neurological deficit, use of neuromonitoring is advisable for all index procedure and selected distractions. Level 4 (case series).

  16. Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers.

    PubMed

    Hartz, Sarah M; Short, Susan E; Saccone, Nancy L; Culverhouse, Robert; Chen, LiShiun; Schwantes-An, Tae-Hwi; Coon, Hilary; Han, Younghun; Stephens, Sarah H; Sun, Juzhong; Chen, Xiangning; Ducci, Francesca; Dueker, Nicole; Franceschini, Nora; Frank, Josef; Geller, Frank; Gubjartsson, Daniel; Hansel, Nadia N; Jiang, Chenhui; Keskitalo-Vuokko, Kaisu; Liu, Zhen; Lyytikäinen, Leo-Pekka; Michel, Martha; Rawal, Rajesh; Rosenberger, Albert; Scheet, Paul; Shaffer, John R; Teumer, Alexander; Thompson, John R; Vink, Jacqueline M; Vogelzangs, Nicole; Wenzlaff, Angela S; Wheeler, William; Xiao, Xiangjun; Yang, Bao-Zhu; Aggen, Steven H; Balmforth, Anthony J; Baumeister, Sebastian E; Beaty, Terri; Bennett, Siiri; Bergen, Andrew W; Boyd, Heather A; Broms, Ulla; Campbell, Harry; Chatterjee, Nilanjan; Chen, Jingchun; Cheng, Yu-Ching; Cichon, Sven; Couper, David; Cucca, Francesco; Dick, Danielle M; Foroud, Tatiana; Furberg, Helena; Giegling, Ina; Gu, Fangyi; Hall, Alistair S; Hällfors, Jenni; Han, Shizhong; Hartmann, Annette M; Hayward, Caroline; Heikkilä, Kauko; Hewitt, John K; Hottenga, Jouke Jan; Jensen, Majken K; Jousilahti, Pekka; Kaakinen, Marika; Kittner, Steven J; Konte, Bettina; Korhonen, Tellervo; Landi, Maria-Teresa; Laatikainen, Tiina; Leppert, Mark; Levy, Steven M; Mathias, Rasika A; McNeil, Daniel W; Medland, Sarah E; Montgomery, Grant W; Muley, Thomas; Murray, Tanda; Nauck, Matthias; North, Kari; Pergadia, Michele; Polasek, Ozren; Ramos, Erin M; Ripatti, Samuli; Risch, Angela; Ruczinski, Ingo; Rudan, Igor; Salomaa, Veikko; Schlessinger, David; Styrkársdóttir, Unnur; Terracciano, Antonio; Uda, Manuela; Willemsen, Gonneke; Wu, Xifeng; Abecasis, Goncalo; Barnes, Kathleen; Bickeböller, Heike; Boerwinkle, Eric; Boomsma, Dorret I; Caporaso, Neil; Duan, Jubao; Edenberg, Howard J; Francks, Clyde; Gejman, Pablo V; Gelernter, Joel; Grabe, Hans Jörgen; Hops, Hyman; Jarvelin, Marjo-Riitta; Viikari, Jorma; Kähönen, Mika; Kendler, Kenneth S; Lehtimäki, Terho; Levinson, Douglas F; Marazita, Mary L; Marchini, Jonathan; Melbye, Mads; Mitchell, Braxton D; Murray, Jeffrey C; Nöthen, Markus M; Penninx, Brenda W; Raitakari, Olli; Rietschel, Marcella; Rujescu, Dan; Samani, Nilesh J; Sanders, Alan R; Schwartz, Ann G; Shete, Sanjay; Shi, Jianxin; Spitz, Margaret; Stefansson, Kari; Swan, Gary E; Thorgeirsson, Thorgeir; Völzke, Henry; Wei, Qingyi; Wichmann, H-Erich; Amos, Christopher I; Breslau, Naomi; Cannon, Dale S; Ehringer, Marissa; Grucza, Richard; Hatsukami, Dorothy; Heath, Andrew; Johnson, Eric O; Kaprio, Jaakko; Madden, Pamela; Martin, Nicholas G; Stevens, Victoria L; Stitzel, Jerry A; Weiss, Robert B; Kraft, Peter; Bierut, Laura J

    2012-08-01

    Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. Primary data. Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD ≤10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset ≤16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01). These results highlight an increased genetic vulnerability to smoking in early-onset smokers.

  17. Translating research into maternal health care policy: a qualitative case study of the use of evidence in policies for the treatment of eclampsia and pre-eclampsia in South Africa

    PubMed Central

    Daniels, Karen; Lewin, Simon

    2008-01-01

    Background Few empirical studies of research utilisation have been conducted in low and middle income countries. This paper explores how research information, in particular findings from randomised controlled trials and systematic reviews, informed policy making and clinical guideline development for the use of magnesium sulphate in the treatment of eclampsia and pre-eclampsia in South Africa. Methods A qualitative case-study approach was used to examine the policy process. This included a literature review, a policy document review, a timeline of key events and the collection and analysis of 15 interviews with policy makers and academic clinicians involved in these policy processes and sampled using a purposive approach. The data was analysed thematically and explored theoretically through the literature on agenda setting and the policy making process. Results Prior to 1994 there was no national maternal care policy in South Africa. Consequently each tertiary level institution developed its own care guidelines and these recommended a range of approaches to the management of pre-eclampsia and eclampsia. The subsequent emergence of new national policies for maternal care, including for the treatment of pre-eclampsia and eclampsia, was informed by evidence from randomised controlled trials and systematic reviews. This outcome was influenced by a number of factors. The change to a democratic government in the mid 1990s, and the health reforms that followed, created opportunities for maternal health care policy development. The new government was open to academic involvement in policy making and recruited academics from local networks into key policy making positions in the National Department of Health. The local academic obstetric network, which placed high value on evidence-based practice, brought these values into the policy process and was also linked strongly to international evidence based medicine networks. Within this context of openness to policy development

  18. Social Anxiety and Onset of Drinking in Early Adolescence

    ERIC Educational Resources Information Center

    Tomlinson, Kristin L.; Cummins, Kevin M.; Brown, Sandra A.

    2013-01-01

    The present study examines several types of social anxiety that may be associated with the onset of alcohol use in middle school students, and whether the relationship differs by sex and grade. Students in the seventh and eighth grades (N = 2,621) completed the Social Anxiety Scale for Adolescents and a measure of lifetime drinking via schoolwide…

  19. Differential Neurodevelopmental Trajectories in Patients With Early-Onset Bipolar and Schizophrenia Disorders

    PubMed Central

    Arango, Celso

    2014-01-01

    Schizophrenia and bipolar disorders share not only clinical features but also some risk factors such as genetic markers and childhood adversity, while other risk factors such as urbanicity and obstetric complications seem to be specific to schizophrenia. An intriguing question is whether the well-established abnormal neurodevelopment present in many children and adolescents who eventually develop schizophrenia is also present in bipolar patients. The literature on adult bipolar patients is controversial. We report data on a subgroup of patients with pediatric-onset psychotic bipolar disorder who seem to share some developmental trajectories with patients with early-onset schizophrenia. These early-onset psychotic bipolar patients have low intelligence quotient, more neurological signs, reduced frontal gray matter at the time of their first psychotic episode, and greater brain changes than healthy controls in a pattern similar to early-onset schizophrenia cases. However, patients with early-onset schizophrenia seem to have more social impairment, developmental abnormalities (eg, language problems), and lower academic achievement in childhood than early-onset bipolar patients. We suggest that some of these abnormal developmental trajectories are more related to the phenotypic features (eg, early-onset psychotic symptoms) of these 2 syndromes than to categorically defined Diagnostic and Statistical Manual of Mental Disorders disorders. PMID:24371326

  20. Are early-onset cannabis smokers at an increased risk of depression spells?

    PubMed

    Fairman, Brian J; Anthony, James C

    2012-04-01

    A recent research focus is a set of hypothesized adult-onset mental health disturbances possibly due to early-onset cannabis use (EOCU, onset <18 years). We seek to estimate the suspected EOCU-associated excess odds of experiencing an incident depression spell during adulthood, with comparisons to never cannabis smokers and those with delayed cannabis onset (i.e., not starting to smoke cannabis until adulthood). The National Surveys on Drug Use and Health (NSDUH) assess non-institutionalized community-dwelling residents of the United States after probability sampling each year. In aggregate, the NSDUH analytical sample included 173,775 adult participants from survey years 2005-2009 (74-76% of designated respondents). Standardized computer-assisted interviews collected information on background determinants, age of first cannabis use, and depression spell onset. Logistic regression was used to estimate EOCU-depression spell associations in the form of odds ratios, with statistical adjustment for sex, age, race/ethnicity, years of cannabis involvement, tobacco cigarette onset, and alcohol onset. About 1 in 10 experienced a depression spell during adulthood, and both early-onset and adult-onset cannabis smokers had a modest excess odds of a depression spell compared to never cannabis smokers, even with covariate adjustment (OR=1.7 and 1.8, respectively; both p<0.001). Estimates for early- and adult-onset cannabis smokers did not statistically differ from one another. Shared diathesis that might influence both EOCU and adult-onset depression spell is controlled no more than partially, as will be true until essentially all known early-life shared vulnerabilities are illuminated. Cannabis smoking initiated at any age signals a modest increased risk of a spell of depression in adulthood, even when adjusted for suspected confounding variables studied here. Delaying cannabis onset until adulthood does not appear to diminish the cannabis-associated risk. Copyright © 2011

  1. Are early-onset cannabis smokers at an increased risk of depression spells?

    PubMed Central

    Fairman, Brian J.; Anthony, James C.

    2012-01-01

    Background A recent research focus is a set of hypothesized adult-onset mental health disturbances possibly due to early-onset cannabis use (EOCU, onset <18 years). We seek to estimate the suspected EOCU-associated excess odds of experiencing an incident depression spell during adulthood, with comparisons to never cannabis smokers and those with delayed cannabis onset (i.e., not starting to smoke cannabis until adulthood). Methods The National Surveys on Drug Use and Health (NSDUH) assess non-institutionalized community-dwelling residents of the United States after probability sampling each year. In aggregate, the NSDUH analytical sample included 173,775 adult participants from survey years 2005–2009 (74–76% of designated respondents). Standardized computer-assisted interviews collected information on background determinants, age of first cannabis use, and depression spell onset. Logistic regression was used to estimate EOCU-depression spell associations in the form of odds ratios, with statistical adjustment for sex, age, race/ethnicity, years of cannabis involvement, tobacco cigarette onset, and alcohol onset. Results About 1 in 10 experienced a depression spell during adulthood, and both early-onset and adult-onset cannabis smokers had a modest excess odds of a depression spell compared to never cannabis smokers, even with covariate adjustment (OR = 1.7 & 1.8, respectively; both p<0.001). Estimates for early- and adult-onset cannabis smokers did not statistically differ from one another. Limitations Shared diathesis that might influence both EOCU and adult-onset depression spell is controlled no more than partially, as will be true until essentially all known early-life shared vulnerabilities are illuminated. Conclusion Cannabis smoking initiated at any age signals a modest increased risk of a spell of depression in adulthood, even when adjusted for suspected confounding variables studied here. Delaying cannabis onset until adulthood does not appear to

  2. Early-Onset Obsessive-Compulsive Disorder: A Subgroup with a Specific Clinical and Familial Pattern?

    ERIC Educational Resources Information Center

    Chabane, Nadia; Delorme, Richard; Millet, Bruno; Mouren, Marie-Christine; Leboyer, Marion; Pauls, David

    2005-01-01

    Background: The familial nature of obsessive-compulsive disorder (OCD) has been previously demonstrated. The identification of candidate symptoms such as age at onset may help to disentangle the clinical and genetic heterogeneity of the disorder. In this study, the specificity of early-onset OCD was investigated, focusing on the effect of gender,…

  3. Global and Temporal Cortical Folding in Patients with Early-Onset Schizophrenia

    ERIC Educational Resources Information Center

    Penttila, Jani; Paillere-Martinot, Marie-Laure; Martinot, Jean-Luc; Mangin, Jean-Francois; Burke, Lisa; Corrigall, Richard; Frangou, Sophia; Cachia, Arnaud

    2008-01-01

    Disturbances in the temporal lobes and alterations in cortical folding in adult on-set schizophrenia are studied using magnetic resonance T1 images of 51 patients. The study showed that patients with early on-set schizophrenia had lower global sulcal indices in both hemispheres and the left collateral sulcus has a lower sulcal index irrespective…

  4. Treatment of Early Onset Schizophrenia: Recent Trends, Challenges and Future Considerations

    PubMed Central

    Vyas, Nora S.; Gogtay, Nitin

    2012-01-01

    Early onset schizophrenia (onset before adulthood) is a rare, severe, and chronic form of schizophrenia. The clinical presentation of schizophrenia at this unusually early age of onset has been associated with premorbid developmental abnormalities, poor response to neuroleptic treatment, greater admission rates, and poor prognosis. This is a brief, condensed review of current treatment strategies for the early onset population highlighting the need for novel treatment strategies for these generally treatment-refractory cases. Based on the current literature, second-generation antipsychotics remain the mainstay of treatment, although current medications provide suboptimal response at best. Based on the adult literature, combining antipsychotic treatment with psychotherapeutic intervention may be a more comprehensive treatment strategy. Indeed, early detection, identification of relevant biomarkers, coupled with advancing knowledge of the neurochemical and neuroanatomic pathways may help design informed and novel treatment strategies. PMID:22485097

  5. The impact of maternal plasma volume expansion and antihypertensive treatment with intravenous dihydralazine on fetal and maternal hemodynamics during pre-eclampsia: a clinical, echo-Doppler and viscometric study.

    PubMed

    Boito, S M E; Struijk, P C; Pop, G A M; Visser, W; Steegers, E A P; Wladimiroff, J W

    2004-04-01

    To establish the effects of plasma volume expansion (PVE) followed by intravenous dihydralazine (DH) administration on maternal whole blood viscosity (WBV) and hematocrit, uteroplacental and fetoplacental downstream impedance and umbilical venous (UV) volume flow in pre-eclampsia. In 13 pre-eclamptic women maternal and fetal hemodynamics were established by means of combined measurement of maternal arterial blood pressure (BP), WBV, hematocrit and uterine artery (UtA) resistance index (RI) in addition to umbilical artery (UA) pulsatility index (PI) and UV volume flow obtained from UV vessel area and UV time-averaged flow velocity. In each woman all parameters were measured four times at baseline, after PVE, after DH and 24 h after the start of treatment. Maternal diastolic BP, hematocrit and WBV display a significant reduction after PVE. In the fetus UA PI decreases significantly whereas a significant increase in UV cross-sectional area was detected. After maternal DH administration, arterial systolic and diastolic BP and UA PI show a significant decrease compared with the measurements following PVE. At 24 h, only maternal systolic and diastolic BP display a significant further decrease. No significant changes were established for the UtA RI, UV time-averaged velocity and UV volume flow during the entire study period. During pre-eclampsia, maternal PVE followed by DH administration results in a significant reduction in maternal diastolic BP, maternal hematocrit and WBV. Maternal PVE is associated with a significant increase in UV cross-sectional area and a non-significant rise of 11% in UV volume flow. Maternal DH administration does not result in any change in UV cross-sectional area. However, UA PI decreases significantly after both PVE and DH treatment. Copyright 2004 ISUOG.

  6. The favorable effects of garlic intake on metabolic profiles, hs-CRP, biomarkers of oxidative stress and pregnancy outcomes in pregnant women at risk for pre-eclampsia: randomized, double-blind, placebo-controlled trial.

    PubMed

    Aalami-Harandi, Rezvan; Karamali, Maryam; Asemi, Zatollah

    2015-01-01

    This study was performed to determine the favorable effects of garlic on metabolic status and pregnancy outcomes among pregnant women at risk for pre-eclampsia. This randomized, double-blind, placebo-controlled trial was conducted among 44 pregnant women, primigravida, aged 18-40 years old at 27 weeks' gestation with positive roll-over test. Participants were randomly assigned to receive either one garlic tablet (equal to 400 mg garlic and 1 mg allicin) (n = 22) or placebo (n = 22) once daily for 9 weeks. Fasting blood samples were taken at baseline and after 9 weeks' intervention to measure metabolic profiles and biomarkers of oxidative stress. Administration of garlic compared with the placebo resulted in decreased levels of serum high sensitivity C-reactive protein (hs-CRP) (-1425.90 versus 1360.50 ng/mL, p = 0.01) and increased plasma glutathione (GSH) (+98.10 versus. -49.87 µmol/l, p = 0.03). A trend toward a significant effect of garlic intake on reducing fasting plasma glucose (FPG) (p = 0.07), insulin (p = 0.09) and increasing quantitative insulin sensitivity check (QUICKI) (p = 0.05) was also observed. Consumption of garlic for 9 weeks among pregnant women at risk for pre-eclampsia led to decreased hs-CRP and increased GSH, but did not affect lipid profiles, total antioxidant capacity (TAC) and pregnancy outcomes.

  7. Mothers' experience of caring for a child with early onset scoliosis: A qualitative descriptive study.

    PubMed

    Lauder, Bonnie; Sinclair, Peter M; Maguire, Jane

    2018-04-01

    This study aimed to identify and describe the experience of parents of children diagnosed with early onset scoliosis living in Australia. Chronic childhood disease has a major impact on health-related quality of life. Caring for a child with a chronic illness is well documented but the specific experiences of parents who care for children with early onset scoliosis, a rare but devastating illness, has not been explored. Numerous studies have described the interrelated psychological, financial, social, physical and logistical factors that impact the experience of the caregiver role with various diseases, but in the case of early onset scoliosis, limited studies have been conducted about the parental experience. A qualitative descriptive design was used. A snowball sampling technique assisted in the recruitment. Parents invited to the study included mothers, fathers and guardians. Data were collected through semistructured interviews and transcribed verbatim. Transcripts were analysed thematically. Data collection complied with the Consolidated criteria for reporting qualitative research guidelines. Twelve mothers of children with early onset scoliosis were interviewed, as only mothers consented to participate. Four major themes emerged: emotional rollercoaster ride, a lack of resources, money talks and pervasive burden. Factors that impacted on the participants' ability to confront, manage and endure caring for a child with early onset scoliosis emerged from the data. The findings suggest there are multiple factors that influence the experience of mothers' caring for a child with early onset scoliosis. The recognition and appropriate management of these factors by healthcare professionals have the potential to improve the quality of life of parents who care for a child with early onset scoliosis. Healthcare professionals have first-line contact with parents of children with early onset scoliosis and are well placed to provide parents with evidence-based education

  8. Evaluation of agreement of placental growth factor (PlGF) tests and the soluble FMS-like tyrosine kinase 1 (sFlt-1)/PlGF ratio, comparison of predictive accuracy for pre-eclampsia, and relation to uterine artery Doppler and response to aspirin.

    PubMed

    Navaratnam, Kate; Abreu, Patricia; Clarke, Helen; Jorgensen, Andrea; Alfirevic, Ana; Alfirevic, Zarko

    2017-09-11

    The objective of this study is to evaluate agreement between PlGF and sFlt-1/PlGF ratio tests and compare their predictive accuracy for pre-eclampsia in high-risk women. Also, to examine for associations of abnormal PlGF or sFlt-1/PlGF ratio with abnormal uterine artery Doppler and platelet response to aspirin. Prospective cohort study, 150 pregnant women at high risk of pre-eclampsia prescribed 75 mg aspirin daily. Uterine artery Dopplers were assessed at 20 +0 -23 +6 weeks. At 33 +0 -35 +6 weeks platelet function aspirin metabolites, PlGF and the sFlt-1/PlGF ratio were measured. Measures were all pre-eclampsia and pre-eclampsia requiring delivery prior to 37 weeks. Overall percent agreement was 89.3% for PlGF tests but 74.7-78% for PlGF tests and the sFlt-1/PlGF ratio. AUCs were 0.70-0.75 for prediction of any pre-eclampsia and 0.92-0.99 for preterm pre-eclampsia. We found a significant association between abnormal PlGF or sFlt-1/PlGF ratio and abnormal uterine artery Doppler (χ 2 5.47, p = .019), but no association with platelet response to aspirin (χ 2 0.12, p = .913). There were no associations between suboptimal aspirin adherence and either abnormal angiogenic markers or uterine artery Dopplers (χ 2 0.144, 0.038, p = .704, .846, respectively). There was good agreement between PlGF tests and limited agreement between PlGF tests and the sFlt-1/PlGF ratio. All tests have heightened predictive accuracy for preterm pre-eclampsia. Abnormal PlGF or sFlt-1/PlGF ratio relates to abnormal uterine artery Doppler but not platelet response to aspirin.

  9. Deferred and Immediate Imitation in Regressive and Early Onset Autism

    ERIC Educational Resources Information Center

    Rogers, Sally J.; Young, Gregory S.; Cook, Ian; Giolzetti, Angelo; Ozonoff, Sally

    2008-01-01

    Deferred imitation has long held a privileged position in early cognitive development, considered an early marker of representational thought with links to language development and symbolic processes. Children with autism have difficulties with several abilities generally thought to be related to deferred imitation: immediate imitation, language,…

  10. [Metabolic side effects of risperidone in early onset schizophrenia].

    PubMed

    Goeb, J-L; Marco, S; Duhamel, A; Kechid, G; Bordet, R; Thomas, P; Delion, P; Jardri, R

    2010-06-01

    Atypical antipsychotics have a favourable risk/benefit profile in early onset schizophrenia (EOS). However, despite increasing use of psychotropic medication in children and adolescents, their endocrine and metabolic side-effects (weight gain, obesity, and related metabolic abnormalities such as hyperglycaemia and dyslipidemia) are of particular concern, especially within this paediatric population that appears to be at greater risk as compared with adults for antipsychotic-induced metabolic adverse effects. In addition to medication, many factors contribute to weigh gain in psychiatric patients, including sedentary lifestyle and poor diet. Excessive weigh gain has several deleterious effects in psychiatric patients, including stigmatization and further social withdrawal, and non compliance with medication. Furthermore, excessive corpulence may evolve to a metabolic syndrome with a high-risk state for future cardiovascular morbidity and mortality in adult age. Because youths are still developing at the time of psychotropic drug exposure, in a context of physiological changes in hormonal and endocrines levels and body composition, most reference values need to be adjusted for gender, age and growth charts. Hence, sex- and age-adjusted BMI percentiles and BMI Z scores are crucial to assess weight gain in children and adolescents. Obesity thresholds have been proposed to define "at risk" categories of patients. In recently issued guidelines, thresholds for antipsychotic-induced weight gain in adults have been set at a 5% increase or one point increase in BMI unit. To date, no definition has reached a consensus in childhood and adolescence. However, some at risk states requiring action are proposed in literature: more than 5% increase in weight within a three-month period; more than half a point increase in BMI Z score; between 85th and 95th BMI percentile plus one adverse health consequence (i.e. hyperglycaemia, dyslipidemia, hyperinsulinemia, hypertension, or

  11. Isolated early onset anemia after rh isoimmunization: a unique presentation in 3 neonates.

    PubMed

    Louis, Deepak; Oberoi, Sapna; Sundaram, Venkataseshan; Trehan, Amita

    2010-08-01

    Rh isoimmunization manifesting as isolated early onset neonatal anemia has not been reported. We describe the presentation of 3 infants who manifested with isolated early severe anemia. All the infants presented early (3 to 7 d of age) with severe pallor. None had clinically significant jaundice. Evidence for hemolysis was present in all and their direct antiglobulin test was positive. To reduce the hemolysis, immunoglobulin was administered after which their hemoglobin improved. This report highlights the possibility of early onset anemia without significant jaundice as the sole manifestation of Rh isoimmunization and the possible beneficial role of immunoglobulin in them.

  12. The impact of early-onset cannabis use on functional brain correlates of working memory.

    PubMed

    Becker, Benjamin; Wagner, Daniel; Gouzoulis-Mayfrank, Euphrosyne; Spuentrup, Elmar; Daumann, Jörg

    2010-08-16

    Cannabis is the most commonly used illicit drug. Prevalence rates are particularly high among adolescents. Neuropsychological studies have identified cannabis-associated memory deficits, particularly linked to an early onset of use. However, it remains unclear, whether the age of onset accounts for altered cortical activation patterns usually observed in cannabis users. Functional magnetic resonance imaging was used to examine cortical activation during verbal working memory challenge in (1) early-onset (onset before the age of sixteen; n=26) and (2) late-onset cannabis users (age at onset at least sixteen; n=17). Early-onset users showed increased activation in the left superior parietal lobe. Correlational analyses confirmed the association between an earlier start of use and increased activity. Contrariwise neither cumulative dose, frequency nor time since last use was significantly associated with cortical activity. Our findings suggest that an early start of cannabis use is associated with increased cortical activation in adult cannabis users, possibly reflecting suboptimal cortical efficiency during cognitive challenge. The maturing brain might be more vulnerable to the harmful effects of cannabis use. However, due to a lack of a non-using control group we cannot exclude alternative interpretations. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  13. Early Onset Obesity and Risk of Metabolic Syndrome Among Chilean Adolescents

    PubMed Central

    Pacheco, Lorena Sonia; Blanco, Estela; Burrows, Raquel; Reyes, Marcela; Lozoff, Betsy

    2017-01-01

    Introduction Obesity and metabolic syndrome (MetS) indicators have increased globally among the pediatric population. MetS indicators in the young elevate their risk of cardiovascular disease and metabolic disorders later in life. This study examined early onset obesity as a risk factor for MetS risk in adolescence. Methods A cohort of Chilean participants (N = 673) followed from infancy was assessed at age 5 years and in adolescence (mean age, 16.8 y). Adiposity was measured at both time points; blood pressure and fasting blood samples were assessed in adolescence only. Early onset obesity was defined as a World Health Organization z score of 2 standard deviations (SDs) or more for body mass index (BMI) at age 5 years. We used linear regression to examine the association between early onset obesity and adolescent MetS risk z score, adjusting for covariates. Results Eighteen percent of participants had early onset obesity, and 50% of these remained obese in adolescence. Mean MetS risk z score in adolescence was significantly higher among those with early onset obesity than among those without (1.0; SD, 0.8 vs 0.2; SD, 0.8 [P < .001]). In the multivariable model, early onset obesity independently contributed to a higher MetS risk score in adolescence (β = 0.27, P < .001), controlling for obesity status at adolescence and sex, and explained 39% of the variance in MetS risk. Conclusion Early onset obesity as young as age 5 years relates to higher MetS risk. PMID:29023232

  14. The clinical and histopathological characteristics of early-onset basal cell carcinoma in Asians.

    PubMed

    Yang, M Y; Kim, J M; Kim, G W; Mun, J H; Song, M; Ko, H C; Kim, B S; Kim, H S; Kim, M B

    2017-01-01

    Basal cell carcinoma (BCC) is by far the most common cancer in white populations. In addition, recent reports have demonstrated an increasing incidence of BCC in Korea. We have observed a significant number of early-onset BCC cases in which the disease occurred in patients younger than 50 years. To investigate the clinicopathological characteristics of early-onset BCC in an Asian population, specifically in Koreans. One hundred and five patients with early-onset BCC were enrolled from a total of 1047 BCC patients who underwent surgery between January 1997 and December 2014 (942 patients over the age of 50 years were designated as the control group). Early-onset BCC accounted for 10.03% of all 1047 cases and the incidence over time displayed an incremental trend. The early-onset group displayed similar results as the control group, with a predominance of female BCC patients and the majority of tumours displaying the following characteristics: small in size, occurring in sun-exposed areas and belonging to the noduloulcerative clinical subtype and nodular histopathological subtype. In comparison with a previous study in a Western population, the incidence of the disease in non-exposed areas of the body, as well as the proportion of tumours of the superficial histological subtype, were lower in Asian patients. Although the clinicopathological characteristics of BCC are well-known, these characteristics have not been determined for early-onset BCC in an Asian population. Therefore, this study is the first report on early-onset BCC in Asians, specifically in a Korean patient group. © 2016 European Academy of Dermatology and Venereology.

  15. Depression and Anxiety Symptoms: Onset, Developmental Course and Risk Factors during Early Childhood

    ERIC Educational Resources Information Center

    Cote, Sylvana M.; Boivin, Michel; Liu, Xuecheng; Nagin, Daniel S.; Zoccolillo, Mark; Tremblay, Richard E.

    2009-01-01

    Background: Depressive and anxiety disorders are among the top ten leading causes of disabilities. We know little, however, about the onset, developmental course and early risk factors for depressive and anxiety symptoms (DAS). Objective: Model the developmental trajectories of DAS during early childhood and to identify risk factors for atypically…

  16. Predictors of Early-Onset Permanent Hearing Loss in Malnourished Infants in Sub-Saharan Africa

    ERIC Educational Resources Information Center

    Olusanya, Bolajoko O.

    2011-01-01

    The objective of this study was to determine the predictors of early-onset permanent hearing loss (EPHL) among undernourished infants in a low-income country where routine screening for developmental disabilities in early childhood is currently unattainable. All infants attending four community-based clinics for routine immunization who met the…

  17. Differentiating early-onset persistent versus childhood-limited conduct problem youth.

    PubMed

    Barker, Edward D; Maughan, Barbara

    2009-08-01

    Among young children who demonstrate high levels of conduct problems, less than 50% will continue to exhibit these problems into adolescence. Such developmental heterogeneity presents a serious challenge for intervention and diagnostic screening in early childhood. The purpose of the present study was to inform diagnostic screening and preventive intervention efforts by identifying youths whose conduct problems persist. The authors examined 1) the extent to which early-onset persistent versus childhood-limited trajectories can be identified from repeated assessments of childhood and early-adolescent conduct problems and 2) how prenatal and early postnatal risks differentiate these two groups. To identify heterogeneity in early-onset conduct problems, the authors used data from a large longitudinal population-based cohort of children followed from the prenatal period to age 13. Predictive risk factors examined were prenatal and postnatal measures of maternal distress (anxiety, depression), emotional and practical support, and family and child characteristics (from birth to 4 years of age). Findings revealed a distinction between early-onset persistent versus childhood-limited conduct problems in youths. Robust predictors of the early-onset persistent trajectory were maternal anxiety during pregnancy (32 weeks gestation), partner cruelty to the mother (from age 0 to 4 years), harsh parenting, and higher levels of child undercontrolled temperament. Sex differences in these risks were not identified. Interventions aiming to reduce childhood conduct problems should address prenatal risks in mothers and early postnatal risks in both mothers and their young children.

  18. Early Onset Substance Use in Adolescents with Depressive, Conduct, and Comorbid Symptoms

    ERIC Educational Resources Information Center

    Stone, Andrea L.; Vander Stoep, Ann; McCauley, Elizabeth

    2016-01-01

    This study investigates whether co-occurring depressive and conduct symptoms in early adolescence are associated with an elevated occurrence of early onset substance. Five hundred twenty-one sixth graders were assessed for depressive symptoms and conduct problems and underwent five substance use assessments during middle school. Logistic…

  19. Common variants at five new loci associated with early-onset inflammatory bowel disease.

    PubMed

    Imielinski, Marcin; Baldassano, Robert N; Griffiths, Anne; Russell, Richard K; Annese, Vito; Dubinsky, Marla; Kugathasan, Subra; Bradfield, Jonathan P; Walters, Thomas D; Sleiman, Patrick; Kim, Cecilia E; Muise, Aleixo; Wang, Kai; Glessner, Joseph T; Saeed, Shehzad; Zhang, Haitao; Frackelton, Edward C; Hou, Cuiping; Flory, James H; Otieno, George; Chiavacci, Rosetta M; Grundmeier, Robert; Castro, Massimo; Latiano, Anna; Dallapiccola, Bruno; Stempak, Joanne; Abrams, Debra J; Taylor, Kent; McGovern, Dermot; Silber, Gary; Wrobel, Iwona; Quiros, Antonio; Barrett, Jeffrey C; Hansoul, Sarah; Nicolae, Dan L; Cho, Judy H; Duerr, Richard H; Rioux, John D; Brant, Steven R; Silverberg, Mark S; Taylor, Kent D; Barmuda, M Michael; Bitton, Alain; Dassopoulos, Themistocles; Datta, Lisa Wu; Green, Todd; Griffiths, Anne M; Kistner, Emily O; Murtha, Michael T; Regueiro, Miguel D; Rotter, Jerome I; Schumm, L Philip; Steinhart, A Hillary; Targan, Stephen R; Xavier, Ramnik J; Libioulle, Cécile; Sandor, Cynthia; Lathrop, Mark; Belaiche, Jacques; Dewit, Olivier; Gut, Ivo; Heath, Simon; Laukens, Debby; Mni, Myriam; Rutgeerts, Paul; Van Gossum, André; Zelenika, Diana; Franchimont, Denis; Hugot, J P; de Vos, Martine; Vermeire, Severine; Louis, Edouard; Cardon, Lon R; Anderson, Carl A; Drummond, Hazel; Nimmo, Elaine; Ahmad, Tariq; Prescott, Natalie J; Onnie, Clive M; Fisher, Sheila A; Marchini, Jonathan; Ghori, Jilur; Bumpstead, Suzannah; Gwillam, Rhian; Tremelling, Mark; Delukas, Panos; Mansfield, John; Jewell, Derek; Satsangi, Jack; Mathew, Christopher G; Parkes, Miles; Georges, Michel; Daly, Mark J; Heyman, Melvin B; Ferry, George D; Kirschner, Barbara; Lee, Jessica; Essers, Jonah; Grand, Richard; Stephens, Michael; Levine, Arie; Piccoli, David; Van Limbergen, John; Cucchiara, Salvatore; Monos, Dimitri S; Guthery, Stephen L; Denson, Lee; Wilson, David C; Grant, Straun F A; Daly, Mark; Silverberg, Mark S; Satsangi, Jack; Hakonarson, Hakon

    2009-12-01

    The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.

  20. Early onset type 2 diabetes: risk factors, clinical impact and management

    PubMed Central

    Idris, Iskandar

    2014-01-01

    Early onset type 2 diabetes mellitus (T2DM) is increasingly prevalent with a significant impact on the individual, healthcare service delivery and planning. The individuals are likely to be obese, lead a sedentary lifestyle, have a strong family history of T2DM, be of black and minority ethnic (BME) origin and come from a less affluent socioeconomic group. They have a heightened risk of developing microvascular and macrovascular complications, often at an earlier stage and with greater frequency than seen in type 1 diabetes. As such, early and aggressive risk factor management is warranted. Early onset T2DM is complex and impacts on service delivery with a need for multidisciplinary care of complications and comorbidities’, in addition to adequate educational and psychological support. This review on the impact of early onset T2DM provides the latest insights into this emerging epidemic. PMID:25364491

  1. Early Onset of Laying and Bumblefoot Favor Keel Bone Fractures.

    PubMed

    Gebhardt-Henrich, Sabine G; Fröhlich, Ernst K F

    2015-11-27

    Numerous studies have demonstrated influences of hybrid, feed, and housing on prevalence of keel bone fractures, but influences of behavior and production on an individual level are less known. In this longitudinal study, 80 white and brown laying hens were regularly checked for keel bone deviations and fractures while egg production was individually monitored using Radio Frequency Identification (RFID) from production until depopulation at 65 weeks of age. These focal birds were kept in eight pens with 20 hens per pen in total. About 62% of the hens had broken keel bones at depopulation. The occurrence of new fractures was temporally linked to egg laying: more new fractures occurred during the time when laying rates were highest. Hens with fractured keel bones at depopulation had laid their first egg earlier than hens with intact keel bones. However, the total number of eggs was neither correlated with the onset of egg laying nor with keel bone fractures. All birds with bumblefoot on both feet had a fracture at depopulation. Hens stayed in the nest for a longer time during egg laying during the ten days after the fracture than during the ten days before the fracture. In conclusion, a relationship between laying rates and keel bone fractures seems likely.

  2. Angiogenic factors for prediction of preeclampsia and intrauterine growth restriction onset in high-risk women: AngioPred study.

    PubMed

    Raia-Barjat, Tiphaine; Prieux, Carole; Gris, Jean-Christophe; Chapelle, Céline; Laporte, Silvy; Chauleur, Céline

    2017-09-22

    The study aimed to compare the level of two angiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng), for the prediction of preeclampsia and intrauterine growth restriction in high-risk pregnant women. A prospective multicenter cohort study of 200 pregnant patients was conducted between June 2008 and October 2010. sFlt1 and sEng were measured by enzyme-linked immunosorbent assay. Forty-five patients developed a placenta-mediated adverse pregnancy outcome. Plasma levels of sFlt1 and sEng were higher in patients who will experience a preeclampsia at 28, 32, and 36 weeks compared with patients with no complication. The same results were observed for intrauterine growth restriction. Plasma levels of sFlt1 and sEng were not significantly different for patients with preeclampsia compare to patients with intrauterine growth restriction. Patients with early pre-eclampsia (PE) had very high rates of angiogenic factors at 20, 24, and 28 weeks. Patients with late PE and early and late intrauterine growth retardation (IUGR) had high rates at 32 and 36 weeks. In high-risk women, angiogenic factors are disturbed before the onset of preeclampsia and this is true for intrauterine growth restriction.

  3. Early Onset of Laying and Bumblefoot Favor Keel Bone Fractures

    PubMed Central

    Gebhardt-Henrich, Sabine G.; Fröhlich, Ernst K. F.

    2015-01-01

    Simple Summary Numerous studies have documented a high prevalence of keel bone fractures in laying hens. In this longitudinal study, 80 white and brown laying hens were regularly checked for keel bone deviations and fractures while egg production was individually monitored. About 62% of the hens had broken keel bones at depopulation. More new fractures occurred during the time when laying rates were highest. Hens with broken keel bones at depopulation had laid their first egg earlier than hens with intact keel bones. All birds with bumblefoot on both feet had a fracture at depopulation. Abstract Numerous studies have demonstrated influences of hybrid, feed, and housing on prevalence of keel bone fractures, but influences of behavior and production on an individual level are less known. In this longitudinal study, 80 white and brown laying hens were regularly checked for keel bone deviations and fractures while egg production was individually monitored using Radio Frequency Identification (RFID) from production until depopulation at 65 weeks of age. These focal birds were kept in eight pens with 20 hens per pen in total. About 62% of the hens had broken keel bones at depopulation. The occurrence of new fractures was temporally linked to egg laying: more new fractures occurred during the time when laying rates were highest. Hens with fractured keel bones at depopulation had laid their first egg earlier than hens with intact keel bones. However, the total number of eggs was neither correlated with the onset of egg laying nor with keel bone fractures. All birds with bumblefoot on both feet had a fracture at depopulation. Hens stayed in the nest for a longer time during egg laying during the ten days after the fracture than during the ten days before the fracture. In conclusion, a relationship between laying rates and keel bone fractures seems likely. PMID:26633520

  4. Early-onset absence epilepsy aggravated by valproic acid: a video-EEG report.

    PubMed

    Belcastro, Vincenzo; Caraballo, Roberto Horacio; Romeo, Antonino; Striano, Pasquale

    2013-12-01

    Early-onset absence epilepsy refers to patients with absence seizures beginning before age 4 and comprises a heterogeneous group of epilepsies. Onset of absence seizures in the first year of life is very rare. We report a boy with absence seizures with onset at age 11 months, whose seizures increased in frequency after the introduction of valproic acid (VPA) treatment and substantially improved upon cessation of treatment. The mechanism of seizure worsening did not involve VPA toxicity, encephalopathy, Glut-1 deficiency or overdosage, and the reason for absence seizure aggravation remained unclear. The patient showed complete control of absence seizures with levetiracetam treatment and the course was benign, both in terms of seizure control and neuropsychological aspects. The similar overall electroclinical picture and outcome between children with early-onset absences and those with CAE support the view that these conditions are a continuum within the wide spectrum of IGE. [Published with video sequences].

  5. Brain Structure Changes Visualized in Early- and Late-Onset Blind Subjects

    PubMed Central

    Leporé, Natasha; Voss, Patrice; Lepore, Franco; Chou, Yi-Yu; Fortin, Madeleine; Gougoux, Frédéric; Lee, Agatha D.; Brun, Caroline; Lassonde, Maryse; Madsen, Sarah K.; Toga, Arthur W.; Thompson, Paul M.

    2009-01-01

    We examine 3D patterns of volume differences in the brain associated with blindness, in subjects grouped according to early and late onset. Using tensor-based morphometry, we map volume reductions and gains in 16 early-onset (EB) and 16 late-onset (LB) blind adults (onset <5 and >14 years old, respectively) relative to 16 matched sighted controls. Each subject’s structural MRI was fluidly registered to a common template. Anatomical differences between groups were mapped based on statistical analysis of the resulting deformation fields revealing profound deficits in primary and secondary visual cortices for both blind groups. Regions outside the occipital lobe showed significant hypertrophy, suggesting widespread compensatory adaptations. EBs but not LBs showed deficits in the splenium and hypertrophy in the isthmus. Gains in the isthmus and non-occipital white matter were more widespread in the EBs. These differences may reflect regional alterations in late neurodevelopmental processes, such as myelination, that continue into adulthood. PMID:19643183

  6. Early-onset Lyme carditis with concurrent disseminated erythema migrans.

    PubMed

    Patel, Kinjan P; Farjo, Peter D; Juskowich, Joy J; Hama Amin, Ali; Mills, James D

    2017-01-01

    Lyme disease is an infection that is estimated to affect over 300,000 people in the United States annually. Typically, it presents with erythema migrans (EM), an annular rash at the site of tick attachment, within 3 to 30 days of inoculation. Untreated patients may progress to early disseminated disease. A further complication, Lyme carditis is rare but may occur several weeks later. It commonly manifests as a variable atrioventricular (AV) conduction block, with a high-grade AV block occurring in only 1% of untreated patients. This case demonstrates an unusually early presentation of Lyme carditis with complete heart block. A 21-year-old male was transferred from an outside emergency department (ED) for possible pacemaker placement due to symptomatic third-degree AV block. Four days earlier the patient presented to the outside ED with fever, chills, and unrecognized EM on his right neck. He was discharged with antipyretics, but no antibiotic therapy. On the day of transfer, he returned with persistent fevers, EM now on his trunk and upper extremities, lightheadedness, and substernal chest pressure. An electrocardiogram revealed the third-degree AV block leading to transfer. Upon arrival, the patient was promptly diagnosed with Lyme carditis. Pacemaker implantation was deferred, and intravenous (IV) ceftriaxone was initiated. Within 48 hours his third-degree AV block improved to a first-degree block. By this time, his EM had also resolved. He was discharged with oral doxycycline and a 30-day event monitor, which ultimately showed persistent first-degree AV block. This case reinforces a unique presentation of Lyme carditis. Disseminated EM and Lyme carditis may present concurrently within 2 weeks of tick attachment. Early recognition and treatment is important for preventing progression to disseminated infection. Lyme-associated AV block will reverse within 48 to 72 hours of initiating IV antibiotic therapy and will not require pacemaker implantation. Lyme carditis

  7. Converging approaches to understanding early onset familial Alzheimer disease: A First Nation study

    PubMed Central

    Cabrera, Laura Y; Beattie, B Lynn; Dwosh, Emily; Illes, Judy

    2015-01-01

    Objectives: In 2007, a novel pathogenic genetic mutation associated with early onset familial Alzheimer disease was identified in a large First Nation family living in communities across British Columbia, Canada. Building on a community-based participatory study with members of the Nation, we sought to explore the impact and interplay of medicalization with the Nation’s knowledge and approaches to wellness in relation to early onset familial Alzheimer disease. Methods: We performed a secondary content analysis of focus group discussions and interviews with 48 members of the Nation between 2012 and 2013. The analysis focused specifically on geneticization, medicalization, and traditional knowledge of early onset familial Alzheimer disease, as these themes were prominent in the primary analysis. Results: We found that while biomedical explanations of disease permeate the knowledge and understanding of early onset familial Alzheimer disease, traditional concepts about wellness are upheld simultaneously. Conclusion: The analysis brings the theoretical framework of “two-eyed seeing” to the case of early onset familial Alzheimer disease for which the contributions of different ways of knowing are embraced, and in which traditional and western ways complement each other on the path of maintaining wellness in the face of progressive neurologic disease. PMID:27092264

  8. The Use of Cannabis as a Predictor of Early Onset of Bipolar Disorder and Suicide Attempts

    PubMed Central

    Leite, Rafaela Torres Portugal; Nogueira, Sarah de Oliveira; do Nascimento, João Paulo Rodrigues; de Lima, Laisa Soares; da Nóbrega, Taís Bastos; Virgínio, Mariana da Silva; Moreno, Lucas Monte da Costa; Sampaio, Bruno Henrique Barbosa; Souza, Fábio Gomes de Matos e

    2015-01-01

    Introduction. Bipolar disorder (BD) implies risk of suicide. The age at onset (AAO) of BD carries prognostic significance. Substance abuse may precede the onset of BD and cannabis is the most common illicit drug used. The main goal of this study is to review the association of cannabis use as a risk factor for early onset of BD and for suicide attempts. Materials and Methods. PubMed database was searched for articles using key words “bipolar disorder,” “suicide attempts,” “cannabis,” “marijuana,” “early age at onset,” and “early onset.” Results. The following percentages in bipolar patients were found: suicide attempts 3.6–42%; suicide attempts and substance use 5–60%; suicide attempts and cannabis use 15–42%. An early AAO was associated with cannabis misuse. The mean age of the first manic episode in individuals with and without BD and cannabis use disorder (CUD) was 19.5 and 25.1 years, respectively. The first depressive episode was at 18.5 and 24.4 years, respectively. Individuals misusing cannabis showed increased risk of suicide. Discussion. Cannabis use is associated with increased risk of suicide attempts and with early AAO. However, the effect of cannabis at the AAO and suicide attempts is not clear. PMID:26097750

  9. Sildenafil citrate therapy for severe early-onset intrauterine growth restriction.

    PubMed

    von Dadelszen, P; Dwinnell, S; Magee, L A; Carleton, B C; Gruslin, A; Lee, B; Lim, K I; Liston, R M; Miller, S P; Rurak, D; Sherlock, R L; Skoll, M A; Wareing, M M; Baker, P N

    2011-04-01

    Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)< 5th percentile] and either the gestational age was <25(+0) weeks or an estimate of the fetal weight was <600 g (excluding known fetal anomaly/syndrome and/or planned termination). Sildenafil treatment was associated with increased fetal AC growth [odds ratio, 12.9; 95% confidence interval (CI), 1.3, 126; compared with institutional Sildenafil-naive early-onset IUGR controls]. Randomised controlled trial data are required to determine whether Sildenafil improves perinatal outcomes for early-onset IUGR-complicated pregnancies. © 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.

  10. Key goals and indicators for successful aging of adults with early-onset disability.

    PubMed

    LaPlante, Mitchell P

    2014-01-01

    Substantial improvements have occurred in the longevity of several groups of individuals with early-onset disabilities, with many now surviving to advanced ages. This paper estimates the population of adults aging with early-onset disabilities at 12-15 million persons. Key goals for the successful aging of adults with early-onset disabilities are discussed, emphasizing reduction in risks for aging-related chronic disease and secondary conditions, while promoting social participation and independence. However, indicators suggest that elevated risk factors for aging-related chronic diseases, including smoking, obesity, and inactivity, as well as barriers to prevention and the diminished social and economic situation of adults with disabilities are continuing impediments to successful aging that must be addressed. Increased provider awareness that people with early-onset disabilities are aging and can age successfully and the integration of disability and aging services systems are transformative steps that will help adults with early-onset disability to age more successfully. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. The onset of galactic winds in early-type galaxies

    NASA Technical Reports Server (NTRS)

    Jones, Christine

    1992-01-01

    We completed the spectral analysis of 31 early-type galaxies to investigate whether their x-ray emission was predominantly due to thermal bremsstrahlung from a hot gaseous corona or emission from discrete, galactic sources such as x-ray binaries. If a corona dominates the x-ray emission, its spectra is expected to be relatively cool (0.5 - 1 keV) compared to the harder emission associated with x-ray binaries in our galaxy, the Magellanic Clouds and M31. While it is generally accepted that the x-ray emission in luminous E and S0 galaxies arises from hot coronae, the status of hot gas in lower luminosity (and hence lower mass) galaxies is less clear. Calculations show that, for a given supernova rate, a critical galaxy luminosity (mass) exists below which the gas cannot be gravitationally confined and a galactic wind is predicted to be effective in expelling gas from the galaxy. Since significant mass (a dark halo) is required to hold a hot, gaseous corona around a galaxy, we expect that the faintest, smallest galaxies will not have a hot corona, but their x-ray emission will be dominated by galactic sources or by an active galactic nuclei. In the sample we tested which spanned the absolute magnitude range from -21.5 to -19.5, we found that except for two galaxies whose x-ray emission was dominated by an active nucleus, that the others were consistent with emission from hot gas. We also found that there is a correlation between gas temperature and galaxy magnitude (mass), such that the brighter, more luminous galaxies have hotter gas temperatures. Thus even at relatively faint magnitudes, the dominant emission from early-type galaxies appears to be hot gas. We also carried out an investigation of the x-ray surface brightness distribution of the x-ray emission for about 100 early type galaxies to determine whether the x-ray emission from galaxies are extended. Extended x-ray emission is expected if the emission is due to a hot gaseous corona. We determined the ratio

  12. Early onset primary pulmonary cryptococcosis in a renal transplant patient.

    PubMed

    Tarai, B; Kher, V; Kotru, P; Sabhikhi, A; Barman, P; Rattan, A

    2010-01-01

    We report a case of primary pulmonary cryptococcosis in a post-renal transplant patient. A 65-year-old male renal transplant patient was admitted to the hospital with a low grade fever of 1 month, radiologically mimicking tuberculosis (TB). Broncho-alveolar fluid (BAL) shows capsulated yeast, and Cryptococcus neoformans was grown on culture supported by cytology and histopathological examination. Cryptococcal antigen was positive (32-fold) in serum and was negative in cerebrospinal fluid (CSF). The patient was given amphotericin B and 5-flucytosine and clinical improvement was seen on a weekly follow up. The serum cryptococcal antigen test might contribute to the early detection and treatment of pulmonary cryptococcosis. The results of antifungal susceptibility were aid in selecting the drug of choice for treatment.

  13. Early onset of puberty and early ovarian failure in CYP7B1 knockout mice

    PubMed Central

    Omoto, Yoko; Lathe, Richard; Warner, Margaret; Gustafsson, Jan-Åke

    2005-01-01

    CYP7B1 is the enzyme responsible for hydroxylation and termination of the estrogenic actions of the androgen metabolite, 5α-androstane-3β, 17β-diol (3βAdiol). 3βAdiol is estrogenic in ERα or ERβ positive cells only if they do not express CYP7B1. In this study we show that female CYP7B1–/– mice experience early onset of growth of the uterus and mammary glands and commence estrus cycles 2 days earlier than their wild-type littermates. Adult mammary glands and uteri appear to be under continuous estrogenic stimulation. We conclude that, by cell-specific regulation of the estrogenicity of 3βAdiol, CYP7B1 performs two major tasks: (i) it allows 3βAdiol to have growth inhibitory effects through ERβ and (ii) it permits estradiol-specific activation of estrogen receptors by protection of certain cells from the estrogenic effects of 3βAdiol. When CYP7B1 is inactivated, 3βAdiol activates estrogen receptors indiscriminately, and the overall effect is prolonged and inappropriate exposure to estrogen. PMID:15710898

  14. Early onset of puberty and early ovarian failure in CYP7B1 knockout mice.

    PubMed

    Omoto, Yoko; Lathe, Richard; Warner, Margaret; Gustafsson, Jan-Ake

    2005-02-22

    CYP7B1 is the enzyme responsible for hydroxylation and termination of the estrogenic actions of the androgen metabolite, 5alpha-androstane-3beta, 17beta-diol (3betaAdiol). 3betaAdiol is estrogenic in ERalpha or ERbeta positive cells only if they do not express CYP7B1. In this study we show that female CYP7B1(-/-) mice experience early onset of growth of the uterus and mammary glands and commence estrus cycles 2 days earlier than their wild-type littermates. Adult mammary glands and uteri appear to be under continuous estrogenic stimulation. We conclude that, by cell-specific regulation of the estrogenicity of 3betaAdiol, CYP7B1 performs two major tasks: (i) it allows 3betaAdiol to have growth inhibitory effects through ERbeta and (ii) it permits estradiol-specific activation of estrogen receptors by protection of certain cells from the estrogenic effects of 3betaAdiol. When CYP7B1 is inactivated, 3betaAdiol activates estrogen receptors indiscriminately, and the overall effect is prolonged and inappropriate exposure to estrogen.

  15. Birdshot Retinochoroidopathy: Differences in Clinical Characteristics between Patients with Early and Late Age of Onset.

    PubMed

    Silpa-Archa, Sukhum; Cao, Jennifer H; Boonsopon, Sutasinee; Lee, Joan; Preble, Janine M; Foster, C Stephen

    2017-10-01

    To describe differences in the clinical characteristics of birdshot retinochoroidopathy (BSRC) patients diagnosed early and later in life. This is a retrospective cohort study. Age was primarily analyzed and 50 years of age at diagnosis was selected as a cut-off point. A total of 144 patients (288 eyes) were included; 68 with early-onset and 76 with late-onset BSRC. The younger group had a statistically significant higher rate of more severe iritis (p = 0.04); an average number of non-steroidal immunosuppressants and biologic agents (NSIB) (p = 0.04); and a prolonged time to initiation of NSIB (p = 0.01). There were only four patients (3%) who had >0.5+ cells in the anterior chamber. Patients with early-onset BSRC carried a higher risk for anterior segment inflammation, had a more prolonged delay to initiation of treatment with NSIB, and required a greater number of NSIBs to achieve remission.

  16. Cognitive Development in Infantile-Onset Pompe Disease Under Very Early Enzyme Replacement Therapy.

    PubMed

    Lai, Chih-Jou; Hsu, Ting-Rong; Yang, Chia-Feng; Chen, Shyi-Jou; Chuang, Ya-Chin; Niu, Dau-Ming

    2016-12-01

    Most patients with infantile-onset Pompe disease die in early infancy before beginning enzyme replacement therapy, which has made it difficult to evaluate the impact of Pompe disease on cognitive development. Patients with infantile-onset Pompe disease can survive with enzyme replacement therapy, and physicians can evaluate cognitive development in these patients. We established an effective newborn screening program with quick clinical diagnostic criteria. Cognitive and motor development were evaluated using the Bayley Scales of Infant and Toddler Development-Third Edition at 6, 12, and 24 months of age. The patients who were treated very early demonstrate normal cognitive development with no significant change in cognition during this period (P = .18 > .05). The cognitive development was positively correlated with motor development (r = 0.533, P = .011). The results indicated that very early enzyme replacement therapy could protect cognitive development in patients with infantile-onset Pompe disease up to 24 months of age. © The Author(s) 2016.

  17. Early onset epilepsy is associated with increased mortality: a population-based study

    PubMed Central

    Moseley, Brian D.; Wirrell, Elaine C.; Wong-Kisiel, Lily C.; Nickels, Katherine

    2013-01-01

    SUMMARY We examined mortality in early onset (age <12 months) epilepsy in a population-based group of children. Children with early onset epilepsy were significantly more likely to die (case fatality, CF 8/60 versus 8/407, p<0.001; mortality rate, MR 14.5/1000 versus 2/1000 person years; standardized mortality ratio, SMR 22.25 versus 5.67). Mortality was greater in children with malignant neonatal (age <1 month) epilepsy (CF 4/12 versus 12/450, p<0.001; MR 54/1000 person years versus 2.7/1000 person year; SMR 46.55 versus 7.22). Given that only 1/8 early onset epilepsy deaths was seizure-related, mortality appears to be more affected by underlying etiology. PMID:23582606

  18. Relevance of the hygiene hypothesis to early vs. late onset allergic rhinitis.

    PubMed

    Matheson, M C; Walters, E H; Simpson, J A; Wharton, C L; Ponsonby, A-L; Johns, D P; Jenkins, M A; Giles, G G; Hopper, J L; Abramson, M J; Dharmage, S C

    2009-03-01

    The hygiene hypothesis proposes that reduced exposure to infections in early life increases the risk of developing allergic conditions including allergic rhinitis. We examined the association between markers of the hygiene hypothesis and allergic rhinitis that developed before 7 years of age and allergic rhinitis that developed after 7 years of age. The Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort (n=8583) study of respiratory disease. Participants have been followed from 7 to 44 years of age. Information on potential risk factors, allergies and respiratory symptoms was collected longitudinally. Using multi-nomial logistic regression, exposure to siblings, infections, tonsillectomy and farm residence during childhood were examined as risk factors for allergic rhinitis that developed before or after 7 years of age. All analyses were adjusted for gender, maternal and paternal atopy, mother's age at participant's birth, paternal socio-economic status in 1968 and personal socio-economic status in 2004. Greater cumulative exposure to siblings before the age of 2 years was strongly inversely associated with early onset allergic rhinitis (<1 year sib exposure: OR=0.6, 95% CI 0.3-1.0; 1-3 years sib exposure: OR=0.6, 95% CI 0.4-0.9; >3 years sib exposure: OR=0.4, 95% CI 0.3-0.8) less so with later onset allergic rhinitis. The risk of early onset allergic rhinitis decreased with increasing viral infections (OR=0.7, 95% CI 0.5-0.9) during childhood. Having a tonsillectomy before 7 years of age increased the risk of early onset allergic rhinitis (OR=1.7, 95% CI 1.2-2.5). None of these factors was associated with later onset allergic rhinitis. Exposures relevant to the hygiene hypothesis were important predictors for the development of early onset but less so for later onset allergic rhinitis. The exact mechanisms by which siblings and infections protect against allergic rhinitis are unclear. The stronger findings for earlier onset allergic rhinitis

  19. [Mutations of amyloid precursor protein in early-onset familial Alzheimer's disease].

    PubMed

    Naruse, S; Tsuji, S; Miyatake, T

    1992-09-01

    Genetic linkage studies of familial Alzheimer's disease (FAD) have suggested that some form of early-onset FAD is linked to proximal long arm of chromosome 21. It has been also suggested that some form of late-onset FAD is linked to long arm of chromosome 19. Goate et al have identified a mis-sense mutation (Val to Ile) in exon 17 of the amyloid precursor protein (APP) gene in 2 of 16 early-onset FAD families, and have shown that the FAD locus in an FAD family is tightly linked to the mis-sense mutation. To determine if the mis-sense mutation is observed in different ethnic origine, we have studied some early-onset FAD families. Two early-onset FAD families showed the existence of the mutation. As the mutation has been identified in different ethnic origine and the mutation has not been observed in normal individuals, it strengthen hypothesis that the mutation is pathogenic. Recently, Val to Phe and Val to Gly mutations have been also identified at the same codon (Codon 717) of the APP gene.

  20. Early onset dementia in New Zealand Pacific boxers: a case series.

    PubMed

    Payman, Vahid; Yates, Susan; Cullum, Sarah

    2018-05-04

    To describe the biopsychosocial characteristics of a series of Pacific men living in South Auckland with a history of boxing presenting with early onset dementia. We discuss the history of boxing in Pacific people and the possibility of increased risk of early onset dementia in New Zealand Pacific men compared to their European counterparts. We reviewed the files of Pacific men with a history of amateur or professional boxing who presented to our memory and older adult mental health services with early onset dementia over a 45-month period. We gathered relevant information to construct a biopsychosocial paradigm as possible explanation of this phenomenon. We identified a series of eight New Zealand Pacific men with early onset dementia and with a history of boxing. Alcohol was a contributing factor in seven of the eight cases, and vascular risk factors in five. Historical, cultural and socio-economic factors underpin the attraction of some Pacific men to boxing as a sport. Given that New Zealand Pacific peoples may have an earlier onset of dementia than their European counterparts, further research is required to establish whether boxing is a contributory factor. Sports physicians should advise young New Zealand Pacific boxers about the long-term risks associated with their sport.

  1. Loss of Nfkb1 leads to early onset aging.

    PubMed

    Bernal, Giovanna M; Wahlstrom, Joshua S; Crawley, Clayton D; Cahill, Kirk E; Pytel, Peter; Liang, Hua; Kang, Shijun; Weichselbaum, Ralph R; Yamini, Bakhtiar

    2014-11-01

    NF-κB is a major regulator of age-dependent gene expression and the p50/NF-κB1 subunit is an integral modulator of NF-κB signaling. Here, we examined Nfkb1-/- mice to investigate the relationship between this subunit and aging. Although Nfkb1-/- mice appear similar to littermates at six months of age, by 12 months they have a higher incidence of several observable age-related phenotypes. In addition, aged Nfkb1-/- animals have increased kyphosis, decreased cortical bone, increased brain GFAP staining and a decrease in overall lifespan compared to Nfkb1+/+. In vitro, serially passaged primary Nfkb1-/- MEFs have more senescent cells than comparable Nfkb1+/+ MEFs. Also, Nfkb1-/- MEFs have greater amounts of phospho-H2AX foci and lower levels of spontaneous apoptosis than Nfkb1+/+, findings that are mirrored in the brains of Nfkb1-/- animals compared to Nfkb1+/+. Finally, in wildtype animals a substantial decrease in p50 DNA binding is seen in aged tissue compared to young. Together, these data show that loss of Nfkb1 leads to early animal aging that is associated with reduced apoptosis and increased cellular senescence. Moreover, loss of p50 DNA binding is a prominent feature of aged mice relative to young. These findings support the strong link between the NF-κB pathway and mammalian aging.

  2. Risk Factors for Early-Onset Peritonitis in Southern Chinese Peritoneal Dialysis Patients.

    PubMed

    Wu, Haishan; Huang, Rong; Yi, Chunyan; Wu, Juan; Guo, Qunying; Zhou, Qian; Yu, Xueqing; Yang, Xiao

    ♦ BACKGROUND: Early peritonitis was confirmed to be associated with a higher risk of early technique failure. However, literature concerning peritonitis within the first 3 months of peritoneal dialysis (PD) initiation is scarce. The present study was to investigate risk factors associated with early-onset peritonitis in PD patients. ♦ METHODS: In this retrospective observational cohort study, all incident PD patients from January 1, 2006, to December 31, 2013, were recruited and followed up until December 31, 2014. According to time-to-first episode of peritonitis, patients were divided into early-onset (≤ 3 months) peritonitis and late-onset (> 3 months) peritonitis. Baseline demographic, clinical, and laboratory data, as well as episodes of peritonitis, were collected. Risk factors associated with early-onset peritonitis were evaluated using logistic regression model. ♦ RESULTS: Of 1,690 patients on PD, 503 (29.8%) developed at least 1 episode of peritonitis and 118 (7.0%) patients presented the first episodes of peritonitis within the first 3 months. A multivariate logistic analysis showed that higher body mass index (BMI) (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.01 - 1.15, p = 0.034), hypoalbuminemia (OR 1.75, 95% CI 1.11 - 2.78, p = 0.017), and catheter exit-site infection (OR 4.14, 95% CI 2.45 - 7.00, p < 0.001) were risk factors independently associated with early-onset peritonitis. Compared to those with late-onset, patients with early-onset peritonitis had a higher overall peritonitis rate (0.76 vs 0.38 per patient-year, p < 0.001) and worse technique survival (p < 0.001), while patient survival did not differ significantly between the 2 groups during the long-term follow-up (p > 0.05). ♦ CONCLUSIONS: Higher BMI, hypoalbuminemia, and catheter exit-site infection were the risk factors associated with early-onset peritonitis in PD patients. Copyright © 2016 International Society for Peritoneal Dialysis.

  3. A Risk Prediction Model for the Assessment and Triage of Women with Hypertensive Disorders of Pregnancy in Low-Resourced Settings: The miniPIERS (Pre-eclampsia Integrated Estimate of RiSk) Multi-country Prospective Cohort Study

    PubMed Central

    Payne, Beth A.; Hutcheon, Jennifer A.; Ansermino, J. Mark; Hall, David R.; Bhutta, Zulfiqar A.; Bhutta, Shereen Z.; Biryabarema, Christine; Grobman, William A.; Groen, Henk; Li, Jing; Magee, Laura A.; Merialdi, Mario; Nakimuli, Annettee; Qu, Ziguang; Sikandar, Rozina; Sass, Nelson; Sawchuck, Diane; Steyn, D. Wilhelm; Widmer, Mariana; Zhou, Jian; von Dadelszen, Peter

    2014-01-01

    Background Pre-eclampsia/eclampsia are leading causes of maternal mortality and morbidity, particularly in low- and middle- income countries (LMICs). We developed the miniPIERS risk prediction model to provide a simple, evidence-based tool to identify pregnant women in LMICs at increased risk of death or major hypertensive-related complications. Methods and Findings From 1 July 2008 to 31 March 2012, in five LMICs, data were collected prospectively on 2,081 women with any hypertensive disorder of pregnancy admitted to a participating centre. Candidate predictors collected within 24 hours of admission were entered into a step-wise backward elimination logistic regression model to predict a composite adverse maternal outcome within 48 hours of admission. Model internal validation was accomplished by bootstrapping and external validation was completed using data from 1,300 women in the Pre-eclampsia Integrated Estimate of RiSk (fullPIERS) dataset. Predictive performance was assessed for calibration, discrimination, and stratification capacity. The final miniPIERS model included: parity (nulliparous versus multiparous); gestational age on admission; headache/visual disturbances; chest pain/dyspnoea; vaginal bleeding with abdominal pain; systolic blood pressure; and dipstick proteinuria. The miniPIERS model was well-calibrated and had an area under the receiver operating characteristic curve (AUC ROC) of 0.768 (95% CI 0.735–0.801) with an average optimism of 0.037. External validation AUC ROC was 0.713 (95% CI 0.658–0.768). A predicted probability ≥25% to define a positive test classified women with 85.5% accuracy. Limitations of this study include the composite outcome and the broad inclusion criteria of any hypertensive disorder of pregnancy. This broad approach was used to optimize model generalizability. Conclusions The miniPIERS model shows reasonable ability to identify women at increased risk of adverse maternal outcomes associated with the hypertensive

  4. Risk of early-onset prostate cancer associated with occupation in the Nordic countries.

    PubMed

    Barry, Kathryn Hughes; Martinsen, Jan Ivar; Alavanja, Michael C R; Andreotti, Gabriella; Blair, Aaron; Hansen, Johnni; Kjærheim, Kristina; Koutros, Stella; Lynge, Elsebeth; Sparèn, Pär; Tryggvadottir, Laufey; Weiderpass, Elisabete; Berndt, Sonja I; Pukkala, Eero

    2017-12-01

    Early-onset prostate cancer is often more aggressive and may have a different aetiology than later-onset prostate cancer, but has been relatively little studied to date. We evaluated occupation in relation to early- and later-onset prostate cancer in a large pooled study. We used occupational information from census data in five Nordic countries from 1960 to 1990. We identified prostate cancer cases diagnosed from 1961 to 2005 by linkage of census information to national cancer registries and calculated standardised incidence ratios (SIRs) separately for men aged 30-49 and those aged 50 or older. We also conducted separate analyses by period of follow-up, 1961-1985 and 1986-2005, corresponding to pre- and post-prostate-specific antigen (PSA) screening. For early-onset prostate cancer (n = 1521), we observed the highest SIRs for public safety workers (e.g. firefighters) (SIR = 1.71, 95% confidence interval [CI]: 1.23-2.31) and military personnel (SIR = 1.97, 95% CI: 1.31-2.85). These SIRs were significantly higher than the SIRs for later-onset disease (for public safety workers, SIR = 1.10, 95% CI: 1.07-1.14 and for military personnel, SIR = 1.09, 95% CI: 1.05-1.13; p heterogeneity  = 0.005 and 0.002, respectively). Administrators and technical workers also demonstrated significantly increased risks for early-onset prostate cancer, but the SIRs did not differ from those of later-onset disease (p heterogeneity >0.05). While our early-onset finding for public safety workers was restricted to the post-PSA period, that for military personnel was restricted to the pre-PSA period. Our results suggest that occupational exposures, particularly for military personnel, may be associated with early-onset prostate cancer. Further evaluation is needed to explain these findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Comparison of Neuropsychological Functioning Between Adults With Early- and Late-Onset DSM-5 ADHD.

    PubMed

    Lin, Yu-Ju; Gau, Susan Shur-Fen

    2017-09-01

    We aimed to compare the visually dependent neuropsychological functioning among adults with Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) ADHD who recalled symptom onset by and after age 7 and non-ADHD controls. We divided the participants, aged 17 to 40 years, into three groups-(a) ADHD, onset <7 years (early-onset, n = 142); (b) ADHD, onset between 7 and <12 years (late-onset, n = 41); (c) non-ADHD controls ( n = 148)-and compared their neuropsychological functioning, measured by the Cambridge Neuropsychological Testing Automated Battery. Both ADHD groups had deficits in attention and signal detectability, spatial working memory, and short-term spatial memory, but only the early-onset group showed deficits in alertness, set-shifting, and planning after controlling for age, sex, and psychiatric comorbidities. There was no statistical difference between the two ADHD groups in neuropsychological functioning. DSM-5 criteria for diagnosing adult ADHD are not too lax regarding neuropsychological functioning.

  6. Cognitive ability in young adulthood predicts risk of early-onset dementia in Finnish men.

    PubMed

    Rantalainen, Ville; Lahti, Jari; Henriksson, Markus; Kajantie, Eero; Eriksson, Johan G; Räikkönen, Katri

    2018-06-06

    To test if the Finnish Defence Forces Basic Intellectual Ability Test scores at 20.1 years predicted risk of organic dementia or Alzheimer disease (AD). Dementia was defined as inpatient or outpatient diagnosis of organic dementia or AD risk derived from Hospital Discharge or Causes of Death Registers in 2,785 men from the Helsinki Birth Cohort Study, divided based on age at first diagnosis into early onset (<65 years) or late onset (≥65 years). The Finnish Defence Forces Basic Intellectual Ability Test comprises verbal, arithmetic, and visuospatial subtests and a total score (scores transformed into a mean of 100 and SD of 15). We used Cox proportional hazard models and adjusted for age at testing, childhood socioeconomic status, mother's age at delivery, parity, participant's birthweight, education, and stroke or coronary heart disease diagnosis. Lower cognitive ability total and verbal ability (hazard ratio [HR] per 1 SD disadvantage >1.69, 95% confidence interval [CI] 1.01-2.63) scores predicted higher early-onset any dementia risk across the statistical models; arithmetic and visuospatial ability scores were similarly associated with early-onset any dementia risk, but these associations weakened after covariate adjustments (HR per 1 SD disadvantage >1.57, 95% CI 0.96-2.57). All associations were rendered nonsignificant when we adjusted for participant's education. Cognitive ability did not predict late-onset dementia risk. These findings reinforce previous suggestions that lower cognitive ability in early life is a risk factor for early-onset dementia. © 2018 American Academy of Neurology.

  7. [Clinical characteristics and renal uric acid excretion in early-onset gout patients].

    PubMed

    Li, Q H; Liang, J J; Chen, L X; Mo, Y Q; Wei, X N; Zheng, D H; Dai, L

    2018-03-01

    Objective: To investigate clinical characteristics and renal uric acid excretion in early-onset gout patients. Methods: Consecutive inpatients with primary gout were recruited between 2013 and 2017. The patients with gout onset younger than 30 were defined as early-onset group while the others were enrolled as control group. Clinical characteristics and uric acid (UA) indicators were compared between two groups. Results: Among 202 recruited patients, the early-onset group included 36 patients (17.8%). Compared with control group, the early-onset group presented more patients with obesity [13 patients (36.1%) vs. 22 patients (13.3%), P< 0.05], significantly higher serum UA level [(634±124)μmol/L vs.(527±169)μmol/L] and glomerular load of UA[(7.2±2.8)mg·min(-1)·1.73m(-2) vs. (4.4±2.2)mg·min(-1)·1.73m(-2)] and estimated glomerular filtration rate (GFR) [(83±21)ml·min(-1)·1.73m(-2) vs. (67±21)ml·min(-1)·1.73m(-2)] (all P< 0.05), lower fractional excretion of UA [4.4% (3.4%,6.1%) vs. 7.2% (5.2%,9.6%), P< 0.05], whereas 24h urinary UA excretion was comparable [(2 788±882)μmol/1.73m(2) vs. (2 645±1 140)μmol/1.73m(2), P= 0.274]. Subgroup analysis of patients without chronic kidney disease showed significantly lower fractional excretion of UA in the early-onset group [4.5%(3.3%,6.1%) vs. 6.7% (5.1%,8.7%), P< 0.05]. Logistic regression analysis showed that obesity ( OR= 3.25) and fractional excretion of UA less than 7% ( OR= 9.01, all P< 0.05) were risk factors of gout early onset. Conclusion: The gout patients with early-onset younger than 30 present high serum and glomerular load of uric acid which might be due to obesity and relative under-excretion of renal uric acid.

  8. Association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism with early-onset bipolar disorder.

    PubMed

    Nassan, Malik; Croarkin, Paul E; Luby, Joan L; Veldic, Marin; Joshi, Paramjit T; McElroy, Susan L; Post, Robert M; Walkup, John T; Cercy, Kelly; Geske, Jennifer R; Wagner, Karen D; Cuellar-Barboza, Alfredo B; Casuto, Leah; Lavebratt, Catharina; Schalling, Martin; Jensen, Peter S; Biernacka, Joanna M; Frye, Mark A

    2015-09-01

    Brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) functional polymorphism has been implicated in early-onset bipolar disorder. However, results of studies are inconsistent. We aimed to further explore this association. DNA samples from the Treatment of Early Age Mania (TEAM) and Mayo Clinic Bipolar Disorder Biobank were investigated for association of rs6265 with early-onset bipolar disorder. Bipolar cases were classified as early onset if the first manic or depressive episode occurred at age ≤19 years (versus adult-onset cases at age >19 years). After quality control, 69 TEAM early-onset bipolar disorder cases, 725 Mayo Clinic bipolar disorder cases (including 189 early-onset cases), and 764 controls were included in the analysis of association, assessed with logistic regression assuming log-additive allele effects. Comparison of TEAM cases with controls suggested association of early-onset bipolar disorder with the rs6265 minor allele [odds ratio (OR) = 1.55, p = 0.04]. Although comparison of early-onset adult bipolar disorder cases from the Mayo Clinic versus controls was not statistically significant, the OR estimate indicated the same direction of effect (OR = 1.21, p = 0.19). When the early-onset TEAM and Mayo Clinic early-onset adult groups were combined and compared with the control group, the association of the minor allele rs6265 was statistically significant (OR = 1.30, p = 0.04). These preliminary analyses of a relatively small sample with early-onset bipolar disorder are suggestive that functional variation in BDNF is implicated in bipolar disorder risk and may have a more significant role in early-onset expression of the disorder. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. A neonate with intestinal volvulus without malrotation exhibiting early jaundice with a suspected fetal onset.

    PubMed

    Hara, Kaori; Kinoshita, Mari; Kin, Takane; Arimitsu, Takeshi; Matsuzaki, Yohei; Ikeda, Kazushige; Tomita, Hiroshi; Fujino, Akihiro; Kuroda, Tatsuo

    2015-01-01

    Intestinal volvulus without malrotation is a rare disease that causes volvulus of the small intestine despite normal intestinal rotation and fixation. We encountered a neonate with this disease who developed early jaundice and was suspected to have a fetal onset. This patient was characterized by early jaundice complicating intestinal volvulus without malrotation and is considered to have exhibited reduced fetal movement and early jaundice as a result of volvulus, necrosis, and hemorrhage of the small intestine in the fetal period. If abdominal distention accompanied by early jaundice is noted in a neonate, intestinal volvulus without malrotation and associated intraabdominal hemorrhage should be suspected and promptly treated.

  10. ABCC6 mutations and early onset stroke: Two cases of a typical Pseudoxanthoma Elasticum.

    PubMed

    Bertamino, Marta; Severino, Mariasavina; Grossi, Alice; Rusmini, Marta; Tortora, Domenico; Gandolfo, Carlo; Pederzoli, Silvia; Malattia, Clara; Picco, Paolo; Striano, Pasquale; Ceccherini, Isabella; Di Rocco, Maja

    2018-04-12

    Pseudoxanthoma elasticum (PXE) is a rare genetic disorder characterized by fragmented and mineralized elastic fibers in the mid-dermis of the skin, eye, digestive tract and cardiovascular system. Clinical presentation includes typical skin lesions, ocular angioid streaks, and multisystem vasculopathy. The age of onset varies considerably from infancy to old age, but the diagnosis is usually made in young adults due to frequent absence of pathognomonic skin and ocular manifestations in early childhood. We report two children with PXE presenting with isolated multisystem vasculopathy and early-onset stroke. In the first patient, diagnosis was delayed until typical dermatologic alterations appeared; in the second patient, next-generation sequencing (NGS) study led to early diagnosis and specific follow-up, underlying the crucial role in idiopathic pediatric stroke of early genetic testing using NGS-based panels. Copyright © 2018 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  11. First impression at stroke onset plays an important role in early hospital arrival.

    PubMed

    Iguchi, Yasuyuki; Wada, Kuniyasu; Shibazaki, Kensaku; Inoue, Takeshi; Ueno, Yuji; Yamashita, Shinji; Kimura, Kazumi

    2006-01-01

    Treatment for acute ischemic stroke should be administered as soon as possible after symptom onset. The aim of this study was to investigate whether or not the patient's and bystander's first impression at stroke onset was associated with hospital arrival time. To investigate the factors influencing the prehospital delay, we prospectively interviewed consecutive stroke patients and bystanders about their first impression at the stroke onset and assessed the methods of transportation, and clinical characteristics. Early arrival was defined as a hospital arrival of within 2 h from stroke onset. One hundred thirty patients were enrolled: 82% were ischemic stroke and 18% were cerebral hemorrhage. The median interval between symptom onset and the hospital arrival was 7.5 h and 30% of patients presented within 2 h of stroke onset. First impression of stroke (odds ratios [OR] 4.56, 95% confidence interval [CI] 1.54-13.5, p=0.006), presence of consciousness disturbance (OR 4.29, CI 1.39-13.3, p=0.011), arrival through other facilities (OR 0.25, CI 0.08-0.76, p=0.015), a history of diabetes (OR 0.23, CI 0.06-0.80, p=0.028) and nocturnal onset (OR 0.19, CI 0.04-0.88, p=0.042) independently contributed to the early arrival. The first impression of patients and bystanders at stroke onset is important in order to reach hospital earlier in Japan. Public educational systems such as those, which advertise stroke warning signs, are necessary.

  12. The cortical damage, early relapses, and onset of the progressive phase in multiple sclerosis.

    PubMed

    Scalfari, Antonio; Romualdi, Chiara; Nicholas, Richard S; Mattoscio, Miriam; Magliozzi, Roberta; Morra, Aldo; Monaco, Salvatore; Muraro, Paolo A; Calabrese, Massimiliano

    2018-05-16

    To investigate the relationship among cortical radiologic changes, the number of early relapses (ERs), and the long-term course of multiple sclerosis (MS). In this cohort study, we assessed the number of cortical lesions (CLs) and white matter (WM) lesions and the cortical thickness (Cth) at clinical onset and after 7.9 mean years among 219 patients with relapsing remitting (RR) MS with 1 (Low-ER), 2 (Mid-ER), and ≥3 (High-ER) ERs during the first 2 years. Kaplan-Meier and Cox regression analyses investigated early factors influencing the risk of secondary progressive (SP) MS. Fifty-nine patients (27%) converted to SPMS in 6.1 mean years. A larger number of CLs at onset predicted a higher risk of SPMS (hazard ratio [HR] 2.16, 4.79, and 12.3 for 2, 5, and 7 CLs, respectively, p < 0.001) and shorter latency to progression. The High-ER compared to the Low-ER and Mid-ER groups had a larger volume of WM lesions and CLs at onset, accrued more CLs, experienced more severe cortical atrophy over time, and entered the SP phase more rapidly. In the multivariate model, older age at onset (HR 1.97, p < 0.001), a larger baseline CL (HR 2.21, p = 0.005) and WM lesion (HR 1.32, p = 0.03) volume, early changes of global Cth (HR 1.36, p = 0.03), and ≥3 ERs (HR 6.08, p < 0.001) independently predicted a higher probability of SP. Extensive cortical damage at onset is associated with florid inflammatory clinical activity and predisposes to a rapid occurrence of the progressive phase. Age at onset, the number of early attacks, and the extent of baseline focal cortical damage can identify groups at high risk of progression who may benefit from more active therapy. © 2018 American Academy of Neurology.

  13. Reconceptualizing Early and Late Onset: A Life Course Analysis of Older Heroin Users

    ERIC Educational Resources Information Center

    Boeri, Miriam Williams; Sterk, Claire E.; Elifson, Kirk W.

    2008-01-01

    Purpose: Researchers' knowledge regarding older users of illicit drugs is limited despite the increasing numbers of users. In this article, we apply a life course perspective to gain a further understanding of older adult drug use, specifically contrasting early- and late-onset heroin users. Design and Methods: We collected qualitative data from…

  14. Memory in Early Onset Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder: Similarities and Differences

    ERIC Educational Resources Information Center

    Udal, Anne H.; Oygarden, Bjorg; Egeland, Jens; Malt, Ulrik F.; Groholt, Berit

    2012-01-01

    Differentiating between early-onset bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) can be difficult. Memory problems are commonly reported in BD, and forgetfulness is among the diagnostic criteria for ADHD. We compared children and adolescents with BD (n = 23), ADHD combined type (ADHD-C; n = 26), BD + ADHD-C (n = 15),…

  15. Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Demographic and Clinical Characteristics

    ERIC Educational Resources Information Center

    Frazier, Jean A.; McClellan, Jon; Findling, Robert L.; Vitiello, Benedetto; Anderson, Robert; Zablotsky, Benjamin; Williams, Emily; McNamara, Nora K.; Jackson, Joseph A.; Ritz, Louise; Hlastala, Stefanie A.; Pierson, Leslie; Varley, Jennifer A.; Puglia, Madeline; Maloney, Ann E.; Ambler, Denisse; Hunt-Harrison, Tyehimba; Hamer, Robert M.; Noyes, Nancy; Lieberman, Jeffrey A.; Sikich, Linmarie

    2007-01-01

    Objective: We examined baseline demographic and clinical profiles of youths enrolled from 2001 to 2006 in the publicly funded multicenter, randomized controlled trial Treatment of Early-Onset Schizophrenia Spectrum Disorders. Method: Youths (8-19 years) with schizophrenia (SZ) and schizoaffective disorder were recruited at four academic sites.…

  16. Functional Connectivity of the Amygdala in Early-Childhood-Onset Depression

    ERIC Educational Resources Information Center

    Luking, Katherine R.; Repovs, Grega; Belden, Andy C.; Gaffrey, Michael S.; Botteron, Kelly N.; Luby, Joan L.; Barch, Deanna M.

    2011-01-01

    Objective: Adult major depressive disorder (MDD) is associated with reduced cortico-limbic functional connectivity thought to indicate decreased top-down control of emotion. However, it is unclear whether such connectivity alterations are also present in early-childhood-onset MDD. Method: A total of 51 children 7 through 11 years of age who had…

  17. CDKL5 and ARX mutations in males with early-onset epilepsy.

    PubMed

    Mirzaa, Ghayda M; Paciorkowski, Alex R; Marsh, Eric D; Berry-Kravis, Elizabeth M; Medne, Livija; Alkhateeb, Asem; Grix, Art; Wirrell, Elaine C; Powell, Berkley R; Nickels, Katherine C; Burton, Barbara; Paras, Andrea; Kim, Katherine; Chung, Wendy; Dobyns, William B; Das, Soma

    2013-05-01

    Mutations in CDKL5 and ARX are known causes of early-onset epilepsy and severe developmental delay in males and females. Although numerous males with ARX mutations associated with various phenotypes have been reported in the literature, the majority of CDKL5 mutations have been identified in females with a phenotype characterized by early-onset epilepsy, severe global developmental delay, absent speech, and stereotypic hand movements. To date, only 10 males with CDKL5 mutations have been reported. Our retrospective study reports on the clinical, neuroimaging, and molecular findings of 18 males with early-onset epilepsy caused by either CDKL5 or ARX mutations. These 18 patients include eight new males with CDKL5 mutations and 10 with ARX mutations identified through sequence analysis of 266 and 346 males, respectively, at our molecular diagnostic laboratory. Our large dataset therefore expands on the number of reported males with CDKL5 mutations and highlights that aberrations of CDKL5 and ARX combined are an important consideration in the genetic forms of early-onset epilepsy in boys. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. CDKL5 and ARX mutations in males with early-onset epilepsy

    PubMed Central

    Mirzaa, Ghayda M.; Paciorkowski, Alex R.; Marsh, Eric D.; Berry-Kravis, Elizabeth M.; Medne, Livija; Grix, Art; Wirrell, Elaine C.; Powell, Berkley R.; Nickels, Katherine C.; Burton, Barbara; Paras, Andrea; Kim, Katherine; Chung, Wendy; Dobyns, William B.; Das, Soma

    2013-01-01

    Mutations in CDKL5 and ARX are known causes of early-onset epilepsy and severe developmental delay in males and females. While numerous males with ARX mutations associated with various phenotypes have been reported in the literature, the majority of CDKL5 mutations have been identified in females with a phenotype characterized by early-onset epilepsy, severe global developmental delay, absent speech, and stereotypic hand movements. To date, only ten males with CDKL5 mutations have been reported. Our retrospective study reports on the clinical, neuroimaging and molecular findings of 18 males with early-onset epilepsy caused by either CDKL5 or ARX mutations. The 18 patients include eight new males with CDKL5 mutations and ten with ARX mutations identified through sequence analysis of 266 and 346 males, respectively, at our molecular diagnostic laboratory. Our large data set therefore expands on the number of reported males with CDKL5 mutations and highlights that aberrations of CDKL5 and ARX combined are an important consideration in the genetic forms of early-onset epilepsy. PMID:23583054

  19. CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy.

    PubMed

    Elia, M; Falco, M; Ferri, R; Spalletta, A; Bottitta, M; Calabrese, G; Carotenuto, M; Musumeci, S A; Lo Giudice, M; Fichera, M

    2008-09-23

    To search for CDKL5 gene mutations in boys presenting with severe early-onset encephalopathy and intractable epilepsy, a clinical picture very similar to that already described in girls with CDKL5 mutations. Eight boys (age range 3-16 years, mean age 8.5 years, SD 4.38) with severe or profound mental retardation and early-onset intractable seizures were selected for CDKL5 gene mutation screening by denaturing high-performance liquid chromatography analysis. We found three unrelated boys carrying three different missense mutations of the CDKL5 gene: c.872G>A (p.C291Y), c.863C>T (p.T288I), and c.533G>C (p.R178P). They presented early-onset, polymorphous, and drug-resistant seizures, mostly myoclonic and tonic or spasms. EEG showed epileptiform abnormalities which were multifocal during wakefulness, and pseudoperiodic bisynchronous during sleep. This study describes three boys carrying CDKL5 missense mutations and their detailed clinical and EEG data, and indicates that CDKL5 gene mutations may represent a cause of severe or profound mental retardation and early-onset intractable seizures, also in boys. Screening for CDKL5 mutations is strongly recommended in individuals with these clinical features.

  20. Maturation, Peer Context, and Indigenous Girls' Early-Onset Substance Use

    ERIC Educational Resources Information Center

    Walls, Melissa L.; Whitbeck, Les B.

    2011-01-01

    This article examines a biosocial model of the impact of puberty on indigenous girls' early-onset substance use by considering the potential mediating role of peer context (i.e., mixed-sex peer groups and substance use prototypes) on the puberty and substance use relationship. Data include responses from 360 girls of a common indigenous cultural…

  1. Two-Year Diagnostic Stability in Early-Onset First-Episode Psychosis

    ERIC Educational Resources Information Center

    Castro-Fornieles, Josefina; Baeza, Immaculada; de la Serna, Elena; Gonzalez-Pinto, Ana; Parellada, Mara; Graell, Montserrat; Moreno, Dolores; Otero, Soraya; Arango, Celso

    2011-01-01

    Background: Only one study has used a prospective method to analyze the diagnostic stability of first psychotic episodes in children and adolescents. The Child and Adolescent First-Episode Psychosis Study (CAFEPS) is a 2-year, prospective longitudinal study of early-onset first episodes of psychosis (EO-FEP). Aim: To describe diagnostic stability…

  2. Neurocognitive Outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders Study

    ERIC Educational Resources Information Center

    Frazier, Jean A.; Giuliano, Anthony J.; Johnson, Jacqueline L.; Yakutis, Lauren; Youngstrom, Eric A.; Breiger, David; Sikich, Linmarie; Findling, Robert L.; McClellan, Jon; Hamer, Robert M.; Vitiello, Benedetto; Lieberman, Jeffrey A.; Hooper, Stephen R.

    2012-01-01

    Objective: To assess neurocognitive outcomes following antipsychotic intervention in youth enrolled in the National Institute of Mental Health (NIMH)-funded Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS). Method: Neurocognitive functioning of youth (ages 8 to 19 years) with schizophrenia or schizoaffective disorder was evaluated…

  3. Early-Onset Physical Frailty in Adults with Diabesity and Peripheral Neuropathy.

    PubMed

    Tuttle, Lori J; Bittel, Daniel C; Bittel, Adam J; Sinacore, David R

    2017-12-07

    Diabesity (obesity and diabetes mellitus) has been identified as a potential contributor to early-onset frailty. Impairments contributing to early onset of physical frailty in this population are not well understood, and there is little evidence of the impact of peripheral neuropathy on frailty. The purpose of this study was to determine impairments that contribute to early-onset physical frailty in individuals with diabesity and peripheral neuropathy. We studied 105 participants, 82 with diabesity and peripheral neuropathy (57 years of age, body mass index [BMI] 31 kg/m 2 ); 13 with diabesity only (53 years of age, BMI 34 kg/m 2 ) and 10 obese controls (67 years of age, BMI 32 kg/m 2 ). Peripheral neuropathy was determined using Semmes Weinstein monofilaments; physical frailty was classified using the 9-item, modified Physical Performance Test; and knee extension and ankle plantarflexion peak torques were measured using isokinetic dynamometry. Participants with diabesity and peripheral neuropathy were 7.4 times more likely to be classified as physically frail. Impairments in lower-extremity function were associated with classification of frailty. Individuals with diabesity and peripheral neuropathy are particularly likely to be classified as frail. Earlier identification and interventions aimed at improving lower-extremity function may be important to mitigate the early-onset functional decline. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  4. Prognosis and response to laser treatment of early-onset hypertrophic port-wine stains (PWS).

    PubMed

    Passeron, Thierry; Salhi, Aicha; Mazer, Jean-Michel; Lavogiez, Céline; Mazereeuw-Hautier, Juliette; Galliot, Chrystèle; Collet-Villette, Anne-Marie; Labreze, Christine; Boon, Laurence; Hardy, Jean-Philippe; Fayard, Virginie; Livideanu, Cristina Bulai; Toubel, Gérard; Georgescou, Gabriela; Gral, Nathalie; Maza, Aude; Lacour, Jean-Philippe

    2016-07-01

    There is limited information regarding early development of soft-tissue and/or bone hypertrophy with facial port-wine stains (PWS). We sought to characterize patients with hypertrophic PWS presenting during childhood. Patients with a facial PWS and underlying hypertrophy that developed before the age of 18 years were included in a multicenter retrospective study. Age at onset of the hypertrophy, its location, association with odontologic problems, presence of other associated complications, and response to laser treatment were recorded. A total of 98 patients were included. The mean age at onset of hypertrophy, retrieved for 77 of 98 patients, was 5.6 years. The hypertrophy was congenital in 26%. Odontologic problems were noted in 39.8% of cases. Other complications, including cataract, asymmetric development of the maxillary bone, and speech delay/disorders, were reported in 18.4%. In all, 67 patients received laser treatment. Only 3% achieved complete or nearly complete clearance of the PWS. As only cases of PWS with early-onset hypertrophy were included, we were unable to calculate the prevalence of this manifestation. PWS with early-onset hypertrophy are associated with a high rate of complications and a poor response to laser treatment. Periodic monitoring is recommended for early detection and treatment of complications. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  5. Developmental Trends and L1 Effects in Early L2 Learners' Onset Cluster Production

    ERIC Educational Resources Information Center

    Tessier, Anne-Michelle; Duncan, Tamara Sorenson; Paradis, Johanne

    2013-01-01

    This study focuses on English onset cluster production in spontaneous speech samples of 10 children aged 5;04-6;09 from Chinese and Hindi/Punjabi first language (L1) backgrounds, each with less than a year of exposure to English. The results suggest commonalities between early second language (L2) learners and both monolingual and adult L2…

  6. Early Onset Ageing and Service Preparation in People with Intellectual Disabilities: Institutional Managers' Perspective

    ERIC Educational Resources Information Center

    Lin, Jin-Ding; Wu, Chia-Ling; Lin, Pei-Ying; Lin, Lan-Ping; Chu, Cordia M.

    2011-01-01

    Although longevity among older adults with intellectual disabilities is increasing, there is limited information on their premature aging related health characteristics and how it may change with increasing age. The present paper provides information of the institutional manager's perception on early onset aging and service preparation for this…

  7. Does theory of mind performance differ in children with early-onset and regressive autism?

    PubMed

    Matthews, Nicole L; Goldberg, Wendy A; Lukowski, Angela F; Osann, Kathryn; Abdullah, Maryam M; Ly, Agnes R; Thorsen, Kara; Spence, M Anne

    2012-01-01

    A deficit in theory of mind (ToM), or the ability to infer the mental states of others, has been implicated as one of the major characteristics of Autism Spectrum Disorder (ASD); however, little attention has been devoted to possible differences in ToM ability within ASD. The current study examined ToM performance in children with early-onset autism and regressive autism in comparison to typically developing children. Results indicated that children in the regressive autism group performed significantly better than the early-onset autism group on the non-verbal appearance-reality task. Additionally, Fisher's exact tests indicated a pattern of lowest scores in the early-onset group and highest scores in the typically developing group, whereas the regressive autism group tended to score in between the early-onset and typically developing groups. The apparent heterogeneity in ToM performance within ASD could account for the lack of universality in ToM ability found in previous studies. © 2011 Blackwell Publishing Ltd.

  8. Serum levels of GDF15 are reduced in preeclampsia and the reduction is more profound in late-onset than early-onset cases.

    PubMed

    Chen, Qi; Wang, Yao; Zhao, Min; Hyett, Jonathan; da Silva Costa, Fabricio; Nie, Guiying

    2016-07-01

    Preeclampsia is a pregnancy specific disorder affecting 3-5% of pregnancies worldwide. It is clinically divided into early-onset and late-onset subtypes. Placental factors are involved in the pathogenesis of preeclampsia. Growth differentiation factor 15 (GDF15), a protein of the transforming growth factor beta superfamily, is highly expressed in the placenta. However, it is unclear whether the circulating levels of GDF15 are altered in preeclampsia at the time of or prior to disease presentation. Serum samples across three trimesters from 29 healthy pregnancies, third trimester sera from 34 women presenting with preeclampsia (early-onset n=16, late-onset n=18) and 66 gestation-age-matched controls, and sera at 11-13weeks of pregnancy from women who later did (n=36) or did not (n=33) develop late-onset preeclampsia, were examined for GDF15 by ELISA. Serum GDF15 levels increased significantly with gestation in normal pregnancy. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia compared to their gestation-age-matched controls. This reduction was apparent in both early-onset and late-onset subtypes, but it was more profound in late-onset cases. At 11-13weeks of gestation, however, serum levels of GDF15 were similar between women who subsequently did and did not develop late-onset preeclampsia. Serum GDF15 increased with gestation age, reaching the highest level in the third trimester. Serum GDF15 was significantly reduced in the third trimester in women presenting with preeclampsia, especially in late-onset cases. However, serum GDF15 was not altered in the first trimester in women destined to develop late-onset preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Development and initial validation of the Classification of Early-Onset Scoliosis (C-EOS).

    PubMed

    Williams, Brendan A; Matsumoto, Hiroko; McCalla, Daren J; Akbarnia, Behrooz A; Blakemore, Laurel C; Betz, Randal R; Flynn, John M; Johnston, Charles E; McCarthy, Richard E; Roye, David P; Skaggs, David L; Smith, John T; Snyder, Brian D; Sponseller, Paul D; Sturm, Peter F; Thompson, George H; Yazici, Muharrem; Vitale, Michael G

    2014-08-20

    Early-onset scoliosis is a heterogeneous condition, with highly variable manifestations and natural history. No standardized classification system exists to describe and group patients, to guide optimal care, or to prognosticate outcomes within this population. A classification system for early-onset scoliosis is thus a necessary prerequisite to the timely evolution of care of these patients. Fifteen experienced surgeons participated in a nominal group technique designed to achieve a consensus-based classification system for early-onset scoliosis. A comprehensive list of factors important in managing early-onset scoliosis was generated using a standardized literature review, semi-structured interviews, and open forum discussion. Three group meetings and two rounds of surveying guided the selection of classification components, subgroupings, and cut-points. Initial validation of the system was conducted using an interobserver reliability assessment based on the classification of a series of thirty cases. Nominal group technique was used to identify three core variables (major curve angle, etiology, and kyphosis) with high group content validity scores. Age and curve progression ranked slightly lower. Participants evaluated the cases of thirty patients with early-onset scoliosis for reliability testing. The mean kappa value for etiology (0.64) was substantial, while the mean kappa values for major curve angle (0.95) and kyphosis (0.93) indicated almost perfect agreement. The final classification consisted of a continuous age prefix, etiology (congenital or structural, neuromuscular, syndromic, and idiopathic), major curve angle (1, 2, 3, or 4), and kyphosis (-, N, or +) variables, and an optional progression modifier (P0, P1, or P2). Utilizing formal consensus-building methods in a large group of surgeons experienced in treating early-onset scoliosis, a novel classification system for early-onset scoliosis was developed with all core components demonstrating

  10. Distinct breast cancer subtypes in women with early-onset disease across races

    PubMed Central

    Singh, Mandeep; Ding, Yi; Zhang, Li-Ying; Song, Dong; Gong, Yun; Adams, Sylvia; Ross, Dara S; Wang, Jin-Hua; Grover, Shruti; Doval, Dinesh Chandra; Shao, Charles; He, Zi-Li; Chang, Victor; Chin, Warren W; Deng, Fang-Ming; Singh, Baljit; Zhang, David; Xu, Ru-Liang; Lee, Peng

    2014-01-01

    Background: Racial disparities among breast cancer (BCa) patients are known but not well studied in early-onset BCa. We analyzed molecular subtypes in early-onset BCa across five major races. Methods: A total of 2120 cases were included from non-Hispanic White (NHW), African American (AA) and Hispanic, Chinese and Indian. Based on ER, PR and HER-2 status, BCa was classified into 4 intrinsic subtypes as Luminal A, Luminal B, HER2/neu overexpression and Triple negative BCa (TNBC) subtypes. Data was stratified according to race and age as younger/early-onset group (40-years and younger) and older group (50-years and older). Results: In early-onset BCa, incidence of TNBC was significantly higher (p = 0.0369) in Indian women followed by AA, Hispanic, NHW and Chinese women. Incidence of Her2 over-expression subtype also was highest in Indian women, followed by Hispanic, Chinese, AA and NHW women. In contrast, Luminal B subtype was most significantly higher in AA women (p = 0.0000) followed by NHW (p = 0.0002), Chinese (p = 0.0003), Hispanic (0.0128) and Indian (p = 0.0468) women. Luminal A subtype was most significantly reduced in Indian women (p = 0.0113) followed by Hispanic, AA, NHW and Chinese women. These results were based on statistical analysis with the mean of older group populations. Conclusions: These results show significant disparities in receptor subtypes across races. This study will contribute in developing optimal clinical trial protocols and personalized management strategies for early-onset BCa patients. PMID:25057437

  11. Treatment of early-onset schizophrenia spectrum disorders (TEOSS): rationale, design, and methods.

    PubMed

    McClellan, Jon; Sikich, Linmarie; Findling, Robert L; Frazier, Jean A; Vitiello, Benedetto; Hlastala, Stefanie A; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E; Ritz, Louise; Anderson, Robert; Hamer, Robert M; Lieberman, Jeffrey A

    2007-08-01

    The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described. Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used. From February 2002 to May 2006, 476 youths were screened, 173 were further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain. The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization.

  12. Incidence of early-onset sepsis in infants born to women with clinical chorioamnionitis.

    PubMed

    Randis, Tara M; Rice, Madeline Murguia; Myatt, Leslie; Tita, Alan T N; Leveno, Kenneth J; Reddy, Uma M; Varner, Michael W; Thorp, John M; Mercer, Brian M; Dinsmoor, Mara J; Ramin, Susan M; Carpenter, Marshall W; Samuels, Philip; Sciscione, Anthony; Tolosa, Jorge E; Saade, George; Sorokin, Yoram

    2018-05-23

    To determine the frequency of sepsis and other adverse neonatal outcomes in women with a clinical diagnosis of chorioamnionitis. We performed a secondary analysis of a multi-center placebo-controlled trial of vitamins C/E to prevent preeclampsia in low risk nulliparous women. Clinical chorioamnionitis was defined as either the "clinical diagnosis" of chorioamnionitis or antibiotic administration during labor because of an elevated temperature or uterine tenderness in the absence of another cause. Early-onset neonatal sepsis was categorized as "suspected" or "confirmed" based on a clinical diagnosis with negative or positive blood, urine or cerebral spinal fluid cultures, respectively, within 72 h of birth. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Data from 9391 mother-infant pairs were analyzed. The frequency of chorioamnionitis was 10.3%. Overall, 6.6% of the neonates were diagnosed with confirmed (0.2%) or suspected (6.4%) early-onset sepsis. Only 0.7% of infants born in the setting of chorioamnionitis had culture-proven early-onset sepsis versus 0.1% if chorioamnionitis was not present. Clinical chorioamnionitis was associated with both suspected [OR 4.01 (3.16-5.08)] and confirmed [OR 4.93 (1.65-14.74)] early-onset neonatal sepsis, a need for resuscitation within the first 30 min after birth [OR 2.10 (1.70-2.61)], respiratory distress [OR 3.14 (2.16-4.56)], 1 min Apgar score of ≤3 [OR 2.69 (2.01-3.60)] and 4-7 [OR 1.71 (1.43-2.04)] and 5 min Apgar score of 4-7 [OR 1.67 (1.17-2.37)] (vs. 8-10). Clinical chorioamnionitis is common and is associated with neonatal morbidities. However, the vast majority of exposed infants (99.3%) do not have confirmed early-onset sepsis.

  13. Parental and Child Characteristics Related to Early-Onset Disordered Eating: A Systematic Review.

    PubMed

    Larsen, Pernille Stemann; Strandberg-Larsen, Katrine; Micali, Nadia; Andersen, Anne-Marie Nybo

    2015-01-01

    After participating in this activity, learners should be better able to: Evaluate the evidence regarding parental and child characteristics related to early-onset disordered eating. Eating disorders are rare in children, but disordered eating is common. Understanding the phenomenology of disordered eating in childhood can aid prevention of full-blown eating disorders. The purpose of this review is to systematically extract and synthesize the evidence on parental and child characteristics related to early-onset disordered eating. Systematic searches were conducted in PubMED/MEDLINE, EMBASE, and PsycInfo using the following search terms: eating disorder, disordered eating, problem eating, anorexia nervosa, bulimia nervosa, binge eating, child, preadolescent, and early onset. Studies published from 1990 to 2013 addressing parental and child characteristics of disordered eating in children aged 6 to 12 years were eligible for inclusion. The search was restricted to studies with cross-sectional, case-control, or longitudinal designs, studies in English, and with abstracts available. Forty-four studies fit these criteria. Most studies were based on community samples with a cross-sectional design. The included studies varied considerably in size, instruments used to assess early-onset disordered eating, and parental and child characteristics investigated. Important determinants included the following: higher body weight, previously reported disordered eating, body dissatisfaction, depression, parental disordered eating, and parental comments/concerns about child's weight and eating. The findings were inconsistent for sex, age, socioeconomic status, ethnicity, self-esteem/worth, and parental body weight. In conclusion, characteristics related to early-onset disordered eating have mainly been explored with a cross-sectional design. Full understanding of causal pathways will require good-quality longitudinal studies designed to address the influence of parental eating

  14. Study protocol: EXERcise and cognition in sedentary adults with early-ONset dementia (EXERCISE-ON).

    PubMed

    Hooghiemstra, Astrid M; Eggermont, Laura H P; Scheltens, Philip; van der Flier, Wiesje M; Bakker, Jet; de Greef, Mathieu H G; Koppe, Peter A; Scherder, Erik J A

    2012-08-16

    Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia. One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an aerobic exercise program in a rehabilitation centre or a flexibility and relaxation program in a rehabilitation centre. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a daily physical activity program set at home making use of pedometers. Measurements take place at baseline (entry of the study), after three months (end of the exercise program) and after six months (follow-up). Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental) activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures. The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life. The present study is registered within The Netherlands National Trial Register (ref: NTR2124).

  15. Study protocol: EXERcise and Cognition In Sedentary adults with Early-ONset dementia (EXERCISE-ON)

    PubMed Central

    2012-01-01

    Background Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia. Methods/Design One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an aerobic exercise program in a rehabilitation centre or a flexibility and relaxation program in a rehabilitation centre. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a daily physical activity program set at home making use of pedometers. Measurements take place at baseline (entry of the study), after three months (end of the exercise program) and after six months (follow-up). Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental) activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures. Discussion The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life. Trial registration The present study is registered within The Netherlands

  16. Premorbid Risk Factors for Major Depressive Disorder: Are They Associated With Early Onset and Recurrent Course?

    PubMed Central

    Wilson, Sylia; Vaidyanathan, Uma; Miller, Michael B.; McGue, Matt; Iacono, William G.

    2014-01-01

    Premorbid risk for major depressive disorder (MDD) and predictors of an earlier onset and recurrent course were examined in two studies in a large, community-based sample of parents and offspring, prospectively assessed from late childhood into adulthood. In Study 1 (N = 2,764 offspring and their parents), parental psychiatric status, offspring personality at age 11, and age-11 offspring internalizing and externalizing symptoms predicted the subsequent development of MDD, as did poor quality parent-child relationships, poor academic functioning, early pubertal development, and childhood maltreatment by age 11. Parental MDD and adult antisocial behavior, offspring negative emotionality and disconstraint, externalizing symptoms, and childhood maltreatment predicted an earlier onset of MDD, after accounting for course; lower positive emotionality, trait anxiety, and childhood maltreatment predicted recurrent MDD, after accounting for age of onset. In Study 2 (N = 7,146), we examined molecular genetic risk for MDD by extending recent reports of associations with glutamatergic system genes. We failed to confirm associations with MDD using either individual SNP-based tests or gene-based analyses. Overall, results speak to the pervasiveness of risk for MDD, as well as specific risk for early-onset MDD; risk for recurrent MDD appears to be largely a function of its often earlier onset. PMID:25422974

  17. Characteristics of familial aggregation in early-onset Alzheimer`s disease: Evidence of subgroups

    SciTech Connect

    Campion, D.; Martinez, M.; Babron, M.C.

    1995-06-19

    Characteristics of familial aggregation of Alzheimer`s Disease were studied in 92 families ascertained through a clinically diagnosed proband with an onset below age 60 years. In each family data were systematically collected on the sibships of the proband, of his father, and of his mother. A total of 926 relatives were included and 81% of the living relatives (i.e., 251 individuals) were directly examined. The estimated cumulative risk among first degree relatives was equal to 35% by age 89 years (95% confidence interval 22 to 47%). This result does not support the hypothesis that an autosomal dominant gene, fully penetrantmore » by age 90 years, is segregating within all these pedigrees. Despite the fact that all probands were selected for an onset before age 60 years it was shown that two types of families could be delineated with respect to age at onset among affected relatives: all secondary cases with an onset below age 60 years were contributed by a particular group of families (type 1 families), whereas all secondary cases with an onset after age 60 years were contributed by another group of families (type 2 families). Although genetic interpretation of these findings is not straightforward, they support the hypothesis of etiologic heterogeneity in the determinism of early-onset Alzheimer`s disease. 58 refs., 5 figs., 2 tabs.« less

  18. Early vs late age at onset frontotemporal dementia and frontotemporal lobar degeneration.

    PubMed

    Seo, Sang Won; Thibodeau, Marie-Pierre; Perry, David C; Hua, Alice; Sidhu, Manu; Sible, Isabel; Vargas, Jose Norberto S; Gaus, Stephanie E; Rabinovici, Gil D; Rankin, Katherine D; Boxer, Adam L; Kramer, Joel H; Rosen, Howard J; Gorno-Tempini, Maria Luisa; Grinberg, Lea T; Huang, Eric J; DeArmond, Stephen J; Trojanowski, John Q; Miller, Bruce L; Seeley, William W

    2018-03-20

    To examine clinicopathologic correlations in early vs late age at onset frontotemporal dementia (FTD) and frontotemporal lobar degeneration (FTLD). All patients were clinically evaluated and prospectively diagnosed at the UCSF Memory and Aging Center. Two consecutive series were included: (1) patients with a clinically diagnosed FTD syndrome who underwent autopsy (cohort 1) and (2) patients with a primary pathologic diagnosis of FTLD, regardless of the clinical syndrome (cohort 2). These series were divided by age at symptom onset (cutoff 65 years). In cohort 1, 48 (25.3%) were 65 years or older at symptom onset. Pathologic causes of behavioral variant FTD (bvFTD) were similar in the early age at onset (EO) and late age at onset (LO) bvFTD groups. In corticobasal syndrome (CBS), however, the most common pathologic substrate differed according to age at onset: progressive supranuclear palsy (42.9%) in LO-CBS and Alzheimer disease (AD; 40.7%) in EO-CBS. In cohort 2, 57 (28.4%) were classified as LO-FTLD. Regarding FTLD major molecular classes, FTLD with transactive response DNA-binding protein of 43 kDa was most common in EO-FTLD (44.4%), whereas FTLD-tau (58.3%) was most common in LO-FTLD. Antemortem diagnosis of a non-FTD syndrome, usually AD-type dementia, was more frequent in LO-FTLD than EO-FTLD (19.3% vs 7.7%, p = 0.017). LO-FTLD was also associated with more prevalent comorbid pathologic changes. Of these, moderate to severe AD neuropathologic change and argyrophilic grain disease were overrepresented among patients who received an antemortem diagnosis of AD-type dementia. Patients with FTD and FTLD often develop symptoms after age 65, and age at onset represents an important consideration when making antemortem neuropathologic predictions. © 2018 American Academy of Neurology.

  19. Early- versus late-onset obsessive-compulsive disorder: investigating genetic and clinical correlates.

    PubMed

    Hemmings, Sîan M J; Kinnear, Craig J; Lochner, Christine; Niehaus, Dana J H; Knowles, James A; Moolman-Smook, Johanna C; Corfield, Valerie A; Stein, Dan J

    2004-09-30

    There is increasing evidence that obsessive-compulsive disorder (OCD) is mediated by genetic factors. Although the precise mechanism of inheritance is unclear, recent evidence has pointed towards the involvement of the serotonergic and dopaminergic systems in the disorder's development. Furthermore, early-onset OCD appears to be a subtype that exhibits distinct clinical features and that is associated with greater familial loading. In the present investigation, South African OCD patients (n=252) were stratified according to age of onset and were clinically assessed. Additionally, selected variants in genes encoding serotonergic and dopaminergic components were investigated in a Caucasian OCD subset (n=180). This subgroup was further stratified to evaluate the role that these candidate genes may play in the genetically homogeneous Afrikaner subset (n=80). Analysis of the clinical data revealed an association between early age of onset and an increased frequency of tics, Tourette's disorder, and trichotillomania (TTM). The genetic studies yielded statistically significant results when the allelic distributions of genetic variants in the dopamine receptor type 4 gene (DRD4) were analysed in the Caucasian OCD cohort. These data support a role for the dopaminergic system, which may be relevant to the development of early-onset OCD.

  20. Exome Sequencing Frequently Reveals the Cause of Early-Onset Chronic Kidney Disease

    PubMed Central

    Vivante, Asaf; Hildebrandt, Friedhelm

    2016-01-01

    The primary causes of chronic kidney disease (CKD) in children differ from those of adult onset CKD. In the United States the most common diagnostic groups of CKD that manifests before 25 years of age are: i) congenital anomalies of the kidneys and urinary tract (CAKUT) (49.1%), ii) steroid-resistant nephrotic syndrome (SRNS) (10.4%), iii) chronic glomerulonephritis (8.1%), and iv) renal cystic ciliopathies (5.3 %), encompassing >70% of CKD together. Recent findings suggest that early-onset CKD is caused by mutations in any one of over 200 different monogenic genes. High-throughput sequencing has very recently rendered identification of causative mutations in this high number of genes feasible. Molecular genetic diagnostics in early onset-CKD (before the age of 25 years) will, i) provide patients and families with a molecular genetic diagnosis, ii) generate new insights into diseases mechanisms, iii) allow etiology-based classification of patient cohorts for clinical studies and, iv) may have consequences for personalized treatment and prevention of CKD. In this review, we will discuss the implications of next-generation sequencing for clinical genetic diagnostics and discovery of novel genes in early-onset CKD. We also delineate the resulting opportunities for deciphering disease mechanisms and therapeutic implications. PMID:26750453

  1. Early onset of delinquency and the trajectory of alcohol-impaired driving among young males.

    PubMed

    Zhang, Lening; Wieczorek, William F; Welte, John W

    2011-12-01

    Building upon the literature in developmental and life-course criminology, the present study assesses the possible association of age onset of delinquency with the trajectory of alcohol-impaired driving using data collected from the three waves of the Buffalo Longitudinal Survey of Young Men (BLSYM). It is argued that as a unique form of delinquency, alcohol-impaired driving among adolescents may be better understood in a broad context of adolescent delinquency involvement. The study adopts the general approach for the analysis of early onset of delinquency and criminal careers in developmental and life-course criminology and hypothesizes that early onset of delinquency is associated with a higher growth of alcohol-impaired driving over time among adolescents when age onsets of alcohol-impaired driving, drinking, and drug use are controlled. Our analysis with the HLM growth modeling method provides support for the hypothesis. Respondents who had an early start in delinquency were likely to have a faster growth of alcohol-impaired driving over the three waves of BLSYM, which implies that these respondents were likely to have a longer path of alcohol-impaired driving in their transition to adulthood. The implication of this finding is discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. EARLY ONSET OF DELINQUENCY AND THE TRAJECTORY OF ALCOHOL-IMPAIRED DRIVING AMONG YOUNG MALES*

    PubMed Central

    Zhang, Lening; Wieczorek, William F.; Welte, John W.

    2011-01-01

    Building upon the literature in developmental and life-course criminology, the present study assesses the possible association of age onset of delinquency with the trajectory of alcohol-impaired driving using data collected from the three waves of the Buffalo Longitudinal Survey of Young Men (BLSYM). It is argued that as a unique form of delinquency, alcohol-impaired driving among adolescents may be better understood in a broad context of adolescent delinquency involvement. The study adopts the general approach for the analysis of early onset of delinquency and criminal careers in developmental and life-course criminology and hypothesizes that early onset of delinquency is associated with a higher growth of alcohol-impaired driving over time among adolescents when age onsets of alcohol-impaired driving, drinking, and drug use are controlled. Our analysis with the HLM growth modeling method provides support for the hypothesis. Respondents who had an early start in delinquency were likely to have a faster growth of alcohol-impaired driving over the three waves of BLSYM, which implies that these respondents were likely to have a longer path of alcohol-impaired driving in their transition to adulthood. The implication of this finding is discussed. PMID:21831528

  3. Functional neuroanatomical associations of working memory in early-onset Alzheimer's disease.

    PubMed

    Kobylecki, Christopher; Haense, Cathleen; Harris, Jennifer M; Stopford, Cheryl L; Segobin, Shailendra H; Jones, Matthew; Richardson, Anna M T; Gerhard, Alexander; Anton-Rodriguez, José; Thompson, Jennifer C; Herholz, Karl; Snowden, Julie S

    2018-01-01

    To characterize metabolic correlates of working memory impairment in clinically defined subtypes of early-onset Alzheimer's disease. Established models of working memory suggest a key role for frontal lobe function, yet the association in Alzheimer's disease between working memory impairment and visuospatial and language symptoms suggests that temporoparietal neocortical dysfunction may be responsible. Twenty-four patients with predominantly early-onset Alzheimer's disease were clinically classified into groups with predominantly amnestic, multidomain or visual deficits. Patients underwent neuropsychological evaluation focused on the domains of episodic and working memory, T1-weighted magnetic resonance imaging and brain fluorodeoxyglucose positron emission tomography. Fluorodeoxyglucose positron emission tomography data were analysed by using a region-of-interest approach. Patients with multidomain and visual presentations performed more poorly on tests of working memory compared with amnestic Alzheimer's disease. Working memory performance correlated with glucose metabolism in left-sided temporoparietal, but not frontal neocortex. Carriers of the apolipoprotein E4 gene showed poorer episodic memory and better working memory performance compared with noncarriers. Our findings support the hypothesis that working memory changes in early-onset Alzheimer's disease are related to temporoparietal rather than frontal hypometabolism and show dissociation from episodic memory performance. They further support the concept of subtypes of Alzheimer's disease with distinct cognitive profiles due to prominent neocortical dysfunction early in the disease course. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Early-onset facioscapulohumeral muscular dystrophy type 1 with some atypical features.

    PubMed

    Dorobek, Małgorzata; van der Maarel, Silvère M; Lemmers, Richard J L F; Ryniewicz, Barbara; Kabzińska, Dagmara; Frants, Rune R; Gawel, Malgorzata; Walecki, Jerzy; Hausmanowa-Petrusewicz, Irena

    2015-04-01

    Facioscapulohumeral muscular dystrophy cases with facial weakness before the age of 5 and signs of shoulder weakness by the age of 10 are defined as early onset. Contraction of the D4Z4 repeat on chromosome 4q35 is causally related to facioscapulohumeral muscular dystrophy type 1, and the residual size of the D4Z4 repeat shows a roughly inverse correlation with the severity of the disease. Contraction of the D4Z4 repeat on chromosome 4q35 is believed to induce a local change in chromatin structure and consequent transcriptional deregulation of 4qter genes. We present early-onset cases in the Polish population that amounted to 21% of our total population with facioscapulohumeral muscular dystrophy. More than 27% of them presented with severe phenotypes (wheelchair dependency). The residual D4Z4 repeat sizes ranged from 1 to 4 units. In addition, even within early-onset facioscapulohumeral muscular dystrophy type 1 phenotypes, some cases had uncommon features (head drop, early disabling contractures, progressive ptosis, and respiratory insufficiency and cardiomyopathy). © The Author(s) 2014.

  5. The Etiology and Clinical Course of Chronic Pancreatitis in Children With Early Onset of the Disease.

    PubMed

    Wejnarska, Karolina; Kolodziejczyk, Elwira; Wertheim-Tysarowska, Katarzyna; Dadalski, Maciej; Sobczynska-Tomaszewska, Agnieszka; Kierkus, Jarosław; Bal, Jerzy; Rygiel, Agnieszka Magdalena; Oracz, Grzegorz

    2016-12-01

    The etiological factors of chronic pancreatitis (CP) in children differ from those in adults. To date, no study has assessed the clinical course of CP in young children. The aim of our study was to evaluate the etiology and the clinical presentation of the disease in children with disease onset before 5 years of age in comparison to later-onset of CP. A total of 276 children with CP, hospitalized from 1988 to 2015, were enrolled in the study. Data on presentation, diagnostic findings, and treatment were reviewed. Two hundred sixty patients were screened for the most frequent mutations in major pancreatitis-associated genes, such as cationic trypsinogen/serine protease gene (PRSS1), serine protease inhibitor, Kazal type 1 gene (SPINK1), and cystic fibrosis transmembrane conductance regulator gene (CFTR). The disease onset before the age of 5 years occurred in 51 patients (group 1), the later onset in 225 patients (group 2). We found no significant discrepancies in distribution of the etiological factors between groups. The youngest patients (group 1) had more pancreatitis episodes (median 5.0 vs 3.00; P < 0.05) and underwent surgeries more frequently (25.5% vs 8.9%; P < 0.05). It could be associated with significantly longer follow-up in early onset group (median 6 vs 4 years; P < 0.05). There were no differences in nutritional status or exocrine and endocrine pancreatic function. Early- and later-onset pancreatitis have similar etiological factors with predominance of gene mutations. The most frequent mutation found was p.Asn34Ser (N34S) in SPINK1 gene. The clinical presentation differed in number of pancreatitis episodes and frequency of surgeries.

  6. Mapping callosal morphology in early- and late-onset elderly depression: an index of distinct changes in cortical connectivity.

    PubMed

    Ballmaier, Martina; Kumar, Anand; Elderkin-Thompson, Virginia; Narr, Katherine L; Luders, Eileen; Thompson, Paul M; Hojatkashani, Cornelius; Pham, Daniel; Heinz, Andreas; Toga, Arthur W

    2008-06-01

    There is some evidence of corpus callosum abnormalities in elderly depression, but it is not known whether these deficits are region-specific or differ based on age at onset of depression. Twenty-four patients with early-onset depression (mean age = 68.00, SD+/-5.83), 22 patients with late-onset depression (mean age = 74.50, SD+/-8.09) and 34 elderly control subjects (mean age = 72.38; SD+/-6.93) were studied. Using 3D MRI data, novel mesh-based geometrical modeling methods were applied to compare the midsagittal thickness of the corpus callosum at high spatial resolution between groups. Neuropsychological correlates of midsagittal callosal area differences were additionally investigated in a subsample of subjects. Depressed patients exhibited significant callosal thinning in the genu and splenium compared to controls. Significant callosal thinning was restricted to the genu in early-onset patients, but patients with late-onset depression exhibited significant callosal thinning in both the genu and splenium relative to controls. The splenium of the corpus callosum was also significantly thinner in subjects with late- vs early-onset depression. Genu and splenium midsagittal areas significantly correlated with memory and attention functioning among late-onset depressed patients, but not early-onset depressed patients or controls. Circumscribed structural alterations in callosal morphology may distinguish late- from early-onset depression in the elderly. These findings suggest distinct abnormalities of cortical connectivity in late- and early-onset elderly depression with possible influence on the course of illness. Patients with a late onset of depression may be at higher risk of illness progression and eventually dementia conversion than early-onset depression, with potentially important implications for research and therapy.

  7. Fathers' Alcohol and Cannabis Use Disorder and Early Onset of Drug Use by Their Children.

    PubMed

    Henry, Kimberly L

    2017-05-01

    The unique influence of fathers' alcohol and cannabis use disorder on children's onset of use of these same substances has been rarely studied. A clear understanding of family history in this context is important for the development of family-based prevention initiatives aimed at delaying the onset of substance use among children. Prospective, longitudinal, and intergenerational data on 274 father-child dyads were used. Logistic regression models were estimated to assess the association between fathers' lifetime incidence of an alcohol and cannabis use disorder and children's onset of use of these same substances at or before age 15. The children of fathers who met the criteria for a lifetime cannabis use disorder were more likely to initiate use of alcohol (odds ratio = 6.71, 95% CI [1.92, 23.52]) and cannabis (odds ratio = 8.13, 95% CI [2.07, 31.95]) by age 15, when background covariates and presence of a lifetime alcohol use disorder were controlled for. No unique effect of fathers' alcohol use disorder on children's onset of alcohol and cannabis use was observed. Fathers' lifetime cannabis use disorder had a unique and robust association with children's uptake of alcohol and cannabis by age 15. Future research is needed to identify the mediating mechanisms that link fathers' disorder with children's early onset.

  8. [Analysis of gene mutation of early onset epileptic spasm with unknown reason].

    PubMed

    Yang, X; Pan, G; Li, W H; Zhang, L M; Wu, B B; Wang, H J; Zhang, P; Zhou, S Z

    2017-11-02

    Objective: To summarize the gene mutation of early onset epileptic spasm with unknown reason. Method: In this prospective study, data of patients with early onset epileptic spasm with unknown reason were collected from neurological department of Children's Hospital of Fudan University between March 2016 and December 2016. Patients with known disorders such as infection, metabolic, structural, immunological problems and known genetic mutations were excluded. Patients with genetic disease that can be diagnosed by clinical manifestations and phenotypic characteristics were also excluded. Genetic research methods included nervous system panel containing 1 427 epilepsy genes, whole exome sequencing (WES), analysis of copy number variation (CNV) and karyotype analysis of chromosome. The basic information, phenotypes, genetic results and the antiepileptic treatment of patients were analyzed. Result: Nine of the 17 cases with early onset epileptic spasm were boys and eight were girls. Patients' age at first seizure onset ranged from 1 day after birth to 8 months (median age of 3 months). The first hospital visit age ranged from 1 month to 2 years (median age of 4.5 months). The time of following-up ranged from 8 months to 3 years and 10 months. All the 17 patients had early onset epileptic spasm. Video electroencephalogram was used to monitor the spasm seizure. Five patients had Ohtahara syndrome, 10 had West syndrome, two had unclear classification. In 17 cases, 10 of them had detected pathogenic genes. Nine cases had point mutations, involving SCN2A, ARX, UNC80, KCNQ2, and GABRB3. Except one case of mutations in GABRB3 gene have been reported, all the other cases had new mutations. One patient had deletion mutation in CDKL5 gene. One CNV case had 6q 22.31 5.5MB repeats. Ten cases out of 17 were using 2-3 antiepileptic drugs (AEDs) and the drugs had no effect. Seven cases used adrenocorticotropic hormone (ACTH) and prednisone besides AEDs (a total course for 8 weeks

  9. Decision making and executive function in male adolescents with early-onset or adolescence-onset conduct disorder and control subjects.

    PubMed

    Fairchild, Graeme; van Goozen, Stephanie H M; Stollery, Sarah J; Aitken, Michael R F; Savage, Justin; Moore, Simon C; Goodyer, Ian M

    2009-07-15

    Although conduct disorder (CD) is associated with an increased susceptibility to substance use disorders, little is known about decision-making processes or reward mechanisms in CD. This study investigated decision making under varying motivational conditions in CD. Performances on the Risky Choice Task (RCT) and the Wisconsin Card Sorting Test (WCST) were assessed in 156 adolescents (84 control subjects, 34 with adolescence-onset CD, and 38 with early-onset CD). The RCT was performed twice, once under normal motivational conditions and once under conditions of increased motivation and psychosocial stress. Increased motivation and stress led to more cautious decision making and changes in framing effects on the RCT in all groups, although such effects were least pronounced in the early-onset CD group. Participants from both CD subgroups selected the risky choice more frequently than control subjects. Under normal motivational conditions, early-onset CD participants chose the risky choice more frequently in trials occurring after small gains, relative to control subjects and adolescence-onset CD participants. Following adjustment for IQ differences, the groups did not differ significantly in terms of WCST performance. Differences in decision making between control subjects and individuals with CD suggest that the balance between sensitivity to reward and punishment is shifted in this disorder, particularly the early-onset form. Our data on modulation of decision making according to previous outcomes suggest altered reward mechanisms in early-onset CD. The WCST data suggest that impairments in global executive function do not underlie altered decision making in CD.

  10. Early onset of bilateral brachial plexopathy during mantle radiotherapy for Hodgkin's disease.

    PubMed

    Churn, M; Clough, V; Slater, A

    2000-01-01

    We report a case of brachial plexus neuropathy occurring in a 50-year-old man treated with standard mantle radiotherapy for early-stage Hodgkin's disease. A dose of 35 Gy in 20 fractions was given to the mantle field, following by a boost to the right side of the neck (8 Gy in four fractions). The onset of symptoms was early in the course of treatment and a gradual and almost full recovery was observed over 3 years after completion ofradiotherapy. The diagnosis was supported by electromyography. The temporal relationship of the radiotherapy and the onset of the brachial plexus neuropathy suggests a cause and effect, but this association is rarely reported after mantle radiotherapy. We review the aetiology of this condition and postulate possible mechanisms in this patient.

  11. Diagnostic accuracy of spot urinary protein and albumin to creatinine ratios for detection of significant proteinuria or adverse pregnancy outcome in patients with suspected pre-eclampsia: systematic review and meta-analysis

    PubMed Central

    Morris, R K; Riley, R D; Doug, M; Deeks, J J

    2012-01-01

    Objective To determine the diagnostic accuracy of two “spot urine” tests for significant proteinuria or adverse pregnancy outcome in pregnant women with suspected pre-eclampsia. Design Systematic review and meta-analysis. Data sources Searches of electronic databases 1980 to January 2011, reference list checking, hand searching of journals, and contact with experts. Inclusion criteria Diagnostic studies, in pregnant women with hypertension, that compared the urinary spot protein to creatinine ratio or albumin to creatinine ratio with urinary protein excretion over 24 hours or adverse pregnancy outcome. Study characteristics, design, and methodological and reporting quality were objectively assessed. Data extraction Study results relating to diagnostic accuracy were extracted and synthesised using multivariate random effects meta-analysis methods. Results Twenty studies, testing 2978 women (pregnancies), were included. Thirteen studies examining protein to creatinine ratio for the detection of significant proteinuria were included in the multivariate analysis. Threshold values for protein to creatinine ratio ranged between 0.13 and 0.5, with estimates of sensitivity ranging from 0.65 to 0.89 and estimates of specificity from 0.63 to 0.87; the area under the summary receiver operating characteristics curve was 0.69. On average, across all studies, the optimum threshold (that optimises sensitivity and specificity combined) seems to be between 0.30 and 0.35 inclusive. However, no threshold gave a summary estimate above 80% for both sensitivity and specificity, and considerable heterogeneity existed in diagnostic accuracy across studies at most thresholds. No studies looked at protein to creatinine ratio and adverse pregnancy outcome. For albumin to creatinine ratio, meta-analysis was not possible. Results from a single study suggested that the most predictive result, for significant proteinuria, was with the DCA 2000 quantitative analyser (>2 mg/mmol) with a

  12. Alcohol intake and early-onset basal cell carcinoma in a case-control study.

    PubMed

    Zhang, Y; Ferrucci, L M; Cartmel, B; Molinaro, A M; Leffell, D J; Bale, A E; Mayne, S T

    2014-12-01

    Previous epidemiological studies of overall alcohol intake and basal cell carcinoma (BCC) are inconsistent, with some evidence for differences by type of alcoholic beverage. While alcohol may enhance the carcinogenicity of ultraviolet (UV) radiation, this has not been evaluated in existing epidemiological studies. To evaluate alcohol intake in relation to early-onset BCC, and explore potential interactions with UV exposure. Basal cell carcinoma cases (n = 380) and controls with benign skin conditions (n = 390) under 40 years of age were identified through Yale Dermatopathology. Participants provided information on lifetime alcohol intake, including type of beverage, during an in-person interview. Self-reported data on indoor tanning and outdoor sunbathing were used to categorize UV exposure. We calculated odds ratios (OR) and 95% confidence intervals (CIs) using unconditional multivariate logistic regression in the full sample and in women only. There was no statistically significant association between lifetime alcohol intake and early-onset BCC overall [above median intake vs. no regular alcohol intake (OR 1·10, 95% CI 0·69-1·73)] or in women only (OR 1·21, 95% CI 0·73-2·01). Similarly, intake of red wine, white wine, beer or spirits and mixed drinks was not associated with early-onset BCC. In exploratory analyses, we saw limited evidence for an interaction (P(interaction) = 0·003), with highest risk for high alcohol and high UV exposures, especially in women, but subgroup risk estimates had wide and overlapping CIs. Overall, we did not observe any clear association between lifetime alcohol intake and early-onset BCC. © 2014 British Association of Dermatologists.

  13. Alcohol intake and early-onset basal cell carcinoma in a case-control study

    PubMed Central

    Zhang, Y; Ferrucci, L.M.; Cartmel, B.; Molinaro, A.M.; Leffell, D.J.; Bale, A.E.; Mayne, S.T.

    2014-01-01

    Background Previous epidemiologic studies of overall alcohol intake and basal cell carcinoma (BCC) are inconsistent, with some evidence for differences by type of alcoholic beverage. While alcohol may enhance the carcinogenicity of ultraviolet (UV) light, this has not been evaluated in existing epidemiologic studies. Objective To evaluate alcohol intake in relation to early-onset BCC, and explore potential interactions with UV exposure. Methods BCC cases (n=380) and controls with benign skin conditions (n=390) under age 40 were identified through Yale Dermatopathology. Participants provided information on lifetime alcohol intake, including type of beverage during an in-person interview. Self-report data on indoor tanning and outdoor sunbathing were used to categorize UV exposure. We calculated odds ratios (OR) and 95% confidence intervals (CI) using unconditional multivariate logistic regression in the full sample and in women only. Results There was no statistically significant association between lifetime alcohol intake and early-onset BCC overall (above median intake vs. no regular alcohol intake OR 1.10, 95% CI 0.69-1.73) or in women only (OR 1.21, 95% CI 0.73-2.01). Similarly, intake of red wine, white wine, beer or hard liquor and mixed drinks was not associated with early-onset BCC. In exploratory analyses, we saw limited evidence for an interaction (pinteraction=0.003), with highest risk for high alcohol and high UV exposures, especially in women, but subgroup risk estimates had wide and overlapping confidence intervals. Conclusions Overall, we did not observe any clear association between lifetime alcohol intake and early-onset BCC. PMID:25059635

  14. Indoor tanning and risk of early-onset basal cell carcinoma

    PubMed Central

    Ferrucci, Leah M.; Cartmel, Brenda; Molinaro, Annette M.; Leffell, David J.; Bale, Allen E.; Mayne, Susan T.

    2011-01-01

    Background Despite a rise in incidence of basal cell carcinoma (BCC) among young people and the ubiquity of indoor tanning in this population, few epidemiologic studies have investigated this exposure-disease relationship. Objective Evaluate the association between indoor tanning and early-onset BCC. Methods BCC cases (n=376) and controls with minor benign skin conditions (n=390) under age 40 were identified through Yale Dermatopathology. Participants provided information on ever indoor tanning, age of initiation, frequency, duration, burns while tanning, and type of tanning device during an in-person interview. We calculated odds ratios (OR) and 95% confidence intervals (CI) using multivariate logistic regression with never indoor tanners as the referent group. Results Ever indoor tanning was associated with a 69% increased risk of early-onset BCC (95% CI=1.15-2.48). This association was stronger among women (OR=2.14, 95% CI=1.31-3.47), for multiple BCCs (OR=2.16, 95% CI=1.26-3.70), and for BCCs on the trunk and extremities (OR=2.81, 95% CI=1.57-5.02). Risk increased dose-dependently with years used regular indoor tanning devices (p-trend=0.003), number of overall burns (p-trend=<0.001) and burns to biopsy site (p-trend=<0.001) from indoor tanning. Approximately one-quarter (27%) of early-onset BCCs (or 43% among women) could be prevented if individuals never tanned indoors. Limitations Potential recall bias of indoor tanning by cases and generalizability of the control population suggest replication in other studies is warranted. Conclusions Indoor tanning was a strong risk factor for early-onset BCC, particularly among women. Indoor tanning should continue to be targeted by both policy-based and behavioral interventions, as the impact on BCC-associated morbidity may be substantial. PMID:22153793

  15. Definition, clinical profile, microbiological spectrum, and prognostic factors of early-onset prosthetic valve endocarditis.

    PubMed

    López, Javier; Revilla, Ana; Vilacosta, Isidre; Villacorta, Eduardo; González-Juanatey, Carlos; Gómez, Itziar; Rollán, María Jesús; San Román, José Alberto

    2007-03-01

    There is no agreement in the best cutoff time to distinguish between early- and late- onset prosthetic valve endocarditis (PVE). Our objectives are to define early-onset PVE according to the microbiological spectrum and to analyse the profile and short-term prognosis of this entity. The microbiological profile of 172 non-drug users, who were patients with PVE, were compared according to the time elapsed from surgery among 640 endocarditis diagnosed between 1996 and 2004. There were no differences in the microbiological profile of patients with PVE occurred within 2 months of valve replacement and those accounting between 2 and 12 months. The proportion of coagulase-negative Staphylococci (CNS) was higher during the first year post-intervention (37 vs. 18%, P = 0.005) and Streptococci viridans were more common after 1 year (18 vs. 1%, P = 0.001). The percentage of methicilin-resistant CNS strains was higher before 1 year (77 vs. 30%, P = 0.004). Early-onset PVE represented 38% of all episodes of PVE, CNS being the most frequent isolated microorganisms (37%), most of them methicilin resistant (77%). In-hospital mortality of patients who needed urgent surgery was 46% and elective surgery 25%. Overall, in-hospital mortality was 38% and no differences were seen between surgical and medical groups (32 vs. 45%, P = 0.30). Periannular complications were associated with higher in-hospital mortality (60 vs. 27%, P = 0.007). According to the microbiological profile, the most appropriate cutoff time to distinguish between early- and late-onset PVE was 1 year. Methicilin-resistant CNS are the most frequent pathogens and periannular complications, the only risk factor for in-hospital mortality.

  16. Does Diagnostic Classification of Early-Onset Psychosis Change over Follow-Up?

    ERIC Educational Resources Information Center

    Fraguas, David; de Castro, Maria J.; Medina, Oscar; Parellada, Mara; Moreno, Dolores; Graell, Montserrat; Merchan-Naranjo, Jessica; Arango, Celso

    2008-01-01

    Objective: To examine the diagnostic stability and the functional outcome of patients with early-onset psychosis (EOP) over a 2-year follow-up period. Methods: A total of 24 patients (18 males (75%) and 6 females (25%), mean age [plus or minus] SD: 15.7 [plus or minus] 1.6 years) with a first episode of EOP formed the sample. Psychotic symptoms…

  17. Clinical and molecular characterization of KCNT1-related severe early-onset epilepsy

    PubMed Central

    Nair, Umesh; Malhotra, Sony; Meyer, Esther; Trump, Natalie; Gazina, Elena V.; Papandreou, Apostolos; Ngoh, Adeline; Ackermann, Sally; Ambegaonkar, Gautam; Appleton, Richard; Desurkar, Archana; Eltze, Christin; Kneen, Rachel; Kumar, Ajith V.; Lascelles, Karine; Montgomery, Tara; Ramesh, Venkateswaran; Samanta, Rajib; Scott, Richard H.; Tan, Jeen; Whitehouse, William; Poduri, Annapurna; Scheffer, Ingrid E.; Chong, W.K. “Kling”; Cross, J. Helen; Topf, Maya; Petrou, Steven

    2018-01-01

    Objective To characterize the phenotypic spectrum, molecular genetic findings, and functional consequences of pathogenic variants in early-onset KCNT1 epilepsy. Methods We identified a cohort of 31 patients with epilepsy of infancy with migrating focal seizures (EIMFS) and screened for variants in KCNT1 using direct Sanger sequencing, a multiple-gene next-generation sequencing panel, and whole-exome sequencing. Additional patients with non-EIMFS early-onset epilepsy in whom we identified KCNT1 variants on local diagnostic multiple gene panel testing were also included. When possible, we performed homology modeling to predict the putative effects of variants on protein structure and function. We undertook electrophysiologic assessment of mutant KCNT1 channels in a xenopus oocyte model system. Results We identified pathogenic variants in KCNT1 in 12 patients, 4 of which are novel. Most variants occurred de novo. Ten patients had a clinical diagnosis of EIMFS, and the other 2 presented with early-onset severe nocturnal frontal lobe seizures. Three patients had a trial of quinidine with good clinical response in 1 patient. Computational modeling analysis implicates abnormal pore function (F346L) and impaired tetramer formation (F502V) as putative disease mechanisms. All evaluated KCNT1 variants resulted in marked gain of function with significantly increased channel amplitude and variable blockade by quinidine. Conclusions Gain-of-function KCNT1 pathogenic variants cause a spectrum of severe focal epilepsies with onset in early infancy. Currently, genotype-phenotype correlations are unclear, although clinical outcome is poor for the majority of cases. Further elucidation of disease mechanisms may facilitate the development of targeted treatments, much needed for this pharmacoresistant genetic epilepsy. PMID:29196579

  18. Canadian patient played key role in uncovering secrets about early-onset Alzheimer's disease.

    PubMed Central

    Lyttle, J

    1996-01-01

    Last June, the University of Toronto announced that Canadian scientists and a team of international researchers had discovered the gene responsible for most cases of early-onset Alzheimer's disease. One of the key players in that discovery had died just 3 months earlier. Frances Hodge, who participated in a battery of tests for the 20 years she lived with the disease, helped lead researchers to gene S182--and an ember of hope for future generations. Images p906-a PMID:8634971

  19. Clinical features of early onset, familial Alzheimer`s disease linked to chromosome 14

    SciTech Connect

    Mullan, M.; Bennett, C.; Figueredo, C.

    1995-02-27

    Early onset familial Alzheimer`s disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the {beta}-amyloid precursor protein ({beta}APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with {beta}APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val {r_arrow} Ile) or a valine to glycine (Val {r_arrow} Gly) change. More recently, a second locus for very early onsetmore » disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the {beta}APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the {beta}APP717 Val {r_arrow} Ile and {beta}APP717 Val {r_arrow} Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or {beta}APP codon 717 mutated families except mean age of onset. 52 refs., 2 figs., 5 tabs.« less

  20. Psychiatric comorbidities of adults with early- and late-onset attention-deficit/hyperactivity disorder.

    PubMed

    Lin, Yu-Ju; Yang, Li-Kuang; Gau, Susan Shur-Fen

    2016-06-01

    We evaluated the psychiatric comorbidities in adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder as a function of recalled symptom onset before and after the age of 7 years and whether the childhood attention-deficit/hyperactivity disorder symptoms were associated with psychiatric comorbidities. In all, 214 adults who were diagnosed with Diagnostic and Statistical Manual of Mental disorders, 5th edition attention-deficit/hyperactivity disorder and 174 non-attention-deficit/hyperactivity disorder controls (aged 17-40 years) received psychiatric interviews to confirm their previous and current attention-deficit/hyperactivity disorder status and other psychiatric diagnoses. Demographics and risks of lifetime psychiatric disorders were compared among three groups: (1) attention-deficit/hyperactivity disorder, onset <7 years (early-onset); (2) attention-deficit/hyperactivity disorder, onset between 7 and 12 years (late-onset) and (3) non-attention-deficit/hyperactivity disorder controls. We also tested the effects of attention-deficit/hyperactivity disorder symptoms on the risk of later psychiatric comorbidities by Cox regression analyses. Regardless of the age of onset, attention-deficit/hyperactivity disorder was significantly associated with a wide range of psychiatric comorbidities. There were similar comorbid patterns between early- and late-onset attention-deficit/hyperactivity disorder. Regardless of attention-deficit/hyperactivity disorder diagnosis, increased severity of attention-deficit/hyperactivity disorder symptoms was associated with higher risks of oppositional defiant disorder, conduct disorder, dysthymia and sleep disorder but not major depression, which was associated with the attention-deficit/hyperactivity disorder diagnosis. Our findings suggest that elevating the threshold of age of onset to 12 years in Diagnostic and Statistical Manual of Mental

  1. Association between the SERPINE1 (PAI-1) 4G/5G insertion/deletion promoter polymorphism (rs1799889) and pre-eclampsia: a systematic review and meta-analysis.

    PubMed

    Zhao, Linlu; Bracken, Michael B; Dewan, Andrew T; Chen, Suzan

    2013-03-01

    The SERPINE1 -675 4G/5G promoter region insertion/deletion polymorphism (rs1799889) has been implicated in the pathogenesis of pre-eclampsia (PE), but the genetic association has been inconsistently replicated. To derive a more precise estimate of the association, a systematic review and meta-analysis was conducted. This study conformed to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed (MEDLINE), Scopus and HuGE Literature Finder literature databases were systematically searched for relevant studies. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the allelic comparison (4G versus 5G) and genotypic comparisons following the co-dominant (4G/4G versus 5G/5G and 4G/5G versus 5G/5G), dominant (4G/4G+4G/5G versus 5G/5G) and recessive (4G/4G versus 4G/5G+5G/5G) genetic models. Between-study heterogeneity was quantified by I(2) statistics and publication bias was appraised with funnel plots. Sensitivity analysis was conducted to evaluate the robustness of meta-analysis findings. Meta-analysis of 11 studies involving 1297 PE cases and 1791 controls found a significant association between the SERPINE1 -675 4G/5G polymorphism and PE for the recessive genetic model (OR = 1.36, 95% CI: 1.13-1.64, P = 0.001), a robust finding according to sensitivity analysis. A low level of between-study heterogeneity was detected (I(2) = 20%) in this comparison, which may be explained by ethnic differences. Funnel plot inspection did not reveal evidence of publication bias. In conclusion, this study provides a comprehensive examination of the available literature on the association between SERPINE1 -675 4G/5G and PE. Meta-analysis results support this polymorphism as a likely susceptibility variant for PE.

  2. Live-born diploid fetus complicated with partial molar pregnancy presenting with pre-eclampsia, maternal anemia, and seemingly huge placenta: A rare case of confined placental mosaicism and literature review.

    PubMed

    Kawasaki, Kaoru; Kondoh, Eiji; Minamiguchi, Sachiko; Matsuda, Fumihiko; Higasa, Koichiro; Fujita, Kohei; Mogami, Haruta; Chigusa, Yoshitsugu; Konishi, Ikuo

    2016-08-01

    A partial molar pregnancy almost always ends in miscarriage due to a triploid fetus. We describe a rare case of a singleton, partial molar pregnancy with a seemingly huge placenta, which continued to delivery of a live-born diploid baby. A 27-year-old primigravida suffered from severe pre-eclampsia and progressive anemia. The uterus was enormously enlarged for the gestational age. A cesarean section was performed because of deterioration of maternal status at 25 weeks' gestation, when more than 3000 mL blood spouted concurrently with the delivery of the placenta. The histological examination showed congestion in the decidua, which indicated disturbance of maternal venous return from the intervillous space. The chromosome complement of the placenta and the neonate were 69,XXX and 46,XX, respectively. We also reviewed all published cases of a singleton, partial molar pregnancy. A literature search yielded 18 cases of a singleton, diploid fetus with partial molar pregnancy. The mean gestational age at delivery was 24.5 ± 6.2 weeks, and fetuses survived outside the uterus in only four cases (22.2%). Intriguingly, previous reports numbered 10 cases with diploid placenta as well as five cases with no karyotyping of the placenta, indicating that they may have included a complete mole in a twin pregnancy or placental mesenchymal dysplasia. In conclusion, this was the first case of placentomegaly that presented manifestations of excessive abdominal distension and maternal severe anemia, and the second case of a singleton, partial molar pregnancy confirmed by chromosome analysis resulting in a diploid living baby. © 2016 Japan Society of Obstetrics and Gynecology.

  3. High-Definition transcranial direct current stimulation in early onset epileptic encephalopathy: a case study.

    PubMed

    Meiron, Oded; Gale, Rena; Namestnic, Julia; Bennet-Back, Odeya; David, Jonathan; Gebodh, Nigel; Adair, Devin; Esmaeilpour, Zeinab; Bikson, Marom

    2018-01-01

    Early onset epileptic encephalopathy is characterized by high daily seizure-frequency, multifocal epileptic discharges, severe psychomotor retardation, and death at infancy. Currently, there are no effective treatments to alleviate seizure frequency and high-voltage epileptic discharges in these catastrophic epilepsy cases. The current study examined the safety and feasibility of High-Definition transcranial direct current stimulation (HD-tDCS) in reducing epileptiform activity in a 30-month-old child suffering from early onset epileptic encephalopathy. HD-tDCS was administered over 10 intervention days spanning two weeks including pre- and post-intervention video-EEG monitoring. There were no serious adverse events or side effects related to the HD-tDCS intervention. Frequency of clinical seizures was not significantly reduced. However, interictal sharp wave amplitudes were significantly lower during the post-intervention period versus baseline. Vital signs and blood biochemistry remained stable throughout the entire study. These exploratory findings support the safety and feasibility of 4 × 1 HD-tDCS in early onset epileptic encephalopathy and provide the first evidence of HD-tDCS effects on paroxysmal EEG features in electroclinical cases under the age of 36 months. Extending HD-tDCS treatment may enhance electrographic findings and clinical effects.

  4. A girl with early-onset epileptic encephalopathy associated with microdeletion involving CDKL5.

    PubMed

    Saitsu, Hirotomo; Osaka, Hitoshi; Nishiyama, Kiyomi; Tsurusaki, Yoshinori; Doi, Hiroshi; Miyake, Noriko; Matsumoto, Naomichi

    2012-05-01

    Recent studies have shown that aberrations of CDKL5 in female patients cause early-onset intractable seizures, severe developmental delay or regression, and Rett syndrome-like features. We report on a Japanese girl with early-onset epileptic encephalopathy, hypotonia, developmental regression, and Rett syndrome-like features. The patient showed generalized tonic seizures, and later, massive myoclonus induced by phone and light stimuli. Brain magnetic resonance imaging showed no structural brain anomalies but cerebral atrophy. Electroencephalogram showed frontal dominant diffuse poly spikes and waves. Through copy number analysis by genomic microarray, we found a microdeletion at Xp22.13. A de novo 137-kb deletion, involving exons 5-21 of CDKL5, RS1, and part of PPEF1 gene, was confirmed by quantitative PCR and breakpoint specific PCR analyses. Our report suggests that the clinical features associated with CDKL5 deletions could be implicated in Japanese patients, and that genetic testing of CDKL5, including both sequencing and deletion analyses, should be considered in girls with early-onset epileptic encephalopathy and RTT-like features. Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  5. In utero arsenic exposure induces early onset of atherosclerosis in ApoE−/− mice

    PubMed Central

    Srivastava, Sanjay; D’Souza, Stanley E.; Sen, Utpal; States, J. Christopher

    2007-01-01

    Consumption of arsenic contaminated drinking water has been linked to higher rates of coronary disease, stroke, and peripheral arterial disease. Recent evidence suggests that early life exposures may play a significant role in the onset of chronic adult diseases. To investigate the potential for in utero exposure to accelerate the onset of cardiovascular disease we exposed pregnant ApoE-knockout (ApoE−/−) mice to arsenic in their drinking water and examined the aortic trees of their male offspring for evidence of early disease 10 and 16 weeks after birth. Mice were maintained on normal chow after weaning. ApoE−/− mice are a commonly used model for atherogenesis and spontaneously develop atherosclerotic disease. Mice exposed to arsenic in utero showed a >2-fold increase in lesion formation in the aortic roots as well as the aortic arch compared to control mice at both 10 and 16 weeks of age. The mice exposed to arsenic also had a 20 – 40% decrease in total triglycerides, but no change in total cholesterol, phospholipids and total abundance of VLDL or HDL particles. Subfractionation of VLDL particles showed a decrease in large VLDL particles. In addition, the arsenic exposed mice showed a vasorelaxation defect in response to acetylcholine suggesting disturbance of endothelial cell signalling. These results indicate that in utero arsenic exposure induces an early onset of atherosclerosis in ApoE−/− mice without a hyperlipidemic diet and support the hypothesis that in utero arsenic exposure may be atherogenic in humans. PMID:17317095

  6. Neurological soft signs in juvenile patients with Asperger syndrome, early-onset psychosis, and healthy controls.

    PubMed

    Mayoral, María; Merchán-Naranjo, Jessica; Rapado, Marta; Leiva, Marta; Moreno, Carmen; Giráldez, Marisa; Arango, Celso; Parellada, Mara

    2010-11-01

    The study of neurological soft signs (NSS) in patients with Asperger syndrome may help us to elucidate the neurological basis of this disorder and to clarify its relationship with other neurodevelopmental disorders. The goal of this study was to compare the prevalence of NSS in a sample of patients with Asperger syndrome, early-onset psychosis and healthy controls. NSS were assessed by means of the Neurological Evaluation Scale in a sample of 29 patients with Asperger syndrome (mean age = 12.86 ± 2.58 years), 30 patients with first-episode early-onset psychoses (mean age 14.17 ± 1.02 years) and 30 healthy controls (mean age 12.33 ± 2.69 years). Significant group differences were found between Asperger syndrome patients and healthy controls both in all the Neurological Evaluation Scale subscales and in the Neurological Evaluation Scale total score. There were no significant differences between both groups of patients in any of the Neurological Evaluation Scale scores. NSS are more prevalent in Asperger syndrome than in healthy controls. The NSS profile was not disorder-specific in our samples of patients with Asperger syndrome and early-onset psychoses. © 2010 Blackwell Publishing Asia Pty Ltd.

  7. Variants of early-onset restrictive eating disturbances in middle childhood.

    PubMed

    Kurz, Susanne; van Dyck, Zoé; Dremmel, Daniela; Munsch, Simone; Hilbert, Anja

    2016-01-01

    This study sought to determine the factor structure of the newly developed self-report screening questionnaire Eating Disturbances in Youth-Questionnaire (EDY-Q) as well as to report the distribution of variants of early-onset restrictive eating disturbances characteristic of avoidant/restrictive food intake disorder (ARFID) in a middle childhood population sample. Using the EDY-Q, a total of 1,444 children aged 8-13 years were screened in elementary schools in Switzerland via self-report. The factor analysis of the 12 items covering ARFID related symptoms was performed using a principal component analysis (PCA). The PCA showed a four factor solution, with clear allocation to the scales covering three variants of early-onset restrictive eating disturbances and weight problems. Inadequate overall food intake was reported by 19.3% of the children, a limited accepted amount of food by 26.1%, and food avoidance based on a specific underlying fear by 5.0%. The postulated factor structure of the EDY-Q was confirmed, further supporting the existence of distinct variants of early-onset restrictive eating disturbances. Avoidant/restrictive eating behavior seems to be a common experience in middle childhood, but results have to be confirmed using validated interviews. © 2015 Wiley Periodicals, Inc.

  8. Distinct 18F-AV-1451 tau PET retention patterns in early- and late-onset Alzheimer's disease.

    PubMed

    Schöll, Michael; Ossenkoppele, Rik; Strandberg, Olof; Palmqvist, Sebastian; Jögi, Jonas; Ohlsson, Tomas; Smith, Ruben; Hansson, Oskar

    2017-09-01

    Patients with Alzheimer's disease can present with different clinical phenotypes. Individuals with late-onset Alzheimer's disease (>65 years) typically present with medial temporal lobe neurodegeneration and predominantly amnestic symptomatology, while patients with early-onset Alzheimer's disease (<65 years) exhibit greater neocortical involvement associated with a clinical presentation including dyspraxia, executive dysfunction, or visuospatial impairment. We recruited 20 patients with early-onset Alzheimer's disease, 21 with late-onset Alzheimer's disease, three with prodromal early-onset Alzheimer's disease and 13 with prodromal late-onset Alzheimer's disease, as well as 30 cognitively healthy elderly controls, that had undergone 18F-AV-1451 tau positron emission tomography and structural magnetic resonance imaging to explore whether early- and late-onset Alzheimer's disease exhibit differential regional tau pathology and atrophy patterns. Strong associations of lower age at symptom onset with higher 18F-AV-1451 uptake were observed in several neocortical regions, while higher age did not yield positive associations in neither patient group. Comparing patients with early-onset Alzheimer's disease with controls resulted in significantly higher 18F-AV-1451 retention throughout the neocortex, while comparing healthy controls with late-onset Alzheimer's disease patients yielded a distinct pattern of higher 18F-AV-1451 retention, predominantly confined to temporal lobe regions. When compared against each other, the early-onset Alzheimer's disease group exhibited greater uptake than the late-onset group in prefrontal and premotor, as well as in inferior parietal cortex. These preliminary findings indicate that age may constitute an important contributor to Alzheimer's disease heterogeneity highlighting the potential of tau positron emission tomography to capture phenotypic variation across patients with Alzheimer's disease. © The Author (2017). Published by Oxford

  9. Early impact basins and the onset of plate tectonics. Ph.D. Thesis - Maryland Univ.

    NASA Technical Reports Server (NTRS)

    Frey, H.

    1977-01-01

    The fundamental crustal dichotomy of the Earth (high and low density crust) was established nearly 4 billion years ago. Therefore, subductable crust was concentrated at the surface of the Earth very early in its history, making possible an early onset for plate tectonics. Simple thermal history calculations spanning 1 billion years show that the basin forming impact thins the lithosphere by at least 25%, and increases the sublithosphere thermal gradients by roughly 20%. The corresponding increase in convective heat transport, combined with the highly fractured nature of the thinned basin lithosphere, suggest that lithospheric breakup or rifting occurred shortly after the formation of the basins. Conditions appropriate for early rifting persisted from some 100,000,000 years following impact. We suggest a very early stage of high temperature, fast spreading "microplate" tectonics, originating before 3.5 billion years ago, and gradually stabilizing over the Archaean into more modern large plate or Wilson Cycle tectonics.

  10. High normal blood pressure in early pregnancy also contribute to early onset preeclampsia and severe preeclampsia.

    PubMed

    He, Dian; Wu, Shaowen; Zhao, Haiping; Zheng, Zihe; Zhang, Weiyuan

    2017-11-27

    This study was to evaluate effects of high normal blood pressure (HNBP