13 research outputs found
Prediction of preeclampsia and its prevention with aspirin
Background: Preeclampsia (PE) affects 2-3% of all pregnancies and is a major
cause of maternal and perinatal morbidity and mortality. The current approach to
screening for PE is based on the identification of risk factors from maternal
characteristics and medical history. This approach, however, fails to identify a high
proportion of cases of PE and does not provide individualised, patient-specific
results. An alternative approach is to combine maternal factors with biophysical and
biochemical markers to estimate the individual probability of developing PE with
higher detection rates. To date, no intervention is proven to reduce the risk of the
disease, and several studies evaluating the use of aspirin for prevention of PE led to
inconclusive results.
Objectives: The aims of the studies included in this thesis are, first, to prospectively
validate in a large European population a first-trimester algorithm for prediction of PE
that combines maternal demographic characteristics and medical history with
biophysical and biochemical markers; second, to compare this method of screening
to the performance of currently used guidelines; third, to evaluate a possible
beneficial effect of aspirin initiated at 11 to 14 weeks of gestation and at a dose of
150 mg in the prevention of PE in a multicentre, double-blind, placebo-controlled
randomised trial; and fourth, to analyse a potential role of cell-free DNA testing in the
prediction of PE.
Methods: Combined screening for PE was applied in the first or second trimester,
and women found to be at high-risk in the first trimester were offered participation in
a double-blind trial of aspirin against placebo in six European countries. We have
recorded maternal characteristics and history, measured the uterine artery pulsatility
index (UtPI) on ultrasound, the mean arterial pressure (MAP), serum concentration
of pregnancy-associated plasma protein A (PAPP-A) and placental growth factor
(PLGF). Pregnancy outcomes were obtained from the hospital maternity records.
Bayes theorem was used to combine the a priori risk from maternal factors with the
results of biomarker measurements and estimate individual probabilities. In the
randomised trial, the analysis was performed in an intention-to-treat basis and the
treatment effect on the primary outcome (the development of PE with delivery before
37 weeks of gestation) was reported with 95% confidence interval (CI), and on secondary outcomes with 99% CI. Cell-free DNA fetal fraction was compared with
other first trimester markers for PE and in a case-control study.
Results: Detection rates of combined screening, for a false-positive rate (FPR) of
10%, were 89% (95% CI 79-96%), 75% (95% CI 70-80%) and 47% (95% CI 44-
51%) for PE <32 weeks, preterm PE and term disease, respectively. The
performance of combined screening was superior to methods based on risk factors
alone, both in the first and second trimesters. The use of aspirin by high-risk women
reduced the incidence of preterm PE by 62% (adjusted odds ratio 0.38, 95% CI 0.20-
0.74). Secondary analyses have shown that the effect of aspirin was influenced by
the level of compliance to treatment and was consistent in different subgroups
according to maternal characteristics and obstetric history, but there was no
evidence of beneficial effect of aspirin in women with chronic hypertension. Aspirin
reduces the length of stay in NICU and costs through a reduction in premature births
before 32 weeks due to PE. Fetal fraction on cell-free DNA testing correlates with
other first trimester markers, but its role in screening for PE is uncertain.
Conclusions: This thesis has demonstrated that combined screening for PE is
superior to current guidelines based on maternal characteristics and history alone,
and that aspirin, at a daily dose of 150 mg and given to high-risk patients from 11 to
14 weeks until 36 weeks of gestation, reduces the incidence preterm PE and the
length of stay in NICU. The effect of the medication depends on good adherence to
treatment and is questionable in patients with chronic hypertension
Evaluation of Cardiac Function in Women With a History of Preeclampsia : A Systematic Review and Meta-Analysis
Peer reviewedPublisher PD
Cell-free DNA screening for rare autosomal trisomies and segmental chromosome imbalances
Funding Information: Ben W. Mol is supported by a NHMRC Investigator grant (GNT1176437). Ben W. Mol reports consultancy for ObsEva and Merck and travel support and research grants from Merck. The authors declare no conflict of interest. The authors wish to acknowledge the staff of Monash Ultrasound for Women, Sydney Ultrasound for Women, and Ultrasound Care for their diligent and compassionate care of the women involved in this study. Open access publishing facilitated by Monash University, as part of the Wiley - Monash University agreement via the Council of Australian University Librarians.Peer reviewedPublisher PD
The accuracy of cell-free DNA screening for fetal segmental copy number variants : A systematic review and meta-analysis
Funding Information: BWM is supported by a NHMRC Investigator grant (GNT1176437). BWM reports consultancy for ObsEva and Merck and travel support and research grants from Merck. MM is employed as a genetic counsellor at a private genetic testing provider. DLR has received research grants from NHMRC and Norman‐Beischer Medical Research Foundation. The authors declare no competing interests. Completed disclosure of interest forms are available to view online as supporting information. Open access publishing facilitated by Monash University, as part of the Wiley - Monash University agreement via the Council of Australian University Librarians.Peer reviewedPublisher PD
Sequential evaluation of the cervix and test for phosphorylated insulin-like growth factor binding protein-1 in the prediction of preterm delivery
INTRODUÇÃO: O antecedente de parto prematuro espontâneo em gestação anterior é considerado o principal e mais importante fator de risco clínico para prematuridade, principal causa de morbidade e mortalidade neonatal. Cerca de 25% das pacientes que tiveram parto prematuro apresentarão recorrência. A prevenção secundária consiste na pesquisa de marcadores de maior risco, com o intuito de instituir medidas terapêuticas apropriadas e de evitar tratamentos desnecessários. A hipótese do presente estudo é a de que existe correlação entre os resultados da avaliação do colo uterino e do teste para proteína-1 fosforilada ligada ao fator de crescimento insulina-símile (phIGFBP-1) e que a utilização de ambos em associação possa predizer a ocorrência de parto prematuro com maior sensibilidade. OBJETIVOS: Averiguar a utilidade da medida do comprimento do colo uterino e do teste para phIGFBP-1 na predição do parto prematuro antes de 37 e de 34 semanas, a existência de relação dos testes entre si, o melhor valor de corte da medida do colo em diferentes idades gestacionais e a melhor época de realização de cada um dos exames. MÉTODO: Foram compilados e submetidos a análise secundária os dados de 101 gestantes com antecedente de parto prematuro atendidas no Setor de Baixo Peso Fetal da Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, entre 2003 e 2008. A medida do comprimento cervical e o teste para phIGFBP-1 foram realizados a cada três semanas, entre 24 e 34 semanas de gestação, e comparados com o desfecho de parto prematuro e nascimento com 34 semanas ou menos, e o melhor valor de corte do colo uterino foi estabelecido por meio de curva de características operacionais. RESULTADOS: Das 101 gestações estudadas, 25 (24,8%) terminaram em parto prematuro, das quais 12 (11,9%) ocorreram com 34 semanas ou menos. As idades gestacionais médias de avaliação foram de 24, 27, 30 e 33 semanas, e os valores de corte do colo uterino foram de 22, 21, 20 e 16 mm, respectivamente. A medida do comprimento do colo apresentou maior sensibilidade (cerca de 70%) e foi capaz de predizer o parto prematuro em todas as avaliações. O teste para phIGFBP-1 não foi útil com 24 semanas, porém foi capaz de detectar de forma independente o risco de prematuridade com 27, com 30 e com 33 semanas. Houve associação estatística dos exames entre si, de forma que o comprimento cervical médio foi menor em gestantes com teste positivo para phIGFBP-1. A associação dos exames elevou a sensibilidade e o valor preditivo negativo de forma significativa. CONCLUSÕES: A medida do comprimento do colo pela ultrassonografia transvaginal constitui bom marcador de risco para parto prematuro com 24 semanas, e o teste para phIGFBP-1 é útil após 27 semanas. A associação dos dois exames possui alta sensibilidade e alto valor preditivo negativo em gestantes de alto risco para prematuridade espontânea, e a realização do primeiro com 24 semanas e do segundo com 27 semanas constitui bom modelo preditivo para o parto prematuroINTRODUCTION: The history of spontaneous preterm birth in a previous pregnancy is considered the main and most important clinical risk factor for preterm birth, the leading cause of neonatal morbidity and mortality. About 25% of these patients will deliver prematurely again. Secondary prevention consists in the search for markers of increased risk, in order to institute appropriate therapeutic actions and to avoid unnecessary treatments. The hypothesis of this study is that there is a correlation between the results of the evaluation of the cervix and the test for phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) and that the use of both in combination can predict the occurrence of preterm delivery with higher sensitivity. OBJECTIVES: To investigate the usefulness of the measurement of the cervical length and phIGFBP-1 rapid test in the prediction of preterm birth before 37 and 34 weeks, the existence of a relationship between the tests themselves, the best cutoff value of cervical length measurement at different gestational ages and the best time to carry out each of the exams. METHODS: Data of 101 women with previous preterm birth assisted at the Obstetrical Clinic of the Hospital das Clínicas, Faculty of Medicine, University of São Paulo between 2003 and 2008 were collected and subjected to secondary analysis. The measurement of cervical length and the phIGFBP-1 test were performed every three weeks, between 24 and 34 weeks gestation, and compared with the outcome of premature birth before 37 and 34 weeks, and the best cutoff value of the cervix was determined by receiver operator characteristic curves. RESULTS: Of the 101 pregnancies studied, 25 (24.8%) ended in preterm birth, of which 12 (11.9%) occurred at 34 weeks or less. The mean gestational age in each evaluation was 24, 27, 30 and 33 weeks, and the cutoff of the cervix were 22, 21, 20 and 16 millimeters, respectively. The measurement of cervical length showed the highest sensitivity (approximately 70%) and was able to predict preterm birth in all evaluations. The phIGFBP-1 test was not useful at 24 weeks, but was able to independently detect the risk of prematurity at 27, 30 and 33 weeks. Statistical association between the exams was observed, so that the mean cervical length was lower in pregnant women testing positive for phIGFBP-1. The combination of both tests significantly increased the sensitivity and negative predictive value. CONCLUSIONS: The measurement of cervical length by transvaginal ultrasound is a good marker of risk for preterm delivery at 24 weeks, and the test for phIGFBP-1 is useful after 27 weeks. The association of the two tests is valuable and shows high sensitivity and high negative predictive value in women at high risk for spontaneous preterm birth, when the first is preformed with 24 weeks, and the second with 27 week
Uterine Artery Doppler in Screening for Preeclampsia and Fetal Growth Restriction
<div><p>Abstract Objective To perform a comprehensive review of the current evidence on the role of uterine artery Doppler, isolated or in combination with other markers, in screening for preeclampsia (PE) and fetal growth restriction (FGR) in the general population. The review included recently published large cohort studies and randomized trials. Methods A search of the literature was conducted usingMedline, PubMed, MeSH and ScienceDirect. Combinations of the search terms “preeclampsia,” “screening,” “prediction,” “Doppler,” “Doppler velocimetry,” “fetal growth restriction,” “small for gestational age” and “uterine artery” were used. Articles in English (excluding reviews) reporting the use of uterine artery Doppler in screening for PE and FGR were included. Results Thirty articles were included. As a single predictor, uterine artery Doppler detects less than 50% of the cases of PE and no more than 40% of the pregnancies affected by FGR. Logistic regression-based models that allow calculation of individual risk based on the combination of multiple markers, in turn, is able to detect ~ 75% of the cases of preterm PE and 55% of the pregnancies resulting in small for gestational age infants. Conclusion The use of uterine artery Doppler as a single predictive test for PE and FGR has poor accuracy. However, its combined use in predictive models is promising, being more accurate in detecting preterm PE than FGR.</p></div
Assessing Feeding Difficulties in Children Presenting with Non-IgE-Mediated Gastrointestinal Food Allergies—A Commonly Reported Problem
Many guidelines have been published to help diagnose food allergies, which have included feeding difficulties as a presenting symptom (particularly for non-IgE-mediated gastrointestinal allergies). This study aimed to investigate the prevalence of feeding difficulties in children with non-IgE-mediated gastrointestinal allergies and the association of such difficulties with symptoms and food elimination. An observational study was performed at Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK. Children aged 4 weeks to 16 years without non-allergic co-morbidities who improved on an elimination diet using a previously published Likert scale symptom score were included. This study recruited 131 children, and 114 (87%) parents completed the questionnaire on feeding difficulties. Feeding difficulties were present in 61 (53.5%) of the 114 children. The most common feeding difficulties were regular meal refusals (26.9%), extended mealtimes (26.7%), and problems with gagging on textured foods (26.5%). Most children (40/61) had ≥2 reported feeding difficulties, and eight had ≥4. Children with feeding difficulties had higher rates of constipation and vomiting: 60.7% (37/61) vs. 35.8% (19/53), p = 0.008 and 63.9% (39/61) vs. 41.5% (22/53), p = 0.017, respectively. Logistic regression analysis demonstrated an association between having feeding difficulties, the age of the child, and the initial symptom score. Gender and the number of foods excluded in the elimination diet were not significantly associated with feeding difficulties. This study found that feeding difficulties are common in children with non-IgE-mediated gastrointestinal allergies, but there is a paucity of food allergy specific tools for establishing feeding difficulties, which requires further research in the long-term and consensus in the short term amongst healthcare professions as to which tool is the best for food allergic children
Análise citogenética em material de abortamento espontâneo Cytogenetic analysis of material from spontaneous abortion
OBJETIVO: Descrever as anormalidades cromossômicas em material de abortamento espontâneo. MÉTODOS: Realizou-se compilação retrospectiva da análise de cariótipo em lâmina corada com Banda G por microscopia óptica e em material de 428 produtos de abortamento encaminhados para estudo. RESULTADOS: Foram observados 145 resultados normais (33,9%) e 237 resultados anormais (55,4%). Em 46 amostras não houve crescimento celular (10,7%). As anormalidades numéricas foram as mais frequentes, destacando-se a trissomia do 16 (41 casos), a triplodia (27 casos), a monossomia do X (26 casos), a tetraploidia (13 casos) e a trissomia do 15 (13 casos). CONCLUSÃO: As alterações citogenéticas representam importante causa de perdas gestacionais e sua detecção auxilia o aconselhamento genético do casal. A trissomia do cromossomo 16 é a alteração mais frequentemente encontrada.<br>OBJECTIVE: To describe chromosomal abnormalities in spontaneous abortion material. METHODS: A retrospective compilation of karyotype analysis of slides stained with Band G was carried out by optical microscopy with materials of 428 abortion products referred for study. RESULTS: There were 145 normal results (33.9%) and 237 abnormal results (55.4%). In 46 samples there was no cell growth (10.7%). Numerical abnormalities were the most frequent, especially trisomy 16 (41 cases), triplodia (27 cases), monosomy X (26 cases), tetraploidy (13 cases) and trisomy 15 (13 cases). CONCLUSION: Cytogenetic alterations are an important cause of pregnancy loss and their detection helps the genetic counseling to the couple. Trisomy 16 is the most often found change