13 research outputs found
A homozygous variant in growth and differentiation factor 2(GDF2)may cause lymphatic dysplasia with hydrothorax and nonimmune hydrops fetalis
The etiology of nonimmune hydrops fetalis is extensive and includes genetic disorders. We describe a term-born female neonate with late onset extensive nonimmune hydrops, that is, polyhydramnios, edema, and congenital bilateral chylothorax. This newborn was successfully treated with repetitive thoracocentesis, total parenteral feeding, octreotide intravenously and finally surgical pleurodesis and corticosteroids. A genetic cause seemed plausible as the maternal history revealed a fatal nonimmune hydrops fetalis. A homozygous truncating variant inGDF2(c.451C>T, p.(Arg151*)) was detected with exome sequencing. Genetic analysis of tissue obtained from the deceased fetal sibling revealed the same homozygous variant. The parents and two healthy siblings were heterozygous for theGDF2variant. Skin and lung biopsies in the index patient, as well as the revised lung biopsy of the deceased fetal sibling, showed lymphatic dysplasia and lymphangiectasia. To the best of our knowledge, this is the first report of an association between a homozygous variant inGDF2with lymphatic dysplasia, hydrothorax and nonimmune hydrops fetalis
STRIDER (Sildenafil TheRapy in dismal prognosis early onset fetal growth restriction): An international consortium of randomised placebo-controlled trials
Background: Severe, early-onset fetal growth restriction due to placental insufficiency is associated with a high risk of perinatal mortality and morbidity with long-lasting sequelae. Placental insufficiency is the result of abnormal formation and function of the placenta with inadequate remodelling of the maternal spiral arteries. There is currently no effective therapy available. Some evidence suggests sildenafil citrate may improve uteroplacental blood flow, fetal growth, and meaningful infant outcomes. The objective of the Sildenafil TheRapy In Dismal prognosis Early onset fetal growth Restriction (STRIDER) collaboration is to evaluate the effectiveness of sildenafil versus placebo in achieving healthy perinatal survival through the conduct of randomised clinical trials and systematic review including individual patient data meta-analysis. Methods: Five national/bi-national multicentre randomised placebo-controlled trials have been launched. Women with a singleton pregnancy between 18 and 30 weeks with severe fetal growth restriction of likely placental origin, and where the likelihood of perinatal death/severe morbidity is estimated to be significant are included. Participants will receive either sildenafil 25 mg or matching placebo tablets orally three times daily from recruitment to 32 weeks gestation. Discussion: The STRIDER trials were conceived and designed through international collaboration. Although the individual trials have different primary outcomes for reasons of sample size and feasibility, all trials will collect a standard set of outcomes including survival without severe neonatal morbidity at time of hospital discharge. This is a summary of all the STRIDER trial protocols and provides an example of a prospectively planned international clinical research collaboration. All five individual trials will contribute to a pre-planned systematic review of the topic including individual patient data meta-analysis
Serum screening with Down's syndrome markers to predict pre-eclampsia and small for gestational age: Systematic review and meta-analysis
<p>Abstract</p> <p>Background</p> <p>Reliable antenatal identification of pre-eclampsia and small for gestational age is crucial to judicious allocation of monitoring resources and use of preventative treatment with the prospect of improving maternal/perinatal outcome. The purpose of this systematic review was to determine the accuracy of five serum analytes used in Down's serum screening for prediction of pre-eclampsia and/or small for gestational age.</p> <p>Methods</p> <p>The data sources included Medline, Embase, Cochrane library, Medion (inception to February 2007), hand searching of relevant journals, reference list checking of included articles, contact with experts. Two reviewers independently selected the articles in which the accuracy of an analyte used in Downs's serum screening before the 25<sup>th </sup>gestational week was associated with the occurrence of pre-eclampsia and/or small for gestational age without language restrictions. Two authors independently extracted data on study characteristics, quality and results.</p> <p>Results</p> <p>Five serum screening markers were evaluated. 44 studies, testing 169,637 pregnant women (4376 pre-eclampsia cases) and 86 studies, testing 382,005 women (20,339 fetal growth restriction cases) met the selection criteria. The results showed low predictive accuracy overall. For pre-eclampsia the best predictor was inhibin A>2.79MoM positive likelihood ratio 19.52 (8.33,45.79) and negative likelihood ratio 0.30 (0.13,0.68) (single study). For small for gestational age it was AFP>2.0MoM to predict birth weight < 10<sup>th </sup>centile with birth < 37 weeks positive likelihood ratio 27.96 (8.02,97.48) and negative likelihood ratio 0.78 (0.55,1.11) (single study). A potential clinical application using aspirin as a treatment is given as an example.</p> <p>There were methodological and reporting limitations in the included studies thus studies were heterogeneous giving pooled results with wide confidence intervals.</p> <p>Conclusion</p> <p>Down's serum screening analytes have low predictive accuracy for pre-eclampsia and small for gestational age. They may be a useful means of risk assessment or of use in prediction when combined with other tests.</p
The relation between serum markers in the second trimester and placental pathology. A study on extremely small for gestational age fetuses
Objectives To examine whether in women who are delivered of an extremely small for gestational age infant, raised levels of second trimester maternal serum alpha-fetoprotein (MSAFP) or human chorionic gonadotrophin (MShCG) levels are related to the presence of placental pathology detected at birth. Design Retrospective cross-sectional study. Setting Department of Obstetrics and Gynaecology, Antenatal Diagnosis Unit, Groningen University Hospital, The Netherlands. Participants Eighty-four women who were delivered of an extremely SGA infant (<2.3rd centile) in whom the MSAFP and the MShCG levels were known and placental pathology reports were available (study group), and 8692 women in whom the MSAFP and MShCG levels were known and the pregnancy outcome was normal (control group). Pregnancies with congenital anomalies were excluded. Analyte levels were expressed in multiples of the median (MoM) for gestational age. Statistical analysis between groups was performed by ANOVA, after logarithmic transformation of the MoMs, to normalise their distribution. Main outcome measures 1. The means of the MSAFP and MShCG concentrations in the study group with and without placental lesions were compared with those in the control population. 2. The means of the MSAFP and MShCG levels in the study group with placental lesions were compared with those in the study group without placental lesions. Results 1. Comparison of study groups with controls: in the study group without placental lesions, the mean log MSAFP MoM (0.062), as well as the mean log MShCG MoM (-0.033), was not significantly different (P = 0.11 and P = 0.68, respectively) from the mean analyte levels in the control population (0.002 and 0.006, respectively). The mean logs of these analytes in the study group with placental lesions (0.162 and 0.129, respectively) were significantly higher compared with the MSAFP and MShCG levels in the control population (P <0.001 for both analytes). 2. Comparison of study groups with each other: the mean log of the MSAFP level of 0.162 in the group with placental lesions was significantly different from the mean of 0.062 of the study group without placental lesions (P <0.025). The higher mean log MShCG MoM of 0.129 in the group with placental lesions was significantly different from the mean log MShCG MoM of -0.033 in the study group without placental lesions (P <0.025). Conclusions Raised levels of second trimester MSAFP and MShCG in women who are subsequently delivered of an extremely small for gestational age infant are related to the presence of pathological changes in the placenta, detectable at birth. It is speculated that these placental pathological changes, which frequently accompany small for gestational age pregnancies, have their origin in the second trimester, when the normal physiological changes of the placenta occur
Prediction of cesarean section risk in women with gestational hypertension or mild preeclampsia at term
Abstract not availableKarin van der Tuuk, Maria G. van Pampus, Corine M. Koopmans, Jan G. Aarnoudse, Paul P. van den Berg, Johannes J. van Beek, Frans J.A. Copraij, Gunilla Kleiverda, Martina Porath, Robbert J.P. Rijnders, Paulien C.M. van der Salm, Leonard P. Morssink, Rob H. Stigter, Ben W.J. Mol, Henk Groen, for the HYPITAT study grou
Word catheter and marsupialisation in women with a cyst or abscess of the Bartholin gland (WoMan-trial):A randomised clinical trial
Objective To compare recurrence of a cyst or abscess of the Bartholin gland after surgical treatment using a Word catheter or marsupialisation. Design Multicentre, open-label, randomised controlled trial. Setting Eighteen hospitals in the Netherlands and one hospital in England. Population Women with a symptomatic cyst or abscess of the Bartholin gland. Methods Women were randomised to treatment with Word catheter or marsupialisation. Main outcome measures The primary outcome was recurrence of the cyst or abscess within 1 year of treatment. The secondary outcomes included pain during and after treatment (measured on a 10-point scale), use of analgesics, and time from diagnosis to treatment. Analysis was by intention-to-treat. To assess whether marsupialisation would reduce the recurrence rate by 5%(from 20 to 15%) we needed to include 160 women (alpha error 0.05, beta error 0.2). Results One hundred and sixty-one women were randomly allocated to treatment by Word catheter (n = 82) or marsupialisation (n = 79) between August 2010 and May 2014. Baseline characteristics were comparable. Recurrence occurred in 10 women (12%) allocated to Word catheter versus eight women (10%) allocated to marsupialisation: relative risk (RR) 1.1, 95% confidence interval (CI) 0.64-1.91; P = 0.70. Pain scores after treatment were also comparable. In the first 24 hours after treatment, 33% used analgesics in the Word catheter group versus 74% in the marsupialisation group (P <0.001). Time from diagnosis to treatment was 1 hour for placement of Word catheter versus 4 hours for marsupialisation (P = 0.001). Conclusions In women with an abscess or cyst of the Bartholin gland, treatment with Word catheter and marsupialisation results in comparable recurrence rates