A core outcome set for trials in miscarriage management and prevention: an international consensus development study.

OBJECTIVE: To develop core outcome sets (COS) for miscarriage management and prevention. DESIGN: Modified Delphi survey combined with a consensus development meeting. SETTING: International. POPULATION: Stakeholder groups included healthcare providers, international experts, researchers, charities and couples with lived experience of miscarriage from 15 countries: 129 stakeholders for miscarriage management and 437 for miscarriage prevention. METHODS: Modified Delphi method and modified nominal group technique. RESULTS: The final COS for miscarriage management comprises six outcomes: efficacy of treatment, heavy vaginal bleeding, pelvic infection, maternal death, treatment or procedure-related complications, and patient satisfaction. The final COS for miscarriage prevention comprises 12 outcomes: pregnancy loss <24 weeks' gestation, live birth, gestation at birth, pre-term birth, congenital abnormalities, fetal growth restriction, maternal (antenatal) complications, compliance with intervention, patient satisfaction, maternal hospitalisation, neonatal or infant hospitalisation, and neonatal or infant death. Other outcomes identified as important were mental health-related outcomes, future fertility and health economic outcomes. CONCLUSIONS: This study has developed two core outcome sets, through robust methodology, that should be implemented across future randomised trials and systematic reviews in miscarriage management and prevention. This work will help to standardise outcome selection, collection and reporting, and improve the quality and safety of future studies in miscarriage

Longer pregnancy and slower fetal development in women with latent "asymptomatic" toxoplasmosis

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to confirm that women with latent toxoplasmosis have developmentally younger fetuses at estimated pregnancy week 16 and to test four exclusive hypotheses that could explain the observed data.</p> <p>Methods</p> <p>In the present retrospective cohort study we analysed by the GLM (general linear model) method data from 730 <it>Toxoplasma</it>-free and 185 <it>Toxoplasma</it>-infected pregnant women.</p> <p>Results</p> <p>At pregnancy week 16 estimated from the date of the last menstruation, the mothers with latent toxoplasmosis had developmentally younger fetuses based on ultrasound scan (<it>P </it>= 0.014). Pregnancy of <it>Toxoplasma</it>-positive compared to <it>Toxoplasma</it>-negative women was by about 1.3 days longer, as estimated both from the date of the last menstruation (<it>P </it>= 0.015) and by ultrasonography (<it>P </it>= 0.025).</p> <p>Conclusion</p> <p>The most parsimonious explanation for the observed data is retarded fetal growth during the first weeks of pregnancy in <it>Toxoplasma</it>-positive women. The phenomenon was only detectable in multiparous women, suggesting that the immune system may play some role in it.</p

Polymorphisms in immunoregulatory genes and the risk of histologic chorioamnionitis in Caucasoid women: a case control study

BACKGROUND: Chorioamnionitis is a common underlying cause of preterm birth (PTB). It is hypothesised that polymorphisms in immunoregulatory genes influence the host response to infection and subsequent preterm birth. The relationship between histologic chorioamnionitis and 22 single nucleotide polymorphisms in 11 immunoregulatory genes was examined in a case-control study. METHODS: Placentas of 181 Caucasoid women with spontaneous PTB prior to 35 weeks were examined for histologic chorioamnionitis. Polymorphisms in genes IL1A, IL1B, IL1RN, IL1R1, tumour necrosis factor (TNF), IL4, IL6, IL10, transforming growth factor beta-1 (TGFB1), Fas (TNFRSF6), and mannose-binding lectin (MBL2) were genotyped by polymerase chain reaction and sequence specific primers. Multivariable logistic regression including demographic and genetic variables and Kaplan-Meier survival analyses of genotype frequencies and pregnancy outcome were performed. RESULTS: Sixty-nine (34%) women had histologic evidence of acute chorioamnionitis. Carriage of the IL10-1082A/-819T/592A (ATA) haplotype [Multivariable Odds ratio (MOR) 1.9, P = 0.05] and MBL2 codon 54Asp allele (MOR 2.0, P = 0.04), were positively associated with chorioamnionitis, while the TNFRSF6-1377A/-670G (AG) haplotype (MOR 0.4, P = 0.03) and homozygosity for TGFB1-800G/509T (GT) haplotype (MOR 0.2, P = 0.04) were negatively associated. CONCLUSION: These findings demonstrate that polymorphisms in immunoregulatory genes IL10, MBL2, TNFRSF6 and TGFB1 may influence susceptibility to chorioamnionitis

Self-recognition of the endothelium enables regulatory T-cell trafficking and defines the kinetics of immune regulation

This study was supported by the British Heart Foundation (PG 09/002/ 2642). AJR is funded by King’s College London British Heart Foundation Centre of Excellence and EI was supported by the Department of Health via National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s and St Tomas’ NHF Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. BG was supported by a British Heart Foundation studentship (FS/10/009/28166) and DC by an Arthritis Research UK Fellowship (18103)

Reliability of recurrent pregnancy loss diagnosis coding in the Swedish National Patient Register: a validation study

Emma Rasmark Roepke,1 Ole Bjarne Christiansen,2 Stefan R Hansson11Department of Obstetrics and Gynecology, Institute of Clinical Sciences Lund, Sk&aring;ne University Hospital, Lund University, Lund, Sweden; 2Department of Obstetrics and Gynecology, Aalborg University Hospital, Clinical Institute at Aalborg University, Aalborg, DenmarkBackground: The Swedish National Patient Registry (NPR) is a nationwide registry that is used extensively for epidemiological research. Using the NPR, we recently found a recurrent pregnancy loss (RPL) incidence of 650/100,000 (0.65%) pregnant women in Sweden. It is of great importance that the quality of the coding is good and reliable in order to use NPR data for research. To specifically study RPL in Sweden, a general validation of this diagnosis in the NPR is needed.Objective: To validate the diagnosis of RPL, defined as &ge;3 consecutive miscarriages before 22 gestational weeks, recorded in the NPR and assess how registered miscarriages were verified clinically (ultrasound or urine/serum hCG) by reviewing the medical records.Materials and methods: In a cohort of 6,852 women diagnosed with RPL in Sweden, during 2003&ndash;2012, a total of 238 complete medical records from 38 hospitals were reviewed. A power calculation estimated that 228 medical records had to be reviewed for a positive predictive value (PPV) of 85% (95% CI) with a power of 90%. The ICD-10 diagnoses used for RPL were N96.9 and O26.2.Results: The diagnosis of RPL was confirmed in 202 out of 238 medical records resulting in a PPV of 85% (95% CI 78&ndash;89%) out of which 59% were verified with ultrasound whereas 35% were verified only by urine/serum hCG.Conclusion: The Swedish NPR is a valuable tool for epidemiological research. We found a high PPV of RPL in the NPR, supporting the use of these data for future research.Keywords: abortius habitualis, recurrent pregnancy loss, validation study, registries, epidemiolog

Validation of second trimester miscarriages and spontaneous deliveries [Corrigendum]

Sneider K, Langhoff-Roos J, Sundtoft IB, Christiansen OB. Clin Epidemiol. 2015;7:517&ndash;527.&nbsp;The authors have advised that a number of errors were made in the data of some of the tables.&nbsp;Page 521, Table 3, there were some errors in the data within the &ldquo;Multiple pregnancies&rdquo; and &ldquo;Major fetal anomaly&rdquo; rows.The correct Table 3 is as follows: &nbsp;Read the original articl

Validation of second trimester miscarriages and spontaneous deliveries

Kirstine Sneider,1 Jens Langhoff-Roos,2 Iben Blaabjerg Sundtoft,3 Ole Bjarne Christiansen4,5 1Department of Clinical Research, Vendsyssel Hospital, Hj&oslash;rring, 2Department of Obstetrics, Rigshospitalet, University of Copenhagen, Copenhagen, 3Department of Obstetrics and Gynecology, Aarhus University Hospital, Aarhus, 4Department of Obstetrics and Gynecology, Aalborg University Hospital, Aalborg, 5The Fertility Clinic, University Hospital, Copenhagen, Denmark Objective: To validate the diagnosis of second trimester miscarriages/deliveries (16+0 weeks to 27+6 weeks of gestation) recorded as miscarriages in the Danish National Patient Registry or spontaneous deliveries in the Danish Medical Birth Registry, and asses the validity of risk factors, pregnancy complications, and cerclage by review of medical records. Materials and methods: In a cohort of 2,358 women with a second trimester miscarriage/delivery in first pregnancy and a subsequent delivery during 1997&ndash;2012, we reviewed a representative sample of 682 medical records. We searched for clinically important information and calculated positive predictive values of the registry diagnoses stratified by type of registry, as well as sensitivity, specificity, positive predictive value, and kappa coefficients of risk factors, pregnancy complications, and cerclage. Results: Miscarriage/spontaneous delivery in the second trimester was confirmed in 621/682 patients (91.1%). Pregnancy complications in second trimester miscarriages were underreported, resulting in low sensitivities and poor to moderate agreements between records and registries. There was a good agreement (kappa &gt;0.6) between medical records and the registries regarding risk factors and cerclage. The diagnosis of cervical insufficiency had &ldquo;moderate&rdquo; kappa values for both miscarriages and deliveries (0.55 and 0.57). Conclusion: Spontaneous second trimester deliveries and miscarriages recorded in the registers were confirmed by medical records in 91%, but register-based information on pregnancy complications need to be improved. We recommend that all pregnancies ending spontaneously beyond the first trimester are included in the national birth registry and described by appropriate variables. Keywords: second trimester, miscarriage, preterm birth, prematurity, registries, reproducibility of results, cerclage, cervical insufficienc