The methodology for developing a prospective meta-analysis in the family planning community

<p>Abstract</p> <p>Background</p> <p>Prospective meta-analysis (PMA) is a collaborative research design in which individual sites perform randomized controlled trials (RCTs) and pool the data for meta-analysis. Members of the PMA collaboration agree upon specific research interventions and outcome measures, ideally before initiation but at least prior to any individual trial publishing results. This allows for uniform reporting of primary and secondary outcomes. With this approach, heterogeneity among trials contributing data for the final meta-analysis is minimized while each site maintains the freedom to design a specific trial. This paper describes the process of creating a PMA collaboration to evaluate the impact of misoprostol on ease of intrauterine device (IUD) insertion in nulliparous women.</p> <p>Methods</p> <p>After the principal investigator developed a preliminary PMA protocol, he identified potential collaborating investigators at other sites. One site already had a trial underway and another site was in the planning stages of a trial meeting PMA requirements. Investigators at six sites joined the PMA collaborative. Each site committed to enroll subjects to meet a pre-determined total sample size. A final common research plan and site responsibilities were developed and agreed upon through email and face-to-face meetings. Each site committed to contribute individual patient data to the PMA collaboration, and these data will be analyzed and prepared as a multi-site publication. Individual sites retain the ability to analyze and publish their site's independent findings.</p> <p>Results</p> <p>All six sites have obtained Institutional Review Board approval and each has obtained individual funding to meet the needs of that site's study. Sites have shared resources including study protocols and consents to decrease costs and improve study flow. This PMA protocol is registered with the Cochrane Collaboration and data will be analyzed according to Cochrane standards for meta-analysis.</p> <p>Conclusions</p> <p>PMA is a novel research method that improves meta-analysis by including several study sites, establishing uniform reporting of specific outcomes, and yet allowing some independence on the part of individual sites with respect to the conduct of research. The inclusion of several sites increases statistical power to address important clinical questions. Compared to multi-center trials, PMA methodology encourages collaboration, aids in the development of new investigators, decreases study costs, and decreases time to publication.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00613366">NCT00613366</a>, <a href="http://www.clinicaltrials.gov/ct2/show/NCT00886834">NCT00886834</a>, <a href="http://www.clinicaltrials.gov/ct2/show/NCT01001897">NCT01001897</a>, <a href="http://www.clinicaltrials.gov/ct2/show/NCT01147497">NCT01147497</a> and <a href="http://www.clinicaltrials.gov/ct2/show/NCT01307111">NCT01307111</a></p

Influence of socioeconomic factors on pregnancy outcome in women with structural heart disease

OBJECTIVE: Cardiac disease is the leading cause of indirect maternal mortality. The aim of this study was to analyse to what extent socioeconomic factors influence the outcome of pregnancy in women with heart disease.  METHODS: The Registry of Pregnancy and Cardiac disease is a global prospective registry. For this analysis, countries that enrolled ≥10 patients were included. A combined cardiac endpoint included maternal cardiac death, arrhythmia requiring treatment, heart failure, thromboembolic event, aortic dissection, endocarditis, acute coronary syndrome, hospitalisation for cardiac reason or intervention. Associations between patient characteristics, country characteristics (income inequality expressed as Gini coefficient, health expenditure, schooling, gross domestic product, birth rate and hospital beds) and cardiac endpoints were checked in a three-level model (patient-centre-country).  RESULTS: A total of 30 countries enrolled 2924 patients from 89 centres. At least one endpoint occurred in 645 women (22.1%). Maternal age, New York Heart Association classification and modified WHO risk classification were associated with the combined endpoint and explained 37% of variance in outcome. Gini coefficient and country-specific birth rate explained an additional 4%. There were large differences between the individual countries, but the need for multilevel modelling to account for these differences disappeared after adjustment for patient characteristics, Gini and country-specific birth rate.  CONCLUSION: While there are definite interregional differences in pregnancy outcome in women with cardiac disease, these differences seem to be mainly driven by individual patient characteristics. Adjustment for country characteristics refined the results to a limited extent, but maternal condition seems to be the main determinant of outcome

Fetal cerebellar hemorrhage in a severely growth-restricted fetus: natural history and differential diagnosis from Dandy-Walker malformation

This is a report of an intracerebellar hemorrhage in a severely growth-restricted fetus with pathological Doppler findings of the fetal and uteroplacental circulations. The diagnosis was made sonographically at 22 weeks of gestation and the natural course of the hemorrhage was followed. Interestingly, the final sonographic appearance of the posterior fossa was quite similar to that of the classic form of Dandy-Walker malformation: absence of the vermis and an enlarged fourth ventricle. However, careful sonographic examination showed that the enlargement of the fourth ventricle was actually caused by a porencephalic cystic lesion of the left cerebellar lobe. Pathological examination revealed complete absence of the vermis and cerebellar hypoplasia. Copyright (C) 2003 ISUOG

Sonographic findings of fetuses with an empty renal fossa and normal amniotic fluid volume

Objective: To review the antenatal sonographic findings and postnatal follow-up of fetuses with empty renal fossa (ERF) and normal amniotic fluid volume. Methods: Sonographic examinations of 13,705 fetuses were retrospectively analyzed and all fetuses with at least one ERF and normal antenatal amniotic fluid volume were included in this study. Results: Forty cases with antenatal ERF were diagnosed. Prenatal diagnosis consisted of pelvic kidney (n = 24), unilateral renal agenesis (n = 13), horseshoe kidney (n = 2) and crossed fused renal ectopia (n = 1). The prevalence of ERF in the low-risk population approximated 3.2%. There was no serious renal complication during a mean follow-up period of 30 months except one case of crossed fused renal ectopia requiring hemodialysis. Conclusion: The underlying cause of ERF in the majority of cases with normal amniotic fluid volume is renal ectopia. Prenatal ultrasonography seems to be highly reliable in diagnosing these anomalies. Prognosis is favorable in the absence of additional extraurinary malformations. Copyright (C) 2004 S. Karger AG, Basel

Prenatal diagnosis and postnatal outcome of pelvic kidneys

Objective To assess the prevalence of pelvic kidneys during prenatal sonographic examinations in the second and third trimesters and to examine postnatal outcome

CAN THE CLASSICAL EUCHROMATIC VARIANTS OF 9q12/qh+ CAUSE RECURRENT ABORTIONS?

Can the classical euchromatic variants of 9q12/qh+ cause recurrent abortions?: Various heteromorphisms of the 9q heterochromatic area have been reported, and the 9q12/qh varient has been postulated to be more prevalent than initially perceived. Of note is that all probands are clinically normal. This paper documents two cases with a G-band within the 9q12h region and recurrent miscarriages. Patient 1 is a 22-year-old woman with a history of 2 miscarriages. Patient 2 is a 19-year-old woman with a history of 3 miscarriages. Chromosome analysis of the patients showed 46,XX,9q12h+. Thus, the existence of a G+ band in 9qh may not be a normal variant in humans. We suggest IVF and preimplantation genetic diagnosis in such patients

CAN THE CLASSICAL EUCHROMATIC VARIANTS OF 9q12/qh+ CAUSE RECURRENT ABORTIONS?

Can the classical euchromatic variants of 9q12/qh+ cause recurrent abortions?: Various heteromorphisms of the 9q heterochromatic area have been reported, and the 9q12/qh varient has been postulated to be more prevalent than initially perceived. Of note is that all probands are clinically normal. This paper documents two cases with a G-band within the 9q12h region and recurrent miscarriages. Patient 1 is a 22-year-old woman with a history of 2 miscarriages. Patient 2 is a 19-year-old woman with a history of 3 miscarriages. Chromosome analysis of the patients showed 46,XX,9q12h+. Thus, the existence of a G+ band in 9qh may not be a normal variant in humans. We suggest IVF and preimplantation genetic diagnosis in such patients