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Back schools for nonspecific low back pain: a systematic review within the framework of the Cochrane Collaboration Back Review Group.

STUDY DESIGN: A systematic review within the Cochrane Collaboration Back Review Group. OBJECTIVES: To assess the effectiveness of back schools for patients with nonspecific low back pain (LBP). SUMMARY OF BACKGROUND DATA: Since the introduction of the Swedish back school in 1969, back schools have frequently been used for treating patients with LBP. However, the content of back schools has changed and appears to vary widely today. METHODS: We searched the MEDLINE and EMBASE databases and the Cochrane Central Register of Controlled Trials to November 2004 for relevant trials reported in English, Dutch, French, or German. We also screened references from relevant reviews and included trials. Randomized controlled trials that reported on any type of back school for nonspecific LBP were included. Four reviewers, blinded to authors, institution, and journal, independently extracted the data and assessed the quality of the trials. We set the high-quality level, a priori, at a trial meeting six or more of 11 internal validity criteria. Because data were clinically and statistically too heterogeneous to perform a meta-analysis, we used a qualitative review (best evidence synthesis) to summarize the results. The evidence was classified into four levels (strong, moderate, limited, or no evidence), taking into account the methodologic quality of the studies. We also evaluated the clinical relevance of the studies. RESULTS: Nineteen randomized controlled trials (3,584 patients) were included in this updated review. Overall, the methodologic quality was low, with only six trials considered to be high-quality. It was not possible to perform relevant subgroup analyses for LBP with radiation versus LBP without radiation. The results indicate that there is moderate evidence suggesting that back schools have better short- and intermediate-term effects on pain and functional status than other treatments for patients with recurrent and chronic LBP. There is moderate evidence suggesting that back schools for chronic LBP in an occupational setting are more effective than other treatments and placebo or waiting list controls on pain, functional status, and return to work during short- and intermediate-term follow-up. In general, the clinical relevance of the studies was rated as insufficient. CONCLUSION: There is moderate evidence suggesting that back schools, in an occupational setting, reduce pain and improve function and return-to-work status, in the short- and intermediate-term, compared with exercises, manipulation, myofascial therapy, advice, placebo, or waiting list controls, for patients with chronic and recurrent LBP. However, future trials should improve methodologic quality and clinical relevance and evaluate the cost-effectiveness of back schools.

Humans↗

Psychological outcomes and risk perception after genetic testing and counselling in breast cancer: a systematic review.

OBJECTIVES: To conduct a systematic review of the effects of genetic counselling and testing for familial breast cancer on women's perception of risk and psychological morbidity. DATA SOURCES: MEDLINE, PsychLIT and EMBASE were searched for the period 1980-2001. STUDY SELECTION: Studies were eligible if published in a peer-reviewed journal in English, included women with a family history of breast cancer who underwent genetic counselling or testing and had either a randomised controlled trial or prospective design, with a pre- and at least one post-counselling assessment. DATA SYNTHESIS: As there was considerable heterogeneity in populations and measures, results were summarised rather than subjected to meta-analysis. RESULTS: Overall, genetic counselling and testing appear to produce psychological benefits and to improve accuracy of risk perception. Carriers of mutations in cancer predisposition genes did not experience significant increases in depression and anxiety after disclosure of their mutation status, while non-carriers experienced significant relief. Women who were tested but declined to learn their results seemed to be at greater risk of a worse psychological outcome. CONCLUSIONS: To date, the data on psychological outcomes after genetic counselling and testing are reassuring. However, few studies used a randomised trial design, limiting the strength of the conclusions. Follow-up to date has been short, and we know little about the long-term impact of testing on patient behaviours, perceptions and psychological state.

Adaptation, Psychological↗

Levetiracetam, oxcarbazepine, remacemide and zonisamide for drug resistant localization-related epilepsy: a systematic review.

OBJECTIVE: To undertake a systematic review and meta-analysis of placebo controlled add-on trials of levetiracetam, oxcarbazepine, remacemide and zonisamide for patients with drug resistant localization related epilepsy. METHODS: We searched Medline, The Cochrane Library and contacted the relevant pharmaceutical companies. Outcomes were 50% or greater reduction in seizure frequency and treatment withdrawal for any reason. Data were synthesised in a meta-analysis. The effect of dose was explored in regression models for levetiracetam and remacemide. RESULTS: We found four trials (1023 patients) of levetiracetam, two (961) of oxcarbazepine, two (388) of remacemide and three (499) of zonisamide. Ignoring dose, the relative risks (95% CI) for a 50% response were 3.78 (2.62-5.44), 2.51 (1.88-3.33), 1.59 (0.91-2.97) and 2.46 (1.61-3.79), respectively. There was evidence for increasing effect with increasing dose for levetiracetam, oxcarbazepine and remacemide. The relative risks for treatment withdrawal were 1.21 (0.88-1.66), 1.72 (1.35-2.18), 1.90 (1.00-3.60) and 1.64 (1.02-2.62), respectively. CONCLUSIONS: These data suggest a useful effect for levetiracetam, oxcarbazepine and zonisamide. Levetiracetam has the more favourable 'responder-withdrawal ratio' followed by zonisamide and oxcarbazepine.

Acetamides↗

Interventions to improve health outcomes for patients with low literacy. A systematic review.

OBJECTIVE: To perform a systematic review of interventions designed to improve health outcomes for persons with low literacy skills. DATA SOURCES: We searched MEDLINE, Cumulative Index to Nursing and Allied Health (CINAHL), Educational Resources Information Center (ERIC), Public Affairs Information Service (PAIS), Industrial and Labor Relations Review (ILLR), PsycInfo, and Ageline from 1980 to 2003. STUDY SELECTION: We included controlled and uncontrolled trials that measured literacy and examined the effect of interventions for people with low literacy on health outcomes, including health knowledge, health behaviors, use of health care resources, intermediate markers of disease status, and measures of morbidity or mortality. Two abstractors reviewed each study for inclusion. Disagreements were resolved by consensus among the research team. DATA EXTRACTION: One reviewer abstracted data from each article into an evidence table; the second reviewer checked each entry. Disagreements about information in evidence tables were resolved by team consensus. Both data extractors independently completed an 11-item quality scale for each article; scores were averaged to give a final measure of article quality. DATA SYNTHESIS: We identified 20 articles examining interventions designed to improve health among people with low literacy. The most common outcome studied was health knowledge; fewer studies examined health behaviors, intermediate markers, or measures of disease prevalence or severity. The effectiveness of interventions appeared mixed. Limitations in research quality and heterogeneity in outcome measures make drawing firm conclusions about effective strategies difficult. Only 5 articles examined the interaction between literacy level and the effect of the intervention; they also found mixed results. CONCLUSIONS: Several interventions have been developed to improve health for people with low literacy. Limitations in study design, interventions tested, and outcomes assessed make drawing conclusions about effectiveness difficult. Further research is required to understand better the types of interventions that are most effective and efficient for overcoming literacy-related barriers to good health.

Clinical Trials as Topic↗

Improving general medical care for persons with mental and addictive disorders: systematic review.

OBJECTIVE: To conduct a systematic review of studies of interventions designed to improve general medical care in persons with mental and addictive disorders. METHODS: Following Cochrane Collaboration guidelines, a comprehensive search through October 2005 was conducted in multiple bibliometric indexes using search terms related to primary medical care and mental health/addictive disorders. Two assessors independently extracted information on linkage, quality, outcomes and costs of care. RESULTS: Six randomized trials met the preestablished search criteria. The interventions spanned a continuum of approaches for improving treatment, ranging from on-site medical consultation, through team-based approaches, to models involving facilitated referrals to primary care. The studies demonstrated a substantial positive impact on linkage to and quality of medical care; there was evidence of health improvement and improved abstinence rates in patients with greater medical comorbidity. The three studies that assessed expenditures found the programs to be cost-neutral from a health-plan perspective. CONCLUSION: A small but growing body of research suggests that a range of models may hold potential for improving these patients' health and health care, at a relatively modest cost. Future work should continue to develop and test approaches to this problem that can be tailored to local system needs and capacities.

Behavior, Addictive↗

Decision aids for patients facing health treatment or screening decisions: systematic review.

OBJECTIVE: To conduct a systematic review of randomised trials of patient decision aids in improving decision making and outcomes. DESIGN: We included randomised trials of interventions providing structured, detailed, and specific information on treatment or screening options and outcomes to aid decision making. Two reviewers independently screened and extracted data on several evaluation criteria. Results were pooled by using weighted mean differences and relative risks. RESULTS: 17 studies met the inclusion criteria. Compared with the controls, decision aids produced higher knowledge scores (weighted mean difference=19/100, 95% confidence interval 14 to 25); lower decisional conflict scores (weighted mean difference=-0.3/5, -0.4 to -0.1); more active patient participation in decision making (relative risk = 2.27, 95% confidence interval 1. 3 to 4); and no differences in anxiety, satisfaction with decisions (weighted mean difference=0.6/100, -3 to 4), or satisfaction with the decision making process (2/100,-3 to 7). Decision aids had a variable effect on decisions. When complex decision aids were compared with simpler versions, they were better at reducing decisional conflict, improved knowledge marginally, but did not affect satisfaction. CONCLUSIONS: Decision aids improve knowledge, reduce decisional conflict, and stimulate patients to be more active in decision making without increasing their anxiety. Decision aids have little effect on satisfaction and a variable effect on decisions. The effects on outcomes of decisions (persistence with choice, quality of life) remain uncertain.

Choice Behavior↗

Improving patients' communication with doctors: a systematic review of intervention studies.

A systematic review of the literature examined intervention studies designed to increase patients' participation in medical consultations. Twenty-five papers describing twenty studies met the inclusion criteria. About half of the intervention studies were randomised placebo controlled experimental designs. The studies were predominantly conducted in outpatient or primary care settings, with 50% of the interventions presented in a written form. Overall, half of the interventions resulted in increased patient participation, with slightly more significant results found for bids for clarification than question-asking. However, of the 10 written interventions only two reported a significant increase in question-asking. Patient satisfaction was the most commonly measured outcome, but few significant improvements were found. However, there were significant improvements in other outcomes, including perceptions of control over health, preferences for an active role in health care, recall of information, adherence to recommendations, attendance, and clinical outcomes. Few studies examined the links between patient characteristics and the success of the interventions. Future research needs to establish which forms of intervention are most effective and practical, for which groups of patients.

Adult↗

Short-stay units and observation medicine: a systematic review.

OBJECTIVES: To conduct a systematic review of how short-stay observation units (SOUs) affect the efficiency of healthcare delivery and the quality of services provided. DATA SOURCES: MEDLINE, CINAHL, Best Evidence and The Cochrane Library were searched for the period 1 January 1960 to 31 July 2000. STUDY SELECTION: Studies were eligible if published in English and rated at National Health and Medical Research Council evidence levels I, II-1, II-2, or II-3; 12 comparative studies published between 1985 and 1998 met these criteria. DATA EXTRACTION: Data pertaining to clinical outcomes, length of stay, re-presentation rates, emergency department efficiency and costs of care were extracted and evaluated independently. DATA SYNTHESIS: As there was considerable heterogeneity in the patient populations and outcomes, results were summarised rather than subjected to meta-analysis. CONCLUSION: SOUs have the potential to increase patient satisfaction, reduce length of stay, improve the efficiency of emergency departments and improve cost effectiveness. However, SOUs have commonly been implemented alongside new clinical protocols, and it is not possible to distinguish the relative benefits of each. As demand increases, providing effective and cost-efficient care will become increasingly important. SOUs may help organisations that are attempting to streamline patient care while maintaining their quality of service delivery.

Delivery of Health Care↗

Videoconferencing in child and adolescent telepsychiatry: a systematic review of the literature.

A systematic review of child and adolescent telepsychiatry was conducted. It was based on a search of the electronic databases MEDLINE and PsycINFO covering the period 1966 to June 2003. Studies were selected for review if they concerned videoconferencing for patient care or consultation, evaluated a clinical service or education, or assessed satisfaction with videoconferences. Twenty-seven articles were identified that fulfilled the selection criteria. These comprised two reports of randomized controlled experiments, 10 of descriptive questionnaire studies or observational surveys, seven case studies and eight other reports. Only three of the studies presented some calculations of cost-effectiveness. When classified by 'Quality of Evidence' criteria, only two studies were in category I (the highest), one was in II-2 and the rest fell into category III (the lowest). Most studies of child and adolescent telepsychiatry examined satisfaction with videoconferencing or described programmes or care regimens. Videoconferencing seemed to improve the accessibility of services and served an educational function. Some papers also mentioned savings in time, costs and travel. Problems with non-verbal communication and the audiovisual quality of the videoconference were mentioned as drawbacks. Telepsychiatry therefore seems to offer several benefits, at least in sparsely populated regions. Well designed and properly controlled trials are required to evaluate the clinical value of this promising method in child psychiatry, where there is a constantly increasing need for services.

Adolescent↗

Multiple chemical sensitivities: A systematic review of provocation studies.

A systematic review of provocation studies of persons reporting multiple chemical sensitivities (MCS) was conducted from databases searched from inception to May 2006. Thirty-seven studies were identified, testing 784 persons reporting MCS, 547 control subjects, and 180 individuals of whom a subset were chemically sensitive. Blinding was inadequate in most studies. In 21 studies odors of chemicals were probably apparent; 19 of these reported positive responses to provocations among chemically sensitive individuals, and 1 study demonstrated that negative expectations were significantly associated with increased symptom reporting after provocations. Seven studies used chemicals at or below odor thresholds, and 6 failed to show consistent responses among sensitive individuals after active provocation. Six studies used forced-choice discrimination and demonstrated that chemically sensitive individuals were not better at detecting odor thresholds than nonsensitive participants. Three studies tested individuals by using nose clips/face masks and confirmed response, possibly mediated through eye exposure. Three studies used olfactory masking agents to conceal stimuli, and none of these found associations between provocations and response. We conclude that persons with MCS do react to chemical challenges; however, these responses occur when they can discern differences between active and sham substances, suggesting that the mechanism of action is not specific to the chemical itself and might be related to expectations and prior beliefs.

Databases as Topic↗

Influencing advance directive completion rates in non-terminally ill patients: a systematic review.

PURPOSE: To conduct a systematic review of educational advance care planning interventions directed at patients without terminal illness to determine their influence on the completion rate of advance directives (AD). MATERIALS AND METHODS: We searched MEDLINE; Cochrane Library, and reference lists of all pertinent retrieved articles for randomized trials (RCTs), restricted to English language and adults > or =18 years. Two investigators independently and in duplicate determined trial eligibility. We included published RCTs evaluating an educational intervention comprised of at least one of; written, audio, or video materials, or direct counseling, and if an outcome included AD completion rate. RESULTS: Nine RCTs (N=3,206) were included. Overall, methodologic quality and reporting transparency were poor. The median composite quality score was 5 (range, 0-10). The odds ratios for AD completion rates ranged from 0.41 to 106.0 across the trials (test of heterogeneity P <.001). The summary odds ratio for these educational interventions was 3.71 (95% C.I. 1.46, 9.40). Trials with greater methodologic rigor and reporting transparency produced a more conservative estimate of effect, 2.42 [0.96, 6.10] versus 28.69 [5.08, 162.06] for less rigorous and poorly reported trials (P =.013). CONCLUSIONS: Advance directive completion rates documenting patient preferences for end-of-life care may be increased by simple patient-directed educational interventions.

Adult↗

The effectiveness of family interventions in people with diabetes mellitus: a systematic review.

AIMS: To conduct a systematic review of reports of published literature to assess which family interventions are effective in improving diabetes-related outcomes in people with diabetes and family members (blood or non-blood relatives) residing in their homes. METHODS: We searched computerized bibliographic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, WOS, ERIC, Cochrane, CDP, and SocAbs) for randomized clinical trials published in any language that evaluated the effectiveness of family-based interventions with no age restriction. Only studies focused on interventions in young populations (< 18 years) and involving a parent were combined in a meta-analysis for glycated haemoglobin (GHb) using DerSimonian and Laird random effects model. Effect sizes for knowledge outcomes were estimated using the Cohen's d (standardized mean differences) formula. RESULTS: Our searches identified 19 randomized controlled trials. Positive effect sizes of family interventions on knowledge for five studies (N = 217) were demonstrated {0.94 [95% confidence interval (CI) 0.67, 1.82]}. A beneficial effect of interventions on GHb for eight studies (N = 505) was also observed using meta-analysis [-0.6 (95% CI -1.2, -0.1)]. CONCLUSIONS: Evidence suggests that family interventions in family or household members of people with diabetes may be effective in improving diabetes-related knowledge and glycaemic control.

Adult↗

Deflazacort for the treatment of Duchenne Dystrophy: a systematic review.

BACKGROUND: To complete a systematic review and meta-analysis based on the clinical question: Is Deflazacort (DFZ), a prednisolone derivative, an effective therapy for improving strength, with acceptable side effects, in children with Duchenne Dystrophy (DD)? METHODS: MEDLINE, EMBASE, Current Contents, Dissertation Abstracts, Health Star, PsychINFO and Cochrane, were searched using the following inclusion criteria: 1) A randomized controlled trial comparing DFZ with placebo or another therapy; 2) Male participants age 2-18 years with DD; 3) Outcomes of (a) any form of strength or functional testing, or (b) any form of side effect. RESULTS: Fifteen studies of potential relevance were identified, with five meeting the inclusion criteria. These five studies included 291 children and were published in English language journals between 1994 and 2000. Two studies compared DFZ versus placebo, two studies compared DFZ with prednisone and one study had both placebo and prednisone comparisions. Two large trials were identified that have not been published in article format. Due to the heterogeneity in outcome measures and the inconsistent reporting of summary statistics a meta-analytic approach could not be taken. CONCLUSIONS: Examining individual studies it appears that DFZ improves strength and functional outcomes compared to placebo, but it remains unclear if it has a benefit over prednisone on similar outcomes. Two trials found that DFZ causes less weight gain than prednisone.

Adolescent↗

Can noninvasive imaging accurately depict intracranial aneurysms? A systematic review.

PURPOSE: To perform a systematic review to determine the accuracy of computed tomographic (CT) angiography, magnetic resonance (MR) angiography, and transcranial Doppler ultrasonography (US) in depicting intracranial aneurysms. MATERIALS AND METHODS: A 1988-1998 literature search for studies with 10 or more subjects in which noninvasive imaging was compared with angiography was undertaken. Studies meeting initial criteria were evaluated by using intrinsically weighted standardized assessment to determine suitability for inclusion. Studies scoring greater than 50% were included. RESULTS: Of 103 studies that met initial criteria, 38 scored greater than 50%. CT angiography and MR angiography had accuracies per aneurysm of 89% (95% CI: 87%, 91%) and 90% (95% CI: 87%, 92%), respectively. For US, data were scanty and accuracy was lower, although the CIs overlapped those of CT angiography and MR angiography. Sensitivity was greater for detection of aneurysms larger than 3 mm than for detection of aneurysms 3 mm or smaller-for CT angiography, 96% (95% CI: 94%, 98%) versus 61% (95% CI: 51%, 70%), and for MR angiography, 94% (95% CI: 90%, 97%) versus 38% (95% CI: 25%, 53%). Diagnostic accuracy was similar for anterior and posterior circulation aneurysms. CONCLUSION: CT angiography and MR angiography depicted aneurysms with an accuracy of about 90%. Most studies were performed in populations with high aneurysm prevalence, which may have introduced bias toward noninvasive examinations.

Cerebral Angiography↗

The epidemiology and natural history of Crohn's disease in population-based patient cohorts from North America: a systematic review.

AIM: To quantify, through systematic review, the epidemiology and natural history of Crohn's disease in North America. METHODS: The selected articles contained: (i) population-based samples of patients followed from the time of diagnosis; and (ii) objective diagnostic criteria for disease. Studies on the natural history of Crohn's disease also contained sufficient follow-up. DATA COLLECTION AND ANALYSIS: For prevalence studies, data on the incidence, prevalence, gender and age at diagnosis were extracted. For natural history studies, data on the disease activity, use of medications and surgery were extracted. MAIN RESULTS: The prevalence of Crohn's disease in North America ranges from 26.0 to 198.5 cases per 100,000 persons. The incidence rates range from 3.1 to 14.6 cases per 100,000 person-years. Most patients have a chronic intermittent disease course, while 13% have an unremitting disease course and 10% have a prolonged remission. Less than half require corticosteroids at any point. During any given year, approximately 10% are treated with corticosteroids and 30% are treated with 5-aminosalicylates. Up to 57% of patients require at least one surgical resection. CONCLUSIONS: Between 400,000 and 600,000 patients in North America have Crohn's disease, and the natural history is marked by frequent exacerbations requiring treatment with corticosteroids, 5-aminosalicylate products and surgery.

Adolescent↗

Transrenal fixation of aortic stent-grafts: short- to midterm effects on renal function--a systematic review.

PURPOSE: To perform a systematic review of the short- to midterm effects of transrenal fixation of aortic stent-grafts on renal function in patients with abdominal aortic aneurysms. MATERIALS AND METHODS: A search of the PubMed, MEDLINE, and EMBASE databases for English-language literature was performed. Studies with at least 10 patients were included for data analysis. Only studies on transrenal fixation of aortic stent-grafts that included follow-up results for renal function were included. A log-linear model was used for meta-analysis to compare transrenal fixation with infrarenal fixation. RESULTS: Twenty-two studies met the inclusion criteria. Because two studies analyzed the same group of patients, one was excluded, for a total of 21 studies. Comparisons between transrenal fixation and infrarenal fixation were found in seven studies. For transrenal versus infrarenal fixation, the combined odds ratio, 95% confidence interval, and P value were found to be statistically significant with respect to postprocedural renal infarction only (combined odds ratio, 5.189; 95% confidence interval: 3.198, 8.420; P < .001). No significant difference was found between transrenal and infrarenal fixation with respect to renal dysfunction, renal artery occlusion, or endoleaks (P > .05). CONCLUSION: Transrenal fixation of aortic stent-grafts seems to be a relatively safe alternative compared with infrarenal fixation in terms of short- to midterm follow-up. Postprocedural renal infarction, however, was significantly higher for transrenal fixation.

Aged↗

Functional treatments for acute ruptures of the lateral ankle ligament: a systematic review.

Our aim with this systematic review was to assess the effectiveness of various functional treatments for acute ruptures of the lateral ankle ligament in adults. We performed an electronic database search using MEDLINE, EMBASE, COCHRANE CONTROLLED TRIAL REGISTER and CURRENT CONTENTS. We evaluated randomized clinical trials describing skeletally mature subjects with an acute rupture of the lateral ankle ligament and compared functional treatments for inclusion in this study. 9 trials met our inclusion criteria. Two reviewers independently assessed the quality of these trials and extracted relevant data on treatment outcome. Where appropriate, results of comparable studies were pooled. Individual and pooled statistics are reported as relative risks (RR) for dichotomous outcome and (weighted) mean differences (W)MD) for continuous outcome measures with 95% confidence intervals (95% CI). Heterogeneity between the trials was tested using a standard chi-square test. Persistent swelling at short-term follow-up was less with lace-up ankle support than with semi-rigid ankle support (RR 4.2 95% CI 1.3-14), an elastic bandage (RR 5.5; 95% CI 1.7-18) and tape (RR 4.1; 95% CI 1.2-14). A semi-rigid ankle support required a shorter period for return to work than an elastic bandage (WMD 4.2; 95% CI 2.4-6.1) (p = 0.7). One trial reported better results for subjective instability using the semi-rigid ankle support than the elastic bandage (RR 8.0; 95% CI 1.0-62). Treatment with tape resulted in more complications, mostly skin problems, than that with an elastic bandage (RR 0.1; 95% CI 0.0-0.8). We found no other statistically significant differences. We conclude that an elastic bandage is a less effective functional treatment. Lace-up supports seem better, but the data are insufficient as a basis for definite conclusions.

Bandages↗

Immunogenetic determinants of preeclampsia and related pregnancy disorders: a systematic review.

OBJECTIVE: We sought to systematically review the impact of immunogenetic factors, specifically human leukocyte antigen (HLA) allele frequencies, maternal homozygosity, couple sharing, and maternal-fetal sharing, on the risk of preeclampsia and intrauterine growth restriction. DATA SOURCES: A computerized search of PubMed databases from 1975 to 2003 was performed with the terms "preeclampsia," "eclampsia," "intrauterine growth restriction," and "human leukocyte antigens" and limited to studies of human subjects in English. No restrictions were placed on study design. All bibliographies were cross-referenced to identify additional pertinent studies. METHODS OF STUDY SELECTION: Titles and abstracts were reviewed carefully. Observational and basic science research studies were selected if their main objective was to assess the relationship of any aspect of HLA genotypes with preeclampsia and related disorders of pregnancy. TABULATION, INTEGRATION, AND RESULTS: Data were abstracted and tabulated from 22 original research studies. Meta-analytic techniques were not performed owing to variations in disease and exposure definitions as well as research methodologies. Studies that examined maternal, paternal, and fetal HLA allele frequencies, maternal homozygosity, and couple sharing yielded inconsistent results. Although the cumulative evidence points to the HLA-DR locus (particularly DR4) as a correlate of preeclampsia, it remains unclear whether any specific HLA allele, haplotype, or susceptibility gene in linkage disequilibrium with the HLA region is responsible. Although genetic evidence is suggestive of gene-gene interaction between mother and fetus, few studies have evaluated the influence of maternal-fetal HLA sharing. CONCLUSION: In the early 1990s, HLA genotypes were dismissed as possible etiologic factors for preeclampsia, based on studies that are heterogeneous with respect to study design, outcome, and exposure assessment. Many of these studies did not take into account the interactions between maternal, paternal, and infant genotypes. Thus, adequately powered studies designed specifically to assess the effect of maternal-fetal HLA sharing on risk of preeclampsia are needed.

Adult↗