nan Kilby

Prognosis for the co‐twin following single‐twin death: a systematic review

Background  Following single‐twin death, the perinatal mortality and morbidity for the surviving co‐twin is increased but difficult to quantify. We present data on prognosis from a systematic review.

Mapping the theories of preeclampsia: the role of homocysteine.

OBJECTIVE: We conducted a systematic review to examine the hypothesized mechanism through which homocysteine could lead to preeclampsia. DATA SOURCES: We searched MEDLINE, EMBASE, BIOSIS, SciSearch, and bibliographies of primary and review articles, and we contacted experts. METHODS OF STUDY SELECTION: Of the 25 relevant primary articles, 8 studies measured total serum homocysteine concentrations before the clinical onset of preeclampsia (1,876 women), whereas 17 measured it afterward (1,773 women). Meta-analytic techniques were used to examine consistency, strength, temporality, dose-response, and plausibility of the disease mechanisms implicating folate, vitamin B6, vitamin B12, genetic polymorphisms, oxidative stress, and endothelial dysfunction in the pathway linking hyperhomocysteinemia to preeclampsia. TABULATION, INTEGRATION, AND RESULTS: Overall, there were higher serum homocysteine concentrations among pregnant women with preeclampsia than among those with uncomplicated pregnancies, but the results were heterogeneous (P = .12; I2 = 38.8%). Among studies with temporality, the size of association was smaller than that among those without (weighted mean difference 0.68 &mgr;mol/L versus 3.36 &mgr;mol/L; P < .006). There was no dose-response relationship between homocysteine concentration and severity of preeclampsia. The mechanisms underlying hyperhomocysteinemia (folate and vitamin B12 deficiency and genetic polymorphisms) were not found to be plausible, but markers of oxidative stress and endothelial dysfunction were higher in hyperhomocysteinemia. CONCLUSION: Homocysteine concentrations are slightly increased in normotensive pregnancies that later develop preeclampsia and are considerably increased once preeclampsia is established. However, because of a lack of consistency in data, dose-response relationship, and biologic plausibility, the observed association cannot be considered causal from the current literature.

Systematic review of the effectiveness of antenatal intervention for the treatment of congenital lower urinary tract obstruction

Please cite this paper as: Morris R, Malin G, Khan K, Kilby M. Systematic review of the effectiveness of antenatal intervention for the treatment of congenital lower urinary tract obstruction. BJOG 2010;117:382–390.

Antenatal ultrasound to predict postnatal renal function in congenital lower urinary tract obstruction: systematic review of test accuracy

Background  Congenital urinary tract obstruction can lead to perinatal mortality and morbidity. Assessing antenatal ultrasound features may help identify fetuses likely to suffer complications.

Accuracy of urinalysis dipstick techniques in predicting significant proteinuria in pregnancy.

OBJECTIVE: To estimate the accuracy of point-of-care dipstick urinalysis in predicting significant proteinuria in pregnancy. DATA SOURCES: Literature from 1970 to February 2002 was identified via 1) general bibliographic databases, that is, MEDLINE and EMBASE, 2) Cochrane Library and relevant specialist register of the Cochrane Collaboration, and 3) checking the reference lists of known primary and review articles. METHODS OF STUDY SELECTION: Studies were selected if the accuracy of dipstick urinalysis techniques in predicting total protein excretion was estimated compared with a reference standard (laboratory estimation of protein excretion). The tests included visually read color-change dipsticks and automated dipstick urinalysis. Study selection, quality assessment, and data abstraction were performed independently and in duplicate. TABULATION, INTEGRATION, AND RESULTS: Data from selected studies were abstracted as 2 × 2 tables comparing the test result with the reference standard. Test accuracy was expressed as likelihood ratios. Summary likelihood ratios were generated as measures of diagnostic accuracy to determine posttest probabilities. The electronic search produced 1,543 citations. After independent review of published articles, a total of 34 articles was obtained for further scrutiny, and 7 studies were considered eligible for inclusion in the review. The 6 studies evaluating visual dipstick urinalysis produced a pooled positive likelihood ratio of 3.48 (95% confidence interval 1.66, 7.27) and a pooled negative likelihood ratio of 0.6 (95% confidence interval 0.45, 0.8) for predicting 300 mg/24-hour proteinuria at the 1+ or greater threshold. CONCLUSION: The accuracy of dipstick urinalysis with a 1+ threshold in the prediction of significant proteinuria is poor and therefore of limited usefulness to the clinician. Accuracy may be improved at higher thresholds (greater than 1+ proteinuria), but available data are sparse and of poor methodological quality. Therefore, it is not possible to make meaningful inferences about accuracy at higher urine dipstick thresholds. There is an urgent need for research in this area of common obstetric practice.

Diagnostic accuracy of spot urinary protein and albumin to creatinine ratios for detection of significant proteinuria or adverse pregnancy outcome in patients with suspected pre-eclampsia: systematic review and meta-analysis.

Objective To determine the diagnostic accuracy of two “spot urine” tests for significant proteinuria or adverse pregnancy outcome in pregnant women with suspected pre-eclampsia. Design Systematic review and meta-analysis. Data sources Searches of electronic databases 1980 to January 2011, reference list checking, hand searching of journals, and contact with experts. Inclusion criteria Diagnostic studies, in pregnant women with hypertension, that compared the urinary spot protein to creatinine ratio or albumin to creatinine ratio with urinary protein excretion over 24 hours or adverse pregnancy outcome. Study characteristics, design, and methodological and reporting quality were objectively assessed. Data extraction Study results relating to diagnostic accuracy were extracted and synthesised using multivariate random effects meta-analysis methods. Results Twenty studies, testing 2978 women (pregnancies), were included. Thirteen studies examining protein to creatinine ratio for the detection of significant proteinuria were included in the multivariate analysis. Threshold values for protein to creatinine ratio ranged between 0.13 and 0.5, with estimates of sensitivity ranging from 0.65 to 0.89 and estimates of specificity from 0.63 to 0.87; the area under the summary receiver operating characteristics curve was 0.69. On average, across all studies, the optimum threshold (that optimises sensitivity and specificity combined) seems to be between 0.30 and 0.35 inclusive. However, no threshold gave a summary estimate above 80% for both sensitivity and specificity, and considerable heterogeneity existed in diagnostic accuracy across studies at most thresholds. No studies looked at protein to creatinine ratio and adverse pregnancy outcome. For albumin to creatinine ratio, meta-analysis was not possible. Results from a single study suggested that the most predictive result, for significant proteinuria, was with the DCA 2000 quantitative analyser (>2 mg/mmol) with a summary sensitivity of 0.94 (95% confidence interval 0.86 to 0.98) and a specificity of 0.94 (0.87 to 0.98). In a single study of adverse pregnancy outcome, results for perinatal death were a sensitivity of 0.82 (0.48 to 0.98) and a specificity of 0.59 (0.51 to 0.67). Conclusion The maternal “spot urine” estimate of protein to creatinine ratio shows promising diagnostic value for significant proteinuria in suspected pre-eclampsia. The existing evidence is not, however, sufficient to determine how protein to creatinine ratio should be used in clinical practice, owing to the heterogeneity in test accuracy and prevalence across studies. Insufficient evidence is available on the use of albumin to creatinine ratio in this area. Insufficient evidence exists for either test to predict adverse pregnancy outcome.

Congenital lower urinary tract obstruction: a population-based epidemiological study.

Please cite this paper as: Malin G, Tonks A, Morris R, Gardosi J, Kilby M. Congenital lower urinary tract obstruction: a population‐based epidemiological study. BJOG 2012;119:1455–1464.

Fetoscopic laser coagulation for severe twin‐to‐twin transfusion syndrome: factors influencing perinatal outcome, learning curve of the procedure and lessons for new centres

Please cite this paper as: Morris R, Selman T, Harbidge A, Martin W, Kilby M. Fetoscopic laser coagulation for severe twin‐to‐twin transfusion syndrome: factors influencing perinatal outcome, learning curve of the procedure and lessons for new centres. BJOG 2010;117:1350–1357.

The accuracy of cell-free fetal DNA-based non-invasive prenatal testing in singleton pregnancies: a systematic review and bivariate meta-analysis

Cell‐free fetal DNA (cffDNA) non‐invasive prenatal testing (NIPT) is rapidly expanding, and is being introduced at varying rates depending on country and condition.

Association and prediction of amniotic fluid measurements for adverse pregnancy outcome: systematic review and meta‐analysis

Measurements of amniotic fluid volume are used for pregnancy surveillance despite a lack of evidence for their predictive ability.