Rk Morris

Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis

Background: Alterations in waveforms in the uterine artery are associated with the development of pre-eclampsia and intrauterine growth restriction. We investigated the predictive accuracy of all uterine artery Doppler indices for both conditions in the first and second trimesters. Methods: We identified relevant studies through searches of MEDLINE, EMBASE, the Cochrane Library and Medion databases (all records to April 2006) and by checking bibliographies of identified studies and consulting with experts. Four of us independently selected studies, extracted data and assessed study validity. We performed a bivariable meta-analysis of sensitivity and specificity and calculated likelihood ratios. Results: We identified 74 studies of pre-eclampsia (total 79 547 patients) and 61 studies of intrauterine growth restriction (total 41 131 patients). Uterine artery Doppler ultrasonography provided a more accurate prediction when performed in the second trimester than in the first-trimester. Most Doppler indices had poor predictive characteristics, but this varied with patient risk and outcome severity. An increased pulsatility index with notching was the best predictor of pre-eclampsia (positive likelihood ratio 21.0 among high-risk patients and 7.5 among low-risk patients). It was also the best predictor of overall (positive likelihood ratio 9.1) and severe (positive likelihood ratio 14.6) intrauterine growth restriction among low-risk patients. Interpretation: Abnormal uterine artery waveforms are a better predictor of pre-eclampsia than of intrauterine growth restriction. A pulsatility index, alone or combined with notching, is the most predictive Doppler index. These indices should be used in clinical practice. Future research should also concentrate on combining uterine artery Doppler ultrasonography with other tests.

Strength of association between umbilical cord pH and perinatal and long term outcomes: systematic review and meta-analysis

Objective To evaluate the association between umbilical cord pH at birth and long term outcomes. Design Systematic review and meta-analysis. Data sources Medline (1966-August 2008), Embase (1980-August 2008), the Cochrane Library (2008 issue 8), and Medion, without language restrictions; reference lists of selected articles; and contact with authors. Study selection Studies in which cord pH at birth was compared with any neonatal or long term outcome. Cohort and case-control designs were included. Results 51 articles totalling 481 753 infants met the selection criteria. Studies varied in design, quality, outcome definition, and results. Meta-analysis carried out within predefined groups showed that low arterial cord pH was significantly associated with neonatal mortality (odds ratio 16.9, 95% confidence interval 9.7 to 29.5, I2=0%), hypoxic ischaemic encephalopathy (13.8, 6.6 to 28.9, I2=0%), intraventricular haemorrhage or periventricular leucomalacia (2.9, 2.1 to 4.1, I2=0%), and cerebral palsy (2.3, 1.3 to 4.2, I2=0%). Conclusions Low arterial cord pH showed strong, consistent, and temporal associations with clinically important neonatal outcomes that are biologically plausible. These data can be used to inform clinical management and justify the use of arterial cord pH as an important outcome measure alongside neonatal morbidity and mortality in obstetric trials.

Percutaneous vesicoamniotic shunting versus conservative management for fetal lower urinary tract obstruction (PLUTO): a randomised trial.

Summary Background Fetal lower urinary tract obstruction (LUTO) is associated with high perinatal and long-term childhood mortality and morbidity. We aimed to assess the effectiveness of vesicoamniotic shunting for treatment of LUTO. Methods In a randomised trial in the UK, Ireland, and the Netherlands, women whose pregnancies with a male fetus were complicated by isolated LUTO were randomly assigned by a central telephone and web-based randomisation service to receive either the intervention (placement of vesicoamniotic shunt) or conservative management. Allocation could not be masked from clinicians or participants because of the invasive nature of the intervention. Diagnosis was by prenatal ultrasound. The primary outcome was survival of the baby to 28 days postnatally. All primary analyses were done on an intention-to-treat basis, but these results were compared with those of an as-treated analysis to investigate the effect of a fairly large proportion of crossovers. We used Bayesian methods to estimate the posterior probability distribution of the effectiveness of vesicoamniotic shunting at 28 days. The study is registered with the ISRCTN Register, number ISRCTN53328556. Findings 31 women with singleton pregnancies complicated by LUTO were included in the trial and main analysis, with 16 allocated to the vesicoamniotic shunt group and 15 to the conservative management group. The study closed early because of poor recruitment. There were 12 livebirths in each group. In the vesicoamniotic shunt group one intrauterine death occurred and three pregnancies were terminated. In the conservative management group one intrauterine death occurred and two pregnancies were terminated. Of the 16 pregnancies randomly assigned to vesicoamniotic shunting, eight neonates survived to 28 days, compared with four from the 15 pregnancies assigned to conservative management (intention-to-treat relative risk [RR] 1·88, 95% CI 0·71–4·96; p=0·27). Analysis based on treatment received showed a larger effect (3·20, 1·06–9·62; p=0·03). All 12 deaths were caused by pulmonary hypoplasia in the early neonatal period. Sensitivity analysis in which non-treatment-related terminations of pregnancy were excluded made some slight changes to point estimates only. Bayesian analysis in which the trial data were combined with elicited priors from experts suggested an 86% probability that vesicoamniotic shunting increased survival at 28 days and a 25% probability that it had a large, clinically important effect (defined as a relative increase of 55% or more in the proportion of neonates who survived). There was substantial short-term and long-term morbidity in both groups, including poor renal function—only two babies (both in the shunt group) survived to 2 years with normal renal function. Seven complications occurred in six fetuses from the shunt group, including spontaneous ruptured membranes, shunt blockage, and dislodgement. These complications resulted in four pregnancy losses. Interpretation Survival seemed to be higher in the fetuses receiving vesicoamniotic shunting, but the size and direction of the effect remained uncertain, such that benefit could not be conclusively proven. Our results suggest that the chance of newborn babies surviving with normal renal function is very low irrespective of whether or not vesicoamniotic shunting is done. Funding UK National Institute of Health Research, Wellbeing of Women, Hannah Eliza Guy Charity (Birmingham Childrens Hospital Charity).

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.

Co-twin prognosis after single fetal death: a systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of the effects on the surviving twin of single fetal death comparing monochorionic to dichorionic twins to report the rates of co-twin death, preterm delivery, and neurologic morbidity in the surviving fetus. DATA SOURCES: MEDLINE (inception–December 2010), EMBASE (inception–December 2010), The Cochrane library (inception–December 2010), Web of Science (inception–December 2010), and British Nursing Index (inception–December 2010) were searched electronically. METHODS OF STUDY SELECTION: Selected studies had more than five cases of single fetal death with reports of co-twin death, neurologic morbidity, or both co-twin death and neurologic morbidity. They also must have defined the gestational age of single fetal death and chorionicity. TABULATION, INTEGRATION, AND RESULTS: The search yielded 1,386 citations. Full manuscripts were retrieved for 204 and 22 were included in the review and meta-analysis. Twenty manuscripts were used to calculate overall summary statistics for monochorionic and dichorionic twins showing rates of co-twin death after single fetal death (15% compared with 3%), rates of preterm delivery after single fetal death (68% compared with 54%), the rate of abnormal postnatal cranial imaging after single fetal death (34% compared with 16%), and the rate of neurodevelopmental impairment after single fetal death (26% compared with 2%). Odds ratios (ORs) were calculated from 16 manuscripts. There was no significant difference reported between preterm delivery of monochorionic or dichorionic twins (OR 1.1, 95% confidence interval [CI] 0.34–3.51, P=.9). After single fetal death, monochorionic twins had higher odds of an abnormal cranial imaging after delivery, this was not significant (OR 3.25, 95% CI 0.66–16.1, P=.12). After single fetal death, monochorionic twins were 4.81-times more likely to have neurodevelopmental morbidity (95% CI 1.39–16.6, P<.05). CONCLUSION: Monochorionic twins are at significantly increased odds of co-twin demise and neurodevelopmental morbidity after single fetal death.

Serum screening with Down's syndrome markers to predict pre-eclampsia and small for gestational age: Systematic review and meta-analysis

BackgroundReliable 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 Downs serum screening for prediction of pre-eclampsia and/or small for gestational age.MethodsThe 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 Downss serum screening before the 25th 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.ResultsFive 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 < 10th 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.There were methodological and reporting limitations in the included studies thus studies were heterogeneous giving pooled results with wide confidence intervals.ConclusionDowns 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.

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.

Effectiveness of fetal cystoscopy as a diagnostic and therapeutic intervention for lower urinary tract obstruction: a systematic review

To determine the effectiveness of fetal cystoscopy in the prenatal diagnosis of and intervention for congenital lower urinary tract obstruction.