DOI: 10.1111/1471-0528.12589
Systematic review
www.bjog.org
Association and prediction of amniotic fluid measurements for adverse pregnancy outcome: systematic review and meta-analysis RK Morris,a,b CH Meller,b,c J Tamblyn,d GM Malin,e RD Riley,f MD Kilby,a SC Robson,g KS Khanh a
Birmingham Centre for Women’s & Children’s Health & School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK b Fetal Medicine Centre, Birmingham Women’s Hospital NHS Foundation Trust, Birmingham, UK c Obstetrics Division, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina d University North Staffordshire NHS Trust Hospital, Stoke on Trent, UK e School of Clinical Sciences, the University of Nottingham, Nottingham, UK f School of Health and Population Sciences, University of Birmingham, Birmingham, UK g Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK h Women’s Health Research Unit, The Blizard Institute, Barts and The London School of Medicine, Queen Mary, University of London, London, UK Correspondence: RK Morris, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK. Email [email protected] Accepted 4 November 2013. Published Online 7 February 2014.
Background Measurements of amniotic fluid volume are used for
pregnancy surveillance despite a lack of evidence for their predictive ability. Objective To evaluate the association and predictive value of
ultrasound measurements of amniotic fluid volume for adverse pregnancy outcome. Search strategy Electronic databases (inception to October 2011),
reference lists, hand searching of journals, contact with experts. Selection criteria Studies comparing measurements of amniotic
fluid volume with adverse outcome, excluding pre-labour ruptured membranes or congenital/structural anomalies. Data collection Data on study characteristics, design, quality.
Random effects meta-analysis to estimate summary odds ratios (prognostic association) and summary sensitivity, specificity and likelihood ratios (predictive ability). Main results Forty-three studies (244 493 fetuses) were included demonstrating a strong association between oligohydramnios (varying definitions) and birthweight 8 cm or amniotic fluid index ≥25 cm) and birthweight >90th centile (OR 11.41, 95% CI 7.09–18.36; n = 1 study, 3960 fetuses). Despite strong associations, predictive accuracy for perinatal outcome was poor. Author’s conclusion Current evidence suggests that
oligohydramnios is strongly associated with being small for gestational age and mortality, and polyhydramnios with birthweight >90th centile. Despite strong associations with poor outcome, they do not accurately predict outcome risk for individuals. Keywords Amniotic fluid, oligohydramnios, predictive accuracy, prognosis, small for gestational age.
Please cite this paper as: Morris RK, Meller CH, Tamblyn J, Malin GM, Riley RD, Kilby MD, Robson SC, Khan KS. Association and prediction of amniotic fluid measurements for adverse pregnancy outcome: systematic review and meta-analysis. BJOG 2014;121:686–699.
Introduction The amniotic fluid is fundamental for proper fetal development and growth, and amniotic fluid volume measurements using prenatal ultrasound have become standard in fetal surveillance, especially in the evaluation of high-risk pregnancies. Alterations in amniotic fluid volume, especially decreased amniotic fluid volume (oligohydramnios),
686
have classically been considered an indicator of adverse perinatal outcome and, therefore, have led to an almost uniform recommendation for delivery following the diagnosis of oligohydramnios, at least for patients at term.1 However, the number of ultrasonographic modalities applied to assess amniotic fluid volume and the various threshold points reflect the inaccuracies inherent in each of these modalities.2–7 Moreover, the association between
ª 2014 Royal College of Obstetricians and Gynaecologists
Amniotic fluid measurement and adverse pregnancy outcome
abnormal amniotic fluid volume and adverse perinatal outcomes came from heterogeneous studies that frequently included patients with preterm ruptured membranes or different underlying medical conditions, and/or fetuses with structural anomalies, clinical situations that may affect the amniotic fluid volume.1 A previous review of randomised controlled trials (RCTs) has concluded that single deepest vertical pocket measurement is the method of choice for the assessment of amniotic fluid volume8 on the basis that neither method was superior but that amniotic fluid index (AFI) led to more diagnoses of oligohydramnios, more inductions of labour and more caesarean deliveries for fetal distress without improving perinatal outcome.8 The observed effect in these RCTs is determined by both test accuracy and the effect of the intervention9 that follows testing; a conclusion of this review was that a systematic review of the accuracy of AFI versus single deepest pocket was needed.8 Therefore we present here a systematic review and meta-analysis of the literature to assess the prognostic association and predictive accuracy of measurements of amniotic fluid for adverse pregnancy outcome and we compare the performance of different techniques of measurement of amniotic fluid.
Methods
were obtained. Translations were obtained for non-English articles. Three reviewers made the final inclusion/exclusion decisions according to adherence to the following criteria. 1 Population. Pregnant women, with or without fetal growth restriction, no evidence of premature rupture of membranes, no evidence of congenital or structural anomalies. 2 Index test. Any measure of amniotic fluid reported by the authors including AFI, amniotic fluid volume and maximum deepest pocket. Any threshold used to define low or high amniotic fluid as reported by the authors of the included studies was accepted. 3 Outcome. Any reference standard looking at compromise of fetal or neonatal wellbeing; including: abnormal cord pH at birth, Apgar scores, perinatal death and composite outcomes such as adverse perinatal outcome. Any reference standard for fetal growth restriction or small for gestational age: Birthweight 0% we also estimated a prediction interval to reveal the potential prognostic effect if the test is applied in a single setting similar to one of the studies from our analysis.21 This was calculated where three or more studies were included in the meta-analysis.21 We plotted summary odds ratio data in forest plots and assessed the between-study heterogeneity in prognostic effect of each test by estimating I2 (the amount of variability in prognostic effects due to between-study heterogeneity)24 and tau-squared.25 Where possible we performed meta-regression or subgroup analysis as appropriate to examine the effect of potential confounding factors: singleton or multiple birth status, timing of test in relation to delivery, gestation of pregnancy at time of testing, highrisk or low-risk population as assessed by the study authors, and study quality were considered to be important factors that may influence the strength of the association between amniotic fluid measurement and adverse outcome. In studies where there were cells in the 2 9 2 table with a value of 0, 0.5 was added to all cells to allow the calculation of log odds ratios and their variances for meta-analysis.26 Meta-analyses were performed where two or more studies reported the same index test and outcome measure. The primary outcomes were considered to be birthweight 1 indicate a prognostic association at the population level, we felt that only an odds ratio >5 would indicate a sufficient discrepancy between amniotic fluid volumes that may have predictive ability at the individual level. Therefore we only considered test accuracy at the individual level (in terms of sensitivity and specificity of a test) when its odds ratio was >5, the 95% CI did not cross 1 and there was statistical significance. We assessed the predictive ability30 of the test by calculating summary sensitivity, specificity and likelihood ratios, again using data from the 2 9 2 tables and synthesising using a bivariate random-effects meta-analysis model.31 Likelihood ratios indicate by how much a given test result raises or lowers the odds of having the disease and have been recommended by Evidence-based Medicine Groups32,33 as they show how the test result informs clinical decision making. All analyses were performed in STATA version 11.0 (StataCorp, College Station, TX, USA) using the metan, metandi and metabias commands.34–36 Summary results were displayed in forest plots generated using STATSDIRECT.
Results Figure 1 summarises the process of literature identification and selection. Of the 6259 potential citations, 43 primary articles were included in the critical appraisal and systematic review. Appendix S4 details the individual study characteristics of the included studies and their references. There were 43 studies included overall, reporting on 244 493 fetuses. The commonest index tests reported were amniotic fluid index ≤5 cm (number of studies, n = 23) and maximum pool depth (MPD) ≤2 cm (n = 6; Figure 1). The outcome measures reported most often were birthweight
Systematic review
www.bjog.org
Association and prediction of amniotic fluid measurements for adverse pregnancy outcome: systematic review and meta-analysis RK Morris,a,b CH Meller,b,c J Tamblyn,d GM Malin,e RD Riley,f MD Kilby,a SC Robson,g KS Khanh a
Birmingham Centre for Women’s & Children’s Health & School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK b Fetal Medicine Centre, Birmingham Women’s Hospital NHS Foundation Trust, Birmingham, UK c Obstetrics Division, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina d University North Staffordshire NHS Trust Hospital, Stoke on Trent, UK e School of Clinical Sciences, the University of Nottingham, Nottingham, UK f School of Health and Population Sciences, University of Birmingham, Birmingham, UK g Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK h Women’s Health Research Unit, The Blizard Institute, Barts and The London School of Medicine, Queen Mary, University of London, London, UK Correspondence: RK Morris, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK. Email [email protected] Accepted 4 November 2013. Published Online 7 February 2014.
Background Measurements of amniotic fluid volume are used for
pregnancy surveillance despite a lack of evidence for their predictive ability. Objective To evaluate the association and predictive value of
ultrasound measurements of amniotic fluid volume for adverse pregnancy outcome. Search strategy Electronic databases (inception to October 2011),
reference lists, hand searching of journals, contact with experts. Selection criteria Studies comparing measurements of amniotic
fluid volume with adverse outcome, excluding pre-labour ruptured membranes or congenital/structural anomalies. Data collection Data on study characteristics, design, quality.
Random effects meta-analysis to estimate summary odds ratios (prognostic association) and summary sensitivity, specificity and likelihood ratios (predictive ability). Main results Forty-three studies (244 493 fetuses) were included demonstrating a strong association between oligohydramnios (varying definitions) and birthweight 8 cm or amniotic fluid index ≥25 cm) and birthweight >90th centile (OR 11.41, 95% CI 7.09–18.36; n = 1 study, 3960 fetuses). Despite strong associations, predictive accuracy for perinatal outcome was poor. Author’s conclusion Current evidence suggests that
oligohydramnios is strongly associated with being small for gestational age and mortality, and polyhydramnios with birthweight >90th centile. Despite strong associations with poor outcome, they do not accurately predict outcome risk for individuals. Keywords Amniotic fluid, oligohydramnios, predictive accuracy, prognosis, small for gestational age.
Please cite this paper as: Morris RK, Meller CH, Tamblyn J, Malin GM, Riley RD, Kilby MD, Robson SC, Khan KS. Association and prediction of amniotic fluid measurements for adverse pregnancy outcome: systematic review and meta-analysis. BJOG 2014;121:686–699.
Introduction The amniotic fluid is fundamental for proper fetal development and growth, and amniotic fluid volume measurements using prenatal ultrasound have become standard in fetal surveillance, especially in the evaluation of high-risk pregnancies. Alterations in amniotic fluid volume, especially decreased amniotic fluid volume (oligohydramnios),
686
have classically been considered an indicator of adverse perinatal outcome and, therefore, have led to an almost uniform recommendation for delivery following the diagnosis of oligohydramnios, at least for patients at term.1 However, the number of ultrasonographic modalities applied to assess amniotic fluid volume and the various threshold points reflect the inaccuracies inherent in each of these modalities.2–7 Moreover, the association between
ª 2014 Royal College of Obstetricians and Gynaecologists
Amniotic fluid measurement and adverse pregnancy outcome
abnormal amniotic fluid volume and adverse perinatal outcomes came from heterogeneous studies that frequently included patients with preterm ruptured membranes or different underlying medical conditions, and/or fetuses with structural anomalies, clinical situations that may affect the amniotic fluid volume.1 A previous review of randomised controlled trials (RCTs) has concluded that single deepest vertical pocket measurement is the method of choice for the assessment of amniotic fluid volume8 on the basis that neither method was superior but that amniotic fluid index (AFI) led to more diagnoses of oligohydramnios, more inductions of labour and more caesarean deliveries for fetal distress without improving perinatal outcome.8 The observed effect in these RCTs is determined by both test accuracy and the effect of the intervention9 that follows testing; a conclusion of this review was that a systematic review of the accuracy of AFI versus single deepest pocket was needed.8 Therefore we present here a systematic review and meta-analysis of the literature to assess the prognostic association and predictive accuracy of measurements of amniotic fluid for adverse pregnancy outcome and we compare the performance of different techniques of measurement of amniotic fluid.
Methods
were obtained. Translations were obtained for non-English articles. Three reviewers made the final inclusion/exclusion decisions according to adherence to the following criteria. 1 Population. Pregnant women, with or without fetal growth restriction, no evidence of premature rupture of membranes, no evidence of congenital or structural anomalies. 2 Index test. Any measure of amniotic fluid reported by the authors including AFI, amniotic fluid volume and maximum deepest pocket. Any threshold used to define low or high amniotic fluid as reported by the authors of the included studies was accepted. 3 Outcome. Any reference standard looking at compromise of fetal or neonatal wellbeing; including: abnormal cord pH at birth, Apgar scores, perinatal death and composite outcomes such as adverse perinatal outcome. Any reference standard for fetal growth restriction or small for gestational age: Birthweight 0% we also estimated a prediction interval to reveal the potential prognostic effect if the test is applied in a single setting similar to one of the studies from our analysis.21 This was calculated where three or more studies were included in the meta-analysis.21 We plotted summary odds ratio data in forest plots and assessed the between-study heterogeneity in prognostic effect of each test by estimating I2 (the amount of variability in prognostic effects due to between-study heterogeneity)24 and tau-squared.25 Where possible we performed meta-regression or subgroup analysis as appropriate to examine the effect of potential confounding factors: singleton or multiple birth status, timing of test in relation to delivery, gestation of pregnancy at time of testing, highrisk or low-risk population as assessed by the study authors, and study quality were considered to be important factors that may influence the strength of the association between amniotic fluid measurement and adverse outcome. In studies where there were cells in the 2 9 2 table with a value of 0, 0.5 was added to all cells to allow the calculation of log odds ratios and their variances for meta-analysis.26 Meta-analyses were performed where two or more studies reported the same index test and outcome measure. The primary outcomes were considered to be birthweight 1 indicate a prognostic association at the population level, we felt that only an odds ratio >5 would indicate a sufficient discrepancy between amniotic fluid volumes that may have predictive ability at the individual level. Therefore we only considered test accuracy at the individual level (in terms of sensitivity and specificity of a test) when its odds ratio was >5, the 95% CI did not cross 1 and there was statistical significance. We assessed the predictive ability30 of the test by calculating summary sensitivity, specificity and likelihood ratios, again using data from the 2 9 2 tables and synthesising using a bivariate random-effects meta-analysis model.31 Likelihood ratios indicate by how much a given test result raises or lowers the odds of having the disease and have been recommended by Evidence-based Medicine Groups32,33 as they show how the test result informs clinical decision making. All analyses were performed in STATA version 11.0 (StataCorp, College Station, TX, USA) using the metan, metandi and metabias commands.34–36 Summary results were displayed in forest plots generated using STATSDIRECT.
Results Figure 1 summarises the process of literature identification and selection. Of the 6259 potential citations, 43 primary articles were included in the critical appraisal and systematic review. Appendix S4 details the individual study characteristics of the included studies and their references. There were 43 studies included overall, reporting on 244 493 fetuses. The commonest index tests reported were amniotic fluid index ≤5 cm (number of studies, n = 23) and maximum pool depth (MPD) ≤2 cm (n = 6; Figure 1). The outcome measures reported most often were birthweight
